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Biomedical subjects

R Kath

Publications and source records attributed to R Kath.

47 records · Page 3Linked to original sources
PubMed1990

Growth-regulatory factors for normal, premalignant, and malignant human cells in vitro.

Normal human cells, cells from nonmalignant proliferative lesions, and primary and metastatic tumor cells can be maintained in vitro and analyzed for requirements for growth in chemically defined media. The human melanocytic cell system with normal melanocytes, precursor nevus cells, and primary and metastatic melanoma cells has been extensively studied for the phenotypic properties of the cells, including their requirements for exogenous growth factors and other mitogens. In high calcium-containing W489 medium, normal melanocytes require four supplements: IGF-I (or insulin); bFGF, TPA, and alpha-MSH. Nevus cells are largely independent of bFGF. Depletion of TPA from medium is not as detrimental to nevus cells as it is to melanocytes, but the phorbol ester is still essential for maintenance of the typical nevic phenotype. Primary melanoma cells require at least one growth factor, IGF-I (or insulin), for continuous proliferation. On the other hand, metastatic cells of melanoma as well as of carcinomas of colon and rectum, bladder, ovary, and cervix are able to proliferate after a short adaptation period in medium depleted of any growth factors and other proteins. Doubling times of metastatic tumor cells in protein-free medium are only 30-60% longer than in FCS-containing medium. The growth autonomy of human tumor cells is apparently due to the endogenous production of growth factors. Likely candidates for autocrine growth stimulation of human tumor cells are TGF-alpha, TGF-beta, and PDGF. Melanoma and colorectal carcinoma cells express functional EGF/TGF-alpha receptors, and produce TGF-alpha, indicating that this growth factor is produced for autocrine stimulation. In addition to the use of anti-growth factor antibodies, other strategies for the inhibition of autocrine growth stimulation include mAbs to growth factor receptors, soluble receptors, receptor-mimicking antiidiotype antibodies, and active immunization against growth factors. Whether any of these therapeutic approaches is clinically feasible will need to be determined in extensive preclinical investigations.

Growth Substances↗
PubMed1990

[Tumor progression and metastasis].

The heterogeneity of cells capable of metastasation has proved to be the greatest obstacle to successful treatment or to prevention of metastatic diseases. This variety appears to be attributable to processes of selection. Cytobiological investigations which are helpful in casting some light at selective mechanisms of metastasation may, perhaps, make substantive contributions to cancer therapy.

Humans↗
PubMed1988

Effects of somatostatin-14 on gastric and pancreatic responses to hormonal and neural stimulation using an isolated perfused rat stomach and pancreas preparation.

To study the role of somatostatin in the regulation of pancreatic and gastric functions, a combined isolated rat stomach and pancreas preparation was developed. This model allowed simultaneous measurements of exocrine and endocrine secretion from the pancreas and gastrin secretion from the stomach. Somatostatin was applied either by a linear gradient or by constant infusion with one concentration in the presence of cerulein, secretin, electric vagal activity, or acetylcholine. Somatostatin did not influence exocrine pancreatic secretion irrespective of what substance was stimulated. In contrast, somatostatin significantly inhibited glucose-dependent insulin and gastrin secretion, either basal or stimulated by vagal activity or acetylcholine. Acetylcholine-induced gastrin secretion was more sensitive to inhibition by somatostatin than insulin. We conclude that in an isolated perfused organ system somatostatin has potent inhibitory effects on endocrine pancreas and stomach but has no effect on exocrine pancreatic volume and enzyme secretion.

Amylases↗
PubMed1987

[Tumor lysis syndrome in a young patient with Burkitt-type lymphoblastic lymphoma].

A tumor lysis syndrome with hyperkalaemia, hyperphosphataemia, hyperuricaemia and hypocalcaemia developed 48 hours after start of combined cytostatic treatment in a 16-year-old boy with Burkitt's lymphoma. Despite prophylactic administration of allopurinol and urinary alkalization, postrenal precipitation of urates and calcium phosphate caused acute renal failure. Ureteric splinting and percutaneous fistulization of the contralateral renal pelvis became necessary. Elevated renal retention values became normal after these measures and infusions with balanced alkalized electrolyte solutions, and the hypocalcaemia was counteracted.

Adolescent↗
PubMed1987

Invasive bronchopulmonary aspergillosis leading to rapidly progressive respiratory failure in a patient with severe aplastic anemia.

A 22-year-old man with severe aplastic anemia was treated with antilymphocyte globulin, prednisone, and oxymetholone. Fourteen days after initiation of treatment he developed a fulminant mediastinal and subcutaneous emphysema leading to respiratory failure refractory to mechanical ventilation. Fiberoptic bronchoscopy showed nodular lesions typical of aspergillus. Cultures of bronchial mucus revealed Aspergillus fumigatus as the responsible pathogen.

Adult↗
PubMed1986

[Therapy of primary resistant or recurrent small cell bronchial carcinoma with vindesine and ifosfamide].

A combination of vindesine (3 mg/m2, day 1) and ifosfamide (60 mg/kg, days 1-5 + Mesna) was administered every three weeks to 11 patients with primary resistant and 23 with recurrent small-cell bronchial carcinoma. All patients had been pre-treated with chemotherapy, 16 in addition with radiotherapy. At the onset of the vindesine-ifosfamide treatment the cancer was in a localized regional stage in ten patients, while in 24 it was in a more widely spread stage. In 29 patients whose treatment results could be evaluated the remission rate was 38%, with two complete and nine partial remissions. In a further eight patients the cancer was arrested. The patients with complete remission (for 46 and 53 weeks, respectively), those with partial remission (median of 39 weeks) and those with stationary disease (median of 31 weeks) survived significantly longer than those with progressing disease (13 weeks). There was no correlation between treatment result and pre-treatment. On recurrence after complete remission or in the localized regional stage the remission rate was 70% and 60%, respectively, and the survival time was extended in 90% of cases. In addition to nausea, alopecia and myelosuppression, side-effects included vomiting, reversible CNS symptoms, polyneuropathy and urotoxicity. On the basis of acceptable toxicity, combined vindesine and ifosfamide constitute an effective treatment of otherwise treatment-refractory cases of small-cell bronchial carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Tumor progression in the human melanocytic system.

The isolation and routine tissue culture of melanocytic cells from normal skin, precursor nevi, primary and metastatic melanomas has allowed the experimental study of different stages of tumor progression. Characteristic differences between cultured normal melanocytes and highly malignant metastatic melanoma cells were: 1) limited life span for normal melanocytes and non-malignant nevus cells versus infinite growth for malignant melanoma cells; 2) inability to grow anchorage-independently versus high colony forming-efficiency in soft agar; 3) non-tumorigenicity versus tumorigenicity in athymic nude mice; 4) dependence on exogenous growth factors and other mitogens versus autonomous growth in protein-free medium; 5) expression of melanocyte-associated antigens versus expression of melanoma-associated antigens; and 6) diploid karyotype versus non-random chromosomal abnormalities. The only major distinction found between advanced primary and metastatic melanomas was that only metastatic melanoma cells proliferated continuously in the absence of growth factors or other proteins. However, advanced primary melanoma cells could be clearly distinguished from dysplastic nevus cells by their growth behavior and growth factor requirements. Only limited information is available on the biologic, genetic, immunologic and molecular properties of dysplastic nevus cells and early (radial growth phase) primary melanoma cells but these cells appear to differ markedly from advanced primary and metastatic cells. The availability of cells from sequential steps of tumor progression in the human melanocytic system offers a unique experimental model for the study of malignant transformation.

Animals↗