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)

Phenotypic markers and cytotoxic function were monitored in cultures of normal human mononuclear cells obtained from peripheral blood or spleen and stimulated by recombinant interleukin-2 (IL-2; 1,500 U/ml). Fresh spleen cells contained less than 5% natural killer (NK) cells (CD3-NKH1+), which increased about threefold after activation with IL-2. In both spleen and peripheral blood cultures, T cells with the NKH1 marker showed the highest relative increment among all cell types studied. Lymphokine-activated killer (LAK) cells from peripheral blood and spleen displayed very similar cytotoxic activity against K562, Daudi, and COLO carcinoma cell lines. Killing of the three targets peaked at 7 days of culture. Antibody-dependent cell cytotoxicity against a B-cell line was mediated by both circulating and splenic LAK cells from 2 to 14 days of culture. Cell sorting experiments showed that K562 targets were killed by both CD5+NKH1+ and CD5-NKH1+ cells whereas Daudi targets are only killed by CD5-NKH1+ activated NK cells from both spleen and peripheral blood. In summary, human spleen LAK cells have similar phenotypic and functional properties to circulating LAK cells, and they may be used for adoptive immunotherapy of human cancer.
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PMID:Human spleen and peripheral blood lymphocytes activated by interleukin-2 have similar phenotypic and functional characteristics. 231 57

The functional and phenotypic characteristics of carcinomatous pleural or peritoneal lymphoid cells cultivated with either rIL 2 or TCGF have been investigated. The cultivation of the lymphoid cells with cytokines was initiated by a mixture of coexisting, viable carcinoma cells for 14 days. Results have indicated that cytokine-activated lymphoid cells from malignant pleural and peritoneal effusions showed considerable cytolytic activity against K562 and Daudi cells. The cell population responsible for LAK and/or CTL effector cells of TCGF-activated lymphoid cells were CD8+ CD11- cells. Further, in rIL 2-expanded cultures from pleural and peritoneal lymphoid cells, the CD4+ Leu 8- population was found to contain effector cells of cytotoxic activity against the tumor cells. It further was seen that the TCGF-activated CD8+ CD11- T cells possessed a more potent killing activity, in comparison to the rIL 2-activated CD4+ Leu8- T cells. However, rIL 2-activated lymphoid cells from ascites in liver cirrhosis (used for a control) showed a higher tumoricidal activity.
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PMID:[In vitro induction of cytotoxic activity against carcinomatous pleural or peritoneal lymphoid cells cultivated with cytokines, and an immunological phenotypic analysis of the effector cells]. 232 66

Soluble interleukin-2 receptor (IL-2R) level and IL-2R positive (IL-2R+) cells were studied in twenty patients with carcinomatous pleural effusions. The mean value of soluble IL-2R level in carcinomatous pleural effusions was 2930 +/- 1722 U/ml and that in sera was 965 +/- 610 U/ml. Soluble IL-2R level in carcinomatous pleural effusions was found to be significantly higher (p less than 0.001) than that in sera of patients with carcinomatous pleural effusions and that in transudates. Serum soluble IL-2R level in patients with carcinomatous pleural effusions was found, to be significantly higher (p less than 0.001) than that in normal controls (264 +/- 70 U/ml). We also studied IL-2R+ cells in pleural fluids and peripheral blood of patients with carcinomatous pleural effusions. The mean percentage of IL-2R+ cells in carcinomatous pleural fluid lymphocytes was 22.8 +/- 17.8%, as compared with 3.0 +/- 2.2% in peripheral blood lymphocytes of normal controls (p less than 0.001). No significant differences were observed among the cell types of lung cancer examined (adenocarcinoma, squamous, small cell and large cell carcinoma) and no correlation among levels of soluble IL-2R and IL-2R+ cell in either pleural fluid or blood. Our results suggest that in patients with carcinomatous pleural effusions, T cell-mediated active immune mechanisms (IL-2/IL-2R system) against cancer cells are more active in pleural fluid than in peripheral blood.
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PMID:[Elevated soluble interleukin-2 receptor and interleukin-2 receptor positive cells in carcinomatous pleural effusions]. 235 70

In breast cancer patients on whom modified radical mastectomy is performed, relatively more of the regional lymph nodes draining the breast carcinoma remain in comparison with standard radical mastectomy. Therefore, investigation of the functions of lymph nodes draining breast carcinoma has become important. Lymphocyte subsets of 33 axillary lymph nodes from 19 breast cancer patients were analysed using flow cytometry. In axillary lymph nodes, both OKT-3(+) cells and OKT-8(+) cells were decreased in comparison with those in peripheral blood. However, the OKT 4/8 ratio was increased in axillary lymph nodes. These findings suggest that axillary lymph nodes are immunologically more functional against cancer spread than peripheral blood. OK-M1(+) cells, Leu-7(+) cells and Leu-11a(+) cells were decreased in axillary lymph nodes in comparison with peripheral blood. The ability of IFN production in axillary lymph nodes and peripheral blood was analysed using the cytopathic effect of VSV-sindbis virus. After 72 hours incubation, IFN production of axillary lymph nodes showed maximum titer. When lymph nodes were co-cultured with OK-432, IFN production of axillary lymph nodes was strongly augmented. IFN production of axillary lymph nodes draining breast carcinoma were increased in comparison with peripheral blood. Axillary lymph nodes draining breast carcinoma would thus seem to be important as cytokine-producing organs. IFN has been found to be an activator of NK cells, cytotoxic T cells and IL-2 production. Axillary lymph nodes may therefore play an important role against the spread of breast cancer.
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PMID:[Interferon production in lymph nodes draining breast carcinoma and its augmentation by OK-432]. 242 12

The membrane molecule termed "7F7-antigen" has been found to be involved in several examples of cell-cell interactions. This 85 kDa glycoprotein with a protein core of about 55 kDa contains N-linked and O-linked carbohydrates. It has an isoelectric point of 8.0-8.5 and is expressed on 20% of peripheral blood mononuclear cells, 35% of peripheral blood B-cells, follicular dendritic cells and vascular endothelium. It is also expressed on activated T-cells and its expression on B-cells, fibroblasts and monocytes increases after treatment with PWM, interferon-gamma and after three days culture, respectively. The MAb 7F7 used to define this antigen inhibits the initiation of T-cell proliferation induced by anti-CD3, PHA, ConA and (weakly) allogenic stimulator cells, but does not affect the growth of IL-2 dependent T-cells and does not interfere with the killing of PHA-blasts by allogenic IL-2 dependent T-cells. 7F7 also inhibits the binding of C3-coated sheep erythrocytes to B-cells, the PMA-induced aggregation of U937 and the binding of activated T-cells to fibroblasts. The 7F7-antigen is expressed on some non-Hodgkin lymphomas of B-cell differentiation, particularly those with follicular structure, but not on Burkitt's lymphoma, ALL or carcinomas of various tissues. It is, however, found on fibrous tissue surrounding infiltrating carcinoma cells. The expression of a melanoma antigen, P3.58, which was shown to be identical to 7F7-antigen correlates with stage and spread of invasive melanoma. It was concluded that the 7F7-antigen, which is probably related to a previously described adherence molecule (ICAM-1), is of biological importance for the initiation of T-cell responses. With the possible exception of melanoma its expression on neoplastic cells in vivo is unlikely to be of importance for the spread of malignant disease.
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PMID:Importance of an 85 kDa membrane glycoprotein for a variety of cell-cell interactions. 246 58

Tumor cell suspension was prepared from resected tumor tissue of various cancer patients. I-RNA was extracted from lymphoid tissues of rabbits immunized with each tumor cell and CFA. Autologous (in some cases, allogeneic) lymphocytes were prepared with blood cell separator and incubated with I-RNA, then, returned to himself. Twenty five cases of non-curatively resected gastric cancer (group A), 27 cases of stage II-IV of esophageal carcinoma (group B), 21 of lung cancer (group C), 14 of colorectal cancer (group D) and 37 cases with metastatic lesions (group E) were treated with this schedule. Five year cumulative survival rate was 21% in group A, 23% in group B, 46% in group C and 61% in group D, respectively. One case of CR and 5 of PR were recognized in group E. In many cases of the responder, lymphocyte count, ratio of Leu 4+, 3a+ subset in the peripheral bloods increased and skin reaction to autologous tumor cell extract, LAI and LMI became to positive. Interferon activity was also increased in the responder. It was reported on the preliminary study of combination treatment with I-RNA sensitized lymphocytes and IL-2.
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PMID:[Adoptive immunotherapy of advanced cancer patients with immune RNA-sensitized lymphocytes]. 247 17

Modification of recombinant human interleukin 2 (rhIL-2) with monomethoxy polyethylene glycol has been shown to alter its pharmacokinetic properties. Therefore, we investigated the pharmacological parameters of schedule and dose in order to assess the impact on the in vivo antitumor activity of this modification. The antitumor efficacy, as well as the toxicity, of polyethylene glycol-interleukin 2 (PEG-IL-2) was compared to that of rhIL-2 in three transplantable syngeneic murine tumor models, Meth A fibrosarcoma, B16 melanoma, and Pan-02 pancreatic carcinoma. At equitoxic dose levels, the antitumor activity of PEG-IL-2 was far superior to that of rhIL-2 in all three tumor models. This efficacy of PEG-IL-2 was dose dependent and was greatest on a Q7D x 2 schedule in Meth A and B16. When the same total doses were further divided and delivered on any of several alternative schedules, either the efficacy was reduced or the toxicity of the treatments was increased. In Pan-02, a rhIL-2-resistant tumor, PEG-IL-2 treatment on either the Q7D x 2, Q4D x 3, or Q3D x 4 schedule resulted in approximately a 200% increase in lifespan; however, the toxicity of the treatment increased as the interval between doses was shortened. Simulations of the pharmacokinetic profiles of these various regimens suggested that the toxicity of PEG-IL-2 and rhIL-2 was related to the minimum plasma concentration that was obtained and the time interval between peak levels. The efficacy of the treatment was associated with the interleukin 2 plasma peak height, since a dose response was observed; however, peak plasma concentration did not appear to be the only parameter which determined efficacy. We hypothesize that this observed schedule dependence is also affected by the kinetics of the host's biological response to rhIL-2.
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PMID:Schedule dependency of the antitumor activity and toxicity of polyethylene glycol-modified interleukin 2 in murine tumor models. 281 8

A new approach to cancer treatment has been developed based on the adoptive transfer of activated lymphocytes into cancer patients. Lymphocytes harvested from patients by leukapheresis are converted into lymphokine-activated killer (LAK) cells by incubation with recombinant interleukin-2 (rIL-2). These LAK cells are then infused back into the patients in combination with intravenous IL-2. Among 25 patients treated with this form of adoptive immunotherapy there were 11 patients with measurable tumor reductions, including 1 complete responder. The majority of responses occurred in patients with metastatic renal cell carcinoma, melanoma and colorectal carcinoma. The toxicities of IL-2, including fluid retention and pulmonary edema, limit therapy, and laboratory investigation is now aimed toward understanding the mechanism of IL-2 toxicity. The use of LAK cells and IL-2 in cancer therapy is still in a developmental stage and needs to be refined before its role can be definitely established.
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PMID:Therapy of cancer using the adoptive transfer of activated killer cells and interleukin-2. 312 51

We report here experiments on the analysis of cellular signal transduction in a series of patients with chronic B cell disorders (B cell chronic lymphocytic leukemia [B-CLL] and prolymphocytic leukemia). We compared the response of the leukemic cells with primary external signals (interleukin 2 [IL-2] or B cell differentiation factors [BCDF or IL-6]) with their response to secondary inducers (the phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA] or the calcium ionophore A23187) that circumvent the first part of the signal transduction pathway by directly activating the key enzyme protein kinase C. One BCDF was synthesized by mitogen-activated peripheral blood B lymphocytes; a second BCDF was constitutively produced by the human bladder carcinoma cell line T24. Changes in morphology, Tac (IL-2 receptor) expression, RNA synthesis measured by 3H-uridine uptake, and immunoglobulin production tested by enzyme-linked immunosorbent assay were used as parameters of successful signal transduction. TPA alone and TPA plus A23187 (synergistically) effectively initiated differentiation in all the leukemia cases. Neither IL-2 nor BCDF (singly or in combinations) caused equivalent responses. On the other hand, IL-2 and BCDF produced a substantial differentiation effect on normal B lymphocytes. Our data suggest that (a) B-CLL cells are able to respond to direct stimulation of the second messenger pathway (through protein kinase C) but not to the physiological stimuli IL-2 or BCDF; (b) the defect in signal transduction appears to be located upstream of protein kinase C (a possible candidate is a G protein); (c) malignant B cells may spontaneously or after treatment with inducers express the IL-2 receptor (Tac antigen) in the absence of a functional differentiating response to IL-2; and (d) signs of proliferation/differentiation in B-CLL samples after incubation with IL-2 or BCDF might be due to contamination of the cell populations with residual normal B cells.
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PMID:Analysis of signal transduction in B chronic lymphocytic leukemia cells. 312 49

Clinical investigations using the adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) to treat patients with advanced cancer have yielded encouraging results. We have thus sought ways to enhance the effectiveness of adoptive immunotherapy while minimizing its toxic side effects. Murine experiments have identified tumor-infiltrating lymphocytes (TIL) as killer cells more effective than LAK cells and less dependent on adjunctive systemically administered IL-2 to mediate antitumor effects. Accordingly, we performed a pilot protocol to investigate the feasibility and practicality of administering IL-2-expanded TIL to humans with metastatic cancers. Twelve patients, including six with melanoma, four with renal cell carcinoma, one with breast carcinoma, and one with colon carcinoma, were treated with varying doses and combinations of TIL (8.0 X 10(9) to 2.3 X 10(11) cells per patient), IL-2 (10,000 to 100,000 U/kg three times daily to dose-limiting toxicity), and cyclophosphamide (CPM) (up to 50 mg/kg). Two partial responses (PR) to therapy were observed: pulmonary and mediastinal masses regressed in a patient with melanoma, and a lymph node mass regressed in a patient with renal cell carcinoma. One additional patient with breast cancer experienced a partial regression of disease in lymph nodal and cutaneous sites with complete elimination of malignant cells from a pleural effusion, although cutaneous disease recurred at 4 weeks. The toxicities of therapy were similar to those ascribed to IL-2; no toxic effects were directly attributable to TIL infusions. In five of six melanoma patients, TIL demonstrated lytic activity specific for the autologous tumor target in short-term chromium-release assays, distinct from the nonspecific lytic activity characteristic of LAK cells. This study represents an initial attempt to identify and use lymphocyte subsets with enhanced tumoricidal capacity in the adoptive immunotherapy of human malignancies.
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PMID:Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: a pilot study. 325 61


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