共查询到20条相似文献,搜索用时 0 毫秒
1.
2.
Prognostic effects of TERT promoter mutations are enhanced by coexistence with BRAF or RAS mutations and strengthen the risk prediction by the ATA or TNM staging system in differentiated thyroid cancer patients
下载免费PDF全文
![点击此处可从《Cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hoonsung Choi MD Jae‐Kyung Won MD PhD Jae Hoon Moon MD PhD Sun Wook Cho MD PhD Kyu Eun Lee MD PhD Young Joo Park MD PhD Ka Hee Yi MD PhD Do Joon Park MD PhD Jeong‐Sun Seo MD PhD 《Cancer》2016,122(9):1370-1379
3.
Chong Li Song Wu Haifeng Wang Xingang Bi Zhao Yang Ying Du Luyun He Zhiming Cai Jiansong Wang Zusen Fan 《Oncotarget》2015,6(23):19542-19551
Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer. 相似文献
4.
5.
6.
The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism
下载免费PDF全文
![点击此处可从《International journal of cancer. Journal international du cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Joana Peixoto Telmo A. Catarino Nathalia Cristina Campanella Weder Menezes Aline Paixão Becker Gisele Caravina de Almeida Marcus M. Matsushita Carlos Clara Luciano Neder Marta Viana‐Pereira Mrinalini Honavar Lígia Castro José Manuel Lopes Bruno Carvalho Rui Manuel Vaz Valdemar Máximo Paula Soares Manuel Sobrinho‐Simões Rui Manuel Reis Jorge Lima 《International journal of cancer. Journal international du cancer》2016,139(2):414-423
Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinicopathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also showed that the poor prognosis conferred by TERTp mutations was restricted to GBM patients carrying the rs2853669 A allele and not in those carrying the G allele. In conclusion, the presence of TERTp mutations was associated with worse prognosis in GBM patients, although such association depended on the status of the rs2853669 SNP. The status of the rs2853669 SNP should be taken in consideration when assessing the prognostic value of TERTp mutations in GBM patients. TERTp mutations and the rs2853669 SNP can be used in the future as biomarkers of glioma prognosis. 相似文献
7.
Reza R. Serizawa Ulrik Ralfkiær Kenneth Steven Gitte W. Lam Sven Schmiedel Joachim Schüz Alastair B. Hansen Thomas Horn Per Guldberg 《International journal of cancer. Journal international du cancer》2011,129(1):78-87
The bladder cancer genome harbors numerous oncogenic mutations and aberrantly methylated gene promoters. The aim of our study was to generate a profile of these alterations and investigate their use as biomarkers in urine sediments for noninvasive detection of bladder cancer. We systematically screened FGFR3, PIK3CA, TP53, HRAS, NRAS and KRAS for mutations and quantitatively assessed the methylation status of APC, ARF, DBC1, INK4A, RARB, RASSF1A, SFRP1, SFRP2, SFRP4, SFRP5 and WIF1 in a prospective series of tumor biopsies (N = 105) and urine samples (N = 113) from 118 bladder tumor patients. We also analyzed urine samples from 33 patients with noncancerous urinary lesions. A total of 95 oncogenic mutations and 189 hypermethylation events were detected in the 105 tumor biopsies. The total panel of markers provided a sensitivity of 93%, whereas mutation and methylation markers alone provided sensitivities of 72% and 70%, respectively. In urine samples, the sensitivity was 70% for all markers, 50% for mutation markers and 52% for methylation markers. FGFR3 mutations occurred more frequently in tumors with no methylation events than in tumors with one or more methylation events (78% vs. 33%; p < 0.0001). FGFR3 mutation in combination with three methylation markers (APC, RASSF1A and SFRP2) provided a sensitivity of 90% in tumors and 62% in urine with 100% specificity. These results suggest an inverse correlation between FGFR3 mutations and hypermethylation events, which may be used to improve noninvasive, DNA‐based detection of bladder cancer. 相似文献
8.
Telomerase reverse transcriptase promoter alterations across cancer types as detected by next‐generation sequencing: A clinical and molecular analysis of 423 patients
下载免费PDF全文
![点击此处可从《Cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Maria Schwaederle PharmD Nithya Krishnamurthy Gregory A. Daniels MD PhD David E. Piccioni MD PhD Santosh Kesari MD PhD Paul T. Fanta MD Richard B. Schwab MD Sandip P. Patel MD Barbara A. Parker MD Razelle Kurzrock MD 《Cancer》2018,124(6):1288-1296
9.
CTCF mediates the TERT enhancer–promoter interactions in lung cancer cells: Identification of a novel enhancer region involved in the regulation of TERT gene
下载免费PDF全文
![点击此处可从《International journal of cancer. Journal international du cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Vegard Eldholm Aage Haugen Shanbeh Zienolddiny 《International journal of cancer. Journal international du cancer》2014,134(10):2305-2313
10.
Christoph F Weikert S Kempkensteffen C Krause H Schostak M Miller K Schrader M 《International journal of cancer. Journal international du cancer》2006,119(6):1396-1402
Epigenetic silencing of tumor suppressor genes by promoter hypermethylation has been shown for a variety of genes in bladder cancer. Various p53 target genes have been investigated, but only few demonstrated promoter hypermethylation when semiquantitative detection methods were applied. To address to the question whether promoter methylation of novel p53 effector genes is a common event in transitional cell carcinoma of the bladder, we selected the p53 target genes apoptotic protein-activating factor (APAF-1), Caspase 8 (CASP-8), death-associated protein kinase, (DAPK-1) and insulin-like growth-factor-binding protein-3 (IGFBP-3), performing quantitative methylation-specific real-time PCR. The individual level of methylation (normalized index of methylation) was correlated with clinicopathological features as well as the biological behavior of the superficial and muscleinvasive tumors. Tissue was obtained from 110 tumor patients and 20 patients without urological malignancy. The median follow-up of the tumor patients was 52 months. Hypermethylation of the promoter region in tumor specimens was common for APAF-1 (100%), DAPK-1 (74%) and IGFBP-3 (66%), but not for CASP-8 (3.6%). It was seen less frequently and with undetectable or low methylation levels in the normal urothelium group. The APAF-1 methylation levels significantly correlated with tumor stage and tumor grade. The APAF-1 and IGFBP-3 methylation levels were able to separate tumors with higher recurrence risk from low-risk tumors in nonmuscleinvasive and muscleinvasive tumors. In multivariate analysis, APAF-1 and IGFBP-3 methylation levels were independent prognostic markers for recurrence in superficial bladder tumors. This study provides new insights into the role of promoter methylation of selected p53 target genes. The extent of promoter methylation of specific genes offers additional prognostical information and is associated with the outcome in patients with nonmuscleinvasive and muscleinvasive bladder cancer. 相似文献
11.
12.
Francis Thomas MD Derek J. Rosario MD Naomi Rubin MD John R. Goepel MD Maysam F. Abbod MIEE PhD James W. F. Catto MD 《Cancer》2012,118(22):5525-5534
BACKGROUND:
The treatment of high‐risk nonmuscle‐invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single‐center series.METHODS:
The authors reviewed all patients with primary, high‐risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow‐up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log‐rank analysis (2‐sided; P < .05).RESULTS:
In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%‐18.3%) at a median of 17.2 months (interquartile range, 8.9‐35.8 months), including 26.5% (95% CI, 22.2%‐31.3%) of the 366 patients who had >5 years follow‐up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease‐specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%‐21.9%) at a median of 28 months (interquartile range, 15‐45 months), including 28.7% (95% CI, 24.5%‐33.3%) of those who had 5 years of follow‐up. Disease‐specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease‐specific mortality were associated with the receipt of bacillus Calmette‐Guerin (P > .6).CONCLUSIONS:
Within a program of conservative treatment, progression of high‐risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette‐Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease. Cancer 2012. © 2012 American Cancer Society. 相似文献13.
S H Vermeulen N Hanum A J Grotenhuis G Casta?o-Vinyals A G van der Heijden K K Aben I U Mysorekar L A Kiemeney 《British journal of cancer》2015,112(3):594-600
Background:
Controversy exists on whether urinary tract infection (UTI) is a risk factor for urinary bladder cancer (UBC). Here, the association is investigated using data from one of the largest bladder cancer case–control studies worldwide.Methods:
Information on (i) history and age at onset of regular cystitis (‘regular low-UTI'') and (ii) number and age at onset of UTI treated with antibiotics (‘UTI-ab'') from 1809 UBC patients and 4370 controls was analysed. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, education, smoking, and use of aspirin/ibuprofen were generated, for men and women separately.Results:
Regular low-UTI was associated with an increased UBC risk (men: OR (95% CI) 6.6 (4.2–11); women: 2.7 (2.0–3.5)), with stronger effects in muscle-invasive UBC. Statistically significant decreased risks (ORs ∼0.65) were observed for up to five UTI-ab, specifically in those who (had) smoked and experienced UTI-ab at a younger age. In women, UTI experienced after menopause was associated with a higher UBC risk, irrespective of the number of episodes.Conclusions:
Regular cystitis is positively associated with UBC risk. In contrast, a limited number of episodes of UTI treated with antibiotics is associated with decreased UBC risk, but not in never-smokers and postmenopausal women. 相似文献14.
Expression of tumor suppressive microRNA‐34a is associated with a reduced risk of bladder cancer recurrence
下载免费PDF全文
![点击此处可从《International journal of cancer. Journal international du cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Angeline S. Andrew Carmen J. Marsit Alan R. Schned John D. Seigne Karl T. Kelsey Jason H. Moore Laurent Perreard Margaret R. Karagas Lorenzo F. Sempere 《International journal of cancer. Journal international du cancer》2015,137(5):1158-1166
Bladder cancer is the fourth most common cancer among men in the United States and more than half of patients experience recurrences within 5 years after initial diagnosis. Additional clinically informative and actionable biomarkers of the recurrent bladder cancer phenotypes are needed to improve screening and molecular therapeutic approaches for recurrence prevention. MicroRNA‐34a (miR‐34a) is a short noncoding regulatory RNA with tumor suppressive attributes. We leveraged our unique, large, population‐based prognostic study of bladder cancer in New Hampshire, United States to evaluate miR‐34a expression levels in individual tumor cells to assess prognostic value. We collected detailed exposure and medical history data, as well as tumor tissue specimens from bladder patients and followed them long‐term for recurrence, progression and survival. Fluorescence‐based in situ hybridization assays were performed on urothelial carcinoma tissue specimens (n = 229). A larger proportion of the nonmuscle invasive tumors had high levels of miR‐34a within the carcinoma cells compared to those tumors that were muscle invasive. Patients with high miR‐34a levels in their baseline nonmuscle invasive tumors experienced lower risks of recurrence (adjusted hazard ratio 0.57, 95% confidence interval 0.34–0.93). Consistent with these observations, we demonstrated a functional tumor suppressive role for miR‐34a in cultured urothelial cells, including reduced matrigel invasion and growth in soft agar. Our results highlight the need for further clinical studies of miR‐34a as a guide for recurrence screening and as a possible candidate therapeutic target in the bladder. 相似文献
15.
16.
17.
18.
Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients 总被引:21,自引:0,他引:21
Chan MW Chan LW Tang NL Lo KW Tong JH Chan AW Cheung HY Wong WS Chan PS Lai FM To KF 《International journal of cancer. Journal international du cancer》2003,104(5):611-616
High frequency loss of 3p21.3 region where RASSF1A located was demonstrated in several tumors. We aimed to investigate the methylation status of RASSF1A and the frequency of LOH in 3p21.3 region in bladder cancer. Three bladder cancer cell lines, 40 cases of bladder TCC and 14 cases of paired voided urine samples were subjected to methylation analysis. By methylation specific PCR, complete methylation of promoter region of RASSF1A gene were detected in cell lines T24 and UMUC3. Demethylation treatment re-expressed RASSF1A in these 2 cell lines. Methylation of RASSF1A was also detected in 47.5% (19/40) of the TCC cases but not in 6 carcinoma in situ (CIS) or 6 normal urothelium samples. For LOH study, loss of 3p21.3 region was detected in 57.9% (11/19) of our cases. Interestingly, methylation of RASSF1A was found in 72.7% (8/11) of the cases with LOH but only in 12.5% (1/8) of the cases without LOH. Methylation of RASSF1A was detected in 50% (7/14) of voided urine samples, but not in normal control. It showed a higher sensitivity than conventional urine cytology in detecting cancer cells, especially for low grade cases. In conclusion, our results demonstrated a high frequency of RASSF1A methylation with frequent LOH in 3p21.3 region in bladder cancer. It suggested that it may be a potential tumor suppressor gene in this chromosomal region and can be silenced by promoter hypermethylation. Detection of aberrant gene methylation in routine voided urine was feasible and may provide a non-invasive and sensitive approach for cancer detection. 相似文献
19.
AbstractAlthough many treatment modalities and schedules for non-muscle-invasive bladder cancer (NMIBC) exist, all yet prove to have limitations. Therefore the search for new forms of therapy continues. One of these forms consists of combining intravesical chemotherapy, typically mitomycin C (MMC), with hyperthermia achieved by a microwave-applicator. We aimed to review the current status of intravesical radiofrequency (RF) induced chemohyperthermia (CHT) for NMIBC with regard to efficacy, adverse-events (AEs) and its future perspective. A search for RF-induced CHT in MEDLINE, Embase, Cochrane and ClinicalTrials.gov databases was performed. Relevant conference abstracts were searched for manually. If applicable, experts on the area were consulted. Papers were selected based on abstract and title. A table of newly published clinical trials since 2011 was constructed. No meta-analysis could be performed based on these new papers. Efficacy proved to be better for RF-induced CHT compared to both MMC alone and bacillus Calmette–Guérin (BCG) instillations, with the latter being based on just one abstract of a randomised controlled trial. The AE rate in CHT is higher compared to MMC instillation, but is similar compared to BCG, albeit different in the type of AE. In almost all studies no severe AEs are reported. Although heterogeneity in methodology exists, RF-induced CHT seems promising. However, alternative methods of applying hyperthermia are starting to present their first results, imposing as effective options too. Intravesical RF-induced CHT may become an alternative for BCG instillation, and possibly for cystectomy, although further level 1 evidence is required for both reliable and reproducible data on efficacy and adverse events. 相似文献
20.
Mónica Martínez-Fernández Marta Due?as Andrew Feber Cristina Segovia Ramón García-Escudero Carolina Rubio Fernando F. López-Calderón Claudio Díaz-García Felipe Villacampa José Duarte María J. Gómez-Rodriguez Daniel Castellano José L. Rodriguez-Peralto Federico de la Rosa Stephan Beck Jesús M. Paramio 《Oncotarget》2015,6(39):42258-42275