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Biomedical subjects

T Toge

Publications and source records attributed to T Toge.

At least 73 records · Page 4Linked to original sources

Multicentric Breast Carcinoma: Evaluation of Clinicopathological and Immunohistochemical Characteristics.

Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.

Journal Article↗

Postoperative adjuvant randomised trial comparing chemoendocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the Nishinihon Cooperative Study Group of Adjuvant Chemoendocrine Therapy for Breast Cancer (ACETBC) of Japan.

Between 1985 and 1988, the effect of using ftorafur (FT) or PSK (an immunotherapy agent) in combination with the conventional postoperative adjuvant therapy using mitomycin (MMC) plus tamoxifen (TAM) was assessed in stage II, oestrogen receptor-positive (ER+) breast cancer patients. Furthermore, in ER- breast cancer stage II patients, the effects of postoperative adjuvant therapy using MMC plus FT were compared with the effects of postoperative adjuvant therapy using MMC plus PSK. Patients had primary stage II breast cancer and had undergone total mastectomy plus axillary dissection or more radical surgery. On the day of surgery, MMC (13 mg/m2) was administered intravenously. Then, ER+ patients received one of three regimens of drug therapy, starting 2 weeks after surgery: regimen A (daily oral treatment with 30 mg of TAM), regimen B (daily oral treatment with 30 mg of TAM and 600 mg of FT) or regimen C (daily oral treatment with 30 mg of TAM and 3 g of PSK) [corrected]. ER- patients received either regimen D (daily oral treatment with 600 mg of FT) or regimen E (daily oral treatment with 3 g of PSK), starting 2 weeks after surgery. Of the 540 ER+ patients registered, 525 were evaluated. The 5-year overall survival rate for ER+ patients was higher for patients who received regimen B (94.2%) than for those who received regimen A (86.9%) or regimen C (89.9%) (P = 0.063). The 5-year relapse-free survival rate was higher for regimen B (88.9%) than for regimen A (78.6%) and regimen C (77.2%) (P = 0.010). Stratified analysis revealed better results with the FT-combined therapy in patients positive for lymph node metastasis and premenopausal patients. These results indicate the effectiveness of using FT in combination with TAM. Of the 376 ER- patients registered, 364 were evaluated. The 5-year overall and relapse-free survival rate for ER- patients did not differ significantly between patients who received regimen D and those who received regimen E.

Adult↗

Association between preoperative plasma CEA levels and the prognosis of gastric cancer following curative resection. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer, Tokyo, Japan.

A large-scale retrospective study was undertaken to evaluate the association between preoperative plasma carcinoembryonic antigen (CEA) levels and the prognosis of 2768 gastric cancer patients who underwent curative gastrectomy between 1983 and 1984 at 66 leading medical institutions in Japan Postoperative follow-up was at least 5 years. Preoperative plasma CEA levels were also analysed against other prognostic factors. Preoperative plasma CEA levels showed strong correlations to the degree of lymph node metastasis (P < 0.001), TNM stage (P = 0.004) and the histopathology of the gastric cancer (P < 0.001). Preoperative CEA levels were also evaluated against survival, after being adjusted for the effect of clinically important factors by multivariate analysis. Patients with lower preoperative plasma CEA levels survived significantly longer than patients with higher CEA levels (P = 0.0001). This analysis demonstrates that curatively resected gastric cancer patients with higher preoperative plasma CEA levels have a poorer prognosis than those with lower levels, despite the adjustment for the effects of major prognostic factors.

Adolescent↗

Gastric tumorigenicity of 1,2-dimethylhydrazine on the background of gastric intestinal metaplasia induced by X-irradiation in CD (SD) rats.

Five-week-old male CD (SD) rats were X-irradiated with a total of 20 Gy in 2 equal fractions with a 3-day interval. After the second irradiation, rats were fed normal diet supplemented with 1% sodium chloride, which is known to increase intestinal metaplasia. 1,2-Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, gastric tumors in the glandular stomach were observed in 2 (3 lesions) of 30 animals in the X-irradiated and DMH-treated group fed diet supplemented with 1% sodium chloride. No gastric tumors were observed in the group which excluded X-irradiation from the experimental protocol.

1,2-Dimethylhydrazine↗

Detection of exfoliated carcinoma cells in colonic luminal washings by identification of deranged patterns of expression of the CD44 gene.

AIMS: To investigate whether colonic cancer cells exfoliated into the lumen of the organ can be detected by identification of their abnormal CD44 gene products. METHODS: Exfoliated cells were obtained by centrifugation of saline wash-outs of 27 surgically resected colon specimens obtained from 15 patients with carcinoma, seven with ulcerative colitis and five with Crohn's disease. After extracting cellular mRNA, amplification by the reverse transcription-polymerase chain reaction (RT-PCR) technique and analysis by Southern blot hybridisation was carried out to examine the levels and patterns of transcription of exons 11(v6), and 12(v7) and intron 9 of the CD44 gene. The transcription of these CD44 components was also examined by RT-PCR of snap-frozen solid tissue specimens from 11 of the above patients with colorectal carcinoma, seven with ulcerative colitis and five with Crohn's disease. RESULTS: Abnormal expression of exons 11(v6) and 12(v7) was detected in exfoliated cells from 11 (73%) of 15 patients with carcinoma, but not in any patients with inflammatory bowel disease (IBD). The retention of intron 9 in CD44 mRNA transcripts was detected in washings from four (27%) carcinoma specimens but not in washings from non-malignant specimens. It was confirmed that in solid tissue samples from the same carcinomas there was abnormal over-expression of numerous alternatively spliced CD44 species containing transcripts of exons 11 and 12 and retention of intron 9. Low level expression of these exons was detected in tissue from inflammatory lesions from five of seven patients with ulcerative colitis and four of five with Crohn's disease. The retention of intron 9 was not seen in normal mucosa nor IBD. CONCLUSION: Abnormal expression of the variant exons and of intron 9 of the CD44 gene in tumour cells exfoliated into the colonic lumen may be helpful markers for the early, non-invasive, diagnosis of colorectal cancer.

Aged↗

[Progress of adjuvant chemotherapy in colon cancer].

There have been no life-prolonging effects of surgical adjuvant chemotherapy with 5-FU alone or in combination with chemotherapeutic drugs, so surgical resection has been considered a standard therapy for colorectal cancer. Recently, clinical trials of modulation therapy with 5-FU and leucovorin showed higher efficacies in advanced colorectal cancer, and significant prolongations of survival time and disease-free interval were reported in a randomized trial of 5-FU and leucovorin for postoperative adjuvant therapy of resected colon cancer. Moreover, in a scientifically well controlled randomized study with 5-FU and levamisole, the significance of this regimen for Dukes C colon cancer has been shown for standard adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[Usefulness of subcutaneous implantable port with new one-way valve].

Because of the development of the subcutaneous implantable port, intra-arterial infusion chemotherapy for malignant tumor has been performed in safety and it is now possible to choose a more effective method of drug administration. Many problems remain, however. In this study, we investigated the performance of subcutaneous implantable port with a new one-way valve with safety, septum intensity and a back stream of blood. This new port was very safe, with good septum intensity and water backflow. In the performance test with a back stream of water into the catheter, water did not back up into the catheter connecting with the port with the one-way valve, but did so without the one-way valve after releasing a load of 2,000 g from the septum. This suggests that the catheter obstruction is decreased by adding a one-way valve to the port.

Catheterization↗

[Repair of the gastric tube-right main bronchus fistula after operation for esophageal cancer--treatment by transposition of pedicled pectoralis major muscle flap].

We have experienced a case who showed the gastric tube-right main bronchus fistula. A 51-year-old male complained cough and vomiting suddenly. He underwent esophagectomy and radio-chemotherapy for advanced esophageal cancer 19 months ago. Chest X-ray showed severe pneumonia, and gastroscopy, bronchoscopy and CT scan showed the fistula between the whole stomach esophageal substitute and right main bronchus. After recovery from the pneumonia with the treatment by continuous suction through the naso-gastric tube, operation was performed. The fistula was repaired with transposition of a pedicled pectralis major muscle successfully. After the operation, respiration was performed independently with two ventilators for right and left lung to avoid increasing air way pressure. His postoperative course was uneventful, and he discharged on the 66th postoperative day. The cause of the fistula was considered to be a peptic ulcer due to residual secretion of gastric acid.

Bronchial Fistula↗

Profile of T-cell receptor V beta gene usage of cytotoxic T cells induced by intrapleural administration of a streptococcal preparation, OK432, in malignant effusions.

T-cell receptor (TCR) gene rearrangements were analyzed in tumor-infiltrating lymphocytes (TIL) using the reverse transcription-polymerase chain reaction (RT-PCR) to determine whether oligoclonal expression of TCRV beta occurs in TIL, and if so, whether it is involved in the clinical response and mechanisms of locoregional immunotherapy using a streptococcal preparation, OK432. Patients with malignant effusion of various origins were treated with intrapleural administration of OK432, and clinical responses were assessed by cytological and chest X-ray examinations. Pleural exudate cells (PEC), obtained before and after the administration of OK432 (designated as pre- and OK432-PEC, respectively), were subjected to TCR analysis. Both pre-PEC and OK432-PEC showed highly diverse expressions of TCRV beta gene usage in either type of PEC. The frequency of TCRV beta 20 gene expression in OK432-PEC was significantly higher than in pre-PEC. Moreover, the over-expression of the TCRV beta 20 gene usage was also induced in the peripheral blood lymphocytes and pre-PEC of patients by in vitro OK432 stimulation, but not in the PBL of one healthy volunteer. Single-strand conformational polymorphism (SSCP) analysis revealed the clonotypes of these TCRV beta 20 genes. Autologous tumor-specific killing activity could be detected in OK432-PEC and was significantly reduced by treatment with a TCRV beta 20-specific monoclonal antibody. These findings suggest that the rearrangement of TCRV beta 20 gene usage may be involved in the autologous tumor-specific action of malignant effusions in the treatment with OK432.

Aged↗

Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors.

We have recently identified a new exon of the CD44 gene and demonstrated abnormal retention of a noncoding section, intron 9, in mRNA from bladder carcinomas. To analyze this further, the present study examined CD44 gene expression in cell lines from 14 esophageal, 3 colonic, and 4 breast carcinomas and in fresh samples from 20 colorectal carcinomas and corresponding normal colonic mucosa, using reverse transcriptase followed by the polymerase chain reaction (RT-PCR). This confirmed that there was abnormal assembly of several exons of the gene in cell lines and in tumor tissues from these organs. However, the most striking new finding was that intron 9 was present in RNA from 11 esophageal, 3 colon, and 1 breast carcinoma cell line, respectively. This was confirmed by RNase and DNase digestion analysis. Moreover, it was detected both in nuclear and cytoplasmic mRNA fractions, indicating that abnormal splicing of pre-mRNA occurs in cancer cells. The abnormal retention of intron 9 in CD44 gene transcripts was also demonstrated in tumor tissues from 16 (80%) of 20 patients with colon carcinoma, but there was no correlation with Dukes' stage. The biological significance of these observations is not yet understood. However, it is clear that, as with the abnormal expression pattern of CD44 variant exons, intron 9 retention is a good-candidate molecular diagnostic tool for colorectal carcinomas.

Base Sequence↗

Retrovirally transmitted gene therapy for gastric carcinoma using herpes simplex virus thymidine kinase gene.

BACKGROUND: Herpes simplex thymidine kinase (HTK) is known to phosphorylate ganciclovir (GCV). Phosphorylated GCV is incorporated into genomic DNA, which leads to inhibition of cell growth and cell death in the replicating cells. Recently, much attention has been drawn to the use of retrovirally mediated gene therapy using HTK as a new therapeutic approach for brain tumors. However, little is known about this phenomenon in gastrointestinal carcinomas. METHODS: The authors transfected the HTK gene packaged in retroviral vector into TMK-1 gastric carcinoma cells (TMK-HTK cells). Sensitivity of TMK-HTK cells to GCV was examined in vitro. Moreover, TMK-HTK cells were transduced into nude mice subcutaneously, and the effects of GCV therapy was examined at the concentration of 20 mg/kg daily for 14 days. RESULTS: TMK-HTK cells were sensitive to GCV at the concentration of 0.1 to 100 micrograms/ml in a dose- and time-dependent manner in vitro. Moreover, 12 of 13 TMK-HTK tumors, which were transduced into nude mice subcutaneously, shrunk from the average diameter of 6.5 mm. CONCLUSION: The results indicate that retrovirally transmitted gene therapy with GCV may provide a new therapeutic approach for treatment of gastric carcinomas.

Animals↗

Preservation of the lower esophageal sphincter during total gastrectomy for gastric cancer to prevent postoperative reflux esophagitis.

The lower esophageal sphincter (LES) is usually removed during total gastrectomy to successfully perform a curative operation. In this study, the preservation of the LES in curative total gastrectomy was attempted to reduce the reflux. An experimental study using dogs has revealed that the high-pressure zone of the LES can be preserved by making a resection at the gastroesophageal junction, which thus helps to protect the reflux. A previous clinicopathological study revealed that the LES can be preserved without any fear of recurrence at the resection site, if the tumor is located more than 2.0 cm and 3.0 cm from the gastroesophageal junction to the oral margin in node-negative and -positive cases, respectively. Clinically, 8 patients underwent an LES-preserving total gastrectomy [LES(+) gastrectomy] while 19 had an LES(-) gastrectomy in the same period. Of the five LES(+) cases examined, all showed a high pressure zone, whereas none of the four LES(-) cases examined showed such a high-pressure zone after the operation. Endoscopic examination showed that only one of the seven LES(+) cases but six of nine LES(-) cases revealed esophagitis.

Anastomosis, Surgical↗

Clinical usefulness of an ATP heat sensitivity test using endoscopic biopsy materials from esophageal cancer patients.

The usefulness of a heat sensitivity test which involved performing an ATP assay on endoscopic biopsy materials for predicting the clinical response to hyperthermia was investigated in esophageal cancer patients. Following in vitro heat treatment of FM3A tumor cells, the heat sensitivity detected by ATPA was significantly correlated with that in the colony-forming assay, and the percent inhibition of the ATP level in the tumor cells was correlated with in vivo tumor growth. The heat sensitivity of the biopsy materials evaluated by ATPA correlated well with that of the resected specimens in 18 esophageal cancer patients, while the clinical response to thermal therapy was well predicted by the heat sensitivity of the biopsy materials evaluated by ATPA in seven of the patients. These results indicate that the heat sensitivity test conducted by performing an ATPA on endoscopic biopsy materials could be a useful indicator for predicting the clinical response to thermal therapy.

Adenosine Triphosphate↗

Progesterone enhancement of stomach tumor development in SD rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.

The effects of chronic progesterone treatment on gastric tumorigenesis were examined in 6-week-old male SD rats. The rats were castrated, progesterone or testosterone pellets were implanted, and, starting one week after the operation, 100 mg/liter of N-methyl-N'-nitro- N-nitrosoguanidine (MNNG) was administered in the drinking water for 16 weeks. Every 2 months the pellets were changed. Group 1 animals received castration plus MNNG while Groups 2 and 3 also received progesterone and testosterone, respectively. In the Group 4 case, progesterone and testosterone were administered alternately for 2-month periods and in Group 5 MNNG was given to intact animals. All survivors were killed one year after the start of MNNG treatment. In Group 1 the incidence of gastric tumors was significantly decreased as compared with the Group 5 value. The Group 2 incidence, in contrast, was similar to that in Group 5, and the size of the observed gastric tumors was massively increased. The area of the pyloric gland mucosa was also greater than in other groups. Testosterone treatment was associated with a less pronounced increase in tumor size and a recovery in incidence. The results indicate that progesterone may exert a promoting influence on gastric tumor development.

Animals↗

[T cell receptor V beta repertoire of locoregional lymphocytes in malignant effusions].

We analyzed the T cell receptor (TCR) V beta repertoire of lymphocytes obtained from patients with malignant effusion treated by locoregional immunotherapy. Polymerase chain reaction using a panel of V beta subfamily specific oligonucleotide primers(V beta 1-20) was employed after reverse transcription of mRNA isolated from the locoregional cells. No major oligoclonality of TCR repertoire was observed in effusion lymphocytes before the treatment. The expression level of V beta 13.1 repertoire was significantly higher in effusion lymphocytes than in peripheral blood lymphocytes before treatment. V beta 20 gene expression increased significantly after locoregional administration of OK-432. It is suggested that TCR V beta 13.1 may be responsible for effusion lymphocytes and TCR V beta 20 for OK-432-related antigenic stimulus.

Adult↗

[Clinical effects of FUT-187 in reflux esophagitis after gastrectomy].

FUT-187 was orally administered to 38 patients with postgastrectomy reflux esophagitis for 4 weeks. The drug reduced the chief subjective symptoms of reflux esophagitis, such as heartburn, chest pain, precordial pain, and dysphagia for solids in 78.1% of patients. Redness, edema and erosion were also reduced in 53.3% of patients as determined endoscopically. Overall, FUT-187 exhibited an excellent therapeutic effect on the reflux esophagitis which was refractory to conventional treatments.

Administration, Oral↗