Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Review of the relationship between the degree of immunosuppression and malignancy in patients on immunosuppressive drugs or immunosuppressed by HIV infection, postoperative blood transfusion or pregnancy provides the most convincing evidence of the importance of intact T cell immunity in resistance to cancer. Defective HLA class I and II antigen expression on tumours arising in non-immunosuppressed individuals and correlation of these changes with increased malignancy and diminished TIL provide the most convincing evidence that one factor necessary to ensure survival of most spontaneous tumours is mutation that enables tumour cells to escape rejection by cytotoxic T cells. These changes are less frequent in tumours in immunosuppressed patients, and preliminary data suggest that use of cytokine therapy is more successful in these tumours and the one in five spontaneous tumours demonstrating normal expression of HLA antigens and high levels of T cell infiltration. These observations suggest that future use of this therapy should be focused on these cases. All modalities of cancer therapy except hormone therapy (ie surgery, radiotherapy and chemotherapy) suppress immune responses. Defects of HLA antigen expression are less marked in early cancer. Combinations of immunotherapy with conventional treatment at presentation, including hormone therapy in view of data demonstrating regeneration of the thymus after castration, needs further investigation. Preliminary results from randomized trials involving nearly 300 individuals accidentally exposed to carcinogens demonstrated nearly 60% reduction of incidence of malignancy at 5 years in the arm receiving non-specific immunotherapy. If confirmed, such an approach might be more cost-effective as an approach for cancer prevention than organ specific cancer screening or vaccination against cancer associated viruses such as hepatitis B or papillomaviruses.
 ...
PMID:T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy. 142 23

The contribution of the cytokine tumor necrosis factor (cachectin; TNF) to host defenses against staphylococcal foreign body infections was studied in vivo. In tissue cages subcutaneously implanted into guinea pigs, progressive infection was initiated by a very low inoculum (100 cfu) of Staphylococcus aureus with a success rate of 100%, as is frequently encountered in related clinical situations. Locally injected autologous bacterial components derived from the cell wall of S. aureus, in particular peptidoglycan, were very active in raising TNF levels in tissue cage fluid and in preventing the development of infection by the 100% infective dose of the test strain. Furthermore, injection of murine recombinant TNF into tissue cages could substitute for the bacterial components in preventing experimental infection by S. aureus. The protective effect of TNF-eliciting bacterial components could be neutralized by anti-TNF antibodies. A local increase in TNF levels might improve host defenses against staphylococcal foreign body infections.
 ...
PMID:Contribution of tumor necrosis factor to host defense against staphylococci in a guinea pig model of foreign body infections. 160 9

Psychological stress (e.g., exposure to a novel environment) causes a rapid rise in body temperature in rats. In this study, we examined the roles of physical activity and the immune cytokine tumor necrosis factor or cachectin (TNF) in this temperature change. The elevation in temperature of rats exposed to cage-switch stress during the day correlated poorly with the increase in activity (r = 0.07; P = 0.84) and, during cage switch at night, correlated negatively (r = 0.64; P = 0.04). TNF was not detected in the plasma or cerebrospinal fluid of rats after exposure to open-field stress. However, the injection of antiserum against TNF 3.5 h before exposure to the stress of being in an open field resulted in a significantly greater hyperthermia than was seen in the control serum-injected rats (1.38 +/- 0.11 vs. 0.79 +/- 0.14 degrees C; P = 0.002). The peak temperature change after cage-switch stress was similarly increased in rats that had been injected with anti-TNF (0.82 +/- 0.08 vs. 0.50 +/- 0.08 degrees C; P = 0.016). This enhanced hyperthermia is similar to the excessively high fever that occurs during the later phase of lipopolysaccharide fever in animals that have been injected with antiserum against TNF. These data support the hypotheses that stress hyperthermia is a true fever and that TNF is an endogenous antipyretic, limiting the magnitude of this fever.
 ...
PMID:Antiserum against tumor necrosis factor increases stress hyperthermia in rats. 231 7

The effects of differential housing on T-helper (TH) cell activation were investigated. BALB/c and C57Bl/6 male mice housed 1 or 4 per cage were administered three i.p. injections of keyhole limpet hemocyanin (KLH) over several weeks. Effects of differential housing on in vitro antigen-specific interleukin (IL)-2 (a TH1 cell derived cytokine) and IL-4 (a TH2 cell derived cytokine) production were observed. BALB/c mice housed alone produced significantly more IL-4 than BALB/c mice housed in groups. C57Bl/6 mice housed alone produced significantly more IL-2 than C57Bl/6 mice housed in groups. Differential housing did not influence either IL-2 production among BALB/c mice or IL-4 production among C57Bl/6 mice. These data demonstrate that environmental conditions can influence cytokine production by both TH-1 dominant (C57Bl/6) and TH-2 dominant (BALB/c) mice.
 ...
PMID:Quantitative differences in interleukin-2 and interleukin-4 production by antigen-stimulated splenocytes from individually- and group-housed mice. 807 76

Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an important cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Suramin prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin-treated mice. On the other hand, the drug is approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin inhibits the action of other factors/cytokines that may also participate in colon-26-mediated cachexia is not yet known.
 ...
PMID:Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo. 822 30

Research from our laboratory has demonstrated that the presentation of an aversive conditioned stimulus produces pronounced suppression of several in vitro measures of immune status. The present study was designed to evaluate the role of central corticotropin-releasing hormone (CRH) in the mechanisms mediating these conditioned effects. The aversive conditioned stimulus was a distinct environment that had previously been associated with electric footshock. Lewis rats received intraventricular administration of either buffered saline or a dose of the CRH-selective receptor antagonist alpha-helical CRH(9-41) (0, 0.5, 5, or 50 micrograms) prior to exposure to the aversive conditioned stimulus or home cage control treatment. The aversive conditioned stimulus produced decreases in splenic natural killer cell activity, splenocyte responsiveness to the mitogens concanavalin A (ConA), phytohemagglutinin (PHA), lipopolysaccharide (LPS), and the combination of ionomycin and phorbol myristate acetate (PMA), blood leukocyte responsiveness to ConA and PHA, and the production of interleukin-2 and interferon-gamma by activated splenocytes. The conditioned stimulus also produced an increase in plasma levels of corticosterone. Pretreatment with alpha-helical CRH(9-14) completely blocked the conditioned stimulus-induced suppression of natural killer cell activity. The CRH antagonist had no attenuative effect on the conditioned suppression of splenocyte or blood leukocyte proliferation in response to mitogens, or the production of interleukin-2 or interferon-gamma by activated splenocytes. There was also no effect of alpha-helical CRH(9-14) on the conditioned stimulus-induced increase in plasma corticosterone. These findings suggest that conditioned stimulus-induced suppression of natural killer cell activity is mediated by a mechanism that involves activity at central CRH receptors, and that this conditioned modulation is independent of HPA activation. Furthermore, these results indicate that the mechanisms involved in conditioned stimulus-induced suppression of proliferative or cytokine production responses are distinct from those involved in the modulation of natural killer cell activity.
 ...
PMID:Corticotropin-releasing hormone is involved in conditioned stimulus-induced reduction of natural killer cell activity but not in conditioned alterations in cytokine production or proliferation responses. 855 20

DNA immunization can result in the induction of Ag-specific cellular and humoral immune responses and in protective immunity in several Ag systems. To evaluate the utility of DNA-based immunization as a potential cancer treatment strategy, we employed an experimental murine tumor, CT26, expressing the model tumor-associated Ag, beta-galactosidase (beta-gal), designated CT26.CL25. A plasmid expressing beta-gal (pCMV/beta-gal) administered by particle-mediated gene delivery to the epidermis using a hand-held, helium-driven "gene gun" induced beta-gal-specific Ab and lytic responses. Immunization with this construct prevented the growth of pulmonary metastatic tumor, and the adoptive transfer of splenocytes generated by pCMV/beta-gal in vivo immunization and cultured in vitro with the beta-gal876-884 immunodominant peptide reduced the number of established pulmonary nodules. DNA immunization alone had little or no impact on the growth of established lung metastases. To enhance the function of DNA immunization for active immunotherapy, a panel of cytokines was added as adjuvants following DNA administration. Significant reduction in the number of established metastases was observed when human rIL-2, mouse rIL-6, human rIL-7, or mouse rIL-12 were given after DNA inoculation; mouse rIL-12 as an adjuvant had the most profound effect. These findings suggest that the cytokines involved in the activation and expansion of lymphocyte populations may improve the therapeutic effects of DNA immunization. Given the ease with which plasmid DNA can be prepared to high purity for safe use in humans with infectious diseases and cancers, DNA immunization administered together with cytokine adjuvant may be an attractive alternative to recombinant viral vaccines.
 ...
PMID:Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. 859 68

A number of cytokines and costimulatory molecules involved in immune activation have recently been identified including IL-12, a heterodimeric cytokine that supports the development of cell-mediated immunity, and B7-1, a costimulatory molecule involved in the activation of T lymphocytes. We explored the use of these immunomodulants as molecularly defined adjuvants in the function of recombinant anticancer vaccines using a murine model adenocarcinoma, CT26, transduced with a model Ag, beta-galactosidase (beta-gal). Although IL-12 given alone to mice bearing tumors established for 3 days did not have consistent antitumor activity, a profound therapeutic effect was observed when IL-12 administration was combined with a recombinant vaccinia virus (rVV) encoding beta-gal called VJS6. On the basis of the reported synergistic effects of IL-12 and the costimulatory molecule B7-1 (CD80) in vitro, we immunized mice with a double recombinant vaccinia encoding both the model tumor Ag and the costimulatory molecule B7-1, designated B7-1 beta-gal rVV. The adjuvant administration of IL-12 after immunization with this virus significantly enhanced survival in tumor-bearing animals. T cell subset depletions demonstrated that the in vivo activity of IL-12 was largely independent of CD4+ T lymphocytes, whereas the in vivo activity of a B7-1 rVV required both CD4+ and CD8+ T cells to elicit maximal therapeutic effect. To our knowledge, this is the first description of B7-1 and IL-12 cooperation in vivo and represents a novel strategy to enhance the efficacy of recombinant anticancer vaccines.
 ...
PMID:IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines: enhancement by simultaneous B7-1 expression. 861 61

Interleukin-6 (IL-6) is a multifunctional cytokine that is produced not only by a variety of normal cells but also by cancer cells. IL-6 produced by cancer cells stimulates the proliferation of these cancer cells in an autocrine/ paracrine manner and causes paraneoplastic syndromes including hypercalcemia, cachexia, and leukocytosis. We have reported previously that a human oral squamous cancer associated with hypercalcemia produces large amounts of IL-6, that animals bearing this cancer exhibit elevated levels of plasma IL-6, and that neutralizing antibodies to human IL-6 reverse hypercalcemia in tumor-bearing animals, indicating an important role of IL-6 in the hypercalcemia in this model. Because these cancer cells overexpress epidermal growth factor receptors (EGFR) with intrinsic tyrosine kinase (TK) activity similar to many other squamous cancers, we examined the effects of herbimycin A, a tyrosine kinase inhibitor, on IL-6 production and hypercalcemia in animals bearing this cancer to develop a new approach to treat the hypercalcemia associated with malignancy. Intraperitoneal administration (once a day for 2 days) of herbimycin A to cancer-bearing hypercalcemic mice reduced the plasma levels of human IL-6 and impaired the hypercalcemia. During 2-day treatment with herbimycin A, no changes were observed in tumor size. Of interest, plasma levels of mouse, but not human, soluble IL-6 receptors were also elevated. However, herbimycin A showed no effects on plasma levels of mouse soluble IL-6 receptors. Herbimycin A suppressed the tyrosine autophosphorylation of EGFR and IL-6 mRNA expression and production, all of which were stimulated by EGF. The data raise the possibility that TK inhibitors may be potential mechanism-based therapeutic agents for the treatment of hypercalcemia associated with squamous cancers which overexpress EGFR.
 ...
PMID:Herbimycin A, a tyrosine kinase inhibitor, impairs hypercalcemia associated with a human squamous cancer producing interleukin-6 in nude mice. 879 10

Exposure to stressors can affect various aspects of immune function, including the antibody response. We have previously reported that rats exposed to an acute session of inescapable tail shock (IS) show long-term reductions in anti-keyhole limpet hemocyanin (KLH) immunoglobulin (Ig) M and IgG and a failure to expand Th1-like cells in response to KLH. To further investigate the potential role of decreased Th1-like cells in the IS-induced reduction of anti-KLH Ig, we examined two isotypes of IgG, IgG1 and IgG2a. Isotype switching is under cytokine control. Interleukin-4 helps B cells switch from making IgM to making IgG1, whereas interferon (IFN)-gamma helps B cells switch from making IgM to making IgG2a. In this paper we report that IS exposure reduces IFN-gamma levels 4 days after exposure to IS+KLH compared with immunized home cage controls. In addition, IS exposure reduced the Th1 cytokine-sensitive anti-KLH IgG2a but not Th2 cytokine-sensitive anti-KLH IgG1. This pattern of isotype reduction suggests that a failure to expand the Th1 cell, which results in less IFN-gamma, may contribute to the the IS-induced reduction in anti-KLH Ig. Glucocorticoids (GCs) differentially regulate Th1 and Th2 cells. Administration of the type II GC receptor antagonist RU-486 before IS blocked the IS-induced suppression in anti-KLH IgM, IgG, and IgG2a. Corticosterone (2.5 mg/kg), however, did not produce the suppression in anti-KLH Ig. These results support a role of corticosterone in mediating IS-induced reductions in in vivo antibody.
 ...
PMID:RU-486 blocks differentially suppressive effect of stress on in vivo anti-KLH immunoglobulin response. 894 73


1 2 3 4 5 6 7 8 9 10 Next >>