[The standard care plan and its utilization].
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Biomedical subjects
Publications and source records attributed to T Nemoto.
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The patient was a 66-year-old man who complained of goiter. A diagnosis of functioning thyroid tumor was made because of high uptake of 131I after T3 suppression test and no response to thyrotropin releasing hormone. The tumor was removed and histologically proven to be follicular carcinoma. Twelve cases of thyroid carcinoma in autonomously functioning thyroid nodules have been reported, and the relation between carcinoma and an autonomously functioning nodule is reviewed from the literature.
A human hybridoma clone (4E3) has been established by fusing lymphocytes from a lymph node taken from a breast cancer patient and human lymphoblastoid cells, LICR-LON-HMy2, by the poly(ethylene glycol) method. 4E3 has been stabilized and continued to secrete IgMk antibody into culture medium (greater than 10 micrograms/ml) for over 1 year. The following characteristics of the antigen strongly suggested that 4E3 recognizes liver-type aldolase B (EC 4.1.2.13): the Mr of the native molecule is 160,000 and that of the subunit is 40,000, and thus it has a tetrameric structure of identical subunits; the antigen is abundant in the liver and kidney of human, mouse and rabbit, and is localized by immunohistochemical methods in the cytoplasm of hepatocytes and in the proximal tubules of the kidney; the antigen is precipitable by 50-80% saturation with (NH4)2SO4; the antigen shows charge-dependent heterogeneity on DEAE-cellulose chromatography. To confirm this notion, aldolase B was purified to homogeneity from the liver of human, mouse and rabbit by phosphocellulose chromatography. During the chromatographic purification, the antigen activity as assayed by enzyme-linked immunosorbent assay (e.l.i.s.a.) was superimposed on the enzymic activity of aldolase. Furthermore, monoclonal antibody 4E3 strongly reacted with purified aldolase B in SDS/polyacrylamide-gel electrophoresis followed by Western blotting and also in e.l.i.s.a. using microplates coated with purified enzyme. The reaction between aldolase B and 4E3 activated the human complement system as assessed by the attachment of C3 to the immune complex of aldolase B and 4E3.
This study improves treatment options and ultimately survival by using systemic chemotherapy in brain metastases from breast carcinoma, since most of these patients have disseminated disease and a dismal prognosis when treated by conventional brain irradiation alone. One hundred consecutive patients with symptomatic brain metastases documented by radionuclide and/or computerized tomography scan were treated with systemic chemotherapy. Fifty of 100 patients demonstrated an objective response of brain metastases which was similar for extracranial metastases. There were 10 complete responders (CR), 40 partial responders (PR), 9 stable, and 41 nonresponders. Median duration of remission was 10+ months for CR and 7 months for PR (range, 2-72 months). Primary chemotherapy of brain metastases yielded responses in 27 of 52 patients (52%) treated with Cytoxan (cyclophosphamide) (C), 5-fluorouracil (F) and prednisone (P); 19 of 35 (54%) receiving CFP-methotrexate (M) and vincristine (V); 3 of 7 (43%) treated with MVP, and 1 of 6 (17%) receiving Cytoxan plus Adriamycin (doxorubicin) (CA). Thirteen of 35 patients (37%) who subsequently had relapse of brain metastases were retreated successfully with secondary chemotherapy. The median survival for CR and PR was 39.5 months and 10.5 months, respectively, in contrast with nonresponder patients who had a median survival of 1.5 months. Thirty-one percent of all treated patients survived more than 12 months. These findings suggest that the chemotherapeutic agents used penetrate the blood-brain barrier inducing regression of brain metastases. This approach offers a significant benefit by simultaneously controlling extracranial disease, improving the response and prolonging survival.
A retrospective review of 483 women who had metastatic breast cancer and were treated between 1942 and 1975 was carried out to examine the effects of improving and aggressive palliative modalities on patient survival. There was a steady increase in the proportion of patients treated by chemotherapy and/or hormonal ablative therapy. Additive hormonal therapy, irradiation, and surgery for palliation decreased in frequency during the same period. Survival time from the first recurrence did not appear to increase in these patients over the period of this study. In spite of increasingly sophisticated palliative therapies, the survival time of patients with metastasis did not appear to be significantly prolonged.
A retrospective analysis of 52 patients with intraductal carcinoma or ductal carcinoma in situ (DCIS) and 30 patients with microinvasive DCIS was performed. All patients but one were treated by mastectomy. The average follow-up was 5 1/2 years. The clinical presentation of the patients having DCIS only included the presence of a mass in 33% (17/52), nipple discharge in 34% (18/52), or suspicious mammographic finding in 33% (17/52), whereas in those patients having DCIS with microinvasion, the initial presenting symptom was a mass in 63% (19/30) of the patients, nipple discharge in 13% (4/30), and mammographic finding in 23% (7/30). The presence of axillary lymph node metastasis was identified in one of the 52 patients with DCIS and six (20%) of the 30 patients with DCIS and microinvasion. Associated carcinomas in the mastectomy specimens of patients with DCIS were as follows: DCIS, 18% (9/51); lobular carcinoma in situ, 13% (7/51); Paget's disease, 8% (4/51); and invasive carcinoma, 2% (1/51). In the 30 patients with microinvasion, DCIS was found in other quadrants in 23% (7/51) of the patients; lobular carcinoma in situ, 7% (2/51); Paget's disease, 13% (4/51); and invasive carcinoma, 7% (2/51). There was one death due to cancer in the patients with DCIS only. Of the patients diagnosed as having DCIS with microinvasion, seven patients have developed metastasis and four have died of the disease.
In 47 postmenopausal women with evaluable breast cancer, oral medroxyprogesterone acetate (MPA) was given at a daily dose level of 400 mg. Patients with negative estrogen receptors, poor performance status, or nonresponse to previous endocrine therapy were excluded from this study. There were 25 (53%) responders to this agent. Periods of remission ranged from 5-26 months with a median of 10 and a mean of 12+ months. Higher rates of response were noted in women over 50 years of age, in patients with osseous metastasis, and in patients with a longer disease-free interval. Adverse effects included weight gain, Cushingoid appearance, skin rash, and vaginal discharge. In this selected group of patients, oral medroxyprogesterone at a dose level of 400 mg/day appeared to provide a significant frequency of tumor response.
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The 4 S transformed androgen receptor from rat prostate and thymus converted to a higher molecular form (5-7 S) on low-salt conditions. The converted receptor retained the DNA-binding capacity as well as the 4 S transformed receptor. This conversion was also demonstrated on glucocorticoid receptor from rat liver and thymus. The sedimentation coefficients of both the converted receptors were affected by sodium molybdate, i.e., the receptors converted to a relatively smaller molecule in the presence of molybdate than in the absence of the reagent. These observations suggest that molybdate directly binds to the transformed receptors and prevents the excessive association of a factor(s) to the transformed receptors.
Binding of androgens including 5 alpha-dihydrotestosterone, testosterone and androstenedione stabilized the androgen receptor from rat submandibular gland with respect to its [3H]methyltrienolone binding activity. Nonandrogenic steroids, 0.5 microM of progesterone and estradiol-17 beta, or 5 microM of triamcinolone acetonide also satisfactorily stabilized the androgen receptor. These results suggest that the association of ligands, even if those ligands were not stereospecific for the androgen receptor, stabilizes the androgen receptor and prevents the loss of its binding capacity.
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A 34-year-old postpartum woman with Burkitt's lymphoma is reported. Lymphoma involved the bilateral breasts chiefly, as well as the brain, ileocecal region and supraclavicular lymph nodes. Fourteen days after bilateral mastectomy, the patient suddenly went into a coma due to rapid progress of brain involvement. However, the coma improved the day after VEPA chemotherapy and radiation were undertaken, and the tumor-involved brain decreased significantly in size following chemoradiotherapy. Chemoradiotherapy produced the almost complete disappearance of the remaining tumor. The patient is now being treated by a maintenance dose of Endoxan and is doing well. Burkitt's lymphoma of the breast in the present case had the clinical characteristics of bilateral involvement with rapid growth arising during lactation and pregnancy.
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Data from the 1982 breast cancer survey of the American College of Surgeons were used to evaluate factors related to clinical, epidemiologic, and survival differences between black and white patients. Breast cancer in blacks was not discovered as early as in whites. Distribution of pathologic types of tumors were similar for both races with the exception of medullary carcinoma, which was more frequent in blacks than in whites. Estrogen receptor-positive tumors were found significantly less frequently in blacks compared with whites. Survival was better for whites compared with blacks within each axillary nodes group 0, 1 to 3, and 4+. Black women with negative or positive estrogen receptors had lower survival rates than white women of the same receptor status. A regression analysis using Cox's proportional hazards model showed race, clinical stage or axillary nodal status, age at diagnosis, and estrogen receptor status as significant predictors of survival. Significant differences between black and white patients were also observed with respect to the report of family history of breast cancer, age at first pregnancy, number of pregnancies, and age at cessation of menses.
Nontransformed glucocorticoid receptor stabilized with sodium molybdate exists as the heterogeneous forms which have slight differences in net charges and sedimentation coefficients. These differences could be detected by sequential analyses with DEAE-Sephacel chromatography and glycerol gradient centrifugation. The heterogeneity in the nontransformed receptor appears to be caused by the association of an acidic component(s) with the transformed receptor.
Rat submandibular gland cytosol contained androgen receptor which had a single class of specific binding and an apparent dissociation constant of (1.1-1.2) X 10(-9) M. The process of transformation was investigated by a slightly modified minicolumn method in which the transformed receptor complexes were separated from the nontransformed receptor and meroreceptor. 10 mM ATP or pyrophosphate at 0 degrees C induced transformation of androgen receptor as did heat or salt treatment. 20 mM of sodium molybdate completely inhibited transformation that resulted from ATP, heat or salt treatment. The nontransformed androgen receptor complexes sedimented at 8 S and eluted at 250-260 mM KCl from DEAE-Sephacel, and its molecular weight was found to be 220 000 on Sephacryl S300 gel chromatography. On the other hand, the transformed androgen receptor complexes sedimented at 4.1-4.3 S (ATP or KCl treatment) or 3.5-3.8 S (heat treatment) and eluted at 60-80 mM KCl from DEAE-Sephacel. The molecular weight of the transformed androgen receptor complexes was 80 000-85 000 (ATP or KCl treatment) or 70 000-80 000 (heat treatment). These results suggest that the transformation of androgen-receptor complexes from rat submandibular gland was induced by the subunit dissociation and that salt bridges may be involved in the subunit interaction.