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Y Ichiyoshi

Publications and source records attributed to Y Ichiyoshi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Multidrug resistance-associated protein expression in clinical gastric carcinoma.

BACKGROUND: We examined the relationship between the expression of a multi-drug resistance-associated protein (MRP) and the biologic factors regarding invasion and metastasis of human gastric cancer. METHODS: In 75 patients with gastric cancer, the expression of MRP was immunohistochemically investigated and the expression of MRP mRNA was also detected using reverse transcription PCR (RT-PCR). Sensitivity to the anticancer agents, cisplatin (CDDP), doxorubicin (DXR), etoposide (VP-16), and mitomycin C (MMC) was examined using the MTT {3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl[2H]-tetra-zolium bromide} assay. The relation between MRP expression and development, invasion, and metastasis of cancer was analyzed, and overexpression of the tumor suppressor gene p53 was investigated, immunohistochemically. RESULTS: Immunohistochemically detected MRP positive tumors were noted in 34 of 75 excised tumors (45%), and confirmed by RT-PCR. There was no significant relation between MRP expression and clinicopathologic features or prognosis. Positive p53 staining was evident in 16 of 34 MRP positive tumors (47%) and 18 of 41 negative ones (44%), and there was no significant correlation between MRP and abnormal p53 expression. The MTT assay showed that MRP positive gastric cancer tissue was less sensitive to CDDP, DXR, and MMC compared with MRP negative ones. A similar tendency was noted with VP-16. CONCLUSIONS: MRP expression relates to the chemosensitivity of tumor cells against some anticancer drugs and is independent of known factors related to the development, invasion, and metastasis of human gastric cancers.

ATP-Binding Cassette Transporters↗
PubMed1996

Microvessel quantification and its possible relation with liver metastasis in colorectal cancer.

BACKGROUND: Several studies have proven the usefulness of microvessel quantification as a prognostic factor for patients with various malignant tumors. The aim of this paper was to clarify the relationship between microvessel density (MVD) as a parameter of tumor angiogenesis and liver metastasis in colorectal cancer. METHODS: A total of 175 patients with advanced colorectal cancer were evaluated (58 with concurrent liver metastases). Microvessel quantification was performed immunohistochemically, using monoclonal antibodies against endothelial protein Factor VIII-related antigen (F8RA) and against endothelial surface marker CD34. Finally, the relationship between MVD and liver metastasis was analyzed. RESULTS: A significant correlation was observed between MVD for F8RA and MVD for CD34 (n = 175, r = 0.9560, P = 0.0001). MVD in the tumors stained for F8RA ranged from 15.2 to 78.6 microvessels per x 200 field (mean 32.8 +/- 11.7), while the tumors with liver metastatic disease compared with the tumors without liver metastasis (F8RA; mean 36.1 +/- 11.3 vs. 31.2 +/- 11.5, P = 0.0090; CD34; mean 64.4 +/- 20.4 vs. 52.0 +/- 19.4, P = 0.0010). CONCLUSIONS: Microvessel quantification within a colorectal tumor using immunohistochemical staining methods has shown a significant correlation between MVD and liver metastasis. Tumors with a greater MVD may thus have a greater hematogenous metastatic propensity.

Aged↗
PubMed1996

Clinical significance of occult micrometastasis lymph nodes from patients with early gastric cancer who died of recurrence.

BACKGROUND: Even after curative resection of an early gastric cancer, some patients die of a recurrence. It is our view that patients with early gastric cancer who died of their disease had occult micrometastases in perigastric lymph nodes at the time of the original diagnosis. In an attempt to identify these micrometastases, lymph nodes dissected from early gastric cancer lesions were stained after operation with monoclonal antibody against cytokeratin, an essential constituent of the cytoskeleton of epithelial cells. METHODS: The 420 dissected lymph nodes from 34 patients with node-negative early gastric cancer who died of a recurrence were examined for the presence of tumor cells. We used immunocytochemical techniques and an antiserum to epithelial membrane antigen. The monoclonal antibody CAM 5.2 recognizes cytokeratin polypeptides (human cytokeratin numbers 8 and 18) commonly present in epithelial cells. Clinicopathologic characteristics and prognosis were determined for patients with cytokeratin-positive cells in the lymph nodes. RESULTS. Of 420 lymph nodes, 15 (3.6%) nodes and 23.5% (8 of 34) of the patients presented with cytokeratin-positive cells at the time of primary operation. The presence of cytokeratin positivity was not related to various clinicopathologic factors. The histologic stage of eight cytokeratin-positive cases was upstaged by the group of cytokeratin-positive lymph nodes from stage I to three of stage II, four of stage III, and one of stage IV, hematogenous recurrences were common, and the prognosis was poorer. CONCLUSIONS: Immunohistochemical techniques aid in identifying micrometastatic disease in lymph nodes missed in routine hematoxylin-eosin staining. Cytokeratin staining of the dissected lymph nodes is recommended to precisely determine tumor stage and prognosis for patients with early gastric cancer.

Adult↗
PubMed1996

Cytokeratin-positive cells in bone marrow for identifying distant micrometastasis of gastric cancer.

Direct evidence of tumour seeding in distant organs at the time of surgery for gastric cancer is not available. An immunocytochemical assay for epithelial cytokeratin protein may fill this gap since it is a feature of epithelial cells that would not normally be present in bone marrow. The bone marrow of 46 patients with primary gastric cancer was examined for tumour cells, using immunocytochemical techniques and antibody reacting with cytokeratin, a component of the intracytoplasmic network of intermediate filaments. The monoclonal antibody CK2 recognises a single cytokeratin polypeptide (human cytokeratin no. 18) commonly present in epithelial cells. The expression of tumour-suppressor genes p53 and RB for the primary lesion was also determined using the monoclonal antibodies PAb 1801 and 3H9 respectively, and the proliferating activity was determined by the Ki-67 antigen labelling index for MIB-1 antibody staining. Of these 46 patients, 15 (32.6%) presented with cytokeratin-positive cells at the time of primary surgery. The positive findings were related to the undifferentiated tissue type and to the prominent depth of invasion, but not to other clinicopathological factors. In 2 of 15 (13.3%) patients, the depth of invasion was limited to the mucosa. The metastatic potential to bone marrow did not relate to expressions of p53 and RB genes, or to the proliferating activity of MIB-1 staining for the primary lesion of gastric cancer. As tumour cells in bone marrow are indicative of the general disseminative capability of an individual tumour, this technique may be useful for identifying patients at high risk of metastasis from a gastric tumour.

Antibodies, Monoclonal↗
PubMed1996

Recurrences and related characteristics of gastric cancer.

We analysed data on 1117 patients with gastric cancer who were treated by curative resection. Attention was focused on invasion and a recurrence of the cancer. Based on a univariate analysis, death following a recurrence and prognosis were related to age of the patients, size of the tumour, tumour location, tumour tissue differentiation, growth pattern, depth of invasion, lymphatic and vascular invasion and lymph node metastasis. In proportion to the growth potential, determined by the level of proliferating cell nuclear antigen (PCNA) labelling, the death related to a recurrence was increased and the prognosis was poorer. Multivariate analysis showed that the three factors of serosal invasion, PCNA labelling index and lymph node dissection were independent prognostic factors. When sites of recurrence were analysed regarding each depth of invasion, haematogenous recurrence, in particular in the liver, occurred even in cases of an early invasion and many types of recurrences, including peritoneal recurrence, were noted in patients with an advanced state of invasion.

Adult↗
PubMed1996

Argyrophilic nucleolar organizer region in endoscopically obtained biopsy tissue: a useful predictor of nodal metastasis and prognosis in carcinoma of the stomach.

BACKGROUND: Argyrophilic nucleolar organizer region (AgNOR) staining is a simple and economical technique for investigating proliferative activity. We examined AgNOR measured in biopsy specimens of carcinoma of the stomach in humans. STUDY DESIGN: Argyrophilic nucleolar organizer region staining was done on 76 biopsy specimens and corresponding resected cancer tissues. All estimations were made at the invasive tumor margin. RESULTS: Of the 76 cases, intratumoral heterogeneity of AgNOR count (more than 1.0 difference) between superficial and deep layers was recognized in six (7.9 percent) cases, all of which were advanced. In biopsy specimens, the AgNOR count ranged from 1.68 to 7.74 (mean, 3.79). A significant correlation was found between AgNOR counts of biopsied materials and those of resected specimens, both in early and advanced cases. Tumors with a high AgNOR count (greater than or equal to 3.79) were more likely to be of a larger size (p < 0.01), to have metastasized to lymph nodes (p < 0.01), and to be associated with a lower survival rate (p < 0.05) compared to tumors with low AgNOR counts. CONCLUSIONS: Estimating the AgNOR count in endoscopically biopsied specimens at the margin of invasive gastric carcinoma is useful for assessing nodal metastasis and clinical prognosis. These preoperative estimates may aid in tailoring the operative procedure and administrating adjuvant therapy.

Adult↗
PubMed1996

[Advances in the treatment of colorectal cancer].

Colorectal cancer is one of the most serious diseases of our time. Recent progress in its treatment is reviewed in this paper. There are many approaches for treating colorectal cancer; extended surgery to function-preserving surgery. The aim of surgical treatment is to excise the tumor completely, so extended surgery has been performed for curative resection of colorectal cancer. However, the quality of life (QOL) of the patients has been extremely impaired. In recent years, surgical treatments for avoiding colostomy, and urinary and sexual difficulties have been widely carried out, and QOL of the patients could be maintained in the postoperative period. Stage-oriented therapy is accepted as the concept of surgical treatment of colorectal cancer. For further improving the clinical results of colorectal cancer, we advocated "type-oriented therapy" which is based on the biological characteristics of colorectal cancer, by determining i.e., p53 abnormalities of cancer cells, serum p53 antibodies, micrometastasis in the bone marrow and/or sensitivity to anticancer drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Growth pattern and p53 overexpression in patients with early gastric cancer.

BACKGROUND: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects well biologic characteristics of the tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with a superficially spreading (Super) type. Abnormality of the p53 suppressor gene plays an important role in alteration of cells leading to development of cancer. p53 point mutations are present even in an early stage of carcinoma. METHOD: In 159 patients with early gastric carcinoma, overexpression of p53 was studied immunohistochemically, using a monoclonal antibody (PAb 1801), and the relationship between growth pattern and p53 overexpression was analyzed. RESULTS: Early gastric carcinoma was grouped into 43 of the Super type, 37 of the expansively penetrating growth (Pen-A) type, 16 of the infiltratively penetrating growth (Pen-B) type, and 63 of the Small mucosal type limited to the mucosal layer. The Pen-A type tumors were characterized by the highest incidence of p53 positive expression and poorest postoperative course. Between the Pen-A type and the Super type, there were significant differences in the incidence of the p53 positive expression (43% vs. 16%), the frequency of recurrence (16% vs. 7%), and disease free interval (574 days vs. 2926 days). CONCLUSION: The authors' observations show that the p53 gene plays an important role in expansion of gastric carcinoma, even in the early stages.

Gene Expression↗
PubMed1995

A human anti-insulin IgG autoantibody apparently arises through clonal selection from an insulin-specific "germ-line" natural antibody template. Analysis by V gene segment reassortment and site-directed mutagenesis.

We analyzed the structural correlates underlying the insulin-dependent selection of the specific anti-insulin IgG1 kappa mAb13-producing cell clone, derived from a patient with insulin-dependent diabetes mellitus treated with recombinant human insulin. First, we cloned the germ-line genes that putatively gave rise to the expressed VH and V kappa segments and used them to generate the full (unmutated) "germ-line revertant" of the "wild-type" (somatically mutated) mAb13, using recombinant PCR methods and an in vitro human C gamma 1 and C kappa expression system. The full "germ-line revertant" bound insulin specifically and in a dose-saturable fashion, but with a relative avidity (AVrel) more than three-fold lower than that of its wild-type counterpart (Avrel, 1.69 x 10(-8) vs 4.91 x 10(-9) g/microliters). Second, we established, by reassorting wild-type and germ-line revertant forms of the mAb13 VH and V kappa segments, that the increased Avrel for insulin of mAb13 when compared with its full "germ-line revertant" counterpart was entirely dependent on the mutations in the VH not those in the V kappa chain. Third, we determined, by site-directed mutagenesis experiments, that of the three mutations in the mAb13 VH segment (Ser-->Gly, Ser-->Thr, and Ser-->Arg at positions 31, 56, and 58, respectively), only Arg58 was crucial in increasing the mAb13 Avrel (from 1.44 x 10(-8) to 5.14 x 10(-9) g/microliters) and affinity (Kd, from 189 to 59 nM) for insulin. The affinity enhancement mediated by the VH segment Arg58 residue reflected about a threefold decrease in dissociation rate constant (Koff, from 4.92 x 10(-3) to 1.54 x 10(-3) s-1) but not an increase in association rate constant (Kon, from 2.60 x 10(4) to 2.61 x 10(4) M-1 s-1), and it contrasted with the complete loss of insulin binding resulting from the substitution of the VH segment Asn52 by Lys. The present findings suggest that human insulin, a self Ag, has the potential to recruit a natural autoantibody-producing cell precursor expressing a specific surface receptor for Ag in unmutated configuration, and drive it through affinity maturation. They also show that binding of insulin by such a receptor can be enhanced or completely abrogated by a single amino acid change.

Amino Acid Sequence↗
PubMed1995

Macroscopic intraoperative diagnosis of serosal invasion and clinical outcome of gastric cancer: risk of underestimation.

Data on 715 Japanese patients with gastric cancer were studied retrospectively with regard to the relationship between macroscopic and microscopic diagnoses of serosal invasion and clinicopathological factors affecting the accuracy of the macroscopic diagnosis. Although there was no macroscopic evidence of serosal invasion intraoperatively (S0 or S1), there was histological evidence of cancer cells on the serosal surface in 69 patients (9.7%). In these serosal invasion-positive cases, the tumors were larger; were located more commonly in the upper third, lesser and greater curvatures of the stomach; were Borrmann type 3 or type 4 tumors, and of an undifferentiated histologic type with an infiltrative growth pattern more commonly, and had more extensive lymphatic and vascular vessel invasion and lymph node metastasis (P < 0.01). Total gastrectomy was done more often for the serosal invasion-positive group, but the extent of lymph node dissection was comparable. Cases of a noncurative resection because of a positive surgical margin were more frequent in the serosal invasion-positive group (8/69 vs. 14/646, P < 0.01), and most had undifferentiated and infiltrative cancers. The 10-year survival rates were 49.2% and 85.5% for patients with and without serosa invasion, respectively. These findings clearly show that the serosal surface, especially in cases of the undifferentiated or infiltrative type of gastric cancer, must be closely inspected intraoperatively.

Aged↗
PubMed1995

[DNA ploidy pattern and p53 overexpression in gastric cancer].

DNA ploidy pattern was determined by flow cytometry and p53 overexpression was investigated immunohistochemically in 145 primary gastric cancers. Aneuploid patterns were found in 78 (65%) and diploid patterns in 67 (46%). Metastasising to lymph nodes was observed more frequently in cases with aneuploid tumors, as compared to those with diploid tumors (p < 0.01). DNA ploidy patterns were related to overexpression of p53. The incidences of overexpression of p53 in aneuploid tumors and diploid ones were 65% and 33%, respectively (p < 0.05). Thus, we suggest that gastric carcinomas with the aneuploid pattern have mutation of tumor suppressor gene p53 and high potential to metastasize to lymph nodes.

Cell Cycle↗
PubMed1995

Clinicopathologic characteristics and outcome of adenocarcinoma of the human gastric cardia in comparison with carcinoma of other regions of the stomach.

BACKGROUND: Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. This study was done to analyze the biologic characteristics of carcinoma of the gastric cardia compared with other gastric carcinomas. STUDY DESIGN: Clinicopathologic features and postoperative prognosis of 68 cases of carcinoma of the cardia were evaluated, in comparison with findings of tumors in other regions of the stomach. RESULTS: From 1975 to 1992, 68 (6.5 percent) of 1,042 patients with carcinoma of the stomach had adenocarcinoma of the cardia. Carcinoma of the cardia was characterized by a more advanced stage compared with carcinoma of other regions of the stomach. The incidence of early stage carcinoma (limited to the submucosal layer) was 11.8 percent in the cardia, 15.8 percent in the upper one-third, and 42.2 percent in the remaining middle and lower thirds of the stomach. When compared to carcinoma in other regions of the stomach, tumors of the cardia had a significantly poorer prognosis and there was a higher incidence of lymph node and hepatic metastasis. The five-year survival rates in patients with adenocarcinoma in the cardia, the upper one-third, and the remaining middle and lower thirds of the stomach were 35.3, 43.7, and 61.9 percent, respectively. Especially for patients with stage II and stage III disease, the prognosis was significantly worse with adenocarcinoma of the cardia than with carcinomas of the other regions of the stomach. CONCLUSIONS: Early detection is crucial to improve the survival of patients with carcinoma of the gastric cardia. Extended dissection of lymph nodes and aggressive postoperative chemotherapy in an attempt to prevent hepatic metastasis are highly recommended.

Adenocarcinoma↗
PubMed1995

[Biological features determining the chemosensitivity of gastric cancer].

We analysed the relationship between several biological properties of gastric cancers and their chemosensitivity determined by MTT assay. Higher chemosensitivity was associated with poor differentiation, aneuploidy, and higher proliferative activity. Lymph node metastasis was more chemosensitive than primary lesion, while liver metastasis was less. Gastric cancer expressing multidrug-resistance associated protein (MRP) showed lower sensitivity to several anticancer drugs, including adriamycin and etoposide. p53 status and susceptibility to apoptosis were also associated with chemosensitivity. Thus, chemosensitivity of clinical gastric cancer might be increased if these characters can be modified by some new biologic therapy.

Antineoplastic Agents↗
PubMed1994

Analysis of the structural correlates for antibody polyreactivity by multiple reassortments of chimeric human immunoglobulin heavy and light chain V segments.

Polyreactive antibodies (Abs) constitute a major proportion of the early Ab repertoire and are an important component of the natural defense mechanisms against infections. They are primarily immunoglobulin M (IgM) and bind a variety of structurally dissimilar self and exogenous antigens (Ags) with moderate affinity. We analyzed the contribution of Ig polyvalency and of heavy (H) and light (L) chain variable (V) regions to polyreactivity in recombinatorial experiments involving the VH-diversity(D)-JH and V kappa-J kappa gene segments of a human polyreactive IgM, monoclonal antibody 55 (mAb55), and those of a human monoreactive anti-insulin IgG, mAb13, in an in vitro C gamma l and C kappa human expression system. These mAbs are virtually identical in their VH and V kappa gene segment sequences. First, we expressed the VH-D-JH and V kappa-J kappa genes of the IgM mAb55 as V segments of an IgG molecule. The bivalent recombinant IgG Ab bound multiple Ags with an efficiency only slightly lower than that of the original decavalent IgM mAb55, suggesting that class switch to IgG does not affect the Ig polyreactivity. Second, we coexpressed the mAb55-derived H or kappa chain with the mAb13-derived kappa or H chain, respectively. The hybrid IgG Ab bearing the mAb55-derived H chain V segment paired with the mAb13-derived kappa V segment, but not that bearing the mAb13-derived H chain V segment paired with the mAb55-derived kappa V segment, bound multiple Ags, suggesting that the Ig H chain plays a major role in the Ig polyreactivity. Third, we shuffled the framework 1 (FR1)-FR3 and complementarity determining region 3 (CDR3) regions of the H and kappa chain V segments of the mAB55-derived IgG molecule with the corresponding regions of the monoreactive IgG mAb13. The mAb55-derived IgG molecule lost polyreactivity when the H chain CDR3, but not the FR1-FR3 region, was replaced by the corresponding region of mAb13, suggesting that within the H chain, the CDR3 provides the major structural correlate for multiple Ag-binding. This was formally proved by the multiple Ag-binding of the originally monoreactive mAb13-derived IgG molecule grafted with the mAb55-derived H chain CDR3. The polyreactivity of this chimeric IgG was maximized by grafting of the mAb55-derived kappa chain FR1-FR3, but not that of the kappa chain CDR3.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1994

VH and V kappa segment structure of anti-insulin IgG autoantibodies in patients with insulin-dependent diabetes mellitus. Evidence for somatic selection.

In some patients with insulin-dependent (type I) diabetes mellitus (IDDM), autoantibodies to insulin are present at diagnosis. After initiation of the treatment with not only animal but also human insulin, anti-insulin, mainly IgG, autoantibodies become a major component of the autoimmune response in virtually all IDDM patients. Their structure, however, is still relatively unknown. We analyzed the structure of the VH and V kappa segments of three human IgG mAb derived from three IDDM patients. The sequences of VH genes of two IgG, mAb13 and mAb48, were 98.3 and 96.6% identical with those of the H11 and 1.9III genes (VHIII family), respectively. The sequence of the VH gene of the third IgG, mAb49, was 98.6% identical with that of the 51p1 gene (VHI family). All three IgG mAb used V kappa III segments. The V kappa III gene sequences of mAb13 and mAb49 were 97.9 and 98.9% identical, respectively, to that of the kv3g gene; the mAb48 V kappa gene sequence was 96.5% identical to that of the kv328 gene. The VH and/or V kappa segments of these anti-insulin IgG mAb are similar to Ig V genes expressed in the fetal, and adult normal and autoimmune B cell repertoires. The nucleotide differences displayed by the three anti-insulin IgG mAb VH gene sequences, when compared with those of the closest reported germ-line genes, were concentrated in the CDR (6.2 x 10(-2) and 0.8 x 10(-2) difference/base in CDR and FR, respectively; p < 0.01, chi 2 test), and yielded a significantly higher putative replacement (R) to silent (S) mutation ratio in the CDR (12.0) than in the framework (0.2). The concentration of nucleotide differences in the CDR and their high R:S putative mutation ratios were consistent with the hypothesis that these expressed VH genes underwent a process of somatic mutation and Ag-driven clonal selection. That such differences constituted somatic point-mutations was formally proved in IgG mAb13, by differentially targeted PCR amplification and Southern blot hybridization of the mAb13-producing cell line DNA. The putative germ-line gene that gave rise to the expressed VH segment was cloned using genomic DNA from PMN of the same patient whose B cells were used for the generation of this mAb. Overall, in the anti-insulin IgG mAb VH and V kappa III genes, the (putative and verified) somatic point-mutations yielded 27 amino acid replacements, of which 14 nonconserved. Four of these resulted in positively charged residues, three Arg and one His.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1993

[A case of nonresectable esophageal cancer treated by the combination of cisplatin, 5-fluorouracil and THP-adriamycin].

An advanced esophageal cancer patient with multiple liver metastases was treated with a combination of CDDP, 5-FU and THP-ADM. Complete response was obtained against esophageal primary lesion endoscopically, and partial response was obtained against liver metastases observed by computed tomography. Bone marrow suppression of grade 3 was observed, but resolved within 2 weeks.

Antibiotics, Antineoplastic↗
PubMed1990

Ruptured amebic liver abscess.

We treated two patients with a ruptured amebic liver abscess. The diagnosis was made at a relatively early stage and treatment was successful for one patient, but an accurate diagnosis of liver abscess was not made and invasive extraintestinal amebiasis led to multiple organ failure and to death for the other. Neither patient had been outside of Japan, and both were heterosexual. The origins of Entamoeba histolytica infection could not be determined. Though the mortality rate is high in cases of ruptured amebic liver abscess, appropriate management can lead to a good prognosis.

Adult↗