Klinik Çalışmalar

Ç.Papila,M.Caner ,I.Papila,H. Yanardağ,H.Cansız

Int.Rev.Allergol.Clin.Immunol,2004;Vol .10,No:2

The major-side effect of most anti-cancer chemotherapeutic drugs is neutropenia,and the administration of these drugs impairs blood-forming functions (e.g the generation of neutrophils,NK cells,etc. ) that are important to maintain to defense systems of the patients .As a result ,chemotherapy may accelerate the risk of tumor metastases and fungal infections .An ımmunomodulating substance ,a biologic response modifier (BRM) or biotherapy is important for the treatment of cancer infections diseases. Beta-glucan primes leukocyte CR3 for enhanced cytotoxicity and synergizes with anti-tumor monoclonal antibodies (mAb)

We studied readily the effect of beta-glucan (1-3,1-6 beta-glucan ) in patients with chemotherapy induced oral mucositis and leucopenia .

Vaclav Vetvicka

JANA,Vol 3, No.4 , 2001

While polysaccaarides have been used for decades in several countries to fight cancer and to stimulate the immune system ,only in recent years have they become a focus of intensive studies . Despite numerous studies ,we are just beginning to understand the precise mechanisms of glucan –cell interactions .The following test represents a short review of the most important observations in this interesting and potentially both commercially and clinically important field.

Gokhan Demir ,H.O Kleın ,Nil Mandel –Molinas ,N.Tuzuner

Int Immunopharmacol. 2007 Jan;7(1):113-6.

AIM: Glucans are glucose polymers that constitute a structural part of fungal cell wall. They can stimulate the innate immunity by activation of monocytes/macrophages. In human studies it has been shown that beta glucan has an immunomodulatory effect and can increase the efficacy of the biological therapies in cancer patients. In this prospective clinical trial we assessed in vivo effects of short term oral beta glucan administration on peripheral blood monocytes and their expression of activation markers in patients with advanced breast cancer. METHODS: 23 female patients with advanced breast cancer were included in the study. Median age of the patients was 52 years. Sixteen healthy females with a median age of 48 years served as the control group for comparing the initial blood samples. Peripheral blood samples were drawn on day zero and patients started receiving oral 1-3, 1-6, D-beta glucan daily. Blood samples were recollected on the 15th day. In the initial samples mean lymphocyte count was significantly lower in the patients with breast cancer (1281+/-306/mm(3) versus 1930+/-573/mm(3), p=0.04). In the patients with breast cancer, mean monocyte count which was 326+124/mm(3) at the beginning, was increased to 496+194/mm(3) at the 15th day (p=0.015). Expression of CD95 (Apo1/Fas) on CD14 positive monocytes was 48.17% at the beginning, which was increased to 69.23 % at the 15th day (p=0.002). Expression of CD45RA on CD14 positive monocytes was 49.9% at the beginning; it was increased significantly to 61.52% on day 15 (p=0.001). CONCLUSION: Oral beta glucan administration seems to stimulate proliferation and activation of peripheral blood monocytes in vivo in patients with advanced breast cancer.

F.Hong, J.Yan , J.T.Baran ,Daniel J.Allendorf ,R.Hansen , G. Ostroff,P.Xing,Nai-Kong V.Cheung and Gordon Ross

The Journal of Immunology ,2004,173 :797-806

Antitumor mAb bind to tumors and activate complement ,coating tumors with iC3b. Intravenously administered yeast beta 1-3 ;1-6 glucan functions as an adjuvant for antitumor mAb by priming the inactivated C3b (iC3b) receptors of circulating granulocytes ,enabling CR3 to trigger cytotoxicity of iC3b-coated tumors . Recent data indicated that barley beta- 1-3, 1-4 glucan given orally similarly potentiated the acticity of antitumor mAb ,leading to enhanced tumor regression and survival . This investigation showed taht orally administered yeast beta 1-3;1-6 glucan functioned similarly to barley beta 1,3-1,4 glucan with anti-tumor mAb .With both oral beta 1-3 glucans ,a requirement for iC3b on tumors and CR3 on granulocytes was confirmed by demonstrating therapeutic failures in mice deficient in C3 or CR3 .Barley and yeast beta 1-3 glucan were labeled with fluorescein to track their oral uptake and proccessing in vivo . Orally administered beta 1-3 glucans were taken up by machrophages that transported them to spleen ,lymph nodes and bone marrow. Within the bone marrow , the machrophages degraded the large beta 1-3 glucans into smaller soluble beta 1-3 glucan fragments that were taken up by the CR3 of marginated granulocytes. Yhese granulocytes with CR3-bound beta- 1-3 glucan fragments that were taken up by the CR3 of marginated granulocytes. These granulocytes with CR3-bound beta-1-3 glucans –fluorescein were shown to kill iC3b-opsonized tumor cells following their recruitment to site of complement activation resembling a tumor coated with mAb .

Vaclav Vetvicka , Brian P.Thorton and Gordon D. Ross

J.Clin.İnvest. 1996,98:50-61

When phagocyte CR3 binds to iC3b on bacteria or yeast ,phagocytosis and degranulation are triggered because of simultaneous recognition of iC3b via aCD11b I-domain binding site and specific microbial polysaccarides via alectin site located COOH-terminal to the I-domain . By contrast ,when phagocyte or natural killer (NK) cell CR3 adheres to iC3b on erythrocytes or tumor cells taht lack CR3-binding membrane polysaccharides ,neither lysis nor cytotoxicity are stimulated. The investigation showed that soluble CR3-specific polysaccharides such as beta-glucan ınduced a primed state of CR3 that could trigger killing of iC3b –target cells that were otherwise resistant to cytotoxicity .Anti-CR3 added before sugars prevented priming ,whereas anti-CR3 added after sugars blocked primed CR3 attachment to iC3b-targets. Polysccharide priming required tyrosine kinase(s) and a magnesium –dependent conformational change of the L-domain taht exposed the CBRM1/15 activation epitope. Unlike LPS or cytokines,polysaccharides did-not up regulate neutrophil CR3 expression nor expose the mAb 24 reporter epitope representing the high affinity ICAM-1 binding state. The current data apparently explain the mechanism of tumoricidal beta-glucans used for ımmunotherapy .These polysaccharides function through binding to phagocyte or NK cell CR3,priming the receptor for cytotoxicity of neoplastic tissues that lack iC3b .