Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of costimulatory signals in T cell induction was evaluated in mice lacking the interleukin-2 (IL-2) gene. In vitro secondary antiviral T cell responses were absent unless IL-2 was added, confirming the crucial role of IL-2 in vitro. In vivo, primary and secondary cytotoxic T cell responses against vaccinia and lymphocytic choriomeningitis virus were within normal ranges. B cell reactivity to vesicular stomatitis virus was not impaired. T helper cell responses were delayed but biologically functional. Natural killer cell activity was markedly reduced but inducible. These normal in vivo immune responses in IL-2-deficient mice question the importance of IL-2 as defined by in vitro studies.
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PMID:Immune responses in interleukin-2-deficient mice. 823 25

25 patients with metastatic colorectal cancer were entered into a phase II trial of combination chemoimmunotherapy using a sequential regimen of 5-fluorouracil (5-FU) and leucovorin and high-dose recombinant human interleukin-2 (rIL-2). Patients initially received three cycles of chemotherapy consisting of 500 mg/m2 of intravenous leucovorin followed by 375 mg/m2 of bolus 5-FU both given daily on days 1-5 of a 21 day cycle. Ten days after the last dose of chemotherapy in cycle 3, patients began high-dose rIL-2 at 720,000 IU/kg intravenously every 8 h to the maximum tolerated number of doses. After 7-10 days of recovery, this rIL-2 treatment was repeated to complete one full course of chemoimmunotherapy. There was no grade IV toxicity associated with 183 cycles of chemotherapy. Other than slight increases in the frequency of diarrhoea, stomatitis and hyperbilirubinaemia, rIL-2 toxicity was similar to that seen in patients given rIL-2 without chemotherapy. Of 23 evaluable patients, the overall response rate (partial + complete response) was 46% with 2 complete responses. Only 3 patients showed major tumour regression during the rIL-2 phase of therapy, but these 3 patients included both complete responders and the 3 most durable responses (15, 16 and 24 months). We conclude that sequential 5-FU/leucovorin and rIL-2 can be given safely without major increases in toxicity over either therapy alone, and although nearly all responses seen are largely attributable to chemotherapy, a contribution of immunotherapy to the minority of patients achieving complete or durable responses cannot be ruled out.
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PMID:Combination chemoimmunotherapy for metastatic colorectal cancer using 5-fluorouracil, leucovorin and interleukin-2. 839 34

Denture stomatitis is usually associated with the presence of yeast, particularly Candida albicans, and several bacteria. In this study mononuclear blood cells were grown in the presence of Candida albicans from a single colony, and interleukin-2 production induced in T lymphocytes was measured. Blood cells were from a population of patients with denture stomatitis and a control group of denture wearers without stomatitis. Induction of interleukin-2 production was correlated with factors that condition denture stomatitis, namely, isolation of Candida albicans in selective medium, age of the denture, and diabetes. Concentrations of interleukin-2 in supernatant and serum were also compared. Significant differences in interleukin-2 production were found between patients with denture stomatitis and controls. Statistical analysis demonstrated a significant association between isolation of Candida albicans and elevated interleukin-2 production in cultures from patients with and without denture stomatitis.
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PMID:Denture stomatitis: quantification of interleukin-2 production by mononuclear blood cells cultured with Candida albicans. 864 30

Mice lacking Itk, a T-cell-specific protein tyrosine kinase, have reduced numbers of T cells and reduced responses to allogeneic major histocompatibility molecules. This study analyzed antiviral immune responses in mice deficient for Itk. Primary cytotoxic T-lymphocyte (CTL) responses were analyzed after infection with lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and vesicular stomatitis virus (VSV). Ex vivo CTL activity was consistently reduced by a factor of two to six for the different viruses. CTL responses after restimulation in vitro were similarly reduced unless exogenous cytokines were added. In the presence of interleukin-2 or concanavalin A supernatant, Itk-deficient and control mice responded similarly. Interestingly, while LCMV was completely eliminated by day 8 in both Itk-deficient and control mice, VV cleared from itk-/- mice with delayed kinetics. Antibody responses were evaluated after VSV infection. Both the T-cell-independent neutralizing immunoglobulin M (IgM) and the T-cell-dependent IgG responses were similar in Itk-deficient and control mice. Taken together, the results show that CTL responses are reduced in the absence of Itk whereas antiviral B-cell responses are not affected.
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PMID:Antiviral immune responses in Itk-deficient mice. 931 99

We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2 (rIL-2) in patients with advanced (stage III IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m(-2) day(-1) 5-FU on days 1-5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8-12 and 15-19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients (20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients (13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus, there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were 2 toxic deaths (6.7%), 1 from hematological causes in group A and I from cardiac causes in group B. Myelosuppression and gastrointestinal toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable that a clinically significant difference between the two treatment groups will be observed even if the calculated patient sample size is achieved.
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PMID:Neo-adjuvant chemo-(immuno-)therapy of advanced squamous-cell head and neck carcinoma: a multicenter, phase III, randomized study comparing cisplatin + 5-fluorouracil (5-FU) with cisplatin + 5-FU + recombinant interleukin 2. 982 40

Vaccinia virus MVA is harmless for humans and animals both locally and parenterally. It offers paraspecific activities similar to those of comparable attenuated viruses of other pox genera, e.g. avipox or parapox. At the systemic level, MVA protects baby mice against lethal challenge with vesicular stomatitis virus (dose-response curve). MVA raises phagocytosis and NK-cell activity in humans and animals, whilst encouraging the induction of interferon alpha, interleukin-2 and -12 and colony-stimulating activity at the same time. The paramunity-inducing properties of MVA make it an ideal vector for the insertion of foreign genes. It is superior to other virus vectors because of its complex function. Inactivated MVA is also suitable as an inducer of paramunity.
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PMID:Paramunity-inducing effects of vaccinia strain MVA. 1050 81

Autologous peripheral blood stem cell transplantation following myeloablative chemotherapy is being increasingly utilized in the treatment of a variety of malignancies. We administered busulfan 16 mg/kg orally, thiotepa 500-700 mg/m2 i.v., and carboplatin 800-1000 mg/m2 i.v. to 56 women with metastatic carcinoma of the breast. Autologous peripheral blood stem cells, which had been collected after a combination of chemotherapy and granulocyte colony-stimulating factor, were infused on day 0. The major toxicities of the conditioning regimen included severe pancytopenia, stomatitis, nausea, emesis, diarrhea, fever, and infection. Transplant-related mortality was 1.8%. The incidence of opportunistic viral infections was 42.9%. Fourteen individuals achieved a complete response. The actuarial survival at 1223 days was 13.7% for the entire group of patients; the actuarial survival at 1009 days was 39.3% among complete responders. The functional status of the immune system was determined following transplantation in a subset of patients. Peripheral blood mononuclear cells were obtained before and after stem cell infusion, and were analyzed phenotypically and functionally. Proliferative and interleukin-2 synthetic ability of these cells was assessed following stimulation with phytohemagglutinin and anti-CD3 antibody. The response to influenza peptides was also ascertained. Proliferative and interleukin-2 synthetic capacity was markedly impaired for over a year. Memory response was virtually absent for up to 2 years following transplantation. The prolonged and marked immunosuppression following this myeloablative regimen was associated with a high incidence of opportunistic viral infections, and may have contributed to disease relapse and progression especially in patients who failed to achieve a complete response following transplantation.
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PMID:Myeloablative chemotherapy with autologous peripheral blood stem cell transplantation for metastatic breast cancer: immunologic consequences affecting clinical outcome. 1051 93

To evaluate the therapeutic effects and systemic toxicities of a capecitabine-based home therapy regimen in patients with metastatic renal cell carcinoma, 30 patients were enrolled in a phase II clinical trial. Treatment consisted of oral capecitabine combined with subcutaneous recombinant human interferon-alpha 2a, recombinant human interleukin-2 and oral 13-cis-retinoic acid. There were two (7%) complete responses (CRs) and eight (27%) partial remissions (PRs), for an overall objective response rate of 34% (95% CI 17-53%). Except one, all responses are ongoing, with a median duration of 9+ and 8+ months for CRs and PRs, respectively. Additionally, 12 patients (40%) reached stable disease. Eight patients (27%) showed continued disease progression despite treatment. Therapy was well tolerated and was given in the outpatient setting. Capecitabine-related World Health Organization (WHO) grade 2 and 3 toxicities were observed in five and two patients respectively, and were limited to fatigue, nausea/vomiting, diarrhoea, stomatitis, dermatitis and hand-and-foot syndrome. The substitution of capecitabine for 5-FU in the pre-existing biochemotherapy regimen did not result in a reduced therapeutic efficacy and showed significant anti-tumour activity in patients with advanced renal cell carcinoma.
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PMID:Capecitabine in the treatment of metastatic renal cell carcinoma. 1094 96

Feline immunodeficiency virus (FIV) infection is characterized by chronic overactivation of immune and inflammatory system, resulting in anergic state and dysfunction of immune cells. Lactoferrin (LF), a glycoprotein present in exocrine secretions and neutrophils, plays an important role in host defense system. Our previous study showed that oral administration of bovine LF (bLF) suppressed oral inflammation, improved the clinical symptoms and decreased serum gamma-globulin as a marker of inflammation in FIV-infected cats with intractable stomatitis. The anti-inflammatory effect was partly involved in regulation of neutrophil function by bLF. In this study, to clarify the relationship between anti-inflammatory effects of bLF and peripheral blood mononuclear cells (PBMC), we examined the effect of bLF on proliferation, cell cycle progression and cytokine expression in mitogen-activated PBMC. MTT [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide] assay showed that bLF inhibited the concanavalin A (ConA)-induced cell proliferation in FIV-infected cats with the asymptomatic carrier and AIDS-related complex (ARC) phase. Bovine LF restored ConA-induced cell cycle progression and resulted in suppression of the induced apoptosis in feline PBMC. Real-time RT-PCR showed that bLF suppressed ConA-induced expression of interferon-gamma and interleukin-2 in cells of the ARC group regardless of the time of its addition to the medium. These results suggest the hypothesis that therapy with bLF may have the potential to improve and protect functions of overactivated lymphocytes by modulating the cell proliferation, cell cycle and cytokines expression in cats in terminal stage of FIV infection.
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PMID:Effect of bovine lactoferrin on functions of activated feline peripheral blood mononuclear cells during chronic feline immunodeficiency virus infection. 1852 62

To protect viral particles from neutralization, sequestration, nonspecific adhesion, and mislocalization following systemic delivery, we have previously exploited the natural tumor-homing properties of antigen-specific CD8+ T cells. Thus, OT-I T cells, preloaded in vitro with the oncolytic vesicular stomatitis virus (VSV), can deliver virus to established B16ova tumors to generate significantly better therapy than that achievable with OT-I T cells, or systemically delivered VSV, alone. Here, we demonstrate that preconditioning immune-competent mice with Treg depletion and interleukin-2 (IL-2), before adoptive T-cell therapy with OT-I T cells loaded with VSV, leads to further highly significant increases in antitumor therapy. Therapy was associated with antitumor immune memory, but with no detectable toxicities associated with IL-2, Treg depletion, or systemic dissemination of the oncolytic virus. Efficacy was contributed by multiple factors, including improved persistence of T cells; enhanced delivery of VSV to tumors; increased persistence of OT-I cells in vivo resulting from tumor oncolysis; and activation of NK cells, which acquire potent antitumor and proviral activities. By controlling the levels of virus loaded onto the OT-I cells, adoptive therapy was still effective in mice preimmune to the virus, indicating that therapy with virus-loaded T cells may be useful even in virus-immune patients. Taken together, our data show that it is possible to combine adoptive T-cell therapy, with biological therapy (Treg depletion+IL-2), and VSV virotherapy, to treat established tumors under conditions where none of the individual modalities alone is successful.
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PMID:Use of biological therapy to enhance both virotherapy and adoptive T-cell therapy for cancer. 1882 7


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