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BCG immunotherapy

Joshua J Meeks, Benedito A Carneiro, Sachin G Pai, Daniel T Oberlin, Alfred Rademaker, Kyle Fedorchak, Sohail Balasubramanian, Julia Elvin, Nike Beaubier, Francis J Giles
The genetic mechanisms associated with progression of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have not been described. We conducted selective next-generation sequencing (NGS) of HR-NMIBC and compared the genomic profiles of cancers that responded to intravesical therapy and those that progressed to muscle-invasive or advanced disease. DNA was extracted from paraffin-embedded sections from 25 HR-NMIBCs (22 with T1HG; 3 with TaHG with or without carcinoma in situ). Ten patients with HR-NMIBC developed progression (pT2+ or N+) ("progressors")...
October 14, 2016: Oncotarget
Alban Fouasson-Chailloux, Benoit Metayer, Pierre Menu, Lydie Khatchatourian, Joelle Glemarec, Marc Dauty
OBJECTIVE: The loosening of total joint replacement is a frequent complication after total hip arthroplasty (THA). Septic osteolysis should always be feared. We report here a rare case of hip arthroplasty infection due to Mycobacterium bovis after Bacillus Calmette-Guerin (BCG) therapy in a context of bladder cancer. OBSERVATIONS: A 70-year-old man was referred to the department of rheumatology in September 2015, because of a total functional disability of the left lower limb...
September 2016: Annals of Physical and Rehabilitation Medicine
Mauro Ragonese, Marco Racioppi, Pier Francesco Bassi, Luca Di Gianfrancesco, Niccolò Lenci, Alessio Filianoti, Salvatore M Recupero
Mitomycin C (MMC) as an intravesical chemotherapeutic agent is a well-known option for treatment of nonmuscle invasive bladder cancer (NMIBC) recurrence; it is probably the most commonly used agent given its low rate of side effects and its efficacy.Both the American Urologic Association (AUA) and European Association of Urology (EAU) consider MMC as a standard treatment for immediate single-dose postoperative treatment and for adjuvant therapy in low and intermediate-risk NMIBC.Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered and the schedule widely used is empirical...
October 4, 2016: Urologia
Marinos Tsiatas, Petros Grivas
Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g., high dose interleukin-2 (IL-2)] and non-muscle invasive bladder cancer (NMIBC) [e.g., intravesical Bacillus Calmette-Guérin (BCG)]. In 2010, the sipuleucel-T vaccine was approved by the FDA for the management of metastatic castration-resistant prostate cancer (mCRPC), based on a phase III trial showing overall survival (OS) benefit compared to placebo...
July 2016: Annals of Translational Medicine
Shirong Cai, Matheswaran Kandasamy, Juwita N Rahmat, Sin Mun Tham, Boon Huat Bay, Yuan Kun Lee, Ratha Mahendran
This study evaluates the ability of Lactobacillus rhamnosus GG (LGG) to activate DC and neutrophils and modulate T cell activation and the impact of bacterial dose on these responses. Murine bone marrow derived DC or neutrophils were stimulated with LGG at ratios of 5 : 1, 10 : 1, and 100 : 1 (LGG : cells) and DC maturation (CD40, CD80, CD86, CD83, and MHC class II) and cytokine production (IL-10, TNF-α, and IL-12p70) were examined after 2 h and 18 h coculture and compared to the ability of BCG (the present immunotherapeutic agent for bladder cancer) to stimulate these cells...
2016: Journal of Immunology Research
Vincenzo Serretta, Cristina Scalici Gesolfo, Fabrizio Di Maida, Giovanni Caruana, Lorenzo Rocchini, Marco Moschini, Renzo Colombo, Alchiede Simonato
INTRODUCTION: Prostatic Specific Antigen (PSA), Bacillus Calmette-Guerin (BCG) increase after intravesical BCG has been reported. The need of prostate biopsy in these patients is object of debate. The aim of our study was to evaluate the effect of intravesical therapy on PSA after transurethral resection (TUR) of nonmuscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Patients undergoing intravesical chemotherapy or immunotherapy for NMIBC were entered...
September 26, 2016: Urologia
Nicholas M Donin, Andrew T Lenis, Stuart Holden, Alexandra Drakaki, Allan Pantuck, Arie Belldegrun, Karim Chamie
PURPOSE: To review the biological mechanisms of action, clinical safety, and efficacy of immunotherapies for urothelial carcinoma (UC). To describe current areas of investigation in immunotherapy, and to highlight ongoing trials and promising investigational agents. MATERIALS AND METHODS: Data was obtained by a search of Pubmed,, and Cochrane databases for English language articles published through February 2016. Applicable abstracts from recent SUO, EAU, AUA, and ASCO meetings were utilized...
July 23, 2016: Journal of Urology
Mahir Maruf, Sam J Brancato, Piyush K Agarwal
Intravesical Bacillus Calmette-Guérin (BCG) has long been the gold standard treatment of nonmuscle invasive bladder cancer. Recently, there has been an emergence of novel immunotherapeutic agents, which have shown promise in the treatment of urothelial cell carcinoma. These agents aim to augment, modify, or enhance the immune response. Such strategies include recombinant BCG, monoclonal antibodies, vaccines, gene therapy, and adoptive T-cell therapy. Here, we review the emerging immunotherapeutics in the treatment of nonmuscle invasive bladder cancer...
June 2016: Cancer Biology & Medicine
Rim Hojeij, Sonia Domingos-Pereira, Marianne Nkosi, Dalila Gharbi, Laurent Derré, John T Schiller, Patrice Jichlinski, Denise Nardelli-Haefliger
Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced...
2016: International Journal of Molecular Sciences
Ciorsdan A Campion, Declan Soden, Patrick F Forde
BACKGROUND: The ever increasing knowledge in the areas of cell biology, the immune system and the mechanisms of cancer are allowing a new phase of immunotherapy to develop. The aim of cancer vaccination is to activate the host immune system and some success has been observed particularly in the use of the BCG vaccine for bladder cancer as an immunostimulant. Reovirus, an orphan virus, has proven itself as an oncolytic virus in vitro and in vivo. Over 80 % of tumour cell lines have been found to be susceptible to Reovirus infection and it is currently in phase III clinical trials...
2016: BMC Cancer
Patrick Vianna Garcia, Fábio Rodrigues Ferreira Seiva, Amanda Pocol Carniato, Wilson de Mello Júnior, Nelson Duran, Alda Maria Macedo, Alexandre Gabarra de Oliveira, Rok Romih, Iseu da Silva Nunes, Odilon da Silva Nunes, Wagner José Fávaro
BACKGROUND: The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom BCG (Bacillus Calmette-Guerin) has failed or is contraindicated are recently increasing due to the development of new drugs. Although agents like mitomycin C and BCG are routinely used, there is a need for more potent and/or less-toxic agents. In this scenario, a new perspective is represented by P-MAPA (Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride), developed by Farmabrasilis (non-profit research network)...
2016: BMC Cancer
Seth P Lerner, Dean F Bajorin, Colin P Dinney, Jason A Efstathiou, Susan Groshen, Noah M Hahn, Donna Hansel, David Kwiatkowski, Michael O'Donnell, Jonathan Rosenberg, Robert Svatek, Jeffrey S Abrams, Hikmat Al-Ahmadie, Andrea B Apolo, Joaquim Bellmunt, Margaret Callahan, Eugene K Cha, Charles Drake, Jonathan Jarow, Ashish Kamat, William Kim, Margaret Knowles, Bhupinder Mann, Luigi Marchionni, David McConkey, Lisa McShane, Nilsa Ramirez, Andrew Sharabi, Arlene H Sharpe, David Solit, Catherine M Tangen, Abdul Tawab Amiri, Eliezer Van Allen, Pamela J West, J A Witjes, Diane Zipursky Quale
The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy...
2016: Bladder Cancer
Ashish M Kamat, Noah M Hahn, Jason A Efstathiou, Seth P Lerner, Per-Uno Malmström, Woonyoung Choi, Charles C Guo, Yair Lotan, Wassim Kassouf
Bladder cancer is a complex disease associated with high morbidity and mortality rates if not treated optimally. Awareness of haematuria as the major presenting symptom is paramount, and early diagnosis with individualised treatment and follow-up is the key to a successful outcome. For non-muscle-invasive bladder cancer, the mainstay of treatment is complete resection of the tumour followed by induction and maintenance immunotherapy with intravesical BCG vaccine or intravesical chemotherapy. For muscle-invasive bladder cancer, multimodal treatment involving radical cystectomy with neoadjuvant chemotherapy offers the best chance for cure...
June 23, 2016: Lancet
Ario Takeuchi, Masaki Shiota, Katsunori Tatsugami, Akira Yokomizo, Masatoshi Eto
No abstract text is available yet for this article.
January 2016: Fukuoka Igaku Zasshi, Hukuoka Acta Medica
Marko Babjuk, Andreas Böhle, Maximilian Burger, Otakar Capoun, Daniel Cohen, Eva M Compérat, Virginia Hernández, Eero Kaasinen, Joan Palou, Morgan Rouprêt, Bas W G van Rhijn, Shahrokh F Shariat, Viktor Soukup, Richard J Sylvester, Richard Zigeuner
CONTEXT: The European Association of Urology (EAU) panel on Non-muscle-invasive Bladder Cancer (NMIBC) released an updated version of the guidelines on Non-muscle-invasive Bladder Cancer. OBJECTIVE: To present the 2016 EAU guidelines on NMIBC. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines published between April 1, 2014, and May 31, 2015, was performed. Databases covered by the search included Medline, Embase, and the Cochrane Libraries...
June 17, 2016: European Urology
Thomasz Golabek, Joan Palou, Oscar Rodríguez, Josep Maria Gaya, Alberto Breda, Humberto Villavicencio
BACKGROUND: Recurrence and progression of T1 grade 3 (T1G3) urothelial bladder carcinomas (UBCs) treated with bacille Calmette-Guérin (BCG) are common events, but the long-term follow-up of the disease remains controversial. OBJECTIVE: To evaluate the long-term outcomes of BCG intravesical therapy in relation to disease recurrence and progression in primary T1G3 UBCs and upper tract disease. PATIENTS AND METHODS: A single-institution, retrospective, population-based analysis of 316 patients with primary T1G3 UBC treated with transurethral resection (TUR) and BCG induction intravesical instillations was performed...
June 9, 2016: World Journal of Urology
Akhil Muthigi, Arvin K George, Sam J Brancato, Piyush K Agarwal
Immunotherapy has long played a role in urothelial cancers with the use of bacille Calmette Guérin (BCG) being a mainstay in the treatment of nonmuscle invasive bladder cancer. Novel therapeutic approaches have not significantly impacted mortality in this population and so a renaissance in immunotherapy has resulted. This includes recombinant BCG, oncolytic viruses, monoclonal antibodies, vaccines, and adoptive T-cell therapy. Herein, we provide a review of the current state of the art and future therapies regarding immunotherapeutic strategies for urothelial carcinoma...
June 2016: Therapeutic Advances in Urology
Omar Fahmy, Mohd Ghani Khairul-Asri, Arnulf Stenzl, Georgios Gakis
Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies...
July 2016: Medical Hypotheses
Ronghua Liu, Feifei Luo, Xiaoming Liu, Luman Wang, Jiao Yang, Yuting Deng, Enyu Huang, Jiawen Qian, Zhou Lu, Xuechao Jiang, Dan Zhang, Yiwei Chu
Biological response modifiers (BRMs) emerge as a lay of new compounds or approaches used in improving cancer immunotherapy. Evidences highlight that cytokines, Toll-like receptor (TLR) signaling, and noncoding RNAs are of crucial roles in modulating antitumor immune response and cancer-related chronic inflammation, and BRMs based on them have been explored. In particular, besides some cytokines like IFN-α and IL-2, several Toll-like receptor (TLR) agonists like BCG, MPL, and imiquimod are also licensed to be used in patients with several malignancies nowadays, and the first artificial small noncoding RNA (microRNA) mimic, MXR34, has entered phase I clinical study against liver cancer, implying their potential application in cancer therapy...
2016: Advances in Experimental Medicine and Biology
Renate Pichler, Josef Fritz, Claudia Zavadil, Georg Schäfer, Zoran Culig, Andrea Brunner
Although Bacillus Calmette-Guérin (BCG) is the most successful immunotherapy for high-risk non-muscle-invasive bladder cancer, approximately 30% of patients are unresponsive to treatment. New biomarkers are important to identify patients who will benefit most from BCG during a worldwide BCG shortage. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded tissue sections of bladder cancer by immunohistochemistry, using monoclonal antibodies to tumor-associated macrophages (TAMs; CD68, CD163), B-lymphocytes (CD20) and T-lymphocyte subsets (CD3, CD4, CD8, GATA3, T-bet, FOXP3 and CD25)...
May 21, 2016: Oncotarget
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