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Targeted therapies for bladder cancer

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https://www.readbyqxmd.com/read/29328475/heat-shock-protein-27-knockdown-using-nucleotide%C3%A2-based-therapies-enhances-sensitivity-to-5-fu-chemotherapy-in-sw480-human-colon-cancer-cells
#1
Takehiro Shimada, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Kohei Shigeta, Takashi Ishida, Yusuke Asada, Hirofumi Suzumura, Kaoru Koishikawa, Shingo Akimoto, Yuko Kitagawa
Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer...
January 3, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29325739/anti-programmed-cell-death-1-ligand-1-pd-1-pd-l1-antibodies-for-the-treatment-of-urothelial-carcinoma-state-of-the-art-and-future-development
#2
REVIEW
Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo
Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29321088/upregulation-of-long-non-coding-rna-tug1-promotes-bladder-cancer-cell-5-proliferation-migration-and-invasion-by-inhibiting-mir-29c
#3
Peng Guo, Guohui Zhang, Jialin Meng, Qian He, Zhihui Li, Yawei Guan
Bladder cancer (BC) is one of the leading causes of cancer-related death in the word. Long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) plays an important role in the development and progression of numerous cancers, including BC. However, the exact role of TUG1 in modulating BC progression is still poorly known. In this study, we found that TUG1 was upregulated and microRNA-29c (miR-29c) was downregulated in BC tissues and cell lines. Overexpression of TUG1 promoted the cell proliferation of T24 and EJ cells, whereas TUG1 knockdown had the opposite effect...
January 10, 2018: Oncology Research
https://www.readbyqxmd.com/read/29317342/imaging-guided-photo-therapeutic-nanoporphyrin-synergized-hsp90-inhibitor-in-patient-derived-xenograft-bladder-cancer-model
#4
Qilai Long, Tzu-Yin Lin, Yee Huang, Xiaocen Li, Ai-Hong Ma, Hongyong Zhang, Randy Carney, Susan Airhart, Kit S Lam, Chong-Xian Pan, Yuanpei Li
Photodynamic therapy is a promising and effective non-invasive therapeutic approach for the treatment of bladder cancers. Therapies targeting HSP90 have the advantage of tumor cell selectivity and have shown great preclinical efficacy. In this study, we evaluated a novel multifunctional nanoporphyrin platform loaded with an HSP90 inhibitor 17AAG (NP-AAG) for use as a multi-modality therapy against bladder cancer. NP-AAG was efficiently accumulated and retained at bladder cancer patient-derived xenograft (PDX) over 7 days...
January 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29304105/dosimetric-evaluation-of-magnetic-resonance-generated-synthetic-ct-for-radiation-treatment-of-rectal-cancer
#5
Hesheng Wang, Kevin Du, Juliet Qu, Hersh Chandarana, Indra J Das
PURPOSE: The purpose of this study was to assess the dosimetric equivalence of magnetic resonance (MR)-generated synthetic CT (synCT) and simulation CT for treatment planning in radiotherapy of rectal cancer. METHODS: This study was conducted on eleven patients who underwent whole-body PET/MR and PET/CT examination in a prospective IRB-approved study. For each patient synCT was generated from Dixon MR using a model-based method. Standard treatment planning directives were used to create a four-field box (4F), an oblique four-field (O4F) and a volumetric modulated arc therapy (VMAT) plan on synCT for treatment of rectal cancer...
2018: PloS One
https://www.readbyqxmd.com/read/29298735/mir-202-inhibits-cell-proliferation-migration-and-invasion-by-targeting-egfr-in-human-bladder-cancer
#6
Liqing Zhang, Jianjiang Xu, Gaodi Yang, Heng Li, Xiuxia Guo
Recent studies have demonstrated that miR-202 is associated with several types of cancer; however, the expression and function of miR-202 have not been investigated in bladder cancer. Here, we analyzed the expression of miR-202 in bladder cancer tissue and adjacent non-cancerous tissues. The effect of miR-202 on proliferation, migration and invasion was evaluated by in-vitro assays. The target gene of miR-202 was assessed by luciferase reporter assay. In this study, miR-202 was found to be significantly downregulated in bladder cancer cell lines and tissues, and was highly correlated with the T classification, N classification, grade, and recurrence...
January 3, 2018: Oncology Research
https://www.readbyqxmd.com/read/29280456/magnetic-resonance-image-guided-adaptive-brachytherapy-in-locally-advanced-cervical-cancer-an-experience-from-a-tertiary-cancer-center-in-a-low-and-middle-income-countries-setting
#7
Umesh Mahantshetty, Rahul Krishnatry, Vinod Hande, Swamidas Jamema, Yogesh Ghadi, Reena Engineer, Supriya Chopra, Lavanya Gurram, Deepak Deshpande, Shyamkishore Shrviastava
PURPOSE: To determine the clinical impact of magnetic resonance image guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC) (stages II and III) in a tertiary care cancer hospital in a low and middle income countries setting. METHODS AND MATERIALS: Ninety-four LACC patients enrolled in a prospective EMBRACE (An International Study on MRI-Guided Brachytherapy in Locally Advanced Cervical Cancer) protocol treated with external radiation therapy (45 Gy in 25 fractions) with or without weekly cisplatin, followed by magnetic resonance IGABT (4 fractions of 7 Gy), were analyzed in detail for dosimetric and clinical outcomes including late toxicities...
November 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29278205/photodynamic-therapy-in-melanoma-where-do-we-stand
#8
Ioana Baldea, Lorin Giurgiu, Ioana Diana Teacoe, Florin Catalin Olteanu, Simona Clichici, Gabriela Adriana Filip
Malignant melanoma is one of the most aggressive malignant tumors with unpredictable evolution. Photodynamic therapy has been successfully used as the first line or palliative therapy for the treatment of lung, esophageal, bladder, non melanoma skin and head and neck cancers. However, classical photodynamic therapy has shown some drawbacks that limit its clinical application in melanoma. The most important challenge is to overcome melanoma resistance, due to melanosomal trapping, presence of melanin, enhanced oxidative stress defense, defects in the apoptotic pathways, immune evasion, neoangiogenesis stimulation...
December 25, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29250197/antiangiogenic-therapies-in-urogenital-malignancies-fiction-or-fact
#9
REVIEW
Friederike Haidl, David Pfister, Axel Heidenreich, Isabel Heidegger
The use of antiangiogenic agents in cancer therapy has become an attractive target in oncological research. However, concerning the uro-oncological field, current guidelines only recommend the use of antiangiogenic agents in metastatic renal cell cancer. Yet in recent years, several approaches for sequential treatment with angiogenesis inhibitors in other urogenital malignancies apart from renal cell cancer are ongoing. Thus, the present review article aims to provide an overview about clinical studies with antiangiogenic agents in prostate-, bladder-, testicular-, as well as penile cancer patients...
2017: Memo
https://www.readbyqxmd.com/read/29245122/reduction-of-cancer-cell-viability-by-synergistic-combination-of-photodynamic-treatment-with-the-inhibition-of-the-id-protein-family
#10
Cornelia Roschger, Thomas Verwanger, Barbara Krammer, Chiara Cabrele
The inhibitor of DNA binding and cell differentiation (Id) proteins are dominant negative regulators of the helix-loop-helix transcription factor family and play a key role during development as well as in vascular disorders and cancer. In fact, impairing the Id-protein activity in cancer cells reduces cell growth and even chemoresistance. Recently, we have shown that a synthetic Id-protein ligand (1Y) consisting of a cyclic nonapeptide can reduce the viability of the two breast cancer cell lines MCF-7 and T47D and of the bladder cancer cells T24 to about 50% at concentrations ≥100μM...
December 5, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29223302/modeling-the-target-dose-fall-off-in-imrt-and-vmat-planning-techniques-for-cervical-sbrt
#11
A Brito Delgado, D Cohen, T Y Eng, D N Stanley, Z Shi, M Charlton, A N Gutiérrez
There has been growing interest in the use of stereotactic body radiotherapy (SBRT) technique for the treatment of cervical cancer. The purpose of this study was to characterize dose distributions as well as model the target dose fall-off for intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques using 6 and 10 MV photon beam energies. Fifteen (n = 15) patients with non-bulky cervical tumors were planned in Pinnacle3 with a Varian Novalis Tx (HD120 MLC) using 6 and 10 MV photons with the following techniques: (1) IMRT with 10 non-coplanar beams (2) dual, coplanar 358° VMAT arcs (4° spacing), and (3) triple, non-coplanar VMAT arcs...
December 6, 2017: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/29207634/treatment-plan-comparison-between-tri-co-60-magnetic-resonance-image-guided-radiation-therapy-and-volumetric-modulated-arc-therapy-for-prostate-cancer
#12
Jong Min Park, So-Yeon Park, Chang Heon Choi, Minsoo Chun, Jin Ho Kim, Jung-In Kim
To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) with magnetic-resonance image-guided radiation therapy compared with volumetric-modulated arc therapy (VMAT) for prostate cancer. Twenty patients with intermediate-risk prostate cancer, who received radical VMAT were selected. Additional tri-Co-60 IMRT plans were generated for each patient. Both primary and boost plans were generated with tri-Co-60 IMRT and VMAT techniques. The prescription doses of the primary and boost plans were 50...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207153/fgfr-inhibitor-bgj398-and-hdac-inhibitor-obp-801-synergistically-inhibit-cell-growth-and-induce-apoptosis-in-bladder-cancer-cells
#13
Toshiya Takamura, Mano Horinaka, Shusuke Yasuda, Seijiro Toriyama, Yuichi Aono, Yoshihiro Sowa, Tsuneharu Miki, Osamu Ukimura, Toshiyuki Sakai
In advanced bladder cancer, cisplatin-based chemotherapy has been the standard treatment for many years, but there are many problems in terms of side-effects. Recently, a number of clinical trials using molecular-targeted agents have been conducted, and new therapies are expected that could replace conventional cytotoxic chemotherapy. We herein report that concurrent treatment with fibroblast growth factor receptor (FGFR) inhibitor BGJ398 and the novel histone deacetylase (HDAC) inhibitor OBP-801/YM753/spiruchostatin A synergistically inhibited cell growth and markedly induced apoptosis in high-grade bladder cancer cells...
December 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29199023/the-current-status-and-future-role-of-the-phosphoinositide-3-kinase-akt-signaling-pathway-in-urothelial-cancer-an-old-pathway-in-the-new-immunotherapy-era
#14
REVIEW
Sandy T Liu, Gavin Hui, Colleen Mathis, Karim Chamie, Allan J Pantuck, Alexandra Drakaki
The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a well studied signaling pathway that regulates diverse cellular functions including proliferation, metabolism, and transcription. Aberrant activation of this pathway has been implicated in multiple cancers. Genomic studies have shown that activating mutations in oncogenes as well as inactivating mutations in tumor suppressor genes are present across a variety of malignancies, including urothelial carcinoma...
November 3, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29194007/product-review-on-the-anti-pd-l1-antibody-atezolizumab
#15
Neil J Shah, William J Kelly, Stephen V Liu, Karin Choquette, Alexander Spira
Immunotherapy as a therapeutic strategy has seized the narrative throughout clinical oncology over the past few years. Once considered a niche treatment for rare cancers, immunotherapy has quickly emerged as the standard of care for many common cancer types. The remarkable rise is largely due to the development of novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1. Offering promising efficacy with a favorable toxicity profile, these agents have been approved for use in several malignancies and are under investigation for many more...
December 1, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29179475/genetic-variants-in-the-inflammation-pathway-as-predictors-of-recurrence-and-progression-in-non-muscle-invasive-bladder-cancer-treated-with-bacillus-calmette-gu%C3%A3-rin
#16
Stephen B Williams, Ashish M Kamat, Chinedu Mmeje, Yuanquing Ye, Maosheng Huang, David W Chang, Colin P Dinney, Xifeng Wu
Inflammation plays a critical role in the etiology of several cancers and may affect their clinical outcome. Our objective was to assess the association of genetic variants within the inflammation pathway with recurrence and progression among non-muscle invasive bladder cancer (NMIBC) patients with or without Bacillus Calmette-Guérin (BCG) treatment. We genotyped 372 single nucleotide polymorphisms (SNPs) in 27 selected genes within the inflammation pathway in 349 patients diagnosed with NMIBC, followed by internal validation in 322 additional patients...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29160225/phosphatidylserine-targeted-single-walled-carbon-nanotubes-for-photothermal-ablation-of-bladder-cancer
#17
Needa A Virani, Carole Davis, Patrick McKernan, Paul Hauser, Robert E Hurst, Joel Slaton, Ricardo P Silvy, Daniel E Resasco, Roger G Harrison
Bladder cancer has a 60-70% recurrence rate most likely due to residual tumour left behind after a transurethral resection (TUR). Failure to completely resect the cancer can lead to recurrence and progression into higher grade tumours with metastatic potential. We present here a novel therapy to treat superficial tumours with the potential to decrease recurrence. The therapy is a heat-based approach in which bladder tumour specific single-walled carbon nanotubes (SWCNTs) are delivered intravesically at a very low dose (0...
November 21, 2017: Nanotechnology
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#18
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29154981/egfr-family-inhibition-identifies-p38-mapk-as-a-potential-therapeutic-target-in-bladder-cancer
#19
Regina Mora Vidal, Sergio Regufe da Mota, Annette Hayden, Hannah Markham, James Douglas, Graham Packham, Simon J Crabb
Objective To investigate perturbations in downstream signalling pathway activation and potential resistance mechanisms to EGFR and/or HER2 inhibition in cell line models of bladder cancer. Methods We undertook a structured screening approach by phosphokinase array, followed by validation steps, to detect activated downstream signalling pathway nodes after therapeutic inhibition of EGFR and/or HER2 in bladder cancer cell lines. Results Erlotinib treatment of RT112 cells induced phosphorylation of 9 activated phospho-protein targets (p38 MAPK (Thr180/Tyr182), GSK-3α/β (Ser21/9), MEK1/2 (Ser218/222, Ser222/226), Akt (Ser473), TOR (Ser2448), Src (Tyr419), p27 (Thr198), p27 (Thr157) and PLCγ-1 (Tyr783)) whereas STAT4 (Tyr693) phosphorylation was reduced...
November 15, 2017: Urology
https://www.readbyqxmd.com/read/29147616/mrna-expression-levels-of-genes-involved-in-antitumor-immunity-identification-of-a-3-gene-signature-associated-with-prognosis-of-muscle-invasive-bladder-cancer
#20
Constance Le Goux, Sophie Vacher, Géraldine Pignot, Mathilde Sibony, Nicolas Barry Delongchamps, Benoit Terris, Eliane Piaggio, Marc Zerbib, Diane Damotte, Ivan Bieche
Immunotherapy for bladder cancer has given promising results. Here we aimed to evaluate the possible involvement and prognostic value of 33 genes involved in the immune response during bladder carcinogenesis. Expression levels were assessed by quantitative real-time RT-PCR in normal and tumor human bladder samples. Immunohistochemistry was performed to evaluate the protein expression of 2 genes and relation of the mRNA and protein levels was analyzed. Tumors were obtained from 154 patients (83 with muscle-invasive bladder cancer [MIBC] and 71 non-MIBC [NMIBC]) who underwent transurethral bladder resection or radical cystectomy between 2002 and 2006...
2017: Oncoimmunology
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