Sublingual Nodules: Diagnostic Markers of Metastatic Breast Cancer.

OBJECTIVE: To evaluate the diagnostic significance of sublingual nodules for metastasis of patients with breast cancer and further to explore the mechanisms of sublingual nodules. METHODS: The image data of 117 in-patients with breast cancer in stage I-IV in Tianjin Medical University Cancer Institute and Hospital from December 2009 to September 2011 were assessed retrospectively. All photos of patients' tongue were recorded by the digital camera of uniform type within 1 month after serological examination and regular re-examined by computed tomography (CT), magnetic resonance imaging and positron emission tomography CT. The presence of sublingual nodules was the positive standard. Chi square test and two-independent-sample test were used to determine the diagnostic value between the status of sublingual nodules and Clinico-pathological characteristics. The optimal cut-off of uric acid (UA) level to diagnose sublingual nodules was determined by receiver operating curve (ROC) analysis. RESULTS: Breast cancer patients with sublingual nodules had a higher risk of recurrence and/or metastasis than patients without it (P<0.001). Sublingual nodules was significantly correlated with increased serum UA level (P=0.001). The optimal cut-off value of UA level to diagnose sublingual nodules was 290 µmol/L. Furthermore, the elevated serum UA level (≥290 µmol/L) was significantly related to breast cancer recurrence and/or metastasis (P<0.001). CONCLUSIONS: Sublingual nodules were potential diagnostic markers for metastatic breast cancer. The formation of sublingual nodules was associated with elevated level of serum UA.

Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment.

Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear.In this study, the Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM.CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245-0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma.A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data.

Prenatal choline supplementation attenuates spatial learning deficits of offspring rats exposed to low-protein diet during fetal period.

Prenatal intake of choline has been reported to lead to enhanced cognitive function in offspring, but little is known about the effects on spatial learning deficits. The present study examined the effects of prenatal choline supplementation on developmental low-protein exposure and its potential mechanisms. Pregnant female rats were fed either a normal or low-protein diet containing sufficient choline (1.1g/kg choline chloride) or supplemented choline (5.0g/kg choline chloride) until delivery. The Barnes maze test was performed at postnatal days 31-37. Choline and its metabolites, the synaptic structural parameters of the CA1 region in the brain of the newborn rat, were measured. The Barnes maze test demonstrated that prenatal low-protein pups had significantly greater error scale values, hole deviation scores, strategy scores and spatial search strategy and had lesser random search strategy values than normal protein pups (all P<.05). These alterations were significantly reversed by choline supplementation. Choline supplementation increased the brain levels of choline, betaine, phosphatidylethanolamine and phosphatidylcholine of newborns by 51.35% (P<.05), 33.33% (P<.001), 28.68% (P<.01) and 23.58% (P<.05), respectively, compared with the LPD group. Prenatal choline supplementation reversed the increased width of the synaptic cleft (P<.05) and decreased the curvature of the synaptic interface (P<.05) induced by a low-protein diet. Prenatal choline supplementation could attenuate the spatial learning deficits caused by prenatal protein malnutrition by increasing brain choline, betaine and phospholipids and by influencing the hippocampus structure.

Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology.

Traditional Chinese medicine (TCM) has been used to treat tumors for years and has been demonstrated to be effective. However, the underlying molecular mechanisms of herbs remain unclear. This study aims to ascertain molecular targets of herbs prolonging survival time of patients with advanced hepatocellular carcinoma (HCC) based on network pharmacology, and to establish a research method for accurate treatment of TCM. The survival benefit of TCM treatment with Chinese herbal medicine (CHM) was proved by Kaplan-Meier method and Cox regression analysis among 288 patients. The correlation between herbs and survival time was performed by bivariate correlation analysis. Network pharmacology method was utilized to construct the active ingredient-target networks of herbs that were responsible for the beneficial effects against HCC. Cox regression analysis showed CHM was an independent favorable prognostic factor. The median survival time was 13 months and the 5-year overall survival rates were 2.61% in the TCM group, while there were 6 months, 0 in the non-TCM group. Correlation analysis demonstrated that 8 herbs closely associated with prognosis. Network pharmacology analysis revealed that the 8 herbs regulated multiple HCC relative genes, among which the genes affected proliferation (KRAS, AKT2, MAPK), metastasis (SRC, MMP), angiogenesis (PTGS2) and apoptosis (CASP3) etc.

A Novel Pharmacological Method to Study the Chinese Medicinal Formula Hua-Zheng-Hui-Sheng-Dan.

Objectives. Hua-Zheng-Hui-Sheng-Dan (HZHSD) was used as an experimental model to explore research methods of large formulae in traditional Chinese medicine (TCM) using current molecular biology approaches. Materials and Methods. The trypan blue exclusion assay was used to determine cell viability and cell numbers. Flow cytometry was used to assess cell cycle distribution and apoptosis. The concentration of cyclin D1 was analyzed by enzyme-linked immunosorbent assay. The median effect principle was used in drug combination studies. An orthogonal experimental design was used to estimate the effects of each herb at different concentrations. The HeLa xenograft mouse model was used to compare the antitumor activity of drugs in vivo. Results. Among the 35 herbs that comprise HZHSD, Radix Rehmanniae Preparata (RRP), Caesalpinia sappan (CS), Evodia rutaecarpa (ER), Folium Artemisiae Argyi (FAA), Leonurus japonicus Houtt (LJH), Tumeric (Tu), Radix Paeoniae Alba (RPA), and Trogopterus Dung (TD) effectively inhibited the proliferation of HeLa and SKOV3 cells. Only RRR had an effect on HeLa and SKOV3 cell viability. According to the median effect principle, Angelica sinensis (Oliv.) (AS), Tabanus (Ta), and Pollen Typhae (PT), which were proven to have a significant synergistic inhibitory effect on the proliferation of HeLa cells, were added to the original eight positive herbs. The combination of RPA and AS had a synergistic effect on inducing cell cycle S phase arrest and decreasing intracellular cyclin D1 in HeLa cells. By orthogonal experimental design, LJH and Tu were considered unnecessary herbs. The small formula (SHZHSD) consisted of RPA, AS, RRR, Ta., TD, PT, ER, CS, and FAA and was able to inhibit cell proliferation and induce cell apoptosis. The antitumor effects of HZHSD and SHZHSD were also compared in vivo. Conclusions. Through molecular biology approaches both in vitro and in vivo, research into single drugs, and analysis using the median effect principle and orthogonal experimental design, the small formula (SHZHSD) was determined from the original formula (HZHSD). SHZHSD exhibited superior antitumor activity compared with the original formula both in vitro and in vivo.

Survival Benefits of Western and Traditional Chinese Medicine Treatment for Patients With Pancreatic Cancer.

Traditional Chinese medicine (TCM) is one of the most common complementary and alternative medicines used in the treatment of patients with cancer worldwide. However, the clinical effect of TCM on patients with pancreatic cancer remains unclear. This study was aimed to explore the efficacy of TCM on selected patients with pancreatic cancer and to study the usefulness of multimodality treatment, including TCM and western medicine (WM), in pancreatic cancer.From January 2009 to October 2013, 107 patients with pancreatic cancer were included in this study. Kaplan-Meier curves were used to assess the differences in survival time. Cox regression analysis was performed to determine survival trends adjusted for clinical and demographic factors.Cox regression analysis suggested that elevated CA19-9 levels (P = 0.048), number of cycles of chemotherapy (P = 0.014), and TCM were independent prognostic factors (P < 0.001). The survival hazards ratio of TCM was 0.419 (95% confidence interval [CI], 0.261-0.671). The median overall survival (OS) was 19 months for patients with TCM treatment, while the median OS was 8 months for those without TCM treatment (P < 0.001). Patients who received multimodality treatment using TCM and WM had the best prognosis with a median OS of 19 months (P < 0.001). Patients with heat-clearing, diuresis-promoting and detoxification TCM treatment had a longer survival time (32.4 months) than those with blood-activating and stasis-dissolving (9.8 months) and tonifying qi and yang treatment (6.1 months; P = 0.008).These results indicate that TCM has an important potential value for improving the prognosis of patients with pancreatic cancer, and multimodality treatment, including TCM and WM, leads to the best prognosis. More importantly, we suggest that heat-clearing, diuresis-promoting, and detoxification TCM treatment may improve the efficacy of TCM in pancreatic cancer.