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Biomedical subjects

U Kim

Publications and source records attributed to U Kim.

At least 73 records · Page 4Linked to original sources

Retardation of prostate tumor progression in the Noble rat by 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase.

The effect of 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase has been evaluated on tumor growth in the Noble rat model of prostatic adenocarcinoma. The growth characteristics of the tumor line 2Pr-121D(1) were consistent with heterogeneity of cell types, composed of androgen-sensitive and androgen-insensitive malignant cells. Both sodium 4-methyl-3-oxo-4-aza-5 alpha-pregnane-20 (s)-carboxylate and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 and 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one significantly retarded tumor progression. Each agent increased tumor volume doubling time by approximately 62%. On the basis of their similarities to female rats and male castrate group, in terms of growth rate, tumor doubling time, and histologic characteristics, the treatments with the 4-methyl-4-aza-steroids appeared to produce effects common to both castration and estrogenization (chronic administration of pharmacologic doses of estrogen). The failure of 5 alpha-reductase inhibitors to be active as antiprostatic agents in vivo has hitherto detracted from their use of therapeutic agents. Present studies demonstrate that the 4-methyl-4-aza-steroidal inhibitors of 5 alpha-reductase may represent an alternative to orchiectomy and chronic estrogen therapy for the management of the hormone-dependent phase of prostate cancer.

5-alpha Reductase Inhibitors↗

Coexistence of myeloid metaplasia with myelofibrosis and hairy-cell leukemia.

A 42-year-old man with severe pancytopenia and myelofibrosis underwent splenectomy seven months after onset of his symptoms; the leukocyte, platelet, and hematocrit levels became normal. Myeloid metaplasia was identified in the liver and spleen. Progressive lymphocytosis started eight months after splenectomy, and after 66 months a florid hairy-cell leukemia was diagnosed; the circulating cells were B type with micro K surface markers. Anemia and thrombocytopenia reappeared and were controlled initially with daily prednisone; chlorambucil was later added. At that time, the peripheral blood had more than 150 megaloblastoid-appearing normoblasts per 100 leukocytes. The PAS stain was positive in 95% to 100% of these cells; the B-cell surface markers were no longer identified. Further treatment failed to control the lymphoproliferative and myeloproliferative syndromes; the patient died 99 months after splenectomy. On autopsy, infiltration by hairy-cell leukemia cells and erythroid precursors was observed in the bone marrow, liver, lymph nodes, and other organs.

Adult↗

Induction of benign prostatic hypertrophy in baboons.

Hormonal manipulation of intact male baboons has produced prostatic features resembling benign prostatic hypertrophy (BPH) in man. Long-acting androgen, testosterone enanthate (TE), given weekly (200 mg i.m.) for up to six months, caused significant gravimetric and volumetric increases in the prostate; a definite glandular and marked stromal hyperplasia with fibrosis developed in the caudal lobe (CD). After twenty weeks of TE treatment, there were dysplastic (atypical) changes in the glandular lining epithelium in the CD, causing pseudostratification of the lining cells with nuclear hyperchromatism. By the twenty-eighth week, there was an increase of stromal tissue with papillary ingrowth or invagination of glandular epithelium in the CD. Serum levels of testosterone and dihydrotestosterone were significantly elevated from 10 nm/ml and 2-3 ng/ml to 30-40 ng/ml and 5-6 ng/ml, respectively. There was a 3 to 4-fold increase in androstenedione levels and an increase in estradiol-17 beta from 20 pg/ml to 80-90 pg/ml. These steroidal levels may have played a direct role in the induction of early BPH in the baboons. Cytoplasmic and nuclear androgen receptor levels were higher in the CD compared to those of the cranial lobe (CR); AR concentration was increased in the cytosol and decreased in the nuclei of both lobes in TE treated animals. Scanning and transmission electron microscopy revealed heavy deposition of collagen fibers (fibrosis) in the central and periurethral regions of the CD after the administration of TE. Glandular as well as epithelial hyperplasia was most notable in the peripheral zone of the CD. These findings are similar to observations established in human BPH, indicating that the baboon prostate may be a useful model for studying various parameters of BPH.

Animals↗

Large mediastinal mass in Hodgkin's disease. Results of two treatment modalities.

Sixty-eight untreated patients with Hodgkin's disease (HD), stages I-III, presenting with a large mediastinal mass were treated as follows: patients with "good-risk HD" (lymphocyte predominant or nodular sclerosis and no "B" symptoms) stages I and II were treated by randomization with involved field radiotherapy (IF RT) or IF RT plus six cycles of combination chemotherapy (CT). Those with "poor-risk HD" (presence of B symptoms or with other histologic types) stages I and II and all patients with stage III were treated by randomization with total nodal radiation (TNR) or TNR + CT. Complete remission (CR) was achieved in 66/68 patients (97%) with the initial RT. A significantly longer duration of remission (p = 0.001), but not of survival (p = 0.08) was observed in patients treated with RT + CT compared to RT alone. Significantly longer duration of remission (p = 0.01), but not of survival, was observed in patients with good-risk stages I-II treated with RT + CT. In this category, remission and survival was better with RT + CT than with RT alone in stage III, but these differences were not statistically significant. In poor-risk patients stages I-II, a trend for longer remission and survival (not significant) was observed in patients treated with RT + CT; in stage III, both treatment modalities gave similar poor results. Both treatment modalities were well tolerated by most patients. One patients died with radiation pneumonitis shortly after completion of TNR. One patient developed a malignant schwannoma after treatment with IF RT, and another one developed acute nonlymphocytic leukemia after TNR + CT. Decrease in the transverse diameter of the heart without overt manifestations of cardiac disease was observed in 59% of the patients evaluated for this parameter.

Adolescent↗

Loss of myoepithelial cell characteristics in metastasizing rat mammary tumors relative to their nonmetastasizing counterparts.

A series of WF rat mammary tumors comprising one transplantable nonmetastasizing line (MT-W9), two predominantly lymphatic (SMT-2A and SMT-077) and one lymphatic and hematogenous (MT-450) metastasizing transplantable lines, and 7,12-dimethylbenz[a]anthracene (DMBA)-induced nonmetastasizing primary tumors was examined for the presence of epithelial and myoepithelial cell characteristics with the use of immunocytochemical techniques. Tumor cells staining for myosin were only occasionally observed in a basal orientation in glandular structures in sections of DMBA-induced and MT-W9 tumors; anti-laminin serum stained the peripheries of the glandular structures in the DMBA-induced and MT-W9 tumors but failed to stain the SMT-2A and SMT-077 tumor cells. In the nonmetastasizing tumors immunologically detectable keratin occurred mainly in the outer cellular layer of glandlike structures, whereas milk fat globule membrane immunoreactivity occurred primarily in the luminal cells. Both these types of immunoreactivity were observed in MT-450 tumor cells, but the pattern of keratin staining was random. No such immunoreactivity occurred in SMT-2A or SMT-077 tumors. No tumor cell-associated staining for fibronectin was seen in any of the tumors examined, although host stromal components stained intensely. The nonmetastasizing tumors contained cuboidal epithelial cells with lumen formation, surface microvilli, and intercellular junctional complexes, together with a relatively undifferentiated elongated cell component. Other elongated cells showed hemidesmosomes, pinocytotic vesicles, tonofilaments, and small bundles of cytoplasmic filaments, suggesting gradations toward a myoepithelial phenotype. The MT-450 tumors were ultrastructurally similar to the nonmetastasizing tumors, but no features of myoepithelial cells were seen, although some cuboidal epithelial cells exhibited prominent tonofilaments. The SMT-2A and SMT-077 tumors consisted of nests of cuboidal-like cells with highly pleomorphic nuclei and much intercellular collagen. The results indicate a progressive loss of cellular differentiation characteristics, particularly those of the myoepithelial cell with increasing malignancy in this system.

9,10-Dimethyl-1,2-benzanthracene↗

Lack of production of myoepithelial variants by cloned epithelial cell lines derived from the TMT-081 metastasizing rat mammary tumor.

A series of cell lines was isolated from the metastasizing rat mammary tumor cell strain TMT-081. MS by single-cell cloning. Feeder cells were required for development of single tumor cells into clonal colonies. The rate, pattern, and incidence of metastases following injection of cells into the mammary fat pads of syngeneic rats were relatively similar for the various cell lines, with dissemination to the lungs and axillary and paraaortic lymph nodes. When a representative cell line termed Rama 800 was subcloned, one subline was nontumorigenic, and another gave a lower incidence of lung metastases, but the remainder had similar in vivo properties to the parental Rama 800 cells. The metastatic properties of Rama 800 cells were not affected by passage in vitro through 60 cell generations. No production of myoepithelial-like variants from Rama 800 cells was observed at the ultrastructural level. Antisera to keratin, actin, laminin, and fibronectin, which normally stain myoepithelial cells and basement membrane, failed to stain Rama 800 cells, either in cultures or in tumor sections. Heterogeneous staining of Rama 800 tumor cells with antiserum to epithelial cell-specific milk fat globule membrane antigens was seen in tumor sections but not in culture. Abundant microvilli and membrane blebs were observed on the surface of cultured Rama 800 cells, but no lumen formation, desmosomes, or tonofilaments were seen, either in vivo or in vitro. The results suggest that the metastatic epithelial-derived cell lines lack the ability to express features of myoepithelial cells, in contrast to cell lines isolated previously from nonmetastasizing rat mammary tumors.

Animals↗

Establishment of two nonmetastasizing and one metastasizing rat mammary carcinoma cell lines.

Two continuous rat mammary tumor cell lines have been established in culture from the lymphogenously metastasizing rat mammary carcinoma TMT-081 and one from the nonmetastasizing MT-100 and some of their in vitro and in vivo characteristics studied. Cell line TMT-081-MS was established as a free-floating cell suspension from the metastasis-free spleen of a rat bearing TMT-081 in the ascites form and is characterized by a high level of mammary tissue specific antigen (MTA), an antigen present on lactating or hormonally stimulated rat mammary tissues but not detected on normal mammary tissue. This line metastasizes in the syngeneic host but is rejected by the nude mouse without metastases. Cell line TMT-081-NM is a line derived from the ascites of a rat also bearing TMT-081 ascites. Cell line MT-100-TC is a line derived from the ascites of a rat bearing the ascites form of MT-100. Neither TMT-081-NM nor MT-100-TC has ever shown metastases in the syngeneic host but they are lethal; in the nude mice they grow rapidly, are lethal, and sometimes show hematogenous metastases. Both grow in small clusters and show a low level of MTA. These cell lines have been in continuous culture for a year and have proliferated and maintained their individual in vitro and in vivo growth characteristics during more than 100 consecutive subcultivations.

Animals↗

Circulating immune complexes in rats with metastasizing or nonmetastasizing mammary tumor.

The dual rat metastatic and nonmetastatic mammary tumor model was characterized by the level of immune complexes in the sera of rats bearing these tumors. Circulating immune complexes (CIC) were measured at various intervals posttumor injection in Wistar-Furth (W/Fu) rats inoculated at 2 months of age with either 1 X 10(6) viable metastasizing (TMT-081) or nonmetastasizing (MT-100) tumor cells into the mammary fat pads. The Raji cell assay was used to measure CIC. No correlation between tumor size and CIC levels in the tumors were observed. While none of the sera from the rats bearing the nonmetastasizing tumors had CIC levels higher than 30 micrograms/ml, a small percentage of the animals bearing the metastasizing tumors had serum CIC levels higher than 30 micrograms/ml. This study suggests no clear difference between the amount of CIC in the sera of animals bearing either metastasizing or nonmetastasizing tumors.

Adenocarcinoma↗

Endobronchial malignant lymphoma: unusual manifestations--a report of two cases.

Two unusual manifestations associated with endobronchial malignant lymphoma are reported. A 58-year-old white female was first seen with massive hemoptysis requiring blood transfusion and pneumonectomy for histiocytic lymphoma (large cell type). The second case was that of a 47-year-old black male treated previously for poorly differentiated lymphocytic lymphoma (medium-sized cell type) who had a relapse in the lungs. Increasingly copious sputum production led to respiratory distress which required extensive radiation therapy and chemotherapy for its control.

Bronchial Neoplasms↗

Differential response to heat of metastatic and non-metastatic rat mammary tumors.

Metastasizing and non-metastasizing transplantable mammary tumors were implanted into female W/Fu rats. A pair of tumors were employed, the SMT-2A and MT-W9B. When these tumors were exposed to water bath heating at 43.5 degrees C for 60 minutes, a significantly longer tumor-free growth delay was obtained in the metastasizing tumor compared to its non-metastasizing counterpart. The protein to phospholipid ratio and the content of arachidonic acid was lower in the metastasizing tumor than in the non-metastasizing one. By way of apparent compensation, the metastasizing tumor contained more linoleic and stearic acid. These observations suggest a relation between metastasizing capacity, thermal sensitivity, and membrane composition.

Adenocarcinoma↗

Graft-versus-host reaction following blood product transfusion.

The observation of graft-versus-host (GVH) reaction after platelet transfusion in a patient with Hodgkin's disease led us to analyze 38 reported cases in the literature, to outline prognostic factors and to characterize patients at risk. Overall mortality was 68 percent. It was higher among children (76 percent) than among adults (62 percent), and among patients with Hodgkin's disease and immune deficiency syndromes (88 percent) than among those with leukemias (23 percent, p less than 0.005). Following blood transfusions from normal donors, mortality was higher (88 percent) than after transfusions from donors with chronic myelocytic leukemia (25 percent, p less than 0.05). Minimal lymphocyte doses necessary to cause GVH reaction are in excess of 10(7)/kg. Adults seem more resistant to homografts than do children, and the host's cellular immune status is of major prognostic importance. Lymphocytes from donors with chronic myelocytic leukemia may be deficient, and after a threshold dose, the number of lymphocytes transfused does not correlate with clinical outcome. Effective prophylactic measures do exist for this complication but satisfactory therapy does not.

Adolescent↗

Interaction of dietary fat and the thymus in the induction of mammary tumors by 7,12-dimethylbenz(a)anthracene.

The interaction of dietary fat and the thymus in the induction of mammary tumors by dimethylbenz(a)anthracene has been examined in female Sprague-Dawley rats. In these experiments, rats fed diets of 0.5% (low fat), 5% (normal fat), or 20% (high fat) corn oil from weaning (21 days of age) were thymectomized or sham thymectomized at 35 days of age and were given 5 mg of dimethylbenz(a)anthracene at 55 days of age. Thymectomy exerted a protective effect in rats fed low and normal fat diets, and this was not reversed by Thymosin Fraction V. In high fat-fed rats, tumorigenesis was increased compared to the low fat groups, and in addition, the protective effect of thymectomy was absent. This differential effect of thymectomy could not be explained on the basis of changes in prolactin concentration, since prolactin levels were decreased in all dietary groups. Neither diet nor thymectomy affected corticosterone levels or the estrus cycle of mature rats. Peripheral blood lymphocytes were, however, decreased by both thymectomy and increasing the fat content of the diet. It is hypothesized that the promoting effect of dietary fat on dimethylbenz(a)anthracene-induced mammary tumorigenesis is mediated via the immune system, although a role for the endocrine system still cannot be ruled out.

9,10-Dimethyl-1,2-benzanthracene↗