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The present study aimed to investigate whether rhamnetin induced apoptosis in human breast cancer cells and the underlying molecular mechanism of this anti cancer effect. The treatment of MCF-7 cells with rhamnetin was able to significantly inhibit cell proliferation and induce caspase-3/9 activity in a dose- and time-dependent manner, compared with untreated cells. In addition, treatment with rhamnetin was able to significantly promote the expression of p53 protein and microRNA (miR-)34a compared with untreated cells. The treatment with rhamnetin also suppressed the expression of Notch1 protein in MCF-7 cells compared with untreated cells. Subsequently, miR-24a expression was promoted in rhamnetin-treated MCF-7 cells using a miR-34a plasmid. The overexpression of miR-34a was able to significantly inhibit cell viability and induce caspase-3/9 activity in MCF-7 cells following treatment with rhamnetin. Furthermore, the overexpression of miR-34a was able to significantly promote the expression of p53 protein and miR-34a, and suppress the expression of Notch1 protein in rhamnetin-treated MCF-7 cells. Therefore, the results of the present study demonstrated that rhamnetin induced apoptosis in human breast cancer cells via the miR-34a/Notch-1 signaling pathway.

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BACKGROUND: Capecitabine monotherapy is usually used for advanced breast cancer (ABC) resistant to anthracycline and taxane, but there are still many other options too. Our meta-analysis assessed whether capecitabine monotherapy was superior or noninferior to the other regimens in ABC pretreated with anthracycline and taxane. MATERIALS AND METHODS: PubMed databases and abstracts from the proceedings of American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched for randomized controlled trials that compared capecitabine monotherapy with other regimens for ABC progression after anthracycline- and taxane-treatment. Hazard ratios (HRs) were used for progression-free survival (PFS) and overall survival (OS). Risk ratios (RRs) were used for overall response rate (ORR) and Grade 3-4 drug-related adverse events. All statistical analyses were conducted with RevMan 5.3 software, and statistical significance was defined as P < 0.05. RESULTS: In total, 4671 patients from eight trials were included. Target therapy as treatment group was involved in four trials, and the other four trials were merely chemotherapy in treatment group. Our study indicated that capecitabine monotherapy was not superior but also noninferior to the other regimens in ORR (RR = 1.32-95% confidence interval [CI] 0.98-1.77, P = 0.07), PFS (HR = 1.03, 95% CI 0.85-1.25, P = 0.76), and OS (HR = 0.96, 95% CI 0.88-1.05, P = 0.40). Subgroup analysis showed that both the other chemotherapy regimens and target drugs failed to improve efficacy compared with capecitabine monotherapy, and target drugs could shorten PFS (HR = 1.22, 95% CI 1.06-1.39, P = 0.004). Incidences of Grade 3-4 hematology toxicity in other regimens group significantly increased compared with capecitabine monotherapy. CONCLUSIONS: Our meta-analysis demonstrated that capecitabine monotherapy could be the first choice for ABC pretreated with anthracycline and taxane due to its efficacy and low toxicity.

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BACKGROUND: The purpose of this study was to compare the effects of pemetrexed and carboplatin plus bevacizumab (PC + B) versus pemetrexed and carboplatin (PC) in lung adenocarcinoma patients with EGFR non-T790M mutations after progression on first-line EGFR-tyrosine kinase inhibitors (TKIs). METHODS: Patients with EGFR-positive lung adenocarcinoma who had received second-line PC with or without bevacizumab harboring EGFR non-T790M mutations after progression on first-line EGFR-TKIs between April 2015 and 2017 at Tianjin Medical University Cancer Institute and Hospital were enrolled in the study. The primary endpoint was progression-free survival and secondary endpoints were overall survival, objective response rate, disease control rate, and safety. RESULTS: A total of 85 patients were eligible for the study: 55 and 30 cases were enrolled in the PC and PC + B groups, respectively. The median progression-free survival was prolonged with PC + B compared to PC (median 8.2 vs. 5.1 months; P = 0.037). The objective response rate was improved with PC + B compared to PC (46.7% vs. 25.5%; P = 0.047) and overall survival prolonged with PC + B compared to PC (median 26.3 vs. 19.2 months; P = 0.012). Safety was similar to previous studies of bevacizumab in non-small cell lung cancer: one patient experienced grade 3 hypertension and proteinuria but did not require the discontinuation of therapy. CONCLUSION: The addition of bevacizumab to PC was superior to PC alone as second-line therapy in patients with advanced non-T90M EGFR-positive lung adenocarcinoma. However, this result needs to be confirmed by prospective clinical trials.

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Programmed death ligand 1 (PD-L1) as one the most important immune checkpoint was verified to involve in chemotherapy resistance in non-small cell lung cancer (NSCLC). Ginsenoside Rg3 is isolated from Chinese herb-Panax ginseng which is recognized to boost immune and has anti-cancer activity against a majority of carcinomas including NSCLC. In this study, we aim to identify whether Rg3 could attenuate the PD-L1 expression induced by resistance to cisplatin and draw out the underlying mechanisms of PD-L1 in this process. Human lung cancer cell lines A549 and A549/DDP (cisplatin-resistance) were used. Cell viability was detected by MTT assay, the PD-L1, Akt and NF-κB p65 protein expression were detected using Western blot analysis, the T cells cytotoxity to tumor cells was detected by crystal violet staining living residual tumor cells after coculture of tumor cells and T cells. The results showed that Rg3 could inhibit the growth and alleviate the resistant to cisplatin of A549/DDP cells. PD-L1 was overexpression in A549/DDP cells than A549 cells. Rg3 could decrease the PD-L1 expression induced by chemoresistance and resume the T cells cytotoxity to cancer cells. NF-κB p65 and Akt were involved in the PD-L1 overexpression and restrained by Rg3. Therefore, Rg3 could be regarded as a new agent targeting PD-L1 in chemotherapy refractory NSCLC.

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BACKGROUND AND AIMS: Patients with pancreatic ductal adenocarcinoma and synchronous liver metastases (PACLM) have an extremely limited life expectancy. We performed a single-center analysis to explore the clinical results and prognostic factors of patients with PACLM receiving palliative care. METHODS: We retrospectively reviewed 189 patients undergoing palliative care at Tianjin Medical University Cancer Hospital over a 15-year period. Clinical characteristics, survival condition, and factors associated with survival were analyzed. Treatment methods included palliative bypass surgery, percutaneous transhepatic cholangiodrainage, drug analgesia, symptomatic treatment, and other nutritional or supportive measures. RESULTS: The overall survival (OS) was 3.6 months for all patients. Multivariate analysis for clinical features showed that Karnofsky performance score (KPS), ascites, cigarette smoking, primary tumor size, and lactate dehydrogenase (LDH) were prognostic variables with statistical significance (P < 0.05). The patients were classified into three groups of patients according to how many of these 5 risk factors were present: 0-1, 2, or 3-5 risk factors. The median OS of the 3 groups of patients were 5.0, 3.3, and 2.5 months, respectively, with a notable statistical significance (P < 0.0001). CONCLUSIONS: KPS<80, ascites, cigarette smoking, primary tumor size≥5 cm, and LDH≥250U/L are effective predictive factors of poor prognosis for patients with PACLM. The stratification of treatment outcome groups based on these factors facilitates evaluation of individual prognosis and can guide clinical decisions.

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Sophoridine is an alkaloid extracted from Sophora alopecuroides that has extensive pharmacological actions. In the present study, the effect of sophoridine on cell growth of human medulloblastoma and its mechanism were investigated. Human medulloblastoma D283-Med cells were incubated with 0, 0.5, 1 or 2 mg/ml sophoridine for 24, 48 or 72 h. Cell proliferation and cytotoxicity were analyzed using MTT and lactate dehydrogenase assays, respectively. Next, analyses of cell apoptosis and caspase-3/8 activity were performed using flow cytometry or spectrophotometry, respectively. Lastly, the change in FoxM1, TrkB, BDNF, NF-κB and AP-1 expression was investigated using western blot analysis. In the present study, treatment with sophoridine significantly suppressed cell growth and induced apoptosis in human medulloblastoma cells. In addition, sophoridine significantly increased cytotoxicity and caspase-3/8 activity in human medulloblastoma. Finally, it was found that sophoridine suppresses the protein expression of FoxM1, TrkB, BDNF NF-κB and AP-1 in human medulloblastoma cells. The present study suggests that sophoridine suppresses cell growth of human medulloblastoma through the inhibition of the FoxM1, NF-κB and AP-1 signaling pathway.

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OBJECTIVE: To evaluate the effects of NF-κB activation on the proliferation and apoptosis throughTLR4/MyD88 signaling pathway in human nasopharyngeal carcinoma (NPC) 5-8F cell lines. METHOD: TLR4 induced by LPS is inhibited by PE anti-human. Real-Time Quantitative PCR and Western blot were employed to evaluate the efficacy of mRNA level and protein expression. The growth inhibition rate of 5-8F by Celecoxib was evaluated with MTT method. The cell cycle and apoptosis were measured with flow cytometric method (FCM). RESULT: By using the specific inhibitor, the protein and gene expression of NF-κB and MyD88 were both significantly lower than the control group (P<. 05). Meanwhile, the down-rugulation of NF-κB could inhibit proliferation of NPC 5-8F cells and promote their apoptosis (P<0. 05). CONCLUSION: By inhibiting TLR4 / MyD88 signaling pathway, the expression of NF-κB in NPC 5-8F cells could decrease, then the cell proliferation was inhibited and cell apoptosis was induced. The results showed that TLR4 / MyD88 / NF-κB induced by LPS is an important pathway in the genesis and development of NPC. This study provides evidence for targeting research of NPC.

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OBJECTIVE: To compare the efficacy of lapatinib or lapatinib plus trastuzumab versus trastuzumab in the neoadjuvant therapy of human epidermal growth factor receptor 2 (HER-2) positive breast cancer. METHODS: MEDLINE database, American Society of Clinical Oncology (ASCO), San Antonio Breast Cancer Symposium (SABCS), European Society for Medical Oncology (ESMO) proceedings and China Biomedical Database were searched for literatures of trastuzumab or lapatinib in neoadjuvant therapy for breast cancer. There was no limit of language or time. A meta-analysis was performed for retrieved literatures meeting the inclusion criteria. RESULTS: A total of 1 794 breast cancer patients from 5 clinical trials were included. And the regimens were lapatinib plus neoadjuvant chemotherapy (n = 719), trastuzumab plus neoadjuvant chemotherapy (n = 714) and both drugs plus neoadjuvant chemotherapy (n = 361). The rate of pathological complete remission (pCR) was lower in lapatinib group than that in trastuzumab group (28.2% vs 35.4%). And the difference was statistically significant (P = 0.004). The pCR rate was significantly higher in lapatinib plus trastuzumab therapy group than that in trastuzumab group (53.2% vs 38.1%, P < 0.001). CONCLUSIONS: Lapatinib can not replace trastuzumab as a first-choice agent in neoadjuvant therapy of HER-2 positive breast cancer. Lapatinib plus trastuzumab achieves better pCR than trastuzumab so that it and may become a first-choice of neoadjuvant therapy for HER-2 positive breast cancer regardless of economic affordability for patients.

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