Biomedical subjects

Y Toh

Publications and source records attributed to Y Toh.

At least 37 records · Page 2Linked to original sources

PubMed2000

[State of the treatment for gastrointestinal cancer].

We reviewed the results of chemotherapy for gastrointestinal cancer. In Western countries, FAMTX or ECF is recognized as the standard therapy for gastric cancer. In Japan, no standard chemotherapeutic regimen has been established yet, but FP or MTX/5-FU are often used as a first line chemotherapy. There have been only a few clinical trials of adjuvant chemotherapy for gastric cancer in which this regimen was identified as having a statistically significant effect. For colon cancer, 5-FU plus LV are now used as the standard therapy. Recently, however, it has been shown that 5-FU + LV combined with CPT-11 is more active than 5-FU + LV alone. The efficacy of oral anticancer agents such as UFT + LV, S-1, and capecitabin have also been shown to be equally or more active than i.v. administration of 5-FU and LV, so that the standard therapy for colon cancer will be changed in near future.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Flow cytometric DNA analysis is useful in detecting multiple genetic alterations in squamous cell carcinoma of the esophagus.

BACKGROUND: Although flow cytometric DNA analysis has been recognized to be a useful prognostic indicator for patients with squamous cell carcinoma of the esophagus, the biologic significance of DNA aneuploidy remains to be elucidated. METHODS: Twenty-five patients with squamous cell carcinoma of the esophagus who underwent a curative subtotal esophagectomy were divided into 2 groups according to the DNA ploidy pattern. Multiple genetic changes, including the gene amplification of bcl-1, epidermal growth factor receptor, and c-myc, and the loss of heterozygosity of multiple tumor suppressor genes, including retinoblastoma, mutated in colorectal carcinoma, adenomatous polyposis coli, and deleted in colorectal carcinoma, in each case were investigated and the frequency of genetic alterations compared between both groups. In addition, the clinical outcome of these patients was also investigated. RESULTS: Eleven of 15 cases in the aneuploid group demonstrated at least 1 genetic change (73.3%) whereas only 2 of 10 cases in the diploid group did so (20.0%) (P<0.05). Both cases in the diploid group with genetic alterations had only 1 genetic change of 7 tested genes whereas 9 of 11 cases in the aneuploid group had multiple genetic alterations. Patients in the aneuploid group also showed a more unfavorable prognosis than patients in the diploid group. CONCLUSIONS: Based on the findings of the current study, flow cytometric DNA analysis is considered to be useful for both detecting multiple genetic alterations and predicting the prognosis of patients with carcinoma of the esophagus.

Aged↗

PubMed1999

Overexpression of metastasis-associated MTA1 mRNA in invasive oesophageal carcinomas.

The MTA1 gene is a recently identified novel candidate breast cancer metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in 47 surgically resected oesophageal squamous cell carcinomas by quantitative reverse transcription polymerase chain reaction. The relative overexpression of MTA1 mRNA (tumour/normal ratio > or = 2) was observed in 16 out of 47 (34.0%) oesophageal carcinomas. Oesophageal tumours overexpressing MTA1 mRNA (T/N ratio > or = 2) showed significantly higher frequencies of adventitial invasion (P < 0.05) and lymph node metastasis (P < 0.05), and tended to have a higher rate of lymphatic involvement than the remaining tumours. Thus, the data suggest that the MTA1 gene might play an important role in invasion and metastasis of oesophageal carcinomas.

Carcinoma, Squamous Cell↗

PubMed1999

A significant morphological transformation is recognized in human esophageal cancer cells with an amplification/overexpression of the cyclin D1 gene.

Amplification and expression status of the CCND1 gene in 12 cell lines derived from esophageal cancer was evaluated and the differences in the cell proliferation and morphology were investigated. Amplification was observed in 6 cell lines, all of which consequently overexpressed the mRNA. Although the amplification of the gene did not contribute to an increase of cell proliferation, an in vitro morphological transformation was observed in the colonies with an amplification of the CCND1 gene. An amplification/overexpression of the CCND1 gene plays an important role in the enhancement of cell transformation in esophageal squamous cell carcinoma cells.

Blotting, Northern↗

PubMed1998

Proliferative activity of cancer cells in front and center areas of carcinoma in situ and invasive sites of esophageal squamous-cell carcinoma.

Intraepithelial carcinoma contiguous with invasive squamous-cell carcinoma is a conspicuous feature of esophageal cancer. However, whether the mechanism of intraepithelial spreading is due to cell proliferation or field carcinogenesis has yet to be clarified. This study investigated the mechanism of intraepithelial spreading by measuring the cell proliferative activity using argyrophilic nucleolar organizer region (AgNOR) and proliferating cell nuclear antigen (PCNA)-positive cell counting. We examined the AgNOR number and PCNA-positive ratio (PCNA ratio) in the center and outer edge of intraepithelial carcinoma and in the center and deep margin of invasive squamous-cell carcinoma of the esophagus in 50 specimens from 18 cases of esophageal squamous-cell carcinoma concomitant with contiguous intraepithelial carcinoma. The proliferative activity was thus found to differ between the normal epithelium and cancerous lesions (p < 0.001), between intraepithelial carcinoma and invasive cancer (p < 0.001) and between deep margin and center areas of invasive cancer (p < 0.005). On the other hand, such activity was observed to be similar in the center and outer edge of the intraepithelial spread. These findings suggest that cell proliferation is the main mechanism of tumor progression at the invasive site of cancer, whereas in intraepithelial carcinomatous areas, "field carcinogenesis" or a paracrine mechanism, and not cell proliferation, is thought to be the cause of intraepithelial spread of esophageal cancer. These results therefore support the concept of field carcinogenesis.

Carcinoma in Situ↗

PubMed1998

A gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes.

Except for melanomas, tumor antigens recognized by cytotoxic T lymphocytes (CTLs) are yet unidentified. We have identified a gene encoding antigenic peptides of human squamous cell carcinomas (SCCs) recognized by human histocompatibility leukocyte antigens (HLA)- A2601-restricted CTLs. This gene showed no similarity to known sequences, and encoded two (125- and 43-kilodalton [kD]) proteins. The 125-kD protein with the leucine zipper motif was expressed in the nucleus of the majority of proliferating cells tested, including normal and malignant cells. The 43-kD protein was expressed in the cytosol of most SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from peripheral blood mononuclear cells (PBMCs) the CTLs restricted to the autologous tumor cells. The 43-kD protein and this nonapeptide (KGSGKMKTE) may be useful for the specific immunotherapy of HLA-A2601(+) epithelial cancer patients.

Amino Acid Sequence↗

PubMed1998

Abdominal incisional hernia occurring after an esophagectomy reconstructed with a gastric tube through an antesternal route: report of a case.

A Japanese man, who had undergone a subtotal esophagectomy reconstructed with a gastric tube through an antesternal route for esophageal carcinoma 16 years previously, was admitted to our hospital because of an abdominal incisional hernia. The abdominal incisional hernia was in his upper abdomen and was difficult to push back into the intraabdominal cavity by hand. The hernia was successfully repaired by operation. We thus conclude that an abdominal incisional hernia is a rare but important late-phase complication occurring after an esophagectomy reconstructed with either an antesternal or retrosternal route, and an operation should be the treatment of choice.

Aged↗

PubMed1998

Abdominal surgery for patients on maintenance hemodialysis.

Despite the growing number of major surgical procedures being performed for patients on maintenance hemodialysis, few reports focus on the management and outcome of such patients, especially those undergoing major abdominal surgery. We conducted a retrospective review of 30 patients on maintenance hemodialysis who underwent abdominal surgery, 20 of whom underwent an elective operation and 10, an emergency operation. The indications of elective surgery included gastrointestinal cancer, biliary tract disease, and abdominal aortic aneurysm, while those for emergency surgery mainly involved gastrointestinal perforation or bleeding. There were no statistically significant differences between the elective group and the emergency group regarding either the mean time on hemodialysis or the preoperative clinical data. The morbidity and mortality rates were 15% and 10%, respectively, for the patients who underwent elective surgery and 50% and 70%, respectively, for those who underwent emergency surgery (P < 0.01 and P < 0.05, respectively). Those patients with more than a 2-year history of hemodialysis had a significantly higher mortality rate following abdominal surgery than those with less than a 2-year history (P < 0.01). Thus, the morbidity and mortality rates of patients on maintenance hemodialysis who require major abdominal surgery are significantly high, which reinforces the need to further improve the intensive perioperative management of such patients.

Abdomen↗

PubMed1998

Induction of apoptosis in human tumour xenografts after oral administration of uracil and tegafur to nude mice bearing tumours.

Various types of anti-neoplastic agents induce apoptosis in vitro, but less is known of the role of this mode of cell death in tumours treated in vivo. We examined the induction of apoptosis by oral anti-neoplastic agents, tegafur and uracil (UFT, a combined preparation of 1 mol tegafur and 4 mol uracil), and the relationship of effects on tumour growth. Seven different human gastrointestinal tumour xenografts were transplanted into nude mice, including two colon adenocarcinomas (KM20C and Col-1), three gastric carcinomas (SC-6, St-40 and 4-1ST) and two pancreatic carcinomas (PAN-4 and PAN-12), followed by oral administration of UFT (24 mg kg(-1) day(-1)) for 9 days. The percentage of apoptotic cells in each tumour was scored in histological sections, chronologically, using a molecular biological-histochemical system and growth inhibition was examined in each tumour. A significant growth inhibition by UFT was observed for all tumours, except PAN-12. In KM20C and SC-6, growth inhibition rates were 61.7% and 60.6% respectively. Quantitative assay for apoptosis showed a remarkable induction of apoptosis in KM20C (4.2%) and SC-6 (3.5%), which were relatively sensitive to UFT. In addition, KM20C and SC-6 showed a higher incidence of spontaneous apoptosis. In five other tumours, which responded to a lesser extent than KM20C and SC-6, UFT altered little the changes in apoptosis (less than 2%) and spontaneous apoptosis was relatively low. Thus, tumours with a higher apoptosis induced by UFT had a higher response to UFT. Apoptosis observed in tumours might serve as a predictor of a preferable response to UFT.

Animals↗

PubMed1998

Relationship between preoperative assessment of organ function and postoperative morbidity in patients with oesophageal cancer.

OBJECTIVE: To find out if strict assessment of organ function preoperatively predicted morbidity and mortality in patients being operated on for oesophageal carcinoma. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 178 patients operated on for oesophageal cancer 1989-1993. INTERVENTIONS: Oesophagectomy and reconstruction (using either stomach or colon) in one stage by a right thoracoabdominal approach in 173, and transhiatal resection in 5 with either poor pulmonary reserve or early lesions. MAIN OUTCOME MEASURES: Correlation between preoperative assessment of organ function and postoperative development of complications. RESULT: 79 patients (44%) developed complications and 6 died (3%). Pulmonary dysfunction preoperatively was significantly associated with the development of all complications (p=0.001) and of postoperative pulmonary complications (p=0.04). No other preoperative assessment correlated significantly with the development of postoperative complications. CONCLUSION: Accurate preoperative assessment of pulmonary function is a valuable indicator of postoperative morbidity.

Aged↗

PubMed1997

Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis.

The mta1 gene is a recently identified novel candidate metastasis-associated gene. The deduced amino acid sequence contains an src homology-3 domain binding motif, a zinc finger motif and possible phosphorylation sites, suggesting that this gene is involved in signal transduction or regulation of gene expression. The purpose of our study was to examine the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in colorectal and gastric carcinomas and thus to evaluate the relevance of the expression of this gene to human carcinoma progression. The expression of MTA1 mRNA in 36 colorectal and 34 gastric carcinoma samples was compared with that in corresponding normal mucosa tissues by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and the results were compared with clinico-pathologic data. A relative overexpression of MTA1 mRNA (tumor/normal ratio > or = 2) was observed in 14 of 36 (38.9%) colorectal carcinomas and 13 of 34 (38.2%) gastric carcinomas. Clinico-pathologic correlations demonstrated that in colorectal carcinomas, tumors overexpressing MTA1 mRNA exhibited a significantly deeper wall invasion and a higher rate of metastasis to lymph nodes, and tended to be at an advanced Dukes' stage with frequent lymphatic involvement. In gastric carcinomas, the tumors overexpressing MTA1 mRNA showed significantly higher rates of serosal invasion and lymph node metastasis and tended to have a higher rate of vascular involvement. Our data suggest that overexpression of the MTA1 gene correlates with tumor invasion and the presence of metastases and that a high expression of MTA1 mRNA may be a potential indicator for assessing the malignant potential of colorectal and gastric carcinomas.

Aged↗

PubMed1997

The effect of radioimmunotherapy using murine monoclonal antibody KIS1 on esophageal squamous cell carcinoma-bearing nude mice.

The monoclonal antibody (MoAb) KIS1 has been shown to react specifically with an antigen of human squamous cell carcinoma (SCC); however, a major problem in its clinical application is that the intact murine antibody induces a human anti-mouse antibody (HAMA). To overcome this problem, we produced the KIS1 F(ab')2 fragment, then radioiodinated the intact KIS1 antibody and its F(ab')2 fragment. Nude mice bearing human esophageal SCC implants were injected with 100 microCi of 131I-intact KIS1 or 131I-KIS1 F(ab')2, and images were obtained using a gamma camera. Radioimmunotherapy (RIT) was performed by injecting the tumor-bearing nude mice with 131I-intact KIS1 or 131I-KIS1 F(ab')2 at a dosage of 300 microCi, following which 7 or 3 days were required to produce high quality tumor images by scintigraphy. The tumor-bearing mice treated with 131I-KIS1 F(ab')2 showed significant tumor growth inhibition, about 5.4 times greater than that of the control group and 1.8 times greater than that of the 131I-intact KIS1 group 21 days after the injection. These results indicate that the KIS1 F(ab')2 fragment is superior to intact KIS1, and that it may be clinically useful for radioimmunodetection followed by tumor targeting therapy for patients with SCC of the esophagus.

Animals↗

PubMed1997

Pathogenicity of glycoprotein C-deficient herpes simplex virus 1 strain TN-1 which encodes truncated glycoprotein C.

A clinical isolate of herpes simplex virus 1 (TN-1) from a stromal keratitis patient was found to be defective in the glycoprotein C (gC) gene (UL44), thus resulting in the production of truncated gC upon infection. To study the pathogenetic role of truncated gC, we prepared a recombinant LTN-8 derived from TN-1 with deletions of the 1.5 kilobase pairs of the gC gene including the initiation codon. A penetration assay revealed LTN-8 to be less efficient in its penetration ability than TN-1, the laboratory strain KOS and RTN-1-20-3, a recombinant derived from TN-1 with the KOS gC gene. The penetration of LTN-8 was facilitated by the addition of TN-1-infected culture medium. TN-1 virus preparations had no hemagglutinating activity. However, the animals infected with TN-1 did develop hemagglutination inhibition (HI) antibodies. The LTN-8-infected animals did not develop HI antibodies. The pathogenicity in BALB/c mice following either corneal, intraperitoneal or intracerebral inoculation did not significantly differ among TN-1, RTN-1-20-3 or LTN-8. Our results indicate that truncated gC was sufficient for the induction of HI antibodies and was also able to facilitate penetration in vitro. Although truncated gC might be a virulence factor acting as a decoy, both truncated gC and intact gC had little effect on the outcome following intracerebral, intraperitoneal or corneal inoculation.

Animals↗

PubMed1997

Development of cancer vaccine by tumor rejection antigens.

Identification of the MAGE genes allowed us the molecular approach to identify genes encoding tumor rejection antigens expressed on human cancer cells. MAGE-1 proteins are normal tissue antigens compartmentalized in the particular testicular cells playing an important role in the early phase of the spermatogenesis. The MAGE-1, -2, -3, -4 and -6 genes are preferentially expressed in many different cancers at both the mRNA and protein levels. The MAGE genes, particularly MAGE-1, became positive in relatively advanced stages of cancers and recurrent cancers. Approximately one-third to half of human cancers except for myelo-monocytic leukemia expressed at least one of these MAGE genes. The MAGE gene products shall be appropriate target molecules for development of new cancer vaccine.

Animals↗

PubMed1997

[Allergic bronchopulmonary aspergillosis in a patient without bronchial asthma who had chronic airway infection with Pseudomonas aeruginosa].

A 25-year-old man was admitted to the hospital because of uncontrollable coughing and sputum production. He had been suffering from coughing and sputum production since he was 7 years old. He was given a diagnosis of bronchiectasis and persistent airway infection with Pseudomonas aeruginosa when he was 16 years old. One year of treatment with erythromycin and another year of treatment with roxithromycin were not effective. After he was referred to our hospital in 1993, he was given clarithromycin together with tosufloxacin for two years as an outpatient. The treatment was not very effective, but some prophylactic effect was seen with regard to prevention of acute exacerbations of Pseudomonas aeruginosa airway infection. Examination after admission revealed a high level of serum IgE (3703 U/ml), a strong skin reaction to aspergillus allergen, and marked central bronchiectasis in both upper lobes. He had no history of eosinophilia or of attacks of dyspnea. Our diagnosis was acute exacerbation of long-standing allergic bronchopulmonary aspergillosis and chronic airway infection. Treatment with oral prednisolone (30 mg per day) together with intravenous cefsulodin for three weeks resulted in marked relief symptoms and improvement in pulmonary function. The delay in correct diagnosis seems to have been caused by the lack of an obvious episode of asthma, and by the fact that the chronic productive coughing was thought to have been due to bronchiectasis, and to chronic bacterial infection. The characteristic bronchiectasis of this patient prompted us to examine the allergic reaction to aspergillus and let us to the correct diagnosis.

Adult↗

PubMed1997

[Long-term results of preoperative hyperthermo-chemo-radiotherapy (HCR) for patients with esophageal carcinoma invading neighboring structures (T4)].

PATIENTS: A total of 180 patients with esophageal carcinoma invading the neighboring structures (T4) were surgically treated by esophagectomy and reconstruction in the Department of Surgery II, Kyushu University from January 1965 to April 1997. Any of these cases with distant node metastasis and demonstrating organ metastasis or a combined resection of adjacent structures were excluded from this study. As a result, twenty-six patients treated with preoperative hyperthermo-chemo-radiotherapy (HCR Group), 39 treated either with preoperative radiotherapy or preoperative chemo-radiotherapy (R or CR Group) and 23 non-treated patients (Non-tx Group) were thus entered in this study. RESULTS: The 3-year survival rates after esophagectomy in HCR Group, R or CR Group and Non-tx Group were 26.5%, 0% and 9%, respectively, while the 5-year survival rate of the HCR group was 15.9%. The group with preoperative HCR thus showed a significantly more favorable outcome than R or CR Group and Non-tx Group. (p < 0.05). DISCUSSION: The significant difference observed in the prognosis was thought to be due to the reinforced effect of local regulation due to hyperthermia. Our data thus suggest that preoperative HCR contributes to the prolonged post-operative survival for carcinoma of the esophagus invading the neighboring structures.

Aged↗

PubMed1996

An integrated microsatellite length analysis using an automated fluorescent DNA sequencer.

Analyzing microsatellite instability (MI) in malignant tumors is thought to be useful for screening cancer patients to identify those patients with a higher risk of developing second malignant tumors. In this paper, we report a new, accurate, and efficient method of detecting MI using an automated fluorescent DNA sequencer and a computer that automatically calculates the size, height, and area of each fluorescent product, making it possible to assess MI more accurately and more rapidly. The primers for amplification of each microsatellite locus are labeled by two different fluorescent dyes, rox (red) and fam (blue). The rox-labeled primer was used for the tumor, whereas the fam-labeled primer was used for the corresponding normal tissue. Two amplified products from both the tumor and the normal tissue were co-loaded into a single lane of the sequencing gel and were analyzed. MI could be detected based on the presence of different waving patterns. Furthermore, several loci could also be analyzed simultaneously for MI in a single lane. Using this method, we examined the frequency of MI in gastric cancer. The results showed that 5 of 22 (22.7 %) gastric cancers were MI-positive, which corresponds to the findings of previous reports that used the radioisotopic method. The improved method may open up the possibility of performing routine examination of MI in many cancer patients and offers hope for the potential clinical application of Ml analysis as a follow-up evaluation of cancer patients.

Chromosome Aberrations↗

PubMed1996

A monoclonal antibody KIS-1 recognizing a new membrane antigen on human squamous-cell carcinoma.

A KIS-1 monoclonal antibody (MAb) (IgG1, kappa) recognizing a membrane antigen on human squamous-cell carcinomas (SCC) was developed to understand their antigenicity using an esophageal SCC as an immunogen. The KIS-1 MAb recognized a membrane antigen on a majority of esophageal, lung, and oral- cavity SCC by immunofluorescent and by immunohistochemical analyses. In contrast, it showed little reactivity to adenocarcinomas from different organs, and none to keratinocyte cell lines. This MAb showed reactivity to the cells in the basal layer of normal esophageal epithelium adjacent to the esophageal SCC, but none of the other normal tissues, including esophageal epithelium far from the SCC and that from patients with non-malignant disease. The KIS-1 MAb immunoprecipitated a 46-kDa membrane protein of the esophageal SCC in non-reducing and in reducing conditions. It recognized the 46- and the 40-kDa proteins of the esophageal SCC by immunoblot analysis. These results suggest that the KIS-1 MAb recognizes a new membrane antigen preferentially expressed on SCC, and that this antigenicity is shared only by the cells in the basal layer of the esophageal epithelium adjacent to SCC. The KIS-1 MAb may be a new tool for understanding the antigenicity of SCC.

Animals↗