CD5+MYC+ predicts worse prognosis in diffuse large B-cell lymphoma.

The dual expression of CD5 and MYC protein (DECM) on B-lymphocytes may arise at a specific stage of de novo diffuse large B-cell lymphoma (DLBCL). This study retrospectively reviewed 210 patients with de novo DLBCL at the Affiliated Hospital of Jiangnan University between 2006 and 2017. DECM was significantly correlated with a worse prognosis than that in either the CD5+ or MYC+ or CD5-MYC- patients. Furthermore, patients with DECM showed a similar outcome to MYC+BCL2+ lymphoma patients who have extremely poor survival rates. Multivariate analysis demonstrated that DECM was a significant independent predictor for overall survival (P < .0001) and progression-free survival (P < .0001) in DLBCL. DLBCL patients with DECM showed significantly inferior clinical outcomes compared to the CD5+, MYC+ or CD5-MYC- patients. Combinational therapeutic modalities might be a candidate approach to improve the prognosis of these patients.

Prognostic significance of serum aspartic transaminase in diffuse large B-cell lymphoma.

BACKGROUND: Liver function is routinely assessed in clinical practice as liver function tests provide sensitive indicators of hepatocellular injury. However, the prognostic value of enzymes that indicate hepatic injury has never been systematically investigated in lymphoma, including diffuse large B-cell lymphoma (DLBCL). METHODS: This study examined the prognostic value of baseline aspartic transaminase (AST) in DLBCL patients. The association between AST and clinical features was analyzed in 179 DLBCL patients treated from 2006 to 2016. All enrolled patients were treated with R-CHOP or R-CHOP-like chemotherapy. Log-rank test, univariable analysis, and subgroup analysis were performed to evaluate the impact of AST on survival. RESULTS: AST 33.3 U/L was considered to be the optimal threshold value for predicting prognosis. A higher AST level was associated with advanced stage (P = 0.001), poorer performance status (P = 0.014), elevated lactate dehydrogenase level (P <  0.0001), presence of B symptoms (P = 0.001), high-risk International Prognostic Index (IPI, IPI 3-5) (P = 0.002), non-germinal center B-cell subtypes (P = 0.038), hepatitis B virus surface antigen positivity (P = 0.045) and more extra nodal involvement (ENI, ENI ≥ 2) (P = 0.027). Patients with a higher AST level had a shorter overall survival (OS) (2-year OS rate, 53.6% vs. 83.6%, P <  0.001). Subgroup analysis indicated that higher AST levels have poorer prognostic values in patients without B symptoms and LDH positive groups. CONCLUSION: A pretreatment AST level is associated with OS in DLBCL patients treated with R-CHOP or similar chemotherapy regimens. A high pretreatment AST level might be a reliable prognostic factor for predicting a dismal outcome in DLBCL patients. Serum AST levels may be investigated for use as an easily determinable, inexpensive biomarker for risk assessment in patients with DLBCL.

[Effect of Brucea javanica fruit oil emulsion combined cisplatin on the growth inhibition of transplanted tumor in human ovarian cancer SKOV3 nude mice: an experimental study].

OBJECTIVE: To study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice. METHODS: Growth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot. RESULTS: The inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05). CONCLUSIONS: Intraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.

[Synergistic effect of beta-elemene injection combined paclitaxel injection on human breast cancer MB-468 cells: an in vitro study].

OBJECTIVE: To observe the synergistic effect of beta-elemene Injection (betaI) combined Paclitaxel Injection (PI) on breast cancer MB-468 cells and to study possible mechanisms. METHODS: Breast cancer MB-468 cells were treated with betaI (2.5, 5.0, 10.0, 20.0, 40.0, 80.0, 160.0, 320.0, and 640.0 microg/mL), PI (0.00100, 0.00200, 0.00400, 0.00800, 0.01600, 0.03125, 0.06250, 0.12500, and 0.25000 microg/mL), and betaI combined PI for 24 h and 48 h respectively. Cell proliferation was determined using SRB assay. Cell apoptosis and cell cycle phase distribution were detected using flow cytometry. The post-intervention expressions of cell cycle proteins [cyclin-dependent kinase (CDK1), cyclin-B1, P21(cip1), and P27(kip1)] were detected by Western blot. RESULTS: Beta-elemene or paclitaxel inhibited the growth of MB-468 cell line. The IC50 and IC20 values treated with beta-elemene for 24 h were 34.20 and 52.59 microg/mL and for 48 h were 10.15 and 17.81 microg/mL respectively, while the IC50 values treated with paclitaxel for 24 h and 48 h were 2.449 and 1.698 microg/mL respectively. Beta-elemene (20 and 40 microg/mL respectively) and Paclitaxel (0.016 and 0.008 microg/mL respectively) synergistically inhibited cell proliferation of MB-468 cells, with Q value > 1.15. Beta-elemene alone (52.59 microg/mL) apparently decreased the expression of cyclin-B1 protein. The expression of cyclin-B1 protein in the combined group was also lower than that in the PI group (1.698 microg/mL). The expression of P27(kip1) was up-regulated when compared with that in the betaI group or the PI group. CONCLUSION: Beta-elemene had synergistic effect with Paclitaxel, and its possible mechanism might be correlated with down-regulating the cell cycle protein cyclin-B1 expression and up-regulating the P27(kip1) expression.

[Comparison of the efficacy of second line EGFR TKIs followed by third line pemetrexed or the reverse sequence in the treatment of advanced lung adenocarcinoma].

OBJECTIVE: To compare the efficacy of second-line EGFR-TKIs followed by third-line pemetrexed with second-line pemetrexed followed by third-line EGFR-TKIs in patients with advanced lung adenocarcinoma. METHODS: From March 2007 to August 2008, 83 patients with advanced lung adenocarcinoma who failed standard first-line chemotherapy were included in this study. The patients who received EGFR-TKIs as second-line therapy followed by third-line pemetrexed were designated as group A (n = 45). The patients who received pemetrexed as second-line therapy followed by third-line EGFR-TKIs were designated as group B (n = 38). PFS and MST were estimated with Kaplan-Meier analysis and the difference between groups were compared with Log-rank test. RESULTS: The progression-free survival (PFS) after second-line therapy in the groups A and B was 8.05 months (95% CI, 5.90 to 10.20) and 4.20 months (95% CI, 3.33 to 5.06), respectively (P = 0.001). The PFS after second-line therapy in smokers and non-smokers was 3.69 months (95% CI, 5.00 to 7.59) and 7.12 months (95% CI, 5.51 to 8.38), respectively (P = 0.007). The PFS of male and female patients was 5.56 months (95% CI, 4.02 to 7.10) and 6.85 months (95% CI, 4.98 to 7.58), respectively (P = 0.279). The PFS after third-line therapy in groups A and B was 6.88 months (95% CI, 5.07 to 8.69) and 7.60 months (95% CI, 5.59 to 9.12) respectively, (P = 0.899). The PFS after third-line therapy in smokers and non-smokers was 4.95 months (95% CI, 2.83 to 7.05) and 8.49 months (95% CI, 6.27 to 10.76), respectively (P = 0.050). The PFS after third-line therapy in male and female patients was 5. 96 months (95% CI, 4.02 to 7.91) amd 8.38 months (95% CI, 5.68 to 11.07), respectively (P = 0.176). The MST in groups A and B was 23.60 months (95% CI, 19.23 to 28.00) and 15.58 months (95% CI, 11.85 to 19.32), respectively (P = 0.021). The MST in smokers and non-smokers was 11.99 months (95% CI, 8.55 to 15.49) and 23.18 months (95% CI, 19.33 to 27.02), respectively (P = 0.001). The MST in male and female patients was 17.40 months (95% CI, 13. 19 to 21.61) and 22.74 months (95% CI, 18.29 to 27.19), respectively (P = 0.111). CONCLUSIONS: Second line EGFR TKIs followed by third line pemetrexed regimen improves the PFS and MST compared with the regimen second line pemetrexed followed by third line EGFR TKIs in patients with advanced lung adenocarcinoma. Smoking status is an independent prognostic factor. Survival is not influenced by gender. Prospective clinical trials are needed to confirm these findings.

[Efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs as second-line treatment for patients with advanced non-small-cell lung cancer].

OBJECTIVE: To compare the efficacy and safety of docetaxol, pemetrexed and EGFR-TKIs in the second-line treatment for patients with advanced non-small cell lung cancer. METHODS: The clinical data of 170 patients with advanced non-small cell lung cancer who failed standard first-line chemotherapy were reviewed. Those who received docetaxol as second-line therapy were designated as group A (n = 60), those who received pemetrexed as second-line therapy were designated as group B (n = 49), and those who received EGFR-TKIs as second-line therapy were designated as group C (n = 61). PFS and MST were estimated by Kaplan-Meier method and the differences between groups were compared by log-rank test. RESULTS: The response rate in the groups A, B and C group was 15.0% (9/60), 24.5% (12/49) and 36.1% (22/61), respectively. The PFS after second-line therapy in the groups A, B and C was 5.49 months (95%CI: 4.03 - 6.95 months), 5.42 months (95%CI: 4.23 - 6.60 months) and 9.31 months (95%CI: 6.88 - 11.73 months), respectively (P = 0.045). The MST after second-line therapy in the groups A, B and C was 14.89 months (95%CI: 11.23 - 18.55 months), 15.81 months (95%CI: 12.11 - 19.52 months) and 17.47 months (95%CI: 13.38 - 21.56 months), respectively (P = 0.574). Regression analysis showed that the performance status score (PS) and response for second-line treatment are independent prognostic factors in each sub-group, and pathological type is an independent prognostic factor in the group C (P = 0.003). CONCLUSIONS: The safety of the three drugs used as second-line treatment for patients with advanced non-small-cell lung cancer, who failed standard first-line chemotherapy, is comparable, but the EGFR-TKIs group has the highest response rate, and the EGFR-TKIs group has the longest PFS with a statistically significant difference, while there is no significant difference in MST among the three groups. When patients receive second-line treatment, the performance status < 2 and the response rate for second-line treatment are independent prognostic factors. Furthermore, pathological type (adenocarcinoma) is also an independent prognostic factor for EGFR-TKIs as second-line treatment.

Three vascular endothelial growth factor polymorphisms (-460C>T, -2578C>A, 1612G>A) with cancer risk: a meta-analysis based on 30 case-control studies.

We evaluated cancer risk with three VEGF polymorphisms (-460C>T, -2578C>A, 1612G>A) based on current available studies. -460C>T did not appear to influence cancer risks. -2578C carriers had a 30% reduction of colorectal cancer (CRC) risk in comparison with AA homozygote (OR: 0.70, CI: 0.56-0.88). 1612G carriers had a striking 84% reduction of gastric cancer risk in comparison with AA homozygote. Multiple pair-wise comparisons suggested a recessive role for both -2578A and 1612A risk allele. Further studies with larger samples, well-matched controls and homogenous ethnic background are warranted to confirm these findings. We recommend more efforts into the investigation of 1612G>A with cancer risks.