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Alghamdi YS, Mashraqi MM, Alsalmi O, Alharthi AA, Gharib AF. Evaluating the polypharmacological potency of indenopyrazole against lung cancer oxidoreductase, chaperone, transferase, and hydrolase proteins. Med Oncol 2025; 42:206. [PMID: 40346388 DOI: 10.1007/s12032-025-02723-3] [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: 02/25/2025] [Accepted: 04/14/2025] [Indexed: 05/11/2025]
Abstract
Lung cancer, the deadliest malignancy worldwide, causes 2.2 million cases and 1.8 million deaths annually, accounting for 18% of cancer deaths. Limited early detection, unaffordable treatments, and drug resistance lead to low survival rates, highlighting the urgent need for developing effective, resistance-proof therapies. In this study, we docked the DrugBank library against Lung Cancer Oxidoreductase, Chaperone, Transferase, and Hydrolase Proteins to identify a multitargeted drug candidate, resulting in identifying a promising drug candidate named Indenopyrazole with docking and MM\GBSA scores ranging from -7.337 to -11.62 and -17.82 to -60.38 kcal/mol, respectively. We also evaluated the interaction pattern of the drug candidate with Molecular Interaction Fingerprints and found that the most interacting residues with its counts are 4TRP, 3ASP, 3GLN, 3GLU, 3LYS, 3PHE, and 3TYR. The pharmacokinetics and comparison with standard values supported the candidate, followed by the density functional theory computations. The study was also validated for the WaterMap for water thermodynamics, and its role in binding pockets has also supported the idea that Indenopyrazole has a multitargeted potency. Further, we extended our studies with 100ns MD Simulation in water to analyse the deviations, fluctuations, and intermolecular interactions, and all the 1000 trajectories were evaluated for total complex energy and binding free energy with MM\GBSA concluding wonderful promising results in support of Indenopyrazole as a multitargeted drug candidate-however, its efficacy needs to be experimentally validated.
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Affiliation(s)
| | - Mutaib M Mashraqi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, 61441, Najran, Saudi Arabia.
| | - Ohud Alsalmi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, 21944, Taif, Saudi Arabia
| | - Afaf Awwadh Alharthi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, 21944, Taif, Saudi Arabia
| | - Amal F Gharib
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, 21944, Taif, Saudi Arabia
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Ahmad S, Bano N, Raza K. Evaluating the polypharmacological potency of FEDPN from ChEMBL BioAssays against lung cancer EGFR, ALK, TrkA and KRAS proteins. Int J Biol Macromol 2025; 306:141703. [PMID: 40043981 DOI: 10.1016/j.ijbiomac.2025.141703] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 02/20/2025] [Accepted: 03/01/2025] [Indexed: 05/03/2025]
Abstract
Lung cancer causes over 2.2 million cases and 1.8 million deaths annually, and the survival rate remains dismal despite therapeutic advancements, highlighting the urgent need for novel drugs. Current single-target treatments are often ineffective due to complex cancer mechanisms and rapid resistance, underscoring the necessity for multitargeted drugs which target multiple pathways simultaneously, enhance therapeutic outcomes, reduce resistance, and significantly improve patient survival. Our study has innovative strategies imperative to achieve these goals and revolutionise lung cancer treatment. In this study, we downloaded the Lung Cancer BioAssays from ChEMBL, categorised them in Active and Inactive, and selected the Active to preprocess, followed by preparing with LigPrep for docking and chosen transferase, and hydrolase proteins (EGFR, ALK, TrkA and KRAS) involved in lung cancer pathways and docked them which identified the best candidate among Active BioAssays 5-fluoro-(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile (FEDPN) as a multitargeted drug candidate. We also evaluated the results with MIFs, which identified VAL, GLU, GLY, LEU, LYS, THR, and TYR as the most interacted residues. We also performed the DFT studies followed by 5 ns WaterMap computations to understand FEDPN's stability, precise interactions, and water thermodynamics on the interacting site. Also, we performed a 100 ns MD simulation in the TIP3P water model and analysed deviation, fluctuations within 2 Å, and many intermolecular interactions followed by binding free energy computations and analysis that supported the results. The complete study backed FEDPN's multitargeted potency-however, experimental studies are needed before its use.
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Affiliation(s)
- Shaban Ahmad
- Department of Computer Science, Jamia Millia Islamia, New Delhi 110025, India.
| | - Nagmi Bano
- Department of Computer Science, Jamia Millia Islamia, New Delhi 110025, India.
| | - Khalid Raza
- Department of Computer Science, Jamia Millia Islamia, New Delhi 110025, India.
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Diao X, Guo C, Jin Y, Li B, Gao X, Du X, Chen Z, Jo M, Zeng Y, Ding C, Liu W, Guo J, Li S, Qiu H. Cancer situation in China: an analysis based on the global epidemiological data released in 2024. Cancer Commun (Lond) 2025; 45:178-197. [PMID: 39659114 PMCID: PMC11833671 DOI: 10.1002/cac2.12627] [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: 07/07/2024] [Revised: 10/26/2024] [Accepted: 10/31/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND Cancer remains a major cause of mortality and a significant economic burden in China. Exploring the disparities in cancer patterns and control strategies between China and developed countries may offer valuable insights for policy formulation and enhance cancer management efforts. This study examined the incidence, mortality, and disability-adjusted life year (DALY) burden of cancer in China, and compared these metrics with those observed in the United States (US) and the United Kingdom (UK). METHODS Data on cancer incidence, mortality, and DALYs for China, the US, and the UK were sourced from the GLOBOCAN 2022 online database and the Global Burden of Disease 2021 study (GBD 2021). We utilized Joinpoint regression models to analyze trends in cancer incidence and mortality across these countries, calculating annual percent changes (APCs) and determining the optimal joinpoints. RESULTS In 2022, China recorded around 4,824,703 new cancer cases and 2,574,176 cancer-related deaths, contributing to 71,037,170 DALYs. China exhibited a lower cancer incidence rate compared to the US and the UK. Although cancer-related mortality in China is slightly lower than that in the UK, it is significantly higher than that in the US. Additionally, China experienced significantly higher DALY rates compared to both the US and UK. The cancer landscape in China was also undergoing significant changes, with a rapid rise in the incidence and burden of lung, colorectal, breast, cervical, and prostate cancers. Meanwhile, the incidence and burden of stomach cancer continued to decline. Although the incidence of liver and esophageal cancers was decreasing, the burden of liver cancer was increasing, while the burden of esophageal cancer remained largely unchanged. CONCLUSIONS The cancer profile of China is shifting from that of a developing country to one more typical of a developed country. The ongoing population aging and the rise in unhealthy lifestyles are expected to further escalate the cancer burden in China. Consequently, it is crucial for Chinese authorities to revise the national cancer control program, drawing on successful strategies from developed countries, while also accounting for the regional diversity in cancer types across China.
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Affiliation(s)
- Xiayao Diao
- Department of Thoracic SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Chao Guo
- Department of Thoracic SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Yukai Jin
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
| | - Bowen Li
- Department of Thoracic SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Xuehan Gao
- Department of Thoracic SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Xin Du
- Department of Thoracic SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Zhenchong Chen
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
| | - Minju Jo
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
| | - Yi Zeng
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
| | - Chao Ding
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
| | - Wenwu Liu
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
| | - Jianrong Guo
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
| | - Shanqing Li
- Department of Thoracic SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP. R. China
| | - Haibo Qiu
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat‐sen University Cancer CenterGuangzhouGuangdongP. R. China
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Ji X, Chen J, Ye J, Xu S, Lin B, Hou K. Epidemiological Analysis of Global and Regional Lung Cancer Mortality: Based on 30-Year Data Analysis of Global Burden Disease Database. Healthcare (Basel) 2023; 11:2920. [PMID: 37998412 PMCID: PMC10671048 DOI: 10.3390/healthcare11222920] [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: 09/09/2023] [Revised: 10/30/2023] [Accepted: 11/03/2023] [Indexed: 11/25/2023] Open
Abstract
The objective of this study was to understand dynamic global and regional lung cancer fatality trends and provide a foundation for effective global lung cancer prevention and treatment strategies. Data from 1990 to 2019 were collected from the Global Burden Disease (GBD) database and statistical analysis was conducted using Excel 2010. Standardization was based on the GBD's world population structure, and the Average Annual Percentage Change (AAPC) was calculated using Joinpoint 4.8.0.1 software. Bayesian age-period-cohort analysis (BAPC) predicted global lung cancer mortality from 2020 to 2030. In 2019, worldwide lung cancer deaths reached 2,042,600, a 91.75% increase from 1990 (1,065,100). The standardized age-specific death rate in 2019 was 25.18 per 100,000. Males had a rate of 37.38 while females had 14.99. Men saw a decreasing trend while women experienced an increase. High- and medium-high-SDI regions had declining rates (-0.3 and -0.8 AAPCs) whereas middle-, low-, and low-middle-SDI regions had increased mortality rates (AAPC = 0.1, AAPC = 0.37, AAPC = 0.13). Several regions, including Oceania, South Asia, East Asia, Western Sub-Saharan Africa, Southeast Asia, and Eastern Sub-Saharan Africa, witnessed rising global lung cancer mortality rates (p < 0.01). The global standardized mortality rate for lung cancer is expected to decrease from 2020 to 2030, but predictions indicate increasing female mortality and decreasing male mortality. Despite overall declines, rising female mortality remains a concern. Effective measures are essential to reduce mortality rates and improve patients' quality of life in the global fight against lung cancer.
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Affiliation(s)
- Xiaoxia Ji
- Medical College, Shantou University, Shantou 515031, China; (X.J.); (J.Y.); (S.X.)
| | - Jingxian Chen
- School of Public Health, Shantou University, Shantou 515063, China;
| | - Junjun Ye
- Medical College, Shantou University, Shantou 515031, China; (X.J.); (J.Y.); (S.X.)
| | - Shuochun Xu
- Medical College, Shantou University, Shantou 515031, China; (X.J.); (J.Y.); (S.X.)
| | - Benwei Lin
- School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1QU, UK;
| | - Kaijian Hou
- School of Public Health, Shantou University, Shantou 515063, China;
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Wang L, Wang Y, Cheng X, Li X, Li J. Impact of coronavirus disease 2019 on lung cancer patients: A meta-analysis. Transl Oncol 2023; 28:101605. [PMID: 36568513 PMCID: PMC9760620 DOI: 10.1016/j.tranon.2022.101605] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 12/11/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
Background The coronavirus disease 2019 (COVID-19) pandemic poses a great challenge to the treatment of lung cancer patients. Materials and methods The PubMed, Embase, and Web of Science databases were searched for studies published before March 15, 2022, and Stata 14.0 software was used to perform a meta-analysis with a random-effects model. The odds ratio (OR) along with the corresponding 95% confidence interval (CI) was reported. Results Our meta-analysis included 80 articles with 318,352 patients involved. The proportion of lung cancer patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 2.4% (95% CI: 0.02-0.03) prior to the Omicron variant outbreak. Among COVID-19 patients, those with lung cancer showed a higher mortality rate than those with other types of malignant solid tumors (OR = 1.82, 95% CI: 1.61-2.06) and non-cancer patients (OR = 4.67, 95% CI: 3.61-6.05); however, no significant difference was observed in the mortality rate between patients with lung cancer and those with hematologic malignancies (OR = 1.07, 95% CI: 0.85-1.33). SARS-CoV-2 infection significantly increased the mortality rate in lung cancer patients (OR = 8.94, 95% CI: 6.50-12.31). By contrast, the all-cause mortality rate in lung cancer patients (OR = 1.04, 95% CI: 0.69-1.57) and the proportion of patients diagnosed with advanced lung cancer (OR = 1.04, 95% CI: 0.85-1.27) did not significantly change before and after the pandemic. Conclusions More attention should be paid on improving the health of lung cancer patients during the COVID-19 pandemic.
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Affiliation(s)
- Linlin Wang
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Ye Wang
- Department of Pediatrics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Xianbin Cheng
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Xingzhao Li
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Jun Li
- Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
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Sager O, Dincoglan F, Demiral S, Uysal B, Gamsiz H, Ozcan F, Colak O, Elcim Y, Gundem E, Dirican B, Beyzadeoglu M. Adaptive radiation therapy (art) for patients with limited-stage small cell lung cancer (LS-SCLC): A dosimetric evaluation. Indian J Cancer 2022; 0:358503. [PMID: 36861709 DOI: 10.4103/ijc.ijc_73_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Background Adaptive radiation therapy (ART) refers to redesigning of radiation therapy (RT) treatment plans with respect to dynamic changes in tumor size and location throughout the treatment course. In this study, we performed a comparative volumetric and dosimetric analysis to investigate the impact of ART for patients with limited-stage small cell lung cancer (LS-SCLC). Methods Twenty-four patients with LS-SCLC receiving ART and concomitant chemotherapy were included in the study. ART was performed by replanning of patients based on a mid-treatment computed tomography (CT)-simulation which was routinely scheduled for all patients 20-25 days after the initial CT-simulation. While the first 15 RT fractions were planned using the initial CT-simulation images, the latter 15 RT fractions were planned using the mid-treatment CT-simulation images acquired 20-25 days after the initial CT-simulation. In order to document the impact of ART, target and critical organ dose-volume parameters acquired from this adaptive radiation treatment planning (RTP) were compared with the RTP based solely on the initial CT-simulation to deliver the whole RT dose of 60 Gy. Results Statistically significant reduction was detected in gross tumor volume (GTV) and planning target volume (PTV) during the conventionally fractionated RT course along with statistically significant reduction in critical organ doses with incorporation of ART. Conclusion One-third of the patients in our study who were otherwise ineligible for curative intent RT due to violation of critical organ dose constraints could be treated with full dose irradiation by use of ART. Our results suggest significant benefit of ART for patients with LS-SCLC.
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Affiliation(s)
- Omer Sager
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Ferrat Dincoglan
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Selcuk Demiral
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Bora Uysal
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Hakan Gamsiz
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Fatih Ozcan
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Onurhan Colak
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Yelda Elcim
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Esin Gundem
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Bahar Dirican
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
| | - Murat Beyzadeoglu
- Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Ankara, Turkey
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He J, Wang Z, Zou T, Wang Y, Li XP, Chen J. The Association Between Genetic Polymorphisms of Transporter Genes and Prognosis of Platinum-Based Chemotherapy in Lung Cancer Patients. Pharmgenomics Pers Med 2022; 15:817-825. [PMID: 36131844 PMCID: PMC9484078 DOI: 10.2147/pgpm.s375284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 08/30/2022] [Indexed: 11/25/2022] Open
Abstract
Objective Platinum-based chemotherapy is the first-line treatment of lung cancer. However, different individual and genetic variation effect therapy for lung cancer. The purpose of this study was to evaluate the association between transport genes genetic polymorphisms and the prognosis of platinum-based chemotherapy in lung cancer patients. Methods A series of 593 patients with treatment of platinum-based chemotherapy were recruited for this study. A total of 21 single-nucleotide polymorphisms in nine transporter genes were selected to investigate their associations with platinum-based chemotherapy prognosis. Results Patients with ABCG2 rs1448784 CC genotype had a significantly shorter PFS than CT or TT genotypes (Additive model: HR = 1.54, 95% CI = 1.02–2.35, P = 0.040). In stratification analysis, SLC22A2 rs316003, SLC2A1 rs4658 were related to PFS and AQP9 rs1867380, SLC2A1 rs3820589, SLC22A2 rs316003 indicated were related to OS of platinum-based chemotherapy prognosis. Conclusion Genetic polymorphisms of rs1448784 in ABCG2 might be potential clinical marker for predicting the prognosis of lung cancer patients treated with platinum-based chemotherapy.
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Affiliation(s)
- Jia He
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Zhan Wang
- Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, 410013, People’s Republic of China
| | - Ting Zou
- National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China
| | - Ying Wang
- Hunan clinical Research Center in Gynecologic Cancer, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, 410013, People’s Republic of China
| | - Xiang-Ping Li
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Juan Chen
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Correspondence: Juan Chen, Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China, Tel +86-731-89753491, Email
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Influenza Vaccination and Risk of Lung Cancer in Patients with Chronic Kidney Disease: A Nationwide, Population-Based Cohort Study. Cancers (Basel) 2022; 14:cancers14122926. [PMID: 35740592 PMCID: PMC9221107 DOI: 10.3390/cancers14122926] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 06/11/2022] [Indexed: 02/04/2023] Open
Abstract
Chronic kidney disease (CKD) is significantly associated with lung cancer incidence. The aim of this study was to elucidate whether influenza vaccination reduces the incidence of lung cancer in patients with CKD. This cohort study enrolled patients with a record of CKD diagnosis from 2000 to 2012 in Taiwan’s National Health Insurance Research Database. Included patients were divided into vaccinated and unvaccinated groups. In total 12,985 patients with CKD were enrolled. Among these patients, 5495 were vaccinated and 7490 were unvaccinated. The risk of lung cancer was significantly lower in the influenza vaccination group after adjusting for age, sex, dialysis status, lung diseases, comorbidities, level of urbanization, and monthly income (adjusted hazard ratio (HR): 0.50, 95% confidence interval (CI; 0.38−0.65), p < 0.05). Lower risk of lung cancer was observed in both sexes, all age groups, dialysis status and co-existed lung diseases. The association between the risk of lung cancer and vaccination appeared to be dose-dependent (adjusted HRs: 0.91 (0.66−1.25), 0.49 (0.34−0.71), and 0.25 (0.17−0.38) for patients who received 1, 2 or 3, and ≥4 vaccinations during the follow-up period, respectively). In conclusion, Influenza vaccination decreased the risk of lung cancer in patients diagnosed with CKD. This potentially protective effect against lung cancer appeared to be dose dependent.
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Lee K, Kang S, Hwang J. Lung Cancer Patients' Characteristics and Comorbidities Using the Korean National Hospital Discharge In-depth Injury Survey Data. J Epidemiol Glob Health 2022; 12:258-266. [PMID: 35648377 PMCID: PMC9470800 DOI: 10.1007/s44197-022-00044-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 05/09/2022] [Indexed: 12/01/2022] Open
Abstract
Background The aim of this study was to assess the incidence of lung cancer and comorbidities in Korea and analyze the lung cancer patient’s characteristics and their comorbidities over the past 12 years. This study also aimed to investigate factors related to death as treatment outcome in discharged lung cancer patients. Methods This study analyzed the data obtained from the Korean National Hospital Discharge In-depth Injury Survey from 2006 to 2017. The quantity of discharged lung cancer patients was assessed by year. Comorbidities were limited to those included in the Elixhauser Comorbidity Index (ECI). A Chi-square test was performed to determine statistically significant differences in the distributions of the ECI and ECI scores according to the presence or absence of metastatic cancer. Logistic regression analysis was used to analyze factors related to death as treatment outcome. Results From 2006 to 2017, the number of discharged male and female patients with lung cancer increased from 31,720 to 42,016 and 10,897 to 18,197, respectively. The increase in the number of lung cancer patients was greater in women than in men (67.0% vs. 32.5%, respectively). The most common associated comorbidities were hypertension, diabetes, and chronic pulmonary disease. The factors related to death as treatment outcome were found to include sex, admission route, number of hospital beds, length of stay, presence or absence of metastatic cancer, and ECI score. Conclusion The number of lung cancer patients in Korea has increased, and a high proportion of these patients have chronic diseases, which negatively would impact the treatment and outcome of lung cancer patients as well as their quality of life. Thus, the management of chronic diseases needs to be prioritized in patients with lung cancer.
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Affiliation(s)
- Kyunghee Lee
- Department of Healthcare Management, Eulji University, 553 Sanseongdae-ro, Sujeong-gu, Seongnam, Kyeonggi-do, 13135, South Korea
| | - Sunghong Kang
- Department of Health Policy and Management, Inje University, 197 Inje-ro, Kimhae, Kyungsangnam-do, 50834, South Korea
| | - Jieun Hwang
- College of Health Science, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungcheongnam-do, 31116, South Korea.
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Maxwell SS, Weller D. Lung cancer and Covid-19: lessons learnt from the pandemic and where do we go from here? NPJ Prim Care Respir Med 2022; 32:19. [PMID: 35637231 PMCID: PMC9151755 DOI: 10.1038/s41533-022-00283-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 05/10/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
| | - David Weller
- Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
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The Fight against Cancer by Microgravity: The Multicellular Spheroid as a Metastasis Model. Int J Mol Sci 2022; 23:ijms23063073. [PMID: 35328492 PMCID: PMC8953941 DOI: 10.3390/ijms23063073] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/10/2022] [Accepted: 03/10/2022] [Indexed: 02/06/2023] Open
Abstract
Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology.
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Sui J, Zhao Q, Zhang Y, Liang G. Dysregulated LINC00961 Contributes to the Vitality and Migration of NSCLC Via miR-19a-3p/miR-19b-3p/miR-125b-5p. DNA Cell Biol 2022; 41:319-329. [PMID: 35244469 DOI: 10.1089/dna.2021.0900] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Accumulating evidence implies that long noncoding RNAs participate in non-small cell lung cancer (NSCLC) tumorigenesis. Our current study synthetically analyzed RNA sequencing data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We identified LINC00961 significantly downregulated in NSCLC tissues. We explored the LINC00961 expression in NSCLC tumor tissues and cell lines with reverse transcription-quantitative polymerase chain reaction analysis. Lentivirus-mediated infection upregulated the expression of LINC00961 in A549 cells. The proliferation and migration capability were also measured in A549 cells. In addition, we performed luciferase reporter gene assay to investigate whether LINC00961 directly interacts with miR-19a-3p/miR-19b-3p/miR-125b-5p. A nude mice model was used to detect the potential biological process of LINC00961 on tumor growth in vivo. The results showed that LINC00961 was significantly down-egulated in NSCLC tissues and cell lines. LV-LINC00961 effectively increased the expression of LINC00961 and decreased the expression of miR-19a-3p/miR-19b-3p/miR-125b-5p. LINC00961 upregulation remarkably inhibited cell proliferation, migration, and invasion while promoting cell apoptosis in A549 cells. Luciferase reporter gene assay revealed that LINC00961 could directly sponge miR-19a-3p/miR-19b-3p/miR-125b-5p. Moreover, overexpressed miR-19a-3p/miR-19b-3p/miR-125b-5p reversed the effect of LINC00961 on cell function of A549 cells. Western blot assays revealed that LINC00961 could partially act as a tumor suppressor via affecting PI3K-AKT/MAPK/mTOR signaling pathway. In addition, overexpressed LINC00961-inhibited tumor growth was demonstrated in vivo. Overexpression of LINC00961 inhibited cell viability, invasion, and induced apoptosis in NSCLC, potentially via suppressing the expression of miR-19a-3p/miR-19b-3p/miR-125b-5p by targeting PI3K-AKT/MAPK/mTOR signaling pathways, which might provide the potential biomarker for NSCLC diagnosis and therapies.
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Affiliation(s)
- Jing Sui
- Research Institute for Environment and Health, Nanjing University of Information Science and Technology, Nanjing, China.,Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Qun Zhao
- Research Institute for Environment and Health, Nanjing University of Information Science and Technology, Nanjing, China
| | - Yanqiu Zhang
- Department of Environmental Occupational Hygiene, Taizhou Center for Disease Control and Prevention, Taizhou, China
| | - Geyu Liang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
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13
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Li Y, Wang C, Peng M. Aging Immune System and Its Correlation With Liability to Severe Lung Complications. Front Public Health 2021; 9:735151. [PMID: 34888279 PMCID: PMC8650611 DOI: 10.3389/fpubh.2021.735151] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 10/08/2021] [Indexed: 12/22/2022] Open
Abstract
Aging is considered to be a decline in physical and physiological events that extensively affect the body's immunity, and is linked with deterioration in both innate and adaptive immune responses. The immune system exhibits profound age-associated variations, known as immunosenescence, comprising a significantly low production of B and T lymphocytes in bone marrow and thymus, a decreased function of mature lymphocytes in secondary lymphoid tissues, a decrease in the synthesis of fresh naïve T cells, and reduced activation of T cells. Elderly individuals face a greater risk for many diseases particularly respiratory diseases due to their poor response to immune challenges as vigorously as the young. The current review explored the aging immune system, highlight the mortality rates of severe lung complications, such as pneumonia, COVID-19, asthma, COPD, lung cancer, IPF, and acute lung injury, and their correlation with aging immunity. This study can be helpful in better understanding the pathophysiology of aging, immune responses, and developing new approaches to improve the average age of the elderly population.
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Affiliation(s)
- Yongtao Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chengfei Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Meilian Peng
- Department of Maternity, Zhejiang Provincial People's Hospital, Hangzhou, China
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14
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Tian W, Yang X, Yang H, Lv M, Sun X, Zhou B. Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway. Cell Death Dis 2021; 12:1030. [PMID: 34718336 PMCID: PMC8557210 DOI: 10.1038/s41419-021-04314-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 10/09/2021] [Accepted: 10/13/2021] [Indexed: 01/15/2023]
Abstract
Globally, lung cancer remains one of the most prevalent malignant cancers. However, molecular mechanisms and functions involved in its pathogenesis have not been clearly elucidated. This study aimed to evaluate the specific regulatory mechanisms of exosomal miR-338-3p/CHL1/MAPK signaling pathway axis in non-small-cell lung cancer. Western blotting and qRT-PCR (reverse transcription-polymerase chain reaction) were used to determine the expression levels of CHL1 and exosomal miR-338-3p in NSCLC (non-small-cell lung cancer). The CHL1 gene was upregulated and downregulated to evaluate its functions in NSCLC progression. In vitro MTS and apoptotic assays were used to investigate the functions of CHL1 and exosomal miR-338-3p in NSCLC progression. The high-throughput sequencing was used to explore differently expressed exosomal miRNAs. The biological relationships between MAPK signaling pathway and CHL1 and exosomal miR-338-3p in NSCLC were predicted through bioinformatics analyses and verified by western blotting. Elevated CHL1 levels were observed in NSCLC tissues and cells. Upregulated CHL1 expression enhanced NSCLC cells’ progression by promoting tumor cells proliferation while suppressing their apoptosis. Conversely, the downregulation of the CHL1 gene inhibited NSCLC cells’ growth and promoted tumor cells’ apoptotic rate. Additionally, CHL1 activated the MAPK signaling pathway. Besides, we confirmed that miR-338-3p directly sponged with CHL1 to mediate tumor cells progression. Moreover, exosomal miR-338-3p serum levels in NSCLC patients were found to be low. BEAS-2B cells can transfer exosomal miR-338-3p to A549 cells and SK-MES-1 cells. In addition, elevated exosomal miR-338-3p levels significantly inhibited tumor cells proliferation and promoted their apoptosis by suppressing activation of the MAPK signaling pathway. Exosomal miR-338-3p suppresses tumor cells' metastasis by downregulating the expression of CHL1 through MAPK signaling pathway inactivation.
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Affiliation(s)
- Wen Tian
- Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Xianglin Yang
- Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China
| | - He Yang
- Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Meiwen Lv
- Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Xinran Sun
- Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China
| | - Baosen Zhou
- Department of Clinical Epidemiology, First Affiliated Hospital, China Medical University, Shenyang, China. .,Department of Epidemiology, School of Public Health, China Medical University, 110122, Shenyang, Liaoning, China.
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15
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Adaptive Diagnosis of Lung Cancer by Deep Learning Classification Using Wilcoxon Gain and Generator. JOURNAL OF HEALTHCARE ENGINEERING 2021; 2021:5912051. [PMID: 34691378 PMCID: PMC8528612 DOI: 10.1155/2021/5912051] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/27/2021] [Accepted: 09/27/2021] [Indexed: 01/15/2023]
Abstract
Cancer is a complicated worldwide health issue with an increasing death rate in recent years. With the swift blooming of the high throughput technology and several machine learning methods that have unfolded in recent years, progress in cancer disease diagnosis has been made based on subset features, providing awareness of the efficient and precise disease diagnosis. Hence, progressive machine learning techniques that can, fortunately, differentiate lung cancer patients from healthy persons are of great concern. This paper proposes a novel Wilcoxon Signed-Rank Gain Preprocessing combined with Generative Deep Learning called Wilcoxon Signed Generative Deep Learning (WS-GDL) method for lung cancer disease diagnosis. Firstly, test significance analysis and information gain eliminate redundant and irrelevant attributes and extract many informative and significant attributes. Then, using a generator function, the Generative Deep Learning method is used to learn the deep features. Finally, a minimax game (i.e., minimizing error with maximum accuracy) is proposed to diagnose the disease. Numerical experiments on the Thoracic Surgery Data Set are used to test the WS-GDL method's disease diagnosis performance. The WS-GDL approach may create relevant and significant attributes and adaptively diagnose the disease by selecting optimal learning model parameters. Quantitative experimental results show that the WS-GDL method achieves better diagnosis performance and higher computing efficiency in computational time, computational complexity, and false-positive rate compared to state-of-the-art approaches.
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16
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Li W, He X, Liu H, Zhu J, Zhang HM. Successful treatment after toxic epidermal necrolysis induced by AZD-9291 in a patient with non-small cell lung cancer: A case report. World J Clin Cases 2021; 9:8846-8851. [PMID: 34734065 PMCID: PMC8546833 DOI: 10.12998/wjcc.v9.i29.8846] [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: 05/12/2021] [Revised: 06/18/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Toxic epidermal necrolysis and Stevens-Johnson syndrome are acute life-threatening skin reactions. AZD9291 has been developed as a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) with activity against T790M mutation.
CASE SUMMARY Herein we report a 68-year-old woman who developed a large area of skin necrosis and was diagnosed with toxic epidermal necrolysis after AZD-9291 ingestion. To the best of our knowledge, this is the first case reported in patients with EGFR T790M mutation in non-small cell lung cancer (NSCLC). Cabozantinib combined with erlotinib had clinically meaningful effectiveness, with additional toxicity that was generally manageable.
CONCLUSION Treatment with AZD-9261 is effective in regressing the growth of the NSCLC and can bring some hope to despairing patients. We hope that more research will be carried out on the association between severe rashes and EGFR-TKIs, and more safe and effective drugs can be developed.
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Affiliation(s)
- Wen Li
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai 201203, China
| | - Xiang He
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai 201203, China
| | - Hui Liu
- Department of Oncology, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai 201203, China
| | - Jiong Zhu
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai 201203, China
| | - Hui-Min Zhang
- Department of Dermatology, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai 201203, China
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17
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Qiu H, Cao S, Xu R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020. Cancer Commun (Lond) 2021; 41:1037-1048. [PMID: 34288593 PMCID: PMC8504144 DOI: 10.1002/cac2.12197] [Citation(s) in RCA: 553] [Impact Index Per Article: 138.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/27/2021] [Accepted: 07/11/2021] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Cancer is one of the leading causes of death and a main economic burden in China. Investigating the differences in cancer patterns and control strategies between China and developed countries could provide reference for policy planning and contribute to improving cancer control measures. In this study, we reviewed the rates and trends of cancer incidence and mortality and disability-adjusted life year (DALY) burden in China, and compared them with those in the United States (US) and the United Kingdom (UK). METHODS Cancer incidence, mortality, and DALY data for China, US and UK were obtained from the GLOBOCAN 2020 online database, Global Burden of Disease (GBD) 2019 study, and Cancer Incidence in Five Continents plus database (CI5 plus). Trends of cancer incidence and mortality in China, US, and UK were analyzed using Joinpoint regression models to calculate annual percent changes (APCs) and identify the best-fitting joinpoints. RESULTS An estimated 4,568,754 newly diagnosed cancer cases and 3,002,899 cancer deaths occurred in China in 2020. Additionally, cancers resulted in 67,340,309 DALYs in China. Compared to the US and UK, China had lower cancer incidence but higher cancer mortality and DALY rates. Furthermore, the cancer spectrum of China was changing, with a rapid increase incidence and burden of lung, breast, colorectal, and prostate cancer in addition to a high incidence and heavy burden of liver, stomach, esophageal, and cervical cancer. CONCLUSIONS The cancer spectrum of China is changing from a developing country to a developed country. Population aging and increase of unhealthy lifestyles would continue to increase the cancer burden of China. Therefore, the Chinese authorities should adjust the national cancer control program with reference to the practices of cancer control which have been well-established in the developed countries, and taking consideration of the diversity of cancer types by of different regions in China at the same time.
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Affiliation(s)
- Haibo Qiu
- Department of Gastric SurgeryState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat‐Sen University Cancer CenterGuangzhouGuangdong510060P. R. China
| | - Sumei Cao
- Department of Cancer Prevention Research CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat‐Sen University Cancer CenterGuangzhouGuangdong510060P. R. China
| | - Ruihua Xu
- Department of Medical OncologyState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat‐Sen University Cancer CenterGuangzhouGuangdong510060P. R. China
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18
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Meng Z, Guo S, Zhou Y, Li M, Wang M, Ying B. Applications of laboratory findings in the prevention, diagnosis, treatment, and monitoring of COVID-19. Signal Transduct Target Ther 2021; 6:316. [PMID: 34433805 PMCID: PMC8386162 DOI: 10.1038/s41392-021-00731-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 07/21/2021] [Accepted: 07/30/2021] [Indexed: 02/07/2023] Open
Abstract
The worldwide pandemic of coronavirus disease 2019 (COVID-19) presents us with a serious public health crisis. To combat the virus and slow its spread, wider testing is essential. There is a need for more sensitive, specific, and convenient detection methods of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Advanced detection can greatly improve the ability and accuracy of the clinical diagnosis of COVID-19, which is conducive to the early suitable treatment and supports precise prophylaxis. In this article, we combine and present the latest laboratory diagnostic technologies and methods for SARS-CoV-2 to identify the technical characteristics, considerations, biosafety requirements, common problems with testing and interpretation of results, and coping strategies of commonly used testing methods. We highlight the gaps in current diagnostic capacity and propose potential solutions to provide cutting-edge technical support to achieve a more precise diagnosis, treatment, and prevention of COVID-19 and to overcome the difficulties with the normalization of epidemic prevention and control.
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Affiliation(s)
- Zirui Meng
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Shuo Guo
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yanbing Zhou
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Mengjiao Li
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Minjin Wang
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Binwu Ying
- Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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19
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Insulin Receptor Substrate 1 Is Involved in the Phycocyanin-Mediated Antineoplastic Function of Non-Small Cell Lung Cancer Cells. Molecules 2021; 26:molecules26164711. [PMID: 34443299 PMCID: PMC8401963 DOI: 10.3390/molecules26164711] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/29/2021] [Accepted: 07/31/2021] [Indexed: 12/11/2022] Open
Abstract
Phycocyanin, derived from marine algae, is known to have noteworthy antineoplastic properties. However, the underlying mechanism involved in phycocyanin-mediated anti-growth function on non-small cell lung cancer (NSCLC) cells is still ambiguous. Here, we investigated the mechanism of action of phycocyanin on H1299, A549, and LTEP-a2 cells. According to the results obtained, insulin receptor substrate 1 (IRS-1) expression was reduced by phycocyanin. Cell phenotype tests showed that siRNA knockdown of IRS-1 expression significantly inhibited the growth, migration, colony formation, but promoted the apoptosis of NSCLC cells. Meanwhile, phycocyanin and IRS-1 siRNA treatment both reduced the PI3K-AKT activities in NSCLC cells. Moreover, overexpression of IRS-1 accelerated the proliferation, colony formation, and migration rate of H1299, A549, and LTEP-a2 cells, which was contradicting to the knockdown results. Overall, this study uncovered a regulatory mechanism by which phycocyanin inhibited the growth of NSCLC cells via IRS-1/AKT pathway, laying the foundation for the potential target treatment of NSCLC.
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20
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Spiegel JM, Ehrlich R, Yassi A, Riera F, Wilkinson J, Lockhart K, Barker S, Kistnasamy B. Using Artificial Intelligence for High-Volume Identification of Silicosis and Tuberculosis: A Bio-Ethics Approach. Ann Glob Health 2021; 87:58. [PMID: 34249620 PMCID: PMC8252970 DOI: 10.5334/aogh.3206] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Although Artificial Intelligence (AI) is being increasingly applied, considerable distrust about introducing "disruptive" technologies persists. Intrinsic and contextual factors influencing where and how such innovations are introduced therefore require careful scrutiny to ensure that health equity is promoted. To illustrate one such critical approach, we describe and appraise an AI application - the development of computer assisted diagnosis (CAD) to support more efficient adjudication of compensation claims from former gold miners with occupational lung disease in Southern Africa. In doing so, we apply a bio-ethical lens that considers the principles of beneficence, non-maleficence, autonomy and justice and add explicability as a core principle. We draw on the AI literature, our research on CAD validation and process efficiency, as well as apprehensions of users and stakeholders. Issues of concern included AI accuracy, biased training of AI systems, data privacy, impact on human skill development, transparency and accountability in AI use, as well as intellectual property ownership. We discuss ways in which each of these potential obstacles to successful use of CAD could be mitigated. We conclude that efforts to overcoming technical challenges in applying AI must be accompanied from the onset by attention to ensuring its ethical use.
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Affiliation(s)
- Jerry M. Spiegel
- School of Population and Public Health, The University of British Columbia, Vancouver, BC, Canada
| | - Rodney Ehrlich
- School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Annalee Yassi
- School of Population and Public Health, The University of British Columbia, Vancouver, BC, Canada
| | | | | | - Karen Lockhart
- School of Population and Public Health, The University of British Columbia, Vancouver, BC, Canada
| | - Stephen Barker
- School of Population and Public Health, The University of British Columbia, Vancouver, BC, Canada
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21
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A Comprehensive Survey on Data Utility and Privacy: Taking Indian Healthcare System as a Potential Case Study. INVENTIONS 2021. [DOI: 10.3390/inventions6030045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Background: According to the renowned and Oscar award-winning American actor and film director Marlon Brando, “privacy is not something that I am merely entitled to, it is an absolute prerequisite.” Privacy threats and data breaches occur daily, and countries are mitigating the consequences caused by privacy and data breaches. The Indian healthcare industry is one of the largest and rapidly developing industry. Overall, healthcare management is changing from disease-centric into patient-centric systems. Healthcare data analysis also plays a crucial role in healthcare management, and the privacy of patient records must receive equal attention. Purpose: This paper mainly presents the utility and privacy factors of the Indian healthcare data and discusses the utility aspect and privacy problems concerning Indian healthcare systems. It defines policies that reform Indian healthcare systems. The case study of the NITI Aayog report is presented to explain how reformation occurs in Indian healthcare systems. Findings: It is found that there have been numerous research studies conducted on Indian healthcare data across all dimensions; however, privacy problems in healthcare, specifically in India, are caused by prevalent complacency, culture, politics, budget limitations, large population, and existing infrastructures. This paper reviews the Indian healthcare system and the applications that drive it. Additionally, the paper also maps that how privacy issues are happening in every healthcare sector in India. Originality/Value: To understand these factors and gain insights, understanding Indian healthcare systems first is crucial. To the best of our knowledge, we found no recent papers that thoroughly reviewed the Indian healthcare system and its privacy issues. The paper is original in terms of its overview of the healthcare system and privacy issues. Social Implications: Privacy has been the most ignored part of the Indian healthcare system. With India being a country with a population of 130 billion, much healthcare data are generated every day. The chances of data breaches and other privacy violations on such sensitive data cannot be avoided as they cause severe concerns for individuals. This paper segregates the healthcare system’s advances and lists the privacy that needs to be addressed first.
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22
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Sung W, Au K, Wu H, Yu C, Wang Y. Improved trends of lung cancer mortality-to-incidence ratios in countries with high healthcare expenditure. Thorac Cancer 2021; 12:1656-1661. [PMID: 33829674 PMCID: PMC8169294 DOI: 10.1111/1759-7714.13912] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 02/12/2021] [Accepted: 02/13/2021] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Lung cancer stage has a significant impact on prognosis, and early detection of lung cancer relies on screenings. Despite the strong relationship between screening and lung cancer staging, the role of healthcare expenditure in lung cancer outcomes remains unknown. The aim of this study was to evaluate the relationship between economic status and clinical outcomes in lung cancer. METHODS Data were obtained from GLOBOCAN and the World Health Organization. Mortality-to-incidence ratios (MIRs) and their change over time, calculated as the difference between the MIRs of 2012 and 2018 (δMIR), were used to evaluate their correlation to expenditures on healthcare and human development index (HDI) disparities via Spearman's rank correlation coefficient. RESULTS Regions such as North America have relatively high crude incidence rates but low MIR values. Furthermore, countries with lower crude incidence rates spent less on healthcare. The results show significant negative associations between HDI, current health expenditure (CHE) per capita, CHE as a percentage of gross domestic product (CHE/GDP), and MIR. As for MIR and δMIR, countries with favorable MIRs also showed improving MIRs based on δMIR. CONCLUSIONS HDI, CHE per capita, CHE/GDP, and development status play noticeable roles in the prognosis of lung cancer, leading to large disparities in clinical outcomes.
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Affiliation(s)
- Wen‐Wei Sung
- Department of UrologyChung Shan Medical University HospitalTaichungTaiwan
- School of Medicine, Chung Shan Medical UniversityTaichungTaiwan
- Institute of Medicine, Chung Shan Medical UniversityTaichungTaiwan
| | - Kwong‐Kwok Au
- Institute of Medicine, Chung Shan Medical UniversityTaichungTaiwan
- Division of Thoracic Surgery, Department of SurgeryChung Shan Medical University HospitalTaichungTaiwan
| | - Han‐Ru Wu
- School of Medicine, Chung Shan Medical UniversityTaichungTaiwan
| | - Chia‐Ying Yu
- School of Medicine, Chung Shan Medical UniversityTaichungTaiwan
| | - Yao‐Chen Wang
- School of Medicine, Chung Shan Medical UniversityTaichungTaiwan
- Institute of Medicine, Chung Shan Medical UniversityTaichungTaiwan
- Division of Pulmonary Medicine, Department of Internal MedicineChung Shan Medical University HospitalTaichungTaiwan
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23
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Zhu P, Gu S, Huang H, Zhong C, Liu Z, Zhang X, Wang W, Xie S, Wu K, Lu T, Zhou Y. Upregulation of glucosamine-phosphate N-acetyltransferase 1 is a promising diagnostic and predictive indicator for poor survival in patients with lung adenocarcinoma. Oncol Lett 2021; 21:488. [PMID: 33968204 PMCID: PMC8100941 DOI: 10.3892/ol.2021.12750] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Accepted: 02/19/2021] [Indexed: 12/30/2022] Open
Abstract
Lung adenocarcinoma, a type of non-small cell lung cancer, is the leading cause of cancer death worldwide. Great efforts have been made to identify the underlying mechanism of adenocarcinoma, especially in relation to oncogenes. The present study by integrating computational analysis with western blotting, aimed to understand the role of the upregulation of glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) in carcinogenesis. In the present study, publicly available gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas to determine the role of GNPNAT1 in lung adenocarcinoma (LUAD). In addition, the association between LUAD susceptibility and GNPNAT1 upregulation were analyzed using Wilcoxon signed-rank test and logistic regression analysis. In LUAD, GNPNAT1 upregulation was significantly associated with disease stage [odds ratio (OR)=2.92, stage III vs. stage I], vital status (dead vs. alive, OR=1.89), cancer status (tumor status vs. tumor-free status, OR=1.85) and N classification (yes vs. no, OR=1.75). Cox regression analysis and the Kaplan-Meier method were utilized to evaluate the association between GNPNAT1 expression and overall survival (OS) time in patients with LUAD. The results demonstrated that patients with increased GNPNAT1 expression levels exhibited a reduced survival rate compared with those with decreased expression levels (P=8.9×10−5). In addition, Cox regression analysis revealed that GNPNAT1 upregulation was significantly associated with poor OS time [hazard ratio (HR): 1.07; 95% confidence interval (CI): 1.04–1.10; P<0.001]. The gene set enrichment analysis revealed that ‘cell cycle’, ‘oocyte meiosis’, ‘pyrimidine mediated metabolism’, ‘ubiquitin mediated proteolysis’, ‘one carbon pool by folate’, ‘mismatch repair progesterone-mediated oocyte maturation’ and ‘basal transcription factors purine metabolism’ were differentially enriched in the GNPNAT1 high-expression samples compared with GNPNAT1 low-expression samples. The aforementioned pathways are involved in the pathogenesis of LUAD. The findings of the present study suggested that GNPNAT1 upregulation may be considered as a promising diagnostic and prognostic biomarker in patients with LUAD. In addition, the aforementioned pathways may be pivotal pathways perturbed by the abnormal expression of GNPNAT1 in LUAD. The findings of the present study demonstrated the therapeutic value of the regulation of GNPNAT1 in lung adenocarcinoma.
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Affiliation(s)
- Pengyuan Zhu
- Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.,School of Medicine, Nantong University, Nantong, Jiangsu 226001, P.R. China.,Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Shaorui Gu
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Haitao Huang
- Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Chongjun Zhong
- Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Zhenchuan Liu
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Xin Zhang
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Wenli Wang
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Shiliang Xie
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Kaiqin Wu
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Tiancheng Lu
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
| | - Yongxin Zhou
- Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, P.R. China
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Relationship Among Three Different Viruses and Primary Lung Cancer. Indian J Surg 2021. [DOI: 10.1007/s12262-020-02339-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
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Li X, Qin K, Yuan C, Song S. The effect of enhancing quality of life in patients intervention for advanced lung cancer: Protocol for a randomized clinical study. Medicine (Baltimore) 2020; 99:e23682. [PMID: 33371108 PMCID: PMC7748172 DOI: 10.1097/md.0000000000023682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 11/13/2020] [Indexed: 01/10/2023] Open
Abstract
OBJECTIVE The objective of this present research is to evaluate the effect of the intervention of enhancing quality of life in patients in patients with advanced lung cancer. METHODS Our research is carried out as a randomized clinical trial which will be implemented from December 2020 to October 2021. It was approved by the Ethics Committee of People's Hospital of Chengyang District (03982790). This study includes 90 patients with advanced lung cancer. Patients diagnosed at our oncology clinic are eligible if they are diagnosed within 8 weeks of a novel diagnosis of stage 3 or stage 4 lung cancer. Patients with hepatic insufficiency, renal failure, and respiratory and heart failure, as well as a series of severe mental illness are excluded from our research. Patients are divided randomly into the intervention group and control group, each group is assigned 45 patients. Through utilizing functional assessment of cancer therapy-lung, the measurement of life quality is conducted. And the measurement of mood is carried out with Hospital Anxiety and Depression Scale. RESULTS Table 1 indicates the patient's life quality and Hospital Anxiety and Depression Scale in both groups. CONCLUSION Enhancing quality of life in patient intervention may be beneficial to improve the life quality in advanced lung cancer patients.Trial registration: The protocol was registered in Research Registry (researchregistry6243).
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Affiliation(s)
| | | | - Chunyan Yuan
- Department of Rehabilitation Medicine, People's Hospital of Chengyang District, Qingdao, China
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Radwan E, Ali M, Faied SMA, Omar HM, Mohamed WS, Abd-Elghaffar SK, Sayed AA. Novel therapeutic regimens for urethane-induced early lung cancer in rats: Combined cisplatin nanoparticles with vitamin-D 3. IUBMB Life 2020; 73:362-374. [PMID: 33332722 DOI: 10.1002/iub.2432] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 11/27/2020] [Accepted: 12/08/2020] [Indexed: 12/24/2022]
Abstract
Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D3 , VI-cancer + cisplatin nanoparticles + vitamin-D3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.
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Affiliation(s)
- Eman Radwan
- Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Maha Ali
- Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Soad M A Faied
- Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Hossam M Omar
- Department of Zoology, Faculty of Science, Assiut University, Assiut, Egypt
| | - Wael S Mohamed
- Department of Polymers and Pigments, National Research Centre, Giza, Egypt
| | - Sary Kh Abd-Elghaffar
- Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut, Egypt
| | - Ayat A Sayed
- Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt
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The relationship between nutritional status and prognosis in patients with locally advanced and advanced stage lung cancer. Support Care Cancer 2020; 29:3357-3365. [DOI: 10.1007/s00520-020-05856-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 10/23/2020] [Indexed: 12/25/2022]
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Dietz C, Infanger M, Romswinkel A, Strube F, Kraus A. Apoptosis Induction and Alteration of Cell Adherence in Human Lung Cancer Cells under Simulated Microgravity. Int J Mol Sci 2019; 20:E3601. [PMID: 31340547 PMCID: PMC6678991 DOI: 10.3390/ijms20143601] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Lung cancer cells are known to change proliferation and migration under simulated microgravity. In this study, we sought to evaluate cell adherence, apoptosis, cytoskeleton arrangement, and gene expression under simulated microgravity. METHODS Human lung cancer cells were exposed to simulated microgravity in a random-positioning machine (RPM). Cell morphology and adherence were observed under phase-contrast microscopy, cytoskeleton staining was performed, apoptosis rate was determined, and changes in gene and protein expression were detected by real-time PCR with western blot confirmation. RESULTS Three-dimensional (3D)-spheroid formation was observed under simulated microgravity. Cell viability was not impaired. Actin filaments showed a shift in alignment from longitudinal to spherical. Apoptosis rate was significantly increased in the spheroids compared to the control. TP53, CDKN2A, PTEN, and RB1 gene expression was significantly upregulated in the adherent cells under simulated microgravity with an increase in corresponding protein production for p14 and RB1. SOX2 expression was significantly upregulated in the adherent cells, but protein was not. Gene expressions of AKT3, PIK3CA, and NFE2L2 remained unaltered. CONCLUSION Simulated microgravity induces alteration in cell adherence, increases apoptosis rate, and leads to upregulation of tumor suppressor genes in human lung cancer cells.
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Affiliation(s)
- Carlo Dietz
- Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany
| | - Manfred Infanger
- Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany
| | - Alexander Romswinkel
- Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany
| | - Florian Strube
- Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany
| | - Armin Kraus
- Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
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Wang J, Zhao Y, Chen Q, Zhang P, Xie W, Feng J, Cao J. Diagnostic value of rapid on-site evaluation during transbronchial biopsy for peripheral lung cancer. Jpn J Clin Oncol 2019; 49:501-505. [PMID: 30855687 DOI: 10.1093/jjco/hyz025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 01/12/2019] [Accepted: 02/08/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND An increasing number of pulmonary lesions-particularly, peripheral lung lesions-are identified with current technological advancements. Notably, the yield of traditional bronchoscopy for the diagnosis of peripheral lung lesions is low. This study evaluated the diagnostic value of rapid on-site evaluation (ROSE) during transbronchial biopsy for peripheral lung cancer. METHODS This study included 641 patients who underwent transbronchial biopsy for suspected lung cancer at the Respiratory Department of Tianjin Medical University General Hospital between January 2012 and December 2016. Based on whether ROSE was used, patients were assigned to the ROSE group (353 patients) or non-ROSE group (288 patients). In the ROSE group, several air-dried smears were processed with Diff-Quik staining; the remaining samples were placed in 10% formalin. Diagnostic yields for central and peripheral lung cancer were compared between the two groups. In addition, ROSE results were compared with final diagnoses. RESULTS Diagnostic yield for peripheral lung cancer, stratified by pathology, was significantly higher in the ROSE group than in the non-ROSE group (42.9% vs. 30.7%, P < 0.05). The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of ROSE for peripheral pulmonary lesions were 90.0%, 89.5%, 94.0%, 82.8% and 89.8%, respectively. Conformance was high between ROSE and final pathologic evaluations during transbronchial biopsy (Kappa = 0.780, P = 0.035). There were no procedure-related deaths. CONCLUSIONS ROSE during conventional transbronchial biopsy improves diagnostic yield, stratified by pathology, for patients with peripheral lung cancer via live feedback. Moreover, ROSE diagnosis correlates with final cytopathological diagnosis.
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Affiliation(s)
- Juan Wang
- Respiratory Department of Tianjin Medical University General Hospital, Tianjin, China
| | - Yaping Zhao
- Respiratory Department of Tianjin Medical University General Hospital Airport Hospital, Tianjin, China
| | - Qianqian Chen
- Respiratory Department of Tianjin Medical University General Hospital, Tianjin, China
| | - Peng Zhang
- Respiratory Department of Tianjin Medical University General Hospital, Tianjin, China
| | - Wei Xie
- Respiratory Department of Tianjin Medical University General Hospital, Tianjin, China
| | - Jing Feng
- Respiratory Department of Tianjin Medical University General Hospital, Tianjin, China
| | - Jie Cao
- Respiratory Department of Tianjin Medical University General Hospital, Tianjin, China
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Wang C, Zhang C, Xu J, Li Y, Wang J, Liu H, Liu Y, Chen Z, Lin H. Association between IL-1R2 polymorphisms and lung cancer risk in the Chinese Han population: A case-control study. Mol Genet Genomic Med 2019; 7:e644. [PMID: 30895747 PMCID: PMC6503014 DOI: 10.1002/mgg3.644] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 02/20/2019] [Accepted: 02/26/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Interleukin-1 receptor 2 (IL-1R2), as an anti-inflammatory cytokine, is involved in the pathogenesis and progression of lung cancer. However, the role of IL-1R2 polymorphisms in patients with lung cancer has yet to be fully elucidated. METHODS Six single-nucleotide polymorphisms (SNPs) in IL-1R2 were genotyped in 259 patients and 346 healthy controls. We used the chi-squared test, genetic model analysis, Haploview analysis, and multifactor dimensionality reduction (MDR) to evaluate the potential association between IL-1R2 polymorphisms and lung cancer susceptibility. Bioinformatics analyses were conducted to analyze the expression level of IL-1R2 and its association with the overall survival of lung cancer. RESULTS Our results found that rs3218977-GG was associated with a decreased risk of lung cancer (odds ratio [OR] = 0.39; 95% confidence interval [CI]: 0.17-0.87; p = 0.023), and rs2072472 had a significant risk-increasing effect in the dominant model (AG + GG vs. AA: OR = 1.54; 95% CI: 1.09-2.20; p = 0.015). The MDR model also revealed that rs2072472 is the most influential risk factor of lung cancer (testing accuracy = 0.543; cross-validation consistency = 10/10; p = 0.032). In addition, our results indicated that the IL-1R2 mRNA level was downregulated in lung cancer patients, whereas the high expression of IL-1R2 was related to a poor prognosis in lung cancer. CONCLUSIONS Our results suggest that genetic variants of IL-1R2 may play a role in lung cancer susceptibility. Further population and functional validations of our findings are warranted.
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Affiliation(s)
- Chaoying Wang
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Chengsheng Zhang
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Junnv Xu
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Yongfu Li
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Jie Wang
- Department of Nursing, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Hui Liu
- Department of Anatomy, Hainan Medical University, Haikou, China
| | - Yueli Liu
- Department of Pharmacology, Hainan Medical University, Haikou, China
| | - Zhong Chen
- Hainan Provincial Third People's Hospital, Sanya, China
| | - Haifeng Lin
- Department of Medical Oncology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China
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Association of MMP9-1562C/T and MMP13-77A/G Polymorphisms with Non-Small Cell Lung Cancer in Southern Chinese Population. Biomolecules 2019; 9:biom9030107. [PMID: 30889876 PMCID: PMC6468416 DOI: 10.3390/biom9030107] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 03/04/2019] [Accepted: 03/12/2019] [Indexed: 12/22/2022] Open
Abstract
Background: Matrix metalloproteinases (MMPs) are capable of degrading and modifying most components of the extracellular matrix (ECM) and the basal membrane (BM), and play crucial roles in cancer invasion and metastasis. MMP gene expressions were regulated primarily at the transcriptional level, which was associated with tumor spread and patient prognosis. Polymorphisms in MMPs have been reported to be associated with non-small cell lung cancer (NSCLC). The objective of this study aim to evaluate the serum levels and polymorphisms of MMP-9 and MMP-13 in non-small cell lung cancer patients compared to normal subjects and their correlation to non-small cell lung cancer histopathology findings in Southern Chinese people. Methods: This case–control study included 245 patients with NSCLC and 258 healthy controls. Genomic DNA was extracted by using DNA extraction kit, genotyping was confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct DNA sequencing, and serum levels of MMP-9 and MMP-13 were measured by using a specific ELISA, Human Matrix Metalloproteinase Enzyme Immunoassay Kits. Statistical analysis was carried out using the SPSS 23.0 software package. Results: The subjects carrying the TT genotype had a decreased risk of lung cancer in MMP9-1562C/T comparing with the CC genotype (p = 0.00, OR = 0.45, 95% CI = 0.29–0.68), and the MMP13-77 AA genotype was associated with a decreased risk of NSCLC by comparing with the GG genotype (p = 0.03, OR = 0.56, 95% CI = 0.33–0.94). Moreover, the C allele of MMP9-1562C/T could increase serum level of NSCLC in compared with the A allele (OR = 1.19, 95% CI = 0.75–1.89). Similarly, the AA genotype of MMP13 might be a marker of decreased serum level of lung cancer (OR = 0.76, 95% CI = 0.51–1.14). Conclusions: The results of these analyses underline the support of the notion that the CC genotype of MMP9-1562C/T and GG genotypes of MMP13-77G/A were associated with the increased risk NSCLC, and the serum levels of MMP9 and MMP13 were consistent with the results of the SNP analysis. MMP13 and MMP9 might be function as a key oncogene in NSCLC with a Southern Chinese population. Combined detection of SNP and enzyme activity between MMP9 and MMP13 are expected to be a potential diagnostic method of non-small cell lung cancer.
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Overexpression of amplified in breast cancer 1 (AIB1) gene promotes lung adenocarcinoma aggressiveness in vitro and in vivo by upregulating C-X-C motif chemokine receptor 4. Cancer Commun (Lond) 2018; 38:53. [PMID: 30103827 PMCID: PMC6090807 DOI: 10.1186/s40880-018-0320-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2017] [Accepted: 07/11/2018] [Indexed: 02/08/2023] Open
Abstract
Background We previously found that overexpression of the gene known as amplified in breast cancer 1 (AIB1) was associated with lymph node metastasis and poor prognosis in patients with lung adenocarcinoma. However, the role of AIB1 in that malignancy remains unknown. The present study aimed to investigate the function of AIB1 in the process of lung adenocarcinoma cell metastasis. Methods A series of in vivo and in vitro assays were performed to elucidate the function of AIB1, while real-time PCR and Western blotting were utilized to identify the potential downstream targets of AIB1 in the process of lung adenocarcinoma metastasis. Rescue experiments and in vitro assays were performed to investigate whether the invasiveness of AIB1-induced lung adenocarcinoma was mediated by C-X-C motif chemokine receptor 4 (CXCR4). Results The ectopic overexpression of AIB1 in lung adenocarcinoma cells substantially enhanced cell migration and invasive abilities in vitro and tumor metastasis in vivo, whereas the depletion of AIB1 expression substantially inhibited lung adenocarcinoma cell migration and invasion. CXCR4 was identified as a potential downstream target of AIB1 in lung adenocarcinoma. The knockdown of AIB1 greatly reduced CXCR4 gene expression at both the transcription and protein levels, whereas the knockdown of CXCR4 in cells with AIB1 ectopic overexpression diminished AIB1-induced migration and invasion in vitro and tumor metastasis in vivo. Furthermore, we found a significant positive association between the expression of AIB1 and CXCR4 in lung adenocarcinoma patients (183 cases), and the co-overexpression of AIB1 and CXCR4 predicted the poorest prognosis. Conclusions These findings suggest that AIB1 promotes the aggressiveness of lung adenocarcinoma in vitro and in vivo by upregulating CXCR4 and that it might be usable as a novel prognostic marker and/or therapeutic target for this disease. Electronic supplementary material The online version of this article (10.1186/s40880-018-0320-1) contains supplementary material, which is available to authorized users.
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Ji X, Fang Y, Liu J. Analysis of the clinicopathological characteristics and their trends among patients with lung cancer undergoing surgery in a tertiary cancer hospital of north China during 2000-2013. J Thorac Dis 2018; 10:3973-3982. [PMID: 30174839 PMCID: PMC6105934 DOI: 10.21037/jtd.2018.06.158] [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: 11/30/2017] [Accepted: 05/28/2018] [Indexed: 11/06/2022]
Abstract
BACKGROUND Lung cancer is the primary cause of death among all cancers in China. However, clinical and pathological features and trends among patients with lung cancer in mainland China are largely unknown. This study analyzed the clinicopathological characteristics and trends of patients newly diagnosed as lung cancer and underwent surgery in a tertiary cancer hospital of north China between 2000 and 2013. METHODS Data were collected retrospectively from medical records. Pathological diagnosis was confirmed by surgery or puncture, bronchoscopy, thoracoscopy, and sputum cytology. RESULTS This study included 3,733 patients with lung cancer (2,252 male and 1,481 female; male-to-female 1.52:1). An increase in the incidence of lung cancer was observed among women. The most frequently observed pathology types were adenocarcinoma (ADC, 63.41%), squamous cell carcinoma (SQ, 24.48%), and small cell carcinoma (SCC, 3.08%). There was a decrease in the proportion of SQ cases and increase in ADC cases. The proportion of male patients with SQ and female patients with ADC increased. Differences between men and women in the distribution of lesions according to pathology were as follows: ADC and SQ were present in 49.73% and 35.92% of male patients, respectively, and in 84.20% and 7.09% of female patients, respectively. Comparing the time period 2000-2006 and 2007-2013, there were no changes in the distribution of pathology among men, while the proportion of ADC and SQ cases among women increased from 74.43% to 85.90% and decreased from 15.07% to 5.71%, respectively. CONCLUSIONS The proportion of female patients with lung cancer who could undergo surgery increased significantly. The proportion of patients with SQ decreased while that of ADC increased, and the increase of ADC was mainly due to the increase in the number of female patients with ADC.
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Affiliation(s)
- Xinqiang Ji
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Medical Record Statistics, Peking University Cancer Hospital& Institute, Beijing 100142, China
| | - Yun Fang
- Beijing Municipal Center for Disease Control and Prevention, Beijing 100020, China
| | - Jing Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Medical Record Statistics, Peking University Cancer Hospital& Institute, Beijing 100142, China
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Ezzeldin N, Farouk H, Kandil DM, Darwish A, El-Bastawisy A. Impact of cell death pathway genes Fas 21377AA and FasL 2844CC polymorphisms on the risk of developing non-small cell lung cancer. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2018. [DOI: 10.1016/j.ejmhg.2017.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Montedori A, Bidoli E, Serraino D, Fusco M, Giovannini G, Casucci P, Franchini D, Granata A, Ciullo V, Vitale MF, Gobbato M, Chiari R, Cozzolino F, Orso M, Orlandi W, Abraha I. Accuracy of lung cancer ICD-9-CM codes in Umbria, Napoli 3 Sud and Friuli Venezia Giulia administrative healthcare databases: a diagnostic accuracy study. BMJ Open 2018; 8:e020628. [PMID: 29773701 PMCID: PMC5961589 DOI: 10.1136/bmjopen-2017-020628] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
OBJECTIVES To assess the accuracy of International Classification of Diseases 9th Revision-Clinical Modification (ICD-9-CM) codes in identifying subjects with lung cancer. DESIGN A cross-sectional diagnostic accuracy study comparing ICD-9-CM 162.x code (index test) in primary position with medical chart (reference standard). Case ascertainment was based on the presence of a primary nodular lesion in the lung and cytological or histological documentation of cancer from a primary or metastatic site. SETTING Three operative units: administrative databases from Umbria Region (890 000 residents), ASL Napoli 3 Sud (NA) (1 170 000 residents) and Friuli Venezia Giulia (FVG) Region (1 227 000 residents). PARTICIPANTS Incident subjects with lung cancer (n=386) diagnosed in primary position between 2012 and 2014 and a population of non-cases (n=280). OUTCOME MEASURES Sensitivity, specificity and positive predictive value (PPV) for 162.x code. RESULTS 130 cases and 94 non-cases were randomly selected from each database and the corresponding medical charts were reviewed. Most of the diagnoses for lung cancer were performed in medical departments.True positive rates were high for all the three units. Sensitivity was 99% (95% CI 95% to 100%) for Umbria, 97% (95% CI 91% to 100%) for NA, and 99% (95% CI 95% to 100%) for FVG. The false positive rates were 24%, 37% and 23% for Umbria, NA and FVG, respectively. PPVs were 79% (73% to 83%)%) for Umbria, 58% (53% to 63%)%) for NA and 79% (73% to 84%)%) for FVG. CONCLUSIONS Case ascertainment for lung cancer based on imaging or endoscopy associated with histological examination yielded an excellent sensitivity in all the three administrative databases. PPV was moderate for Umbria and FVG but lower for NA.
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Affiliation(s)
| | - Ettore Bidoli
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico Aviano, Aviano, Italy
| | - Diego Serraino
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico Aviano, Aviano, Italy
| | - Mario Fusco
- Registro Tumori Regione Campania, ASL Napoli 3 Sud, Brusciano, Italy
| | - Gianni Giovannini
- Health Planning Service, Regional Health Authority of Umbria, Perugia, Italy
| | - Paola Casucci
- Health ICT Service, Regional Health Authority of Umbria, Perugia, Italy
| | - David Franchini
- Health ICT Service, Regional Health Authority of Umbria, Perugia, Italy
| | - Annalisa Granata
- Registro Tumori Regione Campania, ASL Napoli 3 Sud, Brusciano, Italy
| | - Valerio Ciullo
- Registro Tumori Regione Campania, ASL Napoli 3 Sud, Brusciano, Italy
| | | | - Michele Gobbato
- SOC Epidemiologia Oncologica, Centro di Riferimento Oncologico Aviano, Aviano, Italy
| | - Rita Chiari
- Dipartimento di Oncologia, Azienda Ospedaliera Perugia, Perugia, Italy
| | - Francesco Cozzolino
- Health Planning Service, Regional Health Authority of Umbria, Perugia, Italy
| | - Massimiliano Orso
- Health Planning Service, Regional Health Authority of Umbria, Perugia, Italy
| | - Walter Orlandi
- Direzione salute, Regional Health Authority of Umbria, Perugia, Italy
| | - Iosief Abraha
- Health Planning Service, Regional Health Authority of Umbria, Perugia, Italy
- Centro Regionale Sangue, Azienda Ospedaliera di Perugia, Perugia, Italy
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Xu Y, Zhang F, Pan X, Wang G, Zhu L, Zhang J, Wen D, Lu S. Xenograft tumors derived from malignant pleural effusion of the patients with non-small-cell lung cancer as models to explore drug resistance. Cancer Commun (Lond) 2018; 38:19. [PMID: 29764505 PMCID: PMC5993147 DOI: 10.1186/s40880-018-0284-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 03/08/2018] [Indexed: 12/25/2022] Open
Abstract
Background Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions show dramatic responses to specific tyrosine kinase inhibitors (TKIs); however, after 10–12 months, secondary mutations arise that confer resistance. We generated a murine xenograft model using patient-derived NSCLC cells isolated from the pleural fluid of two patients with NSCLC to investigate the mechanisms of resistance against the ALK- and EGFR-targeted TKIs crizotinib and osimertinib, respectively. Methods Genotypes of patient biopsies and xenograft tumors were determined by whole exome sequencing (WES), and patients and xenograft-bearing mice received targeted treatment (crizotinib or osimertinib) accordingly. Xenograft mice were also treated for prolonged periods to identify whether the development of drug resistance and/or treatment responses were associated with tumor size. Finally, the pathology of patients biopsies and xenograft tumors were compared histologically. Results The histological characteristics and chemotherapy responses of xenograft tumors were similar to the actual patients. WES showed that the genotypes of the xenograft and patient tumors were similar (an echinoderm microtubule-associated protein-like 4-ALK (EML4–ALK) gene fusion (patient/xenograft: CTC15035EML4–ALK) and EGFR L858R and T790M mutations (patient/xenograft: CTC15063EGFR L858R, T790M)). After continuous crizotinib or osimertinib treatment, WES data suggested that acquired ALK E1210K mutation conferred crizotinib resistance in the CTC15035EML4–ALK xenograft, while decreased frequencies of EGFR L858R and T790M mutations plus the appearance of v-RAF murine sarcoma viral oncogene homolog B (BRAF) G7V mutations and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A) A86fs frame shift mutations led to osimertinib resistance in the CTC15063EGFR L858R, T790M xenografts. Conclusions We successfully developed a new method of generating drug resistance xenograft models from liquid biopsies using microfluidic technology, which might be a useful tool to investigate the mechanisms of drug resistance in NSCLC. Electronic supplementary material The online version of this article (10.1186/s40880-018-0284-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yunhua Xu
- Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200030, China
| | - Feifei Zhang
- Shanghai LIDE Biotech Co., Ltd, 887 Zuchongzhi Rd, Pudong, Shanghai, 201203, China
| | - Xiaoqing Pan
- Shanghai LIDE Biotech Co., Ltd, 887 Zuchongzhi Rd, Pudong, Shanghai, 201203, China
| | - Guan Wang
- GenomiCare Biotechnology (Shanghai) Co., Ltd., Shanghai, 200233, China
| | - Lei Zhu
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Jie Zhang
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Danyi Wen
- Shanghai LIDE Biotech Co., Ltd, 887 Zuchongzhi Rd, Pudong, Shanghai, 201203, China.
| | - Shun Lu
- Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai, 200030, China.
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Jin K, Zhang K, Zhou F, Dai J, Zhang P, Jiang G. Selection of candidates for surgery as local therapy among early-stage small cell lung cancer patients: a population-based analysis. Cancer Commun (Lond) 2018; 38:5. [PMID: 29764484 PMCID: PMC5993140 DOI: 10.1186/s40880-018-0272-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Accepted: 03/14/2018] [Indexed: 12/12/2022] Open
Abstract
Background Surgery and radiotherapy are considered local therapies for small cell lung cancer (SCLC). The present study aimed to select candidates for surgery as local therapy among patients with stage I or II SCLC, based on the eighth edition of the TNM classification for lung cancer. Methods Patients diagnosed with SCLC between 2004 and 2013 were selected from the Surveillance, Epidemiology, And End Results database. The TNM stage of SCLC in these patients was re-classified according to the eighth edition of the TNM classification for lung cancer. Patients with stage I or II SCLC were included in the present study. Overall survival (OS) and lung cancer-specific survival (LCSS) were separately compared in the different TNM stages between patients who received surgery and radiotherapy as local therapy. Multivariate analysis was applied to evaluate multiple factors associated with survival. Results Among the 2129 patients included in the present study, 387 (18.2%) received surgery, 1032 (48.5%) underwent radiotherapy as local therapy, 154 (7.2%) underwent surgery and radiotherapy, and 556 (26.1%) did not undergo either surgery or radiotherapy. Among patients with T1-2N0 (tumor size ≤ 50 mm without positive lymph nodes) disease, patients who underwent surgery had higher 5-year OS and LCSS rates than patients who received radiotherapy (T1N0: 46.0% vs. 23.8%, P < 0.001, and 58.4% vs. 36.4%, P < 0.001, respectively; T2N0: 42.6% vs. 24.7%, P = 0.004, and 48.8% vs. 31.3%, P = 0.011, respectively). Multivariate analysis results revealed that surgery was associated with low risk of death. However, among T3N0 or T1-2N1 (stage IIB) SCLC patients, patients who underwent surgery did not have higher 5-year OS and LCSS rates than patients who received radiotherapy (T3N0: 16.2% vs. 26.5%, P = 0.085, and 28.7% vs. 30.9%, P = 0.372, respectively; T1-2N1: 20.3% vs. 29.0%, P = 0.146, and 25.6% vs. 35.5%, P = 0.064, respectively). Conclusions Based on the assumption that the overwhelming majority of stage I or II SCLC patients who underwent surgery or radiotherapy also received certain types of systemic therapy, only patients with T1-2N0 SCLC may benefit from surgery as local therapy. Patients with T3N0 or T1-2N1 SCLC may consider radiotherapy as local therapy.
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Affiliation(s)
- Kaiqi Jin
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, P. R. China
| | - Kaixuan Zhang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, P. R. China
| | - Feng Zhou
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, P. R. China
| | - Jie Dai
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, P. R. China
| | - Peng Zhang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, P. R. China.
| | - Gening Jiang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, P. R. China.
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Kim HR, Kang HN, Shim HS, Kim EY, Kim J, Kim DJ, Lee JG, Lee CY, Hong MH, Kim SM, Kim H, Pyo KH, Yun MR, Park HJ, Han JY, Youn HA, Ahn MJ, Paik S, Kim TM, Cho BC. Co-clinical trials demonstrate predictive biomarkers for dovitinib, an FGFR inhibitor, in lung squamous cell carcinoma. Ann Oncol 2018; 28:1250-1259. [PMID: 28460066 DOI: 10.1093/annonc/mdx098] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). Methods The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. Results The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. Conclusions FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.
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Affiliation(s)
- H R Kim
- Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul
| | - H N Kang
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | | | - E Y Kim
- Pulmonology, Yonsei University College of Medicine, Seoul
| | - J Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul
| | - D J Kim
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul
| | - J G Lee
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul
| | - C Y Lee
- Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul
| | - M H Hong
- Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul
| | - S-M Kim
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | - H Kim
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | - K-H Pyo
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | - M R Yun
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | - H J Park
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | - J Y Han
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | - H A Youn
- JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
| | - M-J Ahn
- Division of Hematology & Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - S Paik
- Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul
| | - T-M Kim
- Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - B C Cho
- Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul.,JE-UK Institute for Cancer Research, JEUK Co, Ltd, Gumi-City, Kyungbuk
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Li H, Ma N, Wang J, Wang Y, Yuan C, Wu J, Luo M, Yang J, Chen J, Shi J, Liu X. Nicotine Induces Progressive Properties of Lung Adenocarcinoma A549 Cells by Inhibiting Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Expression and Plasma Membrane Localization. Technol Cancer Res Treat 2018; 17:1533033818809984. [PMID: 30384810 PMCID: PMC6259057 DOI: 10.1177/1533033818809984] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Revised: 09/04/2018] [Accepted: 10/04/2018] [Indexed: 12/11/2022] Open
Abstract
Lung cancer remains one of the most common cancer-related deaths worldwide. The cigarette smoking is a risk factor for lung cancer development. Interestingly, the cystic fibrosis transmembrane conductance regulator encoded by CFTR gene, an ATP-binding cassette transporter-class ion channel that conducts chloride and bicarbonate anions across membrane of epithelial cells, has recently been suggested to play a role in the development and progression of many types of cancer. It has been well-documented that mutations of CFTR gene are the cause of cystic fibrosis, the most common fatal hereditary lung disease in Caucasian population; the function of cystic fibrosis transmembrane conductance regulator in the development of lung cancer however has not yet been established. In the present study, we aimed to interrogate the impact of cystic fibrosis transmembrane conductance regulator on the nicotine-promoted progressive potency in lung adenocarcinoma cells by assessing capacities of cystic fibrosis transmembrane conductance regulator to cell migration, invasion, and clonogenicity and the expression of markers of cell proliferation and lung stem cell-related transcription factors in lung adenocarcinoma A549 cells. The exposure of nicotine exhibited an ability to enhance progressive properties of adenocarcinoma cells including A549 cells, HCC827 cells, and PC-9 cells, alone with an inhibition of cystic fibrosis transmembrane conductance regulator protein expression. Remarkably, an overexpression of cystic fibrosis transmembrane conductance regulator significantly inhibited the progressive potency of A549 cells, including capacity of cell migration and invasion and clonogenicity, along with a decreased expression of cell proliferative markers Ki67, p63, and proliferating cell nuclear antigen, and cancer stem cell marker CD133, stem cell pluripotency-related transcription factors octamer-binding transcription factor ¾, and sex-determining region Y-box 2, regardless of the presence of nicotine. In contrast, opposite effects were observed in A549 cells that the cystic fibrosis transmembrane conductance regulator was knockdown by short hairpin RNA to cystic fibrosis transmembrane conductance regulator. This study thus suggests that cystic fibrosis transmembrane conductance regulator may play a tumor suppressor role in lung cancer cells, which may be a novel therapeutic target warranted for further investigation.
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Affiliation(s)
- Hui Li
- College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia,
China
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia,
China
| | - Ningxia Ma
- College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia,
China
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia,
China
| | - Jing Wang
- Center of Laboratory Medicine, People’s Hospital of Ningxia Hui Autonomous
Region, Yinchuan, Ningxia, China
| | - Ying Wang
- College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia,
China
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia,
China
| | - Chao Yuan
- College of Life Science, Ningxia University, Yinchuan, Ningxia, China
| | - Jing Wu
- College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia,
China
| | - Meihui Luo
- College of Life Science, Ningxia University, Yinchuan, Ningxia, China
| | - Jiali Yang
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia,
China
| | - Juan Chen
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia,
China
| | - Juan Shi
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia,
China
| | - Xiaoming Liu
- College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia,
China
- General Hospital of Ningxia Medical University, Yinchuan, Ningxia,
China
- College of Life Science, Ningxia University, Yinchuan, Ningxia, China
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40
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Maj E, Filip-Psurska B, Milczarek M, Psurski M, Kutner A, Wietrzyk J. Vitamin D derivatives potentiate the anticancer and anti-angiogenic activity of tyrosine kinase inhibitors in combination with cytostatic drugs in an A549 non-small cell lung cancer model. Int J Oncol 2017; 52:337-366. [PMID: 29345296 PMCID: PMC5741374 DOI: 10.3892/ijo.2017.4228] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 11/17/2017] [Indexed: 12/16/2022] Open
Abstract
Numerous in vitro and in vivo studies have demonstrated that calcitriol [1,25(OH)2D3] and different vitamin D analogs possess antineoplastic activity, regulating proliferation, differentiation and apoptosis, as well as angiogenesis. Vitamin D compounds have been shown to exert synergistic effects when used in combination with different agents used in anticancer therapies in different cancer models. The aim of this study was to evaluate the mechanisms of the cooperation of the vitamin D compounds [1,24(OH)2D3 (PRI-2191) and 1,25(OH)2D3] with tyrosine kinase inhibitors (imatinib and sunitinib) together with cytostatics (cisplatin and docetaxel) in an A549 non-small cell lung cancer model. The cytotoxic effects of the test compounds used in different combinations were evaluated on A549 lung cancer cells, as well as on human lung microvascular endothelial cells (HLMECs). The effects of such combinations on the cell cycle and cell death were also determined. In addition, changes in the expression of proteins involved in cell cycle regulation, angiogenesis and the action of vitamin D were analyzed. Moreover, the effects of 1,24(OH)2D3 on the anticancer activity of sunitinib and sunitinib in combination with docetaxel were examined in an A549 lung cancer model in vivo. Experiments aiming at evaluating the cytotoxicity of the combinations of the test agents revealed that imatinib and sunitinib together with cisplatin or docetaxel exerted potent anti-proliferative effects in vitro on A549 lung cancer cells and in HLMECs; however, 1,24(OH)2D3 and 1,25(OH)2D3 enhanced the cytotoxic effects only in the endothelial cells. Among the test agents, sunitinib and cisplatin decreased the secretion of vascular endothelial growth factor (VEGF)-A from the A549 lung cancer cells. The decrease in the VEGF-A level following incubation with cisplatin correlated with a higher p53 protein expression, while no such correlation was observed following treatment of the A549 cells with sunitinib. Sunitinib together with docetaxel and 1,24(OH)2D3 exhibited a more potent anticancer activity in the A549 lung cancer model compared to double combinations and to treatment with the compounds alone. The observed anticancer activity may be the result of the influence of the test agents on the process of tumor angiogenesis, for example, through the downregulation of VEGF-A expression in tumor and also on the induction of cell death inside the tumor.
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Affiliation(s)
- Ewa Maj
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
| | - Beata Filip-Psurska
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
| | - Magdalena Milczarek
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
| | - Mateusz Psurski
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
| | - Andrzej Kutner
- Pharmaceutical Research Institute, 01-793 Warsaw, Poland
| | - Joanna Wietrzyk
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland
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Zhang T, Chen L, Zhang S, Xu Y, Fan Y, Zhang L. Effects of high-intensity focused ultrasound on cisplatin-resistant human lung adenocarcinoma in vitro and in vivo. Acta Biochim Biophys Sin (Shanghai) 2017; 49:1092-1098. [PMID: 29077784 DOI: 10.1093/abbs/gmx107] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Indexed: 01/26/2023] Open
Abstract
It is widely accepted that high-intensity focused ultrasound (HIFU) is a minimally invasive treatment option for different tumors, but its roles and the corresponding mechanism in cisplatin (DDP) chemoresistance in lung adenocarcinoma (LA) remain unclear. In this study, we investigated the response of DDP-resistant LA cells to HIFU and its underlying molecular mechanisms using molecular biology techniques. It was found that HIFU exposure inhibited the proliferation of DDP-resistant A549 (A549/DDP) cells through arresting cell cycle at the G1/G0 phase via the Cyclin-dependent pathway and promoting apoptosis in a Bcl-2-dependent manner. Furthermore, the results also showed that HIFU exposure could down-regulate the expressions of MDR1, MRP1, and LRP mRNAs, as well as P-gp, MRP1, and LRP proteins related to drug resistance in A549/DDP cells. In vivo experiments also demonstrated that HIFU could reduce the size and mass of subcutaneously transplanted tumors produced by A549/DDP cells through mediating Cyclin-dependent and Bcl-2-dependent pathways. These results suggested that HIFU treatment could inhibit the proliferation of DDP-resistant lung cancer cells and might be a novel therapeutic method for patients with DDP resistance.
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Affiliation(s)
- Tao Zhang
- Department of Ultrasound, Ningbo No. 9 Hospital, Ningbo, China
| | - Libin Chen
- Department of Ultrasound, Ningbo First Hospital, Ningbo, China
| | - Shengmin Zhang
- Department of Ultrasound, Ningbo First Hospital, Ningbo, China
| | - Youfeng Xu
- Department of Ultrasound, Ningbo First Hospital, Ningbo, China
| | - Yabo Fan
- Department of Ultrasound, Ningbo No. 9 Hospital, Ningbo, China
| | - Lizhong Zhang
- Department of Ultrasound, Ningbo No. 9 Hospital, Ningbo, China
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Zhang P, Zhu Y, Li Y, Zhu S, Ma R, Zhao M, Li J. Forensic evaluation of STR typing reliability in lung cancer. Leg Med (Tokyo) 2017; 30:38-41. [PMID: 29154002 DOI: 10.1016/j.legalmed.2017.11.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 08/26/2017] [Accepted: 11/10/2017] [Indexed: 01/07/2023]
Abstract
Short tandem repeats (STR) analysis is the gold standard method in the forensics field for personal identification and paternity testing. In cancerous tissues, STR markers are gaining attention, with some studies showing increased instability. Lung cancer, which is one of the most commonmalignancies, has become the most lethal among all cancers. In certain situations, lung cancer tissues may be the only resource available for forensic analysis. Therefore, evaluating the reliability of STR markers in lung cancer tissues is required to avoid false exclusions. In this study, 75 lung cancer tissue samples were examined to evaluate the reliability of various STR markers. Out of the 75 examined samples, 24 of the cancerous samples (32%) showed genetic alterations on at least one STR loci, totaling 55 times. The most common type of STR variation was a partial loss of heterozygosity, with the D5S818 loci having the highest variation frequency and no alterations detected on the D2S441 and Penta E loci. Moreover, STR variation frequencies were shown to increase with an increased patient age and increased clinical and pathological characteristics, thus an older patient with an advanced stage of progression exhibited a higher variation frequency. Overall, this study provides forensic scientists with further insight into STR analysis relating to lung cancer tissue.
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Affiliation(s)
- Peng Zhang
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Ying Zhu
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Yongguo Li
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing 400016, China
| | - Shisheng Zhu
- Faculty of Medical Technology, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China
| | - Ruoxiang Ma
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing 400016, China
| | - Minzhu Zhao
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China; Chongqing Engineering Research Center for Criminal Investigation Technology, Chongqing 400016, China
| | - Jianbo Li
- Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
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Chen YC, Lin AS, Hung YC, Chen KD, Wu CY, Lie CH, Hsiao CC, Chen CJ, Liu SF, Fang WF, Chang JC, Wang TY, Wang YH, Chung YH, Chao TY, Leung SY, Su MC, Lin MC. Whole genome gene expression changes and hematological effects of rikkunshito in patients with advanced non-small cell lung cancer receiving first line chemotherapy. Exp Ther Med 2017; 14:2040-2052. [PMID: 28962123 PMCID: PMC5609175 DOI: 10.3892/etm.2017.4773] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 03/24/2017] [Indexed: 01/18/2023] Open
Abstract
It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC. These patients were randomized to receive combination chemotherapy (cisplatin and gemcitabine) with (n=9, CTH+R group) or without (n=8, CTH group) rikkunshito. The primary endpoint was the treatment response and the categories of the scales of anorexia, nausea, vomiting and fatigue; secondary endpoints included the hematological effect and whole genome gene expression changes. The results of the current study indicated that there were no significant differences in clinical outcomes, including treatment response and toxicity events, between the two groups. Median one-year overall survival (OS) was 12 months in the CTH group and 11 months in the CTH+R group (P=0.058 by log-rank test), while old age (>60 years old) was the only independent factor associated with one-year OS (hazard ratio 1.095, 95% confidence interval, 1.09–1.189, P=0.030). Patients in the CTH+R group experienced significantly greater maximum decreases in both white cell count (P=0.034) and absolute neutrophil count (P=0.030) from the baseline. A total of 111 genes associated with neutrophil apoptosis, the cell-killing ability of neutrophils, natural killer cell activation and B cell proliferation were up-regulated following rikkunshito treatment. A total of 48 genes associated with neutrophil migration, coagulation, thrombosis and type I interferon signaling were down-regulated following rikkunshito treatment. Rikkunshito may therefore affect the blood neutrophil count when used with combination chemotherapy in patients with NSCLC, potentially by down-regulating prostaglandin-endoperoxidase synthase 1, MPL, AMICA1 and junctional adhesion molecule 3, while up-regulating elastase, neutrophil expressed, proteinase 3, cathepsin G and cluster of differentiation 24.
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Affiliation(s)
- Yung-Che Chen
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C.,Division of Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - An-Shen Lin
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Yu-Chiang Hung
- Department of Chinese Medicine and School of Traditional Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Kuang-Den Chen
- Center for Translational Research in Biomedical Science, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Ching-Yuan Wu
- Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi 61361, Taiwan R.O.C
| | - Chien-Hao Lie
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Chang-Chun Hsiao
- Division of Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Chung-Jen Chen
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Shih-Feng Liu
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Wen-Feng Fang
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C.,Department of Respiratory Care, Chang Gung University of Technology, Chiayi 61363, Taiwan R.O.C
| | - Jen-Chieh Chang
- Division of Rheumatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Ting-Ya Wang
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Yi-Hsi Wang
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Yu-Hsiu Chung
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Tung-Ying Chao
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Sum-Yee Leung
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
| | - Mao-Chang Su
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C.,Department of Respiratory Care, Chang Gung University of Technology, Chiayi 61363, Taiwan R.O.C
| | - Meng-Chih Lin
- Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan R.O.C
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44
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Popolo A, Pinto A, Daglia M, Nabavi SF, Farooqi AA, Rastrelli L. Two likely targets for the anti-cancer effect of indole derivatives from cruciferous vegetables: PI3K/Akt/mTOR signalling pathway and the aryl hydrocarbon receptor. Semin Cancer Biol 2017; 46:132-137. [PMID: 28596013 DOI: 10.1016/j.semcancer.2017.06.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Revised: 05/29/2017] [Accepted: 06/01/2017] [Indexed: 12/18/2022]
Abstract
Diets containing high quantities of plant foods are linked with a decreased likelihood of incidence of cancer. Several common plant-based dietary components exert effects on DNA methylation levels, and can positively influence genome stability and the transcription of tumor suppressors and oncogenes. Indole-3-carbinol (I3C) is a substance present in vegetables of the Brassicaeae family, especially broccoli, white cabbage, Brussels sprouts and cauliflower. The in vivo biological effects of I3C are ascribed to a series of oligomeric products (including 3,3'-diindolylmethane), developed under acidic conditions. I3C is one of the many natural products and bioactive compounds found in foods which have recently received much attention for its potential effects in cancer prevention and treatment. In vitro studies report that I3C suppresses the proliferation of different tumor cells, including those isolated from breast, prostate, endometrium, and colon cancers. I3C resulted to be a potent in vivo chemopreventive agent for certain hormone-dependent cancers, including breast and cervical cancer. However, the mechanisms underlying these effects are not well defined. In this review, we have analysed recent literature on the use of indole derivatives against various forms of cancer, and have identified the main signalling pathways involved in their anti-cancer effect as PI3K/Akt/mTOR and the aryl hydrocarbon receptor.
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Affiliation(s)
- Ada Popolo
- Dipartimento di Farmacia, University of Salerno, via Giovanni Paolo II, 84084, Fisciano, Italy
| | - Aldo Pinto
- Dipartimento di Farmacia, University of Salerno, via Giovanni Paolo II, 84084, Fisciano, Italy
| | - Maria Daglia
- Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, Pavia University, Italy
| | - Seyed Fazel Nabavi
- Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | - Luca Rastrelli
- Dipartimento di Farmacia, University of Salerno, via Giovanni Paolo II, 84084, Fisciano, Italy.
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45
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Wei Y, Pu X, Zhao L. Preclinical studies for the combination of paclitaxel and curcumin in cancer therapy (Review). Oncol Rep 2017; 37:3159-3166. [PMID: 28440434 DOI: 10.3892/or.2017.5593] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Accepted: 04/10/2017] [Indexed: 11/05/2022] Open
Abstract
Cancer is one of the most common causes of death and remains the first in China and the second in the US. The common treatments for cancer include surgery, radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy remains one of the most important treatments. However, the efficacy of chemotherapy is limited due to drug induced-toxicities and resistance, particularly multiple drug resistance (MDR). Therefore, discovery and development of novel therapeutic drugs and/or combination therapy are urgently needed to reduce toxicity and improve efficacy. Paclitaxel has been widely used to treat various cancers including cervical, breast, ovarian, brain, bladder, prostate, liver and lung cancers. However, its therapeutic efficacy is limited and MDR is a major obstacle. Recently, numerous preclinical studies have shown that the combination of paclitaxel and curcumin may be an ideal strategy to reverse MDR and synergistically improve their therapeutic efficacy in cancer therapy. This review mainly focuses on the current development and progress of the combination of paclitaxel and curcumin in cancer therapy preclinically.
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Affiliation(s)
- Yumeng Wei
- Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646099, P.R. China
| | - Xinlin Pu
- The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, P.R. China
| | - Ling Zhao
- Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646099, P.R. China
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46
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McIntyre A, Ganti AK. Lung cancer-A global perspective. J Surg Oncol 2017; 115:550-554. [PMID: 28418583 DOI: 10.1002/jso.24532] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Accepted: 12/04/2016] [Indexed: 12/17/2022]
Abstract
Lung cancer is the leading cause of cancer deaths worldwide. While tobacco exposure is responsible for the majority of lung cancers, the incidence of lung cancer in never smokers, especially Asian women, is increasing. There is a global variation in lung cancer biology with EGFR mutations being more common in Asian patients, while Kras mutation is more common in Caucasians. This review will focus on the global variations in lung cancer and its treatment.
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Affiliation(s)
| | - Apar Kishor Ganti
- Department of Internal Medicine, VA Nebraska Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, Nebraska
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47
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Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin through Activation of Wnt5a/PKC Signaling Pathway. Stem Cells Int 2016; 2016:1690896. [PMID: 27895670 PMCID: PMC5118537 DOI: 10.1155/2016/1690896] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2016] [Revised: 08/31/2016] [Accepted: 09/22/2016] [Indexed: 02/07/2023] Open
Abstract
The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells. An exposure of cells to Wnt5a led to a significant reduction of A549/DDP cell apoptosis but not A549 cells. An addition of GF109203X could both strikingly increase the baseline apoptosis and resensitize the Wnt5a-inhibited cell apoptosis. Interestingly, an inhibition of Wnt/PKC signaling pathway could reduce properties of lung cancer stem cells, promote cell apoptosis, and resensitize cisplatin-resistant cells to cisplatin via a caspase/AIF-dependent pathway. These data thus suggested that the Wnt5a could promote lung cancer cell mobility and cisplatin-resistance through a Wnt/PKC signaling pathway and a blockage of this signaling may be an alternative therapeutic strategy for NSCLC patients with resistance to chemotherapies.
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48
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Wang R, Chu GCY, Mrdenovic S, Annamalai AA, Hendifar AE, Nissen NN, Tomlinson JS, Lewis M, Palanisamy N, Tseng HR, Posadas EM, Freeman MR, Pandol SJ, Zhau HE, Chung LWK. Cultured circulating tumor cells and their derived xenografts for personalized oncology. Asian J Urol 2016; 3:240-253. [PMID: 29264192 PMCID: PMC5730836 DOI: 10.1016/j.ajur.2016.08.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 08/16/2016] [Indexed: 02/07/2023] Open
Abstract
Recent cancer research has demonstrated the existence of circulating tumor cells (CTCs) in cancer patient's blood. Once identified, CTC biomarkers will be invaluable tools for clinical diagnosis, prognosis and treatment. In this review, we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample, to derive enough CTCs for accurate and reproducible characterization of the biophysical, biochemical, gene expressional and behavioral properties of the harvested cells. Because of tumor cell heterogeneity, it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis. By analyzing critical steps and technical issues in ex vivo CTC culture, we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells, relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells.
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Affiliation(s)
- Ruoxiang Wang
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Gina C Y Chu
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Stefan Mrdenovic
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Alagappan A Annamalai
- Uro-Oncology Research, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Andrew E Hendifar
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Nicholas N Nissen
- Uro-Oncology Research, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - James S Tomlinson
- Department of Surgery, West Los Angeles VA Hospital, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA
| | - Michael Lewis
- Department of Pathology, West Los Angeles VA Hospital, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, USA
| | | | - Hsian-Rong Tseng
- Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA
| | - Edwin M Posadas
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Michael R Freeman
- Uro-Oncology Research, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Stephen J Pandol
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Haiyen E Zhau
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Leland W K Chung
- Uro-Oncology Research, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.,Uro-Oncology Research, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
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