Modulating pancreatic cancer microenvironment: The efficacy of Huachansu in mouse models via TGF-ß/Smad pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huachansu (HCS) is a traditional Chinese medicine obtained from the dried skin glands of Bufo gargarizans and clinical uses of HCS have been approved in China to treat malignant tumors. The traditional Chinese medicine theory states that HCS relieves patients with cancer by promoting blood circulation to remove blood stasis. Clinical observation found that local injection of HCS given to pancreatic cancer patients can significantly inhibit tumor progression and assist in enhancing the efficacy of chemotherapy. However, the material basis and underlying mechanism have not yet been elucidated. AIM OF THE STUDY: To investigate the therapeutic potential of HCS for the treatment of pancreatic cancer in in situ transplanted tumor nude mouse model. Furthermore, this study sought to elucidate the molecular mechanisms underlying its efficacy and assess the impact of HCS on the microenvironment of pancreatic cancer. To identify the antitumor effect of HCS in in situ transplanted tumor nude mouse model and determine the Chemopreventive mechanism of HCS on tumor microenvironment (TME). METHODS: Using the orthotopic transplantation nude mouse model with fluorescently labeled pancreatic cancer cell lines SW1990 and pancreatic stellate cells (PSCs), we examined the effect of HCS on the pancreatic ductal adenocarcinoma (PDAC) microenvironment based on the transforming growth factor ß (TGF-ß)/Smad pathway. The expression of TGF-ß, smad2, smad3, smad4, collagen type-1 genes and proteins in nude mouse model were detected by qRT-PCR and Western blot. RESULTS: HCS significantly reduced tumor growth rate, increased the survival rate, and ameliorated the histopathological changes in the pancreas. It was found that HCS concentration-dependently reduced the expression of TGF-ß1 and collagen type-1 genes and proteins, decreased the expression of Smad2 and Smad3 genes, and downregulated the phosphorylation level of Smad2/3. Additionally, the gene and protein expression of Smad4 were promoted by HCS. Further, the promoting effect gradually enhanced with the rise of HCS concentration. CONCLUSIONS: The results demonstrated HCS could regulate the activity of the TGF-ß/Smad pathway in PDAC, improved the microenvironment of PDAC and delayed tumor progression. This study not only indicated that the protective mechanism of HCS on PDAC might be attributed partly to the inhibition of cytokine production and the TGF-ß/Smad pathway, but also provided evidence for HCS as a potential medicine for PDAC treatment.

Cinobufacini Inhibits the Development of Pancreatic Cancer Cells through the TGFß/Smads Pathway of Pancreatic Stellate Cells.

This study aimed to test cinobufacini therapeutic potential for pancreatic cancer, verify its potential molecular mechanism, and evaluate the cinobufacini impact on pancreatic cancer microenvironment. First, the effect of cinobufacini-treated pancreatic stellate cells (PSCs) supernatant on the value-added ability of pancreatic cancer (PCCs) was tested. The results show that cinobufacini can effectively reduce the ability of PSCs supernatant to promote the value-added PCCs. Further results show that cinobufacini can effectively reduce the concentration of TGFß in the supernatant of PSCs. Subsequently, the impact of cinobufacini on the transcription and translation levels of key genes in the TGFß/Smads pathway was examined. The results showed that the impact of cinobufacini on the transcription levels of Smad2, Smad3, and Smad7 was in a concentration-dependent manner, while the transcriptional activity of collagen I mRNA was decreased with the increase of cinobufacini concentration. The results of protein expression showed that cinobufacini could upregulate the expression of inhibitory protein Smad7, inhibit the phosphorylation level of p-Smad2/3, and then suppress the expression of type I collagen (collagen I). On the one hand, this study shows that cinobufacini can inhibit the promotion of PSCs on the proliferation of PCCs. On the other hand, cinobufacini can upregulate the expression of the inhibitory molecule, Smad7, through the TGFß/Smads pathway and reduce the phosphorylation level of p-Smad2/3, thereby inhibiting the expression of collagen I and pancreatic fibrosis. cinobufacin can inhibit the proliferation of SW1900 cells by blocking the TGFß/Smads pathway of pancreatic stellate cells. These results provide a clinical basis for the treatment of pancreatic cancer.

Bacteriological Investigation of Chronic Wounds in a Specialized Wound Healing Department: A Retrospective Analysis of 107 Cases.

To investigate the information of chronic wounds, especially in the aspect of microbiological profile and to explore the relationship between the wound culture result and chronic wounds infection, we retrospectively reviewed the medical records of 107 patients with chronic wounds from January 2011 to December 2013. The sociodemographic data, wound-related information, therapeutic type, and wound infection status were extracted. Microbial specimens were obtained and processed using standard hospital procedure for wound culture. The predominant pathogen isolated was Staphylococcus aureus (n = 11, 26.2%), followed by Escherichia coli (n = 6, 14.3%), Enterobacter cloacae (n = 3, 7.1%), and Pseudomonas aeruginosa (n = 3, 7.1%). Sixty percent of the infectious chronic wounds had positive culture, and 96.2% of the noninfectious wounds had negative culture. In conclusion, the microbial characteristics were mostly in the site of lower extremity, gram-negative bacteria, and monopathogen, respectively. Furthermore, the relationship between the wound culture result and chronic wound infection was not exactly coincident. It may be useful for guiding the empiric therapy of chronic wounds.

Combined therapy of percutaneous cryoablation and traditional Chinese medicine can be a promising strategy for elderly or advanced lung cancer patients based on a retrospective clinical study.

Presently, elderly and advanced lung cancer patients have very limited treatment options. With no promising therapy, treatment of these patients is challenging. We have reviewed 119 primary lung cancer patients who received a combined percutaneous cryoablation and traditional Chinese medicine therapy (Cryo-TCM therapy) between 2005 and 2013. Out of 119 patients, 84.1% patients were elderly or advanced lung cancer when receiving cryoablation. Overall Survival time from the time of Diagnosis (DOS) and Cryoablation (COS) was 19 and 10 months respectively, which were longer than data previously published. Patients who accepted only Cryo-TCM therapy got similar DOS as those who were treated with Cryo-TCM and other classic anticancer therapies. Thus, Cryo-TCM therapy can prolong the survival time and can be used as the main therapy for the elderly or advanced lung cancer patients in China both in quality of life and cost effectiveness.