Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The local retention of adoptively transferred lymphokine (IL-2)-activated killer (LAK) cells was examined in 11 patients with head and neck carcinoma. Unseparated lymphocytes, T and natural killer (NK) cells isolated from patients were cultured with IL-2 for 7 days, labelled with 99mTc-HMPAO, and immediately injected back into the respective donors via the superficial temporal artery or locally into the tumour tissue. The injected LAK cells were periodically traced using a gamma camera, and the LAK cell retention rate was calculated from the radioactivity. One hour after the injection, about 70% of the locally infiltrated LAK cells remained in the tumour tissue, while about half of the LAK cells transferred via the regional artery were dislodged from the tissue. LAK cells induced from T cells (T-LAK) were retained in the tissue for a longer time than LAK cells induced from NK cells (NK-LAK). T-LAK were less chemotactic and less adherent to human umbilical vein endothelial cells (EC), and showed lesser migration through EC. Flow cytometric analysis revealed higher expression of CD11a, CD11b, CD18 and CD49d on NK-LAK compared with T-LAK. MoAbs against these adhesion molecules suppressed adhesion and migration of LAK cells. These results indicate that the rapid disappearance of NK-LAK from the tissue is associated with their greater chemotactic and adhesive as well as migratory activities depending on differing expression of adhesion molecules.
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PMID:Longer local retention of adoptively transferred T-LAK cells correlates with lesser adhesion molecule expression than NK-LAK cells. 769 11

IL-2 is a biotherapeutic drug and a biological response modifier. This drug has not been approved by the Food and Drug Administration for general use but continues to undergo clinical trials. Candidates for this therapy are patients with advanced carcinoma that has not responded to standard modalities of treatment. Administration of IL-2 can lead to systemic toxicity, which usually appears to be dose-related. As a result, high-dose therapy requires intensive care. The critical care nurse assesses and documents side effects that occur as a result of IL-2 therapy and must be aware of both the physical and psychological needs of the patient. Through successful assessment and intervention, the nurse can gain the knowledge required to manage, both physically and psychologically, patients who are undergoing this therapy.
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PMID:Interleukin-2 therapy: needs of the patient in a critical care setting. 869 70

To evaluate efficiency of LAK cells from patients with cancer a number of immune functions of patients with advanced carcinoma was investigated. The results showed that: from patients with cancer, lymphocyte transformation (32.83 +/- 52.59), responses of lymphocytes to IL-2 (5.94 +/- 9.31), and to IL-2/PHA (32.25 +/- 43.05), and NK activity (11.18 +/- 6.98), LAK activity (17.86 +/- 9.57) were significantly suppressed (In the healthy donors, the data were 75.70 +/- 52.65, 24.59 +/- 28.25, 125.47 +/- 74.11 respectively, P < 0.001); sIL-2R and TNF concentrations (241.9 +/- 172.5 pmol/L and 1.86 +/- 1.52 ng/ml respectively) in serum from patients with cancer were significantly higher than that of healthy control (134.2 +/- 73.5 pmol/L and 0.63 +/- 0.20 ng/ml respectively, P < 0.05-0.001). Since patients with cancer had suppressed responses of lymphocytes to IL-2, low NK and LAK cell activity, LAK cells from patients with cancer might be less effective than those from healthy donor in the treatment of cancer.
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PMID:[Some immune functions of patients with carcinoma]. 772 Apr 94

Seventy nine advanced cancer patients in a clinical trial were treated with LAK/IL-2 combining with Lycium Barbarum polysaccharides (LBP). Initial results of the treatment from 75 evaluable patients indicated that objective regression of cancer was achieved in patients with malignant melanoma, renal cell carcinoma, colorectal carcinoma, lung cancer, nasopharyngeal carcinoma, malignant hydrothorax. The response rate of patients treated with LAK/IL-2 plus LBP was 40.9% while that of patients treated with LAK/IL-2 was 16.1% (P < 0.05). The mean remission in patients treated with LAK/IL-2 plus LBP also lasted significantly longer. LAK/IL-2 plus LBP treatment led to more marked increase in NK and LAK cell activity than LAK/IL-2 without LBP. The results indicate that LBP can be used as an adjuvant in the biotherapy of cancer.
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PMID:[Observation of the effects of LAK/IL-2 therapy combining with Lycium barbarum polysaccharides in the treatment of 75 cancer patients]. 772 Apr 97

Production of a factor with a biological activity to inhibit the in vitro tumor-cell migration (TCM) from peripheral blood E rosette-forming cells (ERFC), CD4+ and CD8+ T cells in patients with gastric and breast carcinoma was investigated. The cells were stimulated for 2 or 24 hr with allogeneic gastric or breast cancer extracts in samples of cell suspensions. A microculture system at an initial cell concentration from 2,500 cells to 1 cell per well was used. Feeder cells, PHA, IL-2-containing supernatant and cancer extract were added to each well. Ehrlich ascites tumor cells were employed in the migration-inhibition assay. ERFC and CD4+ T cells produced in the culture supernatants a factor inhibiting TCM, when these cells were stimulated with cancer extracts, but not with extracts of benign tissue. Stimulated CD8+ T cells did not produce such a factor. The production of the factor inhibiting TCM in the microculture system was also significantly correlated with the type of cells in the wells, particularly with ERFC and CD4+ T cells, but not with CD8+ T cells (r = 0.94, p < 0.001). It could be suggested that this factor probably took part in in vivo blockading the migration of tumor cells in small cancer foci.
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PMID:Production of a factor inhibiting tumor-cell migration in patients with gastric and breast cancer. 773 49

Autolymphocyte therapy (ALT) is adoptive cellular therapy of neoplastic disease using ex vivo activation of autologous (human) or syngeneic (murine) lymphocytes from tumor-bearing hosts (TBH) by low doses of anti-CD3 monoclonal antibody (MAb) and a mixture of previously prepared autologous cytokines (T3CS). Ex vivo activation by T3CS without tumor antigen results in expansion of CD44+ (memory) T cells. These memory T cells (ALT cells) mediate in vivo anti-tumor specificity and with cyclophosphamide (CY) are capable of curing metastatic disease in murine TBH. To determine whether CY could enhance the effectiveness of CD4+ or CD8+ subsets of ALT cells, C57BL/6J TBH with B16 melanoma or Lewis lung (3LL) carcinoma were treated with adoptive chemoimmunotherapy (ACIT) using CD4-depleted or CD8-depleted ALT cells and CY. ALT cells were derived from splenocytes of B16 or 3LL-TBH and activated ex vivo with T3CS. Depletion of CD4+ or CD8+ T cells was performed before or after activation with T3CS. B16-TBH or 3LL-TBH that received ACIT using CY with B16-derived or 3LL-derived CD8-depleted ALT cells, respectively, demonstrated cure of metastatic disease regardless of whether CD8+ T cells were depleted before or after T3CS activation. B16 or 3LL-TBH that received ACIT using CY with B16 or 3LL-derived CD4-depleted ALT cells also cured metastatic disease but only if CD4+ T cells were depleted after T3CS activation. Interleukin (IL)-2 added to pre-T3CS CD4-depleted ALT cells cultured with T3CS restored anti-tumor activity when combined with CY. TBH cured by ACIT using CY and ALT-cell subsets derived from syngeneic TBH with the identical tumor displayed tumor-specific immunity in rejecting a lethal challenge of identical but not reciprocal tumor. TBH given ACIT using CY and ALT-cell subsets derived from splenocytes of syngeneic TBH with reciprocal tumors rejected lethal challenges of both tumors. Tumor specificity measured by interferon (IFN)-gamma and 51Cr-release assays was demonstrated in pre- or post-T3CS/CD8-depleted, post-T3CS/CD4-depleted and pre-T3CS + IL-2/CD4-depleted ALT-cell subsets. Our data demonstrate that ACIT using CY combined with ex vivo T3CS-activated CD44+ memory T-cell subsets conveys long-term tumor-specific immunity.
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PMID:Adoptive transfer of ex vivo-activated memory T-cell subsets with cyclophosphamide provides effective tumor-specific chemoimmunotherapy of advanced metastatic murine melanoma and carcinoma. 775 64

While the effect of cytokines on the generation of tumor-reactive cytotoxic cells has been a topic of active investigation, the effect of physiological cytokine combinations has not been determined. We have investigated the effect of co-expression of IL-2 and IFN-gamma on the generation of cytotoxic cells against the murine line 1 tumor in vivo. These cytokines were selected because they are normally produced in concert by a subset of T-helper cells called T-helper 1 (Th1). We transfected the line 1 murine carcinoma with cDNA for IL-2 and IFN-gamma, alone or combined. IFN-gamma alone does not elicit rejection of the transfectant, but IL-2 increases the tumorigenic dose by 10,000-fold above the parental cells. Co-expression of IFN-gamma and IL-2 increases this rejection to at least 100,000-fold above parental line 1. Unlike IL-2 transfectants, tumor cells expressing both IFN-gamma and IL-2 can also elicit rejection of admixed parental tumor cells. Finally, the IFN-gamma/IL-2 transfectants are more effective at generating memory cells that are cytolytic for the parental tumor. Our results show that synergistic interactions of Th1 cytokines can remarkably enhance the cytotoxic response to tumors.
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PMID:Synergistic effects of co-expression of the TH1 cytokines IL-2 and IFN-gamma on generation of murine tumor-reactive cytotoxic cells. 776 35

Effectiveness of bispecific-monoclonal-antibody (BsMAb)-mediated cellular anti-tumour activity was evaluated in vitro and in vivo in relation to the additional need for T-cell activation in a new immunocompetent rat tumour model. L37 tumour cells, derived from a squamous-cell carcinoma of the lung of Wag/Rij rats, were transfected with the cDNA coding for the human 38-kDa transmembrane pan-carcinoma-associated antigen EGP-2. Intravenous inoculation of EGP-2-positive L37 cells resulted in a rapid outgrowth of EGP-2-positive tumour nodules in the lungs. A BsMAb BIS-19, recognizing EGP-2 on the transfected tumour cells and the T-cell receptor of the rat, was made and allowed specific lysis of EGP-2-transfected L37 tumour cells by activated rat T lymphocytes in vitro. In vivo T-cell activation, assessed by up-regulation of IL-2-receptor expression, could be induced by daily injection of rat rIL-2. Intravenous treatment of tumour-bearing EGP-2-positive L37 tumour with BIS-19 together with rat rIL-2 resulted in almost complete disappearance of established tumour. In contrast, animals treated with BIS-19 alone, IL-2 alone or a combination of anti-EGP-2, anti-TcR and IL-2 showed much less or no tumour reduction. These results show effectiveness of systemic treatment with BsMAbs to induce anti-tumour activity in established tumours. Immune activation prior to or during treatment with BsMAbs, as achieved with IL-2, appears to be a prerequisite for successful treatment.
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PMID:Reduction of EGP-2-positive pulmonary metastases by bispecific-antibody-redirected T cells in an immunocompetent rat model. 779 Jan 16

Eight pancreas carcinoma cell lines of duct cell origin (PCI-6, 10, 19, 24, 35, 43, 55, and 64) were established. Using one of these lines, PCI-24, human umbilical vein endothelial cells (HUVEC), and several recombinant cytokines, conditions and specificity of anti-PCI LAK induction were investigated, with the focus on a search for lymphokine-activated killer (LAK) activity that differentiates neoplastic (PCI) from non-neoplastic (HUVEC) cells. Interferon-gamma (IFN-gamma), IFN-alpha, IL-4, IL-6, and IL-7, but not tumor necrosis factor-alpha (TNF-alpha) or IL-1 beta, induced a weak LAK activity against PCI-24, whereas IL-2-induced (1000 U/mL) LAK exhibited a far more potent cytotoxicity. When these cytokines were added at the suboptimal dose IL-2 (100 U/mL), no significant augmentation in LAK activity was induced. Staphylococcal protein A (SpA) induced LAK activity as potent as that seen with IL-2 (1000 U/mL). Both IL-2-induced and SpA-induced LAK had a potent, dose-dependent cytotoxicity against HUVEC. HUVEC inhibited both IL-2- and SpA-induced LAK cytotoxicity against PCI-24 to almost the same extent as seen with PCI-24. Thus, two potent LAK-inducers did not generate LAK activity that differentiates neoplastic from non-neoplastic cells. Thus, in vitro cytotoxicity of LAK against non-neoplastic endothelial cells is unavoidable when handling cytokines in LAK induction.
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PMID:Lymphokine-activated killer cytotoxicity against pancreas adenocarcinoma cell lines and vascular endothelial cells. 780 31

We studied the functional response and phenotypic characterization of peripheral blood T cells and their correlation with the clinical stage of disease in 29 males with previously untreated carcinoma of the larynx and 24 healthy male controls. Peripheral blood T cells, phenotypically CD2+ CD3+, were significantly decreased in the patients relative to the controls. Patients with advanced locoregional extension (T4 and N1, 2, 3) also showed a diminution of the CD4+ subpopulation of T cells. DNA synthesis by purified T cells showed similar blastogenic responses in patients and controls; the interleukin-2 production of phytohemagglutinin stimulated lymphocytes was also normal. We conclude that in patients with laryngeal carcinoma there is a phenotypic alteration of the T cells that is variable according to tumor stage, without functional alterations in blastogenic capacity or IL-2 production.
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PMID:Functional and phenotypic analysis of T-lymphocytes in laryngeal carcinoma. 787 26


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