Tumor Biology

Uterine sarcomas are rare and aggressive gynecologic malignancies. In this immunohistochemical (IHC) study, expression of Ki-67, p53, CD10, CD44, desmin, smooth muscle actin, estrogen receptor α (ERα), androgen receptor (AR), progesterone receptor A (PRA), and c-kit and their influence on survival in cases of uterine carcinosarcoma (CS), leiomyosarcoma (LMS), and endometrial stromal sarcoma (ESS) were evaluated. Medical records were reviewed and data collected concerning all uterine sarcomas treated during a 12-year period at Helsinki University Central Hospital. There was sufficient histological material for IHC analysis and slide review in 67 cases. Survival analysis was performed using the Kaplan–Meier method, and median survival times with 95% confidence intervals are given. Survival in cases of LMS was statistically significantly affected by the expression of p53, ERα, and PRA. Striking differences in expression of IHC markers when comparing results with those in earlier studies were the absence of AR immunoreactivity in all uterine sarcomas and low incidence of c-kit (15%; in endometrial stromal sarcoma). None of the markers was statistically significantly associated with survival of ESS and CS patients. The expression of p53, ERα, and PRA in uterine LMS may give prognostic information concerning the behavior of the disease. Hormonal therapy could be recommended as a treatment option in cases of hormone receptor-positive LMS.

Epidemiological evidence suggests that cigarette smoking is the best-established risk factor for renal cell cancer (RCC). However, the effect of smoking on survival of RCC patients remains debated. We therefore conducted a meta-analysis to investigate the impact of smoking status on overall mortality (OM), disease-specific mortality (DSM), overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in patients with RCC. We searched Medline, Embase, and the Cochrane Central Search Library for published studies that analyzed the effect of smoking on survival or mortality of RCC. We selected 14 articles according to predefined inclusion criteria. The smoking status was categorized into never smokers and ever smokers (former smokers and/or current smokers). Summary hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated with a fixed or random effects model. Overall, 14 studies including 343,993 RCC cases were accepted for meta-analysis. Ever smoking was significantly correlated with OM (HR 1.30, 95 % CI 1.07–1.58), while no associated with poorer DSM (HR 1.23, 95 % CI 0.96–1.57). Further analysis found current (HR 1.57, 95 % CI 1.20–2.06) but not former smoking (HR 1.14, 95 % CI 0.79–1.63) was associated with a significantly increased risk of OM. Meanwhile, current smoking was associated with poorer DSM (HR 1.50, 95 % CI 1.10–2.05) in subgroup analysis. Ever smoking was significantly associated with poorer OS (HR 1.45; 95 % CI 1.00–2.09) and poorer CSS (HR 1.01; 95 % CI 1.00–1.02), compared with never smokers. Current smoking was associated with poorer PFS (HR 2.94, 95 % CI 1.89–4.58). This review provides preliminary evidence that current smoking in a patient with RCC is associated with poorer survival, demonstrating active smoking to be an independent risk for prognosis of RCC. Smoking cessation should be recommended for RCC patients.

Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization are widely used palliative treatments for patients with nonsurgical hepatocellular carcinoma. TAE has been shown to increase levels of hypoxia-inducible factor-1 alpha (HIF-1α) in tumors. In this study, we investigated whether RNA interference (RNAi) of HIF-1α could improve the efficacy of TAE to treat HCC. Four treatment groups were assessed using a rat allograft model of HCC: RNAi of HIF-1α combined with TAE, RNAi of HIF-1α only, TAE only, and a control group. Rats were treated by TAE by retrograde placement of a microcatheter into the gastroduodenal artery. The results demonstrated that the RNAi of HIF-1α visibly reduced the expression of HIF-1α and vascular endothelial growth factor, suppressed tumor angiogenesis, and attenuated metastasis, which were all enhanced by TAE. The RNAi of HIF-1α synergized with TAE to significantly inhibit tumor growth. In conclusion, RNAi of HIF-1α augmented the therapeutic effects of TAE and diminished its undesirable effects.

Microparticles (MPs) are substantially increased in patients with operable stage non-small cell lung cancer (NSCLC) prior to lung resection surgery. This study tested the hypothesis that there is a decrease in MPs after surgical intervention. Between March 2012 and January 2015, 33 patients who had operable stage NSCLC were consecutively and prospectively enrolled into the study. Additionally, 31 healthy subjects who were consecutively enrolled in the study period served as age- and gender-matched controls. Circulating MPs (EDAc-MPs, EDAp-MPs, PDAc-MPs, PDAp-MPs) were measured by flow cytometry once in control subjects and twice (i.e., prior to and three months later after surgical intervention) in NSCLC patients. Compared with control subjects, these four types of circulating MPs were significantly higher in NSCLC patients prior to operation (all P < 0.005), but did not differ among the controls and NSCLC patients at 3 months after surgery (all P > 0.2). Additionally, a receiver operating characteristic curve (ROC) showed that these four types of MPs were significantly valuable predictors for detecting early stage NSCLC (all P < 0.004). Circulating MPs which were remarkably increased in the operable stage of NSCLC prior to surgery were substantially decreased 3 months later after surgery. These findings show that circulating MPs might be an accessory biomarker for monitoring those of NSCLC after receiving lung resection surgery.

Esophageal squamous cell carcinoma (ESCC) is the dominant type of esophageal cancer in the East Asian population. MicroRNAs (miRNAs) have been studied to play important roles in tumorigenesis. Single nucleotide polymorphisms (SNPs) in miRNA lead to the aberrant expression and structural alteration of miRNA and are hypothesized to be involved in tumorigenesis and cancer development. We conducted a population-based case-control study to evaluate the association between SNPs in miRNAs and ESCC risk in 1400 ESCC cases and 2185 matched controls. Four SNPs including miR-196a2 rs11614913, miR-146a rs2910164, miR-499 rs3746444, and miR-423 rs6505162 were selected with comprehensive collection strategy and genotyped using the SNaPshot Multiplex System. Odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the strength of association. The CC genotype of miR-196a2 rs11614913 was significantly associated with an increased ESCC risk compared with the TT genotype (OR 1.11, 95 % CI 1.01–1.22, P 0.049) and the TT/TC genotypes (OR 1.09, 95 % CI 1.01–1.19, P 0.043). The association was more pronounced in non-drinkers in the recessive model (OR 1.13, 95 % CI 1.01–1.27, P 0.029). A significantly increased risk of ESCC associated with miR-499 rs3746444 polymorphism was evident among patients who never smoking and drinking. This study suggests that miR-196a2 rs11614913 and miR-499 rs3746444 are associated with an increased ESCC risk in a Chinese population.

The purpose of this study was to elucidate the relationship between pituitary tumor transforming gene (PTTG) and invasiveness in pituitary macroadenomas and to determine the association between PTTG and both the tumor proliferative activity marker proliferation cell nuclear antigen (PCNA) and the angiogenic factor basic fibroblast growth factor. A total of 70 patients with pituitary adenomas who underwent transsphenoidal or craniotomy surgical resection were enrolled. The average age were 42.5 ± 13.7 years (17–64 years) for the invasive group and 46.8 ± 12.1 years (16–71 years) for the non-invasive group, with no significant difference (P = 0.179) between the two groups. RT-PCR analysis of a group of pituitary macroadenomas demonstrated that the expression levels of PTTG and PCNA in invasive pituitary adenomas were significantly higher than in non-invasive pituitary adenomas. Both factors are both closely related to the invasive growth of pituitary adenomas and may possibly serve as important markers of this growth. In conclusion, PTTG may promote invasive tumor growth by stimulating pituitary adenomas proliferation. The mechanisms of tumor growth promotion and invasion of the surrounding structures by PTTG need to be further explored.