Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RA 233, a pyrimido-pyrimidine analogue developed originally as an antiplatelet agent, has reduced the incidence of tumor metastases in clinical trials. However, in animal tumor models antimetastatic therapy using RA 233 has been inconsistent. We therefore tested RA 233 for additional effects, such as its direct action on tumor cells. Using the rat 13726NF mammary adenocarcinoma tumor system, low, nontoxic concentrations of RA 233 had pleiotropic and differential effects on two 13762NF tumor cell clones. The growth of MTC cells (low spontaneous metastatic potential) was not affected by low concentrations of RA 233 (50 microM) or epidermal growth factor (EGF) (up to 10 ng/ml) for 3 days in 0.5-10% fetal bovine serum. In contrast, MTLn3 (high spontaneous metastatic potential) cell cultures maintained for 3 days in low (0.5-1%) serum in the presence of 1.25-10 ng/ml EGF doubled in cell numbers compared with control cultures, and addition of 50 microM RA 233 abrogated the growth-stimulatory effect of EGF. The inhibitory effect of RA 233 on MTLn3 cells was dose dependent and not due to cell toxicity as determined by cell viability, cell growth, and colony formation properties after drug removal. In addition, incubation of MTLn3 cells with 50 microM RA 233 resulted in an increase of p21ras protein expression, whereas there was no effect on the level of p21ras in identically treated MTC cells or when either clone was treated with 10 ng/ml EGF. The results suggest that among the heterogeneous effects of RA 233 on tumor cells, modulation of growth factor responses and regulatory molecules may be important.
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PMID:Pyrimido-pyrimidine modulation of EGF growth-promoting activity and p21ras expression in rat mammary adenocarcinoma cells. 305 58

Nine cases of medullary carcinoma of the thyroid gland (MTC) are reported. Four of the carcinomas were of the familial type. Five of the patients were men and four were women. Patient age ranged from 23 to 66 years, with a mean age of 40 years. The median age of the four patients with the familial MTC was 32 years. A total or a subtotal thyroidectomy was performed in four and five patients, respectively, associated with a modified neck dissection in six patients with involved cervical lymph nodules. An underlying pheochromocytoma of the left adrenal was excised in one patient prior to thyroidectomy. In all cases the parathyroid glands were identified, and in two cases of familial MTC, in which they were grossly enlarged, the parathyroid glands were removed. Four patients died as a result of their disease within 3 years, whereas patients are well 4 to 12 years after surgery. The best chance of cure lies in early diagnosis and an aggressive surgical removal of the primary tumor and any cervical metastases.
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PMID:Medullary carcinoma of the thyroid gland. 357 51

Three rat 13762NF mammary adenocarcinoma clones and cell lines of different metastatic potentials (MTLn3, MTC, and MTPa) were studied for their proton nuclear magnetic resonance spectral characteristics as intact cells in vitro and after chloroform/methanol, neuraminidase, or ethanol treatments. The intact-cell spectral characteristics of the highly metastatic tumor cell clone MTLn3 were clearly distinguished from the less metastatic clone MTC or the parental MTPa cell line on the basis of spectral peaks in the range of 0.9 to 1.45 p.p.m. broad peaks near 2.0 p.p.m., and peaks in the range of 2.75 to 3.2 p.p.m. Glycoproteins are among the molecules known to have resonances in these upfield spectral regions, and these tumor cell subpopulations have previously been shown to possess characteristic quantitative differences in cell surface, metastasis-associated glycoproteins. Treatment of the cells with neuraminidase or ethanol, or extraction with chloroform/methanol increased spectral detail and also revealed characteristic differences in spectral peaks between the tumor cell subpopulations. The identity of the cellular components responsible for these spectral characteristics are unknown, but some clearly arise from differences in the extractable lipids present in the tumor cell subpopulations. Further study will be required to determine if the spectral differences described in this preliminary report are directly related to the known biochemical characteristics of the highly metastatic clone, and if the observations have general relevance to metastatic potential or are a singular feature of these cells. However, these initial results suggest that manipulation of factors which allow unmasking of spectral detail combined with the use of prescribed tumor cell subpopulations may aid in using proton NMR to identify and define biochemical or structural differences related to the metastatic potential of tumor cells.
Clin Exp Metastasis 1987 Sep
PMID:Proton NMR examination of tumor cells of high or low metastatic potential. 365 55

Primary cultures of human medullary thyroid carcinoma tissue were prepared from lymph node metastases in two patients. The parenchymal, cultured cells displayed positive immunocytochemical staining for CT, and the cells also released the hormone into the culture medium. The membrane potential and resistance of the CT-producing cells were 50.1 +/- 8.9 mV and 634 +/- 154 M omega (mean +/- SD, n = 46). TTX sensitive action potentials with maximum rate of rise up to 51 V s-1 were evoked by current injection in Na+-containing solution, whereas TTX insensitive action potentials with maximum rate of rise up to 9 V s-1 were generated in Na+-free solution. These action potentials were reversibly blocked by D-600. We conclude that the action potentials of the human MTC cells have both a Na+ and a Ca2+ component. Ejection of CA2+-free solution close to the cells caused membrane hyperpolarization associated with decreased membrane resistance. The reversal potential of this response was -66.2 +/- 10.9 mV (n = 10), indicating that a permeability increase to Cl- and/or K+ may be involved. We suggest that elevated plasma Ca2+ concentration in vivo may cause increased excitability due to membrane depolarization and resistance increase, thus leading to enhanced Ca2+ influx and hormone secretion.
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PMID:Electrophysiological properties of calcitonin-secreting cells derived from human medullary thyroid carcinoma. 370 81

Spleen cells from rats bearing syngeneic metastatic 13762NF mammary adenocarcinoma clone MTLn3 tumors were fused with the rat myeloma Y3 Ag1.2.3 to generate a panel of monoclonal antibodies (MAbs). The MAbs could be divided into three groups: those cross-reactive with all 13762NF cells; those reactive with cloned MTLn3 and MTC cells; and those predominantly reactive with the highly metastatic MTLn3 cells. One of these MAbs, MT10:21 (an immunoglobulin G2a), binds predominantly to highly metastatic MTLn3 cells and has a high tumor-cell affinity as determined by its saturation kinetics. MAb MT10:21 has a 6-h half-life on the MTLn3 cell surface and a 24-h half-life in the blood of syngeneic rats. Immunoblotting experiments using lysates from the cloned 13762NF sublines revealed that MAb MT10:21 binds to several proteins having relative molecular weights of 72,000, 73,000, and 120,000. Using an immunohistochemical procedure with frozen tissue sections, MAb MT10:21 shows little reactivity with normal rat mammary tissue, irrespective of the stage of the estrous cycle, and it failed to react with a number of other normal fetal and adult tissues. Furthermore, MAb MT10:21 is heterogeneous in its reactivity to cloned sublines of the 13762NF mammary adenocarcinoma, on both tissue cultured cells and tissue sections prepared from tumors growing in situ in the mammary fat pads of syngeneic rats. MAb MT10:21 reacted with certain human breast cancer cell lines and with a subpopulation of metastatic human breast cancer cells in frozen tissue sections from biopsies and autopsies. Metastases from breast cancers reacted more intensely than the primary tumors from which they were derived.
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PMID:Monoclonal antibodies against cell-surface antigens of the metastatic rat 13762NF mammary adenocarcinoma and their cross-reactivity with human breast carcinomas. 377 54

Tumor cell subpopulations have been shown to be heterogeneous in a number of phenotypic characteristics, including responses to cytotoxic drugs. This phenotypic heterogeneity has been used here to study mechanisms associated with Adriamycin (doxorubicin HCl)-induced cytotoxicity. Clonogenic survival and alkaline elution methods were employed to examine the response of two tumor cell subpopulations to Adriamycin. The cells were derived from a primary 13762NF rat mammary adenocarcinoma (clone MTC) and a lung metastasis in the same animal (clone MTLn3). The MTC cells were significantly more resistant to Adriamycin than were the MTLn3 cells; the dose effective in reducing cell survival by 50% was 10-fold higher. Protein-associated DNA strand breakage assayed by alkaline elution was dose-dependent in both clones, and MTC cells were again more resistant to break induction than were MTLn3. These results showed that clonal tumor subpopulations isolated from a primary tumor and its metastases possessed different intrinsic survival responses to Adriamycin treatment in vitro and that this survival response correlated with Adriamycin-induced production of protein-associated DNA single-strand breaks.
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PMID:Survival of rat mammary tumor cell clones and DNA strand damage following adriamycin treatment. 379 58

The importance of host immune status on the spontaneous metastasis of cloned cell lines of the 13762NF rat mammary adenocarcinoma was examined. Cell lines MTLn3 (high metastatic potential), MTF7 and MTLn2 (intermediate metastatic potential) and MTC (low metastatic potential) were subjected to a series of in vivo assays designed to assess how manipulation of the immune system in the syngeneic F344 host would affect the ability of these cells to metastasise. Treatment of tumour bearing rats with the immunosuppressive agents cyclosporin A or cyclophosphamide had little influence on metastasis in this system. Growth of tumours in congenitally athymic nude rats resulted in reduction of observed metastases. In addition, humoral immune response was not detectable during a 23-day period of tumour growth in F344 rats. Excision of the tumour growing in situ reduced the number of metastases when the tumours were resected early (less than 10 days), but at later times tumour resection did not influence the incidence of metastasis. The importance of initial lymphatic rather than haematogenous routes of dissemination was confirmed in experiments where the draining inguinal and axillary lymph nodes were removed at different times either before, or after, subcutaneous mammary fat pad injection of metastatic tumour cells.
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PMID:Effect of host immune status on the spontaneous metastasis of cloned cell lines of the 13762NF rat mammary adenocarcinoma. 406 49

Rat 13762 mammary adenocarcinoma cell clones of differing spontaneous metastatic potentials were tested for their sensitivities to Adriamycin, 5-fluoro-2'-deoxyuridine (FUdR) and methotrexate in vitro. Cells were treated 4 hours with a single dose of drug, and colony formation was used to assay cell survival. Dose-response curves and survival parameters were calculated for local tumor-derived clones MTC and MTF7 and lung metastasis-derived clone MTLn3. The logarithmic curves were analyzed (slope and y-intercepts) for statistical comparisons. Heterogeneous sensitivities to Adriamycin and FUdR were observed, but there was no difference in the sensitivities of the clones to methotrexate cell killing. We could not find correlations between drug response and clonal origin, passage number or metastatic properties. The sensitivities of the clones to Adriamycin and FUdR changed upon in vitro passage, although drift in Adriamycin sensitivity during growth in culture was not statistically significant. The results demonstrate that clonal heterogeneity exists within the 13762 tumor and its metastases in their inherent responses to chemotherapy agents, and in the absence of host selective pressures tumor cells can spontaneously and reproducibly drift in their sensitivities to certain chemotherapeutic drugs.
Clin Exp Metastasis
PMID:Phenotypic drift and heterogeneity in response of metastatic mammary adenocarcinoma cell clones to adriamycin, 5-fluoro-2'-deoxyuridine and methotrexate treatment in vitro. 624 7

Tumor cell clones isolated from a rat 13762NF mammary adenocarcinoma and its spontaneous metastases were heterogeneous in their survival responses to continuous 42 degrees heating. Clones MTLn3 and MTF7 had similar initial survival responses; they were significantly less sensitive than clone MTC. Following the first decrease in survival, different magnitudes of induced thermal resistance were observed. When ratios of the first and resistant slopes of survival curves were compared (the thermotolerance ratio), the order of induced thermal resistance was MTLn3 greater than MTF7 greater than MTC. These clones were compared for the rates of synthesis of heat stress proteins (HSP). The same four major HSP at Mr 112,000, 90,000, 70,000, and 22,000 were induced or enhanced in all 3 clones. The rates of synthesis of these HSP were analyzed through a unique system of computer-assisted video densitometry and digitization. When all 4 HSP were analyzed as a group, the rates were significantly different (p less than 0.017), and the rank order of rates of synthesis was significant with MTLn3 greater than MTF7 greater than MTC. Induction kinetics of the individual HSP were different. Individually, the HSP at Mr 112,000, 90,000, and 22,000 were synthesized at significantly different rates between clones (p less than 0.001) but the Mr 70,000 HSP was not. Absolute total protein synthesis was highest for clone MTLn3, and MTF7 was higher than MTC but only marginally. Although absolute accumulations of these HSP could not be directly compared between these clones, the higher rates of HSP synthesis in these tumor cell clones correlated with more thermal resistance. These data support the working hypothesis that one or more of these HSP have a direct role in the mechanism(s) for inducing thermal resistance in rat tumor cells, but other factors such as total protein synthesis could modify the complex bio-chemical and phenotypic pathways involved in induced HSP and thermal resistance.
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PMID:Heterogeneity in induced heat resistance and its relation to synthesis of stress proteins in rat tumor cell clones. 649 45

Chromosome morphologies revealed by Giemsa-banded karyotypes and chromosome numbers were compared between parental tumor-, lymph node- and lung metastasis-derived rat 13762NF mammary adenocarcinoma cell lines and clones having different spontaneous metastatic potentials. Although chromosome numbers in the cell lines and clones generally correlated with DNA content by flow cytometry, ploidy did not correlate with spontaneous metastatic potentials. Chromosome number and DNA content drifted during prolonged in vitro growth in each of the cell lines and clones. Common chromosome rearrangements were found, confirming a common origin for all the cell lines and clones, and the frequency and appearance of the individual marker chromosomes fluctuated during in vitro growth. Karyotypic analyses revealed that the markers coinciding with phenotypic drift in spontaneous metastatic potential and other biological properties of parental tumor-derived clones MTC and MTF7 and lung metastasis-derived clone MTLn3 involved chromosomes 3, 4, 5, 6, and 8. Clone MTC exhibited a shift in several markers and an increase in metastatic potential at passage T20, while clone MTF7 displayed a lesser spontaneous metastatic potential at high passage (T34) concomitant with an increase in the frequency of certain marker chromosomes. Lung metastasis-derived clone MTLn3 also exhibited a shift in some marker chromosomes, colonization preference and metastatic potential to lung and lymph nodes at high tissue culture passages. The changes in marker chromosomes during in vitro passage of clones MTC and MTLn3 suggested the presence of at least two cell subpopulations which could be responsible for the observed shift in spontaneous metastatic properties. Karyotypic features of the 13762NF cell lines and clones indicate that subtle cytogenetic changes, in contrast to gross chromosomal abnormalities, may be more important in determining metastatic phenotype.
Clin Exp Metastasis
PMID:Chromosome and DNA analyses of rat 13762NF mammary adenocarcinoma cell lines and clones of different metastatic potentials. 654 5


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