UNC0638, a G9a inhibitor, suppresses epithelial­mesenchymal transition­mediated cellular migration and invasion in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with an aggressive clinical history, high risk of recurrence and metastasis, and shorter patient survival due to lack of targeted therapy. In the present study, UNC0638, a chemical G9a inhibitor, was identified to suppress TNBC cell invasion and migration in vitro at a non­cytotoxic concentration. In addition, UNC0638 reduced the size and number of the tumorsphere and decreased anchor­independent colony formation in the two TNBC cell lines. Evaluation of the underlying mechanism revealed that the suppressive effect of UNC0638 is associated with modulation of epithelial­mesenchymal transition through enhancing E­cadherin promoter activities and restoring its expression. Thus, the current data indicates that UNC0638 may be developed as a chemotherapeutic agent to effectively treat metastatic cancers, including TNBC.

Cod skin peptide reduces chemotherapy-induced toxicity in gastric cancer patients.

BACKGROUND AND OBJECTIVES: The present study was conducted to evaluate the effect of cod skin peptide (CSPE) on chemotherapy-induced toxicity in gastric cancer patients. METHODS AND STUDY DESIGN: A cohort of 60 gastric cancer patients for chemotherapy was randomly divided into two groups (n=30 per group), who were orally treated with either supplemental CSPE or placebo apart from chemotherapy. The hematologic and gastrointestinal toxicities experienced by the patients, as well as their Karnofsky Performance Status (KPS) as an index of quality of life was evaluated. RESULTS: Leukocyte counts and haemoglobin levels were significantly reduced in the group treated with peptide (p<0.05), while gastrointestinal toxicity was not affected (p>0.05). KPS consists of 11 categories of quality of life, and the score denoted in deciles ranges from 100 (asymptomatic, normal function) to 0 (death). The KPS score is used to evaluate a cancer patient's ability to function at work and home, the severity of symptoms, and the patient's need for personal and medical care. Treatment with CSPE significantly improved the quality of life of patients, as indicated by increased KPS scores (p<0.05). CONCLUSIONS: CSPE can potentially be considered as a food supplement that can be used to improve the quality of life of cancer patients.

Safety analysis of weekly paclitaxel plus S-1 versus paclitaxel plus 5-fluorouracil/calcium folinate as first-line therapy in advanced gastric cancer: a multicenter open random phase II trial.

PURPOSE: To report the results of a safety analysis from a phase II trial comparing administration of weekly paclitaxel plus S-1 (TS) versus paclitaxel plus 5-fluorouracil (5-FU)/calcium folinate (LV) (TLF) as first-line therapy for advanced gastric cancer. METHODS: Patients (n = 240) with previously untreated advanced gastric cancer were randomly assigned to receive either TS or TLF in a 28-day cycle for six cycles. RESULTS: The clinical features of both sets of patients were similar, with the exception of the incidence of prior chemotherapy (P>0·05). Most treatment-related adverse events occurred at similar rates in both treatment arms. However, patients receiving TS experienced an increase in all-grade especially grade 3/4 neutropenia, with an incidence of 43·7% in the TS arm and 16·3% in the TLF arm, respectively (P<0·05). Other severe adverse events were infrequent and not significantly different between the groups. CONCLUSION: The safety and tolerance of weekly paclitaxel plus S-1 or 5-FU/LV is well in untreated advanced gastric cancer patients.

[A phase II prospective randomized controlled trial of weekly paclitaxel combined with S-1 or fluorouracil for advanced gastric carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma. METHODS: Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed. RESULTS: Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different. CONCLUSIONS: Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.