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Biomedical subjects

P Mallmann

Publications and source records attributed to P Mallmann.

At least 55 records · Page 3Linked to original sources

[Comparison of the cytostatic effect of epirubicin and mitoxantrone on native breast carcinoma cells using the ATP tumor chemosensitivity assay].

This trial was conducted to compare the cytotoxic efficacy of epirubicin (EPI) and mitoxantrone (MX) in clinical tumor samples derived from 34 chemotherapy-native women suffering from breast cancer by utilizing an in vitro ATP tumor chemosensitivity assay (ATP-TCA). An assay evaluability rate of 32/34 (94 %) was achieved. There was no significant difference between EPI and MX when regarding the mean IC90 and IC50 values corresponding to nearly identical overall in vitro response rates observed for both drugs (EPI: 62.5 %; MX 59.4 %). Individual IC90 values showed a weak correlation which was lacking for IC50. Accordingly, a lack of cross-resistance was found in 11/32 tumors (34 %) with 6 tumors showing sensitivity to EPI and resistance to MX and 5 tumors showing resistance to EPI and sensitivity to MX. At lower drug concentrations, a steep slope of the cumulative dose response curves for IC50 could be observed for both cytostatics with an apparent shift to higher concentrations at the IC90 level. For both drugs, a loss of linearity of the IC90 and IC50 dose-response curves was found at maximum concentrations. In conclusion, our results demonstrated an overall equality of EPI and MX in previously untreated breast cancers which already has been found clinically in metastatic disease. Nevertheless, we were able to show that approximately one third of chemotherapy-naive breast carcinomas are not cross-resistant to both EPI and MX. These findings could have implications on planning adjuvant chemotherapy for an individual breast cancer patient.

Adult↗

[Pain therapy with rhenium-186 HEDP in multiple bone metastases].

AIM: Therapeutic means for patients with painful bony metastases are strongly limited. In these patients, a systemic therapy with isotopes can be helpful. The aim of this study was to evaluate the efficacy of rhenium-186 HEDP for pain palliation in patients with disseminated bone metastases. METHODS: 30 patients taking analgesics because of bone pain received one or more injection of 1295 MBq 186Re HEDP for pain palliation. RESULTS: In 70% of the patients, therapy resulted in a significant reduction of pain. The average duration of pain relief was 4 weeks (1 week-2.5 months). The main side effects of therapy were a decrease of platelets (aver. 30000/microliters) and an increase of pain for 1-2 days (flare-phenomenon). CONCLUSION: Therapy with rhenium-186 HEDP can be used complementarily to analgesic therapy in patients with painful, disseminated bone metastases.

Bone Neoplasms↗

Tumor vaccination.

Tumor vaccination is a form of an active specific immunotherapy that aims in the induction of a specific immune response against the tumor. In the last 30 years a great number of studies had been performed using native, not modified tumor cells or different methods of modifying tumor cells. In the last year viral xenogenization of tumor cells had been extensively examined in different studies. In gynecologic cancer patients it could be demonstrated that in a certain part of vaccinated patients an increase of specific cytotoxicity could be induced and that compared with historic controls, a benefit in ovarian cancer patients could be observed. There are further results showing that a pretreatment of tumor-bearing hosts prior to vaccination may enhance subsequent immune reactivity and enhance the susceptibility of tumor cells. This is the rationale of a combination of chemo- and immunotherapy.

Clinical Trials as Topic↗

[Generation and activation of tumor-infiltrating lymphocytes (TIL) within the scope of lymphokine activated killer cell therapy (LAK-TIL therapy) in patients with advanced breast and ovarian carcinoma].

In this study we examined a combined immunotherapy using lymphokine activated tumor infiltrating lymphocytes and active specific immunotherapy with virus-modified tumor cells in disseminated breast and ovarian cancer patients. During the therapy a significant increase in cytotoxicity could be observed, which nevertheless could not be maintained after the end of therapy. In an ongoing prospective randomized study we are using antigen specific stimulated cytotoxic T-lymphocytes to extend this effect.

Adult↗

Monoclonal antibodies and idiotypic network activation for ovarian carcinoma.

Antibodies can be processed by the B- and T-cell systems and may lead to a selective activation of the immune system. The network structure of the immune system implicates the possibility of a selective immunization by the activation of idiotypic cascades. In a retrospective analysis, patients with advanced ovarian carcinoma, who had received MAb, against the cancer-associated antigen CA125 for diagnostic purposes, were analyzed for the production of anti-idiotypic antibodies, survival rate, and immunological effects. Furthermore, we started a prospective and randomized study for ovarian cancer patients, using a different antigen, TAG72, for the induction of idiotypic cascades. Our first results on 58 patients with advanced ovarian carcinomas showed that the induction of anti-idiotypic-antibodies against OC125 mimicking the TAA Class III CA125 leads to a prolongation of the survival rate, and, in extended stages, to an induction of antitumoral immunity, and that the induction of idiotypic cascades is also possible for different antigens like TAG72. Summarizing the activation of idiotypic network cascades seems to be a very effective way of intervention in the immune system of patients with advanced stages of ovarian carcinoma. A prospective study of the adjuvant approach seems to be necessary.

Antibodies, Anti-Idiotypic↗

Immunogenetic and serological investigations in nonpregnant and in pregnant women with a history of recurrent spontaneous abortions. German RSA/IVIG Study Group.

In the context of a controlled multicenter study on intravenous immunoglobulin (IVIG) treatment of patients with a history of unexplained recurrent spontaneous abortions (RSA), a number of controversial immunological parameters were evaluated prior to and during pregnancy with respect to their diagnostic and/or prognostic significance. A total of 390 serum samples from 52 patients were investigated. Sharing of 2 or more HLA (A, B, DR, DQ) antigens was significantly more frequent in RSA couples than in controls. The rate of cytotoxic or Fc-receptor (FcR)-blocking antibodies was not significantly lower in RSA patients than in individuals with normal pregnancies. Both tumor necrosis factor-alpha (TNF-alpha) levels and IgG anticardiolipin antibodies (IgG-ACA) were significantly increased in the patient group. While the occurrence of HLA sharing, cytotoxic/FcR-blocking antibodies and IgG-ACA did not correlate with the outcome of pregnancy, TNF-alpha levels were found to be significantly higher in patients with subsequent miscarriage than in those with successful pregnancy. IgG-ACA, if present, significantly decreased during the course of successful pregnancy but remained high in patients with subsequent abortion. It is concluded that the diagnostic and/or prognostic value of HLA sharing and cytotoxic/FcR-blocking antibodies has been overestimated while TNF-alpha and ACA levels are potential diagnostic markers and/or exhibit prognostic significance in subgroups of RSA patients.

Abortion, Habitual↗

Immunological effects of cefodizime in patients undergoing antineoplastic chemotherapy.

The effects of cefodizime (CDZ) on lymphocyte differentiation were investigated in a randomized study before, on day 4 and on the day after five days of antineoplastic treatment with vepesid, bleomycin and cisplatin. Nine men with testicular cancer received CDZ 2 g i.v. once daily for seven days and 11 received no antibiotic treatment. A significant fall in the absolute numbers of platelets, erythrocytes, leucocytes and all T-cell subsets was observed in both groups. No change in the relative numbers of lymphocyte subpopulations was observed in the control group, whereas a significant rise in the percentage of CD4 positive (T helper/inducer) cells was observed in the CDZ group. Along with a decrease in CD8 positive (T suppressor/cytotoxic) cells, this led to an increase in the CD4/CD8 ratio. In both groups a decrease of mitogen-induced lymphocyte proliferation was observed in the lymphocyte transformation test, particularly leading to a long-lasting impairment of the proliferative capacity of PWM-dependent B lymphocytes. In two patients CDZ may have contributed to an increase in PHA-induced lymphocyte transformation during chemotherapy. It is concluded that CDZ induces an increase in both the percentage of CD4 positive (T helper/inducer) cells and the CD4/CD8 ratio in patients with testicular cancer undergoing antineoplastic therapy.

Adolescent↗

Effect of cefodizime on parameters of cell-mediated immunity in vitro.

A positive effect of cefodizime (CAS 69739-16-8), a new aminothiazolyl cephalosporin, on a number of immunological variables, and in particular phagocytosis, was demonstrated in several test systems. The aim of the present investigation was to establish whether clinically relevant concentrations of cefodizime affect cell-mediated immune variables. Peripheral lymphocytes from healthy subjects were isolated and incubated with cefodizime in increasing concentrations from 0 to 200 mg/l. The effects of cefodizime on membrane-bound antigenic determinants of the lymphocytes were determined in the rosette inhibition test, and its effects on the proliferative capacity of lymphocytes after stimulation with phytohaemagglutinin, concanavalin A and pokeweed mitogen were determined in the lymphocyte transformation test. Cefodizime inhibited rosette formation in a concentration dependent manner. A direct inhibitory effect on proliferation was not, however, demonstrated in the lymphocyte transformation test. Indeed, stimulation of mitogen-induced lymphocyte transformation, particularly of concanavalin A-sensitive cells was observed at concentrations higher than 100 mg/l. The findings in healthy volunteers were reproduced in samples from three female patients with impaired host-defence. These results may suggest a positive effect of cefodizime on the proliferative capacity of the cellular immune system. However, no conclusions can be drawn on the clinical relevance of these findings until the results of in vivo investigations are available.

Animals↗

Determination of tumor necrosis factor alpha (TNF alpha) and interleukin 2 (IL 2) in women with idiopathic recurrent miscarriage.

Some recurrent miscarriages may be due to a host versus graft reaction. Elevated Interleukin 2 (IL2) levels have been found during pregnancy and elevated TNF alpha levels during acute rejection crises of allotransplantats and so we determined IL2- and TNF alpha levels in women with recurrent miscarriages. Samples were taken for serum TNF alpha and IL2 radioimmunoassays (IRE Medgenix, Belgium) from 28 healthy non-pregnant women and in 49 women with at least 3 miscarriages between the 6th and 14th week of pregnancy, 38 women having their first or second miscarriage and 42 pregnant women with no complications. In women with recurrent miscarriage an increase in TNF alpha (P less than 0.05) and a decrease in IL2 serum levels (P less than 0.05) was found compared to women with normal pregnancies. These results support the concept that disturbances of immune tolerance of the fetus may account for some cases of recurrent miscarriage.

Abortion, Habitual↗

Investigations into a possible immunological origin of idiopathic non-immune hydrops fetalis and initial results of prophylactic immune treatment of subsequent pregnancies.

The cause of the non-immune hydrops fetalis (NIHF) remains unsettled despite all efforts. From the immunological point of view of pregnancy as a successful course of an allograft, it would seem possible that the idiopathic NIHF can be caused by an immunologic disorder in the meaning of a host-versus-graft reaction. Of 324 cases of prenatally diagnosed NIHF, 49 (15.1%) could be classified after exclusion of all other causes as idiopathic and in 38 patients, as well as in 38 age- and parity-paired controls, a differentiation of HLA-antigens and a determination of lymphocytotoxic antibodies using the NIH Prolonged Incubations and Cold-Complement-Dependent Cytotoxicity Test (CoCoCy Test) were performed. In cases of idiopathic NIHF, the proportion of parents sharing 4 or 5 HLA antigens was increased significantly (p less than 0.05) compared with the control group. In women with idiopathic NIHF, the incidence of lymphocytotoxic antibodies was decreased, due to the test system used; between 28 and 68% in the NIHF group and 24-80% in the control group. The proportion of women without lymphocytotoxic antibodies was increased in the NIHF group by 72% to 52%, whereas in the control group, in none of the patients could a higher cytotoxicity with a lysing rate of more than 75% be detected. In 8 cases of idiopathic NIHF, where an increased paternal histocompatibility and a decreased incidence and percentage of lymphocytotoxic antibodies were determined, an immunotherapy was performed in order to induce maternal blocking antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antilymphocyte Serum↗

[Locoregional ascites therapy with cytostatic drugs and immune modulators in gynecologic neoplasms].

35 ovarian cancer patients with ascites have been treated intraperitoneally with mitomycin C or mitoxantrone or interferon beta or tumor necrosis factor (TNF). We observed nor or a little bit ascites in 87.5 per cent after TNF and in 66.5 per cent after mitoxantrone. In addition we applied a systemic monochemotherapy. After mitomycin C or interferon beta only in 40 per cent each an effect could be observed. TNF to day is the most effective substance for treating ascites with moderate toxicity.

Ascites↗

[Effect of tamoxifen on parameters of cell-mediated immunity in postmenopausal patients with breast carcinoma].

In 48 postmenopausal breast cancer patients receiving an adjuvant therapy with 30 mg tamoxifen for 22 months on an average the effect of hormonal therapy on different immunologic parameters was examined and compared with an age-matched control group of breast cancer patients without hormonal therapy. Before beginning and after the end of tamoxifen treatment the following examinations were performed: Leucocyte Migrations-Inhibition-Test (LMI-Test) against autologous and homologous tumor and recall antigens, determination of the serum levels of tumor necrosis factor alpha, interleukin 2 and interferon alpha, as well as a determination of lymphocyte subsets (total T-, T-helper-, T-Suppressor- and natural killer cells) in the peripheral blood. Compared to the control group under a tamoxifen therapy the percentage of patients with a migration inhibition in the LMI-test increased, whereas the percentage of patients with an enhancement decreased. There were no changes concerning the LMI-reactivity against recall antigens as well as concerning the serum levels of the different cytokine and the differentiation of T-cell subsets compared to the control group. But we found an increase of natural killer cells. It can be discussed if the clinical effect of a tamoxifen treatment is possibly due to its immunological effect on the nk cell activity.

Aged↗