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Role of human nucleoside transporters in pancreatic cancer and chemoresistance

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World Journal of Gastroenterology 2021年第40期27卷 6844-6860页

作者： Carly Jade Carter Ahmed H Mekkawy david l morris Hepatobiliary and Surgical Oncology Unit Department of SurgerySt George HospitalUniversity of New South WalesSydney 2217New South WalesAustralia Mucpharm Pty ltd Australia

The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5%changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next *** into the mechanisms of pancreatic cancer development,progression and acquired chemoresistance have been constant for the past few decades,thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said *** review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer,more specifically human equilibrative nucleoside transporter 1/2(hENT1,hENT2),and human concentrative nucleoside transporter 1/3(hCNT1,hCNT3),while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic *** review also discusses the incidence,current diagnostic techniques as well as the current therapeutic treatments for pancreatic ***,we address the importance of chemoresistance in nucleoside analogue drugs,in particular,gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.

关键词： Pancreatic cancer Gemcitabine Human nucleoside transporters Human equilibrative nucleoside transporters Human concentrative nucleotide transporters Mucins

Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study

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World Journal of Gastrointestinal Oncology 2020年第5期12卷 549-558页

作者： Peter H Cashin lana Ghanipour Malin Enblad david l morris Department of Surgical Sciences Section of SurgeryUppsala UniversityAkademiska SjukhusetUppsala 75185Sweden Department of Surgery University of New South WalesSydney 2217New South WalesAustralia

BACKGROUND The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy(HIPEC)treatment have never been *** To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free *** All patients with colorectal peritoneal metastases(1996-2015)completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a biinstitutional database(Uppsala and Sydney)were included in the ***-Dindo grade 3-4 morbidity differences between the neutropenia group vs nonneutropenia group were calculated and Kaplan-Meier curves with log rank test were *** and multivariable Cox regression models for diseasefree survival were *** Two hundred and forty-six patients were identified–32 postoperative any-grade neutropenia patients and 214 non-neutropenia *** neutropenia group had more combination oxaliplatin+irinotecan treatment than the nonneutropenia group(66%vs 13%,P=0.0001).The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 *** overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group,P=*** disease-free survival was 16 mo vs 11 mo,respectively,P=*** was an independent prognostic factor for disease-free survival with hazard ratio:0.58,95%confidence interval:0.36-0.95,P=*** 13%of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 *** was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC *** is in direct contrast to the current paradigm of decreasing the treatment intensity.

关键词： Colorectal cancer Peritoneal metastases Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Oxaliplatin Neutropenia

Hepatocytes isolated from neoplastic liver-immunomagnetic purging as a new source for transplantation

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World Journal of Gastroenterology 2008年第32期14卷 5025-5031页

作者： Aravin Gunasegaram Javed Akhter Peng Yao loreena A Johnson Stephen M Riodan david l morris University of New South Wales Department of Surgery St George Hospital Sydney 2044 Australia Gastrointestinal and liver Unit Prince of Wales Hospital University of New South Wales Sydney 2044 Australia

AIM： To investigate whether hepatocytes isolated from macroscopically normal liver during hepatic resection for neoplasia could provide a novel source of healthy hepatocytes, including the development of reliable protocols for malignant cells removal from the hepatocyte preparation. METHODS： Hepatocytes were procured from resected liver of 18 patients with liver tumors using optimised digestion and cell-enrichment protocols. Suspensions of various known quantities of the HT-29 tumor cell line and patient hepatocytes were treated or not with Ep-CAM-antibody-coated immunomagnetic beads in order to investigate the efficacy of tumor-purging by immunomagnetic depletion, using a semi-quantitative RT-PCR method developed to detect tumor cells. Immunomagnetic bead-treated or bead-untreated tumor cell-hepatocyte suspensions were transplanted intra-peritoneally in Balb/C nude mice to assess the rates of tumor development. RESUlTS： Mean viable hepatocyte yield was 9.3×10^6 cells per gram of digested liver with mean viability of 70.5%. Immunomagnetic depletion removed tumor cells to below the RT-PCR detection-threshold of 1 tumor cell in 10^6 hepatocytes, representing a maximum tumor purging efficacy of greater than 400000-fold. Transplanted, immunomagnetic bead-purged tumor cell-hepatocyte suspensions did not form peritoneal tumors in Balb/C nude mice. Co-transplantation of hepatocytes with tumor cells did not increase tumorigenesis of the tumor cells. CONClUSION： Immunomagnetic depletion appears to be an effective method of purging contaminating tumor cells to below threshold for likely tumorigenesis. Along with improved techniques for isolation of large numbers of viable hepatocytes, normal liver resected for neoplasia has potential as another clinically useful source of hepatocytes for transplantation.

关键词： Hepatocyte transplantation Immuno-magnetic purging Isolation of hepatocytes

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射频消融（RFA）辅助的无血切肝技术

中华肝胆外科杂志 2008年第5期14卷 346-348页

作者：姚鹏王晓路 david l morris Department of Surgery St George Hospital University of New South Wales Sydney Australia

肝细胞癌（HCC）是世界上最常见的实体癌之一，而且肝脏是除淋巴结之外最常见转移癌的脏器。肝癌的治疗仍以手术切除为首选，根治性切除术后病人的5年生存率可达40％左右，然而肝切除对于外科医生的技术要求较高，有时术中出血极其难以... 详细信息

肝细胞癌（HCC）是世界上最常见的实体癌之一，而且肝脏是除淋巴结之外最常见转移癌的脏器。肝癌的治疗仍以手术切除为首选，根治性切除术后病人的5年生存率可达40％左右，然而肝切除对于外科医生的技术要求较高，有时术中出血极其难以控制。射频消融广泛地用于治疗无法手术切除的肝癌，甚至在部分病人身上取得了较好的远期效果。Habib第一次描述了RFA辅助的肝切除，他使用单极RFA探针预先处理切除面，术中出血明显地减少（30±10）ml。morris在此基础上设计了一种新颖的双极RFA设备——Inline，其工作原理是双极RFA探针产生了一条精确的凝固带，进而封闭大到4mm的动脉和静脉，肝切除随之可以在这个无血管的平面进行，取得接近不出血的结果。在最近完成的一项国际多医疗中心研究中，笔者发现经过Inline治疗后，术中出血减少了63．88％。该文重点讲述了射频辅助的肝切除技术的原理，使用以及临床结果。射频消融辅助的肝切除可以适用于解剖和非解剖切除。这项技术易于使用，同时术后病人恢复良好。

关键词：肝切除术射频消融(RFA) 术中出血

A multi-sensor appiproach to calving detection

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Information Processing in Agriculture 2024年第1期11卷 45-64页

作者： Anita Z.Chang david l.Swain Mark G.Trotter Institute for Future Farming Systems School of HealthMedicaland Applied SciencesCentral Queensland UniversityRockhamptonQueensland 4700Australia

The advent of remote livestock monitoring systems provides numerous possibilities for improving on-farm productivity,efficiency,and *** potential application for these systems is for the detection of calving *** study describes the integration of data from multiple sensor sources,including accelerometers,global navigation satellite systems(GNsS),an accelerometer-derived rumination algorithm,a walk-over-weigh unit,and a weather station for parturition detection using a support vector machine *** best performing model utilised data from GNsS,the ruminating algorithm,and weather stations to achieve 98.6%accuracy,with 88.5%sensitivity and 100%*** topranking features of this model were primarily GNSS *** study provides an overview as to how various sensor systems could be integrated on-farm to maximise calving detection for improved production and welfare outcomes.

关键词： Accelerometer GNSS GPS Rumination Sensor WOW

Explainable artificial intelligence in breast cancer detection and risk prediction:A systematic scoping review

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Cancer Innovation 2024年第5期3卷 1-22页

作者： Amirehsan Ghasemi Soheil Hashtarkhani david l.Schwartz Arash Shaban‐Nejad Department of Pediatrics Center for Biomedical InformaticsCollege of MedicineUniversity of Tennessee Health Science CenterMemphisTennesseeUSA The Bredesen Center for Interdisciplinary Research and Graduate Education University of TennesseeKnoxvilleTennesseeUSA Department of Radiation Oncology College of MedicineUniversity of Tennessee Health Science CenterMemphisTennesseeUSA

With the advances in artificial intelligence(AI),data‐driven algorithms are becoming increasingly popular in the medical ***,due to the nonlinear and complex behavior of many of these algorithms,decision‐making by such algorithms is not trustworthy for clinicians and is considered a blackbox ***,the scientific community has introduced explainable artificial intelligence(XAI)to remedy the *** systematic scoping review investigates the application of XAI in breast cancer detection and risk *** conducted a comprehensive search on Scopus,IEEE Explore,PubMed,and Google Scholar(first 50 citations)using a systematic search *** search spanned from January 2017 to July 2023,focusing on peer‐reviewed studies implementing XAI methods in breast cancer *** studies met our inclusion criteria and were included in the *** results revealed that SHapley Additive exPlanations(SHAP)is the top model‐agnostic XAI technique in breast cancer research in terms of usage,explaining the model prediction results,diagnosis and classification of biomarkers,and prognosis and survival ***,the SHAP model primarily explained tree‐based ensemble machine learning *** most common reason is that SHAP is model agnostic,which makes it both popular and useful for explaining any model ***,it is relatively easy to implement effectively and completely suits performant models,such as tree‐based *** AI improves the transparency,interpretability,fairness,and trustworthiness of AI‐enabled health systems and medical devices and,ultimately,the quality of care and outcomes.

关键词： breast cancer deep learning explainable artificial intelligence interpretable AI machine learning XAI

Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

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World Journal of Gastroenterology 2024年第29期30卷 3479-3487页

作者： Miriam lópez-Gómez Maria Morales Rebeca Fuerte Marta Muñoz Pedro-david Delgado-lópez Jorge Francisco Gómez-Cerezo Enrique Casado Department of Medical Oncology Precision Oncology LaboratoryInfanta Sofía University HospitalSan Sebastián de los Reyes 28231MadridSpain Department of Medical Oncology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain Department of Internal Medicine Infanta Sofía University HospitalSan Sebastián de los Reyes 28703MadridSpain Department of Pathology Infanta Sofía University HospitalSan Sebastián de los Reyes 28702Spain Department of Neurosurgery Burgos University HospitalBurgos 09006Spain Department of Internal Medicine Infanta Sofía University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain Department of Medical Oncology Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and InnovationSan Sebastian de los Reyes 28702MadridSpain

BACKGROUND Helicobacter pylori(***)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between *** infection and esophageal *** mechanisms underlying this supposedly protective effect remain *** To determine the prevalence of *** infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our *** We retrospectively reviewed the prevalence of *** infection in a cohort of patients diagnosed with esophageal *** or previous proton pump inhibitor(PPI)usage was also *** A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were *** was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal ***,54 patients(60.7%)presented at stages III and *** *** infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous *** infection had stage *** one patient had received prior *** eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI *** In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous *** *** also reviewed the medical history of the patients,concluding that the majority had received or were on PPI *** minimal prevalence of *** infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

关键词： Helicobacter pylori Eradication Esophageal tumor Dysbiosis Proton pump inhibitors Carcinogenesis Microbiota Incidence

Examining the effects of voluntary avoidance behaviour and policy-mediated behaviour change on the dynamics of SARS-CoV-2:A mathematical model

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Infectious Disease Modelling 2024年第3期9卷 701-712页

作者： Gabrielle Brankston david N.Fisman Zvonimir Poljak Ashleigh R.Tuite Amy l.Greer Department of Population Medicine University of GuelphCanada Dalla lana School of Public Health University of TorontoCanada Centre for Immunization Readiness Public Health Agency of CanadaOttawaOntarioCanada

Background Throughout the SARS-CoV-2 pandemic,policymakers have had to navigate between recommending voluntary behaviour change and policy-driven behaviour change to mitigate the impact of the *** individuals will voluntarily engage in self-protective behaviour when there is an increasing infectious disease risk,the extent to which this occurs and its impact on an epidemic is not *** This paper describes a deterministic disease transmission model exploring the impact of individual avoidance behaviour and policy-mediated avoidance behaviour on epidemic outcomes during the second wave of SARS-CoV-2 infections in Ontario,Canada(September 1,2020 to February 28,2021).The model incorporates an information feedback function based on empirically derived behaviour data describing the degree to which avoidance behaviour changed in response to the number of new daily cases *** Voluntary avoidance behaviour alone was estimated to reduce the final attack rate by 23.1%,the total number of hospitalizations by 26.2%,and cumulative deaths by 27.5%over 6 months compared to a counterfactual scenario in which there were no interventions or avoidance behaviour.A provincial shutdown order issued on December 26,2020 was estimated to reduce the final attack rate by 66.7%,the total number of hospitalizations by 66.8%,and the total number of deaths by 67.2%compared to the counterfactual *** Given the dynamics of SARS-CoV-2 in a pre-vaccine era,individual avoidance behaviour in the absence of government action would have resulted in a moderate reduction in disease however,it would not have been sufficient to entirely mitigate transmission and the associated risk to the population in *** action during the second wave of the COVID-19 pandemic in Ontario reduced infections,protected hospital capacity,and saved lives.

关键词： Mathematical modelling COVID-19 SARS-CoV-2 Human behaviour

Electrifying Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ) for focalized heating in oxygen transport membranes

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Journal of Energy Chemistry 2024年第4期91卷 99-110页

作者： Marwan laqdiem Julio García-Fayos laura Almar Alfonso J.Carrillo Álvaro Represa JoséM.lópez Nieto Sonia Escolástico david Catalán-Martinez Jose M.Serra Instituto de Tecnología Química(Universitat Politècnica de València–Consejo Superior de Investigaciones Científicas) Av.Los Naranjos s/nE-46022 ValenciaSpain

Industry decarbonization requires the development of highly efficient and flexible technologies relying on renewable energy resources,especially biomass and solar/wind *** the case of pure oxygen production,oxygen transport membranes(OTMs)appear as an alternative technology for the cryogenic distillation of air,the industrially-established process of producing ***,OTMs could provide oxygen from different sources(air,water,CO_(2),etc.),and they are more flexible in adapting to current processes,producing oxygen at 700^(-1)000℃.Furthermore,OTMs can be integrated into catalytic membrane reactors,providing new pathways for different *** first part of this study was focused on electrification on a traditional OTM material(Ba_(0.5)Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ)),imposing different electric currents/voltages along a capillary *** to the emerging Joule effect,the membrane-surface temperature and the associated O_(2) permeation flux could be ***,the OTM is electrically and locally heated and reaches 900℃on the surface,whereas the surrounding of the membrane was maintained at 650℃.The O_(2)permeation flux reached for the electrified membranes was~3.7 Nml min^(-1)cm^(-2),corresponding to the flux obtained with an OTM non-electrified at 900℃.The influence of depositing a porous Ce_(0.8)Tb_(0.2)O_(2-δ) catalytic/protective layer on the outer membrane surface revealed that lower surface temperatures(830℃)were detected at the same imposed electric ***,the electrification concept was demonstrated in a catalytic membrane reactor(CMR)where the oxidative dehydrogenation of ethane(ODHE)was carried *** reaction is very sensitive to temperature,and here,we demonstrate an improvement of the ethylene yield by reaching moderate temperatures in the reaction chamber while the O_(2) injection into the reaction can be easily fine-tuned.

关键词： Oxygen permeation Oxidative dehydrogenation of ethane Oxygen transport membranes Joule effect Mixed ionic-electronic conductors Catalytic membrane reactors