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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/28217761/modeling-of-chronic-radiation-induced-cystitis-in-mice
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28111893/robot-assisted-partial-prostatectomy-for-anterior-cancer-a-step-by-step-guide
#11
Arnauld Villers, Vincent Flamand, Rodriguez Arquimedes, Philippe Puech, Georges-Pascal Haber, Mihir M Desai, Sebastien Crouzet, Adil Ouzzane, Inderbir S Gill
OBJECTIVES: To describe a step-by-step guide for isolated MRI-detected anterior prostate cancer (APC). PATIENTS AND METHODS: Following IRB approval, over an 8-year period, (2008-2015) 17 consenting patients were enrolled in a prospective, single-arm, single-center, IDEAL phase 2a study. Inclusion criteria comprised pre-urethral, low-intermediate risk APC diagnosed by MRI and targeted biopsies. Patient position and port placement were identical to transperitoneal robot-assited radical prostatectomy procedure...
January 23, 2017: BJU International
https://www.readbyqxmd.com/read/28111042/-immunotherapy-in-uropathology
#12
Virginie Verkarre, Hélène Roussel, Clémence Granier, Eric Tartour, Yves Allory
The algorithms for treatment of metastatic cancers are evolving due to positive results obtained with immunotherapy. Therapeutics approaches to stimulate the immune system have already been used in the treatment of kidney and bladder cancer, such as the administration of cytokines and BCG therapy, confirming the immunogenicity of these tumors. The aim of immunotherapies is not only to activate the immune system against tumor cells, but also to take into account the tumor-induced suppressive microenvironment, in particular by removing the anergy of T-cell lymphocytes, and by targeting the co-stimulation inhibitors molecules...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28107554/inclusion-of-a-variable-rbe-into-proton-and-photon-plan-comparison-for-various-fractionation-schedules-in-prostate-radiation-therapy
#13
Jakob Ödén, Kjell Eriksson, Iuliana Toma-Dasu
PURPOSE: A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions...
January 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28105218/involvement-of-cancer-derived-igg-in-the-proliferation-migration-and-invasion-of-bladder-cancer-cells
#14
Zhengzuo Sheng, Yang Liu, Caipeng Qin, Zhenhua Liu, Yeqing Yuan, Huaqi Yin, Xiaoyan Qiu, Tao Xu
It is widely accepted that immunoglobulin (Ig), the classical immune molecule, is extensively expressed in many cell types other than B-cells (non-B-IgG), including some malignant cells. The expression of Ig in malignant cells has been associated with a poor prognosis. In the present study, immunohistochemical analysis detected strong positive staining of IgG in three bladder cancer cell lines, the cancer cells in 77 bladder cancer patient samples and the cells in 3 cystitis glandularis tissue samples, while negative staining was observed in 4 specimens of normal transitional epithelial tissues...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28094956/radiolabeled-r954-derivatives-for-imaging-bradykinin-b1-receptor-expression-with-positron-emission-tomography
#15
Hsiou-Ting Kuo, Jinhe Pan, Joseph Lau, Chengcheng Zhang, Jutta Zeisler, Nadine Colpo, Francois Benard, Kuo-Shyan Lin
Peptide receptors have emerged as promising targets for diagnosis and therapy. The aberrant overexpression of these receptors in different cancer subtypes allows for the adoption of new treatment strategies that complement conventional chemotherapies. Bradykinin B1 receptor (B1R) is a G protein-coupled receptor that is overexpressed in many cancers, with limited expression in healthy tissues. Previously, we developed 68Ga- and 18F-labeled derivatives of B1R antagonist peptides B9858 and B9958, and successfully targeted B1R-expressing tumor xenografts in vivo...
January 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28077128/treatment-planning-comparison-of-impt-vmat-and-4%C3%AF-radiotherapy-for-prostate-cases
#16
Angelia Tran, Jingjing Zhang, Kaley Woods, Victoria Yu, Dan Nguyen, Gary Gustafson, Lane Rosen, Ke Sheng
BACKGROUND: Intensity-modulated proton therapy (IMPT), non-coplanar 4π intensity-modulated radiation therapy (IMRT), and volumetric-modulated arc therapy (VMAT) represent the most advanced treatment methods based on heavy ion and X-rays, respectively. Here we compare their performance for prostate cancer treatment. METHODS: Ten prostate patients were planned using IMPT with robustness optimization, VMAT, and 4π to an initial dose of 54 Gy to a clinical target volume (CTV) that encompassed the prostate and seminal vesicles, then a boost prescription dose of 25...
January 11, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28075465/monoclonal-antibody-zt-g4-targeting-ron-receptor-tyrosine-kinase-enhances-chemosensitivity-of-bladder-cancer-cells-to-epirubicin-by-promoting-g1-s-arrest-and-apoptosis
#17
Jun-Feng Chen, Bi-Xia Yu, Rui Yu, Liang Ma, Xiu-Yi Lv, Yue Cheng, Qi Ma
Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28065547/comparison-of-the-diabetes-guidelines-from-the-ada-easd-and-the-aace-ace
#18
Susan Cornell
OBJECTIVE: To compare recent diabetes guideline updates from the American Diabetes Association-European Association for the Study of Diabetes (ADA/EASD) and the American Association of Clinical Endocrinologists-American College of Endocrinology (AACE/ACE). SUMMARY: The ADA/EASD guideline continues to advocate a stepwise approach to glycemic control that initiates with metformin and intensifies treatment incrementally to dual and triple therapy at 3-month intervals until the patient is at their individualized goal...
January 5, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28064545/androgen-receptor-activation-a-prospective-therapeutic-target-for-bladder-cancer
#19
Taichi Mizushima, Kathleen A Tirador, Hiroshi Miyamoto
Patients with non-muscle-invasive or muscle-invasive bladder cancer undergoing surgery and currently available conventional therapy remain having a high risk of tumor recurrence or progression, respectively. Novel targeted molecular therapy is therefore expected to improve patient outcomes. Meanwhile, substantially higher incidence of bladder cancer in men has prompted research on androgen-mediated androgen receptor (AR) signaling in this malignancy. Indeed, preclinical evidence has suggested that AR signaling plays an important role in urothelial carcinogenesis and tumor outgrowth as well as resistance to some of the currently available conventional non-surgical therapies...
January 19, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28064454/hgf-met-in-cancer-progression-and-biomarker-discovery
#20
REVIEW
Kunio Matsumoto, Masataka Umitsu, Dinuka M De Silva, Arpita Roy, Donald P Bottaro
Signaling driven by hepatocyte growth factor (HGF) and MET receptor facilitates conspicuous biological responses such as epithelial cell migration, 3-D morphogenesis, and survival. The dynamic migration and promotion of cell survival induced by MET activation are bases respectively for invasion-metastasis and resistance against targeted drugs in cancers. Recent studies indicated that MET in tumor-derived exosomes facilitates metastatic niche formation and metastasis in malignant melanoma. In lung cancer, gene amplification-induced MET activation and ligand-dependent MET activation in autocrine/paracrine manner are causes for resistance to EGF receptor tyrosine kinase inhibitors and ALK inhibitors...
January 8, 2017: Cancer Science
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