Fuzheng Xiaoai Decoction 1 ameliorated cancer cachexia-induced muscle atrophy via Akt-mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Xiaoai Decoction 1 (FZXAD1) is a clinical experience prescription for the treatment of cancer patients at an advanced stage. FZXAD1 has been used for more than 10 years in the clinic and can effectively improve the deficiency syndrome of cancer patients. However, its mechanisms need further clarification. AIM OF THE STUDY: To check the effects of FZXAD1 in colon 26 (C26) cancer cachexia mice and try to clarify the mechanisms of FZXAD1 in ameliorating cancer cachexia symptoms. MATERIALS AND METHODS: An animal model of cancer cachexia was constructed with male BALB/c mice bearing C26 tumor cells. Food intake, body weight and tumor size were measured daily during the animal experiment. Tissue samples in different groups including tumor and gastrocnemius muscle, were dissected and weighed at the end of the assay. Serum biochemical indicators such as total protein (TP), glucose (GLU) and alkaline phosphatase (ALP) were also detected. Network pharmacology-based analysis predicted the possible targets and signaling pathways involved in the effects of FZXAD1 on cancer cachexia therapy. Western blotting assays of the gastrocnemius muscle tissues from C26 tumor-bearing mice were then used to confirm the predicted possible targets of FZXAD1. RESULTS: The results of animal experiments showed that FZXAD1 could ameliorate cancer cachexia by alleviating the muscle wasting as well as kidney atrophy and increasing the body weight of cancer cachexia mice. AKT1, MTOR, MAPK3, HIF1A and MAPK1 were predicted as the core targets of FZXAD1. Western blotting confirmed the prediction that FZXAD1 increased the expression levels of phosphorylated Akt and mTOR in the muscle tissues. In addition, FZXAD1 treatment obviously ameliorated the increased levels of HIF-1α and phosphorylated Erk1/2 in C26 tumor-bearing mice. CONCLUSION: FZXAD1 effectively ameliorated cancer cachexia in an animal model of mice, which is consistent with its efficacy in the treatment of cancer patients. The mechanisms of FZXAD1 might be mainly based on its alleviating effects on muscle atrophy by activating the Akt-mTOR pathway and thus helping to maintain body weight.

Treatment of grey zone lymphoma using the R-CODOX-M/R-IVAC protocol: Two case reports.

RATIONALE: We report our experience with 2 patients diagnosed with grey zone lymphoma (GZL). The histopathological characteristics of lymphomatous tissues in these patients ranged between those of diffuse large B-cell lymphoma (DLBCL) and the classical Hodgkin lymphoma. PATIENT CONCERNS: A 52-year-old female presented to the hospital with a history of lower abdominal pain of metastatic origin for 2 days. She was diagnosed with acute appendicitis and had undergone emergency surgery. A 17-year-old male was admitted to the hospital because of acute left upper abdomen pain. DIAGNOSES: Both patients are diagnosed of GZL primarily based on histopathology. INTERVENTIONS: Both patients were treated with R-CODOX-M/R-IVAC regimen for 4 to 6 cycles. OUTCOMES: The short-term curative effect was complete response; no recurrence was observed as of 32-month follow-up. LESSONS: R-CODOX-M/IVAC regimen exhibited relatively good curative effect. International Prognostic Index score and lactate dehydrogenase level may correlate with prognosis of these patients.

Clinical observation of Shuanghuang Shengbai Granule () on prevention and treatment of myelosuppression caused by chemotherapy in cancer patients.

OBJECTIVE: To study the efficacy and safety of Shuanghuang Shengbai Granule (, SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer patients caused by chemotherapy. METHODS: A total of 330 patients were randomly assigned to the treatment group (220 cases, analysed 209 cases) and the control group (110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The patients in the treatment group at the first day of chemotherapy started to take SSG for 14 days, while the patients in the control group took Leucogon Tablets. The changes of the blood routine, clinical symptoms and immune function in both groups were observed for safety and efficacy evaluation. RESULTS: At the 7th day of chemotherapy, the white blood cells (WBCs) level in the treatment group was significantly higher than that in the control group (P<0.05). After treatment, the WBCs rate in the normal range accounted for 50.2% in the treatment group, the myelosuppression of WBCs and neutrophil were mainly grade I, while 8.1% and 5.7% of patients emerged grade III and grade IV myelosuppression, respectively. The incidence of myelosuppression of the treatment group was significantly lower than that of the control group (P<0.05). The total effective rate of Chinese medicine syndrome in the treatment group was significantly higher than that in the control group (84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were maintained in the normal range. Compared with that before treatment, the levels of CD3+ and CD4+ cells were significantly increased in the treatment group after treatment (P<0.05). The discrepancy of CD3+ and CD4+ cell activity before and after treatment in both groups were significantly different (P<0.05). No obvious adverse event occurred in both groups. CONCLUSION: SSG had a protection effect on bone marrow suppression, and alleviated the clinical symptoms together with clinical safety.

Progesterone and Src family inhibitor PP1 synergistically inhibit cell migration and invasion of human basal phenotype breast cancer cells.

Basal phenotype breast cancer is one of the most aggressive breast cancers that frequently metastasize to brain. The role of sex hormones and their receptors in development of this disease is largely unclear. We demonstrated that mPRα was expressed at a moderate level in a brain metastatic BPBC cell line MB231Br, which was derived from the parent mPRα undetectable MB231 cells. It functioned as an essential mediator for progesterone induced inhibitory effects on cell migration of MB231Br and, when coincubated with PP1, synergistically enhanced the progesterone's inhibitory effect on cell migration and invasion in vitro. Progesterone and PP1 cotreatment induced a cascade of molecular signaling events, such as dephosphorylation of FAK, downregulation of MMP9, VEGF, and KCNMA1 expressions. Our in vitro study demonstrated that mPRα was expressed and functioned as an essential mediator for progesterone induced inhibitory effects on cell migration and invasion in BPBC cells. This inhibitory effect was enhanced by PP1 via FAK dephosphorylation, MMP9, VEGF, and KCNMA1 downregulation mechanisms. Our study provides a new clue toward the development of novel promising agents and pathways for inhibiting nuclear hormonal receptor-negative and endocrine-resistant breast cancers.

Folate intake and the risk of breast cancer: a dose-response meta-analysis of prospective studies.

BACKGROUND: Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs) for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR) for highest versus lowest category = 0.97; 95% CI, 0.90-1.05; P = 0.451). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RR = 0.99; 95% CI, 0.98-1.01; P = 0.361). Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (P = 0.007) and revealed that a daily folate intake of 200-320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg. CONCLUSION/SIGNIFICANCE: Our study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer.

Association between folate intake and the risk of lung cancer: a dose-response meta-analysis of prospective studies.

BACKGROUND: Studies have reported inconsistent results regarding the existence of an association between folate intake and the risk of lung cancer. The purpose of this study was to summarize the evidence from prospective cohort studies regarding this relationship by using a dose-response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: In September 2013, we performed electronic searches in PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate intake on the incidence of lung cancer. Only prospective cohort studies that reported the effect estimates about the incidence of lung cancer with 95% confidence intervals (CIs) for more than 2 categories of folate intake were included. Overall, we examined 9 cohort studies reporting the data of 566,921 individuals. High folate intake had little effect on the risk of lung cancer (risk ratio [RR], 0.92; 95% CI, 0.84-1.01; P = 0.076). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of lung cancer (RR, 0.99; 95% CI, 0.97-1.01; P = 0.318). Subgroup analysis suggested that the potential protective effect of low folate intake (100-299 µg/day) was more evident in women than men, while the opposite was true of high folate intake (>400 µg/day). Finally, subgroup analyses of a 100 µg/day increment in folate intake indicated that its potential protective effect was more evident in men than in women. CONCLUSION/SIGNIFICANCE: Our study revealed that folate intake had little or no effect on the risk of lung cancer. Subgroup analyses indicated that an increased folate intake was associated with a reduced risk of lung cancer in men. Furthermore, low folate intake may be a protective factor for women, and high folate intake for men.

Effect of omega-3 fatty acid supplementation on cancer incidence, non-vascular death, and total mortality: a meta-analysis of randomized controlled trials.

BACKGROUND: Omega-3 fatty acids are known to prevent cardiac death. However, previous observational studies have suggested that omega-3 fatty acids are associated with cancer risk in adults. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of omega-3 fatty acids on the risk of cancer incidence, nonvascular death, and total mortality. METHODS: In February 2013, we performed electronic searches in PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials on cancer incidence, nonvascular death, and total mortality. Relative risk (RR) was used to measure the effect of omega-3 fatty acid supplementation on the risk of cancer incidence, nonvascular death, and total mortality using a random-effect model. The analysis was further stratified by factors that could affect the treatment effects. RESULTS: Of the 8,746 identified articles, we included 19 trials reporting data on 68,954 individuals. These studies reported 1,039 events of cancer, 2,439 events of nonvascular death, and 7,025 events of total mortality. Omega-3 fatty acid supplementation had no effect on cancer incidence (RR, 1.10; 95% CI: 0.97-1.24; P = 0.12), nonvascular death (RR, 1.00; 95% CI: 0.93-1.08; P = 1.00), or total mortality (RR, 0.95; 95% CI: 0.88-1.03; P = 0.24) when compared to a placebo. Subgroup analysis indicated that omega-3 fatty acid supplementation was associated with a reduction in total mortality risk if the proportion of men in the study population was more than 80%, or participants received alpha-linolenic acid. CONCLUSIONS: Omega-3 fatty acid supplementation does not have an effect on cancer incidence, nonvascular death, or total mortality.

Intracoronary versus intravenous administration of abciximab in patients with acute coronary syndrome: a meta-analysis.

BACKGROUND: Abciximab is a widely used adjunctive therapy for acute coronary syndrome (ACS). However, the effect of intracoronary (i.c.) administration of abciximab on cardiovascular events remains unclear when compared with intravenous (i.v.) therapy. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases and reference lists of articles and proceedings of major meetings for obtaining relevant literature. All eligible trials included ACS patients who received either i.c. administration of abciximab or i.v. therapy. The primary outcome was major cardiovascular events, and secondary outcomes included total mortality, reinfarction, and any possible adverse events. Of 660 identified studies, we included 9 trials reporting data on 3916 ACS patients. Overall, i.c. administration of abciximab resulted in 45% reduction in relative risk for major cardiovascular events (RR; 95% confidence interval [CI], 24-60%), 41% reduction in RR for reinfarction (95% CI, 7-63%), and 44% reduction in RR for congestive heart failure relative to i.v. therapy (95% CI, 8-66%); however, compared to i.v. therapy, i.c. administration of abciximab had no effect on total mortality (RR, 0.69; 95% CI, 0.45-1.07). No other significant differences were identified between the effect of i.c. abciximab administration and i.v. therapy. CONCLUSIONS/SIGNIFICANCE: I.c. administration of abciximab can reduce the risk of major cardiovascular events, reinfarction, and congestive heart failure when compared with i.v. therapy.

[Experimental study on the inhibitory effect of Carboxymethyl Pachymaram on hepatitis B virus expression from transfected cells].

OBJECTIVE: To observe the anti-HBV activity of Carboxymethyl Pachymaram (CMP) on the culturing of 2.2.15 cell line. METHODS: Concentrations of 20.0 g/L, 12.0 g/L, 6.0 g/L, 3.0 g/L, 1.5 g/L of CMP were used to evaluate its toxicity to the cell line and the inhibition rates of the secretion of HBsAg and HBeAg in the cultured 2.2.15 cell line. RESULTS: Experiments showed that the mean half toxicity concentration of CMP for 2.2.15 cell line was 13.6 g/L and concentration for 50% inhibition of the secretion of HBsAg and HBeAg were 4.45 g/L, 5.61 g/L and TI were 3.06 and 2.42. CMP showed stronger effect on anti-HBV than aciclovir. CONCLUSION: CMP has good inhibitory effect on the secretion of HBsAg and HBeAg on cultured cell line 2.2.15.