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English K. Brief insight regarding the use of transanal, laparoscopic, and robotic total mesorectal excision for rectal cancer. World J Gastrointest Surg 2025; 17:102487. [PMID: 40291901 PMCID: PMC12019043 DOI: 10.4240/wjgs.v17.i4.102487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/18/2025] [Accepted: 02/14/2025] [Indexed: 03/29/2025] Open
Abstract
In this article, we provide an important commentary on the original study Lu et al, which offers insight into the surgical efficacy of transanal total mesorectal excision (TaTME) vs laparoscopic total mesorectal excision (LapTME) in the management of low-lying locally advanced rectal cancer (LARC). We focus specifically on the rate of postoperative complications between the two using existing data from the literature. We additionally introduce robotic total mesorectal excision (RTME) and look at its postoperative complications relative to the TaTME and LapTME. LARC has been conventionally approached by open surgery. However, minimally invasive techniques have emerged over the past two decades as alternatives to open total mesorectal excision, namely robotic, laparoscopic, and transanal. Each approach has its supporters, but conflicting data on resection outcomes and complications has fueled ongoing debate over the optimal minimally invasive technique for low/mid-LARC. This article aims to extend on the data regarding the use of TaTME and RTME in the treatment of low/mid-LARC and further elaborate on their comparative efficacy relative to LapTME.
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Affiliation(s)
- Kevan English
- Department of Medicine, University of Nebraska Medical Center College of Medicine, Omaha, NE 68198, United States
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2
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Kang Q, Hu X, Chen Z, Liang X, Xiang S, Wang Z. The METTL3/TRAP1 axis as a key regulator of 5-fluorouracil chemosensitivity in colorectal cancer. Mol Cell Biochem 2025; 480:1865-1889. [PMID: 39287889 PMCID: PMC11842504 DOI: 10.1007/s11010-024-05116-8] [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: 01/11/2024] [Accepted: 09/03/2024] [Indexed: 09/19/2024]
Abstract
Colorectal cancer (CRC) remains a significant clinical challenge, with 5-Fluorouracil (5-FU) being the frontline chemotherapy. However, chemoresistance remains a major obstacle to effective treatment. METTL3, a key methyltransferase involved in RNA methylation processes, has been implicated in CRC carcinogenesis. However, its role in modulating CRC sensitivity to 5-FU remains elusive. In this study, we aimed to investigate the role and mechanisms of METTL3 in regulating 5-FU chemosensitivity in CRC cells. Initially, we observed that 5-FU treatment inhibited cell viability and induced apoptosis, accompanied by a reduction in METTL3 expression in HCT-116 and HCT-8 cells. Subsequent assays including drug sensitivity, EdU, colony formation, TUNEL staining, and flow cytometry revealed that METTL3 depletion enhanced 5-FU sensitivity and increased apoptosis induction both in vitro and in vivo. Conversely, METTL3 overexpression conferred resistance to 5-FU in both cell lines. Moreover, knockdown of METTL3 in 5-FU-resistant CRC cell lines HCT-116/FU and HCT-15/FU significantly decreased 5-FU tolerance and induced apoptosis upon 5-FU treatment. Mechanistically, we found that METTL3 regulated 5-FU sensitivity and apoptosis induction by modulating TRAP1 expression. Further investigations using m6A colorimetric ELISA, dot blot, MeRIP-qPCR and RNA stability assays demonstrated that METTL3 regulated TRAP1 mRNA stability in an m6A-dependent manner. Additionally, overexpression of TRAP1 mitigated the cytotoxic effects of 5-FU on CRC cells. In summary, our study uncovers the pivotal role of the METTL3/TRAP1 axis in modulating 5-FU chemosensitivity in CRC. These findings provide new insights into the mechanisms underlying CRC resistance to 5-FU and may offer potential targets for future therapeutic interventions.
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Affiliation(s)
- Qingjie Kang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Xiaoyu Hu
- Chongqing Medical University, Chongqing, 400016, China
| | - Zhenzhou Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Xiaolong Liang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Song Xiang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China
| | - Ziwei Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.
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Wang J, Huang Y, Zheng X, Xie M, Wu Y, Yang L, Yin C. Effect of Nutritional Intervention on Chemotherapy Tolerance and Quality of Life in Patients with Colorectal Cancer Undergoing Postoperative Chemotherapy: A Randomized Controlled Study. Nutr Cancer 2025; 77:414-423. [PMID: 39789810 DOI: 10.1080/01635581.2025.2449719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 12/24/2024] [Accepted: 12/30/2024] [Indexed: 01/12/2025]
Abstract
This study explored the effect of symptom-based individualized nutritional intervention on chemotherapy tolerance and quality of life (QOL) in patients with colorectal cancer (CRC) undergoing postoperative chemotherapy. Postoperative patients with CRC (n = 88) were randomly assigned to the control group (CG, n = 45) and intervention group (IG, n = 43) receiving conventional diet counseling and symptom-based individualized nutritional intervention, respectively, and chemotherapy tolerance, adverse effects, and QOL were compared. Participants in the IG exhibited better nutritional status at the last chemotherapy cycle, with lower Nutrition Risk Screening 2002 (2.37 ± 0.65 vs. 3.78 ± 0.65, p < 0.01) and Patient-Generated Subjective Global Assessment (6.26 ± 0.76 vs. 7.78 ± 0.70, p < 0.01) scores. Compared with CG, relative dose intensity reduction (9.3% vs. 25.89%, p = 0.02), chemotherapy regimen change (25.58% vs. 53.33%, p < 0.01), and chemotherapy delay (13.95% vs. 35.56%, p = 0.019) were lower in the IG. Nausea/vomiting (2.33% vs. 17.78%, p = 0.017), thrombocytopenia (2.33% vs. 28.89%, p < 0.01), and hand-foot syndrome (4.65% vs. 22.22%, p = 0.03) were less frequent in the IG. Participants in the IG had better QOL, with higher physical function scores at cycles 4 (67.91 ± 5.22 vs. 62.22 ± 4.02, p < 0.01) and 8 (72.71 ± 6.31 vs. 57.63 ± 4.75, p < 0.01). Individualized nutritional interventions improved chemotherapy tolerance and QOL and reduced adverse effects in this patient cohort.
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Affiliation(s)
- Jiwei Wang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Yong Huang
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Xilan Zheng
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Ming Xie
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Yin Wu
- Day Chemotherapy Ward, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Li Yang
- Day Chemotherapy Ward, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Chunmei Yin
- Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
- Department of General Surgery, YiBin Hospital of T.C.M, Yibin, Sichuan, China
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Zhang Y, Lu X, Li S, Li Y, Wang J, Fan X. A preliminary study of further attempt at the development, testing and application of an auxiliary equipment for electronic colonoscopy. Sci Rep 2024; 14:31128. [PMID: 39730905 DOI: 10.1038/s41598-024-82415-6] [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: 07/26/2024] [Accepted: 12/05/2024] [Indexed: 12/29/2024] Open
Abstract
Colonoscopy is a valuable tool for colorectal cancer screening and health checkups, with increasing utilization annually. Assisted entry is a standard procedure during electronic colonoscopy. In China, most clinically assisted colonoscopy procedures involve a nurse directly applying abdominal pressure to the patient's abdomen. This maneuver provides a fulcrum for the physician performing the procedure, facilitating smoother access to the colon. To reduce labor, optimize resource utilization, and enhance efficiency, this preliminary study aimed to develop and evaluate an adjunctive pressurized removable lap band for colonoscopy. This prospective randomized controlled trial randomized participants into control and experimental groups for observational comparison during follow-up, mitigating retrospective bias. Data were collected from 150 participants in a tertiary hospital endoscopy department between March and September 2023. Participants were evenly divided into groups using a randomized number table. Demographic data, including gender, age, height, weight, and abdominal circumference, were collected to ensure group representativeness and comparability. No significant pre-test differences were found between the groups. The experimental group demonstrated a significant reduction in examination-only insertion time compared to the control group (p < 0.001), median respectively 2.5, 3. Additionally, compared with control group (41.3%), the experimental group (24%) required fewer nurse assistance (p = 0.024). No significant differences were observed in systolic and diastolic blood pressure changes between the groups (p = 0.07, p = 0.43). However, compared with control group (0.89 ± 1.17), the experimental group (2.19 ± 0.94) reported lower pain scores (p < 0.001). Overall, this preliminary study validates the adjunctive pressurized removable lap band as an effective tool for improving colonoscopy efficiency, reducing patient pain, and conserving medical resources.Trial registration: Registration Authority: Chinese Clinical Trial Registry (ChiCTR). Number: ChiCTR2400082664.
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Affiliation(s)
- Yonghong Zhang
- Endoscopic Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Xiaodan Lu
- Endoscopic Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Siyu Li
- Endoscopic Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.
| | - Yan Li
- Nursing Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Jianan Wang
- Endoscopic Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
| | - Xiaxi Fan
- Endoscopic Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150000, China
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Braun KP, Maurer J, Wolff I, Vogel T, Lebentrau S, May M, Herrmann M. Early detection efforts for colorectal and prostate cancer from the patient's perspective over the course of 12 years: results of the KABOT survey study. Prim Health Care Res Dev 2024; 25:e68. [PMID: 39676729 DOI: 10.1017/s1463423624000653] [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] [Indexed: 12/17/2024] Open
Abstract
AIM This study investigates the level of knowledge and utilization of colorectal cancer (CRC) and prostate cancer (PCa) early detection measures (EDMs) over a period of 12 years in general practice from the patient's perspective. BACKGROUND The role of general practitioners (GPs) in EDMs for CRC and PCa in Germany is not well-documented with comprehensive data. METHODS We conducted a patient-centric survey in the German federal state of Berlin-Brandenburg at a 12-year interval to examine the role of GPs in EDMs for CRC and PCa. In 2009, 55 GPs were tasked with informing 50 consecutive male patients, each aged over 35, about participating in a survey study (study phase 1/SP1). To evaluate changes over 12 years, a new survey involving 50 male patients from each of 150 GPs was conducted from October 2021 to March 2022 (SP2). FINDINGS We thoroughly reviewed the questionnaires of 890 patients, with 755 in SP1 and 135 in SP2. Patients showed greater awareness of recommendations regarding colonoscopy compared to prostate-specific antigen (PSA) testing. GPs were the most frequently reported source of information for both EDMs in our cohort. Comparing the two study phases, no significant difference in specific awareness of colonoscopy or PSA testing was found among men eligible for EDMs. However, there was a notable increase in the role of health insurance companies as a source of information about colonoscopy over time. Nearly 60% of included patients underwent colonoscopy and/or PSA testing as EDMs. CONCLUSION The number of EDMs performed among study participants did not increase over time. Our study confirms that GPs remain the primary source of information about EDMs among the study participants.
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Affiliation(s)
- Kay-Patrick Braun
- Institute of General Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
- MVZ Dr. Braun GmbH, Cottbus, Germany
| | - Julia Maurer
- University Cancer Center UCC-R, University Hospital Regensburg, Regensburg, Germany
| | - Ingmar Wolff
- Department of Urology, University Medicine Greifswald, Greifswald, Germany
| | | | - Steffen Lebentrau
- Department of Urology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
| | - Matthias May
- Department of Urology, St. Elisabeth Hospital Straubing, Straubing, Germany
| | - Markus Herrmann
- Institute of General Medicine, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
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Marzano M, Prosperi P, Grazi GL, Cianchi F, Talamucci L, Bisogni D, Bencini L, Mastronardi M, Guagni T, Falcone A, Martellucci J, Bergamini C, Giordano A. Upfront Surgery vs. Endoscopic Stenting Bridge to Minimally Invasive Surgery for Treatment of Obstructive Left Colon Cancer: Analysis of Surgical and Oncological Outcomes. Cancers (Basel) 2024; 16:3895. [PMID: 39682083 PMCID: PMC11640554 DOI: 10.3390/cancers16233895] [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: 10/28/2024] [Revised: 11/14/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Left colon cancer obstruction treatment is a debated topic in the literature. Stent placement is effective as a bridge-to-surgery strategy, but there are some concerns about the oncological safety for the reported higher risk of local and peritoneal recurrence. This study aims to compare the surgical and oncological outcomes of patients treated with stent followed by elective surgery with those treated with primary resection. METHODS This is a retrospective observational study. We included patients of both sexes, ≥18 years old, with a histological diagnosis of intestinal adenocarcinoma, and admitted to our hospital for left colon cancer obstruction demonstrated by CT scan without metastasis or perforation. They were treated through primary resection (PR) or stent placement followed by elective surgery (SR). The two groups were compared for general characteristics, surgical outcomes, and oncological outcomes (metastasis and local recurrence) at 30 days, 90 days, 1 year, and 3 years. Post-operative quality of life (QoL) was also investigated. RESULTS The SR group showed a shorter hospital stay, a lower post-operative mortality, a lower stoma rate at 1 year, and a higher number of minimally invasive procedures. Oncological outcomes were not different compared to the PR group. The SR group demonstrated better QoL in two out of six items on the EQ-5D-5L test. CONCLUSIONS Stent placement as a bridge-to-surgery strategy is feasible and provides better surgical outcomes in terms of post-operative complications, surgical approach, stoma rate, and QoL. Oncological outcomes were not reported differently, but further studies should be conducted to better evaluate this aspect.
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Affiliation(s)
- Mauro Marzano
- Emergency Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy (P.P.); (J.M.)
| | - Paolo Prosperi
- Emergency Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy (P.P.); (J.M.)
| | - Gian Luca Grazi
- Hepatobiliary Pancreatic Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy;
| | - Fabio Cianchi
- Digestive System Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy;
| | - Luca Talamucci
- Advanced Interventional Endoscopy Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (L.T.); (D.B.)
| | - Damiano Bisogni
- Advanced Interventional Endoscopy Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (L.T.); (D.B.)
| | - Lapo Bencini
- General Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy;
| | - Manuela Mastronardi
- Department of Medicine, Surgery and Health Sciences, General Surgery Unit, University Hospital of Trieste, Strada di Fiume 447, 34149 Trieste, Italy
| | - Tommaso Guagni
- Emergency Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy (P.P.); (J.M.)
| | - Agostino Falcone
- Emergency Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy (P.P.); (J.M.)
| | - Jacopo Martellucci
- Emergency Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy (P.P.); (J.M.)
| | - Carlo Bergamini
- Emergency Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy (P.P.); (J.M.)
| | - Alessio Giordano
- Emergency Surgery Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy (P.P.); (J.M.)
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Hajjafari A, Sadr S, Rahdar A, Bayat M, Lotfalizadeh N, Dianaty S, Rezaei A, Moghaddam SP, Hajjafari K, Simab PA, Kharaba Z, Borji H, Pandey S. Exploring the integration of nanotechnology in the development and application of biosensors for enhanced detection and monitoring of colorectal cancer. INORG CHEM COMMUN 2024; 164:112409. [DOI: 10.1016/j.inoche.2024.112409] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2024]
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Perné MG, Sitar-Tăut AV, Orășan OH, Negrean V, Vlad CV, Alexescu TG, Milaciu MV, Ciumărnean L, Togănel RD, Petre GE, Șimon I, Crăciun A. The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma. Int J Mol Sci 2024; 25:4997. [PMID: 38732222 PMCID: PMC11084444 DOI: 10.3390/ijms25094997] [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: 03/24/2024] [Revised: 04/22/2024] [Accepted: 05/01/2024] [Indexed: 05/13/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.
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Affiliation(s)
- Mirela-Georgiana Perné
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Adela-Viviana Sitar-Tăut
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Olga Hilda Orășan
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Vasile Negrean
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Călin Vasile Vlad
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Teodora-Gabriela Alexescu
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Mircea Vasile Milaciu
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Lorena Ciumărnean
- 4th Department–Internal Medicine, 4th Medical Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Răzvan Dan Togănel
- 6th Department–Surgery, 4th Surgery Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Gabriel Emil Petre
- 6th Department–Surgery, 4th Surgery Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Ioan Șimon
- 6th Department–Surgery, 4th Surgery Discipline, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Republicii Street, Nr. 18, 400015 Cluj-Napoca, Romania
| | - Alexandra Crăciun
- 2nd Department–Molecular Sciences, Discipline of Medical Biochemistry, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, Pasteur Street, Nr. 6, 400349 Cluj-Napoca, Romania
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Safarpour H, Ranjbaran J, Erfanian N, Nomiri S, Derakhshani A, Gerarduzzi C, Miraki Feriz A, HosseiniGol E, Saghafi S, Silvestris N. Holistic exploration of CHGA and hsa-miR-137 in colorectal cancer via multi-omic data Integration. Heliyon 2024; 10:e27046. [PMID: 38495181 PMCID: PMC10943347 DOI: 10.1016/j.heliyon.2024.e27046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 12/14/2023] [Accepted: 02/22/2024] [Indexed: 03/19/2024] Open
Abstract
Colorectal cancer (CRC) ranks among the most widespread malignancies globally, with early detection significantly influencing prognosis. Employing a systems biology approach, we aimed to unravel the intricate mRNA-miRNA network linked to CRC pathogenesis, potentially yielding diagnostic biomarkers. Through an integrative analysis of microarray, Bulk RNA-seq, and single-cell RNA-seq data, we explored CRC-related transcriptomes comprehensively. Differential gene expression analysis uncovered crucial genes, while Weighted Gene Co-expression Network Analysis (WGCNA) identified key modules closely linked to CRC. Remarkably, CRC manifested its strongest correlation with the turquoise module, signifying its pivotal role. From the cohort of genes showing high Gene Significance (GS) and Module Membership (MM), and Differential Expression Genes (DEGs), we highlighted the downregulated Chromogranin A (CHGA) as a notable hub gene in CRC. This finding was corroborated by the Human Protein Atlas database, which illustrated decreased CHGA expression in CRC tissues. Additionally, CHGA displayed elevated expression in primary versus metastatic cell lines, as evidenced by the CCLE database. Subsequent RT-qPCR validation substantiated the marked downregulation of CHGA in CRC tissues, reinforcing the significance of our differential expression analysis. Analyzing the Space-Time Gut Cell Atlas dataset underscored specific CHGA expression in epithelial cell subclusters, a trend persisting across developmental stages. Furthermore, our scrutiny of colon and small intestine Enteroendocrine cells uncovered distinct CHGA expression patterns, accentuating its role in CRC pathogenesis. Utilizing the WGCNA algorithm and TargetScan database, we validated the downregulation of hsa-miR-137 in CRC, and integrated assessment highlighted its interplay with CHGA. Our findings advocate hsa-miR-137 and CHGA as promising CRC biomarkers, offering valuable insights into diagnosis and prognosis. Despite proteomic analysis yielding no direct correlation, our multifaceted approach contributes comprehensive understanding of CRC's intricate regulatory mechanisms. In conclusion, this study advances hsa-miR-137 and CHGA as promising CRC biomarkers through an integrated analysis of diverse datasets and network interactions.
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Affiliation(s)
- Hossein Safarpour
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Javad Ranjbaran
- Department of Clinical Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Nafiseh Erfanian
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Samira Nomiri
- Department of Clinical Biochemistry, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Afshin Derakhshani
- Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, 70124, Bari, Italy
| | - Casimiro Gerarduzzi
- Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada
- Département de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Adib Miraki Feriz
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Edris HosseiniGol
- Department of Computer Engineering, University of Birjand, Birjand, Iran
| | - Samira Saghafi
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
- Department of Internal Medicine, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Nicola Silvestris
- Medical Oncology Unit, Department of Human Pathology “G. Barresi”, University of Messina, Messina, Italy
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Giordano A, Podda M, Montori G, Botteri E, Fugazzola P, Ortenzi M, Guerrieri M, Vettoretto N, Agresta F, Sartori A, Bergamini C, Martellucci J, Guariniello A, Fransvea P, Azzinnaro A, Scatizzi M, Catena F, Coccolini F, Ansaloni L, Sartelli M, Sapienza P, Mingoli A, Prosperi P. Colonic Resection, Stoma, or Self-expanding Metal Stents for Obstructive Left Colon Cancer: the CROSCO-1 study protocol. Minerva Surg 2024; 79:7-14. [PMID: 37705392 DOI: 10.23736/s2724-5691.23.09969-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the most common cancers worldwide. There are several causes of a mechanical left bowel obstructive but CRC accounts for approximately 50% of cases and in 10-30% of whom it is the presenting syndrome. In most cases, the left colon is involved. At present, the range of therapeutic alternatives in the management of obstructive left CRC in emergency conditions (primary resection vs. staged resection with applied self-expanding metallic stents) is broad, whereas internationally validated clinical recommendations in each condition are still lacking. This enormous variability affects the scientific evidence on both the immediate and long-term surgical and oncological outcomes. METHODS CROSCO-1 (Colonic Resection, Stoma or Self-expanding Metal Stents for Obstructive Left Colon Cancer) study is a national, multi-center, prospective observational study intending to compare the clinical results of all these therapeutic regimens in a cohort of patients treated for obstructive left-sided CRC. RESULTS The primary aim of the CROSCO-1 study is the 1-year stoma rate of patients undergoing primary emergency surgical resection (Hartmann procedure or primary resection and anastomosis) compared with patients undergoing staged resection. Secondary outcomes are 30-day and 90-day major morbidity and mortality, 1-year quality of life and the timing of chemotherapy initiation in the two groups. Future CROSCO studies will follow in which, instead, we will evaluate the long-term oncological outcomes of the two treatment strategies. CONCLUSIONS The results of a large prospective cohort study which will analyze what really happens in the common clinical practice of managing patients with obstructive left CRC will have the aim of understanding which is the best strategy in terms of surgical and oncological outcomes. Indeed, the CROSCO-1 study will analyze the early surgical outcomes for patients with obstructed left CRC. Future CROSCO studies will follow in which, instead, we will evaluate the long-term oncological outcomes of the two treatment strategies.
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Affiliation(s)
- Alessio Giordano
- Emergency Surgery Unit, Emergency Department, Careggi University Hospital, Florence, Italy -
| | - Mauro Podda
- General Surgery Unit, Department of Surgery, University Hospital of Cagliari, Cagliari, Italy
| | - Giulia Montori
- Department of General Surgery, ULSS2 Marca Trevigiana, Vittorio Veneto, Treviso, Italy
| | - Emanuele Botteri
- General Surgery Unit, ASST Spedali Civili, Montichiari, Brescia, Italy
| | - Paola Fugazzola
- Division of General Surgery, IRCCS San Matteo Polyclinic Foundation, Pavia, Italy
| | - Monica Ortenzi
- Department of General Surgery, Polytechnical University of Marche, Ancona, Italy
| | - Mario Guerrieri
- Department of General Surgery, Polytechnical University of Marche, Ancona, Italy
| | - Nereo Vettoretto
- General Surgery Unit, ASST Spedali Civili, Montichiari, Brescia, Italy
| | - Ferdinando Agresta
- Department of General Surgery, ULSS2 Marca Trevigiana, Vittorio Veneto, Treviso, Italy
| | - Alberto Sartori
- Department of General Surgery, Montebelluna Hospital, Montebelluna, Treviso, Italy
| | - Carlo Bergamini
- Emergency Surgery Unit, Emergency Department, Careggi University Hospital, Florence, Italy
| | - Jacopo Martellucci
- Emergency Surgery Unit, Emergency Department, Careggi University Hospital, Florence, Italy
| | - Anna Guariniello
- Emergency Surgery Unit, Department of Surgery, S. Maria delle Croci Hospital, Ravenna, Italy
| | - Pietro Fransvea
- Emergency Surgery and Trauma Department, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy
| | | | - Marco Scatizzi
- General Surgery Unit, Department of Surgery, Santa Maria Annunziata and Serristori Hospital, Florence, Italy
| | - Fausto Catena
- Department of General and Emergency Surgery, Bufalini Hospital, Cesena, Italy
| | - Federico Coccolini
- Department of Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy
| | - Luca Ansaloni
- Division of General Surgery, IRCCS San Matteo Polyclinic Foundation, Pavia, Italy
| | - Massimo Sartelli
- General Surgery Unit, Department of Surgery, Macerata Hospital, Macerata, Italy
| | - Paolo Sapienza
- Emergency Department, Umberto I Polyclinic Hospital, Sapienza University, Rome, Italy
| | - Andrea Mingoli
- Emergency Department, Umberto I Polyclinic Hospital, Sapienza University, Rome, Italy
| | - Paolo Prosperi
- Emergency Surgery Unit, Emergency Department, Careggi University Hospital, Florence, Italy
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11
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Beniwal SS, Lamo P, Kaushik A, Lorenzo-Villegas DL, Liu Y, MohanaSundaram A. Current Status and Emerging Trends in Colorectal Cancer Screening and Diagnostics. BIOSENSORS 2023; 13:926. [PMID: 37887119 PMCID: PMC10605407 DOI: 10.3390/bios13100926] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/27/2023] [Accepted: 10/07/2023] [Indexed: 10/28/2023]
Abstract
Colorectal cancer (CRC) is a prevalent and potentially fatal disease categorized based on its high incidences and mortality rates, which raised the need for effective diagnostic strategies for the early detection and management of CRC. While there are several conventional cancer diagnostics available, they have certain limitations that hinder their effectiveness. Significant research efforts are currently being dedicated to elucidating novel methodologies that aim at comprehending the intricate molecular mechanism that underlies CRC. Recently, microfluidic diagnostics have emerged as a pivotal solution, offering non-invasive approaches to real-time monitoring of disease progression and treatment response. Microfluidic devices enable the integration of multiple sample preparation steps into a single platform, which speeds up processing and improves sensitivity. Such advancements in diagnostic technologies hold immense promise for revolutionizing the field of CRC diagnosis and enabling efficient detection and monitoring strategies. This article elucidates several of the latest developments in microfluidic technology for CRC diagnostics. In addition to the advancements in microfluidic technology for CRC diagnostics, the integration of artificial intelligence (AI) holds great promise for further enhancing diagnostic capabilities. Advancements in microfluidic systems and AI-driven approaches can revolutionize colorectal cancer diagnostics, offering accurate, efficient, and personalized strategies to improve patient outcomes and transform cancer management.
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Affiliation(s)
| | - Paula Lamo
- Escuela Superior de Ingeniería y Tecnología, Universidad Internacional de La Rioja, 26006 Logroño, Spain
| | - Ajeet Kaushik
- NanoBioTech Laboratory, Department of Environmental Engineering, Florida Polytechnic University, Lakeland, FL 33805, USA
| | | | - Yuguang Liu
- Departments of Physiology and Biomedical Engineering, Immunology and Surgery, Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA
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12
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Chiang PL, Hao WR, Hong HJ, Chen CC, Chiu CC, Fang YA, Yang TL, Lai YH, Chen MY, Hsu MH, Chiou KR, Lin KJ, Yang TY, Hsiu H, Liu JC. The Effects of Different Types of Sleep Disorder on Colorectal Cancer: A Nationwide Population-Based Cohort Study. Cancers (Basel) 2023; 15:4728. [PMID: 37835421 PMCID: PMC10571828 DOI: 10.3390/cancers15194728] [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: 08/18/2023] [Revised: 09/19/2023] [Accepted: 09/20/2023] [Indexed: 10/15/2023] Open
Abstract
The impact of sleep disorders (SDs), particularly sleep apnea (SA), on the development of colorectal cancer (CRC) has been the subject of significant research. However, the potential contribution of other SDs to the incidence of CRC remains unexplored. The objective of this study was to examine the effects of SDs on the risk of developing CRC. This study assessed CRC risk among individuals diagnosed with SDs compared with age- and sex-matched unaffected individuals. A longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) encompassing 177,707 individuals diagnosed with SDs and 177,707 matched controls. Cox proportional hazard regression analysis was used to determine the relative increased risk of CRC in individuals with SDs and specific subgroups of SDs. The CRC incidences were 1.32-fold higher (95% CI 1.23-1.42) in the overall SD cohort, 1.17-fold higher (95% CI 0.82-1.68) in the SA cohort, 1.42-fold higher (95% CI 1.31-1.55) in the insomnia cohort, 1.27-fold higher (95% CI 1.17-1.38) in the sleep disturbance cohort, and 1.00-fold higher (95% CI 0.77-1.29) in the other SD cohort, after adjusting for age, sex, and comorbidities.
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Affiliation(s)
- Po-Lin Chiang
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Department of General Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Wen-Rui Hao
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Hong-Jye Hong
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung City 404333, Taiwan
| | - Chun-Chao Chen
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Chun-Chih Chiu
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
| | - Yu-Ann Fang
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
| | - Tsung-Lin Yang
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Yu-Hsin Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (Y.-H.L.)
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei City 23561, Taiwan
| | - Ming-Yao Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; (Y.-H.L.)
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei City 23561, Taiwan
| | - Min-Huei Hsu
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei 11031, Taiwan
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
| | - Kuan-Rau Chiou
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Kuan-Jie Lin
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
- Division of Cardiovascular Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
| | - Tsung-Yeh Yang
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
| | - Hsin Hsiu
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, No. 43, Section 4, Keelung Road, Taipei 10607, Taiwan
| | - Ju-Chi Liu
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan (T.-Y.Y.)
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan (K.-J.L.)
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
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Attia H, ElBanna SA, Khattab RA, Farag MA, Yassin AS, Aziz RK. Integrating Microbiome Analysis, Metabolomics, Bioinformatics, and Histopathology to Elucidate the Protective Effects of Pomegranate Juice against Benzo-alpha-pyrene-Induced Colon Pathologies. Int J Mol Sci 2023; 24:10691. [PMID: 37445869 DOI: 10.3390/ijms241310691] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 06/19/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Polycyclic aromatic hydrocarbons, e.g., benzo[a]pyrene (BaP), are common dietary pollutants with potential carcinogenic activity, while polyphenols are potential chemopreventive antioxidants. Although several health benefits are attributed to polyphenol-rich pomegranate, little is known about its interaction with BaP. This study integrates histochemical, microbiomic, and metabolomic approaches to investigate the protective effects of pomegranate juice from BaP-induced pathologies. To this end, 48 Sprague-Dawley rats received, for four weeks, either pomegranate, BaP, both, or neither (n = 12 rats per group). Whereas histochemical examination of the colon indicated tissue damage marked by mucin depletion in BaP-fed animals, which was partially restored by administration of pomegranate juice, the fecal microbiome and metabolome retained their resilience, except for key changes related to pomegranate and BaP biotransformation. Meanwhile, dramatic microbiome restructuring and metabolome shift were observed as a consequence of the elapsed time (age factor). Additionally, the analysis allowed a thorough examination of fecal microbiome-metabolome associations, which delineated six microbiome clusters (marked by a differential abundance of Lactobacillaceae and Prevotellaceae, Rumincococcaceae, and Erysipelotrichaceae) and two major metabolome clusters (a sugar- and amino-acids-dominated metabotype vs. a cluster of fatty acids and hydrocarbons), with sugar alcohols maintaining a unique signature. In conclusion, using paired comparisons to minimize inter-individual animal variations allowed the dissection of temporal vs. treatment-derived variations. Microbiome-metabolome association clusters may be further exploited for metabotype prediction and gut-health biomarker discovery.
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Affiliation(s)
- Heba Attia
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Shahira A ElBanna
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Rania A Khattab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Mohamed A Farag
- Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Aymen S Yassin
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
| | - Ramy K Aziz
- Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Center for Genome and Microbiome Research, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- Microbiology and Immunology Research Program, Children's Cancer Hospital Egypt 57357, Cairo 11617, Egypt
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14
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Ren Q, Chen Y, Shao X, Guo L, Xu X. Lymph nodes primary staging of colorectal cancer in 18F-FDG PET/MRI: a systematic review and meta-analysis. Eur J Med Res 2023; 28:162. [PMID: 37143144 PMCID: PMC10157899 DOI: 10.1186/s40001-023-01124-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 04/23/2023] [Indexed: 05/06/2023] Open
Abstract
OBJECTIVE To assess the diagnostic efficacy of 18F-FDG PET/MRI for lymph node (LN) metastasis primary staging in patients with colorectal cancer (CRC). METHODS This study was conducted and reported in accordance with the PRISMA-DTA statement. Electronic databases (PubMed, Embase, Cochrane Library) were searched for studies on 18F-FDG PET/MRI for diagnosing LN metastasis. The pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to assess the diagnostic performance. Heterogeneity was identified and processed using meta-regression and sensitivity analysis. All data analyses were performed via STATA 15 and Meta-Disc 1.4 software. RESULTS There were finally 7 studies included, involving a total of 184 patients. The Spearman rank correlation coefficient was 0.108 (P = 0.818), with no threshold-effect observed. The pooled SEN was 0.81 (95%CI 0.66-0.90) and the SPE was 0.89 (95% CI 0.73-0.96). In sub-groups, prospective groups demonstrated to have the highest SEN of 0.92 (95%CI 0.79-1.00). The studies conducted by Catalano et al. and Kang et al. were considered to be potential sources of heterogeneity. CONCLUSION 18F-FDG PET/MRI has shown remarkable diagnostic performance in identification of LN metastases in newly diagnosed CRC patients. It would be of great application value for the primary staging of CRC lymph node metastases.
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Affiliation(s)
- Qingwei Ren
- Department of Gastroenterology, Dongyang Hospital of Traditional Chinese Medicine, Dongyang, China
| | - Yanyan Chen
- Department of Medical Oncology, Dongyang Women & Children Hospital, No. 40, Wuning East Road, Dongyang, 322100, China.
| | - Xuejun Shao
- Department of Gastroenterology, Dongyang Hospital of Traditional Chinese Medicine, Dongyang, China
| | - Lanzhong Guo
- Department of Medical Oncology, Dongyang Women & Children Hospital, No. 40, Wuning East Road, Dongyang, 322100, China
| | - Xinxin Xu
- Department of Gastroenterology, Dongyang Hospital of Traditional Chinese Medicine, Dongyang, China
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15
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Ploukou S, Birtsou C, Gavana M, Tsakiridou K, Dandoulakis M, Symintiridou D, Moraiti E, Parisis A, Smyrnakis E. General Practitioners’ attitudes and beliefs on barriers to
colorectal cancer screening: A qualitative study. POPULATION MEDICINE 2023. [DOI: 10.18332/popmed/161128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023] Open
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16
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General practice-based cancer research publications: a bibliometric analysis 2013-2019. Br J Gen Pract 2022; 73:e133-e140. [PMID: 36702582 PMCID: PMC9762764 DOI: 10.3399/bjgp.2022.0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 09/09/2022] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND General practice plays a critical role in the prevention, diagnosis, management, and survivorship care of patients with cancer. Mapping research outputs over time provides valuable insights into the evolving role of general practice in cancer care. AIM To describe and compare the distribution of cancer in general practice research publications by country, cancer type, area of the cancer continuum, author sex, and journal impact factor. DESIGN AND SETTING A bibliometric analysis using a systematic approach to identify publications. METHOD MEDLINE and Embase databases were searched for studies published between 2013 and 2019, which reported on cancer in general practice. Included studies were mapped to the cancer continuum framework. Descriptive statistics were used to present data from the included studies. RESULTS A total of 2798 publications were included from 714 journals, spanning 79 countries. The publication rate remained stable over this period. Overall, the US produced the most publications (n = 886, 31.7%), although, per general population capita, Denmark produced nearly 10 times more publications than the US (20.0 publications per million compared with 2.7 publications per million). Research across the cancer continuum varied by country, but, overall, most studies focused on cancer screening, diagnosis, and survivorship. More than half of included studies used observational study designs (n = 1523, 54.4%). Females made up 66.5% (n = 1304) of first authors, but only 47.0% (n = 927) of last authors. CONCLUSION Cancer in general practice is a stable field where research is predominantly observational. There is geographical variation in the focus of cancer in general practice research, which may reflect different priorities and levels of investment between countries. Overall, these results support future consideration of how to improve under-represented research areas and the design, conduct, and translation of interventional research.
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Tsai HY, Bronner MP, March JK, Valentine JF, Shroyer NF, Lai LA, Brentnall TA, Pan S, Chen R. Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer. Cancer Lett 2022; 549:215915. [PMID: 36113636 PMCID: PMC11262000 DOI: 10.1016/j.canlet.2022.215915] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 09/02/2022] [Accepted: 09/08/2022] [Indexed: 01/12/2023]
Abstract
Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between the expression of TRAP1 and antioxidant genes in colon tumor tissues using the GSE106582 database. Using a luciferase reporter assay, we detected increased transcriptional activation of antioxidant response elements (AREs) in G-TPP-treated DLD1 and RKO cells but not in SW48 cells. We found that G-TPP induced upregulation of GRP78, CHOP and PARP cleavage in G-TPP-sensitive cells (SW48). In contrast, G-TPP treatment of G-TPP-resistant cells (DLD1 and RKO) resulted in excessive activation of the antioxidant gene NRF2, leading to ROS detoxification and improved cell survival. The NRF2 target genes HO1 and NQO1 were upregulated in G-TPP-treated DLD1 cells, making the cells more resistant to G-TPP treatment. Furthermore, treatment with both a NRF2 inhibitor and a TRAP1 inhibitor led to excessive ROS production and exacerbated G-TPP-induced cell death in G-TPP-resistant cells. Taken together, dual targeting of TRAP1 and NRF2 may potentially overcome colon cancer resistance by raising cellular ROS levels above the cytotoxic threshold.
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Affiliation(s)
- Hong-Yuan Tsai
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
| | - Mary P Bronner
- Department of Pathology, University of Utah, Salt Lake City, UT, USA; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Jordon K March
- Department of Pathology, University of Utah, Salt Lake City, UT, USA
| | - John F Valentine
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA
| | - Noah F Shroyer
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Lisa A Lai
- Department of Medicine, University of Washington, Seattle, WA, USA
| | | | - Sheng Pan
- Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Ru Chen
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
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18
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Zhang C, Stampfl-Mattersberger M, Ruckser R, Sebesta C. Kolorektales Karzinom. Wien Med Wochenschr 2022; 173:216-220. [DOI: 10.1007/s10354-022-00975-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 09/06/2022] [Indexed: 11/09/2022]
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Bispo IMC, Granger HP, Almeida PP, Nishiyama PB, de Freitas LM. Systems biology and OMIC data integration to understand gastrointestinal cancers. World J Clin Oncol 2022; 13:762-778. [PMID: 36337313 PMCID: PMC9630993 DOI: 10.5306/wjco.v13.i10.762] [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: 03/16/2021] [Revised: 05/22/2021] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) cancers are a set of diverse diseases affecting many parts/ organs. The five most frequent GI cancer types are esophageal, gastric cancer (GC), liver cancer, pancreatic cancer, and colorectal cancer (CRC); together, they give rise to 5 million new cases and cause the death of 3.5 million people annually. We provide information about molecular changes crucial to tumorigenesis and the behavior and prognosis. During the formation of cancer cells, the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and CRC. The genomically stable subtype is observed in GC and pancreatic cancer. Besides these genomic subtypes, CRC has epigenetic modification (hypermethylation) associated with a poor prognosis. The pathway information highlights the functions shared by GI cancers such as apoptosis; focal adhesion; and the p21-activated kinase, phosphoinositide 3-kinase/Akt, transforming growth factor beta, and Toll-like receptor signaling pathways. These pathways show survival, cell proliferation, and cell motility. In addition, the immune response and inflammation are also essential elements in the shared functions. We also retrieved information on protein-protein interaction from the STRING database, and found that proteins Akt1, catenin beta 1 (CTNNB1), E1A binding protein P300, tumor protein p53 (TP53), and TP53 binding protein 1 (TP53BP1) are central nodes in the network. The protein expression of these genes is associated with overall survival in some GI cancers. The low TP53BP1 expression in CRC, high EP300 expression in esophageal cancer, and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor prognosis. The Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival rates. In conclusion, GI cancers are very diverse at the molecular level. However, the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug targets.
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Affiliation(s)
- Iasmin Moreira Costa Bispo
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Henry Paul Granger
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Palloma Porto Almeida
- Division of Experimental and Translational Research, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, Brazil
| | - Patricia Belini Nishiyama
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Leandro Martins de Freitas
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
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Santos MO, Alves MDC, Lins Neto MADF, Moura FA. MUSCLE DEPLETED OBESITY IN INDIVIDUALS SCREENED FOR COLORECTAL CÂNCER. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:450-455. [PMID: 36515341 DOI: 10.1590/s0004-2803.202204000-81] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 07/20/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most incident cancer in the world and the second leading cause of cancer death. Significant decreases in incidence and mortality can be achieved by reducing risk factors and adhering to healthy lifestyle recommendations, as well as screening for the disease. OBJECTIVE To evaluate the clinical nutritional profile of individuals at medium risk screened for CRC residing in the city of Piranhas/Alagoas. METHODS Cross-sectional study conducted from September to October 2020, with individuals at medium risk for CRC, of both sexes and aged between 50 and 70 years old. Participants were screened for CRC with fecal immunochemical testing (FIT) and colonoscopy. Personal, socioeconomic, clinical, lifestyle and nutritional assessment data were collected. The latter was performed using anthropometric data (weight, height, arm circumference and triceps skinfold thickness), body composition (bioimpedance) and physical examination. Descriptive analysis of data frequencies and dichotomization according to the presence or absence of overweight was performed, followed by comparison of means and medians and frequencies by chi-square or Fisher's exact test. RESULTS In total, 82 people agreed to undergo the clinical nutritional assessment, most of them female (56.1%; n=46), adults (56.1%; n=46), with a mean age of 59.02 years (±6.30 SD). Pre-cancerous lesions were identified in 54.5% (n=42) of those screened, 52.4% (n=43) were smokers or former smokers, and 65.9% (n=54) did not practice scheduled physical activity. Nutritional assessment showed that 64.6% (n=53) were overweight according to body mass index. On the other hand, the muscle mass, % arm muscle circumference adequacy and body muscle mass (kg) markers showed that 32.9% (n=27) and 47.6% (n=39) of the subjects were muscle depleted, respectively. Above all, overweight participants had, in parallel, lower muscle mass (P<0.05), suggesting sarcopenic obesity in this population. CONCLUSION Obesity is one of the main risk factors for CRC; when concomitant with sarcopenia, it favors worse health outcomes. In this context, evidence shows the need to assess muscle composition in people with obesity, especially through other methods of assessing body composition. Our results add to the evidence on the importance of the population being guided about screening and adherence to healthy lifestyle recommendations, especially strategies aimed at weight control and the practice of physical activity.
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Affiliation(s)
- Monise Oliveira Santos
- Universidade Federal de Alagoas, Programa de Pós-graduação em Nutrição (PPGNUT), Maceió, AL, Brasil
| | - Marla de Cerqueira Alves
- Universidade Federal de Alagoas, Programa de Pós-graduação em Nutrição (PPGNUT), Maceió, AL, Brasil
| | | | - Fabiana Andréa Moura
- Universidade Federal de Alagoas, Programa de Pós-graduação em Nutrição (PPGNUT), Maceió, AL, Brasil.,Universidade Federal de Alagoas, Programa de Pós-graduação em Ciências Médicas (PPGCM), Maceió, AL, Brasil
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21
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Exploring the Interplay between Metabolism and Tumor Microenvironment Based on Four Major Metabolism Pathways in Colon Adenocarcinoma. JOURNAL OF ONCOLOGY 2022; 2022:2159794. [PMID: 35747126 PMCID: PMC9213191 DOI: 10.1155/2022/2159794] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 05/11/2022] [Accepted: 05/14/2022] [Indexed: 11/17/2022]
Abstract
Tumor metabolism plays a critical role in tumor progression. However, the interaction between metabolism and tumor microenvironment (TME) has not been comprehensively revealed in colon adenocarcinoma (COAD). We used unsupervised consensus clustering to establish three molecular subtypes (clusters) based on the enrichment score of four major metabolism pathways in TCGA-COAD dataset. GSE17536 was used as a validation dataset. Single-cell RNA sequencing data (GSE161277) was employed to further verify the reliability of subtyping and characterize the correlation between metabolism and TME. Three clusters were identified and they performed distinct prognosis and molecular features. Clust3 had the worst overall survival and the highest enrichment score of glycolysis. 86 differentially expressed genes (DEGs) were identified, in which 11 DEGs were associated with favorable prognosis and 75 DEGs were associated with poor prognosis. Striking correlations were observed between hypoxia and glycolysis, clust3 and hypoxia, and clust3 and angiogenesis (P < 0.001).We constructed a molecular subtyping system which was effective and reliable for predicting COAD prognosis. The 86 identified key DEGs may be greatly involved in COAD progression, and they provide new perspectives and directions for further understanding the mechanism of metabolism in promoting aggressive phenotype by interacting with TME.
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22
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Diagnostic performance of [ 18F]-FDG PET/MR in evaluating colorectal cancer: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2022; 49:4205-4217. [PMID: 35705874 DOI: 10.1007/s00259-022-05871-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/09/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE To calculate the diagnostic performance of [18F]-FDG PET/MR in colorectal cancer (CRC). METHODS This study was designed following the PRISMA-DTA guidelines. To be included, published original articles (until December 31, 2021) that met the following criteria were considered eligible: (1) evaluated [18F]-FDG PET/MR as the diagnostic method to detect CRC; (2) compared [18F]-FDG PET/MR with histopathology as the reference standard, or clinical/imaging composite follow-up when pathology was not available; (3) provided adequate crude data for meta-analysis. The diagnostic pooled measurements were calculated at patient and lesion levels. Regarding sub-group analysis, diagnostic measurements were calculated in "TNM staging," "T staging," "N staging," "M staging," and "liver metastasis" sub-groups. Additionally, we calculated the pooled performances in "rectal cancer: patient-level" and "rectal cancer: lesion-level" sub-groups. A hierarchical method was used to pool the performances. The bivariate model was conducted to find the summary points. Analyses were performed using STATA 16. RESULTS A total of 1534 patients from 18 studies were entered. The pooled sensitivities in CRC lesion detection (tumor, lymph nodes, and metastases) were 0.94 (95%CI: 0.89-0.97) and 0.93 (95%CI: 0.82-0.98) at patient-level and lesion-level, respectively. The pooled specificities were 0.89 (95%CI: 0.84-0.93) and 0.95 (95%CI: 0.90-0.98) at patient-level and lesion-level, respectively. In sub-groups, the highest sensitivity (0.97, 95%CI: 0.86-0.99) and specificity (0.99, 95%CI: 0.84-1.00) were calculated for "M staging" and "rectal cancer: lesion-level," respectively. The lowest sensitivity (0.81, 95%CI: 0.65-0.91) and specificity (0.79, 95%CI: 0.52-0.93) were calculated for "N staging" and "T staging," respectively. CONCLUSION This meta-analysis showed an overall high diagnostic performance for [18F]-FDG PET/MR in detecting CRC lesions/metastases. Thus, this modality can play a significant role in several clinical scenarios in CRC staging and restaging. Specifically, one of the main strengths of this modality is ruling out the existence of CRC lesions/metastases. Finally, the overall diagnostic performance was not found to be affected in the post-treatment setting.
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23
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Plasma CXCL3 Levels Are Associated with Tumor Progression and an Unfavorable Colorectal Cancer Prognosis. J Immunol Res 2022; 2022:1336509. [PMID: 35664357 PMCID: PMC9162872 DOI: 10.1155/2022/1336509] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/26/2022] [Accepted: 04/08/2022] [Indexed: 12/01/2022] Open
Abstract
Background The CXC chemokines belong to a unique family of chemotactic cytokines that influence the initiation, progression, and clinical outcome of many tumor types. Herein, we investigated the association of the CXC-chemokine ligand 3 (CXCL3) with tumor progression and an unfavorable prognosis for colorectal cancer (CRC). Methods The quantitative real-time polymerase chain reaction was used to explore the expression of CXCL3 in CRC tissue, adjacent tissue, and plasma. The usefulness of plasma levels of CXCL3 for the diagnosis of CRC was evaluated by receiver operating characteristic curve analysis. Pearson's correlation analysis assessed relationships among plasma CXCL3, cancer tissue CXCL3, and plasma carcinoembryonic antigen (CEA). Kaplan–Meier analysis was used to assess the survival of CRC patients with high and low expression levels of CXCL3. Survival differences were compared by log-rank test. Results Initial analysis of the GSE156720 dataset identified CXCL3 as the most enriched CXCL gene in CRC patients. Higher CXCL3 levels were detected in CRC tissue than in adjacent tissue (P < 0.001). Compared to healthy controls, CRC patient plasma CXCL3 levels were higher (P < 0.001). The area under the curve was 0.81 with a sensitivity of 0.71 and specificity of 0.82, distinguishing CRC from other tumor types. Plasma CXCL3 was positively related to CXCL3 in cancer tissue (r = 0.78, P < 0.01), and also to plasma CEA (r = 0.50, P < 0.01). Plasma CXCL3 was also related to tumor size (P = 0.034), staging (P < 0.001), tumor stage (P = 0.003), differentiation (P = 0.001), and lymph node metastasis (P = 0.007), but not to sex (P = 0.853), age (P = 0.691), tumor site (P = 1.347), or distant metastasis (P = 1.218). Conclusions CXCL3 levels were increased in CRC patients, with plasma CXCL3 levels associated with tumor progression and an unfavorable CRC prognosis. The results of this study suggest that plasma CXCL3 may be a novel diagnostic and prognostic biomarker for CRC.
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24
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Zhao Z, Zhou Y, Jiang M, Dang L. Application Value of MRI Combined with MSCT in Diagnosis and Staging of Colon Carcinoma. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:2593844. [PMID: 35651927 PMCID: PMC9150994 DOI: 10.1155/2022/2593844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/12/2022] [Accepted: 04/20/2022] [Indexed: 12/04/2022]
Abstract
Objective To clarify the application value of magnetic resonance imaging (MRI) combined with multislice spiral computed tomography (MSCT) in the diagnosis and staging of colon carcinoma (CC). Methods A total of 103 patients with histopathologically diagnosed CC were enrolled. Patient clinical and imaging data were collected, and MRI and MSCT images were analyzed to assess the accuracy of MRI, MSCT, and their combination in diagnosing tumor (T) staging of CC. Results Among the 103 cases of histopathologically diagnosed CC, 26 cases (25.24) were in stage T1-2, 72 cases (69.90) were in stage T3, and 5 cases (4.85) were in stage T4. The accuracy of MRI in diagnosing stage T1-2, T3, and T4 was 80.77%, 88.89%, and 60.00%, respectively, with an average of 76.55%. The accuracy rates of MSCT in diagnosing T1-2, T3, and T4 stages were 73.08%, 90.27%, and 60.00%, respectively, with an average of 74.45%. The accuracy rates of MRI+MSCT in diagnosing T1-2, T3, and T4 were 88.46%, 95.83%, and 80.00%, respectively, with an average of 88.10%. Conclusions Compared with single use of MRI or MSCT, MRI+MSCT provides accurate imaging data with higher accuracy, which is more helpful for the T-staging evaluation of CC.
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Affiliation(s)
- Zhiwei Zhao
- Medical Imaging Center, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, 830011 Xinjiang, China
| | - Yong Zhou
- Medical Imaging Center, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Urumqi, 830011 Xinjiang, China
| | - Meng Jiang
- Department of Gastroenterology, People's Hospital of Tongchuan, Tongchuan, 727000 Shaanxi, China
| | - Ling Dang
- Department of Gastroenterology, People's Hospital of Tongchuan, Tongchuan, 727000 Shaanxi, China
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Dikeocha IJ, Al-Kabsi AM, Chiu HT, Alshawsh MA. Faecalibacterium prausnitzii Ameliorates Colorectal Tumorigenesis and Suppresses Proliferation of HCT116 Colorectal Cancer Cells. Biomedicines 2022; 10:biomedicines10051128. [PMID: 35625865 PMCID: PMC9138996 DOI: 10.3390/biomedicines10051128] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/07/2022] [Accepted: 05/09/2022] [Indexed: 12/12/2022] Open
Abstract
Faecalibacterium prausnitzii is one of the most abundant commensals of gut microbiota that is not commonly administered as a probiotic supplement. Being one of the gut’s major butyrate-producing bacteria, its clinical significance and uses are on the rise and it has been shown to have anti-inflammatory and gut microbiota-modulating properties in the treatment of inflammatory bowel illness, Crohn’s disease, and colorectal cancer. Colorectal cancer (CRC) is a silent killer disease that has become one of the leading causes of cancer-related death worldwide. This study aimed to evaluate the anti-tumorigenic and antiproliferative role of F. prausnitzii as well as to study its effects on the diversity of gut microbiota in rats. Findings showed that F. prausnitzii probiotic significantly reduced the colonic aberrant crypt foci frequency and formation in Azoxymethane (AOM)-induced CRC in rats. In addition, the administration of F. prausnitzii lowered the lipid peroxidation levels in the colon tissues. For in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, the cell-free supernatant of F. prausnitzii suppressed the growth of HCT116 colorectal cancer cells in a time/dose-dependent manner. 16S rRNA gene sequencing using rat stool samples showed that the administration of F. prausnitzii modulated the gut microbiota of the rats and enhanced its diversity. Hence, these findings suggest that F. prausnitzii as a probiotic supplement can be used in CRC prevention and management; however, more studies are warranted to understand its cellular and molecular mechanisms of action.
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Affiliation(s)
- Ifeoma Julieth Dikeocha
- Faculty of Medicine, University of Cyberjaya, Persiaran Bestari, Cyberjaya 63000, Malaysia; (I.J.D.); (A.M.A.-K.)
| | | | - Hsien-Tai Chiu
- Department of Chemistry, National Cheng Kung University, Tainan City 70101, Taiwan;
- Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan
| | - Mohammed Abdullah Alshawsh
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
- Correspondence:
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Weighted correlation network analysis revealed novel long non-coding RNAs for colorectal cancer. Sci Rep 2022; 12:2990. [PMID: 35194111 PMCID: PMC8863977 DOI: 10.1038/s41598-022-06934-w] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 02/07/2022] [Indexed: 12/25/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, which after breast, lung and, prostate cancers, is the fourth prevalent cancer in the United States. Long non-coding RNAs (lncRNAs) have an essential role in the pathogenesis of CRC. Therefore, bioinformatics studies on lncRNAs and their target genes have potential importance as novel biomarkers. In the current study, publicly available microarray gene expression data of colorectal cancer (GSE106582) was analyzed with the Limma, Geoquery, Biobase package. Afterward, identified differentially expressed lncRNAs and their target genes were inserted into Weighted correlation network analysis (WGCNA) to obtain modules and hub genes. A total of nine differentially expressed lncRNAs (LINC01018, ITCH-IT, ITPK1-AS1, FOXP1-IT1, FAM238B, PAXIP1-AS1, ATP2B1-AS1, MIR29B2CHG, and SNHG32) were identified using microarray data analysis. The WGCNA has identified several hub genes for black (LMOD3, CDKN2AIPNL, EXO5, ZNF69, BMS1P5, METTL21A, IL17RD, MIGA1, CEP19, FKBP14), blue (CLCA1, GUCA2A, UGT2B17, DSC2, CA1, AQP8, ITLN1, BEST4, KLF4, IQCF6) and turquoise (PAFAH1B1, LMNB1, CACYBP, GLO1, PUM3, POC1A, ASF1B, SDCCAG3, ASNS, PDCD2L) modules. The findings of the current study will help to improve our understanding of CRC. Moreover, the hub genes that we have identified could be considered as possible prognostic/diagnostic biomarkers. This study led to the determination of nine lncRNAs with no previous association with CRC development.
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Colorectal Cancer. Fam Med 2022. [DOI: 10.1007/978-3-030-54441-6_183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Razi Soofiyani S, Ahangari H, Soleimanian A, Babaei G, Ghasemnejad T, Safavi SE, Eyvazi S, Tarhriz V. The role of circadian genes in the pathogenesis of colorectal cancer. Gene 2021; 804:145894. [PMID: 34418469 DOI: 10.1016/j.gene.2021.145894] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/07/2021] [Accepted: 08/06/2021] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is the third most frequent cancer in human beings and is also the major cause of death among the other gastrointestinal cancers. The exact mechanisms of CRC development in most patients remains unclear. So far, several genetically, environmental and epigenetically risk factors have been identified for CRC development. The circadian rhythm is a 24-h rhythm that drives several biologic processes. The circadian system is guided by a central pacemaker which is located in the suprachiasmatic nucleus (SCN) in the hypothalamus. Circadian rhythm is regulated by circadian clock genes, cytokines and hormones like melatonin. Disruptions in biological rhythms are known to be strongly associated with several diseases, including cancer. The role of the different circadian genes has been verified in various cancers, however, the pathways of different circadian genes in the pathogenesis of CRC are less investigated. Identification of the details of the pathways in CRC helps researchers to explore new therapies for the malignancy.
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Affiliation(s)
- Saiedeh Razi Soofiyani
- Clinical Research Development Unit of Sina Educational, Research and Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran; Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Ahangari
- Department of Food Science and Technology, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Soleimanian
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Ghader Babaei
- Department of Clinical Biochemistry, Urmia University of Medical Sciences, Urmia, Iran
| | - Tohid Ghasemnejad
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Esmaeil Safavi
- Faculty of Veternary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran; Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Shirin Eyvazi
- Biotechnology Research Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran; Department of Biology, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
| | - Vahideh Tarhriz
- Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
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Khalyfa AA, Punatar S, Aslam R, Yarbrough A. Exploring the Inflammatory Pathogenesis of Colorectal Cancer. Diseases 2021; 9:79. [PMID: 34842660 PMCID: PMC8628792 DOI: 10.3390/diseases9040079] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/21/2021] [Accepted: 10/23/2021] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer is one of the most commonly diagnosed cancers worldwide. Traditionally, mechanisms of colorectal cancer formation have focused on genetic alterations including chromosomal damage and microsatellite instability. In recent years, there has been a growing body of evidence supporting the role of inflammation in colorectal cancer formation. Multiple cytokines, immune cells such T cells and macrophages, and other immune mediators have been identified in pathways leading to the initiation, growth, and metastasis of colorectal cancer. Outside the previously explored mechanisms and pathways leading to colorectal cancer, initiatives have been shifted to further study the role of inflammation in pathogenesis. Inflammatory pathways have also been linked to some traditional risk factors of colorectal cancer such as obesity, smoking and diabetes, as well as more novel associations such as the gut microbiome, the gut mycobiome and exosomes. In this review, we will explore the roles of obesity and diet, smoking, diabetes, the microbiome, the mycobiome and exosomes in colorectal cancer, with a specific focus on the underlying inflammatory and metabolic pathways involved. We will also investigate how the study of colon cancer from an inflammatory background not only creates a more holistic and inclusive understanding of this disease, but also creates unique opportunities for prevention, early diagnosis and therapy.
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Affiliation(s)
- Ahamed A Khalyfa
- Department of Gastroenterology, Franciscan Health, Olympia Fields, IL 60461, USA; (S.P.); (R.A.)
| | | | | | - Alex Yarbrough
- Department of Gastroenterology, Franciscan Health, Olympia Fields, IL 60461, USA; (S.P.); (R.A.)
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30
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Buhagiar A, Seria E, Borg M, Borg J, Ayers D. Overview of microRNAs as liquid biopsy biomarkers for colorectal cancer sub-type profiling and chemoresistance. CANCER DRUG RESISTANCE (ALHAMBRA, CALIF.) 2021; 4:934-945. [PMID: 35582382 PMCID: PMC8992439 DOI: 10.20517/cdr.2021.62] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/01/2021] [Accepted: 09/24/2021] [Indexed: 11/27/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide. It has also been demonstrated that over the last ten years the incidence of CRC among younger people below the age of 50 is also increasing. Screening for colorectal cancer is of utmost importance; the rationale behind screening is to target the malignancy and reduce the incidence and mortality of the disease. Diagnostic methods to screen for incidence or relapse are therefore a requisite to detect cancer as early as possible. Scientific findings demonstrate that many deaths are due to lack of screening and therefore early identification will lead to greater survivability. In colorectal cancer, diagnostic tests include liquid biopsy biomarkers. Since the discovery of microRNAs (miRNAs), many studies have demonstrated the relationship between miRNAs and the various sub-types of CRC. Several miRNAs have been identified after analysing serum or plasma samples in patients, and such miRNAs were found to be significantly dysregulated. Such findings place the possibility of miRNAs to be at the epicentre of novel diagnostic techniques for CRC identification and sub-type stratification, including other characteristics associated with CRC development such as patient prognosis. The following review serves to underline the latest findings for miRNAs with such potential for routine diagnostic employment in CRC diagnostics and treatments.
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Affiliation(s)
- Alfred Buhagiar
- Faculty of Medicine and Surgery, University of Malta, Msida 2080, Malta
| | - Elisa Seria
- Centre for Molecular Medicine and Biobanking, University of Malta, Msida 2080, Malta
| | - Miriana Borg
- Faculty of medical sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
| | - Joseph Borg
- Faculty of Health Sciences, University of Malta, Msida 2080, Malta
| | - Duncan Ayers
- Centre for Molecular Medicine and Biobanking, University of Malta, Msida 2080, Malta
- Faculty of Biology, Medicine and Health Sciences, The University of Manchester, Manchester M13 9PL, UK
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Morley CP, Schad LA, Tumiel-Berhalter LM, Brady LA, Bentham A, Vitale K, Norton A, Noronha G, Swanger C. Improving Cancer Screening Rates in Primary Care via Practice Facilitation and Academic Detailing: A Multi-PBRN Quality Improvement Project. J Patient Cent Res Rev 2021; 8:315-322. [PMID: 34722799 PMCID: PMC8530242 DOI: 10.17294/2330-0698.1855] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
PURPOSE In the United States, cancer screening rates are often below national targets. This project implemented practice facilitation and academic detailing aimed at increasing breast, cervical, and colorectal cancer screening rates in safety-net primary care practices. METHODS Three practice-based research networks across western and central New York State partnered to provide quality improvement strategies on breast, cervical, and colorectal cancer screening. Pre/postintervention screening rates for all participating practices were collected annually, as were means across all practices over 7 years. Simple ordinary least squares linear regression was used to calculate the trend for each cancer type and test for statistical significance (ie, P≤0.05), using the ordinal time point as a fixed effect. RESULTS An overall increase in mean screening rates was seen over the duration of this project for colorectal (24.6% preintervention to 48.0% in year 7 of intervention; P<0.001) and breast cancer (37.0% preintervention to 48.6% in year 7; P=0.460). Mean cervical cancer screening rates decreased (35.5% preintervention to 31.4% in year 7; P=0.209). Success in increasing screening rates varied across regions of New York State. CONCLUSIONS Practice facilitation and academic detailing were successful in significantly increasing, on average, colorectal cancer screening rate. Cervical cancer screening showed an overall decrease, likely due to difficulties for primary care practices in tracking and implementation, as many patients seek this service at outside gynecology facilities. Regional differences, guideline changes, and practice reorganization each may have played a part in observed trends. A standardization of queries being used to pull screening rates is an important step in increasing the reliability of these data.
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Affiliation(s)
- Christopher P Morley
- Department of Public Health and Preventive Medicine, State University of New York (SUNY) Upstate Medical University, Syracuse, NY
| | - Laura A Schad
- Department of Public Health and Preventive Medicine, State University of New York (SUNY) Upstate Medical University, Syracuse, NY
| | - Laurene M Tumiel-Berhalter
- Department of Family Medicine, SUNY University at Buffalo, Buffalo, NY
- University at Buffalo Clinical and Translational Science Institute, Buffalo, NY
| | - Laura A Brady
- Department of Family Medicine, SUNY University at Buffalo, Buffalo, NY
| | | | - Karen Vitale
- University of Rochester Clinical and Translational Science Institute, Rochester, NY
| | - Amanda Norton
- A. Mandatory, Inc. (consulting for SUNY Upstate Medical University), Groton, NY
| | - Gary Noronha
- Center for Primary Care, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
| | - Carlos Swanger
- Center for Primary Care, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY
- Health Reach for the Homeless, Rochester Regional Health, Rochester, NY
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Norouzi A, Besharat S, Isapanah Amlashi F, Nasrabadi M, Gharanjik I, Ashkbari A, Riahi Z, Kaabe S, Shahabi Nasab I, Roshandel G, Sohrabi A, Amiriani T, Semnani S. Detection Rate of Colorectal Polyps in Symptomatic Candidates of Colonoscopy: When Should We Do a Total Colonoscopy? Middle East J Dig Dis 2021; 13:314-320. [PMID: 36606014 PMCID: PMC9489442 DOI: 10.34172/mejdd.2021.240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 06/08/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The incidence of colorectal cancer is increasing in the northeast of Iran. Colorectal polyps are among the proposed risk factors noted, especially in the elder population. This study was designed to study the diagnosed cases of intestinal polyps detected from 2011 to 2016 in the northeast of Iran. METHODS The population consisted of symptomatic candidates referred to the colonoscopy center in Gorgan city. Based on the available colonoscopy and pathology reports, 1706 cases were enrolled after the exclusion of cases without sufficient data. RESULTS Among 1709 (55.5% males and 44.5% females) cases, 1405 cases with 1912 polyps were detected. Among them, 345 (25%) aged less than 50 years. Tubular adenoma (N = 826, 43.2%) and hyperplastic polyps (N = 519, 27.1%) were the top two histological findings. Out of 1405 patients with polyps, 660 (39.6%) polyps were detected in proximal colon (15.6% in proximal and 24% in both proximal and distal). Malignancies were detected in 13.2% (0.8% malignant polyps and 12.4% malignant masses). CONCLUSION A considerable number of colorectal adenomas in proximal colon and in patients younger than 50 years old, suggesting to schedule colorectal cancer screening from at least 10 years younger and continuing colonoscopy up to the proximal area.
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Affiliation(s)
- Alireza Norouzi
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Sima Besharat
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fazel Isapanah Amlashi
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Maryam Nasrabadi
- Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
| | - Isan Gharanjik
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ali Ashkbari
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Zoha Riahi
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Sajjad Kaabe
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Iman Shahabi Nasab
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Ahmad Sohrabi
- Infectious Disease Research Center, Golestan University of Medical Sciences, Gorgan, Iran
| | - Taghi Amiriani
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Shahryar Semnani
- Golestan Research Center of Gastroentrology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
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Hu X, Chen Q, Guo H, Li K, Fu B, Chen Y, Zhao H, Wei M, Li Y, Wu H. Identification of Target PTEN-Based miR-425 and miR-576 as Potential Diagnostic and Immunotherapeutic Biomarkers of Colorectal Cancer With Liver Metastasis. Front Oncol 2021; 11:657984. [PMID: 34490081 PMCID: PMC8418231 DOI: 10.3389/fonc.2021.657984] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 07/28/2021] [Indexed: 12/19/2022] Open
Abstract
A major complication of colorectal cancer (CRC), one of the most common and fatal types of cancers, is secondary liver metastasis. For patients with this fate, there are very few biomarkers available in clinical application, and the disease remains incurable. Recently, increasing studies demonstrated that tumorigenesis and development are closely related to immune escape, indicating that the roles of immune-related indicators might have been neglected in the past in colorectal cancer liver metastases (CRLM). Here, we unveil that elevated miR-425 and miR-576 promote CRLM through inhibiting PTEN-mediated cellular immune function. Specifically, miR-425 and miR-576 were identified for their significant upregulation in CRLM compared with the primary CRC tissues based on GSE81581 (n = 8) and GSE44121 (n = 18) datasets. Besides, we determined that the two microRNAs (miRNAs) coparticipated in restraining P53 and transforming growth factor beta (TGF-β) signaling pathways associated with tumor metastasis, and both shortened the overall survival of the patients with metastatic susceptibility. Notably, in situ hybridization on relatively large samples of paired CRC tissues (n = 157) not only substantiated that the expression of miR-425 and miR-576 was dramatically upregulated in CRLM but also revealed that they were closely related to tumor deterioration, especially liver metastases. Moreover, we further confirmed that the combination of miR-425 and miR-576 was an effective predictive model for liver metastases and poor clinical outcomes. Mechanically, downregulated PTEN (GSE81558, n = 6) was verified to be a shared target of miR-425 and miR-576 acting as metastasis-related oncogenes, on account of the presence of binding sites (+2928-+2934 and +4371-+4378, respectively) and the collaborative suppression of P53/TGF-β signaling in CRLM, which was further confirmed in CRC cells (HCT116 and SW480) based on systematic molecular biology experiments. Importantly, the target PTEN was strongly associated with microsatellite instability, tumor microenvironment, and immune cell infiltration. Thus, we speculate that miR-425 and miR-576 are novel biomarkers for CRLM prevention and immunotherapy and upstream inhibitors of the PTEN-P53/TGF-β function axis.
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Affiliation(s)
- Xiaoyun Hu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Qiuchen Chen
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Hao Guo
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Kuo Li
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Boshi Fu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Yu Chen
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Haishan Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Minjie Wei
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
| | - Yalun Li
- Department of Anorectal Surgery, First Hospital of China Medical University, Shenyang, China
| | - Huizhe Wu
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.,Liaoning Key Laboratory of Molecular Targeted Anti-tumor Drug Development and Evaluation, Liaoning Cancer Immune Peptide Drug Engineering Technology Research Center, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, China Medical University, Shenyang, China.,Department of Gene Detection, Liaoning Medical Diagnosis and Treatment Center, Shenyang, China
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Martellucci CA, Flacco ME, Morettini M, Giacomini G, Palmer M, Fraboni S, Pasqualini F. Wide variability in colorectal cancer screening uptake by general practitioner: Cross-sectional study. J Med Screen 2021; 29:21-25. [PMID: 34369814 DOI: 10.1177/09691413211035795] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Despite several interventions, colorectal cancer (CRC) screening uptake remains below acceptable levels in Italy. Among the potential determinants of screening uptake, only a few studies analysed the role of general practitioners (GPs). The aim was to evaluate the variation in screening uptake of the clusters of subjects assisted by single GPs. SETTING Ancona province, Central Italy. METHODS Cross-sectional study, including all residents aged 50-69 years, who were offered the public screening programme with biannual faecal immunochemical tests. Demographic (of all GPs) and screening data (of all eligible residents) for years 2018-2019 were collected from the official electronic datasets of the Ancona Local Health Unit. The potential predictors of acceptable screening uptake, including GP's gender, age, and number of registered subjects, were evaluated using random-effect logistic regression, with geographical area as the cluster unit. RESULTS The final sample consisted of 332 GP clusters, including 120,178 eligible subjects. The overall province uptake was 38.0% ± 10.7%. The uptake was lower than 30% in one-fifth of the GP clusters, and higher than 45% in another fifth. At multivariable analysis, the significant predictors of uptake were younger GP age (p = 0.010) and lower number of registered subjects (p < 0.001). None of the GP clusters with 500 subjects or more showed an uptake ≥45%. CONCLUSIONS The wide variation across GPs suggests they might substantially influence screening uptake, highlighting a potential need to increase their commitment to CRC screening. Further research is needed to confirm the role of the number of registered subjects.
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Affiliation(s)
| | - Maria E Flacco
- Department of Medical Sciences, 9299University of Ferrara, University of Ferrara, Ferrara, Italy
| | - Margherita Morettini
- Oncologic Screening Department, Hygiene and Public Health Service, Area 2 of the Regional Health Agency of the Marche Region, Italy
| | - Giusi Giacomini
- Oncologic Screening Department, Hygiene and Public Health Service, Area 2 of the Regional Health Agency of the Marche Region, Italy
| | - Matthew Palmer
- Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | - Stefania Fraboni
- Oncologic Screening Department, Hygiene and Public Health Service, Area 2 of the Regional Health Agency of the Marche Region, Italy
| | - Francesca Pasqualini
- Oncologic Screening Department, Hygiene and Public Health Service, Area 2 of the Regional Health Agency of the Marche Region, Italy
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35
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Blackman EL, Ragin C, Jones RM. Colorectal Cancer Screening Prevalence and Adherence for the Cancer Prevention Project of Philadelphia (CAP3) Participants Who Self-Identify as Black. Front Oncol 2021; 11:690718. [PMID: 34395256 PMCID: PMC8363251 DOI: 10.3389/fonc.2021.690718] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 06/30/2021] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION Colorectal cancer is the third leading cause of cancer-related deaths among Black men and women. While colorectal cancer screening (CRCS) reduces mortality, research assessing within race CRCS differences is lacking. This study assessed CRCS prevalence and adherence to national screening recommendations and the association of region of birth with CRCS adherence, within a diverse Black population. METHODS Data from age-eligible adults, 50-75 years, (N = 357) participating in an ongoing, cross-sectional study, was used to measure CRCS prevalence and adherence and region of birth (e.g., Caribbean-, African-, US-born). Prevalence and adherence were based on contemporaneous US Preventive Services Task Force guidelines. Descriptive statistics were calculated and adjusted prevalence and adherence proportions were calculated by region of birth. Adjusted logistic regression models were performed to assess the association between region of birth and overall CRCS and modality-specific adherence. RESULTS Respondents were 69.5% female, 43.3% married/living with partner, and 38.4% had <$25,000 annual income. Overall, 78.2% reported past CRCS; however, stool test had the lowest prevalence overall (34.6%). Caribbean (95.0%) and African immigrants (90.2%) had higher prevalence of overall CRCS compared to US-born Blacks (59.2%) (p-value <0.001). African immigrants were five times more likely to be adherent to overall CRCS compared to US-born Blacks (OR = 5.25, 95% CI 1.34-20.6). Immigrants had higher odds of being adherent to colonoscopy (Caribbean OR = 6.84, 95% CI 1.49-31.5; African OR = 7.14, 95% CI 1.27-40.3) compared to US-born Blacks. CONCLUSIONS While Caribbean and African immigrants have higher prevalence and adherence of CRCS when compared US-born Blacks, CRCS is still sub-optimal in the Black population. Efforts to increase CRCS, specifically stool testing, within the Black population are warranted, with targeted interventions geared towards US-born Blacks.
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Affiliation(s)
- Elizabeth L. Blackman
- Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, PA, United States
- Cancer Prevention and Control Program, Fox Chase Cancer Center- Temple University Health System, Philadelphia, PA, United States
- African Caribbean Cancer Consortium, Philadelphia, PA, United States
| | - Camille Ragin
- Cancer Prevention and Control Program, Fox Chase Cancer Center- Temple University Health System, Philadelphia, PA, United States
- African Caribbean Cancer Consortium, Philadelphia, PA, United States
| | - Resa M. Jones
- Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, PA, United States
- Cancer Prevention and Control Program, Fox Chase Cancer Center- Temple University Health System, Philadelphia, PA, United States
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36
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Autophagy Induction by Trichodermic Acid Attenuates Endoplasmic Reticulum Stress-Mediated Apoptosis in Colon Cancer Cells. Int J Mol Sci 2021; 22:ijms22115566. [PMID: 34070303 PMCID: PMC8197497 DOI: 10.3390/ijms22115566] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/14/2021] [Accepted: 05/19/2021] [Indexed: 12/26/2022] Open
Abstract
Colorectal cancer (CRC) is the third leading malignant tumor in the world, which has high morbidity and mortality. In this study we found that trichodermic acid (TDA), a secondary metabolite isolated from the plant endophytic fungus Penicillium ochrochloronthe with a variety of biological and pharmacological activities, exhibited the antitumor effects on colorectal cancer cells in vitro and in vivo. Our results showed that TDA inhibited the proliferation of colon cancer cells in a dose-dependent manner. TDA induces sustained endoplasmic reticulum stress, which triggers apoptosis through IRE1α/XBP1 and PERK/ATF4/CHOP pathways. In addition, we found that TDA mediated endoplasmic reticulum stress also induces autophagy as a protective mechanism. Moreover, combined treatment of TDA with autophagy inhibitors significantly enhanced its anticancer effect. In conclusion, our results indicated that TDA can induce ER stress and autophagy mediated apoptosis, suggesting that targeting ER stress and autophagy may be an effective strategy for the treatment of CRC.
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Greiner B, Gandhi R, Abrol R, Patel M, Hartwell M. National disparities in colorectal cancer screening in patients with comorbid conditions: an analysis of the Behavioral Risk Factor Surveillance System. J Osteopath Med 2021; 121:657-662. [PMID: 33892528 DOI: 10.1515/jom-2021-0066] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 03/29/2021] [Indexed: 01/05/2023]
Abstract
CONTEXT Each year, approximately 53,200 people die in the U.S. from colorectal cancer (CRC), indicating a need to increase screening efforts. Some studies have suggested mammography use is higher in patients with comorbid conditions, a reflection of increased follow up. Another study found that patients with obesity were less likely to be screened for CRC than nonobese patients. However, no study has assessed the impact of multiple comorbidities on CRC screening. OBJECTIVES To analyze CRC screening rates in patients with comorbidities compared with healthy patients, and to assess whether the number of comorbid diagnoses impacted screening rates. METHODS A cross sectional analysis of patients who received CRC screening was performed using the 2018 and 2019 Behavioral Risk Factor Surveillance System (BRFSS). Respondents were classified as having had CRC screening if they answered "yes" to either of the following: "Have you ever had a blood stool test?" or "Have you ever had a sigmoidoscopy/colonoscopy?" Respondents younger than age 50 were excluded. A weighted multivariate logistic regression model was constructed to determine adjusted risk ratios (ARR). Confidence intervals (CI) were reported at 95%. RESULTS We identified 279,784 respondents who met inclusion criteria. Of those, 79.7% (sample n=222,879; population N=46,304,360) of respondents had received CRC screening. Patients with diabetes, hypertension, skin cancer, chronic obstructive pulmonary disease (COPD), arthritis, depression, and chronic kidney disease were significantly more likely to be screened than those without comorbidities. There was no statistically significant difference in screening rates between patients with and without cardiovascular disease. Compared with patients with zero comorbidities, those with one were significantly more likely to receive screening (ARR, 1.11; CI, 1.09-1.12) as were those with two to four (ARR, 1.2; CI, 1.18-1.22). Patients with five or more comorbidities were significantly less likely to be screened than those with two to four (ARR, 1.12; CI, 1.1-1.14). CONCLUSIONS Patients with one or more comorbidities were more likely to be screened than those without comorbidities, but those with five or more conditions were less likely to be screened than patients with two to four conditions. This indicates that physicians may be more fatigued and less likely to recommend CRC screening to patients with many comorbidities compared with patients diagnosed with only a few conditions. The results of this study add to the literature by identifying an interaction between the number of comorbidities and likelihood of being screened for CRC.
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Affiliation(s)
- Benjamin Greiner
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Ronak Gandhi
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Robinder Abrol
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Milee Patel
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
| | - Micah Hartwell
- Department of Psychiatry and Behavioral Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA
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Gersten O, Barbieri M. Evaluation of the Cancer Transition Theory in the US, Select European Nations, and Japan by Investigating Mortality of Infectious- and Noninfectious-Related Cancers, 1950-2018. JAMA Netw Open 2021; 4:e215322. [PMID: 33843999 PMCID: PMC8042523 DOI: 10.1001/jamanetworkopen.2021.5322] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
IMPORTANCE Despite cancer being a leading cause of death worldwide, scant research has been carried out on the validity of the cancer transition theory, the idea that as nations develop, they move from a situation where infectious-related cancers are prominent to one where noninfectious-related cancers dominate. OBJECTIVE To examine whether cancer transitions exist in the US, select European countries, and Japan. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, annual cause-of-death data from the 1950s to 2018 for the US, England and Wales, France, Sweden, Norway, and Japan were extracted from the Human Mortality Database and the World Health Organization (WHO). Statistical analysis was performed from April 2020 to February 2021. MAIN OUTCOMES AND MEASURES Age-standardized death rates for all ages and both sexes combined were estimated for cancers of the stomach, cervix, liver, lung, pancreas, esophagus, colorectum, breast, and prostate. RESULTS The results of the analysis show that for all countries in this study except for Japan, mortality from infectious-related cancers has declined steadily throughout the period, so that by the end of the period, for Norway, England and Wales, Sweden, and the US, rates were approximately 20 deaths per 100 000 population. Regarding noninfectious-related cancers, at the beginning of the period, all countries exhibited an increasing trend in rates, with England and Wales having the greatest peak of 215.1 deaths per 100 000 population (95% CI 213.7-216.6 deaths per 100 000 population) in 1985 followed by a decline, with most of the other countries reaching a peak around 1990 and declining thereafter. Furthermore, there is a visible crossover in the trends for infectious-related and noninfectious-related cancers in Japan and Norway. This crossover occurred in 1988 in Japan, when the rates for both types of cancers stood at 116 per 100 000 population (95% CI, 115.0-116.5 per 100 000 population), and in 1955 in Norway, when they passed each other at 100 per 100 000 population (95% CI, 96.4-105.3 per 100 000 population). CONCLUSIONS AND RELEVANCE In this cross-sectional study, the findings suggest that cancer mortality patterns parallel the epidemiological transition, which states that as nations develop, they move from a stage where infectious diseases are prominent to one where noninfectious diseases dominate. An implication is that the epidemiological transition theory as originally formulated continues to be relevant, despite some researchers arguing that there should be additional stages beyond the original 3.
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Affiliation(s)
- Omer Gersten
- Nu-Trek, San Diego, California
- Department of Bioinformatics and Biostatistics, University of California, San Diego Extension, La Jolla
| | - Magali Barbieri
- Department of Demography, University of California, Berkeley
- French Institute for Demographic Studies, Paris, France
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Ferlizza E, Solmi R, Sgarzi M, Ricciardiello L, Lauriola M. The Roadmap of Colorectal Cancer Screening. Cancers (Basel) 2021; 13:1101. [PMID: 33806465 PMCID: PMC7961708 DOI: 10.3390/cancers13051101] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 02/24/2021] [Accepted: 02/27/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.
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Affiliation(s)
- Enea Ferlizza
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
| | - Rossella Solmi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
| | - Michela Sgarzi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
| | - Luigi Ricciardiello
- Gastroenterology Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy;
| | - Mattia Lauriola
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy; (R.S.); (M.S); (M.L.)
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Wang X, Huang J, Ji X, Zhu Z. [Application of artificial intelligence for detection and classification of colon polyps]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:310-313. [PMID: 33624608 DOI: 10.12122/j.issn.1673-4254.2021.02.22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Colorectal cancer is one of the most common cancers worldwide, and colonoscopy has proven to be a preferable modality for screening and surveillance of colorectal cancer. This review discusses the clinical application of artificial intelligence (AI) and computer-aided diagnosis for automated colonoscopic detection and diagnosis of colorectal polyps for better understanding of the application of AI-based computer-aided diagnosis systems especially in terms of machine learning, deep learning and convolutional neural network for screening and surveillance of colorectal cancer.
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Affiliation(s)
- X Wang
- Information Center, First Affiliated Hospital of Kunming Medical University, Kunming 65003, China
| | - J Huang
- Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming 65003, China
| | - X Ji
- Day Surgery Center, First Affiliated Hospital of Kunming Medical University, Kunming 65003, China
| | - Z Zhu
- Day Surgery Center, First Affiliated Hospital of Kunming Medical University, Kunming 65003, China
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A short deletion in the DNA-binding domain of STAT3 suppresses growth and progression of colon cancer cells. Aging (Albany NY) 2021; 13:5185-5196. [PMID: 33535185 PMCID: PMC7950243 DOI: 10.18632/aging.202439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Accepted: 11/25/2020] [Indexed: 01/14/2023]
Abstract
In this study, we investigated the effect of a short deletion in the DNA-binding domain of STAT3 (STAT3del) on the transcriptional activation of STAT3 target genes and its relationship with colon carcinogenesis. We used the CRISPR-CAS9 gene editing system to delete a short sequence encoding amino acids 400-411 in the DNA-binding domain (amino acid sequence: 317-567) from STAT3 gene in SW480, SW620 and HCT116 colon cancer cells. ChIP sequencing analysis showed that STAT3del occupancy was significantly reduced in 1029 genes and significantly increased in 475 genes compared to wild-type STAT3. The mutation altered the DNA motifs recognized by STAT3del as compared to the wild-type STAT3. We observed a strong correlation between expression of the STAT3 target genes and the loss or gain of STAT3del binding to their promoters. CCK-8, wound healing, and TUNEL assays showed reduced proliferation, migration, and survival of SW480, SW620 and HCT-116 cells expressing STAT3del as compared to the corresponding controls. These findings demonstrate that a short deletion in the DNA-binding domain of STAT3 alters its genome-wide DNA-binding and transcriptional profile of STAT3-target proteins, and suppresses the growth, progression and survival of colon cancer cells.
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Hsa-miR-3658 down-regulates OCT4 gene expression followed by suppressing SW480 cell proliferation and migration. Biochem J 2020; 477:2281-2293. [PMID: 32478824 DOI: 10.1042/bcj20190619] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2019] [Revised: 05/20/2020] [Accepted: 06/01/2020] [Indexed: 01/04/2023]
Abstract
The pluripotency factor, OCT4 gene is a stemness marker that is involved in the tumorigenicity of different cancer types and knowing about molecular mechanisms of its regulation is crucially important. To date, a few microRNAs (miRNAs) are known to be regulators of OCT4 gene expression. Looking for the novel miRNAs which are capable of regulating OCT4 gene expression, our bioinformatics analysis introduced hsa-miR-3658 (miR-3658) as a bona fide candidate. Then, RT-qPCR results indicated that miR-3658 expression is decreased in colorectal cancer (CRC) tumor tissues, compared with normal pairs. Furthermore, RT-qPCR and western blot analysis showed that the OCT4 gene has been down-regulated following the miR-3658 overexpression. Consistently, dual-luciferase assay supported the direct interaction of miR-3658 with the 3'-UTR sequence of OCT4 gene. Unlike in HCT116 cells, overexpression of miR-3658 in SW480 cells brought about growth inhibition, cell cycle arrest and reduced cell migration, detected by flow cytometry, and scratch test assay. Overall, these findings demonstrated that miR-3658 as a tumor suppressor miRNA exerts its effect against OCT4 gene expression, and it has the potential of being used as a prognostic marker and therapeutic target against colorectal cancer.
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Antioxidant and Chemopreventive Effect of Aliophen ® Formulation Based on Malts and Hops. Antioxidants (Basel) 2020; 10:antiox10010029. [PMID: 33396660 PMCID: PMC7823394 DOI: 10.3390/antiox10010029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/18/2020] [Accepted: 12/22/2020] [Indexed: 11/17/2022] Open
Abstract
Experimental and clinical studies evidenced the health effects of moderate consumption of beer, mainly due to the presence of bioactive compounds, such as polyphenols, vitamins, or fibers. To exploit the potential beneficial effect on health and in disease prevention of these compounds, a new beverage based on barley malts and hops named Aliophen® has been designed, through a patented production process, with a high total polyphenolic amount compared to alcohol-free beer and similar to the one present in light and dark beers. In the present study, the antioxidant activity of Aliophen® against low-density lipoprotein (LDL) oxidation and its ability to protect erythrocytes from hemolysis have been characterized. Moreover, the chemopreventive effect of Aliophen® against colon cancer has been assessed, employing a mouse model of chemically induced carcinogenesis using azoxymethane (AOM). Data obtained showed that Aliophen at a low dose (3 mg/kg) inhibited the formation of preneoplastic lesions, polyps, and tumors. At higher doses (300 mg/kg) the protective effect was measured in the first phase of the onset of cancer. The antioxidant properties of Aliophen® were also observed in AOM-treated mice where it increased the serum antioxidant capacity. Based on the data presented, Aliophen® can exert promising health effects, including an anticancer capacity presumably associated with its antioxidant properties.
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Anyfantakis D. A Young Male With Anorexia, Abdominal Complaints and Marked Blood Eosinophilia. Cureus 2020; 12:e12314. [PMID: 33520512 PMCID: PMC7837640 DOI: 10.7759/cureus.12314] [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] [Indexed: 12/03/2022] Open
Abstract
Peripheral blood eosinophilia represents a frequent finding in routine clinical practice when absolute eosinophil count is found to be greater than 0.5 x 109/L (500/µL). Common causes include parasitic infections, allergic reactions, and hyper-eosinophilic syndrome. Eosinophilia secondary to malignancy represents an uncommon presentation. Here we report an atypical case of a 47-year-old previously healthy male who presented to a primary care setting complaining of fatigue and anorexia for the last two weeks. The evaluation revealed leucocytosis and peripheral hypereosinophilia with an absolute eosinophil count of 14.13×109/L (37%). Following an extensive diagnostic work in a secondary care centre he was finally diagnosed with rectal carcinoma. This case highlights that solid malignancy should be considered in patients with marked peripheral eosinophilia.
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Pączek S, Łukaszewicz-Zając M, Mroczko B. Chemokines-What Is Their Role in Colorectal Cancer? Cancer Control 2020; 27:1073274820903384. [PMID: 32103675 PMCID: PMC7066593 DOI: 10.1177/1073274820903384] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related death. It
is the second most frequently diagnosed malignancy in Europe and third
worldwide. Colorectal malignancies diagnosed at an early stage offer a promising
survival rate. However, advanced tumors often present distant metastases even
after the complete resection of a primary tumor. Therefore, novel biomarkers of
CRC are sorely needed in the diagnosis and prognosis of this common malignancy.
A family of chemokines are composed of small, secreted proteins. They are best
known for their ability to stimulate the migration of several cell types. Some
investigations have indicated that chemokines are involved in cancer
development, including CRC. This article presents current knowledge regarding
chemokines and their specific receptors in CRC progression. Moreover, the prime
aim of this review is to summarize the potential role of these proteins as
biomarkers in the diagnosis and prognosis of CRC.
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Affiliation(s)
- Sara Pączek
- Department of Biochemical Diagnostics, Medical University of Bialystok, Poland
| | | | - Barbara Mroczko
- Department of Biochemical Diagnostics, Medical University of Bialystok, Poland.,Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Poland
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Naringin Combined with NF-κB Inhibition and Endoplasmic Reticulum Stress Induces Apoptotic Cell Death via Oxidative Stress and the PERK/eIF2α/ATF4/CHOP Axis in HT29 Colon Cancer Cells. Biochem Genet 2020; 59:159-184. [PMID: 32979141 DOI: 10.1007/s10528-020-09996-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Accepted: 09/18/2020] [Indexed: 02/06/2023]
Abstract
Currently, combination therapy is considered the most effective solution for a selective chemotherapeutic effect in the treatment of colon cancer. This study investigated the death of both colon cancer HT29 cells and healthy vascular smooth muscle TG-Ha-VSMC cells (VSMCs) induced by naringin combined with endoplasmic reticulum (ER) stress and NF-κB inhibition. Naringin combined with tunicamycin and BAY 11-7082 suppressed the proliferation of HT29 cells in a dose-dependent manner and induced particularly apoptotic death without significantly affecting healthy VSMCs according to Annexin V/PI staining and AO/EB staining analyses. Insufficient antioxidant defense and heat shock response as well as excessive ROS generation were observed in HT29 cells following combination therapy. Quantitative real-time PCR and western blot analysis demonstrated that drug combination-induced mitochondrial apoptosis was activated through the ROS-mediated PERK/eIF2α/ATF4/CHOP pathway. Additionally, naringin combination significantly reduced the sXBP expression induced by tunicamycin+BAY 11-7082 in a dose-dependent manner. In conclusion, this study found that naringin combined with tunicamycin+BAY 11-7082 efficiently induced apoptotic cell death in HT29 colon cancer cells via oxidative stress and the PERK/eIF2α/ATF4/CHOP pathway, suggesting that naringin combined with tunicamycin plus BAY 11-7082 could be a new combination therapy strategy for effective colon cancer treatment with minimal side effects on healthy cells.
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Bergamini C, Giordano A, Maltinti G, Alemanno G, Cianchi F, Coratti A, Manetti R, Valeri A, Prosperi P. Obstructive left side colon cancer: time for a tailored operative approach? MINERVA CHIR 2020; 75:244-254. [PMID: 32456396 DOI: 10.23736/s0026-4733.20.08299-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) obstruction is frequent but doubts remain on the best treatment. The aim of this study is to analyze the different operative approach used for CRC treatment and evaluate the outcomes for the different cases. METHODS Patients were collected from January 2014 to December 2019 and divided in four groups: two "P" groups, namely the Hartmann's procedure (PH) group and the primary anastomosis (PA) group, and two "S" groups, namely the deviating stoma (SD) group and the self-expanding metallic stent (SS) group. The main endpoints were the quality of life and the oncologic safety. RESULTS One hundred and eight patients were enrolled. The mean follow-up time was 39 months. The stomas were performed less frequently in SS but lasted more in that group. Only 45% underwent reversal surgery. Cumulative operating time was greater in S versus P groups. The rate of major complications was similar. PA had greater overall survival and disease-free survival rates than PH. CONCLUSIONS The various options of treatment should have different indications: primary anastomosis in stable patients, Hartmann in critical cases, SEMS for palliative intent and stoma when neo-adjuvant therapy is needed.
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Affiliation(s)
- Carlo Bergamini
- Unit of Emergency Surgery, Department of Emergency, Careggi University Hospital, Florence, Italy -
| | - Alessio Giordano
- Unit of Emergency Surgery, Department of Emergency, Careggi University Hospital, Florence, Italy
| | - Gherardo Maltinti
- Unit of Emergency Surgery, Department of Emergency, Careggi University Hospital, Florence, Italy
| | - Giovanni Alemanno
- Unit of Emergency Surgery, Department of Emergency, Careggi University Hospital, Florence, Italy
| | - Fabio Cianchi
- Department of Emergency, Unit of General and Endocrine Surgery, Careggi University Hospital, Florence, Italy
| | - Andrea Coratti
- Department of Robotic Oncologic Surgery, Careggi University Hospital, Florence, Italy
| | - Roberto Manetti
- Unit of Operative Endoscopy, Department of Robotic Oncologic Surgery, Careggi University Hospital, Florence, Italy
| | - Andrea Valeri
- Unit of Emergency Surgery, Department of Emergency, Careggi University Hospital, Florence, Italy
| | - Paolo Prosperi
- Unit of Emergency Surgery, Department of Emergency, Careggi University Hospital, Florence, Italy
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Wu P, Zhu H, Zhuang Y, Sun X, Gu N. Combined Therapeutic Effects of 131I-Labeled and 5Fu-Loaded Multifunctional Nanoparticles in Colorectal Cancer. Int J Nanomedicine 2020; 15:2777-2787. [PMID: 32368054 PMCID: PMC7185645 DOI: 10.2147/ijn.s215137] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 01/26/2020] [Indexed: 12/20/2022] Open
Abstract
Background Owing to its combined effects, the co-delivery of different therapeutics is a promising option for the treatment of cancer. In the present study, tumor-targeting poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles were developed for the transportation of two molecules, namely chemotherapeutic drug 5-fluorouracil (5Fu) and radionuclide iodine-131 (131I), in a single platform. Methods The obtained nanoparticles (Cetuximab [Cet]-PEG-PLA-5Fu-131I) were spherical (diameter approximately 110 nm) and pH-sensitive. The targeting effect of nanoparticles via Cet was confirmed in colorectal cancer cells using a fluorescent assay. The combined effects of Cet-PEG-PLA-5Fu-131I on cell viability and apoptosis were evaluated in colorectal cancer cells by Cell Counting Kit-8 and flow cytometry assays. Results Blank nanoparticles (Cet-PEG-PLA) showed good biocompatibility, and Cet-PEG-PLA-5Fu-131I nanoparticles were the most effective in terms of inhibition of cell viability and induction of apoptosis compared with monotherapy using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I. In the xenograft mouse model, compared with using Cet-PEG-PLA-5Fu or Cet-PEG-PLA-131I alone, Cet-PEG-PLA-5Fu-131I nanoparticles exhibited prolonged circulation in the blood and accumulation in the tumor, thus resulting in enhanced antitumor efficacy. Additionally, combined radio-chemotherapy with Cet-PEG-PLA-5Fu-131I nanoparticles was associated with smaller tumor sizes than monotherapy, revealing the superior antitumor effects of Cet-PEG-PLA-5Fu-131I nanoparticles. These effects were further evidenced by histological and immunohistochemical analyses. Conclusion The multifunctional Cet-PEG-PLA-5Fu-131I nanoparticles are promising candidates for the co-delivery of 5Fu-mediated chemotherapy and 131I-mediated radiotherapy.
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Affiliation(s)
- Pingping Wu
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People's Republic of China.,Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People's Republic of China
| | - Huayun Zhu
- Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People's Republic of China
| | - Yan Zhuang
- Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People's Republic of China
| | - Xiaofeng Sun
- Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210009, People's Republic of China
| | - Ning Gu
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing 210096, People's Republic of China
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CXCL-8 in Preoperative Colorectal Cancer Patients: Significance for Diagnosis and Cancer Progression. Int J Mol Sci 2020; 21:ijms21062040. [PMID: 32192002 PMCID: PMC7139325 DOI: 10.3390/ijms21062040] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 03/14/2020] [Accepted: 03/15/2020] [Indexed: 12/11/2022] Open
Abstract
Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.
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50
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Ferlizza E, Solmi R, Miglio R, Nardi E, Mattei G, Sgarzi M, Lauriola M. Colorectal cancer screening: Assessment of CEACAM6, LGALS4, TSPAN8 and COL1A2 as blood markers in faecal immunochemical test negative subjects. J Adv Res 2020; 24:99-107. [PMID: 32257432 PMCID: PMC7113625 DOI: 10.1016/j.jare.2020.03.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 02/27/2020] [Accepted: 03/01/2020] [Indexed: 12/17/2022] Open
Abstract
Prevention is essential to reduce Colorectal Cancer (CRC) mortality. We previously reported a panel of four genes: CEACAM6, LGALS4, TSPAN8, COL1A2 (CELTiC) able to discriminate patients with CRC. Here, we assessed the CELTiC panel by quantitative polymerase chain reaction, in the blood of 174 healthy subjects, who resulted negative to the faecal immunochemical test (FITN). Using non-parametric statistic and multinomial logistic models, the FITN were compared to previously analysed subjects: 36 false positive FIT (NFIT), who were negative at colonoscopy, 36 patients with low risk lesions (LR) and 92 patients with high risk lesions or CRC (HR/CRC). FITN showed a significantly lower expression of the four genes when compared to HR/CRC. Moreover, FITN showed a significantly lower expression of TSPAN8 and COL1A2 compared to NFIT and LR patients. The multinomial logistic model confirmed that TSPAN8 alone specifically discriminated FITN from NFIT, LR and HR/CRC, while LGALS4 was able to differentiate FITN from false positive FIT. Finally, ROC curves analysis of the comparisons between FITN and HR/CRC, LR or NFIT reported AUC greater than 0.87, with a sensitivity and specificity of 83% and 76%, respectively. The CELTiC panel was confirmed a useful tool to identify CRC patients and to discriminate false FIT positive subjects.
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Affiliation(s)
- Enea Ferlizza
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
| | - Rossella Solmi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
| | - Rossella Miglio
- Department of Statistical Sciences, University of Bologna, Via Belle Arti 42, 40100 Bologna, Italy
| | - Elena Nardi
- Department of Statistical Sciences, University of Bologna, Via Belle Arti 42, 40100 Bologna, Italy
| | - Gabriella Mattei
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
| | - Michela Sgarzi
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
| | - Mattia Lauriola
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy
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