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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/28533484/insights-from-animal-models-of-bladder-cancer-recent-advances-challenges-and-opportunities
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28501564/wntless-promotes-bladder-cancer-growth-and-acts-synergistically-as-a-molecular-target-in-combination-with-cisplatin
#7
Sebastian C Schmid, Anuja Sathe, Ferdinand Guerth, Anna-Katharina Seitz, Matthias M Heck, Tobias Maurer, Sarah M Schwarzenböck, Bernd J Krause, Wolfgang A Schulz, Robert Stoehr, Jürgen E Gschwend, Margitta Retz, Roman Nawroth
PURPOSE: To analyze the contribution of Wnt signaling pathway to bladder cancer growth in order to identify suitable target molecules for therapy. MATERIAL AND METHODS: Expression of Wnt 2/4/7, LRP5/6, TCF1/2/4, LEF-1, and β-actin was detected by reverse transcription polymerase chain reaction in a panel of 9 and for Wntless (WLS) in 17 bladder cancer cell lines. Protein expression of WLS was detected in 6 cell lines. Wnt/β-catenin activity was analyzed using the TOPflash/FOPflash luciferase reporter assay...
May 10, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28499607/evaluation-of-intensity-modulated-radiation-therapy-dose-painting-for-localized-prostate-cancer-using-68-ga-hbed-cc-psma-pet-ct-a-planning-study-based-on-histopathology-reference
#8
Constantinos Zamboglou, Ilias Sachpazidis, Khodor Koubar, Vanessa Drendel, Rolf Wiehle, Simon Kirste, Michael Mix, Florian Schiller, Panayiotis Mavroidis, Philipp T Meyer, Martin Werner, Anca L Grosu, Dimos Baltas
PURPOSE: To demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose painting using (68)Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer (PCa). METHODS AND MATERIALS: 10 patients had PSMA PET/CT scans prior to prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of 30%. Two IMRT plans were generated for each patient: Plan(77) which consisted of whole-prostate IMRT to 77Gy, and Plan(95) which consisted of whole-prostate IMRT to 77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35 fractions)...
May 9, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28498805/foxm1-predicts-overall-and-disease-specific-survival-in-muscle-invasive-urothelial-carcinoma-and-presents-a-differential-expression-between-bladder-cancer-subtypes
#9
Sebastien Rinaldetti, Ralph Markus Wirtz, Thomas Stefan Worst, Markus Eckstein, Cleo Aaron Weiss, Johannes Breyer, Wolfgang Otto, Christian Bolenz, Arndt Hartmann, Philipp Erben
Forkhead box M1 (FOXM1) is a late cell cycle gene that plays a crucial role in carcinogenesis and chemotherapeutic drug resistance. In this study, the impact of FOXM1 expression on patient outcome was investigated for the first time in formalin fixed and paraffin embedded (FFPE) samples of chemotherapy naïve muscle-invasive bladder cancer (MIBC) patients. Expression analyses were performed on the Mannheim cohort (n=84) and validated on the independent Chungbuk cohort (n=61). In a Cox' proportional hazards model, a distinct FOXM1 expression cut-off dividing both cohorts in a 'high-risk' and 'low-risk' group has been determined...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28495553/the-expanding-repertoire-of-targets-for-immune-checkpoint-inhibition-in-bladder-cancer-what-lies-beneath-the-tip-of-the-iceberg-pd-l1
#10
REVIEW
Alexander Sankin, Deepa Narasimhulu, Peter John, Benjamin Gartrell, Mark Schoenberg, Xingxing Zang
Over the last decade, a new understanding of tumor-immune system interplay has been ushered in, lead in large part by the discovery of immune checkpoints mediated through B7-CD28 family interactions. Therapeutic blockade of the PD-L1 immune checkpoint pathway has already shown great success as a cancer immunotherapy for advanced urothelial carcinoma, leading to durable clinical remissions in an otherwise incurable disease. There are newly described members of the B7-CD28 family including B7-H3, B7x, and HHLA2...
May 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28487862/naturally-occurring-canine-invasive-urinary-bladder-cancer-a-complementary-animal-model-to-improve-the-success-rate-in-human-clinical-trials-of-new-cancer-drugs
#11
REVIEW
Christopher M Fulkerson, Deepika Dhawan, Timothy L Ratliff, Noah M Hahn, Deborah W Knapp
Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/28472723/activity-of-phosphatase-sensitive-5-aminolevulinic-acid-prodrugs-in-cancer-cell-lines
#12
Viktorija Herceg, Norbert Lange, Eric Allémann, Andrej Babič
5-aminolevulinc acid (5-ALA)-based photodynamic therapy (PDT) and photodiagnosis (PD) present many advantages over treatments with conventional photosensitizers (PS). It offers great tumor specificity, reduced photosensitivity reactions caused by PS accumulation in non-targeted tissues and also inherent PS metabolism into endogenous non-fluorescent heme. However, chemical instability, low bioavailability and poor pharmacokinetic profile limit systemic efficacy of 5-ALA. Here, we present a comprehensive in vitro evaluation of novel phosphatase-sensitive prodrugs of 5-ALA...
April 26, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28472430/evaluation-of-secondary-dose-and-cancer-risk-for-out-of-field-organ-in-esophageal-cancer-imrt-in-a-chinese-hospital-using-atom-phantom-measurements
#13
Yaping Qi, Lijuan He, Zhi Wang, Yuanyuan Liu, Hongdong Liu, Wanli Huo, X George Xu, Zhi Chen
There have been few studies on the secondary cancer after radiation treatment in Chinese hospitals. This study has measured out-of-field absorbed organ doses from intensity-modulated radiation therapy (IMRT) radiotherapy for esophageal cancer in a Chinese hospital and evaluated the risks of secondary cancer. The dose measurements were based on the thermo-luminescence dosemeter (TLD) and the ATOM® phantom, which represents an adult male. Over 100 TLD chips were placed in 35 different organ sites and one group of the same TLDs was set as background contrast...
May 3, 2017: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/28469299/systemic-therapy-in-bladder-cancer
#14
REVIEW
Ian G Pinto
Systemic chemotherapy is essential for the management of muscle-invasive bladder cancer (MIBC) and metastatic bladder cancer (BCa). Neoadjuvant chemotherapy is key to the management of MIBC with many cisplatin-based regimens. Adjuvant chemotherapy may be considered for selected patients who did not receive neoadjuvant therapy. Systemic chemotherapy with radiotherapy is a critical component of a trimodal bladder-preserving approach and is superior to radiotherapy alone. Cisplatin-based chemotherapy has been the mainstay for metastatic BCa...
April 2017: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/28453558/tumor-targeted-sn38-inhibits-growth-of-early-stage-non-small-cell-lung-cancer-nsclc-in-a-kras-p53-transgenic-mouse-model
#15
Alexander Y Deneka, Leora Haber, Meghan C Kopp, Anna V Gaponova, Anna S Nikonova, Erica A Golemis
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities...
2017: PloS One
https://www.readbyqxmd.com/read/28447562/dosimetric-advantages-of-a-clinical-daily-adaptive-plan-selection-strategy-compared-with-a-non-adaptive-strategy-in-cervical-cancer-radiation-therapy
#16
Agustinus J A J van de Schoot, Peter de Boer, Jorrit Visser, Lukas J A Stalpers, Coen R N Rasch, Arjan Bel
BACKGROUND: Radiation therapy (RT) using a daily plan selection adaptive strategy can be applied to account for interfraction organ motion while limiting organ at risk dose. The aim of this study was to quantify the dosimetric consequences of daily plan selection compared with non-adaptive RT in cervical cancer. MATERIAL AND METHODS: Ten consecutive patients who received pelvic irradiation, planning CTs (full and empty bladder), weekly post-fraction CTs and pre-fraction CBCTs were included...
May 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28440434/preclinical-studies-for-the-combination-of-paclitaxel-and-curcumin-in-cancer-therapy-review
#17
Yumeng Wei, Xinlin Pu, Ling Zhao
Cancer is one of the most common causes of death and remains the first in China and the second in the US. The common treatments for cancer include surgery, radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy remains one of the most important treatments. However, the efficacy of chemotherapy is limited due to drug induced-toxicities and resistance, particularly multiple drug resistance (MDR). Therefore, discovery and development of novel therapeutic drugs and/or combination therapy are urgently needed to reduce toxicity and improve efficacy...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28428185/investments-in-cancer-research-awarded-to-uk-institutions-and-the-global-burden-of-cancer-2000-2013-a-systematic-analysis
#18
Mahiben Maruthappu, Michael G Head, Charlie D Zhou, Barnabas J Gilbert, Majd A El-Harasis, Rosalind Raine, Joseph R Fitchett, Rifat Atun
OBJECTIVES: To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000-2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs). DESIGN: Systematic analysis of all open-access data. SETTING AND PARTICIPANTS: Public and philanthropic funding to all UK cancer research institutions, 2000-2013...
April 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28427860/differential-mtor-pathway-profiles-in-bladder-cancer-cell-line-subtypes-to-predict-sensitivity-to-mtor-inhibition
#19
Andrew M Hau, Manando Nakasaki, Kazufumi Nakashima, Goutam Krish, Donna E Hansel
BACKGROUND: Molecular classification of bladder cancer has been increasingly proposed as a potential tool to predict clinical outcomes and responses to chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR) inhibition as a chemotherapeutic strategy and characterized the expression profile of mTOR signaling targets in representative bladder cancer cell lines from basal, luminal, and either basal/luminal ("non-type") molecular subtypes. MATERIALS AND METHODS: Protein and mRNA expression of mTOR signaling components from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype (T24 and J82) bladder cancer cell line subtypes were determined by Western blot and database mining analysis of the Cancer Cell Line Encyclopedia...
April 18, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28423681/sulforaphane-for-the-chemoprevention-of-bladder-cancer-molecular-mechanism-targeted-approach
#20
REVIEW
Andrew Leone, Gregory Diorio, Wade Sexton, Michael Schell, Mark Alexandrow, Jed W Fahey, Nagi B Kumar
The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa...
March 8, 2017: Oncotarget
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