Biomedical subjects

Junshin Fujiyama

Publications and source records attributed to Junshin Fujiyama.

13 recordsLinked to original sources

PubMed2005

Results of total gastrectomy with extended lymphadenectomy for gastric cancer in elderly patients.

BACKGROUND AND OBJECTIVES: The incidence of gastric cancer, in people over 70 years of age, has increased remarkably. Aggressive lymphadenectomy with gastrectomy has been reported to improve survival in patients with gastric cancer. Because complication rates following gastrectomy increase with advancing age, we sought to determine whether this procedure was merited in elderly patients with gastric cancer. METHODS: We performed a retrospective analysis of 202 patients who underwent total gastrectomy with extended lymphadenectomy for gastric carcinoma. Postoperative complication rates were compared between patients over and under 70 years of age. RESULTS: The 10-year survival rates of patients under and over 70 years of age following total gastrectomy with extended lymphadenectomy were not significantly different. Although medical comorbidities in each group were similar, pulmonary dysfunction was significantly more common following total gastrectomy in patients over 70 years than in patients under 70 years. Moreover, logistic regression analysis revealed that patient's age was the only variable that independently correlated with the presence of postoperative complications. CONCLUSIONS: The prognosis of the gastric cancer patients over 70 years of age was similar to that of younger patients after total gastrectomy with extensive lymphadenectomy. However, pulmonary dysfunction was significantly more common in patients over 70 years old.

Age Factors↗

PubMed2004

Transanal excision of a large rectal polyp assisted by transsacral manipulation of the rectum.

Standard transanal excision of the rectal polyps is curative and is less invasive than transsacral resection or low anterior resction, but it is difficult to resect tumors that are distant from the anal verge. Moreover, in the case of large polyps, the risks of complications, such as hemorrhage or perforation, increase because exposure on the oral side of the tumor is poor. If exposure can be improved, transanal excision can be performed safely and completely when the polyp is large and distant from the anal verge. We used transsacral manual assistance to achieve transanal resection of a large tubulovillous adenoma of the rectum that was hard to be resected using the traditional transanal approach.

Aged↗

PubMed2004

[Fundamental studies on locally injected methotrexate bound to activated carbon particles (MTX-CH)].

We developed a new dosage formulation of methotrexate bound to activated carbon particles (MTX-CH). In this study, subcutaneous injection of MTX-CH was examined for its long-acting effect at the injection sites, anti-tumor effect and acute toxicity in mice. MTX-CH- or MTX aqueous solution (MTX-SOL)- was injected locally into tumors growing on the back of BALB/c mice at a dosage of 30 mg/kg as methotrexate (MTX). (1) The MTX concentration at the injection sites remained higher in mice with MTX-CH than that with MTX-SOL. (2) A marked effect on the control of tumor growth by MTX-CH was noted after repeated injections throughout the observation period. These results suggest that MTX-CH is superior to MTX-SOL due to longer-acting effects at the administration site and have a better control of tumor growth than MTX aqueous solution (MTX-SOL).

Adsorption↗

PubMed2004

[Utility of dopa decarboxylase as a novel marker for the detection of peritoneal micro-metastases of gastric cancer with realtime RT-PCR].

We have examined the utility of DDC as a novel marker for the detection of peritoneal micrometastases of gastric cancer. DDC mRNA in the peritoneal wash from 114 gastric cancer patients was quantified for a comparison of carcinoembryonic antigen (CEA) mRNA by means of real-time RT-PCR with a fluorescently labeled probe to predict peritoneal recurrence. The cut-off value was set at the upper limit of the quantitative value for non-cancer patients, and those above this cut-off value constituted the micrometastasis (MM+) group. Thirteen of 15 cases with peritoneal dissemination were MM+DDC (87% sensitivity), and one of 48 t1 cases was MM+ (98% specificity). DDC levels in peritoneal washes from patients with synchronous peritoneal metastases were more than 50 times higher than in those from patients without metastasis (p<0.01). For 15 cases of peritoneal dissemination (seven cases were cytologically positive), DDC was positive in 13 cases (87% sensitivity), but CEA failed to detect micrometastases in four cases (73% sensitivity), indicating that DDC is in some cases superior to CEA for the detection of peritoneal micrometastases of gastric cancer in terms of sensitivity as well as specificity, especially for poorly differentiated adenocarcinomas. Combination of CEA and DDC improved the accuracy of diagnosis up to 93%. These results suggest that DDC is potentially a novel marker for peritoneal dissemination of gastric cancer and that quantitative RT-PCR of DDC is reliable and efficient for the selection of patients for adjuvant intraperitoneal chemotherapy to prevent peritoneal recurrence.

Biomarkers, Tumor↗

PubMed2003

Cisplatin incorporated in microspheres: development and fundamental studies for its clinical application.

A new drug delivery formulation, biodegradable glycolic acid-lactic acid copolymer (PGLA) microspheres incorporating cisplatin (CDDP-MS) has been developed for the treatment of peritoneal carcinomatosis. Scanning electron microscopy showed that CDDP-MS has a smooth surface and few cisplatin crystals in the hollow. An electron probe micro analyzer revealed that cisplatin was located mainly in the matrix in the state of a molecule. Release profile in vitro of CDDP from microspheres showed that the initial burst was 21.2% and the remaining CDDP was released slowly thenceforth over 14 days. Hydrolysis of CDDP-MS progresses very slowly during the 14 days, but there was no morphological change in the SEM views. The dimethylformamide content entrapped within CDDP-MS, determined by a gas chromatography, was 136 ppm at the evaporation temperature of 47 degrees C. The 50% lethal dose value of CDDP-MS, calculated by the Litchfield-Wilcoxon method, was reduced to 57% of the cisplatin solution. Therapeutic experiment on mice with peritoneal carcinomatosis showed that CDDP-MS did not enhance therapeutic effect as compared with the same dose dosage of a cisplatin aqueous solution but large quantities of cisplatin could be given in case of CDDP-MS owing to less toxicity.

Animals↗

PubMed2003

Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays.

The number of known mRNA transcripts in the mouse has been greatly expanded by the RIKEN Mouse Gene Encyclopedia project. Validation of their reproducible expression in a tissue is an important contribution to the study of functional genomics. In this report, we determine the expression profile of 57,931 clones on 20 mouse tissues using cDNA microarrays. Of these 57,931 clones, 22,928 clones correspond to the FANTOM2 clone set. The set represents 20,234 transcriptional units (TUs) out of 33,409 TUs in the FANTOM2 set. We identified 7206 separate clones that satisfied stringent criteria for tissue-specific expression. Gene Ontology terms were assigned for these 7206 clones, and the proportion of 'molecular function' ontology for each tissue-specific clone was examined. These data will provide insights into the function of each tissue. Tissue-specific gene expression profiles obtained using our cDNA microarrays were also compared with the data extracted from the GNF Expression Atlas based on Affymetrix microarrays. One major outcome of the RIKEN transcriptome analysis is the identification of numerous nonprotein-coding mRNAs. The expression profile was also used to obtain evidence of expression for putative noncoding RNAs. In addition, 1926 clones (70%) of 2768 clones that were categorized as "unknown EST," and 1969 (58%) clones of 3388 clones that were categorized as "unclassifiable" were also shown to be reproducibly expressed.

Animals↗

PubMed2003

[Possible involvement of inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers].

Our previous study using a cDNA microarray demonstrated that positive identification of differently expressed genes among gastric cancer cells involved in peritoneal dissemination could be accomplished. One of these genes with overexpression is inositol 1, 4, 5-trisphosphate receptor type 3 (IP3R3). IP3R3 is an intracellular Ca2+ release channel responsible for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned, and their genes have been classified into a family. But the role of the IP3 signaling pathway in the peritoneal dissemination of gastric cancers is still unclear. In this study, IP3R3 is overexpressed in gastric cancer cell lines established from malignant ascites, but weakly expressed in gastric cancer cell lines established from primary tumor as well as in normal gastric epithelial cells. IP3R1 and 2 are expressed only weakly or not at all in these cells. The antagonist of IP3R, 2-APB, inhibited cell proliferation and induced apoptosis of gastric cancer cells from malignant ascites at concentrations of 100 nM to 100 microM in a dose dependent manner. Conversely, 2-APB showed a weak effect on other gastric cancer cells established from primary tumors (SNU1), lymph node metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and myeloid leukemia cell HL60 cells. This suggests that this inhibitory effect depends on the level of IP3R3 expression. As cells that express IP3R3 mRNA (i.e., pancreatic aciner cells) are known to have a secretory function in which IP3/Ca2+ signaling has been shown to be involved, IP3R3 may be a prerequisite for secretion in gastric cancer cells. These results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and that IP3R3 may be a molecular target of the peritoneal dissemination of gastric cancer. Its antagonist, 2-APB, may thus be useful for the treatment of gastric cancer, especially for peritoneal dissemination.

Apoptosis↗

PubMed2002

[Detection of sentinel lymphatic region with activated carbon particles in lymph node dissection for colorectal cancer].

Sentinel node navigation surgery (SNNS) for gastrointestinal cancer has been examined using various methods, but the SN concept has not been established. For 18 patients who had colorectal cancer without macroscopic nodal metastases, we had attempted to detect sentinel lymph nodes (SNs) with activated carbon particles and investigate the existence of nodal metastases histologically. SNs were detected in 17 of 18 patients. Thus activated carbon particles are a useful tracer for SN detection. Three patients had microscopic nodal metastases, and two had nodal metastases in SNs. Although the remaining patient was a false negative case which had nodal metastases in non-SNs only, the nodal metastases were within the sentinel lymphatic region (SLR) which includes SNs. It is considered possible to safely perform minimally invasive lymphadenectomy for colorectal cancer without macroscopic nodal metastases, by means of SLR dissection using activated carbon particles.

Charcoal↗

PubMed2002

[Endoscopic local injection of anticancer drugs bound to carbon particles for treatment of advanced rectal cancer, when surgical treatment was contraindicated].

Generally, patients with advanced rectal cancer in whom surgical treatment is contraindicated receive radiation or chemotherapy. In such patients, we have administered local injection of methotrexate and mitomycin C bound to activated carbon particles. Four patients received intratumoral injection of the dosage formulation (total dose 100-400 mg of methotrexate or 8-32 mg of mitomycin C) under colonofiberscope. After the treatment, bleeding and pain were lessened in all 4 patients. In two patients, the tumor markedly decreased in size and there was no regrowth prior to death 12-14 months after the treatment. In another patient, bleeding and pain disappeared until the patient died of pulmonary and liver metastases. The fourth patient is alive without regrowth 5 months after treatment. Side effects were not severe.

Aged↗

PubMedDate not supplied

Local administration of methotrexate bound to activated carbon particles (MTX-CH) for treating cancers in mice.

PURPOSE: A new dosage formulation of methotrexate (MTX-CH) was developed to control cancer growth by local administration. MATERIALS AND METHODS: BALB/c mice received a subcutaneous inoculation with transplantable Colon 26 cancer cells on the back. When cancerous tumor became 7 mm in diameter, MTX-CH or MTX aqueous solution (MTX-sol) was injected into the tumor. The MTX concentration in the tumor was compared between the MTX-CH group and the MTX-sol group. The tumor growth was assessed in single or repeated local administration experiments. RESULTS: The MTX concentrations were significantly higher for longer periods in the MTX-CH group than those in the MTX-sol group. Repeated MTX-CH administration was significantly more effective for suppressing the tumor growth compared with repeated MTX-sol administration. CONCLUSION: MTX-CH is superior to MTX-sol in controlling the tumor growth by local administration because of its long-acting effect.

Animals↗

PubMedDate not supplied

Possible involvement of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in the peritoneal dissemination of gastric cancers.

Our previous study using cDNA microarray showed that differentially expressed genes among gastric cancer cells involved in peritoneal dissemination could be positively identified. One of these genes, which is overexpressed, is inositol 1,4,5-trisphosphate receptor type 3 (IP3R3). IP3R3 is responsible for the intracellular Ca2+ release channel and for mobilizing stored Ca2+. Three different receptor types have been molecularly cloned and their genes have been classified into a family. However, the role of the IP3 signaling pathway in the peritoneal dissemination of gastric cancer is still unclear. In the study presented here, the IP3R3 is showed to be overexpressed in gastric cancer cell lines established from malignant ascites, but weakly expressed in a gastric cancer cell line established from primary tumor as well as normal gastric epithelial cells. IP3R1 and 2 are only weakly or not expressed in these cells. The antagonist of IP3R, 2APB, inhibited cell proliferation and induced apoptosis in gastric cancer cells from malignant ascites at concentrations of 100 nM to 100 microM in a dose-dependent manner. On the other hand, 2APB showed a weak effect on other gastric cancer cells established from primary tumors (SNU1), lymph node metastases or liver metastases (MKN1 or 74), methothelial cell lines Met5A and myeloid leukemia HL60 cells. This suggests that this inhibitory effect depends on the level of IP3R3 expression. As cells which express IP3R3 mRNA (i.e. pancreas ascinar cells) are known to have a secretory function in which IP3/Ca2+ signaling has been shown to be involved, IP3R3 may be a prerequisite for secretion of an enzyme, such as protease, in gastric cancer cells. These results indicate that IP3R3 may be specifically involved in gastric cancer peritoneal dissemination and that IP3R3 may be a molecular target of the peritoneal dissemination of gastric cancer. Its antagonist, 2APB, may thus be useful for the specific treatment of peritoneal dissemination of gastric cancer.

Apoptosis↗

PubMedDate not supplied

Combination of L-3-phosphoserine phosphatase and CEA using real-time RT-PCR improves accuracy in detection of peritoneal micrometastasis of gastric cancer.

Peritoneal metastasis is the most frequent form of recurrence for advanced gastric cancer. We previously performed a global analysis of the gene expression of gastric cancer cell lines established from peritoneal metastasis with cDNA microarray. One of the up-regulated genes is L-3-phosphoserine phosphatase (L3-PP). We have examined its potential as a novel marker for the detection of peritoneal micrometastasis of gastric cancer. L3-PP mRNA in peritoneal wash from 88 gastric cancer patients was quantified for comparison of carcinoembryonic antigen (CEA) mRNA by means of real-time RT-PCR with a fluorescently-labeled probe to predict peritoneal recurrence. The quantity of L3-PP and CEA correlated with wall penetration. The cut-off value was set at the upper limit of the quantitative value of T1 cases (tumor invades within submucosa) and those above the cut-off value constituted the micrometastasis (MM+) group; eight out of 14 cases with peritoneal dissemination were MM+ L3-PP (57.1% sensitivity) and two out of 57 T1 and T2 cases were MM+ (93% specificity). For two out of 14 cases of peritoneal dissemination only L3-PP could detect micrometastasis of gastric cancer, indicating that L3-PP is superior to CEA especially in poorly-differentiated adenocarcinoma. The combination of CEA and L3-PP improved the accuracy of diagnosis up to 85.7%. Consequently, free cancer cells that cannot be detected by CEA mRNA could be detected using L3-PP mRNA. CEA alone was not sufficient, but L3-PP and CEA in combination can attain a higher accuracy of detection.

Actins↗

PubMedDate not supplied

Dextran sulfate suppresses cell adhesion and cell cycle progression of melanoma cells.

We have reported that dextran sulfate is a possible candidate for an antimetastatic drug because it inhibits cell adhesion. It has been demonstrated that dextran sulfate can detach cancer cells adhering to the bottom of plastic flasks, and that the detached cells do not readhere or proliferate. In this study, we investigated the effects of dextran sulfate on cancer cells, focusing on cell cycle regulators as well as cell adhesion molecules. The effects of dextran sulfate on the cell cycle were examined by flow cytometry, and changes in gene expression caused by dextran sulfate were analyzed by cDNA microarray to identify changes in adhesion and cell cycle genes. By flow cytometry, treatment with dextran sulfate increased the percentage of cells in the G1/G0-phase, and decreased those in the S- and G2/M-phases. Analysis by cDNA microarray revealed decreased expression of several genes essential for progression of the G1- and S-phases. The expression of the adhesion factors involved in metastases was also suppressed. Furthermore, we confirmed these changes in the gene expression by Northern and Western blotting. Our results indicate that dextran sulfate suppresses cell adhesion and cell cycle progression, both of which are essential for metastasis, suggesting that dextran sulfate could be used as an antimetastatic agent.

Animals↗