Natural ingredients from Chinese materia medica for pulmonary hypertension.

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition.

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT) is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. METHODS: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/ß-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo. RESULTS: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of ß-catenin, inhibited wnt/ß-catenin signaling pathway. CONCLUSION: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

[Analysis of the status of DACH1 gene promoter methylation in endometrial carcinoma and its clinical significance].

OBJECTIVE: To analyze the status of DACH1 gene promoter methylation and explore its association with the expression of DACH1 gene promoter methylation and clinical significance of endometrium carcinoma (EC). METHODS: From February 2004 to August 2008, a total of 80 EC tissue samples with comprehensive surgical pathology staging were collected and used for this study. Twenty normal endometrium tissues in 2008 were abstained from the fractional curettage because of dysfunctional uterine bleeding as control. All samples were confirmed pathologically. Methylation specific PCR (MSP) was performed to detect the promoter methylation of DACH1 gene, and analyze its influence on the expression of DACH1 and the relationship between DACH1 promoter methylation and clinicopathological factors in EC. DACH1 protein expression was detected by western blot. Chi-square test and Pearson test were used for statistical analysis. RESULTS: The rate of promoter methylation of DACH1 gene in the EC tissues was significantly higher than that in the normal endometrium issues (30% vs. 5%, P < 0.05). There was an association between the expression of DACH1 and DACH1 gene promoter methylation (r = -0.30, P < 0.01). There was statistical difference between the methylation of DACH1 and the pathological grade (P < 0.05) or histological type (P < 0.05). But DACH1 gene methylation was not related with the age, stage, myometrial invasion depth and lymphnode metastasis (P > 0.05). CONCLUSIONS: DACH1 gene promoter methylaion could lead to a decrease or absence in the DACH1 expression in EC. The promoter methylation of DACH1 gene may induce the inhibition of DACH1 expression, which might be one of the mechanisms of DACH1 gene inactivation in human EC.

Aberrant expression of chemokine receptor CCR4 in human gastric cancer contributes to tumor-induced immunosuppression.

The chemokine receptor CCR4 is preferentially expressed on certain immune cells and some hematological tumor cells, which play pivotal roles in suppression of host immune response. However, the reasons for the upmodulation of CCR4 and its immune functions in solid tumors remain unclear. Herein, we aimed to determine the expression profiles of CCR4 in gastric cancer cells and its role in regulating antitumor immunity. CCR4 expression was assessed in 63 cases of gastric carcinomas by immunohistochemistry. We found cancer cells in lymphocyte-rich carcinomas more frequently showed moderate to strong positive staining for CCR4 than those in conventional carcinomas (P = 0.041), and also found a positive relationship between expression of CCR4 and tumor necrosis factor-α (P = 0.012). Stimulation of gastric cell lines with various cytokines showed that tumor necrosis factor-α uniquely upmodulated CCR4 expression through activation of nuclear factor-κB. Additional coculture experiments showed the forced expression of CCR4 in SGC-7901 cells caused a significant reduction of γ-interferon and elevation of interleukin-10 secretion in the supernatants from cocultured SGC-7901 cells and PBMCs. In addition, granzyme A production in cancer cell-cocultured CD56(+) natural killer cells was significantly downregulated. Inhibition of the overexpressed CCR4 in cancer cells by an inhibitor of CCR4, compound 39, proved to partly restore the antitumor immunity in respect of the inverse changes in those factors. Our studies suggest that the aberrant expression of CCR4 in human gastric cancer could contribute to tumor-induced immunosuppression. Conceivably, downmodulation of CCR4 expression could be a promising immunotherapy for human gastric cancer.

Lymphangiogenic characteristics of triple negativity in node-negative breast cancer.

PURPOSE: Triple-negativity breast cancer (TNBC), being negative for the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, represents a subgroup of breast cancer with a poor clinical outcome. The aim of the study was to determine whether TNBC is associated with lymphangiogenesis in node-negative breast carcinomas. METHODS: The authors investigated the clinicopathologic characteristics, lymphatic vessel density (LVD), and expression of 2 lymphangiogenic factors, vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D), in 21 lymph node-negative TNBCs and 70 lymph node-negative non-TNBCs. RESULTS: TNBC correlated with younger age (below 35 year) and higher histological grade. It also correlated with a higher intratumoral and peritumoral LVD, positive lymphatic invasion, and positive VEGF-C and VEGF-D expression. CONCLUSIONS: For the first time, this study indicated a link between triple-negativity breast cancer and lymphangiogenesis. Lymphangiogenesis might help explain the special malignant phonotype of breast cancer, and lymphangiogenesis inhibitors might be a novel choice for triple-negativity breast cancer patients.

[Effects of planting density and nitrogen application rate on soil microbial activity under wheat/forage rape multiple cropping].

A field experiment was conducted to study the effects of planting density and nitrogen application rate on the topsoil (0-15 cm) microbial activity under wheat/forage rape multiple cropping. The results showed that multiple-cropping forage rape with wheat could significantly increase soil microbial biomass C (Cmic), soil microbial biomass N (Nmic), soil bacteria number (SBN), soil fungi number (SFN) and soil actinomyces number (SAN), but decrease soil microbial biomass C/N (Cmic/Nmic). The Cmic/Nmic and SBN increased with increasing planting density of forage rape, while Nmic and SAN were in adverse. SFN increased significantly with increasing nitrogen application rate, but Cmic and Nmic decreased first, increased then, and decreased again, with the highest in treatment 1000 kg x hm(-2) N. Also with increasing nitrogen application rate, the SFN and SAN during harvest stage of forage rape decreased first and increased then, while the SAN during seedling stage increased first and decreased then. Soil microbial activities at rape harvest stage were all higher than those at seedling stage, except for SAN in treatment 600 kg x hm(-2) N. SBN and SAN were positively correlated with Cmic and Nmic, but negatively correlated with/Nmic. No significant correlation was observed between SFN and Cmic, and SMBN and Cmic/Nmic.

Magnetic resonance axillography for preoperative diagnosis of the axillopectoral muscle (Langer's axillary arch): a case report.

The axillary arch of Langer is the most common muscular variation in the axilla. Recognition of anatomic variations is important for surgeons to perform safe axillary surgery. We describe a case of a woman with breast cancer, in whom sentinel lymph node biopsy was successfully performed and the presence of this anomaly preoperatively diagnosed by magnetic resonance axillography.

Anastrozole-induced remission of diaphragmatic paralysis from metastatic breast cancer treated with multiple prior therapies.

We describe a woman with metastatic breast cancer treated with multiple rounds of prior cytotoxic and endocrine therapies, who presented with ipsilateral diaphragmatic paralysis. The use of anastrozole, a highly selective nonsteroidal aromatase inhibitor (1 mg daily), successfully induced remission of metastatic tumors in our patient, who is partially recovering from diaphragmatic paralysis.

MR-axillography oriented surgical sampling for assessment of nodal status in the selection of patients with breast cancer for axillary lymph nodes dissection.

BACKGROUND: We have reported that magnetic resonance axillography (MR-axillography) is the best method for assessing lymph node size and representing the relation of the lymph node to normal anatomy. METHODS: The four largest nodes on MR-axillography were sampled in 62 consecutive patients with breast cancer undergoing axillary clearance. Axillary clearance yielded a mean of 17.0 (range 5-28) nodes. RESULTS: A method of preliminary sampling of four nodes in the axilla oriented by MR-axillography was assessed in all cases, 22 of whom were histologically node positive. Based on the sampled nodes, lymph node metastases were detected in 20 of 22 (91%) of the node-positive patients. Based on the sampled nodes, of the 19 patients with macrometastatic nodes, lymph node metastases were detected in all 19 (100%), but only in 1 of the 3 (33%) patients with only one micrometastatic node. CONCLUSIONS: This experience indicates that sampling the four largest nodes by MR-axillography orientation accurately identifies patients with macrometaststic nodes. This result may be comparable to that of surgical sampling performed by the most skilled surgeons.