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Biomedical subjects

M Pfreundschuh

Publications and source records attributed to M Pfreundschuh.

At least 181 records · Page 10Linked to original sources
PubMed1989

Effects of recombinant tumor necrosis factor (rHuTNF alpha) on human neutrophils and monocytes: in vitro, ex vivo and in vivo.

In in vitro experiments, tumor necrosis factor (rHuTNF alpha) was found to inhibit spontaneous and directed migration of normal human neutrophils and monocytes. RHuTNF alpha showed no chemoattractant activity. In conjunction with a Phase-2 clinical trial, we also studied in vivo rHuTNF alpha effects on neutrophil and monocyte number and function. At the time of maximal plasma TNF levels (30 min), marked neutropenia and monocytopenia were observed. Isolated neutrophils were activated for superoxide production but were unable to migrate. Monocyte migration was inhibited at later times. Neutrophil migratory function recovered between 4 and 8 h but was again depressed at 24 h. The data demonstrate the complexity of the response to TNF, comprising direct and indirect effects which are concentration-, time- and place-dependent. They further suggest that the only neutrophils and monocytes available for participation in an anti-tumor activity of TNF in vivo are those present in the tumor at the outset.

Chemotaxis, Leukocyte↗
PubMed1989

[Mechanism of resistance to tumor necrosis factor].

To find clues as to the possible mechanisms of resistance against the cytotoxic activity of tumor necrosis factor (TNF), we developed TNF-resistant and TNF-sensitive subclones of the human cervic carcinoma cell line ME 180 and the mammary carcinoma cell line BT-20. Resistant subclones were selected by gradually increasing the TNF concentration in the culture medium over 4 months or 20 passages. Resistance to TNF was conserved in the absence of TNF after nearly 3 years and less than 100 passages. There were no differences in the number and affinity of TNF receptors between the sensitive and resistant clones. Similarly, SDS-PAGE of cell lysates showed identical bands. Sensitivity to actinomycin D, mitomycin C, and interferon-gamma was the same. No TNF message could be demonstrated in either subclone. As tumors grown in nude mice derived from the sensitive and resistant clones responded equally well to an intratumoral injection of TNF, we conclude that different mechanisms are responsible for sensitivity and resistance to the cytotoxic effect of TNF in vitro and in vivo.

Animals↗
PubMed1989

[In vivo imaging of Hodgkin's lymphomas using monoclonal antibodies].

The Hodgkin- and Reed-Sternberg cell associated monoclonal antibody HRS-1 was labeled with radioactive iodine and injected into 6 patients with Hodgkin's lymphoma for immunoscintigraphic imaging. Four of five patients who received 131I-labeled HRS-1 had a positive immunoscintigram. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Bony disease was demonstrated by immunoscintigraphy in this patient. These preliminary results demonstrate that immunoscintigraphy with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value of immunoscintigraphy in Hodgkin's lymphoma must be determined in a larger series of patients. Several modifications of the technique such as the use of Fab or F(ab')2 fragments should further improve the results.

Adolescent↗
PubMed1988

Monoclonal glucose-oxidase-anti-glucose-oxidase (GAG) immunosandwich assay for the detection of monoclonal antibodies on routine hematological smears.

A murine monoclonal antibody specific for aspergillus niger glucose oxidase has been prepared and used in an unlabeled antibody bridge technique for the detection of monoclonal antibodies. This procedure--the monoclonal glucose oxidase anti-glucose oxidase (GAG) immunosandwich assay--provides excellent immunocytochemical labeling of routine hematological films in combination with optimal preservation of cellular details. In contrast to conventional immunofluorescence procedures, routine hematological films can be used, and these can be stored before and after the immunolabeling. Compared with other immunoenzyme techniques such as those using alkaline phosphatase or peroxidase, the GAG assay is as sensitive and has the advantage that no problems with endogenous enzyme activity are encountered. The availability of alcohol-resistant disclosing reagents allows for routine hematological counterstaining which provides a very clear visualization of both the immunoreaction and the individual morphology of the blood cells.

Antibodies, Monoclonal↗
PubMed1988

Prognostic risk factors in advanced Hodgkin's lymphoma. Report of the German Hodgkin Study Group.

In a national multicentre trial in the FRG patients with Hodgkin's lymphoma in stages CS/PS III B/IV were entered into the HD 3 protocol and received induction chemotherapy with 3 x (COPP + ABVD). Patients in complete remission (CR) received consolidation therapy by either radiotherapy (20 Gy IF) or chemotherapy (COPP + ABVD). Patients not in CR received salvage therapy (40 Gy in case of persisting nodal disease, else 4 x CEVD chemotherapy). Between July 1983 and May 1987 230 untreated patients aged 15 to 60 qualified for this HD 3 protocol. This analysis is based on the first 137 patients evaluable for response. Of these, 86 (63%) achieved CR after induction chemotherapy. Including salvage therapy a total of 104 patients (76%) achieved CR. Univariate and multivariate prognostic risk factor analyses were performed using freedom from treatment failure (FFTF) as endpoint. Sex, age, splenectomy, bone marrow, liver and bone involvement had no prognostic impact nor had stage according to the Ann Arbor classification. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml appeared as significant risk factors (p less than 0.01, relative risk 2.3). The two parameters were not independent. Comparing a group A (ESR less than or equal to 80 and AP less than or equal to 230) versus a pooled group B (ESR greater than 80 and/or AP greater than 230) increased the difference (p less than 0.001, relative risk of 2.8) which was also significant for survival (p less than 0.04).

Adolescent↗
PubMed1988

[Therapy of Hodgkin's lymphomas. Results of the German Hodgkin's Disease Study Group].

Between July 1983 and May 1987 143 untreated patients with Hodgkin's lymphoma in stages I-IIIA with risk factors qualified for the HD1 protocol, and 230 patients in stages IIIB/IV qualified for HD3. Patients in HD1 received a combined chemo-radiotherapy (2 x COPP + ABVD + 20 Gy EF vs. 40 Gy EF). Patients in HD3 received induction chemotherapy (3 x COPP + ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 x COPP + ABVD). In HD1, 73 of 89 evaluable patients (82%) achieved a complete remission. The survival of patients in stages I-IIIA with risk factors treated according to HD1 is as good as the survival of patients in stages I and II without risk factors. In HD3, 86 of 137 patients (63%) achieved complete remission after induction chemotherapy with 3 x COPP + ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 x CEVD in case of persisting disseminated disease), a total of 76% complete remissions in stages IIIB/IVAB were achieved. An ESR greater than 80 mm/h was the most significant single risk factor in stages IIIB/IV for induction of CR and freedom from progression.

Adolescent↗
PubMed1988

Phase I study of 24-hour continuous intravenous infusion of recombinant human tumor necrosis factor.

Sixteen patients with cancer were treated with a 24-h continuous intravenous infusion of recombinant human tumor necrosis factor (rHuTNF) to investigate the spectrum of side-effects, the maximum tolerated dose, the pharmacokinetics, and possible antitumor effects. Fever, chills, and flu-like symptoms were the most common side-effects. The maximum tolerated dose was 6 x 10(5) U/m2 (261 micrograms/m2). Severe hypotension, fluid retention, watery diarrhea, and central nervous deficits culminated in a profound prostration as the dose-limiting toxicity. No allergic reactions, positive skin tests, or antibodies against rHuTNF were observed. Plasma levels of rHuTNF were detected at doses of greater than or equal to 3 x 10(5) U/ml2. Maximal plasma levels were 19 U/ml (8.2 ng/ml). No objective tumor responses were observed.

Adult↗
PubMed1987

Disseminated testicular cancer with bulky disease: results of a phase-II study with cisplatin ultra high dose/VP-16/bleomycin.

This is a preliminary analysis of the AIO-Testicular Tumour Study Group trial in patients with disseminated bulky testicular cancer. Treatment plan: cisplatin 35 mg/m2 days 1-5, VP-16 120 mg/m2 days 1-5 (two daily divided doses), bleomycin 15 mg/m2 days 1, 8, 15. Of 98 patients at present evaluable 63% had complete remission or have no evidence of disease (CR/NED), 30% had partial remission (PR) and 7% had no change or progressive disease (NC/P). Relapse-free survival is 93% for the CR/NED group after a median follow up of 2.2 years: the overall survival for the entire patient population is 70%. Toxicity included predominantly granulocytopenic fever and infection with septicaemia, thrombocytopenia, nausea, vomiting, neurotoxicity and lung toxicity, with 7% fatal toxicity. A prospective randomized trial is warranted to evaluate the apparent superior activity of ultra high dose cisplatin in combination with VP-16 and bleomycin.

Adolescent↗
PubMed1987

[Therapy studies of the German Hodgkin's Study Group. Intermediate results of the study protocols HD1, HD2, and HD3].

Between July 1983 and September 1986 358 untreated patients with Hodgkin's lymphoma qualified for the protocols HD1 (stages I to IIIA with risk factors), HD2 (stage IIIA), and HD3 (stages IIIB and IVAB). Patients in HD1 received a combined chemo-radiotherapy (2 X COPP/ABVD + 40 Gy EF vs. 2 X COPP/ABVD + 20 Gy EF). Patients in HD2 were randomized into radiotherapy (TNI 40 Gy) vs. combined chemo-radiotherapy (2 X COPP/ABVD + 20 Gy IF). Patients in HD3 received induction chemotherapy (3 X COPP/ABVD) and were randomized into consolidation by radiotherapy (20 Gy IF) vs. chemotherapy (1 X COPP/ABVD). In HD1, 51 out of 65 evaluable patients (78%) achieved a complete remission. The survival of HD1 patients is as good as the survival of patients in stages I and II without risk factors. In HD3, 58 out of 93 patients (62%) achieved complete remission after induction chemotherapy with COPP/ABVD. This is significantly better than the 31% complete remission rate observed in a pilot study with COPP alone (p less than 0.01). Including salvage therapy (radiotherapy in case of persisting nodal disease; chemotherapy with 4 X CEVD in case of persisting disseminated disease), a total of 71% complete remissions in stages IIIB/IVAB were achieved. The progression-free survival of HD3 patients who received consolidation therapy is significantly longer than of patients who refused consolidation therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

[Clinical relevance of immunotyping of oncologic and hematologic diseases].

Progress in immunology and molecular biology have provided a better understanding of etiology, pathogenesis and biology of many oncological and hematological diseases. In clinical practice, certain new methods of immunotyping (IT) are of diagnostic importance in assigning undifferentiated tumors to lymphoid, epithelial or mesenchymal origin and in defining subgroups of leukemias and lymphomas. The demonstration of rearrangements of gene coding for immunoglobulins or T-cell receptors assigns hematological malignancies of early differentiation to the B- or T-cell lineage, discriminates between reactive lymphoid changes and clonal lymphoid expansion and detects persistent clonal growth after therapy. In certain clinical entities (e.g. ALL) the immunological subtypes are of importance for differential therapy. By means of IT new clinical entities have been defined (Ki-1-lymphoma, T gamma-lymphoproliferative, LFA-1-deficiency) and the pathomechanisms of others have been elucidated (Bernard-Soulier-disease Syndrome, Glanzmann-Nägeli thrombasthenia). Of immediate therapeutic importance is the identification by IT of receptors for specific hormones or biological response modifiers on malignant cells. In-vivo diagnosis by monoclonal antibodies opens a way to define more exactly the extent of malignant disease by scintigrams or NMR.

B-Lymphocytes↗
PubMed1986

[Clinical relevance of immune phenotyping of malignant lymphomas].

The characterization of malignant lymphomas with immunological methods (immunophenotyping) is gaining increasing importance in clinical hematology. Immunophenotyping is not only a basis of modern classifications of non-Hodgkin's lymphomas (e.g. the Kiel classification), it can also be helpful in the differentiation of lymphomas from epithelial or mesenchymal tumors. The immunological identification of subgroups of acute lymphocytic leukemia (c-ALL, T-ALL and B-ALL) bears significant meaning for differential therapy. Other applications of immunophenotyping of malignant lymphomas in the near future will be the demonstration of receptors for certain lymphokines (e.g. for therapy with interleukin-2 or tumor-necrosis-factor), the detection of specific cell surface antigens (for immunotherapy with monoclonal antibodies) and the demonstration of immunological markers for resistance to cytotoxic drugs. A general application of immunophenotyping of malignant lymphomas in clinical hematology will depend on a better standardization of the immunological reagents, a simplification of logistic problems and a significant reduction of the costs.

Antigens, Neoplasm↗