Changes in The Kinase Expression Panel of K562 Human Leukemia After Avemar Treatment
Background: The positive effect of the wheat germ extract Avemar has already been proved in cancer. Compared to the control group significantly longer survival times were achieved in both in vivo experiments and clinical studies. Inhibition of cell growth was also detected in K562 human leukaemia cell line in vitro. Avemar given p.o.(3 g/kg) resulted in significant increase of the survival time compared to the control group (p<0.005 Mann-Whitney) in i.v. implanted K562 xenograft model, which was practically the same as the effect of Gleevec treatment. Since, the mechanism(s) of action of Avemar is still not properly characterized a kinase expression panel in K562 in vitro model was examined. Methods: K562 cells (8x105 cell/ml), were treated with Avemar (500 µg/ml) and mRNS from 3-3 parallel samples and their appropriate controls were isolated 24, 48 hours after the treatment and 24 hours after washing the cells previously treated with Avemar for 48 hours. To determine the kinase expression pattern Kinase OpenArray™ plates were used, having over 500 kinase genes with controls in quadruplicates in each plate. Changes in expression was declared if the average value was over 1 (2-fold change in mRNA copy number) and the standard deviation was relatively small (2xSTDEV = AVERAGE). Results: We have found 16 kinases which expression has temporary or durative (maintained for 24 hour after washing) decreased (e.g.: CCL2, ABR, FLT1, EphB6, TGFa) and 30 which expression has increased (e.g.: CPT1B, IRE1, ITK, RON, LTK, EphB2, FASTK). Conclusions: Our result demonstrated that many of the kinases which expression was altered by Avemar treatment is known to participate in cell cycle, cell migration, apoptosis and signal transduction. Thus, our results might shed light on the main mechanism(s) of action of Avemar and raise the possibility to identify the active substance(es) of this natural extract.
Fermented wheat germ extract (avemar) inhibits adjuvant arthritis
|Agarwal RP, Bálint G, Blazsó G, Ehrenfeld M, Falkay G, Hidvégi M, Kennepohl E, Lapis K, Pirogova NA, Raso E, Resetár A, Shoenfeld Y, Szende B, Telekes A, Thurzó L, Vágvölgyi A|
Anti-inflammatory efficacy of the fermented wheat germ extract (FWGE, Avemar) in the rat adjuvant arthritis (AA) model was examined. To Wistar rats with AA, different doses of FWGE and anti-inflammatory drugs (indomethacin, dexamethasone) as monotherapies were administered and FWGE and either diclofenac or dexamethasone were also given in combination. Besides plethysmographies of the paws, histological investigations of synovial tissues were also performed along with detection of CD4+ and CD8+ T lymphocytes. Gene expressions of COX-1 and 2 were determined by real-time polymerase chain reaction (PCR). FWGE monotherapy significantly inhibited the development of the secondary (immune-mediated) response in AA, and dexamethasone and indomethacin exerted inhibitory effects in a degree comparable to that of FWGE. Histological analysis of the affected joints confirmed the results. FWGE inhibited COX-1 and -2, while indomethacin enhanced COX-2 gene expressions. FWGE had an additive interaction with diclofenac. It is concluded that FWGE has significant anti-inflammatory efficacy confirmed by plethysmography, histology, and real-time PCR.
|5-fluorouracyl, adjuvant arthritis, anti-inflammatory effect, Avemar, COX-1 inhibition, COX-2 inhibition, Dacarbazine, fermented wheat germ extract|
Synergistic effect of Avemar on proinflammatory cytokine production and Ras-mediated cell activation
|Dower SK, Duda E, Kiss-Tóth E, Kúsz E, Nagy T, Polgár T, Qwarnstrom EE, Resetár A, Telekes A, Tömösköziné FR|
Macrophages activated by lipopolysaccharide and/or phorbol esters exhibited high sensitivity to Avemar, a fermented wheat germ extract. Avemar synergized with lipopolysaccharide and PMA in the induction of the transcription of cytokine genes and release of inflammatory cytokines. At higher concentrations the preparation had a significant negative effect on the proliferation and survival of activated myeloid cell types. Avemar treatment induced the synthesis of ICAM-1 and synergized with the ICAM-inducing effect of TNF, but had no effect on VCAM-1 expression on microvascular endothelial cells. The effect of Avemar on signaling pathways, which are involved in cell activation was studied on HeLa cells as a model system. Avemar treatment increased the activity of stress kinases in a concentration-dependent way, resulting in the activation of AP-1 transcription factor. NF-kappa B-sensitive reporters were also activated by Avemar; in contrast, no effect of the preparation was observed on PKA-sensitive signaling pathways.
A medical nutriment has supportive value in the treatment of colorectal cancer
|Agarwal RP, Balogh A, Bocsi J, Go VL, Hidvégi M, Hoffmann A, Jakab F, Kahán Z, Kharkevitch GY, Lapis K, Mayer A, Nichelatti M, Prónai L, Sápy P, Sebestyen G, Shoenfeld Y, Szentpétery F, Telekes A, Thurzó L, Vágvölgyi A|
MSC (Avemar) is a medical nutriment of which preclinical and observational clinical studies suggested an antimetastatic activity with no toxicity. This open-label cohort trial has compared anticancer treatments plus MSC (9 g once daily) vs anticancer treatments alone in colorectal patients, enrolled from three oncosurgical centres; cohort allocation was on the basis of patients' choice. Sixty-six colorectal cancer patients received MSC supplement for more than 6 months and 104 patients served as controls (anticancer therapies alone): no statistical difference was noted in the time from diagnosis to the last visit between the two groups. End-point analysis revealed that progression-related events were significantly less frequent in the MSC group (new recurrences: 3.0 vs 17.3%, P<0.01; new metastases: 7.6 vs 23.1%, P<0.01; deaths: 12.1 vs 31.7%, P<0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P=0.0184) and overall survivals (P=0.0278) probabilities. Survival predictors in Cox's proportional hazards were UICC stage and MSC treatment. Continuous supplementation of anticancer therapies with MSC for more than 6 months is beneficial to patients with colorectal cancer in terms of overall and progression-free survival.
|cohort study, colorectal cancer, Dacarbazine, fermented wheat germ extract, growth inhibition, progression-free and overall survival, progression-free survival|
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