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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal human mammary epithelial cell (HMEC) cultures originating from 2 mammoplasty reduction surgical samples were transfected with replication-defective SV 40 DNA. Two independent cell lines designated as S2T2 and S1T3, selected for their increased proliferation potential and lifespan, were propagated for greater than 22 months in culture. They maintained a near-diploid karyotype with few chromosomal markers such as trisomy 1q (S1T3) and trisomy 8q (S2T2), which are most common in breast cancer in vivo. Immortalized S1T3 cells were not tumorigenic, whereas S2T2 cells produced slowly growing tumors in nude mice. One tumor was propagated in vitro and the transformed NS2T2 cell line subsequently raised 100% large tumors in the nude mouse. Rearrangement of the SV40 genome was observed in NS2T2 cells, which was not associated with increased expression of large T antigen. S1T3, S2T2 and transformed NS2T2 cell lines expressed cytokeratins CK18, CK19, the mammary-specific antigen DF3, and functional EGF receptors. Single-step immortalization and malignant transformation of human breast epithelial cells can thus occur upon transfection with SV40 large T oncogene. The chromosomal abnormalities observed in these cell lines suggest that they could offer a model for the study of breast-tumor progression in vitro.
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PMID:Single-steep transformation of human breast epithelial cells by SV40 large T oncogene. 132 42

The ability of monoclonal antibody (MAb 108), an immunoglobulin G (IgG)2a against the epidermal growth factor receptor (EGF-R), to interact with lung cancer cell lines was investigated. 125I-EGF bound with high affinity to non-small-cell lung cancer (NSCLC) cells, and MAb 108 inhibited specific binding of nine NSCLC cell lines in a dose-dependent manner (IC50 = 0.3-3 micrograms per ml). 125I-MAb 108 bound with high affinity (kd = 2 nM) to a single class of sites (Bmax = 70,000 per cell) using NSCLC neuroendocrine cell line NCI-H460. Specific 125I-MAb 108 binding was inhibited with high affinity by MAb 108 but not by a control antibody IgG using large-cell carcinoma cell line NCI-H1299. 125I-MAb 108 binding was not internalized at 37 degrees C using NSCLC neuroendocrine cell line NCI-H460 and adenocarcinoma cell line NCI-H23. Also, 1 microgram per ml of MAb 108 but not of a control IgG inhibited the clonal growth of NCI-H23 and squamous cell carcinoma cell line NCI-H157 in vitro. Also, MAb 108 inhibited xenograft formation of cell lines NCI-H460, NCI-H157, and NCI-H727 in nude mice in vivo. After a palpable tumor had formed using NCI-H460 cells, injection of 100 micrograms of MAb 108 (intraperitoneally three times weekly) inhibited xenograft volume in nude mice by approximately 50%. These data suggest that MAb 108 may interact with EGF receptors on lung cancer cell lines and inhibit NSCLC proliferation.
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PMID:Epidermal growth factor receptor monoclonal antibodies inhibit the growth of lung cancer cell lines. 132 29

The effects of EGF and TGF-beta 1 on the proliferation of 2 ovarian carcinoma cell lines (IGROV1 and OVCCR1) were evaluated. The cell lines were adapted to grow in a restricted serum (0.5%) medium. EGF was required for proliferation of both ovarian cell lines. Low doses of TGF-beta 1 inhibited clonogenic capacity and attenuated the EGF-mediated stimulation of DNA synthesis in OVCCR1 cells. TGF-beta 1 inhibited OVCCR1 cell proliferation by blocking the cell cycle at the G1/S transition. TGF-beta 1 did not affect either clonal or monolayer growth of IGROV1 cells. Both cell lines express type-I and type-III TGF-beta receptors, suggesting that the unresponsiveness of IGROV1 cells to TGF-beta 1 occurs at a post-receptor level. TGF-beta 1 mRNA was detected in OVCCR1 cells and in 8 out of 11 of the ovarian tumor specimens examined.
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PMID:Transforming growth factor beta 1 (TGF-beta 1) inhibits growth of a human ovarian carcinoma cell line (OVCCR1) and is expressed in human ovarian tumors. 133 Sep 35

Correlation between the expression of growth factor/receptor systems or the alterations of tumor suppressor genes and biological malignancy of gastric cancer was described. Overexpression of many growth factors/receptors, such as EGF, TGF alpha, EGF receptor and ERBB2, and reduction of type I receptor for TGF beta may be linked with new prognostic factors of gastric carcinomas. The expression of cripto, a novel gene of EGF family, shows a tendency to correlate with tumor staging of well differentiated gastric adenocarcinomas. p53 gene abnormalities take place in 60% of gastric carcinomas including early stage carcinoma. Loss of heterozygosity on chromosomes 1q, 7p and 7q is frequently observed in advanced gastric carcinomas of well differentiated type. Molecules which regulate tumor invasion and metastasis such as nm23, tissue inhibitor of metalloproteinase (TIMP) and endogenous galactoside-binding lectin may provide for prognostic factors of gastric cancer.
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PMID:[New prognostic factors in human gastric carcinomas]. 134 86

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

Female BDF1 mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25 micrograms/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40-53% inhibition of tumor volumes, 38-43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp6]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp6]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.
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PMID:Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice treated with an agonist or antagonist of LH-RH, an analog of somatostatin, or a combination. 135 75

Interleukin-6 (IL-6 or BSF-2/IFN beta 2) is a component of normal human skin. IL-6 was immunologically detected in basal keratinocytes, endothelial cells and in a number of mononucleated cells and fibroblasts in normal skin and sudoriparous ducts. In psoriasis, intense labelling of the cytoplasm in the vicinity of keratinocyte membranes was detected in all epidermal layers and other skin appendages. The fact that this interleukin acts synergistically with respect to IL-1 and Tumour Necrosis Factor (TNF) strengthens the hypothesis whereby IL-6 may contribute via its receptor action to EGF function in modulating cell hyper-proliferation in psoriasis.
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PMID:Interleukin-6 in normal skin and psoriasis. 135 48

In summary, evidence is beginning to accumulate in support of a major role for tyrosine kinase receptors (and their activating growth factors) and steroid hormones and their receptors in normal development and differentiation of the mammary gland. A point of intersection of their mechanisms of action in growth control appears to be the induction of nuclear protooncogenes such as c-myc. When c-myc is amplified, as it is in many breast cancers, EGF and FGF receptor tyrosine kinase action becomes transforming, not simply mitogenic. A source of the transforming factors could be either stromal or epithelial. This mechanism could function early in the progression of breast cancer. c-erbB-2 and EGF receptor overexpression and amplification, when they occur, appear to render tumors even more malignant and of especially poor prognosis. These mechanisms could function late in the progression of breast cancer. Transgenic mouse studies have begun to echo these themes. They have established that a growth factor (TGF-alpha) and its receptor (EGF receptor), which appear to be important in normal mouse and human proliferation and gland development, and a protooncogene (c-myc), commonly amplified and overexpressed in human and mouse breast cancer, can each contribute to mammary carcinogenesis. The mechanisms of the two are likely to be distinct. myc is likely to be acting as a tumor initiator in combination with normal proliferative factors, whereas TGF-alpha is likely to be acting as a hyperproliferative (promotional) factor in combination with a normal background of mutational events. The role of unmutated but amplified erbB-2 in the transgenic mouse is not yet known.
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PMID:Tyrosine kinase receptor--nuclear protooncogene interactions in breast cancer. 136 Feb 36

The goal of this study was to evaluate the extracellular matrix (ECM) as a model for growing human lung cancers and to study the feasibility of its application for cellular and molecular studies of tumor biology. Bovine corneal endothelial cell ECM coated dishes were evaluated as a growth substrate for tumor cultures. Growth success, morphology and oncoprotein/growth factor expression for 74 different lung cancers (adenocarcinoma, epidermoid carcinoma and small cell carcinoma) were compared after seeding fresh surgical explants onto bovine corneal endothelial cell ECM and plastic culture substrate. Nineteen out of 74 tumors (26%) plated on ECM demonstrated measurable growth. Growth on ECM was superior to growth on plastic for the lung tumors. All 19 tumor cultures showed malignant morphology and functions. They were examined under the light microscope, and in all cases pre- and post-cytology confirmed malignancy. Tumor cells seeded on ECM retained their malignant phenotype in comparison to tumors grown on plastic. Several oncoproteins (c-myc, c-Ha-ras, c-erbB-2) and growth factors/receptors (EGF, EGF-R, TGF alpha) were immunostained. These analyses were performed immediately after disaggregation of tumor cells obtained surgically and after seeding on ECM or plastic. Strong expression of oncoproteins/growth factors was detected in tumor cells immediately after surgery or when the cells were plated on ECM. On the other hand, moderate or no expression was observed in the same type of cells on plastic.
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PMID:Human lung cancers growing on extracellular matrix: expression of oncogenes and growth factors. 136 16

Significant advances have recently been made in a number of areas concerning central nervous system (CNS) neoplasia. Particularly salient are the following: (1) gene amplification is related to increasing grade of human glioma malignancy and occurs in approximately 40% of the most common and most malignant variety of glioma, glioblastoma multiforme (GBM), (2) by far the most commonly amplified gene in glioblastomas is the epidermal growth factor receptor (EGFR) gene, which is amplified in about one third of GBMs, (3) a small percentage of GBMs amplify N-myc or the novel sequence gli, (4) the EGFR gene is rearranged in at least half of gliomas in which it is amplified, and (5) EGFR gene rearrangement results in external domain deletions that yield truncated EGF receptors. Antibodies specific for the mutant EGF receptor fusion junction have been successfully produced and provide stimulating new potential avenues for tumor imaging and therapy. For pediatric CNS neoplasms, only medulloblastoma has been investigated in adequate numbers; a small percentage exhibit amplification of either the N-myc or c-myc genes.
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PMID:Amplified cellular oncogenes in neoplasms of the human central nervous system. 137 22


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