The Influence of Venous Characteristics on Peripherally Inserted Central Catheter-Related Symptomatic Venous Thrombosis in Cancer Patients.

BACKGROUND: With increasing use, peripherally inserted central catheters (PICCs) are associated with the risk of venous thrombosis. Few studies have focused on the relationships between venous thrombosis and venous characteristics. This study aimed to identify effects of venous characteristics on symptomatic PICC-related venous thrombosis in cancer patients and explore the relationship between venous characteristics and blood flow velocity. METHODS: The data of patients who underwent placement of PICC were retrospectively studied between January 2015 and September 2017. Symptomatic PICC-related venous thrombosis was confirmed by ultrasound. Univariable, multivariable logistic regression analyses were performed to identify the risk factors associated with PICC-related venous thrombosis. In October 2017, 169 patients with PICCs were enrolled prospectively, and the relationships between blood flow velocity and venous characteristics were recorded and analyzed. RESULTS: A total of 2933 cancer patients were enrolled in this study; of these patients, 68 experienced symptomatic venous thrombosis. In the bivariate analysis, body mass index (BMI), history of venous thrombosis, triglycerides, tumor category, vessel diameter, vessel depth and arm circumference were associated with thrombosis. The multivariable analyses showed that arm circumference, vascular diameter, triglyceride level and tumor category were independent risk factors for thrombosis. Blood flow velocity was positively correlated with vessel depth and arm circumference but not with vessel diameter. CONCLUSION: Different venous characteristics can lead to different blood flow rates, which can affect the incidence of thrombosis. A vein depth of greater than 1.07cm or less than 0.57cm was associated with a higher incidence of PICC-related venous thrombosis, and the greater the arm circumference and vessel diameter, the greater the risk of venous thrombosis.

Antiproliferative effect and autophagy induction of curcumin derivative ZYX02-Na on the human lung cancer cells A549.

At present, a large number of curcumin derivatives had been produced and identified aiming to replace the curcumin in view of its low bioavailability and stability. Here, a novel curcumin derivative ZYX02-Na was first used to reduce the cell viability of human non-small cell lung cells A549, which was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and Western blot analysis showed that ZYX02-Na could lead to cell cycle arrest in G0/G1 phase, which demonstrated that ZYX02-Na inhibited the proliferation of A549 cells. Furthermore, the AMPK/mTOR/4E-BP1 signaling pathway was activated in ZYX02-Na-treated A549 cells. Besides, wounding healing and transwell experiments showed that ZYX02-Na could also inhibited the migration ability of A549 cells. Moreover, we also found that ZYX02-Na could induce autophagy of A549 cells by acridine orange staining, GFP-LC3 subcellular localization observation and Western blotting analysis, respectively. In short, our current studies indicated that ZYX02-Na possessed the antiproliferation effect and autophagy induction on A549 cells, while in vivo anticancer study of ZYX02-Na needs to be done in future.

CircRNA_101237 promotes NSCLC progression via the miRNA-490-3p/MAPK1 axis.

Non-small cell lung cancer (NSCLC) is a common type of lung cancer, characterized by a poor prognosis. In the last several years, more and more studies have demonstrated the significant roles played by circular RNAs (circRNAs) in different human tumors progression including NSCLC. The present study was to explore the mechanism of hsa_circ_101237 in regulating non-small cell lung cancer (NSCLC). Totally 303 NSCLC cases were enrolled. A549 and H1299 cells were transfected. Cells viability, migration and invasion were determined by CCK-8 assay and transwell experiment, respectively. Luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were performed. hsa_circ_101237, miR-490-3p and MAPK1 expression in tissues/cells were detected by qRT-PCR. The study found an elevation in the expression of Hsa_circRNA_101237 in both NSCLC tissues and cell line. High Hsa_circRNA_101237 expression predicted poor survival in NSCLC. Meanwhile, we found that hsa_circRNA_101237 expression sponged miR-490-3p to enhance MAPK1 expression, thus significantly promoting NSCLC cell lines proliferation, migration, and invasion. MAPK1 restoration prevented NSCLC cells proliferation, migration, and invasion to be repressed due to hsa_circRNA_101237 knockdown. To sum up, as revealed by the study, hsa_circRNA_101237 promoted the expression of MAPK1 via miRNA-490-3p sponge, thus affecting the NSCLC as an important onco-circRNA.

MicroRNA-96-5p represses breast cancer proliferation and invasion through Wnt/ß-catenin signaling via targeting CTNND1.

Low miR-96-5p expression is characteristic of many cancers but its role in breast cancer (BCa) remains poorly defined. Here, the role of miR-96-5p in BC development was assessed. We demonstrate that exogenously expressing miR-96-5p inhibits the proliferative, migratory and invasive capacity of BCa cells. Mechanistically, miR-96-5p in BCa cells was found to target and downregulate catenin delta 1 (CTNND1) leading to decreased ß-catenin expression, a loss of WNT11 signaling, reduced cyclin D1 levels and lower MMP7 expression. Exogenously expressing CTNND1 alleviated these effects. In summary, we are the first to reveal that miR-96-5p inhibits the proliferative, invasive and migratory phenotypes of BCa cells the targeting of CTNND1 and subsequent Wnt/ß-catenin signaling. These data highlight miR-96-5p as a novel target for BC treatment.

Raddeanin A promotes apoptosis and ameliorates 5-fluorouracil resistance in cholangiocarcinoma cells.

BACKGROUND: Bile duct cancer is characterized by fast metastasis and invasion and has been regarded as one of the most aggressive tumors due to the absence of effective diagnosis at an early stage. Therefore, it is in the urgent demand to explore novel diagnostic approaches and therapeutic strategies for bile duct cancer to improve patient survival. Raddeanin A (RA) is extracted from the anemone raddeana regel and has been demonstrated to play antitumor roles in various cancers. AIM: To investigate the effects of RA treatment on bile duct cancer cells. METHODS: In this study, four cholangiocarcinoma cell lines (RBE, LIPF155C, LIPF178C, and LICCF) treated with RA were used to test the cell viability. The RA-associated cell functional analysis, 5-fluorouracil (5-Fu) effectiveness as well as cell cycle- and apoptosis-related protein expression were investigated. RESULTS: RA reduced cell viability in a dose-dependent pattern in four cell lines, and the migration and colony formation abilities were also impaired by RA in RBE and LIPF155C cell lines. RA sensitized cell lines to 5-Fu treatment and enhanced the effects of 5-Fu in cholangiocarcinoma. Also, RA decreased protein expression of Wee1, while the combinational effect of RA and 5-Fu decreased protein expressions of cyclooxygenase-2, B cell lymphoma 2, and Wee1 but increased protein levels of Bax, cyclin D1, and cyclin E. CONCLUSION: Taken together, the results suggest that RA acts as an anti-cancer agent and enhancer of 5-Fu in bile duct cancer cells via regulating multiple cell cycle and apoptosis-related proteins. This finding provides novel clues to exploring a novel antitumor drug for bile duct cancer.

[Meta-analysis on gemcitabine of fixed-dose rate infusion plus oxaliplatin as first-line therapy for advanced pancreatic cancer].

BACKGROUND & OBJECTIVE: Recent clinical trials showed that gemcitabine (GEM) of fixed-dose rate infusion has certain effect on advanced pancreatic cancer. Some meta-analyses suggest that GEM plus cisplatin (DDP) or its analogues is better than GEM alone in treating advanced pancreatic cancer. This study was to evaluate the efficacy of GEM of fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as first-line therapy for advanced pancreatic cancer by meta-analysis. METHODS: Two reviewers performed the meta-analysis of all relative studies through searching the international literature, including MEDLINE, EMBASE, ASCO abstracts. This meta-analysis included all randomized evidences to compare GEMOX regimen with GEM alone with respect to overall survival rate and adverse events in patients with advanced pancreatic cancer. RESULTS: Two randomized controlled trials (including 869 patients) were screened from 182 reports. GEMOX regimen was better than GEM alone in terms of 6-month survival rate [risk difference (RD)=0.09, 95% confidence interval (CI)=0.03-0.16, P=0.005], 1-year survival rate (RD=0.05, 95% CI=-0.01-0.11, P=0.08), and objective remission rate (RD=0.06, 95% CI=0.02-0.10, P=0.006). WHO grade 3-4 adverse events analysis revealed that GEMOX was associated with a reduction in anemia (RD=-0.05, 95% CI=-0.08 - -0.01, P=0.01); the addition of oxaliplatin, however, significantly increased neuropathy (RD= 0.14, 95% CI=0.04-0.24, P=0.009) and nausea/vomiting (RD=0.13, 95% CI=0.08-0.18, P<0.001). The occurrence rates of neutropenia and thrombocytopenia were similar in the 2 groups. CONCLUSION: Analyses of the available evidences suggest GEMOX regimen is promising as the first-line therapy for advanced pancreatic cancer, which encourages further clinical trials.

Meta-analysis of inoperable pancreatic cancer: gemcitabine combined with cisplatin versus gemcitabine alone.

OBJECTIVES: To compare the therapeutic effects of gemcitabine (GEM) monotherapy with GEM-cisplatin (DDP) combination chemotherapy in patients with advanced stage pancreatic cancer (APCa) through meta-analysis. METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-DDP combination chemotherapy and GEM alone in APCa. A quantitative meta-analysis using updated information based on inclusion criteria from all available RCTs was carried out by two reviewers. The primary meta-analysis involved the overall survival (OS), objective remission rate (ORR) and toxicity. RESULTS: The meta-analysis included six RCTs. There was no significant advantage for the GEM-DDP combination group in 6-month survival rate (P = 0.24) or clinical benefit rate (P = 0.58). There was a marginal significant improvement for the GEM-DDP combination group in ORR (RD = 6%, P = 0.05; RD, risk difference = risk in the GEM-DDP combination group - risk in the GEM alone group). Moreover, there was a significant improvement for the combination group in 6-month TTP/TTF (RD = 9%, P = 0.02). WHO grade 3-4 toxicity was higher for the GEM-DDP combination group in terms of neutropenia (RD = 6%, P = 0.08), thrombocytopenia (RD = 8%, P = 0.17) and vomiting/nausea (RD = 11%, P = 0.07); none reached significant difference. CONCLUSION: GEM-DDP combination should not be recommended and GEM monotherapy remains the standard treatment for patients with APCa.