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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
Christopher R Heery, Ravi A Madan, Mark N Stein, Walter M Stadler, Robert S DiPaola, 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...
July 28, 2016: Oncotarget
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
Ravi A Madan, James L Gulley, William L Dahut
No abstract text is available yet for this article.
September 2016: Lancet Oncology
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
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...
June 21, 2016: Heart, Lung & Circulation
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
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
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...
2016: Journal of Medical Case Reports
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...
May 12, 2016: Oncotarget
Richa Puri, Richa Kaur Bhatia, Ravi Shankar Pandey, Upendra Kumar Jain, Om Prakash Katare, Jitender Madan
Recently, the anticancer activity of telmisartan (TEL) has been discovered against prostate cancer. Nevertheless, despite favorable therapeutic profile, poor aqueous solubility and suboptimal oral bioavailability hamper the anticancer efficacy of TEL. Therefore, in present investigation, sigma-2 receptor ligand, 3-(4-cyclohexylpiperazine-1-yl) propyl amine (CPPA) anchored nanostructured lipid particles of telmisartan (CPPA-TEL-NLPs) were engineered using stearic acid for targeting prostate cancer, PC-3 cells...
May 16, 2016: Drug Development and Industrial Pharmacy
Neetu Saini, Rupinder Kaur Sodhi, Lotika Bajaj, Ravi Shankar Pandey, Upendra Kumar Jain, Om Prakash Katare, Jitender Madan
BACKGROUND AND OBJECTIVE: Metformin hydrochloride (MTF-HCl) is extensively recommended by physicians for the treatment of polycystic ovary syndrome (PCOS). Mechanistically, MTF-HCl activates AMP-dependent kinase-α (AMPK-α) pathway to decrease the glucose production, enhances fatty acid oxidation and elevates the uptake of glucose in tissues. However, despite favourable physicochemical properties, oral administration of MTF-HCl is associated with impaired bioavailability (50-60%), lactic-acidosis and frequent dosing (500mg 2-3 times a day) in PCOS that ultimately influence the patient compliance...
August 1, 2016: Colloids and Surfaces. B, Biointerfaces
Fatima H Karzai, Ravi A Madan, William L Dahut
Androgen-deprivation therapy (ADT) is a fundamental element of treatment for nonlocalized prostate cancer and for patients with high-risk disease who are not candidates for radical treatment. ADT has been linked to metabolic syndrome, which involves changes in metabolic factors. While distinct from classic metabolic syndrome, this type does include changes in body composition, lipid profiles and insulin resistance. The constellation of risk factors may be associated with cardiovascular morbidity and the onset of diabetes mellitus...
August 2016: Future Oncology
Lynn Shi, Sharmila Dorbala, Diana Paez, Leslee J Shaw, Katherine A Zukotynski, Thomas N B Pascual, Ganesan Karthikeyan, João V Vitola, Nathan Better, Nadia Bokhari, Madan M Rehani, Ravi Kashyap, Maurizio Dondi, Mathew Mercuri, Andrew J Einstein
OBJECTIVES: The aim of this study was to investigate gender-based differences in nuclear cardiology practice globally, with a particular focus on laboratory volume, radiation dose, protocols, and best practices. BACKGROUND: It is unclear whether gender-based differences exist in radiation exposure for nuclear cardiology procedures. METHODS: In a large, multicenter, observational, cross-sectional study encompassing 7,911 patients in 65 countries, radiation effective dose was estimated for each examination...
April 2016: JACC. Cardiovascular Imaging
Amandeep Kaur, Kiran Jyoti, Shweta Rai, Rupinder Sidhu, Ravi Shankar Pandey, Upendra Kumar Jain, Anju Katyal, Jitender Madan
In the present investigation, non-aggregated cationic and unmodified nanoparticles (TT-C-NLPs4 and TT-NLPs1) were prepared of about 49.2 ± 6.8-nm and 40.8 ± 8.3-nm, respectively. In addition, spherical shape, crystalline architecture and cationic charge were also noticed. Furthermore, integrity and conformational stability of TT were maintained in both TT-C-NLPs4 and TT-NLPs1, as evidenced by symmetrical position of bands and superimposed spectra, respectively in SDS-PAGE and circular dichroism. Cellular uptake in RAW264...
May 2016: Journal of Microencapsulation
Julius Strauss, Ravi A Madan, James L Gulley
INTRODUCTION: Over the past few years, trials evaluating immunotherapies, particularly immune checkpoint inhibitors, have revolutionized the standard model of cancer treatment, demonstrating significant antitumor responses and improved clinical outcomes across a wide array of tumors types. Yet, despite these compelling data, a major limitation has been that only a fraction of patients mount a response to single-agent immune checkpoint inhibition. However, a growing amount of preclinical and clinical data suggests that combining immune checkpoint inhibition, either with other immune checkpoint inhibitors or with therapeutic cancer vaccines, has the potential to improve the proportion of patients seeing long-term durable responses with these therapies...
July 2016: Expert Opinion on Biological Therapy
Lisa M Cordes, James L Gulley, Ravi A Madan
PURPOSE OF REVIEW: In recent clinical trials, immunotherapeutic agents have demonstrated promising results for the treatment of prostate cancer. This review discusses emerging immunotherapies for prostate cancer and their evolving role in sequencing and combination therapy. RECENT FINDINGS: Therapeutic vaccines including PROSTVAC and DCVAC/PCa have completed promising phase 2 trials for the treatment of prostate cancer and phase 3 trials are underway. Recent evidence supports a synergistic relationship between immunotherapy agents themselves, antiandrogens and with cytotoxic chemotherapy...
May 2016: Current Opinion in Oncology
João V Vitola, Fernando Mut, Erick Alexánderson, Thomas N B Pascual, Mathew Mercuri, Ganesan Karthikeyan, Nathan Better, Madan M Rehani, Ravi Kashyap, Maurizio Dondi, Diana Paez, Andrew J Einstein
BACKGROUND: Comparison of Latin American (LA) nuclear cardiology (NC) practice with that in the rest of the world (RoW) will identify areas for improvement and lead to educational activities to reduce radiation exposure from NC. METHODS AND RESULTS: INCAPS collected data on all SPECT and PET procedures performed during a single week in March-April 2013 in 36 laboratories in 10 LA countries (n = 1139), and 272 laboratories in 55 countries in RoW (n = 6772). Eight "best practices" were identified a priori and a radiation-related Quality Index (QI) was devised indicating the number used...
February 22, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
Julius Strauss, Ravi A Madan
In recent years, therapeutic cancer vaccines have emerged as a viable and promising treatment for prostate cancer. Beyond sipuleucel-T, phase III trials are evaluating multiple vaccine platforms in men with this disease. Growing data evaluating vaccine therapies suggests that these agents are more effective in patients with more indolent and possibly also earlier stages of disease. In addition, a wealth of preclinical data has shown that traditional prostate cancer treatments including anti androgens, cytotoxic and radiation therapies may provide immunologic synergy when given in combination with vaccine platforms...
July 2016: Expert Review of Vaccines
Poonam Gautam, Dolly Mushahary, Wazid Hassan, Santosh Kumar Upadhyay, Taruna Madan, Ravi Sirdeshmukh, Curam Sreenivasacharlu Sundaram, Puranam Usha Sarma
Aspergillus fumigatus (A. fumigatus) is a medically important opportunistic fungus that may lead to invasive aspergillosis in humans with weak immune system. Proteomic profiling of this fungus on exposure to itraconazole (ITC), an azole antifungal drug, may lead to identification of its molecular targets and better understanding on the development of drug resistance against ITC in A. fumigatus. Here, proteome analysis was performed using 2-DE followed by mass spectrometric analysis which resulted in identification of a total of 259 unique proteins...
July 1, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
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