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Targeted therapies for bladder cancer

Patrícia Manuela Ribeiro Pereira, Sandrina Silva, Mafalda Bispo, Mónica da Rocha Zuzarte, Célia Gomes, Henrique Girão, José A S Cavaleiro, Carlos A Fontes Ribeiro, Joao P C Tome, Rosa Fernandes
Here we report the rational design of a new third-generation photosensitizer (PS), a chlorin conjugated with galactodendritic units, ChlGal8, to improve the effectiveness of bladder cancer treatment. ChlGal8 shows better photo-chemical and -physical properties than a recently reported homologous porphyrin, PorGal8. In addition to inheriting excellent photostability, ability to generate singlet oxygen and to interact with the proteins galectin-1 and human serum albumin (HSA), ChlGal8 exhibits high absorption in the red region of the electromagnetic spectrum...
October 17, 2016: Bioconjugate Chemistry
R J Cassidy, X Yang, T Liu, M Thomas, S G Nour, A B Jani
PURPOSE: Sexual dysfunction after radiotherapy for prostate cancer remains an important late adverse toxicity. The neurovascular bundles (NVB) that lie posterolaterally to the prostate are typically spared during prostatectomy, but in traditional radiotherapy planning they are not contoured as an organ-at-risk with dose constraints. Our goal was to determine the dosimetric feasibility of "NVB-sparing" prostate radiotherapy while still delivering adequate dose to the prostate. METHODS: Twenty-five consecutive patients with prostate cancer (with no extraprostatic disease on pelvic magnetic resonance imaging [MRI]) who that were treated with external beam radiotherapy, with the same primary planning target volume margins, to a dose of 79...
October 13, 2016: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
Rafael Morales-Barrera, Cristina Suárez, Ana Martínez de Castro, Fabricio Racca, Claudia Valverde, Xavier Maldonado, Juan Maria Bastaros, Juan Morote, Joan Carles
Bladder cancer is one of the leading causes of death in Europe and the United States. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients with median overall survival of 15months and a 5-year survival rate of ⩽10%...
October 1, 2016: Cancer Treatment Reviews
Suresh Rana, ChihYao Cheng, Li Zhao, SungYong Park, Gary Larson, Carlos Vargas, Megan Dunn, Yuanshui Zheng
INTRODUCTION: The purpose of this study was to evaluate the dosimetric and radiobiological impact of intensity modulated proton therapy (IMPT) and RapidArc planning for high-risk prostate cancer with seminal vesicles. METHODS: Ten high-risk prostate cancer cases were included in this retrospective study. For each case, IMPT plans were generated using multiple field optimisation (MFO) technique (two fields) with XiO treatment planning system (TPS), whereas RapidArc plans were generated using double-arc technique (two full arcs) with Eclipse TPS...
May 11, 2016: Journal of Medical Radiation Sciences
Patrícia M R Pereira, Sandrina Silva, José S Ramalho, Célia M Gomes, Henrique Girão, José A S Cavaleiro, Carlos A F Ribeiro, João P C Tomé, Rosa Fernandes
Conventional photodynamic agents used in clinic are porphyrin-based photosensitizers. However, they have low tumour selectivity, which may induce unwanted side-effects and damage to healthy tissues. In this study, we used a porphyrin with dendritic units of galactose (PorGal8) developed by us, which can target the galactose-binding protein, galectin-1, known to be overexpressed in many tumour tissues. In vitro and in vivo studies had been conducted for the validation of PorGal8 effectiveness. We showed a specific uptake of PorGal8 and induction of apoptotic cell death by generating oxidative stress and alterations in the cytoskeleton of bladder cancer cells overexpressing galectin-1...
October 5, 2016: European Journal of Cancer
Jen-Yu Cheng, Eng-Yen Huang, Shun-Neng Hsu, Chong-Jong Wang
OBJECTIVE: To compare the dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using the simultaneous integrated boost (SIB) technique to that of the traditional midline-block (MB) technique for boosting the parametrium in patients with cervical cancer. METHODS: Treatment plans using VMAT or IMRT with the SIB technique (VMAT-SIB and IMRT-SIB) and IMRT followed by the MB technique (IMRT-MB) were generated for each of 10 cervical cancer patients...
October 6, 2016: British Journal of Radiology
De Gui Wang, Mei-Jun Zhao, Yong-Qiang Liu, Xiang-Wen Liu, Hai-Tao Niu, Yan-Feng Song, Ying-Xia Tian
Adenovirus-mediated gene therapy is a promising strategy for bladder cancer treatment. However, the loss of the coxsackie and adenovirus receptor (CAR) in bladder cancer cells decreases the infection efficiency of the therapeutic adenovirus. In this study, we constructed an Arg-Gly-Asp (RGD)-modified adenovirus, RGDAd-UPII-TK, that carries a suicide gene called HSV-TK that is driven by a human UPII promoter. Then, we tested the bladder cancer specificity of the UPII promotor and the expression of the HSV-TK protein...
September 28, 2016: Oncotarget
J Huang, X Chen, T X Lin
Bladder cancer is one of the most common malignant tumors of the urinary system in China, but it is still difficult to be accurate in the diagnosis and treatment. The rapid development of high-throughput sequencing technology and data analysis of biological information pushes the medicine to enter into the precise times. In the review, the recent progress of molecular subtype, assessment of immune and metastatic status, efficacy prediction of chemotherapy, immunotherapy and targeted therapy are summarized. It provides new ideas and methods for accurate diagnosis and treatment of bladder cancer...
October 1, 2016: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
Sergiu Scobioala, Christopher Kittel, Nicolas Wissmann, Uwe Haverkamp, Mohammed Channaoui, Omar Habibeh, Khaled Elsayad, Hans Theodor Eich
BACKGROUND: Comparing radiation treatment plans to ascertain the optimal intensity-modulated radiation technique for low-risk prostate cancer. METHODS: Treatment plans for 20 randomly selected patients were generated using the same dose objectives. A dosimetric comparison was performed between various intensity-modulated techniques, including protons. All treatment plans provided conventional treatment with 79.2Gy. Dosimetric indices for the target volume and organs at risk (OAR), including homogeneity index and four conformity indices were analyzed...
September 27, 2016: Radiation Oncology
Philipp H Baldia, Angela Maurer, Timon Heide, Michael Rose, Robert Stoehr, Arndt Hartmann, Sarah V Williams, Margaret A Knowles, Ruth Knuechel, Nadine T Gaisa
Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis)...
September 22, 2016: Oncotarget
Francesco Soria, Marco Moschini, Andrea Haitel, Gregory J Wirth, Kilian M Gust, Alberto Briganti, Morgan Rouprêt, Tobias Klatte, Melanie R Hassler, Pierre I Karakiewicz, Shahrokh F Shariat
PURPOSE: The aim of this study was to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with bladder cancer (BCa) and to assess its association with oncological outcomes. METHODS: This retrospective single-center study included 354 patients with BCa treated with radical cystectomy (RC). HER2 status was assessed with immunohistochemistry and scored according to HercepTest. Conditional survival and competing risk regression were performed to assess the association between HER2 expression and survival outcomes...
September 21, 2016: Urologic Oncology
Sai-Qi Wang, Cong Wang, Li-Ming Chang, Kai-Rui Zhou, Jun-Wei Wang, Yu Ke, Dong-Xiao Yang, Hong-Ge Shi, Ran Wang, Xiao-Li Shi, Li-Ying Ma, Hong-Min Liu
Paclitaxel, a taxane, is a cytotoxic chemotherapeutic agent that targets microtubules. It has become a front-line therapy for a broad range of malignancies, including lung, breast, gastric, esophageal, and bladder carcinomas. Although paclitaxel can inhibit tumor development and improve survival, poor solubility, myelotoxicity, allergic reactions, and drug resistance have restricted its clinical application. Paclitaxel is frequently combined with other chemotherapeutics to enhance the antitumor effects and reduce side effects...
September 21, 2016: Oncotarget
Michał Biegała, Adam Hydzik
This study describes a comparative analysis of treatment plans in 48 patients with prostate cancer treated with ionizing radiation. Each patient was subjected to the intensity-modulated radiation therapy (IMRT) and arc technique. In each treatment plan, the organs at risk were assessed: the urinary bladder, rectum and heads of the femur, as well as the volume of normal tissue. The following features were compared: treatment time, conformity indices for the planning target volume, mean doses and standard deviation in organs at risk, and organ volumes for each particular dose...
July 2016: Journal of Medical Physics
Ashesh Jani, Eduard Schreibmann, Peter J Rossi, Joseph W Shelton, Karen Godette, Peter Nieh, Viraj A Master, Omer Kucuk, Mark Goodman, Raghuveer Halkar, Sherrie Cooper, Zhengjia Chen, David M Schuster
: The purpose was to evaluate the role of the synthetic amino acid positron emission tomography (PET) radiotracer fluciclovine ((18)F) in modifying the clinical and planning target volume (CTV and PTV) definition in post-prostatectomy patients undergoing salvage radiotherapy and to evaluate the resulting dosimetric consequences to surrounding organs at risk. METHODS: 96 patients were enrolled in a randomized prospective intention to treat clinical trial for potential salvage radiotherapy for recurrent prostate cancer after prostatectomy...
September 8, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Martina Becker-Schiebe, Ali Abaci, Tahera Ahmad, Wolfgang Hoffmann
AIM: To determine the influence of IGRT in terms of toxicities compared to non-IGRT patients undergoing definitive RT. BACKGROUND: Image-guided radiotherapy (IGRT) enables immediate correction of target movement by online imaging. For prostate cancer patients undergoing radiation therapy (RT), a geographical miss of the prostate may result in increased dose-volume effects in the rectum and bladder. METHODS: A total of 198 prostate cancer patients treated between 2003 and 2013 were recruited randomly for this evaluation...
May 2016: Reports of Practical Oncology and Radiotherapy
Sabrina T Heijkoop, Henrike Westerveld, Nina Bijker, Raphael Feije, Abdul W Sharfo, Niek van Wieringen, Jan Willem M Mens, Lukas J A Stalpers, Mischa S Hoogeman
PURPOSE/OBJECTIVE: It is unknown whether the historically found dosimetric advantages of treating gynecologic cancer with the patient in a prone position with use of a small-bowel displacement device (belly-board) remain when volumetric arc therapy (VMAT) is used and whether these advantages depend on the necessary margin between clinical target volume (CTV) and planning target volume (PTV). The aim of this study is to determine the best patient position (prone or supine) in terms of sparing organs at risk (OAR) for various CTV-to-PTV margins and VMAT dose delivery...
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Jingjing Pan, Xu Li, Wenjing Wu, Mei Xue, Huilian Hou, Wen Zhai, Wei Chen
Chemoresistance constitutes the major failing of clinical therapy for bladder cancer. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Long non-coding RNAs (lncRNAs) have been implicated in chemotherapeutic drug resistance. Urothelial Cancer Associated 1 (UCA1), an lncRNA, is reportedly upregulated in human bladder carcinoma and promotes cancer cell proliferation, migration, invasion, and drug resistance. In the present study, knockdown of UCA1 decreased chemosensitivity to cisplatin/gemcitabine by suppressing cell proliferation and inducing apoptosis, while overexpression of UCA1 increased chemosensitivity in bladder cancer cells...
August 31, 2016: Cancer Letters
Michael E Hurwitz, Joseph Sokhn, Daniel P Petrylak
PURPOSE OF REVIEW: Over the last 10 years, harnessing of the immune system to attack tumors has been one of the major breakthroughs in cancer, primarily through the use of immune checkpoint inhibitors (ICIs). This review will summarize current immune treatments in urologic malignancies and ongoing trials with novel combinations and in different disease settings. RECENT FINDINGS: Patients with urologic malignancies such as kidney and bladder cancer have benefited significantly from these advances with the approval of ICIs in both of these diseases...
November 2016: Current Opinion in Urology
Mathilde B H Thomsen, Iver Nordentoft, Philippe Lamy, Søren Høyer, Søren Vang, Jakob Hedegaard, Michael Borre, Jørgen B Jensen, Torben F Ørntoft, Lars Dyrskjøt
Patients with metastatic bladder cancer have a median survival of only 13-14 months. Precision medicine using targeted therapy may improve survival. Here we investigated spatial and temporal tumour evolution and tumour heterogeneity in order to evaluate the potential use of targeted treatment of metastatic bladder cancer. We performed a proof-of-concept study by whole exome sequencing of multiple tumour regions (n = 22) from three patients with metastatic bladder cancer. DNA from primary and metastatic tumour biopsies was analysed for mutations using Mutect and potential therapeutic targets were identified...
November 2016: Molecular Oncology
Xiang Zhuang, Mengxin Lv, Zhenyu Zhong, Luyu Zhang, Rong Jiang, Junxia Chen
BACKGROUND: Integrin-linked kinase (ILK) is a multifunctional adaptor protein which is involved with protein signalling within cells to modulate malignant (cancer) cell movement, cell cycle, metastasis and epithelial-mesenchymal transition (EMT). Our previous experiment demonstrated that ILK siRNA inhibited the growth and induced apoptosis of bladder cancer cells as well as increased the expression of Ribonuclease inhibitor (RI), an important cytoplasmic protein with many functions. We also reported that RI overexpression inhibited ILK and phosphorylation of AKT and GSK3β...
2016: Journal of Experimental & Clinical Cancer Research: CR
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