K. Roszkowski

Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and d-galactose

SummaryAccording to our hypothesis, organ-specific lectins (e.g., the d-galactose-specific hepatic binding protein) play an important role in the organ location of metastatic malignant cells. The rapid clearance and uptake by the liver of tritiated α-acid-(asialo)glycoprotein from the circulation of Balb/c mice was markedly delayed after preinjection of d-galactose or arabinogalactan. The preinjection (1h) and regular application (for 3 days after tumor cell inoculation in Balb/c mice) of the receptor blocking agents d-galactose and arabinogalactan prevented the settling of sarcoma L-1 tumor in the liver completely, but did not influence the settling in the lung. Other galactans, dextrans, and phosphate-buffered saline showed no effect. Therefore, when lectins were blocked with competitive-specific glycoconjugates, colonization was prevented.

Immunomodulation by Propionibacteria

Summary The ability of bacteria and bacterial products to modulate the immune response to unrelated antigens is well documented. Propionibacteria are amongst the most potent immunomodulators stimulating cell populations involved in nonspecific resistance. Generally, the activated immune system provides protection from infectious pathogens and malignancies via mechanisms of recognition and elimination. Accordingly, administration of propionibacteria could be shown to be of benefit in the treatment of neoplastic and infectious diseases. Thus, it can be recommended for further clinical investigations.

Glycoprotein modifications of sarcoma L-1 tumor cells by tunicamycin, swainsonine, bromoconduritol or 1-desoxynojirimycin treatment inhibits their metastatic lung colonization in Balb/c-mice

SummarySynthesis and expression of cell surface carbohydrates appear to be involved in recognition events associated with tumor invasion and metastasis. Thus, the potential of murine sarcoma L-1 cells to form experimental lung metastases after i.v. injection was assessed after inhibiting tumor cell protein glycosylation with tunicamycin, swainsonine, bromoconduritol, or 1-desoxynojirimycin. Incubation of sarcoma L-1 cells with 0.5 μg (or above) of these substances/ml medium for 20–24 h significantly inhibited lung colonization. Cytotoxic side effects or additional organ manifestations could not be found. Gas liquid chromatographic examinations of carbohydrates from treated L-1 cells indicated that sugar synthesis was evidently inhibited. These results suggest that specific glycan structures on tumor cells are required for expression of the metastatic phenotype.

Intestinal Microflora of BALB/c-Mice and Function of Local Immune Cells

BALB/c-mice were treated for 7 days with oral nonabsorbable dosages of mezlocillin to achieve digestive tract decontamination. Such a procedure resulted in rapid eradication of most species of aerobic and anaerobic intestinal microflora. Various functions of peritoneal macrophages (e.g. chemiluminescence response, chemotactic motility, bactericidal and cytostatic ability) and lymphocyte proliferation were decreased in decontaminated animals as compared to non-treated controls.

Bacteria of Human Physiological Microflora Liberate Immunomodulating Peptides

Human isolates of Propionibacterium acnes and Staphylococcus saprophyticus could be shown to liberate low molecular weight peptides (MW less than 6.500 D) with immunomodulating activity. FACS analyses of BALB/c-mouse lymphoid cells from the thymus and spleen revealed an enhanced percentage of T-helper cells after peptide administration. Intestinal microflora decontamination of BALB/c-mice considerably reduced immune cell function and lymphatic tissue proliferation. Apparently, lack of peptide production or liberation correlated to immunosuppression. Substitution of peptides (from P. acnes or S. saprophyticus) to decontaminated mice reconstituted immune cell function and proliferation. Cortisone-resistant thymocytes were used as an experimental equivalent of functional cells in the thymus. Thus, cortisone treatment of BALB/c-mice significantly reduced the number of thymocytes, however, administration of microbial peptides restored the thymus population.

Biological Properties of Staphylococcal Lipoteichoic Acid and Related Macromolecules

Lipoteichoic acids (LTAs) and related macromolecules (e.g. cell surface substance, CSS; cell surface antigen, CSA; cell surface complex, CSC) are a group of phosphate-containing polymers associated with the cell walls of Gram-positive bacteria (32). They may be considered as surface-reactive antigens (immunogens, biological response modyfiers) as well as membrane components which mediate the attachment of certain bacteria (S. saprophyticus, S. aureus, group A streptococci) to host cell tissues.

Lectins: Mediators of Adhesion for Bacteria In Infectious Diseases and for Tumor Cells in Metastasis

Adhesion of bacteria and adhesion of tumor cells have much in common, especially the participation of lectins in this process. In the future it might be possible to inhibit the metastatic process into the liver (e.g. during surgical operations of malignant tumors) and bacterial adherence to mucosal linings or plastic devices by blocking of adhesion molecules (lectins) with appropriate glycoconjugates. Initial clinical trials are very promising.

Small-cell lung cancer and immunochemotherapy withPropionibacterium granulosum KP 45

SummarySeventy-nine patients with small-cell lung cancer were treated with vincristin, methotrexate, and cyclophosphamide in inductive therapy and with methotrexate, cyclophosphamide, and procarbazine in maintenance therapy. Patients were divided at random into two groups: one group received chemotherapy alone and the second group was additionally subjected to systemic immunotherapy withPropionibacterium granulosum strain KP-45. In general, differences in the frequency of therapy response and in duration of remission could not be stated between the two groups of patients, but patients responding to chemotherapy showed a significantly longer remission time and lower complication rates. This benificial effect of chemoimmunotherapy is not related to a direct antitumor activity of the immunomodifier used, but to the lowered risk of myelosuppression and infections. Immunomodulation in combination with chemo- and/or radiotherapy can be recommended for the treatment of small-cell lung cancer.

Comparative study on the macrolides erythromycin and clarithromycin : antibacterial activity and influence on immune responses

The in vitro activity of erythromycin and clarithromycin (a new macrolide antibiotic) on clinical bacterial isolates as well as their effects on the cellular and humoral immune responses in BALB/c-mice and on human granulocytes/monocytes was investigated. Treatment of BALB/c-mice for 7 days with these drugs did not influence the delayed type hypersensitivity to oxazolone nor the production of IgG and IgM immunoglobulins. In vitro, exposure of granulocytes to erythromycin resulted in increased phagocytosis only in higher concentrations (20 mcg/ml), whereas clarithromycin enhanced chemiluminescence response of granulocytes in concentrations ranging from 2.5-20 mcg/ml. Subinhibitory concentrations of both substances modified Staphylococcus aureus and made them more susceptible for granulocyte phagocytosis.

Effects of β-Lactam Antibiotics Imipenem/Cilastatin and Cefodizime on Cellular and Humoral Immune Responses in BALB/c-Mice

Summary The effects of a 7-day chemotherapy with two broad-spectrum β-lactam antibiotics (imipenem/cilastatin and cefodizime) on the humoral and cellular immune responses in BALB/c-mice were investigated. Antibiotic dosages were calculated on a body weight basis from therapeutical dosages in human medicine. Treatment of experimental mice with imipenem/cilastatin and cefodizime did not influence the production of immunoglobulines (IgM and IgG) nor the delayed type hypersensitivity to oxazolone. In vitro, exposure of human granulocytes to imipenem/cilastatin and cefodizime did not interfere with their phagocytic activity as determined by chemiluminescence assay. Subinhibitory concentrations of both antibiotics modified Staphylococcus aureus and made them more susceptible for granulocyte phagocytosis in chemiluminescence assays.