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Biomedical subjects

T Akiyoshi

Publications and source records attributed to T Akiyoshi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma.

Growth factor receptors transmit intracellular signals that may be important in carcinogenesis. The Grb7 protein was recently identified as a substrate of the epidermal growth factor receptor and related Her2/ erbB2 receptor-linked tyrosine kinase activity. The Grb7 gene has been found to be coamplified with Her2/erbB2 in breast carcinomas. In this study, Grb7 expression was studied in 32 human esophageal cancers. A human Grb7 cDNA encoding for N-terminal amino acids was isolated and found to be 90% homologous to the murine counterpart. Although there was no amplification of the Grb7 gene in esophageal cancers, Grb7 mRNA was found to be overexpressed in 14 cancers (43.8%) but not in adjacent normal esophageal mucosa. It is noteworthy that coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 was detected in 10 esophageal carcinomas (31.3%) and was significantly related to extramucosal tumor invasion (P = 0.02), whereas such a relationship was not shown by each sole expression. These findings suggest a possible relationship of Grb7 signaling in association with expression of tyrosine kinase receptors in aggressive human esophageal cancer.

Amino Acid Sequence↗
PubMed1997

Analysis of ornithine decarboxylase messenger ribonucleic acid expression in colorectal carcinoma.

PURPOSE: Ornithine decarboxylase (ODC) is a rate-limiting enzyme for polyamine synthesis. An elevated protein level of ODC was observed in the tumors. There has been, however, little information reported so far on the expression of ODC messenger ribonucleic acid (mRNA) in clinical colorectal carcinomas. In vitro studies disclosed that the transcriptions of the ODC gene is regulated by the c-myc gene. METHODS: The expression of ODC and c-myc mRNA in biopsy specimens obtained from both tumor tissue and the corresponding normal tissue was examined by the reverse transcriptase polymerase chain reaction method in 40 cases of colorectal carcinoma. RESULTS: The expression of ODC mRNA was observed in both tumor tissue and normal tissue. The tumor to normal ratio of ODC mRNA was higher in cases with deeply invasive tumors than in cases with shallow tumors, and it was also higher in Dukes B or C cases than in Dukes A cases. There was a significant correlation between the tumor to normal ratio of c-myc mRNA and that of ODC mRNA in each case. CONCLUSIONS: These findings suggested that 1) the study of the expression of ODC mRNA may be useful for preoperatively predicting more advanced disease of colon carcinoma, and 2) there was a significant correlation between expression of ODC and c-myc mRNA in the clinical samples, which was similar to the findings of a previous in vitro study.

Adult↗
PubMed1997

Efficient induction of antitumor cytotoxic T lymphocytes from a healthy donor using HLA-A2-restricted MAGE-3 peptide in vitro.

The antigenic peptides encoded by tumor-rejection antigen genes, MAGE-1 and -3, have been identified, and various methods have been utilized for the in vitro induction of MAGE-specific, cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using synthetic peptides. However, all of these methods are technically demanding and thus have a relatively limited usefulness. We herein report a simple and efficient method for the vitro induction of specific CTL by using the HLA-A2-restricted MAGE-3 peptide from the PBMC of a healthy donor. CTL responses could thus be efficiently induced from unseparated PBMC by stimulation with freshly isolated, peptide-pulsed PBMC as antigen-presenting cells and by using interleukin-7 and keyhole limpet hemocyanin for the primary culture. The induced CTL could thus recognize and lyse not only HLA-A2 target cells pulsed with the peptide but also HLA-A2 tumor cells expressing MAGE-3, in an HLA-class-I-restricted manner. This simple method may, therefore, become a useful tool for investigating the potential peptides for tumor antigens as well as for developing various immunotherapeutic approaches for human malignant tumors.

Antigens, Neoplasm↗
PubMed1997

Quantitative analysis of cytokine mRNA expression in peripheral blood mononuclear cells following treatment with interleukin-2.

After activation with interleukin-2 (IL-2), peripheral blood mononuclear cells (PBMC) have been reported to induce the expression of mRNA coding various cytokines, including interleukin(IL)-1alpha, -1beta and tumor necrosis factor alpha (TNF alpha). We examined the cytokine mRNA expression of PBMC following treatment with IL-2 in vitro and in vivo by a quantitative method using the reverse transcription/polymerase chain reaction (RT-PCR). After stimulating PBMC with IL-2 in vitro, peak levels of IL-1alpha mRNA were reached between 3 h and 12 h, and thereafter declined. The IL-1beta expression increased, with levels peaking at 1-6 h and, had decreased by 96 h. The expression of TNF alpha was elevated both 1-3 h and 24-48 h after stimulation. The peak levels of IL-1alpha and -1beta mRNA and the early elevation of TNF alpha mRNA mainly accounted for the cytokine mRNA expression in adherent cells; however, the late induction of TNF alpha mRNA was observed in nonadherent cells. In patients with advanced carcinoma, the IL-1alpha and -1beta mRNA expression were elevated after IL-2 treatment for 5 consecutive days, while the expression of TNF alpha mRNA also increased. These results indicate that the quantitative RT-PCR method appears to be useful for analyzing the cytokine mRNA expression of PBMC after treatment with IL-2.

Carcinoma↗
PubMed1997

T-stem cell leukemia/lymphoma with both myeloid lineage conversion and T-specific delta recombination.

We evaluated retrospectively the clinical and biological characteristics of six patients with CD7+ early T-acute lymphoblastic leukemia and lymphoma (T-ALL/LBL) originating from prothymocyte stage I (pro-T I) or II cells. Patients exhibited mediastinal mass (five of six) and lymphoadenopathy (five of six) but without leukocytosis and circulating blast cells (six of six). All patients achieved a complete remission. All but one had a relapse with a transformation to the mixed type (triphenotype--three cases, biphenotype-two cases) including myeloid features in three patients. The altered phenotypes were myeloperoxidase (MPO)+ (three of five), CD13+ (four of five), CD33+ (three of five) and CD19+ (three of five). The difference for MPO-positivity were observed between the bone marrow (BM)- and lymph node (LN)-blast cells (three of three). On cytogenetic analysis, there is no common abnormality in these patients. Immunomolecular analysis revealed T-cell lineage specific delta gene rearrangements [D delta 2-J delta 1 (five of six) and V delta 1-J delta 1 (one of six)] in all cases. Furthermore, D delta 2-J delta 1 occurred even in the cases with the pro-T I phenotype. Rearrangements of TCR beta, gamma or immunoglobulin heavy chain genes occurred in three patients. The same rearranged band(s) appeared at both diagnosis and relapse, indicating the same originality of the pro-T leukemic cell clone (three of three). We suggest that this type of CD7+ early T-ALL/LBL was transformed from a pro-T I or II cell, such as T-stem cell leukemia/lymphoma, which is a subtype of CD7+ stem cell leukemia as defined by Kurtzberg et al. This study reveals that pro-T I and II cells might be capable of myeloid, T- and B-lymphoid differentiation, and T-cell lineage specific TCR delta recombination occurs.

Adult↗
PubMed1997

A bag carrier for continuous intravenous hyperalimentation.

We designed a new bag-carrier device system for continuous intravenous hyperalimentation. The patient carries it on his shoulder and can both walk up and down stairs and go out. The use of this device is simple and easy, and was found to increase the patient's opportunity to engage in physical activity.

Equipment Design↗
PubMed1997

Expression of MAGE and BAGE genes in Japanese breast cancers.

BACKGROUND: The MAGE and BAGE genes code for distinct antigens, which are recognized on melanoma cells as well as on other various tumor cells by autologous cytolytic T lymphocytes. These antigens may thus constitute useful targets for specific immunotherapy, since no expression of MAGE or BAGE genes has been recognized in normal tissue except for the testis. PATIENTS AND METHODS: We studied the MAGE-1, MAGE-3, and BAGE gene expression observed in 49 Japanese breast cancers. Gene expression was evaluated by reverse transcription polymerase chain reaction. RESULTS: Out of 49 tumor tissue specimens of primary breast cancers, the expression of MAGE-1, -3 and BAGE was recognized in 15 (31%), 12 (24%), and 4 (8%) tumors, respectively. The expression of MAGE and BAGE genes is not recognized in normal breast tissue. The expression of the MAGE-3 gene was frequently recognized in tumors with lymphatic and/or vascular vessel permeations. Either MAGE-1 or -3 gene expressions were induced in 1 of 3 MAGE-1 negative breast cell lines or 1 of 3 MAGE-3 negative breast cell lines by the treatment with 5-aza-2'-deoxycytidine. CONCLUSIONS: These findings suggest that: 1) the identification of such antigens coded by MAGE or BAGE genes may thus offer the possibility of using specific immunotherapy, and 2) the use of a demethylating agent may increase the number of patients who might be candidates for MAGE specific immunotherapy.

Antigens, Neoplasm↗
PubMed1997

Clinical significance of tissue inhibitor of metalloproteinase expression in gastric carcinoma.

Tissue inhibitor of metalloproteinase (TIMP) has been reported to inhibit tumour invasion through an inactivation of matrix metalloproteinase (MMP) both in vitro and in vivo. Among the TIMP family, TIMP-1 possesses not only proteinase inhibitory activity but also a growth-promoting function. However, the significance of the expression of TIMP-1 in human gastric carcinoma tissue has yet to be clarified. In 50 examined cases of gastric carcinoma, 44 (88%) cases showed a higher expression of TIMP-1 mRNA in the biopsy samples from the tumour tissue (T) than in the biopsy samples from the corresponding normal tissue (N), as determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In a multivariate analysis, the T/N ratio of TIMP-1 mRNA was found to be an independent factor influencing the depth of tumour invasion and was the second most important factor in determining the prognosis of patients. As RT-PCR assay can be performed on biopsy specimens obtained before surgery, an evaluation of the TIMP-1 expression in biopsy specimens by RT-PCR may thus provide useful preoperative information on tumour aggressiveness.

Adult↗
PubMed1997

Neoadjuvant chemoimmunotherapy with cisplatin and low-dose interleukin-2 for locally advanced esophageal carcinoma

After a single dose of cisplatin, the ability of peripheral blood mononuclear cells (PBMC) to generate lymphokine-activated killer (LAK) cells was significantly augmented in cancer patients. Based on this clinical finding, the patients with locally advanced esophageal carcinoma were thus treated with a combination of cisplatin and low-dose interleukin-2 (IL-2) in a neoadjuvant setting. Four patients with squamous cell carcinoma of the esophagus (T3 or T4 disease) were preoperatively treated with a regimen consisting of 50 mg/m2 cisplatin on day 1, followed by IL-2 from day 4 through day 8, when the ability of PBMC to generate LAK cells had been shown to be significantly augmented. After two to four courses of the preoperative therapy, one patient achieved a histologic CR, one showed PR and one MR. No severe toxicity was encountered. All patients thereafter underwent surgery. The median survival of these patients was 47.5 months and three of the patients had been disease free for 43 to 62 months after the initiation of the therapy. The combination of cisplatin and low-dose IL-2 administered in a neoadjuvant setting seems to result in an improved survival of locally advanced squamous cell carcinoma of the esophagus.

Journal Article↗
PubMed1997

[Cancer vaccine therapy using peptides derived from tumor-rejection antigens].

A number of genes coding tumor antigens have recently been isolated from human melanoma cell lines. The antigens encoded by these genes are recognized by autologous cytotoxic T lymphocytes (CTL) in the context of HLA class I molecules, and the antigenic peptides have been identified. These tumor-rejection antigens include tumor-specific shared antigens, differentiation antigens, or antigens specific for individual tumors. Tumor-specific CTLs have been generated from peripheral blood mononuclear cells (PBMC) of healthy donors or patients with malignant tumors by in vitro stimulation with peptide epitopes derived from tumor-rejection antigens. Furthermore, induction of peptide-specific CTL in PBMC has been observed in patients following the immunization with the antigenic peptides in vivo. Based on these findings, clinical vaccine trials using these antigenic peptides have recently begun in patients with melanoma as well as other tumors that express these antigens, and some tumor responses have been seen in a limited number of patients. Therefore, in order to evaluate the efficacy of the vaccine therapy against various malignant tumors, further clinical studies are now under way.

Antigens, Neoplasm↗
PubMed1997

[Studies on the taste perceptive threshold for 4 basic taste qualities at various sites of lingual surface].

Using filter-paper-disk method for 20 approximately 23 year-old 60 healthy females, taste perceptive thresholds for 4 basic taste qualities (sweetness, saltiness, sourness and bitterness) were measured detailedly at various sites of the lingual surface (lingual apex, lingual center, lingual margin, lingual radix). Sucrose, sodium chloride, sodium tartarate and quinine hydrochloride as taste-producing substances were used for the sweetness, saltiness, sourness and bitterness, respectively. The results revealed the apical site to be most sensitive to all of the sweetness, saltiness and sourness (and especially to the saltiness) and to be followed by marginal and radical sites in sensitiveness. The radical site was revealed to be most sensitive only to the bitterness, and the central site was remarkably hyposensitive to all of these taste qualities. These experimental results differ, in many respects, from those results of study which have been published by Kiesow in 1894 and are already established today (lingual sensitivity to taste qualities is found separately by site: sweetness, sourness and bitterness and highly perceptible at apical, marginal and radical sites, respectively, and saltiness is not very differently perceptible by site), indicating that further detailed reexamination will be needed to know how taste perceptive thresholds for 4 basic taste qualities are distributed in the lingual surface.

Adult↗
PubMed1997

Induction of antitumor cytotoxic T lymphocytes from the peripheral blood mononuclear cells of cancer patients using HLA-A2-restricted MAGE-3 peptide in vitro.

As the basis for the application of MAGE antigens to therapeutic use, the induction of peptide-specific CTLs has been investigated by the stimulation of peripheral blood mononuclear cells (PBMCs) with antigenic peptides derived from MAGE genes. However, the cross-reactivity of the peptide-induced CTLs to the target cells endogenously presenting the MAGE epitope, especially in cancer patients, remains controversial, despite the use of complicated manipulations. Because we recently developed a new simplified method to induce peptide-specific CTLs that killed MAGE expressing tumor cells from the PBMCs of a healthy donor, we examined the induction of specific CTLs by stimulation of PBMCs with HLA-A2-restricted MAGE-3 peptide in HLA-A2(+) cancer patients whose tumors expressed MAGE-3 by using the simple method. The CTL responses could thus be induced from unseparated PBMCs by stimulation with freshly isolated, peptide-pulsed PBMCs as antigen-presenting cells and by using interleukin 7 and keyhole limpet hemocyanin for the primary culture. All CTLs induced from the PBMCs of four cancer patients tested could thus lyse the HLA-A2 target cells pulsed with the peptide, and moreover, two of the CTLs were also able to kill HLA-A2 tumor cells expressing MAGE-3 in a HLA class I and A2-restricted manner. Therefore, these findings seem to indicate that HLA-A2-restricted MAGE-3 peptide may be potentially useful for specific immunotherapy in cancer patients.

Antigens, Neoplasm↗
PubMed1996

Molecular detection of circulating solid carcinoma cells in the peripheral blood: the concept of early systemic disease.

Detection of the mRNA of selected genes by reverse transcriptase-polymerase chain reaction (RT-PCR) is a sensitive and powerful tool for detecting cancer cells in bone-marrow or peripheral-blood samples. In this study, we determined whether carcinoembryonic antigen (CEA) mRNA is detectable in the peripheral blood of patients with gastrointestinal or breast cancer. In addition, we studied selected patients undergoing surgical procedures to assess whether tumor manipulation during operation enhances cancer-cell dissemination. Peripheral blood from 55 patients with gastrointestinal or breast cancer and from 22 control cases was analysed for CEA mRNA using RT-PCR. For 15 selected cases undergoing curative surgery for cancer, samples were also obtained during and after surgery. The lower limit of detection was 1 to 10 CEA-positive cells diluted among 1 x 10(7) blood mononuclear cells. The test was positive for 20 of the 55 patients with cancer (36%). None of the 22 control samples were positive. An increase in positivity was observed with increasing stage of disease; however, even some patients with early-stage cancer showed positive results. In addition, CEA mRNA could be detected in the peripheral blood during operation in 3 of 13 patients whose pre-operative CEA mRNA in the peripheral blood had been negative. These findings suggest that, (1) RT-PCR amplification of CEA mRNA is an efficient means of detecting circulating solid cancer cells in the peripheral blood, although long-term clinical studies should be done to evaluate its usefulness; (2) not only breast cancer but also gastrointestinal cancer might be better regarded as a systemic disease even in early stages of carcinoma; and (3) surgical manipulation can provoke cancer-cell dissemination.

Adult↗
PubMed1996

Relaxation of insulin-like growth factor 2 gene imprinting in esophageal cancer.

Paternal allele-specific expression is identified for the insulin-like growth factor 2 (IGF2) gene. Relaxation or loss of IGF2 imprinting, however, has been reported in several neoplasms. We studied the expression of IGF2 mRNA in 35 squamous cancers of the esophagus and searched for the presence or absence of relaxation of IGF2 imprinting. In 28 (80%) cases, IGF2 mRNA was overexpressed in the tumor tissues (T) compared to the normal tissues (N). The patients whose tumor invaded the adventitia showed a higher T/N ratio than those whose tumor was restricted to the musculi propria layer. Heterozygosity was determined by using the Apa I polymorphism in exon 9. Thirteen of 35 cases showed heterozygosity. In these 13 cases, a similar analysis was performed on cDNA obtained by reverse transcriptase-polymerase chain reaction. Consequently, 7 cases disclosed relaxation of IGF2 imprinting in the tumor tissue. The cases of esophageal cancer with relaxation of IGF2 imprinting showed a higher T/N ratio and deeper invasion than those without relaxation. The results suggest that overexpression of IGF2 mRNA plays an important role in esophageal cancer and, in certain cases, is associated with relaxation of IGF2 imprinting.

Esophageal Neoplasms↗
PubMed1996

Expression of ornithine decarboxylase mRNA in gastric carcinoma.

BACKGROUND: Ornithine decarboxylase (ODC) is a key rate-limiting enzyme in polyamine biosynthesis. Several studies using an enzyme assay revealed that the ODC activity was higher in tumor tissue than in normal tissue. However, there is little information on the mRNA status of ODC in surgical specimens. ODC is a transcriptional target gene of c-myc. METHODS: cDNA was obtained by reverse transcription (RT) from fresh specimens of 56 surgical pairs of primary gastric carcinomas and corresponding normal tissue specimens. The ODC and c-myc mRNAs were subsequently detected by means of the polymerase chain reaction. The tumor/normal (T/N) ratio of ODC expression was calculated after correcting for glyceraldehyde-3-phosphate dehydrogenase as an internal control. The T/N ratio of ODC was plotted against that of c-myc. RESULTS: The corrected expression levels of ODC mRNA in the tumor were greater than those of the normal mucosa in 36 of 56 cases (64%). The cases of tumor with vascular vessel invasion showed a higher T/N ratio than those without vascular invasion (P < 0.01). Similarly, female patients showed a higher T/N ratio than male patients (P < 0.01). There was a significant correlation between the expressions of both ODC and c-myc genes (P < 0.05). CONCLUSIONS: The findings imply that (1) overexpression of ODC mRNA in tumor tissue may correlate with aggressive biologic behavior, such as vascular vessel invasion, and (2) there is an intimate correlation between ODC and c-myc genes.

Base Sequence↗
PubMed1996

Postoperative chemotherapy for colorectal cancer by combining 5-fluorouracil infusion and 1-hexylcarbamoyl-5-fluorouracil administration after curative resection.

BACKGROUND: Colorectal cancer is one of the major malignant diseases and, recently, its incidence appears to be increasing. Surgical resectability is an important prognostic determinant; however, recurrent tumors are commonly noted, even after apparently curative surgery. Because such metastatic disease cannot be cured, better adjuvant therapies are urgently called for. METHODS: We studied the effect of postoperative chemotherapy using 5-fluorouracil (5-FU) infusions and 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration for curatively resected Stage II to IV colorectal cancer. This study was prospectively randomized and controlled and 251 (93.3%) of 269 patients were determined to be candidates for statistical assessment. The inductive regimen for Group A included a total of 6 5-FU intravenous injections, 10 mg/kg, on postoperative days 0, 1, 2, 7, 8, and 9. For maintenance therapy, Group A also received oral HCFU, 300 mg daily for 52 weeks beginning 2 weeks after surgery. The regimen for Group B included only 5-FU injections of Group A. RESULTS: There were no differences in the prognostic factors or doses of 5-FU between Groups A and B. In addition, no difference was observed in the toxicity rate between the two groups. Group A, with 5-FU infusions plus oral HCFU administration, produced a reduction in the recurrence rate and a prolongation of the survival time for patients with rectal cancer. In a retrospective analysis, this protocol was also effective for patients with Stage III to IV, wall invasion-positive, and lymph node metastasis-positive colorectal cancers. CONCLUSIONS: This study suggests that the combination of 5-FU infusions and the continuous oral administration of HCFU is a reasonable therapeutic approach for patients with surgically resected colorectal cancer and a high risk of recurrence.

Adult↗