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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the cheek pouch of the Syrian hamster as an experimental model for oral carcinogenesis, it has been shown that the expression of transforming growth factor-alpha (TGF-alpha) is consistently associated with the malignant transformation process. We have recently shown that production of TGF-alpha has been localized to normal hamster oral epithelium and bone marrow eosinophils. In this study we investigated the production of this cytokine in other normal hamster adult tissues. By using an EGF-radioreceptor assay, immunohistochemistry, Northern blot analysis, and in situ hybridization we have now further detected the presence of TGF-alpha mRNA and/or protein in the kidney, stomach, and pancreas of normal adult hamster. Together with the previously reported detection of TGF-alpha in oral mucosa and bone marrow eosinophils, these adult normal tissue/cellular sources can serve as sites of TGF-alpha production. The availability of hamster specific reagents (cDNA and monoclonal antibodies) and the delineation of the various adult tissues that could produce TGF-alpha make the Syrian hamster a suitable model for the study of how this multifunctional cytokine can influence normal and pathological processes.
Lymphokine Cytokine Res 1991 Oct
PMID:Localization of transforming growth factor-alpha in adult Syrian hamster tissues. 176 41

Clinical research on interferons (IFN) still focuses on the treatment of advanced cancer. The research strategy eventually must be reevaluated. The cellular minimal deviations that are seen in early phases of carcinogenesis might be the most rational target for immune interventions. That biologic response modifiers have considerable capacity to prevent induction and development of malignant neoplasias has been demonstrated in several animal systems. Even the few clinical studies available at present on the treatment of preneoplastic lesions with IFN have definitely shown more success than those involving treatment of advanced tumors. In addition, there is experimental evidence that IFN might be suitable candidates for immunoprevention. The major problems hampering a wider application of IFN in immunoprevention is that they cause adverse effects. Unfortunately, we do not know much about the specific mechanisms involved in the immune control of human tumor development during the initial and the latency phases of carcinogenesis. More research is needed in this area. In this article the state of the art of using IFN for treating preneoplastic lesions is reviewed, and also we report some of our experimental results on IFN and anticancerogenesis.
J Interferon Cytokine Res 1996 May
PMID:Interferons in precancer and cancer prevention: where are we? 872 73

Downregulation of HLA class I expression is a common event in tumor biology. Various underlying mechanisms have been defined in different tumors, but the knowledge of HLA loss mechanisms in cervical carcinoma is limited. To identify causalities for loss of surface expression, we performed a detailed investigation of HLA class I phenotypes and genotypes in 5 primary cervical tumors and on derivative cell lines. Protein expression on primary tissues and cell lines was evaluated by immunohistochemistry and flow cytometry respectively, using a broad panel of allele-specific monoclonal antibodies. Loss of expression was seen in 3 cases, comprising B15-locus loss, B15-allelic loss, and loss of an A74/B15 haplotype and an A24 allele of the other haplotype. Cytokine treatment induced re-expression of the B15-locus loss, suggesting a regulatory defect underlying lack of constitutive expression in this tumor. In contrast, molecular analyses at the DNA and/or RNA level showed that the other, non-inducible, losses were associated with chromosomal HLA gene defects. Loss of heterozygosity analysis was performed to confirm larger genomic deletions. This study shows that HLA gene defects by mutation or loss of heterozygosity as well as regulatory defects are involved in cervical carcinogenesis. The resulting changes in HLA expression may directly affect the efficacy of the immune response to these human papillomavirus-related neoplasms. Heterogeneity in the underlying loss mechanisms may offer individual tumors various opportunities to escape immune surveillance, and may severely compromise T-cell based therapy.
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PMID:HLA class I phenotype and genotype alterations in cervical carcinomas and derivative cell lines. 969 55

Signals from the TGF-betas are mediated by the TGF-beta receptors and their substrates, the Smad proteins. Inactivation of either of the two transmembrane serine/threonine kinases called the TGF-beta type I and type II receptors is now known to underlie a wide variety of human pathologies including, especially carcinogenesis. Numerous studies have now demonstrated that the TGF-beta receptor complex and its downstream signaling intermediates constitute a tumor suppressor pathway. We review here a specific pathway of mutational inactivation of the TGF-beta type II receptor resulting from microsatellite instability and demonstrate that, by contrast, the most common mechanism of loss of expression of the TGF-beta type II receptor involves transcriptional repression. This provides a new target for therapeutic intervention.
Cytokine Growth Factor Rev
PMID:Molecular mechanisms of inactivation of TGF-beta receptors during carcinogenesis. 1070 63

Cytokine transforming growth factor-beta1 plays an important role in physiological processes during ontogenesis, cell differentiation, immune responses, carcinogenesis, inflammation, wound healing, fibroproduction, progression of renal insufficiency and arteriosclerotic lesion development. Its biological function is influenced through the two signal peptide polymorphisms. We describe a new, economical, easy and fast alternative method which allows detection of both polymorphisms from one PCR product with subsequent restriction analysis with two different restriction enzymes. This method could facilitate further research on the role of this cytokine in human disease.
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PMID:Alternative method for diagnosis of two polymorphisms in the human transforming growth factor-beta1 by PCR-mediated double site-directed mutagenesis. 1076 4

On the basis of studies using the Min mouse model of colon carcinogenesis, we have recently proposed that a fibre-like food (short-chain fructo-oligosaccharides, sc-FOS) fermented in the colon may stimulate a mechanism of cancer immunosurveillance. In the present paper, we have investigated the expression of cytokines as potential effector molecules. Interleukin (IL-)4, IL-5, IL-13, IL-15 and interferon (INF)-gamma mRNAs were detected by a multi-probe ribonuclease protection assay in C57BL/6J and Min mouse colons. IL-15 mRNA expression was significantly amplified (P=0.01) by the sc-FOS-enriched diet in the colon of Min mice.
Cytokine 2001 May 21
PMID:Cytokine mRNA expression in mouse colon: IL-15 mRNA is overexpressed and is highly sensitive to a fibre-like dietary component (short-chain fructo-oligosaccharides) in an Apc gene manner. 1144 26

The role of A/G polymorphism at nucleotide -1082 in the interleukin-10 (IL-10) promoter was assessed by following the disease course of 253 patients who had had a routine diagnostic Hybrid Capture human papillomavirus (HPV) test because of cytologic or colposcopic abnormalities of the uterine cervix. At baseline, 97 (78%) of the 125 high-risk HPV-positive and 83 (65%) of the 128 HPV-negative patients had equivocal cytologic atypia classified as P3 by the Papanicolaou classification, and the rest of the patients had mild colposcopic atypia with cytologic results of no oncogenic significance. In the high-risk HPV-infected patients, the frequency distribution of the nt -1082 genotypes (A/A: 28%; A/G: 52%; G/G: 20%) did not differ significantly from that in the controls (A/A: 25%; A/G: 51%; G/G: 24%; p = 0.70). On the other hand, the nt -1082 G allele tended to decrease susceptibility to equivocal cytologic atypia unrelated to HPV infection (A/G: OR = 0.56 [95% CI: 0.31-1.02], G/G: OR = 0.27 [95% CI: 0.11-0.63], p for trend = 0.05). With respect to the development of high-grade cervical intraepithelial neoplasia (CIN), the established risk factors, such as high-risk HPV infection (RR = 104.6, 95% CI: 14.2-769.9) and cytologic atypia (RR = 9.6, 95% CI: 2.34-39.7) but not the various nt -1082 genotypes (A/A: reference; A/G: RR = 1.11 [95% CI: 0.59-2.08]; G/G: RR = 0.62 [95% CI: 0.25-1.50]) were found to increase the risk for high-grade CIN. In conclusion, the nt -1082 polymorphism had no influence on the early phase of cervical carcinogenesis but may determine different susceptibilities to cervical abnormalities unrelated to HPV infection.
J Interferon Cytokine Res 2004 Apr
PMID:IL-10 promoter nt -1082A/G polymorphism and human papillomavirus infection in cytologic abnormalities of the uterine cervix. 1514 70

Evidence indicates that the testis possesses a reduced capacity to mount inflammatory and rejection responses, which undoubtedly contributes to the ongoing survival of the highly immunogenic germ cells. The contribution of local cytokine expression to this condition was investigated in adult male rats treated with lipopolysaccharide to induce inflammation. Cytokine mRNA and protein expression were determined in tissue extracts and fluids by Northern blot analysis, quantitative PCR, or RNAse protection assay and specific ELISAs. Testicular expression of the proinflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor-alpha was considerably attenuated compared with the liver (control tissue); in contrast, the testicular IL-6 response was enhanced. Expression of IL-10, a type 2 immunoregulatory cytokine, was similar in both testis and liver, whereas the immunoregulatory/anti-inflammatory cytokines transforming growth factor-beta(1) and activin A were constitutively elevated in both normal and inflamed testes. The IL-1beta and transforming growth factor-beta(1) proteins were present principally in their latent (inactive) forms, indicating that enzymic processing is an important control mechanism for these two cytokines within the testis. These data indicate that inflammatory and regulatory cytokine activity is regulated at both transcriptional and posttranslational levels in a testis-specific manner. It is concluded that a novel pattern of suppression of proinflammatory cytokine responses and normal or elevated expression of immunoregulatory cytokines may be responsible for reduced inflammatory responses and enhanced graft survival in the testis. These data have important implications for the understanding and treatment of male autoimmune infertility, testicular inflammation. and carcinogenesis.
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PMID:Cytokine profiles in the testes of rats treated with lipopolysaccharide reveal localized suppression of inflammatory responses. 1566 66

Studies using transgenic and knockout mice have demonstrated that particular cytokines influence lung tumor growth and identified prostaglandin E2 (PGE2), prostacyclin (PGI2) and nitric oxide (NO) as critical mediators of this process. PGE2 and NO were pro-tumorigenic while PGI2 was antitumorigenic. We describe herein an in vitro experimental approach to examine interactions among cytokines, prostaglandins (PGs) and NO. PGE2, PGI2, and NO levels were assayed in culture media from non-tumorigenic mouse lung epithelial cell lines, their spontaneous transformants and mouse lung tumor-derived cell lines, before or after exposure to the cytokines TNFalpha, IFNgamma and IL1beta, alone and in combination. More PGE2 than PGI2 was produced by neoplastic cells, while the opposite was observed in non-tumorigenic lines. Cytokine exposure magnified the extent of these differential concentrations. The PGE2 to PGI2 ratio was also greater in chemically-induced mouse lung tumors than in adjacent tissue or control lungs, supporting the physiological relevance of this in vitro model. Expression of PG biosynthetic enzymes in these cell lines correlated with production of the corresponding PGs. Cytokine treatment enhanced NO production by inducing the inflammation-associated biosynthetic enzyme, inducible NO synthase (iNOS), but this did not correlate with the neoplastic status of cells. Inhibition of iNOS or cyclooxygenase 2 activity using aminoguanidine or NS-398 respectively, demonstrated that NO did not affect PG production nor did PGs influence NO production. Since lack of iNOS inhibits mouse lung tumor formation, we propose that this is independent of any modulation of PG synthesis in epithelial cells. The similar normal/neoplastic trends in PGE2 to PGI2 ratios both in vitro and in vivo, together with an amplification of this difference upon cytokine exposure, are consistent with the hypothesis that cytokines released during inflammation exacerbate differences in the behavior of neoplastic and normal lung cells.
Carcinogenesis 2005 Jul
PMID:Cytokines differentially regulate the synthesis of prostanoid and nitric oxide mediators in tumorigenic versus non-tumorigenic mouse lung epithelial cell lines. 1574 62

The activin growth factors consist of dimeric proteins made up of activin beta subunits and have been shown to be essential regulators of diverse systems in physiology. Four subunits are known to be expressed in mammalian cells: betaA, betaB, betaC, and betaE. Surprisingly, deletion of activin betaC and betaE subunits in vivo does not affect embryonic development or adult physiology which has led to the activin betaC and betaE subunits being regarded as non-essential and unimportant. The steady accumulation of circumstantial evidence to the contrary has led this lab to reassess the role of the activin betaC subunit. Activin betaC protein is expressed more widely than indicated by mRNA localisation. Experiments overexpressing activin betaC subunit or adding exogenous Activin C in vitro are contradictory but suggest roles for activin betaC in regulating Activin A action in apoptosis and homeostasis. Sequestration of betaA subunits by dimerisation with betaC subunits to form Activin AC represents an intracellular regulator of Activin A bioactivity. Activins play a pivotal role in normal physiology and carcinogenesis, so any molecule, such as the activin betaC subunit, that can affect activin action is potentially significant. Advancing our understanding of the physiological role of the activin betaC subunit requires new tools and reagents. Direct detection of the Activin AC dimer will be essential and will necessitate the purification of heteromeric Activin AC protein. In addition, there is a need for the development of an in vivo model of activin betaC subunit overexpression. With development of these tools, research into activin action in development and physiology can expand to include the less well understood members of the activin family such as activin betaC.
Cytokine Growth Factor Rev
PMID:Should activin betaC be more than a fading snapshot in the activin/TGFbeta family album? 1592 36


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