Biomedical subjects

Morito Monden

Publications and source records attributed to Morito Monden.

At least 127 records · Page 7Linked to original sources

PubMed2004

[Phase I study of gemcitabine (GEM) and UFT combination chemotherapy for unresectable/recurrent pancreatic cancer].

A phase I study of gemcitabine (GEM) and UFT combination chemotherapy was performed for unresectable pancreatic cancer. The regimen included UFT orally from day 1 through day 6 and from day 8 through 13, GEM intravenously on day 7 and 14, and 1 week rest as 1 course. Administration of more than 2 courses was attempted for each patient, with the same dosage levels at all 3 scheduled steps. Nine patients were enrolled in the study. Leukopenia and neutropenia of grade 3 occurred in 2 of 6 patients at level 2, and maximum tolerated dose (MTD) was considered to be 800 mg/m2 for GEM and 250 mg/m2 for UFT. Clinical effects of the patients included: 2 PR, 4 NC, and 3 PD, for a response rate of 22% (2/9 patients). Reduced CA19-9 level of less than half of that at starting time was observed in 4 of 9 (44%) patients. The recommended dose for the phase II study is GEM 800 mg/m2 and UFT 250 mg/m2 with consideration of application to outpatients and continuing courses.

Aged↗

PubMed2004

[Analysis of microsatellite instability and p53 LOH in advanced colorectal cancers--first report of the No. 3 protocol].

In order to establish the most appropriate protocol of adjuvant chemotherapy for colorectal cancers, several cooperative studies have been undertaken by the Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma (KCSGCCC). In the No. 3 protocol of KCSGCCC, several cancer-associated molecular markers were analyzed to investigate a possible correlation with chemosensitivity and/or patient's prognosis. Here, we report the preliminary results of the analysis of microsatellite instability (MSI) and p53 LOH in 559 cases of Stage II, III colorectal cancer. The MSI was detected in 51 cases (9%) and was shown to have a significant correlation with right-sided localization and histology (poorly differentiated, mucinous). p53 LOH was positive in 225 cases (40%) and was shown to have a significant correlation with left-sided localization and histology (well to moderately differentiated). These results might support the concept of 2 distinct pathways of colorectal carcinogenesis, e.g., RER pathway and LOH pathway.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

[Weekly administration of paclitaxel as a second-line chemotherapy for advanced and recurrent gastric cancer].

Chemotherapy with TS-1 has recently become the first-line chemotherapy for recurrent and unresectable gastric cancer in Japan. Therefore, the establishment of a second-line chemotherapy is needed for cases that show resistance and aberrant effect to TS-1. In this study, 7 patients were treated with weekly administrations of paclitaxel after TS-1 treatment. We assessed the therapeutic effect and feasibility of chemotherapy with weekly administration of paclitaxel. Our results showed that weekly administration of paclitaxel could be a promising regimen as a second-line chemotherapy after TS-1.

Aged↗

PubMed2004

High expression of two genes selected by iAFLP: a new prognostic factor of estrogen receptor-positive breast cancer.

To detect patients with poor prognosis among those with estrogen receptor (ER)-positive breast cancer, who generally show good prognosis, we analyzed gene expression profiles of 35 ER-positive tumors by using a high through-put RT-PCR technique, iAFLP. High expression of six genes out of 7,508 was related to poor prognosis in this group. From these six genes, NFE2L2 and TIAL1 were selected as genes associated with poor prognosis by means of a validation study with another set of 56 ER-positive breast cancers. High expression of these two genes was determined to be significantly predictive for poor prognosis of patients with ER-positive breast cancer, and may help to achieve optimal selection of adjuvant treatment for such patients.

Adult↗

PubMed2004

Application of RT-PCR to clinical diagnosis of micrometastasis of colorectal cancer: A translational research study.

We previously reported in a retrospective study that CEA-based RT-PCR was useful for predicting the prognosis of patients with node-negative colorectal cancer. RT-PCR is well established for laboratory use, but many issues remain to be resolved prior to its clinical application. In addition to the false positive rate of RT-PCR, we addressed several issues, including the timing of lymph node sampling, stability of RNA after surgery, and reproducibility of results. After appropriate modification, including development of a tissue sampling kit, a multi-institutional clinical study was commenced prospectively from November 2001, and 100 patients were enrolled for examination of micrometastasis. RNA was stable in lymph nodes for up to 3 h after surgical resection. This range of sampling time was acceptable to the surgeons. RNA was well preserved in RNA later at -20 degrees C for 3 weeks. Dilutions of MKN45 and LoVo cells served as positive controls for conventional PCR since these controls were found to be highly stable and ensured reproducibility. Moreover, simultaneous use of quantitative PCR (Light Cycler) ensured double confirmation of the results. Our clinical study showed that the quality of RNA was excellent or good in most samples (98 of 100; 98%). Twenty-four of 98 (24.5%) cases were judged to be micrometastasis-positive. In conclusion, the current translational research study established a clinically feasible RT-PCR system for micrometastasis. Our system could potentially be useful as a clinical tool.

Colorectal Neoplasms↗

PubMed2004

[Influence on 5-fluorouracil metabolism by combination of interferon-alpha and 5-fluorouracil against human hepatocellular carcinoma xenografts].

To investigate the effect of biochemical modulation on antitumor activity shown by the combination of 5-Fluorouracil (5-FU) and interferon-alpha (IFN-alpha), experimental therapy was performed on human hepatocellular carcinoma cell (HuH7, PLC/PLF/5) xenografts inoculated into nude mice, using 5-FU and IFN-alpha, either alone or in combination. These agents showed antitumor activity in different degrees. Although IFN-alpha, given as 100,000 units/mouse/3 times/week subcutaneously x 6, and 5-FU, given as 0.5 mg/mouse/3 times/week intraperitoneally, showed addititive antitumor effect against HuH7 and PLC/PLF/5, the activities of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), uridine phosphorylase (UP) and uridine kinase (UK) were not significantly influenced in the tumors treated with the 5-FU/IFN-alpha combination, compared with those treated with 5-FU or IFN-alpha alone. This suggested that antitumor activity of 5-FU and IFN-alpha in combination was not significantly involved in 5-FU metabolism in two human hepatocellular carcinoma cell lines examined.

Animals↗

PubMed2004

[Long-term prognosis of hepatocellular carcinoma patients treated with adoptive immunotherapy].

Adoptive immunotherapy was performed for patients with multiple hepatocellular carcinoma (HCC) using LAK cells via the hepatic arterial catheter. One case study: A 45-year-old male patient was performed an absolute-non-cure operation. The operation was a success. However, some residual tumors remained in the liver. After the operation, adoptive immunotherapy was performed for 7 times in 5 weeks. The total inoculated LAK cells were 6.9x10(9). After the adoptive immunotherapy, no residual tumors were detected in the liver. He survived for 7 years in remission. Our results show that adoptive immunotherapy with LAK cells is useful and effective for patients with multiple HCC.

Aged↗

PubMed2004

[Case report--Complete response of liver metastasis of rectal cancer after combination chemotherapy of CPT-11 + UFT-E].

A 54-year-old man underwent abdominoperineal resection for rectal cancer. Adjuvant chemotherapy was not performed because of stage I cancer. Nine months after the operation, solitary liver metastasis, and elevated CEA and CA19-9, were found during the postoperative work-up. A combination chemotherapy of CPT-11 and UFT-E was performed before scheduled liver resection. 150 mg/m2 of CPT-11 was administered on days 1 and 15. 375 mg/m2/day of UFT-E was divided in half and administered on days 3-7, 10-14, 17-21, and 24-28 as one course of treatment. This regimen was repeated every 5 weeks. The patient had a grade 2 diarrhea and nentropenia during the treatment. Bowel obstruction was also observed after 5 courses of treatment, which required hospitalization. In addition, the liver metastasis had disappeared. There was no evidence of recurrence after 8 months of chemotherapy. It was suggested that CPT-11+UFT-E combination chemotherapy was effective for advanced colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

[A case of successful treatment with combined 5-fluorouracil, adriamycin, cisplatin (FAP) therapy followed by Gemcitabine, UFT therapy and intra-arterial FAP therapy for unresectable advanced gallbladder cancer].

The prognosis of unresectable advanced gallbladder cancer is extremely poor. We presented a 61-year-old female with unresectable advanced gallbladder cancer who received FAP therapy, Gemcitabine + UFT therapy, and an intra-arterial FAP therapy that followed. She is still alive 18 months after the first diagnosis. It may be possible to improve the prognosis by maintaining QOL using the combination of chemotherapies such as FAP, Gemcitabine, and UFT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

[Successful treatment for advanced cholangiocellular carcinoma with intrahepatic metastasis and/or portal vein tumor thrombi by intraarterial chemotherapy combined with 5-fluorouracil, adriamycin and cisplatin (FAP)--two cases report].

The patients of unresectable cholangiocellular carcinoma (CCC) have extremely poor prognosis. Case 1 was a 72-year-old male who had CCC in the left lobe of liver with intrahepatic metastasis. From June 2003, he received hepatic arterial infusion chemotherapy (FAP: 5-fluorouracil 250 mg/day continuous infusion, day 1-5, adriamycin 10 mg/day, day 1, and CDDP 10 mg/day, day 1). After 5 courses, abdominal CT revealed that the main tumor had regressed. Case 2 was a 66-year-old male who had CCC with portal vein tumor thrombus of anterior branch (Vp2). He received FAP arterial infusion chemotherapy that was a same regimen as with the case 1 patient. After 5 courses were administered, Abdominal CT revealed that the size of the main tumor at S8 had not changed, and that portal vein tumor thrombus had disappeared. In both cases, there was no complication related to the chemotherapy. They are alive for more than 1 year after chemotherapy had started. FAP hepatic arterial infusion chemotherapy might be promising as an effective therapy for non-resectable CCC without extra hepatic metastasis.

Aged↗

PubMed2004

[Cases of postoperative hepatic metastasis from gastric cancer in which hepatic arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin was performed after TS-1 chemotherapy].

The prognosis of patients with hepatic metastasis of gastric cancer is poor, and standard therapies for patients are not established. Here we present two cases of hepatic metastasis from gastric cancer. In both cases, no other organ metastasis except the liver was confirmed, in which hepatic arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin (FAP) were performed because TS-1 chemotherapy was not an effective chemotherapy. Case 1: An 80-year-old man had distal gastrectomy for type 2 gastric cancer (Stage II) in January 2001. A liver S8 metastatic recurrence was discovered in the 18th month post operation. After chemotherapy with TS-1 for 5 courses, a hepatic arterial infusion treatment was performed for 7 courses. The effect was PR, but the treatment was canceled because of a catheter obstruction. The patient is living without recurrence. Case 2: This case was a 73-year-old man who had distal gastrectomy for type 0 IIc gastric cancer (Stage IA) in May 1999. Multiple hepatic metastases recurred in the 32nd month post operation. After chemotherapy with TS-1 for 2 courses, a hepatic arterial infusion treatment was performed for 10 courses. The effect was CR, but a peritoneal recurrence was discovered, and a systemic chemotherapy was performed. The patient is living without recrudescence of hepatic metastasis. The hepatic arterial infusion chemotherapy with FAP was effective for gastric cancer patients with liver metastasis because TS-1 chemotherapy was not an effective chemotherapy. It is necessary to consider combined chemotherapy in addition to systemic chemotherapy.

Aged↗

PubMed2004

[Two cases of advanced and recurrent gastric cancer treated with the combination of chemotherapy and radiation].

Recently, new promising anti-tumor agents such as TS-1, taxanes, and CPT-11 have been approved for gastric cancer treatment. These agents showed a better response and may contribute to a patient's survival and quality of life. However, there are cases with advanced and recurrent gastric cancer that are resistive or tolerant to these agents. We report two cases in which the patients had suffered symptomatic local recurrence during the chemotherapy. Consequently, they had been treated with radiotherapy in order to improve their clinical status. We also discuss the significance of radiotherapy in gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

[A case of long-term survivor with multiple pulmonary metastases of HCC after hepatic resection].

A 52-year-old male was admitted to our hospital with huge hepatoma of the right lobe. He underwent a right lobectomy of the liver in July 1999. After five months from the surgery, multiple recurrences in the liver and lung were revealed with Computed tomography (CT). TAE was performed for intrahepatic recurrence and a combination therapy, consisting of UFT and interferon-alpha, was started for pulmonary metastasis. Then 5-FU/CDDP/interferon-alpha therapy was given in 2001 and TS-1/interferon-beta therapy was given thereafter in 2002. Consequently, the patient survived for 31 months with no disturbance in quality of life. No intrahepatic recurrence was also detected during the survival period. It was suggested that a good prognosis may be expected, even in the HCC case with distant metastasis after hepatic resection, if the primary cite was curatively treated.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

[Evaluation of ten intravenous catheters for operability and safety in the infusion room].

We have a randomized trial to compare the operability and safety of ten 24-gauge intravenous catheters in the infusion room. In the present study, we used 3 intravenous catheters without safety covers (Jelco plus, Surflo flash, Intima) and 7 intravenous catheters with safety covers (Supercath, Introcan safety, Surshield surflo II, Insyte autoguard, Safetouch cath, Protective plus, Acuvance plus). All catheters were used 40 times. The detainment rate of the first time puncture and the incidence of needle accidents with Jelco plus and Insyte autoguard were 98% and 0%, respectively, against 100% and 0%, respectively, for all other catheters. There was no difference in the incidence of these two events in all groups (ANOVA; p > 0.05). On the other hand, all intravenous catheters with safety covers revealed that 1) an in situ needle has a resistance to the catheter (i.e., a resistance during catheter release), and/or 2) blood exposure can not be sufficiently avoided.

Catheterization, Peripheral↗

PubMed2004

[Hepatic arterial infusion chemotherapy (HAIC)--hepatocellular carcinoma].

Hepatic arterial infusion chemotherapy (HAIC) has been often selected as a therapeutic option for advanced hepatocellular carcinoma (HCC) with intrahepatic metastases or portal vein thrombosis, which is not eligible for hepatic resection, tumor ablation, or embolization. Among various regimens, HAIC, consisting of 5-fluorouracil (5-FU) in combination with either low-doses of cisplatin (CDDP) or interferon-alpha has been reported to improve the response rates for advanced HCC. As both regimens require the use of an implanted port-catheter system, maintaining the patency of hepatic arteries is an important factor for the intrahepatic drug distribution and the efficacy of HAIC. Recently, a new product, CDDP powder has been also developed for intraarterial use, which adds a new option to HAIC. However, the long-term outcome or the survival benefit remains unclear with HAIC, and it may be significantly affected by liver function and cirrhosis. None of the regimens have been proved to be the standard for HAIC, and prospective multi-center clinical studies with standardized protocol are needed in the future.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

A Bayesian missing value estimation method for gene expression profile data.

MOTIVATION: Gene expression profile analyses have been used in numerous studies covering a broad range of areas in biology. When unreliable measurements are excluded, missing values are introduced in gene expression profiles. Although existing multivariate analysis methods have difficulty with the treatment of missing values, this problem has received little attention. There are many options for dealing with missing values, each of which reaches drastically different results. Ignoring missing values is the simplest method and is frequently applied. This approach, however, has its flaws. In this article, we propose an estimation method for missing values, which is based on Bayesian principal component analysis (BPCA). Although the methodology that a probabilistic model and latent variables are estimated simultaneously within the framework of Bayes inference is not new in principle, actual BPCA implementation that makes it possible to estimate arbitrary missing variables is new in terms of statistical methodology. RESULTS: When applied to DNA microarray data from various experimental conditions, the BPCA method exhibited markedly better estimation ability than other recently proposed methods, such as singular value decomposition and K-nearest neighbors. While the estimation performance of existing methods depends on model parameters whose determination is difficult, our BPCA method is free from this difficulty. Accordingly, the BPCA method provides accurate and convenient estimation for missing values. AVAILABILITY: The software is available at http://hawaii.aist-nara.ac.jp/~shige-o/tools/.

Algorithms↗

PubMed2003

Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells.

BACKGROUND: The coordinated activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) is critical for the induction of vascular and visceral smooth muscle cell (SMC) dedifferentiation. We previously reported that on the forced activation of both MAPKs, visceral SMCs secrete a non-heparin-binding protein factor(s) that is involved in the dedifferentiation of neighboring SMCs. In this study, we sought to identify the dedifferentiation factor(s) derived from vascular SMCs (VSMCs). METHODS AND RESULTS: We fractionated the VSMC dedifferentiation factor(s) in the conditioned medium obtained from differentiated VSMCs in which both ERK and p38MAPK were forcedly activated and identified epiregulin as a major autocrine/paracrine factor for VSMC dedifferentiation. The epiregulin-induced VSMC dedifferentiation was mediated through the coordinated activation of ERK and p38MAPK. Unsaturated lysophosphatidic acid and platelet-derived growth factor-BB, which are potent VSMC dedifferentiation factors, rapidly upregulated epiregulin mRNA expression in an ERK- and p38MAPK-dependent manner. Reverse transcriptase-polymerase chain reaction and/or immunohistological analyses revealed the restricted expression of epiregulin in human atherosclerotic and balloon-injured rat arteries, in which the phenotypic modulation of medial VSMCs occurred in vivo. CONCLUSIONS: Epiregulin is released from VSMCs primed by atherogenic factors and acts as a major autocrine/paracrine factor for VSMC dedifferentiation. It may be involved in the progression of vascular remodeling such as atherosclerosis.

Animals↗

PubMed2003

Mutational analysis of BARD1 in familial breast cancer patients in Japan.

Since BRCA1,which is a breast cancer susceptibility gene, form heterodimers with BARD1, it is speculated that BARD1 mutations might affect the function of BRCA1, contributing to breast carcinogenesis. Thus, in the present study, we have conducted mutational analysis of BARD1 in familial breast cancer patients (n=60) who were tested negative for both BRCA1 and BRCA2 germline mutations. We have been unable to show any clearly deleterious mutations but identified four missence mutations (Ser/Cys 241, Arg/Ser 378, Asn/Ser 470, Val/Met 507), one silent mutation (His/His 506), and one frameshift (in-frame) mutation (1139del21bp). Of these six mutations, one (Asn/Ser 470) was considered as a putative germline mutation since such a mutation was not observed in any of the healthy controls (n=152) but the other five mutations were considered as common genetic polymorphisms since they were frequently observed in the healthy controls. These genetic polymorphisms were further analyzed in their association with breast cancer risk by a case-control study using the population-based breast cancers (n=143) and healthy controls (n=155), which showed that carriers of the variant allele Met at codon 507 are significantly associated with the increased risk of breast cancer (adjusted odds ratio=2.05, 95% confidential interval=1.01-4.16) in postmenopausal women and that the other genetic polymorphisms are not associated with breast cancer risk. These results suggest that BARD1 mutations are responsible for, if any, a very small number of familial breast cancers. Genetic polymorphism of BARD1 (Val/Met 507) could be useful in the selection of postmenopausal women at a high risk for developing breast cancer.

Breast Neoplasms↗