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Targeted therapies for bladder cancer

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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
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28414557/polydopamine-and-peptide-decorated-doxorubicin-loaded-mesoporous-silica-nanoparticles-as-a-targeted-drug-delivery-system-for-bladder-cancer-therapy
#6
Yi Wei, Li Gao, Lu Wang, Lin Shi, Erdong Wei, Baotong Zhou, Li Zhou, Bo Ge
We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28408175/an-oncofetal-glycosaminoglycan-modification-provides-therapeutic-access-to-cisplatin-resistant-bladder-cancer
#7
Roland Seiler, Htoo Zarni Oo, Davide Tortora, Thomas M Clausen, Chris K Wang, Gunjan Kumar, Marina Ayres Pereira, Maj S Ørum-Madsen, Mette Ø Agerbæk, Tobias Gustavsson, Mie A Nordmaj, Jamie R Rich, Nada Lallous, Ladan Fazli, Sherry S Lee, James Douglas, Tilman Todenhöfer, Shaghayegh Esfandnia, Dulguun Battsogt, John S Babcook, Nader Al-Nakouzi, Simon J Crabb, Igor Moskalev, Bernhard Kiss, Elai Davicioni, George N Thalmann, Paul S Rennie, Peter C Black, Ali Salanti, Mads Daugaard
BACKGROUND: Although cisplatin-based neoadjuvant chemotherapy (NAC) improves survival of unselected patients with muscle-invasive bladder cancer (MIBC), only a minority responds to therapy and chemoresistance remains a major challenge in this disease setting. OBJECTIVE: To investigate the clinical significance of oncofetal chondroitin sulfate (ofCS) glycosaminoglycan chains in cisplatin-resistant MIBC and to evaluate these as targets for second-line therapy. DESIGN, SETTING, AND PARTICIPANTS: An ofCS-binding recombinant VAR2CSA protein derived from the malaria parasite Plasmodium falciparum (rVAR2) was used as an in situ, in vitro, and in vivo ofCS-targeting reagent in cisplatin-resistant MIBC...
April 10, 2017: European Urology
https://www.readbyqxmd.com/read/28396613/expression-of-human-epidermal-growth-factor-receptor-2-in-bladder-urothelial-carcinoma
#8
Mohamed Reda El Ochi, Mohamed Oukabli, Elarbi Bouaiti, Hafsa Chahdi, Adil Boudhas, Mohamed Allaoui, Ahmed Ameur, Mohamed Abbar, Abderrahmane Al Bouzidi
BACKGROUND: Urothelial bladder carcinoma (UBC) is one of the most prevalent cancers in men worldwide. Human epidermal growth factor receptor 2 (HER2) expression has been detected in a wide range of urothelial carcinoma. Despite many reports in the literature, the prognostic significance of this overexpression remains unclear. The aim of this study was to assess the expression of HER2 in urothelial bladder carcinomas and its association with clinical and pathological parameters. METHODS: 103 cases of UBC were diagnosed in our department between January 2014 and December 2015...
2017: BMC Clinical Pathology
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#9
REVIEW
Lydia Dyck, Kingston H G Mills
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen-presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T-cell exhaustion...
April 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28377094/t-cell-target-antigens-across-major-gynecologic-cancers
#10
REVIEW
Alba Rodriguez-Garcia, Nicholas G Minutolo, John M Robinson, Daniel J Powell
Immunotherapies have achieved remarkable success in treating different forms of cancer including melanoma, non-small cell lung carcinoma, bladder cancer, synovial cell sarcoma, and multiple myeloma using immune checkpoint blockade or gene-engineered T-cells. Although gynecologic cancers have not been historically classified as immunogenic tumors, growing evidence has shown that they are in fact able to elicit endogenous antitumor immune responses suggesting that patients with these cancers may benefit from immunotherapy...
April 2, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28366271/targeted-therapies-in-the-treatment-of-urothelial-cancers
#11
REVIEW
Jeanny B Aragon-Ching, Donald L Trump
Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later...
March 30, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28355688/-a-randomized-study-of-intensity-modulated-radiation-therapy-versus-three-dimensional-conformal-radiation-therapy-for-pelvic-radiation-in-patients-of-post-operative-treatment-with-gynecologic-malignant-tumor
#12
J Ni, Z M Yin, S H Yuan, N F Liu, L Li, X X Xu, H M Lou
Objective: To study the difference between intensity-modulated radiation therapy (IMRT) and three dimensional conformal radiation therapy (3D-CRT) for pelvic radiation of post-operative treatment with gynecologic malignant tumor. Methods: A prospective investigation study was conducted on 183 patients of post-operative patients with whole pelvic radiation therapy of cervical cancer or endometrial cancer in Zhejiang Cancer Hospital [IMRT group (n=85) and 3D-CRT group (n=98)] from Oct. 2015 to Oct. 2016. The two groups received same dose (45 Gy in 25 fractions)...
March 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/28349190/-when-should-the-primary-tumor-of-metastatic-bladder-or-prostate-cancer-be-treated-using-a-nonsurgical-regimen
#13
D Bottke, C Bolenz, S Ott, A Cebulla, T Wiegel
BACKGROUND: Patients with metastatic and locally advanced bladder or prostate cancer may suffer from pelvic symptoms such as pain, obstruction, and hemorrhage. Local tumor growth is associated with significant morbidity and systemic therapy is often ineffective. Local therapies such as bladder irrigation, transurethral resection of the prostate, and fulguration of bleeding vessels provide relief but often require repeated treatments. OBJECTIVES: The aim of this work was to review the current status of palliative pelvic radiotherapy for metastatic bladder and prostate cancer...
March 27, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28348108/comprehensive-somatic-genome-alterations-of-urachal-carcinoma
#14
Seungchul Lee, Jingu Lee, Sung Hoon Sim, Yeonghun Lee, Kyung Chul Moon, Cheol Lee, Woong-Yang Park, Nayoung Kd Kim, Se-Hoon Lee, Hyunju Lee
BACKGROUND: Urachal cancer is a rare cancer that develops in the urachus. Because of its rarity, standard treatment therapies for urachal cancer are not established, and chemotherapeutic regimens for bladder cancer have been unsuccessful for patients with urachal cancer. Hence, we aim to understand a systematic molecular characterisation of urachal cancer. METHODS: We identified somatic single-nucleotide variations (SNVs)/indels and somatic copy number aberrations (SCNAs) in the 17 patients by using whole-exome sequencing (WES) and OncoScan platform (Affymetrix) as follows: tumour-normal paired sequencing (WES, n=10), tumour-only sequencing (WES, n=1; targeted deep sequencing, n=16), and OncoScan (n=17)...
March 27, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28346378/dna-repair-pathway-alterations-in-bladder-cancer
#15
REVIEW
Kent W Mouw
Most bladder tumors have complex genomes characterized by a high mutation burden as well as frequent copy number alterations and chromosomal rearrangements. Alterations in DNA repair pathways-including the double-strand break (DSB) and nucleotide excision repair (NER) pathways-are present in bladder tumors and may contribute to genomic instability and drive the tumor phenotype. DNA damaging such as cisplatin, mitomycin C, and radiation are commonly used in the treatment of muscle-invasive or metastatic bladder cancer, and several recent studies have linked specific DNA repair pathway defects with sensitivity to DNA damaging-based therapy...
March 27, 2017: Cancers
https://www.readbyqxmd.com/read/28339109/validation-of-dynamic-treatment-couch-tracking-for-prostate-sbrt
#16
Stefanie Ehrbar, Simon Schmid, Alexander Jöhl, Stephan Klöck, Matthias Guckenberger, Oliver Riesterer, Stephanie Tanadini-Lang
PURPOSE: In stereotactic body radiation therapy (SBRT) of prostatic cancer, a high dose per fraction is applied to the target with steep dose gradients. Intrafractional prostate motion can occur unpredictably during the treatment and lead to target miss. This work investigated the dosimetric benefit of motion compensation with dynamic treatment-couch tracking for prostate SBRT treatments in the presence of prostatic motion. METHODS: Ten SBRT treatment plans for prostate cancer patients with integrated boosts to their index lesion were prepared...
March 24, 2017: Medical Physics
https://www.readbyqxmd.com/read/28306559/immunotherapy-a-new-treatment-paradigm-in-bladder-cancer
#17
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
#18
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
#19
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
#20
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
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