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Heterogeneity of germline variants in high risk breast and ovarian cancer susceptibility genes in India

Precision Clinical Medicine 2018年第2期1卷 75-87页

作者： Archana Sharma-Oates Abeer M.Shaaban Ian Tomlinson Luke Wynne Jean-Baptiste Cazier Sudha Sundar centre for Computational Biology Haworth BuildingUniversity of BirminghamEdgbastonBirminghamB152TTUK Institute of cancer and Genomic Sciences College of Medical and Dental SciencesHaworth BuildingUniversity of BirminghamEdgbastonBirminghamB152TTUK Department of Cellular Pathology University Hospitals Birmingham NHS Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohn WayBirminghamB152THUK pan-birmingham gynaecological cancer centre City HospitalDudley RoadBirminghamWest MidlandsB187QHUK

Breast and ovarian cancers now account for one in three cancers in Indian women and their incidence is *** differences in the clinical presentation of breast and ovarian cancers exist between India and the United *** example,Indian patients with breast cancer typically present a decade earlier than in the *** for this could be multifactorial,including differences in underlying biology,environmental risks,and other systematic factors including access to *** possible explanation lies in variable incidence or penetrance of germline mutations in genes such as BRCA1 and *** performed a methodical database and literature review to investigate the prevalence and spectrum of high-risk cancer susceptibility genes in Indian patients with breast and ovarian *** identified 148 articles,but most studies were small,with inconsistent inclusion criteria and based on heterogeneous technologies,so that mutation frequency could not be reliably *** were also often lacking on penetrance,histopathology,and survival *** filtering out unsuitable studies,only 13 remained,comprising 1028 ***-scale research studies are urgently needed to determine mutation prevalence,spectra,and clinico-pathological features,and hence derive guidelines for screening,treatment,and prevention specific to the Indian population.

关键词： BRCA1 BRCA2 hereditary cancer sporadic cancer India breast cancer ovarian cancer

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卵巢癌的诊断

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英国医学杂志中文版 2016年第12期19卷 697-703页

作者： Sudha Sundar Richard D Neal 刘晨王淑珍 pan birmingham gynaecological cancer centre Sandwell and West Birmingham Hospital NHS Trust Birmingham and School of Cancer Sciences University of Birmingham Birmingham B 15 2TT UK North Wales centre for Pfimary Care Research Bangor University Wales UK 首都医科大学附属北京朝阳医院妇产科

卵巢癌是全球女性第七位最常见的癌症，2012年，有23．9万新发病例。和许多其他类型的癌症一样，不同地区卵巢癌的发病率和病死率差异很大，经济发达地区的发病率更高。卵巢癌发病率最高的年龄组是50-70岁，75％的病例发生在55岁以后308... 详细信息

卵巢癌是全球女性第七位最常见的癌症，2012年，有23．9万新发病例。和许多其他类型的癌症一样，不同地区卵巢癌的发病率和病死率差异很大，经济发达地区的发病率更高。卵巢癌发病率最高的年龄组是50-70岁，75％的病例发生在55岁以后3080％的病例在出现症状时已处于疾病晚期，5年生存率很低。在英国，各分期卵巢癌总的5年生存率为46％。

关键词：卵巢癌常见癌症新发病例发病率

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Correlation and prognostic significance of beta-galactoside alpha-2,6-sialyltransferase and serum monosialylated alpha-fetoprotein in hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第42期11卷 6701-6706页

作者： Terence CW Poon Clarissa HS Chiu Paul BS Lai Tony SK Mok Benny Zee Anthony TC Chan Joseph JY Sung Philip J Johnson Department of Medicine and Therapeutics Sir YK Pao cancer centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Department of Clinical Oncology Sir YK Pao cancer centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China Department of Surgery Sir YK Pao cancer centre the Chinese University of Hong Kong Prince of Wales Hospital NT Hong Kong China cancer Research UK Institute for cancer Studies University of birmingham Vincent Drive Edgbaston Birmingham B15 2TT United Kingdom

AIM： To investigate the correlation between tissue ST6Gal I and serum msAFP in HCC patients, and to investigate their prognostic significance. METHODS： Preoperative sera, paired tumorous and non-tumorous tissues were collected from 19 consecutive patients who had undergone surgical resection of HCC. ST6Gal I activities in the tissues were measured by an in vitro microsomal enzyme activity assay. The percentages of tumor-specific msAFP in the sera were also estimated by an isoelectric focusing-immunoblotting assay. RESULTS： The tumor ST6Gal I activity was negatively correlated with serum msAFP percentage （r = -0.53, P = 0.019）. Both decreased tumor ST6Gal I activity and increased serum msAFP percentage were associated with poor tumor cell differentiation. Univariate analyses showed that both decreased tumor ST6Gal I activity （P = 0.028）, increased serum msAFP percentage （P = 0.034） and poor tumor cell differentiation （P = 0.031）were associated with shorter overall survival. Multivariate analysis using the Cox regression model showed that the preoperative serum msAFP percentage （P = 0.022） and tumor cell differentiation status （P = 0.048） were independent prognostic indicators for patient overall survival. CONCLUSION： Our results indicate that the presence of msAFP in blood circulation is associated with a decreased activity of ST6Gal I activity in HCC. Both tissue ST6Gal I and serum msAFP are potential prognostic markers for patients with operable HCC.

关键词： Alpha-fetoprotein Beta-galactoside alpha-2,6-sialyltransferase Hepatocellular carcinoma Patientsurvival Cell differentiation

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Changes in human hepatic metabolism in steatosis and cirrhosis

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World Journal of Gastroenterology 2017年第15期23卷 2685-2695页

作者： Zoe Schofield Michelle AC Reed Philip N Newsome David H Adams Ulrich L Günther Patricia F Lalor Sci-Phy-4-Health EPSRC Research and Training Centre in Physical Sciences for HealthCollege of Engineering and Physical Sciences School of cancer Sciences at the University of birmingham centre for Liver Research and National Institute for Health Research(NIHR)birmingham Liver Biomedical Research Unit 不详

AIMTo understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver *** have carried out pilot study using 1H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver *** in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARLD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARLD samples were also detected using our *** high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance.

关键词： Human Liver Metabolomics Steatosis Nuclear magnetic resonance Alcohol

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Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer

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World Journal of Gastroenterology 2018年第39期24卷 4436-4447页

作者： Joanne Marie O'Rourke Vandana Mridhu Sagar Tahir Shah Shishir Shetty centre for Liver Research Institute of Biomedical ResearchBirmingham B15 2TTUnited Kingdom NIHR birmingham Biomedical Research centre University of Birmingham and University Hospitals Birmingham NHS Foundation Trust

Hepatocellular carcinoma(HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm for inflammation-induced cancer. The causes of chronic liver disease promote the development of transformed or premalignant hepatocytes and predisposes to the development of HCC. For HCC to grow and progress it is now clear that it requires an immunosuppressive niche within the fibrogenic microenvironment of cirrhosis. The rationale for targeting this immunosuppression is supported by responses seen in recent trials with checkpoint inhibitors. With the impact of immunotherapy, HCC progression may be delayed and long term durable responses may be seen. This makes the management of the underlying liver cirrhosis in HCC even more crucial as studies demonstrate that measures of liver function are a major prognostic factor in HCC. In this review, we discuss the development of cancer in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumourigenic climate and the implications this has for patient management.

关键词： Hepatocellular cancer Carcinogenesis Inflammation Fibrosis Immunotherapy

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Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system

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Burns & Trauma 2021年第1期9卷 558-572页

作者： Jon Hazeldine Robert J.Dinsdale David N.Naumann Animesh Acharjee Jonathan R.B.Bishop Janet M.Lord Paul Harrison Institute of Inflammation and Ageing University of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom National Institute for Health Research Surgical Reconstruction and Microbiology Research centre Heritage BuildingQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Scar Free Foundation birmingham centre for Burns Research University Hospital Birmingham Foundation TrustQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Academic Department of Military Surgery and Trauma Royal Centre for Defence MedicineQueen Elizabeth Hospital BirminghamMindelsohnWayEdgbastonBirminghamWest MidlandsB152THUnited Kingdom Institute of cancer and Genomic Sciences Centre for Computational BiologyUniversity of BirminghamEdgbastonBirminghamWest MidlandsB152TTUnited Kingdom

Background:Traumatic injury is associated with increased concentrations of cell-free DNA(cfDNA)in the circulation,which contribute to post-injury *** endonuclease deoxyribonuclease 1(DNase-1)is responsible for removing 90%of circulating ***,DNase activity was reported to be significantly reduced following major non-traumatic brain injury(TBI),but the processes responsible were not ***,it is not known how quickly following injury DNase activity is reduced and whether this also occurs after ***:At 3 post-injury time points(≤1,4–12 and 48–72 hours),blood samples were obtained from 155 adult trauma patients that had sustained an isolated TBI(n=21),TBI with accompanying extracranial injury(TBI^(+))(n=53)or an extracranial injury only(ECI)(n=81).In addition to measuring cfDNA levels and the activity and expression of DNase,circulating concentrations of monomeric globular action(G-actin),an inhibitor of DNase-1,and the actin scavenging proteins gelsolin(GSN)and vitamin D binding protein(VDBP)were determined and values compared to a cohort of healthy ***:Significantly elevated concentrations of plasma cfDNA were seen in TBI,TBI^(+)and ECI patients at all study time points when compared to healthy *** levels were significantly higher at≤1 hour post-injury in ECI patients who subsequently developed multiple organ dysfunction syndrome when compared to those who did *** DNase-1 protein was significantly elevated in all patient groups at all sampling time *** contrast,DNase enzyme activity was significantly reduced,with this impaired function evident in TBI^(+)patients within minutes of *** concentrations of G-actin were elevated in all patient cohorts in the immediate aftermath of injury and this was accompanied by a significant reduction in the levels of GSN and ***:The post-traumatic increase in circulating cfDNA that occurs following extracranial trauma and TBI

关键词： Cell-free DNA Deoxyribonuclease Extracellular actin scavenging system Pre-hospital Trauma

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Prognostic prediction and expression validation of NSD3 in pan-cancer analyses

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BIOCELL 2023年第5期47卷 1003-1019页

作者： SHA LI YAQIONG LIU CHAOLING YAO ANJI XU XIAOLING ZENG YUXIN GE XIAOWU SHENG HAILIN ZHANG XIAO ZHOU YING LONG Translational Medicine centre Hunan Cancer HospitalThe Affiliated Cancer Hospital of XiangyaSchool of MedicineCentral South UniversityChangshaChina Hunan Provincial Clinical Research centre for Oncoplastic Surgery Hunan Cancer HospitalThe Affiliated Cancer Hospital of XiangyaSchool of MedicineCentral South UniversityChangshaChina School of Medicine College of MedicineNursing and Health ScienceNational University of IrelandGalwayIreland Central Laboratory Hunan Cancer HospitalThe Affiliated Cancer Hospital of XiangyaSchool of MedicineChangshaChina

Background:Nuclear receptor binding SET domain protein-3(NSD3)is a histone lysine methyltransferase and a crucial regulator of carcinogenesis in several *** aimed to investigate the prognostic value and potential function of NSD3 in 33 types of human ***:The data were obtained from The cancer Genome ***-Meier analysis,CIBERSORT,gene set enrichment analysis,and gene set variation analysis were *** expression of NSD3 was measured using quantitative real-time polymerase chain reaction and western ***:The expression of NSD3 was altered in pan-cancer *** with higher levels of NDS3 generally had shorter overall survival and disease-specific *** of NSD3 were positively correlated with DNA copy number variation(CNV)in ***3 expression was also associated with tumor mutation burden and microsatellite *** levels of immune-cell infiltration differed significantly between high and low NSD3 ***3 negatively correlated with levels of CD8+T *** enrichment analysis showed that while NSD3 expression was positively associated with several immune cell-related and histone methylation-related pathways,it was negatively correlated with cell metabolism-related,drug transport-related,and drug metabolismrelated ***3 levels in the cell lines tested were significantly *** U251 and NCI-H23 cells,silencing NSD3 inhibited cell proliferation and promoted ***:NSD3 expression was changed in pan-cancer samples that was also verified in cell ***3 was associated with CNV and immune-cell infiltration.A poor prognosis was predicted in patients with high expression of ***3 might hence be a potential marker for predicting tumor prognosis.

关键词： NSD3 pan-cancer Prognosis Immune cell infiltration TMB MSI

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Newly developed self-expandable Niti-S MD colonic metal stent for malignant colonic obstruction

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World Journal of Gastrointestinal Surgery 2020年第4期12卷 138-148页

作者： Yuki Miyasako Toshio Kuwai Sauid Ishaq Kanae Tao Hirona Konishi Ryoichi Miura Yuki Sumida Kazutaka Kuroki Yuzuru Tamaru Ryusaku Kusunoki Atsushi Yamaguchi Hirotaka Kouno Hiroshi Kohno Department of Gastroenterology National Hospital OrganizationKure Medical Center and Chugoku Cancer CenterKure 737-0023Japan Gastroenterology Department Russells Hall HospitalBirmingham City UniversityBirmingham B179BEUnited Kingdom St George’s University University Centre GrenadaWest IndiesGrenada

BACKGROUND Colonic stents are increasingly used to treat acute malignant colonic *** Wall Flex and Niti-S D type stents are the commonly used self-expandable metallic stents available in Japan since *** Flex stent has a risk of stentrelated perforation because of its axial force,while the Niti-S D type stent has a risk of obstructive colitis because of its weaker radial ***-S MD type stents not only overcome these limitations but also permit delivery through highly flexible-tipped smaller-caliber *** To compare the efficacy and safety of the newly developed Niti-S MD type colonic *** This single-center retrospective observational study included 110 patients with endoscopic self-expandable metallic stents placed between November 2011 and December 2018:Wall Flex(Group W,n=37),Niti-S D type(Group N,n=53),and Niti-S MD type(Group MD,n=20).The primary outcome was clinical success,defined as a resolution of obstructive colonic symptoms,confirmed by clinical and radiological assessment within 48 *** secondary outcome was technical success,defined as accurate stent placement with adequate stricture coverage on the first attempt without *** The technical success rate was 100%in Groups W,N,and MD,and the overall clinical success rate was 89.2%(33/37),96.2%(51/53),and 100%(20/20)in Groups W,N,and MD,*** adverse events included pain(3/37,8.1%),poor expansion(1/37,2.7%),and fever(1/37,2.6%)in Group W and perforation due to obstructive colitis(2/53,3.8%)in Group N(likely due to poor expansion).Late adverse events(after 7 d)included stent-related perforations(4/36,11.1%)and stent occlusion(1/36,2.8%)in Group W and stent occlusion(2/51,3.9%)in Group *** stent-related perforation rate in Group W was significantly higher than that in Group N(P<0.05).No adverse event was observed in Group *** In our early and limited experience,the newly developed Niti-S MD type colonic stent was effective

关键词： Colonic stenting New endoscopic colonic stent Malignant colonic obstruction Niti-S WallFlex

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Inflammatory bowel disease-related colorectal cancer:Past,present and future perspectives

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World Journal of Gastrointestinal Oncology 2022年第3期14卷 547-567页

作者： Snehali Majumder Uday Nagesh Shivaji Rangarajan Kasturi Alben Sigamani Subrata Ghosh Marietta Iacucci Department of Clinical Research Narayana HealthBangalore 560099KarnatakaIndia National Institute for Health Research birmingham Biomedical Research centre University Hospitals BirminghamBirmingham B152THUnited Kingdom Institute of Immunology and Immunotherapy University of BirminghamBirmingham B152THUnited Kingdom Department of Gastroenterology Narayana HealthBangalore 560099India

Inflammatory bowel disease-related colorectal cancer(IBD-CRC)is one of the most serious complications of IBD contributing to significant mortality in this cohort of *** is often associated with diet and lifestyle-related gut microbial dysbiosis,the interaction of genetic and environmental factors,leading to chronic gut *** to the“common ground hypothesis”,microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with *** the many underlying factors known to increase the risk of IBD-CRC,perhaps the most important factor is chronic persistent *** persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite *** pathways have been identified,regulated by many positive and negative factors involved in the development of cancer,which in this case follows the‘inflammation-dysplasia-carcinoma’*** to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC,among which colonoscopic surveillance is the most widely accepted and implemented modality,forming part of many national and international ***,the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons—cost-benefit to health systems,resource requirements,and also because of studies showing conflicting long-term *** review provides a comprehensive overview of past,present,and future perspectives of *** explore and analyse evidence from studies over decades and current best practices followed *** the future directions section,we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.

关键词： Inflammatory bowel disease Colorectal cancer Colitis-associated cancer Surveillance in inflammatory bowel disease Dye-spray colonoscopy Adenomas Dysplasia Colectomy

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Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer

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Chinese Journal of cancer 2016年第10期35卷 535-545页

作者： Bo Qiu Pei-Rong Ding Ling Cai Wei-Wei Xiao Zhi-Fan Zeng Gong Chen Zhen-Hai Lu Li-Ren Li Xiao-Jun Wu Rene-Olivier Mirimanoff Zhi-Zhong pan Rui-Hua Xu Yuan-Hong Gao State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat?sen University Cancer Center Department of Radiation Oncology Sun Yat?sen University Cancer Center Department of Colorectal Surgery Sun Yat?sen University Cancer Center Department of Radiation Oncology Centre Hospitalier Universitaire Vaudois Department of Medical Oncology Sun Yat?sen University Cancer Center

Background: Complete resection of locally advanced sigmoid colon cancer(LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemora?diotherapy(neo CRT) followed by surgery as treatment of selected patients with unresectable ***: We studied the patients with unresectable LASCC who received neo CRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external?beam radiotherapy to 50 Gy and capecitabine?based chemotherapy every 3 weeks. Surgery was scheduled 6–8 weeks after ***: Twenty?one patients were included in this study. The median follow?up was 42 months(range, 17–57 months). All patients completed neo CRT and surgery. Resection with microscopically negative margins(R0 resection) was achieved in 20 patients(95.2%). Pathologic complete response was observed in 8 patients(38.1%). Multivisceral resection was necessary in only 7 patients(33.3%). Two patients(9.5%) experienced grade 2 postopera?tive complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0(yp M0) disease, the cumulative probability of 3?year local recurrence?free survival, disease?free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3?year overall survival was 95.2% and bladder function was well ***: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate.

关键词：手术切除结肠癌患者化疗晚期前放 CRT 生存率

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