MSKCC, Memorial Sloan Kettering Cancer Center

  • 文章类型: Journal Article
    Some early-stage clear cell renal cell carcinomas (ccRCCs) of ≤7 cm are associated with a poor clinical outcome. In this study, we investigated molecular biomarkers associated with aggressive clinical T1 stage ccRCCs of ≤7 cm, which were used to develop a risk prediction tool toward guiding the decision of treatment. Among 1069 nephrectomies performed for ccRCC of ≤7 cm conducted between January 2008 and December 2014, 177 cases with available formalin-fixed paraffin-embedded tissue were evaluated. An aggressive tumor was defined as a tumor exhibiting synchronous metastasis, recurrence, or leading to cancer-specific death. Expression levels of six genes (FOXC2, CLIP4, PBRM1, BAP1, SETD2, and KDM5C) were measured by reverse-transcription polymerase chain reaction (qRT-PCR) and their relation to clinical outcomes was investigated. Immunohistochemistry was performed to validate the expression profiles of selected genes significantly associated with clinical outcomes in multivariate analysis. Using these genes, we developed a prediction model of aggressive ccRCC based on logistic regression and deep-learning methods. FOXC2, PBRM1, and BAP1 expression levels were significantly lower in aggressive ccRCC than non-aggressive ccRCC both in univariate and multivariate analysis. The immunohistochemistry result demonstrated the significant downregulation of FOXC2, PBRM1, and BAP1 expression in aggressive ccRCC. Adding immunohistochemical staining results to qRT-PCR, the aggressive ccRCC prediction models had the area under the curve (AUC) of 0.760 and 0.796 and accuracy of 0.759 and 0.852 using the logistic regression method and deep-learning method, respectively. Use of these biomarkers and the developed prediction model can help stratify patients with clinical T1 stage ccRCC.
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  • 文章类型: Journal Article
    目的:回顾已发表的膀胱平滑肌肉瘤病例,并报告2例。
    方法:使用关键字\'膀胱\'搜索数据库Pubmed和Hinari,“平滑肌肉瘤”和“平滑肌肿瘤”。对确定的14篇文章进行了审查,我们又提出了两个案例。
    结果:报告的100多例病例中,77人被审查。关于标准治疗缺乏共识,对肿瘤的自然史和预后知之甚少,由于其发病率非常低。这些肿瘤发生在任何性别的老年人中,并以攻击行为为特征。通常会有不利的结果,肺部是最常见的转移部位。我们报告的另外两个病例具有不同的呈现和结果。
    结论:由于这种罕见肿瘤的治疗经验有限,没有足够的数据表明最佳管理策略和预后.
    OBJECTIVE: To review the published cases of leiomyosarcoma of the urinary bladder and to report two further cases.
    METHODS: The databases Pubmed and Hinari were searched using the keywords \'bladder\', \'leiomyosarcoma\' and \'smooth muscle neoplasm\'. The 14 articles identified were reviewed, and we present a further two cases.
    RESULTS: Of more than 100 cases reported, 77 were reviewed. There is a lack of consensus about the standard treatment, and little is known about the natural history and prognosis of the tumour, due to its very low incidence. These tumours occur in older adults of either sex and are characterised by an aggressive behaviour. There is usually an unfavourable outcome, with the lungs being the most common site of metastasis. The two further cases we report had a different presentation and outcome.
    CONCLUSIONS: Because of the limited experience with this rare tumour, there are insufficient data to suggest the optimum management strategy and prognosis.
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  • 文章类型: Journal Article
    尽管通过最近引入靶向药物如多激酶抑制剂在晚期肾癌的治疗方面取得了重大改善,这种疾病的长期获益仍然有限,且仍有大量未满足的医疗需求.通过在一小部分患者中诱导持久的反应,癌症免疫疗法显示了其潜力。然而,迄今为止使用的非特异性免疫干预(高剂量)细胞因子与显著的副作用相关.特异性癌症免疫疗法可以通过攻击肿瘤细胞同时保留正常组织来规避这些问题,其中使用多肽疫苗接种是最有前途的策略之一。我们在这里总结了研究IMA901的I期和II期试验的临床和翻译数据。临床获益与针对IMA901肽的可检测T细胞反应的显着关联,以及在治疗患者中令人鼓舞的生存数据,促使开始了一项随机研究,一线晚期RCC的III期对照试验,预计到2015年底生存结果。还讨论了与最近发现的所谓检查点抑制剂的潜在组合策略。
    Despite a major improvement in the treatment of advanced kidney cancer by the recent introduction of targeted agents such as multi-kinase inhibitors, long-term benefits are still limited and a significant unmet medical need remains for this disease. Cancer immunotherapy has shown its potential by the induction of long-lasting responses in a small subset of patients, however, the unspecific immune interventions with (high dose) cytokines used so far are associated with significant side effects. Specific cancer immunotherapy may circumvent these problems by attacking tumor cells while sparing normal tissue with the use of multi-peptide vaccination being one of the most promising strategies. We here summarize the clinical and translational data from phase I and II trials investigating IMA901. Significant associations of clinical benefit with detectable T cell responses against the IMA901 peptides and encouraging survival data in treated patients has prompted the start of a randomized, controlled phase III trial in 1st line advanced RCC with survival results expected toward the end of 2015. Potential combination strategies with the recently discovered so-called checkpoint inhibitors are also discussed.
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