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https://www.readbyqxmd.com/read/28644303/prostate-cancer-immunotherapy-the-path-forward
#1
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28534538/prostate-cancer-better-vistas-ahead-potential-and-pitfalls-of-immunotherapy
#2
Ravi A Madan, James L Gulley
No abstract text is available yet for this article.
May 23, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28434181/management-options-for-biochemically-recurrent-prostate-cancer
#3
REVIEW
Farhad Fakhrejahani, Ravi A Madan, William L Dahut
Prostate cancer is the most common solid tumor malignancy in men worldwide. Treatment with surgery and radiation can be curative in organ-confined disease. Unfortunately, about one third of men develop biochemically recurrent disease based only on rising prostate-specific antigen (PSA) in the absence of visible disease on conventional imaging. For these patients with biochemical recurrent prostate cancer, there is no uniform guideline for subsequent management. Based on available data, it seems prudent that biochemical recurrent prostate cancer should initially be evaluated for salvage radiation or prostatectomy, with curative intent...
May 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28376158/role-of-antigen-spread-and-distinctive-characteristics-of-immunotherapy-in-cancer-treatment
#4
James L Gulley, Ravi A Madan, Russell Pachynski, Peter Mulders, Nadeem A Sheikh, James Trager, Charles G Drake
Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple malignancies. One mechanism of action of these treatments is to induce an immune response against antigen-bearing tumor cells; the resultant cell death releases secondary (nontargeted) tumor antigens. Secondary antigens prime subsequent immune responses (antigen spread)...
April 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28373007/avelumab-for-metastatic-or-locally-advanced-previously-treated-solid-tumours-javelin-solid-tumor-a-phase-1a-multicohort-dose-escalation-trial
#5
Christopher R Heery, Geraldine O'Sullivan-Coyne, Ravi A Madan, Lisa Cordes, Arun Rajan, Myrna Rauckhorst, Elizabeth Lamping, Israel Oyelakin, Jennifer L Marté, Lauren M Lepone, Renee N Donahue, Italia Grenga, Jean-Marie Cuillerot, Berend Neuteboom, Anja von Heydebreck, Kevin Chin, Jeffrey Schlom, James L Gulley
BACKGROUND: Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. METHODS: This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data...
May 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28302712/improved-survival-after-acute-graft-versus-host-disease-diagnosis-in-the-modern-era
#6
Hanna J Khoury, Tao Wang, Michael T Hemmer, Daniel Couriel, Amin Alousi, Corey Cutler, Mahmoud Aljurf, Joseph H Antin, Mouhab Ayas, Minoo Battiwalla, Jean-Yves Cahn, Mitchell Cairo, Yi-Bin Chen, Robert Peter Gale, Shahrukh Hashmi, Robert J Hayashi, Madan Jagasia, Mark Juckett, Rammurti T Kamble, Mohamed Kharfan-Dabaja, Mark Litzow, Navneet Majhail, Alan Miller, Taiga Nishihori, Muna Qayed, Helene Schoemans, Harry C Schouten, Gerard Socie, Jan Storek, Leo Verdonck, Ravi Vij, William A Wood, Lolie Yu, Rodrigo Martino, Matthew Carabasi, Christopher Dandoy, Usama Gergis, Peiman Hematti, Melham Solh, Kareem Jamani, Leslie Lehmann, Bipin Savani, Kirk R Schultz, Baldeep M Wirk, Stephen Spellman, Mukta Arora, Joseph Pidala
A cute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease...
May 2017: Haematologica
https://www.readbyqxmd.com/read/28239472/analyses-of-the-peripheral-immunome-following-multiple-administrations-of-avelumab-a-human-igg1-anti-pd-l1-monoclonal-antibody
#7
Renee N Donahue, Lauren M Lepone, Italia Grenga, Caroline Jochems, Massimo Fantini, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
BACKGROUND: Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28179594/nuclear-cardiology-practice-in-asia-analysis-of-radiation-exposure-and-best-practice-for-myocardial-perfusion-imaging%C3%A3-results-from-the-iaea-nuclear-cardiology-protocols-cross-sectional-study-incaps
#8
Thomas N B Pascual, Mathew Mercuri, Noura El-Haj, Henry Hee-Sung Bom, Vikram Lele, Mouaz H Al-Mallah, Osnat Luxenburg, Ganesan Karthikeyan, Joao Vitola, John J Mahmarian, Nathan Better, Leslee J Shaw, Madan M Rehani, Ravi Kashyap, Diana Paez, Maurizio Dondi, Andrew J Einstein
BACKGROUND: This paper examines the current status of radiation exposure to patients in myocardial perfusion imaging (MPI) in Asia.Methods and Results:Laboratories voluntarily provided information on MPI performed over a 1-week period. Eight best practice criteria regarding MPI were predefined by an expert panel. Implementation of ≥6 best practices (quality index [QI] ≥6) was pre-specified as a desirable goal for keeping radiation exposure at a low level. Radiation effective dose (ED) in 1,469 patients and QI of 69 laboratories in Asia were compared against data from 239 laboratories in the rest of the world (RoW)...
March 24, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28130133/inhalable-bioresponsive-chitosan-microspheres-of-doxorubicin-and-soluble-curcumin-augmented-drug-delivery-in-lung-cancer-cells
#9
Kiran Jyoti, Ravi Shankar Pandey, Preeti Kush, Dinesh Kaushik, Upendra Kumar Jain, Jitender Madan
In present investigation, doxorubicin (Dox) and soluble curcumin (Cur-2-HP-β-CD-complex) combination was simultaneously loaded in inhalable bioresponsive chitosan microspheres (Dox/Cur-2-HP-β-CD-complex-elastin-CMs) bearing a substrate-stimuli, elastin. The mean particle size and mean aerodynamic diameter of inhalable bioresponsive microspheres displayed noteworthy differences after incorporation of elastin. Moreover, combination of Dox and soluble curcumin was molecularly dispersed in microspheres matrix as substantiated by a range of spectral techniques...
May 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27901066/greater-efficacy-of-atorvastatin-versus-a-non-statin-lipid-lowering-agent-against-renal-injury-potential-role-as-a-histone-deacetylase-inhibitor
#10
Ravi Shankar Singh, Dharmendra Kumar Chaudhary, Aradhana Mohan, Praveen Kumar, Chandra Prakash Chaturvedi, Carolyn M Ecelbarger, Madan M Godbole, Swasti Tiwari
Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors have been shown to improve diabetic nephropathy. However, whether they provide protection via Histone deacetylases (HDAC) inhibition is not clear. We conducted a comparative evaluation of Atorvastatin (AT) versus the non-statin cholesterol-lowering drug, Ezetimibe (EZT) on severity of diabetic nephropathy. Streptozotocin-treated male Wistar rats were fed a cholesterol-supplemented diet and gavaged daily with vehicle, AT or EZT. Control rats received normal diet and gavaged vehicle (n = 8-9/group)...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27622067/tarp-vaccination-is-associated-with-slowing-in-psa-velocity-and-decreasing-tumor-growth-rates-in-patients-with-stage-d0-prostate-cancer
#11
Lauren V Wood, Antonio Fojo, Brenda D Roberson, Meghan S B Hughes, William Dahut, James L Gulley, Ravi A Madan, Philip M Arlen, Marianna Sabatino, David F Stroncek, Luciano Castiello, Jane B Trepel, Min-Jung Lee, Howard L Parnes, Seth M Steinberg, Masaki Terabe, Julia Wilkerson, Ira Pastan, Jay A Berzofsky
T-cell receptor alternate reading frame protein (TARP) is a 58-residue protein over-expressed in prostate and breast cancer. We investigated TARP peptide vaccination's impact on the rise in PSA (expressed as Slope Log(PSA) or PSA Doubling Time (PSADT)), validated tumor growth measures, and tumor growth rate in men with Stage D0 prostate cancer. HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) and wild-type (27-35) TARP peptides administered as a Montanide/GM-CSF peptide emulsion or as an autologous peptide-pulsed dendritic cell vaccine every 3 weeks for a total of five vaccinations with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria with a booster dose of vaccine for all patients at 48 and 96 weeks...
August 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27486817/samarium-153-edtmp-quadramet%C3%A2-with-or-without-vaccine-in-metastatic-castration-resistant-prostate-cancer-a-randomized-phase-2-trial
#12
Christopher R Heery, Ravi A Madan, Mark N Stein, Walter M Stadler, Robert S Di Paola, Myrna Rauckhorst, Seth M Steinberg, Jennifer L Marté, Clara C Chen, Italia Grenga, Renee N Donahue, Caroline Jochems, William L Dahut, Jeffrey Schlom, James L Gulley
PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27485137/analyses-of-pretherapy-peripheral-immunoscore-and-response-to-vaccine-therapy
#13
Benedetto Farsaci, Renee N Donahue, Italia Grenga, Lauren M Lepone, Peter S Kim, Brendan Dempsey, Janet C Siebert, Nuhad K Ibrahim, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
Tumor immunoscore analyses, especially for primary colorectal cancer and melanoma lesions, provide valuable prognostic information. Metastatic lesions of many carcinoma types, however, are often not easily accessible. We hypothesized that immune cells in peripheral blood may differ among individual patients with metastatic disease, which, in turn, may influence their response to immunotherapy. We thus analyzed immune cell subsets within peripheral blood mononuclear cells to determine if a "peripheral immunoscore" could have any prognostic significance for patients before receiving immunotherapy...
September 2, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27473889/radium-223-in-prostate-cancer-emitting-the-right-signals
#14
Ravi A Madan, James L Gulley, William L Dahut
No abstract text is available yet for this article.
September 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27471994/immunotherapy-in-genitourinary-malignancies
#15
Max M Wattenberg, Lawrence Fong, Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: Active investigation suggests immune checkpoint inhibitor therapy and therapeutic cancer vaccines provide clinical benefit for genitourinary malignancies including prostate cancer, renal cell carcinoma, and bladder cancer. Recent developments in the utility of immune checkpoint inhibitor and vaccine therapy for the management of genitourinary malignancies are highlighted in this review. RECENT FINDINGS: Dramatic responses to checkpoint inhibitor therapy have been demonstrated in renal cell carcinoma and bladder cancer with recent Food and Drug Administration approvals in both indications...
November 2016: Current Opinion in Urology
https://www.readbyqxmd.com/read/27425184/nuclear-cardiology-practices-and-radiation-exposure-in-the-oceania-region-results-from-the-iaea-nuclear-cardiology-protocols-study-incaps
#16
MULTICENTER STUDY
Sinjini Biswas, Nathan Better, Thomas N B Pascual, Mathew Mercuri, João V Vitola, Ganesan Karthikeyan, James Westcott, Erick Alexánderson, Adel H Allam, Mouaz H Al-Mallah, Henry Hee-Seung Bom, Salah E Bouyoucef, Albert Flotats, Scott Jerome, Philip A Kaufman, Vikram Lele, Osnat Luxenburg, John J Mahmarian, Leslee J Shaw, S Richard Underwood, Madan Rehani, Ravi Kashyap, Maurizio Dondi, Diana Paez, Andrew J Einstein
BACKGROUND: There is concern about radiation exposure with radionuclide myocardial perfusion imaging (MPI). This sub-study of the International Atomic Energy Agency (IAEA) Nuclear Cardiology Protocols Study reports radiation doses from MPI, and use of dose-optimisation protocols in Australia and New Zealand (ANZ), and compares them with data from the rest of the world. METHODS: Data were collected from 7911 MPI studies performed in 308 laboratories worldwide in one week in 2013, including 439 MPI studies from 34 ANZ laboratories...
January 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/27385895/a-rare-case-of-extensive-skeletal-muscle-metastases-in-adenocarcinoma-cervix-identified-by-18-f-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-scan
#17
Madan Gopal Vishnoi, Anurag Jain, Arun Ravi John, Dharmesh Paliwal
Adenocarcinoma cervix is an uncommon histological subtype of carcinoma cervix; further incidence of skeletal muscle metastases is even rarer. We report the identification of extensive fluorodeoxyglucose (FDG) avid metastatic skeletal muscle deposits in a known case of adenocarcinoma cervix. The largest lesion representative of muscle deposit in the right deltoid was histopathologically confirmed to be metastatic poorly differentiated carcinoma. This report also serves to highlight the importance of (18)F-FDG positron emission tomography/computed tomography (CT) as compared to conventional imaging modalities such as CT and ultrasonography and comments better over the description of invasiveness as well as the extent of disease in carcinoma cervix...
July 2016: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/27328856/a-phase-ii-clinical-trial-of-trc105-anti-endoglin-antibody-in-adults-with-advanced-metastatic-urothelial-carcinoma
#18
Andrea B Apolo, Fatima H Karzai, Jane B Trepel, Sylvia Alarcon, Sunmin Lee, Min-Jung Lee, Yusuke Tomita, Liang Cao, Yunkai Yu, Maria J Merino, Ravi A Madan, Howard L Parnes, Seth M Steinberg, Beatriz Walter Rodriguez, Ben K Seon, James L Gulley, Philip M Arlen, Nancy A Dawson, William D Figg, William L Dahut
BACKGROUND: In this trial we assessed the efficacy and tolerability of TRC105, a chimeric monoclonal antibody that targets CD105 (endoglin) in patients with advanced, previously treated urothelial carcinoma (UC). PATIENTS AND METHODS: Patients received TRC105 15 mg/kg every 2 weeks on days 1 and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) at 6 months. Secondary end points included safety, toxicity, and overall survival (OS)...
May 27, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27268217/postpartum-spontaneous-coronary-vertebral-and-mesenteric-artery-dissections-a-case-report
#19
Sean Spence, Maneesh Sud, Ravi Bajaj, Anna Zavodni, Sharron Sandhu, Mina Madan
BACKGROUND: Spontaneous coronary artery dissection is a rare cause of myocardial infarction that must always be considered on a clinician's differential diagnosis, particularly in patients <50-years old with a paucity of typical vascular risk factors. CASE PRESENTATION: We describe a case of a 33-year-old white woman, 3 weeks postpartum, presenting with retrosternal chest and back pain, neck pain and stiffness, and intermittent headaches. Subsequent workup revealed concurrent spontaneous dissections in three separate medium-sized arterial beds...
June 8, 2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27192116/the-ido1-selective-inhibitor-epacadostat-enhances-dendritic-cell-immunogenicity-and-lytic-ability-of-tumor-antigen-specific-t-cells
#20
Caroline Jochems, Massimo Fantini, Romaine I Fernando, Anna R Kwilas, Renee N Donahue, Lauren M Lepone, Italia Grenga, Young-Seung Kim, Martin W Brechbiel, James L Gulley, Ravi A Madan, Christopher R Heery, James W Hodge, Robert Newton, Jeffrey Schlom, Kwong Y Tsang
Epacadostat is a novel inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1) that suppresses systemic tryptophan catabolism and is currently being evaluated in ongoing clinical trials. We investigated the effects of epacadostat on (a) human dendritic cells (DCs) with respect to maturation and ability to activate human tumor antigen-specific cytotoxic T-cell (CTL) lines, and subsequent T-cell lysis of tumor cells, (b) human regulatory T cells (Tregs), and (c) human peripheral blood mononuclear cells (PBMCs) in vitro...
June 21, 2016: Oncotarget
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