Purpose: Secreted protein acidic and rich in cysteine (SPARC) is an extracellular glycoprotein overexpressed in various malignancies, including esophageal squamous cell carcinoma (ESCC), and is involved in tumor development and progression. This study was initially designed to investigate the biological roles of SPARC in ESCC cell lines by silencing SPARC expression.Methods: The expression of SPARC was examined in eight human ESCC cell lines. Eca109 and HKESC cell lines with high SPARC expression were selected and transiently transfected with SPARC-targeted small interfering RNAs (siRNAs) and subsequently evaluated its impact on cell proliferation, migration and invasion in vitro, as well as the underlying mechanism.Results: Knockdown of SPARC by the specified siRNAs in Eca109 and HKESC cell lines resulted in dramatically downregulation of SPARC expression, and significantly decreased cell migration and invasion involving epithelial-mesenchymal transition (EMT) in vitro. Moreover, SPARC-targeted siRNA reduced the activation of phosphorylated focal adhesion kinase (p-FAK) and extracellular regulated protein kinase (p-ERK). Furthermore, downregulation of either FAK or SPARC expression with specified siRNAs inhibited the phosphorylation of ERK and inhibited cell migration and invasion. However, decreased SPARC expression showed no impact on cell proliferation, survival or apoptosis of Eca109 and HKESC cells when comparing to control transfected groups.Conclusions: These results demonstrated that downregulation of SPARC could decrease cell migration and invasion involving EMT via the p-FAK/p-ERK pathway that might serve as a novel therapeutic target against ESCC.

Serum lactate dehydrogenase (LDH) level is predictive of prognosis in various malignancies. Nevertheless, the association between the prognosis of patients with advanced triple-negative breast cancer (TNBC) and LDH is not well understood. This explorative and retrospective study was conducted to clarify the issue. We found that abnormal baseline LDH levels (> 250 IU/L) were significantly associated with age (> 40 y vs. ≤ 40 y, OR: 0.383, P = 0.031) and number of metastatic sites (2 vs. 1, OR: 4.619, P = 0.006; ≥ 3 vs. 1, OR: 4.727, P = 0.002). The progression-free survival (PFS) of patients with post-treatment LDH higher than baseline (Group 1) was significantly shorter than that in patients with LDH decreased to normal (Group 3) and those with normal baseline and post-treatment LDH (Group 4) (Group 3 vs. Group 1, HR: 0.517, P = 0.038; Group 4 vs. Group 1, HR: 0.346, P < 0.001). Overall survival (OS) in patients with abnormal baseline LDH was significantly shorter than in patients with normal baseline LDH (abnormal vs. normal, HR: 2.073, P < 0.001). Patients whose post-treatment LDH decreased to normal had the most objective response (complete and partial responses) rate after first-line chemotherapy (Group 3 vs. Group 1, OR: 0.074, P < 0.001). In this exploratory analysis, baseline LDH levels associated with OS, while LDH changes after first-line chemotherapy associated with PFS and the chemotherapeutic response. These results show that LDH may have important prognostic value for the survival and chemotherapeutic response in patients with advanced TNBC.

Background: This study was initially designed to examine whether oxaliplatin-based regimen was superior to cisplatin-based regimen in tumour remission as first-line chemotherapy for advanced gastric cancer (GC). Methods: Literature in EMBASE, PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was searched. Only phase II or III randomized controlled trials (RCTs) comparing the effectiveness and safety between oxaliplatin-based and cisplatin-based regimens as first-line treatment for advanced GC were selected. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. The primary endpoints were complete remission rate (CRR), partial remission rate (PRR), objective response rate (ORR), and disease control rate (DCR). The second endpoint was the toxicity response. Results: 2,140 patients from six phase II or III RCTs were included. Compared to cisplatin-based therapy, subjects who received oxaliplatin-based treatment had significantly higher PRR (OR: 1.25, 95%CI: 1.05-1.48, P =0.01, I 2 =0%), ORR (OR: 1.21, 95%CI: 1.02-1.44, P =0.03, I 2 =0%) and DCR (OR: 1.76, 95%CI: 1.31-2.38, P =0.0002, I 2 =25%), but not CRR (OR: 0.70, 95%CI: 0.37-1.31, P =0.27, I 2 =0%). In addition, oxaliplatin-based therapy significantly decreased all grades of leukopenia, neutropenia, anemia, febrile neutropenia, nausea, stomatitis, creatinine elevation and thromboembolism, as well as grades 3-4 of leukopenia, neutropenia, anemia and febrile neutropenia than cisplatin-based regimen. However, oxaliplatin-based treatment strikingly increased the risk of thrombocytopenia, sensory neuropathy, diarrhea, fatigue and liver dysfunction. Conclusions: Oxaliplatin-based regimen is superior to cisplatin-based regimen in tumour remission as first-line chemotherapy for advanced GC, and is associated with less toxicity and better tolerability.

Background DNA aneuploidy has attracted growing interest in clinical practice. Nevertheless, its prognostic value in gastric cancer patients remains controversial. This meta-analysis aims to explore the impact of DNA ploidy status on the survival of gastric cancer patients. Methods We used PubMed and Web of Science databases to retrieve relevant articles. The correlation between DNA aneuploidy and the clinicopathological features of gastric cancer, such as stage, depth of invasion (T), lymph node metastasis (N), distant metastasis (M), differentiation (G), tumor types (Lauren classification) and overall survival (OS) were evaluated. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were collected carefully from each article OS was presented with HRs. The relationships between DNA aneuploidy and each characteristic were analyzed using risk ratios (RR) and a 95% confidence interval (CI). Significance was established using P < 0.05. Funnel plot was conducted to detect the publication bias. Results After careful selection, 25 studies involving 3449 cases were eligible for further analyses. Patients with DNA aneuploidy were considered at risk of more advanced stages (stage III-IV vs. stages I-II, RR = 1.23; 95% CI, 1.07 to 1.42; P = 0.003), lymph node metastasis (N+ vs. N-: RR = 1.43; 95% CI, 1.12 to 1.82, P = 0.004), and intestinal tumor type (intestinal vs. diffuse: RR = 1.45; 95% CI, 1.02 to 2.06; P = 0.04). And an adverse relation was observed between DNA aneuploidy and tumor differentiation. While no association was found between DNA aneuploidy and distant metastasis ( P = 0.42) nor depth of tumor invasion ( P = 0.86). Regarding overall survival, aneuploid tumors were associated with worse survival in all patients ( P < 0.00001). Conclusions We found that DNA aneuploidy was an important predictor for gastric cancer patients, and should be used as a potential biomarker for further classification in gastric cancer. Electronic supplementary material The online version of this article (10.1186/s12885-019-5869-9) contains supplementary material, which is available to authorized users.