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Biomedical subjects

M Micksche

Publications and source records attributed to M Micksche.

At least 109 records · Page 6Linked to original sources

Generation of suppressor cells for natural killer activity in cancer patients after surgery.

Natural killer (NK) cell activity was examined in breast cancer patients before and after surgery, and the cells involved in the postoperative depression of cytotoxicity were characterized. NK activity against K562 target cells determined in 4-hour 51Cr release assay of blood lymphocytes from preoperative patients was comparable to that of normal donors. After surgery the patients showed a decrease in NK activity but not in number of large granular lymphocytes in the effector cell populations. When blood mononuclear cells from postoperative patients were depleted of monocytes by adherence to a serum-coated plastic dish and a Sephadex G10 column and then cultured for 24 hours, they showed an increase in NK activity. Furthermore, adherent blood cells of postoperative patients, but not of normal donors or preoperative patients, suppressed the lytic function of NK cells of normal individuals. Twenty-four-hour preculture of suppressor and effector cells was required for suppression of cytotoxicity. Neither postoperative sera nor culture supernatants of suppressor monocytes and effector cells suppressed NK activity. In contrast, the lymphoproliferative response to mitogen was not affected by surgery, and postoperative blood monocytes did not inhibit the mitogenic response of normal lymphocytes. The results suggest that the appearance of suppressor monocytes in the circulation could be one cause of depression of NK activity in postoperative cancer patients.

Adult↗

[Human interferons -- features and chances (author's transl)].

Interferons are soluble cellular products secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. In viral infections, interferon controls the spread of viruses by inhibiting viral protein synthesis and/or nucleic acid replication and by activating cellular immune responses which effectively eliminate virus-infected cells. Immune interferon, produced in a cellular immune response as the result of an infection, tumour, or hypersensitivity reaction, governs the local immune response to the abrogation of that tumour or other injury by directly reducing cell multiplication and recruiting cytotoxic cells. Clinical trials have shown some effectiveness of interferon in the treatment of chronic viral infections as well as some possible antitumour effects. Because of the extreme scarcity of human interferon and the use of highly impure preparations, the results to date are not conclusive. Therapeutic effectiveness rather than prophylactic effects, has still to be proved by controlled clinical studies with purified interferon under economically feasible conditions.

Fibroblasts↗

Reactivity to autologous non-T-cells and suppressor function of human autologous rosettes.

A subset of human peripheral blood T-cells can form rosettes with autologous erythrocytes (autologous rosettes). Fractionation of T-cells by autologous rosette centrifugation demonstrated that the autologous rosettes, but not the non-rosetting cells, have the capacity to respond with increased DNA synthesis to autologous non-T-cells in the autologous mixed lymphocyte reaction (MLR) and to suppress the mitogenic response after activation with concanavalin A (Con A). Furthermore, the autologous rosettes, autologous MLR and Con A-induced suppressor activity were particularly enriched in the nylon wool non-adherent T-cells and depleted in the nylon wool adherent T-cells. These results suggest that the same or at least largely overlapping T-cell subsets are responsible for the autologous rosettes, autologous MLR and Con A-induced suppressor function.

Animals↗

In vitro augmentation of natural killing activity by OK-432.

OK-432, a streptococcal preparation, augmented the natural killing (NK) activity of peripheral blood lymphocytes of normal donors and cancer patients against both NK sensitive and resistant human target cells in vitro. The enhancement of NK activity was evident after 4 h pretreatment and maximum by 16-24 h. The manifestation of OK-432 induced augmentation required active cell metabolism, RNA and protein synthesis but no DNA synthesis of lymphocytes. The supernatants produced by OK-432 stimulated lymphocyte cultures had no enhancing substance nor interferon. Anti-interferon antibodies did not inhibit boosting activity of OK-432. Large granular lymphocytes were involved in both spontaneous and OK-432 induced cytotoxic activity. The proportion of lymphocytes conjugating to target cells was not changed by OK-432. These results suggest that OK-432 augments cytotoxic activity of large granular lymphocytes having ability to recognize target cells independent of interferon induction.

Adult↗

An improved antigenic marker of human lung carcinomas and its use in radioimmunoassays.

An antigenic activity in pleural effusions of patients with squamous-cell carcinoma of the lung has been prepared in highly purified form by a 5-step fractionation scheme. The purified substance, designated LuCA (lung cancer antigen), was assessed during the course of the fractionation procedure by a radioimmunometric assay carried out with specific soluble reagents. Sensitive saturation-binding assays showed no or only weak uptake of the 125I-labelled antigen preparation by a panel of antisera specific for known bronchogenic tumour markers, and for normal human serum proteins. The preparation appeared to contain lung-tumour-associated antigens, one of them probably distinct for squamous-cell carcinomas. The antigen fraction consists of acid-soluble glycoproteins, and was demonstrated by SDS-polyacrylamide gel electrophoresis as a single band in the mol. wt region of 43,000. The gel-filtration elution volume appeared to indicate the occurrence of the antigenic activity in multiples of this smaller unit. Pilot radioimmunoassays performed with LuCA and an absorbed specific antiserum suggest the possible suitability of the marker preparation for screening lung-cancer patients.

Antigens, Neoplasm↗

[Local immunotherapy. Alternative therapy for malignant cutaneous lesions (demonstration on 30 patients with malignant melanoma) (author's transl)].

Experimental data in animal models and clinical experience with a systemic immunotherapeutic approach in patients with tumours were the determining factors in the decision to test the local effect of this form of therapy on primary and secondary malignant lesion of the skin. The antitumour effect of local immunotherapy seems to be based on the induction of a cell-mediated immune challenge reaction in close contact with the malignant neoplasm. A trial of local immunotherapy was undertaken in 30 patients with melanoma with local recurrence of the primary tumour or multiple metastases involving the skin. The therapeutic indications and clinical response are discussed.

Adult↗

Serum lysozyme levels in patients with solid tumors.

Serum lysozyme has been demonstrated to be an indicator for macrophage activity in the tumor-bearing host. Therefore, we investigated lysozyme levels in the sera of 336 untreated tumor patients (121 malignant melanoma, 61 lung cancers, 70 cervical cancers, 49 breast cancers and 35 benign breast tumors, and 36 healthy controls). Patients with malignant melanoma and lung cancer had significantly higher lysozyme levels than the healthy controls. Within the clinical stages in melanoma, there was a decrease of lysozyme in stages II and III in comparison to stage I, but still above that of the control values. Patients with benign breast tumors had normal levels, whereas in breast cancer patients of stages I and II there was a significant reduction in the lysozyme levels. In stages III and IV no differences to the control group could be detected. In patients with cervical cancer (FIGO II and III) serum lysozyme levels were found to be within the normal range. From this study it can not be concluded that serum lysozyme reflects the immunological reactivity of the tumor bearer. Nevertheless, the reduced levels in stages I and II of breast cancer might point to an immunological defect.

Breast Neoplasms↗

Cell-mediated immunity in patients with cervical cancer.

In 16 patients with cervical carcinoma (stages II and III) tumor-specific and general immune reactivity was investigated. Cancer patients' skin reactivity was different from that of controls insofar as there was a decreased response to streptokinase-streptodornase as well as to DNCB. Absence of DNCB sensitization was mainly in stage III patients. Cell-mediated immunity to autologous and/or allogeneic tumor-associated antigens (TAA) was demonstrated in vivo and in vitro. 3 of 8 patients had positive skin reactions to autologous TAA and 8 of 14 reacted to allogeneic TAA. In the lymphocyte migration inhibition test, 8 of 14 patients reacted to autologous tumor membrane preparations and 3 of 10 to allogeneic pooled preparations. In addition, there was some indication of cross-reaction with antigens from a human squamous cell carcinoma of the lung. There was no reaction in vitro to normal cervical tissue and no association between tumor-specific reactions and herpes simplex virus type II antibodies could be demonstrated. Patients with DNCB sensitization and in vivo as well as in vitro lymphocyte reactivity to TAA had a better prognosis than nonreacting patients, indicating the value of combined immunological tests.

Adult↗

[Prognostic factors in the drug therapy of metastasizing breast cancer].

175 patients with metastatic breast cancer, treated with chemotherapy, were analyzed retrospectively to identify the characteristics of prognostic importance in predicting response to chemotherapy and survival from onset of the chemotherapy. The most significant factors were the sites of metastatic disease and an estimate of the total extent of disease.

Antineoplastic Agents↗

[Immunoreactions of the delayed type in patients with multiple sclerosis (author's transl)].

Skin tests were performed in 34 multiple sclerosis patients. The incidence of positive reactions was reduced in these patients compared with healthy controls, with regard to different recall antigens with the exception of varidase, as well as the PHA and DNCB. No definite differences in reaction between patients who had been suffering from multiple sclerosis for a long time or for a short time, could be established. However, there was a certain dependence on the stage of the disease in so far as positive reactions were less frequent during the acute episode--more pronounced during the subsiding attack than at the onset of the episode--, than during the interval between two attacks. These results suggest that multiple sclerosis is primarily characterised by a weakness of cell-mediated immunity and that this weakness becomes more pronounced during the acute episode. The differences between the skin test reactions performed during the individual phases of the disease are too slight to assist in defining the acute episodes. It may be possible to identify changes in the reaction level via long-term studies.

Humans↗

[Immunological studies and immunotherapeutic possibilities in inoperable bronchogenic carcinoma (author's transl)].

By establishing an immune profile combined with detailed clinical observation an attempt was made to assess the value of various therapeutic measures, especially immunological methods, in the treatment of inoperable bronchogenic carcinoma. The results indicated that in advanced cases specific immunological measures or stimulation of the immune mechanism only play a supportive role. Toxic side-effects or tumour enhancement were absent.

Aged↗

[Inhibition of tumor growth and metastases in mice with Lewis lung tumors by vitamin A and BCG].

The anti-tumor effect of vitamin A and/or BCG was investigated in Lewis lung tumor system. Tumor growth and lung metastases were significantly suppressed, when tumor cells were mixed with BCG and inoculated subcutaneously into vitamin A-treated animals. Survival time was also prolonged by the same treatment. Vitamin A alone, without BCG, showed no effect on tumor growth, lung metastases or survival time.

Animals↗

[Immune stimulation with vitamin A therapy in patients with pulmonary neoplasms].

Based on a clinical trial, in which patients with unresectable bronchogenic cancer were treated with a combination of vitamin A plus chemotherapy, or vitamin A plus radiotherapy, a study was initiated in which vitamin A alone was given for tumor treatment. 9 male patients with metastatic unresectable squamous cell carcinoma of the lung were treated with vitamin A palmitate or 13-cis vitamin A acid. Up to seven treatment courses were given during a period of 60 weeks. Through weekly evaluation of the patients' immune status, an immune potentiating effect of the vitamin A therapy could be demonstrated. An increase of lymphocyte blastogenesis response to PHA which is significant (p less than 0.001) compared with the pretreatment values, was found in all patients at the end of one vitamin A treatment course. Increased delayed cutaneous hypersensitivity reactions were observed also in all patients. The immune potentiating effects of vitamin A therapy, as well as the demonstrated direct effect on the tumor, introduces a wide range of combination therapies.

Carcinoma, Bronchogenic↗

[Immuno-chemotherapy in patients with disseminated metastasizing stage III melanoma. Randomized study with methyl-CCNU versus C. parvum plus methyl-CCNU].

34 patients with disseminated malignant melanoma (stage III) were randomized to the following therapy groups: Chemotherapy (MeCCNU, NSC 99441; 200 mg/m2, given orally every 8 weeks), or immuno-chemotherapy (1 mg Corynebacterium parvum i.v., on days 1-4 + MeCCNU 200 mg/m2 on day 8, repeated every 7 weeks). Total therapy response rate was 33%; total and partial remissions were achieved in 26% of the patients receiving chemotherapy, and in 40% under immuno-chemotherapy. Interim life table analysis shows that in the group receiving C. parvum + MeCCNU 50% of the patients survived more than 12 months, whereas in the group with MeCCNU survival of 50% was 6 months. Pretreatment with C. parvum did not only potentiate the therapeutic effect, but also reduce the myelosuppression of MeCCNU.

Bacterial Vaccines↗

[Clinical and immunological studies with OK-432 (Streptococcus pyogenes) on immunotherapy in cancer patients].

In a phase I study, the bacterial vaccine OK-432 (streptococcus pyogenes) was investigated in eight patients with advanced malignant tumors. Besides a fever reaction after i.v. application no toxic side effects were observed. Additionally, its therapeutic effectiveness could be demonstrated by i.v. and local therapy. There was also observed an increase of lymphocyte blastogenesis response in patients under treatment with OK-432.

Bacterial Vaccines↗

Correlation of immune response with clinical stage in Lewis lung tumor-bearing mice.

The effect of Lewis lung tumor growth in mice on the induction of primary immune response to SRBC, was investigated by PFC assay for measuring antibody activity and by footpad test as a correlate for delayed type hypersensitivity reactions. With the appearance of micrometastases in the lungs there was a decline in the humoral and cellular immune response to the SRBC. An increase of number and size of metastases in the lungs led to a further depression of the immune reactivity. Since the reduction of general immune response in mice bearing this tumor is not due to a direct influence of tumor cells, it might be assumed that suppressor cells or factors, are actively abrogating the general and also the tumor directed immune reactions.

Animals↗