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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/28306559/immunotherapy-a-new-treatment-paradigm-in-bladder-cancer
#1
Nicole N Davarpanah, Akira Yuno, Jane B Trepel, Andrea B Apolo
PURPOSE OF REVIEW: T-cell checkpoint blockade has become a dynamic immunotherapy for bladder cancer. In 2016, atezolizumab, an immune checkpoint inhibitor, became the first new drug approved in metastatic urothelial carcinoma (mUC) in over 30 years. In 2017, nivolumab was also approved for the same indication. This overview of checkpoint inhibitors in clinical trials focuses on novel immunotherapy combinations, predictive biomarkers including mutational load and neoantigen identification, and an evaluation of the future of bladder cancer immunotherapy...
March 16, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28297436/simultaneously-integrated-boost-sib-spares-oar-and-reduces-treatment-time-in-locally-advanced-cervical-cancer
#2
Christine H Feng, Yasmin Hasan, Malgorzata Kopec, Hania A Al-Hallaq
We performed a dosimetric comparison of sequential IMRT (sIMRT) and simultaneously integrated boost (SIB) IMRT to boost PET-avid lymph nodes while concurrently treating pelvic targets to determine the potential of SIB IMRT to reduce overall treatment duration in locally advanced cervical cancer. Ten patients receiving definitive radiation therapy were identified retrospectively. RTOG consensus guidelines were followed to delineate the clinical target volume and organs at risk (OAR), which were then expanded per IMRT consortium guidelines to yield the planning target volume (PTV)...
September 2016: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28291936/dosimetric-benefits-of-intensity-modulated-radiotherapy-and-volumetric-modulated-arc-therapy-in-the-treatment-of-postoperative-cervical-cancer-patients
#3
Xia Deng, Ce Han, Shan Chen, Congying Xie, Jinling Yi, Yongqiang Zhou, Xiaomin Zheng, Zhenxiang Deng, Xiance Jin
As the advantage of using complex volumetric-modulated arc therapy (VMAT) in the treatment of gynecologic cancer has not yet been fully determined, the purpose of this study was to investigate the dosimetric advantages of VMAT by comparing directly with whole pelvic conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT) in the treatment of 15 postoperative cervical cancer patients. Four-field CRT, seven-field IMRT, and two-arc VMAT plans were generated for each patient with identical objective functions to achieve clinically acceptable dose distribution...
January 2017: Journal of Applied Clinical Medical Physics
https://www.readbyqxmd.com/read/28290459/contemporary-update-on-neoadjuvant-therapy-for-bladder-cancer
#4
REVIEW
Daniel P Nguyen, George N Thalmann
Administration of neoadjuvant chemotherapy preceding radical cystectomy in patients with bladder cancer remains a matter of debate. Results of prospective, randomized studies have demonstrated an overall absolute survival benefit of 5% at 5 years, provided cisplatin-based combination regimens are used. Owing to the perception of a modest survival benefit, the medical community has been slow to adopt the use of neoadjuvant chemotherapy. Other reasons for the underuse of neoadjuvant chemotherapy range from patient ineligibility to fear of delaying potentially curative surgery in nonresponders...
March 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28281901/tp53-and-its-potential-therapeutic-role-as-a-target-in-bladder-cancer
#5
Chiara Ciccarese, Francesco Massari, Ana Blanca, Giampaolo Tortora, Rodolfo Montironi, Liang Cheng, Marina Scarpelli, Maria R Raspollini, Nuno Vau, Jorge Fonseca, Antonio Lopez-Beltran
Despite more than 30 years of research on p53 resulting in >50,000 publications, we are now beginning to figure out the complexity of the p53 pathway, gene ontology and conformational structure of the molecule. Recent years brought great advances in p53 related drugs and the potencial ways in which p53 is inactivated in cancer. Areas covered: We searched for related publications on Pubmed and ClinicalTrial.gov using the following keywords 'p53, Tp53, p53 and bladder cancer, p53 and therapeutic target'. Relevant articles improved the understanding on p53 pathways and their potential as candidate to targeted therapy in bladder cancer...
April 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28279796/tetrahydroporphyrin-tetratosylat-thpts-a-near-infrared-photosensitizer-for-targeted-and-efficient-photodynamic-therapy-pdt-of-human-bladder-carcinoma-an-in-vitro-study
#6
Mandy Berndt-Paetz, Annett Weimann, Nadine Sieger, Stanislaw Schastak, Yasser M Riyad, Jan Griebel, Vinodh K A Arthanareeswaran, Jens-Uwe Stolzenburg, Jochen Neuhaus
BACKGROUND: Efficacy of PDT in muscle-invasive bladder cancer is hampered by low tissue penetration of most photosensitizers by short excitation wavelength. THPTS is excitable at near-infrared (760nm) allowing tissue penetration up to 15mm. We examined the cellular effects of THPTS-PDT in human bladder cancer cells. MATERIAL AND METHODS: We used four human transitional carcinoma cell lines, epithelial bladder progenitors (HBLAK) and bladder smooth muscle cells (HBSMC)...
March 6, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28279147/dosimetric-comparison-and-evaluation-of-4-stereotactic-body-radiotherapy-techniques-for-the-treatment-of-prostate-cancer
#7
Jan Seppälä, Sami Suilamo, Mikko Tenhunen, Liisa Sailas, Heli Virsunen, Erna Kaleva, Jani Keyriläinen
PURPOSE: The aim of this study was to compare dosimetric characteristics, monitor unit, and delivery efficiency of 4 different stereotactic body radiotherapy techniques for the treatment of prostate cancer. METHODS: This study included 8 patients with localized prostate cancer. Dosimetric assets of 4 delivery techniques for stereotactic body radiotherapy were evaluated: robotic CyberKnife, noncoplanar intensity-modulated radiotherapy, and 2 intensity-modulated arc therapy techniques (RapidArc and Elekta volumetric-modulated arc therapy)...
April 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/28259975/gene-expression-profiling-in-bladder-cancer-identifies-potential-therapeutic-targets
#8
Syed A Hussain, Daniel H Palmer, Wing-Kin Syn, Joseph J Sacco, Richard M D Greensmith, Taha Elmetwali, Vijay Aachi, Bryony H Lloyd, Puthen V Jithesh, John Arrand, Darren Barton, Jawaher Ansari, D Ross Sibson, Nicholas D James
Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles...
March 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28244409/external-validation-and-optimization-of-international-consensus-clinical-target-volumes-for-adjuvant-radiation-therapy-in-bladder-cancer
#9
Abhinav V Reddy, John P Christodouleas, Tianming Wu, Norman D Smith, Gary D Steinberg, Stanley L Liauw
PURPOSE: International consensus (IC) clinical target volumes (CTVs) have been proposed to standardize radiation field design in the treatment of patients at high risk of locoregional failure (LRF) after radical cystectomy. The purpose of this study was to externally validate the IC CTVs in a cohort of postsurgical patients followed up for LRF and identify revisions that might improve the IC CTVs' performance. METHODS AND MATERIALS: Among 334 patients with pT3 to pT4 bladder cancer treated with radical cystectomy, LRF developed in 58 (17%), of whom 52 had computed tomography scans available for review...
March 15, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28237713/poly-l-glutamic-acid-drug-delivery-system-for-the-intravesical-therapy-of-bladder-cancer-using-wga-as-targeting-moiety
#10
C Apfelthaler, M Anzengruber, F Gabor, M Wirth
In the management of bladder cancer, surgical resection of the tumour is usually followed by intravesical instillation of immunomodulatives and/or chemotherapeutics. The purpose of this local intravesical therapy is to eliminate residual malignant cells after surgical intervention. The main limitation of a localised adjuvant therapy is the insufficient concentration of the active pharmaceutical ingredient (API) in malignant cells due to the unique structure of the human urothelium making it an exclusively hard to overcome barrier in the human body...
February 22, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28217761/modeling-of-chronic-radiation-induced-cystitis-in-mice
#11
Bernadette M M Zwaans, Sarah Krueger, Sarah N Bartolone, Michael B Chancellor, Brian Marples, Laura E Lamb
PURPOSE: Radiation cystitis (RC), a severe inflammatory bladder condition, develops as a side-effect of pelvic radiation therapy in cancer patients. There are currently no effective therapies to treat RC, in part due to the lack of preclinical model systems. In this study, we developed a mouse model for RC and used a small animal radiation research platform (SARRP) to simulate the targeted delivery of radiation as used with human patients. METHODS AND MATERIALS: To induce RC, C3H mice received a single radiation dose of 20Gy delivered through two beams...
October 2016: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/28210516/immunohistochemical-investigation-of-her-akt-mtor-pathway-and-cellular-adhesion-molecules-in-urothelial-carcinomas
#12
Nikolaos Koletsas, Triantafyllia Koletsa, Spyros Choidas, Konstantinos Anagnostopoulos, Stavros Touloupidis, Thomas Zaramboukas, Georgia Raptou, Nikolaos Papadopoulos, Maria Lambropoulou
Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs). Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections...
2017: Pathology Research International
https://www.readbyqxmd.com/read/28205537/her2-alterations-in-muscle-invasive-bladder-cancer-patient-selection-beyond-protein-expression-for-targeted-therapy
#13
Bernhard Kiss, Alexander W Wyatt, James Douglas, Veronika Skuginna, Fan Mo, Shawn Anderson, Diana Rotzer, Achim Fleischmann, Vera Genitsch, Tetsutaro Hayashi, Maja Neuenschwander, Christine Buerki, Elai Davicioni, Colin Collins, George N Thalmann, Peter C Black, Roland Seiler
Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205191/novel-and-expanded-oncology-drug-approvals-of-2016-part-1-new-options-in-solid-tumor-management
#14
REVIEW
Todd C Knepper, James Saller, Christine M Walko
The nonradiologic medical management of solid tumors has evolved from the use of traditional cytotoxic agents to modern targeted therapies, monoclonal antibodies, and immunotherapies. Advances in the understanding of cancer biology and therapeutic strategies have resulted in increasing numbers of new drug applications and approvals. Consequently, practicing oncologists need to learn how the newly available agents function and what toxicities to watch for, as well as ways to optimize the use of both new drugs and previously approved drugs with new indications...
February 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28191808/chemoradiation-for-organ-preservation-in-the-treatment-of-muscle-invasive-bladder-cancer-our-institutional-experience
#15
Sweety Gupta, Sudarsan De, Nitin Leekha, Shailesh Chand Sahay, Prekshi Chaudary, Shashank Srinivasan, Malay Nandy
AIM: To assess outcome of chemoradiotherapy for organ preservation in muscle invasive bladder cancer. MATERIAL AND METHODS: 41 patients treated between January 2010 to January 2015 were evaluated in the present study. All patients T staged ranging from cT2-T4a and had undergone maximal transurethral resection of bladder tumour (TURBT). After maximum bladder tumour resection patients were treated with Radiotherapy with or without concurrent chemotherapy. 8 weeks after completion of treatment response was assessed by check cystoscopy, urine cytology and CECT scan Abdomen...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28176958/prognostic-significance-of-microrna-100-in-solid-tumors-an-updated-meta-analysis
#16
Jiangfeng Wang, Miao Yu, Shanghui Guan, Guangyu Zhang, Jianbo Wang, Yufeng Cheng
OBJECTIVE: The aim of this study was to identify prognostic significance of microRNA-100 (miR-100) in solid tumor. METHODS: Literature search was conducted in databases such as PubMed, Embase, and Web of Science, using the following words "(microRNA-100 OR miR-100 OR mir100) AND (tumor OR neoplasm OR cancer OR carcinoma OR malignancy)." The search was updated up until July 10, 2016. Newcastle-Ottawa scale was used to evaluate the quality of studies. Pooled hazard ratio (HR) with 95% confidence interval (CI) for patients' survival was calculated by using a fixed-effects or a random-effects model on the basis of heterogeneity...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28169993/the-evolving-genomic-landscape-of-urothelial-carcinoma
#17
REVIEW
Alexander P Glaser, Damiano Fantini, Ali Shilatifard, Edward M Schaeffer, Joshua J Meeks
Survival of patients with urothelial carcinoma (including bladder cancer and upper tract urothelial carcinoma) is limited by our current approaches to staging, surgery, and chemotherapy. Large-scale, next-generation sequencing collaborations, such as The Cancer Genome Atlas, have already identified drivers and vulnerabilities of urothelial carcinoma. This disease has a high degree of mutational heterogeneity and a high frequency of somatic mutations compared with other solid tumours, potentially resulting in an increased neoantigen burden...
February 7, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28165132/nonmuscle-invasive-bladder-cancer-what-s-changing-and-what-has-changed
#18
Ramanitharan Manikandan, Oscar Rodriguez, Rubén Parada, Joan Palou Redorta
PURPOSE: Nonmuscle-invasive bladder cancer (NMIBC) is a challenging disease to manage primarily due to its varied clinical course. The management of NMIBC has witnessed a widespread change with respect to its diagnosis and treatment. Although transurethral resection (TUR) and adjuvant bacillus Calmette-Guerin (BCG) stills remain the cornerstone, newer protocols has come into vogue to achieve optimal care. On the basis of a literature review, we aimed to establish 'what changes has already occurred and what is expected in the future' in NMIBC...
February 3, 2017: Urologia
https://www.readbyqxmd.com/read/28159930/compared-planning-dosimetry-of-tomo-vmat-and-imrt-in-rectal-cancer-with-different-simulated-positions
#19
Jang-Chun Lin, Jo-Ting Tsai, Li-Jhen Chen, Ming-Hsien Li, Wei-Hsiu Liu
OBJECTIVES: To compare treatment plans for helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for locally advanced rectal cancer (LARC). MATERIALS AND METHODS: This retrospective study from December 2010 to June 2013 included 20 patients with LARC who received neoadjuvant concurrent chemoradiotherapy (CCRT) with radiation doses of greater than 50.4 Gy. Dosimetric quality was evaluated based on doses to organs at risk (OARs), including small bowel, urinary bladder and bilateral femoral head, over the same coverage of the clinical target volume (CTV)...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28131548/an-orally-bioavailable-chk1-inhibitor-cct244747-sensitizes-bladder-and-head-and-neck-cancer-cell-lines-to-radiation
#20
Radhika Patel, Holly E Barker, Joan Kyula, Martin McLaughlin, Magnus T Dillon, Ulrike Schick, Hind Hafsi, Alan Thompson, Vincent Khoo, Kevin Harrington, Shane Zaidi
PURPOSE: Chk1 inhibition increases cell sensitivity to both chemotherapy and radiotherapy in several tumour types and is, therefore, a promising anti-cancer approach. Although several Chk1 inhibitors have been developed, their clinical progress has been hampered by low bioavailability and off-target toxicities. MATERIALS AND METHODS: We characterized the radiosensitizing activity of CCT244747, the first orally bioavailable Chk1 inhibitor. We used a panel of bladder and head and neck cancer cell lines and monitored the effect of combining CCT244747 with radiation both in in vitro and in vivo models...
January 25, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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