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)

The biological behavior of early-stage invasive carcinoma of the uterine cervix is not always predictable. Therefore it is important to identify new biological markers which could more accurately predict the evolution of the disease. Amplification and/or overexpression of the c-myc gene were frequently observed in advanced-stage cervical cancers and were shown to be associated with tumor progression. More interesting was the study on 93 patients with early-stage carcinoma showing that c-myc gene overexpression was significantly related to a higher risk of relapse. A combination of c-myc expression and nodal status provided a very accurate indication of the risk of relapse. Indeed, in the subgroup of patients with negative nodes, the 3-year disease-free survival rate was 93% (95% confidence interval CI: 79-98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% CI: 26-63%) when c-myc was overexpressed. Moreover the c-myc overexpression was related to a 6.1-times higher risk of distant metastases, suggesting that activation of this proto-oncogene may lead to metastatic ability of tumor cells. These data clearly show that patients with c-myc overexpression are high risk patients who thus might benefit from intensive treatment.
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PMID:The c-myc proto-oncogene in invasive carcinomas of the uterine cervix: clinical relevance of overexpression in early stages of the cancer. 217 73

During tumor progression, micrometastases at their earliest stages have been difficult to analyze qualitatively or quantitatively because of a lack of suitably sensitive markers to discriminate small numbers of tumor cells from normal tissue cell populations. To overcome this problem, the Escherichia coli beta-galactosidase (lacZ) gene was introduced into human EJ Ha-ras oncogene-transfected BALB/c 3T3 cells with subsequent injection of transfected cells into athymic nude mice. Using a chromogenic substrate (5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside), the lacZ-bearing tumor cells at primary tumor sites as well as at secondary organs stain intensely blue and can be easily distinguished from the host tissue cells hours, days, or weeks postinjection. Staining of lacZ-bearing tumor cells is specific and extremely sensitive in detecting micrometastatic foci in lungs and other organs, including brain and kidney for the first time. Stable integration of the lacZ and ras genes into cultured cells and subsequent tumor cells was verified by Southern blot analyses. The lacZ gene appears to be a stable marker during tumor progression in vivo based both on phenotypic (5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside staining) and on genotypic (Southern blot analysis) evidence. Furthermore, 5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside staining of tumor cells can also be used together with alkaline phosphatase staining relatively specific for endothelial cells to relate the topographies of metastatic cells and host blood vessels in embedded sections. By using the lacZ gene as a sensitive quantitative marker, analyses of micrometastasis development in the lung indicate that the ras oncogene contributes to the metastatic phenotype in this EJ Ha-ras model system, although further genetic and/or phenotypic alterations appear to be necessary for long-term growth and development into overt metastases. These findings demonstrate the effectiveness and sensitivity of the bacterial lacZ gene as a phenotypic marker in tumor progression studies, providing both a qualitative and a quantitative tool in virtually any tumor system for examining micrometastasis formation in target organs and the relationship of tumor cells to host organ microenvironments.
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PMID:Bacterial lacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression. 218 31

In a multicenter trial, 49 patients with histologically proven advanced gastric cancer were treated with a combination chemotherapy consisting of etoposide 120 mg/m2 d 4, 5, 6 adriamycin 20 mg/m2 d 1, 7 and cisplatinum 40 mg/m2 d 2, 8. Therapy was repeated every 4 weeks, 45 patients were evaluable for response after 8 weeks of treatment. Eight patients achieved a partial remission (PR: 18%), 17 patients had no change (NC: 38%), and 20 patients showed tumor progression (P: 44%). Four patients with primarily inoperable tumor and without distant metastases who achieved a partial remission, underwent second look operation with curative intention. All 4 patients died within 12 months after second look operation due to tumor recurrence. Median survival time of all patients was 9 months. Toxicity was considerable. WHO grade 3/4 toxicity appeared in 20-30% of patients (nausea, vomiting, loss of appetite, leucopenia). After 3 cycles complete alopecia was present in 70% of patients. Severe infection, requiring treatment, occurred in 10 patients. Five patients discontinued therapy because of intolerable subjective toxicity. The observed response rate of 18% objective partial remissions is disappointing and does not give support to the communications reporting response rates over 50% with EAP and other regimens including cisplatinum. In conclusion, and considering the high subjective and objective toxicity of this regimen, it can not be recommended for standard use in patients with advanced gastric cancer.
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PMID:Etoposide, adriamycin, and cisplatinum (EAP) combination chemotherapy for advanced gastric cancer. A phase II trial by the "Chemotherapiegruppe Gastrointestinaler Tumoren (CGT)". 220 5

In 1984, Philippe Shubik wrote in an editorial in the Journal of the National Cancer Institute that: 'In terms of general biology, the multicellular organisms have evolved a complex series of defensive responses to extracellular injury involving various inflammatory reactions and their systemic concomitants. Needless to say, these reactions are by no means always successful from the standpoint of the host and indeed may well be the immediate cause of the obvious ill effects noted. The unicellular organisms, in contrast, react to injury by dividing and moving. In the search for the features that may link chemical, physical, and viral carcinogens apart from their ability to induce neoplasia, only one characteristic in common is obvious, namely, their ability to produce intracellular change or injury while leaving the cell viable. Perhaps the initial and fundamental characteristics of neoplasia is a reversion of the cell to unicellular behavior. Division and invasiveness are the characteristics of the neoplastic cell, and increased motility certainly seems to be the most likely mechanism for invasion'. Dr. Shubik presented these views as a basis for 'further discussion' regarding the nature of the neoplastic response. We hope that this presentation will augment Shubik's plea by reviewing his idea in the context of our current knowledge of tumor development. In addition, we will attempt to integrate the concept of the unicellular behavior of tumor cells with Foulds' and subsequently Nowell's insightful hypothesis concerning tumor progression.
Cancer Metastasis Rev 1990 Jul
PMID:Transformation injury and the unicellular phenotype of malignant cells. 220 71

A recently established model for local breast cancer recurrence using the 13762NF rat mammary adenocarcinoma was used to evaluate biologic and biochemical properties related to clinical outcome for this class of tumors. Sublines isolated from local tumor regrowths following surgical resection differed from each other and from the 'parental' cell lines for multiple phenotypes, including metastatic propensity. Local recurrence- and primary tumor-derived sublines were examined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE), lectin binding to electrophoretically separated proteins, and lactoperoxidase-catalyzed cell surface iodination; and differential protein patterns were compared to tumor progression and metastatic potential. 2D-PAGE revealed several quantitatively different spots which correlated with lung colonization potential. In particular, quantities of an apparently unique, non-cell-surface protein, P50.9 (Mr approximately 50,900, pI approximately 7.3) correlated inversely with metastatic propensity, suggesting that it may be associated with, among other possibilities, the negative regulation of the metastatic phenotype. P50.9 was unrelated to four similarly sized metastasis-associated proteins--tumor autocrine motility factor; the rat analog of tumor suppressor, p53; rat cytokeratin 14 or procathepsin D--as determined by amino acid analysis. A major wheat germ agglutinin binding sialoglycoprotein, gp93 (Mr approximately 93,000), was present in smaller amounts as cells were passaged in vivo and re-established as in vitro cultures [MTF7 greater than 'primary' tumor-derived lines (sc1, sc3) much greater than local recurrence-derived lines (LR1, LR1a, LR3, LR4, LR5, LR6)]. Besides cell surface glycoprotein losses, two of six local recurrence-derived sublines expressed a wheat germ agglutinin-binding sialoglycoprotein, gp110 (Mr approximately 110,000), previously undetected on any of the other cell lines including the parental populations. gp110 was found in LR3 and LR6 which were relatively highly metastatic; however, correlation with metastatic potential failed because gp110 was not present on the metastatic parental cell line, MTF7. These results demonstrate specific quantitative and qualitative protein differences associated with the selection of locally recurrent mammary tumors.
Clin Exp Metastasis
PMID:Tumor progression- and metastasis-associated proteins identified using a model of locally recurrent rat mammary adenocarcinomas. 222 68

Tumor progression has been reported to be often accompanied by a loss of sensitivity to various elements of the immune system. In the present study, three variants of malignancy of AKR lymphoma were compared as to the host reaction they elicit. Splenectomy caused an acceleration of growth of the low-metastasizing tumor, slightly inhibited the growth of the tumor of intermediate malignancy and significantly inhibited the development of the high-metastasizing lymphoma. These results suggest that splenic elements exert an inhibitory effect on the low-metastasizing tumor and a growth-stimulatory effect on the more malignant ones. While decreased sensitivity to various host defense mechanisms following tumor progression has been amply documented, the present study shows a more severe phenomenon: increased malignancy can be accompanied by a deviation of the host immune reaction from tumor growth inhibition to growth stimulation.
Invasion Metastasis 1990
PMID:Change in the role of the spleen from protective to harmful following tumor progression in AKR lymphoma. 222 17

We selected for a prospective surveillance study 167 patients with untreated grades 1 and 2 prostate cancer. The tumors were classified regarding modal deoxyribonucleic acid value (ploidy) by flow cytometry, cytological grade by transrectal fine needle aspiration biopsy and local tumor stage. Of the patients 146 could be evaluated. Mean followup was 50 months. The initial ploidy was statistically correlated to cytological grade but not to initial local tumor stage, prostatic acid phosphatase activity or patient age. Initial ploidy and cytological grade had a prognostic value regarding local tumor progression when considered as single predictors and in combination. Two patients with diploid and 8 with nondiploid tumors initially had metastases during the surveillance. Five patients (1 with diploid and 4 with nondiploid disease) died of prostatic cancer. Modal deoxyribonucleic acid value and cytological grade were of prognostic value in untreated prostate cancer.
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PMID:The prognostic value of modal deoxyribonucleic acid in low grade, low stage untreated prostate cancer. 223 35

In order to evaluate the relevance of protooncogene alterations in gastric cancer and to specifically relate these alterations to types and stages of the neoplasia, we studied oncogenes of possible interest in gastric tumors with different clinical parameters. Fifty DNAs from primary gastric adenocarcinoma were analyzed, by the Southern blotting technique, for the presence of amplification or rearrangements of seven different protooncogenes: c-myc, c-erbB2, c-Ki-ras, c-Ha-ras, c-N-ras, hst, and c-mos. All the tumors analyzed were histologically classified and staged. Amplification of the following genes was found: c-myc (2 of 50), hst (3 of 50), c-erbB2 (3 of 50), and c-Ki-ras (5 of 50). The simultaneous amplification of hst (3 cases), c-myc (1 of 3), or c-Ki-ras (2 of 3) was observed. Analysis of DNAs from atrophic and metaplastic gastric mucosa (which can be regarded as preneoplastic lesions) of the 10 patients showing gene amplification demonstrated that this was limited to neoplastic cells. Considering protooncogene amplification in general (i.e., involving different genes and occurring to different degrees) and clinical parameters of tumors, we found a statistically significant association between amplification and both tumor progression and presence of metastases. Therefore, at least for the genes analyzed, amplification is a relatively infrequent phenomenon and represents a late event in the temporal development of gastric cancer.
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PMID:Heterogeneous protooncogene amplification correlates with tumor progression and presence of metastases in gastric cancer patients. 225 24

It is generally accepted that the genome of tumor cells is less stable than that of most normal cells, and it has been hypothesized that this genomic instability is probably involved in the process of tumor progression. However, the rate of occurrence of classical spontaneous mutations in tumor cells is too low to account for the rapid changes that can occur during tumor progression. Thus it is likely that other types of changes, such as gene amplification, must be involved in tumor progression. Gene amplification has been extensively studied in relation to the development of drug resistance. Low levels of amplification can occur spontaneously in tumor cell populations, but the amplified genes are lost rapidly unless prolonged selective pressure is applied. This paper argues that unstable increases in the expression of genes, probably as a result of low levels of amplification, may be all that is required for some of the stages in the process of tumor progression. This may be particularly true for the steps involved in metastasis formation. Recent studies have suggested that microenvironmental conditions known to occur in tumors (hypoxia, nutrient deprivation) may induce gene amplification in cells. This suggests the possibility that such conditions could promote tumor progression.
Cancer Metastasis Rev 1990 Sep
PMID:Tumor progression: potential role of unstable genomic changes. 225 13

The ploidy, DNA heterogeneity and the phases of the cell cycle of the tumor were analyzed, by means of single-cell DNA cytophotometry, in 329 patients with locally advanced prostatic carcinoma to find out and establish prognostic factors apart from those already known (stage, grade). Follow-up periods ranged from 1 to 9 years. 253 (76.8%) of the 329 patients had carcinoma stage T3 Nx M0, and 76 of them (23.1%) had carcinoma stage T3/T4 N2-4 M1. 11.8% of the patients showed a cytological grade of malignancy I, while 64.3% had grade II carcinoma and 23.8% had grade III carcinoma. Single-cell DNA cytophotometry demonstrated aneuploidy rates of up to 71% and diploidy rates of up to 23.8% for the higher grades of malignancy, i.e. grades II and III, whereas the diploidy rate established for grade I was 68% and the respective aneuploidy rate was 21%. These differences are significant (p less than 0.001). There was a significant correlation between the results of DNA cytophotometry and the clinical course of the disease. Only 3 (3.7%) of the patients with diploid tumor cell nuclei developed metastases and local tumor progression within 8 years, whereas patients with aneuploid tumor cell nuclei showed metastases and local tumor progression within 8-22 months. These patients died of carcinoma after an average 18 months following primary diagnosis.
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PMID:Nuclear DNA analysis: the relevance of ploidy, DNA heterogeneity and phases of the cell cycle in 329 patients with prostatic carcinoma. A study on a follow-up of eight years. 228 53


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