Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines can have both negative and positive effects on cells undergoing carcinogenesis. The promotion and progression phases of carcinogenesis may be affected by autocrine loops involving cytokines with growth factor activities such as IL-1, IL-2, low molecular weight B cell growth factor, TNF, IL-3, GM-CSF, M-CSF and IL-9. Aberrations in cytokine receptors such as the truncated EGF receptor present in v-erB promotes the growth of neoplastic cells. Aberrant signaling mechanisms, as found with spleen focus-forming virus, which mimics the ligand that activates the erythropoietin receptor, can also contribute to proliferation of preneoplastic and neoplastic cells. In contrast, cytokines such as interferons, LIF, TGF-beta, TNF and leukoregulin, with antiproliferative or differentiating activities, are sometimes capable of inhibiting carcinogenesis. Transfection of tumor cells with cytokine genes, such as IL-2, IL-4 and TNF, can cause suppression of in vivo tumor cell growth by mobilizing host immune and inflammatory cell responses. Thus cytokines and their receptors may play a direct role in early stages of tumor cell development and growth.
 ...
PMID:Cytokines as positive and negative regulators of tumor promotion and progression. 132 42

Peptide growth factors are proteins that stimulate cellular proliferation by binding to specific cell membrane receptors. Evidence is accumulating that abnormal regulation of growth factors may contribute to carcinogenesis. The epithelial growth factors, EGF and TGF-alpha, which share the same receptor, EGFR, may play a pivotal role in the development and maintenance of head and neck cancer; preliminary studies concerning TGF-beta and IL-2 are inconclusive. There is increased production of TGF-alpha and EGFR mRNA in the majority of fresh tissues and cell lines from patients with SCCHN. This increase results from transcriptional activation of the gene(s). Therapies directed at the regulation of gene transcription may be useful in chemoprevention or modulation of disease. Nuclear studies that target up-regulated growth factor receptors may improve the ability to detect microscopic regional metastatic disease.
 ...
PMID:The role of peptide growth factors in head and neck carcinoma. 140 94

Using the experimental model of brain tumors induced by ethyl-nitrosourea (ENU), human recombinant interleukin-2 (rIL-2) and tumor necrosis factor-alpha (TNF-alpha) were administered to Wistar rats in early stages of carcinogenesis. The results obtained suggest that IL-2 does not influence the development of nervous system tumors. In contrast, TNF-alpha was capable of modulating the development of ENU-induced tumors, producing a reduction in the number of schwannomas and a delay in the appearance of intraparenchymatous brain tumors.
 ...
PMID:Influence of recombinant interleukin-2 and tumor necrosis factor-alpha on the development of ethyl nitrosourea-induced brain tumors. 145 Apr 89

In a previous study we showed that endometrial carcinoma (EC) patients have a T cell deficiency manifested in a reduced ability to be stimulated in vitro by PHA and to produce IL-2. In an attempt to understand the mechanism responsible for this alteration we present in this paper a study on T cells characterized by the ability to form rosettes, with human erythrocytes, following Con-A activation (designated auto-rosette forming cells--ARFC). These cells are also known to manifest suppressive activity. We show that the frequency of ARFC in con-A activated peripheral blood leukocytes (PBMC) of EC patients is significantly (2-5 fold) higher than that of healthy age-matched controls or that of patients with stage--I colon or vaginal cancer. Endometrial carcinoma is known to be associated with long term exposure to estrogens unopposed by progestins. Examining the possible role of estrogens in increasing the frequency of ARFC from EC patients, we found that in vitro addition of estradiol to Con-A stimulated PBMC from healthy donors increased the frequency of ARFC to levels found in EC patients. Tamoxifen, an anti estrogen drug, reduced the frequency of the estrogen stimulated ARFC to the original low level. Our results suggest a dual role for estrogen in carcinogenesis as well as in immunomodulation.
 ...
PMID:Frequency and activity of autorosette forming cells in Con-A activated PBL from women with hyperplasia or carcinoma of the endometrium--possible role of estrogens. 196 3

The ovarian surface epithelium (OSE) takes part in the lysis and repair of the ovulatory site. It also forms invaginations and cysts that give rise to the majority of ovarian epithelial carcinomas. In the present study, we investigated the capacity of cultured human OSE to secrete cytokines that may contribute to the regulation of ovarian functions and may influence ovarian carcinogenesis. Bioassays, combined with antibody neutralization experiments, showed that OSE cells in short-term culture secrete bioactive interleukin-1 (IL-1), interleukin-6 (IL-6), macrophage colony-stimulating factor (CSF-1), granulocyte colony-stimulating factor (G-CSF), and limited granulocyte-macrophage colony-stimulating factor (GM-CSF). There was a tendency for these factors to be absent or secreted in reduced amounts in SV40-immortalized OSE lines and in two ovarian carcinoma lines. No IL-2, IL-3, or IL-4 was detected. The results show that normal OSE cells secrete factors that are known to have regulatory effects on follicular growth and differentiation, ovulation, and the distribution of intraovarian cells of the immune system. In addition, the results suggest that the secretion of cytokines by ovarian carcinomas represents the retention of normal precursor cell properties, rather than new characteristics acquired as a result of neoplastic progression.
 ...
PMID:Secretion of bioactive interleukin-1, interleukin-6, and colony-stimulating factors by human ovarian surface epithelium. 769 Nov 94

1,3-Butadiene (BD) is an indirect alkylating agent that has greater cancer potency in the mouse than in the rat. The purpose of the present study was to compare the mutagenic potency of BD at the hprt locus of T-lymphocytes of exposed mice and rats and to determine whether mutations induced in this marker gene can be used as a quantitative indicator for species differences in susceptibility to cancer. To this end, experiments were conducted to define the effects of exposure duration and the time elapsed after exposures on the frequency of hprt mutations (Mf) in T-cells from female B6C3F1 mice and F344 rats of similar age (4-5 weeks) when exposed to BD by inhalation. The accumulation of hprt mutations in T-cells from thymus was assessed in animals necropsied 2 weeks after exposure to 0 or 1250 ppm BD for 1 or 2 weeks, while the time course for the appearance of hprt mutant T-cells (i.e., the phenotypic expression and cell migration) in thymus and spleen was evaluated in animals necropsied at weekly/biweekly intervals up to 10 weeks after exposure for 2 weeks. At necropsy, T-cells were isolated from thymus and spleen and cultured in the presence of IL-2, concanavalin A, and 6-thioguanine (Walker and Skopek, Mutat. Res., 288, 151-162, 1993). BD exposures of 1 and 2 weeks led to mutagenic effects in mouse thymus, with the average Mfs being 3- and 5-fold greater than background values, respectively. In rat thymus, there was only a 1.7-fold increase in Mfs after 2 weeks of BD exposure. In the mutant expression experiment, hprt Mfs in thymus and spleen of both species increased for several weeks post-exposure and then declined. Hprt Mfs in thymus reached maximum levels at 2 weeks post-exposure in mice (Mfs = 11.3 +/- 2.4 x 10(-6)) and at 3 weeks post-exposure in rats (4.9 +/- 1.2 x 10(-6)), while hprt Mfs in spleen reached peak levels at 5 weeks post-exposure in mice (19.7 +/- 1.9 x 10(-6)) and 4 weeks post-exposure in rats (10.1 +/- 1.8 x 10(-6)). Background Mfs for mouse and rat thymus and spleen ranged from 1.6 +/- 0.3 x 10(-6) to 3.0 +/- 1.1 x 10(-6). Statistical analyses of the hprt Mf data for spleen demonstrated that, under these exposure conditions, the mutagenic potency of BD (represented by the difference in the areas under the phenotypic expression curves of treated versus control animals) was 5-fold greater in mice than in rats. The magnitude of the species differences in mutagenic potency, observed after 2 weeks of BD exposure, resembles the species differences in metabolism more closely than the species differences in cancer potency.
Carcinogenesis 1998 Jun
PMID:Comparison of the mutagenic potency of 1,3-butadiene at the hprt locus of T-lymphocytes following inhalation exposure of female B6C3F1 mice and F344 rats. 966 40

Two kinds of cinnamaldehyde derivative, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoxy-cinnamaldehyde (BCA), were studied for their immunomodulatory effects. These compounds were screened as anticancer drug candidates from stem bark of Cinnamomum cassia for their inhibitory effect on farnesyl protein transferase activity. Ras activation, which is accompanied with its farnesylation, has been known to be important in immune cell activation as well as in carcinogenesis. Treatment of these cinnamaldehydes to mouse splenocyte cultures induced suppression of lymphoproliferation following both Con A and LPS stimulation in a dose-dependent manner. A dose of I microM of HCA and BCA inhibited the Con A-stimulated proliferation by 69% and 60%, and the LPS-induced proliferation by 29% and 21%, respectively. However, the proliferation induced by PMA plus ionomycin was affected by neither HCA nor BCA treatment. Decreased levels of antibody production by HCA or BCA treatment were observed in both SRBC-immunized mice and LPS-stimulated splenocyte cultures. The exposure of thymocytes to HCA or BCA for 48 h accelerated T-cell differentiation from CD4 and CD8 double positive cells to CD4 or CD8 single positive cells. The inhibitory effect of cinnamaldehyde on lymphoproliferation was specific to the early phase of cell activation, showing the strongest inhibition of Con A- or LPS-stimulated proliferation when added concomitantly with the mitogens. In addition, the treatment of HCA and BCA to splenocyte cultures attenuated the Con A-triggered progression of cell cycle at G1 phase with no inhibition of S to G2/M phase transition. Although cinnamaldehyde treatment had no effect on the IL-2 production by splenocyte cultures stimulated with Con A, it inhibited markedly and dose-dependently the expression of IL-2Ralpha and interferon-gamma. Taken together, the results in this study suggest both HCA and BCA inhibit the lymphoproliferation and induce a T-cell differentiation through the blockade of early steps in signaling pathway leading to cell growth.
 ...
PMID:Cinnamaldehyde inhibits lymphocyte proliferation and modulates T-cell differentiation. 984 96

The modifying effects of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on macrophage and lymphocyte functions were investigated in mice. Female BALB/c mice were gavaged with auraptene at a dose of 100, 200 or 400 mg/kg once a day for 10 consecutive days. Glucose consumption of peritoneal macrophages was significantly higher than that in the control group (P < 0.05-0.001) in auraptene-treated mice at all doses at 24, 48 and 72 h incubation except for mice given 200 mg/kg auraptene at 24 h incubation. Activity of acid phosphatase in peritoneal macrophages was significantly increased in mice treated with auraptene at a dose level of 100 mg/kg (P < 0.001). Activity of beta-glucuronidase in peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.001), but there was no significant difference in lactate dehydrogenase activity of peritoneal macrophages at any dose. Interleukin (IL)-1beta production of peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.05-0.001). Tumor necrosis factor alpha production of peritoneal macrophages in mice gavaged with auraptene at a dose of 200 mg/kg was significantly higher than that in the control group (P < 0.05). Auraptene did not affect proliferation of spontaneous splenic lymphocytes in mice at any dose. Stimulation indices in mice given auraptene at a dose of 200 mg/kg were significantly higher than that in the control group (P < 0.05). When spleenic lymphocytes were cultured without concanavalin A (Con A), IL-2 and interferon (IFN) gamma productions were not detectable in the supernatant. However, IL-2 and IFN production stimulated by Con A were significantly increased in mice gavaged with auraptene at dose levels of 100 and 200 mg/kg (P 0.05-0.001). Auraptene did not enhance spontaneous IL-4 production by splenocytes. There was no significant difference in IL-4 production of splenic lymphocytes stimulated by Con A in all groups. These findings might suggest that oral administration of citrus auraptene effectively enhanced macrophage and lymphocyte functions in mice.
Carcinogenesis 1999 Aug
PMID:Immunomodulatory action of citrus auraptene on macrophage functions and cytokine production of lymphocytes in female BALB/c mice. 1042 94

The literature supports an association of chronic inflammation with the development of tumors. The colon contains a specialized lymphocyte population that may influence various stages of colon carcinogenesis. Dietary factors are known to affect both inflammation and tumor development in this tissue. Diets high in n-6 fatty acids are considered to be proinflammatory and tumor-promoting whereas n-3 fatty acids are not. This study examined the proliferative response of colonic lymphocytes (CL) from BALB/c mice fed a diet high in either corn oil or menhaden oil when cultured in the presence of proinflammatory cytokines. CL were isolated from mice fed one of the experimental diets and cultured in the presence of anti-CD2, IL-1beta, IL-2, or TNF-alpha. Proliferation of CL in culture was measured by BrdU incorporation. CL from mice fed the high n-3 diet showed lower rates of proliferation following exposure to the inflammatory cytokines than CL from mice fed the high n-6 diet. CL from the high n-3 group showed the same proliferative potential as those from the n-6 diet group following exposure to a combination of anti-CD2 and TNF. Results from this study indicate that diets high in n-3 fatty acids slow the inflammatory response in the colon as compared to diets high in n-6 fatty acids. The n-3 lipids do not appear to compromise overall immune potential, however.
 ...
PMID:Proliferation of colonic lymphocytes in response to inflammatory cytokines is lower in mice fed fish oil than in mice fed corn oil. 1068 May 89

Additional studies are needed to identify the active ingredients in Allium Sativum (garlic) that are responsible for the observed antitumor activity and immune stimulation. Garlic seems to detoxify chemical carcinogens and prevent carcinogenesis and can also directly inhibit the growth of cancer cells. Current data suggest that low molecular weight sulfur compounds and protein F4 have immune-stimulation properties. Garlic is reported to stimulate immunity, including macrophage activity, natural killer and killer cells, and LAK cells, and to increase the production of IL-2, TNF, and interferon-gamma. These cytokines are associated with the beneficial Th1 antitumor response, which is characteristic of effective cancer immunotherapies. As is true of BCG, garlic stimulates the proliferation of macrophages and lymphocytes and protects against the suppression of immunity by chemotherapy and ultraviolet radiation. Garlic is clearly not a panacea for cancer, but its broad range of beneficial effects are worthy of serious consideration in clinical trials for the prevention and treatment of cancer.
 ...
PMID:The potential application of Allium sativum (garlic) for the treatment of bladder cancer. 1069 54


1 2 3 4 5 Next >>