Expression of Smoothened protein in CD34-positive cells of chronic myeloid leukemia and its significance / 白血病·淋巴瘤

Objective To detect the expression of Hedgehog signaling pathway receptor Smoothened (Smo) protein in chronic myeloid leukemia (CML) CD34-positive (CD34+) cells, and to explore the role of Hedgehog signaling pathway in CML stem/progenitor cells. Methods Seventeen chronic phase (CP) and 6 advanced phase (AP) CML patients who were diagnosed in West China Hospital of Sichuan University from September 2010 to March 2011 and 10 People (healthy people and patients without hematologic malignances) as control were included in this study. The expression levels of Smo protein were detected by the protocol of indirect immunofluorescence labeling for cytometry and analyzed statistically. Results The mean of relative fluorescence intensity of Smo protein was 282.5±102.4, 188.8±55.4 and 354.0±297.9 in the CML-CP, CML-AD and control groups, respectively. The difference between CML-CP and CML-AD groups was statistically significant (P= 0.032). However, there were no significant differences between the CML-CP, CML-AD groups and control group (both P>0.05). The percentage of CD34+Smo+cells was (58.9±24.2)％, (42.6±17.6)％and (55.9±29.7) ％ in the CML-CP, CML-AD and control groups, respectively. There were still no significant differences between the CML-CP, CML-AD groups and control group (F= 0.950, P= 0.398). The mean of relative fluorescence intensity of Smo protein in the CML-CP patients with tyrosine kinase inhibitor (TKI) (9 cases) administered and without TKI (8 cases) were 282.3 ±122.6 and 282.6 ±82.4, respectively. There were no significant differences between the two groups(P=0.157). Conclusions Flow cytometry can qualitatively and quantitatively detect the expression level of Smo protein in CML CD34+cells. Smo expression is associated with stage of CML;TKI could not inhibit the activation of the Hedgehog signaling pathway in CML CD34+cells.

Roles of Sonic Hedgehog Signaling During Tooth Root and Periodontium Formation / 대한소아치과학회지

The aim of this study was to understand the roles of Sonic Hedgehog (SHH) signaling during tooth root and periodontium formation. In this study, we generated the dental mesenchyme-specific Smoothened (Smo) activated/inactivated mice with the activity of Cre recombinase under the control of osteocalcin promoter.In the Smo activated mutant molar sections at the postnatal 28 days, we found extremely thin root dentin and widened pulp chamber. Picrosirius red staining showed loosely arranged fibers in the periodontal space and decreased cellular cementum with some root resorption. Immunohistochemical staining showed less localization of matrix proteins such as Bsp, Dmp1, Pstn, and Ank in the cementum, periodontal ligament, and/or cementoblast.In the Smo inactivated mutant mouse, there was not any remarkable differences in the localization of these matrix proteins compared with the wild type. These findings suggest that adequate suppressing regulation of SHH signaling is required in the development of tooth root and periodontium.

Expressions and clinical significances of SMO, STAT3 and MMP-9 in triple negative breast cancer / 中国免疫学杂志

Objective:To investigate the expressions and clinical significances of SMO , STAT3 and MMP-9 in triple negative breast cancer ( TNBC) .Methods:The expressions of SMO , STAT3 and MMP-9 were immunohistochemically detected in 33 cases of TNBC, 30 cases of mammary hyperplasia and 18 cases of normal breast tissue , and the relationships among SMO , STAT3 and MMP-9 and clinicopathological parameters and prognosis of TNBC patients were analyzed .Results:In TNBC and mammary hyperplasia tissue , the positive expression rates of SMO were 90.9%and 60.0%,the positive expression rates of STAT3 were 96.9% and 73.3%, the positive expression rates of MMP-9 were 90.9% and 36.7%, respectively, however, expressions of them were completely absent in normal breast tissue .The significant correlations were observed between expressions of SMO , STAT3 and MMP-9 in TNBC, mammary hyperplasia and normal breast tissue (P<0.05).The expression of SMO and STAT3 was correlated with superior histologic grade and tumor stage .The expression of MMP-9 was correlated with metastasis of lymph node .The positive correlation was manifested between SMO and STAT3(r=0.361,P<0.05),between SMO and MMP-9 (r=0.633,P<0.01),between MMP-9 and STAT3 (r=0.803,P<0.01) in TNBC.The survival time of TNBC patients was correlated with SMO expression and pTNM (P<0.05).Conclusion:SMO, STAT3 and MMP-9 may play important roles in development of TNBC and may be an important therapeutic target in TNBC .

Hedgehog signal pathway and the mechanism of tumorigenesis / 国际外科学杂志

As one of the most major disease,malignant tumor is harmful to human health.Althought it' s exact pathogenesis is still not clear,it is certainly that the formation of cancer is typical of containing many factors and having gone through many steps.Resulting from the abnormal activation of a series of proto-oncogene as well as the inactivation caused by many anti-oncogene mutation,some signal pathways work abnormally.In recent years,the study of Hedgehog ( Hh),as the signal pathway,shows that Hh encodes a series of secreted signaling protein,having an important effect on the differentiation and proliferation of cells in the process of embryogenesis.The occurrence of abnormal activation of Hh signaling pathway plays a significant role in the process of tumorigenesis.Signal paths of Hh signaling protein include as much as following at least:patched(Ptch),smoothened (Smo),fused (Fu),suppressor of fused (SuFu),costaⅠ-2 (Cos)-2 and cubitus interruptus (Ci) and so on.In this paper,the function of Hh genetic family and the mechanism of its relation to many kinds of human cancers will be givien a brief overview.

Utility of Smo as a Prognostic Marker for Human Bladder Tumors / 대한비뇨기과학회지

PURPOSE: Smoothened(Smo) encodes a 1,024 amino acid transmembrane protein that acts as a transducer of the hedgehog(Hh) signal and maps to 7q31-q32 in humans. In the absence of Hh, Patched(Ptc) prevents Smo from signaling. When M-Hh-N binds to Ptc, however, Smo is free to upregulate downstream genes in the network. Activating mutations in Smo have been identified in sporadic basal cell carcinomas. This study was performed to evaluate the significance of Smo expression in humanzbladder cancer. MATERIALS AND METHODS: Tumor tissues were obtained from 140 patients with bladder cancer and normal bladder mucosa were acquired from 17 patients without bladder cancer as controls. Smo expression was assessed from paraffin sections of tissues using immunohistochemistry and graded on a scale of 0-12 according to the intensity and rate of staining. Differences of Smo expression between the bladder tumors and normal mucosa were compared. The relationships between their expression and the pathological or clinical characteristics such as tumor stage, grade, recurrence, and progression were also analyzed. RESULTS: There was no difference in the Smo expression in comparisons between the bladder cancers and the normal tissues(4.96+/-1.92 vs.4.52+/-0.87, p=0.111). Superficial bladder tumors had a higher Smo expression compared with normal tissues(0.005). Smo expression in the superficial and low-grade bladder tumors were higher than in the invasive and high-grade bladder tumors(p=0.002 and 0.001, respectively). The progression status was correlated with Smo expression but not the recurrence status(p=0.041 and 0.357, respectively). However, the Smo expression levels were not associated with the overall survival of patients(p=0.406). CONCLUSIONS: The results of this study showed that the enhanced expression of Smo was correlated with superficial, low-grade bladder cancer and tumors without progression. These results suggest that Smo is closely correlated with the differentiation and progression of bladder cancer and may, therefore, be useful as a prognostic marker for bladder cancer in the clinical setting.