Biomedical subjects

Morito Monden

Publications and source records attributed to Morito Monden.

At least 55 records · Page 3Linked to original sources

PubMed2006

Expression of type I interferon receptor as a predictor of clinical response to interferon-alpha therapy of gastrointestinal cancers.

Interferon (IFN) is used in the treatment of many malignancies and viral disorders. We recently reported a significant correlation between the efficacy of IFN-alpha combined with chemotherapy in the treatment of advanced hepatocellular carcinoma (HCC) and IFN-alpha/type I IFN receptor (IFNAR2) expression. It is possible that the expression of IFNAR2 in gastrointestinal cancerous tissue, apart from HCC, may predict the efficacy of IFN-alpha combination therapy. We investigated the expression of IFNAR2 in 100 gastrointestinal cancerous tissues. IFNAR2 expression was examined using immunohistochemistry, in surgically resected tissue samples (20 esophageal, 20 gastric, 20 colorectal, 20 cholangiocarcinoma, and 20 pancreatic samples). The expression rate of IFNAR2 was 35.0% (7/20), 25.0% (5/20), 20.0% (4/20), 45.0% (9/20), and 25.0% (5/20) in esophageal, gastric cancer, colorectal, cholangiocarcinoma and pancreatic cancer samples, respectively. In our previous report, the expression rate of IFNAR2 in HCC samples was 64.8% (59/91). Thus, the expression rates of IFNAR2 in the five types of gastrointestinal cancers tested here were low, compared with HCC. The clinical efficacy of IFN-alpha mono- or combination therapies in patients with gastrointestinal neoplasms is expected to be lower than in patients with HCC based on the expression level of IFNAR2.

Gastrointestinal Neoplasms↗

PubMed2006

[FAIT (FU arterial infusion and interferon therapy) for hepatocellular carcinoma].

We summarised the beneficial effects of FAIT (FU Arterial Infusion and Interferon Therapy) for advanced hepatocellular carcinoma (HCC). In the 55 patients of HCC with portal venous tumour thrombi (PVTT) treated with FAIT alone, 24 (43.6%) showed objective response, 4 (7.3%) showed no response, and 27 (49.1%) showed progressive disease. In the 15 patients of HCC with PVTT treated with FAIT and surgery, all of the cases (100%) survived over 1 year; without FAIT and surgery, 10 patients (67%) were died within 1 year. Concerning the mechanism of FAIT, we reported the synergistic effects of IFNalpha and 5-FU, in terms of the influence to cell cycle progression leading into the S phase via p27Kip1, an apoptosis-inducing effect through a reduction of Bcl-xl, and an immuno-modulatory effect via the TRAIL/TRAIL-receptor pathway. FAIT is a promising modality for advanced HCC with tumour thrombi in the major portal branches.

Antineoplastic Agents↗

PubMed2006

[S-1 treatment against advanced HCC].

We have reported a remarkably high anti-tumor efficacy using intra arterial 5-FU infusion chemotherapy combined with subcutaneous interferon-alpha injection to treat advanced hepatocellular carcinoma (HCC) with portal vein thrombus. However, we have been confirming distant metastases along with a prognosis extension as hepatic lesions could possibly be controlled to a certain extent. Even though there has been no effective chemotherapy against hepatocellular carcinoma with distant metastases, we performed S-1 and interferon-alpha combination chemotherapy for the cases where good results were exhibited from interferon-alpha combined with arterial 5-FU infusion. As a result, we confirmed CR in the anti-tumor effect against distant metastases with no severe adverse effects. It was suggested that a combination therapy of S-1 and interferon-alpha may be one of the most effective treatment modalities against advanced HCC with distant metastases.

Administration, Oral↗

PubMed2006

[The progress of hepatic arterial infusion chemotherapy for hepatocellular carcinoma].

Hepatic arterial infusion (HAI) chemotherapy has been selected as a therapeutic option for highly advanced hepatocellular carcinoma (HCC) with tumor thrombi in major portal branches or intrahepatic metastases. Conventional therapies have no clinical effect on highly advanced HCC. Recent advances of an implanted portcatheter system have facilitated repeated arterial infusion of chemotherapeutic agents, and HAI chemotherapy with several anticancer drugs provides a useful choice for advanced HCC. In various regimens of HAI chemotherapy, low-dose cisplatin and 5-fluorouracil (5-FU) therapy or combination therapy of interferon (IFN)-alpha/5-FU have been reported to improve the response rates for advanced HCC. However, the survival benefit of HAI chemotherapy may be affected by liver function. None of these regimens have been proved to be the standard for HAI chemotherapy. We previously reported that the beneficial effects of combination therapy of IFN-alpha/5-FU for advanced HCC. IFN-alpha/5-FU combination therapy may be a promising treatment modality for advanced HCC.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Assessment of the severity of liver disease and fibrotic change: the usefulness of hepatic CT perfusion imaging.

This study assessed the utility of CT perfusion for quantitative assessment of liver function and fibrosis. Tissue blood flow (TBF), tissue blood volume (TBV), mean transit time (MTT) and hepatic arterial fraction (HAF) were measured with CT perfusion using the deconvolution algorithm in 38 patients with chronic liver diseases and 10 patients without liver disease. Using Child-Pugh classification, 21 patients were classified as Child A, 10 as Child B, and 7 as Child C. In 20 patients, the degree of fibrosis was quantitated in surgically-resected specimens and compared with the perfusion parameters. The mean TBF, TBV, MTT and HAF of patients with-out liver disease were 103.9+/-18 ml/min/100 g, 12.5+/-2.0 ml/100 g, 11.1+/-1.6 sec and 18.4+/-5.6%, respectively (+/-SD). The mean TBF of patients with Child A, B and C were 95.1+/-24, 86.7+/-29 and 75.5+/-6.5 ml/min/100 g, respectively. TBF tended to decrease with the severity of chronic liver disease. The mean HAF of patients with Child A, B and C were 18.6+/-8.3, 29.8+/-11.2 and 40.2+/-11.1%, respectively. HAF of patients without liver disease was significantly different from those of Child B and C (p<0.05, each). However, there were no significant differences in TBV and MTT between each groups. HAF correlated significantly with the degree of fibrosis (R2=0.588, p<0.05). Our results showed that parameters of CT perfusion correlated significantly with the severity of liver fibrosis and cirrhosis. Quantitative measurement of hepatic tissue blood flow by CT perfusion is useful for evaluation of the severity of disease and fibrotic change.

Adult↗

PubMed2006

[Intra arterial infusion chemotherapy combined with interferon-alpha following palliative hepatic resection against advanced hepatoma with portal venous tumor thrombus in the major trunk and multiple nodules--a preliminary study].

Recently, we reported the beneficial effects of intra arterial 5-FU infusion chemotherapy combined with interferon-alpha (IFN-alpha/5-FU combined chemotherapy) for advanced hepatocellular carcinoma (HCC). This report describes the preliminary results of treatment of IFN-alpha/5-FU combined chemotherapy following palliative hepatic resection for advanced hepatocellular carcinoma with tumor thrombus in the main trunk of the portal vein with multiple nodules in the whole liver. The 15 patients of HCC with portal venous tumour thrombi (PVTT) and multiple intra-hepatic multiple nodules (IM3) were treated with IFN-alpha/5-FU combined chemotherapy following palliative surgery in this study. No leukopenia, thrombocytopenia, or myelosuppression was observed in any of the 15 patients. Other adverse effects were, in general, clinically manageable. Concerning the anti-tumor effect, 6 showed an objective response and 9 showed a progressive disease; the response rate was 40.0% (6/15). The 1-year and 3-year survival rates were 48% and 21% in all 15 cases, respectively. In conclusion, IFN-alpha/5-FU combined therapy may be a promising modality for advanced HCC with tumor thrombi in the major trunk with multiple nodules after following palliative surgery.

Antimetabolites, Antineoplastic↗

PubMed2006

[A successful case of hepatocellular carcinoma with portal venous tumor thrombus (Vp2) treated by transcatheter arterial chemoembolization].

We reported a case of hepatocellular carcinoma (HCC) with portal venous tumor thrombus (PVTT) (Vp2) successfully treated by transcatheter arterial chemoembolization (TACE), and the tumor showed complete response and the patient survived for 28 months. A 67-year-old male was diagnosed with HCC in the area of subsegment 5 with PVTT from the P5 to the posterior branch. He was treated by segmental TACE. The tumor markers decreased within normal limits, and localized hepatic infraction in the subsegment 5 and atrophy of the PVTT were recognized. He survived for 28 months with no tumor recurrence after the first TACE. This case suggested that embolization might play a part of treatment to HCC with PVTT, if the liver function was preserved and the lesion of liver infraction was limited.

Aged↗

PubMed2006

[Surgical treatment for peritoneal dissemination of hepatocellular carcinoma after percutaneous ethanol injection therapy--a case report].

We report a 73-year-old man who underwent surgery for peritoneal dissemination of hepatocellular carcinoma (HCC) after percutaneous ethanol injection therapy (PEIT). He received posterior segmentectomy for HCC in 1997. Four years after the first hepatic resection, a recurrence lesion in the right caudal lobe of the liver was detected by computed tomography (CT). He underwent percutaneous ethanol injection therapy (PEIT) and transcatheter arterial embolization (TAE). He was referred to our hospital for further treatment. Abdominal CT revealed an early-enhanced lesion (3.2 cm in size) in the right caudal lobe of the liver and an irregular mass lesion (1.5 cm in size) in the cranial. We diagnosed the disease as recurrent HCC and carried out partial hepatectomy, removal of peritoneal dissemination and a reconstruction of the inferior vena cava. A histological feature of the tumor was a moderately differentiated HCC, and there was no lymphatic structure in the tumor, and no connection to the residual liver. Therefore, we diagnosed the tumor as peritoneal dissemination of HCC. We think that this is a rare but a serious complication of PEIT and every effort should be attempted to prevent this complication, especially in the treatment of superficial and larger HCC.

Aged↗

PubMed2005

Living-donor liver transplantation with renoportal anastomosis for patients with large spontaneous splenorenal shunts.

BACKGROUND: End-stage liver disease is often accompanied by large spontaneous splenorenal shunts and thrombosed portal vein. Renoportal anastomosis for spontaneous splenorenal shunts in living-donor liver transplantations is one of the solutions for the treatment of these patients. However, the long-term outcome, portal venous hemodynamics after liver transplantation, and the effects of altering the renal venous drainage remained unknown. METHODS: We performed three living-donor liver transplantations with renoportal anastomosis for the treatment of spontaneous splenorenal shunts between 1999 and 2004. We then evaluated the outcome of this procedure using short- and long-term follow-ups in which the postoperative graft function, renal function, radiological images and portal hemodynamics were examined. RESULTS: All three patients who underwent a living-donor liver transplantation with renoportal anastomosis are alive with normal graft function and a patent renoportal anastomosis. The portal hemodynamics were similar to those in conventional living-donor liver transplantation recipients, and had no harmful effect on allograft function. Left renal function returned to normal after the temporal impairment in two cases, and remained slightly impaired in one, although it was negligible clinically. CONCLUSIONS: Living-donor liver transplantation with renoportal anastomosis for the treatment of spontaneous splenorenal shunts in patients with end-stage liver disease is a life-saving and safe technique and should be discussed as a treatment option for patients with splenorenal shunts.

Adult↗

PubMed2005

Bile acid promotes the proliferation of squamous cell carcinoma of the esophagus, independent of its inducing COX-2 expression.

BACKGROUND: We have reported G1 progression and cyclooxygenase-2 (COX-2) induction during carcinogenesis of the squamous epithelium of the esophagus. As bile acid induces COX-2 expression and promotes carcinogenesis in the digestive tract, we investigated the effect of bile acid on the proliferation of squamous cell carcinoma of the esophagus (ESCC). MATERIALS AND METHODS: MTT assay, Western blot analysis of COX-2 and cell cycle-related molecules in the G1 phase (Rb, CDC25A, cyclin D1), and CDK2 kinase assay were performed on chenodeoxycholic acid (CDCA) exposure to ESCC cell lines (TE2R, TE3, TE13, TE15). RESULTS: In the presence of gradient bile acid concentration (up to 100 microm), growth of ESCC cell lines was stimulated at a low concentration (maximally at 20-30 microm), but suppressed at a higher concentration. Only a low dose of bile acid induced the expression of cyclin D1 and CDC25A and showed high Rb phosphorylation and high CDK2 kinase activity. In contrast, bile acid progressively induced COX-2 expression in a dose-dependent manner, regardless of its biphasic effects on cell proliferation, and a COX-2 specific inhibitor (JTE-522) did not suppress growth stimulation by a low dose of bile acid. CONCLUSIONS: Bile acid at a low dose stimulates the proliferation of ESCC by inducing G1-regulating molecules. However, COX-2 expression, which is also induced by bile acid, does not affect cell proliferation. Further work is needed to elucidate its role in carcinogenesis.

Bile Acids and Salts↗

PubMed2005

Overexpression of ADAM9 enhances growth factor-mediated recycling of E-cadherin in human colon cancer cell line HT29 cells.

Growth factor-mediated stimulation of epithelial cells induces the disassembly of E-cadherin-mediated cell-cell adhesion. We found that overexpression of a disintegrin and metalloprotease 9 (ADAM9) enhanced growth factor-mediated induction of endocytosis and dynamic recycling of E-cadherin in HT29 human colon cancer cells. In addition, ubiquitination and degradation of E-cadherin were reduced in these cells. ADAM9 constitutively interacted with E-cadherin, and the two proteins co-localized at the plasma membrane of HT29 cells. Administration of a metalloprotease inhibitor or overexpression of an ADAM9 mutant lacking metalloprotease activity attenuated growth factor-dependent endocytosis and recycling of E-cadherin as well as scattering of HT29 cells. These results suggest that the metalloprotease activity of ADAM9 mediates growth factor-induced endocytosis and dynamic recycling of E-cadherin and prevents E-cadherin degradation.

ADAM Proteins↗

PubMed2005

Inhibition of cell movement and proliferation by cell-cell contact-induced interaction of Necl-5 with nectin-3.

Immunoglobulin-like Necl-5/Tage4/poliovirus receptor (PVR)/CD155, originally identified as the PVR, has been shown to be up-regulated in cancer cells and to enhance growth factor-induced cell movement and proliferation. In addition, Necl-5 heterophilically trans-interacts with nectin-3, a cell-cell adhesion molecule known to form adherens junctions in cooperation with cadherin. We show here that Necl-5 was down-regulated from cell surface upon cell-cell contacts in NIH3T3 cells. This down-regulation of Necl-5 was initiated by its interaction with nectin-3 and was mainly mediated by clathrin-dependent endocytosis. Then, the down-regulation of Necl-5 induced in this way reduced movement and proliferation of NIH3T3 cells. These results indicate that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cell-cell contacts may be at least one mechanism underlying contact inhibition of cell movement and proliferation.

Animals↗

PubMed2005

Steroid-free living-donor liver transplantation in adults.

To examine the benefits of steroid avoidance in adult living donor liver transplantation, we compared the clinical courses of nine recipients receiving basiliximab or daclizumab and 13 historical patients who received steroids. The 1-year patient and graft survival and the incidence of acute cellular rejection were similar in both groups. The side effects of immunosuppression tended to be more frequent in the steroid group. Hepatitis C virus (HCV)-RNA levels measured early after transplantation remained suppressed in the steroid-free group. Steroid avoidance was beneficial in the recipients, as both steroid side effects and recurrence of HCV could be avoided.

Acute Disease↗

PubMed2005

Oxaliplatin, a potent inhibitor of survivin, enhances paclitaxel-induced apoptosis and mitotic catastrophe in colon cancer cells.

BACKGROUND: Clinical studies have demonstrated that oxaliplatin, a novel platinum derivative, is a potent chemotherapeutic agent, especially when combined with other reagents. The aim of the present study was to explore the mechanism of such action. METHODS: Using colon cancer cell lines, we examined changes in cell cycle, apoptosis and mitotic catastrophe induced by oxaliplatin and/or paclitaxel. RESULTS: Oxaliplatin at its IC(50) induced apoptosis and cell cycle arrest at G(2)-M phase. Western blot analyses indicated that oxaliplatin decreased mitosis-commencing protein cdc2 and anti-apoptotic proteins, phospho-Bcl(2) and Bcl-xl in the three colon cancer cells tested. Since cdc2 stabilizes survivin, a putative IAP (inhibitor of apoptosis) family member, through phosphorylation of Thr34, we examined the level of survivin and found a marked decrease due to oxaliplatin. This finding is of particular interest because survivin is a promising molecular target against various human cancers and a key molecule involved in both apoptosis and mitotic catastrophe. When used in combination with paclitaxel (taxol), a putative apoptosis-inducing reagent, the isobologram indicated that the taxol-oxaliplatin sequence or taxol plus oxaliplatin had synergic or additive effects, while the oxaliplatin-taxol sequence resulted in a prominent antagonism. The taxol-oxaliplatin sequence caused marked growth inhibition of DLD1 and SW480 cells, possibly due to upregulation of apoptotic and non-apoptotic pathways, respectively. Morphological surveys indicated that the non-apoptotic process could be mitotic catastrophe. CONCLUSION: Our results suggest that oxaliplatin that potently inhibited survivin may exert outstanding cytotoxic effects when combined with certain chemoreagents through enhancement of apoptosis and mitotic catastrophe.

Antineoplastic Agents↗

PubMed2005

Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling.

The prognosis of patients with advanced gastric cancer remains unfavorable. Even after curative resection, 40% of patients with advanced gastric cancer die of recurrence. Conventional clinicopathlogic findings are sometimes inadequate for predicting recurrence in individuals. Hence, we tried to construct a new diagnostic system, which predicts recurrence in patients with advanced gastric cancer after curative resection based on molecular analysis. Gastric cancer progression is a function of multiple genetic events that may affect the expression of large number of genes. We performed gene expression profiling with 2,304 genes in 60 advanced gastric cancer patients who underwent curative resection using a PCR array technique, a high-throughput quantitative RT-PCR technique. The diagnostic system, which was constructed from the learning set comprised of 40 patients with the most informative 29 genes, classified each case into a good-signature or poor-signature group. Then, we confirmed the predictive performance in an additional test set comprised of 20 patients, and the prediction accuracy for recurrence was 75%. Kaplan-Meier analysis revealed significant difference between the good-signature and the poor-signature group (p = 0.0125). Especially in patients with smaller tumor (< or = 5 cm), less developed LN metastasis (N(0,1)), or earlier stage (stages I and II), the prediction accuracy was high (88.9%, 84.6%, or 81.8%, respectively). Our diagnostic system based on systematic analysis of gene expression profiling can predict the recurrence at clinically meaningful level. By combining our system with conventional clinicopathologic factors, we can improve the prediction of recurrence in patients with advanced gastric cancer who underwent curative surgery.

Aged↗

PubMed2005

Changes over time in thymidine phosphorylase and dihydropyrimidine dehydrogenase when colon cancer samples are left at room temperature.

The changes over time in thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) were studied when colon cancer samples were left at room temperature. The TP levels and the TP/DPD ratio showed no changes over time in either the tumor or normal tissues. DPD levels increased over time in the normal tissues (P = 0.015), but showed no changes in the tumor tissues. When the DPD level in normal tissues is to be examined, the samples should be frozen as soon as possible. In all other cases, the ELISA results will not be affected if the samples are frozen within 6 h after collection.

Colon↗

PubMed2005

Fusion image of positron emission tomography and computed tomography for the diagnosis of local recurrence of rectal cancer.

BACKGROUND: The aim of this study was to evaluate the clinical and therapeutic value of digital fusion image (FI) of positron emission tomography (PET) using (18)F-fluorodeoxy glucose and computed tomography (CT) in patients who were suspected of having a local recurrence of rectal cancer. METHODS: Forty-two patients (32 men and 10 women; mean age, 61.4 years, range, 40-79 years) with a suspicion of local recurrence after curative resection of rectal cancer were prospectively recruited and underwent (18)F-fluorodeoxy glucose-PET and CT. The FI was reconstructed with a commercially available digital software program, T-B Fusion. Wilcoxon signed rank test was used to compare FI with CT alone or PET alone. RESULTS: FI yielded a correct diagnosis in 39 (93%) of 42 patients, whereas CT alone and PET alone did so in 33 (79%) and 37 (88%) patients, respectively. FI had better diagnostic accuracy than CT alone (P = .0138) and PET alone (P = .0156). Overall, FI altered patient management in 11 (26.2%) patients on the basis of additional information, including differentiation of the tumor from the postoperative scar in 6 patients, exact anatomical location in 3 patients, and both in 2 patients. CONCLUSIONS: FI has a potential clinical value in the treatment of suspected local recurrence of rectal cancer.

Adenocarcinoma↗

PubMed2005

Correlation between histological effects on the main tumors and nodal status after chemoradiotherapy for squamous cell carcinoma of the esophagus.

BACKGROUND AND OBJECTIVES: Although the histological effectiveness of preoperative chemoradiotherapy against the main tumor is reported to be the strongest prognostic factor for patients with esophageal cancer, it remains unknown whether such chemoradiotherapy is equally effective against metastatic lymph nodes. METHODS: We studied 103 consecutive patients with esophageal cancer, who were given preoperative chemoradiotherapy followed by surgery. The histological effectiveness against the main tumor of the chemoradiotherapy was correlated with lymph mode metastasis and other clinico-pathological factors. RESULTS: The histological effectiveness against the main tumor was grade 3 in 26 patients, grade 2 in 49 and grade 1 in 28. The number of pathological node-negative patients was 21 (80.8%), 19 (38.8%), and 7 (25.0%) in those having grade 3, 2, and 1 responses of their main tumors, respectively. The average number of pathological metastatic lymph nodes was 0.19, 1.4, and 4.4 in patients with grade 3, 2, and 1 responses, respectively. Endoscopic biopsy after the chemoradiotherapy could not accurately diagnose the pathological complete response (CR) of the main tumors, with a high false negative rate (60.9%). CONCLUSIONS: The effects of chemoradiotherapy against main tumors significantly correlated with nodal status. Most patients with main tumors of pathological CR are node-negative. Patients with a grade 2 response have at most a few positive nodes. Surgery would be most beneficial for such patients.

Adult↗