|
1
|
Ugai S, Liu L, Kosumi K, Kawamura H, Hamada T, Mima K, Arima K, Okadome K, Yao Q, Matsuda K, Zhong Y, Mizuno H, Chan AT, Garrett WS, Song M, Giannakis M, Giovannucci EL, Zhang X, Ogino S, Ugai T. Long-term yogurt intake and colorectal cancer incidence subclassified by Bifidobacterium abundance in tumor. Gut Microbes 2025; 17:2452237. [PMID: 39937126 PMCID: PMC11834522 DOI: 10.1080/19490976.2025.2452237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 12/27/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025] Open
Abstract
Evidence suggests a tumor-suppressive effect of the intake of yogurt, which typically contains Bifidobacterium. We hypothesized that long-term yogurt intake might be associated with colorectal cancer incidence differentially by tumor subgroups according to the amount of tissue Bifidobacterium. We utilized the prospective cohort incident-tumor biobank method and resources of two prospective cohort studies. Inverse probability weighted multivariable Cox proportional hazards regression was used to assess differential associations of yogurt intake with the incidence of colorectal carcinomas subclassified by the abundance of tumor tissue Bifidobacterium. During follow-up of 132,056 individuals, we documented 3,079 incident colorectal cancer cases, including 1,121 with available tissue Bifidobacterium data. The association between long-term yogurt intake and colorectal cancer incidence differed by Bifidobacterium abundance (P heterogeneity = 0.0002). Multivariable-adjusted hazard ratios (HRs) (with 95% confidence intervals) in individuals who consumed ≥2 servings/week (vs. <1 serving/month) of yogurt were 0.80 (0.50-1.28) for Bifidobacterium-positive tumor and 1.09 (0.81-1.46) for Bifidobacterium-negative tumor. This differential association was also observed in a subgroup analysis of proximal colon cancer (P heterogeneity = 0.018). Long-term yogurt intake may be differentially associated with the incidence of proximal colon cancer according to Bifidobacterium abundance, suggesting the antitumor effect of yogurt intake on the specific tumor subgroup.
Collapse
Affiliation(s)
- Satoko Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Li Liu
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Keisuke Kosumi
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Hidetaka Kawamura
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Surgery, Fukushima Medical University, Fukushima, Japan
| | - Tsuyoshi Hamada
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kosuke Mima
- Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kazuo Okadome
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Qian Yao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kosuke Matsuda
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Yuxue Zhong
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Hiroki Mizuno
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T. Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Wendy S. Garrett
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Marios Giannakis
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Edward L. Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Yale University School of Nursing, Orange, CT, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology Program, Dana-Farber/Harvard Cancer Center, Boston, MA, USA
- Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| |
Collapse
|
|
2
|
Yuan Z, Li J, Na Q. Recent advances in biomimetic nanodelivery systems for the treatment of glioblastoma. Colloids Surf B Biointerfaces 2025; 252:114668. [PMID: 40168694 DOI: 10.1016/j.colsurfb.2025.114668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/24/2025] [Accepted: 03/26/2025] [Indexed: 04/03/2025]
Abstract
Glioblastoma remain one of the deadliest malignant tumors in the central nervous system, largely due to their aggressiveness, high degree of heterogeneity, and the protective barrier of the blood-brain barrier (BBB). Conventional therapies including surgery, chemotherapy and radiotherapy often fail to improve patient prognosis due to limited drug penetration and non-specific toxicity. We then present recent advances in biomimetic nanodelivery systems, focusing on cell membrane coatings, nanoenzymes, and exosome-based carriers. By mimicking endogenous biological functions, these systems demonstrate improved immune evasion, enhanced BBB traversal, and selective drug release within the tumor microenvironment. Nevertheless, we acknowledge unresolved bottlenecks related to large-scale production, stability, and the intricacies of regulatory compliance. Looking forward, we propose an interdisciplinary roadmap that combines materials engineering, cellular biology, and clinical expertise. Through this collaborative approach, this work aims to optimize biomimetic nanodelivery for glioma therapy and ultimately improve patient outcomes.
Collapse
Affiliation(s)
- Zhenru Yuan
- General Hospital of Northern Theater Command, Liaoning 110016, China
| | - Jing Li
- General Hospital of Northern Theater Command, Liaoning 110016, China
| | - Qi Na
- General Hospital of Northern Theater Command, Liaoning 110016, China.
| |
Collapse
|
|
3
|
Khalid AQ, Zaidan TN, Bhuvanendran S, Magalingam KB, Mohamedahmed SM, Ramdas P, Radhakrishnan AK. Insights into the Anticancer Mechanisms Modulated by Gamma and Delta Tocotrienols in Colorectal Cancers. Nutr Rev 2025; 83:e1295-e1310. [PMID: 39181121 DOI: 10.1093/nutrit/nuae108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/27/2024] Open
Abstract
Colorectal cancer (CRC) is a growing concern all over the world. There has been a concerted effort to identify natural bioactive compounds that can be used to prevent or overcome this condition. Tocotrienols (T3s) are a naturally occurring form of vitamin E known for various therapeutic effects, such as anticancer, antioxidant, neuroprotective, and anti-inflammatory activities. The literature evidence suggests that two T3 analogues, ie, gamma (γ)- and delta (δ)-T3, can modulate cancers via several cancer-related signaling pathways. The aim of this review was to compile and analyze the existing literature on the diverse anticancer mechanisms of γT3 and δT3 exhibited in CRC cells, to showcase the anticancer potential of T3s. Medline was searched for research articles on anticancer effects of γT3 and δT3 in CRC published in the past 2 decades. A total of 38 articles (26 cell-based, 9 animal studies, 2 randomized clinical trials, and 1 scoping review) that report anticancer effects of γT3 and δT3 in CRC were identified. The findings reported in those articles indicate that γT3 and δT3 inhibit the proliferation of CRC cells, induce cell cycle arrest and apoptosis, suppress metastasis, and produce synergistic anticancer effects when combined with well-established anticancer agents. There is preliminary evidence that shows that T3s affect telomerase functions and support anticancer immune responses. γT3 and δT3 have the potential for development as anticancer agents.
Collapse
Affiliation(s)
- Ali Qusay Khalid
- Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Malaysia
| | - Tabarek Najeeb Zaidan
- Department of Food Science and Nutrition, Faculty of Applied Sciences, UCSI University, UCSI Heights, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Saatheeyavaane Bhuvanendran
- Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Malaysia
| | - Kasthuri B Magalingam
- Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Malaysia
| | - Shaza M Mohamedahmed
- Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Malaysia
| | - Premdass Ramdas
- Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Malaysia
| | - Ammu K Radhakrishnan
- Food as Medicine Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, 47500 Bandar Sunway, Malaysia
| |
Collapse
|
|
4
|
Wu Y, Jiang X, Yu Z, Xing Z, Ma Y, Qing H. Mechanisms of Anti-PD Therapy Resistance in Digestive System Neoplasms. Recent Pat Anticancer Drug Discov 2025; 20:1-25. [PMID: 38305306 DOI: 10.2174/0115748928269276231120103256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 09/25/2023] [Accepted: 10/03/2023] [Indexed: 02/03/2024]
Abstract
Digestive system neoplasms are highly heterogeneous and exhibit complex resistance mechanisms that render anti-programmed cell death protein (PD) therapies poorly effective. The tumor microenvironment (TME) plays a pivotal role in tumor development, apart from supplying energy for tumor proliferation and impeding the body's anti-tumor immune response, the TME actively facilitates tumor progression and immune escape via diverse pathways, which include the modulation of heritable gene expression alterations and the intricate interplay with the gut microbiota. In this review, we aim to elucidate the mechanisms underlying drug resistance in digestive tumors, focusing on immune-mediated resistance, microbial crosstalk, metabolism, and epigenetics. We will highlight the unique characteristics of each digestive tumor and emphasize the significance of the tumor immune microenvironment (TIME). Furthermore, we will discuss the current therapeutic strategies that hold promise for combination with cancer immune normalization therapies. This review aims to provide a thorough understanding of the resistance mechanisms in digestive tumors and offer insights into potential therapeutic interventions.
Collapse
Affiliation(s)
- Yuxia Wu
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Xiangyan Jiang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Zeyuan Yu
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Zongrui Xing
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Yong Ma
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Huiguo Qing
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| |
Collapse
|
|
5
|
Ogino S, Ugai T. The global epidemic of early-onset cancer: nature, nurture, or both? Ann Oncol 2024; 35:1071-1073. [PMID: 39293513 PMCID: PMC11624085 DOI: 10.1016/j.annonc.2024.08.2336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 08/26/2024] [Indexed: 09/20/2024] Open
Affiliation(s)
- S Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston; Broad Institute of MIT and Harvard, Cambridge; Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston; Division of Nutrition, Harvard Medical School, Boston, USA; Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan.
| | - T Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston
| |
Collapse
|
|
6
|
Nishihara K, Nakano S, Yamaji T, Goto A, Hidaka A, Shimazu T, Kuchiba A, Saito M, Kunishima F, Nakaza R, Kato I, Sawada N, Inoue M, Tsugane S, Iwasaki M. Height, body mass index, physical activity, and risk of colorectal cancer in relation to expression of insulin receptor: The Japan Public Health Center-based Prospective Study. Int J Cancer 2024; 155:1751-1761. [PMID: 38970390 DOI: 10.1002/ijc.35075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 05/30/2024] [Accepted: 06/06/2024] [Indexed: 07/08/2024]
Abstract
To ascertain the involvement of insulin receptors (IRs) in colorectal carcinogenesis, we investigated the association of height, body mass index (BMI), and physical activity with colorectal cancer (CRC) and two subtypes of CRC according to the expression level of IR. We utilized data from a large-scale, population-based prospective cohort study of 18,158 middle-aged and elderly subjects in Akita and Okinawa, Japan. In the statistical analysis, we used the Cox proportional hazards model and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subtypes as defined by immunohistochemistry of IRβ, a transmembrane subunit of IR. In the IRβ-defined subtypes, height showed no apparent association with the risk of IRβ-positive CRC. In contrast, a multivariable HR of IRβ-positive CRC was 1.77 (95% CI = 1.04-3.03) with a BMI of ≥30.0 kg/m2 (i.e., obesity), compared to a BMI of <25.0 kg/m2. Further, an increase in physical activity was significantly associated with decreased risk of IRβ-positive CRC (multivariable HR per 5 METs-hour/day = 0.93, 95% CI = 0.88-0.99). Meanwhile, we found no significant association between any exposure and IRβ-negative CRC. Likewise, heterogeneity between the two subtypes of CRC was not statistically significant. These findings imply that obesity and physical activity exert promoting and suppressing effects on the development of CRC expressing IRs, respectively.
Collapse
Affiliation(s)
- Kenshiro Nishihara
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Shiori Nakano
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Atsushi Goto
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Department of Public Health, Yokohama City University, Yokohama, Japan
| | - Akihisa Hidaka
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Department of Diabetes and Endocrinology, JCHO Tokyo Yamate Medical Centre, Tokyo, Japan
| | - Taichi Shimazu
- Division of Behavioral Sciences, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Aya Kuchiba
- Graduate School of Health Innovation, Kanagawa University of Human Services, Kawasaki, Japan
- Division of Biostatistical Research, Institute for Cancer Control/Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan
| | - Masahiro Saito
- Department of Diagnostic Pathology, Hiraka General Hospital, Yokote, Japan
| | - Fumihito Kunishima
- Department of Diagnostic Pathology, Okinawa Prefecture Chubu Hospital, Uruma, Japan
| | - Ryouji Nakaza
- Department of Clinical Laboratory, Nakagami Hospital, Okinawa, Japan
| | - Ikuma Kato
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Manami Inoue
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Division of Prevention, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- International University of Health and Welfare Graduate School of Public Health, Tokyo, Japan
| | - Motoki Iwasaki
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| |
Collapse
|
|
7
|
Li S, Hao L, Hu X. Biological Roles and Clinical Therapeutic Applications of Tumor-Associated Macrophages in Colorectal Liver Metastasis. J Inflamm Res 2024; 17:8429-8443. [PMID: 39529996 PMCID: PMC11552512 DOI: 10.2147/jir.s493656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
Colorectal cancer (CRC) commonly metastasizes to the liver, and this poses a significant clinical challenge. Tumor-associated macrophages (TAMs), key players within the TME, play a significant role in promoting CRC metastasis by secreting various chemokines, growth factors, and cytokines. This review not only aims to enhance our knowledge of TAMs' functions in CRC progression and metastasis but also examines innovative therapeutic strategies to address the clinical problem of colorectal liver metastasis (CLM). By targeting TAMs, we may be able to develop more effective treatments and offer hope to patients suffering from this devastating disease.
Collapse
Affiliation(s)
- Shenghao Li
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China
| | - Liyuan Hao
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China
| | - Xiaoyu Hu
- Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China
| |
Collapse
|
|
8
|
Chen DS, Chen ZP, Zhu DZ, Guan LX, Zhu Q, Lou YC, He ZP, Chen HN, Sun HC. Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults: 30 years’ overview and forecasted trends. World J Gastrointest Oncol 2024; 16:4177-4193. [DOI: 10.4251/wjgo.v16.i10.4177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 08/18/2024] [Accepted: 08/28/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND Hepatobiliary and pancreatic (HBP) cancers impose a considerable burden on young populations (aged 15 to 49 years), resulting in a substantial number of new cases and fatalities each year. In young populations, the HBP cancers shows extensive variance worldwide and the updated data in China is lacking.
AIM To investigate the current status, trends, projections, and underlying risk factors of HBP cancers among young populations in China.
METHODS The Global Burden of Disease Study 2019 provided data on the annual incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rate (ASIR), mortality rate (ASMR), and DALYs rate (ASDR) of HBP cancers in young Chinese adults between 1990 and 2019. Temporal trends were assessed using estimated annual percentage change and hierarchical clustering. Sex-specific mortality and DALYs caused by various risks were analyzed across China and other regions, with future trends until 2035 projected using the Bayesian age-period-cohort model.
RESULTS From 1990 to 2019, incident cases, deaths, DALYs, ASIR, ASMR, and ASDR for liver cancer (LC) in young Chinese individuals decreased, classified into 'significant decrease' group. Conversely, cases of gallbladder and biliary tract cancer and pancreatic cancer rose, categorized as either 'significant increase' or 'minor increase' groups. The contribution of risk factors to mortality and DALYs for HBP tumors increased to varying degrees. Healthy lifestyle behaviors, such as tobacco control, weight management, alcohol moderation, and drug avoidance, could lower HBP cancers incidence. Moreover, except for LC in females, which is likely to initially decline slightly and then rise, the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young adults.
CONCLUSION HBP cancers burden among young adults in China is expected to increase until 2035, necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these cancers.
Collapse
Affiliation(s)
- De-Sheng Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Ze-Ping Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Dong-Zi Zhu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Lv-Xin Guan
- Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong Province, China
| | - Qi Zhu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Yi-Chao Lou
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Ze-Ping He
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Hao-Nan Chen
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Hong-Cheng Sun
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| |
Collapse
|
|
9
|
Espelage L, Wagner N, Placke JM, Ugurel S, Tasdogan A. The Interplay between Metabolic Adaptations and Diet in Cancer Immunotherapy. Clin Cancer Res 2024; 30:3117-3127. [PMID: 38771898 DOI: 10.1158/1078-0432.ccr-22-3468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 11/07/2023] [Accepted: 04/15/2024] [Indexed: 05/23/2024]
Abstract
Over the past decade, cancer immunotherapy has significantly advanced through the introduction of immune checkpoint inhibitors and the augmentation of adoptive cell transfer to enhance the innate cancer defense mechanisms. Despite these remarkable achievements, some cancers exhibit resistance to immunotherapy, with limited patient responsiveness and development of therapy resistance. Metabolic adaptations in both immune cells and cancer cells have emerged as central contributors to immunotherapy resistance. In the last few years, new insights emphasized the critical role of cancer and immune cell metabolism in animal models and patients. During therapy, immune cells undergo important metabolic shifts crucial for their acquired effector function against cancer cells. However, cancer cell metabolic rewiring and nutrient competition within tumor microenvironment (TME) alters many immune functions, affecting their fitness, polarization, recruitment, and survival. These interactions have initiated the development of novel therapies targeting tumor cell metabolism and favoring antitumor immunity within the TME. Furthermore, there has been increasing interest in comprehending how diet impacts the response to immunotherapy, given the demonstrated immunomodulatory and antitumor activity of various nutrients. In conclusion, recent advances in preclinical and clinical studies have highlighted the capacity of immune-based cancer therapies. Therefore, further exploration into the metabolic requirements of immune cells within the TME holds significant promise for the development of innovative therapeutic approaches that can effectively combat cancer in patients.
Collapse
Affiliation(s)
- Lena Espelage
- Department of Dermatology, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany
| | - Natalie Wagner
- Department of Dermatology, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany
| | - Jan-Malte Placke
- Department of Dermatology, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany
| | - Selma Ugurel
- Department of Dermatology, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany
| | - Alpaslan Tasdogan
- Department of Dermatology, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany
| |
Collapse
|
|
10
|
Zou H, Liu C, Ruan Y, Fang L, Wu T, Han S, Dang T, Meng H, Zhang Y. Colorectal medullary carcinoma: a pathological subtype with intense immune response and potential to benefit from immune checkpoint inhibitors. Expert Rev Clin Immunol 2024; 20:997-1008. [PMID: 38459764 DOI: 10.1080/1744666x.2024.2328746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 03/06/2024] [Indexed: 03/10/2024]
Abstract
INTRODUCTION Different pathological types of colorectal cancer have distinguished immune landscape, and the efficacy of immunotherapy will be completely different. Colorectal medullary carcinoma, accounting for 2.2-3.2%, is characterized by massive lymphocyte infiltration. However, the attention to the immune characteristics of colorectal medullary carcinoma is insufficient. AREA COVERED We searched the literature about colorectal medullary carcinoma on PubMed through November 2023to investigate the hallmarks of colorectal medullary carcinoma's immune landscape, compare medullary carcinoma originating from different organs and provide theoretical evidence for precise treatment, including applying immunotherapy and BRAF inhibitors. EXPERT OPINION Colorectal medullary carcinoma is a pathological subtype with intense immune response, with six immune characteristics and has the potential to benefit from immunotherapy. Mismatch repair deficiency, ARID1A missing and BRAF V600E mutation often occurs. IFN-γ pathway is activated and PD-L1 expression is increased. Abundant lymphocyte infiltration performs tumor killing function. In addition, BRAF mutation plays an important role in the occurrence and development, and we can consider the combination of BRAF inhibitors and immunotherapy in patients with BRAF mutant. The exploration of colorectal medullary carcinoma will arouse researchers' attention to the correlation between pathological subtypes and immune response, and promote the process of precise immunotherapy.
Collapse
Affiliation(s)
- Haoyi Zou
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Chao Liu
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yuli Ruan
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, China
| | - Lin Fang
- Phase I Clinical Research Center, The Affiliated Hospital of Qingdao University in Shandong, Qingdao, China
| | - Tong Wu
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shuling Han
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Tianjiao Dang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Hongxue Meng
- Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
- Key Laboratory of Tumor Immunology in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, China
- Clinical Research Center for Colorectal Cancer in Heilongjiang, Harbin Medical University Cancer Hospital, Harbin, China
| |
Collapse
|
|
11
|
Wildgoose P, Servidio-Italiano F, Raphael MJ, Slovinec D’Angelo M, Macaulay C, Kassam S, Nixon N, Perea J, Hamilton S, Ramjeesingh R, Gill S, Pollett A, Ogino S, Ugai T, Gupta A. Addressing the Rising Trend in Early-Age-Onset Cancers in Canada. Curr Oncol 2024; 31:4063-4078. [PMID: 39057175 PMCID: PMC11276492 DOI: 10.3390/curroncol31070303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 07/11/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
A multi-disciplinary symposium on early-age onset cancer (EAOC) was held in October 2023 to explore challenges experienced by this rapidly growing population. A major outcome of the symposium was recognition of the remarkable similarities of EAOC patients' journeys across cancer sites. Prevention and early detection of cancer are hindered by a lack of awareness among patients and family doctors that cancer can and does occur in younger persons. Distinct characteristics of the disease-such as a later stage at diagnosis and more aggressive tumor biology-require more potent treatments, which result in profound physical and psychosocial consequences that are unique to this age group. EAOC patient empowerment emerged as another key theme of the symposium. The development of a greater number of specialized clinics was called for, and patient support groups were recognized for the vital role they play in empowering patients and their families. Leading-edge medical advancements hold tremendous hope across the spectrum of EAOC care. New technologies based on genomic profiling, immunotherapy and microbiome alteration contribute to the development of highly effective, personalized approaches to treatment. All symposium participants expressed their commitment to speak with one resounding voice to advocate for equitable access to leading care practices for EAOC patients; thus, a fourth symposium is planned for November 2024.
Collapse
Affiliation(s)
- Petra Wildgoose
- Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada;
| | - Filomena Servidio-Italiano
- Colorectal Cancer Resource & Action Network (CCRAN), Toronto, ON M4W 3E2, Canada; (F.S.-I.); (M.S.D.); (C.M.)
| | | | - Monika Slovinec D’Angelo
- Colorectal Cancer Resource & Action Network (CCRAN), Toronto, ON M4W 3E2, Canada; (F.S.-I.); (M.S.D.); (C.M.)
| | - Cassandra Macaulay
- Colorectal Cancer Resource & Action Network (CCRAN), Toronto, ON M4W 3E2, Canada; (F.S.-I.); (M.S.D.); (C.M.)
| | - Shaqil Kassam
- Southlake Stronach Regional Cancer Centre, Newmarket, ON L3Y 2P9, Canada;
| | - Nancy Nixon
- Tom Baker Cancer Centre, Calgary, AB T2N 4N2, Canada;
| | - José Perea
- Department of Medicine, Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain;
| | - Sarah Hamilton
- BC Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (S.H.); (S.G.)
| | - Ravi Ramjeesingh
- Nova Scotia Cancer Centre, Dalhousie University, Halifax, NS B3H 1V8, Canada;
| | - Sharlene Gill
- BC Cancer Agency, Vancouver, BC V5Z 4E6, Canada; (S.H.); (S.G.)
| | - Aaron Pollett
- Division of Diagnostic Medical Genetics, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada;
| | - Shuji Ogino
- Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - Tomotaka Ugai
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA;
| | - Abha Gupta
- Adolescent & Young Adult (AYA) Oncology Program, Princess Margaret Hospital, Toronto, ON M5G 2M9, Canada;
| |
Collapse
|
|
12
|
Kawamura H, Ugai T, Takashima Y, Okadome K, Shimizu T, Mima K, Akimoto N, Haruki K, Arima K, Zhao M, Väyrynen JP, Wu K, Zhang X, Ng K, Nowak JA, Meyerhardt JA, Giovannucci EL, Giannakis M, Chan AT, Huttenhower C, Garrett WS, Song M, Ogino S. Appendectomy and Long-term Colorectal Cancer Incidence, Overall and by Tumor Fusobacterium nucleatum Status. Ann Surg 2024:00000658-990000000-00870. [PMID: 38708875 PMCID: PMC11538369 DOI: 10.1097/sla.0000000000006315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2024]
Abstract
OBJECTIVE To test hypotheses that appendectomy history might lower long-term colorectal cancer risk and that the risk reduction might be strong for tumors enriched with Fusobacterium nucleatum, bacterial species implicated in colorectal carcinogenesis. BACKGROUND The absence of the appendix, an immune system organ and a possible reservoir of certain pathogenic microbes, may affect the intestinal microbiome, thereby altering long-term colorectal cancer risk. METHODS Utilizing databases of prospective cohort studies, namely the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of appendectomy history with colorectal cancer incidence overall and subclassified by the amount of tumor tissue Fusobacterium nucleatum (Fusobacterium animalis). We used an inverse probability weighted multivariable-adjusted duplication-method Cox proportional hazards regression model. RESULTS During the follow-up of 139,406 participants (2,894,060 person-years), we documented 2811 incident colorectal cancer cases, of which 1065 cases provided tissue F. nucleatum analysis data. The multivariable-adjusted hazard ratio of appendectomy for overall colorectal cancer incidence was 0.92 (95% CI, 0.84-1.01). Appendectomy was associated with lower F. nucleatum-positive cancer incidence (multivariable-adjusted hazard ratio, 0.53; 95% CI, 0.33-0.85; P=0.0079), but not F. nucleatum-negative cancer incidence (multivariable-adjusted hazard ratio, 0.98; 95% CI, 0.83-1.14), suggesting a differential association by F. nucleatum status (Pheterogeneity=0.015). This differential association appeared to persist in various participant/patient strata including tumor location and microsatellite instability status. CONCLUSIONS Appendectomy likely lowers the future long-term incidence of F. nucleatum-positive (but not F. nucleatum-negative) colorectal cancer. Our findings do not support the existing hypothesis that appendectomy may increase colorectal cancer risk.
Collapse
Affiliation(s)
- Hidetaka Kawamura
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Koriyama, Fukushima, Japan
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Yasutoshi Takashima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kazuo Okadome
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Takashi Shimizu
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kosuke Mima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Melissa Zhao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Juha P. Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Jonathan A. Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
| | | | - Edward L. Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew T. Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Curtis Huttenhower
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Wendy S. Garrett
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
- Tokyo Medical and Dental University (Institute of Science Tokyo), Tokyo, Japan
| |
Collapse
|
|
13
|
Takashima Y, Kawamura H, Okadome K, Ugai S, Haruki K, Arima K, Mima K, Akimoto N, Nowak JA, Giannakis M, Garrett WS, Sears CL, Song M, Ugai T, Ogino S. Enrichment of Bacteroides fragilis and enterotoxigenic Bacteroides fragilis in CpG island methylator phenotype-high colorectal carcinoma. Clin Microbiol Infect 2024; 30:630-636. [PMID: 38266708 PMCID: PMC11043012 DOI: 10.1016/j.cmi.2024.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 12/04/2023] [Accepted: 01/13/2024] [Indexed: 01/26/2024]
Abstract
OBJECTIVES Data support that enterotoxigenic Bacteroides fragilis (ETBF) harbouring the Bacteroides fragilis toxin (bft) gene may promote colorectal tumourigenesis through the serrated neoplasia pathway. We hypothesized that ETBF may be enriched in colorectal carcinoma subtypes with high-level CpG island methylator phenotype (CIMP-high), BRAF mutation, and high-level microsatellite instability (MSI-high). METHODS Quantitative PCR assays were designed to quantify DNA amounts of Bacteroides fragilis, ETBF, and each bft gene isotype (bft-1, bft-2, or bft-3) in colorectal carcinomas in the Health Professionals Follow-up Study and Nurses' Health Study. We used multivariable-adjusted logistic regression models with the inverse probability weighting method. RESULTS We documented 4476 colorectal cancer cases, including 1232 cases with available bacterial data. High DNA amounts of Bacteroides fragilis and ETBF were positively associated with BRAF mutation (p ≤ 0.0003), CIMP-high (p ≤ 0.0002), and MSI-high (p < 0.0001 and p = 0.01, respectively). Multivariable-adjusted odds ratios (with 95% confidence interval) for high Bacteroides fragilis were 1.40 (1.06-1.85) for CIMP-high and 2.14 (1.65-2.77) for MSI-high, but 1.02 (0.78-1.35) for BRAF mutation. Multivariable-adjusted odds ratios for high ETBF were 2.00 (1.16-3.45) for CIMP-high and 2.86 (1.64-5.00) for BRAF mutation, but 1.09 (0.67-1.76) for MSI-high. Neither Bacteroides fragilis nor ETBF was associated with colorectal cancer-specific or overall survival. DISCUSSION The tissue abundance of Bacteroides fragilis is associated with CIMP-high and MSI-high, whereas ETBF abundance is associated with CIMP-high and BRAF mutation in colorectal carcinoma. Our findings support the aetiological relevance of Bacteroides fragilis and ETBF in the serrated neoplasia pathway.
Collapse
Affiliation(s)
- Yasutoshi Takashima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Hidetaka Kawamura
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kazuo Okadome
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Satoko Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Kosuke Mima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Wendy S Garrett
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Cynthia L Sears
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Cancer Immunology Program, Dana-Farber Harvard Cancer Centre, Boston, MA, USA.
| |
Collapse
|
|
14
|
Lee HY, Song M, Stopsack KH, Peng C, Phipps AI, Wang M, Ogino S, Sasamoto N, Ugai T. The Cancer Spectrum Theory. Cancer Discov 2024; 14:589-593. [PMID: 38571425 DOI: 10.1158/2159-8290.cd-23-1494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2024]
Abstract
SUMMARY Biological characteristics of tumors are heterogeneous, forming spectra in terms of several factors such as age at onset, anatomic spatial localization, tumor subtyping, and the degree of tumor aggressiveness (encompassing a neoplastic property spectrum). Instead of blindly using dichotomized approaches, the application of the multicategorical and continuous analysis approaches to detailed cancer spectrum data can contribute to a better understanding of the etiology of cancer, ultimately leading to effective prevention and precision oncology. We provide examples of cancer spectra and emphasize the importance of integrating the cancer spectrum theory into large-scale population cancer research.
Collapse
Affiliation(s)
- Hwa-Young Lee
- Graduate School of Public Health and Healthcare Management, The Catholic University of Korea, Seoul, Republic of Korea
- Catholic Institute for Public Health and Healthcare Management, The Catholic University of Korea, Seoul, Republic of Korea
| | - Minkyo Song
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Baltimore, Maryland
| | - Konrad H Stopsack
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Cheng Peng
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Amanda I Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington
- Department of Epidemiology, University of Washington, Seattle, Washington
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts
| | - Naoko Sasamoto
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, Massachusetts
| | - Tomotaka Ugai
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
- Cancer Epidemiology Program, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts
| |
Collapse
|
|
15
|
Bunyavanich S, Becker PM, Altman MC, Lasky-Su J, Ober C, Zengler K, Berdyshev E, Bonneau R, Chatila T, Chatterjee N, Chung KF, Cutcliffe C, Davidson W, Dong G, Fang G, Fulkerson P, Himes BE, Liang L, Mathias RA, Ogino S, Petrosino J, Price ND, Schadt E, Schofield J, Seibold MA, Steen H, Wheatley L, Zhang H, Togias A, Hasegawa K. Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop. J Allergy Clin Immunol 2024; 153:954-968. [PMID: 38295882 PMCID: PMC10999353 DOI: 10.1016/j.jaci.2024.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/19/2024] [Accepted: 01/24/2024] [Indexed: 02/29/2024]
Abstract
Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.
Collapse
Affiliation(s)
| | - Patrice M Becker
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | | | - Jessica Lasky-Su
- Brigham & Women's Hospital and Harvard Medical School, Boston, Mass
| | | | | | | | | | - Talal Chatila
- Boston Children's Hospital and Harvard Medical School, Boston, Mass
| | | | | | | | - Wendy Davidson
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Gang Dong
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Gang Fang
- Icahn School of Medicine at Mount Sinai, New York, NY
| | - Patricia Fulkerson
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | | | - Liming Liang
- Harvard T. H. Chan School of Public Health, Boston, Mass
| | | | - Shuji Ogino
- Brigham & Women's Hospital and Harvard Medical School, Boston, Mass; Harvard T. H. Chan School of Public Health, Boston, Mass; Broad Institute of MIT and Harvard, Boston, Mass
| | | | | | - Eric Schadt
- Icahn School of Medicine at Mount Sinai, New York, NY
| | | | - Max A Seibold
- National Jewish Health, Denver, Colo; University of Colorado School of Medicine, Aurora, Colo
| | - Hanno Steen
- Boston Children's Hospital and Harvard Medical School, Boston, Mass
| | - Lisa Wheatley
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Hongmei Zhang
- School of Public Health, University of Memphis, Memphis, Tenn
| | - Alkis Togias
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Md
| | - Kohei Hasegawa
- Massachusetts General Hospital and Harvard Medical School, Boston, Mass
| |
Collapse
|
|
16
|
Yi Y, Wang T, Xu W, Zhang SH. Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring. World J Diabetes 2024; 15:378-391. [PMID: 38591094 PMCID: PMC10999040 DOI: 10.4239/wjd.v15.i3.378] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 12/30/2023] [Accepted: 02/06/2024] [Indexed: 03/15/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development. As a bridge between the mother and the fetus, the placenta has nutrient transport functions, endocrine functions, etc., and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status. Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus. There are many reports on the placental pathophysiological changes associated with GDM, the impacts of GDM on the growth and development of offspring, and the prevalence of GDM in offspring after birth. Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases. This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.
Collapse
Affiliation(s)
- Yan Yi
- Department of Ultrasonography, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, Hubei Province, China
| | - Tao Wang
- Clinical Molecular Immunology Center, Yangtze University, Jingzhou 434023, Hubei Province, China
| | - Wei Xu
- Department of Ultrasonography, The First Affiliated Hospital of Yangtze University, Jingzhou 434000, Hubei Province, China
| | - San-Hong Zhang
- Department of Pediatric, Xiantao First People’s Hospital, Xiantao 433000, Hubei Province, China
| |
Collapse
|
|
17
|
Perdomo S, Abedi-Ardekani B, de Carvalho AC, Ferreiro-Iglesias A, Gaborieau V, Cattiaux T, Renard H, Chopard P, Carreira C, Spanu A, Nikmanesh A, Cardoso Penha RC, Antwi SO, Ashton-Prolla P, Canova C, Chitapanarux T, Cox R, Curado MP, de Oliveira JC, Dzamalala C, Fabianova E, Ferri L, Fitzgerald R, Foretova L, Gallinger S, Goldstein AM, Holcatova I, Huertas A, Janout V, Jarmalaite S, Kaneva R, Kowalski LP, Kulis T, Lagiou P, Lissowska J, Malekzadeh R, Mates D, McCorrmack V, Menya D, Mhatre S, Mmbaga BT, de Moricz A, Nyirády P, Ognjanovic M, Papadopoulou K, Polesel J, Purdue MP, Rascu S, Rebolho Batista LM, Reis RM, Ribeiro Pinto LF, Rodríguez-Urrego PA, Sangkhathat S, Sangrajrang S, Shibata T, Stakhovsky E, Świątkowska B, Vaccaro C, Vasconcelos de Podesta JR, Vasudev NS, Vilensky M, Yeung J, Zaridze D, Zendehdel K, Scelo G, Chanudet E, Wang J, Fitzgerald S, Latimer C, Moody S, Humphreys L, Alexandrov LB, Stratton MR, Brennan P. The Mutographs biorepository: A unique genomic resource to study cancer around the world. CELL GENOMICS 2024; 4:100500. [PMID: 38325367 PMCID: PMC10943582 DOI: 10.1016/j.xgen.2024.100500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 10/24/2023] [Accepted: 01/10/2024] [Indexed: 02/09/2024]
Abstract
Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.
Collapse
Affiliation(s)
- Sandra Perdomo
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Behnoush Abedi-Ardekani
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Ana Carolina de Carvalho
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Aida Ferreiro-Iglesias
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Valérie Gaborieau
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Thomas Cattiaux
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Hélène Renard
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Priscilia Chopard
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Christine Carreira
- Evidence Synthesis and Classification Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Andreea Spanu
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Arash Nikmanesh
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | | | - Samuel O Antwi
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, USA; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Patricia Ashton-Prolla
- Experimental Research Center, Genomic Medicine Laboratory, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Cristina Canova
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padua, Padova, Italy
| | - Taned Chitapanarux
- Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Riley Cox
- Ontario Tumour Bank, Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Maria Paula Curado
- Department of Epidemiology, A.C. Camargo Cancer Center, São Paulo, Brazil
| | | | | | | | - Lorenzo Ferri
- Departments of Surgery and Oncology, McGill University, Montreal, QC, Canada
| | | | - Lenka Foretova
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
| | - Steven Gallinger
- Mount Sinai Hospital; Ontario Institute for Cancer Research (OICR), Toronto, ON, Canada
| | - Alisa M Goldstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA
| | - Ivana Holcatova
- Institute of Public Health & Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Oncology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
| | | | - Vladimir Janout
- Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic
| | - Sonata Jarmalaite
- Laboratory of Genetic Diagnostic, National Cancer Institute, Vilnius, Lithuania; Department of Botany and Genetics, Institute of Biosciences, Vilnius University, Vilnius, Lithuania
| | - Radka Kaneva
- Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria
| | - Luiz Paulo Kowalski
- Department of Epidemiology, A.C. Camargo Cancer Center, São Paulo, Brazil; University of São Paulo Medical School, São Paulo, Brazil
| | - Tomislav Kulis
- Department of Urology, University Hospital Center Zagreb, Zagreb, Croatia; University of Zagreb School of Medicine, Zagreb, Croatia
| | - Pagona Lagiou
- National and Kapodistrian University of Athens, Athens, Greece
| | - Jolanta Lissowska
- The Maria Sklodowska-Cure National Research Institute of Oncology, Warsaw, Poland
| | - Reza Malekzadeh
- Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Dana Mates
- Occupational Health and Toxicology, National Center for Environmental Risk Monitoring, National Institute of Public Health, Bucharest, Romania
| | - Valerie McCorrmack
- Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France
| | - Diana Menya
- Moi University, School of Public Health, Eldoret, Kenya
| | - Sharayu Mhatre
- Division of Molecular Epidemiology and Population Genomics, Centre for Cancer Epidemiology, Tata Memorial Centre, Mumbai, India
| | | | - André de Moricz
- Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical Centre & Kilimanjaro Christian Medical University College, Moshi, Tanzania
| | | | - Miodrag Ognjanovic
- IOCPR- International Organization for Cancer Prevention and Research, Serbia, Belgrade
| | | | - Jerry Polesel
- Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Mark P Purdue
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
| | - Stefan Rascu
- Urology Department, "Carol Davila" University of Medicine and Pharmacy - "Prof. Dr. Th. Burghele" Clinical Hospital, Bucharest, Romania
| | | | - Rui Manuel Reis
- Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil; Life and Health Sciences Research Institute (ICVS), School of Medicine, Minho University, Braga, Portugal
| | | | | | - Surasak Sangkhathat
- Translational Medicine Research Center, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | | | - Tatsuhiro Shibata
- Laboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Japan; Division of Cancer Genomics, National Cancer Center Research Institute, Chuo-ku, Japan
| | | | - Beata Świątkowska
- Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Łódź, Poland
| | - Carlos Vaccaro
- Instituto Medicina Traslacional e Ingenieria Biomedica - CONICET, Buenos Aires, Argentina
| | | | - Naveen S Vasudev
- Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Marta Vilensky
- Instituto de Oncología Angel Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina
| | | | - David Zaridze
- Clinical Epidemiology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia
| | - Kazem Zendehdel
- Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghislaine Scelo
- Observational & Pragmatic Research Institute Pte., Ltd., Singapore, Singapore
| | - Estelle Chanudet
- Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Jingwei Wang
- Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK
| | - Stephen Fitzgerald
- Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK
| | - Calli Latimer
- Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK
| | - Sarah Moody
- Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK
| | - Laura Humphreys
- Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK
| | - Ludmil B Alexandrov
- Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA; Department of Bioengineering, University of California San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
| | - Michael R Stratton
- Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK
| | - Paul Brennan
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
| |
Collapse
|
|
18
|
Kim HJ, Kim YH. Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances. Int J Mol Sci 2024; 25:2984. [PMID: 38474231 DOI: 10.3390/ijms25052984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 03/01/2024] [Accepted: 03/02/2024] [Indexed: 03/14/2024] Open
Abstract
Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms in melanoma genesis. It highlights how mutations, particularly in the BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes, affect critical signaling pathways. The evolution of diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers for early detection and prognosis, is also discussed. The therapeutic landscape has transformed with targeted therapies and immunotherapies, improving patient outcomes. This paper examines the efficacy, challenges, and prospects of these treatments, including recent clinical trials and emerging strategies. The potential of novel treatment strategies, including neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy, is explored. These advances emphasize the challenges of therapy resistance and the importance of personalized medicine. This review underlines the necessity for evidence-based therapy selection in managing the increasing global incidence of melanoma.
Collapse
Affiliation(s)
- Hyun Jee Kim
- Department of Dermatology, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea
| | - Yeong Ho Kim
- Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
| |
Collapse
|
|
19
|
Hamasaki H. Effects of Tai Chi in diabetes patients: Insights from recent research. World J Diabetes 2024; 15:1-10. [PMID: 38313854 PMCID: PMC10835502 DOI: 10.4239/wjd.v15.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 12/10/2023] [Accepted: 12/28/2023] [Indexed: 01/12/2024] Open
Abstract
Tai Chi, a practice that combines elements of both exercise and mindfulness, offers a wide range of health benefits. The body of evidence concerning the impact of Tai Chi on diabetes has recently been growing. This editorial aims to provide a concise summary of the current state of evidence for Tai Chi's effects on individuals with type 2 diabetes (T2D). The review includes 3 randomized controlled trials (RCTs) and 5 systematic reviews and meta-analyses, all of which investigate the effectiveness of Tai Chi on various health outcomes in individuals with T2D. Tai Chi demonstrates a significant effect to enhance glycemic control, lower blood pressure, improve serum lipid profiles, reduce insulin resistance, positively influence obesity-related indices, and improve overall quality of life in individuals with T2D. However, it is noteworthy that recent RCTs have reported inconsistent findings regarding the effects of Tai Chi on glycemic control and insulin resistance. The author also delves into potential mechanisms by which Tai Chi may exert its influence on the human body. Finally, the editorial highlights the critical issues that warrant further exploration in the future.
Collapse
Affiliation(s)
- Hidetaka Hamasaki
- Department of Endocrinology and Metabolism, Internal Medicine, Hamasaki Clinic, Kagoshima 890-0046, Japan
| |
Collapse
|
|
20
|
Peng Z, Ding Y, Zhang P, Lv X, Li Z, Zhou X, Huang S. Artificial Intelligence Application for Anti-tumor Drug Synergy Prediction. Curr Med Chem 2024; 31:6572-6585. [PMID: 39420717 DOI: 10.2174/0109298673290777240301071513] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 01/25/2024] [Accepted: 02/15/2024] [Indexed: 10/19/2024]
Abstract
Currently, the main therapeutic methods for cancer include surgery, radiation therapy, and chemotherapy. However, chemotherapy still plays an important role in tumor therapy. Due to the variety of pathogenic factors, the development process of tumors is complex and regulated by many factors, and the treatment of a single drug is easy to cause the human body to produce a drug-resistant phenotype to specific drugs and eventually leads to treatment failure. In the process of clinical tumor treatment, the combination of multiple drugs can produce stronger anti-tumor effects by regulating multiple mechanisms and can reduce the problem of tumor drug resistance while reducing the toxic side effects of drugs. Therefore, it is still a great challenge to construct an efficient and accurate screening method that can systematically consider the synergistic anti- tumor effects of multiple drugs. However, anti-tumor drug synergy prediction is of importance in improving cancer treatment outcomes. However, identifying effective drug combinations remains a complex and challenging task. This review provides a comprehensive overview of cancer drug synergy therapy and the application of artificial intelligence (AI) techniques in cancer drug synergy prediction. In addition, we discuss the challenges and perspectives associated with deep learning approaches. In conclusion, the review of the AI techniques' application in cancer drug synergy prediction can further advance our understanding of cancer drug synergy and provide more effective treatment plans and reasonable drug use strategies for clinical guidance.
Collapse
Affiliation(s)
- Zheng Peng
- Department of Clinical Laboratory, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, Guangxi, China
| | - Yanling Ding
- Department of Clinical Laboratory, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, China
| | - Pengfei Zhang
- Department of Pulmonary and Critical Care Medicine, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, Guangxi, China
| | - Xiaolan Lv
- Department of Clinical Laboratory, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, China
| | - Zepeng Li
- Department of Infectious Disease, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, Guangxi, China
| | - Xiaoling Zhou
- Department of Gastroenterology, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, Guangxi, China
| | - Shigao Huang
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| |
Collapse
|
|
21
|
Dolbnya AD, Popov IA, Pekov SI. Molecular Biomarkers in Cholangiocarcinoma: Focus on Bile. Curr Top Med Chem 2024; 24:722-736. [PMID: 38303538 DOI: 10.2174/0115680266290367240130054142] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/12/2024] [Accepted: 01/17/2024] [Indexed: 02/03/2024]
Abstract
Hepatobiliary system cancers have demonstrated an increasing incidence rate in the past years. Without the presence of early symptoms, the majority of such cancers manifest with a set of similar symptoms, such as cholestasis resulting in posthepatic icterus. Differential diagnosis of hepatobiliary cancers is required for the therapy selection, however, the similarity of the symptoms complicates diagnostics. Thus, the search for molecular markers is of high interest for such patients. Cholangiocarcinoma (CCA) is characterized by a poor prognosis due to a low resectability rate, which occurs because this disease is frequently beyond the limits of surgical therapy at the time of diagnosis. The CCA is diagnosed by the combination of clinical/biochemical features, radiological methods, and non-specific serum tumor biomarkers, although invasive examination is still needed. The main disadvantage is limited specificity and sensitivity, which complicates early diagnostics. Therefore, prognostic and predictive biomarkers are still lacking and urgently needed for early diagnosis. In contrast to serum, bile is more accessible to identify biliary disease due to its simpler composition. Moreover, bile can contain higher concentrations of tumor biomarkers due to its direct contact with the tumor. It is known that the composition of the main bile component - bile acids, may vary during different diseases of the biliary tract. This review summarizes the recent developments in the current research on the diagnostic biomarkers for CCA in serum and bile and provides an overview of the methods of bile acids analysis.
Collapse
Affiliation(s)
- Andrey D Dolbnya
- Siberian State Medical University, Tomsk, 634050, Russian Federation
| | - Igor A Popov
- Siberian State Medical University, Tomsk, 634050, Russian Federation
- Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russian Federation
| | - Stanislav I Pekov
- Siberian State Medical University, Tomsk, 634050, Russian Federation
- Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russian Federation
- Skolkovo Institute of Science and Technology, Moscow, 121205, Russian Federation
| |
Collapse
|
|
22
|
Mima K, Hamada T, Inamura K, Baba H, Ugai T, Ogino S. The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities. Gut Microbes 2023; 15:2269623. [PMID: 37902043 PMCID: PMC10730181 DOI: 10.1080/19490976.2023.2269623] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 10/06/2023] [Indexed: 10/31/2023] Open
Abstract
Accumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers. While a minority of early-onset cancers in the digestive system are associated with cancer-predisposing high penetrance germline genetic variants, the majority of those cancers are sporadic and multifactorial. Although potential etiological roles of diets, lifestyle, environment, and the microbiome from early life to adulthood (i.e. in one's life course) have been hypothesized, exact contribution of each of these factors remains uncertain. Diets, lifestyle patterns, and environmental exposures have been shown to alter the oral and intestinal microbiome. To address the rising trend of early-onset cancers, transdisciplinary research approaches including lifecourse epidemiology and molecular pathological epidemiology frameworks, nutritional and environmental sciences, multi-omics technologies, etc. are needed. We review current evidence and discuss emerging research opportunities, which can improve our understanding of their etiologies and help us design better strategies for prevention and treatment to reduce the cancer burden in populations.
Collapse
Affiliation(s)
- Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic Medicine, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kentaro Inamura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Cancer Epidemiology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Cancer Epidemiology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
| |
Collapse
|
|
23
|
Xing W, Li X, Zhou Y, Li M, Zhu M. Lactate metabolic pathway regulates tumor cell metastasis and its use as a new therapeutic target. EXPLORATION OF MEDICINE 2023:541-559. [DOI: https:/doi.org/10.37349/emed.2023.00160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 04/17/2023] [Indexed: 09/04/2023] Open
Abstract
Abnormal energy metabolism is one of the ten hallmarks of tumors, and tumor cell metabolism provides energy and a suitable microenvironment for tumorigenesis and metastasis. Tumor cells can consume large amounts of glucose and produce large amounts of lactate through glycolysis even in the presence of oxygen, a process called aerobic glycolysis, also known as the Warburg effect. Lactate is the end product of the aerobic glycolysis. Lactate dehydrogenase A (LDHA), which is highly expressed in cancer cells, promotes lactate production and transports lactate to the tumor microenvironment and is taken up by surrounding stromal cells under the action of monocarboxylate transporter 1/4 (MCT1/4), which in turn influences the immune response and enhances the invasion and metastasis of cancer cells. Therapeutic strategies targeting lactate metabolism have been intensively investigated, focusing on its metastasis-promoting properties and various target inhibitors; AZD3965, an MCT1 inhibitor, has entered phase I clinical trials, and the LDHA inhibitor N-hydroxyindole (NHI) has shown cancer therapeutic activity in pre-clinical studies. Interventions targeting lactate metabolism are emerging as a promising option for cancer therapy, with chemotherapy or radiotherapy combined with lactate-metabolism-targeted drugs adding to the effectiveness of cancer treatment. Based on current research, this article outlines the role of lactate metabolism in tumor metastasis and the potential value of inhibitors targeting lactate metabolism in cancer therapy.
Collapse
Affiliation(s)
- Weimei Xing
- Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, China
| | - Xiaowei Li
- Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, China
| | - Yuli Zhou
- Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, China
| | - Mengsen Li
- Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, China; Department of Medical Oncology, Second Affiliated Hospital, Hainan Medical University, Haikou 570311, Hainan, China; Institution of Tumour, First Affiliated Hospital, Hainan Medical University, Haikou 570102, Hainan, China
| | - Mingyue Zhu
- Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, Hainan, China
| |
Collapse
|
|
24
|
Zhang X, Zhang Y, Wen L, Ouyang JL, Zhang W, Zhang J, Wang Y, Liu Q. Neurological Sequelae of COVID-19: A Biochemical Perspective. ACS OMEGA 2023; 8:27812-27818. [PMID: 37576681 PMCID: PMC10413374 DOI: 10.1021/acsomega.3c04100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Accepted: 07/17/2023] [Indexed: 08/15/2023]
Abstract
Exogenous factors can induce protein expression and modify the proteome which sustains for a certain period of time. The proteins of SARS-CoV-2 are high in valine plus glycine, which possess potent affinity to divalent cations such as calcium. Calcium buildup changes the protein expression profile by enabling the efficient synthesis of proteins rich in amino acids with calcium affinity. Subsequent formation of insoluble and stiff calcium oxalate and aggregates confers cellular stress and causes cell senescence. This scenario accounts for sequelae seen in some patients following recovery from COVID-19.
Collapse
Affiliation(s)
- Xiaoxiao Zhang
- School
of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
- Yunnan
Key Laboratory of Stem Cell and Regenerative Medicine, Biomedical
Engineering Research Center, Kunming Medical
University, Kunming 650500, China
| | - Ying Zhang
- Guangzhou
Center for Disease Control and Prevention, Guangzhou 510440, China
| | - Ling Wen
- GI
Medicine, Guangzhou Twelfth People’s
Hospital, Guangzhou 510620, Guangdong, China
| | - Jess Lan Ouyang
- School
of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
| | - Weiwei Zhang
- School
of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
| | - Jiaming Zhang
- School
of Chemistry, Sun Yat-sen University, Guangzhou 510275, China
| | - Yuchuan Wang
- School of
Basic Medical Sciences, North China University
of Science and Technology, Tangshan, Hebei 063210, China
| | - Qiuyun Liu
- School
of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
| |
Collapse
|
|
25
|
Ugai T, Shimizu T, Kawamura H, Ugai S, Takashima Y, Usui G, Väyrynen JP, Okadome K, Haruki K, Akimoto N, Masugi Y, da Silva A, Mima K, Zhang X, Chan AT, Wang M, Garrett WS, Freeman GJ, Meyerhardt JA, Nowak JA, Song M, Giannakis M, Ogino S. Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma. Clin Transl Immunology 2023; 12:e1453. [PMID: 37538192 PMCID: PMC10394676 DOI: 10.1002/cti2.1453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 05/19/2023] [Accepted: 05/25/2023] [Indexed: 08/05/2023] Open
Abstract
Objectives The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of Fusobacterium nucleatum. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of F. nucleatum in colorectal carcinoma. Methods We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and KRAS, BRAF and PIK3CA mutations. Results Fusobacterium nucleatum DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue (P = 0.0077). For one category-unit increase in three ordinal F. nucleatum categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28) and 0.50 (0.25-0.99), respectively (P trend = 0.032). Conclusions Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor F. nucleatum enrichment) tend to be used by different tumor subgroups.
Collapse
Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
- Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Takashi Shimizu
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Hidetaka Kawamura
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Satoko Ugai
- Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Yasutoshi Takashima
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Genki Usui
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Juha P Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
- Department of Medical OncologyDana‐Farber Cancer Institute and Harvard Medical SchoolBostonMAUSA
- Cancer and Translational Medicine Research Unit, Medical Research Center OuluOulu University Hospital and University of OuluOuluFinland
| | - Kazuo Okadome
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Yohei Masugi
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | | | - Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical SciencesKumamoto UniversityKumamotoJapan
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of MedicineBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
- Department of NutritionHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of MedicineBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
- Clinical and Translational Epidemiology UnitMassachusetts General Hospital and Harvard Medical SchoolBostonMAUSA
- Division of GastroenterologyMassachusetts General HospitalBostonMAUSA
- Department of Immunology and Infectious DiseasesHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Molin Wang
- Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonMAUSA
- Channing Division of Network Medicine, Department of MedicineBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
- Department of BiostatisticsHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Wendy S Garrett
- Department of Medical OncologyDana‐Farber Cancer Institute and Harvard Medical SchoolBostonMAUSA
- Department of Immunology and Infectious DiseasesHarvard T.H. Chan School of Public HealthBostonMAUSA
- Department of Molecular MetabolismHarvard T.H. Chan School of Public HealthBostonMAUSA
- Harvard T.H. Chan Microbiome in Public Health CenterBostonMAUSA
- Broad Institute of MIT and HarvardCambridgeMAUSA
- Department of MedicineBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Gordon J Freeman
- Department of Medical OncologyDana‐Farber Cancer Institute and Harvard Medical SchoolBostonMAUSA
| | - Jeffrey A Meyerhardt
- Department of Medical OncologyDana‐Farber Cancer Institute and Harvard Medical SchoolBostonMAUSA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Mingyang Song
- Department of NutritionHarvard T.H. Chan School of Public HealthBostonMAUSA
- Clinical and Translational Epidemiology UnitMassachusetts General Hospital and Harvard Medical SchoolBostonMAUSA
- Division of GastroenterologyMassachusetts General HospitalBostonMAUSA
| | - Marios Giannakis
- Department of Medical OncologyDana‐Farber Cancer Institute and Harvard Medical SchoolBostonMAUSA
- Broad Institute of MIT and HarvardCambridgeMAUSA
- Department of MedicineBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of PathologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMAUSA
- Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonMAUSA
- Broad Institute of MIT and HarvardCambridgeMAUSA
- Cancer Immunology and Cancer Epidemiology ProgramsDana‐Farber Harvard Cancer CenterBostonMAUSA
| |
Collapse
|
|
26
|
Jin Z, Zhou Q, Cheng JN, Jia Q, Zhu B. Heterogeneity of the tumor immune microenvironment and clinical interventions. Front Med 2023; 17:617-648. [PMID: 37728825 DOI: 10.1007/s11684-023-1015-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 06/24/2023] [Indexed: 09/21/2023]
Abstract
The tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales. Owing to the existence of TIME, clinical outcomes can differ when a similar treatment strategy is provided to patients. Therefore, a comprehensive assessment of TIME heterogeneity is essential for developing precise and effective therapies. Facilitated by advanced technologies, it is possible to understand the complexity and diversity of the TIME and its influence on therapy responses. In this review, we discuss the potential reasons for TIME heterogeneity and the current approaches used to explore it. We also summarize clinical intervention strategies based on associated mechanisms or targets to control immunological heterogeneity.
Collapse
Affiliation(s)
- Zheng Jin
- Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China
- Key Laboratory of Tumor Immunotherapy, Chongqing, 400037, China
- Research Institute, GloriousMed Clinical Laboratory (Shanghai) Co. Ltd., Shanghai, 201318, China
- Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, China
| | - Qin Zhou
- Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China
- Key Laboratory of Tumor Immunotherapy, Chongqing, 400037, China
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China
| | - Jia-Nan Cheng
- Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
- Key Laboratory of Tumor Immunotherapy, Chongqing, 400037, China.
| | - Qingzhu Jia
- Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
- Key Laboratory of Tumor Immunotherapy, Chongqing, 400037, China.
| | - Bo Zhu
- Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
- Key Laboratory of Tumor Immunotherapy, Chongqing, 400037, China.
| |
Collapse
|
|
27
|
Cai JA, Zhang YZ, Yu ED, Ding WQ, Li ZS, Zhong L, Cai QC. Association of cigarette smoking with risk of colorectal cancer subtypes classified by gut microbiota. Tob Induc Dis 2023; 21:99. [PMID: 37529669 PMCID: PMC10377954 DOI: 10.18332/tid/168515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 06/17/2023] [Accepted: 06/19/2023] [Indexed: 08/03/2023] Open
Abstract
INTRODUCTION Both cigarette smoking and gut microbiota play important roles in colorectal carcinogenesis. We explored whether the association between smoking and colorectal cancer (CRC) risk varies by gut microbial enterotypes and how smoking-related enterotypes promote colorectal carcinogenesis. METHODS A case-control study was conducted. Fecal microbiota was determined by 16S rDNA sequencing. The cases with CRC or adenoma were subclassified by gut microbiota enterotypes. Multivariate analyses were used to test associations between smoking and the odds of colorectal neoplasm subtypes. Mann-Whitney U tests were used to find differential genera, genes, and pathways between the subtypes. RESULTS Included in the study were 130 CRC patients (type I: n=77; type II: n=53), 120 adenoma patients (type I: n=66; type II: n=54), and 130 healthy participants. Smoking increased the odds for type II tumors significantly (all p for trend <0.05) but not for type I tumors. The associations of smoking with increased odds of colorectal neoplasm significantly differed by gut microbiota enterotypes (p<0.05 for heterogeneity). An increase in carcinogenic bacteria (genus Escherichia shigella) and a decrease in probiotics (family Lachnospiraceae and Ruminococcaceae) in type II tumors may drive disease progression by upregulating oncogenic signaling pathways and inflammatory/oxidative stress response pathways, as well as protein phospholipase D1/2, cytochrome C, and prostaglandin-endoperoxide synthase 2 expression. CONCLUSIONS Smoking was associated with a higher odds of type II colorectal neoplasms but not type I tumors, supporting a potential role for the gut microbiota in mediating the association between smoking and colorectal neoplasms.
Collapse
Affiliation(s)
- Jia-An Cai
- Department of Gastroenterology and Endoscopy, Huashan Hospital, Fudan University, Shanghai, China
| | - Yong-Zhen Zhang
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
- Department of Gastroenterology, 928 Hospital of PLA Joint Logistics Force, Haikou, China
| | - En-Da Yu
- Department of General Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
| | - Wei-Qun Ding
- Department of Gastroenterology and Endoscopy, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhao-Shen Li
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
- National Clinical Research Center for Digestive Diseases, Shanghai, China
| | - Liang Zhong
- Department of Gastroenterology and Endoscopy, Huashan Hospital, Fudan University, Shanghai, China
| | - Quan-Cai Cai
- Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China
- National Clinical Research Center for Digestive Diseases, Shanghai, China
| |
Collapse
|
|
28
|
Zhao M, Lau MC, Haruki K, Väyrynen JP, Gurjao C, Väyrynen SA, Dias Costa A, Borowsky J, Fujiyoshi K, Arima K, Hamada T, Lennerz JK, Fuchs CS, Nishihara R, Chan AT, Ng K, Zhang X, Meyerhardt JA, Song M, Wang M, Giannakis M, Nowak JA, Yu KH, Ugai T, Ogino S. Bayesian risk prediction model for colorectal cancer mortality through integration of clinicopathologic and genomic data. NPJ Precis Oncol 2023; 7:57. [PMID: 37301916 PMCID: PMC10257677 DOI: 10.1038/s41698-023-00406-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 05/25/2023] [Indexed: 06/12/2023] Open
Abstract
Routine tumor-node-metastasis (TNM) staging of colorectal cancer is imperfect in predicting survival due to tumor pathobiological heterogeneity and imprecise assessment of tumor spread. We leveraged Bayesian additive regression trees (BART), a statistical learning technique, to comprehensively analyze patient-specific tumor characteristics for the improvement of prognostic prediction. Of 75 clinicopathologic, immune, microbial, and genomic variables in 815 stage II-III patients within two U.S.-wide prospective cohort studies, the BART risk model identified seven stable survival predictors. Risk stratifications (low risk, intermediate risk, and high risk) based on model-predicted survival were statistically significant (hazard ratios 0.19-0.45, vs. higher risk; P < 0.0001) and could be externally validated using The Cancer Genome Atlas (TCGA) data (P = 0.0004). BART demonstrated model flexibility, interpretability, and comparable or superior performance to other machine-learning models. Integrated bioinformatic analyses using BART with tumor-specific factors can robustly stratify colorectal cancer patients into prognostic groups and be readily applied to clinical oncology practice.
Collapse
Affiliation(s)
- Melissa Zhao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
| | - Mai Chan Lau
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Juha P Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, Oulu, Finland
| | - Carino Gurjao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Sara A Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Andressa Dias Costa
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Jennifer Borowsky
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kenji Fujiyoshi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Tsuyoshi Hamada
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jochen K Lennerz
- Department of Pathology, Center for Integrated Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | | | - Reiko Nishihara
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kimmie Ng
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
| | - Mingyang Song
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Kun-Hsing Yu
- Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
| |
Collapse
|
|
29
|
Moslehian MS, Shabkhizan R, Asadi MR, Bazmani A, Mahdipour M, Haiaty S, Rahbarghazi R, Sakhinia E. Interaction of lncRNAs with mTOR in colorectal cancer: a systematic review. BMC Cancer 2023; 23:512. [PMID: 37280524 DOI: 10.1186/s12885-023-11008-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 05/25/2023] [Indexed: 06/08/2023] Open
Abstract
Colorectal cancer (CRC) is the third most widespread cancer and the fourth leading lethal disease among different societies. It is thought that CRC accounts for about 10% of all newly diagnosed cancer cases with high-rate mortality. lncRNAs, belonging to non-coding RNAs, are involved in varied cell bioactivities. Emerging data have confirmed a significant alteration in lncRNA transcription under anaplastic conditions. This systematic review aimed to assess the possible influence of abnormal mTOR-associated lncRNAs in the tumorigenesis of colorectal tissue. In this study, the PRISMA guideline was utilized based on the systematic investigation of published articles from seven databases. Of the 200 entries, 24 articles met inclusion criteria and were used for subsequent analyses. Of note, 23 lncRNAs were prioritized in association with the mTOR signaling pathway with up-regulation (79.16%) and down-regulation (20.84%) trends. Based on the obtained data, mTOR can be stimulated or inhibited during CRC by the alteration of several lncRNAs. Determining the dynamic activity of mTOR and relevant signaling pathways via lncRNAs can help us progress novel molecular therapeutics and medications.
Collapse
Affiliation(s)
- Marziyeh Sadat Moslehian
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Roya Shabkhizan
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Reza Asadi
- Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahad Bazmani
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University Of Mashhad, Mashhad, Iran
| | - Mahdi Mahdipour
- Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, Iran
| | - Sanya Haiaty
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Biochemistry and Clinical Laboratories, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Imam Reza St., Golgasht St, Tabriz, Iran.
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Ebrahim Sakhinia
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Tabriz Genetic Analysis Centre (TGAC), Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
|
30
|
Baglaenko Y, Wagner C, Bhoj VG, Brodin P, Gershwin ME, Graham D, Invernizzi P, Kidd KK, Korsunsky I, Levy M, Mammen AL, Nizet V, Ramirez-Valle F, Stites EC, Williams MS, Wilson M, Rose NR, Ladd V, Sirota M. Making inroads to precision medicine for the treatment of autoimmune diseases: Harnessing genomic studies to better diagnose and treat complex disorders. CAMBRIDGE PRISMS. PRECISION MEDICINE 2023; 1:e25. [PMID: 38550937 PMCID: PMC10953750 DOI: 10.1017/pcm.2023.14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/21/2023] [Accepted: 04/25/2023] [Indexed: 06/13/2024]
Abstract
Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body's natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.
Collapse
Affiliation(s)
| | | | | | | | | | - Daniel Graham
- The Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Pietro Invernizzi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), IRCCS Fondazione San Gerardo dei Tintori, Monza, Italy
| | - Kenneth K. Kidd
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA
| | | | - Michael Levy
- Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew L. Mammen
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, USA
| | - Victor Nizet
- School of Medicine, University of California San Diego, San Diego, CA, USA
| | | | - Edward C. Stites
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA
| | | | - Michael Wilson
- Weill Institute for Neurosciences, Department of Neurology, UCSF, San Francisco, CA, USA
| | - Noel R. Rose
- Autoimmune Association, Clinton Township, MI, USA
| | | | - Marina Sirota
- Bakar Computational Health Sciences Institute, UCSF, San Francisco, CA, USA
- Department of Pediatrics, UCSF, San Francisco, CA, USA
| |
Collapse
|
|
31
|
Moon JY, Kye BH, Ko SH, Yoo RN. Sulfur Metabolism of the Gut Microbiome and Colorectal Cancer: The Threat to the Younger Generation. Nutrients 2023; 15:nu15081966. [PMID: 37111185 PMCID: PMC10146533 DOI: 10.3390/nu15081966] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/13/2023] [Accepted: 04/18/2023] [Indexed: 04/29/2023] Open
Abstract
Colorectal cancer diagnosed in individuals under 50 years old is called early-onset colorectal cancer (EOCRC), and its incidence has been rising worldwide. Simultaneously occurring with increasing obesity, this worrisome trend is partly explained by the strong influence of dietary elements, particularly fatty, meaty, and sugary food. An animal-based diet, the so-called Western diet, causes a shift in dominant microbiota and their metabolic activity, which may disrupt the homeostasis of hydrogen sulfide concentration. Bacterial sulfur metabolism is recognized as a critical mechanism of EOCRC pathogenesis. This review evaluates the pathophysiology of how a diet-associated shift in gut microbiota, so-called the microbial sulfur diet, provokes injuries and inflammation to the colonic mucosa and contributes to the development of CRC.
Collapse
Affiliation(s)
- Ji-Yeon Moon
- Division of Colorectal Surgery, Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 442-723, Republic of Korea
| | - Bong-Hyeon Kye
- Division of Colorectal Surgery, Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 442-723, Republic of Korea
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon 442-723, Republic of Korea
| | - Ri Na Yoo
- Division of Colorectal Surgery, Department of Surgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 442-723, Republic of Korea
| |
Collapse
|
|
32
|
Wang H, Cai Y, Jin M, Huang CQ, Ning C, Niu S, Fan L, Li B, Zhang M, Lu Z, Dong X, Luo Z, Zhong R, Li H, Zhu Y, Miao X, Yang X, Chang J, Li N, Tian J. Identification of specific susceptibility loci for the early-onset colorectal cancer. Genome Med 2023; 15:13. [PMID: 36869385 PMCID: PMC9983269 DOI: 10.1186/s13073-023-01163-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 02/15/2023] [Indexed: 03/05/2023] Open
Abstract
BACKGROUND The incidence of early-onset colorectal cancer (EOCRC; patients < 50 years old) has been rising rapidly, whereas the EOCRC genetic susceptibility remains incompletely investigated. Here, we aimed to systematically identify specific susceptible genetic variants for EOCRC. METHODS Two parallel GWASs were conducted in 17,789 CRC cases (including 1490 EOCRC cases) and 19,951 healthy controls. A polygenic risk score (PRS) model was built based on identified EOCRC-specific susceptibility variants by using the UK Biobank cohort. We also interpreted the potential biological mechanisms of the prioritized risk variant. RESULTS We identified 49 independent susceptibility loci that were significantly associated with the susceptibility to EOCRC and the diagnosed age of CRC (both P < 5.0×10-4), replicating 3 previous CRC GWAS loci. There are 88 assigned susceptibility genes involved in chromatin assembly and DNA replication pathways, mainly associating with precancerous polyps. Additionally, we assessed the genetic effect of the identified variants by developing a PRS model. Compared to the individuals in the low genetic risk group, the individuals in the high genetic risk group have increased EOCRC risk, and these results were replicated in the UKB cohort with a 1.63-fold risk (95% CI: 1.32-2.02, P = 7.67×10-6). The addition of the identified EOCRC risk loci significantly increased the prediction accuracy of the PRS model, compared to the PRS model derived from the previous GWAS-identified loci. Mechanistically, we also elucidated that rs12794623 may contribute to the early stage of CRC carcinogenesis via allele-specific regulating the expression of POLA2. CONCLUSIONS These findings will broaden the understanding of the etiology of EOCRC and may facilitate the early screening and individualized prevention.
Collapse
Affiliation(s)
- Haoxue Wang
- Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Research Center of Public Health, Renmin Hospital of Wuhan University, Wuhan, 430071, China
| | - Yimin Cai
- Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Research Center of Public Health, Renmin Hospital of Wuhan University, Wuhan, 430071, China
| | - Meng Jin
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China
| | - Chao Qun Huang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China
| | - Caibo Ning
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Siyuan Niu
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Linyun Fan
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin Li
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zequn Lu
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuesi Dong
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zilin Luo
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rong Zhong
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Heng Li
- Department of Urology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Zhu
- Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Research Center of Public Health, Renmin Hospital of Wuhan University, Wuhan, 430071, China
| | - Xiaoping Miao
- Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Research Center of Public Health, Renmin Hospital of Wuhan University, Wuhan, 430071, China.,Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Xiaojun Yang
- Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
| | - Jiang Chang
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Ni Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. .,Chinese Academy of Medical Sciences Key Laboratory for National Cancer Big Data Analysis and Implement, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Jianbo Tian
- Department of Epidemiology and Biostatistics, School of Public Health, TaiKang Center for Life and Medical Sciences, Wuhan University, Research Center of Public Health, Renmin Hospital of Wuhan University, Wuhan, 430071, China.
| |
Collapse
|
|
33
|
Ugai T, Akimoto N, Haruki K, Harrison TA, Cao Y, Qu C, Chan AT, Campbell PT, Berndt SI, Buchanan DD, Cross AJ, Diergaarde B, Gallinger SJ, Gunter MJ, Harlid S, Hidaka A, Hoffmeister M, Brenner H, Chang-Claude J, Hsu L, Jenkins MA, Lin Y, Milne RL, Moreno V, Newcomb PA, Nishihara R, Obon-Santacana M, Pai RK, Sakoda LC, Schoen RE, Slattery ML, Sun W, Amitay EL, Alwers E, Thibodeau SN, Toland AE, Van Guelpen B, Zaidi SH, Potter JD, Meyerhardt JA, Giannakis M, Song M, Nowak JA, Peters U, Phipps AI, Ogino S. Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases. J Gastroenterol 2023; 58:229-245. [PMID: 36648535 PMCID: PMC10203916 DOI: 10.1007/s00535-023-01955-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 01/01/2023] [Indexed: 01/18/2023]
Abstract
BACKGROUND The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. METHODS Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. RESULTS There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. CONCLUSIONS Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.
Collapse
Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404, Boston, MA, 02215, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404, Boston, MA, 02215, USA
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404, Boston, MA, 02215, USA
| | - Tabitha A Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
- Alvin J. Siteman Cancer Center, St Louis, MO, USA
| | - Conghui Qu
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Peter T Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Sonja I Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Daniel D Buchanan
- Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, Australia
- Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Parkville, VIC, Australia
- Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia
| | - Amanda J Cross
- Department of Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London, UK
| | - Brenda Diergaarde
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, and UPMC Hillman Cancer Center, Pittsburgh, PA, USA
| | - Steven J Gallinger
- Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Marc J Gunter
- Nutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Sophia Harlid
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
| | - Akihisa Hidaka
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Michael Hoffmeister
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (Deutschen Konsortium für Translationale Krebsforschung), German Cancer Research Center (Deutsches Krebsforschungszentrum), Heidelberg, Germany
| | - Jenny Chang-Claude
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Cancer Epidemiology Group, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Li Hsu
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Mark A Jenkins
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
| | - Yi Lin
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Roger L Milne
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
| | - Victor Moreno
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, Barcelona, Spain
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain
- Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Polly A Newcomb
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Reiko Nishihara
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404, Boston, MA, 02215, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mireia Obon-Santacana
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, Barcelona, Spain
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
- Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029, Madrid, Spain
| | - Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA
| | - Lori C Sakoda
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Robert E Schoen
- Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Martha L Slattery
- Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
| | - Wei Sun
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
| | - Efrat L Amitay
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Elizabeth Alwers
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Stephen N Thibodeau
- Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Amanda E Toland
- Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
| | - Bethany Van Guelpen
- Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Syed H Zaidi
- Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - John D Potter
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
- Research Centre for Hauora and Health, Massey University, Wellington, New Zealand
| | | | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404, Boston, MA, 02215, USA
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Amanda I Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave., EBRC Room 404, Boston, MA, 02215, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
| |
Collapse
|
|
34
|
Abboud K, Umoru G, Esmail A, Abudayyeh A, Murakami N, Al-Shamsi HO, Javle M, Saharia A, Connor AA, Kodali S, Ghobrial RM, Abdelrahim M. Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology. Cancers (Basel) 2023; 15:1433. [PMID: 36900226 PMCID: PMC10000896 DOI: 10.3390/cancers15051433] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/16/2023] [Accepted: 02/20/2023] [Indexed: 02/26/2023] Open
Abstract
The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk-benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.
Collapse
Affiliation(s)
- Karen Abboud
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Godsfavour Umoru
- Department of Pharmacy, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Humaid O. Al-Shamsi
- Department of Oncology, Burjeel Cancer Institute, Burjeel Medical City, Abu Dhabi P.O. Box 92510, United Arab Emirates
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ashish Saharia
- JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA
| | - Ashton A. Connor
- JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA
| | - Sudha Kodali
- JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA
| | - Rafik M. Ghobrial
- JC Walter Jr Center for Transplantation and Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX 77030, USA
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA
- Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Internal Medicine, Weill Cornell Medical College, New York, NY 14853, USA
| |
Collapse
|
|
35
|
Dey A, Mitra A, Pathak S, Prasad S, Zhang AS, Zhang H, Sun XF, Banerjee A. Recent Advancements, Limitations, and Future Perspectives of the use of Personalized Medicine in Treatment of Colon Cancer. Technol Cancer Res Treat 2023; 22:15330338231178403. [PMID: 37248615 PMCID: PMC10240881 DOI: 10.1177/15330338231178403] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 04/18/2023] [Accepted: 03/13/2023] [Indexed: 08/29/2024] Open
Abstract
Due to the heterogeneity of colon cancer, surgery, chemotherapy, and radiation are ineffective in all cases. The genomic profile and biomarkers associated with the process are considered in personalized medicine, along with the patient's personal history. It is based on the response of the targeted therapies to specific genetic variations. The patient's genetic transcriptomic and epigenetic features are evaluated, and the best therapeutic approach and diagnostic testing are identified through personalized medicine. This review aims to summarize all the necessary, updated information on colon cancer related to personalized medicine. Personalized medicine is gaining prominence as generalized treatments are finding it challenging to contain colon cancer cases which currently rank fourth among global cancer incidence while being the fifth largest in total death cases worldwide. In personalized therapy, patients are grouped into specific categories, and the best therapeutic approach is chosen based on evaluating their molecular features. Various personalized strategies are currently being explored in the treatment of colon cancer involving immunotherapy, phytochemicals, and other biomarker-specific targeted therapies. However, significant challenges must be overcome to integrate personalized medicine into healthcare systems completely. We look at the various signaling pathways and genetic and epigenetic alterations associated with colon cancer to understand and identify biomarkers useful in targeted therapy. The current personalized therapies available in colon cancer treatment and the strategies being explored to improve the existing methods are discussed. This review highlights the advantages and limitations of personalized medicine in colon cancer therapy. The current scenario of personalized medicine in developed countries and the challenges faced in middle- and low-income countries are also summarized. Finally, we discuss the future perspectives of personalized medicine in colon cancer and how it could be integrated into the healthcare systems.
Collapse
Affiliation(s)
- Amit Dey
- Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Chennai, India
| | - Abhijit Mitra
- Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Chennai, India
| | - Surajit Pathak
- Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Chennai, India
| | - Suhanya Prasad
- Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Białystok, Poland
| | | | - Hong Zhang
- School of Medicine, Department of Medical Sciences, Orebro University, Örebro, Sweden
| | - Xiao-Feng Sun
- Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Antara Banerjee
- Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Chennai, India
| |
Collapse
|
|
36
|
Implication of gut microbes and its metabolites in colorectal cancer. J Cancer Res Clin Oncol 2023; 149:441-465. [PMID: 36572792 DOI: 10.1007/s00432-022-04422-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 10/14/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer with a significant impact on loss of life. In 2020, nearly 1.9 million new cases and over 9,35,000 deaths were reported. Numerous microbes that are abundant in the human gut benefit host physiology in many ways. Although the underlying mechanism is still unknown, their association appears to be crucial in the beginning and progression of CRC. Diet has a significant impact on the microbial composition and may increase the chance of getting CRC. Increasing evidence points to the gut microbiota as the primary initiator of colonic inflammation, which is connected to the development of colonic tumors. However, it is unclear how the microbiota contributes to the development of CRCs. Patients with CRC have been found to have dysbiosis of the gut microbiota, which can be identified by a decline in commensal bacterial species, such as those that produce butyrate, and a concurrent increase in harmful bacterial populations, such as opportunistic pathogens that produce pro-inflammatory cytokines. We believe that using probiotics or altering the gut microbiota will likely be effective tools in the fight against CRC treatment. PURPOSE In this review, we revisited the association between gut microbiota and colorectal cancer whether cause or effect. The various factors which influence gut microbiome in patients with CRC and possible mechanism in relation with development of CRC. CONCLUSION The clinical significance of the intestinal microbiota may aid in the prevention and management of CRC.
Collapse
|
|
37
|
Najafi S, Majidpoor J, Mortezaee K. The impact of microbiota on PD-1/PD-L1 inhibitor therapy outcomes: A focus on solid tumors. Life Sci 2022; 310:121138. [DOI: 10.1016/j.lfs.2022.121138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 10/02/2022] [Accepted: 10/25/2022] [Indexed: 11/06/2022]
|
|
38
|
Yu I, Wu R, Tokumaru Y, Terracina KP, Takabe K. The Role of the Microbiome on the Pathogenesis and Treatment of Colorectal Cancer. Cancers (Basel) 2022; 14:5685. [PMID: 36428777 PMCID: PMC9688177 DOI: 10.3390/cancers14225685] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/13/2022] [Accepted: 11/16/2022] [Indexed: 11/22/2022] Open
Abstract
The gut microbiome has long been known to play a role in various aspects of health modulation, including the pathogenesis of colorectal cancer (CRC). With immunotherapy recently emerging as a successful treatment in microsatellite instability high (MSI-high) CRC, and with a newly demonstrated involvement of the gut microbiome in the modulation of therapeutic responses, there has been an explosion of research into the mechanisms of microbial effects on CRC. Harnessing and reprogramming the microbiome may allow for the expansion of these successes to broader categories of CRC, the prevention of CRC in high-risk patients, and the enhancement of standard treatments. In this review, we pull together both well-documented phenomena and recent discoveries that pertain to the microbiome and CRC. We explore the microbial mechanisms associated with CRC pathogenesis and progression, recent advancements in CRC systemic therapy, potential options for diagnosis and prevention, as well as directions for future research.
Collapse
Affiliation(s)
- Irene Yu
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14203, USA
| | - Rongrong Wu
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | - Yoshihisa Tokumaru
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
| | | | - Kazuaki Takabe
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY 14203, USA
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
- Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
- Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan
- Department of Breast Surgery, Fukushima Medical University, Fukushima 960-1295, Japan
| |
Collapse
|
|
39
|
Kosumi K, Mima K, Kanemitsu K, Tajiri T, Takematsu T, Sakamoto Y, Inoue M, Miyamoto Y, Mizumoto T, Kubota T, Miyanari N, Baba H. Self-expanding metal stent placement and pathological alterations among obstructive colorectal cancer cases. World J Gastrointest Endosc 2022; 14:704-717. [PMID: 36438885 PMCID: PMC9693689 DOI: 10.4253/wjge.v14.i11.704] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/23/2022] [Accepted: 10/25/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Experimental studies suggest that self-expanding metal stents (SEMSs) enhance the aggressive behavior of obstructive colorectal cancer. The influence of SEMS placement on pathological alterations remains to be elucidated.
AIM To determine whether SEMS placement is associated with molecular or pathological features of colorectal carcinoma tissues.
METHODS Using a nonbiased molecular pathological epidemiology database of patients with obstructive colorectal cancers, we examined the association of SEMS placement with molecular or pathological features, including tumor size, histological type, American Joint Committee on Cancer (AJCC)-pTNM stage, and mutation statuses in colorectal cancer tissues compared with the use of transanal tubes. A multivariable logistic regression model was used to adjust for potential confounders.
RESULTS SEMS placement was significantly associated with venous invasion (P < 0.01), but not with the other features examined, including tumor size, disease stage, mutation status, and lymphatic invasion. In both the univariable and multivariable models with adjustment for potential factors including tumor location, histological type, and AJCC-pT stage, SEMS placement was significantly associated with severe venous invasion (P < 0.01). For the outcome category of severe venous invasion, the multivariable odds ratio for SEMS placement relative to transanal tube placement was 19.4 (95% confidence interval: 5.24–96.2). No significant differences of disease-free survival and overall survival were observed between SEMS and transanal tube groups.
CONCLUSION SEMS placement might be associated with severe venous invasion in colorectal cancer tissue, providing an impetus for further investigations on the pathological alterations by SEMSs in colorectal cancer development.
Collapse
Affiliation(s)
- Keisuke Kosumi
- Department of Gastroenterological Surgery, Kumamoto University, Kuma- moto 860-8556, Japan
| | - Kosuke Mima
- Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto 860-0008, Japan
| | - Kosuke Kanemitsu
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 860-8556, Kumamoto, Japan
| | - Takuya Tajiri
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 860-8556, Kumamoto, Japan
| | - Toru Takematsu
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 860-8556, Kumamoto, Japan
| | - Yuki Sakamoto
- Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto 860-0008, Japan
| | - Mitsuhiro Inoue
- Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto 860-0008, Japan
| | - Yuji Miyamoto
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 860-8556, Kumamoto, Japan
| | - Takao Mizumoto
- Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto 860-0008, Japan
| | - Tatsuo Kubota
- Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto 860-0008, Japan
| | - Nobutomo Miyanari
- Department of Surgery, National Hospital Organization Kumamoto Medical Center, Kumamoto 860-0008, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Honjo 860-8556, Kumamoto, Japan
| |
Collapse
|
|
40
|
Ugai T, Liu L, Tabung FK, Hamada T, Langworthy BW, Akimoto N, Haruki K, Takashima Y, Okadome K, Kawamura H, Zhao M, Kahaki SMM, Glickman JN, Lennerz JK, Zhang X, Chan AT, Fuchs CS, Song M, Wang M, Yu K, Giannakis M, Nowak JA, Meyerhardt JA, Wu K, Ogino S, Giovannucci EL. Prognostic role of inflammatory diets in colorectal cancer overall and in strata of tumor-infiltrating lymphocyte levels. Clin Transl Med 2022; 12:e1114. [PMID: 36437503 PMCID: PMC9702366 DOI: 10.1002/ctm2.1114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Certain dietary patterns can elicit systemic and intestinal inflammatory responses, which may influence adaptive anti-tumor immune responses and tumor behavior. We hypothesized that pro-inflammatory diets might be associated with higher colorectal cancer mortality and that the association might be stronger for tumors with lower immune responses. METHODS We calculated an empirical dietary inflammatory pattern (EDIP) score in 2829 patients among 3988 incident rectal and colon carcinoma cases in the Nurses' Health Study and Health Professionals Follow-up Study. Using Cox proportional hazards regression analyses, we examined the prognostic association of EDIP scores and whether it might be modified by histopathologic immune reaction (in 1192 patients with available data). RESULTS Higher EDIP scores after colorectal cancer diagnosis were associated with worse survival, with multivariable-adjusted hazard ratios (HRs) for the highest versus lowest tertile of 1.41 (95% confidence interval [CI]: 1.13-1.77; Ptrend = 0.003) for 5-year colorectal cancer-specific mortality and 1.44 (95% CI, 1.19-1.74; Ptrend = 0.0004) for 5-year all-cause mortality. The association of post-diagnosis EDIP scores with 5-year colorectal cancer-specific mortality differed by degrees of tumor-infiltrating lymphocytes (TIL; Pinteraction = .002) but not by three other lymphocytic reaction patterns. The multivariable-adjusted, 5-year colorectal cancer-specific mortality HRs for the highest versus lowest EDIP tertile were 1.59 (95% CI: 1.01-2.53) in TIL-absent/low cases and 0.48 (95% CI: 0.16-1.48) in TIL-intermediate/high cases. CONCLUSIONS Pro-inflammatory diets after colorectal cancer diagnosis were associated with increased mortality, particularly in patients with absent or low TIL.
Collapse
|
|
41
|
Ikeda Y, Taniguchi K, Yoshikawa S, Sawamura H, Tsuji A, Matsuda S. A budding concept with certain microbiota, anti-proliferative family proteins, and engram theory for the innovative treatment of colon cancer. EXPLORATION OF MEDICINE 2022. [DOI: 10.37349/emed.2022.00108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a multifactorial chronic disease. Patients with IBD have an increased risk of developing colorectal cancer which has become a major health concern. IBD might exert a role of engrams for making the condition of specific inflammation in the gut. Dysregulation of immune cells induced by the command of engrams might be crucial in the pathogenesis of damages in gut epithelium. The anti-proliferative (APRO) family of anti-proliferative proteins characterized by immediate early responsive gene-products that might be involved in the machinery of the carcinogenesis in IBD. Herein, it is suggested that some probiotics with specific bacteria could prevent the development and/or progression of the IBD related tumors. In addition, consideration regarding the application of studying APRO family proteins for the comprehension of IBD related tumors has been presented. It is hypothesized that overexpression of Tob1, a member of APRO family proteins, in the epithelium of IBD could suppress the function of adjacent cytotoxic immune cells possibly via the paracrine signaling.
Collapse
Affiliation(s)
- Yuka Ikeda
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Kurumi Taniguchi
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Sayuri Yoshikawa
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Haruka Sawamura
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Ai Tsuji
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| | - Satoru Matsuda
- Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506, Japan
| |
Collapse
|
|
42
|
Ugai T, Sasamoto N, Lee HY, Ando M, Song M, Tamimi RM, Kawachi I, Campbell PT, Giovannucci EL, Weiderpass E, Rebbeck TR, Ogino S. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat Rev Clin Oncol 2022; 19:656-673. [PMID: 36068272 PMCID: PMC9509459 DOI: 10.1038/s41571-022-00672-8] [Citation(s) in RCA: 223] [Impact Index Per Article: 74.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2022] [Indexed: 02/07/2023]
Abstract
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. Increased use of screening programmes has contributed to this phenomenon to a certain extent, although a genuine increase in the incidence of early-onset forms of several cancer types also seems to have emerged. Evidence suggests an aetiological role of risk factor exposures in early life and young adulthood. Since the mid-20th century, substantial multigenerational changes in the exposome have occurred (including changes in diet, lifestyle, obesity, environment and the microbiome, all of which might interact with genomic and/or genetic susceptibilities). However, the effects of individual exposures remain largely unknown. To study early-life exposures and their implications for multiple cancer types will require prospective cohort studies with dedicated biobanking and data collection technologies. Raising awareness among both the public and health-care professionals will also be critical. In this Review, we describe changes in the incidence of early-onset cancers globally and suggest measures that are likely to reduce the burden of cancers and other chronic non-communicable diseases.
Collapse
Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Naoko Sasamoto
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA
| | - Hwa-Young Lee
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Institute of Convergence Science, Convergence Science Academy, Yonsei University, Seoul, Republic of Korea
| | - Mariko Ando
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Rulla M Tamimi
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
| | - Ichiro Kawachi
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Peter T Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Timothy R Rebbeck
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA
- Zhu Family Center for Global Cancer Prevention, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
| |
Collapse
|
|
43
|
Arima K, Zhong R, Ugai T, Zhao M, Haruki K, Akimoto N, Lau MC, Okadome K, Mehta RS, Väyrynen JP, Kishikawa J, Twombly TS, Shi S, Fujiyoshi K, Kosumi K, Ogata Y, Baba H, Wang F, Wu K, Song M, Zhang X, Fuchs CS, Sears CL, Willett WC, Giovannucci EL, Meyerhardt JA, Garrett WS, Huttenhower C, Chan AT, Nowak JA, Giannakis M, Ogino S. Western-Style Diet, pks Island-Carrying Escherichia coli, and Colorectal Cancer: Analyses From Two Large Prospective Cohort Studies. Gastroenterology 2022; 163:862-874. [PMID: 35760086 PMCID: PMC9509428 DOI: 10.1053/j.gastro.2022.06.054] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 05/20/2022] [Accepted: 06/15/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Evidence supports a carcinogenic role of Escherichia coli carrying the pks island that encodes enzymes for colibactin biosynthesis. We hypothesized that the association of the Western-style diet (rich in red and processed meat) with colorectal cancer incidence might be stronger for tumors containing higher amounts of pks+E coli. METHODS Western diet score was calculated using food frequency questionnaire data obtained every 4 years during follow-up of 134,775 participants in 2 United States-wide prospective cohort studies. Using quantitative polymerase chain reaction, we measured pks+E coli DNA in 1175 tumors among 3200 incident colorectal cancer cases that had occurred during the follow-up. We used the 3200 cases and inverse probability weighting (to adjust for selection bias due to tissue availability), integrated in multivariable-adjusted duplication-method Cox proportional hazards regression analyses. RESULTS The association of the Western diet score with colorectal cancer incidence was stronger for tumors containing higher levels of pks+E coli (Pheterogeneity = .014). Multivariable-adjusted hazard ratios (with 95% confidence interval) for the highest (vs lowest) tertile of the Western diet score were 3.45 (1.53-7.78) (Ptrend = 0.001) for pks+E coli-high tumors, 1.22 (0.57-2.63) for pks+E coli-low tumors, and 1.10 (0.85-1.42) for pks+E coli-negative tumors. The pks+E coli level was associated with lower disease stage but not with tumor location, microsatellite instability, or BRAF, KRAS, or PIK3CA mutations. CONCLUSIONS The Western-style diet is associated with a higher incidence of colorectal cancer containing abundant pks+E coli, supporting a potential link between diet, the intestinal microbiota, and colorectal carcinogenesis.
Collapse
Affiliation(s)
- Kota Arima
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Rong Zhong
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Melissa Zhao
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Koichiro Haruki
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Naohiko Akimoto
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Mai Chan Lau
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kazuo Okadome
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Raaj S Mehta
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Juha P Väyrynen
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Junko Kishikawa
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Tyler S Twombly
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Shanshan Shi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Kenji Fujiyoshi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Keisuke Kosumi
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Yoko Ogata
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Fenglei Wang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Mingyang Song
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Xuehong Zhang
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Charles S Fuchs
- Yale Cancer Center, New Haven, Connecticut; Department of Medicine, Yale School of Medicine, New Haven, Connecticut; Smilow Cancer Hospital, New Haven, Connecticut; Genentech, South San Francisco, California
| | - Cynthia L Sears
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Walter C Willett
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Jeffrey A Meyerhardt
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - Wendy S Garrett
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts
| | - Curtis Huttenhower
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Jonathan A Nowak
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Marios Giannakis
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, Massachusetts.
| |
Collapse
|
|
44
|
Ding Q, Kong X, Zhong W, Liu W. Fecal biomarkers: Non-invasive diagnosis of colorectal cancer. Front Oncol 2022; 12:971930. [PMID: 36119474 PMCID: PMC9479095 DOI: 10.3389/fonc.2022.971930] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 08/10/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer in the world in terms of morbidity and mortality, which brings great health hazards and economic burdens to patients and society. A fecal examination is an effective method for clinical examination and the most commonly used method for the census. It is simple, non-invasive, and suitable for large-scale population screening. With the development of molecular biology, lots of efforts have been made to discover new fecal biomarkers for the early screening of colorectal cancer. In this review, we summarize and discuss the recent advances of fecal biomarkers for CRC screening or diagnosis, including DNA biomarkers, RNA biomarkers, protein biomarkers, gut microbes and volatile organic compounds focusing on their diagnostic evaluation for CRC, which can provide a basis for the further development of new and effective CRC fecal screening and early diagnosis techniques.
Collapse
Affiliation(s)
| | | | - Weilong Zhong
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| | - Wentian Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China
| |
Collapse
|
|
45
|
Zhang P. Influence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health. Int J Mol Sci 2022; 23:ijms23179588. [PMID: 36076980 PMCID: PMC9455721 DOI: 10.3390/ijms23179588] [Citation(s) in RCA: 112] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/21/2022] [Accepted: 08/23/2022] [Indexed: 11/16/2022] Open
Abstract
Food components in our diet provide not only necessary nutrients to our body but also substrates for the mutualistic microbial flora in our gastrointestinal tract, termed the gut microbiome. Undigested food components are metabolized to a diverse array of metabolites. Thus, what we eat shapes the structure, composition, and function of the gut microbiome, which interacts with the gut epithelium and mucosal immune system and maintains intestinal homeostasis in a healthy state. Alterations of the gut microbiome are implicated in many diseases, such as inflammatory bowel disease (IBD). There is growing interest in nutritional therapy to target the gut microbiome in IBD. Investigations into dietary effects on the composition changes in the gut microbiome flourished in recent years, but few focused on gut physiology. This review summarizes the current knowledge regarding the impacts of major food components and their metabolites on the gut and health consequences, specifically within the GI tract. Additionally, the influence of the diet on the gut microbiome-host immune system interaction in IBD is also discussed. Understanding the influence of the diet on the interaction of the gut microbiome and the host immune system will be useful in developing nutritional strategies to maintain gut health and restore a healthy microbiome in IBD.
Collapse
Affiliation(s)
- Ping Zhang
- Center for Integrative Conservation, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun 666303, China
| |
Collapse
|
|
46
|
Yao S, Campbell PT, Ugai T, Gierach G, Abubakar M, Adalsteinsson V, Almeida J, Brennan P, Chanock S, Golub T, Hanash S, Harris C, Hathaway CA, Kelsey K, Landi MT, Mahmood F, Newton C, Quackenbush J, Rodig S, Schultz N, Tearney G, Tworoger SS, Wang M, Zhang X, Garcia-Closas M, Rebbeck TR, Ambrosone CB, Ogino S. Proceedings of the fifth international Molecular Pathological Epidemiology (MPE) meeting. Cancer Causes Control 2022; 33:1107-1120. [PMID: 35759080 PMCID: PMC9244289 DOI: 10.1007/s10552-022-01594-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 05/20/2022] [Indexed: 01/19/2023]
Abstract
Cancer heterogeneities hold the key to a deeper understanding of cancer etiology and progression and the discovery of more precise cancer therapy. Modern pathological and molecular technologies offer a powerful set of tools to profile tumor heterogeneities at multiple levels in large patient populations, from DNA to RNA, protein and epigenetics, and from tumor tissues to tumor microenvironment and liquid biopsy. When coupled with well-validated epidemiologic methodology and well-characterized epidemiologic resources, the rich tumor pathological and molecular tumor information provide new research opportunities at an unprecedented breadth and depth. This is the research space where Molecular Pathological Epidemiology (MPE) emerged over a decade ago and has been thriving since then. As a truly multidisciplinary field, MPE embraces collaborations from diverse fields including epidemiology, pathology, immunology, genetics, biostatistics, bioinformatics, and data science. Since first convened in 2013, the International MPE Meeting series has grown into a dynamic and dedicated platform for experts from these disciplines to communicate novel findings, discuss new research opportunities and challenges, build professional networks, and educate the next-generation scientists. Herein, we share the proceedings of the Fifth International MPE meeting, held virtually online, on May 24 and 25, 2021. The meeting consisted of 21 presentations organized into the three main themes, which were recent integrative MPE studies, novel cancer profiling technologies, and new statistical and data science approaches. Looking forward to the near future, the meeting attendees anticipated continuous expansion and fruition of MPE research in many research fronts, particularly immune-epidemiology, mutational signatures, liquid biopsy, and health disparities.
Collapse
Affiliation(s)
- Song Yao
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY, 14263, USA.
| | - Peter T Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Tomotaka Ugai
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Gretchen Gierach
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Mustapha Abubakar
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | | | - Jonas Almeida
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Paul Brennan
- International Agency for Research On Cancer (IARC/WHO), Genomic Epidemiology Branch, Lyon, France
| | - Stephen Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Todd Golub
- Broad Institute of MIT and Harvard, Boston, MA, USA
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Samir Hanash
- Department of Clinical Cancer Prevention, MD Anderson Cancer Institute, Houston, TX, USA
| | - Curtis Harris
- Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Cassandra A Hathaway
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Karl Kelsey
- Department of Epidemiology, Brown School of Public Health, Brown University, Providence, RI, USA
| | - Maria Teresa Landi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Faisal Mahmood
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Christina Newton
- Department of Population Science, American Cancer Society, Atlanta, GA, USA
| | - John Quackenbush
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Scott Rodig
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Nikolaus Schultz
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Guillermo Tearney
- Department of Pathology and Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
| | - Shelley S Tworoger
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Molin Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Timothy R Rebbeck
- Zhu Family Center for Global Cancer Prevention, Harvard T.H. Chan School of Public Health and Dana-Farber Cancer Institute, Boston, MA, USA
| | - Christine B Ambrosone
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY, 14263, USA
| | - Shuji Ogino
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Boston, MA, USA.
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
|
47
|
Wang F, Ugai T, Haruki K, Wan Y, Akimoto N, Arima K, Zhong R, Twombly TS, Wu K, Yin K, Chan AT, Giannakis M, Nowak JA, Meyerhardt JA, Liang L, Song M, Smith‐Warner SA, Zhang X, Giovannucci EL, Willett WC, Ogino S. Healthy and unhealthy plant-based diets in relation to the incidence of colorectal cancer overall and by molecular subtypes. Clin Transl Med 2022; 12:e893. [PMID: 35998061 PMCID: PMC9398226 DOI: 10.1002/ctm2.893] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 04/30/2022] [Accepted: 05/09/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Plant-based foods have been recommended for health. However, not all plant foods are healthy, and little is known about the association between plant-based diets and specific molecular subtypes of colorectal cancer (CRC). We examined the associations of healthy and unhealthy plant-based diets with the incidence of CRC and its molecular subtypes. METHODS While 123 773 participants of the Nurses' Health Study and the Health Professionals Follow-up Study had been followed up (3 143 158 person-years), 3077 of them had developed CRC. Healthy and unhealthy plant-based diet indices (hPDI and uPDI, respectively) were calculated using repeated food frequency questionnaire data. We determined the tumoural status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations. RESULTS Higher hPDI was associated with lower CRC incidence (multivariable hazard ratio [HR] comparing extreme quartiles, 0.86, 95% confidence interval [CI]: 0.77, 0.96; P-trend = .04), whereas higher uPDI was associated with higher CRC incidence (multivariable HR comparing extreme quartiles, 1.16, 95% CI: 1.04, 1.29; P-trend = .005). The association of hPDI significantly differed by KRAS status (P-heterogeneity = .003) but not by other tumour markers. The hPDI was associated with lower incidence of KRAS-wildtype CRC (multivariable HR comparing extreme quartiles, 0.74, 95% CI: 0.57, 0.96; P-trend = .004) but not KRAS-mutant CRC (P-trend = .22). CONCLUSIONS While unhealthy plant-based diet enriched with refined grains and sugar is associated with higher CRC incidence, healthy plant-based diet rich in whole grains, fruits and vegetables is associated with lower incidence of CRC, especially KRAS-wildtype CRC.
Collapse
|
|
48
|
Caruso C, Ligotti ME, Accardi G, Aiello A, Candore G. An immunologist's guide to immunosenescence and its treatment. Expert Rev Clin Immunol 2022; 18:961-981. [PMID: 35876758 DOI: 10.1080/1744666x.2022.2106217] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION : The ageing process causes several changes in the immune system, although immune ageing is strongly influenced by individual immunological history, as well as genetic and environmental factors leading to inter-individual variability. AREAS COVERED : Here, we focused on the biological and clinical meaning of immunosenescence. Data on SARS-CoV-2 and Yellow Fever vaccine have demonstrated the clinical relevance of immunosenescence, while inconsistent results, obtained from longitudinal studies aimed at looking for immune risk phenotypes, have revealed that the immunosenescence process is highly context-dependent. Large projects have allowed the delineation of the drivers of immune system variance, including genetic and environmental factors, sex, smoking, and co-habitation. Therefore, it is difficult to identify the interventions that can be envisaged to maintain or improve immune function in older people. That suggests that drug treatment of immunosenescence should require personalized intervention. Regarding this, we discussed the role of changes in lifestyle as a potential therapeutic approach. EXPERT OPINION : Our review points out that age is only part of the problem of immunosenescence. Everyone ages differently because he/she is unique in genetics and experience of life and this applies even more to the immune system (immunobiography). Finally, the present review shows how appreciable results in the modification of immunosenescence biomarkers can be achieved with lifestyle modification.
Collapse
Affiliation(s)
- Calogero Caruso
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Mattia Emanuela Ligotti
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Giulia Accardi
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Anna Aiello
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| | - Giuseppina Candore
- Laboratorio di Immunopatologia e Immunosenescenza, Dipartimento di Biomedicina, Neuroscienze e Diagnostica Avanzata, Università di Palermo, Palermo, Italy
| |
Collapse
|
|
49
|
Puca F, Fedele M, Rasio D, Battista S. Role of Diet in Stem and Cancer Stem Cells. Int J Mol Sci 2022; 23:ijms23158108. [PMID: 35897685 PMCID: PMC9330301 DOI: 10.3390/ijms23158108] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/20/2022] [Accepted: 07/21/2022] [Indexed: 11/16/2022] Open
Abstract
Diet and lifestyle factors greatly affect health and susceptibility to diseases, including cancer. Stem cells’ functions, including their ability to divide asymmetrically, set the rules for tissue homeostasis, contribute to health maintenance, and represent the entry point of cancer occurrence. Stem cell properties result from the complex integration of intrinsic, extrinsic, and systemic factors. In this context, diet-induced metabolic changes can have a profound impact on stem cell fate determination, lineage specification and differentiation. The purpose of this review is to provide a comprehensive description of the multiple “non-metabolic” effects of diet on stem cell functions, including little-known effects such as those on liquid-liquid phase separation and on non-random chromosome segregation (asymmetric division). A deep understanding of the specific dietetic requirements of normal and cancer stem cells may pave the way for the development of nutrition-based targeted therapeutic approaches to improve regenerative and anticancer therapies.
Collapse
Affiliation(s)
- Francesca Puca
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 78705, USA;
- Department of Oncology, IRBM Science Park SpA, 00071 Pomezia, Italy
| | - Monica Fedele
- Institute for Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy;
| | - Debora Rasio
- Department of Clinical and Molecular Medicine, La Sapienza University, 00185 Rome, Italy;
| | - Sabrina Battista
- Institute for Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), 80131 Naples, Italy;
- Correspondence:
| |
Collapse
|
|
50
|
Inamura K, Hamada T, Bullman S, Ugai T, Yachida S, Ogino S. Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science. Gut 2022; 71:gutjnl-2022-327209. [PMID: 35820782 PMCID: PMC9834441 DOI: 10.1136/gutjnl-2022-327209] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 06/28/2022] [Indexed: 02/06/2023]
Abstract
Cancer is generally regarded as a localised disease, with the well-established role of the tumour microenvironment. However, the realm of cancer goes beyond the tumour microenvironment, and cancer should also be regarded as a systemic and environmental disease. The exposome (ie, the totality of exposures), which encompasses diets, supplements, smoking, alcohol, other lifestyle factors, medications, etc, likely alters the microbiome (inclusive of bacteria, viruses, archaea, fungi, parasites, etc) and immune system in various body sites and influences tumour phenotypes. The systemic metabolic/inflammatory status, which is likely influenced by exposures and intestinal physiological changes, may affect tissue microenvironment of colorectum and any other organs. Germline genomic factors can modify disease phenotypes via gene-by-environment interactions. Although challenges exist, it is crucial to advance not only basic experimental research that can analyse the effects of exposures, microorganisms and microenvironmental components on tumour evolution but also interdisciplinary human population research that can dissect the complex pathogenic roles of the exposome, microbiome and immunome. Metagenomic, metatranscriptomic and metabolomic analyses should be integrated into well-designed population research combined with advanced methodologies of artificial intelligence and molecular pathological epidemiology. Ideally, a prospective cohort study design that enables biospecimen (such as stool) collection before disease detection should be considered to address reverse causation and recall biases. Robust experimental and observational research together can provide insights into dynamic interactions between environmental exposures, microbiota, tumour and immunity during carcinogenesis processes, thereby helping us develop precision prevention and therapeutic strategies to ultimately reduce the cancer burden.
Collapse
Affiliation(s)
- Kentaro Inamura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic Medicine, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Susan Bullman
- Human Biology Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Tomotaka Ugai
- Department of Epidemiology, Harvard University T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Shinichi Yachida
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
- Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan
- Division of Genomic Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Shuji Ogino
- Department of Epidemiology, Harvard University T.H. Chan School of Public Health, Boston, Massachusetts, USA
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, Massachusetts, USA
| |
Collapse
|