Biotherapy (Dordrecht, Netherlands)最新文献

The antitumor effect of extracts obtained from the fruit body of Agaricus blazei Murill was examined in a double-grafted tumor system, in which BALB/c mice received simultaneous intradermal injections of Meth-A tumor cells in both the right (10(6) cells) and left flank (2 x 10(5) cells), and were then injected with 5 mg of extracts of A. blazei in the right tumor on days 3, 4 and 5. Intratumoral administration of ethanol-soluble (Fraction 1), water-ethanol-soluble (Fraction 2), ammonium oxalate-soluble (Fraction 3) and ammonium oxalate-insoluble (Fraction 4) fractions resulted in inhibition of tumor growth, with Fraction 3 showing the most tumoricidal activity, producing regression of the right tumor and inhibition of growth of the left, non-injected tumor. The maximum effect was obtained using 0.5 mg of Fraction 3 and this amount was used in subsequent experiments. The antitumor effect of intratumorally administered Fraction 3 was enhanced by oral ad lib administration of feed containing 0.083% of Fraction 3. When immunized spleen cells from mice that had been cured by intratumoral administration of 0.5 mg of Fraction 3 were directly injected (2 x 10(7) cells/mouse) into the Meth-A tumor, tumor growth was inhibited. The tumor cells on day 7 from the Fraction 3-treated right tumor and from the left tumor were cultured for 24 h and their culture supernatants were assayed for neutrophil or macrophage chemotactic activity. Significant macrophage chemotactic factor activity was detected in the culture media from the left tumor tissue. Serum levels of immunosuppressive acidic protein (IAP), produced by activated macrophages and neutrophils, increased transiently soon after intradermal injection of 0.5 mg of Fraction 3. These results suggest that regression of the left non-injected tumor was due to an immune reaction, involving induction of cytotoxic cells in the spleen, and the release of chemotactic factors in the distant tumor.

Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Hodgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non-neoplastic (reactive) cells recruited and activated by H-RS cells-derived cytokines. H-RS cells can be functionally regarded as antigen-presenting cells (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated immune response along with a hyperplastic inflammatory reaction which involves several cell types including T- and B-cells, neutrophils, eosinophils, plasma cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS cells and their reactive neighboring cells are able to cross-talk via a complex network of cytokine- and cell contact-dependent interactions. As a result of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and non-neoplastic cells, H-RS cells may receive several proliferative and anti-apoptotic signals favoring the cellular expansion and tumor cell survival in HD. The ineffective T-cell immune response elicited by the abnormal APC function of H-RS cells may further contribute to the biologic and clinical progression of HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander reactive cell populations might be beneficial in the treatment of HD patients.

The effects of weekly subcutaneous recombinant human erythropoietin (r-hEPO) administration on anemia during chemotherapy including cisplatin and 5-fluorouracil in patients with head and neck carcinomas were examined. Weekly subcutaneous r-hEPO administration in cancer patients has not been investigated previously. Patients were treated with r-hEPO 100 IU/kg (2 patients), 200 IU/kg (6 patients), or 400 IU/kg (5 patients), or placebo, and effectiveness was evaluated by monitoring hemoglobin concentration changes after administration for 8 weeks. Hemoglobin concentrations in all 3 r-hEPO dosage groups were higher than that in the control group during chemotherapy. All r-hEPO doses produced improvements in the anemia induced by chemotherapy; however, the 400 IU/kg dose was most effective. The requirement for blood transfusions decreased in patients receiving r-hEPO therapy, and no significant side-effects were associated with r-hEPO administration. These results suggest that chemotherapy-induced anemia can be prevented by weekly subcutaneous r-hEPO administration.

Whether heat shock proteins (hsp) will be therapeutic targets in arthritis depends on their role in pathogenesis. In this article, three possibilities are considered. Firstly, an excessive immune response to bacterial hsp could be arthritogenic - as may occur in reactive arthritis. In these circumstances therapy would be directed to down-regulating this immune response, or altering the nature of the immune response e.g. by changing cytokine production from interferon-g to IL-4. However this approach depends on the immune response to bacterial hsp not being critical for control of the bacterial infection. Secondly, an immune response to bacterial hsp may induce autoimmunity by cross-reactivity, e.g. with the homologous human. This could also be modulated in the same way with a lower likelihood of interfering with control of the infectious agent, since only a component of the immune response against the bacterial hsp will be cross-reactive with self. Thirdly, recent experiments raise the possibility that joint inflammation might be controlled by T cells which recognizes self hsp, particularly hsp60. Therapies might enhance this response; protection from experimental arthritis by prior immunization with hsp60 is well established. Whether similar approaches will be viable after arthritis is established remains to be seen.

Hematopoietic growth factors (HGFs) sustain the survival, proliferation and differentiation of hematopoietic stem cells and some functions of mature blood cells. In man several HGFs have been characterised and cloned so far, and this has allowed investigators to confer the rationale for the clinical application of these molecules in hematology and oncology. In particular G-CSF and GM-CSF are currently utilised to abrogate the hematological toxicity of chemotherapy for standard and dose-intensified therapy, neutropenia following bone marrow and peripheral blood stem cell transplantation. Moreover there has recently been great interest in the ex vivo expansion of hematopoietic stem and progenitor cells for a variety of applications, such as in vitro tumor cell purging or for reducing the volume of blood processed by the leukapheresis. Several combinations of HGFs have been described to sustain the ex vivo survival and proliferation of these cells disclosing new opportunities in the field of stem cells transplants.

For ages naso-oro-pharyngeal cavity was considered as gate of entry to living organism for air and food. In recent years, however, the thoughts have changed considerably. Several lines of evidence indicate that the oral cavity with adjacent cavities plays a pivotal role for the recognition of signals coming from the surrounding world. These signals in form of food, germs, poisonous substances are initially analyzed in oral cavity and messages are distributed by a variety of communication pathways into pertinent parts of the body. All these diverse functions are performed by anatomical structures present in the naso-oro-pharyngeal cavity. The following article describes some of the functions discovered recently.

Weekly injection of a protein-bound polysaccharide PSK in mice with Lewis Lung Cancer (LLC) significantly decreased the number of lung metastatic foci concomitant with enhancement of cytostatic activity in the bronchoalveolar lavage (BAL) cells. These effects were more marked when the agent was given intratracheally, inducing a larger number of pulmonary macrophages, lymphocytes and neutrophils concomitant with increases in BAL tumor necrosis factor-alpha (TNF-alpha), mouse inflammatory protein-alpha (MIP-1alpha), mouse inflammatory protein-beta (MIP-1beta), interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6), but not interleukin-2 (IL-2) and interleukin-4 (IL-4). Pre-treatment with anti TNF-alpha antibody reduced these effects. The time course and production of PSK-induced cytokines were similar between the tumor-bearing mice and control mice. BAL neutrophils in mice with LLC showed a tendency toward acceleration of O2- production compared with circulating neutrophils. Pulmonary macrophage phagocytosis was also significantly higher in the LLC mice. These results suggest that enhancement of cytostasis appears to be induced by activation and/or improvement of function in inflammatory and immune cells through cytokines under immunomodulator treatment in lung metastasis, possibly via a TNF-alpha-dependent mechanism.