Angiotensin-converting-Enzym-Hemmer (ACEI) und Angiotensin-Rezeptor-Blocker (ARB) sind häug verwendete Antihypertensiva. Weil Eekte auf aber-rante Gefäßbildung und veränderte Immunantwort beschrieben wurden, wurde geprüft, ob sie mit einem besseren Ansprechen auf die neoadjuvante Strahlentherapie des Rektumkarzinoms assoziiert sind. D azu werteten die Forscher retrospek-tiv zum einen die Daten von 115 Pa-tienten aus, die zwischen 1999 und 2012 an der Universität von Wisconsin wegen eines Rektumkarzinoms mit oder ohne begleitende Chemotherapie neoadjuvant bestrahlt worden waren, um eine kurati-ve Resektion zu ermöglichen. 25 von ih-nen (21,7 %) nahmen zum Zeitpunkt der Strahlentherapie ACEI oder ARB ein. Unabhängig davon wurden die Daten ei-ner Kohorte von 186 Patienten analysiert, die ebenfalls wegen eines Rektumkarzi-noms zwischen 1995 und 2010 an der Universität von Hawaii neoadjuvant be-strahlt worden waren, wobei 49 von ih-nen (26,3 %) ACEI/ARB einnahmen. Den Wisconsin-Daten zufolge war die Einnahme von ACE/ARB mit einer Ver-dreifachung der pathologischen Kom-plettremissionen (pCR) assoziiert (52 vs. 17 %; p = 0,001). In der 2. Kohorte zeigte sich eine signikante Verdoppelung der pCR-Rate bei ACEI/ARB-Einnahme (24 vs. 12 %, p = 0,03). Signikante Unter-schiede bezüglich Patientencharakteris-tika oder Art, Dauer und Intensität der onkologischen erapie bestanden zwi-schen den Gruppen mit und ohne Ein-nahme von Antihypertensiva nicht. Auch zeigten sich keine Assoziationen zwischen pCR-Rate und der Einnahme von anderen Medikamenten. In der mul-tivariaten Analyse aller Daten zusam-men war die Einnahme von ACEI/ARB ein starker Prädiktor für eine pCR (Odds Ratio 4,02; p < 0,001). Damit war die ACEI/ARB-Einnahme sogar ein stärkerer Prädiktor für pCR als klini-sches Stadium oder Grading in der Bi-opsie. Ein Eekt auf das lokalrezidiv-, metastasenfreie oder Gesamtüberleben ließ sich nicht zeigen. Das führen die Forscher auf die zu geringe Zahl der Pa-tienten und die zu kurze Dauer der Be-obachtung (4,1 bzw. 5,3 Jahre) zurück. Fazit: Bei Patienten mit Rektumkarzi-nom war die Einnahme von ACEI/ARB in 2 unabhängigen Kohorten mit einer signikanten Steigerung der pCR-Rate nach der neoadjuvanten erapie asso-ziiert. Morris ZS et al. Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Cancer. 2016;122(16):2487-95. Intensivierung der neoadjuvanten Therapie beim lokal fortgeschrittenen Rektumkarzinom Standard beim lokal fortgeschrittenen Rektumkarzinom ist die totale meso-rektale Exzision mit einer Fluoruracil(FU)-basierten Radiochemotherapie vor und einer adjuvanten Chemotherapie nach der Operation. Ein deutlicher Überlebensvorteil gegenüber einer Operation alleine oder mit adjuvanter Chemotherapie konnte damit aber bisher nicht gezeigt werden. D eshalb wurde in einer Phase-III-Stu-die das Überleben nach modizier-ten multimodalen erapien untersucht. 495 erwachsene chinesische Patienten mit lokal fortgeschrittenem Rektumkar-...

PURPOSE In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% ( P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% ( P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% ( P = .971 by log-rank test), respectively. CONCLUSION mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

ObjectivesRecent studies suggest that an elevated preoperative platelet to lymphocyte ratio (PLR) may be considered a poor prognostic biomarker in patients with colorectal cancer (CRC). The aim of this study was to evaluate the prognostic impact of PLR in patients with CRC.MethodsWe enrolled 1314 patients who underwent surgery for CRC between 2005 and 2011. Preoperative PLR level was stratified into quintiles for Kaplan-Meier analysis and multivariable Cox proportional hazard regression models.ResultsHigher PLR quintiles were significantly associated with poorer overall survival (P = 0.002). Multivariate analysis showed that PLR was an independent risk factor for overall survival (OS) (P = 0.034). Patients in PLR quintile 5 had lower overall survival than in quintile 1 (hazard ratio (HR) = 1.701, 95% confidence interval (CI): 1.267–2.282, P < 0.001). Although patients in PLR quintile 5 had significantly lower disease-free survival (DFS) than in quintile 1 (HR = 1.522, 95% CI: 1.114–2.080, P = 0.008), this association was not significant after multivariable adjustment (P = 0.075). In the subgroup analysis, PLR remained an independent factor in terms of advanced tumor stage (III, IV), male sex, carcinoembryonic antigen (≤ 5 ng/ml), age (> 65 years) and body mass index (≤ 25) (P < 0.05 for all measurements). The results remained unchanged when the PLR was analyzed as a dichotomous variable by applying different cut-off values of 150, 185, 220.ConclusionsElevated preoperative PLR was independently associated with an increased risk of mortality in patients with CRC. The utility of PLR may help to improve prognostic predictors.

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Aim. To investigate the correlation between Sirtuin 3 (SIRT3) expression and the clinical outcome of patients with colon cancer. Methods. The tumor specimens from 127 patients with colon cancer were obtained for SIRT3 immunohistochemical staining. Patients were followed up. In in vitro study, SIRT3 gene was inhibited to observe the effects of SIRT3 on the biological behavior of cultured colon cells. Results. The SIRT3 expression level was found to be significantly associated with the lymph node metastasis (P < 0.001) and tumor stages (P < 0.001). The colon cancer-specific survival was 64.6% among patients with high SIRT3 expressions and 88.6% among patients with low SIRT3 expressions (log-rank P = 0.016). The overall survival was 80.2% among patients with low SIRT3 expressions and 55.9% among patients with high SIRT3 expressions (log-rank P = 0.002). In vitro study showed that silencing of SIRT3 gene inhibited the proliferation, invasion, and cells migration but increased the apoptosis in the cultured colon cell lines. Conclusion. This study provides evidence supporting that SIRT3 is closely associated with the clinical outcomes of colon cancer. SIRT3 may be considered as a marker for colon cancer.

IntroductionCyclooxygenase-2 (COX-2) is believed to be an important enzyme in the carcinogenesis of hepatocellular carcinoma (HCC). However, it is still controversial whether COX-2 expression can be regarded as a prognostic factor for HCC patients. We performed a systematic review and meta-analysis of studies assessing the clinical and prognostic significance of COX-2 expression in HCC.Material and methodsIdentification and review of publications assessing clinical or prognostic significance of COX-2 expression in HCC until November 1, 2014. A meta-analysis was performed to clarify the association between COX-2 expression and clinical outcomes.ResultsA total of 11 publications met the criteria and included 943 cases. Analysis of these data showed that COX-2 expression was not significantly correlated with capsular formation (OR = 0.84, 95% confidence interval (CI): 0.46–1.55, p = 0.58), tumor TNM stage (OR = 0.73, 95% CI: 0.23–2.33, p = 0.59), vascular invasion (OR = 1.04, 95% CI: 0.25–4.35, p = 0.96), tumor size (OR = 0.78, 95% CI: 0.21–2.86, p = 0.71), or tumor differentiation degree (OR = 1.08, 95% CI: 0.42–2.79, p = 0.87). However, in the identified studies, COX-2 expression was strongly associated with high alpha-fetoprotein level (OR = 1.83, 95% CI: 1.01–3.33, p = 0.05), HBsAg status (OR = 1.85, 95% CI: 1.13–3.03, p = 0.01), decreased overall survival (relative risk (RR): 1.54, 95% CI: 1.18–2.02, p = 0.001) and decreased disease-free survival (RR = 1.49, 95% CI: 1.22–1.81, p < 0.001).ConclusionsThis meta-analysis shows that COX-2 expression in HCC is associated with decreased overall and disease-free survival and thus marks a worse prognosis. Nevertheless, more large sample and well-designed studies are warranted to confirm this finding.

a b s t r a c t miR-362-5p is down-regulated in high-risk neuroblastoma and can function as a tumor suppressor. However, its role remains poorly understood. We show that miR-362-5p is down-regulated in metastatic neuroblastoma compared with primary neuroblastoma. Overexpression of miR-362-5p inhibits cell proliferation, migration and invasion of neuroblastoma cells in vitro and suppresses tumor growth of neuroblastoma in vivo. Phosphatidylinositol 3-kinase (PI3K)-C2b is a target of miR-362-5p. Knockdown of PI3K-C2b by siRNA had a similar effect to overexpression of miR-362-5p on SH-SY5Y cells. Overexpression of PI3K-C2b partially reversed tumor-suppressive effects of miR-362-5p. We suggest that miR-362-5p suppresses neuroblastoma cell growth and motility, partially by targeting PI3K-C2b.

ObjectiveThe aim of this study was to evaluate the prognostic value of both platelet to lymphocyte ratio (PLR) and metabolic syndrome (MetS) in colorectal cancer (CRC) patients.Patients and methodsWe retrospectively enrolled 1,163 CRC patients. Preoperative values of PLR were stratified into three groups according to cut-off values of 120 and 220. The Kaplan–Meier analysis was used to calculate cumulative survival rate related to PLR and MetS. Cox proportional hazard regression models were used to analyze potential risk factors and the prognosis associated with PLR and MetS in CRC patients.ResultsPLR was significantly higher in the MetS(+) group as compared to MetS(−) group (P=0.039). An elevated PLR was significantly associated with mortality (P=0.014), but not the existence of MetS (P=0.235). In multivariate regression analysis, PLR was an independent risk factor for overall survival (OS) (P=0.046). For the subgroup with a PLR >220, MetS was an independent predictor for both OS and disease-free survival (P=0.039 and P=0.047, respectively) by multivariate analysis adjusting for confounding covariates. In addition, the presence of MetS was associated with a 2-fold increased risk of mortality and tumor recurrences (hazard ratio [HR] =2.0 and HR =1.9, P<0.05, respectively).ConclusionPreoperative PLR was associated with MetS in CRC patients. Testing for the combined presence of PLR and MetS could potentially improve the predictive accuracy of CRC prognosis.