Introduction:We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC.Methods: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. Results:The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n ¼ 30, 95% confidence interval: 6.6-11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n ¼ 9, 30%), which returned to normal after symptomatic treatment.Conclusions: This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFRmutant NSCLC-LM who had failed on tyrosine kinase inhibitor.

The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors' knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5%) presented peritoneal metastases and 43 (48.3%) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95% confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95% CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.

Our objective is to investigate the expression of CD147 and metallo-proteinase 9 (MMP9) in patients with basal-like breast cancer (BLBC) so as to determine whether these two genes may be correlated with prognosis of BLBC. We examined the expression of the CD147 and MMP9 in BLBC by immunohistochemistry. Furthermore, we analyzed the correlation between BLBC and several factors related to tumor progression, along with the prognostic value of BLBC. BLBC was significantly associated with CD147 and MMP9 expression (P = 0.000), and prone to lymph node metastasis and distant metastasis. Patients with BLBC showed shorter disease-free survival (P = 0.005) and overall survival (OS) (P = 0.011). In univariate analysis, CD147, MMP9, lymph node metastasis and clinical stage are independent prognostic factors affecting OS. In multivariate analysis, only clinical stage was identified as an independent prognostic factor. Patients with BLBC have a high expression of CD147 and MMP9; BLBC is correlated with a poor prognosis.

The poor prognosis in non-small-cell lung cancer has driven the development of novel targeted therapies. Vascular endothelial growth factor is the most potent force in mediating tumor angiogenesis, and many angiogenesis inhibitors have been developed for oncology treatment. We performed a study to characterize the efficacy, safety and tumor suppression of three lung cancer related anti-angiogenic drugs (bevacizumab, endostar and apatinib) using transgenic zebrafish embryo and human lung cancer xenotransplantation model. All three drugs demonstrated remarkable angiogenesis and tumor inhibition effect in the zebrafish model, within the nonlethal dose range. Endostar and bevacizumab showed competitive anti-tumor efficacy. The anti-tumor performance of apatinib was hamstrung by its elevated toxicity at 35 °C. The addition of pemetrexed to anti-angiogenesis therapy had no obvious additional benefit in tumors.

One purified polysaccharide protein tyrosine phosphatase (PTP) was isolated from the roots of Polygala tenuifolia. The aim of the present study is to investigate the antitumor effect of PTP on human ovarian cancer OVCAR-3 cells and explore the molecular mechanism of the action involved. The results of MTT assay and apoptosis detection assay showed that PTP inhibited cellular proliferation of OVCAR-3 cells and induced apoptotic cellular death via arresting cell circle at the G0/G1 phase. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis identified that bcl-2 gradually decreased at both transcription and protein levels after PTP treatment for 48 h in OVCAR-3 cells, while those of bax, cytochrome c, caspase-3, and caspase-9 increased. In addition, the low expression of NF-κB in PTP-treated OVCAR-3 cells would trigger the extrinsic pathway of programmed cell death signaling in tumor cells. These results together suggest that PTP may induce apoptosis of OVCAR-3 cells through a mitochondrial pathway.