A case of EMRC for basaloid squamous carcinoma of the cervical esophagus.

Basaloid squamous carcinoma (BSC) of the esophagus is a rare esophageal tumor. A 79-year-old man with a history of proximal gastrectomy for gastric adenocarcinoma in 2000 was followed-up by esophagogastroduodenoscopy (EGD) annually. In June 2010, EGD revealed a new protruding lesion in the cervical esophagus.

Advanced therapies using autologous bone marrow cells for chronic liver disease.

The radical treatment currently for decompensated liver cirrhosis is still liver transplantation. However, liver transplants are not widely performed worldwide and development of genuine regeneration therapy for liver cirrhosis is an urgent task. We have developed a novel murine model [the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model], and reported that infused GFP-positive bone marrow cells repopulated cirrhotic liver.

Risk factors for delayed bleeding from endoscopic submucosal dissection of gastric neoplasms.

Objective: Delayed bleeding is a major complication of endoscopic submucosal dissection (ESD) of gastric neoplasms. We aimed to clarify risk factors for delayed bleeding from ESD.

Material And Methods: This study included 447 patients in whom 544 gastric neoplasms were resected by ESD between April 2006 and March 2011 in Yamaguchi University Hospital.

Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean.

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P(meta) = 1.

Guidelines on nutritional management in Japanese patients with liver cirrhosis from the perspective of preventing hepatocellular carcinoma.

Aim:   The Japanese Nutritional Study Group for Liver Cirrhosis (JNUS) was assembled in 2008 with the support of a Health Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan. The goal of the study group was to propose new nutritional guidelines for Japanese patients with liver cirrhosis (LC), with the aim of preventing hepatocellular carcinoma.

Methods:   Between 2008 and 2010, the member investigators of JNUS conducted various clinical and experimental studies on nutrition on LC.

Heat-shock protein 27 plays the key role in gemcitabine-resistance of pancreatic cancer cells.

Pancreatic cancer is one of the most fatal types of cancer in developed countries. Most patients have locally advanced or metastatic cancerous lesions when they are diagnosed, due to the progressive, invasive and metastatic capacity of this disease to liver, lymph nodes and distant organs during early stages. Although the only curative therapy is complete surgical resection, the disease has usually already progressed by the time of diagnosis, and the majority of patients have metastatic disease.

Evaluation of a novel non-invasive (13) C-glucose breath test for the identification of diabetes mellitus in cirrhotic patients.

Aim:   Diabetes mellitus (DM) has been reported to worsen the long-term prognosis of cirrhotic patients, and many studies have reported that DM is an independent risk factor for hepatocellular carcinoma. However, an accurate diagnosis of DM is sometimes difficult in cirrhotic patients. Recently, a novel non-invasive (13) C-glucose breath test has been reported to be useful for diagnosing insulin resistance in non-cirrhotic patients.

Guideline on the use of new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update.

The "Guideline on the Use of New Anticancer Drugs for the Treatment of Hepatocellular Carcinoma" was prepared by the Study Group on New Liver Cancer Therapies established by the "Research Project on Emergency Measures to Overcome Hepatitis" under the auspices of the Health and Labour Sciences Research Grant. The Guideline brings together data collected by the Study Group on the use and incidence of adverse events in 264 patients with advanced hepatocellular carcinoma (HCC) treated using sorafenib and in 535 patients with advanced HCC treated using miriplatin at 16 participating institutions up until 22 December 2010, as well as referring to the published studies, academic presentations, and reports from the private sector. The aim of this Guideline is to facilitate understanding and current thinking regarding the proper usage of new anticancer drugs towards actual use in therapy.

Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model.

Purpose: We previously developed medaka non-alcoholic steatohepatitis (NASH) model. The model showed similar histology with human NASH so we analyzed the effect of drug using medaka NASH activity score (MNAS). In this study we analyzed the effect of ezetimibe, a small intestine cholesterol transporter inhibitor, on NASH.

Granulocyte colony-stimulating factor and interleukin-1β are important cytokines in repair of the cirrhotic liver after bone marrow cell infusion: comparison of humans and model mice.

We previously described the effectiveness of autologous bone marrow cell infusion (ABMi) therapy for patients with liver cirrhosis (LC). We analyzed chronological changes in 19 serum cytokines as well as levels of specific cytokines in patients after ABMi therapy and in a mouse model of cirrhosis generated using green fluorescent protein (GFP)/carbon tetrachloride (CCl4). We measured expression profiles of cytokines in serum samples collected from 13 patients before and at 1 day and 1 week after ABMi.

Timeline for development of autologous bone marrow infusion (ABMi) therapy and perspective for future stem cell therapy.

Liver cirrhosis patients generally progress to liver failure. To cure this progressive disease, we developed a novel cell therapy using bone marrow cells; autologous bone marrow cell infusion (ABMi) therapy. We previously described the possible action mechanism of ABMi therapy in the cirrhotic liver, and showed the timeline and results of clinical studies of ABMi therapy.

Stem cell therapy in chronic liver disease.

Purpose Of Review: To provide an overview of the current status of liver regeneration therapies for liver cirrhosis and future prospects.

Recent Findings: Various clinical studies for liver disease have been reported, including hepatic administration of autologous CD34-positive cells induced by granulocyte colony-stimulating factor, portal vein administration of CD133-positive mononuclear cells, and administration of autologous bone marrow-derived mesenchymal stem cells. Effectiveness of these approaches has been shown in some patients.

Hepatic arterial infusion chemotherapy in combination with pegylated interferon-α-2b for advanced hepatocellular carcinoma.

Background/aims: We previously reported that combination therapy comprising hepatic arterial infusion chemotherapy (HAIC) with 3 drugs, namely, cisplatin (CDDP), 5-fluorouracil (5-FU) (low-dose FP) and isovorin and interferon (IFN)-α-2b was not beneficial for patients with advanced hepatocellular carcinoma (HCC). In this study, we investigated the efficacy of combination therapy comprising HAIC and pegylated interferon (PEG-IFN)-α-2b in advanced HCC patients by comparing our results with previous data.

Methodology: From a total of 29 patients, 12 received HAIC and PEGIFN- α-2b (PEG-IFN group) and 17 received HAIC and IFN-α-2b (IFN group).

[Autologous bone marrow cell infusion therapy for liver cirrhosis--now and future].

Infused (transplanted) green fluorescent protein (GFP)-positive bone marrow cells (BMCs) migrated into the peri-portal regions of the cirrhotic mouse liver induced continuous CCl4 injection without irradiation (without bone marrow ablation). The infused GFP-positive BMCs differentiated into hepatoblasts detected with Liv2-antibody and then differentiated into albumin-producing hepatocytes. The differentiation "niche" induced by persistent liver damage due to continuous CCl4 injection seems to be an essential factor.

Autologous bone marrow cell infusions suppress tumor initiation in hepatocarcinogenic mice with liver cirrhosis.

We have previously reported the efficacy and safety of autologous bone marrow cell infusion (ABMi) therapy for liver cirrhosis patients without hepatocellular carcinoma in a multicenter clinical trial. However, since liver cirrhosis is highly oncogenic, evaluation of the effects of ABMi on the mechanisms of hepatocarcinogenesis is of great importance. Therefore, frequent ABMi was performed in hepatocarcinogenic mice, and its effects on hepatocarcinogenesis were analyzed.

Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma.

Background: Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs.

Methods: A total of 50 HCC patients [Child-Pugh A/B, 34/16 patients; maximum tumor size 2.

Therapeutic potential of canine bone marrow stromal cells (BMSCs) in the carbon tetrachloride (CCl4) induced chronic liver dysfunction mouse model.

Regenerative medicine using bone marrow cells is an attractive therapy for the cure of patients with severe liver disease. Here, we show the therapeutic potential of canine bone marrow stromal cells (BMSCs) in mouse models of CCl(4)-induced chronic liver dysfunction. We used two different models for xenotransplantation, nude mice and cyclosporine A (CSA) immunosuppressed mice.

A randomized phase II trial of intra-arterial chemotherapy using SM-11355 (Miriplatin) for hepatocellular carcinoma.

Background: SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference.

Methods: Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery.

Preoperative evaluation of early colorectal cancer using an ultrasound mini probe.

Background/aims: We investigated whether endoscopic ultrasonography (EUS) can assess the depth of invasion of early colorectal cancer exhibiting the V pit pattern on magnifying endoscopy with submucosal invasion of 1,000 μm or deeper.

Methodology: Among 38 colorectal tumors exhibiting the V pit pattern on magnifying endoscopy, the findings on EUS with a mini-probe (15 MHz) were compared with histopathological findings. The diagnostic accuracy, sensitivity and specificity of EUS were examined separately in tumors exhibiting the Vi or V5 pit pattern.

Matrix metalloproteinases (MMPs) activity in cultured canine bone marrow stromal cells (BMSCs).

Autologous bone marrow stromal cells (BMSCs) infusion therapy improves the hepatic fibrosis. To investigate the mechanism of remission, we evaluated the matrix metalloproteinase (MMP)-2 and -9 activity in canine BMSCs and the effect of pro-inflammatory cytokines on their expression. The activity and the gene expression of MMPs were analyzed by gelatin zymography and quantitative RT-PCR, respectively.

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma and future treatments for the poor responders.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The most common problem associated with HCC is a high risk of intrahepatic recurrence despite radical treatment, and in many patients, this recurrence has fatal consequences. For patients with advanced-stage HCC according to the Barcelona Clinic Liver Cancer staging system, the multikinase inhibitor sorafenib is the current standard of care.

Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients.

Background: In 2003, we initiated a clinical trial to examine autologous bone marrow cell infusion (ABMi) therapy for cirrhotic patients and reported the clinical effect of the therapy. To analyze how splenectomy may potentiate the effects of bone marrow cell infusion on cirrhosis, we performed a mouse study and a clinical trial on patients with cirrhosis.

Methods: In mice, we analyzed the effect of splenectomy on bone marrow cell infusion in four experimental groups (group A, splenectomy + bone marrow cell infusion + CCl(4); group B, sham operation + bone marrow cell infusion + CCl(4); group C, splenectomy + CCl(4); group D, sham operation + CCl(4)).

Identification of four isoforms of aldolase B down-regulated in hepatocellular carcinoma tissues by means of two-dimensional Western blotting.

Background: Hepatocellular carcinoma (HCC) is one of the most lethal diseases, and one of the major causes of death in Japan. Our previous research of proteomics for cancerous and paired non-cancerous tissues from patients with HCC with hepatitis C virus infection (HCV-HCC) by means of the combination of two-dimensional gel electrophoresis (2-DE) and liquid chromatography tandem mass spectrometry (LC-MS/MS) reported that four of numerous spots of weaker intensity in cancerous tissues than in paired non-cancerous tissues were identified as four isoforms of liver type aldolase (aldolase B). In the present study, two-dimensional (2-D) Western blot analysis demonstrated a significantly lower expression of four isoforms of aldolase B in cancerous than in non-cancerous tissues.

TNFR1-mediated signaling is important to induce the improvement of liver fibrosis by bone marrow cell infusion.

The importance of TNF-α signals mediated by tumor necrosis factor receptor type 1 (TNFR1) in inflammation and fibrosis induced by carbon tetrachloride (CCl(4)), and in post-injury liver regeneration including a GFP/CCl(4) model developed as a liver repair model by bone marrow cell (BMC) infusion, was investigated. In mice in which TNFR1 was suppressed by antagonist administration or by knockout, liver fibrosis induced by CCl(4) was significantly decreased. In these mice, intrahepatic macrophage infiltration and TGF-β1 expression were reduced and stellate cell activity was decreased; however, expression of MMP-9 was also decreased.

Up-regulation of 42 kDa tubulin alpha-6 chain fragment in well-differentiated hepatocellular carcinoma tissues from patients infected with hepatitis C virus.

We performed proteomic differential display analysis of hepatitis C virus-associated 21 human hepatocellular carcinoma (HCV-HCC) tissues by using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). One of the numerous spots which was located next to three spots of glutamine synthetase showed stronger intensity in well-differentiated HCC tissues compared to non-cancerous tissues. Samples from 6 out of 21 patients showed up-regulation of this spot compared to non-cancerous tissues.