Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients treated with high doses of interleukin-2 (IL-2) develop profound anorexia, malaise, loss of energy, mucositis, nausea, and vomiting, which may contribute to poor nutrition. We hypothesized that total parenteral nutrition (TPN) administration would ameliorate these changes and could improve fluid and electrolyte balance. A retrospective analysis of protein and energy intake was performed in 21 sequential patients who received a normal diet (controls) and 16 subsequent patients who received TPN during IL-2 treatment. The effect of TPN on laboratory abnormalities induced by IL-2 was also evaluated. Within 24 h of starting IL-2, mean energy intake declined to 2.5-2.8 kcal/kg in controls in contrast to the energy intake of 25-29 kcal/kg in patients receiving TPN. Protein nutrition was affected in a similar fashion, with a markedly lower protein intake in controls (0.08-0.12 g/kg) than in the TPN group (1.02-1.10 g/kg). TPN improved serum calcium and potassium concentrations, particularly during spontaneous diuresis after completion of IL-2 treatment. Unexpectedly, TPN decreased the frequency and severity of cholestatic jaundice caused by IL-2. Patients receiving TPN had an increased propensity for hyperglycemia and hypophosphatemia. High-dose intravenous bolus IL-2 therapy resulted in a markedly negative nutritional balance in control patients. A brief period of TPN during IL-2 treatment was well tolerated and corrected calorie and protein malnutrition. TPN administration also improved control of serum electrolytes. TPN did not adversely affect tumor progression or patient survival.
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PMID:Effects of total parental nutrition (TPN) during high-dose interleukin-2 treatment for metastatic cancer. 945 39

Basic studies on transduction of the interleukin-2 (IL-2) gene into tumor cells were carried out in order to develop a new immunotherapy for head and neck carcinomas. We transduced the IL-2 gene into KB cells using defective herpes simplex viral (HSV) amplicon vector as the gene transfer vehicle. A high level of IL-2 was produced by IL-2 gene transduced KB cells (KB/IL-2). Human peripheral blood mononuclear cells (PBMC) cultured in medium containing the culture supernatant of KB/IL-2 cells showed stronger cytotoxic activity against KB cells than the control. In in vivo studies, high levels of IL-2 and interferon-gamma (IFN-gamma) were detected in the serum of nude mice transplanted with KB/IL-2 cells. The spleen cells of KB/IL-2 cell-transplanted nude mice exhibited high cytotoxic activity. Three of 5 nude mice transplanted with KB/IL-2 cells were completely cured of their tumor, and all 3 mice survived for over 120 days. All 5 nude mice transplanted with KB/lacZ cells, and all 5 nude mice transplanted with KB cells died within 120 days as a result of tumor progression. In conclusion, transduction of IL-2 gene tumor cells was corroborated by the high level of IL-2 produced by KB/IL-2 cells. The mechanisms of tumor rejection on KB/IL-2 transplanted nude mice were thought to be that effector cells stimulated by IL-2 derived from transplanted KB/IL-2 cells killed tumor cells, and IFN-gamma produced by activated NK cells showed a synergistic effect on tumor cells-killing.
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PMID:[Basic studies on IL-2 gene therapy for head and neck carcinoma]. 971 Oct 80

Lymphocytopenia is a prognostic factor for shorter survival in advanced lung cancer and it is likely related to an interleukin-2 (IL-2) deficiency occurring during cancer progression. Major surgery itself for cancer is known to induce lymphocytopenia in the postoperative period. Postoperative lymphocyte decrease in colorectal cancer can be prevented by preoperative administration of recombinant human (rhIL-2), indicating that it is possible to drive appropriately important host defence agents during critical events, such as major surgery. The aim of this study is to verify if recombinant human interleukin-2 (rhIL-2) administered preoperatively is able to prevent the lymphocyte decrease occurring after radical surgery in operable lung cancer. This phase II study included 40 patients with operable NSCLC screened as stage II or IIIA, randomized to receive rhIL-2, 9000000 IU subcutaneously twice daily for 3 days before surgery (treated group, 20 patients) or not (control group, 20 patients). At baseline, there were no significant differences in total lymphocyte number and lymphocyte subsets (T-cell, T-helper, CD8+, natural killer, CD4/CD8 ratio) between groups. Postoperatively the control group showed a decrease in total lymphocyte count, T-lymphocyte count, T-helper cell number and CD4/CD8 ratio, significant at the 14th postoperative day relative to baseline values. In contrast, in the rhIL-2 treated group, at the 3rd and at the 14th postoperative days, a significant increase was observed over both baseline and control group values of total lymphocyte count, T-cells and T-helper cells. NK cell number increased significantly only over the control group. CD4/CD8 ratio was increased at the 14th postoperative day significantly over both baseline and control values. At pathological staging after surgery, four patients in the rhIL-2 group and four in the control group resulted in stage pIIIB; one patient in the rhIL-2 group resulted in stage IV (contralateral metastasis). Indeed, 15/20 rhIL-2 treated patients and 16/20 control patients were radically operated. After a 24-month follow-up, 12/20 rhIL-2 treated patients were alive and 8/15 radically operated were disease-free; 8/20 control patients were alive and 4/16 radically operated were disease-free. Toxicity was mild to moderate and easy manageable; treatment was suspended in one patient due to skin rash with hypotension grade II. The preoperative administration of rhIL-2 is feasible and prevents lymphocyte decrease occurring postoperatively after surgery for lung cancer. Further studies are required to assess the impact on survival.
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PMID:Phase-II randomized study of pre-operative IL-2 administration in operable NSCLC. 973 54

The purpose of the present study was to evaluate the therapeutic efficacy of locally administered low-dose interleukin-2 (IL-2) and a polysaccharopeptide (PSP) derived from Cariolous versicolor in a herpes virus Type 2-transformed murine tumor (H238) model and to determine possible mechanisms of action. BALB/c mice were inoculated subcutaneously (s.c.) with H238 tumor cells and randomized into groups: a) no tumor and no treatment control, b) tumor and no treatment control, c) tumor + IL-2 at 0 to 4 days, d) tumor + PSP at 0 to 10 days, e) tumor + IL-2 at 0 to 4 days + PSP at 0 to 10 days, and f) tumor + IL-2 at 15 to 19 days + PSP at 15 to 25 days. The IL-2 was administered s.c. at 2 x 10(4) i.u./mouse/injection; PSP was given s.c. at 2 mg/mouse/injection. No obvious toxicity was noted during the treatments. IL-2 and, to a lesser extent, PSP significantly slowed (p < 0.05) tumor progression when given alone immediately after tumor cell injection. The combination of the two modalities did not significantly enhance the antitumor effect of IL-2 alone. However, mice receiving both agents had IL-2 in the plasma, their tumors expressed low levels of transforming growth factor-beta, and their splenocyte response to mitogenic stimulation was significantly higher than in untreated controls. Changes in blood leukocyte populations and splenic oxidative burst capacity were associated with tumor presence, but not with the type of treatment. In vitro assays showed that both IL-2 and PSP can suppress the uptake of 3H-thymidine by tumor cells and that the effect is more pronounced whent the agents are used in combination. These results indicate that IL-2 and PSP can slow progression of H238 tumors and that the mechanisms of action may be related to their direct cytotoxic effects, as well to their immunomodulatory properties.
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PMID:Immunotherapy with low-dose interleukin-2 and a polysaccharopeptide derived from Coriolus versicolor. 1085

Cancer cells do not elicit a clinically sufficient anti-tumor immune response that results in tumor rejection. Recently, many investigators have been trying to enhance anti-tumor immunity and encouraging results have been reported. This review will discuss current anti-cancer immunotherapy; interleukin-2 therapy, tumor vaccine secreting Granulocyte macrophage-colony stimulating factor, dendritic cells fused with tumor cells, and CD40 ligand immunotherapy. Moreover, we introduce our two kinds of CD40 ligand immuno-genetherapy; (1) oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium (published in BLOOD 2000), (2) cancer vaccine transfected with CD40 ligand ex vivo for neuroblastoma (unpublished). Both approaches resulted in a high degree of protection against the tumor progression and they are simple and safe in the murine system.
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PMID:CD40 ligand immunotherapy in cancer: an efficient approach. 1191 21

A novel approach to cancer gene therapy is to implant microcapsules containing nonautologous cells engineered to secrete molecules with antineoplastic properties. The efficacy of this treatment is now tested in a mouse model bearing HER-2/neu-positive tumors. Nonautologous mouse myoblasts (C(2)C(12)) were genetically modified to secrete interleukin-2 linked to the Fv region of a humanized antibody with affinity to HER-2/neu. The resulting fusion protein, sFvIL-2, would encompass immune-stimulatory cytokine activity now targeted to the HER-2/neu-expressing tumor. These recombinant cells were then immunoprotected with alginate-poly-L-lysine-alginate microcapsules before implantation into tumor-bearing mice. Treatment with these encapsulated cells led to a delay in tumor progression and prolonged survival of the animals. The long-term efficacy was limited by an inflammatory reaction against the implanted microcapsules probably because of the secreted cytokine and antigenic response against the xenogeneic fusion protein itself. However, over the short term (initial 2 weeks), efficacy was confirmed when a significant amount of biologically active interleukin-2 was detected systemically, and targeting of the fusion protein to the HER-2/neu-expressing tumor was shown immunohistochemically. The tumor suppression in the treated animals was associated with increased apoptosis and necrosis in the tumor tissue, thus demonstrating successful targeting of the antiproliferative effect to the tumors by this delivery paradigm. In conclusion, this new approach to systemic cancer gene therapy needs to be modified to provide long-term delivery, but has demonstrated short-term efficacy and potential to become a cost-effective, benign, and non-viral-based adjunct to the current armory of anticancer strategies.
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PMID:A novel approach to tumor suppression with microencapsulated recombinant cells. 1213 69

The data are presented on polychemotherapy given to 17 children with advanced refractory malignant tumors using whole body hyperthermia and hyperglycemia. All patients suffered tumor progression throughout treatment and afterwards. Adjuvant Roncoleukin (interleukin-2) was administered in 5. Such salvage therapy was followed by overall tumor regression in 29.3%. Overall 4-year survival in such cases was 19%. Immunological monitoring of adjuvant whole body hyperthermia and interleukin-2 was carried out.
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PMID:[Salvage thermochemotherapy in advanced refractory malignant tumors in children]. 1245 61

Therapy of metastasized renal cell carcinoma is based on systemic immunotherapeutic strategies, if surgical resection is not possible. The costs of inhalative Interleukin-2 therapy in case of pulmonary metastases as off-label-use are not accepted by compulsory health insurance yet.We report on a female patient with pulmonary metastasized renal cell carcinoma who had tumor progression after immunochemotherapy that followed complete response after inhalative therapy with Interleukin-2.
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PMID:[Complete remission of pulmonary metastasis from renal cell carcinoma through inhalation therapy with Interleukin-2 after unsuccessful systemic immunochemotherapy]. 1537 56

Preclinical data suggest that one method of inducing autoimmunity to tumor is the administration and subsequent withdrawal of cyclosporine A following chemotherapy and that this effect may be enhanced with interferon and interleukin-2. Consequently, we performed a phase II trial in patients with advanced melanoma to explore this approach. Thirty-three patients were treated with BCNU (150 mg/m2 iv every 8 weeks), cisplatin (25 mg/m2 iv days 1-3) every 4 weeks, DTIC (220 mg/m2 iv days 1-3 every 4 weeks) along with tamoxifen (10 mg po BID days 1-4). Cyclosporine A at 3 mg/kg/day in two divided doses was given on days 4-21, alpha-interferon 1 million units/m2 subcutaneously every other day on days 4-21 and interleukin-2 1 million units/m2 BID subcutaneously days 21-28 were also given. Of the 33 patients, 3 patients (9%) had complete response and 8 patients (24%) had a partial response for a total response rate of 33% (95% confidence interval 18-52%). Median duration of response was 17 months (range 3+ to 24+ months). Six patients continue to show no signs of tumor progression for 3+, 5+, 10+, 24+, 60+, and 72+ months. Toxicity was generally well tolerated and included myelosuppression and fatigue. This regimen is feasible and generally tolerable and has produced an antitumor response rate comparable with inpatient biochemotherapy regimens.
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PMID:Cyclosporine A, alpha-lnterferon and interleukin-2 following chemotherapy with BCNU, DTIC, cisplatin, and tamoxifen: a phase II study in advanced melanoma. 1577 61

A phase I trial was conducted to evaluate the feasibility, safety, and efficacy of a dendritic cell-based vaccination in patients with metastatic renal cell carcinoma (RCC). Autologous mature dendritic cells derived from peripheral blood monocytes were pulsed with the HLA-A2-binding MUC1 peptides (M1.1 and M1.2). For the activation of CD4(+) T-helper lymphocytes, dendritic cells were further incubated with the PAN-DR-binding peptide PADRE. Dendritic cell vaccinations were done s.c. every 2 weeks for four times and repeated monthly until tumor progression. After five dendritic cell injections, patients additionally received three injections weekly of low-dose interleukin-2 (1 million IE/m(2)). The induction of vaccine-induced T-cell responses was monitored using enzyme-linked immunospot and Cr release assays. Twenty patients were included. The treatment was well tolerated with no severe side effects. In six patients, regression of the metastatic sites was induced after vaccinations with three patients achieving an objective response (one complete response, two partial responses, two mixed responses, and one stable disease). Additional four patients were stable during the treatment for up to 14 months. MUC1 peptide-specific T-cell responses in vivo were detected in the peripheral blood mononuclear cells of the six patients with objective responses. Interestingly, in patients responding to the treatment, T-cell responses to antigens not used for vaccinations, such as adipophilin, telomerase, or oncofetal antigen, could be detected, indicating that epitope spreading might occur. This study shows that MUC1 peptide-pulsed dendritic cells can induce clinical and immunologic responses in patients with metastatic RCC.
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PMID:Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. 1674 Jul 31


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