Efficacy and safety of fosaprepitant in the prevention of nausea and vomiting following highly emetogenic chemotherapy in Chinese people: A randomized, double-blind, phase III study.

The prevention of chemotherapy-induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2-d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0-120 hr, overall phase [OP]). It was assessed by using a non-inferiority model, with a non-inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi-square analysis. Six hundred and twenty-six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin-based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well-tolerated control of nausea and vomiting associated with HEC in Chinese patients.

miR-106a* inhibits the proliferation of esophageal carcinoma cells by targeting CDK2-associated Cullin 1 (CACUL1).

Previous studies suggest that aberrant microRNA expression is common in plenty of cancers. The expression of miR-106a* was decreased in follicular lymphoma, but the expression and functions of miR-106a* in esophageal carcinoma (EC) remain unclear. In this study, we explored the expression and anti-oncogenic roles of miR-106a* in human EC. The expression of miR-106a* is significantly decreased in EC tissues and EC cell lines. Overexpression of miR-106a* suppressed EC cell proliferation, clonogenicity, G1/S transition, and induced apoptosis in vitro, but inhibition of miR-106a* facilitated cell proliferation, clonogenicity, G1/S transition. Luciferase reporter assay results showed that CDK2-associated Cullin 1 (CACUL1) was a direct target of miR-106a* in EC cells. Moreover, silencing CACUL1 resulted in the same biologic effects of miR-106a* overexpression in EC cells, which included suppressed EC cell proliferation, clonogenicity, and blocked G1/S transition through CDK2 pathway by inhibiting cell cycle regulators (Cyclin A, Cyclin E). Our data indicate that miR-106a* might play an anti-oncogenic role in EC by regulating CACUL1 expression, which suggest miR-106a* as a new potential diagnostic and therapeutic target for EC.

MiR-30a suppresses non-small cell lung cancer progression through AKT signaling pathway by targeting IGF1R.

MicroRNAs play critical roles in the development and progression of human cancers. Although miR—30a has been suggested to function as a tumor repressor in several tumors, its role in non—small cell lung cancer (NSCLC) has not been investigated in detail. This study investigated the expression and role of miR—30a in human NSCLC. The expression of miR—30a is significantly decreased in clinical NSCLC tissues and cell lines. Overexpression of miR—30a inhibited NSCLC cell proliferation, G1/S and S/G2 transition in vitro, whereas suppression of miR—30a facilitated NSCLC cell proliferation, G1/S and S/G2 transition. Using a luciferase reporter assay, insulin—like growth factor 1 receptor (IGF1R) was determined to be a direct target of miR—30a. Furthermore, silencing IGF1R resulted in the same biologic effects of miR—30a overexpression in NSCLC cells, which included suppressed NSCLC cell proliferation and trigering cell cycle arrest through PI3K/AKT signaling pathway by inhibiting cell cycle regulators (CDK2, CDK4, Cyclin A2 , Cyclin D1). These results demonstrate that miR—30a influences NSCLC progression through PI3K/AKT signaling pathway by targeting IGF1R in A549 cells, which suggest miR—30a as a novel strategy for NSCLC diagnosis and treatment.

Further evidence for the contribution of the BRCA1-interacting protein-terminal helicase 1 (BRIP1) gene in breast cancer susceptibility.

BRCA1-interacting protein C-terminal helicase 1 (BRIP1) is a DNA helicase that influences the DNA repair ability and tumor suppressor function of BRCA1. Truncating BRIP1 mutations have been described as cancer susceptibility alleles. To evaluate BRIP1 polymorphisms as risk factors for breast cancer, we performed a detailed analysis of possible single nucleotide polymorphisms (rs2048718, rs4988344, rs8077088, rs6504074, rs4986764, rs4986763, rs11079454, rs7213430, rs34289250, rs4988345, and rs12937080) using the MassARRAY system. A total of 319 patients with breast cancer and 306 healthy control females from the Chinese Han population enrolled in the study. A weak association was found between the rs4986764 allele (exon 18) and breast cancer. The frequency of the rs4986764 C allele was significantly higher in breast cancer patients than in healthy controls [χ(2) = 4.089, P = 0.043, odds ratio (OR) = 0.781, 95% confidence interval (CI) = 0.614-0.992]. Additionally, our study is the first to identify a significant association between rs7213430 and breast cancer. Compared to healthy controls, patients with breast cancer had a higher frequency of the rs7213430 A allele (χ(2) = 8.865, P = 0.003, OR = 0.700, 95%CI = 0.553-0.886). Furthermore, linkage disequilibrium was observed in two blocks (D' > 0.9). While significantly more T-A-C haplotypes (P = 0.001, block 1) were found in breast cancer patients, the frequency of T-T haplotypes (P = 0.008, block 2) was significantly higher in healthy controls. The possible association among rs4986764, rs7213430, and breast cancer risk merits further validation in an independent case-control study.