Carbohydrate-binding proteins (plant/human lectins and autoantibodies from human serum) as mediators of release of lysozyme, elastase, and myeloperoxidase from human neutrophils.

Analysis of cell surface glycosylation not only provides information about cell properties such as their state of differentiation or histogenetic lineage. The carbohydrate chains also provide potentially functional binding sites to endogenous carbohydrate-binding proteins. This interaction can elicit consequent signalling processes. Because of the importance of neutrophils in the host defence system, we monitored the effect of the binding of such sugar receptors to their cell surface on the release of the enzymatic activities of lysozyme, elastase, and myeloperoxidase. Besides the mannose-binding lectin concanavalin A and the immunomodulatory alpha/beta-galactoside-binding lectin from Viscum album L., three preparations of human sugar receptors - beta-galactoside-binding lectin (M(r) 14 kDa) and two affinity-purified polyclonal IgG fractions from serum with the capacity to recognize alpha- or beta-galactosides, respectively - were used. Two animal lectins from chicken liver and intestine that bind beta-galactosides, as well as the lectin-like human serum amyloid P component, were included in order to assess the importance of slight differences in ligand recognition. Cytochalasin B-enhanced enzyme release was invariably seen with the two plant lectins and the chicken liver beta-galactoside-binding lectin, but the related intestinal lectin did not increase enzyme release. The mammalian homologue of these avian lectins triggered lysozyme secretion, and the lactoside-binding IgG fraction enhanced the amount of extracellular elastase activity slightly but significantly. Thus, the actual lectin, not the nominal specificity of sugar receptors, is crucial for elucidation of responses. Due to the highly stimulatory activity of the two plant lectins, neutrophils from patients with non-cancerous diseases and from patients with lung cancer were monitored for the extent of lectin-mediated enzyme release. Only the concanavalin A-mediated reactivity of the neutrophils was associated with the type of disease.

Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy.

Superoxide production by neutrophils is believed to contribute to the efficiency of the host defence system. This activity is stimulated by the mannose-specific lectin concanavalin A, the N-acetylglucosamine/neuraminic acid-specific wheat germ agglutinin and the galactoside-specific lectins from Viscum album and human placenta. To assess whether this aspect of immune function is affected in cancer patients without or with treatment, neutrophil preparations from 69 patients were examined. Reductions in O2.(-)-production were observed for bronchial carcinoma patients after incubation with concanavalin A and the human lectin, while samples from breast cancer patients without or with treatment exhibited no significantly altered activity in the presence of each of the four agglutinins. Chemotherapy of lung and colorectal carcinoma patients reduced the neutrophilic response to concanavalin A and Viscum album agglutinin. As similarly shown for 9 specimens from other carcinoma types and from hemopoietic malignancies, there is no general impairment of responsiveness. In addition to the property of the lectin, the large extent of interindividual variation should be taken into account when it is attempted to enhance this factor of the host defence system against infections and malignant cells.

Relevance of DNA-fluorimetry and short-term resistance testing for adjuvant treatment of non-small cell lung carcinomas.

In a clinical study 127 patients with previously untreated stage III non-small cell lung carcinomas (NSCLC) were investigated using flow cytometry and an in vitro short-term test for predicting resistance to cytostatic agents. Patients with aneuploid tumors and tumors with high proliferative activity had significantly shorter survival times than those with diploid or low proliferating tumors. The aim of this study was to find out whether groups of patients classified according to the additionally observed prognostic factors, experience an advantage or disadvantage from particular modalities of treatment. Seventy-nine patients had surgery alone, 18 patients were treated additionally with chemotherapy, and 30 patients with radiation. Patients with aneuploid, low proliferating and in vitro resistant tumors showed no different survival rates after treatment with chemo- and radiotherapy adjuvant to surgery. In contrast, patients with high proliferating tumors died earlier under adjuvant chemotherapy and radiation. Patients with in vitro chemosensitive tumors had shorter survival times after irradiation than patients who had surgery alone or who were treated with adjuvant chemotherapy.

[Ineffectiveness of high-dosage methotrexate in patients with small cell bronchial cancer]. / Ineffektivität von hochdosiertem Methotrexat bei Patienten mit kleinzelligem Bronchialkarzinom.

5 patients with small-cell lung cancer were treated with high-dose methotrexate (1.75-16 g). No significant tumor reduction could be demonstrated. High-dose methotrexate therapy cannot be recommended for the treatment of small-cell lung cancer. Other established and successful regimens are available.

A randomized study of combination chemotherapy (VAC-FMC) with or without immunostimulation by Corynebacterium parvum in metastatic breast cancer.

A total of 156 patients with metastatic breast cancer were entered into a prospective multi-center trial in September 1975. All patients were treated monthly with vincristine, adriamycin and cyclophosphamide (VAC) six times, followed by 5-fluorouracil, methotrexate and cyclophosphamide (FMC) until progression was documented. By random assignment, the patients received 5 mg/m2 Corynebacterium parvum (CP) subcutaneously on day 1, in addition to VAC/FMC. Of the 150 evaluable patients, 33 of 76 (45%) and 36 of 74 (49%) had complete or partial response to VAC/FMC plus CP, respectively. The Kaplan-Maier curves of duration of remission and survival were almost identical (medians 14.5 vs 12.1 months and 22.2 vs 21.1 months, respectively). The hematologic and gastrointestinal toxicity were also similar in the two study groups. However, 19 of 74 (26%) patients developed skin ulcers after repeated injections of CP. These patients showed prolonged survival (P = 0.002, log rank test). These results suggest that adding nonspecific immunostimulation with CP to currently available chemotherapy on day 1 is of no benefit to most patients with metastatic breast cancer, but may select an "immunoreactive subgroup with increased local toxicity and survival.