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T cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第46期27卷 7956-7968页

作者： michelle R Goulart Konstantinos Stasinos Rachel Elizabeth Ann Fincham Francesca R Delvecchio hemant m kocher Centre for Tumour Biology Barts Cancer Institute-A CRUK Centre of Excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre The Royal London HospitalBarts Health NHS TrustLondon E11BBUnited Kingdom Centre for Experimental medicine and Rheumatology William Harvey Research InstituteQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic ductal adenocarcinoma(PDAC)is a highly devastating disease with a dismal 5-year survival *** has a complex tumour microenvironment;characterised by a robust desmoplastic stroma,extensive infiltration of immunesuppressive cells such as immature myeloid cells,tumour-associated macrophages,neutrophils and regulatory T cells,and the presence of exhausted and senescent T *** cross-talk between cells in this fibrotic tumour establishes an immune-privileged microenvironment that supports tumour cell escape from immune-surveillance,disease progression and spread to distant *** tumours,considered to be non-immunogenic or cold,express low mutation burden,low infiltration of CD8+cytotoxic lymphocytes that are localised along the invasive margin of the tumour border in the surrounding fibrotic tissue,and often display an exhausted ***,we review the role of T cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of T cells as therapy.

关键词： Immunosuppression T cell exhaustion Tumour microenvironment Pancreatic ductal adenocarcinoma Pancreatic cancer stroma

Natural killer cells in pancreatic cancer stroma

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World Journal of Gastroenterology 2021年第24期27卷 3483-3501页

作者： Rachel Elizabeth Ann Fincham Francesca Romana Delvecchio michelle R Goulart Joe Poe Sheng Yeong hemant m kocher Barts Cancer Institute-CRUK Centre of Excellence Queen Mary University of LondonLondon EC1M 6BQUnited Kingdom Institute of molecular and Cellular Biology Agency for ScienceTechnology and ResearchSingapore 138673Singapore Centre for Tumour Biology Barts Cancer Institute-CRUK Centre of ExcellenceQueen Mary University of LondonLondon EC1M 6BQUnited Kingdom

Pancreatic cancer remains one of medicine’s largest areas of unmet *** five-year survival rates of<8%,little improvement has been made in the last 50 *** presenting with advance stage disease,treatment options are **... 详细信息

Pancreatic cancer remains one of medicine’s largest areas of unmet *** five-year survival rates ofmprovement has been made in the last 50 *** presenting with advance stage disease,treatment options are *** date,surgery remains the only potentially curative option,however,with such late disease presentation,the majority of patients are ***,new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer *** killer(NK)cells are crucial effector units in cancer *** used as a prognostic biomarker in a range of malignancies,NK cells have received much attention as an attractive target for immunotherapies,both as cell therapy and as a pharmaceutical *** this interest,the role of NK cells in pancreatic cancer remains poorly ***,increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to ***,we review the role of NK cells in pancreatic cancer,examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.

关键词： Pancreatic cancer Natural killer cells Tumour microenvironment Pancreatic cancer stroma Stromal cells

Pancreatic cancer organotypics: High throughput, preclinical models for pharmacological agent evaluation

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World Journal of Gastroenterology 2014年第26期20卷 8471-8481页

作者： Stacey J Coleman Jennifer Watt Prabhu Arumugam Leonardo Solaini Elisabeta Carapuca mohammed Ghallab Richard P Grose hemant m kocher Centre for Tumour Biology Barts Cancer Institute - a CR-UK Centre of ExcellenceQueen Mary University of LondonJohn Vane Science CentreCharterhouse SquareLondon EC1M 6BQUnited Kingdom Barts and the London HPB Centre The Royal London HospitalBarts Health NHS TrustLondon EC1M 6BQUnited Kingdom

Pancreatic cancer carries a terrible prognosis,as the fourth most common cause of cancer death in the Western *** is clearly a need for new therapies to treat this *** of the reasons no effective treatment has been developed in the past decade may in part,be explained by the diverse influences exerted by the tumour *** tumour stroma cross-talk in pancreatic cancer can influence chemotherapy delivery and response ***,appropriate preclinical in vitro models which can bridge simple 2D in vitro cell based assays and complex in vivo models are required to understand the biology of pancreatic *** we discuss the evolution of 3D organotypic models,which recapitulare the morphological and functional features of pancreatic ductal adenocarcinoma(PDAC).Organotypic cultures are a valid high throughput preclinical in vitro model that maybe a useful tool to help establish new therapies for PDAC.A huge advantage of the organotypic model system is that any component of the model can be easily modulated in a short *** allows new therapies that can target the cancer,the stromal compartment or both to be tested in a model that mirrors the in vivo situation.A major challenge for the future is to expand the cellular composition of the organotypic model to further develop a system that mimics the PDAC environment more *** discuss how this challenge is being met to increase our understanding of this terrible disease and develop novel therapies that can improve the prognosis for patients.

关键词： 3D organotypic model Pancreatic cancer Pancreatic stellate cell Stroma Preclinical models

Risk-adjustment in hepatobiliarypancreatic surgery

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World Journal of Gastroenterology 2005年第16期11卷 2450-2455页

作者： hemant m kocher Paris P Tekkis Palepu Gopal Ameet G Patel Simon Cottam Irving S Benjamin Academic Department of Surgery King's College Hospital Denmark HillLondon SE5 9RYUK Department of Anaesthesia King's College Hospital Denmark HillLondon SE5 9RYUK

AIm: The present study evaluates the performance of the POSSUm, the American Society of Anesthetists (ASA), APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery. We describe especially the limitations and advantages of risk in stratifying the patients. mETHODS: We investigated 177 randomly chosen patients undergoing elective complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors. Primary endpoint was in-hospital mortality and morbidity. Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality. RESULTS: The operative mortality in the series was 3.95%. This compared well with the p-POSSUm and APACHE predicted mortality of 4.31% and 4.29% respectively. Postoperative complications amounted to 45% with 24 (13.6%) patients having a major adverse event. On multrvariate analysis the pre-operative POSSUm physiological score (OR = 1.18, P = 0.009) was superior in predicting complications compared to the ASA (P= 0.108), APACHE (P= 0.117) or Childs classification (P= 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR), pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUm variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery. CONCLUSION: morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities.

关键词： Hepatobiliarypancreatic surgery Risk adjustment Operative mortality Operative morbidity Regression models

Design of crown pillar thickness using finite element method and multivariate regression analysis

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International Journal of mining Science and Technology 2017年第6期27卷 955-964页

作者： Kumar hemant Deb Debasis Chakravarty D. Department of mining Engineering Indian Institute of Technology (Indian School of Mines) Dhanbad 826004 India Department of mining Engineering Indian Institute of Technology Kharagpur 721302 India

minerals are now being extracted from deep mines due to drying up of resource in shallow ground. The need for suitable supports and ground control mechanisms for safe mining necessitates proper pillar design with filling technology. In addition, high horizontal stress may cause collapse of hanging wall and footwall rocks, hence designing of suitable crown pillars is absolutely necessary for imposing overall safety of the stopes. This paper provides a methodology for the evaluation of the required thickness of crown pillars for safe operation at depth ranging from 600 m to 1000 m. Analyses are conducted with the results of 108 non-linear numerical models considering Drucker-Prager material model in plane strain condition. material properties of ore body rock and thickness of crown pillars are varied and safety factors of pillars estimated. Then, a generalized statistical relationship between the safety factors of crown pillars with the various input parameters is developed. The developed multivariate regression model is utilized for generating design/stability charts of pillars for different geo-mining *** design charts can be used for the design of crown pillar thickness with the depth of the working,taking into account the changes of the rock mass conditions in underground metal mine.

关键词： Cut and fill mining Crown pillar FEm Regression model Design chart

Identification of EST–SSRs and molecular diversity analysis in mentha piperita

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The Crop Journal 2015年第4期3卷 335-342页

作者： Birendra Kumar Umesh Kumar hemant Kumar Yadav CSIR-Central Institute of medicinal and Aromatic Plant Sciences P.O.CIMAP Near Kukrail Picnic Spot CSIR-National Botanical Research Institute Rana Pratap Marg Academy of Scientific and Innovative Research (AcSIR)

EST sequences of mentha piperita available in the public domain(NCBI) were exploited to develop SSR markers. A total of 1316 ESTs were assembled into 155 contigs and 653 singletons and of these, 110 sequences were found to contain 130 SSRs, with a frequency of1 SSR/3.4 kb. Dinucleotide repeat SSRs were most frequent(72.3%) with the AG/CT(43.8%)repeat motif followed by AT/AT(16.2%). Primers were successfully designed for 68SSR-containing sequences(62.0%). The 68 primers amplified 13 accessions of m. piperita and 54 produced clear amplicons of the expected size. Of these 54, 33(61%) were found to be polymorphic among m. piperita accessions, showing from 2 to 4 alleles with an average of2.33 alleles/SSR, and the polymorphic information content(PIC) value varied between 0.13 and 0.51(average 0.25). All the amplified SSRs showed transferability among four different species of mentha, with a highest in mentha arvensis(87.0%) and minimum in mentha citrata(37.0%). The newly developed SSRs markers were found to be useful for diversity analysis, as they successfully differentiated among species and accessions of mentha.

关键词： EST–SSRs Genetic diversity mentha piperita Polymorphic information content Transferability

Petrophysical insights into pore structure in complex carbonate reservoirs using NmR data

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Petroleum Research 2024年第3期9卷 439-450页

作者： Ilius mondal Kumar hemant Singh Department of Earth Science Indian Institute of Technology BombayIndia

The study delves into pore structure attributes within the complex Eocene carbonate of an Indian offshore field,encompassing pore throat,radius and their *** magnetic Resonance(NmR)experimental data reveals crucial insights into pore structures and fluid *** study compares the NmR T_(2) distribution curve with capillary pressure data from the mercury Injection Capillary Pressure(mICP)technique,deriving linear and nonlinear conversion coefficients to transform NmR T_(2) spectra into equivalent pore radius *** radius-dependent porosity partitioning,linked to permeability and the distribution of irreducible water,is conducted utilizing NmR-derived *** the T_(2) cut-off analysis,a two-segment fractal analysis of NmR T_(2) distribution is also carried *** analysis unveils associations between fractal dimensions and various petrophysical parameters,including permeability,porosity,T_(2)Lm,irreducible water saturation and *** NmR-derived pore radius distribution is mostly unimodal,occasionally slightly *** different pore size classes(less than 0.05μm to more than 5μm)are analysed in relation to permeability,porosity and irreducible *** pores(m)contribute more to irreducible water with low porosity and *** fractal dimension of large pores correlates strongly with porosity,permeability,T_(2)Lm,irreducible water and Rso suggesting significant impact on reservoir seepage *** addition to porosity partitioning,the current study demonstrates effectiveness in modelling modified permeability and correlating it with in situ permeability when applied to field NmR log data from the study *** numerous studies focus on sandstone,our study marks the pioneering attempt at a comprehensive analysis on complex carbonate reservoirs.

关键词： Pore structure NmR T_(2)distribution Irreducible water Fractal analysis Permeability

STUDIES ON mOLECULAR WEIGHT DISTRIBUTION OF CARBON FIBER POLYmER PRECURSORS SYNTHESIZED USING mIXED SOLVENTS

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Chinese Journal of Polymer Science 2012年第5期30卷 664-673页

作者： G.Santhana Krishnan A.Burkanudeen N.murali hemant Phadnis materials Science Division CSIRNational Aerospace LaboratoriesBangalore-560017India Post Graduate and Research Department of Chemistry Jamal Mohammed CollegeBharathidasan UniversityTiruchirappalliIndia malvern Application Laboratory Naimex HouseBangalore-560045India

The molecular weight distributions were estimated for carbon fiber polymer precursors such as poly（acrylonitrile-co-itaconic acid） synthesized by semi batch solution polymerization in mixed solvents media with the azonitrile compounds as initiator under the different ratios of solvent and non solvent from 0.75 to 2.5 in weight. The copolymer was characterized by using Fourier transform infrared spectroscopy （FTIR） and nuclear magnetic resonance （1H-NmR） analyses. The molecular weight distributions were evaluated by mv/mn ratios estimated from viscosity and osmotic measurements, and mw/mn estimated from size exclusion chromatography. The molecular weight distributions of these polymers as determined from m, Jmn and mw/mn are 2.9 to 3,2 and 2.0 to 2.5 respectively. The molecular distributions were close to a narrow distribution of 2.0 when the solvent/non-solvent ratio was varied between 1.4 and 2.0. Intrinsic viscosity [η] as a function of molecular weight of poly（acrylonitrile-co-itaconic acid） was evaluated by means of low angle laser light scattering with size exclusion chromatography （SEC-LALLS） and viscometry with SEC （SEC-VISCO）. The relationship between [η] and mw for poly（acrylonitrile-co-itaconic acid） in DmF at 50℃ was [q] = 1.1×10-5 mw0.79, where [η] is obtained in dL/g.

关键词： molecular weight distribution Size exclusion chromatography Osmometry Viscometry Polyacrylonitrilecopolyrner.

Papillary carcinoma of breast: minireview

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World Journal of Clinical Cases 2016年第1期4卷 20-24页

作者： Sachin B Ingle hemant G murdeshwar Saleha Siddiqui Department of Pathology MIMSR Medical College Department of Pathology Dr.V.M.Government Medical College

The term "intracystic papillary ductal carcinoma in situ " constitutes only 0.5% to 1% of all breast *** is usually seen in postmenopausal age ***,we are presenting a minireview about this unusual breast malignancy us... 详细信息

关键词： Papillary carcinoma breast Intracystic Solid Diagnosis and management