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Survival in men older than 75 years with low- and intermediate-grade prostate cancer managed with watchful waiting with active surveillance

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Family Medicine and Community Health 2015年第3期3卷 25-36页

作者： Tzuyung D.Kou Siran M.Koroukian Pingfu Fu Derek Raghavan Gregory S.Cooper Li Li Department of Epidemiology and Biostatistics Case Western Reserve University School of MedicineClevelandOHUSA Case Comprehensive cancer Center Case Western Reserve University School of MedicineClevelandOHUSA levine cancer institute Carolinas Healthcare SystemCharlotteNCUSA Department of Family Medicine-Research Division Case Western Reserve University School of MedicineClevelandOHUSA

Objective:Recent studies have reported the underuse of active surveillance or watchful wait-ing for low-risk prostate cancer in the United *** study examined prostate cancer-specific and all-cause death in elderly patients older than 75 years with low-risk tumors managed with active treatment versus watchful waiting with active surveillance(WWAS).Methods:We performed survival analysis in a cohort of 18,599 men with low-risk tumors(early and localized tumors)who were 75 years or older at the time of prostate cancer diagnosis in the linked Surveillance,Epidemiology,and End Results(SEER)-Medicare database(from 1992 to 1998)and who were followed up through December *** was defined as having an-nual screening for prostate-specific antigen and/or digital rectal examination during the follow-up *** risks of prostate cancer-specific and all-cause death were compared by Cox regression *** propensity score matching technique was used to address potential selection ***:In patients with well-differentiated(Gleason score 2-4)and localized disease,those managed with WWAS without delayed treatment had higher risk of all-cause death(hazard ratio 1.20,95%confidence interval 1.13-1.28)but a substantially lower risk of prostate cancer-specific death(hazard ratio 0.62,confidence interval 0.51-0.75)than patients undergoing active *** managed with WWAS with delayed treatment had comparable mortality ***-tivity analyses based on propensity score matching yielded similar ***:In men older than 75 years with well-differentiated and localized prostate cancer,WWAS without delayed treatment had a lower risk of prostate cancer-specific death and compa-rable all-cause death as compared with active *** patients in whom treatment was delayed had comparable mortality *** results support WWAS as an initial management option for older men with well-differentiated and localized prostate cancer.

关键词： Epidemiology watchful waiting prostate cancer

Clinical utilities and biological characteristics of melanoma sentinel lymph nodes

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World Journal of Clinical Oncology 2016年第2期7卷 174-188页

作者： Dale Han Daniel C Thomas Jonathan S Zager Barbara Pockaj Richard L White Stanley PL Leong Department of Surgery Yale University School of Medicine Department of Cutaneous Oncology Moffitt Cancer Center Mayo Clinic Division of Surgical Oncology Carolinas Medical CenterLevine Cancer Institute Center for Melanoma Research and Treatment California Pacific Medical Center

An estimated 73870 people will be diagnosed with melanoma in the United States in 2015,resulting in 9940 *** majority of patients with cutaneous melanomas are cured with wide local ***,current evidence supports the use of sentinel lymph node biopsy(SLNB) given the 15%-20% of patients who harbor regional node *** importantly,the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in earlystage melanoma,particularly in intermediate thickness *** review examines the development of SLNB for melanoma as a means to determine a patient's nodal status,the efficacy of SLNB in patients with melanoma,and the biology of melanoma metastatic to sentinel lymph *** randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of *** the rapidly advancing molecular and surgical technologies,the technical aspects of diagnosis,identification,and management of regional lymph nodes in melanoma continues to evolve and to ***,there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive *** further data provides sufficient evidence to alter national consensusbased guidelines,SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN.

关键词： Melanoma Metastasis Review Biologic characteristics Sentinel lymph node Sentinel lymph node biopsy

Prognostic Value of Lymphocyte Vascular Density and E-Cadherin in Inflammatory Breast cancer

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Journal of cancer Therapy 2014年第14期5卷 1380-1387页

作者： Paul H. levine Heather J. Hoffman Audra MacNeil Salman Hashmi Sherry X. Yang Stephen Hewitt Kenneth L. van Golen Sandra M. Swain Department of Epidemiology and Biostatistics Milken Institute School of Public Health The George Washington University Washington DC USA National Clinical Target Validation Laboratory Division of Cancer Treatment & Diagnosis National Cancer Institute Bethesda USA Laboratory of Pathology Center for Cancer Research National Cancer Institute Bethesda USA Department of Biological Sciences Center for Translational Cancer Research The University of Delaware Newark USA Washington cancer institute MedStar Washington Hospital Center Washington DC USA

Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients. Materials and Methods: This study involved the 100 cases identified in the Inflammatory Breast cancer Registry (IBCR) whose tumors were previously evaluated for the four assays noted above. Living patients were recontacted and survival data were available for up to 17 years. Overall survival (OS) was analyzed through the Kaplan-Meier method stratified by E-cadherin, LVD, VEGF-D, and response to chemotherapy. The differences in OS curves were compared using the log-rank test. Results: The median OS for patients with high LVD was 6.63 years (95% CI: 4.06 to 10.14), compared to median at 10 years not reached in those with low LVD (p = 0.03). There was a trend towards a longer median OS in patients with high E-cadherin (10.14, 95% CI: 6.63 to 11.67), compared with those with low E-cadherin (6.26, 95% CI: 3.42 to undeterminable). VEGF-D levels showed no correlation with survival. Conclusion: Low LVD significantly predicts better survival. High E-cadherin expression, as with non-IBC breast cancer and several other malignancies, tends to be associated with a better prognosis.

关键词： IBC Prognostic Markers E-Cadherin Lymphocyte Vascular Density

Targeting adenosine receptor 2B in triple negative breast cancer

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Journal of cancer Metastasis and Treatment 2018年第1期4卷 171-177页

作者： Carola A.Neumann Kevin levine Steffi Oesterreich Department of Pharmacology&Chemical Biology University of Pittsburgh Medical Center Hillman Cancer CenterWomens Cancer Research CenterMagee Womens Research InstitutePittsburghPA 15213USA Department of Pathology University of PittsburghPittsburghPA 15261USA

In the review“Role of adenosine in tumor progression:focus on A2B receptor as potential therapeutic target”,Sorrentino and Morello make a compelling case for considering adenosine 2B receptor(A2BR)as a target in cancer therapy(J cancer Metastasis Treat 2017;3:127-38).A large body of evidence has accumulated suggesting A2BR to play an active role in tumor immune suppression and ***,this commentary will discuss the intriguing possibility of targeting A2BR in specific breast cancers that express high levels of A2BR and attract infiltrating immune cells.

关键词： breast cancer cancer

Arnold *** and my career development

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Journal of Molecular Cell Biology 2019年第7期11卷 546-550页

作者： Yigong Shi institute of Biology Westlake Institute for Advanced StudySchool of Life SciencesWestlake UniversityHangzhou 310024China

I have known Arnold ***,whom we fondly call Arnie,for over 22 *** important decisions in my careerjob offer by Princeton University,the move from Princeton to Tsinghua,and professional development in China-were made with critical and helpful in put from Arnie.I continue to count on him for advice on the growth ofthe newly founded Westlake University.

关键词： Arnie helpful University

The many faces of p53:something for everyone

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Journal of Molecular Cell Biology 2019年第7期11卷 524-530页

作者： Arnold J.levine institute for Advanced Study PrincetonNJ 08540USA

The p53 gene,from discovery to classification:the first 10 years Forty years ago four research laboratories in London,Paris,NewYork/Bethesda,and Princeton uncovered the existence of the p53 protein (Deleo et al.,1979;Lane and Crawford,1979;Linzer and levine,1979;Kress et al.,1979).Each laboratory came upon this protein for a different reason and with a different experimental approach that uncovered this unanticipated ***,the four papers permitted one to con elude the following:(i) in SV40-infected and transformed cells the SV40-e ncoded on cogene protein,the large T-antigen,formed a protein complex with a cellular-encoded protein of -53000 daltons in size,(ii) This p53 protein was detected at high levels in a variety of transformed cells derived from viral,chemical,or inherited (teratocarcinomas) transformation events,(iii) Nontransformed cells expressed lower levels of the p53 protein,(iv) Animals bearing tumors produced antibodies directed against the p53 protein.

关键词： discovery years protein

A Pilot Trial Testing the Feasibility of Using Molecular-Guided Therapy in Patients with Recurrent Neuroblastoma

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Journal of cancer Therapy 2012年第5期3卷 602-612页

作者： Giselle L. Saulnier Sholler William Ferguson Genevieve Bergendahl Erika Currier Shannon R. Lenox Jeffrey Bond Marni Slavik William Roberts Deanna Mitchell Don Eslin Jacqueline Kraveka Joel Kaplan Nehal Parikh Suman Malempati Gina Hanna Emily Eugster David Cherba Jeremy Miller Craig Webb Cardinal Glennon Children’s Hospital Saint Louis University School of Medicine St. Louis University St. Louis USA Center for cancer Genomics and Computational Biology Pediatric Oncology Translational Research Program at the Van Andel Research Institute in Grand Rapids Grand Rapids USA Center for Children’s cancer and Blood Disorders Arnold Palmer Hospital for Children MD Anderson Cancer Center Orlando Orlando USA Department of Pediatric Oncology Helen DeVos Children’s Hospital Michigan State University Grand Rapids USA Department of Pediatric Oncology Oregon Health Science University Portland USA Division of Hematology/Oncology 2J Connecticut Children’s Medical Center Hartford USA Pediatric Hematology/Oncology Medical University of South Carolina Charleston USA Pediatric Oncology Levine Children’s Hospital Charlotte USA Rady Children’s Hospital San Diego University of California San Diego School of Medicine at the University of California San Diego San Diego USA Vermont cancer Center Department of Medicine University of Vermont Burlington USA

Background: Neuroblastoma is the most common extracranial solid tumor in children, and treatment options for recurrent neuroblastoma are limited. Using molecular profiling to target the molecular vulnerabilities of neuroblastoma with existing therapeutic agents may result in a rational, data-driven approach with potential to improve clinical outcomes. Methods: The primary objective of this pilot study was to evaluate the feasibility of supporting real-time treatment decisions through predictive modeling of genome-wide mRNA gene expression data from neuroblastoma tumor biopsies. Feasibility was defined as completion of tumor biopsy, histopathological evaluation, RNA extraction and quality control, gene expression profiling within a CLIA-certified laboratory, bioinformatic analysis, generation of a drug predicttion report, molecular tumor board review yielding a formulated treatment plan, and independent medical monitor review within a 2-week period. Results: Five patients with multiply relapsed or refractory neuroblastoma were enrolled between April and June 2010. All biopsies passed histopathology and RNA quality control. Generation of gene expression data and its analysis (3-7 days), reports which linked this data into medically actionable drug candidates (1-5 days), molecular tumor board (1-3 days) and independent medical monitor review (1 day) were all completed in real-time. The average time was 10.5 days for all patients. Conclusion: This study shows that it is feasible to create therapeutic treatment plans based on genomic profiling in less than 12 days. This warrants further testing in a Phase I study to determine safety of predicted treatments and evaluate whether the information obtained in these analyses would result in patient benefit.

关键词： Neuroblastoma Molecular Guided Therapy Predictive Therapies Molecular Profiling Genomic Profiling Pediatric cancer

On the reciprocal sum of a sum-free sequence

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Science China Mathematics 2013年第5期56卷 951-966页

作者： CHEN YongGao School of Mathematical Sciences and institute of Mathematics Nanjing Normal University

Let ,4 = {1 ≤ a1 〈 a2 〈 ...} be a sequence of integers. ,4 is called a sum-free sequence if no ai is the sum of two or more distinct earlier terms. Let A be the supremum of reciprocal sums of sum-free sequences. In 1962, ErdSs proved that A 〈 103. A sum-free sequence must satisfy an ≥ （k ~ 1）（n - ak） for all k, n ≥ 1. A sequence satisfying this inequality is called a x-sequence. In 1977, levine and O＇Sullivan proved that a x-sequence A with a large reciprocal sum must have al = 1, a2 = 2, and a3 = 4. This can be used to prove that λ 〈 4. In this paper, it is proved that a x-sequence A with a large reciprocal sum must have its initial 16 terms： 1, 2, 4, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 45, and 50. This together with some new techniques can be used to prove that λ 〈 3.0752. Three conjectures are posed.

关键词： sum-free sequences A-sequences g-sequences Erdos reciprocal sum constants

Imaging Immunity: Creating a Quantitative Spatiotemporal Understanding of Host Defense

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Imaging Immunity: Creating a Quantitative Spatiotemporal Und...