[Retracted] Inhibition airway remodeling and transforming growth factor­ß1/Smad signaling pathway by astragalus extract in asthmatic mice.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the P­smad2 western blotting data shown in Fig. 7 were strikingly similar to data appearing in different form (namely, the bands appeared in the reverse orientation) in Fig. 4A in another article [Lv Z­D, Na D, Liu F­N, Du Z­M, Sun Z, Li Z, Ma X­Y, Wang Z­N and Xu H­M: Induction of gastric cancer cell adhesion through transforming growth factor­beta1­mediated peritoneal fibrosis. J Exp Clin Cancer Res 29: 139, 2010], which was written by mostly different authors at different research institutes (the author Zheng­Hai Qu did appear as an author on both papers). Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, and due to a lack of overall confidence in the presented data, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 29: 564­568, 2012; DOI: 10.3892/ijmm.2011.868].

Clinicopathological characteristics and prognosis of early-stage HER2 low-expression breast cancer: A single-center retrospective study.

Background: Owing to the emergence of drugs targeting human epidermal growth factor receptor 2 (HER2), remarkable prognostic enhancement has been seen for patients with HER2-positive breast carcinoma. However, anti-HER2 medicines are applicable merely to individuals with HER2-positive tumors, and the benefit for those with low HER2 expression is unclear. The DESTINY-Breast04 phase III and RC48 clinical trial results showed the benefit of antibody-drug couples for low HER2-expressing individuals with breast carcinoma, challenging the traditional dichotomy between HER2-negative and -positive tumors. Hence, the purposes of the present work are to explore the clinicopathological traits and prognostic differences in the HER2-low expression Chinese population with early-stage breast carcinoma. Methods: Data from the database of the Breast Center of the Affiliated Hospital of Qingdao University were collected from January 2008 to December 2017. We screened a total of 4,598 patients, of which 2,837 had HER2-0 tumors and 1,761 had HER2-low tumors. Additionally, clinicopathological characteristics, survival, and prognostic information were obtained. Difference comparisons were made between HER2-0 and HER2-low groups regarding the clinical traits and outcomes. Results: We enrolled 4598 patients, with the HR-positive subjects suffering from HER2-low breast carcinoma higher in proportion than the HR-negative patients. In contrast to HER2-0 tumors, the HER2-low tumors were linked to an older median age at diagnosis, T1 tumors, N1 stage, a higher Ki-67 index, as well as inferior histological grade. Insignificant inter-group difference was noted regarding overall survival (OS), although the HER2-0 group exhibited better disease-free survival (DFS) than the HER2-low group for the entire (P = 0.003), lymph node-negative (P = 0.009) and HR-positive (P = 0.007) populations. According to the multivariate regression finding, low HER2 expression was an inferior DFS prognostic factor in the HER2-negative population with early-stage breast cancer (HR,1.33;95% CI, 1.06-1.66; P = 0.013). Conclusion: The clinical traits of the HER2-low carcinomas differed from those of HER2-0 tumors. Despite the insignificant inter-group difference in OS, the differences in DFS were found for the overall, lymph node-negative and HR-positive subjects, suggesting the possibility of HER2-low as an inferior prognostic factor for disease progression in early-stage breast cancer.

[Retracted] TGF­ß1 induces peritoneal fibrosis by activating the Smad2 pathway in mesothelial cells and promotes peritoneal carcinomatosis.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the fluorescence microscopy data shown in Fig. 6A and B were strikingly similar to data appearing in different form in Fig. 7 in a previously published paper [Lv Z­D, Na D, Liu F­N, Du Z­M, Sun Z, Li Z, Ma X­Y, Wang Z­N and Xu H­M: Induction of gastric cancer cell adhesion through transforming growth factor­beta1­mediated peritoneal fibrosis. J Exp Clin Cancer Res 29: 139, 2010], which featured some of the same authors, although the data were shown to portray results obtained under different experimental conditions. Furthermore, the data in Fig. 7A for the 'TGF­ß1' and the 'TGF­ß1 + siRNAcon' experiments contained an overlapping section, such that these data appeared to have been derived from the same original source, even though they were intended to show the results from differently performed experiments. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, and due to a lack of overall confidence in the presented data, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 29: 373­379, 2012; DOI: 10.3892/ijmm.2011.852].

Efficacy and Safety of Albumin-Bound Paclitaxel Compared to Docetaxel as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer.

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as neoadjuvant chemotherapy (NAC) for breast cancer remains controversial. We conducted a retrospective study to compare the efficacy and safety of nab-paclitaxel with those of docetaxel as neoadjuvant regimens for HER2-negative breast cancer. METHODS: In this retrospective analysis, a total of 159 HER2-negative breast cancer patients who had undergone operation after NAC were consecutively analyzed from May 2016 to April 2018. Patients were classified into the nab-paclitaxel group (n = 79, nab-paclitaxel 260 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) and the docetaxel group (n = 80, docetaxel 75 mg/m2, epirubicin 75 mg/m2, and cyclophosphamide 500 mg/m2) according to the drug they received for neoadjuvant treatment. The efficacy and adverse events were evaluated in the two groups. RESULTS: The pathological complete response (pCR)(ypT0/isN0) rate was significantly higher in the nab-paclitaxel group than in the docetaxel group (36.71% vs 20.00%; P = 0.031). The multivariate analysis revealed that therapeutic drugs, lymph node status, and tumor subtype were the most significant factor influencing treatment outcome. At a median follow-up of 47 months, disease-free survival (DFS) was not significantly different in those assigned to nab-paclitaxel compared with docetaxel (82.28% vs 76.25%; P = 0.331). The incidence of peripheral sensory neuropathy in the nab-paclitaxel group was higher than that in the docetaxel group (60.76% vs 36.25%; P = 0.008), while the incidence of arthralgia was observed more frequently in the docetaxel group (57.50% vs 39.97%; P = 0.047). CONCLUSIONS: Compared with docetaxel, nab-paclitaxel achieved a higher pCR rate, especially those patients with triple-negative breast cancer or lymph node negative breast cancer. However, there was no significant difference in DFS between the two groups. This study provides a valuable reference for the management of patients with HER2-negative breast cancer.

miR-135b promotes proliferation and metastasis by targeting APC in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The aim of our study was to investigate the functional role of microRNA-135b (miR-135b) in TNBC. A real-time polymerase chain reaction assay was used to quantify miR-135b expression levels in 90 paired TNBC tissue and adjacent normal tissue samples. Wound-healing and transwell assays were performed to evaluate the effects of miR-135b expression on the migration and invasion of TNBC cells. Luciferase reporter and western blot analyses were used to verify whether the mRNA encoding APC is a major target of miR-135b. In the current study, we found that miR-135b was highly expressed in TNBC tissue and cells, and the expression levels were correlated with lymph node status and TNM stage. In TNBC cells, the ectopic expression of miR-135b promoted cell proliferation and invasion in vitro. In addition, our study proved that the overexpression of miR-135b significantly suppressed APC expression by targeting the 3'-untranslated region of APC, whereas enhanced APC expression could partially abrogate the miR-135b-mediated promotion of carcinogenic traits in TNBC cells. Taken together, our study demonstrated that miR-135b expression promoted the proliferation and invasion of TNBC by downregulating APC expression, indicating that miR-135b may serve as a promising target for the treatment of TNBC patients.

DLC-3 suppresses cellular proliferation, migration, and invasion in triple-negative breast cancer by the Wnt/ß-catenin pathway.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Our study investigated the functional role of DLC-3 in TNBC. The expression of DLC-3 was assessed by immunohistochemistry in TNBC to evaluate the clinicopathologic significance of DLC-3. Recombinant lentiviral vectors encoding the DLC-3 gene were constructed for transfection into MDA-MB-231. Real-time qPCR and western blot analysis were employed to evaluate the expression of DLC-3, ß-catenin, GSK-3ß and c-myc in DLC-3-transfected cells. Moreover, cell proliferation assays, cell colony formation assays, and cell migration and invasion assays were performed to elucidate the role of DLC-3 in TNBC development and progression. Our data revealed that DLC-3 was downregulated in TNBC, and its expression level was associated with lymph node status and differentiation grade in breast cancer. Both real-time qPCR and western blot analyses showed that the DLC-3 gene and protein were overexpressed in the DLC-3-transfected MDA-MB-231 cells. In addition, the expression of GSK-3ß was upregulated and the expression of ß-catenin and c-myc gene was downregulated in the DLC-3-transfected cells. Furthermore, DLC-3 overexpression inhibited cell proliferation, colony formation, migration, and invasion in vitro. DLC-3, functioning as a tumor-suppressor gene, inhibits cell growth and invasion in TNBC, possibly through regulation of the Wnt/ß-catenin signaling pathway.

MiR-212-5p Suppresses the Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer by Targeting Prrx2.

BACKGROUND/AIMS: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Our study investigated the functional role of miR-212-5p in TNBC. METHODS: Realtime PCR was used to quantify miR-212-5p expression levels in 30 paired TNBC samples and adjacent normal tissues. Wound healing and Transwell assays were used to evaluate the effects of miR-212-5p expression on the invasiveness of TNBC cells. Luciferase reporter and Western blot assays were used to verify whether the mRNA encoding Prrx2 is a major target of miR-212-5p. RESULTS: MiR-212-5p was downregulated in TNBC, and its expression levels were related to tumor size, lymph node status and vascular invasion in breast cancer. We also observed that the miR-212-5p expression level was significantly correlated with a better prognosis in TNBC. Ectopic expression of miR-212-5p induced upregulation of E-cadherin expression and downregulation of vimentin expression. The expression of miR212-5p also suppressed the migration and invasion capacity of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. Moreover, our study observed that miR-212-5p overexpression significantly suppressed Prrx2 by targeting its 3'-untranslated region (3'-UTR) region, and Prrx2 overexpression partially abrogated miR-212-5p-mediated suppression. CONCLUSIONS: Our study demonstrated that miR-212-5p inhibits TNBC from acquiring the EMT phenotype by downregulating Prrx2, thereby inhibiting cell migration and invasion during cancer progression.

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.

Blocking TGF-ß1 by P17 peptides attenuates gastric cancer cell induced peritoneal fibrosis and prevents peritoneal dissemination in vitro and in vivo.

Our previous study demonstrated that the peritoneal stroma environment favors proliferation of tumor cells by serving as a rich source of growth factors and chemokines known to be involved in tumor metastasis. In this study, we investigated the interaction between gastric cancer cells and peritoneal mesothelial cells, and determined the effects of TGF-ß1 in this processing. Human peritoneal tissues and peritoneal wash fluid were obtained, which examined by hematoxylin and eosin staining or ELISA for measurements of TGF-ß1 levels. The peritoneal mesothelial cells were co-incubated with the supernatants of gastric cancer, the expression of TGF-ß1, collagen and fibronectin was observed by ELISA and western blot. We then investigated the effects of serum-free conditioned media from HSC-39 gastric cancer cells on the peritoneum of nude mice, and the effects of peritoneal fibrosis on the development of peritoneal metastasis in vivo. The peritoneum from gastric patients were thickened and contained extensive fibrosis. After co-culture both gastric tumor cells and mesothelial cells, we found that TGF-ß1 expression was greatly increased in the co-culture system compared to individual culture condition. Serum-free Conditioned Media from HSC-39 was able to induce extracellular matrix expression in vitro and in vivo, and tumorigenicity in mice with peritoneal fibrosis was greater than in mice with normal peritoneum, while blocking TGF-ß1 by peptide P17 can partially inhibit these effects. In conclusion, these results indicated that the interaction of gastric cancer with peritoneal fibrosis and determined that TGF-ß1 plays a key role in induction of peritoneal fibrosis, which in turn affected dissemination of gastric cancer.

Silencing of Prrx1b suppresses cellular proliferation, migration, invasion and epithelial-mesenchymal transition in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive tumour subtype associated with poor prognosis. The mechanisms involved in TNBC progression remains largely unknown. To date, there are no effective therapeutic targets for this tumour subtype. Paired-related homeobox 1b (Prrx1b), one of major isoforms of Prrx1, has been identified as a new epithelial-mesenchymal transition (EMT) inducer. However, the function of Prrx1b in TNBC has not been elucidated. In this study, we found that Prrx1b was significantly up-regulated in TNBC and associated with tumour size and vascular invasion of breast cancer. Silencing of Prrx1b suppressed the proliferation, migration and invasion of basal-like cancer cells. Moreover, silencing of Prrx1b prevented Wnt/ß-catenin signaling pathway and induced the mesenchymal-epithelial transition (MET). Taken together, our data indicated that Prrx1b may be an important regulator of EMT in TNBC cells and a new therapeutic target for interventions against TNBC invasion and metastasis.

miR-655 suppresses epithelial-to-mesenchymal transition by targeting Prrx1 in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks effective targeted therapies. The epithelial-to-mesenchymal transition (EMT) is a key contributor in the metastatic process. In this study, we found that miR-655 was down-regulated in TNBC, and its expression levels were associated with molecular-based classification and lymph node metastasis in breast cancer. These findings led us to hypothesize that miR-655 overexpression may inhibit EMT and its associated traits of TNBC. Ectopic expression of miR-655 not only induced the up-regulation of cytokeratin and decreased vimentin expression but also suppressed migration and invasion of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. In addition, we found that miR-655 was negatively correlated with Prrx1 in cell lines and clinical samples. Overexpression of miR-655 significantly suppressed Prrx1, as demonstrated by Prrx1 3'-untranslated region luciferase report assay. Our study demonstrated that miR-655 inhibits the acquisition of the EMT phenotype in TNBC by down-regulating Prrx1, thereby inhibiting cell migration and invasion during cancer progression.

Down-regulation of BRMS1 by DNA hypermethylation and its association with metastatic progression in triple-negative breast cancer.

Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene in several solid tumors. However, the expression and function of BRMS1 in triple-negative breast cancer (TNBC) have not been reported. In this study, we found that BRMS1 was down-regulation in breast cancer cell lines and primary TNBC, while decreased expression of BRMS1 mRNA was significantly associated with lymph node metastasis. And this down-regulation was found to be in accordance with aberrant methylation of the gene. Hypermethylation of the gene was observed in 53.4% (62/116) of the TNBC primary breast carcinomas, while it was found in only 24.1% (28/116) of the corresponding nonmalignant tissues. In addition, BRMS1 expression was restored in MDA-MB-231 after treatment with the demethylating agent, 5-aza-2-deoxycytidine (5-Aza-dC), and demethylation of the highly metastatic cells MDA-MB-231 induced invasion suppression of the cells. Furthermore, the suppression of BRMS1 by siRNA transfection enhanced cancer cells invasion. Collectively, our results suggest that the aberrant methylation of BRMS1 frequently occurs in the down-regulation of BRMS1 in TNBC and that it may play a role in the metastasis of breast cancer.

Lack of an association between XRCC2 R188H polymorphisms and breast cancer: an update meta-analysis involving 35,422 subjects.

PURPOSE: Several studies have investigated the associations between XRCC2 R188H polymorphism and the susceptibility to breast cancer, but the results have been inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: PubMed and China National Knowledge Infrastructure (CNKI) searches were carried out for relevant studies published before March 2015. Meta-analysis was performed with the Stata, version 11.0. RESULTS: A total of 17 case-control studies, including 17,986 cases and 17,436 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygous model, dominant model, and recessive model. When all the studies were pooled into the meta-analysis, there was no evidence showing a significant association between XRCC2 R188H polymorphism and breast cancer risk (for homozygous model, OR=0.84, 95% CI=0.62-1.14; for dominant model: OR=0.76, 95% CI=0.53-1.09; and for recessive model: OR=1.04, 95% CI=0.98-1.10). In the subgroup analysis by ethnicity, no significant association was found between the polymorphism and breast cancer risk. CONCLUSIONS: In conclusion, this meta-analysis indicates that the XRCC2 R188H polymorphism is not a risk factor for developing of breast cancer.

NKD1 down-regulation is associated with poor prognosis in breast invasive ductal carcinoma.

As a negative modulator of the canonical Wnt signaling pathway, Naked1 (NKD1) is widely expressed in many normal tissues. However, the expression and clinicopathological significance of NKD1 in patients with breast cancer is still unclear. The aim of this study was to evaluate NKD1 expression in breast cancer and to investigate the question of whether reduced expression of NKD1 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of NKD1 and relevance with clinicopathological factors in the breast invasive ductal carcinoma. Reduction of NKD1 was significantly correlated with lymph node metastasis, histological grade and ER expression in breast cancer. Patients with negative NKD1 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive NKD1 expression. This interpretation is in keeping with the results obtained from our in vitro experiments on MDA-MB-231 cells, we demonstrated that upregulation of NKD1 expression by infect with an adenovirus containing a NKD1 vector significantly reduced the migration of breast cancer cells. These data suggest that NKD1 plays an important role in invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.

CXCL12 chemokine expression suppresses human breast cancer growth and metastasis in vitro and in vivo.

Chemokine receptors are now known to play an important role in cancer growth and metastasis. However, there is little information regarding chemokine expression in breast cancer. The aim of this study was to evaluate CXCL12 expression in breast cancer and to investigate the question of whether reduced expression of CXCL12 may have any pathological significance in breast cancer development or progression. In this study, we performed western blotting and immunohistochemistry to evaluate the expression of CXCL12 and relevance with clinicopathological factors in the invasive ductal carcinoma. Reduction of CXCL12 was significantly correlated with tumor size, lymph node metastasis, TNM stage and Her-2 expression in breast cancer. Patients with negative CXCL12 expression had significantly lower cumulative postoperative 5 year survival rate than those with positive CXCL12 expression. In addition, we demonstrated that upregulation of CXCL12 expression by infection with an adenovirus containing a CXCL12 vector significantly inhibited cell growth and reduced the migration of breast cancer cells. Furthermore, animal studies revealed that nude mice injected with the Ad-CXCL12 cell lines featured a lighter weight than the control cell lines. These data suggest that CXCL12 plays an important role in cell growth and invasion in human breast cancer and it appears to be a potential prognostic marker for patients with breast cancer.

Curcumin induces apoptosis in breast cancer cells and inhibits tumor growth in vitro and in vivo.

Curcumin has shown therapeutic and/or adjuvant therapeutic effects on the treatment of some patients with breast cancer. However, its mechanisms of action are largely unknown. This study was designed to investigate its antitumor effect and underlying mechanisms in human breast cancer MDA-MB-231 and MCF-7 cells. The MTT assay was used to evaluate cell viability, and flow cytometry, acridine orange staining and transmission electron microscopy were used to detect apoptosis for cultured cells. The protein expression in cells was evaluated by western blot analysis. Breast tumors were established by subcutaneous injection of MDA-MB-231 cells in nude BALB/c mice, and curcumin was administered to the mice. The size of tumors was monitored and the weight of tumors was examined. The exposure of breast cancer cells to curcumin resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner. We also found that the expression of Bcl-2 protein decreased and the expression of Bax protein increased which lead to an increase of the Bax/Bcl-2 ratio. In mice bearing MDA-MB-231 xenograft tumors, administration of curcumin showed a significant decrease of tumor volumes and tumor weight compared with the control. Our results showed that curcumin exhibited antitumor effects in breast cancer cells with an induction of apoptosis.

Mesothelial cells differentiate into fibroblast-like cells under the scirrhous gastric cancer microenvironment and promote peritoneal carcinomatosis in vitro and in vivo.

Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer (SGC), and myofibroblast provides a favorable environment for the peritoneal dissemination of gastric cancer. The aim of this study was to determine whether myofibroblast originates from peritoneal mesothelial cells under the influence of the tumor microenvironment. Immunohistochemical studies of peritoneal biopsy specimens from patients with peritoneal lavage cytological (+) status demonstrate the expression of the epithelial markers cytokeratin in fibroblast-like cells entrapped in the stroma, suggesting that these cells stemmed from local conversion of mesothelial cells. To confirm this hypothesis in vitro, we co-incubated mesothelial cells with SGC or non-SGC to investigate morphology and function changes. As we expected, mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype with loss of epithelial morphology and decrease in the expression of cytokeratin and E-cadherin when exposed to conditioned medium from HSC-39, and the induction of mesothelial cells can be abolished using a neutralizing antibody to transforming growth factor-beta1 (TGF-ß1) as well as by pre-treatment with SB431542. Moreover, we found that these mesothelial cells-derived cells exhibit functional properties of myofibroblasts, including the ability to increase adhesion and invasion of SGC. In summary, our current data demonstrated that mesothelial cells are a source of myofibroblasts under the SGC microenvironment which provide a favorable environment for the dissemination of gastric cancer; TGF-ß1 produced by autocrine/paracrine in peritoneal cavity may play a central role in this pathogenesis.

Astragalus extract attenuates allergic airway inflammation and inhibits nuclear factor κB expression in asthmatic mice.

BACKGROUND: Astragalus membranaceus from traditional Chinese herbal medicines previously showed that it possesses a strong anti-inflammatory activity. The purpose of this study was to elucidate the effect of astragalus on allergen-induced airway inflammation and airway hyperresponsiveness and investigate its possible molecular mechanisms. METHODS: Female BALB/c mice sensitized and challenged with ovalbumin (OVA) developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts and cytokine and chemokine levels. In vivo airway responsiveness to increasing concentrations of methacholine was measured 24 hours after the last OVA challenge using whole-body plethysmography. The expression of inhibitory κB-α and p65 in lung tissues was measured by Western blotting. RESULTS: Astragalus extract attenuated lung inflammation, goblet cell hyperplasia and airway hyperresponsiveness in OVA-induced asthma and decreased eosinophils and lymphocytes in bronchoalveolar lavage fluid. In addition, astragalus extract treatment reduced expression of the key initiators of allergic T(H)2-associated cytokines (interleukin 4, interleukin 5) (P < 0.05). Furthermore, astragalus extract could inhibit nuclear factor κB (NF-κB) expression and suppress NF-κB translocation from the cytoplasm to the nucleus in lung tissue samples. CONCLUSIONS: Taken together, our current study demonstrated a potential therapeutic value of astragalus extract in the treatment of asthma and it may act by inhibiting the expression of the NF-κB pathway.

Transforming growth factor-ß 1 enhances the invasiveness of breast cancer cells by inducing a Smad2-dependent epithelial-to-mesenchymal transition.

Metastasis is unequivocally the most lethal aspect of breast cancer and the most prominent feature associated with disease recurrence, the molecular mechanisms whereby epithelial-to-mesenchymal transition (EMT) mediates the initiation and resolution of breast cancer metastasis remains poorly understood. Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine that is intimately involved in regulating numerous physiological processes, including cellular differentiation, homeostasis and EMT. Recent findings have implicated high levels of TGF-ß1 were associated with poor outcome, whereas inhibition of TGF-ß signaling reduces metastasis in breast cancer, suggesting that the chemo-therapeutic targeting of TGF-ß1 or TGF-ß signaling may offer new inroads in ameliorating metastatic disease in breast cancer patients. In this study, we showed immunohistochemical evidence for EMT, which is associated with TGF-ß1 expression, at the invasion front of breast cancer in vivo. The data also indicated that human breast cancer cell lines, MCF-7 and MDA-MB-435S, of epithelial cell characteristics were induced to undergo EMT by TGF-ß1 and dependent on the Smad2 signaling pathway. Following TGF-ß1 treatment, cells showed dramatic morphological changes assessed by phase contrast microscopy, accompanied by decreased epithelial marker and increased mesenchymal markers. Importantly, cell invasion was also enhanced in the EMT process, while knockdown of the Smad2 gene by silencing siRNA partially inhibited these effects in MDA-MB435S (P<0.05). These data suggested that EMT of breast cancer induced by TGF-ß1 is dependent on Smad2 signaling and promotes breast cancer cell metastasis.