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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/28641522/advances-on-ppar%C3%AE-research-in-the-emerging-era-of-precision-medicine
#1
Pinyi Lu, Zhongming Zhao
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily that functions as a ligand-inducible transcription factor. It regulates glucose and lipid metabolism, immunity, and cellular growth and differentiation. Thiazolidinediones (TZDs) are potent insulin sensitizers that function by activating PPARs, with a high specificity for PPARγ. Due to their ability to preserve pancreatic beta cell function and reduce insulin resistance, TZDs have become one of the most prescribed classes of medications for type 2 diabetes (T2D) since their approval by the US Food and Drug Administration (FDA) and initial use in 1997...
June 21, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28639203/development-of-therapeutic-dsp21-322-for-cancer-treatment
#2
Moo Rim Kang, Gongcheng Li, Tiejun Pan, Jin-Chun Xing, Long-Cheng Li
Small activating RNAs (saRNAs) are a class of artificially designed short duplex RNAs targeted at the promoter of a particular gene to upregulate its expression via a mechanism known as RNA activation (RNAa) and hold great promise for treating a wide variety of diseases including those undruggable by conventional therapies. The therapeutic benefits of saRNAs have been demonstrated in a number of preclinical studies carried out in different disease models including cancer. With many tumor suppressor genes (TSGs) downregulated due to either epigenetic mechanisms or haploinsufficiency resulting from deletion/mutation, cancer is an ideal disease space for saRNA therapeutics which can restore the expression of TSGs via epigenetic reprogramming...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#3
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28627610/silencing-dek-downregulates-cervical-cancer-tumorigenesis-and-metastasis-via-the-dek-p-ser9-gsk-3%C3%AE-p-tyr216-gsk-3%C3%AE-%C3%AE-catenin-axis
#4
Xiaoyang Xu, Lin Zou, Qiuhui Yao, Yanbo Zhang, Li Gan, Liangdan Tang
Cervical cancer is the second most common gynecological malignancy. The mechanisms of the genesis and progression of cervical cancer are complicated and not thoroughly understood. DEK is reported as an oncogene in various cancers, such as acute myeloid leukemia, bladder cancer, breast cancer and hepatocellular cancer. However, its role in cervical cancer has not been well studied. In our study, we confirmed the DEK protein as an oncoprotein in cervical cancer tissues which is correlated to cervical cancer FIGO staging and tumor type...
June 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28625477/challenges-and-advances-in-the-diagnosis-biology-and-treatment-of-urothelial-upper-tract-and-bladder-carcinomas
#5
REVIEW
Jeanny B Aragon-Ching
Urothelial carcinomas span the bladder, ureter, and renal pelvis, and while there had been stagnation in the field of drug approval for the past two decades, there is now accelerated and regular US FDA approval of 5 immunotherapy agents. However, patients who inherently do not respond or progress on such therapies still represent an area of increased unmet need. In this special Seminars issue, we explore varying aspects of bladder urothelial carcinoma treatment with targeted therapies, the unique presentation and challenges in the treatment of upper tract and renal pelvis tumors, as well as new and emerging diagnostic imaging tools for varying genitourinary cancers...
July 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28619755/epidermal-growth-factor-receptor-egfr-targeted-photoimmunotherapy-pit-for-the-treatment-of-egfr-expressing-bladder-cancer
#6
Reema Railkar, L Spencer Krane, Q Quentin Li, Thomas Sanford, Mohammad Rashid Siddiqui, Diana Haines, Srinivas Vourganti, Sam J Brancato, Peter L Choyke, Hisataka Kobayashi, Piyush K Agarwal
The use of light as a means of therapy for bladder cancer (BC) has a long history but has been hampered by a lack of tumor specificity and therefore, damage to the normal bladder mucosa. Here, we describe a targeted form of photo-therapy called photoimmunotherapy (PIT) which targets EGFR-expressing BC. Anti-EGFR antibody panitumumab (pan) was labeled with the photo-absorber (PA), IRDye 700Dx (IR700), to create a pan IR700 antibody-PA conjugate which is activated by near-infrared radiation (NIR). BC tissue microarray (TMA) and BC cell lines were analyzed for expression of EGFR...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28609792/-systematic-review-on-conservative-treatment-options-in-non-muscle-invasive-bladder-cancer-patients-refractory-to-bacillus-calmette-gu%C3%A3-rin-instillation-therapy
#7
Thomas Martini, Felix Wezel, Niklas Löbig, Michael J Mitterberger, Daniela Colleselli
Background Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure...
June 13, 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28599664/angiotensin-ii-type-2-receptor-promotes-apoptosis-and-inhibits-angiogenesis-in-bladder-cancer
#8
Nana Pei, Yingying Mao, Pengfei Wan, Xinglu Chen, Andrew Li, Huiying Chen, Jinlong Li, Renqiang Wan, Yanling Zhang, Hongyan Du, Baihong Chen, Guangyu Jiang, Minghan Xia, Colin Sumners, Guixue Hu, Dongsheng Gu, Hongwei Li
BACKGROUND: Bladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), which include the angiotensin type 1 (AT1R), type 2(AT2R), and Mas receptors, play an important role in tumorigenesis and may guide us in meeting those needs. RESULTS: In this study, we first observed that AT1R and Mas expression levels were significantly upregulated in BCa specimens while AT2R was significantly downregulated...
June 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28586028/atm-mediates-dab2ip-deficient-bladder-cancer-cell-resistance-to-ionizing-radiation-through-the-p38mapk-and-nf-%C3%AE%C2%BAb-signaling-pathway
#9
Hui He, Rulve Chang, Tingting Zhang, Chen Yang, Zhaolu Kong
Although surgery remains the standard therapy for the treatment of bladder cancer (BCa), the data from previous clinical studies suggest that there is an increase in the number of patients with a preference for bladder preservation strategies, including radiotherapy, to improve their life quality. Our preliminary results showed that disabled homolog 2 interactive protein (DAB2IP), a putative tumor suppressor gene, is often downregulated in BCa with a radioresistant phenotype. Subsequent investigations revealed that elevated expression of ataxia‑telangiectasia mutated (ATM) induced by DAB2IP‑knockdown may be the key event in BCa cell resistance to ionizing radiation (IR)...
June 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28583311/next-generation-sequencing-of-nonmuscle-invasive-bladder-cancer-reveals-potential-biomarkers-and-rational-therapeutic-targets
#10
Eugene J Pietzak, Aditya Bagrodia, Eugene K Cha, Esther N Drill, Gopa Iyer, Sumit Isharwal, Irina Ostrovnaya, Priscilla Baez, Qiang Li, Michael F Berger, Ahmet Zehir, Nikolaus Schultz, Jonathan E Rosenberg, Dean F Bajorin, Guido Dalbagni, Hikmat Al-Ahmadie, David B Solit, Bernard H Bochner
BACKGROUND: Molecular characterization of nonmuscle invasive bladder cancer (NMIBC) may provide a biologic rationale for treatment response and novel therapeutic strategies. OBJECTIVE: To identify genetic alterations with potential clinical implications in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: Pretreatment index tumors and matched germline DNA from 105 patients with NMIBC on a prospective Institutional Review Board-approved protocol underwent targeted exon sequencing analysis in a Clinical Laboratory Improvement Amendments-certified clinical laboratory...
June 2, 2017: European Urology
https://www.readbyqxmd.com/read/28579283/optimizing-management-of-upper-tract-urothelial-carcinoma
#11
REVIEW
Matthew T Campbell, Amishi Y Shah, Surena F Matin, Arlene O Siefker-Radtke
Upper tract urothelial cancer (UTUC) is a rare cancer of the urothelium, comprising only a fraction of cases as compared to urothelial tumors of the bladder. As a result, systemic treatment approaches in bladder cancer are often applied to patients with UTUC. Given the anatomical location of these tumors, the age, the comorbid conditions of these patients with UTUC, and the need for radical nephroureterectomy for treatment, most patients have substantial impairment of renal reserve. There is growing evidence for the benefit of perioperative chemotherapy in this disease...
June 1, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28556678/emerging-drugs-for-urothelial-bladder-cancer
#12
Kerwin Cumberbatch, Tianfang He, Zachary Thorogood, Benjamin A Gartrell
Metastatic urothelial carcinoma has been associated with poor prognosis and a median survival of approximately 12-14 months with standard therapy. Treatment options for decades have been limited to platinum based chemotherapy as first line with few therapeutic options available to the majority who will ultimately progress beyond platinum. Areas covered: This review focuses on the various targeted, antiangiogenic, chemotherapeutic and immunotherapeutic agents currently being developed for the treatment of urothelial carcinoma...
June 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28549556/evaluation-of-a-commercial-automatic-treatment-planning-system-for-prostate-cancers
#13
Kanabu Nawa, Akihiro Haga, Akihiro Nomoto, Raniel A Sarmiento, Kenshiro Shiraishi, Hideomi Yamashita, Keiichi Nakagawa
Recent developments in Radiation Oncology treatment planning have led to the development of software packages that facilitate automated intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) planning. Such solutions include site-specific modules, plan library methods, and algorithm-based methods. In this study, the plan quality for prostate cancer generated by the Auto-Planning module of the Pinnacle(3) radiation therapy treatment planning system (v9.10, Fitchburg, WI) is retrospectively evaluated...
May 23, 2017: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/28548125/next-generation-sequencing-based-molecular-characterization-of-primary-urinary-bladder-adenocarcinoma
#14
Somak Roy, Dinesh Pradhan, Wayne L Ernst, Stephanie Mercurio, Yana Najjar, Rahul Parikh, Anil V Parwani, Reetesh K Pai, Rajiv Dhir, Marina N Nikiforova
Primary bladder adenocarcinoma is a rare and aggressive tumor with poor clinical outcomes and no standard of care therapy. Molecular biology of this tumor is unknown due to the lack of comprehensive molecular profiling studies. The study aimed to identify genomic alterations of clinical and therapeutic significance using next-generation sequencing and compare genomic profile of primary bladder adenocarcinoma with that of high-grade urothelial carcinoma and colorectal adenocarcinoma. A cohort of 15 well-characterized primary bladder adenocarcinoma was subjected to targeted next-generation sequencing for the identification of mutations and copy-number changes in 51 cancer-related genes...
May 26, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28533484/insights-from-animal-models-of-bladder-cancer-recent-advances-challenges-and-opportunities
#15
REVIEW
Bincy Anu John, Neveen Said
Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524002/mirna-expression-in-bladder-cancer-and-their-potential-role-in-clinical-practice
#16
Ana Blanca, Liang Cheng, Rodolfo Montironi, Holger Moch, Francesco Massari, Michelangelo Fiorentino, Maria Rosaria Raspollini, Marina Scarpelli, Antonio Lopez-Beltran
To date more than 3000 miRNA sequences have been described in humans and reg¬istered at miRBase since their discovery. However, the functions of only a few of these miRNAs have been experimentally determined using deep sequencing technology. Aberrant miRNA expression has been associated with differentiation, invasion and metastasis in several cancers. In this context, recent reports have suggested that miRNAs play important roles in the regulation of target genes by binding to complementary regions of messenger transcripts to repress their translation or regulate degradation...
May 18, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28516152/cdk4-6-inhibitors-in-cancer-therapy-a%C3%A2-novel-treatement-strategy-for-bladder-cancer
#17
REVIEW
Qi Pan, Anuja Sathe, Peter C Black, Peter J Goebell, Ashish M Kamat, Bernd Schmitz-Draeger, Roman Nawroth
Patients with metastatic bladder cancer (mBC) treated with cisplatin-based chemotherapy have a limited median survival of only around 14 months [1]. Despite over 30 years of basic and clinical research, until recently no therapeutic options beyond cisplatin-based therapy had entered clinical routine and, at least in the US, none of the tested agents had been approved for second-line treatment. This has changed with the advent of immune checkpoint blockade, including especially PD-1/PD-L1 inhibitors. The high response rates of 24% over a 14...
April 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28512267/exploratory-investigation-of-psca-protein-expression-in-primary-breast-cancer-patients-reveals-a-link-to-her2-neu-overexpression
#18
Theresa Link, Friederike Kuithan, Armin Ehninger, Jan Dominik Kuhlmann, Michael Kramer, Andreas Werner, Axel Gatzweiler, Barbara Richter, Gerhard Ehninger, Gustavo Baretton, Michael Bachmann, Pauline Wimberger, Katrin Friedrich
BACKGROUND: Prostate stem cell antigen (PSCA) has been suggested as biomarker and therapeutic target for prostate cancer. Recent advances showed that PSCA is up-regulated in other cancer entities, such as bladder or pancreatic cancer. However, the clinical relevance of PSCA-expression in breast cancer patients has not yet been established and is therefore addressed by the current study. METHODS: PSCA-protein expression was assessed in 405 breast cancer patients, using immunohistochemistry (PSCA antibody MB1) and tissue microarrays...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#19
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507621/expression-of-fgfr3-protein-and-gene-amplification-in-urinary-bladder-lesions-in-relation-to-schistosomiasis
#20
Olfat Hammam, Tarek Aboushousha, Ali El-Hindawi, Hosni Khairy, Heba Khalil, Amira Kamel, Maha Akl, Ahmed Abdel-Hady, Mona Magdy, Mohamed Badawy, Amr El Kholy, Khalid Al Osili, Nora Kamel, Shady Anis, Tarek El Leithy
BACKGROUND: Bladder cancer represents the fifth most common malignancy worldwide and a major cause of cancer-related morbidity and death. Incidence and mortality rates have remained relatively constant over the past four decades. Urothelial bladder cancers have identified multiple risk factors. AIM: We aimed at evaluating the expression of the FGFR3 protein and gene amplification in the urothelial cells of neoplastic and non-neoplastic urothelial lesions of the urinary bladder, and correlation with tumour grade, stage and associated bilharziasis...
April 15, 2017: Open Access Macedonian Journal of Medical Sciences
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