No abstract

PLR and NLR measurements can provide important diagnostic and prognostic results in patients with resectable gastric cancer.

Background VEGF/VEGFR2 pathway is the central therapeutic target in anti-angiogenic treatment in multiple cancers. However, little work has been carried out concerning the pro-malignancy functions of VEGFR2 that are independent of its pro-angiogenesis effects in gastric cancer. Here, we demonstrated that VEGFR2 up-regulation in gastric cancer tissues was a prognostic marker for poor disease-free survival and overall survival of gastric cancer patients. Methods Immunohistochemistry was used to detect VEGFR2 and VTN expressions in specimens. Kaplan–Meier curves were constructed for survival analysis. Stably knockdown cell lines and overexpression cell lines were constructed by small interfering RNA and plasmids transfection. Real-time PCR and Western blot were used to confirm the expressions of target genes at both RNA and protein levels. Cell proliferation was measured by using Cell Counting Kit-8 and xenograft models. Microarray and bioinformatic analysis were also performed to identify the relationship between Vitronectin (VTN) and VEGFR2. Results When overexpressed in gastric cancer cells, VEGFR2 increased cellular proliferation and invasion in vitro and tumor formation in xenograft models. By using integrating microarray and bioinformatic analysis, we identifiedVTN as a downstream of VEGFR2 pathway. In gain- and loss-of function analysis in gastric cancer cells, VTN was further verified in consistent with VEGFR2 in expression levels and in regulating cell growth and motility in vitro and in vivo . Moreover, in gastric cancer samples, VTN was as also revealed as a poor prognostic factor. Conclusions Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects. Implications Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects, which may provide a new and valuable target for design of therapies for intervention and a new cognitive perspective for the anti-angiogenesis therapies. Electronic supplementary material The online version of this article (10.1186/s12885-019-5322-0) contains supplementary material, which is available to authorized users.

Temozolomide (TMZ), a DNA alkylating agent, represents the most important chemotherapeutic option for the treatment of glioblastoma in the clinic. Despite its frequent use, the therapeutic efficacy of TMZ remains very limited due to its frequent resistance in glioblastoma. Previous evidence suggested that curcumin (CUM), an ingredient of the Indian spice turmeric, is able to sensitize glioblastoma to TMZ treatment. However, the underlying molecular mechanism remains elusive. In the present study, we performed in vitro and in vivo experiments to evaluate the interaction of CUM and TMZ on the inhibition of glioblastoma and to investigate its potential mechanisms of action using U87MG cell lines and xenograft mouse models. We demonstrated that CUM enhanced the therapeutic response to TMZ in U87MG glioblastoma by enhancing apoptosis. We then proceeded to investigate the potential apoptotic signaling pathways that are involved. We observed a synergistic effect of the combination of CUM and TMZ in generating reactive oxygen species (ROS) production, suggesting that ROS may contribute to the impact of CUM on sensitizing TMZ treatment. We also showed that CUM and TMZ treatment alone significantly suppressed phosphorylated AKT and mTOR, whereas their combination achieved a more pronounced inhibitory effect. These data indicated that blockage of AKT/mTOR signaling appeared to contribute to the elevated apoptosis caused by the combination treatment with CUM and TMZ. In conclusion, this study provided molecular insights into the effects of CUM on the therapeutic response of glioblastoma to TMZ and opened new avenues for optimizing the therapeutic effects of TMZ-based therapies.

Gastric cancer is the fourth most frequent cancer and the second cause of cancer-related mortalities worldwide. Platelets play an important and multifaceted role in cancer progression. Elevated mean platelet volume (MPV) detected in peripheral blood has been identified in various types of cancer. In the present study, we investigated the application value of MPV in early diagnostic and prognostic prediction in patients with resectable gastric cancer. In total, 168 patients with resectable gastric cancer were included and separated into the gastric cancer and healthy control groups according to median pre-operatic MPV value (MPV low, <10.51 or MPV high, ≥10.51). The results showed that the pre-operatic MPV level was significantly higher in gastric cancer patients compared with the healthy subjects. Low pre-operatic MPV level correlated with improved clinicopathological features, including decreased depth of invasion, less lymphonodus metastasis and early tumor stage. The Kaplan-Meier plots showed that the patients with higher pre-operatic MPV had decreased overall survival (OS) and disease-free survival (DFS). Surgical tumor resection resulted in a significant decrease in the MPV level. The patients whose MPV level decreased following surgery had an improved OS. Multivariate Cox regression analysis revealed that the depth of invasion, lymphonodus metastasis, American Joint Committee on Cancer (AJCC) stage, and changes in MPV following surgery were prognostic factors affecting OS, and the AJCC stage and pre-operatic MPV were prognostic factors affecting DFS. In conclusion, MPV measurement can provide important diagnostic and prognostic results in patients with resectable gastric cancer.

The aim of the study was to investigate the application value of neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) in the prediction of chemotherapy response and prognosis in patients with advanced gastric cancer. In total, 120 patients with unresectable gastric cancer were included and separated into two groups according to the median values of NLR or PLR (NLR low: <4.62 or NLR high: ≥4.62 and PLR low: <235 or PLR high: ≥235, respectively). Low baseline NLR level correlated with improved clinicopathological characteristics, including smaller tumor size, well differentiation and less metastasis. Low baseline PLR level also associated with less metastasis. Patients with a low baseline level of NLR or PLR had an improved response to chemotherapy. Patients with a higher baseline NLR and PLR had decreased progression-free survival (PFS) and overall survival (OS) ratios. Alterations in the NLR and PLR levels were associated with therapeutic efficacy and prognosis. The patients who remained in or switched to the low NLR level subgroup subsequent to first-line chemotherapy had an improved response and improved OS ratios, compared to the patients remaining in or switching to the high NLR level group. Similar results were observed when the PLR level was investigated. In conclusion, baseline NLR and PLR measurements, as well as changes of NLR and PLR following chemotherapy can predict the prognostic results in patients with unresectable gastric cancer.

Armanni-Ebstein lesions were first described by Luciano Armanni, a pathologist at the University of Naples, during autopsy studies undertaken in 1872, as a unique vacuolar nephropathy associated with poorly controlled diabetes that involves selective renal epithelial cell glycogen accumulation. However, within the last two decades, a broader range of vacuolar changes, including lipid deposition, have also been termed Armanni-Ebstein (AE) lesions, creating some confusion on possible etiology. We would suggest that the term AE phenomenon would be best reserved for the original clear cell change associated with glycogen deposition, and that this should be clearly distinguished from subnuclear lipid vacuolization ("basal vacuolization"). Although there is obvious inter-relation between these two types of vacuoles, they appear morphologically and biochemically distinct from each other. More precise classification may assist in clarifying the causal processes and possible diagnostic significance of different types of renal epithelial vacuolization at autopsy.

Multiple cancers arise from sites of infection, chronic irritation, and inflammation. It has been widely accepted that pancreatic cancer is an inflammation-driven cancer. In this study, we investigated the application value of systemic inflammatory markers, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), in the prediction of chemotherapy response and prognosis in patients with late pancreatic cancer. 122 patients with inoperable pancreatic cancers were included and separated into two groups according to median values of NLR or PLR (NLR low:<3.81 or NLR high:≥3.81, and PLR low:<142.14 or PLR high≥142.14, respectively). Baseline NLR and PLR levels were significantly higher in pancreatic cancer patients compared with the healthy subjects. Neither of the baseline NLR or PLR levels could predict outcomes. Patients with low baseline level of NLR, but not PLR, had better responses to chemotherapy. Changes in NLR, but not PLR levels, were associated with the therapeutic efficacy. Patients who stayed in or dropped into the low NLR level subgroup after first-line chemotherapy had better responses, comparing to those stayed in or jumped into the high NLR level group. No similar results could be observed when the PLR level was investigated. Therefore, NLR is a more sensitive biomarker than PLR in the prediction of chemotherapy response of patients.