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Biomedical subjects

M Ikeguchi

Publications and source records attributed to M Ikeguchi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Are argyrophilic nucleolar organizer regions good prognostic indicators of survival of patients with esophageal cancer with lymph node metastasis?

Argyrophilic nucleolar organizer regions (AgNORs) were evaluated in 95 samples from primary esophageal squamous cell carcinomas and 75 samples from metastatic lymph nodes. The number of AgNORs per nucleus in primary tumors with positive nodes (n=53, 6.1+/-1.8) was greater than that in primary tumors with negative nodes (n=42, 3.8+/-1.1, P<0.001). In 39 of 53 patients with positive nodes, the numbers of AgNORs per nucleus in metastatic lymph nodes were lower than those in primary tumors. The 5-year survival rate of these patients was 23.7%. However, the numbers of AgNORs per nucleus in metastatic lymph nodes were greater than those of primary tumors in 14 of 53 patients with positive nodes, and 11 of these 14 patients died from recurrence of cancer within 3 years after surgery. These observations suggest that the proliferative activity of cancer cells might be suppressed in the regional lymph nodes. However, cancer cells with higher proliferative activity in the regional lymph nodes than in the primary tumors might overcome immunological defenses and subsequent further metastasis might occur.

Aged↗
PubMed1996

Limited operation for gastric cancer in the elderly.

The relationship between operative procedures for treatment of patients with gastric carcinoma and complications was studied with special reference to the age of patients, who were divided into four groups: 50-59 years; 60-69 years; 70-79 years; and over 80 years. Preoperative risk factors that were common in patients over 70 years of age were hypertension and cardiac disease. The selected operative procedures were similar for each age group. However, neither proximal gastrectomy nor reconstruction by jejunal interposition was selected for patients of 80 years and over. In these patients, resection of the neighbouring organs was seldom performed and lymph node dissection was usually limited to the primary and secondary nodes. There was no significant difference in the rate of postoperative complications between groups. Although only limited surgery was performed for patients of 80 years and over, there was no significant difference in age-corrected cumulative survival rate between groups. Therefore, limited resection and/or lymph node dissection may allow safe surgical treatment for patients of 80 years and over with gastric carcinoma, without any negative effect on prognosis.

Age Distribution↗
PubMed1996

Hypotonic intraperitoneal cisplatin chemotherapy for peritoneal carcinomatosis in mice.

The intraperitoneal (i.p.) administration of cisplatin (CDDP) is one of the most effective therapies for cancers that are confined to the abdominal cavity. However, the effect of fluid osmolarity on the therapeutic efficacy of i.p. administration of CDDP has not been well established. In the current study, hypotonic (154 mosmol 1-1), isotonic (308 mosmol 1-1) and hypertonic (616 mosmol 1-1) solutions of CDDP were prepared for an evaluation of their therapeutic efficacy in an experimental system. After i.p. administration, uptake of CDDP in vivo by tumor cells in hypotonic solution was significantly greater than in isotonic or hypertonic solution. The 50% lethal dose (LD50) value of CDDP in hypotonic solution (12.1 mg kg(-1)) was lower than that in isotonic solution (16.9 mg kg(-1)) and than that in hypertonic solution (28.6 mg kg(-1)). However, when a dose equal to one-half of the LD50 was administered in each solution to mice with i.p. tumours, survival of mice given the CDDP in hypotonic solution was significantly prolonged as compared with the survival of the other mice. These results demonstrate that the therapeutic efficacy of i.p. CDDP in mice is augmented when the drug is administered in hypotonic solution.

Animals↗
PubMed1996

A synthetic peptide study on the molten globule of alpha-lactalbumin.

We investigated the conformations of peptides that encompass the B helix or C helix region formed in the molten globule of bovine alpha-lactalbumin to get information on the molecular mechanism that stabilizes the molten globule. The CD spectra show that the isolated B and C helices are intrinsically unstable. The chemical shifts, NOE connectivities, and CD spectrum indicate that no helical structure is induced in the C helix region (86-99) by extending the peptide sequence to include the hydrophobic cluster region (101-107), although the hydrophobic cluster region can be regarded as a possible initiation site for folding of the protein. We also clarified that the isolated B helix (23-34) peptide does not directly interact with the C helix or hydrophobic cluster region. These results suggest that the B and C helices in the molten globule are stabilized by their interaction with other parts of the protein.

Amino Acid Sequence↗
PubMed1995

Identification and characterization of a hepatoma cell-specific enhancer in the mouse multidrug resistance mdr1b promoter.

The expression of multidrug resistance/P-glycoprotein genes mdr1b(mdr1) and mdr1a(mdr3) is elevated during hepatocarcinogenesis. To investigate the regulation of mdr1b gene expression, we used transient transfection expression assays of reporter constructs containing various 5'-mdr1b flanking sequences in hepatoma and non-hepatoma cells. We found that nucleotides -233 to -116 preferentially enhanced the expression of reporter gene in mouse hepatoma cell lines in an orientation- and promoter context-independent manner. DNase I footprinting using nuclear extracts prepared from hepatoma and non-hepatoma cells identified four protein binding sites at nucleotides -205 to -186 (site A), -181 to -164 (site B), -153 to -135 (site C), and -128 to -120 (site D). Further analyses revealed that, while site B alone played a major part for the enhancer function, sites A and B combined conferred full enhancer activity. Site-directed mutagenesis results also supported these results. Gel retardation experiments using oligonucleotide competitors revealed that the site B contains a dominant binding protein. This is the first report demonstrating a cell type-specific enhancer in the mdr locus. The role of this enhancer in the activation of mdr1b gene during hepatocarcinogenesis is discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Infiltration of dendritic cells into regional lymph nodes in gastric cancer.

BACKGROUND: Dendritic cells (DC), including epidermal Langerhans cells, are potent antigen-presenting cells that can carry and present tumor antigens to helper T-cells. An immunohistochemical study was performed to clarify the relationship between the extent of infiltration by DCs in primary gastric cancer and that in the regional lymph nodes. METHODS: Paraffin blocks were prepared for staining with antibody against S-100 protein in 121 cases of gastric cancer. Infiltration of S-100 protein-positive DCs was evaluated in the primary tumor and in the peritumoral, primary, secondary, and tertiary nodes. RESULTS: The extent of infiltration by DCs into the regional lymph nodes decreased significantly with an increasing distance of the nodes from the primary tumor. Correlation of the extent of such infiltration was observed among the peritumoral, primary, secondary, and tertiary nodes. However, the extent of infiltration into the primary tumor did not correlate with that into the primary, secondary, and tertiary nodes. Infiltration by DCs of the peritumoral nodes correlated with that of the tumor, particularly when lymph node metastasis was absent. There was no significant difference in the extent of infiltration into the peritumoral nodes even when lymph nodes were involved. However, infiltration of DCs increased in the primary and secondary nodes when the primary nodes were involved. CONCLUSION: Infiltration of DCs may be regulated in the primary lesion of gastric cancer. The peritumoral lymph nodes serve as transmitters of DCs from the primary tumor to the regional lymph nodes. DCs in the regional lymph nodes are important for establishing immunologic defense mechanisms in cases of gastric cancer when metastasis is absent or limited to the primary nodes.

Dendritic Cells↗
PubMed1995

Aneuploidy of tumor cells in cases of gastric cancer with esophageal invasion: another indicator of poor prognosis.

The prognosis of patients with gastric cancer with esophageal invasion is extremely poor. To evaluate factors related to this poor prognosis, we analyzed 200 patients with gastric cancer located in the upper third of the stomach. These patients underwent gastrectomy and were divided into two groups in terms of the presence (E[+] group; n = 62) or absence (E[-] group; n = 138) of histological evidence of esophageal invasion. Even when apparently curative surgery was performed, the 5-year survival rate of patients with E[+] gastric cancer (45.8%) was significantly lower than of patients with E[-] gastric cancer (71.6%). In the E[+] group, the 5-year survival rate of patients who had tumors with infiltrative growth and DNA aneuploidy was only 10.0%. These patients had a high frequency of peritoneal metastasis at operation (5/16; 31.3%); even when apparently curative operations were performed, 50% of these patients died from peritoneal metastatic recurrence within 2 years after surgery. Gastric adenocarcinoma with esophageal invasion accompanied by infiltrative growth and DNA aneuploidy had a high potential for peritoneal metastasis. This combination is associated with the most pessimistic prognosis for patients with gastric cancer with esophageal invasion.

Adenocarcinoma↗
PubMed1995

Gastric cancer in the young, with special reference to 14 pregnancy-associated cases: analysis based on 2,325 consecutive cases of gastric cancer.

Clinicopathologic features of gastric cancer in young women were analyzed with special reference to pregnancy (P). Among 2,325 consecutive patients, there were 152 young patients under 40 years of age (57 males and 95 females), and 14 P-associated cases were identified. The male-to-female ratio was 1.7:1.0 on the whole, but 1.0:1.7 in the young group with more females predominating as the age of patients decreased. Among characteristics of gastric cancer in the young females, we noted a significantly higher frequency of both Borrmann type 4 cancer and poorly differentiated adenocarcinoma with the scirrhus type of growth and peritoneal metastasis. These characteristics were more pronounced in the P-associated cases. Although we were unable to determine the mechanism for these tendencies, our findings suggest that the development and growth of gastric cancer in young women may be influenced by their natural, biological and hormonal circumstances. The prognosis of the young women with or without associated pregnancy was good after curative surgery. Both early detection of gastric cancer and subsequent potentially curative surgery are the best ways to obtain good survival for young women, as is the case for members of other age and sex groups.

Adenocarcinoma↗
PubMed1995

Number of argyrophilic nucleolar organizer regions is a good indicator of lymph node metastasis in patients with esophageal carcinoma.

The number of argyrophilic nucleolar organizer regions (AgNORs) was evaluated as a predictor of lymph node metastasis in 45 patients who had undergone resection of advanced squamous cell carcinoma of the esophagus. The mean AgNOR score of carcinomas was 5.0 +/- 1.8, and it was greater than that of normal esophageal epithelium adjacent to a carcinoma (2.3 +/- 0.5, P < 0.001). The AgNOR score of tumors from 26 patients with lymph node metastasis was 6.1 +/- 1.6, and it was greater than that of tumors from 19 patients without lymph node metastasis (3.7 +/- 1.0, P < 0.001). The AgNOR scores of metastatic lymph nodes (4.9 +/- 1.5) from 26 patients with lymph node metastasis were closely related to the number of metastatic lymph nodes of individual patients (r = 0.582, P < 0.0001). The 3-year survival rate in patients with low AgNOR scores (AgNOR score < 5, n = 22) was 56.2%. By contrast, that in patients with high AgNOR scores (AgNOR score > or = 5, n = 20) was only 13.1%. There was a statistically significant difference between the two survival curves (P < 0.05). These results indicate that the AgNOR score is a good indicator of lymph node metastasis and suggest that it might also be a useful prognostic marker in patients with esophageal cancer.

Aged↗
PubMed1995

Long-term survival of 5 years following initial surgery for gastric cancer and simultaneous disseminated peritoneal metastasis: report of a case.

We report herein the rare case of a patient who survived for 5 years and 10 months after commencing treatment for gastric cancer with simultaneous disseminated peritoneal metastasis. A 45-year-old man was diagnosed as having advanced gastric cancer following the discovery of numerous nodules in the peritoneal cavity at laparotomy. The patient was treated by palliative gastrectomy and continuous hyperthermic peritoneal perfusion (CHPP) immediately after surgery on November 11, 1987. Postoperatively, he underwent radiofrequency (RF) hyperthermia with intraperitoneal cisplatin a total of seven times. He continued on a combination of uracil and tegafur (UFT) administered orally with a protein-bound beta-D-glucan extracted from the mycelia of Cariolus versicolor (PSK). Long-term survival was achieved following the initial palliative gastrectomy despite simultaneous disseminated peritoneal metastasis.

Adenocarcinoma, Scirrhous↗
PubMed1995

The superreactive disulfide bonds in alpha-lactalbumin and lysozyme.

The disulfide reduction kinetics in equine lysozyme (ELZ), which is a Ca(2+)-binding lysozyme, and human (HLA) and equine alpha-lactalbumin (ELA) at pH 8.5 and 25 degrees C by excess dithiothreitol were studied, and it was found that in ELZ there is no superreactive disulfide bond, while one of the disulfides is reduced very quickly by the reducing agent in HLA and ELA, as in bovine alpha-lactalbumin. The local conformation around the surface disulfide in ELZ seems to be more similar to that in hen egg-white lysozyme than in alpha-lactalbumin. The four disulfides in ELZ were reduced slowly in an apparently single-exponential form, and the bound Ca2+ lowered the reduction rate. The torsion energy on each of the disulfides in three alpha-lactalbumin and eight c-type lysozymes whose native conformations have been experimentally or theoretically analyzed was calculated, and it was found that torsion imposed on the surface disulfide between Cys 6 and Cys 120 in alpha-lactalbumin is a main cause of the superreactivity and all of lysozymes, including the Ca(2+)-binding ones, have no such strained surface bond.

Animals↗
PubMed1995

Interphase cytogenetics of gastric carcinoma: fluorescence in situ hybridization (FISH) applied to cells obtained from formalin-fixed paraffin-embedded tissues.

The interphase cytogenetics in formalin-fixed and paraffin-embedded gastric cancer tissues were examined by fluorescence in situ hybridization (FISH) with alpha-satellite DNA probes. Two gastric carcinoma cell lines, TMK-1 and MKN-28, were first analyzed cytogenetically. Of 25 TMK-1 cell karyotypes, chromosome 7 showed trisomy and chromosome 17 showed disomy in 18 cells. Most MKN-28 cells showed disomy of both chromosomes 7 and 17. Suspensions of singly isolated TMK-1 and MKN-7 cells were obtained from the cultured cells, and from paraffin-embedded tissue specimens fixed with formalin for 0, 1, 3 and 5 days obtained from xenotransplanted tumors in nude mice. The numbers of chromosomes 7 and 17 analyzed with the karyotypic preparations coincided well with those determined by FISH, even in the paraffin-embedded specimens. The number of tumor cells showing no signals, however, increased in the specimens after 5 days formalin fixation. In 10 surgically removed gastric carcinomas, the predominant signal number for chromosomes 7 and 17 in the cells of paraffin-embedded tissues was two (disomy), except in one papillary carcinoma, which was trisomic for chromosome 7. Large subpopulations (more than 20%) showing trisomy were found in four cases for chromosome 7 and in five cases for chromosome 17. A higher frequency of trisomy was found in well differentiated than in poorly differentiated carcinomas. These findings suggest that the FISH technique is a useful tool for detecting chromosomal aberrations in gastric adenocarcinoma cells, even in paraffin-embedded specimens, as long as the tissues are fixed with formalin for an appropriate time.

Adenocarcinoma↗
PubMed1995

Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion.

OBJECTIVE: To evaluate the effects of continuous hyperthermic peritoneal perfusion (CHPP) together with standard chemotherapy on the prognosis of patients with gastric cancer invading the serosa. DESIGN: Retrospective study. SETTING: University hospital, Japan. SUBJECTS: 174 patients who had undergone curative resection for gastric cancer invading the serosa (T3) between 1980 and 1989, 78 of whom had been randomised to be treated with CHPP after operation and 96 who received standard chemotherapy. INTERVENTIONS: CHPP was done immediately after operation; 8-10 l fluid containing 80-100 mg/m2 mitomycin C was perfused at a rate of 100-200 ml/minute, and inflow and out flow temperatures were maintained at 44-45 degrees C and 40-42 degrees C, respectively. This was followed by a standard regimen of mitomycin C and 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil (1:4) (UFT). The control group received the standard regimen only. MAIN OUTCOME MEASURES: Five year survival and patterns of recurrence in three groups: no lymph node metastases, 1-9, and 10 or more. RESULTS: Only in the group with 1-9 lymph node metastases was there an appreciable but not significant difference in 5 year survival: 66% compared with 44% (p = 0.084). The mean disease free survival for patients with peritoneal metastases was 30 months in the CHPP group compared with 23 months among the controls. CONCLUSION: CHPP improved prognosis in patients with T3 gastric cancer who had only 1-9 metastatic lymph nodes.

Aged↗
PubMed1994

Clinicopathologic differences between carcinoma in the gastric remnant stump after distal partial gastrectomy for benign gastroduodenal lesions and primary carcinoma in the upper third of the stomach.

BACKGROUND: This study evaluated the prognosis of patients with carcinoma in the gastric remnant stump after distal gastrectomy for benign disease (stump cancer). METHODS: Twenty patients with resected stump cancer were studied and compared with 266 patients with resected primary cancer in the upper third of the stomach (primary cancer). RESULTS: The percentages of lymph nodes with metastases located at the lesser curvature and the left gastric artery, respectively, were 50.0% and 25.2% in patients with primary cancer and 15.0% and 5.0% in patients with stump cancer. In patients with remnant gastric cancer, lymph node metastases at jejunal mesentery near anastomotic site were found in 2 of 20 (10.0%). The 5-year survival rates were 62.1% and 52.5% for patients with curatively resected primary cancer (n = 203) and stump cancer (n = 17), respectively, and there was no statistical difference between the two groups. There was a distinct difference in terms of patterns of recurrence between patients with curatively resected primary cancer and those with stump cancer. The percentages of peritoneal and hematogenic metastases, respectively, were 40.6% and 31.3% in primary cancer and 0% and 83.3% in stump cancers. CONCLUSION: The lymph flow from the remnant stomach seems to be changed by the initial operation, and as a result, in stump cancer, metastatic lymph nodes are located at different places from those associated with primary cancer. Even when curative surgery is performed in patients with stump cancer, it is important to follow up patients and check for possible metastasis to the liver.

Carcinoma↗
PubMed1994

Does the extent of lymph node dissection affect the postoperative survival of patients with gastric cancer and disseminating peritoneal metastasis?

For patients with gastric cancer and either P1 or P2 peritoneal metastasis, no definite consistent policy with respect to the extent of lymph node dissection has yet been established. In palliatively gastrectomized patients, we analyzed the relationship between the extent of lymphadenectomy and postoperative survival. In patients with P1, an R2 or R3 lymphadenectomy was associated with a significantly improved postoperative survival as compared to an R1 dissection, while this, however, was not the case in patients with P2. As this study was not intended to be a prospective randomized study, a definite conclusion should be avoided. However, our findings suggest that in patients with P1, surgery should not be confined to a resection of the primary lesion, but should also include an R2 or R3 lymphadenectomy.

Female↗
PubMed1994

Conformational comparison between alpha-lactalbumin and lysozyme.

Comparisons of the conformation behavior between LA and LZ (especially BLA and HEL) are described, which have contributed to the development and understanding of the molten globule folding intermediate of protein. BLA (and other LAs) is clearly a very good model protein for fundamental studies of molten globule protein conformation and the mechanism of protein unfolding/folding in vitro. Our work for about 20 years, on the conformational characterizations of proteins in the LA-LZ family, primarily based on macroscopic observations, led to three important findings: 1) equilibrium intermediate of unfolding/folding of LA is in the molten globule state, as assumed later for many proteins; 2) kinetic (transient) folding intermediates of BLA and HEL are the same as the equilibrium intermediate of BLA, and they include the framework remaining in the N state; and 3) the bound Ca2+, which is the main factor explaining the apparent difference in the conformational behavior between BLA and HEL, is found in some LZs. The conformational characterization of two Ca(2+)-binding LZs (ELZ and PLZ) by CD, calorimetry, X-ray, and NMR structural analysis is shown in detail and the mechanism of molecular evolution is discussed for the LA-LZ family. However, first concept of the molten globule has gradually changed with the definition of the collapsed form, the N-like or the U-like molten globule and so on, based on the results of measurements at residual resolutions including X-ray, NMR, and isotope exchange of some proteins. Our recent data on such microscopic measurements of LAs in the molten globule state are therefore compared with those of various proteins by other researchers. The roles of the disulfide bonds to stabilize the molten globule state are also discussed with our conformational research results on disulfide-reduced BLA. It is hoped that the multidimensional-NMR can be used for the 3D structural analysis of proteins in the LA-LZ family in the U, I, and N states in the solutions, and that our conformational work on the proteins done in vitro can be applied to understand the conformational events of proteins in vivo.

Amino Acid Sequence↗
PubMed1993

Unfolding of the molten globule state of alpha-lactalbumin studied by 1H NMR.

The urea-induced unfolding of the molten globule state of bovine alpha-lactalbumin was investigated by 1H nuclear magnetic resonance. In the molten globule state, most of the aromatic resonances deviate from their random coil values, indicating that aromatic side chains form some ordered structures in the molten globule state. When the urea concentration increases, the resonances are shifted, and the deviations from the random coil values are diminished. Because the chemical shifts of several random coil peptides are found to be independent of urea concentration, the urea-induced shifts of the resonances in the molten globule state reflect the unfolding transition of some ordered structures. The unfolding transitions measured by individual aromatic resonances do not coincide with each other. The unfolding transition curves obtained from some aromatic resonances are also different from those of the secondary structures measured by circular dichroism spectra. These results clearly show that the unfolding of the molten globule state of alpha-lactalbumin is not a cooperative two-state process.

Animals↗