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Full-Text Articles in Medicine and Health Sciences

Insights From Hur Biology Point To Potential Improvement For Second-Line Ovarian Cancer Therapy., Yu-Hung Huang, Weidan Peng, Narumi Furuuchi, James B Duhadaway, Masaya Jimbo, Andrea Pirritano, Charles J Dunton, Gary S Daum, Benjamin E Leiby, Jonathan Brody, Md, Janet A Sawicki Apr 2016

Insights From Hur Biology Point To Potential Improvement For Second-Line Ovarian Cancer Therapy., Yu-Hung Huang, Weidan Peng, Narumi Furuuchi, James B Duhadaway, Masaya Jimbo, Andrea Pirritano, Charles J Dunton, Gary S Daum, Benjamin E Leiby, Jonathan Brody, Md, Janet A Sawicki

Kimmel Cancer Center Faculty Papers

This retrospective study aimed to investigate the role that an RNA-binding protein, HuR, plays in the response of high-grade serous ovarian tumors to chemotherapeutics. We immunohistochemically stained sections of 31 surgically-debulked chemo-naïve ovarian tumors for HuR and scored the degree of HuR cytoplasmic staining. We found no correlation between HuR intracellular localization in tumor sections and progression free survival (PFS) of these patients, 29 of whom underwent second-line gemcitabine/platin combination therapy for recurrent disease. Ribonucleoprotein immunoprecipitation (RNP-IP) analysis of ovarian cancer cells in culture showed that cytoplasmic HuR increases deoxycytidine kinase (dCK), a metabolic enzyme that activates gemcitabine. The effects …


Romidepsin For The Treatment Of Relapsed/Refractory Peripheral T Cell Lymphoma: Prolonged Stable Disease Provides Clinical Benefits For Patients In The Pivotal Trial., Francine Foss, Steven Horwitz, Barbara Pro, H Miles Prince, Lubomir Sokol, Barbara Balser, Julie Wolfson, Bertrand Coiffier Mar 2016

Romidepsin For The Treatment Of Relapsed/Refractory Peripheral T Cell Lymphoma: Prolonged Stable Disease Provides Clinical Benefits For Patients In The Pivotal Trial., Francine Foss, Steven Horwitz, Barbara Pro, H Miles Prince, Lubomir Sokol, Barbara Balser, Julie Wolfson, Bertrand Coiffier

Kimmel Cancer Center Faculty Papers

BACKGROUND: Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD). Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130), including 15 % with confirmed/unconfirmed complete response and a median duration of response of …


Analysis Of Tumor Template From Multiple Compartments In A Blood Sample Provides Complementary Access To Peripheral Tumor Biomarkers., William M Strauss, Chris Carter, Jill Simmons, Erich Klem, Nathan Goodman, Behrad Vahidi, Juan Romero, Michael Masterman-Smith, Ruth O'Regan, Keerthi Gogineni, Lee Schwartzberg, Laura Austin, Paul W Dempsey, Massimo Cristofanilli Mar 2016

Analysis Of Tumor Template From Multiple Compartments In A Blood Sample Provides Complementary Access To Peripheral Tumor Biomarkers., William M Strauss, Chris Carter, Jill Simmons, Erich Klem, Nathan Goodman, Behrad Vahidi, Juan Romero, Michael Masterman-Smith, Ruth O'Regan, Keerthi Gogineni, Lee Schwartzberg, Laura Austin, Paul W Dempsey, Massimo Cristofanilli

Kimmel Cancer Center Faculty Papers

Targeted cancer therapeutics are promised to have a major impact on cancer treatment and survival. Successful application of these novel treatments requires a molecular definition of a patient's disease typically achieved through the use of tissue biopsies. Alternatively, allowing longitudinal monitoring, biomarkers derived from blood, isolated either from circulating tumor cell derived DNA (ctcDNA) or circulating cell-free tumor DNA (ccfDNA) may be evaluated. In order to use blood derived templates for mutational profiling in clinical decisions, it is essential to understand the different template qualities and how they compare to biopsy derived template DNA as both blood-based templates are rare …


Antimetabolite Ttl-315 Selectively Kills Glucose-Deprived Cancer Cells And Enhances Responses To Cytotoxic Chemotherapy In Preclinical Models Of Cancer., James Duhadaway, George C Prendergast Jan 2016

Antimetabolite Ttl-315 Selectively Kills Glucose-Deprived Cancer Cells And Enhances Responses To Cytotoxic Chemotherapy In Preclinical Models Of Cancer., James Duhadaway, George C Prendergast

Kimmel Cancer Center Faculty Papers

Maintaining thiol homeostasis is an imperative for cancer cell survival in the nutrient-deprived microenvironment of solid tumors. Despite this metabolic vulnerability, a selective approach has yet to be developed to disrupt thiol homeostasis in solid tumors for therapeutic purposes. In this study, we report the identification of 2-mercaptopropionyl glycine disulfide (TTL-315) as a novel antimetabolite that blocks cell survival in a manner conditional on glucose deprivation. In the presence of glucose, TTL-315 lacks cytotoxic effects in normal cells where it is detoxified by reduction to 2-mercaptopropionyl glycine, a compound with known clinical pharmacologic and safety profiles. In several rodent models …