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Hepatobiliary Surgery and Nutrition 2022年第2期11卷 338-339页

作者： Abdallah Al Farai Mansour Al Moundhri Fabrizio Panaro Department of Surgical Oncology Sultan Qaboos Comprehensive Cancer Care and Research CentreMuscatSultanate of Oman Sultan Qaboos comprehensive cancer Care and Research Centre MuscatSultanate of Oman Department of Surgery/Division of HBP Surgery and Transplantation St.Eloi HospitalMontpellier University Hospital-School of MedicineMontpellierFrance

In July 2021 a new governmental cancer center,the Sultan Qaboos comprehensive cancer Care and Research Centre(SQCCCRC)(Figure 1)open its doors to provide excellent,evidenced-based patient-centered care for cancer patients in the Sultanate of Oman.SQCCCRC is dedicated to treat cancer patients while building an environment to continuously advance clinical and scientific innovation in the treatment of cancer.

关键词： cancer Care cancer

Synergetic role of integrating the departments of cancer registry and clinical research at an academic Comprehensive Cancer Center

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World Journal of Methodology 2017年第2期7卷 33-36页

作者： McKenzie Bedra Tammy Vyskocil Jennifer Emel Crystal Edwards Cherif Boutros Tate cancer center University of Maryland Baltimore Washington Medical Center Department of Surgery University of Maryland School of Medicine

Integration of the cancer registry and clinical research departments can have a significant impact on the accreditation process of a Commission on cancer(Co C) Program.Here in we demonstrate that the integration of both departments will benefit as there is increased knowledge, manpower and crossover in job responsibilities in our Co C-accredited Academic Comprehensive Cancer Center.In our model this integration has led to a more successful cooperative interaction among departments, which has in turn created an enhanced combined effect on overall output and productivity.More manpower for the cancer registry has led to increased caseloads, decreased time from date of first contact to abstraction, quality of data submissions, and timely follow-up of all patients from our reference date for accurate survival analysis along with completeness of data.In 2016, our Annual Facility report showed an additional 163 cases over prediction by the state of Maryland cancer Registry and a 39% increase in case completeness.As proof of the synergetic effectiveness of our model within one year of its implementation, the cancer center was able to apply for, and was awarded membership from Alliance for Clinical Trials in Oncology, Central IRB, and in turn led to increased clinical trial accrual from 2.8% in 2014 compared to 13.2% currently.Our cancer registry in year one submitted over 150 more cases than predicted, improved quality outcome measures displayed by our cancer Program Practice Profile reports and had more timely and complete data submissions to national and state registries.This synergetic integration has led to a better understanding, utilization and analysis of data by an integrated team with Clinical Research expertise.

关键词： cancer registry Clinical research Commission on cancer Synergetic integration American College of Surgeons

Glutamine-released ammonia acts as an unprecedented signaling molecule activating lipid production

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Genes & Diseases 2023年第2期10卷 307-309页

作者： Chunming Cheng Scott Kelsey Deliang Guo Department of Radiation Oncology Ohio State Comprehensive Cancer CenterArthur G. James Cancer Hospital and Richard J. Solove Research Instituteand College of Medicine at The Ohio State UniversityColumbusOH 43210USA center for cancer Metabolism James Comprehensive Cancer Center at The Ohio State UniversityColumbusOH 43210USA

In healthy humans, ammonia circulates in the bloodstream at a concentration around 11–32 μmol/L. Whether ammonia plays any physiological role has been unknown until a recent report published in Nature Metabolism.1 Ammonia, long thought to be a toxic waste product of amino acid metabolism, needs to be excreted from the human body as urea. Intriguingly, in this paper, Cheng et al1 for the first time reported that ammonia is not a waste product;rather, it is an unprecedented signaling molecule tying glucose and glutamine to lipid production in human cells. This study revealed that ammonia released from glutamine triggers a cascade of cellular processes leading to the activation of lipogenesis machinery for lipid production (Fig. 1). This discovery has major implications for developing treatments for human diseases such as cancers and metabolic syndromes, as dysregulated metabolism is a hallmark of these diseases.

关键词： ammonia metabolism Ammonia

CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

Modeling the relationship between gene expression and mutational signature

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Quantitative Biology 2023年第1期11卷 31-43页

作者： Limin Jiang Hui Yu Yan Guo Department of Internal Medicine Comprehensive Cancer CenterUniversity of New Mexico AlbuquerqueNM 87109USA

Background:Mutational signatures computed from somatic mutations,allow an in-depth understanding of tumorigenesis and may illuminate early prevention strategies.Many studies have shown the regulation effects between somatic mutation and gene expression dysregulation.Methods:We hypothesized that there are potential associations between mutational signature and gene expression.We capitalized upon RNA-seq data to model 49 established mutational signatures in 33 cancer types.Both accuracy and area under the curve were used as performance measures in five-fold cross-validation.Results:A total of 475 models using unconstrained genes,and 112 models using protein-coding genes were selected for future inference purposes.An independent gene expression dataset on lung cancer smoking status was used for validation which achieved over 80%for both accuracy and area under the curve.Conclusion:These results demonstrate that the associations between gene expression and somatic mutations can translate into the associations between gene expression and mutational signatures.

关键词： mutational signature gene expression support vector machine random forest extreme gradient boost

Genetic and epigenetic dependencies in colorectal cancer development

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Gastroenterology Report 2022年第1期10卷 115-131页

作者： Sehej Parmar Hariharan Easwaran cancer Genetics and Epigenetics OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMDUSA

Recent studies have mapped key genetic changes in colorectal cancer(CRC)that impact important pathways contributing to the multistep models for CRC initiation and development.In parallel with genetic changes,normal and cancer tissues harbor epigenetic alterations impacting regulation of critical genes that have been shown to play profound roles in the tumor initiation.Cumulatively,these molecular changes are only loosely associated with heterogenous transcriptional programs,reflecting the heterogeneity in the various CRC molecular subtypes and the paths to CRC development.Studies from mapping molecular alterations in early CRC lesions and use of experimental models suggest that the intricate dependencies of various genetic and epigenetic hits shape the early development of CRC via different pathways and its manifestation into various CRC subtypes.We highlight the dependency of epigenetic and genetic changes in driving CRC development and discuss factors affecting epigenetic alterations over time and,by extension,risk for cancer.

关键词： colorectal cancer epigenetics aging classification subtyping DNA methylation consensus molecular subtypes

Impact of conditioning regimen on peripheral blood hematopoietic cell transplant

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World Journal of Clinical Oncology 2019年第2期10卷 86-97页

作者： Michael Burns Anurag K Singh Carrie C Hoefer Yali Zhang Paul K Wallace George L Chen Alexis Platek Timothy B Winslow Austin J Iovoli Christopher Choi Maureen Ross Philip L McCarthy Theresa Hahn Department of Medicine Roswell Park Comprehensive Cancer Center Department of Radiation Medicine Roswell Park Comprehensive Cancer Center Department of Flow Cytometry Roswell Park Comprehensive Cancer Center center for Immunotherapy Roswell Park Comprehensive Cancer Center

AIM To investigate infused hematopoietic cell doses and their interaction with conditioning regimen intensity +/-total body irradiation(TBI) on outcomes after peripheral blood hematopoietic cell transplant(PBHCT).METHODS Our retrospective cohort included 247 patients receiving a first, T-replete, human leukocyte antigen-matched allogeneic PBHCT and treated between 2001 and2012. Correlations were calculated using the Pearson product-moment correlation coefficient. Overall survival and progression free survival curves were generated using the Kaplan-Meier method and compared using the log-rank test.RESULTS Neutrophil engraftment was significantly faster after reduced intensity TBI based conditioning [reduced intensity conditioning(RIC) + TBI] and > 4 × 10~6 CD34+cells/kg infused. A higher total nucleated cell dose led to a higher incidence of grade II-IV acute graft-versus-host disease in the myeloablative + TBI regimen group(P = 0.03), but no significant difference in grade III-IV graft-versus-host disease. A higher total nucleated cell dose was also associated with increased incidence of moderate/severe chronic graft-versus-host disease, regardless ofconditioning regimen. Overall and progression-free survival were significantly better in patients with a RIC + TBI regimen and total nucleated cell dose > 8 ×10~8/kg(3 years, overall survival: 70% vs 38%, P = 0.02, 3 years, progression free survival: 64% vs 38%, P = 0.02).CONCLUSION TBI and conditioning intensity may alter the relationship between infused cell doses and outcomes after PBHCT. Immune cell subsets may predict improved survival after unmanipulated PBHCT.

关键词： Total body radiation Peripheral blood hematopoietic cell transplant Total nucleated dose Neutrophil engraftment Graft-versus-host-disease

De novo nucleotide biosynthetic pathway and cancer

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Genes & Diseases 2023年第6期10卷 2331-2338页

作者： Jie Chen Siqi Yang Yingge Li Xu Ziwen Pingfeng Zhang Qibin Song Yi Yao Huadong Pei cancer center Renmin Hospital of Wuhan UniversityWuhanHubei 430062China Lombardi Comprehensive Cancer Center Georgetown University Medical CenterWashingtonD.C.20057USA

De novo nucleotide biosynthetic pathway is a highly conserved and essential biochemical pathway in almost all organisms.Both purine nucleotides and pyrimidine nucleotides are necessary for cell metabolism and proliferation.Thus,the dysregulation of the de novo nucleotide biosynthetic pathway contributes to the development of many human diseases,such as cancer.It has been shown that many enzymes in this pathway are overactivated in different cancers.In this review,we summarize and update the current knowledge on the de novo nucleotide biosynthetic pathway,regulatory mechanisms,its role in tumorigenesis,and potential targeting opportunities.

关键词： Biosynthetic pathway cancer de novo synthesis Metabolism Nucleotide

Yttrium-90 microsphere selective internal radiation therapy for liver metastases following systemic chemotherapy and surgical resection for metastatic adrenocortical carcinoma

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World Journal of Clinical Oncology 2018年第1期9卷 20-25页

作者： Mina S Makary Lawrence S Krishner Evan J Wuthrick Mark P Bloomston Joshua D Dowell Division of Vascular and Interventional Radiology Department of Radiology the Ohio State University Comprehensive Cancer Center Division of Medical Oncology Department of Internal Medicine the Ohio State University Comprehensive Cancer Center Department of Radiation Oncology the Ohio State University Comprehensive Cancer Center Division of Surgical Oncology Department of Surgery and James Cancer Hospital and Richard Solove Research Institute the Ohio State University Comprehensive Cancer Center

Adrenocortical carcinoma(ACC)is a rare malignancy with generally poor outcomes and limited treatment options.While surgical resection can be curative for early local disease,most patients present with advanced ACC owing to nonspecific symptoms.For those patients,treatment options include systemic chemotherapy and locoregional therapies including radiofrequency ablation and transarterial chemoembolization.We present the first reported case of utilizing yttrium-90 microsphere selective internal radiation therapy(SIRT)in combination with first line EDP-M(Etoposide,Doxorubicin,Cisplatin,Mitotane)chemotherapy and debulking surgical primary tumor resection for treatment of metastatic ACC.Stable complete radiologic response has been maintained after twelve months with resolution of clinical symptoms.These findings prompt the need for further consideration and studies to elucidate the role of SIRT in combination with systemic and surgical treatment for metastatic ACC.

关键词： Adrenocortical carcinoma Hepatic metastases Radioembolization Yttrium-90

Phase‘separating'53BP1 from DSB repair

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Genes & Diseases 2023年第1期10卷 1-3页

作者： Youwei Zhang Department of Pharmacology Case Comprehensive Cancer CenterSchool of MedicineCase Western ReserveUniversityClevelandOH44106USA

Eukaryotic chromosomes occupy specific territories in the nucleus,which is key for genome stability and function.Based on the spatiotemporal organization and compaction pattern,eukaryotic chromatins can be recognized as transcriptionally active and loosely packed euchromatin in the nuclear interior and transcriptionally repressive and highly compacted heterochromatin at the nuclear periphery or around nucleoli(Fig.1).

关键词： function. separating interior