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)

Apoptosis, or programmed cell death, is an endogenous cellular process whereby an external signal activates a metabolic pathway that results in cell death. This form of cell death appears to be a common feature in many biological processes where cell deletion is a mechanism for altering tissue structure and function. Historically, apoptosis has been studied using histological techniques; however, more recent interest has focused on analyzing this process at the biochemical level. A biochemical hallmark of apoptosis is a characteristic form of DNA degradation in which the genome is cleaved at internucleosomal sites, generating a 'ladder' of DNA fragments when analyzed by agarose gel electrophoresis. A number of assay systems have been developed to study this nuclease activity. For example, nuclease activity has been analyzed by measuring the release of endogenous DNA from apoptotic cells, by flow cytometric analysis of apoptotic cells and by analyzing in situ apoptotic nuclease activity in polyacrylamide gels containing DNA. Use of these assay systems has enabled investigators to study the signal transduction pathways that mediate apoptosis and to characterize the endonuclease itself. Future biochemical studies in this field will focus on isolating the genes and gene products that mediate apoptosis.
Cancer Metastasis Rev 1992 Sep
PMID:A biochemical hallmark of apoptosis: internucleosomal degradation of the genome. 132 65

Most of the cytotoxic anticancer drugs in current use have been shown to induce apoptosis in susceptible cells. The fact that disparate agents, which interact with different targets, induce cell death with some common features (endonucleolytic cleavage of DNA, changes in chromatin condensation) suggests that cytotoxicity is determined by the ability of the cell to engage this so-called 'programmed' cell death. The mechanism of the coupling of a stimulus (drug-target interaction) to a response (cell death) is not known, but modulation of this coupling may affect the outcome of drug treatment. This review surveys the recent evidence which supports the idea that the drug-target interaction per se is not the sole determinant of cellular sensitivity of cytotoxic drugs. Studies of the signals which might engage apoptosis, the genes which modulate it and the biochemical process of drug-induced apoptosis itself are described, where possible, for glucocorticoids, topoisomerase inhibitors, alkylating agents, antimetabolites and antihormones. It is suggested that identification of the gene products which couple the stimulus to the response, and so determine intrinsic cellular sensitivity (and resistance), will be important targets for new types of drugs. These might then allow responses to occur in the major cancers of man, which are chemoresistant.
Cancer Metastasis Rev 1992 Sep
PMID:Apoptosis induced by anticancer drugs. 132 66

61 squamous cell cancers (27 laryngeal, 12 hypopharyngeal, 14 tonsillary, 8 tongue) with different keratinization and grading and seven lymph node metastases of HPV 16/18 positive carcinomas were analysed for the presence of HPV-DNA by in situ hybridisation. 65.5% of them were found to be positive. Twelve laryngeal carcinomas (44%), five tonsillary tumours (35.7%), eight tumours of the hypopharynx (66.6%) and three tongue carcinomas (37.5%) were shown to contain HPV 16/18 DNA. The detection rates of HPV 6/11 were lower. 44 of the analysed tumours (72.1%) had a grading G2. 29 of these tumours (65.9%) were HPV positive. Only eight of the patients were no heavy smokers or alcoholic drinkers. One of the lymph node metastases was positive for HPV 16/18. The results indicate that HPV may be involved in the pathogenesis of squamous cell carcinomas of head and neck tumours.
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PMID:[Type 6/11 and 16/18 squamous epithelial cancers of the upper respiratory tract and digestive system. An in situ hybridization study]. 132 98

A 31-year-old woman is reported with in the genital region multiple squamous carcinomas of the skin (buttock), vulva, vagina, anus and cervix uteri. All these carcinomas were HPV 16 positive as tested by DNA in situ hybridization. The existence of areas with normal epithelium between all tumor localisations and the absence of distant metastases indicate multicentric development of these multiple carcinomas. The presence of HPV 16 DNA in all carcinoma cells, as detected by DNA in situ hybridisation, argues for an etiological role of HPV 16 in the development of these multiple tumors.
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PMID:Multiple HPV 16-related squamous cell carcinomas of the vulva, vagina, anus, skin and cervix in a 31-year-old woman. 133 Jul 60

The ploidy status of the deoxyribonucleic acid of a malignant lung tumor provides additional information besides histologic grading and tumor staging according to lymph node infiltration and tumor metastasis. Ninety-nine surgical specimens from patients with non-small-cell lung carcinoma were investigated by flow cytometry. Deoxyribonucleic acid aneuploidy was found in 48% of the primary tumors. Patients with deoxyribonucleic acid-euploid tumors showed better survival (p < 0.01) than those with deoxyribonucleic acid-aneuploid carcinomas independent of tumor stage. Deoxyribonucleic acid ploidy status of the primary tumor was compared with that of N2 lymph node metastases in 29 cases. Seven samples showed a change from deoxyribonucleic acid aneuploidy in the primary tumor to deoxyribonucleic acid euploidy in the lymph node metastases. Survival was significantly better for patients with euploid primary tumors and lymph node metastases, followed by patients with deoxyribonucleic acid-aneuploid primary tumors and euploid lymph node metastases. Survival was poorest in patients with deoxyribonucleic acid-aneuploid primary tumors and lymph node metastases. It was observed that only the simultaneous determination of deoxyribonucleic acid ploidy of primary tumors and lymph node metastases permits accurate prognostic evaluation in case of lymph node infiltration.
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PMID:Prognostic value of deoxyribonucleic acid aneuploidy in primary non-small-cell lung carcinomas and their metastases. 133 22

DNA was extracted from fresh frozen tissues of eight patients with primary oral squamous carcinoma. Samples of normal oral mucosa were available in seven cases and metastatic tumor in two cases. The samples were probed for human papillomavirus types 16 and 18 by Southern hybridization. In one case of squamous carcinoma of the floor of the mouth, human papillomavirus type 16 was identified in the primary tumor and a lymph node metastasis, but it was not detectable in normal oral mucosa from this patient. Human papillomavirus DNA was not detected in any other sample of primary tumor, metastasis, or normal oral mucosa. Restriction enzyme digests of the human papillomavirus positive primary tumor and its metastasis revealed that the viral DNA was identical to the prototype human papillomavirus type 16 and present at 50 to 100 copies per cell in an episomal state with no evidence of integration into the host DNA. Compared to the human papillomavirus DNA in the primary tumor, the viral DNA in the metastasis was of the same type, in the same physical state, and at the approximately the same copy number. The consistent maintenance of human papillomavirus DNA in metastases from human papillomavirus positive primary tumors supports the hypothesis that human papillomaviruses are cofactors in the pathogenesis of some carcinomas.
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PMID:Human papillomavirus type 16 in an oral squamous carcinoma and its metastasis. 133 29

Forty-four cases of newly diagnosed invasive ductal breast cancer were studied by static cytometry at the time of diagnosis and were followed for 10 years to determine if the survival rate correlated with the nuclear DNA measurements. In 22 cases the stem line was in the 2c range, in 15 cases in the 3c range and in 7 cases in the 4c range. Thirty-four percent (n = 15) of the patients died of metastases during the first five years, 11% (n = 5) died of metastases between 5 and 10 years, and 55% (n = 24) survived for > 10 years without metastases. No correlation between increased tumor cell proliferation and recurrence of tumors could be found. In this study all patients with diploid tumors, tumor size T1 and negative lymph node status survived for > 10 years. In the presence of node metastasis (T1N1M0) all patients (n = 4) having tumors with the stem line in the 2c range survived for 5 years but only 2/4 for > 10 years. The percentage of patients surviving for 10 years showed no significant differences between the groups: in the 2c range, 59% (13/22); in the 3c range, 53% (8/15); and in the 4c range, 43% (3/7). The small number of cases does not allow definitive statistical conclusions, although the logistic regression analyses showed that stem line, pT and pN were the important prognostic factors for five-year survival. However, only pT and especially pN were of prognostic value for 10-year survival.
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PMID:DNA cytophotometric analysis of breast cancer. Follow-up for 10 years. 133 66

To study mechanisms involved in evolution of soft tissue sarcomas, we compared DNA ploidy and karyotypes at different stages of their disease in two patients with myxoid liposarcomas (MLS), one with a fibrosarcoma (FS), and two with rhabdomyosarcomas (RMS). None of the MLS samples revealed clearcut histologic changes in later samples as compared to their primaries, and the DNA ploidy in all samples was diploid. In one patient karyotypes at four different times during the 19 yr of his disease all revealed a t(11;12) (p15;q13), but additional clonal chromosomal abnormalities occurred only in later recurrences. In another patient the karyotypes obtained in the 26th and 28th yr of his disease were similar and included the t(12;16) (q13;p11), characteristic of MLS. A comparison with karyotypes of six other MLS patients at different disease stages suggests that the presence of a t(12;16) may correlate with less aggressive clinical behavior. The histology of the FS remained low-grade and the DNA ploidy diploid. The karyotype, however, showed evolution. In both MLS and FS, chromosomal changes thus seem to be a more sensitive marker for tumor progression than histologic changes or DNA ploidy. In one embryonal RMS, karyotypes obtained 7 and 11 yr after the primary diagnosis were different but clearly had a common "progenitor." In one alveolar RMS, the primary and the synchronous lung and lymph node metastases all revealed a t(2;13). The findings in RMS suggest that polyploidization is an early event in tumor evolution, especially in the alveolar subtype, which may be followed by additional chromosomal changes. In addition, DNA ploidy was measured in eight other RMSs. Among the RMSs the embryonal subtype was characterized by DNA aneuploidy, whereas three of the alveolar cases were in the tetraploid range and one was peridiploid. In local recurrences and in metastases changes in DNA index were observed in half the cases.
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PMID:DNA ploidy and karyotype in recurrent and metastatic soft tissue sarcomas. 134 14

The expression of the protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c-fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell carcinomas of the lung and correlated with clinical parameters of the patients (patient survival, presence of metastases and tumor stage) and with biological characteristics of the tumors (tumor growth in nude mice, DNA-ploidy, proliferative activity, drug-resistance and P-glycoprotein or gluathione S-transferase expression). By means of immunohistochemistry, expression of c-erbB1 oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu) proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p = 0.021). In addition, these tumors were more frequently drug resistant (p = 0.0067). A significant correlation between the growth of the squamous lung carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p = 0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic factors for the aggressiveness of squamous cell carcinomas of the lung and for the response of these tumors to chemotherapy. No significant correlation was found between the expression of the c-erbB1 or c-fos gene products and stage, metastasis and DNA-ploidy. In contrast to these results, no relationship was found between c-neu or c-myc gene products expression and any of the clinical or biological parameters examined. Aneuploid squamous cell carcinomas of the lung expressed p53 more frequently than diploid tumors (p = 0.027). However, there was no significant difference between p53 expression and stage, survival of patients, metastasis, growth of the tumors in nude mice, proliferative activity and drug-resistance of the tumors.
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PMID:Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. 134 20

The etiology of human breast cancer is poorly understood and no specific marker of transformation has been identified. Amplification of HER-2/neu, as reported in a comprehensive study by Slamon et al, was found to be the most powerful predictor of disease-free and overall survival after the status of the axillary lymph nodes. Our study examines the HER-2/neu oncogene in 61 primary human breast cancers at both the DNA level (by Southern blotting) and the protein level (by immunohistochemical methods). Of the 61 tumors analyzed in our study, 17 (28%) had amplification of HER-2/neu. There was no significant correlation of HER-2/neu amplification with age, tumor diameter or hormone receptor status; however, amplification and overexpression of HER-2/neu was significantly correlated with the status of the axillary lymph nodes (P = 0.02). Of 16 patients with amplification of HER-2/neu, 14 (88%) had positive regional nodes. One of the two node negative cases with amplified HER-2/neu had bone marrow micrometastasis. Overall, 16 out of 17 (94%) tumors of the patients having amplified HER-2/neu had metastatic disease at the time of diagnosis. In summary, HER-2/neu amplification is associated with early tumor dissemination in primary human breast cancer and may be a marker of poor prognosis.
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PMID:HER-2/neu amplification and overexpression in primary human breast cancer is associated with early metastasis. 134 94


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