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Experience with peritoneal mesothelioma at the Milan National Cancer Institute

World Journal of Gastrointestinal Oncology 2010年第2期2卷 76-84页

作者： Marcello Deraco Dario Baratti Antonello Domenico Cabras Nadia Zaffaroni Federica Perrone Raffaella Villa Jenny Jocollè Maria Rosaria Balestra Shigeki Kusamura Barbara Laterza Silvana Pilotti Department of Surgery National Cancer Institute Department of Pathology National Cancer Institute Department of Experimental Oncology National Cancer Institute

Diffuse malignant peritoneal mesothelioma (DMPM) is an uncommon and rapidly fatal tumor.Therapeutic options have traditionally been limited and ineffective.The biologic and molecular events correlated with poor responsiveness to therapy are still poorly understood.In recent years,an innovative treatment approach involving aggressive cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has reportedly resulted in improved outcome,as compared to historical controls.Since 1995,at the National Cancer Institute (NCI) of Milan (Italy),patients with DMPM have been treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC).In the present paper,clinical experiences and basic science investigations on DMPM at Milan NCI are reviewed.Perioperative and long-term outcome results with CRS and HIPEC are presented.Clinico-pathological prognostic factors were investigated by multivariate analysis.The pathologic features and immunohistochemical markers related to DMPM biologic behavior were assessed in a large case-series uniformly treated at our institution.The prevalence and prognostic role of telomere maintenance mechanisms,which account for the limitless cell replicative potential of many malignancies,were studied.The dysregulation of the apoptotic pathways may play a role in the relative chemo-resistance of DMPM and a better understanding of apoptosis-related mechanisms could result in novel targeted therapeutic strategies.On this basis,the expression of survivin and other IAP family members (IAP-1,IAP-2,and X-IAP),the pro-apoptotic protein Smac/DIABLO,and antigens associated with cell proliferation (Ki-67) and apoptosis (caspase-cleaved cytokeratin-18) were analyzed.Finally,analyses of EGFR,PDGFRA and PDGFRB were performed to ascertain if deregulation of RTK could offer useful alternative therapeutic targets.

关键词： Peritoneal mesothelioma Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Telomerase Surviving Apoptosis Receptor tyrosin kinase

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cancer Complementary and Alternative Medicine Research at the US National Cancer Institute

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Chinese Journal of Integrative Medicine 2012年第5期18卷 325-332页

作者： Libin Jia The Chinese Journal of Integrated Traditional and WesternMedicine Press and Springer-Verlag Berlin Heidelberg 2011 Office of cancer Complementary and Alternative Medicine Division of Cancer Treatment and Diagnosis National Cancer Institute National Institutes of Health Bethesda Maryland USA

The United States National Cancer Institute （NCI） supports complementary and alternative medicine （CAM） research which includes different methods and practices （such as nutrition therapies） and other medical systems （such as Chinese medicine）. In recent years, NCI has spent around $120 million each year on various CAM-related research projects on cancer prevention, treatment, symptom/side effect management and epidemiology. The categories of CAM research involved include nutritional therapeutics, pharmacological and biological treatments, mind-body interventions, manipulative and body based methods, alternative medical systems, exercise therapies, spiritual therapies and energy therapies on a range of types of cancer. The NCI Office of cancer Complementary and Alternative Medicine （OCCAM） supports various intramural and extramural cancer CAM research projects. Examples of these cancer CAM projects are presented and discussed. In addition, OCCAM also supports international research projects.

关键词： complementary and alternative medicine Chinese medicine cancer research

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Risk Stratification Treatment of Pediatric Rhabdomyosarcoma: South Egypt Cancer Institute Experience

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Journal of cancer Therapy 2012年第5期3卷 595-601页

作者： Hamza Abbas Amany M. Ali Heba Abdel Razik Sayed Mohamed A. Salem Mohammed Hamdy Department of Surgical Oncology South Egypt Cancer Institute Assiut University Assiut Egypt Diagnostic Radiology Department South Egypt Cancer Institute Assiut University Assiut Egypt Pediatric Oncology Department South Egypt Cancer Institute Assiut University Assiut Egypt The Radiation Oncology Department South Egypt Cancer Institute Assiut University Cairo Egypt

Risk stratification allows tailoring of treatment protocol using, for selected patients, reduced total chemotherapy exposure, including decreases in alkylator therapy and avoidance of agents with recognized risk of late complications (anthracyclines), elimination of irradiation and reduction of radiotherapy dose. Patients and Methods: Twenty-nine newly diagnosed pediatric rhabdomyosarcoma patients attended the pediatric oncology department between January 2008 and May 2011. Patients were divided into 3 groups according to age, stage, group, pathology and site of the tumor. Treatment protocol tailored according to risk group. Results: Twenty-nine newly diagnosed pediatric rhabdomyosarcoma patients were evaluated. Seven patients had low risk, Intermediate risk included 12 patients, and 10 patients had high risk. After three years median follow up, event free survival was 51.7% for all patients however it was 86%, 67% and 10% for low, intermediate and high risk respectively (P = 0.0002). There was statistical difference for survival among different sites, histology, clinical group and stage as risk factors within each risk group, no statistically survival significance of any of these factors within the same risk group. Conclusion: Risk stratification is the best single predictor factor for pediatric rhabdomyosarcoma and allows tailoring of the treatment protocol. For selected patients, reductions in total chemotherapy exposure, elimination of irradiation in selected low risk patients and reduction of radiotherapy dose according to postoperative margin and nodal status is safe.

关键词： Pediatric Rhabdomyosarcoma and Risk

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砷对核苷酸切除修复的抑制

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科学通报 2012年第2期57卷 3208-3208页

作者：沈胜文王川 Michael Weinfeld 乐晓春 Department of Laboratory Medicine and Pathology Cross Cancer Institute University of Alberta

砷对DNA修复的抑制被认为是其产生共致突变作用/共致癌作用的一种途径.本文综述了有关砷化合物影响核苷酸切除修复（NER）的报道.对于核苷酸切除修复是如何被砷抑制的,目前已有好几种推测机制.

关键词：核苷酸切除修复砷化合物致突变作用 DNA修复致癌作用

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Prognostic Significance of Absolute Lymphocytic Count Recovery in Pediatric Patients with Acute Lymphoblastic Leukemia at South Egypt Cancer Institute

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Journal of cancer Therapy 2019年第12期10卷 958-970页

作者： Azza Shibl Noha Gaber Nelly Alieldin Heba Sayed Department of Pediatric Oncology South Egypt Cancer Institute (SECI) Assiut University Assiut Egypt Department of Clinical Pathology South Egypt Cancer Institute (SECI) Assiut University Assiut Egypt Department of cancer Epidemiology National Cancer Institute Cairo Egypt

Background: Leukemia is the most common cause of disease-related death in childhood despite significant improvement in survival and modern risk stratification. Prognostic significance of absolute lymphocytic count (ALC) recovery was studied in pediatric patients with acute lymphoblastic leukemia?(ALL). Methods: One hundred twenty one patients newly diagnosed asALL ≤ 18 yearstreated at pediatric oncology department, South Egypt Cancer Institute from 2011 to 2015 were enrolled. Age, sex, initial total leucocytic count, immunophenotyping, central nervous system (CNS) involvement, mediastinal mass, bone marrow (BM) response on day fifteen and after finishing induction remission were compared to ALC recovery on day 15 (ALC-15) and day 29 (ALC-29) of induction response. Also, prognostic impact of ALC recovery on event free survival (EFS) and overall survival (OS) was evaluated. Results: ALC didn’t show any significant relation to known patients’ prognostic factors. Patients with low ALC didn’t show significant lower response on day 15 and post induction evaluation from those with high ALC (p = 0.74, 0.6 respectively). ALC-15 ≥ 500 cells/uL showed a prognostic significance as patients with ALC-15 500 cells/uL had a poorer outcome (4- EFS 47.8% ± 0.12%) than patients with ALC-15 ≥ 500 cells/uL who carried a better outcome (4-EFS 66.3% ± 0.05%). Neither ALC-500 (day 29) nor ALC-350 (day 15 & day 29) had impact on OS or EFS. In multivariate analysis, ALC-15 500 cells/uL still had a poor impact on outcome (OR 2.56, 95% CI 1.27 - 5.14) with d15-BM response (OR 2.99, 95% CI 1.35 - 6.61) and age 10 (OR 1.96, 95% CI 1.01 - 3.69). Conclusions: ALC-15 has an independent prognostic impact on outcome as well as simple, inexpensive, and easy to interpret. Although, it’s utility in risk stratification of ALL still need a confirmation through a multicenter study with uniform variables, large cohort and long duration of follow up.

关键词： ALC Pediatric ALL Outcome

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A revision of the InfiniumPurify R package for genome-wide correction of tumor purity in Infinium DNA methylation array data

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Genes & Diseases 2023年第3期10卷 698-700页

作者： Phuc H.Hoang Division of cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892USA

Understanding DNA methylation(DNAm)alterations in tumors is important to develop novel therapeutic targets and powerful biomarkers,and to gain insights into tumorigenesis processes.As many studies have highlighted the confounding effects of tumor purity in DNAm analyses,1,2,3 various tools have also been developed to tackle the issue.2,3,4 Among them,InfiniumPurify R package is a popular and widely cited tool,2,3,5 consisting of a set of statistical methods to estimate and account for tumor purity in cancer DNAm analyses.

关键词： alterations purity correction

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ezQTL:A Web Platform for Interactive Visualization and Colocalization of QTLs and GWAS Loci

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Genomics, Proteomics & Bioinformatics 2022年第3期20卷 541-548页

作者： Tongwu Zhang Alyssa Klein Jian Sang Jiyeon Choi Kevin M.Brown Division of cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892USA

Genome-wide association studies(GWAS)have identified thousands of genomic loci associated with complex diseases and traits,including cancer.The vast majority of common traitassociated variants identified via GWAS fall in non-coding regions of the genome,posing a challenge in elucidating the causal variants,genes,and mechanisms involved.Expression quantitative trait locus(eQTL)and other molecular QTL studies have been valuable resources in identifying candidate causal genes from GWAS loci through statistical colocalization methods.While QTL colocalization is becoming a standard analysis in post-GWAS investigation,an easy web tool for users to perform formal colocalization analyses with either user-provided or public GWAS and eQTL datasets has been lacking.Here,we present ezQTL,a web-based bioinformatic application to interactively visualize and analyze genetic association data such as GWAS loci and molecular QTLs under different linkage disequilibrium(LD)patterns(1000 Genomes Project,UK Biobank,or user-provided data).This application allows users to perform data quality control for variants matched between different datasets,LD visualization,and two-trait colocalization analyses using two state-of-the-art methodologies(eCAVIAR and HyPrColoc),including batch processing.ezQTL is a free and publicly available cross-platform web tool,which can be accessed online at https://analysistools.***.gov/ezqtl.

关键词： Genome-wide association study Expression quantitative trait locus Colocalization Linkage disequilibrium Visualization

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Neutrophil elastase:From mechanisms to therapeutic potential

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Journal of Pharmaceutical Analysis 2023年第4期13卷 355-366页

作者： Weilin Zeng Yingqiu Song Runze Wang Rong He Tianlu Wang Department of Radiotherapy Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyang110000China Department of Surgery Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyang110000China

Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

关键词： Neutrophil elastase Sivelestat COVID-19 Pathophysiological mechanisms Therapeutic potential

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Heat shock factor 1 is a direct anti-amyloid factor:connecting neurodegeneration and uncontrolledgrowth

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Neural Regeneration Research 2022年第3期17卷 559-560页

作者： Zijian Tang Chengkai Dai Mouse cancer Genetics Program Center for Cancer ResearchNational Cancer InstituteFrederickMDUSA

Worldwide,more than 40 million people are afflicted with Alzheimer's disease(AD)(Esquerda-Canals et al.,2017).AD is a devastating neurodegenerative disroder characterized by progressive decline in cognitive abilities.A hallmark of AD and other neurodegenerative disorders in humans is the aggregation of proteins into amyloid fibrils and their deposition into plaques and intracellular inclusions(Iadanza et al.)。

关键词： amyloid al. Alzheimer

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Management and Clinico-Pathologic Aspects of Non-Melanoma Skin cancer of the Head and Neck: A Retrospective Institutional Based Study at the Egyptian National Cancer Institute

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Journal of cancer Therapy 2019年第10期10卷 846-862页

作者： Ihab Samy Fayek Mohammed Ahmed Rifaat Dalia Bilal Mohammed Surgical Oncology Department National Cancer Institute Cairo University Egypt Epidemiology and Statistics Department National Cancer Institute Cairo University Egypt.

Background: Reviewing and analyzing the Clinico-pathologic aspects of non-melanoma skin cancer of the head and neck (NMSCHN), type of management, prognostic factors, and disease-free survival (DFS) in a period of 5 years at the National Cancer Institute—Cairo University—Egypt. Materials and Methods: A retrospective study of two hundred patients with NMSCHN was treated at the National Cancer Institute—Cairo University—Egypt from January 2008 to December 2012. The mean follow-up was 6 months (1 - 84 months). Results: 117 males and 83 females with 90% ≥ 50 years old. The scalp (27.5%), the periorbital region (13%), the cheek (12.5%) and the nose (12.5%) are the main anatomical sites affected. BCC represented 71.5% with nodular type (79%) predominance;SCC represented 21% with GII (61.1%) the commonest grade. Surgery was the main modality of treatment (93%) with local flaps only (63.9%) and primary closure (14.7%) were the main surgical options following wide local excision. Positive and close margins were detected in 23.5% of excised specimens. No significant association was found between disease-free survival (DFS) and pathology, treatment modality, the occurrence of complications or safety margin status. Conclusion: NMSCHN lesions should be surgically excised in specialized high volume centers with readily available peripheral margin control and should be operated by senior experienced surgeons.

关键词： Basal Cell Carcinoma Squamous Cell Carcinoma Non-Melanoma Skin cancer

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