Annexin A2 (AnxA2) association with the clinicopathological data in different breast cancer subtypes: A possible role for AnxA2 in tumor heterogeneity and cancer progression.

BACKGROUND: Breast cancer is a highly heterogeneous type of neoplasia with molecular and biochemical alterations in the ductal epithelium. AnxA2 has a diverse functions and through intracellular interaction with other molecules promotes carcinogenesis. AIMS: To study the possible involvement of AnxA2 in breast cancer heterogeneity and cancer progression. PATIENTS AND METHODS: Tumor tissue and serum were obtained from different breast cancer subtypes. Tumor tissues were processed for histopathological studies. AnxA2 levels were assessed in the tissues by H scoring and in the serum by ELISA. AnxA2 levels were correlated with HER2 and Ki67 and with clinicopathological data. Normal breast tissues and serum from healthy subjects were used as controls. RESULTS: AnxA2 showed a peculiar distribution in tumor tissues and nearby interstitial tissues. Pattern of expressions varied in different subtypes with the highest expression in triple negative subtype. Tissue and serum AnxA2 showed significant co-upregulations in breast cancer. Moreover, they showed positive correlations with HER2 and Ki67 and associations with clinicopathological data including cancer staging and lymph node metastasis. CONCLUSION: For the best of our knowledge this is the first study showing correlation between AnxA2, the proposed prognostic marker and the well-established tumor markers; HER2 and Ki67. AnxA2 might contribute to breast cancer heterogeneity and is associated with poor prognosis. AnxA2 might be a prognostic marker and an additional marker for breast cancer grading and clinical staging. Interestingly, tissue and serum AnxA2 showed a strong correlation. Thus, assessing serum AnxA2 can be a noninvasive prognostic tool.

Mutual inter-regulation between iNOS and TGF-ß1: Possible molecular and cellular mechanisms of iNOS in wound healing.

Abnormal wound healing with excessive scarring is a major health problem with socioeconomic and psychological impacts. In human, chronic wounds and scarring are associated with upregulation of the inducible nitric oxide synthase (iNOS). Recently, we have shown physiological regulation of iNOS in wound healing. Here, we sought to investigate the possible mechanistic role of iNOS in wound healing using biochemical and immunohistochemical assays. We found: (a) iNOS is the main source of wound nitric oxide (NO), (b) NOS inhibition in the wound, downregulated iNOS protein, mRNA and enzymatic activity, and reduced wound NO, and (c) iNOS inhibition resulted in delayed healing at early time points, and excessive scarring at late time points. Furthermore, molecular and cellular analysis of the wound showed that iNOS inhibition significantly (P < 0.05) increased TGF-ß1 mRNA and protein levels, fibroblasts and collagen deposition. These latter findings suggest that iNOS might be exerting its action in the wound by signaling through TGF-ß1 that activates wound fibroblasts to produce excessive collagen. Our current findings provide further support that iNOS is crucial for physiological wound healing, and suggest that dysregulation of iNOS during the inflammatory phase impairs healing, and results in disfiguring post-healing scarring. Thus, the mutual feedback regulation between iNOS and TGF-ß1 at the gene, protein and functional levels might be the mechanism through which iNOS regulates the healing. Monitoring and maintenance of wound NO levels might be important for healing and avoiding long-term complications in susceptible people including patients with diabetic wounds, venous ulcers or keloid prone.

Role of adipose tissue derived stem cells differentiated into insulin producing cells in the treatment of type I diabetes mellitus.

Generation of new ß cells is an important approach in the treatment of type 1 diabetes mellitus (type 1 DM). Adipose tissue-derived stem cells (ADSCs) might be one of the best sources for cell replacement therapy for diabetes. Therefore, this work aimed to test the possible role of transplanted insulin-producing cells (IPCs) differentiated from ADSCs in treatment of streptozotocin (STZ) induced type I DM in rats. Type 1 DM was induced by single intra peritoneal injection with STZ (50 mg/kg BW). Half of the diabetic rats were left without treatment and the other half were injected with differentiated IPCs directly into the pancreas. ADSCs were harvested, cultured and identified by testing their phenotypes through flow cytometry. They were further subjected to differentiation into IPCs using differentiation medium. mRNA expression of pancreatic transcription factors (pdx1), insulin and glucose transporter-2 genes by real time PCR was done to detect the cellular differentiation and confirmed by stimulated insulin secretion. The pancreatic tissues from all groups were examined 2 months after IPC transplantation and were subjected to histological, Immunohistochemical and morphometric study. The differentiated IPCs showed significant expression of pancreatic ß cell markers and insulin secretion in glucose dependent manner. Treatment with IPCs induced apparent regeneration, diffused proliferated islet cells and significant increase in C-peptide immune reaction. We concluded that transplantation of differentiated IPCs improved function and morphology of Islet cells in diabetic rats. Consequently, this therapy option may be a promising therapeutic approach to patient with type 1 DM if proven to be effective and safe.