Expressão diferencial de microRNAs no câncer de próstata

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Grupos de apoio para homens com câncer de próstata: revisão integrativa da literatura

This article is an integrative literature review to analyze the contribution of national and international studies examining the use of psychological support groups as a care strategy for patients diagnosed with prostate cancer. The electronic databases consulted were: LILACS, MedLine and PsycINFO, over a period of 20 years (1989-2009) with pre-defined criteria for inclusion. Eleven studies were selected, and based on their contributions some considerations are presented regarding the factors that favor male participation in the support groups and the potential benefits of such participation; as well as their main concerns and the influence of gender identity in the process of coping with illness. Furthermore, studies suggest some models of group intervention, along with orientation for the coordinators which emphasize the importance of these groups as an effective strategy to aid in the process of coping of prostate cancer patients.

A spatial-temporal approach to surveillance of prostate cancer disparities in population subgroups

BACKGROUND: Prostate cancer mortality disparities exist among racial/ethnic groups in the United States, yet few studies have explored the spatiotemporal trend of the disease burden. To better understand mortality disparities by geographic regions over time, the present study analyzed the geographic variations of prostate cancer mortality by three Texas racial/ethnic groups over a 22-year period. METHODS: The Spatial Scan Statistic developed by Kulldorff et al was used. Excess mortality was detected using scan windows of 50% and 90% of the study period and a spatial cluster size of 50% of the population at risk. Time trend was analyzed to examine the potential temporal effects of clustering. Spatial queries were used to identify regions with multiple racial/ethnic groups having excess mortality. RESULTS: The most likely area of excess mortality for blacks occurred in Dallas-Metroplex and upper east Texas areas between 1990 and 1999; for Hispanics, in central Texas between 1992 and 1996: and for non-Hispanic whites, in the upper south and west to central Texas areas between 1990 and 1996. Excess mortality persisted among all racial/ethnic groups in the identified counties. The second scan revealed that three counties in west Texas presented an excess mortality for Hispanics from 1980-2001. Many counties bore an excess mortality burden for multiple groups. There is no time trend decline in prostate cancer mortality for blacks and non-Hispanic whites in Texas. CONCLUSION: Disparities in prostate cancer mortality among racial/ethnic groups existed in Texas. Central Texas counties with excess mortality in multiple subgroups warrant further investigation.

Is a 3-mm intrafractional margin sufficient for daily image-guided intensity-modulated radiation therapy of prostate cancer?

PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction. MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage was assessed on the post-treatment CT image set. RESULTS: During one treatment fraction (21.4+/-5.5 min), there were reductions in the volumes of the prostate and SVs receiving the prescribed dose (median reduction 0.1% and 1.0%, respectively, p<0.001) and in the minimum dose to 0.1 cm(3) of their volumes (median reduction 0.5 and 1.5 Gy, p<0.001). Of the 46 patients, three patients' prostates and eight patients' SVs did not maintain dose coverage above 70 Gy. Rectal filling correlated with decreased percentage-volume of SV receiving 75.6, 70, and 60 Gy (p<0.02). CONCLUSIONS: The 3-mm intrafractional margin was adequate for prostate dose coverage. However, a significant subset of patients lost SV dose coverage. The rectal volume change significantly affected SV dose coverage. For advanced-stage prostate cancers, we recommend to use larger margins or improve organ immobilization (such as with a rectal balloon) to ensure SV coverage.

An educational workshop on the early detection of prostate cancer

The authors have developed an education program for GPs to facilitate informed choice about PSA testing.

Generation of an epigenetic signature by chronic hypoxia in prostate cells

Increasing levels of tissue hypoxia have been reported as a natural feature of the aging prostate gland and may be a risk factor for the development of prostate cancer. In this study, we have used PwR-1E benign prostate epithelial cells and an equivalently aged hypoxia-adapted PwR-1E sub-line to identify phenotypic and epigenetic consequences of chronic hypoxia in prostate cells. We have identified a significantly altered cellular phenotype in response to chronic hypoxia as characterized by increased receptor-mediated apoptotic resistance, the induction of cellular senescence, increased invasion and the increased secretion of IL-1 beta, IL6, IL8 and TNFalpha cytokines. In association with these phenotypic changes and the absence of HIF-1 alpha protein expression, we have demonstrated significant increases in global levels of DNA methylation and H3K9 histone acetylation in these cells, concomitant with the increased expression of DNA methyltransferase DMNT3b and gene-specific changes in DNA methylation at key imprinting loci. In conclusion, we have demonstrated a genome-wide adjustment of DNA methylation and histone acetylation under chronic hypoxic conditions in the prostate. These epigenetic signatures may represent an additional mechanism to promote and maintain a hypoxic-adapted cellular phenotype with a potential role in tumour development.

Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer

Monocarboxylate Transporter 2 (MCT2) is a major pyruvate transporter encoded by the SLC16A7 gene. Recent studies pointed to a consistent overexpression of MCT2 in prostate cancer (PCa) suggesting MCT2 as a putative biomarker and molecular target. Despite the importance of this observation the mechanisms involved in MCT2 regulation are unknown. Through an integrative analysis we have discovered that selective demethylation of an internal SLC16A7/MCT2 promoter is a recurrent event in independent PCa cohorts. This demethylation is associated with expression of isoforms differing only in 5'-UTR translational control motifs, providing one contributing mechanism for MCT2 protein overexpression in PCa. Genes co-expressed with SLC16A7/MCT2 also clustered in oncogenic-related pathways and effectors of these signalling pathways were found to bind at the SLC16A7/MCT2 gene locus. Finally, MCT2 knock-down attenuated the growth of PCa cells. The present study unveils an unexpected epigenetic regulation of SLC16A7/MCT2 isoforms and identifies a link between SLC16A7/MCT2, Androgen Receptor (AR), ETS-related gene (ERG) and other oncogenic pathways in PCa. These results underscore the importance of combining data from epigenetic, transcriptomic and protein level changes to allow more comprehensive insights into the mechanisms underlying protein expression, that in our case provide additional weight to MCT2 as a candidate biomarker and molecular target in PCa.

Economic burden of malignant neoplasms in Shandong province [山东省恶性肿瘤经济负担分析]

Objective: To evaluate the economic burden of malignant neoplasms in Shandong province in order to provide scientific evidence for policy-making. Methods: The main sources for this study were the data from the third sampling survey of death cause in 2006 and cancer prevalence survey in 2007 in Shandong province. The direct medical cost was calculated based on the survey data. The indirect cost due to mortality and morbidity were estimated with human capital approach based on the data of disability-adjusted life years derived from the two surveys and gross domestic product (GDP) data. The total economic burden was the sum of direct medical cost and indirect cost. The uncertainty analysis was conducted according to the methodology in global burden of disease study. Results: The total cost of cancer in Shandong province in 2006 estimated was 18 057 million Yuan RMB (95% confidence interval:16 817 － 19 393 million), which accounted for 0. 83% of the total GDP. The direct medical cost，indirect mortality cost and indirect morbidity cost accounted for 17.28%, 78.53%, and 4.20% of total economic burden of malignant neoplasms, respectively. Liver，lung and stomach cancer were the top three tumors with heavier economic burden, with accounted for more than one half (57. 83%) of the total economic burden of all cancers. The uncertainty of total burden estimated was around ± 7%, which mainly derived from the uncertainty of indirect economic burden. Conclusion: The influence of cancers on social economy is dominated by the loss of productivity, especially by the productivity loss due to premature death. Liver, lung and stomach cancer are the major cancers for disease control and prevention in Shandong province. Abstract in Chinese 目的 评价山东省恶性肿瘤经济负担,为卫生决策提供科学依据. 方法 以2006年山东省第3次死因回顾抽样凋查资料和2007年山东省恶性肿瘤现患状况抽样调查资料为基础,测算全省直接医疗成本;采用人力资本法测算死亡间接负担和伤残间接负担;参考全球疾病负担研究的方法对测算结果的不确定性进行分析. 结果 2006年山东省因恶性肿瘤导致的总经济负担为180.57亿元(95%CI=16 817～19 393),占全省GDP总量的0.83%,其中直接医疗成本占总负担的17.28%,死亡造成的间接经济负担占78.53%,伤残所致间接经济负担占4.20%;肝癌、肺癌和胃癌为山东省经济负担最重的3种恶性肿瘤,总经济负担合计占全部恶性肿瘤的57.83%;总经济负担估计结果的不确定性范围在±7%左右,主要取决于间接经济负担的不确定性. 结论 恶性肿瘤对社会经济的影响主要通过生产力的损失产生作用,并以死亡所致生产力损失为主;肝癌、肺癌和胃癌应是山东省恶性肿瘤预防控制的重点.

Estimation of disability weights on malignant neoplasms in Shandong province [山东省现患恶性肿瘤残疾权重的测量]

Objective To determine stage-specific and average disability weights (DWs) of malignant neoplasm and provide support and evidence for study on burden of cancer and policy development in Shandong province. Methods Health status of each cancer patient identified during the cancer prevalence survey in Shandong, 2007 was investigated. In line with the GBD methodology in estimating DWs, the disability extent of every case was classified and evaluated according to the Six-class Disability Classification version and then the stage-specific weights and average DWs with their 95 % confidence intervals were calculated, using SAS software. Results A total of 11 757 cancer cases were investigated and evaluated. DWs of specific stage of therapy, remission, metastasis and terminal of all cancers were 0.310, 0.218, 0.450 and 0.653 respectively. The average DW of all cancers was 0.317(95 % CI:0.312-0.321). Weights of different stage and different cancer varied significantly, while no significant differences were found between males and females. DWs were found higher (>0.4) for liver cancer, bone cancer, lymphoma and pancreas cancer. Lower DWs (<0.3) were found for breast cancer, cervix uteri, corpus uteri, ovarian cancer, larynx cancer, mouth and oropharynx cancer. Conclusion Stage-specific and average DWs for various cancers were estimated based on a large sample size survey. The average DWs of 0.317 for all cancers indicated that 1/3 healthy year lost for each survived life year of them. The difference of DWs between different cancer and stage provide scientific evidence for cancer prevention strategy development. Abstract in Chinese 目的 测算各种恶性肿瘤的分病程残疾权重和平均残疾权重,为山东省恶性肿瘤疾病负担研究及肿瘤防治对策制定提供参考依据. 方法 在山东省2007年恶性肿瘤现患调查中对所有恶性肿瘤患者的健康状况进行调查,参考全球疾病负担研究的方法 ,利用六级社会功能分级标准对患者残疾状况进行分级和赋值,分别计算20种恶性肿瘤的分病程残疾权重和平均残疾权重及其95%CI. 结果 共调查恶性肿瘤患者11757例,所有恶性肿瘤治疗期、恢复期、转移期和晚期的残疾权重分别为0.310、0.218、0.450和0.653,平均残疾权重为0.317(95%CI:0.312～0.321).不同恶性肿瘤和不同病程阶段的残疾权重差别显著,性别间差异无统计学意义.肝癌、骨癌、淋巴瘤和胰腺癌平均残疾权重较高(>0.4),乳腺癌、子宫体癌、子宫颈癌、卵巢癌、喉癌和口咽部癌症相对较低(<0.3). 结论 山东省恶性肿瘤平均残疾权重为0.317,即恶性肿瘤患者每存活1年平均损失近1/3个健康生命年;不同恶性肿瘤和不同病程阶段的残疾权重差别为肿瘤防治对策的制定具有重要意义.