Risk Factors of PICC-Related Venous Thrombosis in Breast Cancer Patients Undergoing Chemotherapy.

BACKGROUND: To analyze the risk factors of a peripherally inserted central catheter (PICC)-related venous thrombosis in patients with breast cancer undergoing chemotherapy and explore its preventive measures. METHODS: Data of 780 patients with breast cancer who underwent PICC chemotherapy in our hospital from January 2014 to June 2015 were retrospectively analyzed. The incidence of catheter-related thrombosis was observed, and related factors of venous thrombosis were analyzed. RESULTS: Among the 780 patients with breast cancer, 36 developed PICC-related venous thrombosis. The incidence of which was 4.62% (36/780). The PICC retention time ranged between 60 and 136 days, and the median time was 92 days. Thrombosis was found to occur within seven days after catheterization in three patients (8.33%), between 7 and 30 days in 18 patients (50%), between 31 and 92 days in 12 patients (33.3%), and ≥92 days in three patients (8.33%). Basilic vein puncture-induced thrombosis occurred in 25 patients (3.68%), and median cubital vein and cephalic vein puncture-induced thrombosis occurred in 11 patients (10.78%). The difference was statistically significant (P = 0.001). Thrombosis was not associated with age, punctured limb, platelet count, or chemotherapy drugs (P > 0.05). CONCLUSION: Blood vessel puncture was the main factor that affected PICC-related thrombosis in breast cancer chemotherapy. The basilic vein should be the primary choice for blood vessel puncture. Prolonged catheter retention does not increase the risk of thrombosis.

Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy versus endocrine therapy only for advanced breast cancer: a systematic review and meta-analysis.

BACKGROUND: The resistance to endocrine therapy poses a significant challenge to the management of advanced breast cancer with hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her-2) negative. The purpose of this study was to further examine the efficacy and safety of cyclin-dependent kinase 4/6 inhibitors (CDK4/6Is) in combination with endocrine therapy as a recovery treatment for advanced breast cancer patients. METHODS: The risk of bias for each included study was assessed using the Cochrane Risk of Bias Tool. The Cochrane Q value, combined with the I2 statistics, were selected to be tested for heterogeneity across the studies. The generic inverse variance was used to pool the hazard ratio and 95% CI of progression-free survival (PFS) and overall survival (OS), while pooled RRs and 95% CI were conducted using the Mantel-Haenszel to appraise the overall response rate (ORR), clinical benefit rate (CBR), and any adverse effects. RESULTS: Eight random clinical trials were finally identified. The analysis showed that the duration of PFS was significantly longer in the CDK4/6Is group than in the control group (hazard ratio, 0.55; 95% CI, 0.51-0.60; P<0.00001), and treatment with CDK4/6Is-endocrine therapy resulted in longer OS than treatment with endocrine therapy only (hazard ratio, 0.79; 95% CI, 0.66-0.96; P=0.001). As for any adverse events, the analysis showed a remarkable rise in bone marrow suppression, especially neutropenia and leukopenia (respectively, RR =32.04; 95% CI, 17.14-59.90, RR =30.65; 95% CI, 16.51-56.91), but not in gastrointestinal toxicity. CONCLUSIONS: Highly selective CDK4/6Is were well tolerated, effective drugs in advanced breast cancer patients with HR-positive and Her-2 negative.

Value of the level of methylation of RASSF1A and WIF-1 in tissue and serum in neoadjuvant chemotherapeutic assessment for advanced breast cancer.

This study assessed the clinical efficacy of the neoadjuvant chemotherapy TAC scheme in treatment of patients with locally advanced breast cancer, and the value of the level of Ras association domain family 1A (RASSF1A) gene methylation and the Wnt inhibitory factor (WIF)-1 gene in tissue and serum of patients in clinical outcome prediction. In total, 126 patients were consecutively selected to receive TAC scheme (docetaxel, pirarubicin/epirubicin and cyclophosphamide) for at least four cycles with the total effective rate. The incidence of complications, progression-free survival and survival rate were recorded. Tumor tissues and peripheral blood samples collected in this study was used to detect methylation positive rate of RASSF1A and WIF-1 by methylation-specific PCR method and the relative level of expression of RASSF1A and WIF-1 mRNA by reverse transcription PCR method. Of the 126 patients, there were 18 cases with complete response (CR), 32 cases with partial response (PR), 50 cases with stable disease (SD), and 26 cases with disease progression (PD) with a total effective rate of 79.37%. Comparison on baseline data of effective group and ineffective group showed no difference (P>0.05), and comparison on adverse reactions occurrence showed no difference (P>0.05). Progression-free survival of the effective group was prolonged with a significant increase in survival rate (P<0.05). Positive rates of RASSF1A methylation and WIF-1 in tissue and serum of the patients in the effective group were significantly lower than those in the ineffective group, but the mRNA of RASSF1A and WIF-mRNA was significantly higher than the ineffective group (P<0.05). The sensitivity of clinical outcome prediction using tissue RASSF1A methylation was 67.0%, the specificity 15.4%, positive predictive value 69.0% and negative predictive value 31.0%. The above-mentioned indexes of tissue WIF-1 were 76.0, 31.4, 72.2 and 27.8, respectively. The indexes of serum RASSF1A were 85.0, 50.0, 76.2 and 23.8%, respectively, and the indexes of serum WIF-1 were 94.0, 75.0, 81.0 and 19.0%, respectively. The receiver operating characteristic curve analysis suggested that the accuracy of clinical outcome prediction using tissue RASSF1A mRNA level was 0.812. The sensitivity 85.2%, the specificity 76.3% and the critical value 0.4256. These indexes of tissue WIF-1 were 0.833, 86.7%, 75.4% and 0.3562 for CR, PR, SD and PD, respectively. These indexes of serum RASSF1A were 0.864, 88.3%, 77.4% and 0.2564, respectively, and for serum WIF-1 were 0.882, 89.4%, 73.5% and 0.1562, respectively. In conclusion, the detection of RASSF1A and WIF-1 gene methylation and level of mRNA expression in tissue and serum of patients with locally advanced breast cancer has an important application value in predicting clinical efficacy of neoadjuvant chemotherapy of the TAC scheme.

Effects and mechanism of downregulation of COX­2 expression by RNA interference on proliferation and apoptosis of human breast cancer MCF­7 cells.

The aim of the present study was to investigate the effects of RNA interference with prostaglandin-endoperoxide synthase 2 (COX­2) gene on the proliferation and apoptosis of breast cancer MCF­7 cells, as well as the underlying mechanism. The present study constructed the eukaryotic expression vector of the targeted COX­2 gene, transfected the MCF­7 cells and screened the stably expressed clone. Changes in the COX­2 gene expression in breast cancer MCF­7 cells prior to and following transfection were examined; the proliferation and apoptosis of MCF­7 cells were analyzed. Furthermore, changes in the protein levels of survivin, B-cell lymphoma 2 (Bcl­2) and Bcl-2-associated X (Bax) genes were detected. RNA interference mediated by a lentiviral expression vector significantly decreased the protein expression levels of the COX­2 gene, and therefore, the proliferation and growth of breast cancer MCF­7 cells was significantly suppressed and the apoptotic rate increased. Of note, the mRNA and protein expression levels of survivin and Bcl­2 decreased, while those of Bax increased following COX-2 silencing. RNA interference markedly deactivated the COX­2 gene, suppressed the proliferation of breast cancer MCF­7 cells, and, to a certain extent, enhanced the induced spontaneous apoptosis, which is regulated by the Bax gene. These results provided evidence for the potential applications of RNA interference of the targeted COX­2 gene in gene therapy for the treatment of breast cancer.

[Effects of cucurmosin on the cell proliferation and apoptosis in human pancreatic PANC-1 cells].

OBJECTIVE: To observe the effects of cucurmosin (CUS) on the cell proliferation and apoptosis in pancreatic PANC-1 cells. METHODS: The inhibition of CUS on the PANC-1 cell growth was observed using MTT assay. The inhibition ratio of CUS on the pancreatic orthotopic transplantation was in vivo observed in the NOD/SCID mouse model. The changes of microstructure of the apoptosis-inducing effect of CUS on PANC-1 was observed under electron microscope. The cell cycle and apoptosis after CUS intervention was detected using flow cytometry. The Caspase-3 activity after CUS treatment was detected using enzyme linked immunospecific assay (ELISA). RESULTS: Treatment with CUS at the dose of 0.125, 0.25, and 0.5 mg/kg inhibited the growth of pancreatic carcinoma PANC-1 xenografs with the ratio of 45.2%, 50.0%, and 59.7%, respectively (P < 0.05). After exposure to 10 microg/mL CUS for 24 h, most cells presented typical morphologic changes of apoptosis such as chromatin condensation and shrunken nucleus. The apoptotic cells increased. Some nuclear shrinkage and fragmentation, as well as the apoptotic body were observed when cells were exposed to CUS for 72 h. Being exposed to 0, 2.5, 10.0, and 40.0 microg/mL of the CUS for 72 h, the percentage of G0/G1 phase cells was 46.56% +/- 5.08%, 53.33% +/- 5.05%, 67.50% +/- 6.50%, and 77.00% +/- 6.73%, respectively (P < 0.05). The apoptosis ratio was 2.50% +/- 0.13%, 8.30% +/- 1.23%, 23.40% +/- 2.45%, and 48.50% +/- 3.65% shown by Annexin V/PI (P < 0.05). The Caspase-3 activity (unit) was 0.009 +/- 0.002, 0.011 +/- 0.003, 0.035 +/- 0.009, and 0.065 +/- 0.009, respectively (P < 0.05). These data showed that CUS induced the apoptosis of PANC-1 cells in a dose-dependent maner. Being exposed to 40.0 microg/mL of the CUS for 24, 48, and 72 h, the percentage of G0/ G1 phase cells was 56.60% +/- 6.65%, 67.83% +/- 6.76%, and 77.00% +/- 6.73%, respectively (P < 0.05), the apoptosis ratio was 16.51% +/- 2.97%, 38.51% +/- 2.38%, and 48.50% +/- 3.65% shown by Annexin V/PI (P < 0.05). These data showed that CUS induced apoptosis of PANC-1 cells in the G0/G1 phase of the cell cycle in a time-dependent maner. CONCLUSION: CUS significantly inhibited the growth of PANC-1 cells possibly through the G0/G1 cell cycle arrest and apoptosis.