Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sensitivity of human melanoma and lung cancer strains transplanted to nude mice to the synthetic hormone of hypothalamus--melanostatin has been defined. Correlation has been noted between the rate of melanoma growth inhibition, decrease in the rate of Na-fluorescent accumulation in the tumor and the tendency towards depression of the activity of energetic metabolism enzymes (SDH and alpha-GPDH) in the treated tumors as compared to control. Moderate lymphopenia and absence of effect on the same enzymes of the lymphocytes was also observed. Fluorescent probes can be used in the estimation of the drug action on the tumor and organs.
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PMID:[The action of hypothalamic hormone on athymic mice with transplantable strains of human tumors]. 290 87

Tumoricidal activity of Soviet-synthesized oxoplatinum and cycloplatam was shown to influence human tumor strains (melanoma, cancer of the kidney, Burkitt's lymphoma) transplanted to nude mice. Their therapeutic effect was associated with lymphopenia; however, they did not suppress the chemically determined activity of succinate dehydrogenase and alpha-glycerophosphate dehydrogenase.
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PMID:[Comparative study of platinum complexes in athymic mice with human tumors]. 318 35

Oxoplatinum (USSR) caused a more pronounced anticancer effect than platidiam (CSSR) when treating nude mice with the transplantable human melanoma. Moderate lymphopenia was found with therapeutic doses of oxoplatinum and platidiam, but there was no direct inhibition of the energy metabolism of lymphocytes in the peripheral blood. In the cancer cells and in the lymphocytes infiltrating the tumour oxoplatinum caused a significant decrease in the alpha-GPDG activity realizing the binding of the glycolysis and oxidation which might evidence for a definite selective action of oxoplatinum on the human melanoma.
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PMID:[Effect of oxoplatin and platidiam on human melanoma strains and functional activity of blood lymphocytes in athymic mice]. 320 91

Adoptive immunotherapy with interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells (IL-2/LAK) is a technically demanding cancer therapy dependent upon large scale isolation and culture of lymphocytes. An important question is whether this technology can be accomplished routinely outside of highly specialized centers. In addition, no systematic examination of laboratory correlates of IL-2/LAK therapy in humans has been reported to date. The objectives of this report are to address two issues relevant to IL-2/LAK therapy. (a) Can IL-2/LAK therapy be accomplished outside of previously identified centers of expertise? (b) What are the relevant laboratory/clinical parameter correlations? The six institutions in the National Cancer Institute extramural trial treated 83 evaluable patients with renal cancer, malignant melanoma, or colon cancer with IL-2/LAK by a uniform protocol. Patients received 5 days of IL-2 priming, then daily leukaphereses for 5 days starting 48 h after IL-2 to harvest cells. Mononuclear cells were isolated, then cultured in roller bottles in 1-liter aliquots for 3 to 4 days at a cell density of 1.5 x 10(6) per ml with recombinant IL-2, 1500 units per ml. Cells were harvested and administered to patients with additional IL-2. Administration of IL-2 regularly induced lymphopenia and rebound lymphocytosis. Leukapheresis yields and numbers of LAK cells generated in culture and reinfused into patients correlated directly with peak lymphocyte counts achieved by IL-2 administration. Mean mononuclear cell recovery per 5 days of leukapheresis (+/- SEM) was 14.3 +/- 0.8 x 10(10). Average volume of cells cultured per patient was 95 liters (range, 41 to 235). Mean yield of cells harvested from cultures was 53%. Mean total number of LAK cells infused per patient was 7.6 +/- 0.4 x 10(10) (range, 2 to 15.2 x 10(10]. LAK activity was measured in vitro by lysis of 51Cr-labeled natural killer-resistant Daudi and fresh tumor targets. LAK effector cells regularly lysed these targets in vitro. Neither tumor reduction nor clinical toxicity correlated with dose or with cytolytic activity of LAK cells, or with other laboratory parameters including base-line lymphocyte count and IL-2-induced lymphocytosis. We conclude: (a) large quantities of LAK effector cells with tumoricidal activity can be generated routinely at different centers; (b) neither in vitro LAK activity nor numbers of LAK cells infused were predictive of clinical efficacy or toxicity. There is a need to identify other laboratory or clinical parameters more predictive of IL-2/LAK therapeutic efficacy or toxicity.
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PMID:Laboratory correlates of adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells in humans. 326 May 37

Twenty patients with disseminated melanoma were treated with interferon alfa-2a, given by intramuscular (IM) injection three times a week in escalating doses from 15 to 50 X 10(6) U/m2. Of 18 patients considered evaluable, two had complete remission and in two others the disease was stabilized. Laboratory tests 6 hours after injection of interferon alfa-2a indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity. Sequential changes (measured before injection of interferon alfa-2a on days 3, 10, and 31) consisted of neutropenia, thrombocytopenia, and a slight increase in OKT4 positive T cells compared with OKT8 positive T cells. NK activity against the K562 target cells was increased in most patients during the first week of treatment, returning to near or below pretreatment levels thereafter. This response contrasted with a delayed increase against melanoma target cells in 10 patients. The latter correlated with an increase in mitogen-stimulated interleukin-2 (IL2) production, and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. Changes in cortisol levels may explain some effects on the immune system, such as depression of IL2 and immunoglobulin production in vitro, and the differences noted in clinical responses during the present study compared with those observed with interferon alfa-2b given by intravenous (IV) injection in 5-day cycles. These results suggest that interferon alfa-2a has antitumor activity in certain melanoma patients, in particular those with metastases to pulmonary or subcutaneous sites. Assays of IL2 production and LAK activity may assist in the selection of patients who respond to interferon alfa-2a and help to optimize treatment regimens.
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PMID:Immunological effects of recombinant interferon alfa-2a in patients with disseminated melanoma. 348 11

Studies were initiated to assess the response of patients with disseminated melanoma to recombinant alpha interferon (rIFN-alpha A) and to monitor effects of rIFN-alpha A on several tests of immune function. Twenty patients were treated with rIFN-alpha A given by i.m. injection in escalating doses from 15 to 50 X 10(6) um-2. The responses of two patients were considered unevaluable. Of the remainder there was complete remission of tumour in two and stable disease in two. Subsequent progression of tumour in one of the latter patients coincided with development of antibodies to IFN. Side effects (usually fatigue) were dose rate limiting in 11 patients. Laboratory tests on samples taken 6 hours after rIFN-alpha A indicated a marked lymphopenia and a reduction in natural killer (NK) cell activity particularly against K562 target cells. Longer term changes measured in samples taken 2 days after the previous rIFN-alpha A injections consisted of neutropenia and an increase in the T4/T8 ratio due mainly to a relative increase in OKT4 positive T cells compared to OKT8 positive T cells. NK activity against the K562 target cell increased in most patients during the first week of treatment and then returned to below or near pretreatment levels thereafter against the K562 target cell. This contrasted with NK activity against the melanoma target cell which showed a more gradual increase over the duration of the treatment in 6 patients. The latter correlated with an increase in mitogen stimulated IL 2 production from their blood lymphocytes and may indicate that the cytotoxic activity resulted from lymphokine-activated killer (LAK) cells. These results confirm the activity of rIFN-alpha A against melanoma in certain patients. They suggest that further studies are needed to select patients who may respond to rIFN-alpha A and to optimize treatment regimens. Tests of IL 2 production and LAK activity may assisted in achieving these objectives.
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PMID:Effects of recombinant leukocyte interferon (rIFN-alpha A) on tumour growth and immune responses in patients with metastatic melanoma. 387 53

Two hundred-eighty patients were randomized to receive either BCNU, hydroxyurea and imidazole carboxamide (BHD), BHD plus levamisole, or high-dose DTIC plus actinomycin D. There was no difference in response rate in the three groups (24%, 25% and 22%). Females responded better than males and, as expected, those with a better performance status responded more favorably than those with poor performance status. Patients whose primary site of melanoma was on the extremities did significantly better than those melanomas originating on the trunk or head and neck. Patients with lymphocyte counts greater than 2000/mm3 fared better than those with lymphopenia. Those responders who received high-dose DTIC plus actinomycin D had a significantly longer length of response than those receiving the immunotherapy limb. This was also true in those patients who had a prior disease-free interval of greater than 6 months before being placed in this study. Although there was no difference in survival from the start of treatment in all patients, those patients receiving high-dose DTIC plus actinomycin D and who had a prior disease-free interval of greater than 6 months, had significantly superior survival when compared to the immunotherapy limb. It is concluded that the addition of Levamisole to BHD does not improve response rate and may in certain subsets be detrimental to disease-free response and survival. High-dose DTIC plus actinomycin D is equally effective to BHD.
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PMID:Combination chemotherapy plus levamisole in the treatment of disseminated malignant melanoma. A Southwest Oncology Group study. 636 30

A series of investigations was employed to determine if metastases of intraocular melanomas could be induced by experimental manipulations. Syngeneic B16F10 melanoma cells transplanted intracamerally into C57BL/6 mice produced progressively growing intraocular tumors, yet formed only occasional pulmonary metastases. Neither enucleation nor mechanical manipulation of the melanoma-containing eye promoted a significant increase in the incidence of metastases. Likewise, immunologic impairment in the form of natural killer cell deficiency, T-lymphocyte deficiency, or gamma-irradiation-induced lymphopenia failed to produce spontaneous metastases in intraocular melanoma-bearing mice. However, enucleation in consort with immune impairment (T-cell deficiency) produced a sharp increase in the incidence and number of pulmonary metastases in intraocular melanoma-bearing mice. Further studies showed that external pressure to the tumor-containing globe (without enucleation) produced extensive metastases in athymic, nude mice. By contrast, atraumatic enucleation of rapidly frozen eyes prevented metastasis of intraocular melanomas in similar hosts. Collectively, the results indicate that induction of distant metastases in hosts harboring intraocular melanomas requires two simultaneous processes: (1) mechanical manipulation of the melanoma-containing eye, and (2) concomitant impairment of T-cell-dependent immune processes. The data strongly suggest that mechanical manipulation of melanoma-containing eyes produces intravascular showers of melanoma cells that are rejected by T-cell-dependent immune processes in the immunocompetent host. In the absence of these normal T-cell-dependent immune mechanisms, enucleation-induced showers of blood-borne melanoma cells gain a foothold in the lung and form progressive metastases.
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PMID:Enucleation in consort with immunologic impairment promotes metastasis of intraocular melanomas in mice. 638 75

The microcytotoxicity assay and the leukocyte migration inhibition test were unable to reveal any specific reactivity in patients suffering from localized skin melanoma. The non-specific reactivity measured by the microcytotoxicity assay, the so-called NK activity was found to be associated to the cells bearing Fc receptors, irrespective of T and non-T identity. Further more the NK activity depends on the target cell used (established cell lines versus short-term cultures) and the lymphocyte/target cell ratio. The NK activity measured by microcytotoxicity assay and the leucocyte migration inhibition test were compared by simultaneous implementation of the two test systems. No correlation between significant leucocyte migration inhibition and NK activity was found. In a tumor neutralization test workout in a nude mouse model, it was found that patient lymphocytes decreased the number of tumor takes and increase the latency period. However, the specificity of these reactions were uncertain.
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PMID:The NK function elucidated with respect to effector cells, target cells and other immunological in vitro tests. 668 40

We examined the number of T-Lymphocytes in 14 malignant melanoma patients using the sheep erythrocyte rosette test and the PHA stimulation test. These investigations were carried out before the operation under general anesthesia was performed as well as 1, 7, 14, 21, and 28 days after the operation. 16 patients with various large surface skin operations in local anesthesia served as a control group. Among them there were also 5 malignant melanoma cases. The tests preoperatively accomplished yielded normal results (T-lymphocytes 65.7 +/- 2.95%, PHA stimulation 79.01 +/- 1.69%) for all 19 melanoma patients. 24 hours after the operation the average portion of T-lymphocytes decreased in relation to the whole lymphocytes and reached only the level of 53.8 +/- 7.8%. After 7 days it amounted to 57.5 +/- 8.5%, after 14 days to 59.5 +/- 7.8%, after 21 days to 62.3 +/- 5.4% and after 28 days to 62.8 +/- 6.1%. The PHA stimulation was significantly diminished only after 24 hours, but not longer after 7 days. A correlation between the diminution of T-lymphocytes observed 14 and more days after the operation and the duration of the general anesthesia may be suggested in single cases. -- Patients operated under local anesthesia showed after 2 and 24 hours a significant diminution of T-lymphocytes. After 7 days the values had returned to normal levels (66.7 +/- 5.9%).
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PMID:[Comparative examinations of the effect of general and local anesthesia upon the T-lymphocytes in melanoma operations (author's transl)]. 697 60


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