64 research outputs found
Epigenetic modulation on sphere
Background : Cancer stem cell properties are highly relevant to the biology of treatment-resistant cancers. Epigenetic modification regulates gene expressions by chromatin remodeling during malignant transformation. The aim of this study was to elucidate the possible strategy for cancer stem cells focusing on epigenetic modification. Methods : We made cancer sphere from HepG2 cells, and we added Histone deacetylase (HDAC) inhibitor, valproic acid to cancer sphere. And we compared methylation status and the gene expression between normal HepG2 and cancer sphere groups, and between cancer sphere and sphere with HDAC inhibitor treatment groups. Results : Valproic acid (VPA) cancelled this spheroid formation. In comparison between normal HepG2 and cancer sphere, the number of methylation status changes more than 0.1 of beta level was 826 probes, and we could isolate some epithelial-mesenchymal transition (EMT) related genes. And VPA reduced the expressions of EMT related genes in sphere with RT-PCR. On the other hand, in comparison between cancer sphere and sphere with VPA treatment, we detected 29 probe of methylation status change, and VPA reduced the expressions of Bcl-6 in sphere. Conclusions : HDAC inhibitor affected the methylation status of cancer stem cells. Histone-acetylation might overcome treatmet-resistant cancer through the regulation of cancer stem cell
VOLUME REDUCTION OF MITRAL REGURGITATION IS MAIN CONTRIBUTOR TO INCREASE OF CARDIAC FORWARD FLOW AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH PREPROCEDURAL FUNCTIONAL MITRAL REGURGITATION; HEMODYNAMIC ANALYSIS USING ECHOCARDIOGRAPHY
High expression of cancer stem cell markers in cholangiolocellular carcinoma
Purpose
Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC.
Methods
The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically.
Results
Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative.
Conclusion
CLC may have stronger features derived from HpSCs than an intermediate type of CHC
Hand-assisted laparoscopic splenectomy for a huge splenic vascular lesion with aneurysms in a patient with impending Kasabach-Merritt syndrome-like phenomenon
Splenic vascular lesions are relatively rare and are usually found incidentally. However, the vascular lesions associated with Kasabach-Merritt syndrome, such as hemangioma, can be life-threatening. We herein describe the case of a young adult female patient with a huge splenic vascular lesion, aneurysms of the splenic artery, and increased plasma levels of fibrin/fibrinogen degradation products and D-dimers. Hand-assisted laparoscopic splenectomy was performed, after which the coagulopathy was drastically improved. Minimally invasive surgical intervention such as hand-assisted laparoscopic splenectomy should be considered as the first treatment choice in such a case
Reduction of T-Box 15 gene expression in tumor tissue is a prognostic biomarker for patients with hepatocellular carcinoma
Genome-wide analysis is widely applied to detect molecular alterations during oncogenesis and tumor progression. We analyzed DNA methylation profiles of hepatocellular carcinoma (HCC), and investigated the clinical role of most heypermethylated of tumor, encodes T-box 15 (TBX15), which was originally involved in mesodermal differentiation. We conducted a genome-wide analysis of DNA methylation of tumor and non-tumor tissue of 15 patients with HCC, and revealed TBX15 was the most hypermethylated gene of tumor (Beta-value in tumor tissue = 0.52 compared with non-tumor tissue). Another validation set, which comprised 58 HCC with radical resection, was analyzed to investigate the relationships between tumor phenotype and TBX15 mRNA expression. TBX15 mRNA levels in tumor tissues were significantly lower compared with those of nontumor tissues (p < 0.0001). When we assigned a cutoff value = 0.5-fold, the overall survival 5-year survival rates of the low-expression group (n = 17) were significantly shorter compared with those of the high-expression group (n = 41) (43.3% vs. 86.2%, p = 0.001). Multivariate analysis identified low TBX15 expression as an independent prognostic factor for overall and disease-free survival. Therefore, genome-wide DNA methylation profiling indicates that hypermethylation and reduced expression of TBX15 in tumor tissue represents a potential biomarker for predicting poor survival of patients with HCC
ショウニ ノ タンカン カクチョウガタ スイ タンカン ゴウリュウ イジョウ セツジョレイ ニ ハツガン カンレン イデンシ HDAC ガ コウハツゲン シテイタ 1レイ
Pancreaticobiliary maljunction(PBM)is the congenital malformation that the junction of the pancreatic and bile ducts is located outside of the duodenal wall anatomically, so sphincter function preventing to mix the bile and pancreatic juice does not act. In PBM, the mutual reflux of bile and pancreatic juice induces various diseases and becomes the cause of biliary tract cancer generation. PBM is divided into PBM with the biliary dilatation and PBM without the biliary dilatation. From the perspective of carcinogenesis, surgery to separate the pancreatic juice and bile by excision of extrahepatic biliary tract and hepaticojejunostomy is commonly performed in the former, the treatment of the latter is controversial, for instance ; the only cholecystectomy should be performed and excision of extrahepatic biliary tract is unnecessary or excision of extrahepatic biliary tract and hepaticojejunostomy should be done. In addition, histone acetylation and histone deacetylation is one of the important regulatory mechanism of gene transcription, the error of the balance between histone acetyltransferase(HAT)and histone deacetylase(HDAC)leads to carcinogenesis. In other words, HDAC has a carcinogenic potential. Overexpression of HDAC was found in the both resected gallbladder and bile duct mucosa of infant PBM patient with the biliary dilatation performed the excision of extrahepatic biliary tract and hepaticojejunostomy in our department. Appropriate treatment for PBM has not been established yet, but even infant case with PBM has carcinogenesis potential just like this case. In conclusion, further accumulation of cases including PBM without the biliary dilatation was thought to be essential though the excision of extrahepatic biliary tract and hepaticojejunostomy still seems to be required for infant PBM patient with the biliary dilatation
ニクガンテキ モンミャク シンシュウ ヨウセイ カンガン セツジョゴ ノ Systemic IFN+Low dose FP ノ ユウヨウセイ : リロンテキ コンキョ ト リンショウテキ コウカ
Background and Aims : Despite a recent progress of treatment for hepatocellular carcinoma (HCC), the prognosis of advanced HCC with macroscopic vascular invasion remains unsatisfactory. We investigated anti-tumor effect of IFNα using experimental model and show the outcome of our systemic adjuvant therapy consisting of IFNα,5FU and cisplatin(IFP)after hepatectomy on advanced HCC with macroscopic portal invasion. Methods[: Basic study]Anti-tumor effects such as inhibition of invasion, proliferation of pegylated IFN α2b(PegIFNα)was evaluated using MH134mouse HCC cells, in vitro and vivo. [Clinical study]: Thirty patients who had HCC with Vp2or more of macroscopic portal invasion(Vp2; portal vein tumor thrombus in its2nd order branch)were included. Those patients were retrospectively divided into two groups : the systemic IFNα,5FU and cisplatin group (n=14, IFP group); and the no adjuvant therapy group(n=16, control). Clinicopathological variables were compared between the two groups, including patient survival and disease-free survival. Results[: Basic]In vitro, the proliferation was significantly suppressed by Peg-IFNα, and invasion potential was also inhibited. In vivo, tumor growth was significantly suppressed compared to control (0.5vs.5.0cm, p<0.05), and liver metastases was decreased(number :19vs.6, p<0.05). [Clinical]The overall and disease-free survival rate in IFP group was significantly higher than in control group(1y :100% vs38%,3y :65% vs25%, P<0.01,1y :36% vs25%,3y :36% vs19%, P<0.01). Regarding the recurrent patterns,5of9patients in IFP group had controllable tumors in the remnant liver, although12of13patients in control group had distant metastasis or multiple recurrences in the residual liver. Conclusion : Our new adjuvant regimen of systemic IFP may be a promising strategy after radical resection for HCC with macroscopic portal invasion
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