Effect of trastuzumab interchain disulfide bond cleavage on Fcγ receptor binding and antibody-dependent tumour cell phagocytosis.

The Fc domain of human IgG1 binds to Fcγ receptors (FcγRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents.

Subtypes of metabolic syndrome and of other risk factors in Japanese women with erosive esophagitis.

Obesity and metabolic syndrome (MS) are strongly associated with erosive esophagitis (EE). The prevalence of MS and EE, and the distribution of adipose tissue have been known to differ markedly between men and women. Although the prevalence of EE in men with MS is known to be higher in visceral fat type MS (V-type MS) than in subcutaneous fat type MS (S-type MS), the association between EE and the types of MS in women with MS is unclear.

Cleavage of the interchain disulfide bonds in rituximab increases its affinity for FcγRIIIA.

The Fc region of human IgG1 mediates effector function via binding to Fcγ receptors and complement activation. The H and L chains of IgG1 antibodies are joined by four interchain disulfide bonds. In this study, these bonds within the therapeutic IgG1 rituximab (RTX) were cleaved either by mild reduction followed by alkylation or by mild S-sulfonation; consequently, two modified RTXs - A-RTX (alkylated) and S-RTX (S-sulfonated) - were formed, and both were almost as potent as unmodified RTX when binding CD20 antigen.

Visceral fat predominance is associated with non-alcoholic fatty liver disease in Japanese women with metabolic syndrome.

Aim: Metabolic syndrome (MS) is likely to be associated with non-alcoholic fatty liver disease (NAFLD). The prevalence of NAFLD in visceral fat type MS (V-type MS) is known to be higher than in subcutaneous fat type MS (S-type MS) in men with MS, and a larger subcutaneous fat area is reported to be not associated with NAFLD in women. We elucidated differences between V-type S-type MS in Japanese women with MS.

Visceral fat predominance is associated with erosive esophagitis in Japanese men with metabolic syndrome.

Background And Aim: Although visceral fat is strongly associated with metabolic syndrome (MS), the association between erosive esophagitis (EE) and visceral and subcutaneous fat types in individuals with MS has remained unclear. In this study, we divided individuals with MS into those with visceral and subcutaneous fat types, and determined the differences in the presence of EE between the types of MS in Japanese men.

Methods: The participants were 265 men with MS who underwent a medical checkup including upper gastrointestinal endoscopy and abdominal ultrasonography.

Usefulness of differentiating metabolic syndrome into visceral fat type and subcutaneous fat type using ultrasonography in Japanese males.

Background: Although metabolic syndrome (MS) is likely to be associated with nonalcoholic fatty liver disease (NAFLD), visceral fat type MS and subcutaneous fat type MS have not been distinguished. In this study, we divided persons with MS into those with visceral and subcutaneous fat types by ultrasonography (US), and elucidated differences between these types of MS in Japanese males.

Methods: The subjects were 628 males with MS who underwent a medical checkup including abdominal US.

Reconstruction of the gastrointestinal tract by hemi-double stapling method for the esophagus and jejunum using EEA OrVil in laparoscopic total gastrectomy and proximal gastrectomy.

We report the method of anastomosis based on a hemi-double stapling technique (hereinafter, HDST) using a trans-oral anvil delivery system (EEA OrVil) for reconstructing the esophagus and lifted jejunum following laparoscopic total gastrectomy or proximal gastric resection. As a basic technique, end-to-side anastomosis was used for the cut-off stump of the esophagus and lifted jejunum. After the gastric lymph node dissection, the esophagus was cut off obliquely to the long axis using an automated stapler.

TNF receptor II fusion protein with tandemly repeated Fc domains.

The extracellular domain of tumour necrosis factor (TNF) receptor II fused with the human IgG1 Fc region (TNFRII-Fc), as well as antibodies against TNF, has been used to treat rheumatoid arthritis. However, TNFRII-Fc is less effective than these antibodies in terms of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against cells bearing TNF on the cell surface. We hypothesized that these activities could be increased by fusing TNFRII with tandemly repeated Fc (TNFRII-Fc-Fc).

Hemoperfusion with a high-mobility group box 1 adsorption column can prevent the occurrence of hepatic ischemia-reperfusion injury in rats.

Objective: High-mobility group box 1, a ubiquitous nonhistone chromosomal protein, is passively released from necrotic cells and actively secreted by inflammatory cells. Extracellular high-mobility group box 1 has recently been recognized to be a mediator of hepatic ischemia-reperfusion injury; however, the kinetics of high-mobility group box 1 during hepatic ischemia-reperfusion and the role of high-mobility group box 1 in ischemia-reperfusion injury still remain poorly understood. This study was designed to assess the localization and the kinetics of high-mobility group box 1 during hepatic ischemia-reperfusion injury and the effects of high-mobility group box 1 adsorption column in hepatic ischemia-reperfusion injury.

A resected case of liver metastasis from colon cancer that occurred 13 years after a colectomy.

A 73-year-old man, who underwent a potentially curative resection of cancer of the descending colon 13 years before, was found to have a well-defined hepatic tumor on ultrasonography. A lateral segmentectomy was performed for a solitary hepatic tumor. Histopathological examination of the tumor indicated well differentiated adenocarcinoma compatible with the metastasis from the previous descending colon cancer.

Role of peroxisome proliferator-activated receptor-gamma (PPARgamma) during liver regeneration in rats.

Background And Aim: Peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the nuclear receptor superfamily, is widely expressed in adipocytes and other tissues, including the liver. Several reports have shown that PPARgamma activation induced cell-cycle arrest and apoptosis in tumor cells. We investigated the role of the PPARgamma/ligand system and the effect of the PPARgamma agonist during liver regeneration.

Increased expression of fractalkine is correlated with a better prognosis and an increased number of both CD8+ T cells and natural killer cells in gastric adenocarcinoma.

Background: Fractalkine (CX3CL1) is the only CX3C chemokine that can chemoattract natural killer (NK) cells, CD8+ T cells, monocytes, and dendritic cells. Although experimental studies have demonstrated that Fractalkine expression by tumor cells is related to the infiltrating lymphocytes and initiates antitumor immunity, the clinical significance of Fractalkine remains to be elucidated in gastric adenocarcinoma.

Methods: Tissue sections from 158 patients with curatively resected T2 or T3 gastric adenocarcinoma were immunohistochemically stained for Fractalkine.

Experimental investigation of the role of endothelin-1 in idiopathic portal hypertension.

Background And Aim: The authors' previous report revealed that endothelin-1 might be released from B lymphocytes in cirrhotic patients with hypersplenism. Other investigators have shown that persistent exposure to environmental contaminants including arsenic might induce idiopathic portal hypertension. The aim of this study was to experimentally identify how endothelin-1 is involved in the development of idiopathic portal hypertension and which cells produce endothelin-1 in the spleen.

Our experiences in surgical treatment for hilar cholangiocarcinoma.

Background/aims: Although resection for hilar cholangiocarcinoma usually requires difficult surgical manipulations, it is only one therapeutic modality for a permanent cure or a desirable prognosis. We verified our own experiences after surgical treatment for hilar cholangiocarcinoma.

Methodology: This study included 24 patients with hilar cholangiocarcinoma from 1981 to 2002.

FR-167653, a selective p38 MAPK inhibitor, exerts salutary effect on liver cirrhosis through downregulation of Runx2.

Liver cirrhosis remains a difficult-to-treat disease with a substantial morbidity and mortality rate. There is an emerging body of data purporting a pivotal role of the activated p38 mitogen-activated protein kinase (MAPK) in the process of cirrhosis. Several anticirrhotic agents have been developed over the past few years, and most of them exert their effects by indirectly inhibiting the p38 pathway.

Fractalkine-CX3CR1 axis regulates tumor cell cycle and deteriorates prognosis after radical resection for hepatocellular carcinoma.

Background And Objectives: Fractalkine is the only CX3C chemokine, and its receptor, CX3CR1, is expressed on NK cells, CD8+ T cells, monocytes, and dendritic cells (DC). Although studies have reported that fractalkine regulates the host immune response, the roles of the fractalkine-CX3CR1 axis in tumor biology and the clinical results of hepatocellular carcinoma (HCC) remain unknown.

Methods: Fractalkine and CX3CR1 expression in HCC were evaluated and compared with the clinicopathologic features, including tumor progression determined by proliferating cell nuclear antigen (PCNA) antibody and patient prognosis after surgery.

Expression of hypoxia inducible factor-1alpha during liver regeneration induced by partial hepatectomy in rats.

Background/aims: It has been well established that hypoxia inducible factor-1alpha (HIF-1alpha) transcribes essential factors in cell preservation, including angiogenesis, during hypoxia. However, the transition of HIF-1alpha expression during liver regeneration remains unknown. In this study, a role of HIF-1alpha was experimentally elucidated in relation to sinusoidal endothelial reconstruction during liver regeneration.

Tetracycline analogues (doxycycline and COL-3) induce caspase-dependent and -independent apoptosis in human colon cancer cells.

Tetracycline analogues (TCNAs) possess cytotoxic activities as well as matrix metalloproteinase (MMP) inhibitory properties. Previously, we demonstrated that doxycycline (DOXY) could induce apoptosis in human HT29 colon cancer cells. In present study, the molecular apoptotic mechanisms induced by two kinds of TCNAs, designated as DOXY and COL-3 (chemically modified tetracycline-3; 6-demethyl, 6-deoxy, 4-dedimethylamino tetracycline), were evaluated in cultured HT29 cells.

Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma.

Background: Macrophage migration inhibitory factor (MIF) is a pivotal cytokine that regulates inflammatory and immune responses. Recently, many investigators reported that MIF is expressed highly in several tumors, including hepatocellular carcinoma (HCC). However, the role of MIF in tumor angiogenesis and patient prognosis has not been examined in patients with HCC.

Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma.

Background: The gap junction (GJ) plays important roles in the maintenance of tissue homeostasis, the control of cell growth and differentiation, and the prevention of experimental hepatocarcinogenesis. In this study, we examined the relationship between the expression of the GJ protein connexin (Cx) 32 in 24 human hepatocellular carcinomas (HCCs) and 29 non-carcinomatous liver specimens (NCLs) of 31 patients.

Methods: An immunohistochemical study of Cx32 was done in 24 HCCs and 29 NCLs from 31 patients who had undergone hepatic resection.

Doxycycline inhibits cell proliferation and invasive potential: combination therapy with cyclooxygenase-2 inhibitor in human colorectal cancer cells.

Matrix metalloproteinases (MMPs) and cyclooxygenase (COX) enzymes play pivotal roles in the metastatic process of colorectal cancers. Inhibition of both MMPs and COX could be an attractive option for the inhibition of cell growth and invasion. Two human colorectal cancer cell lines, LS174T and HT29, were challenged with MMP inhibitor (doxycycline), selective COX-2 inhibitor (NS-398), or a combination of these agents to evaluate cancer cell proliferation and invasion.

Transforming growth factor-beta1 induced hepatocyte apoptosis--a possible mechanism for growth of colorectal liver metastasis.

The mechanisms of colonization and growth of metastatic liver tumors from colorectal cancers remain obscure. Forty-three resected colorectal metastatic liver tumors with surrounding livers were evaluated for apoptotic index (AI), proliferation index (PI), and immunohistochemical expressions of TGF-beta1. TGF-beta receptor II, Fas, and Fas-ligand.

Transforming growth factor-beta1 released from the spleen exerts a growth inhibitory effect on liver regeneration in rats.

Several previous reports indicated that partial hepatectomy (PH) when combined with splenectomy enhances the regenerative capacity of the liver, most probably due to the removal of unknown inhibitory factors released from the spleen. Transforming growth factor (TGF)-beta1 is a major antiproliferative factor for the hepatocytes, and the role of splenic TGF-beta1 in liver regeneration is yet to be clarified. The splenic expression of TGF-beta1 and its secretion into the portal circulation from the spleen were evaluated in a standardized two-thirds hepatectomy model in rats.

Sequential changes of connexin32 and connexin26 in ischemia-reperfusion of the liver in rats.

Serial changes in expression of hepatic gap junction components, connexin32 and connexin26 expressions during ischemia (60 min)-reperfusion injury of the liver were evaluated by immunofluorescence staining and reverse transcription-polymerase chain reaction in rats. Hepatic tissue calcium content and liver enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase), were also examined. Connexin expressions were down-regulated during ischemia and steeply increased during the early reperfusion period.

Serum endostatin predicts tumor vascularity in hepatocellular carcinoma.

Background: Tumor angiogenesis is a strong prognostic factor in patients with hepatocellular carcinoma (HCC). However, to the authors' knowledge, details regarding the serum levels of proangiogenic and antiangiogenic growth factors controlling this process are not yet known.

Methods: Serum endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) levels were measured by the enzyme immunoassay method in prospectively collected samples from 33 HCC patients who had received no preoperative therapy.