CAD/POLD2 gene expression is associated with poor overall survival and chemoresistance in bladder urothelial carcinoma.

CAD/POLD2 gene expression is associated with poor overall survival and chemoresistance in bladder urothelial carcinoma. Oncotarget. 2018 Jul 03;9(51):29743-29752 Authors: Givechian KB, Garner C, Garban H, Rabizadeh S, Soon-Shiong P Abstract Somatic mutations in DNA repair genes have been clinically associated with chemosensitivity, although few studies have interrogated the nucleotide synthesis pathways that supply DNA repair processes. Previous work suggests that bladder urothelial carcinoma is uniquely enriched for mutations in nucleotide excision repair genes, and that these mutations are associated with response to platinum-based therapy and favorable survival. Conversely, the de novo pyrimidine synthesis pathway has recently emerged as a putative clinical target. This anabolic process is thought to supply DNA repair processes such as nucleotide excision repair; that is, DNA repair enzymes may require a sufficient nucleotide supply available to reverse the intended genotoxic damage of systemic chemotherapy in rapidly proliferating cancer cells. Therefore, we explored the prognostic complementarity between de novo pyrimidine synthesis and nucleotide excision repair expression in a total of 570 bladder urothelial carcinoma patients. Ultimately, we show that the de novo pyrimidine synthesis gene CAD is associated with poor survival (P = 0.008) and is co-altered with the nucleotide excision repair gene POLD2. High expression of POLD2 was also associated w...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Joe Abdo1, Christopher S. Wichman2, Nicholas E. Dietz1,3, Pawel Ciborowski4, John Fleegel1, Sumeet K. Mittal1,5 and Devendra K. Agrawal1* 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States 2Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States 3Department of Pathology, CHI Health Creighton University Medical Center, College of Medicine, Omaha, NE, United States 4Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE, United States 5Norton Thoracic Institute, St....
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
We report that the disruption of excitation-contraction coupling contributes to impaired force generation in the mouse model of Sod1 deficiency. Briefly, we found a significant reduction in sarcoplasmic reticulum Ca2+ ATPase (SERCA) activity as well as reduced expression of proteins involved in calcium release and force generation. Another potential factor involved in EC uncoupling in Sod1-/- mice is oxidative damage to proteins involved in the contractile response. In summary, this study provides strong support for the coupling between increased oxidative stress and disruption of cellular excitation contraction mac...
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Opinion statementMuscle-invasive bladder cancer (MIBC) has high metastatic potential at diagnosis but is still often curable with aggressive management, which may give patients the best odds for a favorable clinical outcome. The standard-of-care management of MIBC includes a radical cystectomy and pelvic lymph node dissection. If the patient is cisplatin-eligible, neoadjuvant cisplatin-based combination chemotherapy should also be given. Post-surgery adjuvant treatments include observation, chemotherapy, radiation, or enrollment in a clinical trial. Several adjuvant immunotherapy trials with checkpoint inhibitors, which bl...
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Survivin plays an important part in apoptosis pathways by inhibition of several caspases. Survivin is expressed in carcinoma cells, but not in normal tissue. ERCC-1 is a protein, which plays an important role in the nucleotide excision repair pathway. We hypothesized that the degree of immunohistochemical expression of these markers might be associated with overall survival.
Source: Urologic Oncology: Seminars and Original Investigations - Category: Urology & Nephrology Authors: Source Type: research
In conclusion, independently of the TP53 mutation status and tumor grade, CIS/GEN induced gene modulation accompanied by changes in cell morphologies, which confirm the antiproliferative activity of the treatment protocol. These findings help to understand the pathways modulated by these antineoplastic agents and may provide insights for anti-cancer chemotherapy. PMID: 28577130 [PubMed - as supplied by publisher]
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Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
Immune checkpoint modulators, such as antibodies targeting CTLA-4 or PD-1, are now being approved for treatment of patients with unresectable or metastatic melanoma and advanced squamous non-small cell lung cancer (NSCLC) who have progressed on or after platinum-based chemotherapy. Efficacy was also evidenced on other tumor types (renal cell carcinoma, bladder, Hodgkin lymphoma, colorectal carcinoma (CRC) ···). However, there is still needs to identify predictive biomarkers of response in order to select patients who will benefit from treatments. PD-L1 expression was proposed to be a good candidate for...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Immune Checkpoints: Poster Presentations - Proffered Abstracts Source Type: research
We present an 81-year-old man with stage 3 chronic obstructive pulmonary disease and a history of aortic aneurysm repair. The computed tomography scans indicated thickening and irregularity of the bladder wall, with left external iliac lymph node metastasis. His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0. Transurethral resection of the bladder tumor was performed, and the pathological specimen showed that the tumor was composed of undifferentiated malignant cells with sheets and nests arranged in a syncytial pattern, as well as an urothelial carcinoma lesion. A prominent lymphoid reaction ...
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