Aberrant signal transduction in Indian triple-negative breast cancer patients

Aim of Study: The aim of this study is to correlate the prominin-1 or CD133 association with functional pathway markers of cancer stemness in Indian triple-negative breast cancer (TNBC) patient samples. Materials and Methods: TNBC samples were confirmed for the absence of hormone receptors (estrogen receptor–ER/progesterone receptor) and human epidermal growth factor receptor-2 or proto-oncogene neu or erbB2 or CD340 by immunohistochemical analysis. Formalin-fixed paraffin-embedded samples of patients were used to collect the total RNA. Then, one-step reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the cancer stemness-related transcript levels in the different samples. The RT-PCR products were analyzed semi-quantitatively on agarose gels. The band intensities of respective samples for different transcripts were analyzed by densitometry. Results: TNBC-confirmed samples had shown increased levels of CD133 transcript than control tissues. Further, elevated CD133 transcripts are correlated with higher transcript levels of NOTCH1/FZD7/transforming growth factor-beta receptor Type III R/patched-1 pathway mediators. Conclusions: This work has clearly indicated that there is a correlation between CD133 and functional pathways that control cancer stem cells in TNBC. These observations may indicate the possible association between cancer stemness and TNBC malignancy

Neurovascular Manifestation of Loeys-Dietz Syndrome: A Case Report

Loeys-Dietz syndrome (LDS) is an autosomal dominant disorder caused by heterozygous mutations in the genes encoding transforming growth factor-beta receptor type 1 or 2. It is typically characterized by a triad of hypertelorism, cleft palate or bifid uvula, and arterial tortuosity with aneurysm or dissection. Characteristic vascular abnormalities such as tortuosity, aneurysms, dissections, and stenosis are the most severe complications of LDS and can occur in the neurovascular system. We report a 5-year-old boy who presented with headaches and neurovascular abnormalities and was diagnosed with LDS with a novel mutation of the TGFBR1 gene. It is the first Korean report of neurovascular abnormalities in LDS.

The Clinical Significance of Transforming Growth Factor (TGF) beta1, TGF beta Receptor beta II, p53 Protein and K-ras Point Mutation in Pancreatic Cancer

PURPOSE: Many cancers, including pancreatic cancer, harbor defects in TGF beta signaling and are resistant to TGF beta mediated growth inhibition. In addition, the expression of the p53 gene and mutations in K-ras might play an important role in the multistep carcinogenesis of pancreatic cancer. This study examined the expression level of TGF beta 1, TGF beta receptorII (T beta RII), p53 protein and K-ras mutation in pancreatic cancer, along with their role and clinical significance. METHODS: The overexpression of TGF beta 1, T beta RII and p53 protein was evaluated using an immunohistochemical assay. The K-ras mutation was analyzed by PCR-RFLP in the surgical resected pancreatic tissue from 26 pancreatic ductal adenocarcinomas and 5 normal pancreases. RESULTS: Immunohistochemical analysis of TGF beta 1 and T beta RII revealed positive immunostaining in 73.1% and 76.9% of the tumors, respectively, which were significantly higher than the normal pancreas (P=0.008). The p53 protein was positive in none of the 5 normal ducts and 16 out of 26 (61.5%) pancreatic carcinoma specimens. The K-ras mutation was positive in none of the 5 normal ducts, and in 20 of the 26 pancreatic carcinoma specimens (76.9%). The presence of TGF beta1 and T beta RII in the cancer samples was significantly associated with node metastasis, advanced tumor stage (P<0.01), and a short survival time (P<0.05). The p53-positive pancreatic cancers showed a significantly lower survival rate than those with p53-negative tumors (P<0.05). There was no correlation between K-ras mutations and the survival rates. CONCLUSION: The detection of K-ras mutations and TGF beta 1, T beta RII and p53 protein overexpression can predict the prognosis of pancreatic carcinoma patients.

Expression of TβRⅡRH mRNA in PBMCs of patients with lupus nephritis / 中华风湿病学杂志

Objective To investigate the association of TGF-β receptor typeⅡ(TβRⅡ)mRNA with lupus nephritis (LN) and disease activity by testing its expression levelin peripheral blood mononuclear cells (PBMCs).Methotis Forty-four patients with LN were included in this study.They were all had active LN.Twepty-eight LN patients were taking glueocorticoids and/or immunosuppressive agents and sixteen had never taken steroids or immunosuppressive agents.The expression levels of T13R H mRNA were semi-quantitativelydetermined by reverse transcription-polymerase chain reaction(RT-PCR).Resuits The expression levels of TβRⅡ mRNA in PBMCs from LN patients(1.7±1.0)were lower than those of non-lupus nephritis(4.0±3.1) and healthy subiects(4.1±2.5),(P<0.01).The difference of the expression levels between patients who took and had never taken glucocorticoids and/or immunosuppressive drugs was significantly statistically(P<0.05).The expression levels of TβRⅡ mRNA in PBMCs of patients with LN were correlated significantly with the systemic lupus erythematosus disease activity index (SLEDAI)scores(r-0.309.P<0.05),titers of anti-dsDNA antibody(r=-0.401,P<0.01)and serum complement C3 level(r=0.621,P<0.01).Conclusion This study suggests that TβRⅡ may be involved in the development of LN,and the TβRⅡ mRNA expression levels in PBMCs from patients with SLE are significantly correlated with LN activity.Glucocortieoids or immunosuppressive drugs can increase the expression levels of TβRⅡ mRNA and ameliorate renal damage.

EXPRESSIONS OF TRANSFORMING GROWTH FACTOR-BETA 1 AND ITS TYPE Ⅱ RECEPTOR IN EXPERIMENTAL RAT ASCENDING AORTIC ANEURYSM / 解剖学报

Objective To investigate the expressions and significance of transforming growth factor-beta 1(TGF?1) and its typeⅡ receptor(TGF?RⅡ) in experimental rat ascending aortic aneurysm of rat model.Methods The rat ascending aortic aneurysm models were made by banding ascending aorta of young Wistar rats.The ascending aortas were taken 4 months after operation.Immunohistochemistry staining and Western blotting were used to investigate the expressions of TGF?1 and TGF?RⅡ.Result Immunohistochemistry staining results showed that TGF?1 expressed in all layers of the aortic aneurysm and the control.TGF?RⅡ was extensively located in the hyperplastic intima and tunica media smooth muscle cells in the aortic aneurysm,while there was only a little positive staining in the control group.Western blotting results indicated that the expression levels of TGF?1 and TGF?RⅡ in the aortic aneurysm were stronger than the control,P