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

A highly immunogenic C3H-derived UV-induced tumor was cotransfected with a murine transforming growth factor type beta 1 (TGF-beta 1) cDNA and a neomycin-resistance gene. Stable clones were isolated and used in vitro and in vivo to determine the effects of endogenously produced TGF-beta on cytolytic T-lymphocyte (CTL) responses. Tumor cells producing TGF-beta, though retaining expression for class I major histocompatibility complex molecules and the tumor-specific antigen, did not stimulate primary CTL responses in vitro and were not effective in vivo for directly stimulating primary CTL or in priming for CTL responses. Furthermore, TGF-beta-producing tumors grew progressively in transiently immunosuppressed mice without losing the tumor antigen; thus, TGF-beta produced by tumors may promote escape from immune surveillance.
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PMID:A highly immunogenic tumor transfected with a murine transforming growth factor type beta 1 cDNA escapes immune surveillance. 213 15

TGF-beta 1 is demonstrated to inhibit skin keratinocyte proliferation when added during the G1 phase of the cell cycle. Human foreskin keratinocytes transformed with either HPV-16 or -18 or SV40, however, were resistant to the growth inhibitory effects of TGF-beta 1. Since TGF-beta 1 appears to inhibit keratinocyte growth through down-regulation of c-myc, it was hypothesized that these DNA tumor viruses might be modulating the response to TGF-beta 1 via this pathway. Transient expression of proteins HPV-16 E7, adenovirus type 5 E1A, and SV40 large T antigen is demonstrated to block TGF-beta 1 suppression of c-myc transcription. This effect was not observed with DNA tumor virus transforming proteins mutated in their pRB binding domain. These observations indicate that pRB or another protein that interacts with this binding domain mediates TGF-beta 1 regulation of c-myc gene expression and growth inhibition.
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PMID:TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. 214 May 28

In Rous sarcoma virus (RSV)-infected chickens, wounding leads to tumor formation with nearly 100% frequency in tissues that would otherwise remain tumor-free. Identifying molecular mediators of this phenomenon should yield important clues to the mechanisms involved in RSV tumorigenesis. Immunohistochemical staining showed that TGF-beta is present locally shortly after wounding, but not unwounded controls. In addition, subcutaneous administration of recombinant transforming growth factor-beta 1 (TGF-beta 1) could substitute completely for wounding in tumor induction. A treatment protocol of four doses of 800 nanograms of TGF-beta resulted in v-src-expressing tumors with 100% frequency; four doses of only 10 nanograms still led to tumor formation in 80% of the animals. This effect was specific, as other growth factors with suggested roles in wound healing did not elicit the same response. Epidermal growth factor (EGF) or TGF-alpha had no effect, and platelet-derived growth factor (PDGF) or insulin-like growth factor-1 (IGF-1) yielded only occasional tumors after longer latency. TGF-beta release during the wound-healing response may thus be a critical event that creates a conducive environment for RSV tumorigenesis and may act as a cofactor for transformation in this system.
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PMID:Mediation of wound-related Rous sarcoma virus tumorigenesis by TGF-beta. 216 44

During the period 1978-1987, 255 patients with pathologically proven hepatocellular carcinoma (HCC) were assessed to be unresectable by laparotomy. Of them 155 had their tumors chiefly confined in the right or left lobe. Second stage resection was performed in 26 (16.8%) after marked reduction of the tumor by combination treatment with hepatic artery ligation (HAL) + hepatic artery infusion chemotherapy (HAI) + multifractionated radiotherapy (MFD) with linear accelerator, or radioimmunotherapy using 131I-anti human HCC ferritin antibody (131I-FtAb), which yielded the highest second stage resection rate (29.8%, 14/47) as compared to HAL + HAI or HAL + cryosurgery (16.9%, 12/71), HAL or HAI (0%, 0/37) alone. The 3 year survival rate of the 26 patients with second stage resection was 74.3%, comparable with those of small HCC resection (82.7%, n = 111) and radical resection of large HCC (56.1%, n = 122) in the same period. Experimental study using nude mice bearing human HCC also showed the superiority of triple (MFD or 131I-FtAb + Cisplatin PDD + mixed bacterial vaccine MBV) versus double (MFD or 131I-FtAb + PDD, or MFD or 131I-FtAb + MBV) and double versus single treatment modality. Both experimental and clinical data indicated that immunosuppression after radiotherapy was prevented by adjuvant immunotherapy (MBV). Thus, this treatment model provides an opportunity for resection or even cure in a part of patients with unresectable HCC confined in one lobe.
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PMID:[Multimodality treatment and two-stage resection for unresectable hepatocellular carcinoma--experimental and clinical studies]. 216 21

TGF-beta stimulates the anchorage-dependent proliferation of some cells and inhibits the proliferation of others. Although the ability of TGF-beta to affect different cell types in opposite ways is puzzling, it may not reflect fundamental differences in the initial cellular responses to TGF-beta. Instead, the different types of cellular responses may be because TGF-beta initiates a number of changes in all responsive cells, some of which may lead to proliferation and others, to proliferative arrest. Depending on the individual responses of specific cell types and on the environment of the cells, the balance of the effects of these changes could lead to cellular proliferation or inhibition of proliferation. This hypothesis is discussed in more detail below, with specific reference to the effects of TGF-beta on the expression of genes encoding proteases, protease inhibitors, ECM components, and growth and differentiation factors. TGF-beta also promotes the anchorage-independent growth of some cells in soft agar, but inhibits the anchorage-independent proliferation of some tumor cells. In stimulating proliferation TGF-beta often acts synergistically with EGF, FGF, TGF-alpha, or PDGF. The observed increase in soft agar growth in response to TGF-beta could be explained by a model which proposes that TGF-beta stimulates the accumulation of the ECM, which supports the action of the growth factors (e.g., EGF, TGF-alpha, PDGF, and FGF) that directly stimulate cellular proliferation. The ability of TGF-beta to inhibit the proliferation of some cells in soft agar again reminds us that the mechanism of action of this growth factor is not readily described by a single model. Although its proven ability to regulate the expression of genes that encode proteins that constitute or modify the ECM ensures TGF-beta a role in ECM remodeling, the complexity of the multiple cellular responses to this growth factor suggest that there is another aspect of the function of this growth factor. Perhaps the observations that TGF-beta stimulates the production of FSH and PDGF are the tip of the iceberg. If TGF-beta regulates a subset of genes that encode growth factors and their receptors, then this could help to explain the many and varied cellular responses to TGF-beta. By regulating genes encoding other hormones and growth factors, TGF-beta might be a "master morphogen" during development and orchestrate the local elaboration of growth factors and hormones by individual cell types.
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PMID:Transforming growth factor-beta and its actions on cellular growth and differentiation. 216 98

The possible role of changes in TGF-beta expression in the multistage development of thyroid cancer was assessed. The presence of TGF-beta 1 in thyroid epithelial cells was analyzed in sections of normal and tumor tissue using an immunoperoxidase technique employing an antibody directed against the amino-terminal 30 amino acids of mature TGF-beta 1. Specific immunostaining was clearly detected in epithelial cells in 58% of malignant thyroid tumours (including follicular, papillary, and anaplastic variants). However, no positive cells were seen in any of 7 benign tumors nor in any normal thyroid epithelium. Within the cancer group as a whole, there was no significant correlation with pathological grade or clinical stage of tumor but in one subgroup--follicular carcinomas--a significant association was noted between TGF-beta immunostaining and the presence of a specific mutation of the H-ras oncogene (codon 61, gln----arg). We conclude that a major alteration in expression of TGF-beta occurs specifically in the malignant stage of tumor development in thyroid follicular epithelium and speculate on its possible role in this process.
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PMID:Immunocytochemically detectable TGF-beta associated with malignancy in thyroid epithelial neoplasia. 218 93

Communication among individual cell types that populate connective tissues such as cartilage or bone is of critical importance in determining the phenotypic properties of these tissues under both physiologic and pathologic conditions. Cytokines, which may be defined as soluble products released from one cell that can modulate the activity of other cells, play a critical role in this process of cell communication. The introduction of molecular biologic techniques has permitted identification of specific cytokines previously characterized on the basis of biologic activities. Cloning and sequencing of these products have provided formal evidence for their existence and allowed identification of the full spectrum of their biologic activities. These results have established that individual cytokines may have multiple biologic activities and that multiple cytokines share common functional properties. Based on these results, the term "cytokine" has been used more generally to include products originally described as growth or differentiation factors, e.g., interleukins, monokines, or lymphokines. Cytokines have an important role in the initiation and control of skeletal tissue growth and development and in regulating bone remodeling in the adult organism. As in other connective tissues, these effects are mediated via paracrine, autocrine, and endocrine mechanisms. In skeletal tissues, cytokines may modulate the activity of resident cells by an additional mechanism. Factors produced locally within bone or arriving via the circulation are incorporated into the mineralized bone matrix, and their release during skeletal remodeling could provide the basis for coupling the activity of bone resorbing and forming cells. The principal cytokines that have been shown to affect skeletal tissues include factors previously described as monokines or lymphokines such as interleukin-1 (IL-1), tumor necrosis factors (TNF-alpha and TNF-beta), and interferon-gamma (IFN-gamma); the colony-stimulating factors; and the so-called growth and differentiation factors including transforming growth factors-alpha and -beta (TGF-alpha and TGF-beta), insulinlike growth factor-I (IGF-I), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). Although the effects of the individual cytokines are diverse, it is possible to classify individual factors based on their effects on specific aspects of bone formation or resorption. Significant progress has been made recently toward elucidating the mechanisms of action of the cytokines. Binding studies using radiolabeled ligands have characterized the specific cell surface receptors and defined their distribution and properties among skeletal tissue cells. Various so-called signal transduction pathways have been implicated in mediating these effects...
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PMID:Skeletal tissue response to cytokines. 220 72

Carcinogenesis is a multistep process, involving the irreversible conversion of a stem cell to a terminal-differentiation-resistant cell ("initiation"), followed by the clonal expansion of this cell ("promotion") and by the acquisition of other genetic alterations leading to malignancy ("progression"). The initiation and progression steps seem to be facilitated by mutagenesis. Promotion has been associated with agents and conditions that cause mitogenesis. Gap junctional intercellular communication, a fundamental biological process regulating cell growth and differentiation, has been postulated to play a major role in carcinogenesis. The hypothesis is supported by the fact that many cancer cells have some dysfunction in gap junctional intercellular communication, many tumor-promoting chemicals and several oncogenes (i.e., ras, src, mos, neu, but not myc) reduce gap junctional intercellular communication, and several growth factors (i.e., EGF, TGF-beta, bovine pituitary extract) inhibit gap junction function. This integrative concept postulates that chemical promoters, oncogenes coding for growth factors, receptors, or transmembrane signaling elements, and growth factors can isolate an initiated cell from the suppressing influence of surrounding normal cells by down-regulating the transfer of ions and small molecules through gap junctions.
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PMID:Modulation of intercellular communication during radiation and chemical carcinogenesis. 221 20

Homogeneous subpopulations, which are endowed with low or high metastatic potential, were selected from Lewis lung carcinoma (3LL) in an attempt to correlate metastatic phenotype with specific properties of tumor cells. Since the growth of malignant cells at secondary sites could depend on their ability to respond to microenvironments, the growth factor dependence of 3LL variants has been studied. The ability of variant lines to grow in monolayer and in soft agar cultures, either in the presence or absence of different growth factors or serum, was analyzed and correlated with their metastatic potential. The reported results demonstrate that tumor cells expressing higher metastatic potential also exhibit higher capacity to grow and proliferate in all the culture conditions tested, independently of the addition of exogenous growth factors or serum. Moreover, since highly metastasizing cells express a significant amount of TGF-beta 1 mRNA, a pattern of autocrine growth is postulated for 3LL metastatic cells. One relevant aspect of the phenotype of transformed cells is their reduced adhesion to solid substrates; this phenomenon is thought to reflect the invasive and metastatic potential of tumor cells. Since the adhesion of the cells to substrata is mediated by molecules of the extracellular matrix, the expression of extracellular matrix receptors (integrins) was studied on 3LL metastatic variants. In particular, through immunochemical and biochemical studies we investigated the expression of the laminin receptor(alpha 6/beta 1) and of a novel receptor (integrin: alpha 6/beta 4), of unknown function. The receptors were quantitated on the cell surface of 3LL variants by the use of specific monoclonal antibodies which recognize, respectively, different epitopes of alpha 6, beta 4 or beta 1 subunits. Results demonstrate that the novel integrin alpha 6/beta 4, is specifically expressed in highly metastasizing 3LL cells, whereas the laminin receptor alpha 6/beta 1 is expressed in all 3LL variants. In conclusion, data presented demonstrate that 3LL cells endowed with higher metastatic potential are more independent of the microenvironmental conditions in that they possess a higher autocrine capacity than the lower metastasizing ones, and could acquire higher capacity to invade through the expression on their cell surface of specific receptors for cell adhesion (the novel integrin, defined as alpha 6/beta 4).
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PMID:Metastatic phenotype: growth factor dependence and integrin expression. 228 30

Shionogi carcinoma 115 (SC115) has been accepted for 20 years as an androgen-responsive mouse mammary tumor. We have recently established an androgen-dependent cloned cell line (SC-3) from a SC115 tumor. We found in the present study that the growth of SC-3 cells can be stimulated by 10(-8) M testosterone (up to 100-fold) even in a protein-free medium beginning from plating [Ham's F-12: Eagle's minimum essential medium (1:1, v/v)]. In the protein-free culture, the proliferation of SC-3 cells was also found to be stimulated by acidic or basic fibroblast growth factor (FGF) alone (up to 50-fold) among various growth factors examined such as FGFs, insulin, insulin-like growth factor (IGF)-I, IGF-II, nerve growth factor, platelet-derived growth factor, epidermal growth factor, transforming growth factor (TGF)-alpha and TGF-beta. The testosterone (10(-8) M)- or FGF (10 ng/ml)-induced growth of SC-3 cells was abolished only by TGF-beta (greater than or equal to 1 ng/ml) among various growth factors examined. We show for the first time in this study an androgen-dependent growth of cancer cells (SC-3) in a protein-free medium. In the protein-free medium, growth of SC-3 cells is also stimulated by FGFs, and the androgen- or FGF-induced growth is inhibited only by TGF-beta.
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PMID:Effects of androgen, fibroblast growth factors or other various growth factors on growth of Shionogi carcinoma cells in a protein-free medium. 228 36


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