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Biswas S, Kanodia R, Seervi S, Kaur R, Shukla S, Singh S, Banerjee J, Banerjee S. Portrayal of the complex molecular landscape of multidrug resistance in gastric cancer: Unveiling the potential targets. Exp Cell Res 2025; 449:114580. [PMID: 40306607 DOI: 10.1016/j.yexcr.2025.114580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 04/27/2025] [Accepted: 04/27/2025] [Indexed: 05/02/2025]
Abstract
Gastric cancer (GC) is an aggressive malignancy among all Gastrointestinal cancer (GIC) types. Worldwide, among all cancer types, gastric cancer incidence and related mortality remain in fifth position. Multidrug resistance (MDR) in GC presents a major challenge to chemotherapy, and it significantly affects patient survival. A better understanding of the dynamic interaction of cellular factors contributing to MDR phenotype, e.g., the presence and expression of variants of MDR-related genes, including various drug-detoxifying and drug-efflux transporters, and expression of regulatory ncRNAs affecting the expression of MDR-related genes, is required to comprehend the molecular mechanisms for MDR development in GCs. This review article provides a holistic discussion of the cellular factors involved in the MDR development in GC cells, i.e., their roles and cross-talk between specific molecules that give rise to drug-sensitive and drug-resistant phenotypes. Moreover, the pharmacological perspective of drug resistance and the underlying biological processes that allow the escape of GC cells from the cytotoxic effects of drugs have also been discussed. Additionally, this review article provides an in-depth discussion on most potential candidates that can serve as MDR biomarkers in GIC cancer and the growing research interest in non-coding RNAs (ncRNAs) in GC. Notably, the miRNAs, circRNAs, and lncRNAs are not only emerging as crucial prognostic biomarkers of MDR in gastric cancers but also as potential targets for personalized medicine to combat the MDR challenge in GC patients.
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Affiliation(s)
- Siddhant Biswas
- School of Biotechnology and Bioengineering, Institute of Advanced Research (IAR), Koba, Institutional Area, Gandhinagar, Gujarat, 382426, India
| | - Riya Kanodia
- School of Biotechnology and Bioengineering, Institute of Advanced Research (IAR), Koba, Institutional Area, Gandhinagar, Gujarat, 382426, India
| | - Suman Seervi
- School of Biotechnology and Bioengineering, Institute of Advanced Research (IAR), Koba, Institutional Area, Gandhinagar, Gujarat, 382426, India
| | - Rajinder Kaur
- Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India
| | - Sakshi Shukla
- School of Biotechnology and Bioengineering, Institute of Advanced Research (IAR), Koba, Institutional Area, Gandhinagar, Gujarat, 382426, India
| | - Samer Singh
- Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
| | - Juni Banerjee
- School of Biotechnology and Bioengineering, Institute of Advanced Research (IAR), Koba, Institutional Area, Gandhinagar, Gujarat, 382426, India.
| | - Shuvomoy Banerjee
- School of Biotechnology and Bioengineering, Institute of Advanced Research (IAR), Koba, Institutional Area, Gandhinagar, Gujarat, 382426, India.
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Bahrambanan F, Alizamir M, Moradveisi K, Heddam S, Kim S, Kim S, Soleimani M, Afshar S, Taherkhani A. The development of an efficient artificial intelligence-based classification approach for colorectal cancer response to radiochemotherapy: deep learning vs. machine learning. Sci Rep 2025; 15:62. [PMID: 39748016 PMCID: PMC11696929 DOI: 10.1038/s41598-024-84023-w] [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: 06/11/2024] [Accepted: 12/19/2024] [Indexed: 01/04/2025] Open
Abstract
Colorectal cancer (CRC) is a form of cancer that impacts both the rectum and colon. Typically, it begins with a small abnormal growth known as a polyp, which can either be non-cancerous or cancerous. Therefore, early detection of colorectal cancer as the second deadliest cancer after lung cancer, can be highly beneficial. Moreover, the standard treatment for locally advanced colorectal cancer, which is widely accepted around the world, is chemoradiotherapy. Then, in this study, seven artificial intelligence models including decision tree, K-nearest neighbors, Adaboost, random forest, Gradient Boosting, multi-layer perceptron, and convolutional neural network were implemented to detect patients responder and non-responder to radiochemotherapy. For finding the potential predictors (genes), three feature selection strategies were employed including mutual information, F-classif, and Chi-Square. Based on feature selection models, four different scenarios were developed and five, ten, twenty and thirty features selected for designing a more accurate classification paradigm. The results of this study confirm that random forest, Gradient Boosting, decision tree, and K-nearest neighbors provided more accurate results in terms of accuracy, by 93.8%. Moreover, Among the feature selection methods, mutual information and F-classif showed the best results, while Chi-Square produced the worst results. Therefore, the suggested artificial intelligence models can be successfully applied as a robust approach for classification of colorectal cancer response to radiochemotherapy for medical studies.
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Affiliation(s)
- Fatemeh Bahrambanan
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Meysam Alizamir
- Institute of Research and Development, Duy Tan University, Da Nang, Vietnam.
- School of Engineering & Technology, Duy Tan University, Da Nang, Vietnam.
| | - Kayhan Moradveisi
- Civil Engineering Department, University of Kurdistan, Sanandaj, Iran
| | - Salim Heddam
- Faculty of Science, Agronomy Department, Hydraulics Division, University 20 Août 1955, Route El Hadaik BP 26, 21000, Skikda, Algeria
| | - Sungwon Kim
- Department of Railroad Construction and Safety Engineering, Dongyang University, Yeongju, 36040, Republic of Korea
| | - Seunghyun Kim
- Department of Biology, University of California San Diego, San Diego, CA, 92093, USA
| | - Meysam Soleimani
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Saeid Afshar
- Department of Molecular Medicine and Genetics, Medical School, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Amir Taherkhani
- Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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Harrison J, Sullivan F, Keenan K, Kulu H. All-cancer incidence and mortality in Pakistanis, Bangladeshis, and their descendants in England and Wales. BMC Public Health 2024; 24:3352. [PMID: 39623351 PMCID: PMC11610263 DOI: 10.1186/s12889-024-20813-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/21/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND This paper identifies differences in all-cancer incidence and mortality between Pakistani-born (PB), Bangladeshi-born (BB), their descendants, and the White British (WB) in England and Wales. Pakistanis and Bangladeshis are the most marginalised and disadvantaged groups in England and Wales yet, are found to have low cancer mortality and low all-cause mortality. Previous studies though have not looked at generational differences, applied individual-level data nor separated Pakistanis and Bangladeshis from each other and other Asian groups. METHODS We use the Office for National Statistics Longitudinal Study of England and Wales which is a 1% representative sample of the population. We apply event history analysis on a study period from 1971 to 2016, following individuals from age 20 until a first cancer incidence, censoring at emigration or death. We observe 10,885,500 person-years and 71,926 cancer incidences for WB; 125,700 person-years and 295 events for PB; 53,900 person-years and 113 events for BB and 26,900 person-years and 24 events for descendants. Following incidence, we study a maximum of ten years until a death from cancer, or censoring. In this second analysis on mortality our sample has 329,700 person-years and 31,689 cancer deaths for WB; 1,200 person-years and 104 events for PB; 400 person-years and 50 events for BB and 100 person-years and 10 events for descendants. RESULTS Results from the fully adjusted models show that the risk of cancer incidence is lower for PB, BB and descendants compared to the WB native group. Estimated hazard ratio (HR) equals 0.42 for PB (95% confidence interval (CI): 0.38-0.47), for BB HR is 0.38 (CI: 0.32-0.46) and, for descendants HR is 0.36 (CI: 0.24-0.54). Results for cancer mortality after incidence show HR for PB is 0.93 (CI: 0.76-1.12), for BB it is 0.95 (CI: 0.72-1.25) and for descendants HR equals 1.62 (CI: 0.87-3.02 - significant at 90%). CONCLUSIONS Using high quality representative data, we show that lower incidence of cancer and not better survival is the driver of the low cancer mortality previously found. This advantage persists across immigrant generations, but all-cancer mortality following incidence may be elevated for descendants.
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Affiliation(s)
- Joseph Harrison
- School of Geography and Sustainable Development, University of St Andrews, Irvine Building, North Street, St Andrews, KY16 9AL, UK.
| | - Frank Sullivan
- School of Medicine, University of St Andrews, St Andrews, UK
| | - Katherine Keenan
- School of Geography and Sustainable Development, University of St Andrews, Irvine Building, North Street, St Andrews, KY16 9AL, UK
| | - Hill Kulu
- School of Geography and Sustainable Development, University of St Andrews, Irvine Building, North Street, St Andrews, KY16 9AL, UK
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GNANGNON Freddy HR, KPOSSOU AR, N'TCHA K, AMIDOU SA, ZOSSOU V, TOUME C, ALLODJI RS, HOUINATO DS, GBESSI DG, SEHONOU J. Survie et facteurs pronostiques du cancer primitif du foie à Cotonou (République du Bénin) de 2014 à 2020. MEDECINE TROPICALE ET SANTE INTERNATIONALE 2024; 4:mtsi.v4i3.2024.418. [PMID: 39575094 PMCID: PMC11577100 DOI: 10.48327/mtsi.v4i3.2024.418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 05/17/2024] [Indexed: 11/24/2024]
Abstract
Introduction Le cancer primitif du foie (CPF) occupait la 6e et la 3e place dans le monde respectivement en termes d'incidence et de mortalité en 2020. L'objectif de ce travail était d’étudier la survie et les facteurs pronostiques du cancer primitif du foie à Cotonou en République du Bénin. Matériels et méthodes Il s'est agi d'une étude de cohorte rétrospective qui a inclus les enregistrements de 150 patients atteints d'un CPF, répertoriés par le Registre des cancers de Cotonou, sur une période de sept ans allant du 1er janvier 2014 au 31 décembre 2020. Le logiciel R 3.6.1 a été utilisé pour l'analyse des données. La méthode de Kaplan-Meier a permis d'estimer la survie des patients. La comparaison des courbes de survie a été faite par le test du Log-Rank. Le modèle de Cox à risque proportionnel a été établi pour identifier les facteurs prédictifs de la mortalité. Le seuil de significativité statistique a été fixé à 5 %. Résultats L’âge moyen des sujets était de 51,7 ± 14,9 ans et le sex-ratio de 2,7. La moitié des décès était survenue dans les deux premiers mois ayant suivi le diagnostic. Les facteurs pronostiques, après l'analyse multivariée, étaient: l’âge ≥ 60 ans (HRa = 1,7; IC 95 % [1,10-2,51]), la notion de consommation d'alcool (Hazard Ratio ajusté, HRa = 3,7; [1,33-9,42]), l'itinéraire thérapeutique (HRa = 1,9; [1,24-3,02]), l'infection par le virus de l'hépatite B (HRa = 7,7; [3,26-12,29]), l'infection par le virus de l'hépatite C (HRa = 3,6; [1,38-9,43]) et le délai de consultation ≥4 semaines (HRa = 2,0; [1,01-4,05]). Conclusion La mortalité des patients atteints de CPF à Cotonou est élevée avec une médiane de survie de deux mois. Des facteurs, pour l'essentiel modifiables, sont associés à cette mortalité.
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Affiliation(s)
- Houéhanou Rodrigue GNANGNON Freddy
- Clinique universitaire de chirurgie viscérale, Centre national hospitalier universitaire-Hubert Koutoukou Maga (CNHUHKM), Cotonou, Bénin
- Registre des cancers de Cotonou, ministère de la Santé, Bénin
- Laboratoire d’épidémiologie des maladies chroniques et neurologiques, Faculté des sciences de la santé, Cotonou, Bénin
- Institut national de la santé et de la recherche médicale ((INSERM) U1094, Institut de recherche et développement (IRD) U270, Univ. Limoges, Centre hospitalier universitaire de Limoges, EpiMaCT - Épidémiologie des maladies chroniques en zone tropicale, Institut d’épidémiologie et de neurologie tropicale, OmegaHealth, Limoges, France
| | - Aboudou Raïmi KPOSSOU
- Clinique universitaire d'hépato-gastroentérologie, Centre national hospitalier universitaire-Hubert Koutoukou Maga (CNHU-HKM), Cotonou, Bénin
| | - Koffi N'TCHA
- Registre des cancers de Cotonou, ministère de la Santé, Bénin
- Laboratoire d’épidémiologie des maladies chroniques et neurologiques, Faculté des sciences de la santé, Cotonou, Bénin
| | - Salmane Ariyah AMIDOU
- Registre des cancers de Cotonou, ministère de la Santé, Bénin
- Laboratoire d’épidémiologie des maladies chroniques et neurologiques, Faculté des sciences de la santé, Cotonou, Bénin
| | - Vincent ZOSSOU
- Institut de formation et de recherche en informatique, (IFRIUAC), Cotonou, Bénin
- École polytechnique d'Abomey-Calavi, (EPAC-UAC), 01 P.O. Box 2009, Cotonou, Bénin
| | - Cosme TOUME
- Registre des cancers de Cotonou, ministère de la Santé, Bénin
| | - Rodrigue S. ALLODJI
- Université Paris-Saclay, UVSQ, Univ. Paris-Sud, Inserm, Équipe radiation epidemiology, CESP, 94805, Villejuif, France
- Institut national de la santé et de la recherche médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), U1018, 94805, Villejuif, France
| | - Dismand Stephan HOUINATO
- Laboratoire d’épidémiologie des maladies chroniques et neurologiques, Faculté des sciences de la santé, Cotonou, Bénin
- Institut national de la santé et de la recherche médicale ((INSERM) U1094, Institut de recherche et développement (IRD) U270, Univ. Limoges, Centre hospitalier universitaire de Limoges, EpiMaCT - Épidémiologie des maladies chroniques en zone tropicale, Institut d’épidémiologie et de neurologie tropicale, OmegaHealth, Limoges, France
| | - Dansou Gaspard GBESSI
- Clinique universitaire de chirurgie viscérale, Centre national hospitalier universitaire-Hubert Koutoukou Maga (CNHUHKM), Cotonou, Bénin
| | - Jean SEHONOU
- Clinique universitaire d'hépato-gastroentérologie, Centre national hospitalier universitaire-Hubert Koutoukou Maga (CNHU-HKM), Cotonou, Bénin
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Unal U, Gov E. Drug Repurposing Analysis for Colorectal Cancer through Network Medicine Framework: Novel Candidate Drugs and Small Molecules. Cancer Invest 2023; 41:713-733. [PMID: 37682113 DOI: 10.1080/07357907.2023.2255672] [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: 10/12/2022] [Revised: 02/04/2023] [Accepted: 09/01/2023] [Indexed: 09/09/2023]
Abstract
This study aimed to reveal the drug-repurposing candidates for colorectal cancer (CRC) via drug-repurposing methods and network biology approaches. A novel, differentially co-expressed, highly interconnected, and co-regulated prognostic gene module was identified for CRC. Based on the gene module, polyethylene glycol (PEG), gallic acid, pyrazole, cordycepin, phenothiazine, pantoprazole, cysteamine, indisulam, valinomycin, trametinib, BRD-K81473043, AZD8055, dovitinib, BRD-A17065207, and tyrphostin AG1478 presented as drugs and small molecule candidates previously studied in the CRC. Lornoxicam, suxamethonium, oprelvekin, sirukumab, levetiracetam, sulpiride, NVP-TAE684, AS605240, 480743.cdx, HDAC6 inhibitor ISOX, BRD-K03829970, and L-6307 are proposed as novel drugs and small molecule candidates for CRC.
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Affiliation(s)
- Ulku Unal
- Department of Bioengineering, Adana Alparslan Türkeş Science and Technology University, Adana, Turkey
| | - Esra Gov
- Department of Bioengineering, Adana Alparslan Türkeş Science and Technology University, Adana, Turkey
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Constantin A, Constantin R, Achim F, Socea B, Predescu D. Pregnancy and Gastric Cancer: A Narrative Review. Diagnostics (Basel) 2023; 13:1909. [PMID: 37296761 PMCID: PMC10252424 DOI: 10.3390/diagnostics13111909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/22/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Cases of digestive cancers diagnosed during pregnancy are rare. The increasing prevalence of pregnancy in women aged 30-39 years (and not exceptionally 40-49 years) could explain the frequent co-occurrence of cancers and pregnancy. The diagnosis of digestive cancers in pregnancy is difficult due to the overlap between neoplasm symptomatology and the clinical picture of pregnancy. A paraclinical evaluation may also be difficult depending on the trimester of the pregnancy. Diagnosis is also delayed by practitioners' hesitation to use invasive investigations (imaging, endoscopy, etc.) due to fetal safety concerns. Therefore, digestive cancers are often diagnosed during pregnancy in advanced stages, where complications such as occlusions, perforations, and cachexia have already arisen. In this review, we highlight the epidemiology, clinical aspects, paraclinical evaluation, and particularities of the diagnosis and treatment of gastric cancer during pregnancy.
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Affiliation(s)
- Adrian Constantin
- Department of Esophageal and General Surgery, Sf. Maria Clinical Hospital Bucharest, 011192 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| | - Roxana Constantin
- Department of Obstetrics and Gynecology, Sanador Hospital, 010991 Bucharest, Romania
| | - Florin Achim
- Department of Esophageal and General Surgery, Sf. Maria Clinical Hospital Bucharest, 011192 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
| | - Bogdan Socea
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
- Department of Surgery, Sf. Pantelimon Emergency Clinical Hospital, 021659 Bucharest, Romania
| | - Dragos Predescu
- Department of Esophageal and General Surgery, Sf. Maria Clinical Hospital Bucharest, 011192 Bucharest, Romania
- Faculty of Medicine, Carol Davila University of Medicine and Pharmacy Bucharest, 050474 Bucharest, Romania
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The Expression of ARMCX1 in Gastric Cancer Contributes to Prognosis and Influences Chemotherapy. J Immunol Res 2023; 2023:2623317. [PMID: 36726491 PMCID: PMC9886469 DOI: 10.1155/2023/2623317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 10/26/2022] [Indexed: 01/24/2023] Open
Abstract
The altered expression of ARMCX1 in patients with gastric cancer has been reported frequently, yet its correlation to prognosis and chemotherapy needs to be unveiled. In combination of the gene expression data retrieved from TCGA database and bioinformatic analysis, this study discovered 590 differentially expressed genes in the cancerous biopsies isolated from gastric patients, compared with controls. Among which, ARMCX1 exhibited great potential to serve as a prognostic biomarker for gastric patients; furthermore, patients with low expression of ARMCX1 could be more sensitive to these 9 chemotherapeutic agents: A-770041, AMG-706, ATRA, BEZ235, bortezomib, CGP60474, dasatinib, HG-64-1, and pazopanib, rather than the other chemotherapeutic agents. This study helps the improvement of evaluating the prognosis of gastric cancer patients, and would help optimize chemotherapeutic strategies in consideration of the expression of ARMCX1.
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Chandra S, Goswami A, Mandal P. Molecular Heterogeneity of Cervical Cancer Among Different Ethnic/Racial Populations. J Racial Ethn Health Disparities 2022; 9:2441-2450. [PMID: 34741276 DOI: 10.1007/s40615-021-01180-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/22/2021] [Accepted: 10/22/2021] [Indexed: 12/29/2022]
Abstract
The study aimed to find differential gene mutation profile and gene expression status among different ethnic/racial human populations relevant for cervical cancer pathogenesis. The study was based on freely available datasets of The Cancer Genome Atlas (TCGA) of cervical cancer samples in Genomic Data Commons (GDC) data portal. We identified that choline metabolism in cancer and Ras signaling pathways were significantly associated with the Hispanic and Latino group of cervical cancer patients. In these pathways, mutations in the PIK3CA gene, especially E545K, were significantly associated with the Hispanic and LATINO group. We found that AFF3 gene mutation was associated with downregulation of its expression only among the White racial category of cervical cancer cases. Additionally, hypomethylation of the CpG position in the S shore region of the PM20D1 gene was associated with overexpression among the Asian category of cervical cancer cases. Heterogeneity of the molecular profile of AFF3 and PM20D1 gene among racial groups reflects the potential of differential targeted therapy of cervical cancer.
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Affiliation(s)
- Sanchita Chandra
- Biomedical Genetics Laboratory, Department of Zoology, The University of Burdwan, Burdwan, 713104, West Bengal, India
| | - Anindita Goswami
- Biomedical Genetics Laboratory, Department of Zoology, The University of Burdwan, Burdwan, 713104, West Bengal, India
| | - Paramita Mandal
- Biomedical Genetics Laboratory, Department of Zoology, The University of Burdwan, Burdwan, 713104, West Bengal, India.
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Yu L, Zhang MM, Hou JG. Molecular and cellular pathways in colorectal cancer: apoptosis, autophagy and inflammation as key players. Scand J Gastroenterol 2022; 57:1279-1290. [PMID: 35732586 DOI: 10.1080/00365521.2022.2088247] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Colorectal carcinogenesis (CRC) is one of the most aggressive forms of cancer, particularly in developing countries. It accounts for the second and third-highest reason for cancer-induced lethality in women and men respectively. CRC involves genetic and epigenetic modifications in colonic epithelium, leading to colon adenocarcinoma. The current review highlights the pathogenic mechanisms and multifactorial etiology of CRC, influenced by apoptosis, inflammation, and autophagy pathways. METHODS We have carried out a selective literature review on mechanisms contributing to the pathogenesis of CRC. RESULTS Resistance to senescence and apoptosis of the mesenchymal cells, which play a key role in intestinal organogenesis, morphogenesis and homeostasis, appears important for sporadic CRC. Additionally, inflammation-associated tumorigenesis is a key incident in CRC, supported by immune disruptors, adaptive and innate immune traits, environmental factors, etc. involving oxidative stress, DNA damage and epigenetic modulations. The self-digesting mechanism, autophagy, also plays a twin role in CRC through the participation of LC3/LC3-II, Beclin-1, ATG5, other autophagy proteins, and Inflammatory Bowel Disease (IBD) susceptibility genes. It facilitates the promotion of effective surveillance pathways and stimulates the generation of malignant tumor cells. The autophagy and apoptotic pathways undergo synergistic or antagonistic interactions in CRC and bear a critical association with IBD that results from the pro-neoplastic effects of persistent intestinal inflammation. Conversely, pro-inflammatory factors stimulate tumor growth and angiogenesis and inhibit apoptosis, suppressing anti-tumor activities. CONCLUSION Hence, research attempts for the development of potential therapies for CRC are in progress, primarily based on combinatorial approaches targeting apoptosis, inflammation, and autophagy.
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Affiliation(s)
- Lei Yu
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Miao-Miao Zhang
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
| | - Ji-Guang Hou
- Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, China
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Moussavou-Boundzanga P, Itoudi Bignoumba P, Mouinga-Ondeme A, Iroungou B, Bivigou-Mboumba B, Marchio A, Saibou M, Moussavou Kombila JB, Pineau P. Drastic sex-dependent etiological distribution in severe liver diseases from Gabon. Front Oncol 2022; 12:907554. [PMID: 36185278 PMCID: PMC9521596 DOI: 10.3389/fonc.2022.907554] [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: 03/29/2022] [Accepted: 08/22/2022] [Indexed: 12/15/2022] Open
Abstract
Chronic liver diseases still represent a worrying public health issue in Sub-Saharan Africa. In this region, emphasis is generally made on hepatocellular carcinoma (HCC) albeit liver cirrhosis (LC) is also responsible for an important death toll. Very few studies have compared the presentation and etiologies of cancer and cirrhosis of the liver in Middle Africa. We conducted a comparative retrospective analysis of 74 and 134 cases of patients with HCC and LC treated in Libreville, Gabon. Viral or lifestyle risk factors, clinical symptoms, and biological features were compared. We observed that ages of diagnosis were 53.2 ± 15.7 years and 48.6 ± 18.6 years for HCC and LC with remarkably low M:F sex ratios (1.3-1.8). Ethanol consumption was highly prevalent in both disease types (65.0%-70.0%). Chronic viral infections with hepatitis B (HBV) or C (HCV) virus were also widespread with slight domination of the former in both diseases (43.4% vs. 34.3%, and 35.9% vs. 28.5%). Patients with HCC were presenting very late with a mean diameter of the main nodule of 84 ± 50 mm and a multifocal pattern in 72.7% of cases. HCC developed on a cirrhotic liver in 91.7% of cases. Serum AFP was frankly elevated (>400 ng/ml) in only 35.8% of HCC cases. The most striking feature of the HCC series was the contrasted contribution of distinct pathogenic etiologies involving sex, viral, metabolic, and toxic factors. A frequently dysmetabolic condition synergizing with hepatitis C (anti-HCV, 73.8% vs 22.7%, p < 0.0001) in females and a male cancer promoted by recreational toxicants and chronic hepatitis B (HBsAg, 83.5% vs 35.9%, p < 0.0001) were observed. Men with HCC were considerably younger than women (46.8 ± 14.5 years vs. 62.2 ± 12.2 years, p < 0.0001). Further studies are now warranted to identify routes of HCV transmission and if they are still fueling reservoirs of future patients. Public policies to prevent alcohol-related harm have also to be urgently implemented in Gabon.
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Affiliation(s)
- Pamela Moussavou-Boundzanga
- Laboratoire de Biologie Moléculaire et Cellulaire (LABMC), Université des Sciences et Techniques de Masuku (USTM), Franceville, Gabon
- Unité des Infections Rétrovirales et Pathologies Associées, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | | | - Augustin Mouinga-Ondeme
- Unité des Infections Rétrovirales et Pathologies Associées, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon
| | - Berthe Amelie Iroungou
- Unité Mixte de Recherche Centre International de Recherches Médicales de Franceville et Service de Santeí Militaire (CIRMF-SSM), Libreville, Gabon
| | - Berthold Bivigou-Mboumba
- Unité Mixte de Recherche Centre International de Recherches Médicales de Franceville et Service de Santeí Militaire (CIRMF-SSM), Libreville, Gabon
| | - Agnès Marchio
- Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur, Paris, France
| | - Maryam Saibou
- Service de Gastroentérologie, Centre Hospitalier Universitaire de Libreville (CHUL), Libreville, Gabon
| | | | - Pascal Pineau
- Unité « Organisation nucléaire et oncogenèse », INSERM U993, Institut Pasteur, Paris, France
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11
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Najar MA, Arefian M, Sidransky D, Gowda H, Prasad TSK, Modi PK, Chatterjee A. Tyrosine Phosphorylation Profiling Revealed the Signaling Network Characteristics of CAMKK2 in Gastric Adenocarcinoma. Front Genet 2022; 13:854764. [PMID: 35646067 PMCID: PMC9136244 DOI: 10.3389/fgene.2022.854764] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 03/28/2022] [Indexed: 12/24/2022] Open
Abstract
Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine protein kinase which functions via the calcium-triggered signaling cascade with CAMK1, CAMK4, and AMPKα as the immediate downstream substrates. CAMKK2 is reported to be overexpressed in gastric cancer; however, its signaling mechanism is poorly understood. We carried out label-free quantitative tyrosine phosphoproteomics to investigate tyrosine-mediated molecular signaling associated with CAMKK2 in gastric cancer cells. Using a high-resolution Orbitrap Fusion Tribrid Fourier-transform mass spectrometer, we identified 350 phosphotyrosine sites mapping to 157 proteins. We observed significant alterations in 81 phosphopeptides corresponding to 63 proteins upon inhibition of CAMKK2, among which 16 peptides were hyperphosphorylated corresponding to 13 proteins and 65 peptides were hypophosphorylated corresponding to 51 proteins. We report here that the inhibition of CAMKK2 leads to changes in the phosphorylation of several tyrosine kinases such as PKP2, PTK2, EPHA1, EPHA2, PRKCD, MAPK12, among others. Pathway analyses revealed that proteins are differentially phosphorylated in response to CAMKK2 inhibition involved in focal adhesions, actin cytoskeleton, axon guidance, and signaling by VEGF. The western blot analysis upon inhibition and/or silencing of CAMKK2 revealed a decrease in phosphorylation of PTK2 at Y925, c-JUN at S73, and STAT3 at Y705, which was in concordance with the mass spectrometry data. The study indicates that inhibition of CAMKK2 has an anti-oncogenic effect in gastric cells regulating phosphorylation of STAT3 through PTK2/c-JUN in gastric cancer.
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Affiliation(s)
- Mohd. Altaf Najar
- Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India
| | - Mohammad Arefian
- Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India
| | - David Sidransky
- Department of Oncology and Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Harsha Gowda
- Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India
- Institute of Bioinformatics, International Technology Park, Bangalore, India
- Manipal Academy of Higher Education (MAHE), Manipal, India
| | - T. S. Keshava Prasad
- Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India
| | - Prashant Kumar Modi
- Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India
- *Correspondence: Prashant Kumar Modi, ; Aditi Chatterjee,
| | - Aditi Chatterjee
- Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India
- Institute of Bioinformatics, International Technology Park, Bangalore, India
- *Correspondence: Prashant Kumar Modi, ; Aditi Chatterjee,
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12
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Ilic M, Ilic I. Epidemiology of stomach cancer. World J Gastroenterol 2022; 28:1187-1203. [PMID: 35431510 PMCID: PMC8968487 DOI: 10.3748/wjg.v28.i12.1187] [Citation(s) in RCA: 219] [Impact Index Per Article: 73.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/30/2021] [Accepted: 02/15/2022] [Indexed: 02/06/2023] Open
Abstract
Despite a decline in incidence and mortality during the last decades, stomach cancer is one of the main health challenges worldwide. According to the GLOBOCAN 2020 estimates, stomach cancer caused approximately 800000 deaths (accounting for 7.7% of all cancer deaths), and ranks as the fourth leading cause of cancer deaths in both genders combined. About 1.1 million new cases of stomach cancer were diagnosed in 2020 (accounting for 5.6% of all cancer cases). About 75% of all new cases and all deaths from stomach cancer are reported in Asia. Stomach cancer is one of the most lethal malignant tumors, with a five-year survival rate of around 20%. There are some well-established risk factors for stomach cancer: Helicobacter pylori infection, dietary factors, tobacco, obesity, and radiation. To date, the most important way of preventing stomach cancer is reduced exposure to risk factors, as well as screening and early detection. Further research on risk factors can help identify various opportunities for more effective prevention. Screening programs for stomach cancer have been implemented in a few countries, either as a national or opportunistic screening of high-risk individuals only. Generally, due to its high aggressiveness and heterogeneity, stomach cancer still remains a severe global health problem.
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Affiliation(s)
- Milena Ilic
- Department of Epidemiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
| | - Irena Ilic
- Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
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13
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Ray AK, Luis PB, Mishra SK, Barry DP, Asim M, Pandey A, Chaturvedi M, Gupta J, Gupta S, Mahant S, Das R, Kumar P, Shalimar, Wilson KT, Schneider C, Chaturvedi R. Curcumin Oxidation Is Required for Inhibition of Helicobacter pylori Growth, Translocation and Phosphorylation of Cag A. Front Cell Infect Microbiol 2021; 11:765842. [PMID: 35004346 PMCID: PMC8740292 DOI: 10.3389/fcimb.2021.765842] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 12/02/2021] [Indexed: 01/22/2023] Open
Abstract
Curcumin is a potential natural remedy for preventing Helicobacter pylori-associated gastric inflammation and cancer. Here, we analyzed the effect of a phospholipid formulation of curcumin on H. pylori growth, translocation and phosphorylation of the virulence factor CagA and host protein kinase Src in vitro and in an in vivo mouse model of H. pylori infection. Growth of H. pylori was inhibited dose-dependently by curcumin in vitro. H. pylori was unable to metabolically reduce curcumin, whereas two enterobacteria, E. coli and Citrobacter rodentium, which efficiently reduced curcumin to the tetra- and hexahydro metabolites, evaded growth inhibition. Oxidative metabolism of curcumin was required for the growth inhibition of H. pylori and the translocation and phosphorylation of CagA and cSrc, since acetal- and diacetal-curcumin that do not undergo oxidative transformation were ineffective. Curcumin attenuated mRNA expression of the H. pylori virulence genes cagE and cagF in a dose-dependent manner and inhibited translocation and phosphorylation of CagA in gastric epithelial cells. H. pylori strains isolated from dietary curcumin-treated mice showed attenuated ability to induce cSrc phosphorylation and the mRNA expression of the gene encoding for IL-8, suggesting long-lasting effects of curcumin on the virulence of H. pylori. Our work provides mechanistic evidence that encourages testing of curcumin as a dietary approach to inhibit the virulence of CagA.
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Affiliation(s)
- Ashwini Kumar Ray
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
- Department of Microbiology, Saheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi, India
- Department of Environmental Studies, University of Delhi, New Delhi, India
| | - Paula B. Luis
- Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN, United States
| | | | - Daniel P. Barry
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Mohammad Asim
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Achyut Pandey
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Maya Chaturvedi
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Jyoti Gupta
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Shilpi Gupta
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Shweta Mahant
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, India
| | - Rajashree Das
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, India
| | - Pramod Kumar
- Department of Chemistry, Sri Aurobindo College, University of Delhi, New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Keith T. Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, United States
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, United States
| | - Claus Schneider
- Department of Pharmacology and Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN, United States
| | - Rupesh Chaturvedi
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
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14
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Long non-coding RNA X-inactive-specific transcript contributes to cisplatin resistance in gastric cancer by sponging miR-let-7b. Anticancer Drugs 2021; 31:1018-1025. [PMID: 33009035 DOI: 10.1097/cad.0000000000000942] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
X-inactive-specific transcript (XIST) is a 19 kb noncoding RNA which is oncogenic in many cancers including gastric cancer. It is reported that XIST contributes to gastric cancer cells resistant to cisplatin, but specific mechanisms governing this resistance remain unclear. We firstly examined the XIST level in gastric cancer cells and tumor specimens. We confirmed that XIST is overexpressed in gastric cancer cells and tumors, which further contributed to the poor prognosis of patients with gastric cancer. We also confirmed that high XIST level contributes to the cisplatin resistance in gastric cancer cells. Subsequently, we predicted microRNAs that have the potential to interact with XIST and found that Let-7b-5p may directly interact with XIST. We confirmed the direct interaction between XIST and Let-7b-5p and identified a negative correlation between the level of Let-7b-5p and XIST in gastric cancer tumors. Meanwhile, Let-7b-5p inhibitor treatment can partially rescued the effect of XIST-specific small interfering RNA on cell proliferation and apoptosis by regulating Aurora kinase B expression. XIST functions as an oncogene in gastric cancer which contributes to the cisplatin resistance by interacting with Let-7b-5p.
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15
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Najar MA, Aravind A, Dagamajalu S, Sidransky D, Ashktorab H, Smoot DT, Gowda H, Prasad TSK, Modi PK, Chatterjee A. Hyperactivation of MEK/ERK pathway by Ca 2+ /calmodulin-dependent protein kinase kinase 2 promotes cellular proliferation by activating cyclin-dependent kinases and minichromosome maintenance protein in gastric cancer cells. Mol Carcinog 2021; 60:769-783. [PMID: 34437731 DOI: 10.1002/mc.23343] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 01/04/2023]
Abstract
Although CAMKK2 is overexpressed in several cancers, its role and relevant downstream signaling pathways in gastric cancer (GC) are poorly understood. Treatment of AGS GC cells with a CAMKK2 inhibitor, STO-609, resulted in decreased cell proliferation, cell migration, invasion, colony-forming ability, and G1/S-phase arrest. Quantitative phosphoproteomics in AGS cells with the CAMKK2 inhibitor led to the identification of 9603 unique phosphosites mapping to 3120 proteins. We observed decreased phosphorylation of 1101 phosphopeptides (1.5-fold) corresponding to 752 proteins upon CAMKK2 inhibition. Bioinformatics analysis of hypo-phosphorylated proteins revealed enrichment of MAPK1/MAPK3 signaling. Kinase enrichment analysis of hypo-phosphorylated proteins using the X2K Web tool identified ERK1, cyclin-dependant kinase 1 (CDK1), and CDK2 as downstream substrates of CAMKK2. Moreover, inhibition of CAMKK2 and MEK1 resulted in decreased phosphorylation of ERK1, CDK1, MCM2, and MCM3. Immunofluorescence results were in concordance with our mass spectroscopy data and Western blot analysis results. Taken together, our data reveal the essential role of CAMKK2 in the pathobiology of GC through the activation of the MEK/ERK1 signaling cascade.
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Affiliation(s)
- Mohd A Najar
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India
| | - Anjana Aravind
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India
| | - Shobha Dagamajalu
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India
| | - David Sidransky
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Hassan Ashktorab
- Department of Medicine, Howard University, Washington, District of Columbia, USA
| | - Duane T Smoot
- Department of Medicine, Meharry Medical Center, Nashville, Tennessee, USA
| | - Harsha Gowda
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India.,Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India.,Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
| | - T S Keshava Prasad
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India
| | - Prashant K Modi
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India
| | - Aditi Chatterjee
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, India.,Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India.,Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India
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16
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Menati Rashno M, Mehraban H, Naji B, Radmehr M. Microbiome in human cancers. Access Microbiol 2021; 3:000247. [PMID: 34888478 PMCID: PMC8650843 DOI: 10.1099/acmi.0.000247] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 06/17/2021] [Indexed: 12/19/2022] Open
Abstract
A microbiome is defined as the aggregate of all microbiota that reside in human digestive system and other tissues. This microbiota includes viruses, bacteria, fungi that live in various human organs and tissues like stomach, guts, oesophagus, mouth cavity, urinary tract, vagina, lungs, and skin. Almost 20 % of malignant cancers worldwide are related to microbial infections including bacteria, parasites, and viruses. The human body is constantly being attacked by microbes during its lifetime and microbial pathogens that have tumorigenic effects in 15-20 % of reported cancer cases. Recent scientific advances and the discovery of the effect of microbes on cancer as a pathogen or as a drug have significantly contributed to our understanding of the complex relationship between microbiome and cancer. The aim of this study is to overview some microbiomes that reside in the human body and their roles in cancer.
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Affiliation(s)
| | - Hamed Mehraban
- Department of Biology, Payame Noor University (PNU), Tehran, Iran
| | - Behnaz Naji
- Department of Microbiology, Damghan Branch, Islamic Azad University, Damghan, Iran
| | - Mohadeseh Radmehr
- Department of Microbiology, Damghan Branch, Islamic Azad University, Damghan, Iran
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17
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Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities. Molecules 2021; 26:molecules26092506. [PMID: 33923028 PMCID: PMC8123278 DOI: 10.3390/molecules26092506] [Citation(s) in RCA: 114] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/13/2021] [Accepted: 04/19/2021] [Indexed: 02/07/2023] Open
Abstract
Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.
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18
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Najar MA, Modi PK, Ramesh P, Sidransky D, Gowda H, Prasad TSK, Chatterjee A. Molecular Profiling Associated with Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2)-Mediated Carcinogenesis in Gastric Cancer. J Proteome Res 2021; 20:2687-2703. [PMID: 33844560 DOI: 10.1021/acs.jproteome.1c00008] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death worldwide. We showed previously that calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), a serine-threonine kinase, is highly expressed in gastric cancer and leads to progression. In the present study, we identified the molecular networks involved in CAMKK2-mediated progression of gastric adenocarcinoma. Treatment of gastric cancer cell lines with a CAMKK2 inhibitor, STO-609, resulted in decreased cell migration, invasion, and colony-forming ability and a G1/S-phase arrest. In addition, tandem mass tag (TMT)-based quantitative proteomic analysis resulted in the identification of 7609 proteins, of which 219 proteins were found to be overexpressed and 718 downregulated (1.5-fold). Our data identified several key downregulated proteins involved in cell division and cell proliferation, which included DNA replication licensing factors, replication factor C, origin recognition complex, replication protein A and GINS, and mesenchymal markers, upon CAMKK2 inhibition. Immunoblotting and immunofluorescence results showed concordance with our mass spectroscopy data. Taken together, our study supports CAMKK2 as a novel therapeutic target in gastric cancer.
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Affiliation(s)
- Mohd Altaf Najar
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India
| | - Prashant Kumar Modi
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India
| | - Poornima Ramesh
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India
| | - David Sidransky
- Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
| | - Harsha Gowda
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India.,Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka 560066, India.,Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India
| | - T S Keshava Prasad
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India
| | - Aditi Chatterjee
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India.,Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka 560066, India.,Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India
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19
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Laparoscopic intersphincteric resection with hand-sewn coloanal anastomosis in the treatment of low rectal cancer: 10-year experience. Eur Surg 2021. [DOI: 10.1007/s10353-021-00694-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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20
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Farhud DD, Zokaei S, Keykhaei M, Hedayati M, Zarif Yeganeh M. In-Vitro Fertilization Impact on the Risk of Breast Cancer: A Review Article. IRANIAN JOURNAL OF PUBLIC HEALTH 2021; 50:438-447. [PMID: 34178791 PMCID: PMC8214614 DOI: 10.18502/ijph.v50i3.5583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background Due to the increasing prevalence of infertility, the number of referrals to infertility treatment centers has also increased. Nowadays, assisted reproductive technology (ART), including in vitro fertilization (IVF), is a treatment for infertility or genetic problems. Considering the possible consequences of this method among women undergoing in vitro fertilization (IVF) and kids conceived by IVF, extensive research has been conducted in this regard. Methods Overall, 100 articles were entered into the study, and relevant articles were searched and extracted from PubMed, Springer, and Google Scholar databases. In IVF procedure, medications such as Clomiphene citrate and gonadotropins are used to stimulate and mature follicles and thus increase ovulation. Results There are conflicting opinions on this issue. Some findings report a slight increase in cancer risk for hormone-sensitive cancers including breast cancer. The long-term use of IVF medications can increase estrogen hormones and cause excessive expression of genes, resulting in an increased risk of breast cancer, which is one of the most frequent cancers among women. Conclusion There are some risks to be aware of, which followed the hypothesis that long IVF treatment process may lead to breast cancer among IVF candidates. Furthermore, the risk of breast cancer may be increased in those women with a positive family history and related inherited genes. Therefore, women candidates for IVF should be informed of the probable implications of the reproductive therapy techniques.
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Affiliation(s)
- Dariush D Farhud
- School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.,Department of Basic Sciences, Iranian Academy of Medical Sciences, Tehran, Iran
| | - Shaghayegh Zokaei
- School of Advanced Medical Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
| | - Mohammad Keykhaei
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Marjan Zarif Yeganeh
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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21
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Okubo K, Arigami T, Matsushita D, Kijima T, Shimonosono M, Uenosono Y, Yanagita S, Kurahara H, Mori S, Ohtsuka T, Natsugoe S. Clinical impact of creatine phosphokinase and c-reactive protein as predictors of postgastrectomy complications in patients with gastric cancer. BMC Cancer 2021; 21:95. [PMID: 33485312 PMCID: PMC7825180 DOI: 10.1186/s12885-021-07801-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 01/11/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Postoperative complications have been linked to the morbidity and mortality of several cancers. However, predicting whether complications will occur in the early period after surgery or not is challenging. Hence, this study aimed to examine the diagnostic accuracy of serum creatine phosphokinase (CPK) and c-reactive protein (CRP) in predicting the development of postgastrectomy complications. METHODS We retrospectively analyzed 188 patients with gastric cancer (GC) who underwent gastrectomy. The diagnostic accuracy of serum CPK and CRP was investigated using the areas under the curves (AUC). The CPK ratio was defined as the CPK on postoperative day (POD) 1 to the CPK on a preoperative day. RESULTS Out of 188 patients, 48 (25.5%) developed postoperative complications. The complications group had a greater operative time (p = 0.037), higher CPK ratio on POD1 (p < 0.0001), and a higher serum CRP level on POD3 (p = 0.001). The AUC for the CPK ratio was 0.772, with an optimal cutoff value of 7.05, whereas that for CRP was 0.659, with an optimal cutoff value of 11.4 mg/L. The CPK ratio on POD1 (p < 0.0001) and the CRP on POD3 (p = 0.007) were independent factors for predicting the development of postgastrectomy complications. The CPK ratio on POD1 and the CRP on POD3 predicted postgastrectomy complications in 41 patients (85.4%). According to combined value of both CPK ratio and CRP level, the positive predictive value and the negative predictive value was 0.70 and 0.829. And sensitivity and specificity were 0.438 and 0.936. CONCLUSION The CPK ratio on POD1 and the CRP on POD3 after gastrectomy for GC were predictive factors for complication development and may be employed to prevent the development of such complications and improve the prognosis of patients with GC.
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Affiliation(s)
- Keishi Okubo
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
| | - Takaaki Arigami
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
- Department of Onco-biological Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Daisuke Matsushita
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takashi Kijima
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Masataka Shimonosono
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Yoshikazu Uenosono
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shigehiro Yanagita
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Hiroshi Kurahara
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shinichiro Mori
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
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22
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Predictive value of β-catenin in bladder cancer: a systematic review and meta-analysis. Biosci Rep 2020; 40:226086. [PMID: 32797169 PMCID: PMC7475297 DOI: 10.1042/bsr20202127] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 08/06/2020] [Accepted: 08/12/2020] [Indexed: 12/21/2022] Open
Abstract
Recently, some studies have suggested that the abnormal expression of β-catenin in bladder cancer (BC) is associated with the progression and survival of BC, but there are still some controversies. Hence, we elaborated on the relationship between β-catenin expression and BC through a systematic literature review and meta-analysis. As of March 2020, Embase, PubMed, the Cochrane Library, Science Direct/Elsevier, Medline and CNKI were used for systematic literature retrieval to investigate the correlation between β-catenin expression and BC. Meta-analysis was performed using Review Manager and Stata software. Fourteen studies were included, including 865 BC tissues and 106 controls. Combined ORs were identified with 95% confidence intervals (95% CIs) in a random- or fixed-effects model. We illustrated that there was a significant correlation between β-catenin and BC, that there was abnormally high expression of β-catenin in BC tissues compared with normal bladder tissues (P<0.05), and that the combined OR was 14.69 [5.73, 37.65]. Furthermore, the aberrant expression rates of β-catenin in high-grade and invasive bladder neoplasm tissues were greater than those in low-grade and non-muscle-invasive bladder tissues (P<0.05), and the combined ORs were 0.31 [0.23, 0.43] and 0.21 [0.15, 0.29]. Finally, we found through meta-analysis that the higher the expression level of β-catenin, the shorter was the progression-free survival (PFS) of patients with BC (P<0.05), and the combined OR was 2.74 [1.22, 6.14]. The present study suggests that the abnormal expression of β-catenin is associated with aggressive behavior and poor prognosis of BC, and β-catenin may be a molecular marker of the malignant degree and poor prognosis of BC.
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Mohammadi M. Role of Obesity in the Tumorigenesis of Gastric Cancer. Int J Prev Med 2020; 11:148. [PMID: 33209218 PMCID: PMC7643578 DOI: 10.4103/ijpvm.ijpvm_153_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Accepted: 08/01/2019] [Indexed: 11/22/2022] Open
Abstract
Gastric cancer as a common cancer is a multi-factorial disease that is dependent on parallel effects of environment and genetics. Endogenous and host factors, including gender and several genetic backgrounds are known risk factors also many environmental factors, including smoking, diet, infection and increasing body weight and body mass index (BMI) are associated with the gastric cancer. Epidemiological data have consistently demonstrated a positive relation between obesity and gastric cancer, whereas mechanistic studies have sought to uncover obesity related carcinogenic pathways. Biological mechanisms and the relationship between obesity and cancer are complex and not well understood. Different effective factors include obesity-related hormones and adipokines, growth factors, modulation of energy balance and calorie restriction, inflammatory processes and multiple signaling pathways that affect cancer cell promotion and progression. In this review, we will discuss the recent advances in the understanding of the association of obesity changes in the gastric cancer.
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Affiliation(s)
- Masoumeh Mohammadi
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Lin YJ, Lin CN, Sedghi T, Hsu SH, Gross CP, Wang JD, Wang SY. Treatment patterns and survival in hepatocellular carcinoma in the United States and Taiwan. PLoS One 2020; 15:e0240542. [PMID: 33052942 PMCID: PMC7556438 DOI: 10.1371/journal.pone.0240542] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 09/28/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Survival in hepatocellular carcinoma (HCC) is lower in the USA than in Taiwan. Little is known about the extent to which differences in stage at diagnosis and treatment contribute to this difference. We examined treatment patterns and survival in HCC and analyzed factors driving the difference. METHODS Using a uniform methodology, we identified patients aged 66 years and older with newly diagnosed HCC between 2004 and 2011 in the USA and Taiwan. We compared treatment within 6 months after HCC diagnosis and 2-year stage-specific survival between the two countries. RESULTS Compared with patients in Taiwan (n = 32,987), patients in the USA (n = 7,003) were less likely to be diagnosed as stage IA (4% vs 8%) and II (13% vs 22%), or receive cancer-directed treatments (41% vs 58%; all p < .001). Stage-specific 2-year survival rates were lower in the USA than in Taiwan (stage IA: 57% vs 77%; stage IB: 38% vs 63%; stage II: 40% vs 57%, stage III: 14% vs 18%; stage IV: 4% vs 5%, respectively; all p < .001 except p = .018 for stage IV). Differences in age and sex (combined), stage, and receipt of treatment accounted for 3.8%, 17.0%, and 16.8% of the survival difference, respectively, leaving 62.5% unexplained. CONCLUSIONS Differential stage at diagnosis and treatment were substantially associated with the survival difference, but approximately two-thirds of the difference remained unexplained. Identifying the main drivers of the difference could help improve HCC survival in the USA.
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Affiliation(s)
- Yih-Jyh Lin
- Division of General and Transplant Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Liver Cancer Collaborative Oncology Group, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chia-Ni Lin
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Tannaz Sedghi
- Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale University School of Medicine, New Haven, Connecticut, United States of America
| | - Sylvia H. Hsu
- Department of Chronic Disease Epidemiology, Yale University School of Public Health, New Haven, Connecticut, United States of America
- Schulich School of Business, York University, Toronto, Ontario, Canada
| | - Cary P. Gross
- Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale University School of Medicine, New Haven, Connecticut, United States of America
- Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America
| | - Jung-Der Wang
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shi-Yi Wang
- Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale University School of Medicine, New Haven, Connecticut, United States of America
- Department of Chronic Disease Epidemiology, Yale University School of Public Health, New Haven, Connecticut, United States of America
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HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level. Cell Death Dis 2020; 11:780. [PMID: 32951010 PMCID: PMC7502082 DOI: 10.1038/s41419-020-02946-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 05/26/2020] [Accepted: 05/27/2020] [Indexed: 12/28/2022]
Abstract
Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.
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Hajizadeh M, Johnston G, Manos D. Socio-economic inequalities in lung cancer incidence in Canada, 1992–2010: results from the Canadian Cancer Registry. Public Health 2020; 185:189-195. [DOI: 10.1016/j.puhe.2020.04.023] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 04/16/2020] [Accepted: 04/21/2020] [Indexed: 01/12/2023]
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Laparoscopic Proximal Gastrectomy with Jejunal Interposition for Early Proximal Gastric Cancer. J Gastrointest Cancer 2020; 52:536-541. [DOI: 10.1007/s12029-020-00420-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Hammami A, Elleuch N, Jaziri H, Ben Cheikh Y, Braham A, Ajmi S, Ben Slama A, Ksiaa M, Jmaa A. Synchronous Hepatocellular Carcinoma in a Patient with Primary Gastric Cancer: An Exceptional Association. Case Rep Gastroenterol 2020; 14:299-305. [PMID: 32595434 PMCID: PMC7315167 DOI: 10.1159/000506188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 01/27/2020] [Indexed: 11/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer. Liver cirrhosis of any etiology is considered the main risk factor for the development of HCC. However, HCC in noncirrhotic livers remains an uncommon finding. The association of HCC with a primary gastric adenocarcinoma was described in the literature as part of a hepatoid adenocarcinoma which is a special type of primary gastric carcinoma characterized by histologic similarities to HCC with excessive production of α-fetoprotein. Herein, we report the case of a 50-year-old male patient, with no history of pre-existing liver disease, who was admitted due to epigastric pain and vomiting. He was diagnosed with HCC in noncirrhotic liver associated with primary gastric adenocarcinoma. To our knowledge, this is the first case report of synchronous HCC and gastric cancer with no hepatoid adenocarcinoma features in Tunisia.
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Affiliation(s)
- Aya Hammami
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Nour Elleuch
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Hanen Jaziri
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Yasser Ben Cheikh
- Department of Medical imaging, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Ahlem Braham
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Salem Ajmi
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Aida Ben Slama
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Mehdi Ksiaa
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
| | - Ali Jmaa
- Department of Gastroenterology, Faculty of Medicine, Ibn Al Jazzar, University Hospital of Sahloul, Sousse, Tunisia
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Preoperative imaging evaluation of the absolute indication criteria for endoscopic submucosal dissection in early gastric cancer patients. Wideochir Inne Tech Maloinwazyjne 2020; 16:45-53. [PMID: 33786116 PMCID: PMC7991940 DOI: 10.5114/wiitm.2020.94270] [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: 12/23/2019] [Accepted: 02/24/2020] [Indexed: 11/18/2022] Open
Abstract
Introduction Gastric cancer (GC) is a common malignant tumor with a high mortality rate. Aim To determine the accuracy of preoperative imaging information obtained from the combined use of general gastroscopy (GS), endoscopic ultrasonography (EUS), and multi-detector computed tomography (MDCT) regarding absolute indication of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC). Material and methods The relationship between clinical features of 794 EGC patients and lymph node metastasis (LNM) was analyzed. Multivariate logistic regression analysis was used to investigate the risk factors for LNM. Additionally, the accuracy of diagnosis of imaging techniques for ESD indications was determined by receiver operating characteristic (ROC) analysis. Results Data showed that tumor size > 2 cm (p = 0.0071), T1b stage (p < 0.0001), undifferentiated histology (p < 0.0001), and vascular invasion (p = 0.0007) were independent risk factors for LNM in patients with EGC. Indications for ESD have a specificity of 100% for the diagnosis of patients with LNM. Additionally, the diagnostic efficacy of the use of GS, EUS, and MDCT in identifying node positive status, T1a disease, tumor size ≤ 2 cm, and ulceration was found to be moderate with area under the curve (AUC) of receiver operating characteristic curve (ROC) of 0.71, 0.64, 0.72, and 0.68, respectively. Furthermore, the use of imaging techniques for overall indication criteria for ESD had a moderate utility value with an AUC of 0.71. Conclusions Our data suggested that, based on the combined use of GS, EUS, and MDCT, a high specificity of patient selection for ESD treatment can be achieved.
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Chen Y, Zhang T, Liu X, Li Z, Zhou D, Xu W. Melatonin suppresses epithelial‑to‑mesenchymal transition in the MG‑63 cell line. Mol Med Rep 2019; 21:1356-1364. [PMID: 31894324 DOI: 10.3892/mmr.2019.10902] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 10/31/2019] [Indexed: 11/06/2022] Open
Abstract
Epithelial‑to‑mesenchymal transition (EMT) is a major process involved in tumor progression and metastasis. Melatonin is secreted by the pineal gland and has been documented as a potential therapeutic agent for multiple tumors. However, the effects of melatonin on EMT during osteosarcoma (OA) development remain undefined. The present study explored the biological functions and effects of melatonin on EMT induced by transforming growth factor β1 (TGF‑β1) and its underlying mechanisms in MG‑63 cells. Using western‑blotting and immunofluorescence, it was found that the switch in E‑cadherin/N‑cadherin and vimentin expression was induced by TGF‑β1, which was reversed by melatonin through the suppression of Snail and matrix metalloproteinase 9 (MMP‑9), through hypoxia‑inducible factor 1α (HIF‑1α) inhibition. These findings demonstrated that the anticancer effects of melatonin against OA MG‑63 cells is through the suppression of EMT via HIF‑1α/Snail/MMP‑9 signaling.
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Affiliation(s)
- Yongjun Chen
- Department of Orthopaedics, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, P.R. China
| | - Tao Zhang
- Department of Immunology, Basic and Forensic Medicine of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014060, P.R. China
| | - Xiongwei Liu
- Department of Orthopaedics, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, P.R. China
| | - Zengyan Li
- Department of Nephrology, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, P.R. China
| | - Dongming Zhou
- Department of Orthopaedics, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, P.R. China
| | - Wensheng Xu
- Department of Orthopaedics, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 014010, P.R. China
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Szatanek R, Weglarczyk K, Stec M, Baran J, Parlinska-Wojtan M, Siedlar M, Baj-Krzyworzeka M. Autologous tumor‑derived microvesicles influence gene expression profiles and enhance protumorigenic chemotactic potential, signal transduction and cellular respiration in gastric cancer cells. Int J Oncol 2019; 56:359-367. [PMID: 31789386 DOI: 10.3892/ijo.2019.4923] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 10/18/2019] [Indexed: 11/06/2022] Open
Abstract
Tumor‑derived microvesicles (TMVs) interact with a variety of different cell types within the immune system, including lymphocytes, monocytes, dendritic cells and tumor cells that they have originated from. In the present study, the effects of autologous‑TMVs (auto‑TMVs) on gene expression, chemotaxis, intercellular signaling and cellular metabolism were examined in cells of the gastric cancer (GC) cell line 1415 (GC1415). The effects of auto‑TMVs on mRNA gene expression in GC1415 cells were assessed using pathway‑focused PCR arrays. A chemotaxis assay was performed using the HoloMonitor M4 System. Signaling pathways were evaluated using western blot analysis, and cellular respiration was measured using the Seahorse XF Cell Mito Stress Test. Exposure of the GC1415 cells to auto‑TMVs led to the overexpression (75 genes) and underexpression (96 genes) of genes that are associated with signal transduction, metabolism, chemotaxis, angiogenesis and metastasis. The auto‑TMVs were indicated to induce chemotaxis and activate the PI3K/AKT signaling pathway in GC1415 cells. However, the MAPK/ERK signaling pathway was not indicated to be activated. Furthermore, studies on cellular respiration in GC1415 cells exposed to auto‑TMVs demonstrated a metabolic shift to glycolysis. The results of the current study thus indicate that auto‑TMVs may exert an effect on tumor cell function.
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Affiliation(s)
- Rafal Szatanek
- Department of Clinical Immunology, Jagiellonian University Medical College, 30‑663 Krakow, Poland
| | - Kazimierz Weglarczyk
- Department of Clinical Immunology, Jagiellonian University Medical College, 30‑663 Krakow, Poland
| | - Malgorzata Stec
- Department of Clinical Immunology, Jagiellonian University Medical College, 30‑663 Krakow, Poland
| | - Jaroslaw Baran
- Department of Clinical Immunology, Jagiellonian University Medical College, 30‑663 Krakow, Poland
| | | | - Maciej Siedlar
- Department of Clinical Immunology, Jagiellonian University Medical College, 30‑663 Krakow, Poland
| | - Monika Baj-Krzyworzeka
- Department of Clinical Immunology, Jagiellonian University Medical College, 30‑663 Krakow, Poland
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An L, Gaowa S, Cheng H, Hou M. Long-Term Outcomes Comparison of Endoscopic Resection With Gastrectomy for Treatment of Early Gastric Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2019; 9:725. [PMID: 31440467 PMCID: PMC6693408 DOI: 10.3389/fonc.2019.00725] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Accepted: 07/22/2019] [Indexed: 01/13/2023] Open
Abstract
Background: Endoscopic resection (ER) and gastrectomy have been both accepted as curative treatments for early gastric cancer. We intended to compare ER with gastrectomy treatments on safety of patients, disease-free survival and overall survival for early gastric cancer through this systematic review. Methods: A literature search was performed in Pubmed, Embase, and Cochrane Library databases. Studies that have compared ER with gastrectomy for early gastric cancer were included in this meta-analysis. We searched for clinical studies published before March 2019. Stata 12.0 software was used for systematic analysis. Results: Nine studies were included in this systematic review, ER treatment was associated with a shorter length of stay (WMD = -8.53, 95% CI -11.56 to -5.49), fewer postoperative complications (OR = 0.47, 95% CI 0.34-0.65). ER can be performed safely with shorter hospital stay and fewer postoperative complications than gastrectomy. Recurrence rate was higher for ER than for gastrectomy treatment (HR = 3.56, 95% CI 1.86-6.84), mainly because metachronous gastric cancers developed only in the ER treatment. However, most of the metachronous gastric cancers could be curatively treated with ER again, and it didn't affect overall survival of patients with early gastric cancer. There was no difference in overall survival rate between ER and gastrectomy (HR = 0.84, 95% CI 0.63-1.13). Conclusions: ER and gastrectomy are both acceptable for curative treatment of early gastric cancer. However, due to the comparable overall survival and lower postoperative complications and shorter length of stay, ER is better than gastrectomy for early gastric cancer, who met the indication for ER treatment.
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Affiliation(s)
- Liangliang An
- Department of General Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Sharen Gaowa
- Department of Pathology, College of Basic Medicine, Inner Mongolia Medical University, Hohhot, China
| | - Haidong Cheng
- Department of General Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Mingxing Hou
- Department of General Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
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Jakubek M, Kejík Z, Kaplánek R, Hromádka R, Šandriková V, Sýkora D, Antonyová V, Urban M, Dytrych P, Mikula I, Martásek P, Král V. Strategy for improved therapeutic efficiency of curcumin in the treatment of gastric cancer. Biomed Pharmacother 2019; 118:109278. [PMID: 31387004 DOI: 10.1016/j.biopha.2019.109278] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 07/24/2019] [Accepted: 07/25/2019] [Indexed: 02/08/2023] Open
Abstract
Gastric cancer is a common oncological disease. Although enormous efforts have been expended, possible therapeutic modalities are still limited. For this reason, new therapeutic approaches and agents are highly requested and intensively developed. One strategy is the application of natural agents, such as curcumin, with proven anticancer effects and low toxicity for patients. Therefore, this review discusses the potential application of curcumin in the therapy of gastric cancer and its potential incorporation in therapeutic regimens. Because one of the largest impediments for widespread curcumin application is its limited bioavailability (caused mainly by its very low water solubility), studied strategies (drug delivery systems and curcumin derivatization) aimed to solve this obstacle are discussed in more detail.
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Affiliation(s)
- Milan Jakubek
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 121 00 Prague 2, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic.
| | - Zdeněk Kejík
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 121 00 Prague 2, Czech Republic
| | - Robert Kaplánek
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic
| | - Róbert Hromádka
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Research and Development Center C2P s.r.o., Jungmannova 101, 503 51 Chlumec nad Cidlinou, Czech Republic
| | - Viera Šandriková
- Research and Development Center C2P s.r.o., Jungmannova 101, 503 51 Chlumec nad Cidlinou, Czech Republic
| | - David Sýkora
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic
| | - Veronika Antonyová
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 121 00 Prague 2, Czech Republic
| | - Marian Urban
- Food Research Institute Prague, Radiová 1285/7, 1285/7, Prague 10, Czech Republic
| | - Petr Dytrych
- 1st Department of Surgery - Department of Abdominal, Thoracic Surgery and Traumatology, First Faculty of Medicine, Charles University and General University Hospital in Prague, U Nemocnice 2, 128 08 Prague 2, Czech Republic
| | - Ivan Mikula
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic
| | - Pavel Martásek
- Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 121 00 Prague 2, Czech Republic
| | - Vladimír Král
- BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, 252 50 Vestec, Czech Republic; Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 2, 121 00 Prague 2, Czech Republic; Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Technická 5, 166 28 Prague 6, Czech Republic
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PARP1: A potential biomarker for gastric cancer. Pathol Res Pract 2019; 215:152472. [DOI: 10.1016/j.prp.2019.152472] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 05/13/2019] [Accepted: 05/23/2019] [Indexed: 12/14/2022]
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35
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Zhang Y, Xu C. G allele of rs7853346 polymorphism in PTENP1 enhances the proliferation of multiple myeloma cancer stem cells by promoting the expression of PTENP1 and its downstream signaling molecules. J Cell Biochem 2019; 120:19738-19748. [PMID: 31338886 DOI: 10.1002/jcb.29280] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2018] [Accepted: 03/22/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Yehua Zhang
- Department of Hematology, Xingtai People's Hospital, Xingtai, Hebei, China
| | - Changqing Xu
- Emergency Department, Xingtai Third Hospital, Xingtai, Hebei, China
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36
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Ikuse T, Blanchard TG, Czinn SJ. Inflammation, Immunity, and Vaccine Development for the Gastric Pathogen Helicobacter pylori. Curr Top Microbiol Immunol 2019; 421:1-19. [PMID: 31123883 DOI: 10.1007/978-3-030-15138-6_1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
It has been over 30 years since a link was established between H. pylori infection of the gastric mucosa and the development of chronic gastric diseases. Research in rodent models supported by data from human tissue demonstrated that the host immune response to H. pylori is limited by host regulatory T cells. Immunization has been shown to induce a potent Th1- and Th17-mediated immune response capable of eradicating or at least significantly reducing the bacterial load of H. pylori in the stomach in small animal models. These results have not translated well to humans. Clinical trials employing many of the strategies used in rodents for oral immunization including the use of a mucosal adjuvant such as Escherichia coli LT or delivery by attenuated enteric bacteria have failed to limit H. pylori infection and have highlighted the potential toxicity of exotoxin-based mucosal adjuvants. A recent study, however, utilizing a recombinant fusion protein of H. pylori urease and the subunit B of E. coli LT, was performed on over 4000 children. Efficacy of over 70% was demonstrated against naturally acquired infection compared to control volunteers one year post-immunization. Efficacy was reduced, but still above 50% at three years. This study provided new insight into the strategies for developing an improved vaccine for widespread use in countries with high infection rates and where gastric cancer (GC) remains one of the most common causes of death due to cancer.
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Affiliation(s)
- Tamaki Ikuse
- Department of Pediatric and Adolescent Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Thomas G Blanchard
- Department of Pediatrics, University of Maryland School of Medicine, 13-015 Bressler Research Building, 655 West Baltimore Street, Baltimore, MD, 21201, USA.
| | - Steven J Czinn
- Department of Pediatrics, University of Maryland School of Medicine, 13-015 Bressler Research Building, 655 West Baltimore Street, Baltimore, MD, 21201, USA
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Wang CJ, Zhu CC, Xu J, Wang M, Zhao WY, Liu Q, Zhao G, Zhang ZZ. The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer 2019; 18:115. [PMID: 31272462 PMCID: PMC6609402 DOI: 10.1186/s12943-019-1032-0] [Citation(s) in RCA: 186] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 05/22/2019] [Indexed: 12/21/2022] Open
Abstract
Background UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear. Methods We collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells’ migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo. Results UCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, −26b, −193a and − 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model. Conclusions UCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment. Electronic supplementary material The online version of this article (10.1186/s12943-019-1032-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Chao-Jie Wang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Chun-Chao Zhu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Jia Xu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Ming Wang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Wen-Yi Zhao
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Qiang Liu
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Gang Zhao
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China
| | - Zi-Zhen Zhang
- Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pu Jian Road, Shanghai, 200127, China.
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Colquhoun A, Hannah H, Corriveau A, Hanley B, Yuan Y, Goodman KJ. Gastric Cancer in Northern Canadian Populations: A Focus on Cardia and Non-Cardia Subsites. Cancers (Basel) 2019; 11:E534. [PMID: 30991639 PMCID: PMC6520747 DOI: 10.3390/cancers11040534] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/29/2019] [Accepted: 04/04/2019] [Indexed: 12/24/2022] Open
Abstract
In northern Canada where there is a high prevalence of Helicobacter pylori infection, there is a paucity of information on gastric cancer by the topographical subsites cardia (CGC) and non-cardia (NCGC). Here we describe the incidence of CGC and NCGC, separately, among northern Canadian populations. We used data from the Cancer Incidence in Five Continents Volumes X (CI5X) and XI (CI5XI) to obtain CGC and NCGC incidence for Canada and for Yukon (YT), a northern Canadian territory. Using these data with those provided by the Government of the Northwest Territories (NT), we estimated standardized incidence ratios comparing northern populations to Canada as a whole. We also estimated age-standardized incidence rates to permit comparisons across populations globally. NT and YT populations were disproportionately impacted by gastric cancer, particularly NCGC. This was especially true for Indigenous populations: NCGC incidence rates among NT Indigenous men were 2.7 times the rates among all men in Canada, while rates among NT Indigenous women were 3.1 times the rates among all women in Canada. Similarly, age-standardized rates of NCGC among Indigenous NT residents were comparable to global regions where there is a high burden of NCGC. This study has, for the first time, quantified the incidence of CGC and NCGC for the NT and YT, providing new insights into the burden of these cancers among northern Canadian populations.
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Affiliation(s)
- Amy Colquhoun
- School of Public Health, University of Alberta, Edmonton, AB T6G 1C9, Canada; (Y.Y.); (K.J.G.)
| | - Heather Hannah
- Department of Health and Social Services, Government of the Northwest Territories, Yellowknife, NT X1A 2L9, Canada; (H.H.); (A.C.)
| | - André Corriveau
- Department of Health and Social Services, Government of the Northwest Territories, Yellowknife, NT X1A 2L9, Canada; (H.H.); (A.C.)
| | - Brendan Hanley
- Department of Health and Social Services, Government of Yukon, Whitehorse, YT Y1A 1Z4, Canada;
| | - Yan Yuan
- School of Public Health, University of Alberta, Edmonton, AB T6G 1C9, Canada; (Y.Y.); (K.J.G.)
| | - Karen J. Goodman
- School of Public Health, University of Alberta, Edmonton, AB T6G 1C9, Canada; (Y.Y.); (K.J.G.)
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada
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Abstract
Potatoes have been a staple food in many countries throughout the years. Potatoes have a high glycaemic index (GI) score, and high GI has been associated with several chronic diseases and cancers. Still, the research on potatoes and health is scarce and contradictive, and we identified no prospective studies that had investigated the association between potatoes as a single food and the risk of pancreatic cancer. The aim of this study was to prospectively investigate the association between potato consumption and pancreatic cancer among 114 240 men and women in the prospective HELGA cohort, using Cox proportional hazard models. Information on diet (validated FFQ’s), lifestyle and health was collected by means of a questionnaire, and 221 pancreatic cancer cases were identified through cancer registries. The mean follow-up time was 11·4 (95 % CI 0·3, 16·9) years. High consumption of potatoes showed a non-significantly higher risk of pancreatic cancer in the adjusted model (hazard ratio (HR) 1·44; 95 % CI 0·93, 2·22, Pfor trend 0·030) when comparing the highest v. the lowest quartile of potato consumption. In the sex-specific analyses, significant associations were found for females (HR 2·00; 95 % CI 1·07, 3·72, Pfor trend 0·020), but not for males (HR 1·01; 95 % CI 0·56, 1·84, Pfor trend 0·34). In addition, we explored the associations by spline regression, and the absence of dose–response effects was confirmed. In this study, high potato consumption was not consistently associated with a higher risk of pancreatic cancer. Further studies with larger populations are needed to explore the possible sex difference.
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Hoyt M, Reger M, Marley A, Fan H, Liu Z, Zhang J. Vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. Am J Clin Nutr 2019; 109:392-401. [PMID: 30624568 DOI: 10.1093/ajcn/nqy251] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 08/22/2018] [Indexed: 11/13/2022] Open
Abstract
Background Vitamin K inhibits prostate cancer cells, and an altered expression of vitamin K-dependent proteins in prostate tumors has been linked to their aggressiveness and progression. However, little is known about the effect of vitamin K intake on prostate cancer in human populations. Objectives We evaluated the associations of dietary intake of phylloquinone (vitamin K-1), menaquinones (vitamin K-2), and total vitamin K with the development of prostate cancer among participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. Design Dietary intake of vitamin K was assessed with the Dietary Questionnaire (DQX) at baseline and the Dietary History Questionnaire (DHQ) at the third anniversary of randomization by using high-performance liquid chromatography-based food-composition data obtained from the USDA and published studies. During a median follow-up of 11.8 y, 2978 cases of prostate cancer (including 490 advanced cases) were identified from the 28,356 men who completed DQX. Similarly, 2973 cases of prostate cancer (including 647 advanced cases) were documented from the 48,090 men who completed DHQ. Cox proportional hazards regression was used to estimate prostate cancer risk in relation to the dietary intake of vitamin K. Results After adjustment for confounders, dietary intakes of phylloquinone, menaquinones, and total vitamin K, assessed with either the DQX or DHQ, were not significantly associated with the risk of advanced, nonadvanced, and total prostate cancer. These results remained virtually the same when vitamin K intake was modeled as a categorical (divided into quintiles) or continuous (per IQR increase) variable or after outliers of total vitamin K intake (defined as a value that falls above the sum of third quartile and twice the IQR) were excluded. Conclusions The present study does not suggest that vitamin K intake influences the occurrence of total and advanced prostate cancer in the general US population.
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Affiliation(s)
| | - Michael Reger
- Departments of Epidemiology.,Public Health Programs, College of Health Professions, Ferris State University, Big Rapids, MI
| | | | | | - Ziyue Liu
- Biostatistics, Indiana University Richard M Fairbanks School of Public Health, Indianapolis, IN
| | - Jianjun Zhang
- Departments of Epidemiology.,Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN
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Kandhavelu J, Subramanian K, Khan A, Omar A, Ruff P, Penny C. Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression. Microrna 2019; 8:68-75. [PMID: 30073936 DOI: 10.2174/2211536607666180803100246] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 06/05/2018] [Accepted: 07/31/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. METHODS The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis. RESULTS We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated. CONCLUSION These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.
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Affiliation(s)
- Jeyalakshmi Kandhavelu
- Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa
| | - Kumar Subramanian
- Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa
| | - Amber Khan
- Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa
| | - Aadilah Omar
- Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa
| | - Paul Ruff
- Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa
| | - Clement Penny
- Oncology Division, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, Wits, 2050, Johannesburg, South Africa
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Zhang LF, Ren KW, Zuo L, Zou JG, Song NH, Mi YY, Wang ZJ, Zhang W. VEGF gene rs3025039C/T and rs833052C/A variants are associated with bladder cancer risk in Asian descendants. J Cell Biochem 2019; 120:10402-10412. [PMID: 30609111 DOI: 10.1002/jcb.28324] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 11/28/2018] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Polymorphisms of vascular endothelial growth factor (VEGF) gene were evaluated in a number of studies to evaluate bladder cancer (BCa) susceptibility but with controversial conclusions. MATERIAL AND METHODS We performed a pooled analysis and used odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) to investigate the correlation between VEGF gene rs3025039C/T and rs833052C/A variants and risk of BCa. Furthermore, we utilized in silico tools to demonstrate the relationship of VEGF expression correlated with BCa susceptibility and survival time. RESULTS A total of eight studies including 4359 BCa patients and 5417 control subjects were enrolled in our study. For VEGF rs3025039C/T, a significant association was indicated between this variant and BCa risk in homozygote comparison (OR = 1.51; 95% CI = 1.13-2.02; P heterogeneity = 0.815) and recessive genetic model (OR = 1.49; 95% CI = 1.12-1.99; P heterogeneity = 0.874), in particular in an Asian population subgroup. For VEGF rs833052C/A, we observed a positive association between this variant and BCa susceptibility in Asian descendants. Results from in silico tool showed evidence that VEGF expression in bladder carcinoma tissue is higher than that in normal counterpart (transcripts per kilobase million = 7.21 vs 6.85; P < 0.05). CONCLUSIONS The VEGF gene rs3025039C/T and rs833052C/A variants may contribute to the risk of developing BCa, especially in Asian descendants. Future larger sample studies should be continued to focus on this issue in more detail.
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Affiliation(s)
- Li-Feng Zhang
- Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.,Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ke-Wei Ren
- Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin, China
| | - Li Zuo
- Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
| | - Jian-Gang Zou
- Department of Urology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
| | - Ning-Hong Song
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yuan-Yuan Mi
- Department of Urology, Third Affiliated Hospital of Nantong University, Wuxi, China.,Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
| | - Zeng-Jun Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Zhang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Liu Y, Wu X, Wang G, Hu S, Zhang Y, Zhao S. CALD1, CNN1, and TAGLN identified as potential prognostic molecular markers of bladder cancer by bioinformatics analysis. Medicine (Baltimore) 2019; 98:e13847. [PMID: 30633156 PMCID: PMC6336601 DOI: 10.1097/md.0000000000013847] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 09/17/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Bladder cancer (BC) is one of the most common malignant neoplasms in the genitourinary tract. We employed the GSE13507 data set from the Gene Expression Omnibus (GEO) database in order to identify key genes related to tumorigenesis, progression, and prognosis in BC patients. METHODS The data set used in this study included 10 normal bladder mucosae tissue samples and 165 primary BC tissue samples. Differentially expressed genes (DEGs) in the 2 types of samples were identified by GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online website DAVID. The online website STRING was used to construct a protein-protein interaction network. Moreover, the plugins in MCODE and cytoHubba in Cytoscape were employed to find the hub genes and modules in these DEGs. RESULTS We identified 154 DEGs comprising 135 downregulated genes and 19 upregulated genes. The GO enrichment results were mainly related to the contractile fiber part, extracellular region part, actin cytoskeleton, and extracellular region. The KEGG pathway enrichment results mainly comprised type I diabetes mellitus, asthma, systemic lupus erythematosus, and allograft rejection. A module was identified from the protein-protein interaction network. In total, 15 hub genes were selected and 3 of them comprising CALD1, CNN1, and TAGLN were associated with both overall survival and disease-free survival. CONCLUSION CALD1, CNN1, and TAGLN may be potential biomarkers for diagnosis as well as therapeutic targets in BC patients.
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Hu D, Liu Q, Lin X, Zhang H, Lin J, Zheng X, Peng F. Association of RAGE gene four single nucleotide polymorphisms with the risk, invasion, metastasis and overall survival of gastric cancer in Chinese. J Cancer 2019; 10:504-509. [PMID: 30719146 PMCID: PMC6360312 DOI: 10.7150/jca.26583] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 12/08/2018] [Indexed: 11/17/2022] Open
Abstract
Objectives: The receptor for advanced glycation end products (RAGE) is an oncogenic trans-membranous receptor expressed in many cells. The aim of this study was to clarify the association between RAGE gene 4 single nucleotide polymorphisms (SNPs) and the risk, invasion, metastasis and overall survival of gastric cancer. Methods and Results: We performed a hospital-based case-control study involving 369 gastric cancer patients and 493 cancer free controls. Four widely-studied SNPs, rs1800625 (T-429C), rs1800624 (T-374A), rs2070600 (Gly82Ser) and rs184003 (G1704T) in RAGE gene, were genotyped by the polymerase chain reaction - ligase detection reaction method. The RAGE gene rs1800625 TT genotype and T allele were significantly associated with a reduced risk of gastric cancer (TT vs. CC: adjusted odds ratio [OR]: 0.72, 95% CI: 0.55-0.95, p=0.021; T vs. C: adjusted OR: 0.67, 95% CI: 0.46-0.97, p=0.032). No hints of significance were detected for the other three SNPs in association with gastric cancer risk. Moreover, rs1800625 and rs184003 were significantly associated with tumor clinical stage (p=0.010 and 0.032, respectively). Survival curves differed significantly between the genotypes of rs1800625. Conclusions:RAGE gene SNP rs1800625 was significantly associated with gastric cancer risk, and rs1800625 and rs184003 were related to tumor clinical stage, indicating that RAGE gene may be a gastric cancer-susceptibility gene.
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Affiliation(s)
- Dan Hu
- Department of Pathology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Qing Liu
- Department of Cardiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Xiandong Lin
- Department of Pathology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Hejun Zhang
- Department of Pathology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Jinxiu Lin
- Department of Cardiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Xiongwei Zheng
- Department of Pathology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
| | - Feng Peng
- Department of Cardiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
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Evaluation of Gastric Carcinomas Histological Patterns in Relation to Tumors Aggressiveness Parameters. CURRENT HEALTH SCIENCES JOURNAL 2018; 44:342-346. [PMID: 31123609 PMCID: PMC6421475 DOI: 10.12865/chsj.44.04.03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Accepted: 10/31/2018] [Indexed: 12/16/2022]
Abstract
Gastric carcinomas are frequent tumors with variable growth patterns that may interfere with the evaluation of histopathological prognostic parameters of the lesions. In this study we analyzed the incidence and statistical relation of histological growth patterns depending on the prognostic parameters of gastric carcinomas for 95 cases. Pure forms were present in 82.2% of cases, from which more frequent subtypes were low grade tubular carcinomas and poorly cohesive with signet-ring cells carcinomas. Mixed forms were present in 17.8% of cases, with the highest incidence of tumors containing well differentiated tubular carcinoma and poorly differentiated papillary carcinoma areas. Analysis of the identified types and subtypes in relation to the histological prognostic parameters indicated significant differences regarding the tumor stage, the mixed subtypes being more frequent in advanced stages. Although mixed subtypes were more commonly associated with vascular and perineural invasion, the aspects were statistically insignificant. Together with tumor stage, the lymphovascular and/or perineural invasion should be taken into consideration as prognostic indicators in the postoperative management of gastric cancer.
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Militano V, Muthu S, Farooq N, Sajjan R. First case on fluorodeoxyglucose positron emission tomography/computerized tomography of a distant skip metastases to parotid node from esophageal adenocarcinoma. World J Nucl Med 2018; 17:302-304. [PMID: 30505232 PMCID: PMC6216740 DOI: 10.4103/wjnm.wjnm_82_17] [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] [Indexed: 11/17/2022] Open
Abstract
We are presenting the first case of a gastro-oesophageal junction adenocarcinoma with metastasis only to the intraparotid lymph node simulating Warthin's tumor. A 66-year-old man underwent an esophagogastroduodenoscopy that found circumferential ulcerated esophageal tumor beginning 40 cm from incisors resulting in stricture and two discrete erosions in the proximal third of esophagus. Biopsies from the stricture have demonstrated a poorly differentiated gastric adenocarcinoma. Computerized tomography (CT) confirmed the site of primary without evidence of distant metastasis. Positron emission tomography/CT showed high uptake in the known carcinoma in distal esophagus involving the gastro-oesophageal junction extending into the cardia of the stomach, the maximum standardized uptake value (SUVmax) 7.4. Furthermore, there was a focus of high-grade tracer activity, SUVmax 6.2, in the left intraparotid nodule which was initially thought to represent Warthin's tumor rather than metastasis; there was no evidence to suggest metastases elsewhere. Fine needle aspiration and biopsy from the enlarged intraparotid lymph node revealed that the histology was consistent with a poorly differentiated adenocarcinoma, metastasis from upper gastrointestinal tract.
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Affiliation(s)
- Vincenzo Militano
- Department of Nuclear Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
| | - Sivakumar Muthu
- Department of Nuclear Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
| | - Naheed Farooq
- Department of General Surgery, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
| | - Rakesh Sajjan
- Department of Nuclear Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom
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Azimzadeh-Isfanjani A, Safaralizadeh R, Hosseinpour-Feizi M, Shokouhi B, Nemati M, Moaddab SY. Expression of miR-520c in intestinal type gastric adenocarcinoma. J Gastrointest Oncol 2018; 9:1184-1189. [PMID: 30603140 DOI: 10.21037/jgo.2018.08.09] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background MicroRNAs are small non-coding RNAs that participate in post-transcriptional gene regulation in cells thereby playing active role in pathological conditions and have been nominated as new class of biomarkers in disease including cancer. miR-520c has been reported as potential oncogenic micro-RNA in several previous studies. Gastric cancer is the most common cancer of digestive tract and the fourth prevalent cancer worldwide with the intestinal-type gastric adenocarcinoma (IGA) the dominant type of gastric malignancies. This study aimed to explore miR-520c putative role, in IGA and patient's clinicopathological features. Methods Total RNA was first extracted from 42 pairs of IGA tissues and relevant non-tumorous adjacent tissues. cDNA was synthesized from extracted RNAs using specific primers for miR-520c. The level of miR-520c was quantified using SYBER Green Real-Time PCR master mix. The relationship between miR-520c expression and clinicopathological features were examined. Results Our study resulted in no differential expression of miR-520c in IGA. There was no significant correlation between miR-520c expression and clinicopathological features including tumor grade, genus and age groups. Conclusions To our knowledge, this is the first report about exploring miR-520c expression in IGA tissue samples. Our results do not verify miR-520c previously established oncogenic role in IGA.
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Affiliation(s)
| | - Reza Safaralizadeh
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | | | - Behrouz Shokouhi
- Pathology Department, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masuomeh Nemati
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Seyyed-Yaghoub Moaddab
- Liver and Gastroenterology Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Ahmadi A, Salehi F, Ahmadimirghaed Z. Cancer trends in a province of Southwest of Iran, 2003-2016. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2018; 23:80. [PMID: 30294348 PMCID: PMC6161484 DOI: 10.4103/jrms.jrms_68_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 04/09/2018] [Accepted: 06/19/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Awareness of the trends of cancer incidence in each geographic region is an important. The aim of present study was to determine the incidence trends of cancer in Chaharmahal and Bakhtiari (Ch and B) province in Southwest of Iran. MATERIALS AND METHODS In this secondary data analysis, retrospective existing data were used from cancer registry reports in Ch and B in Southwest of Iran in 2003-2016. Data on epidemiologic trend were analyzed using Joinpoint software package and annual percentage change (APC) with 95% confidence interval (95% CI) was computed. RESULTS Age-standardized incidence rate per 100,000 persons in the province in 2003 was 31.74 that increased to 147.14 in 2016. APC during 2003-2016 was 12.58% (CI: 9.3-16) and significant, which was 10.22% (7.4-13.1) and 14.47% (10.2-18.9) in men and women, respectively. Incidence of the stomach, breast, colorectal, thyroid, lymph node, and ovarian cancers is increasing and the highest incidence was observed in two age groups of 25-34 and 55-64 years. CONCLUSION In general, cancers are of increasing trend. Surveillance and monitoring the incidence of cancer and studying the causes of environmental or genetic in the cancer changes can help for cancer prevention and control.
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Affiliation(s)
- Ali Ahmadi
- Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
- Department of Epidemiology and Biostatistics, School of Public Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Fatemeh Salehi
- Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Zenab Ahmadimirghaed
- Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Yin X, Xiong W, Wang Y, Tang W, Xi W, Qian S, Guo Y. Association of CYP2E1 gene polymorphisms with bladder cancer risk: A systematic review and meta-analysis. Medicine (Baltimore) 2018; 97:e11910. [PMID: 30278485 PMCID: PMC6181476 DOI: 10.1097/md.0000000000011910] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Human cytochrome P450 (CYP) is an enzyme responsible for the metabolic activation of many carcinogens, including nitrosamines. CYP2E1 represents a major CYP isoform and is expressed in the human urothelial cells. Recent studies have investigated the association of CYP2E1 gene polymorphisms with bladder cancer risk but have shown contradictory results. Hence, we performed a systematic literature review and meta-analysis to assess the association between CYP2E1 gene polymorphisms and bladder cancer. METHODS Systematic literature searches were conducted with PubMed, Excerpt Medica Database, Science Direct/Elsevier, China National Knowledge Infrastructure, and the Cochrane Library up to January 2018 for studies that involved the association of CYP2E1 gene polymorphisms with bladder cancer risk. A meta-analysis was performed with Review Manager and Stata software. Combined odds ratios (ORs) were identified with 95% confidence intervals (CIs) in a random or fixed effects model. ETHICS The protocol was approved by the institutional review board of each study center. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki. RESULTS Eight studies were identified, including 1733 cases of bladder cancer and 1814 normal controls. Our results illustrated that there are significant associations between CYP2E1 gene polymorphisms and bladder cancer in all genetic models (P < .05). The combined ORs and 95% CIs were as follows for each model: additive model [OR 0.56; 95% CI (0.38-0.82)]; dominant model [OR 0.79; 95% CI (0.67-0.93)]; recessive model [OR 0.61; 95% CI (0.41-0.89)]; codominant model [OR 0.80; 95% CI (0.67-0.96)]; allele model [OR 0.75; 95% CI (0.59-0.95)]. A subgroup study showed that there are also significant associations between CYP2E1 gene polymorphisms and bladder cancer in Asian people. However, there are no significant associations between CYP2E1 gene polymorphisms and bladder cancer in Caucasian populations. CONCLUSIONS The present study provides evidence for an association between CYP2E1 gene polymorphisms and bladder cancer progression, and suggests that CYP2E1 gene polymorphisms might be a protective factor against bladder cancer in Asian people. However, studies with larger sample sizes are needed to confirm the correlation between CYP2E1 gene polymorphisms and bladder cancer.
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Affiliation(s)
- Xiangrui Yin
- Department of Urology, Chongqing Hospital of Traditional Chinese Medicine
| | - Wei Xiong
- Department of Urology, Chongqing Hospital of Traditional Chinese Medicine
| | - You Wang
- Department of Urology, Chongqing Hospital of Traditional Chinese Medicine
| | - Wei Tang
- Department of Urology, First Affiliated Hospital, Medical University of Chongqing, Chongqing, China
| | - Wang Xi
- Department of Urology, Chongqing Hospital of Traditional Chinese Medicine
| | - Shengqiang Qian
- Department of Urology, Chongqing Hospital of Traditional Chinese Medicine
| | - Yu Guo
- Department of Urology, Chongqing Hospital of Traditional Chinese Medicine
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Chen YH, Lin KH, Wang HM, Yu HC, Tsai KW, Hsu PI. The efficacies of esomeprazole- versus pantoprazole-based reverse hybrid therapy for Helicobacter pylori
eradication. ADVANCES IN DIGESTIVE MEDICINE 2018. [DOI: 10.1002/aid2.13070] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Yan-Hua Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
- Physical Examination Center; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
| | - Kung-Hung Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
- Physical Examination Center; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
| | - Huay-Min Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
| | - Hsien-Chung Yu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
- Physical Examination Center; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
| | - Kuo-Wang Tsai
- Department of Medicine Education and Research; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine; Kaohsiung Veterans General Hospital; Kaohsiung Taiwan
- National Yang Ming University; Kaohsiung Taiwan
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