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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In searching an animal model to study metastasis formation we used cultured cells of experimental rhabdomyosarcomas and their inoculation tumors in adult nude mice. Supplementing earlier observations (Katenkamp et al. 1987) we found that long-term cultured sarcoma cells induce tumors in adult nude mice which do not metastasize spontaneously but produce lung metastases after repeated incomplete tumor removal. Possible factors and mechanisms responsible for metastasis emergence are discussed. The metastasis model introduced may be apt to study cellular changes at cytogenetic and molecular biological level that occur during tumor progression and metastatic dissemination.
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PMID:Metastasis induction by incomplete tumor resection. A new metastasis model using inoculation sarcomas in adult nude mice after long-term cultivation of sarcoma cells. 139 12

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.
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PMID:In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections. 154 28

The effects of acute and chronic ethanol administration on tumor progression and metastasis were studied in rat models of leukemia and breast cancer, respectively. Acute administration of 1.5-3.5 g of ethanol/kg body weight significantly reduced survival of rats injected with CRNK-16 leukemia cells in a dose-related manner. Acute administration of 2.5-3.5 g of ethanol/kg body weight, one hour before tumor inoculation, or chronic consumption of liquid diet containing ethanol for two weeks before and three weeks after tumor inoculation, significantly increased the number of lung metastases of MADB106 mammary adenocarcinoma. The ethanol-induced increase in the number of metastases was not correlated with plasma levels of corticosterone and was not altered by the opiate antagonist naltrexone. Incubation of spleen cells in vitro in the presence of ethanol, at concentrations comparable to those measured in the blood of ethanol-treated rats, significantly suppressed natural killer (NK) cell activity against MADB106 cells in a standard chromium-release assay and decreased the binding of effector to MADB106 tumor cells. However, neither acute nor chronic ethanol administration in vivo altered splenic NK activity against this tumor in the same in vitro assay, in which the ethanol would have been washed away. These results suggest that, in the presence of ethanol, tumor progression is facilitated. The possibility that this facilitation is related to ethanol-induced impairment of the normal tumoricidal interaction between NK and tumor cells is discussed.
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PMID:Ethanol increases tumor progression in rats: possible involvement of natural killer cells. 157 4

To better understand the metastatic behavior of pulmonary adenocarcinoma, we studied the differences in carbohydrate antigens between primary tumors and their metastases using three monoclonal antibodies (FH-2 defining Lewis [Le]x, AH-6 defining Le(y), and FH-6 defining sialyl Le(x-i)) on 56 autopsy cases (including 15 cases in which primary tumors were surgically resected) and 116 cases of surgically resected pulmonary adenocarcinoma. Metastatic lesions were divided into two groups according to the route of metastasis: group 1 comprised lymphatic metastases, such as lymph node and contralateral lung metastases, and group 2 comprised hematogenous metastases, such as extrathoracic spread. Both primary tumors and metastatic lesions with well-differentiated glandular patterns showed higher positive rates for Le(y) than the poorly differentiated lesions. Such a difference in the antigen expression in relation to tumor differentiation was barely demonstrated for Le(x) and sialyl Le(x-i). Discordance in antigen expression between primary and metastatic lesions (ie, positive primary tumors with negative metastatic lesions and negative primary tumors with positive metastatic lesions) was observed in the following order of frequency: extrathoracic metastatic lesion, contralateral lung, mediastinal lymph node (N2), and ipsilateral peribronchial and hilar (N1) lymph nodes. This study revealed increased biologic diversity of pulmonary adenocarcinoma in cell surface antigens following tumor progression, especially in extrathoracic metastasis.
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PMID:Tumor-associated carbohydrate antigens in primary pulmonary adenocarcinomas and their metastases. 164 35

The hypomethylating chemotherapeutic drug 5-aza-2'-deoxycytidine (5AzadC) has been shown to induce cell differentiation in some systems, while promoting neoplastic transformation in others. Using both in vitro and in vivo models, we have explored the relationship between oncogene expression and the susceptibility of cells to malignant transformation by 5AzadC. The study involved several nontumorigenic subclones of NIH3T3 fibroblasts, including cells transfected with deregulated c-myc, as well as phenotypic revertants expressing v-Ki-ras or long terminal repeat-activated c-Ha-ras. Transient 5AzadC treatment of the oncogene-bearing cell lines was associated with a rapid and efficient neoplastic transformation. In some cases, over 50% of the cell population exhibited loss of contact inhibition of growth within 1 week of treatment. The transformants were capable of forming s.c. tumors and experimental lung metastases in recipient nude mice. In contrast, 5AzadC failed to induce malignant properties in control 3T3 cultures transfected with the bacterial neor gene; rather, treatment of these cells was associated with differentiation into adipocytes and myotubes. The differential response to 5AzadC was also observed in vivo, in mice first inoculated s.c. with the premalignant cells and then treated with 5AzadC 24 h later. In agreement with the in vitro model, tumor development in mice correlated with the presence of cells with activated ras or myc oncogenes. Cytidine analogs that do not inhibit DNA methylation (i.e., 6-azacytidine and 1-beta-D-arabinofuranosyl cytosine) had no effect on cell phenotype. The results indicate that exposure of cells to 5AzadC can lead to tumor progression both in vitro and in vivo and suggest that preexisting alterations in oncogene expression may facilitate the evolution of cancerous growth induced by hypomethylating agents.
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PMID:Increased sensitivity of nontumorigenic fibroblasts expressing ras or myc oncogenes to malignant transformation induced by 5-aza-2'-deoxycytidine. 170 37

From the pregnancy-dependent mouse mammary tumor TPDMT-4, four autonomous sublines were established after its independent progression under different conditions. Despite their similar growth rates in inguinal fat pads, three sublines formed lung metastases, and one did not when they were injected i.v. into mice as a single cell suspension. The TPDMT-4 tumor and the nonmetastatic subline expressed mRNA for the orf gene of mouse mammary tumor virus, whereas all metastatic sublines did not. This suggested that the loss of its expression may have been a prerequisite for the progression toward metastatic ability. To identify the gene(s) participating in the generation and the progression of TPDMT-4, the expression of 23 different oncogenes was analyzed. The expression of int-2 was detected in TPDMT-4 and in all sublines, indicating that TPDMT-4 was generated by activation of this gene, whereas hst expression occurred only in the metastatic sublines. These results demonstrated that the hst gene may contribute to tumor progression from a nonmetastatic to a metastatic phenotype in the mouse mammary tumor system.
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PMID:Association of hst gene expression with metastatic phenotype in mouse mammary tumors. 196 96

The formation and propagation of several subpopulations of human melanoma cells from a heterogeneous parental population was accomplished with the use of the Membrane Invasion Culture System (MICS) in vitro under sterile conditions. Five sequentially selected subpopulations of melanoma cells showed an increasing ability to do the following: a) invade reconstituted basement membranes in vitro; b) form experimental lung metastases in vivo; and c) express steady-state levels of human type IV collagenase, a marker for metastatic potential. In addition, the morphology and expression of 35S-methionine-labeled cell surface proteins changed with sequential selection. The adaptation of the MICS assay for studying tumor cell subpopulations allows the morphological, biochemical and molecular characterization of events associated with tumor progression in an in vitro model.
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PMID:Selection of invasive and metastatic subpopulations from a heterogeneous human melanoma cell line. 222 75

The curing chance of cancer disseminated to the lungs depends on the global curing chance of that specific tumor, the extent and distribution of its systemic spread and the availability of additional treatment modalities besides surgery. Of all tumors occurring in childhood and adolescence only osteosarcoma, Wilms tumor and Ewing's sarcoma preferentially disseminate to the lungs and such are the most promising candidates for successful treatment. In osteosarcoma with pulmonary dissemination surgical removal of the metastases is indispensable. In Wilms tumor chemoradiotherapy may replace or be used as an adjunct to surgery while in Ewing's sarcoma with primary pulmonary metastases chemoradiotherapy is the treatment of choice. Although metachronous lung metastases may still cured in osteosarcoma and Wilms tumor, they tend to be fatal however in Ewing's sarcoma. A small chance of success itself should not contraindicate metastasectomy but only the actual technically impossible intervention or the definite demonstration of tumor progression no longer controllable of different location. However, even palliative metastasectomy may be indicated in an individual patient.
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PMID:Surgical treatment of pulmonary metastases in childhood. 243 85

47 tumor samples, 45 of which were obtained at thoracotomy for non-small cell lung cancer were examined for mutational activation of the oncogenes H-ras, K-ras, and N-ras. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. ras gene mutations were present in nine of 35 adenocarcinomas of the lung (all K-ras), in two of two lung metastases of colorectal adenocarcinomas (1 x K-ras, 1 x N-ras) and in one adenocarcinoma sample obtained at autopsy (H-ras). All K-ras and H-ras mutations were in either position 1 or 2 of codon 12, while the N-ras mutation was in position 2 of codon 61. The potential clinical significance of K-ras activation was analyzed using the combined results of this and of our earlier study (S. Rodenhuis et al., New Engl. J. Med., 317: 929-935, 1987). Lung adenocarcinomas with K-ras mutations tended to be smaller and were less likely to have spread to regional lymph nodes at presentation. With a median follow up of 10 months, survival data are still immature. None of six adenocarcinomas of nonsmokers had a K-ras mutation and only one of four who had stopped smoking more than 5 years before. We conclude that mutational K-ras activation is present in about a third of adenocarcinomas of the lung and that the mutational event may be a direct result of one or more carcinogenic ingredients of tobacco smoke. Studies involving larger numbers of patients are required to confirm the association of K-ras activation with smoking and the inverse relation with tumor progression.
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PMID:Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. 304 48

A spontaneous murine mammary carcinoma, designated SP1, grew more aggressively in the mammary gland than in the subcutis exhibiting a 10-fold lower 50% lethal tumor dose and the ability to metastasize spontaneously from the orthotopic mammary gland site. The appearance of metastasis could be abrogated by resection of the primary tumor up to 21 days postinjection, arguing against the possibility that metastasis occurred due to trauma of the injection and/or healing processes. In addition, tumor cells recovered from lung metastases exhibited an increased ability to metastasize when reinjected into either the s.c. or mammary sites. Tumor cells from lung metastases showed low levels of Class I major histocompatibility (MHC) antigens, like the parental SP1 cells, but were found to express differentiation markers typical of normal basal and luminal mammary epithelium. SP1 tumors expressed increased Class I MHC antigens, as well as high levels of basal and luminal breast epithelial markers, within 7 days of implantation into the mammary gland. On the other hand, SP1 tumors growing in the subcutis never expressed increased Class I MHC levels and expressed the epithelial marker antigens at lower levels and not until at least 21 days of growth. Removal of host epithelium by cauterization of the mammary bud at 3 weeks had no effect on the increased growth, metastasis and acquired heterogeneity of MHC and epithelial associated antigens, suggesting that the mammary gland stroma was responsible for the observed phenomenon. These findings suggest that the mammary gland either selects distinct tumor subpopulations, or induces a phenotypic change leading to tumor progression and the generation of metastatic subpopulations.
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PMID:Expression of epithelial-like markers and class I major histocompatibility antigens by a murine carcinoma growing in the mammary gland and in metastases: orthotopic site effects. 319 95


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