Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While stimulating the growth of fibroblasts, transforming growth factor beta 1 (TGF-beta 1) inhibits the growth of various normal and malignant cell lines in vitro. We studied the effects of TGF-beta 1 in vivo. The level of TGF-beta 1 in serum was maximally elevated 2 h after injecting 1 muCi of 125I-TGF-beta 1 into the peritoneal cavity of nude mice. Five h after the i.p. administration of 10 micrograms of unlabeled TGF-beta 1, 20 ng/ml of TGF-beta-like material in serum were detected by a radioreceptor assay on A549 lung carcinoma cells. Trichloracetic acid-precipitable 125I-TGF-beta 1 was taken up by liver, spleen, lungs, kidneys, and tumor tissue but not by the brain. At doses exceeding 2 micrograms/day, TGF-beta 1 induced a generalized interstitial fibrosis and a cachexia, which was not mediated by elevated serum levels of tumor necrosis factor alpha as determined by Western blot analysis and enzyme-linked immunosorbent assay. A total of 200,000 cells of the estrogen receptor-negative human breast cancer line MDA-MB-231, which had been shown to be maximally growth inhibited in vitro by 40 pM TGF-beta 1 and to have high-affinity receptors (9, 11, 12), were injected into the mammary fat pad of each nude mouse. The duration of treatment was 16 days with ten animals in the control group and five animals in the treated groups. The dose ranged from 1 to 4 micrograms per animal daily. The treatment was started 24 h after the injection of the tumor cells. Tumor growth was not significantly affected at either nontoxic or toxic doses of TGF-beta 1. Thus, we have demonstrated that TGF-beta 1, apart from being a local growth factor, has systemic effects, such as cachexia and multiple fibrosis. Its role as an antitumor agent may be limited.
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PMID:Transforming growth factor beta 1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice. 205 95

The growth-modulating effects of recombinant alpha- and beta-forms of human interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) were examined with several human cell lines. Exposure to combinations of IL-1 and IFN-gamma resulted in three categories of cell response. The first was cell lines in which IL-1 stimulated growth and offset the growth inhibitory effects of IFN-gamma. These lines included the lung carcinoma CALU-1 and the colon carcinoma SW-48. The second was some of the cell lines that were refractory to IL-1 and that were inhibited by IFN-gamma alone. These included the cervical carcinoma HeLa, the transformed milk line HBL-100, and the myelogenous leukemia K562. The third group consisted of cells in which growth inhibition by IL-1 and IFN-gamma was additive. These included the mammary carcinomas MCF-7 and MDA-MB-415. The exception to this latter group was ME-180 in which significant additive inhibitory effects could not be demonstrated. IL-1 alone primarily induced a cytostatic effect in growth-inhibited cell lines. The cytolytic effect induced by IFN-gamma was increased in the presence of IL-1. The data support the conclusion that the effects on growth of IL-1 and IFN-gamma are mediated by different mechanisms.
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PMID:Modulation of cell proliferation by human recombinant interleukin-1 and immune interferon. 311 Apr 77

Several native and recombinant forms of human interleukin-1 (IL-1) and recombinant murine IL-1 were assayed for their ability to inhibit the growth of cell lines established from malignant and nonmalignant human sources. The amount of growth-inhibitory activity was compared to the units of half-maximal [3H]thymidine incorporation in mouse thymocyte cultures exposed to IL-1. Three malignant human mammary cell lines (MCF-7, T47D, and MDA-MB-415) were growth inhibited in the presence of both native and the alpha and beta forms of recombinant human IL-1. MDA-MB-415 was most sensitive. Although most sources of IL-1 showed good correlation between units of activity and percentage of growth inhibition, native IL-1 from Genzyme Corporation induced a cytotoxic effect. Murine IL-1 was less growth inhibitory than the human forms of the monokine. Human embryonic lung (HEL), adult fibroblast (CRL 1445), and transformed milk (HBL-100) lines were not growth inhibited when tested against any IL-1 source. A lung carcinoma (CALU-1) and a colon carcinoma (SW-48) were not inhibited by either the alpha or beta forms of human recombinant IL-1.
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PMID:Lymphocyte-activating and growth-inhibitory activities for several sources of native and recombinant interleukin 1. 348 21

Crude membrane (CM) extracts were prepared from five cultured breast tumor lines (MDA-MB-157, MDA-MB-231, ZR75-1, HS0578T, and MCF-7) which had been infected with vesicular stomatitis virus (VSV) to augment their antigenicity. In skin test trials, CM extracts of uninfected MCF-7 cells elicited positive response in 0 of 13 (0%) tests in breast cancer patients, while VSV-MCF-7 elicited positive responses in 11 of the same 13 patients (84.6%). CM extracts of VSV-ZR75-1 and VSV-MCF-7 elicited greater delayed hypersensitivity responses (mm induration at 48 hr) in breast cancer patients than in patients with lung carcinoma or melanoma. Although the sensitivity of VSV-ZR75-1 was too low (ten of 28, or 35.7% of tests positive) to be useful as a skin test antigen, VSV-MCF-7 elicited positive responses in 30 of 38 (78.9%) tests in breast cancer patients, as compared to two of 15 (13.3%) and two of 13 (15.4%) of tests in patients with lung carcinoma and melanoma, respectively. The "virus-augmented" CM extract of cultured MCF-7 cells exhibited markedly greater sensitivity as compared to control MCF-7 extracts (P less than .005), with a high degree of specificity for breast cancer patients as compared to patients with the other neoplasms (P less than .00001). The results of skin testing with VSV-MCF-7 CM extracts demonstrated antigenic cross-reactivity with a large number of breast cancer patients, a finding of great importance for any potential immunotherapy and/or immunodiagnosis.
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PMID:Breast cancer skin test antigens of increased sensitivity prepared from vesicular stomatitis virus-infected tumor cells. 628 Aug 32

RS7, a murine IgG1 antibody raised against human lung carcinoma, possesses pancarcinoma reactivity. The antigen defined by this antibody is present in tumors of the lung, stomach, bladder, breast, ovary, uterus, and prostate. Efficient targeting and therapy by radiolabeled RS7 has been demonstrated previously in animals bearing Calu-3 (an adenocarcinoma of the lung) xenografts. In this study, the efficiency of tumor targeting and the efficacy of therapy of this antibody in nude mice bearing the MDA-MB-468 human breast carcinoma were evaluated. The tumor:nontumor ratios of RS7 were 1.9-2.1 times higher than those for Ag8 (the control antibody) on day 14, except for the heart. These values were similar to that of RS7 in the Calu-3 xenograft model. Radioimmunotherapy using 250 microCi of 131I-labeled RS7 in animals bearing approximately 0.1 cm3 tumors (approximately 10 days old) caused the disappearance of tumors in 6 of 10 animals at 2 weeks postinjection. Tumors eventually disappeared from all animals, and animals remained tumor-free until the termination of the study (11 weeks of duration), except for one animal that developed a transient reappearance of tumor. The tumors in animals that received an equal dose of 131I-labeled Ag8, or unlabeled RS7 or Ag8, either were unchanged or continued to grow. Treatment that used 275 microCi of 131I-labeled RS7 in animals carrying established tumors (1 month old, approximately 0.2-0.3 cm3) showed that this antibody is effective in controlling the growth of this tumor. Tumors in the treatment group began to disappear between the second and third weeks after the injection of the radiolabeled antibody. Seven of 10 animals remained tumor free at 15 weeks after the injection. Tumors in animals that received an equal dose of control antibody persisted but grew at a slower pace compared to the untreated group. No systemic toxicity was observed.
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PMID:In vitro and in vivo reactivity of an internalizing antibody, RS7, with human breast cancer. 749 60

Previous studies demonstrated that metastatic MDA-MB-435 breast carcinoma cells synthesized and secreted less of the extracellular matrix protein thrombospondin 1 (TSP1) than nonmetastatic breast carcinoma cell lines, a trend also observed for melanoma and lung carcinoma cell lines. To directly examine the effect of tumor cell TSP1 expression on tumor growth and metastasis. MDA-MB-435 cells were transfected with full length THBS-1 cDNA linked to a constitutive cytomegalovirus promoter, or with the cytomegalovirus vector alone. Injection of transfected clones that overexpressed TSP1 into the mammary fat pad of nude mice resulted in a dose-dependent inhibition of primary tumor size and an inhibition of spontaneous pulmonary metastases, which occurred in 21-30% of THBS-1 transfectants compared to 44-49% of controls (P = 0.007). An additional clone was identified that overexpressed a COOH-terminally truncated TSP1. This clone produced larger primary tumors and an increase in the occurrence of metastases relative to control transfectants, suggesting the participation of a previously understudied region of TSP1 in the regulation of tumor progression. The THBS-1 and control transfectants did not exhibit significant differences in growth, colonization, or motility in vitro. However, a relative reduction in capillary densities in primary tumors formed by the wild-type THBS-1 transfectants was observed, suggestive of an angiostatic effect. The data indicate that tumor cell production of TSP1 can exert a significant inhibitory effect on tumor progression in the MDA-MB-435 breast carcinoma cell line, which may be attributable in part to a reduction in angiogenesis.
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PMID:Transfection of thrombospondin 1 complementary DNA into a human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis. 752 99

We reported previously that the adenovirus E1a gene reversed the transformed phenotype of one human melanoma and one fibrosarcoma cell line (S. Frisch, Proc. Natl. Acad. Sci. USA, 88: 9077-9081, 1991). To determine the generality of the tumor suppression effects of E1a, a diversity of tumor cell lines, including A204 rhabdomyosarcoma, RD rhabdomyosarcoma, Saos-2 osteosarcoma, NCI-H23 non-small cell lung carcinoma, MDA-MB435S breast carcinoma, and ras-transformed MDCK kidney epithelial cells, were infected with a retrovirus bearing the 12S E1a coding sequence. We demonstrate here that the expression of E1a severely reduced the anchorage-independent and tumorigenic growth of these cell lines without affecting their growth under normal culture conditions. The parental tumor cells used in this study did not overexpress c-erbB-2/neu, and E1a did not affect its expression in these cells. Thus, tumor suppression by E1a can operate in a wide variety of human tumor cells by c-erbB-2/neu-independent mechanisms. E1a also sensitized these cell lines to the cytotoxic effects of the anticancer drugs etoposide and cisplatin. The results suggest that E1a could prove useful for the gene therapy of a wide variety of human cancers.
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PMID:Adenovirus E1a-mediated tumor suppression by a c-erbB-2/neu-independent mechanism. 758 33

The biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15-kDa glycoprotein (GCDFP-15), is presently unknown. We have added GCDFP-15 to cell culture medium and tested its effect on proliferation of 4 human breast-cancer cell lines (MCF7, BT474, MDA-MB231 and T47D) and a "normal" human immortal breast-cell line (MCF10A). These breast-cell lines showed a mitogenic response to GCDFP-15 (10 micrograms/ml). GCDFP-15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA-MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto-regulatory effect of endogenous GCDFP-15 synthesized by the T47D cells. GCDFP-15 was ineffective on 2 colon-cancer cell lines (HT29 and NIC-H716), on the IMR32 neuroblastoma cell line and on the NIC-H209 small-cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP-24) was tested, following the same experimental design, on the 5 breast-cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP-15 observed in this study in both "normal" and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP-15 in breast-cancer progression should be considered.
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PMID:Mitogenic effect of the 15-kDa gross cystic disease fluid protein (GCDFP-15) on breast-cancer cell lines and on immortal mammary cells. 782 19

It was recently found that urokinase-type plasminogen activator (uPA) is involved in the cleavage of its receptor (uPAR) on cultured cells, thereby releasing one of the receptor's 3 domains (the ligand binding domain I) and leaving the 2 others [uPAR(2 + 3)] anchored to the cell surface. With monoclonal antibodies (MAbs) we have now identified human uPAR(2 + 3) in lysates of invasive human MDA-MB-231 mammary carcinomas xenografted into nude mice. The production of peptide antibodies recognizing different domains of murine uPAR made it possible to identify a similar cleaved form of uPAR, murine uPAR(2 + 3), in extracts of primary Lewis lung carcinomas. Cleavage of uPAR also occurs in cultured MDA-MB-231 cells and Lewis lung carcinoma cells. This cleavage is inhibited by anticatalytic antibodies to either human or murine uPA, respectively, indicating that it is catalyzed by either uPA or plasmin generated by uPA. The amount of uPAR(2 + 3) may therefore be directly related to the activity of the uPA system and it is possible that the level of uPAR(2 + 3) in cancer tissue may prove to be a stronger prognostic parameter than the levels of either full-length uPAR or UPA.
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PMID:A cleaved form of the receptor for urokinase-type plasminogen activator in invasive transplanted human and murine tumors. 792 82

Work from our laboratory indicates that HLA class II induction by IFN- gamma in the retinoblastoma (RB) protein-defective breast carcinoma line MDA-468-S4 (S4) requires reconstitution of functional RB. To determine whether RB is required for HLA class 11 expression in multiple tumor types, the RB-defective non-small cell lung carcinoma line H2009 and its RB-reconstituted subclones were examined for class II inducibility. Surface HLA-DR (DR) was not inducible by IFN-gamma in H2009. However, unlike the RB-reconstituted subclones of S4, DR surface expression was not detected in the H2009 RB-positive subclones. IFN-gamma induction of CIITA, a major regulator of class II transcription, suggested that H2009 retained at least part of the IFN-gamma signaling pathway leading to class II expression. Examination of class II mRNA indicated that IFN-gamma induction of RB was rescued in the RB-positive subclones of H2009, confirming the requirement for RB for HLA class II inducibility and revealing that RB is required for inducibility in developmentally distinct tumor types. However, DRA inducibility was not rescued in the H2009 RB-positive subclones, which explained the lack of surface DR induction in the RB-positive H2009 subclones. DPA and DPB were also only weakly inducible in the RB-reconstituted H2009 subclones, compared with the previously described, S4 RB-positive subclones. Finally, data reported here indicates that RB's ability to inhibit IFN-gamma-induced apoptosis is not a viable explanation for why RB expression rescues DRB inducibility in H2009.
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PMID:Apoptosis-independent retinoblastoma protein rescue of HLA class II messenger RNA IFN-gamma inducibility in non-small cell lung carcinoma cells. Lack of surface class II expression associated with a specific defect in HLA-DRA induction. 878 10


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