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Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

World Journal of Gastroenterology 2018年第7期24卷 794-809页

作者： Mercedes Rubio-Manzanares Dorado Luis Miguel Marín Gómez Daniel Aparicio Sánchez sheila pereira arenas Juan Manuel Praena-Fernández Juan Jose Borrero Martín Francisco Farfán López Miguel ángel Gómez Bravo Jordi Muntané Relat Javier Padillo Ruiz Department of Hepatobiliary and Pancreatic Surgery Virgen del Rocio University Hospital Oncology Surgery Cell Therapy and Organ Transplantation Group Institute of Biomedicine of Seville (IBiS) Virgen del Rocio University Hospital University of Seville Statistics Methodology and Evaluation of Research Unit Virgen del Rocio University Hospital Pathology Department Virgen del Rocio University Hospital

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude *** This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUNEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical *** In our experie

关键词： Immunohistological analysis Pancreatic cancer Patient-derived xenograft Animal model Nude mice

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Metabolic disease and the liver: A review

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World Journal of Hepatology 2024年第1期16卷 33-40页

作者： Márcia Vargas sheila de Castro Cardoso Toniasso Patricia G Riedel Camila pereira Baldin Francielle Lopes dos Reis Robson Martins pereira Maria Carlota Borba Brum Dvora Joveleviths Mario Reis Alvares-da-Silva Program of Graduate Science in Gastroenterology and Hepatology Federal University of Rio Grande do SulPorto Alegre 90040-060Rio Grande do SulBrazil School of Medicine Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Program of Graduate Science in Gastroenterology and Hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90410000Brazil Medicine Faculty Federal University of Rio Grande do Sul Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Division of Gastroenterology and Hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90035007Brazil

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin *** presence of metabolic comorbidities coexisting with liver disease varies substantially among *** is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with *** steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of *** diagnosis is based on the presence of steatosis,noninvasive scores and altered liver *** scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely ***,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical ***,there is no definite pharmacological treatment for the *** public health policies to treat patients with risk factors for MASLD prevention is essential.

关键词： Nonalcoholic fatty liver disease Primary care Metabolic risk Liver Metabolism

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Immunohistochemical expression of thymidylate synthase and prognosis in gastric cancer patients submitted to fluoropyrimidine-based chemotherapy

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Chinese Journal of Cancer Research 2018年第5期30卷 526-536页

作者： Marina Alessandra pereira Marcus Fernando Kodama Pertille Ramos ANDre Roncon Dias sheila Friedrich Faraj Cinthya dos Santos Cirqueira EvANDro Sobroza de Mello Bruno Zilberstein Venancio Avancini Ferreira Alves Ulysses Ribeiro Jr Department of Gastroenterology Cancer InstituteUniversity of Sao Paulo Medical School Department of Pathology Cancer InstituteUniversity of Sao Paulo Medical School Department of Pathology Instituto Adolfo Lutz

Objective： Adjuvant chemotherapy with 5-fluorouracil （5-FU） has been widely used in gastric cancer （GC） patients to prevent relapse after curative resection. 5-FU acts by inhibiting thymidylate synthase （TS）, and high levels of TS correlate with resistance to treatment with fluoropyfimidines. The aim of this study was to evaluate the expression of TS in GC patients, and its relation with clinicopathological characteristics and prognosis in adjuvant chemotherapy with 5-FU. Methods： We retrospectively evaluated 285 patients who underwent D2-gastrectomy with curative intent. TS expression was determined by immunohistochemistry （IHC） in tumor cells by tissue microarray （TMA）. TS level was evaluated according to the intensity and percentage of cells marked by a score system. Patients were divided in three groups according to their TS-score： negative, low and high. Results： TS expression was positive in 92.3% of GC. TS-high, TS-low and TS-negative were observed in 46.3%, 46.0% and 7.7% of patients, respectively. High-TS GC were associated with older age （P=0.007）, high neutrophil/lymphocyte ratio （P=0.048）, well/moderately differentiated histology （P=0.001）, intestinal Lauren type （P〈0.001） and absence of perineural invasion （P=0.003）. Among 285 patients, 133 stage IUIII patients （46.7%） received chemotherapy with 5-FU. In survival analysis, TS-high was associated with worse disease-free survival （DFS） in stage III GC patients who received 5-FU-based chemotherapy （P=0.007）. Multivariate analysis revealed that total gastrectomy, poorly differentiated tumors and high TS-score were associated with worse DFS in stage III GC patients. Conclusions： High TS-score in stage III GC was associated with poor DFS in patients treated with fluoropyrimidine-based chemotherapy.

关键词： Gastric cancer adjuvant therapy thymidylate synthase 5-fluorouracil-based chemotherapy

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