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Biomedical subjects

J Sakamoto

Publications and source records attributed to J Sakamoto.

At least 127 records · Page 7Linked to original sources

Postremission therapy without prednisolone improves survival in adults with acute leukemia.

This prospective randomized clinical trial was to clarify whether postremission therapy without prednisolone (PSL) was more effective than therapy with PSL in improving the 5-year survival of adults with acute leukemia. Thirty consecutive adult patients with newly achieved complete remission were randomized to receive postremission therapy either with or without PSL between September 1985 and September 1988. The patients ranged from 16 to 57 years in age. Patients treated without PSL had a significantly better 5-year survival rate than those receiving PSL according to Kaplan-Meier analysis (53.5% vs 15.3%, p < 0.05). In the group treated without PSL, eight out of 15 patients were alive at 72 months, and seven patients maintained their first complete remission at 72 months. Among patients with acute lymphoblastic leukemia (ALL) who were treated without PSL the median duration of remission was 24 months, and the survival rate at 72 months was 50.0%. On the other hand, the median survival was only 13 months for the 5 patients with ALL treated with PSL. Thus, it is desirable that adults with acute leukemia are treated by postremission therapy without PSL.

Acute Disease↗

[Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA 102: whole IgG versus F(ab')2 fragments].

In order to improve cancer imaging with radiolabeled antibodies, three factors appeared to be of particular importance: (1) The selection of the most favorable monoclonal antibody directed to tumor-associated antigen. (2) The use of F(ab')2 or Fab fragments. (3) Selection of the most convenient isotope. Monoclonal antibody CEA 102 was produced by immunization by purified CEA, and its F(ab')2 fragments were compared with whole IgG as a radiotracer for radioimmunodetection of the colorectal cancer. Fragments were eliminated from the circulation twice as fast as whole IgG, and tumor-to-background ratio was achieved more than 1 at 2-3 days with F(ab')2, but 6-7 days with whole IgG in tumor bearing nude mice. In clinical study, F(ab')2 demonstrated clear image on the 1 at day after injection, whereas achievement of the image was possible on the 3rd day in whole IgG. These results indicated that fragments are preferred over whole IgG. Therefore fragments make it possible to preclude dual isotope subtraction methods, and omit the long delays before imaging. They also make it possible to use short half life radionuclides with excellent photon properties, such as 123I and 99mTc.

Animals↗

Cloning and tissue-specific expression of the brain calcium channel beta-subunit.

A cDNA clone encoding a protein with high homology to the beta-subunit of the rabbit skeletal muscle dihydropyridine-sensitive calcium channel was isolated from a rat brain cDNA library. This rat brain beta-subunit cDNA hybridizes to a 3.4 kb message that is expressed in high levels in the cerebral hemispheres and hippocampus but is significantly reduced in cerebellum. The open reading frame encodes 597 amino acids with a predicted mass of 65 679 Da which is 82% homologous with the skeletal muscle beta-subunit. The brain cDNA encodes a unique 153 amino acid C-terminus and predicts the absence of a muscle-specific 50 amino acid internal segment. It also encodes numerous consensus phosphorylation sites suggesting a role in calcium channel regulation. The corresponding human beta-subunit gene was localized to chromosome 17. Hence the encoded brain beta-subunit, which has a primary structure highly similar to its isoform in skeletal muscle, may have a comparable role as an integral regulatory component of a neuronal calcium channel.

Amino Acid Sequence↗

A monoclonal antibody to the beta subunit of the skeletal muscle dihydropyridine receptor immunoprecipitates the brain omega-conotoxin GVIA receptor.

Antibodies against the subunits of the dihydropyridine-sensitive L-type calcium channel of skeletal muscle were tested for their ability to immunoprecipitate the high affinity (Kd = 0.13 nM) 125I-omega-conotoxin GVIA receptor from rabbit brain membranes. Monoclonal antibody VD2(1) against the beta subunit of the dihydropyridine receptor from skeletal muscle specifically immunoprecipitated up to 86% of the 125I-omega-conotoxin receptor solubilized from brain membranes whereas specific antibodies against the alpha 1, alpha 2, and gamma subunits did not precipitate the brain receptor. Purified skeletal muscle dihydropyridine receptor inhibited the immunoprecipitation of the brain omega-conotoxin receptor by monoclonal antibody VD2(1). The dihydropyridine receptor from rabbit brain membranes was also precipitated by monoclonal antibody VD2(1). However, neither the neuronal ryanodine receptor nor the sodium channel was precipitated by monoclonal antibody VD2(1). The omega-conotoxin receptor immunoprecipitated by monoclonal antibody VD2(1) showed high affinity 125I-omega-conotoxin binding, which was inhibited by unlabeled omega-contoxin and by CaCl2 but not by nitrendipine or by diltiazem. An antibody against the beta subunit of the skeletal muscle dihydropyridine receptor stained 58- and 78-kDa proteins on immunoblot of the omega-conotoxin receptor, partially purified through heparin-agarose chromatography and VD2(1)-Sepharose chromatography. These results suggest that the brain omega-conotoxin-sensitive calcium channel contains a component homologous to the beta subunit of the dihydropyridine-sensitive calcium channel of skeletal muscle and brain.

Animals↗

Alternating immunochemotherapy of advanced gastric carcinoma: a randomized comparison of carbazilquinone and PSK to carbazilquinone in patients with curative gastric resection.

A total of 103 patients with advanced gastric carcinoma were randomized after curative surgery to receive an alternate administration of carbazilquinone (CQ) and PSK (Krestin) or carbazilquinone alone. Each course of therapies started 1 week after the surgical operation and therapy schedules consisted of 9 courses. In each course of 6 weeks, CQ (2 mg/m2/week) was administered on day 0, 8, and 15. In combined immunochemotherapy group, PSK was given orally in 3-divided doses of 2 g/m2/day from the day of the third CQ administration for consecutive 4 weeks. Estimated survival rate and cumulative survival curve were compared utilizing the data up to 7 years after the operation. There was no overall significant difference in survival rates between the CQ plus PSK group and the CQ alone group, but a group of patients whose disease was classified as S1 + S2(N1-2) survived significantly longer when treated with the combination of CQ and PSK. Neither in more advanced cases (greater than S3 or greater than N3) nor in cancers of early stages, the addition of PSK provided an additive effect. The favorable result obtained in one subgroup treated with PSK, suggests that the use of this agent in treating gastric cancers should be carefully evaluated in terms of serosal infiltration and nodal metastasis.

Adenocarcinoma↗

The role of adjuvant chemotherapy following cystectomy for invasive bladder cancer: a prospective comparative trial.

We assigned 91 patients with deeply invasive, pathological stage P3, P4 or N+ and Mo transitional cell carcinoma of the bladder (with or without squamous or glandular differentiation) to adjuvant chemotherapy or to observation after radical cystectomy and pelvic lymph node dissection. For most patients chemotherapy was planned as 4 courses at 28-day intervals of 100 mg./M.2 cisplatin, 60 mg./M.2 doxorubicin and 600 mg./M.2 cyclophosphamide. A significant delay was shown in the time to progression (p = 0.0010) with 70% of the patients assigned to chemotherapy free of disease at 3 years compared to 46% in the observation group. Median survival time for patients in the chemotherapy group was 4.3 years compared to 2.4 years in the observation group (p = 0.0062). In addition to treatment groups, important prognostic factors included age, gender and lymph node status. The number of involved lymph nodes was the single most important variable. We recommend adjuvant chemotherapy for patients with invasive transitional cell carcinoma after definitive surgical resection.

Antineoplastic Combined Chemotherapy Protocols↗

[Cases of advanced cholangiocarcinoma showing partial response by the combination chemotherapy including protracted continuous infusion of 5-FU combined with intravenous administration of low-dose leucovorin and intra-arterial administration of MMC and CQ].

We treated a patient with advanced cholangiocarcinoma with a new combination chemotherapy (modified MQF). The regimen consisted of intra-arterial administration of MMC (20 mg/body) and CQ (4 mg/body), protracted continuous infusion of 5-FU (500 mg/body) and intravenous administration of low-dose leucovorin (30 mg/body). More than 50% reduction in the liver tumor for over 4 weeks was obtained by the therapy. As for toxicity, diarrhea and stomatitis were observed.

Adenoma, Bile Duct↗

[Expression and clinical significance of type-1 blood group antigens (Lea, Leb, CA19-9) in colorectal cancer--comparison with CEA].

The immunohistochemical analysis using the monoclonal antibodies to the blood group associated antigens Lea, Leb, CA19-9, and CEA, were performed on the tissues of the colorectal cancers, adenomas, normal mucosae and distant metastatic lesions, to determine whether the given degree of expression have some relation to the prognosis of patients or the potential of metastasis. We also analysed the serum levels of CA19-9 and CEA by RIA and compared them with the results of immunopathology. The more pronounced expression of CEA, Lea, Leb, and CA19-9 was observed in proportion to the progress of the cancer. In those cases of immunohistochemically Lea negative results in tissues, CA19-9 was not detected either in the serum level nor in tissue sections, therefore all cases of Lea negative results were eliminated in the evaluation of the clinical significance of CA19-9. Positive expression of CA19-9 in tissue of cancer indicated a poor prognosis of the patient and high risk of distant metastasis. Higher intensity of staining was observed in hepatic metastasis, in comparison with the primary lesion. These studies demonstrated that immunohistochemical analysis of CA19-9 and blood group antigens in useful tool for evaluation of prognosis and risk of metastasis in colorectal cancer.

Adult↗

[Estimation of sample size in randomized controlled clinical trials--elimination of various systematic biases by the utilization of computer network system].

Although sample size calculation is mandatory in clinical trials, the power of most of the published small size clinical studies, was only about 0.25 instead of 0.80 which is normally required in a standard randomized controlled trial. This phenomenon is probably due to the publication bias. In a cancer clinical study, the ideal sample size needed in a trial exceeds over a thousand, when significance level was fixed under 0.05 and treatment difference is estimated from 10 to 15%. In such cases, evaluation of a new treatment in less common cancers or in a specified strata become unfeasible. Although statistically plausible clinical trial is difficult, small trials of newly advocated treatment is likely to be performed elsewhere, and presentation of these haphazard results might propagate a wrong information about the new treatment. To prevent the dissemination of these biased results, 1) preregistration of all planned clinical trials to an authorized organization before the initiation of the trial, 2) randomization of the patients entered in the trial from the first case, and 3) registration of all available data of the patients and meta-analysis of preregistered multiple trials, should be the most effective counterplans. In order to achieve those functions, installation of a computer assisted coordinating center is considered to be the best solution for the proper evaluation of the clinical trial as well as for the evaluation of a new treatment. With the collaboration of regional affiliating hospitals, a pilot study have started to establish a computer network system.

Database Management Systems↗

[From a statistical standpoint].

Issues in the statistical evaluation for therapeutic efficacy of surgical adjuvant modality therapy on the patients suffering from gastrointestinal cancers were mentioned as follows: 1) When a therapeutic effect is evaluated, it is important that a well-controlled, randomized trial should be requested under the statistical consideration. 2) On a series of systematized process such as protocol planning, coordination and administration, analysis and its interpretation, such a trial should be enough to complete several conditions which are mutually understood and coordinated between doctors and statisticians, and which are rich in knowledge and skill for the trial in each institutions. 3) Method of overview and its application for clinical data has been mentioned as an method of exploratory trials.

Antineoplastic Agents↗

[The expression of the blood related antigens in intestinal metaplasia of the stomach in gastric cancer].

The monoclonal antibodies detecting blood group related antigens of the Lewis systems have been used to define the immunoanatomic distribution of these antigens within the normal gastric mucosa and in gastric cancer tissues. In this study we analysed the presence of these antigens in histologically intestinal metaplasia of the stomach by the immunoperoxidase method. In normal gastric mucosa, Lewisb was distinctly expressed in normal foveolar epithelia and Lewisa was present in foveolar epithelia in half of the cases. Lewisx and Lewisy were detected in deep gastric glands. In intestinal metaplasia, more pronounced expression of Lewisa and decreased expression of Lewisb were observed. Lewisx and Lewisy were absent in most specimens of intestinal metaplasia. These pattern of expression of Lewis antigens in intestinal metaplasia were very similar to those observed in well and moderately differentiated adenocarcinomas of the stomach. These results indicate that well and moderately differentiated adenocarcinomas of the stomach have very similar character with the intestinal metaplasia in terms of the Lewis blood group antigen expression.

Adenocarcinoma↗

[Importance of the histopathological type of the tumor as a parameter for recurrence and for prognosis of gastric cancers].

Importance of histopathological type of tumor for the prediction of recurrence and prognosis of gastric cancers was analysed in 4419 patients who underwent surgery in Aichi Cancer Center during the 23 years from 1965 to 1987. Correlation of initial recurrence site and the histology of the tumor was examined by the categorical discriminant analysis in 617 patients. Among these patients, 62% of liver metastasis was caused by well differentiated type cancers whereas 71% of peritoneal recurrence was poorly differentiated type cancers. Cox's regression tree type analysis was performed for 2893 cases with curative gastrectomy and the maximum difference in risk ratio was observed whether the tumor microscopically penetrated the serosal layer of the stomach. Difference of the prognosis due to histopathological type of the tumor appeared after correction of the s and n factors and in the early stages poorly differentiated type had better prognosis than well differentiated type cancers. On the contrary, in more advanced cases well differentiated type tumors had much better prognosis than poorly differentiated type cancers. From these results, we suggest that the consideration of histopathological type of the tumor should be implemented as an important parameter for the evaluation of prognosis of the gastric cancers.

Female↗

[Carbohydrate antigens as a tumor-associated antigen and prognostic indicators in carcinomas of the breast, esophagus, stomach, colorectum, and pancreas].

The immunohistochemical analysis using the monoclonal antibodies to the carbohydrate antigens were performed and suggested that CA19-9 is a tumor-associated antigen in gastric cancer, Leb, Ley, CA19-9, CSLEX1, SLX in colorectal cancer and pancreatic cancer, and Lex, Ley, and CSLEX1 in breast and esophageal cancers, respectively. Expression of the type 2 carbohydrate antigens had relation to the prognosis of patients with breast cancer. In colorectal cancer, the patients with high degree of expression of CA19-9 had a poor prognosis, and high risk of distant metastasis. Higher intensity of staining was observed in hepatic in comparison with primary lesion. Thus carbohydrate antigens showed important role as tumor-associated antigens and good indicator for evaluation of prognosis.

Antigens, Tumor-Associated, Carbohydrate↗

[The preoperative and postoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of gastric cancer. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer].

Preoperative and postoperative carcinoembryonic antigen (CEA) levels were studied in 3,532 patients with Surgically treated gastric cancer in 52 institutions from 1980 to 1981. These patients had disease resectable with curative intent and were followed for a minimum of 5 years or until death. Among 2,749 Stage I cases, 33 had recurrence and proved to be histologically stage I. A pair matching case control study between these 33 cases and matched 33 stage I controls without recurrence proved that the preoperative CEA level was relatively higher in cases with recurrence (p = 0.079). In Stage II and III cases, an analysis of variance using a cut off level as a block factor was performed. Among 315 Stage II cases, preoperative CEA levels were significantly higher in cases with recurrence than in cases without recurrence. In 468 Stage III cases, no correlations between preoperative CEA levels and high risks of cancer recurrence were detected. In Stage I and Stage II cases, CEA levels significantly increased at the time of recurrence. In conclusion, preoperative high serum CEA levels might be considered one of the risk factors for recurrence of Stage I and II gastric cancers, and monitoring the postoperative CEA levels might be useful in early detection of recurrence.

Analysis of Variance↗

Expression of Lewis(a), Lewis(b), and sialated Lewis(a) antigens in early and advanced human gastric cancers.

An immunohistochemical analysis of the expression of Lewis(a), Lewis(b), and sialated Lewis(a) blood group antigens was performed on specimens of human non-involved stomach (n = 91), early gastric cancers (n = 41), and advanced gastric cancers (n = 50). In non-involved stomach, Lewis(a) and Lewis(b) were detected mainly in surface epithelium, although sialated Lewis(a) was scarcely expressed. These blood group-related antigens were rarely observed in deep glands. In gastric cancers, Lewis(a) showed a tendency to be expressed in well or moderately differentiated carcinomas, and this was observed to be more marked in advanced tumors. There was no obvious difference in positive ratios of Lewis(b) between degrees of differentiation of the cancers. Sialated Lewis(a) was not detected in early cancers, and its frequent expression in well- or moderately differentiated, advanced carcinomas suggested an association with both cancer differentiation and progression. These results indicate that knowledge of the expression of blood group antigens may help interpret the antigenic alterations occurring in the course of carcinogenesis, differentiation, and progression of gastric cancers.

Adenocarcinoma↗