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Biomedical subjects

T Mitomi

Publications and source records attributed to T Mitomi.

At least 73 records · Page 4Linked to original sources

[Chemotherapy for patients with recurrent breast cancer and quality of life].

Chemotherapy plays a major indispensable role in treating patients with recurrent breast cancer. Although standard regimens such as CAF, FAC or CMF yield approximately a 50% response rate, the response usually lasts only for 6 months or so on average. For those who have an unfavorable response to chemotherapy, significant portions of their remaining time are to be consequently lost with only identifying damaging effects of treatment, depressed quality of life. Because of this dismal outcome, many of the patients are deeply discouraged about the future, and there is a desperate need for better treatment. Autologous stem cell support, originally practiced in the form of autologous bone marrow transplantation, has been found instrumental in treating breast cancer, and our pilot study started some fifteen years ago showed a higher response rate and survival rate compared to conventional chemotherapy. Moreover, there have been some long-term disease-free survivors with probable cures among complete responders. This is because quality of life is not a mere rating of health status, and is something perceived by each patient individually, reflecting the way in which individual patients feel about their health status. Although high-dose chemotherapy with autologous stem cell support will cause quite a lower quality of life for a significant period of time, it has been fairly well accepted and tolerated by many patients who would be able to maintain some degree of hope. The need to incorporate patients' values, preferences and hopes is what distinguishes quality of life from all other health measures, and physicians' values ought to play no major role in the decision making process when the outcome is often palliation and treatments may be unpleasant.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical usefulness of FUT-187 (sepimostat mesilate) on reflux esophagitis and gastritis after gastrectomy].

The efficacy and safety of the proteolytic enzyme inhibitor FUT-187 were evaluated in postgastrectomy reflux esophagitis and gastric remnant inflammation. FUT-187 was administered orally in a dose of 50 mg four times daily, after meals and bedtime, for periods of 4 to 8 weeks. The subjects consisted of 4 patients with postgastrectomy reflux esophagitis and 9 patients with gastric remnant inflammation. In the endoscopic classification of lesions, postgastrectomy reflux esophagitis was classified as erosive or ulcerative and gastric remnant inflammation as superficial. The general improvement rating, general improvement rating of endoscopic findings, and final global improvement rating were 85% (11/13), 82% (9/11), and 85% (11/13), respectively. Neither adverse reactions nor abnormal laboratory findings due to the test drug were noted. Based on the results of this study, it may be concluded that FUT-187 is an effective drug with a wide margin of safety for postgastrectomy reflux esophagitis and gastric remnant inflammation.

Administration, Oral↗

Effect of the proteoglycan (PSK) on lymphocyte subsets in normal rats.

The effect of the proteoglycan biologic response modifier, PSK, on lymphocyte subsets was investigated in normal rats. Six-week-old male SPF Wistar-Imamichi rats were fed a diet containing 2% PSK. Peripheral blood lymphocytes (PBL), thoracic duct lymphocytes (TDL), and those existing in the thymus, spleen and Peyer's patches were collected for analysis of subsets of T cells, helper/inducer T (Th) cells, suppressor/cytotoxic T (Ts) cells and B cells compared with those of the control group. In the PBL, differential and absolute counts of T and Th cells were lower in the group fed PSK (the PSK group) than the control group. There was no difference in Ts cells between the groups, and the PSK group showed a higher B-cell differential count. In the case of TDL, the PSK group showed greater absolute counts of T and Th cells than the control group. In tissue lymphocytes, differential T and Th cell counts were significantly greater in the PSK group than the control group, as observed first in Peyer's patches and later in the spleen. No differences between the groups were observed in these counts in the thymus. Changes in body distribution of T and Th cells induced by PSK treatment first appeared in lymphocytes in Peyer's patches, followed by PBL and TDL, and those in the spleen. No such changes were observed in the thymic lymphocytes.

Animals↗

Hepatic cytokeratin changes in obstructive jaundice: before and after biliary drainage.

We investigated the changes in hepatic cytokeratins in obstructive jaundice by immunohistochemistry. The results can be summarized as follows: 1) In accordance with the progression of the jaundice, the lobular and cellular distribution of cytokeratin reactivity in hepatocytes expanded. 2) Cytokeratin reactivity in obstructive jaundice was improved by removal of the bile duct obstruction (decompression), but this decompressive effect deteriorated in the case of prolonged jaundice. 3) It is suggested that the specific lobular and cellular distribution and/or the changes in cytokeratin aggregation might be of value in determining the stage and in predicting the prognosis of obstructive jaundice.

Animals↗

HLA-DR4 antigen and lymph node metastases in poorly differentiated adenocarcinoma of the stomach.

BACKGROUND: The authors investigated whether HLA antigens could act as a predictor of the risk of lymph node metastasis in patients with gastric cancer. METHODS: The microcytotoxicity assay was used to examine 51 HLA antigens of the A, B, C, DR, and DQ loci in 573 patients who underwent resection of gastric cancer. The incidence of HLA antigens in patients with or without lymph node metastasis was analyzed using the chi-square method. RESULTS: The incidence of patients with HLA-DR4 antigen with or without lymph node metastasis was 45.9% and 34.8%, respectively (P = 0.0098, corrected P = 0.49). The relative risk of lymph node metastasis in patients with HLA-DR4 was 1.6. In poorly differentiated adenocarcinoma, the incidence of HLA-DR4 antigen in patients with lymph node metastasis was significantly higher (47.5%) than in patients without lymph node metastasis (18.5%), if corrected P values were tested (P = 0.0007, corrected P = 0.0387). The relative risk of lymph node metastasis in patients with poorly differentiated adenocarcinoma with DR4 was 4.0. CONCLUSIONS: The data suggest an association between the presence of HLA-DR4 and an increased risk of lymph node metastasis, especially in poorly differentiated adenocarcinoma.

Adenocarcinoma↗

The strategy to treat disseminated neuroblastoma utilizing bone marrow transplantation: what is the surgeon's role?

The current role of surgery was evaluated in seven consecutive patients with high-risk neuroblastoma (six stage 4 patients and one stage 3, abdominal origin, and all over 12 months of age at diagnosis) treated with new modalities utilizing bone marrow transplantation (BMT). In six of these seven patients, a grossly complete excision of the primary tumor was achieved, and four have survived for 133, 69, 39, and 28 months with no further evidence of disease. The remaining patient with celiac neuroblastoma only underwent a biopsy during a second-look laparotomy after chemoradiotherapy, and thereafter developed local and distant recurrences and ultimately succumbed to the tumor. The timing of surgical intervention varied, either before or after chemotherapy, and did not appear to affect the ultimate survival. Although surgical excision of the primary tumor remains a very high priority in the overall treatment scheme, the most important factor remains the eradication of the tumor by well-planned courses of intensive chemotherapy (e.g., A1 Protocol of the Study Group of Japan). Thus, after having induced complete remission, for consolidation, it is necessary to kill all remaining tumor cells by giving supralethal doses of chemotherapy including total body irradiation (TBI) assisted by BMT.

Adrenal Gland Neoplasms↗

Quantification of serum-soluble HLA class I antigens in patients with gastric cancer.

The amount of sHLA-I in serum was examined in 74 patients with gastric cancer and 15 normal healthy controls. For mAbs, W6/32 specific for HLA-A, -B, -C, and biotin IOT2 specific for HLA class I associated with beta 2 microglobulin, were used to determine the values of sHLA-I using an ELISA. The patients in stage-IV gastric cancer showed lower values of sHLA-I (445.4 +/- 247.1 ng/ml) than those in stage I (725.9 +/- 575.8 ng/ml), stage II (752.8 +/- 255.0 ng/ml), and normal controls (868.9 +/- 715.0 ng/ml) (P < 0.05). In analysis of the patients with HLA-A24, the allele that has been reported to secrete more sHLA-I than other alleles, the results were nearly the same. These results suggest that the secretion of sHLA-I is low in patients with very advanced cancer. However, there was no correlation between the sHLA-I level and the metastasis or prognosis in longitudinal studies in 11 patients.

Adult↗

Histologic type and gastric acid secretion in gastric cancer.

We investigated gastric acid secretion in 638 gastric cancer patients with respect to the association between aging and histologic types. In intestinal type tumors in which invasion is restricted to the mucosa, and in diffuse type tumors where the tumor invaded the serosa there was a significantly negative correlation between acid secretion and age. However, no relationship was found between gastric acid output and age in signet ring cell carcinoma. On the other hand, a significantly negative correlation between acid secretion and age was shown in male patients with well differentiated type and in females with signet ring cell carcinoma. In conclusion, low acid secretion related to aging may play an important role in developing cancer cells in intestinal type tumors especially in the male elderly, and in diffuse type tumors in the female elderly, respectively.

Adult↗

Serum c-erbB-2 in breast cancer patients.

The c-erbB-2 oncogene product in serum (serum c-erbB-2) was measured by an enzyme-immunoassay kit. The 12 U/ml cut-off level was estimated as the mean plus two standard deviations for 250 healthy women. With this cut-off level increased serum c-erbB-2 was found in 12.0% of primary breast cancer cases (n = 25), in 4.9% of non-recurrent breast cancer patients (n = 82), and in 31.4% of patients with recurrent breast cancer (n = 35). In patients with primary and recurrent breast cancer, whose sera were assayed concurrently for serum c-erbB-2, CEA and CA15-3, the positive rates of these markers were fairly similar. However, their combined use significantly increased the sensitivity as compared to the use of any one marker alone.

Adult↗

Production and properties of mouse monoclonal anti-adriamycin antibody.

Eight mouse IgG1 monoclonal anti-Adriamycin antibodies were produced in culture and in ascites in BALB/c nude mice. The binding constant and specificity was measured by an inhibition ELISA method. The assay was an indirect method using horseradish peroxidase-labeled goat Fab' antibody and 2mM ABTS (2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) containing 2.5 mM H2O2 as a color reaction reagent. The binding constant of the antibodies was 10(6) to 10(8) M-1. The antibodies possessed different specificities and affinities to the adriamycin. Though adriamycin is a low molecular weight (M.W. 579.99) hapten antigen, it possesses several epitopes as antigenic determinant sites. The antigenic epitopes of the adriamycin, which until recently were unknown, were analyzed by the monoclonal antibodies.

Animals↗

Inhibitory effect of simultaneous intraportal administration of 5-fluorouracil, uracil and degradable starch microspheres on experimental hepatic micrometastasis, is of colon cancer.

This study was designed to examine the optimal regimen of 5-fluorouracil (5-FU), uracil and degradable starch microspheres (DSM) to prevent the hepatic metastasis of colorectal cancer. BALB/C mice were used as a model of hepatic micrometastasis of mouse transplantable colorectal cancer, Colon 26. We intraportally administered to the mice 5-FU at a dose of 34.8 mg/kg body weight; uracil at the dose equal to, or 8 times higher than that of 5-FU in molar weight and DMS at a dose of 5 mg/kg body weight. We investigated the hepatic and serum concentrations of 5-FU and uracil and the inhibitory effect of various combinations of the three substances on hepatic metastasis. The study showed that concurrent use of 5-FU with uracil at a dose 8 times higher than that of 5-Fu could keep 5-FU concentration high in hepatic tissue and relatively low in serum. This tendency became more marked with the presence of DSM. These findings support the previous study results that uracil antagonizes breakdown of 5-FU in the liver and with the aid of DSM, retards excretion of 5-FU from the liver. Further investigations for clinical application of this method will lower the incidence of hepatic metastasis of colorectal cancer.

Animals↗

[Chemotherapy with autologous stem cell support for breast cancer].

The importance of dose intensity in breast cancer chemotherapy has been stressed in recent years with clear correlations demonstrated between dose intensity and clinical outcome of the patients in both therapeutic and adjuvant settings. In addition to various and intense supportive care, autologous stem cell support (ASCS) has been used over the past 15 years in order to overcome myelotoxicity of cancer chemotherapy. ASCS was initially practiced in the form of bone marrow transplantation, and more recently peripheral stem cell transplantation has been combined in addition to administration of G-CSF. Our pilot study in patients with recurrent/advanced breast cancer showed a higher response rate and a higher survival rate as compared to conventional chemotherapy, and there have been some long-term disease-free survivors with probable cures among complete responders with ASCS-supported chemotherapy. In adjuvant settings for patients with a high risk for recurrence who had been given a high-dose, the ASCS-supported regimen showed a higher disease-free survival rate as compared to those who were treated with conventional adjuvant therapy. Whether these apparently better results in our pilot studies hold true generally remains to be seen with well-scheduled randomized clinical trials.

Antineoplastic Agents↗

[Early phase II study of FUT-187 (sepimostat mesilate) on reflux esophagitis--mainly on postgastrectomy reflux esophagitis].

An early phase II clinical study with the proteolysis inhibitor FUT-187 was carried out on patients with reflux esophagitis. FUT-187 was administered orally at the dose of 300 mg/day or 400 mg/day four times daily, after meals and at bedtime, for 4 consecutive weeks. The total number of patients admitted to this study was 40, of whom 9 were assigned to 300 mg/day group and 31 to 400 mg/day group. The rate of effectiveness on postgastrectomy reflux esophagitis was 88% (7/8) in 300 mg/day group and 85%(22/26) in 400 mg/day group when "improved" or better final general improvement ratings were taken into consideration, and 75% (6/8) in 300 mg/day group and 69% (9/13) in 400 mg/day group when "improved" or better endoscopic general improvement ratings were used. The overall safety rating "no problem as to the drug safety" was 89% (8/9) in 300 mg/day group and 71% (22/31) in 400 mg/day group. The main side effect was diarrhea, which was experienced in 6 patients in 400 mg/day group. However, it was resolved by discontinuation of the drug treatment. Other symptoms of gastrointestinal upsets, such as nausea and anorexia, were also induced. Based on these results, it may be concluded that FUT-187 can be a drug with clinical utility that benefits postgastrectomy reflux esophagitis at the dose level of 300 mg/day or less.

Administration, Oral↗

A clinico-pathological study of adult histiocytosis X involving the brain.

Adult histiocytosis X involving the CNS caused progressive spastic paraparesis. The diagnosis was made by immunoreactive anti-S100 protein antibody staining and from the presence of Birbeck granules in biopsy specimens of skin lesions. Neuropathological examination showed massive proliferation and infiltration of S-100 containing histiocyte-like cells and reactive astrocytes throughout the CNS.

Brain Diseases↗

[A case of gastric cancer with multiple liver metastasis treated with low dose CDDP therapy on an outpatient basis after palliative gastrectomy].

A 59-year-old-male with advanced gastric cancer and multiple liver metastasis was treated by intravenous administration of MMC (30 mg/body) and oral administration of HCFU (400mg/body/day) initially after palliative gastrectomy. CT scan revealed that liver metastatic lesions were undetectable at three months after operation. Seven months later, administration of HCFU was discontinued because liver metastatic lesions were observed again. Intravenous administration of MMC (10mg/body)+ACR (20mg/body) was performed four times weekly, but liver metastatic lesions were increasing in size. From 15 months after operation intravenous administration of CDDP (25mg/body/week) was started on an outpatient basis. After administration of CDDP 6 times, liver metastatic lesions were diminished in size. By CT scan the maximum percent reduction of liver metastatic lesions was 97% and duration of partial response was seven months. Eight months later, liver metastatic lesions regrew. At 28 months after operation, the patient died of liver metastatic lesions. This low dose regimen of CDDP on an outpatient basis is potentially useful in the treatment of advanced gastric cancer with multiple liver metastasis.

Ambulatory Care↗

Evaluation of prognoses of patients with gastric cancer by the responsiveness of peripheral blood lymphocyte to OK432 in vitro.

The response of peripheral blood lymphocytes to the streptococcal preparation OK432 was examined in vitro in 193 gastric cancer patients. When the patients were divided by stimulation index (SI) into two groups, SI > or = 20 and SI < 20, the response rate of SI > or = 20 group of stage IV was 37.5%, and higher than those of the other stages (p < 0.05). In the relationship between SI and the survival period in stage III, the SI > or = 20 group showed longer survival than the SI < 20 group (p < 0.05). There was no statistically significant difference in survival between SI > or = 20 and SI < 20 in stage IV, but no member of the SI < 20 group survived more than 2 years, whereas the five-year survival of the SI > or = 20 group was 38.9%. In the overall survival of stage III and IV, the SI > or = 20 group showed longer survival than the SI < 20 group (p = 0.001). The lymphoproliferative responses to OK432 decreased in very advanced gastric cancer patients and this might lead to poor prognosis.

Cell Division↗

Estimation of the functional reserve of the human liver by urinary D-glucaric acid excretion after vitamin C administration.

The excretion of D-glucaric acid in the urine (uGA) correlates with the total liver content of hepatic cytochrome P-450, the metabolism of which depends on adenosine triphosphate (ATP) being produced by intrahepatic cellular mitochondria. Five cases of compensated liver cirrhosis group with less than 0.4 mg/kg/min of the maximum removal rate of indocyanine green (ICGR max), and 5 cases with normal hepatic function (control group), were monitored for uGA before and after P-450 activation induced by administration of 1 g of vitamin-C. Before vitamin-C administration, no differences in uGA excretion were observed comparing the cirrhosis with the control group. After administration of vitamin-C, the excretion of uGA was significantly lower in the cirrhosis group. The measurement of uGA is considered to represent vitamin-C induced activation by P-450, and is a new method for evaluation of the functional reserve of the liver.

Adenosine Triphosphate↗