Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While there are a growing number of cancer survivors, this population is at increased risk of developing second primary malignancies (SPMs). We described the incidence, most common tumor sites, and trends in burden of SPM among survivors of the most commonly diagnosed smoking-related cancers. The current study was a population-based study of patients diagnosed with a primary malignancy from the top 10 smoking-related cancer sites between 2000 and 2014 from Surveillance, Epidemiology, and End Results data. SPM risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). Trends in the burden of SPM were assessed using Joinpoint regression models. A cohort of 1,608,607 patients was identified, 119,980 (7.5%) of whom developed SPM (76% of the SPMs were smoking-related). The overall SIR of developing second primary malignancies was 1.51 (95% CI, 1.50-1.52) and the EAR was 73.3 cases per 10,000 PYR compared to the general population. Survivors of head and neck cancer had the highest risk of developing a SPM (SIR = 2.06) and urinary bladder cancer had the highest excess burden (EAR = 151.4 per 10,000 PYR). The excess burden of SPM for all smoking-related cancers decreased between 2000 and 2003 (annual percentage change [APC] = -13.7%; p = 0.007) but increased slightly between 2003 and 2014 (APC = 1.6%, p = 0.032). We show that 1-in-12 survivors of smoking-related cancers developed an SPM. With the significant increase in the burden of SPM from smoking-related cancers in the last decade, clinicians should be cognizant of long-term smoking-related cancer risks among these patients as part of their survivorship care plans.
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PMID:Trends in the risk and burden of second primary malignancy among survivors of smoking-related cancers in the United States. 3061 63

The clinical role of APC promoter methylation in patients with bladder cancer remains to be determined. The relevant databases (PubMed, EMBASE, EBSCO, Wangfang, CNKI and Cochrane Library) were searched to get eligible studies. The overall odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs) were calculated to assess the effects of APC promoter methylation on bladder cancer risk and clinicopathological features. 2214 patients with bladder cancer and 665 controls were identified. APC promoter methylation was significantly higher in bladder cancer than in nonmalignant tissue and urine samples (tissue: OR = 11.14, 95% CI = 4.29-28.91, P < 0.001; urine: OR = 24.31, 95% CI = 6.26-94.38, P < 0.001), but not in blood samples (P = 0.242). The relationship was observed between APC promoter methylation and gender (male vs. female: OR = 1.46, 95% CI = 0.96-2.22, P = 0.074), tumor stage (stage T2-T4 vs. Ta-T1: OR = 3.00, 95% CI = 1.66-5.42, P < 0.001), and tumor grade (grade 3-4 vs. grade 1-2: OR = 1.99, 95% CI = 1.15-3.42, P = 0.013). But no correlation was found between APC promoter methylation and age, lymph node status, and tumor number (P > 0.1). APC gene was not associated with overall survival of bladder cancer. Our findings indicate that APC promoter methylation may be associated with the development and progression of bladder cancer and may serve as a promising noninvasive biomarker using urine samples for the detection of bladder cancer.
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PMID:APC promoter methylation is correlated with development and progression of bladder cancer, but not linked to overall survival: a meta-analysis. 3086 94

Accumulating evidence suggest that microRNAs play crucial roles in the development and progression of bladder cancer (BC). Here, we found that miR-212-3p was significantly down-regulated and negatively correlated with nuclear factor IA (NFIA) in human BC tissues. Bioinformatics analysis predicted that NFIA was a target gene of miR-212-3p. Then BC cell lines, T24 and J82 cells were transfected with miR-212-3p mimics or siNFIA to obtain miR-212-3p overexpression or NFIA knockdown cell lines, respectively. Quantitative real-time PCR was used to determine the expression of miR-212-3p and NFIA. Western blot analysis was utilized to detect NFIA expression. MTT assay showed either miR-212-3 overexpression or NFIA knockdown significantly inhibited the BC cell proliferation. Double staining with Annexin V-APC and 7-AAD showed the total number of apoptotic BC cells were remarkably increased after miR-212-3p overexpression or NFIA knockdown. Collectively, our results indicated that miR-212-3p targeting NFIA might serve as a promising target for BC.
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PMID:MiR-212-3p inhibits cell proliferation and promotes apoptosis by targeting nuclear factor IA in bladder cancer. 3150 58

Avoiding immune destruction is essential for tumorigenesis. Current research into the interaction between tumor and immunological niches complement tumor pathology beyond cancer genetics. Intrinsic host defense immunity is a specialized innate immunity component to restrict viral infection. However, whether intrinsic immunity participates in tumor pathology is unclear. Previously, we identified a zinc-finger antiviral protein ZAP that is commonly downregulated in a panel of clinical cancer specimens. However, whether ZAP has an impact on tumor development was unknown. Here we report ZAP as a genuine tumor suppressor. Pan-caner analysis with TCGA data from 712 patients and large-scale immunohistochemistry in tissue microarrays from 1552 patients reveal that ZAP is prevalently downregulated, and associated with poor survival in liver, colon, and bladder cancer patients. Ectopic over-expression of ZAP inhibits the malignant phenotypes of colorectal tumor by cell cycle arrest. Using RNA immunoprecipitation and RNA decay assays, we demonstrate that ZAP directly and specifically binds to and degrades the transcript of TRAILR4, which in turn represses TRAILR4 expression and inhibits the aggressiveness of colorectal cancer cells. Furthermore, our CRISPR-engineered mice models show that loss-of-function of ZAP synergizes with APC-deficiency to drive malignant colorectal cancer in vivo. Overall, we identify a previously unknown function of the antiviral factor ZAP in colorectal tumorigenesis, linking intrinsic immunity to tumor pathogenetics.
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PMID:Zinc-finger antiviral protein acts as a tumor suppressor in colorectal cancer. 3277 Jan 42

A 41-yr-old, otherwise healthy, premenopausal woman presented at our uro-oncology clinic with a diagnosis of muscle-invasive bladder cancer following a transurethral resection of the bladder performed at another center. After a thorough discussion with the patient, she was enrolled in the phase II PURE-01 trial (NCT02736266), testing three cycles of neoadjuvant pembrolizumab (200mg) every 3 wk before radical cystectomy. Before treatment, imaging studies were obtained as per the protocol using computed tomography (CT), [18F]fluorodeoxyglucose positron emission tomography/CT, and multiparametric magnetic resonance imaging of the bladder, defining a clinically localized T2N0M0 stage. As per the protocol, potential biomarkers were assessed, including PD-L1 expression (84% combined positive score), tumor mutational burden (16.67 mut/Mb), and genomic profiling (FoundationONE assay; somatic mutation in TP53, EZH2, APC, TERT, CDKN1A, CDKN1B, and ARID1A genes, and truncation in BRCA2 gene). After immunotherapy, the patient underwent a robot-assisted radical cystectomy with extended pelvic lymph node dissection. The final pathology report revealed absence of residual disease (ie, pathological complete response, ypT0ypN0). During follow-up, the only relevant and permanent immune-mediated adverse event was hypothyroidism secondary to an autoimmune thyroiditis. It appeared 2 mo after radical cystectomy and it was managed successfully with hormonal replacement therapy. Two years after treatment, the patient is asymptomatic and free from disease recurrence. PATIENT SUMMARY: Increasing evidence suggests that frontline neoadjuvant immunotherapy may be beneficial for patients diagnosed with non-locally advanced, muscle-invasive bladder cancer (cT2N0), with fewer drawbacks than traditional chemotherapy. Although further studies are needed in support, this vision opens the opportunity for future clinical trials testing the potential incremental benefits of immunotherapy and the utility of novel biomarker- and imaging-based strategies to assess response to therapy.
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PMID:Neoadjuvant Chemotherapy or Immunotherapy for Clinical T2N0 Muscle-invasive Bladder Cancer: Time to Change the Paradigm? 3284 46


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