Role of TGF-β1 and its Receptors in Breast Carcinogenesis:Evaluation of Gene Expression Patterns and Clinical Implications

OBJECTIVE Transforming growth factor β1 （TGF-β1） is a multifunc- tional cytokine that may play an important role in tumor development and progression. METHODS We evaluated gene expression patterns of TGF-β1 and its receptors [transforming growth factor β type Ⅰ receptor （TβR- Ⅰ ） and transforming growth factor β type Ⅱ receptor （TβR- Ⅱ ）] in tumor tissue from patients with breast cancer or with benign breast diseases （BBD） and adjacent normal tissue from the patients with breast cancer. Included in the study were 527 breast cancer patients and 213 BBD patients who participated in the Shanghai Breast Cancer Study. RESULTS The expression levels of the TGF-β1, TβR- Ⅰ and TβR-Ⅱ genes in breast tissue were quantified using real-time PCR. TIER- Ⅱ expression in cancer tissue was decreased by over 50% as compared to either adjacent normal tissue from the same patients or benign tumor tissue from BBD patients （p〈0.001）. TGF-β1 expression was lower by approximately 20% in cancer tissue compared to adjacent normal tissue （p=0.14） or to benign tumor tissue （p=0.002）. Although TβR-Ⅰ expression was also reduced in cancer tissue compared to adjacent normal tissue, or benign tumor tissue, the magnitude of the reduction was less apparent than that for TβR- Ⅱ. Compared to patients with the lowest tertile value for TβR- Ⅱ, patients with median tertile value for TβR- Ⅱ had more favorable overall survival （HR 0.47, 95% CI 0.27-0.85） and disease-free survival （HR 0.65, 95% CI 0.39-1.06）. No apparent associations, however, were observed between TGF-β1 or TβR- Ⅰ expression and overall or disease-free survival. CONCLUSION The results from this study support the hypothesis that a decreased level of TβR-Ⅱ gene expression, and thus reduced TGF-β1 sensitivity, is related to breast tumor progression.

Effects of combined chemical design(Cu addition) and topographical modification(SLA) of Ti-Cu/SLA for promoting osteogenic, angiogenic and antibacterial activities

Cu has been proved to possess various beneficial biological activities, while sandblasting and acid etching(SLA) is widely used to modify the commercial dental implant in order to improve osseointegration. Based on the above, a novel antimicrobial dental implant material, Ti-Cu alloy, was treated with SLA, to combine chemical design(Cu addition) and topographical modification(SLA). In this work, the effects of SLA treated Ti-Cu alloys(Ti-Cu/SLA) on osteogenesis, angiogenesis and antibacterial properties were evaluated from both in vitro and in vivo tests, and Ti/SLA and Ti-Cu(without SLA) were served as control groups. Benefiting by the combined effects of chemical design(Cu addition) and micro-submicron hybrid structures(SLA),Ti-Cu/SLA had significantly improved inhibitory effects on oral anaerobic bacteria(P. gingivalis and S.mutans) and could induce upregulation of osteogenic-related and angiogenic-related genes expression in vitro. More importantly, in vivo studies also demonstrated that Ti-Cu/SLA implants had wonderful biological performance. In the osseointegration model, Ti-Cu/SLA implant promoted osseointegration via increasing peri-implant bone formation and presenting good bone-binding, compared to Ti/SLA and Ti-Cu implants. Additionally, in the peri-implantitis model, Ti-Cu/SLA effectively resisted the bone resorption resulted from bacterial infection and meanwhile promoted osseointegration. All these results suggest that the novel multiple functional Ti-Cu/SLA implant with rapid osseointegration and bone resorption inhibition abilities has the potential application in the future dental implantation.

Plasticity of male germline stem cells and their applications in reproductive and regenerative medicine

Spermatogonial stem cells （SSCs）, also known as male germline stem cells, are a small subpopulation of type A spermatogonia with the potential of self-renewal to maintain stem cell pool and differentiation into spermatids in mammalian testis. SSCs are previously regarded as the unipotent stem cells since they can only give rise to sperm within the seminiferous tubules. However, this concept has recently been challenged because numerous studies have demonstrated that SSCs cultured with growth factors can acquire pluripotency to become embryonic stem-like cells. The in vivo and in vitro studies from peers and us have clearly revealed that SSCs can directly transdifferentiate into morphologic, phenotypic, and functional cells of other lineages. Direct conversion to the cells of other tissues has important significance for regenerative medicine. SSCs from azoospermia patients could be induced to differentiate into spermatids with fertilization and developmental potentials. As such, SSCs could have significant applications in both reproductive and regenerative medicine due to their unique and great potentials. In this review, we address the important plasticity of SSCs, with focuses on their self-renewal, differentiation, dedifferentiation, transdifferentiation, and translational medicine studies.