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Novel Immunogenic Epitopes in the NaPi-IIb Protein: Production of Monospecific Antibodies Using Synthetic Peptides Outlined on Isoform Specific Regions of the Type IIb Sodium-Dependent Phosphate Transporter (NaPi-IIb)

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Journal of Cancer Therapy 2016年第2期7卷 129-151页

作者： Ângela Alice Amadeu Megale Jorge Mário da Costa Ferreira Júnior Letícia Batista Azevedo Rangel Maria Del Pilar Estevez Diz Max Senna Mano paulo marcelo gehm hoff Priscila Hess Lopes Roberto Jun Arai Wilmar Dias da Silva Laboratório de Imunoquímica Instituto Butantan S&atildeo Paulo Brazil Departamento de Ciências Farmacêuticas Universidade Federal do Espírito Santo Espírito Santo Brazil Departamento de Pesquisa Clínica Instituto do C&acircncer do Estado de S&atildeo Paulo S&atildeo Paulo Brazil

NaPi-IIb is a multiple passage protein membrane which is primarily responsible for phosphate uptake in the kidney and in the small intestine. Beyond its physiological functions, their involvement with carcinogenesis was initially described in mid-2003, due to its distinct level of expression in normal and tumor cells of the ovary. Although less common than cervical cancer, epithelial ovarian cancer is considered the most lethal gynecologic malignancy, which is mainly due to diagnosis in the advanced stages as a result of the absence of symptoms during the onset of the disease and the lack of tools for early detection. Here, we produce antibodies that are anti-synthetic peptides that are derived from the regions of second extracellular loop of NaPi-IIb, which is a non-overlapping portion of MX35 epitope. These two 15 distinct amino acid residue peptides, designated as Let#1 and Let#2, are engineered in a very thorough way to detect specific sites only in this isoform, thus excluding cross-reactivity with other carriers of the same family. The lack of immunogenicity of small peptides is surpassed by the conjugation with carrier proteins. Using immunochemical methods, we demonstrate that polyclonal antibodies that are mono-specific for the Let#1 and Let#2 peptides recognize proteins that express similar amino acid sequences during blood circulation. Additionally, using flow cytometry, we identify NaPi-IIb in NIH:OVCAR-3 cells. The clear identification of two shorter peptides on the extracellular loop of NaPi-IIb, which are far from the monoclonal antibody MX35-recognizing epitopes, adds new promising tools for ovarian cancer follow-up and staging.

关键词： NaPi2b Peptides Antibodies Ovarian Cancer

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结肠癌化疗的最新进展(英文)

结肠癌化疗的最新进展(英文)

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中国医师协会内镜医师分会成立大会、中国第十四届内镜医学学术大会、《中国内镜杂志》创刊十周年学术讨论会、恩德思奖（Endoscopics Award）颁奖大会

作者： paulo M.hoff FACP Assoclate Professor of Medicine MD

关键词：结肠癌 FOLFOX FOLFIRI

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Primary prevention of colorectal cancer:Myth or reality?

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World Journal of Gastroenterology 2014年第41期20卷 15060-15069页

作者： Marcela Crosara Teixeira Maria Ignez Braghiroli Jorge Sabbaga paulo M hoff Division of Medical Oncology Instituto do Cancer do Estado de S?o PauloHospital Sírio Libanês

Colorectal cancer incidence has been rising strongly in parallel with economic *** the past few decades,much has been learned about the lifestyle,dietary and medication risk factors for this *** respect to lifestyle,compelling evidence indicates that prevention of weight gain and maintenance of a reasonable level of physical activity can positively influence in lowering the *** there is controversy about the role of specific nutritional factors,consideration of dietary pattern as a whole appears useful for formulating *** quite often recommended,the role for many supplements,including omega-3,vitamin D,folate,and vitamin B6,remains *** calcium and vitamin D supplementation appear to add a modest benefit,particularly in those with a low daily *** regard to chemoprevention,medications such as aspirin and nonsteroidal antiinflammatory drugs,and postmenopausal hormonal replacement for women might be associated with substantial reductions in colorectal cancer risk,though their utility is affected by their side effect ***,the role of agents such as statins,bisphosphonates and antioxidants have yet to be ***,primary prevention strategies focusing on modifying environmental,lifestyle risk factors,and chemopreventive drugs are options that have already been tested,and may impact on colon cancer incidence.

关键词： Primary prevention Colorectal cancer Physical acti

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Better Management of Adverse Events Favors Sorafenib Treatment of HCC Patients and Impact on Survival

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Journal of Cancer Therapy 2016年第4期7卷 275-284页

作者： Regiane S. S. M. Alencar Luciana Kikuchi Cláudia M. Tani Aline L. Chagas Cinira C. Camargo Túlio E. F. Pfiffer paulo M. G. hoff Flair J. Carrilho Sao paulo Clínicas Liver Cancer Group Instituto do Cancer do Estado de Sao Paulo (ICESP) Hospital das Clínicas Department of Gastroenterology University of Sao Paulo School of Medicine Sao Paulo Brazil Medical Oncology Instituto do Cancer do Estado de Sao Paulo (ICESP) Sao Paulo Brazil

Introduction: Sorafenib is an orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC) and is the only systemic treatment associated with a survival benefit in advanced stage. The aims of this study were to evaluate the tolerance and survival of sorafenib-treated patients, and to identify potential prognostic factors of survival. Methods: A total of 88 HCC patients treated with sorafenib from June 2010 to January 2014 were retrospectively reviewed. Tumour stage, liver function and adverse events to sorafenib were analyzed. Univariate and multivariate analysis were carried out to identify predictors of survival in patients with advanced HCC treated with sorafenib. Results: There were 64 (73%) males included in this study, with a median age of 61.16 years. Eight (91%) patients had Child-Pugh class A cirrhosis. Most patients were classified as BCLC C (82%). Hepatitis C virus was the predominant cause of HCC (68%). Sorafenib was the initial treatment modality in 43%. Median time of sorafenib therapy was 8.23 months. Overall survival in 1 year was 57.3% and 36.7% in 2 years. The median survival was 16.3 months. In the univariate analysis of the OS based on Child-Pugh score did not demonstrate a significant difference in our study (p = 0.62). The presence of dermatologic adverse event predicted a better overall survival in the multivariate analysis. Better survival was also observed in patients with AFP level <100 ng/ml in the start of sorafenib therapy (p = 0.001). Patients that used Sorafenib for ≥6 months had shown better outcome. None of the patients discontinued sorafenib because of adverse effects. Conclusions: Advanced HCC patients treated with sorafenib who experienced dermatologic adverse event and low AFP level <100 ng/ml showed better overall survival. As expected, longer sorafenib therapy (≥6 months) was associated to better survival. Even in the presence of adverse events, the use of sorafenib should be continu

关键词： Management of Adverse Event Hepatocellular Carcinoma Sorafenib Therapy Predictors of Overall Survival Dermatologic Adverse Event

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Endoscopic sleeve gastroplasty in class Ⅲ obesity:Efficacy, safety, and durability outcomes in 404 consecutive patients

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World Journal of Gastrointestinal Endoscopy 2023年第6期15卷 469-479页

作者： Daniel Barry Maselli Anna Carolina hoff Ashley Kucera Emily Weaver Laura Sebring Lori Gooch Kathleen Walton Daniel Lee Taylor Cratty Selena Beal Srikar Nanduri Kendall Rease Christina S Gainey Laura Eaton Brian Coan Christopher E McGowan Department of Endobariatrics True You Weight LossCaryNC 27513United States Bariatric Endoscopy Angioskope ClinicSão Josédos Campos 12243-680São PauloBrazil Gastroenterology and Hepatology University of North Carolina SystemChapel HillNC 27599United States UltaMed Corporation UltaMed CorporationFort LauderdaleFL 33308United States

BACKGROUND Endoscopic sleeve gastroplasty(ESG) is an effective therapy for class Ⅰ-Ⅱ obesity, but there are knowledge gaps in the published literature about its implementation in patients with class Ⅲ obesity [body mass index(BMI) ≥ 40 kg/m2].AIM To evaluate the safety, clinical efficacy, and durability of ESG in adults with class Ⅲ *** This was a retrospective cohort study that used prospectively collected data on adults with BMI ≥ 40 kg/m2who underwent ESG and longitudinal lifestyle counseling at two centers with expertise in endobariatric therapies from May 2018-March 2022. The primary outcome was total body weight loss(TBWL) at 12 mo. Secondary outcomes included changes in TBWL, excess weight loss(EWL) and BMI at various time points up to 36 mo, clinical responder rates at 12 and 24 mo, and comorbidity improvement. Safety outcomes were reported through the study duration. One-way ANOVA test was performed with multiple Tukey pairwise comparisons for TBWL, EWL, and BMI over the study *** 404 consecutive patients(78.5% female, mean age 42.9 years, mean BMI 44.8 ± 4.7 kg/m2) were enrolled. ESGs were performed using an average of 7 sutures, over 42 ± 9 min, and with 100% technical success. TBWL was 20.9 ± 6.2% at 12 mo, 20.5 ± 6.9% at 24 mo, and 20.3 ± 9.5% at 36 mo. EWL was 49.6 ± 15.1% at 12 mo, 49.4 ± 16.7% at 24 mo, and 47.1 ± 23.5% at 36 mo. There was no difference in TBWL at 12, 15, 24, and 36 mo from ESG. TBWL exceeding 10%, 15%, and 20% was achieved by 96.7%, 87.4%, and 55.6% of the cohort at 12 mo, respectively. Of the cohort with the relevant comorbidity at time of ESG, 66.1% had improvement in hypertension, 61.7% had improvement in type Ⅱ diabetes, and 45.1% had improvement in hyperlipidemia over study duration. There was one instance of dehydration requiring hospitalization(0.2% serious adverse event rate).CONCLUSION When combined with longitudinal nutritional support, ESG induces effective and durable weight loss in adults with c

关键词： Endoscopic sleeve gastroplasty Obesity Bariatric Endobariatrics Class III obesity Comorbidities

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