High STAT4 Expression Indicates Better Disease-free Survival in Patients with Gastric Cancer.

BACKGROUND: The aim of this study was to investigate the significance of signal transducer and activator of transcription 4 (STAT4) expression and the correlation between STAT4 and interferon gamma (IFN-γ) in patients with gastric cancer. PATIENTS AND METHODS: Sixty-two patients who underwent gastrectomy for gastric cancer were enrolled in the study. STAT4 and IFNG mRNA expression was evaluated by quantitative real-time polymerase chain reaction (PCR). Immunohistochemistry was performed to examine CD8+ T-cells, and STAT4 and IFN-γ expression. RESULTS: STAT4 mRNA expression was significantly correlated with IFNG mRNA expression (p<0.05). Regarding disease-free survival, there was a significant difference between the groups with high and low STAT4 expression (5-year disease-free survival: 77.8% and 56.4%, p<0.05). Univariate analysis revealed that tumor differentiation and STAT4 expression were significant factors for tumor recurrence. CONCLUSION: High expression of STAT4 in gastric cancer predicted a better clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after gastrectomy.

Inferior vena cava stenosis-induced sinusoidal obstructive syndrome after living donor liver transplantation

The sinusoidal obstructive syndrome (SOS) is a complication that usually follows hematopoietic stem cell transplantation. It is also known as veno-occlusive disease, which is a rare complication of living donor liver transplantation (LDLT). Herein, we reported a 34 year-old female patient presenting SOS after LDLT. Its underlying cause was presumed to be associated with liver abscess and subsequent inferior vena cava stenosis. SOS led to graft failure, thus requiring retransplantation with a deceased donor liver graft. The underlying causes of SOS are complex pathologic entity with multifactorial etiology. It is likely that its multifactorial etiology includes a decrease of hepatic venous outflow that is caused by graft liver infection and inferior vena cava stenosis.

Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.

UNLABELLED: Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells. MATERIALS AND METHODS: The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine. RESULTS: HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner. CONCLUSION: Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.

Expression of Stathmin1 in gastric adenocarcinoma.

BACKGROUND: Over expression of Stathmin1 (STMN1), activation-induced cytidine deaminase (AID) and protein kinase C iota (PKCi) proteins participate in the regulation of carcinogenesis. In the present study, we investigated the expression of STMN1 in patients with gastric adenocarcinoma and also determined the correlation of STMN1 with AID and PKCi proteins. MATERIALS AND METHODS: This study was conducted in the Tokushima University Hospital between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma. Stathmin1, AID and PKCi protein expressions were evaluated by immuno-histochemistry in gastric adenocarcinoma. RESULTS: A strong expression of STMN1 was significantly associated with gender- and poorly differentiated gastric adenocarcinoma (p<0.05). A high mRNA level of STMN1 was found in the tumor tissue of gastric adenocarcinoma compared to non-tumor tissue (p<0.05). In addition, STMN1 expression was significantly correlated with AID and PKCi protein expressions in gastric adenocarcinoma (p<0.05). CONCLUSION: High mRNA level of the Stathmin1 gene was significantly expressed in gastric tumor tissue than non-tumor and strong expression of STMN1 protein is correlated with poorly-differentiated gastric adenocarcinoma.

The role of activation-induced cytidine deaminase expression in gastric adenocarcinoma.

BACKGROUND: Gastric adenocarcinoma is one of the most common malignant tumors and the leading cause of malignancy-related death worldwide. Studies have reported overexpression of activation-induced cytidine deaminase (AID) and protein kinase c iota (PKCi) proteins showing involvement in the regulation of carcinogenesis. In the present study, we investigated the expression of AID and PKCi in patients with gastric adenocarcinoma and determined the correlation between these proteins. MATERIALS AND METHODS: This study was conducted between September 2009 and September 2010 on a total of 59 patients with gastric adenocarcinoma at the Tokushima University Hospital. AID, PKCi and mutated p53 protein expressions were evaluated by immunohistochemistry in gastric adenocarcinoma. RESULTS: High AID and PKCi expression was significantly (p<0.05) associated with poorly-differentiated gastric adenocarcinoma. In addition, PKCi expression was significantly correlated with clinicopathological findings such as a lymph node metastasis, and venous and lymphatic invasion (p<0.05). Furthermore, AID expression was significantly correlated with PKCi and mutated p53 protein expression in gastric adenocarcinoma (p<0.05). CONCLUSION: High AID and PKCi expressions were significantly correlated with poorly-differentiated gastric adenocarcinoma.

Хавдрын үүдэл эсийн зохицуулгад “sonic hedgehog” дохиоллын үүрэг / Шинэ санаа Шинэ нээлт

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigeniccapacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs.METHODS:Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44,EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJgenes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM).RESULTS:The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathwayPtch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal markerVimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited.CONCLUSION:EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.

Элэгний мэс засалд гарсан сүүлийн үеийн ололт амжилтууд: Элэгний үйл ажиллагааны нөөцийг үнэлэх, загварчлах болон чиглүүлэх / Шинэ санаа Шинэ нээлт

INTRODUCTION: Recent technical innovation in liver surgery is remarkable. Now, for example, a preoperative 3D-simulation of the liver is a routine modality, and indispensable (or essential) for liver surgery. The aim of this presentation is to clarify various kinds of progresses and future perspective in liver surgery. PREOPERATIVE MODALITIES 1) One-stop shopping of 3D-simulation of the liver: We newly developed 3D-simulation using a software of SYNAPSE VINCENT Ver. 3.1 (Fujifilm Medical, Tokyo, Japan), in which biliary system is simultaneously reconstructed in one dynamic MD-CT. This technique avoids position error which occurred in 3D fusion image using another modality such as DIC–CT or MRCP, as well as unnecessary radiation exposure. 2) Assessment of partial functional reserve: We have reported new methods to astimate regional hepatic functional reserve using hepatocyte-phase of EOB-MRI (J Gastroenterol 2012), and fusion image of 3D-CT and asialoscintigraphy using 99m-Tc galactosyl human albumin. The method of EOB-MRI utilized character of hepatocyte-uptake of EOB through membrane transporters on hepatocytes. The other used fusion of both asialoscintigram of hepatic functional reserve and 3D-simulation by the above-mentioned software. Those techniques provided accurate estimation of partial functional volume, and help surgeons’ decision making of resection volume. INTRAOPERATIVE MODALITIES: 1) Navigation using iPad: navigation using iPad in which preoperative 3D-image data are uploaded in advance, tumor location, accurate and anatomical orientation can confirm in the operative field during operation. This technique enable not only operators also assistants or students to better understand precise anatomy. 2) Indocyanine green (ICG) fluorescent image-guided navigation: this technique using HyperEye Medical System (MIZUHO IKAKOGYO Co., Ltd. Tokyo, Japan) help us to confirm tattooing of target segment and parenchymal intersegmental plane, and detect hepatic tumors (metastatic and HCC) near liver surface as well as invisible tumor inside the liver. CONCLUSIONS: Various advancements such as preoperative 3D-simulation including partial functional reserve estimation and intraoperative navigation techniques enabled surgeons to easily and safely perform hepatic resection.

Хавдрын үүдэл эсийн зохицуулгад “sonic hedgehog” дохиоллын үүрэг / Шинэ санаа Шинэ нээлт

Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigenic capacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs. METHODS: Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for 14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44, EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJ genes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM). RESULTS: The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathway Ptch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal marker Vimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited. CONCLUSION: EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.