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Scoring microvascular invasion in hepatocellular carcinoma:are we meeting the grade?

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Hepatobiliary Surgery and Nutrition 2024年第1期13卷 184-187页

作者： Derek j.Erstad kenneth K.Tanabe Division of Surgical Oncology Baylor College of MedicineHoustonTXUSA Division of Gastrointestinal and Oncologic Surgery Harvard Medical School and Massachusetts General HospitalBostonMAUSA

Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related mortality and has rising global incidence(1).A perplexing aspect of this disease is the high rate of recurrence(50-70%)after curative-intent,margin negative surgical resection(2).While de novo HCC arising from baseline chronic liver inj.ry is a driver of late recurrences,most recurrences occur over a short interval and are thought to be spread from the index malignancy.

关键词： Microvascular invasion(MVI) hepatocellular carcinoma(HCC) hepatectomy

Individual and geospatial factors associated with receipt of colorectal cancer screening:a state-wide mixed-level analysis

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Family Medicine and Community Health 2024年第S2期12卷 18-25页

作者： j.nnifer E Bayly Mara A Schonberg Marcia C Castro kenneth j.Mukamal Beth Israel Deaconess Medical Center BostonMassachusettsUSA Harvard Medical School BostonMassachusettsUSA Department of Global Health and Population Harvard T H Chan School of Public HealthBostonMassachusettsUSA

Background Colorectal cancer(CRC)is the second leading cause of cancer death in US adults but can be reduced by *** roles of individual and contextual factors,and especially physician supply,in attaining universal CRC screening remains *** We used data from adults 50-75 years old participating in the 2018 New York(NY)Behavioural Risk Factor Surveillance System linked to county-level covariates,including primary care physician(PCP)density and gastroenterologist(GI)*** were analysed in *** analyses included(1)ecological and geospatial analyses of county-level CRC screening prevalence and(2)individual-level Poisson regression models of receipt of screening,adj.sted for socioeconomic and county-level contextual *** Mean prevalence of up-to-date CRC screening was 71%(95%CI 70%to 73%)across NY’s 62 ***-level CRC screening demonstrated significant spatial patterning(Global Moran’s I=0.14,p=0.04),consistent with the existence of county-level contextual *** both county-level and individual-level analyses,lack of health insurance was associated with lower likelihood of up-to-date screening(?−1.09(95%CI−2.00 to-0.19);adj.sted prevalence ratio 0.68(95%CI 0.60 to 0.77)),even accounting for age,race/ethnicity and *** contrast,county-level densities of both PCPs and GIs were completely unassociated with screening at either the county or individual *** expected,other determinants at the individual level included education status and *** In this state-wide representative analysis,physician density was completely unassociated with CRC screening,although health insurance status remains strongly *** similar screening environments,broadened insurance coverage for CRC screening is likely to improve screening far more effectively than increased physician supply.

关键词： state screening county

Targeting CC Chemokine Ligand 2 (CCL2) for Cancer Skeletal Metastasis

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中国肺癌杂志 2009年第6期12卷 I0007-I0007页

作者： Yi LU Cai ZHONG Qiuyan CHEN Eva COREY Zhi YAO Atsushi MIZOKAMI Qinghua ZHOU Evan T. KELLER kenneth j. pienta j.an ZHANG Department of Medicine University of Pittsburgh Pittsburgh PA 15240 Department of Immunology Tianjin Medical University Tianjinj China Laboratory of Clinical Chemistry Tianjin Chest Hospital Tianjin China Department of Nasopharyngeal Carcinoma Cancer Center Sun Yatsen University Guangzhou China Department of Urology University of Washington Seattle WA 98195 Department of Urology Kanazawa University Graduate School of Medical Sciences Kanazawa Japan Tianj.n Lung Cancer Institute Tianjin Medical University General Hospital Tianjin China Department of Internal Medicine and Urology University of Michigan Ann Arbor MI48105

Prostate, breast, and lung cancer preferentially metastasize to bone resulting in bone lesions and thus high mortality. However, the

关键词：癌细胞 CCL2 肿瘤治疗化疗

The prostate cancer bone marrow niche： more than j.st ＇fertile soil＇

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Asian j.urnal of Andrology 2012年第3期14卷 423-427,I0007页

作者： Elisabeth A Pedersen Yusuke Shiozawa kenneth j.pienta Russell S Taichman Department of Periodontics and Oral Medicine University of Michigan School of Dentistry Ann Arbor M148109-1078 USA Departments of Urology and Internal Medicine University of Michigan Medical School Ann Arbor MI 48109-1078 USA

The hematopoietic stem cell （HSC） niche in the bone marrow has been studied extensively over the past few decades, yet the bone marrow microenvironment that supports the growth of metastatic prostate cancer （PCa） has only been recently considered to be a specialized ＇niche＇ as well. New evidence supports the fact that disseminated tumor cells （DTCs） of PCa actually target the HSC niche, displace the occupant HSCs and take up residence in the pre-existing niche space. This review describes some of the evidence and mechanisms by which DTCs act as molecular parasites of the HSC niche. Furthermore, the interactions between DTCs, HSCs and the niche may provide new targets for niche-directed therapy, as well as insight into the perplexing clinical manifestations of metastatic PCa disease.

关键词： dormancy hematopoietic stem cell metastasis niche osteoblasts prostate cancer

Therapy decisions for the symptomatic patient wil metastatic castration-resistant prostate cancer

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Asian j.urnal of Andrology 2015年第6期17卷 936-938,I0008页

作者： Mark C Markowski kenneth j.pienta j.hns Hopkins University School of Medicine Baltimore MD 21287 USA.

Metastatic prostate cancer continues to kill approximately 30,000 men per year. Since 2010, five new therapeutic agents have been Food and Drug Administration （FDA） approved to treat metastatic castration-resistant prostate cancer （mCRPC）. With the increasingnumber of therapies available to clinicians, the most effective sequence in which to implement these treatments remains unknown. The presence or absence of symptoms （i.e., bony pain, visceral crisis） is a key parameter that informs the decision-making process regarding therapy. Treatment algorithms based on： 1） asymptomatic/minimal symptoms, 2） moderate symptoms or chemotherapy ineligible or 3） symptomatic disease need to be developed.

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Why ecosystem characteristics predicted from remotely sensed data are unbiased and biased at the same time-and how this affects applications

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Forest Ecosystems 2024年第1期11卷 24-31页

作者： Goran Ståhl Terj. Gobakken Svetlana Saarela Henrik j.Persson Magnus Ekstrom Sean P.Healey Zhiqiang Yang j.han Holmgren Eva Lindberg kenneth Nystrom Emanuele Papucci Patrik Ulvdal Hans OleØrka Erik Næsset Zhengyang Hou Håkan Olsson Ronald E.McRoberts Department of Forest Resource Management Swedish University of Agricultural Sciences90183UmeåSweden Faculty of Environmental Sciences and Natural Resource Management Norwegian University of Life SciencesÅsNorway USDA Forest Service Rocky Mountain Research StationOgdenUTUSA The Key Laboratory for Silviculture and Conservation of Ministry of Education Beijing Forestry UniversityBeijing100083China Department of Forest Resources University of MinnesotaSt.PaulMNUSA

Remotely sensed data are frequently used for predicting and mapping ecosystem characteristics,and spatially explicit wall-to-wall information is sometimes proposed as the best possible source of information for ***,wall-to-wall information typically relies on model-based prediction,and several features of model-based prediction should be understood before extensively relying on this type of *** such feature is that model-based predictors can be considered both unbiased and biased at the same time,which has important implications in several areas of *** this discussion paper,we first describe the conventional model-unbiasedness paradigm that underpins most prediction techniques using remotely sensed(or other)auxiliary *** this point of view,model-based predictors are typically ***,we show that for specific domains,identified based on their true values,the same model-based predictors can be considered biased,and sometimes severely *** suggest distinguishing between conventional model-bias,defined in the statistical literature as the difference between the expected value of a predictor and the expected value of the quantity being predicted,and design-bias of model-based estimators,defined as the difference between the expected value of a model-based estimator and the true value of the quantity being *** show that model-based estimators(or predictors)are typically design-biased,and that there is a trend in the design-bias from overestimating small true values to underestimating large true ***,we give examples of applications where this is important to acknowledge and to potentially make adj.stments to correct for the design-bias *** argue that relying entirely on conventional model-unbiasedness may lead to mistakes in several areas of application that use predictions from remotely sensed data.

关键词： Bias Model-based inference Design-based inference

Circulating tumor cells shielded with extracellular vesicle-derived CD45 evade T cell attack to enable metastasis

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2114-2131页

作者： Chuan Yang Xueping Wang kenneth K.W.To Caimei Cui Min Luo Shaocong Wu Lamei Huang Kai Fu Can Pan Zeyu Liu Teng Fan Caibo Yang Fang Wang Liwu Fu State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060P.R.China School of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong KongChina LABVIV Technology(Shenzhen)Co. LtdShenzhen 518057China

Circulating tumor cells(CTCs)are precursors of distant metastasis in a subset of cancer patients.A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer *** remains elusive how CTCs evade immune surveillance and elimination by immune *** this study,we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle(EVs)-derived CD45(termed as CD45^(+)CTCs)that resisted T cell attack.A higher percentage of CD45^(+)CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer ***,CD45^(+)tumor cells orchestrated an immunosuppressive milieu and CD45^(+)CTCs exhibited remarkably stronger metastatic potential than CD45−CTCs in ***,CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells,thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune ***,these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis,providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

关键词： CD45 metastasis prevention

Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yuj.e Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu kenneth Kin Wah To Chenglai Xia j.anye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

Metastatic prostate cancer remains incurable, why?

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Asian j.urnal of Urology 2019年第1期6卷 26-41页

作者： Liang Dong Richard C.Zieren Wei Xue Theo M.de Reij.e kenneth j.pienta The Brady Urological Institute Johns Hopkins School of MedicineBaltimoreMDUSA Department of Urology Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Urology Amsterdam UMCUniversity of AmsterdamAmsterdamthe Netherlands

Metastatic prostate cancer patients present in two waysdwith already disseminated disease at the time of presentation or with disease recurrence after definitive local *** deprivation therapy is given as the most effective initial treatment to ***,after the initial response,almost all patients will eventually progress despite the low levels of *** at this stage is termed castration resistant prostate cancer(CRPC).Before 2010,the taxane docetaxel was the first and only life prolonging agent for metastatic CRPC(mCRPC).The last decade has witnessed robust progress in CRPC therapeutics ***,enzalutamide,apalutamide and sipuleucel-T have been evaluated as first-and second-line agents in mCRPC patients,while cabazitaxel was approved as a second-line ***-223 dichloride was approved in symptomatic patients with bone metastases and no known visceral metastases pre-and ***,despite significant advances,mCRPC remains a lethal *** primary and acquired resistance have been observed in CRPC patients treated by these new *** could be solely cell intrinsic or it is possible that the clonal heterogeneity in treated tumors may result from the adaptive responses to the selective pressures within the tumor *** aim of this review is to list current treatment agents of CRPC and summarize recent findings in therapeutic resistance mechanisms.

关键词： Prostate cancer Heterogeneity Drug resistance Novel treatment