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Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats

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World Journal of Gastroenterology 2006年第12期12卷 1905-1911页

作者： Claudia PMS de Oliveira Fernanda I Simplicio Vicencia MR de Lima Katia Yuahasi Fabio P Lopasso venancio af alves Dulcinéia SP Abdalla Flair J Carrilho Francisco RM Laurindo Marcelo G de Oliveira University of Sāo Paulo School of Medicine Department of Gastroenterology Saoo Paulo SP Brazil School of Medicine Department of Pathology Sāo Paulo SP Brazil University of So Paulo Medical School Heart Institute InCor Sāo Paulo SP Brazil University of Sāo Paulo School of Pharmaceutical Sciences Department of Clinical and Toxicological Analysis Sao Paulo SP Brazil State University of CamDinas. Chemistry Department. Campinas. SE Brazil

AIM： To evaluate the potential of S-nitroso-N-acetylcysteine （SNAC） in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease （NafLD） in an animal model.METHODS： NafLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals （n=6）（1.4 mg/kg/day of SNAC, orally） were compared to 2 control groups： one （n=6） received PBS solution and the other （n=6） received NAC solution （7 mg/kg/d）. Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution. LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein （LDL） suspensions （200 pg protein/mL） were incubated with CuCl2 （300 μmol/L） in the absence and presence of SNAC （300 μmol/L） for 15 h at 37 ℃ Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid （LA）（18.8 μmol/L） oxidation was induced by soybean lipoxygenase （SLO）（0.056 μmol/L） at 37 ℃ in the presence and absence of N-acetylcysteine （NAC） and SNAC （56 and 560 pmol/L） and monitored at 234 nm. RESULTS： Animals in the control group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NafLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group （0.7±0.2 nmol/mg vs 3.2±0.4 nmol/mg protein, respectively, P〈0.05）, while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates. CONCLUSION： Oral

关键词： Nitric oxide S-nitroso-N-acetylcysteine Oxidative stress Nonalcoholic fatty liver disease

Immunohistochemistry panel segregates molecular types of hepatocellular carcinoma in Brazilian autopsy cases

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World Journal of Gastroenterology 2016年第27期22卷 6246-6256页

作者： Aloísio Felipe-Silva Alda Wakamatsu Cinthya dos Santos Cirqueira venancio Avancini Ferreira alves LIM 14-Patologia Hepatica Faculdade de Medicina da USP01246-903 Sao Paulo SPBrazil Department of Pathology Medical Research Laboratory LIM14University of Sao Paulo School Of Medicine01246-903 Sao Paulo SPBrazil

AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC).METHODS: In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related kinase (ERK)1, ERK2, Ki67, cyclin D1, caspase 3 and p53, were detected by immunohistochemistry on tissue microarrays. The expression levels were scored and statistically assessed for correlation with HCC ***: Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin

关键词： Hepatocellular carcinoma Epidermal growth factor receptor Autopsy Immunohistochemistry Liver Classification

Spontaneous rupture of hepatic hemangiomas:A review of the literature

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World Journal of Hepatology 2010年第12期2卷 428-433页

作者： Marcelo af Ribeiro Francine Papaiordanou Juliana M Gonalves Eleazar Chaib Department of Surgery Medical SchoolUniversity of Santo Amaro Professor of Surgery at University Cidade de So Paulo Universidade Cidade de So Paulo Medical Student at Universidade Cidade de So Paulo Liver and Portal Hypertension Surgery Clinicas HospitalUniversity of So Paulo Medical School Nuffield Department of Surgery Churchill HospitalUniversity of Oxford

Hepatic hemangiomas are congenital vascular malformations,considered the most common benign mesenchymal hepatic tumors,composed of masses of blood vessels that are atypical or irregular in arrangement and size. Hepatic hemangiomas can be divided into two major groups:capillary hemangiomas and cavernous hemangiomas These tumors most frequently affect females (80%) and adults in their fourth and fifth decades of life. Most cases are asymptomatic although a few patients may present with a wide variety of clinical symptoms,with spontaneous or traumatic rupture being the most severe complication. In cases of spontaneous rupture,clinical manifestations consist of sudden abdominal pain,and anemia secondary to ahaemoperitoneum. Disseminated intravascular coagulopathy can also occur. Haemodynamic instability and signs of hypovolemic shock appear in about one third of cases. As the size of the hemangioma increases,so does the chance of rupture. Imaging studies used in the diagnosis of hepatic hemangiomas include ultrasonography,dynamic contrast-enchanced computed tomography scanning,magnetic resonance imaging,hepatic arteriography,digital subtraction angiography,and nuclear medicine studies. In most cases hepatic hemangiomas are asymptomatic and should be followed up by means of periodic radiological examination. Sur gery should be restricted to specific situations. Absolute indications for surgery are spontaneous or trau m atic rupture with hemoperitoneum,intratumoral blee ding and consumptive coagulopathy (Kassabach-Merrit syndrome). In a patient presenting with acute abdo minal pain due to unknown abdominal disease,sponta neous rupture of a hepatic tumor such as a hemangio ma should be considered as a rare differential diagnosis.

关键词： Hepatic hemangioma Giant hepatic hemangioma Liver tumor Spontaneous rupture Surgery

Surgical treatment of fibrolamellar hepatocellular carcinoma:an underestimated malignant tumor?

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Hepatobiliary & Pancreatic Diseases International 2014年第6期13卷 618-621页

作者： Paulo Herman Aline Lopes Chagas Marcos Vinicius Perini Fabricio Ferreira Coelho Gilton Marques Fonseca venancio Avancini Ferreira alves Flair José Carrilho Ivan Cecconello Digestive Surgery Division Department of GastroenterologyUniversity of Sao Paulo School of MedicineAvenida Doutor Enéas de Carvalho Aguiar255Instituto Central9°andarSala 9074CEP:05403-900Cerqueira Cesar-Sao PauloSPBrazil Digestive Surgery Division Department of GastroenterologyUniversity of Sao Paulo School of MedicineAvenida Doutor Enéas de Carvalho Aguiar255Instituto Central9°andarSala 9074CEP:05403-900Cerqueira Cesar-Sao PauloSPBrazil Department of Pathology University of Sao Paulo School of MedicineAvenida Doutor Enéas de Carvalho Aguiar255Instituto Central9°andarSala 9074CEP:05403-900Cerqueira Cesar-Sao PauloSPBrazil Digestive Surgery Division Department of GastroenterologyUniversity of Sao Paulo School of MedicineAvenida Doutor Enéas de Carvalho Aguiar255Instituto Central9°andarSala 9074CEP:05403-900Cerqueira Cesar-Sao PauloSPBrazil

BACKGROUND： Fibrolamellar hepatocellular carcinoma （FLHCC） is a rare disease with an indolent behavior. Its prognosis is better than that of patients with hepatocellular carcinoma. The authors present their experience with resection of FLHCC. METHODS： Twenty-one patients with FLHCC were treated at our institution between 1990 and 2012. Of these patients, 14 were subjected to resection of the tumor. Patient demographics, medical history, results of imaging studies and laboratory tests, surgical data, and pathologic findings were evaluated. RESULTS： The median age of the patients at the diagnosis of the tumor was 20 years and 14 patients were female. None of the patients had tumor-associated chronic liver disease or cirrhosis. The mean tumor size was 12.8 cm （range 6-19） and 18 patients had a single liver nodule. Fourteen patients were subjected to hepatectomy and six of them had lymph node metastases resected. Pathologic evaluation revealed that 5 （35.7%） patients had major vascular invasion. Tumor recurrence was seen in 8 patients （66.7%）, during a follow-up. The median survival time for patients who were subjected to resection was 36 months. The 5-year overall survival rate and disease free survival rate were 28.0% and 8.5%, respectively. Univariate analysis showed that vascular invasion was the only variable associated with the disease free survival ***： Despite an aggressive treatment, patients with FLHCC presented unexpected low survival rates. It seems that an underestimated malignant behavior is attributed to this disease, and that the forms of adjuvant treatment should be urgently evaluated.

关键词： fibrolamellar hepatocellular carcinoma hepatectomy hepatocellular carcinoma lymph node excision survival

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 883-893页

作者： Brendha Cação Coimbra Marina Alessandra Pereira Leonardo Cardili venancio Avancini Ferreira alves Evandro Sobroza de Mello Ulysses Ribeiro Jr Marcus Fernando Kodama Pertille Ramos Department of Gastroenterology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil Department of Pathology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão Paulo 01246000Brazil

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological *** We retrospectively reviewed 284 GC patients who underwent ***-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive *** PD-L1+PT staged as pN+were also tested for PD-L1 expression in their ***-L1(-)GC with pN+served as the comparison *** Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the *** PD-L1(-)PT,9.1%(4/44)had PD-L1+in the *** agreement between PT and LNM had a kappa value of *** tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both *** was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched *** disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

关键词： Gastric cancer Lymph node Programmed death ligand 1 Stomach neoplasms Immunohistochemistry Metastasis

Characterization of monocarboxylate transporter activity in hepatocellular carcinoma

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World Journal of Gastroenterology 2014年第33期20卷 11780-11787页

作者： Venncio af alves Céline Pinheiro Filipa Morais-Santos Aloisio Felipe-Silva Adhemar Longatto-Filho Fátima Baltazar Laboratory of Medical Investigation (LIM) 14 Department of Pathology University of S?o Paulo School of Medicine S?oPaulo SP 1246-903 Brazil Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho 4704-553 Braga Portugal ICVS/3B’s-PT Government Associate Laboratory 4710-057 Braga/ Guimar?es Portugal Barretos School of Health Sciences Dr. Paulo Prata-FACISB Barretos S?o Paulo SP 13083-970 Brazil Molecular Oncology Research Center Barretos Cancer Hospital Barretos Sao Paulo 14780-000 Brazil Molecular Oncology Research Center Barretos Cancer Hospital Pio XII Foundation Barretos 14780-000 Brazil

AIM: To assess the immunoexpression of hypoxia-related markers in samples from cirrhosis and primary and metastatic hepatocellular carcinoma (HCC).

关键词： Hepatocellular carcinoma Monocarboxylate transporters Glycolysis Cirrhosis Glucose transporter-1

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

Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer

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Chinese Journal of Cancer Research 2022年第6期34卷 612-622页

作者： Marina Alessandra Pereira Marcus Fernando Kodama Pertille Ramos André Roncon Dias Leonardo Cardili Rafael Dyer Rodrigues de Moraes Renan Ribeiro E Ribeiro venancio Avancini Ferreira alves Bruno Zilberstein Evandro Sobroza de Mello Ulysses Ribeiro Jr Department of Gastroenterology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil Department of Pathology Instituto do Cancer do Estado de Sao PauloHospital das ClinicasFaculdade de MedicinaUniversidade de Sao Paulo(ICESP-HCFMUSP)Sao PauloSP 01246-000Brazil

Objective:Remnant gastric cancer(RGC)is usually associated with a worse *** they are less common and very heterogeneous tumors,new prognostic and reliable determinants are required to predict patients’clinical course for *** study aimed to investigate the tumor-infiltrating lymphocytes(TILs)and programmed cell death ligand 1(PD-L1)status as prognostic biomarkers in a cohort of patients with RGC to develop an immunerelated ***:Patients with gastric cancer(GC)who underwent curative intent gastrectomy were retrospectively *** resections with histological diagnosis of gastric adenocarcinoma were enrolled in the *** risk score based on immune parameters was developed using binary logistic regression *** were divided into high-risk(HR),intermediate-risk(IR),and low-risk(LR)groups based on their immune *** markers(CD3+,CD4+/CD8+T cells and PD-L1)were selected for their potential prognostic,therapeutic value,and evaluated by immunohistochemistry(IHC).Results:A total of 42 patients with RGC were enrolled in the *** score based on immune parameters exhibited an accuracy of 79%[the area under the receiver operating characteristic curve(AUC)=0.79,95%confidence interval(95%CI),0.63-0.94,P=0.002],and the population was divided into 3 prognostic groups:10(23.8%)patients were classified as LR,15(35.7%)as IR,and 17(40.5%)as HR *** were no differences in clinicopathological and surgical characteristics between the three *** survival analysis,HR and IR groups had worse disease-free survival and overall survival rates compared to the LR *** the multivariate analysis,lymph node metastasis and the immune score risk groups were independent factors related to worse ***:A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with ***,tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic bi

关键词： Stomach neoplasms gastric remnant tumor-infiltrating lymphocytes immune microenvironment

Percutaneous radiofrequency ablation for early hepatocellular carcinoma: Risk factors for survival

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World Journal of Gastroenterology 2014年第6期20卷 1585-1593页

作者： Luciana Kikuchi Marcos Menezes Aline L Chagas Claudia M Tani Regiane SSM Alencar Marcio A Diniz Venncio af alves Luiz Augusto Carneiro D’Albuquerque Flair José Carrilho So Paulo Clínicas Liver Cancer Group Instituto do Cancer do Estado de So Paulo Hospital das Clínicas Department of Gastroenterology University of So Paulo School of Medicine So Paulo Clínicas Liver Cancer Group Instituto do Cancer do Estado de So Paulo Hospital das Clínicas Department of Radiology University of So Paulo School of Medicine So Paulo Clínicas Liver Cancer Group Instituto do Cancer do Estado de So Paulo Hospital das Clínicas Department of Pathology University of So Paulo School of Medicine

AIM: To evaluate outcomes of radiofrequency ablation (RFA) therapy for early hepatocellular carcinoma (HCC) and identify survival- and recurrence-related factors.

关键词： Hepatocellular carcinoma Radiofrequency ablation Overall survival Disease-free survival