Search PubMed⌕ Search

Biomedical subjects

Morito Monden

Publications and source records attributed to Morito Monden.

At least 199 records · Page 11Linked to original sources
PubMed2002

A successful resection and long-term survival of a patient with intrahepatic recurrences of combined hepatocellular-cholangiocarcinoma: report of a case.

Because of the low incidence rate of combined hepatocellular-cholangiocarcinoma (combined HCC-CC), the clinicopathological features of a recurrent tumor of this disease remain to be elucidated. We describe a 47-year-old Japanese woman with a 5-cm diameter mass lesion in the liver. A hepatectomy and dissection of the local lymph nodes were performed and a histological examination of the resected specimen showed combined HCC-CC. After a follow-up of 15 months, intrahepatic recurrence was observed, and a hepatectomy was performed again followed by hepatic arterial infusion chemotherapy. A histological examination revealed that the recurrent tumors consisted of only cholangioacarcinoma. A disease-free survival was obtained for about 7 years after the recurrence. To improve the poor prognosis of combined HCC-CC, clinicopathological features of this disease and the therapy selection for recurrent tumors should be discussed.

Bile Duct Neoplasms↗
PubMed2002

Extraction and analysis of carcinoembryonic antigen in lymph nodes: a new approach to the diagnosis of lymph node metastasis of colorectal cancer.

PURPOSE: To detect lymph node metastasis of colorectal cancer, we extracted protein from lymph nodes and determined the concentration of carcinoembryonic antigen. METHODS: In Experiment 1, a total of 237 lymph nodes from 23 colorectal cancer patients were examined histologically after immersion in 200 microl of saline for 2 hours. Concentrations of protein and carcinoembryonic antigen in each saline sample were determined by protein assay and immunoradiometric assay, respectively. Each value of carcinoembryonic antigen in the saline was divided by extracted protein, and the carcinoembryonic antigen levels in lymph nodes were represented as nanograms per milligram of protein. In Experiment 2, 63 lymph nodes from 8 colorectal cancer patients were cut into 2 pieces and immersed in 1 ml of saline for 15 minutes, and they were subjected to reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen and histologic examination, respectively, after measurement of the carcinoembryonic antigen concentration in the extract. RESULTS: From 236 of 237 lymph nodes in Experiment 1, an average of 3,249.4 microg/ml protein was successfully extracted. Histologic examination revealed that 33 of 236 lymph nodes had colorectal cancer metastases, with a significantly higher concentration of carcinoembryonic antigen on average (655.5 ng/mg protein) than in the 203 lymph nodes without metastasis (18.2 ng/mg protein; P < 0.0001). In Experiment 2, 19 of 63 lymph nodes examined were positive for metastasis in both reverse transcriptase-polymerase chain reaction and histology and showed a significantly higher carcinoembryonic antigen concentration on average (1,003.9 ng/mg protein) than the 42 lymph nodes that demonstrated no metastasis by either method (18.0 ng/mg protein; P < 0.0001). The remaining two lymph nodes, which were positive by reverse transcriptase-polymerase chain reaction but negative by histology, showed high carcinoembryonic antigen concentrations of 514.7 and 61,970.5 ng/mg protein, respectively. CONCLUSION: This simple method of protein extraction and determination of carcinoembryonic antigen concentration in lymph nodes may provide an alternative tool for the diagnosis of colorectal cancer metastasis.

Carcinoembryonic Antigen↗
PubMed2002

Ischemia-reperfusion injury of the liver with special reference to calcium-dependent mechanisms.

Ischemia-reperfusion (I/R) injury is a complex process involving numerous intracellular signaling pathways, mediators, cells, and pathophysiological disturbances; its prevention during liver surgery is of utmost importance. In this review, we divide hepatic I/R injury into two phases, intracellular and extracellular, for a better understanding of the processes involved. Ca2+ and Ca2+-dependent reactions play an important role as a trigger in the former phase, while the subsequent generation of bioactive substances plays a predominant role in the latter phase. These findings indicate that a combination of different therapeutic approaches against Ca2+-dependent steps may help prevent I/R injury of the liver.

Apoptosis↗
PubMed2002

Expression of p57/Kip2 protein in extrahepatic bile duct carcinoma and intrahepatic cholangiocellular carcinoma.

BACKGROUND: Evaluation of the biological character of carcinomas requires understanding of cell cycle regulators. P57 (Kip2) belongs to the Cip/Kip family and is known to be one of the universal negative regulators of cell cycle. METHODS: In the present study, therefore, we investigated p57 expression in 37 extrahepatic bile duct carcinomas (BDC) and 28 intrahepatic cholangiocellular carcinomas (CCC). RESULTS: The average p57 labeling index (LI) in BDC and CCC were 60.8 +/- 7.9 and 58.6 +/- 18.6, respectively, which were significantly lower (p = 0.0008 and p = 0.0408, respectively) than those in normal duct epithelia (73.1 +/- 7.9, 70.4 +/- 8.2). p57 LI was significantly lower in BDC and CCC cases with biological aggressive phenotypes such as poor differentiation (p = 0.0260 and p = 0.0069), lymph node metastasis (p = 0.0274 and p = 0.0214), high Ki-67 LI (p = 0.0164 and p = 0.0343) and cyclin D1 overexpression (p = 0.0359 and p = 0.0255). CONCLUSION: These findings suggest that decreased p57 expression is related to the increased activity of cell proliferation and also the progression of these carcinomas.

Adult↗
PubMed2002

Association of frabin with specific actin and membrane structures.

BACKGROUND: Frabin is an actin filament (F-actin)-binding protein with GDP/GTP exchange activity specific for Cdc42 small G protein. Expression of frabin forms filopodia-like microspikes through the direct activation of Cdc42, and lamellipodia through indirect activation of Rac small G protein. Frabin consists of the F-actin-binding domain (FAB), the Dbl homology domain (DH), the first pleckstrin homology domain (PH1), the FYVE-finger domain (FYVE), the second PH domain (PH2) from the N-terminus in this order. Although DH and PH1 show exchange activity, FAB, in addition to DH and PH1, is required for the formation of microspikes, whereas FYVE and PH2, in addition to DH and PH1, are required for the formation of lamellipodia. RESULTS: Various truncated mutants of frabin were co-expressed with a dominant active mutant (DA) of Cdc42, Rac1DA, or full-length frabin in L fibroblasts. FAB was recruited to the Cdc42DA-formed filopodia-like microspikes. FAB and a fragment containing DH, PH1, FYVE and PH2 were recruited to the Rac1DA-formed membrane ruffles. Furthermore, each of these fragments served as a dominant negative mutant of frabin when co-expressed with full-length frabin, and inhibited the full-length frabin-formed morphological changes. CONCLUSION: These results suggest that frabin recognizes a specific actin structure(s) through FAB and a specific membrane structure(s) through FAB and the region containing DH, PH1, FYVE and PH2. It is likely that frabin associates with the specific actin and membrane structures and activates Cdc42 and Rac in the vicinity of these structures, eventually leading to morphological changes.

Actins↗
PubMed2002

Molecular analysis of diminutive, flat, depressed colorectal lesions: are they precursors of polypoid adenoma or early stage carcinoma?

BACKGROUND: The diminutive, flat depressed colorectal lesion is a possible precursor of early stage carcinoma. However, the significance of this lesion in colon carcinogenesis remains unclear. METHODS: Eighty-one diminutive flat lesions (<5 mm diameter) with a central depression (DPdep) were resected colonoscopically and their molecular characteristics were investigated. In parallel, 68 diminutive polyps (<5 mm diameter) with a polypoid growth pattern but no depression (DPpo) were analyzed as controls. After histopathologic diagnosis, only neoplastic tissues were stained by immunohistochemistry for p53 gene and cyclooxygenase 2 (COX-2) and the proliferation marker, Ki-67. Mutation of the K-ras gene was analyzed with the polymerase chain reaction-restriction fragment length polymorphism method by using DNA from microdissected tissue in paraffin sections. RESULTS: Seventy-nine of 81 DPdep and 35 of 68 DPpo were diagnosed as neoplastic. Mild, moderate, and severe dysplasia were found in, respectively, 56, 15, and 8 DPdep polyps, and in 34, 1, and 0 DPpo polyps. Thus, DPdep were more likely to be neoplastic and to exhibit moderate and severe dysplasia compared with DPpo (p < 0.0001). No DPdep or DPpo was positive for the p53 protein. The proportion of specimens with K-ras codon 12 mutation was 13.4% in diminutive polyps (DP), and tended to be lower in DPdep (8.6%) than in DPpo (25.0%) (p = 0.073). The median (interquartile range) of the Ki-67 index of DPdep tended to be lower than that of DPpo (respectively, 0.0 [0.0-5.9] vs. 4.5 [0.0-17.1]; p = 0.0281). COX-2 overexpression was observed in 12 of 77 (15.6%) DP and there was no significant difference between DPdep (3 of 23, 13.0%) and DPpo (9 of 54, 16.7%). CONCLUSION: Diminutive, flat, depressed lesions in this study had low rates of the genetic alterations associated with malignant progression. This indicates that either a different neoplastic mechanism is operative or that these lesions have a lower malignant potential than indicated by their histopathologic features.

Colonic Polyps↗
PubMed2002

Real-time rapid reverse transcriptase-polymerase chain reaction for intraoperative diagnosis of lymph node micrometastasis: clinical application for cervical lymph node dissection in esophageal cancers.

BACKGROUND: New molecular techniques have been designed to detect cancer micrometastases that are otherwise missed by conventional histologic examination. The aim of this study was to establish a sensitive and rapid genetic assay to detect lymph node micrometastasis and to assess its usefulness clinically for cervical lymphadenectomy in esophageal cancer. We have recently shown that metastasis in the lymph node chain along the recurrent laryngeal nerves (rec LNs) is a predictor of cervical node metastasis in esophageal cancer. In our retrospective study, the positive rate of cervical lymph node metastasis with rec LNs metastasis was 51.6%, and the rate without rec LNs metastasis was 11.6%. There was a significant difference in both positive rates (P =.0002). METHODS: Rec LNs obtained from 50 patients with esophageal cancer were assessed prospectively by intraoperative histopathologic examination (HE) and genetic analysis. The latter involved a real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) system with multiple markers, carcinoembryonic antigen, squamous cell carcinoma, and melanoma antigen-3, whose messenger RNAs are highly and frequently expressed in esophageal cancers. Cervical lymphadenectomy was subsequently performed in a subset of these patients. RESULTS: Ten of 50 patients (20%) were scored as node positive by HE, and 24 patients (48%) were scored positive by genetic diagnosis, including 9 HE-positive cases. Genetic diagnosis of rec LNs accurately predicted all 9 cases with cervical lymph node metastasis and 2 cases with cervical lymph node recurrence, whereas HE missed 2 cases with cervical lymph node metastasis and 2 cases with cervical lymph node recurrence. CONCLUSIONS: Our real-time rapid RT-PCR assay can improve the sensitivity of HE for detection of lymph node metastasis and might be potentially useful for intraoperative genetic diagnosis for subsequent cervical lymphadenectomy in esophageal cancer surgery.

Aged↗
PubMed2002

Overexpression of beta 1,4N-acetylgalactosaminyl- transferase mRNA as a molecular marker for various types of cancers.

OBJECTIVE: To determine GalNAcT mRNA expression in human carcinoma cell lines and primary tumor tissues. Assessment of the potential use of GalNAcT mRNA as a molecular marker for detection of metastatic cancer cells in the peripheral blood of patients with hepatocellular carcinoma. METHODS/RESULTS: We investigated GalNAcT mRNA expression in various human cancer cell lines and primary cancer tissues using RT-PCR assay for GalNAcT mRNA. The expression of GalNAcT mRNA was detected in 25 of 26 cancer cell lines tested and in the majority of primary tumors from different organs: 8 of 10 colon cancers, 9 of 9 breast cancers, 11 of 12 esophageal cancers, 14 of 14 gastric cancers, 4 of 18 pancreatic cancers, 6 of 12 biliary tract cancers, 17 of 18 hepatocellular carcinomas and 13 of 14 lung cancers. Semi-quantitative analysis with duplex RT-PCR showed that the amount of the GalNAcT mRNA was enhanced in cancer tissues as compared to the surrounding cancer-free tissues. Blood specimens of 5 of 14 patients with hepatocellular carcinoma were positive for GalNAcT mRNA, all of whom developed recurrent disease in less than 24 months. Peripheral blood samples of 30 normal subjects were negative for GalNAcT mRNA. CONCLUSION: Our results suggest that the RT-PCR assay for GalNAcT mRNA could be a potentially useful molecular marker for detecting cancer dissemination in blood circulation of patients with malignancy.

Adult↗
PubMed2002

Clinical relevance of fusion images using (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography in local recurrence of rectal cancer.

Local recurrence of rectal cancer is a critical issue. Anatomical images, such as computed tomography (CT) or magnetic resonance imaging (MRI), are sometimes insufficient for preoperative evaluation. A useful modality for diagnosis of local recurrence of rectal cancer is (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), but it does not give adequate information about anatomy. To utilize the advantages of these techniques, this study was done to validate the accuracy of using fused images and their usefulness in the decision making for surgical intervention of local recurrence of rectal cancer by directly comparing the fused images with resected specimens. PET and CT/MRI were performed for patients suspected of local recurrence of rectal cancer (n=4). PET image data were re-calculated to fit CT/MRI images and manually superimposed on the anatomical images. Fusion images were compared with resected specimens. Radical operation was carried out for three patients. Fusion images provided information on precise tumor location, and extent of tumor invasion as well as the diagnosis of tumor recurrence. All patients underwent curative operation with negative surgical margins, and the information provided by the fusion images was confirmed by comparison with resected specimens. In all cases, preoperative evaluation of tumor recurrence with fusion images provided more useful clinical information for the management of patients than the anatomical images alone. PET images, when combined with MRI or CT, may prove to be a useful adjunct in the management of patients being evaluated for resection of local recurrence of rectal cancer.

Aged↗
PubMed2002

Immunohistochemical assessment of localization and frequency of micrometastases in lymph nodes of colorectal cancer.

PURPOSE: Micrometastases are often found in regional lymph nodes of colorectal cancer (CRC). The aim of this study is to examine the extent and distribution of such lymph nodes. EXPERIMENTAL DESIGN: We immunohistochemically assessed localization and frequency of micrometastases in 878 lymph nodes from 98 patients with CRC. The anatomical position of lymph nodes was defined as level 1 to level 3 according to distance from the main tumor. RESULTS: The frequency of micrometastasis increased through observation of the 4-microm-thick lymph node sections, from one to two to five slices. With five slices, micrometastasis was frequently and extensively present in 49.1, 35.7, and 53.3% patients of histologically node-negative patients, node-positive patients at level 1, and node-positive patients at level 2, respectively. We then assessed the value of the presence of micrometastasis in node-negative patients with regard to prognosis, but no significant impact was obtained. To examine the reproducibility of the results obtained with immunohistochemistry, serial sectioning (four consecutive slices at seven different levels) of lymph nodes was additionally performed in lymph nodes initially diagnosed as micrometastasis positive. Immunohistochemical detection revealed that the sectioning level highly affected the results. CONCLUSIONS: Our results indicated frequent presence of micrometastasis in lymph nodes of CRC and that micrometastasis in node-negative CRC patients did not help in predicting the outcome, in part because of the limited reproducibility with immunohistochemistry.

Adult↗
PubMed2002

[Molecular biology-based surgery for the future progress of cancer treatment].

The basic surgical procedures for all diseases and organs were established by the end of the 20th century. However, the results of surgical treatment in cancer patients are still unsatisfactory. Despite radical resection based on the conventional diagnostic system for cancer metastases, disease recurrence and relapse are major problems in the clinical field of oncology. Standarized therapy without understanding the biology of tumors has not contributed significantly to cancer patients. Here, we propose that molecular biology-based surgery, or a strategy of surgical oncology based on information obtained from new molecular techniques should be urgently established to improve the management of cancer patients.

Forecasting↗
PubMed2002

[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.

Administration, Oral↗
PubMed2002

Cancer cell contact causes oscillatory and polarized rise of cytoplasmic ionized calcium concentration in human umbilical vein endothelial cells.

The rise of cytoplasmic ionized Ca2+ concentration ([Ca2+]i) is an important factor in cellular signal transduction, which regulates a variety of cellular functions in vascular endothelial cells (vECs) such as morphological change, secretion of vaso-active molecules, or endothelial permeability. It is also known that the loss of vEC integrity plays pivotal roles in several physiological or pathological phenomena, such as inflammation or cancer metastasis. The aim of this study was to clarify the mode of cancer cell induced vEC retraction by cell to cell contact. Digital imaging analysis using Ca2+ indicator, fluo-3, clearly demonstrated an oscillatory intracellular and intercellular [Ca2+]i wave originated from the site of human breast cancer cell line MCF-7 cell contact in HUVECs, which was not inhibited by extracellular Ni2+ and was inhibited by pretreating the cells by paraformaldehyde. Although this phenomenon could be observed in malignant cells including murine malignant melanoma cell line, BL6, as well as benign cells including human fibroblast cell line, WI38, inert neutrophils did not cause vEC retraction nor [Ca2+]i oscillation. Thus, cancer cells could activate vECs by a cell to cell contact to cause retraction via common property of non-blood cells.

Animals↗
PubMed2002

[Development and research of the new therapy for hepatocellular carcinoma--combined interferon and 5-fluorouracil therapy].

The prognosis of hepatocellular carcinoma(HCC) invading the major branches of the portal vein(Vp3 or 4) is extremely poor. Recently, we reported the efficacy of the combination therapy with subcutaneous interferon(IFN)-alpha and intra-arterial 5-FU for intractable HCC with Vp3 or Vp4. Forty-eight consecutive patients with HCC and Vp3 or 4 were treated with the combination therapy consisting of continuous arterial infusion of 5-FU(450-500 mg/day, 5 days/week, for the initial 2 weeks) and subcutaneous injection of IFN(5 MIU, 3 times/week, 4 weeks). The treatment outcome of these cases was very good. In addition, it is considered direct antitumor effect, the angiogenesis depression effect, and the indirect antitumor effect through immunocompetent cell, may concerned, as the mechanism. In conclusion, combination therapy with subcutaneous IFN and intra-arterial 5-FU is therefore a promising treatment modality for intractable HCC with Vp3 or 4.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[The introduction of preoperative staging laparoscopy and molecular diagnosis of peritoneal lavages for the treatment of advanced gastric cancer].

In this study, intra-peritoneal chemotherapy was performed for advanced gastric cancer with serosal invasion. We assessed the efficacy of the chemotherapy using quantitative genetic diagnosis with peritoneal lavages collected before and after chemotherapy at staging laparoscopy and/or gastrectomy. Cases in which genetic diagnosis of peritoneal lavages showed negative results, or changed from positive to negative after chemotherapy, had a good prognosis. On the other hand, cases in which genetic diagnosis showed positive results after chemotherapy had worse prognosis. Intra-peritoneal chemotherapy may be indicated for patients with a positive genetic diagnosis only and cases becoming negative as a result of this therapy may have a better prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Hepatocellular carcinoma recurrence in PEI site--a case report].

The patient was 63-year-old male. Abdominal CT revealed a tumor at S2/S3, which led to a diagnosis of hepatocellular carcinoma, in April 1998. On April 15, 1998 transcathetereal arterial embolization was performed and on May 11, 1998 percutaneous ethanol injection therapy was given, but a viable lesion remained. On July 2, 1998, partial resection of S2/S3 was performed. There was an intrahepapic metastatic lesion at Glisson's site of the main tumor, which was suspected of implantation. In December 2000, the patient had a high AFP level, and a recurrent tumor was observed at S3 on abdominal CT. In June 2001, S3 subsegmentectomy was performed, because the recurrent tumor existed in the Glisson S3 area.

Carcinoma, Hepatocellular↗
PubMed2002

[A case of postoperative multiple hepatic metastasis from gastric cancer successfully treated by percutaneous microwave coagulation therapy and hepatic arterial infusion chemotherapy].

A 61-year-old male who underwent radical resection for gastric cancer was diagnosed with multiple hepatic metastasis 2 years and 2 months after the surgery. He first underwent percutaneous microwave hepatic coagulation therapy with segmental hepatic blood flow occlusion and obtained complete coagulation of the main tumor. Consecutively, he received hepatic arterial infusion chemotherapy (FAP: 5-FU, cisplatin, adriamycin) against residual multiple hepatic tumors. These hepatic recurrent lesions disappeared completely after 3 sessions of arterial infusion chemotherapy. At present, this patient is alive with no recurrent lesions, 1 year and 6 months from the beginning of treatment for hepatic metastasis. Recently, we tried hepatic arterial infusion chemotherapy (FAP) in four cases in which the recurrence from gastric cancer was not only in the liver but elsewhere. The response rate (CR and PR) was 75% and no major side effects were observed. In conclusion, some cases can obtain longer survival if the multimoderate therapy including hepatic arterial infusion chemotherapy (FAP) and microwave coagulation therapy are effective.

Aged↗