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)

We have developed transgenic mice that inherit albumin promoter-regulated simian virus 40 (SV40) large T antigen gene, expressed specifically in hepatocytes. These mice all develop multifocal hepatocellular carcinomas at around 5 months and die of liver insufficiency by 7 months. Sequential morphological observation of hepatocarcinogenesis revealed 5 distinct stages: (I) newborn to 2 weeks of age, neither recognizable histological changes nor cellular replication in spite of T antigen expression; (II) between 3 and 7 weeks, diffuse cytomegalic change of hepatocytes with numerous abnormal mitoses, usually resulting in cell death; (III) from 7 weeks onwards, quasi-regenerative small hepatocyte foci with a decreased tendency for cytomegaly in spite of T antigen expression, rapidly replacing the hepatic tissue; (IV) 11 weeks of age and thereafter, neoplastic foci and nodules with enzymatic alteration; (V) 20 weeks of age and thereafter, gross hepatocellular carcinomas with occasional pulmonary metastases. Considerable variation existed both in morphological and enzymatic features and T antigen expression among neoplastic lesions, including carcinomas. Thus, these transgenic mice clearly show a multistep process in hepatocarcinogenesis with remarkable synchrony and provide a promising model for analyzing the essential events of carcinogenesis at different stages.
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PMID:Hepatocarcinogenesis in transgenic mice carrying albumin-promoted SV40 T antigen gene. 168 56

Squamous cell carcinomas (SCC) of the mouse skin were produced by three different protocols of chemical carcinogenesis, i.e., complete carcinogenesis with 7,12-dimethylbenz(a)anthracene (DMBA) two-stage carcinogenesis with DMBA as initiator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) as promoter and three stage carcinogenesis with DMBA, TPA and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as third-stage agent or progressor. Tumors were sequentially studied at weeks 38-52 of treatment. Although no significant differences in the rate of appearance of gamma-glutamyl transpeptidase (GGT) could be seen, a larger number of SCC produced by complete carcinogenesis protocols were GGT-negative. This coincided with the higher grade of malignancy of these tumors as evaluated by histopathology. In general terms high-grade tumors were seen more frequently in the complete carcinogenesis experiment than in the other two protocols. SCC produced by complete carcinogenesis also exhibited a markedly higher DNA index than the SCC from the other experimental groups. All three protocols were very effective in producing late metastasizing tumors, and no significant differences could be established in the incidence of spontaneous lung metastasis. This shows that, contrary to general knowledge, if adequately observed for more than 40 weeks, SCC of the murine skin is able to metastasize in the lung in approximately 30% of cases. Nevertheless, complete carcinogenesis-induced SCC were usually of higher histological grade, a proportion of these were GGT-negative and produced more multiple or diffuse metastases than the tumors induced by the multistage protocols.
Invasion Metastasis 1991
PMID:Metastatic potential of mouse skin carcinomas produced by different protocols of chemical carcinogenesis. 168 75

Transforming growth factor-alpha (TGF-alpha) is frequently coexpressed with its receptor, epidermal growth factor receptor (EGF-R), in several types of carcinoma and sarcoma. It is believed that this results in an autocrine stimulation of tumor growth in these tumors. We have found that TGF-alpha and EGF-R/c-erbB RNAs were co-expressed at significantly higher levels in papillary thyroid carcinomas and their lymph-node metastases than in non-neoplastic thyroid tissues. We also observed a low level of expression of RNA specific for insulin-like growth factor I in these tumors, which was highest in a lymph-node metastasis. Autocrine stimulation by TGF-alpha may thus be a common feature of papillary carcinomas of the thyroid. Since EGF is known to induce proliferation and dedifferentiation of normal thyroid cells in culture, TGF-alpha and its receptor may play an important role in thyroid carcinogenesis.
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PMID:Co-expression of the genes encoding transforming growth factor-alpha and its receptor in papillary carcinomas of the thyroid. 169 67

Tumors derived from a Li-Fraumeni syndrome cancer-susceptible family were examined for expression of the retinoblastoma susceptibility gene (RB). Whereas RB expression was normal in a primary breast carcinoma and its metastases from one member of this family, overexpression of RB was found in an adrenocortical carcinoma from another family member. This was in contrast to normal RB expression in normal tissue of this patient, the adrenocortical adenocarcinoma cell line SW-13, and the fibroblast cell line MRC-5, and low level RB expression in normal adrenal tissue. The overexpression in the adrenocortical carcinoma resulted in increased synthesis of the RB-encoded protein and did not appear to be associated with RB amplification or rearrangement. This result is novel as it is usually the loss of expression or production of an altered RB transcript exhibiting deletions that is associated with carcinogenesis. In light of the recent discovery of p53 point mutations in the affected Li-Fraumeni syndrome family members tested, RB overexpression may constitute a secondary event in Li-Fraumeni syndrome tumorigenesis.
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PMID:Overexpression of the retinoblastoma gene in a familial adrenocortical carcinoma. 175 10

Gastrin is trophic to colon cancers that possess gastrin receptors. Whether fasting serum gastrin concentrations are high in patients with colon cancer is controversial. We therefore studied the effect of food on serum gastrin concentrations in patients with colon cancer and control subjects. Fasting serum gastrin was greater, though not significantly so, in patients with colon cancer before surgery (mean (SD) 17.4 (3.6) pmol/l, n = 16) compared with control subjects (12.6 (1.9) pmol/l, n = 14). Postprandial increases in serum gastrin were significantly and persistently higher than normal in the cancer patients. These increases were due to a subset of six patients with serum gastrin concentrations greater than the control mean + 2 SD at 20 and 40 minutes (62 pmol/l-146 pmol/l). Four of the six patients had intra-abdominal metastases. The extent of the increase may well correlate with that of the disease. Surgical resection of the tumour resulted in a fall in serum gastrin values and probably reflects the cause of the hypergastrinaemia. Hypergastrinaemia may, therefore, be an important aetiological factor in colon carcinogenesis.
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PMID:Postprandial hypergastrinaemia in patients with colorectal cancer. 175 67

Renal pelvic carcinoma was induced in mice by giving N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Initially, differences in renal pelvic carcinogenesis by BBN were examined in three male mouse strains: NON/Shi, which demonstrate spontaneous hydronephrosis with incidences of 10-30%, and DS/Shi and B6C3F1, which do not exhibit hydronephrosis. When mice of these strains were given 0.05% BBN in the drinking water for 12 weeks followed by water without BBN for 8 weeks, renal pelvic carcinoma morphologically similar to human carcinomas developed in 8 of 23 NON/Shi mice (35%). Metastasis to the lung was found in one of them (13%). B6C3F1 and DS/Shi mice had no pelvic tumors, but the response to urinary bladder carcinogenesis in NON/Shi mice was nearly equal to that in DS/Shi and B6C3F1 mice. These results suggest that renal pelvic carcinogenesis is related to the presence of stagnant urine containing carcinogen in the renal pelvis. In a second experiment, we examined renal pelvic carcinogenesis in NON/Shi mice given BBN for 4 weeks followed by water without BBN for 32 weeks. The incidence of renal pelvic carcinoma (28%) was similar to that in the first experiment, but the incidence of metastasis was markedly elevated to 60%. These results indicate that BBN treatment can induce renal pelvic carcinoma which often metastasizes to the lung in NON/Shi mice.
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PMID:Renal pelvic carcinoma which shows metastatic potential to distant organs, induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice. 177 60

Speciation and carcinogenesis result from genomic instability at the gametic or at the somatic levels. After an infinity of trials they occur, by chromosome rearrangements, in single individuals or in single cells and evolve by similar chromosomal or clonal evolutions. Loss of heterozygosity for the first event is essential in both processes: in evolution, a chromosomal rearrangement, a pericentric inversion or a Robertsonian fusion, must become homozygous to ensure a reproductive barrier for a new species; Knudson's two-event sequence is a similar situation in cancer. Position effect is equally important: we have shown overexpression of the SOD1 gene in the orangutan phylum probably by an intrachromosomal rearrangement; the t(9;22) in CML acts by typical position effect. Parental imprinting underlies the evolution of genome function and the unset of certain cancers. Evolution and malignancy are interweaved by viruses and oncogenes since the dawn of life. Cancer uses its intelligence to expand and to destroy the other tissues, using subtle metabolic pathways and a variety of tricks to metastasize other cells. It always wins but saws the branch on which it sits. Mankind also grows exponentially, killing thousands of other species, poisoning the oceans and soft waters, polluting the atmosphere, all for his egoistic needs. Man also travels and metastasizes other Earths. He modifies his genome or that of other species, and develops new technologies for his reproduction. He can destroy the planet in an eyeblink. To be or not to be the malignant primate, that will be the dilemma for the 21st Century.
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PMID:The malignant primate? 180 19

The growth of human prostate cancer and its relationship to the surrounding stroma are controlled by complex mechanisms that are incompletely understood. Clearly, peptide growth factors appear to have crucial roles in these processes. One of these factors, TGF-beta, and its family members are notable for their wide spectrum of biological effects. In terms of growth, TGF-beta inhibits the growth of prostate cancer cells in a cytostatic fashion while stimulating the growth of critical stromal cells, such as fibroblasts. Since the inhibitory effects of TGF-beta on prostate cancer cells appear to diminish as the process of transformation progresses towards less differentiated states, the net effect on prostate tumour growth may be positive. Recent evidence suggests that the inhibitory effects of TGF-beta on growth, at least, might be mediated through the RB tumour suppressor gene product and the proto-oncogene c-myc. Beyond its direct growth effects, TGF-beta also alters the response of prostate cancer cells to positive mitogenic factors, such as members of the EGF and FGF families, suggesting that growth control is a delicate balance between positive and negative influences. Non-mitogenic responses to TGF-beta by prostate cancer cells, the immune system, the stroma and the vascular system provide evidence that TGF-beta might also be important in the processes of carcinogenesis, tumour establishment and metastases. In addition, TGF-beta appears to influence metabolic pathways important to drug metabolism and steroidogenesis. In vivo, limited evidence suggests that TGF-beta can alter the growth and differentiation of some tumour types but appears to be very toxic when administered in high doses. A better understanding of the response of prostate cancer cells to members of the TGF-beta family may open new avenues of treating and controlling this disease.
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PMID:Response of prostate cancer cells to peptide growth factors: transforming growth factor-beta. 184 49

We have reviewed retrospectively the records of 157 patients, less than or equal to 30 years of age with nasopharyngeal carcinoma (NPC) from 218 such cases identified in the tumor registry files of three major teaching hospitals in Taipei, Taiwan. These cases were diagnosed between 1 January 1982 and 31 December 1985, with a minimum follow-up of 2 years. The average age was 25, with a male/female ratio of 1.67. The TNM (tumor size, nodes, metastases) classification of 127 patients showed T1, 22%; T2, 33.1%; T3, 23.6%; T4, 21.3%; N0, 26%; N1, 16.5%; N2, 27.6%; N3, 30%; and M1, 13.4%. Antibody titer to Epstein-Barr virus capsular antigen (EBVCA) were elevated in 45 of 48 patients tested. Of the 29 patients who had hepatitis B (HB) viral survey done 34.5% were positive for HB surface antigen (HBsAg). Of 13 patients with elevated EBVCA antibody who were also tested for HB, six were HBsAg carrier. Actuarial survival rates of 2 and 3 years are 70 and 62%, respectively, among the 90 patients who were followed regularly or to death. HBsAg carriers and patients with M1 disease had a shorter survival time. We concluded that patients less than 30 years of age seemed to have an increased incidence of NPC, compared to that in an earlier report. Our patients frequently presented with advanced stage and poor prognosis. The high rate of HB carrier raises the possibility that HBV may play a role in the carcinogenesis and tumor growth in some NPC patients. Future prospective studies are needed.
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PMID:Nasopharyngeal carcinoma in young patients. 184 56

Results from epidemiological studies have generally indicated an association of dietary saturated animal fats with human breast cancer risk. Some studies, however, have suggested a similar association for some polyunsaturated vegetable fats shown to promote both rodent mammary carcinogenesis and metastasis. This study was performed to evaluate the effects of corn oil on growth and metastasis of MDA-MB-435 human breast cancer cells, which have a propensity for metastasis. Corn oil is rich in the omega-6 fatty acid linoleic acid. Fifty-eight female athymic nude mice (NCr-nu/nu) were fed a high-fat diet (23% wt/wt corn oil; 12% linoleic acid) or a low-fat diet (5% wt/wt corn oil; 2.7% linoleic acid). Seven days after diets were started, tumor cells (1 x 10(6) were injected into a mammary fat pad. The time to appearance of solid tumors and the tumor size were recorded. After 15 weeks, the study was terminated, and autopsies were performed to determine the weight of the primary tumor and the extent of metastasis. The latent interval for tumor appearance in the animals fed the high-fat diet was shorter than that in the low-fat diet group, and the tumor growth rate in the high-fat diet group showed a small but statistically significant increase compared with the low-fat diet group. Primary tumors developed in 27 of the 29 mice on the high-fat diet and in 21 of the 29 on the low-fat diet. Of the mice with palpable primary tumors, 18 of 27 in the high-fat diet group and eight of 21 in the low-fat diet group had macroscopic lung metastases. The extent of metastasis in the high-fat diet group was independent of the primary tumor weight, but only those in the low-fat diet group with primary tumors weighing more than 2 g developed metastases. These results suggest that a high-fat diet rich in omega-6 polyunsaturated fatty acid can enhance metastasis of human breast cancer cells in this mouse model. The findings support the need for further study of the relationship between dietary polyunsaturated fats and breast cancer risk and for experiments to determine the effect on metastasis of only a 50% difference in fat intake--the dietary goal of the proposed clinical trials of low-fat dietary intervention in breast cancer patients.
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PMID:Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. 173 78


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