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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/28807748/dosimetric-analysis-and-preliminary-clinical-result-of-image-guided-brachytherapy-with-or-without-hybrid-technique-for-cervical-cancer-using-varisource-titanium-ring-applicator-with-siriraj-ring-cap
#1
Pittaya Dankulchai, Suphalerk Lohasammakul, Janjira Petsuksiri, Pitchayut Nakkrasae, Lalida Tuntipumiamorn, Chumpot Kakanaporn, Yaowalak Chansilpa
PURPOSE: Titanium ring cap applicator (VariSource) was applied in treating cervical cancer patients by using image-guided brachytherapy (IGBT). However, its sizes appeared to be relatively large for most of our patients. Thus, we have developed a specific applicator "Siriraj Ring Cap," which is slightly smaller and more suitable for our patients. This study was to evaluate effectiveness of this equipment. METHODS AND MATERIALS: Locally advanced cervical cancer patients were treated with external beam radiation therapy with or without concomitant chemotherapy...
August 11, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28807237/mitochondrial-dysfunctions-in-bladder-cancer-exploring-their-role-as-disease-markers-and-potential-therapeutic-targets
#2
REVIEW
Antonella Cormio, Francesca Sanguedolce, Clara Musicco, Vito Pesce, Giuseppe Calò, Pantaleo Bufo, Giuseppe Carrieri, Luigi Cormio
Bladder cancer (BC) is a major cause of mortality worldwide as it currently lacks fully reliable markers of disease outcome and effective molecular targets for therapy. Mitochondria play a key role in cell metabolism but the role of mitochondrial dysfunctions in BC has been scarcely investigated. In this review, we explored current evidence for the potential role of mitochondrial DNA (mtDNA) alterations (point mutations and copy number) as disease markers in BC. Some germline mtDNA mutations detectable in blood could represent a non-invasive tool to predict the risk of developing BC...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28794159/p63%C3%AE-protein-upregulates-heat-shock-protein-70-expression-via-e2f1-transcription-factor-1-promoting-wasf3-wave3-mmp9-signaling-and-bladder-cancer-invasion
#3
Honglei Jin, Qipeng Xie, Xirui Guo, Jiheng Xu, Annette Wang, Jingxia Li, Junlan Zhu, Xue-Ru Wu, Haishan Huang, Chuanshu Huang
Bladder cancer (BC) is the sixth most common cancer in the United States and is the number one cause of death among patients with urinary system malignancies. This makes the identification of invasive regulator(s)/effector(s) as the potential therapeutic targets for managing BC a high priority. p63 is a member of the p53 family of tumor suppressor genes/proteins, plays a role in the differentiation of epithelial tissues, and is believed to function as a tumor suppressor. However, whether and how p63 functions in BC cell invasion after tumorigenesis remains unclear...
August 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28793245/sox2-is-a-marker-for-stem-like-tumor-cells-in-bladder-cancer
#4
Fengyu Zhu, Weiqing Qian, Haojie Zhang, Yu Liang, Mingqing Wu, Yingyin Zhang, Xiuhong Zhang, Qian Gao, Yang Li
It has been reported that functionally distinct cancer stem cells (CSCs) exist in human bladder cancer (BCa). Here, we found that Sox2, a transcription factor that is well characterized as a marker for stem cells, is upregulated in both mouse and human BCa. Sox2 expression is absent in normal urothelial cells, but it begins to be expressed in pre-neoplastic bladder tumors and continues to be expressed in invasive mouse BCa. Using s as a reporter of Sox2 transcriptional expression, we demonstrated that Sox2-expressing cells mark a subpopulation of tumor cells that fuel the growth of established BCa...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28791405/silibinin-suppresses-bladder-cancer-cell-malignancy-and-chemoresistance-in-an-nf-%C3%AE%C2%BAb-signal-dependent-and-signal-independent-manner
#5
Yi Sun, Zhenfeng Guan, Wencai Zhao, Yazhuo Jiang, Qing Li, Yongyi Cheng, Yonggang Xu
Because bladder cancer (BCa) is the 9th most common malignant tumor and 13th leading cause of death due to cancer, therapeutic approaches have attracted a great deal of attention from both clinicians and BCa patients. Although the development of surgery and targeted drugs has brought new challenges for the traditional concept of BCa therapy, various types of chemotherapy remain the final treatment method for many BCa patients. However, chemoresistance inevitably appears, leading to the failure of chemotherapy...
August 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28790515/transient-receptor-potential-melastatin-channel-family-member-2-friend-or-foe
#6
Joseph Y Cheung, Barbara A Miller
Transient receptor potential melastatin 2 (Trpm2) channels are nonvoltage-activated channels permeable to monovalent and divalent cations, and are expressed in heart, brain, kidney, vasculature, and hematopoietic cells. Trpm2 is overexpressed in bladder, lung, breast, liver, head, and neck cancers. Classically, Trpm2 activation induces cell injury and death by Ca(2+) overload or enhanced inflammatory response. Recent studies show that Trpm2 protects lungs from endotoxin-induced injury by reducing reactive oxygen species production in phagocytes; and improves cardiac function after ischemia-reperfusion injury by preserving mitochondrial respiration and cellular adenosine triphosphate levels while decreasing reactive oxygen species levels...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28781797/effect-of-modern-high-quality-prostate-intensity-modulated-radiation-therapy-on-outcome-evidence-from-a-community-radiation-oncology-program
#7
Johnny Kao, Amanda Zucker, Jonathan Timmins, Shankar Taramangalam, Jeffrey Pettit, Aaron J Woodall, Edward Loizides, Andrew T Wong
Radiation technique for prostate cancer has continuously evolved over the past several decades. The aim of the present study was to describe the effects of implementing modern prostate intensity-modulated radiation therapy (M-IMRT) on dosimetry and outcome. Between January 2010 and April 2012, 48 consecutive patients were treated with conventional prostate IMRT (C-IMRT) to a dose of 81 Gy. Between May 2012 and April 2015, 50 consecutive patients were treated with M-IMRT to the entire prostate to a dose of 75...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28765327/the-kmt1a-gata3-stat3-circuit-is-a-novel-self-renewal-signaling-of-human-bladder-cancer-stem-cells
#8
Tingyi Wen, Zhao Yang, Luyun He, Kaisu Lin, Yun Zhang, Aihua Deng, Yong Liang, Chong Li
Bladder cancer (BC) is one of the most common urinary malignancies worldwide characterized by a high rate of recurrence and no targeted therapy method. Bladder cancer stem cells (BCSCs) play a crucial role in tumor initiation, metastasis and drug-resistance. However, the regulatory signaling and self-renewal mechanisms of BCSCs remain largely unknown. Here, we identified a novel signal, the KMT1A-GATA3-STAT3 circuit, which promoted the self-renewal and tumorigenicity of human BCSCs.<br />Experimental Design: In a discovery step, human BCSCs and bladder cancer non-stem cells (BCNSCs) isolated from primary BC samples #1 and #2, and the BC cell line EJ were analyzed by transcriptome microarray...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28764881/dosimetric-impact-of-intrafraction-changes-in-mr-guided-high-dose-rate-hdr-brachytherapy-for-prostate-cancer
#9
Alexandra Rink, Jette Borg, Anna Simeonov, Gerald O'Leary, Joelle Helou, Cynthia Ménard, Peter Chung, David A Jaffray, Alejandro Berlin
PURPOSE: To assess changes in implant and treatment volumes through the course of a prostate high-dose-rate brachytherapy procedure and their impact on plan quality metrics. METHODS AND MATERIALS: Sixteen MRI-guided high-dose-rate procedures included a post-treatment MR (ptMR) immediately after treatment delivery (135 min between MR scans). Target and organs at risk (OARs) were contoured, and catheters were reconstructed. The delivered treatment plan was applied to the ptMR image set...
July 29, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28760506/a-comparison-of-treatment-plan-quality-between-tri-co-60-intensity-modulated-radiation-therapy-and-volumetric-modulated-arc-therapy-for-cervical-cancer
#10
Jong Min Park, So-Yeon Park, Jung-In Kim, Hyun-Cheol Kang, Chang Heon Choi
PURPOSE: To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for cervical cancer. METHODS: A total of 20 patients who received postoperative radiotherapy for cervical cancer were selected. For each patient, a tri-Co-60 IMRT plan for which the target volume was the planning target volume (PTV) generated by adding 1mm isotropic margins from the clinical target volume (CTV) and a VMAT plan for which the target volume was the PTV generated by adding 7mm and 10mm margins from the CTV were generated...
July 28, 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28755959/an-open-label-single-arm-phase-ii-multicenter-study-of-the-safety-and-efficacy-of-cg0070-oncolytic-vector-regimen-in-patients-with-bcg-unresponsive-non-muscle-invasive-bladder-cancer-interim-results
#11
Vignesh T Packiam, Donald L Lamm, Daniel A Barocas, Andrew Trainer, Benjamin Fand, Ronald L Davis, William Clark, Michael Kroeger, Igor Dumbadze, Karim Chamie, A Karim Kader, Dominic Curran, John Gutheil, Arthur Kuan, Alex W Yeung, Gary D Steinberg
OBJECTIVES: CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non-muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy...
July 26, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28740925/characterization-of-efficacy-and-toxicity-after-high-dose-pelvic-reirradiation-with-palliative-intent-for-genitourinary-second-malignant-neoplasms-or-local-recurrences-after-full-dose-radiation-therapy-in-the-pelvis-a-high-volume-cancer-center-experience
#12
Sophia C Kamran, Lauren C Harshman, Mandar S Bhagwat, Vinayak Muralidhar, Paul L Nguyen, Neil E Martin, Stephanie La Follette, Sarah Faso, Akila N Viswanathan, Jason A Efstathiou, Clair J Beard
PURPOSE: The use of large-field external beam reirradiation (re-RT) after pelvic radiation therapy (RT) for genitourinary (GU) cancers has not been reported. We report the results of such treatment in patients with either symptomatic GU second malignant neoplasms or locally recurrent pelvic tumors after initial RT for whom surgery or further systemic therapy was not an option. METHODS AND MATERIALS: The records of 28 consecutive patients with advanced, bulky GU malignancies treated with high-dose, large-field re-RT with palliative intent between 2008 and 2014 were retrospectively reviewed...
April 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/28729397/the-igf1r-insr-inhibitor-bi-885578-selectively-inhibits-growth-of-igf2-overexpressing-colorectal-cancer-tumors-and-potentiates-the-efficacy-of-anti-vegf-therapy
#13
Michael P Sanderson, Marco H Hofmann, Pilar Garin-Chesa, Norbert Schweifer, Andreas Wernitznig, Stefan Fischer, Astrid Jeschko, Reiner Meyer, Jurgen Moll, Thomas Pecina, Heribert Arnhof, Ulrike Weyer-Czernilofsky, Stephan K Zahn, Günther R Adolf, Norbert Kraut
Clinical studies of pharmacological agents targeting the insulin like growth factor (IGF) pathway in unselected cancer patients have so far demonstrated modest efficacy outcomes, with objective responses being rare. As such, the identification of selection biomarkers for enrichment of potential responders represents a high priority for future trials of these agents. Several reports have described high IGF2 expression in a subset of colorectal cancers (CRC), with focal IGF2 amplification being responsible for some of these cases...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28711929/predictive-value-of-molecular-subtyping-in-nmibc-by-rt-qpcr-of-erbb2-esr1-pgr-and-mki67-from-formalin-fixed-tur-biopsies
#14
Johannes Breyer, Ralph Markus Wirtz, Wolfgang Otto, Mark Laible, Kornelia Schlombs, Philipp Erben, Maximilian Christian Kriegmair, Robert Stoehr, Sebastian Eidt, Stefan Denzinger, Maximilian Burger, Arndt Hartmann
Expression of ESR1, PGR, HER2 and Ki67 is important for risk stratification and therapy in breast cancer. Hormone receptor expression can also be found in MIBC, reflecting luminal and basal subtypes of breast cancer. Thus the purpose was to investigate on the mRNA expression of the aforementioned markers and their prognostic value in pT1 bladder cancer. Retrospective analysis of clinical data and Formalin-Fixed Paraffin-Embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder was performed...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711481/simultaneous-integrated-boost-sib-for-treatment-of-gynecologic-carcinoma-intensity-modulated-radiation-therapy-imrt-vs-volumetric-modulated-arc-therapy-vmat-radiotherapy
#15
Irina Vergalasova, Kim Light, Junzo Chino, Oana Craciunescu
The aim of this study was to quantitatively compare dosimetric criteria between intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans for patients undergoing radiation treatment of gynecologic carcinoma with a simultaneous integrated boost (SIB) technique. IMRT and VMAT plans were retrospectively analyzed for 20 patients. The elective volume was planned to receive 45 Gy in 25 fractions of 1.8 Gy, with the integrated boost volume (involved nodes) receiving 55 Gy simultaneously...
July 12, 2017: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/28705507/dosimetric-comparison-of-rapidplan-and-manually-optimized-plans-in-volumetric-modulated-arc-therapy-for-prostate-cancer
#16
Kazuki Kubo, Hajime Monzen, Kentaro Ishii, Mikoto Tamura, Ryu Kawamorita, Iori Sumida, Hirokazu Mizuno, Yasumasa Nishimura
PURPOSE: This study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer. METHODS: We used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D95%, and D2% to planning target volume (PTV), mean dose, V50Gy, V70Gy, V75Gy, and V78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity...
July 10, 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28703782/understanding-the-role-of-non-coding-rnas-in-bladder-cancer-from-dark-matter-to-valuable-therapeutic-targets
#17
REVIEW
Cecilia Pop-Bica, Diana Gulei, Roxana Cojocneanu-Petric, Cornelia Braicu, Bogdan Petrut, Ioana Berindan-Neagoe
The mortality and morbidity that characterize bladder cancer compel this malignancy into the category of hot topics in terms of biomolecular research. Therefore, a better knowledge of the specific molecular mechanisms that underlie the development and progression of bladder cancer is demanded. Tumor heterogeneity among patients with similar diagnosis, as well as intratumor heterogeneity, generates difficulties in terms of targeted therapy. Furthermore, late diagnosis represents an ongoing issue, significantly reducing the response to therapy and, inevitably, the overall survival...
July 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28702647/an-enhanced-htert-promoter-driven-crispr-cas9-system-selectively-inhibits-the-progression-of-bladder-cancer-cells
#18
Xinbo Huang, Chengle Zhuang, Changshui Zhuang, Tiefu Xiong, Yawen Li, Yaoting Gui
The current therapies for treating tumors are lacking in efficacy and specificity. Synthetic biology principles may bring some new possible methods for curing cancer. Here we present a synthetic logic circuit based on the CRISPR/Cas9 system. The CRISPR/Cas9 technology has been applied in many biological fields, including cancer research. In this study, the expression of Cas9 nuclease was controlled indirectly by an enhanced hTERT promoter using the GAL4/upstream activating sequence (UAS) binding system. Cas9 was driven by 5XUAS, single guide RNA (sgRNA) was used to target mutant or wild-type HRAS, and the fusion gene GAL4-P65 was driven by the enhanced hTERT promoter...
July 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28687357/circular-rna-mylk-as-a-competing-endogenous-rna-promotes-bladder-cancer-progression-through-modulating-vegfa-vegfr2-signaling-pathway
#19
Zhenyu Zhong, Mengge Huang, Mengxin Lv, Yunfeng He, Changzhu Duan, Luyu Zhang, Junxia Chen
Accumulating evidences indicate that circular RNAs (circRNAs) play a vital role in modulating gene expression. However, the mechanisms underlying circRNAs remain largely elusive. Here, we screened circRNA and mRNA expression profiles of bladder carcinoma (BC) using microarray analysis. We found that circRNA-MYLK and VEGFA were significantly up-regulated and co-expressed in BC. Importantly, circRNA-MYLK levels were related to the progression of stage and grade of BC. Mechanistically, we demonstrated that circRNA-MYLK could directly bind to miR-29a and relieve suppression for target VEGFA, which activated VEGFA/VEGFR2 signaling pathway...
September 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28677729/centromere-protein-u-is-a-potential-target-for-gene-therapy-of-human-bladder-cancer
#20
Sheng Wang, Beibei Liu, Jiajun Zhang, Wei Sun, Changyuan Dai, Wenyan Sun, Qingwen Li
To investigate the role of centromere protein U (CENPU) in human bladder cancer (BCa), CENPU gene expression was evaluated in human BCa tissues. We used real-time quantitative PCR (qPCR) and found that CENPU gene expression in human BCa tissues was higher compared to that observed in cancer-adjacent normal tissues. High CENPU expression was found to be strongly correlated with tumor size and TNM stage. Kaplan-Meier survival analysis indicated that high CENPU levels were associated with reduced survival. We used a lentivirus to silence endogenous CENPU gene expression in the BCa T24 cell line...
June 30, 2017: Oncology Reports
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