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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/28931343/impact-of-bowel-gas-and-body-outline-variations-on-total-accumulated-dose-with-intensity-modulated-proton-therapy-in-locally-advanced-cervical-cancer-patients
#1
Thomas Berger, Jørgen Breede Baltzer Petersen, Jacob Christian Lindegaard, Lars Ulrik Fokdal, Kari Tanderup
INTRODUCTION: Density changes occurring during fractionated radiotherapy in the pelvic region may degrade proton dose distributions. The aim of the study was to quantify the dosimetric impact of gas cavities and body outline variations. MATERIAL AND METHODS: Seven patients with locally advanced cervical cancer (LACC) were analyzed through a total of 175 daily cone beam computed tomography (CBCT) scans. Four-beams intensity-modulated proton therapy (IMPT) dose plans were generated targeting the internal target volume (ITV) composed of: primary tumor, elective and pathological nodes...
September 21, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28927521/when-the-guardian-sleeps-reactivation-of-the-p53-pathway-in-cancer
#2
REVIEW
Olaf Merkel, Ninon Taylor, Nicole Prutsch, Philipp B Staber, Richard Moriggl, Suzanne D Turner, Lukas Kenner
The p53 tumor suppressor is inactivated in most cancers, thus suggesting that loss of p53 is a prerequisite for tumor growth. Therefore, its reintroduction through different means bears great clinical potential. After a brief introduction to current knowledge of p53 and its regulation by the ubiquitin-ligases MDM2/MDMX and post-translational modifications, we will discuss small molecules that are able to reactivate specific, frequently observed mutant forms of p53 and their applicability for clinical purposes...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28916750/comprehensive-multiregional-analysis-of-molecular-heterogeneity-in-bladder-cancer
#3
Mathilde Borg Houlberg Thomsen, Iver Nordentoft, Philippe Lamy, Søren Vang, Line Reinert, Christophe Kamungu Mapendano, Søren Høyer, Torben F Ørntoft, Jørgen Bjerggaard Jensen, Lars Dyrskjøt
Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28915710/insights-from-animal-models-of-bladder-cancer-recent-advances-challenges-and-opportunities
#4
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913158/dosimetry-and-first-human-experience-with-89-zr-panitumumab
#5
Liza Lindenberg, Stephen Adler, Ismail B Turkbey, Francesca Mertan, Anita Ton, Khanh Do, Shivaani Kummar, Esther Mena Gonzalez, Sibaprasad Bhattacharyya, Paula M Jacobs, Peter Choyke
(89)Zr-panitumumab is a novel immuno-PET radiotracer. A fully humanized IgG2 antibody, panitumumab binds with high affinity to the extracellular ligand binding domain of EGFR. Immuno-PET with radiolabeled panitumumab is a non-invasive method that could characterize EGFR expression in tumors and metastatic lesions. It might also assist in selecting patients likely to benefit from targeted therapy as well as monitor response and drug biodistribution for dosing guidance. Our objective was to calculate the maximum dosing for effective imaging with minimal radiation exposure in a small subset...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28903367/exploratory-investigation-of-psca-protein-expression-in-primary-breast-cancer-patients-reveals-a-link-to-her2-neu-overexpression
#6
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...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28895563/characteristics-and-clinical-significance-of-histological-variants-of-bladder-cancer
#7
REVIEW
Marco Moschini, David D'Andrea, Stephan Korn, Yasin Irmak, Francesco Soria, Eva Compérat, Shahrokh F Shariat
In the past 10 years evidence for the clinical relevance of variant histology in urinary bladder cancer has been increasing. This increase has resulted in new classifications of urothelial cancers by the WHO in 2016, highlighting the importance of an accurate morphological description of pathological specimens for the therapeutic management of patients with bladder cancer. The rising awareness of the importance of an accurate pathological report manifests itself in the increasing prevalence of reporting of variant histology in daily practice...
September 12, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28893347/mir-203-suppresses-bladder-cancer-cell-growth-and-targets-the-twist1
#8
Jie Shen, Jianhua Zhang, Minhui Xiao, Junfeng Yang, Ningnan Zhang
MiR-203 is an epigenetically silenced tumor-suppressive microRNA in tumors. This study was designed to investigate theeffects of miR-203 on the proliferation, migration, invasion and apoptosis of bladder cancer (BCa) cells. The expression levels of miR-203 in BCa tissues, the normal adjacent tissues, and the BCa cell lines were detected. BCa cells were transfected with miR-203 mimic and inhibitor to investigate the effect of miR-203 on cell functions and the epithelial mesenchymal transition (EMT). Cotransfection with miR-203 inhibitor and shRNA of the predicted target gene Twist1 (si-Twist1) was performed to investigate the target relationship of miR-203 and Twist1...
September 6, 2017: Oncology Research
https://www.readbyqxmd.com/read/28891033/targeted-alpha-therapy-of-mcrpc-dosimetry-estimate-of-213-bismuth-psma-617
#9
Clemens Kratochwil, Karl Schmidt, Ali Afshar-Oromieh, Frank Bruchertseifer, Hendrik Rathke, Alfred Morgenstern, Uwe Haberkorn, Frederik L Giesel
PURPOSE: PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter (213)Bi. METHODS: Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of (68)Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions...
September 11, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28888113/tissue-engineered-human-3d-model-of-bladder-cancer-for-invasion-study-and-drug-discovery
#10
Cassandra Ringuette Goulet, Geneviève Bernard, Stéphane Chabaud, Amélie Couture, Alexandre Langlois, Bertrand Neveu, Frédéric Pouliot, Stéphane Bolduc
The tumour microenvironment is critical to both the initiation and maintenance of tumorigenesis. Reconstitution of the microenvironment is a major challenge for in vitro cancer models. Indeed, conventional 2D culture systems cannot replicate the complexity, diversity and dynamic nature of the tumour microenvironment. In this study, we have developed a 3D endotheliazed vesical equivalent by using tissue engineering from primary human cells in which non-invasive or invasive bladder cancer (BCa) cell lines, cultured as compact spheroids, were incorporated...
August 29, 2017: Biomaterials
https://www.readbyqxmd.com/read/28886961/a-feasibility-study-of-using-advanced-external-beam-techniques-to-create-a-vaginal-cuff-brachytherapy-like-endometrial-boost-plan
#11
Zachary Grelewicz, Brooke Zerrusen, Vythialingam Sathiaseelan, Hualin Zhang
The purpose of this study was to explore the feasibility of using advanced external beam radiation therapy (EBRT) planning techniques for creating plans that could be used as a possible alternative for high-dose rate (HDR) vaginal cuff brachytherapy (VCBT) boost in treating endometrial cancer. The computed tomography (CT) images of a total of 4 female patients who had endometrial cancer treated with HDR-VCBT were selected for this study. A typical HDR-VCBT target volume, 0.5-cm-thick shell volume around the cylinder applicator in the prescribed treatment length was contoured and used as the planning target volume (PTV) in both the HDR VCBT and the EBRT VCBT-like plans...
September 5, 2017: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/28882129/igf1r-activation-and-the-in-vitro-antiproliferative-efficacy-of-igf1r-inhibitor-are-inversely-correlated-with-igfbp5-expression-in-bladder-cancer
#12
Yann Neuzillet, Elodie Chapeaublanc, Clémentine Krucker, Leanne De Koning, Thierry Lebret, François Radvanyi, Isabelle Bernard-Pierrot
BACKGROUND: The insulin growth factor (IGF) pathway has been proposed as a potential therapeutic target in bladder cancer. We characterized the expression of components of the IGF pathway - insulin growth factor receptors (INSR, IGF1R, IGF2R), ligands (INS, IGF1, IGF2), and binding proteins (IGFBP1-7, IGF2BP1-3) - in bladder cancer and its correlation with IGF1R activation, and the anti-proliferative efficacy of an IGF1R kinase inhibitor in this setting. METHODS: We analyzed transcriptomic data from two independent bladder cancer datasets, corresponding to 200 tumoral and five normal urothelium samples...
September 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28871988/bladder-preserving-therapy-patterns-of-care-a-survey-of-us-radiation-oncologists
#13
Abhishek A Solanki, Brendan Martin, Mark Korpics, Christina Small, Matthew M Harkenrider, Timur Mitin
PURPOSE: Clinical trials have demonstrated the efficacy of bladder-preserving chemoradiation therapy (BPT) in muscle-invasive bladder cancer but have differed in the radiation therapy dose/fractionations, radiation therapy targets, and concurrent chemotherapy regimens used. No data exist on the technical and practical approaches actually used in clinical practice throughout the United States when delivering BPT. We performed a survey to explore radiation oncologists' practice patterns...
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28871659/overexpression-of-her-2-via-immunohistochemistry-in-canine-urinary-bladder-transitional-cell-carcinoma-a-marker-of-malignancy-and-possible-therapeutic-target
#14
F Millanta, J Impellizeri, L McSherry, G Rocchigiani, L Aurisicchio, G Lubas
Transitional cell carcinoma (TCC) is the most commonly diagnosed neoplasm in the urinary bladder. Distant metastases to the regional lymph nodes, lungs, abdominal organs or bones are noted in up to 50% of dogs at time of death. Surgical excision is often not practical as TCC typically involve the trigone of the bladder and/or occurs multifocally throughout the bladder with field cancerization. Therapeutic approaches are very challenging and the requirement to evaluate alternative therapeutic protocols that may prolong survival times in dogs bearing these tumours is compelling...
September 4, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28864844/checkpoint-inhibitors-the-new-treatment-paradigm-for-urothelial-bladder-cancer
#15
REVIEW
Heather Katz, Emnet Wassie, Mohamed Alsharedi
Bladder cancer is the most common malignancy involving the genitourinary system (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). In the USA, it is the fifth most common cancer and approximately 79,000 new cases will be diagnosed in 2017 (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The mortality from bladder cancer is approximately 17,000 deaths each year (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The incidence rate for bladder cancer is higher in men compared to women. Risk factors are predominantly related to tobacco smoking, although infection with Schistosoma haematobium is another risk factor in selected populations (Antoni et al...
September 1, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28837140/met-smad3-snail-circuit-mediated-by-mir-323a-3p-is-involved-in-regulating-epithelial-mesenchymal-transition-progression-in-bladder-cancer
#16
Jiangfeng Li, Xin Xu, Shuai Meng, Zhen Liang, Xiao Wang, Mingjie Xu, Song Wang, Shiqi Li, Yi Zhu, Bo Xie, Yiwei Lin, Xiangyi Zheng, Ben Liu, Liping Xie
Bladder cancer (BCa) is the one of the most common cancers with high incidence, occurrence and low 5-year survival rate. Emerging evidence indicates that DLK1-DIO3 genomic region especially the miRNA cluster in this region is involved in several pathologic processes and various cancers, and miR-323a-3p is a member of this miRNA cluster. In this study, we investigate the function and regulatory network of miR-323a-3p in BCa. miR-323a-3p is frequently downregulated in BCa tissues and three cell lines compared with adjacent non-tumorous tissues and bladder normal cell line (SV-HUC-1)...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28830009/humanization-of-jaa-f11-a-highly-specific-anti-thomsen-friedenreich-pancarcinoma-antibody-and-invitro-efficacy-analysis
#17
Swetha Tati, John C Fisk, Julia Abdullah, Loukia Karacosta, Taylor Chrisikos, Padraic Philbin, Susan Morey, Diala Ghazal, Fatma Zazala, Joseph Jessee, Sally Quataert, Stephen Koury, David Moreno, Jing Ying Eng, Vladislav V Glinsky, Olga V Glinskii, Muctarr Sesay, Anthony W Gebhard, Karamveer Birthare, James R Olson, Kate Rittenhouse-Olson
JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells. JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types. Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework. The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11)...
August 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28819387/tbk1-promote-bladder-cancer-cell-proliferation-and-migration-via-akt-signaling
#18
Wei Chen, Kewang Luo, Zhiyi Ke, Bin Kuai, Shiyang He, Wei Jiang, Weiren Huang, Zhiming Cai
Bladder cancer is a challenging and fatal malignancy and the improvement in prognosis is limited over years. Deep understanding the mechanism of bladder cancer tumorigenesis and progression will help to discover novel and effective treatment strategies. In this study, we identify non-canonical IkB kinase TBK1 is up-regulated in bladder cancer tissue and cell lines. Knockdown of TBK1 markedly inhibits cell proliferation and migration. Inhibition of TBK1 kinase activity by BX795 significantly attenuates bladder cancer cell proliferation and migration...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#19
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
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
#20
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
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