Sonic Hedgehog (Shh) plays an essential role in vertebrate organogenesis as well as the development of some cancers, including breast cancer. The aim of the present study was to characterize more precisely its role in breast carcinogenesis and elucidate its regulation mechanisms. The expression of Shh was investigated in 97 breast carcinomas and 22 paired non-tumorous tissues (distant from the primary tumor) by immunohistochemistry and in four breast cell lines by Western blotting. We also analyzed the methylation status of the Shh gene with methylation-specific PCR and assessed whether nuclear factor-kappa B (NF-jB) and Gli1 were expressed in breast tissues by immunohistochemistry. Our results showed that Shh protein expression in breast carcinomas was significant higher than that in normal breast tissues (P < 0.01). The upregulation of Shh in breast carcinomas was correlated significantly with early clinical stage (P < 0.05). In addition, we found a substantial increase in Shh expression at both the mRNA and protein levels in several human breast carcinoma cell lines. The expression level of nuclear Gli1 was positively associated with the expression level of Shh in breast tissues (P < 0.001). Promoter region hypomethylation (43/61, 70.5%) was frequently observed in breast carcinomas and significantly associated with Shh up-regulation (P < 0.05). The DNA methyltransferase inhibitor 5-azacytidine (5-Aza) reduced the methylation of Shh promoter and increased the expression of Shh protein in MDA-MB-435 and MCF-10A cells. Furthermore, most of the breast carcinoma cases with Shh up-regulation had increased expression of NF-jB (35/49, 71.4%; P < 0.001). Taken together, these observations suggest that Shh overexpression is a critical event in breast carcinogenesis, and Shh promoter hypomethylation and NF-jB up-regulation are responsible for the up-regulation of Shh. (Cancer Sci 2010; 101: 927-933)

Seven in absentia homolog1 (SIAH1) was reported as a tumor suppressor and played an important role in regulating cell apoptosis. However, its effects on the breast carcinogenesis remain unclear. In this study, our aims were to examine the relationship between SIAH1 and Bcl-2-interacting mediator of cell death (Bim) and to explore the effects of SIAH1 on the breast carcinogenesis. Immunohistochemical analysis in 231 cases of breast tissues showed that the expression of SIAH1 and Bim were significantly decreased in the breast carcinogenesis. Moreover, SIAH1 expression was significantly correlated with Bim. Both SIAH1 and Bim expression were significantly higher in well to moderately differentiated and in early-stage breast cancer. Reverse transcription (RT)-polymerase chain reaction (PCR) and Western blot analysis in paired breast cancer tissues and breast cell lines found that the expression of SIAH1 was lower in the breast cancer tissues and cell lines. SIAH1 inducing apoptosis of the breast cancer cells was dependent on Bim. However, SIAH1 inhibiting invasion of the breast cancer cells was independent of Bim. The increase of the function of SIAH1 to upregulate the expression of Bim may play an important role in the progression of breast cancer. Restoration of the function of SIAH1 may be a new therapeutic target of human breast cancer.

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Background Pseudomyxoma peritonei (PMP) is a rare disease, the prognosis of overall survival (OS) is affected by many factors, present study aim to de ne independent prediction indicators and establish a nomogram for PMP patients.Methods 119 PMP patients received cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in our center for the rst time were included between 01/06/2013 and 22/11/2019 . The log-rank test was used to compare the OS rate among groups, subsequently, variables with P<0.10 were subjected to multivariate Cox model for de ning independent prediction indicators.Finally, the nomogram prediction models will be established and for internal validation.Results Multivariate analysis showed Sex, D-Dimer, CA125, CA19-9, PCI, and degree of radical surgery were independently associated with OS in PMP patients. A nomogram was plotted based on the independent predictive factors and undergone internal validation, ROC analysis was performed to calculate discrimination ability of the nomogram, the C-index was 0.880 (95%CI: 0.806-0.933) and calibration plots showed good performance.Conclusions Six independent prognostic factor for predicting survival in PMP patients were di ned, the nomogram has a good discrimination ability for individual risk predition, more researches are needed to verify and improve the prediction model.Although several demonstrated factors could affect the prognosis of patients with PMP, to our best knowledge, there were very few studies had established prediction model for PMP patients. In present study, we want to reevaluate whether all the above traditional factors have predictive value for PMP patients, simultaneously, we intend to evaluate the predictive value of new tumor markers (CA724 and CA242) for PMP. On this foundation, a tumor markers based model to predict the prognosis of PMP will be established, which may be helpful in the prognosis judgment and treatment intervention for PMP patients. Methods PatientsThe ethics committee of Peking University Aerospace School of Clinical Medicine approved of present study, all patients signed informed consent before CRS and consented to be followed up after surgery.We retrieved the diagnostic name of'pseudomyxoma peritonei'in the special follow-up database from Peking University Aerospace School of Clinical Medicine between 01/06/2013 and 22/11/2019, a total of 886 patients with PMP diagnosis were acquired. In order to ensure the reliability of the research, 734 patients with PMP whose operation were performed not in our center were excluded from present study, the detailed reasons were as follows, for rst, different hospitals may use different instruments or methods to detect tumor markers, which cannot guarantee the consistency of test results; secondly, although CRS combined with HIPEC are the optimal treatment for PMP patients, we found that there were still many patients who had only undergone CRS or chemotherapy (intravenous or intraperitoneal) in nonspecilist hospitals, PMP treatment is best in a...

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