Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways.

BACKGROUND: Metformin is the first line of oral antidiabetic drug in the biguanide class for treatment of type 2 diabetes. Increasing evidence has suggested that it is a potential anti-tumor drug. However, the mechanisms underlying inhibiting tumor development remain elusive, especially in bladder tumors. METHODS: T24 and J82 cell lines were used as an in vitro model, and 24 female SD rats were used to build an N-methyl-N-nitrosourea (MNU)-induced orthotopic rat bladder cancer model. Transfection of lentivirus-based shRNA was used to construct the STAT3-KNOCKDOWN T24 cell line. After metformin treatment, the viability of bladde cancer cells was determined by CCK8. Cell cycle distribution and apoptosis were assessed by flow cytometry. The migration and invasion abilities of cells were evaluated by wound healing and transwell asssays. The inactivation of stat3 pahtway was examined by qRTPCR, western blot and Immunofluorescence. RESULTS: Metformin can effectively inhibit precancerous progression to invasive cancer in an MNU-induced rat orthotopic bladder tumor model, although it could not completely suppress normal cells transforming into tumor cells. While the MNU could induce 50 % rats (4/8) to develop invasive bladder cancers, the rats co-administrated with metformin failed to develop invasive tumors but retained at precancerous or non-invasive stages, exhibiting as dysplasia, papillary tumor and/or carcinoma in situ (CIS). Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin. In vitro experiments revealed that the metformin could efficiently inhibit STAT3 activation, which was associated with the cell cycle arrest, reduction of cell proliferation, migration and invasiveness, and increase in apoptotic cell death of bladder cancer cell lines. CONCLUSIONS: These findings provide for the first time the evidence that metformin can block precancerous lesions progressing to invasive tumors through inhibiting the activation of STAT3 pathway, and may be used for treatment of the non-invasive bladder cancers to prevent them from progression to invasive tumors.

Effects of hyperbaric oxygen on aggressive periodontitis and subgingival anaerobes in Chinese patients.

OBJECTIVE: To investigate the effects of hyperbaric oxygen (HBO2) on aggressive periodontitis (AgP), and subgingival obligate anaerobes in Chinese patients. MATERIALS AND METHODS: Sixty cases of Chinese patients with AgP were randomly divided into two groups -the HBO2 group (30 cases) and the control group (30 cases). Study teeth were divided into four groups -: the HBO2 therapy, the HBO2 + scaling scaling group, the scaling group and the control group. Subgingival anaerobic organisms were measured with anaerobic culture, and number of obligate anaerobes and facultative anaerobes and Bacteroides melaninogenicus was counted. Comparisons of changes in the clinical indices, and subgingival anaerobes were made between the groups. RESULTS: Highly significant differences in gingival index (GI), probing depth (PD), attachment loss (AL), and Plaque index (PLI), and tooth odontoseisis (TO) were seen in the HBO2, the HBO2 + scaling and the scaling groups when compared with the control group (P<0.01). The number of subgingival anaerobes as well as the types of obligate anaerobes and facultative anaerobes and the number of Bacteroides melaninogenicus were reduced markedly in these three treatment groups. Highly statistical differences in clinical indices, subgingival anaerobe number and types of obligate anaerobes and facultative anaerobes and Bacteroides melaninogenicus were found when comparisons were made between the HBO2 + scaling and the HBO2 groups, as well as between the HBO2 + scaling and the scaling groups. Clinical follow-ups indicated that the GI, PD, AL, TO, PLI and subgingival anaerobes number of the three therapeutic groups were reduced more severely than the control group. CONCLUSIONS: HBO2 had good therapeutic effects on Chinese patients with AgP. HBO2 therapy combined with scaling and root planing was the most beneficial in the treatment of AgP. The therapeutic effect of HBO2 on AgP is most likely through inhibition of the growth of subgingival anaerobes. Clinical follow-ups suggest that the effect could last more than 2 years.

[Effects and holding time of hyperbaric oxygen on human severe periodontitis].

OBJECTIVE: This paper studied the therapeutic effects and holding time of hyperbaric oxygen (HBO) on human severe periodontitis. METHODS: 30 cases with periodontitis were selected and randomly divided into 2 groups, i.e. the HBO group and control group. For HBO group, they were exposed to a pressure of 0.25 MPa. For control group, they were rinsed with gargle. Gingival indices (GI), sulcus bleeding indices (SBI), plaque index (PLI), probing depth (PD), attachment loss (AL) and gingival crevicular fluid (GCF) were measured during both the first and last clinical visits, and 1 year after HBO therapy. The gingival blood flow (GBF) were measured by Laser Doppler Flowmeter. RESULTS: HBO can decrease GI of patients with periodontitis by 1.1 decrease SBI by 1.2, lower PD and AL by 0.7 mm, decrease the volume of GCF by 2.0, and significant differences could be seen in the above indices between pre and post HBO therapy. The GBF had a 1.8 folds increase after HBO exposure. GI and SBI one year after HBO therapy were larger than that of the time after HBO therapy. There were no significant differences in the PLI, PD, AL, GCF, GBF between post HBO therapy and 1 year after HBO therapy. CONCLUSION: HBO had good therapeutic effects on human severe periodontitis, the effects can keep more than 1 year.

[Effects of fast decompression on prostaglandins content in cerebral tissue of guinea pigs].

Objective. To investigate the effect of fast decompression on prostaglandins in cerebral tissue. Method. 26 guinea pigs were divided into 2 groups randomly. The animals in group FDC (group 1) were treated with fast decompression and formed decompression sickness, but those in control group (group 2) were not treated with decompression. The contents of prostaglandin E2 (PGE2), 6-keto-prostaglandin F1a (6-K-PGF1a) and thromboxane B2 (TXB2) in cerebral tissue of the animals were determined by enzyme immunoassay. Result. The content of PGE2 in cerebral tissue of FDC animals was twice as much as that in control animals. The content of TXB2 in cerebral tissue of FDC animals was 3 times as high as that in control animals, and that of 6-K-PGF1a in cerebral tissue of FDC animals was 2.6 times as that in control animals. It showed very significant differences as compared with control group (P<0.01). Conclusion. The content of PGs in cerebral tissue increased markedly after fast decompression, and may cause cerebral injury.