ABSTRACT
OBJECTIVES: Mesenchymal stem cells are viewed as the first choice in regenerative medicine. This study aimed to elucidate the influence of BM-MSCs transplantation on angiogenesis in a rat model of unilateral peripheral vascular disease. MATERIALS AND METHODS: Twenty-one rats were arbitrarily allocated into three groups (7/group). Group I: control sham-operated rats, Group II: control ischemic group: Rats were subjected to unilateral surgical ligation of the femoral artery, and Group III: ischemia group: Rats were induced as in group II, 24 hr after ligation, they were intramuscularly injected with BM-MSCs. After scarification, gastrocnemius muscle gene expression of stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor receptor 2 (VEGFR2), von Willebrand factor (vWF), and hypoxia-inducible factor-1α (HIF-1α) were analyzed by quantitative real-time PCR. Muscle regeneration and angiogenesis evaluation was assessed through H&E staining of the tissue. Furthermore, Pax3 and Pax7 nuclear expression was immunohistochemically assessed. RESULTS: Rats treated with BM-MSCs showed significantly raised gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF compared with control and ischemia groups. H&E staining of the gastrocnemius showed prominent new vessel formation. Granulation tissue within muscles of the ischemic treated group by BM-MSCs showed cells demonstrating nuclear expression of Pax3 and Pax7. CONCLUSION: BM-MSCs transplantation has an ameliorating effect on muscle ischemia through promoting angiogenesis, detected by normal muscle architecture restoration and new blood vessel formations observed by H&E, confirmed by increased gene expression levels of SDF-1, CXCR4, VEGFR2, and vWF, decreased HIF-1α gene expression, and increased myogenic Pax7 gene expression.
ABSTRACT
OBJECTIVES: Detection of Immunohistochemical (IHC) expression of PDL-1 by tumor cells and stromal tumor infiltrating lymphocytes (TILs) in colorectal carcinoma, to investigate the possibility of using it as a targeted therapy, as well as, correlation of this expression with the clinico-pathologic parameters of the tumors. MATERIALS AND METHODS: Colorectal tissue sections were collected from 60 colectomy specimens were taken from Kasr El Ainy Hospital, Faculty of Medicine, Cairo University. Exclusion criteria included cases with missing data and cases who received chemotherapy or radiotherapy. IHC expression of PDL-1 was investigated in tumor cells (T) and stromal TILs separately. PDL-1 positivity was defined as PDL-1 expression on ≥ 5% of membranous positive cell staining of any intensity. RESULTS: PDL-1 (T) expression was detected in 25% of cases and showed statistically significant correlation with higher tumor grade and right sided colon tumors (P value < 0.05). PD-L1 stromal TILs expression was detected in 38.3 % of cases. Insignificant statistical relation between Stromal TILs PDL-1 expression and the tumor extent (T) was detected (P value = 0.07), however, the expression of PDL-1 in lymphocytes was inversely proportional to the tumor extent (invasion). There were linear relation between PDL-1 expression stromal (TILs) (33.3%) and PDL-1 expression in tumor cells (28.2%) and positive lympho-vascular invasion but it was statistically insignificant (P value = 0.4 and 0.2 respectively). Despite there were no statistical relation between either PDL-1 (T) and PDL-stromal TILS and Perineural invasion (P value =1 and 0.5) but inverse relation was noticed with more PDL-1 expression in tumor cells (24.5%) and TILS (40.8%) with negative Perineural invasion. CONCLUSION: Our results supported PDL-1 expression in CRC by both TC and TILs, with higher expression in subset of tumors that are high grade highlighting them as candidates for anti- PD-1/PDL-1 therapy.
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