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

Neonatal human prostatic epithelial cells (NP-2s) were transfected by strontium phosphate coprecipitation with a plasmid (pRSV-T) containing the SV40 early region genes. The cells transfected with pRSV-T, but not the sham-transfected controls, formed rapidly growing, multilayered colonies within 2 weeks at a frequency of 1 x 10(-4) in a serum-free medium (P4-8F). In all, 28 colonies of transformed cells were isolated. Three of these have been cultured for a sufficient length of time to show that their growth potentials are well beyond that of the normal progenitor cells (NP-2s). There is also little or no indication of the culture "crisis" commonly seen in SV40-transformed cells in these transfected lines. All contain cytokeratins and SV40 T-antigen as revealed by immunofluorescence, have ultrastructural features of epithelial cells, and are pseudodiploid. None have produced tumors within 1 year after s.c. injection into nude mice. The transformed as well as the parental NP-2s cells require bovine pituitary extract for growth in serum-free medium and are stimulated by transforming growth factor beta 1 (TGF-beta 1) and epidermal growth factor in clonal growth assays. In contrast, a prostatic carcinoma cell line (PC-3) is inhibited by TGF-beta 1. This serum-free system and immortalized transfected clones will be useful for studying the action of putative prostatic carcinogens and tumor-promoting agents.
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PMID:Transformation of human neonatal prostate epithelial cells by strontium phosphate transfection with a plasmid containing SV40 early region genes. 254 97

Previous studies have established that colon carcinoma cells secrete several polypeptide growth factors, including TGF-alpha/EGF and TGF-beta, suggesting that these and related molecules function in an autocrine/paracrine fashion to modulate tumor-cell growth. To investigate this possibility, we have studied the expression of transforming growth factor receptors in a panel of human colon carcinoma cell lines and in several untransformed epithelial cell populations. The results have revealed that neoplastic colon cells express receptors for both TGF-alpha/EGF and TGF-beta. Immunoprecipitation identified the TGF-alpha/EGF receptor as a structurally intact 170-kDa protein. No evidence for over-expression was found. TGF-alpha (and EGF) enhanced receptor autophosphorylation, indicating that these receptors were biochemically functional. TGF-beta blocked DNA synthesis in non-neoplastic epithelial cells but not in tumorigenic colon populations. There was no correlation with TGF-beta receptor number or dissociation constant. However, chemical cross-linking studies revealed a TGF-beta receptor subtype of 75 kDa in 3 of the 4 colon carcinoma cells which was undetectable in normal IEC epithelial cultures, suggesting a possible association between 75-kDa receptor expression and refractoriness to growth inhibition of TGF-beta. Together, these data support the concept that locally-produced growth regulators can function in an autocrine or paracrine manner to influence the proliferation of colon carcinoma cells.
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PMID:Expression of TGF-alpha/EGF and TGF-beta receptors in human colon carcinoma cell lines. 254 33

Cell motility (i.e., movement) is an essential component of normal development, inflammation, tissue repair, angiogenesis, and tumor invasion. Various molecules can affect the motility and positioning of mammalian cells, including peptide growth factors, (e.g., EGF, PDGF, TGF-beta), substrate-adhesion molecules (e.g., fibronectin, laminin), cell adhesion molecules (CAMs), and metalloproteinases. Recent studies have demonstrated a group of motility-stimulating proteins which do not appear to fit into any of the above categories. Examples include: 1) scatter factor (SF), a mesenchymal cell-derived protein which causes contiguous sheets of epithelium to separate into individual cells and stimulates the migration of epithelial as well as vascular endothelial cells; 2) autocrine motility factor (AMF), a tumor cell-derived protein which stimulates migration of the producer cells; and 3) migration-stimulating factor (MSF), a protein produced by fetal and cancer patient fibroblasts which stimulates penetration of three-dimensional collagen gels by non-producing adult fibroblasts. SF, AMF, and MSF are soluble and heat labile proteins with Mr of 77, 55, and 70 kd by SDS-PAGE, respectively, and may be members of a new class of cell-specific regulators of motility. Their physiologic functions have not been established, but available data suggest that they may be involved in fetal development and/or tissue repair.
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PMID:Protein factors which regulate cell motility. 255 6

When applied to the skin, phorbol esters (PEs) elicit signs of acute inflammation, suggesting they may induce the release of mediators from mast cells. Therefore, we have studied the effects of PEs on purified rat peritoneal and thoracic mast cells both alone and in conjunction with the calcium ionophore, A23187, and various other secretagogues that interact with immunoglobulin E (e.g., anti-IgE and Con A) or other cell surface receptors, e.g., somatostatin and compd 48/80. PEs alone caused little or no release of histamine. However, the PE 12-O-tetradecanoylphorbol-13-acetate (TPA, 10 ng/ml) tremendously potentiated release induced by the calcium ionophore A23187, reducing the EC50 for A23187 from 832 ng/ml to 56 ng/ml. In the presence of suboptimal A23187 (50 ng/ml), only active tumor promoting PEs elicited histamine release. The EC50 values of the various active PEs were: TPA 5 ng/ml; 4 beta-PDD, 83 ng/ml; and 4-O-methyl-TPA, 807 ng/ml, with maximal histamine release ranging from 54 to 80%. TPA synergistically enhanced stimulation of histamine release by anti-IgE and Con A over the entire concentration-response range. In contrast, this synergism was absent when cells were stimulated with somatostatin and compd 48/80. Phorbol esters may act by increasing the activity of a calcium/phospholipid-dependent protein kinase (Ca/PL-PK). Mast cells do have Ca/PL-PK activity, and TPA in the presence of suboptimal A23187 induces protein phosphorylation comparable with other secretagogues. These results suggest that in the purified mast cell, PE-induced mediator release increases the sensitivity of release mechanisms for calcium, acts syngergistically with secretagogues interacting with IgE, and as suggested from structure-activity relationships, occurs via a specific mechanism of action perhaps involving the Ca/PL-PK.
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PMID:Characterization of the effects of phorbol esters on rat mast cell secretion. 257 54

Normal kidney and renal cell carcinoma tissues from ten patients were studied for mRNA and DNA for both transforming growth factors alpha and beta 1. Northern and Southern hybridizations were conducted on samples extracted from the solid tumor and surrounding normal tissues and two tumor-derived cell lines. Low levels of constitutive expression of TGF-alpha mRNA were detected in all normal kidney tissues; six of the ten patients, however, demonstrated an increased (2- to 8-fold) expression of TGF-alpha in the tumor versus normal kidney as determined by densitometry of RNA blots. All ten patients had elevated mRNA levels for TGF-beta 1 in the tumor (2.5-to 22-fold increase) relative to normal kidney. Two tumor-derived cell lines also expressed TGF-alpha and TGF-beta 1 mRNA. Southern blot hybridization of the DNA extracted from the normal tumor pairs revealed no gene amplification or gross rearrangement for either the TGF-alpha or TGF-beta 1 genes. These results demonstrate the expected constitutive expression of TGF-beta 1 by normal kidney; however, the constitutive expression of TGF-alpha by Northern blot analysis in normal adult human kidney is previously unreported. Enhanced expression of TGF-alpha and TGF-beta 1 mRNA in solid tumor may be related to the development of renal cell carcinoma.
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PMID:Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma. 258 39

We have previously reported that the J774A.1 macrophage-like tumor cell line produces two potent monokines which stimulate the growth of osteoblasts and chondrocytes. These growth factors, which have an affinity for heparin-agarose, have been termed HEP I (a 30 Kd PDGF-like molecule) and HEP II (an approximately 20 Kd molecule), respectively, based on their elution profile. Unlike HEP I, HEP II does not stimulate the growth of fibroblasts. Extensive biological and chromatographic studies disclosed that HEP II appears to be a unique bone cell mitogen unlike any known growth factor, including the FGFs, IL-1s, and TNFs, EGF, IGF-I and -II, TGF-beta, beta 2 microglobulin, G-CSF, CSF-1 and GM-CSF. To characterize more fully the effects of the macrophage-derived monokines on osteoblast growth and function, clones were derived from calvaria explant cultures. Two clones, SDFRC-2.05 and SDFRC-3, were developed and found to exhibit osteoblastic characteristics, including high levels of alkaline phosphatase, synthesis of type I but not type III collagen, and an increased intracellular cAMP production in response to PTH. The SDFRC-3 cells exhibited a polygonal morphology like that of the explant-derived cells while SDFRC-2.05 cells exhibited a more fibroblastic morphology. When tested on the explant cultures and clones, HEP I and HEP II were found to stimulate DNA synthesis and increase protein per culture, but decreased alkaline phosphatase activity. Clone SDFRC-3 was found to be more responsive to HEP II than clone SDFRC-2.05. Both monokines were found to be more potent mitogens for bone cells than TGF-beta. HEP II, but not HEP I or TGF-beta, induced a transformation of bone cells from a polygonal to a fibroblastic morphology, suggesting the induction of migration prior to proliferation. Thus, macrophages may be responsible not only for bone repair but also for ensuring the linkage of bone formation to resorption during physiological remodeling.
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PMID:Monokines produced by macrophages stimulate the growth of osteoblasts. 263 Jan 69

Proliferation and metastasis of cancer are affected by the interactions between cancer cells and the host cells; in particular, host reactive cells regulate proliferation and metastasis or cancer cells directly through various soluble factors. However, recent studies revealed that cytokines and growth factors released by macrophages and lymphocytes promote proliferation and metastasis of cancer cells, whereas they act for controlling infection or healing wounds. For example, transforming growth factor (TGF) released by lymphocytes and macrophages induces transformation of normal cells to malignant cells; and TGF-alpha promotes the production of PDGF & TGF-beta, which results in the proliferation of cancer cells. It is also known that TGF-beta suppresses proliferation of T.B lymphocytes and production of TNF-alpha. Oxygen radicals are also considered to be involved in the transformation that cancer cells increase their malignancy. This paper will deal with the host-tumor interactions, introducing our experimental results.
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PMID:[Enhancement of cancer growth and metastasis by host reactive cells and their secreting factors]. 267 96

Treatment consisting of surgery and/or radiation therapy for patients with squamous cell carcinoma of the head and neck has frequently been successful in earlier stages of disease. Advanced and non-resectable tumor stages have a very poor cure rate. We initiated this trail to assess the role of the potentiation between cis-PDD and radiation previously reported in advanced head and neck tumors. Eighteen patients were investigated in this study. The treatment consisted of cis-PDD and hyperfractionated radiotherapy. Seventeen (94%) of the patients responded to the treatment regimen with either a complete regression (5/18 = 33%) or a partial regression (11/18 = 61%) of the tumor. Median survival was short and lasted 12+ months among complete responders and 8+ months among partial responders. However all patients did experience an increased and not tolerable incidence of delayed radiation toxicity such as mucositis combined with necrotic stomatitis. Both complications limited the compliance to the therapy. Because of these complications we had to stop the ongoing study.
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PMID:Radiosensitizing with cis-platin in advanced head and neck cancer. Results and problems. 269 49

Transforming growth factor beta (TGF-beta is a multifunctional regulator of cell growth. It has become increasingly clear that TGF-beta action depends on the responsive cell types. Thus TGF-beta stimulates proliferation of mesenchymal cells and, in contrast, inhibits the growth of a large variety of epithelial cells. Recent studies, albeit controversial, support the notion that a gradient in mRNA transcripts encoding TGF-beta is maintained along the crypt-villus continuum of the small intestine in close correlation with the stage of differentiation of the enterocyte. Exogenous TGF-beta has been shown to inhibit the proliferation of a non-transformed rat jejunal crypt cell line. Additional salient findings have indicated that colon carcinoma cell lines recalcitrant to the restraining action of TGF-beta on proliferation are poorly differentiated, and that moderately differentiated colon tumor lines do retain, at least partly, their responsiveness to TGF-beta. To the best of our knowledge, no evidence is available pertaining to a contributory role of TGF-beta in the signalling mechanisms regulating growth and differentiation of normal colonic epithelial cells. In addition, we are ignorant of whether the interesting findings related to a functional relationship between TGF-beta and colon carcinoma cells lines (vide supra) are applicable to colonic preneoplastic and tumor cells in their natural habitat. In this review, we dwell on the available facts and missing observations, and present conceivable hypotheses pertaining to a putative role of TGF-beta in colon differentiation and neoplasia.
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PMID:Transforming growth factor-beta in intestinal epithelial differentiation and neoplasia (review). 269 92

A culture model for invasion of rat mesothelial cell layer by rat ascites hepatoma cells has been developed. By using this quantitative model, the preculture with macrophages (0.1 less than macrophage/tumor cell less than 1.0) was found to enhance both the in vitro and in vivo invasive potentials of the tumor cells. This potentiation appears to be mediated partly by oxygen radicals generated by the cocultured macrophages. The in vitro invasive capacity was also augmented by pretreating the tumor cells with TGF-beta or with activated platelets. A factor with anti-invasive potential (IIF) was extracted from rat liver. It inhibited the directed migration but not the growth of the tumor cells and was effective on their in vivo invasion and metastasis, as well.
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PMID:Potentiation and inhibition of tumor cell invasion by host cells and mediators. 270 5


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