j) Telekes A, Kiss-Tóth E, Nagy T, Qwarnstrom EE, Kúsz E, Polgár T, Resetár A, Dower SK, Duda E., Synergistic effect of Avemar on proinflammatory cytokine production and Ras-mediated cell activation, Ann N Y Acad Sci. 2005 Jun;1051:515-28. 

 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. 

 l) Illmer C, Madlener S, Horvath Z, Saiko P, Losert A, Herbacek I, Grusch M, Krupitza G, Fritzer-Szekeres M, Szekeres T., Immunologic and biochemical effects of the fermented wheat germ extract Avemar, Exp Biol Med (Maywood). 2005 Feb;230(2):144-9. 

 Avemar (MSC) is a nontoxic fermented wheat germ extract demonstrated to have antitumor effects. Avemar has the potential to significantly improve the survival rate in patients suffering from malignant colon tumors. We studied its effects in the HT-29 human colon carcinoma cell line. Avemar had an inhibiting effect on colonies of HT-29 cells with an IC50 value of 118 microg/ml (7 days of incubation); this value could be decreased to 100 and 75 microg/ml in the presence of vitamin C. In the cell line examined, Avemar induced both necrosis and apoptosis, as demonstrated by Hoechst/propidium iodide staining. The incubation of cells with 3200 microg/ml Avemar for 24 hrs caused necrosis in 28% and the induction of apoptosis in 22% of the cells. Avemar inhibited the cell-cycle progression of HT-29 cells in the G1 phase of the cell cycle. In addition, Avemar inhibited the activity of the key enzyme of de novo DNA synthesis, ribonucleotide reductase. In addition, we determined the effects of Avemar on the activity of cyclooxygenase-1 and -2. Both enzymes were significantly inhibited by Avemar with IC50 values of 100 and 300 microg/ml, respectively. We outline new explanations for its antitumor activity, which might serve as the basis for further studies using Avemar. 

 n) Fajka-Boja R, Hidvégi M, Shoenfeld Y, Ion G, Demydenko D, Tömösközi-Farkas R, Vizler C, Telekes A, Resetar A, Monostori E., Fermented wheat germ extract induces apoptosis and downregulation of major histocompatibility complex class I proteins in tumor T and B cell lines, Int J Oncol. 2002 Mar;20(3):563-70. 

 The fermented wheat germ extract (code name: MSC, trade name: Avemar), with standardized benzoquinone content has been shown to inhibit tumor propagation and metastases formation in vivo. The aim of this study was to understand the molecular and cellular mechanisms of the anti-tumor effect of MSC. Therefore, we have designed in vitro model experiments using T and B tumor lymphocytic cell lines. Tyrosine phosphorylation of intracellular proteins and elevation of the intracellular Ca2+ concentration were examined using immunoblotting with anti-phosphotyrosine antibody and cytofluorimetry by means of Ca2+ sensitive fluorescence dyes, Fluo-3AM and FuraRed-AM, respectively. Apoptosis was measured with cytofluorimetry by staining the DNA with propidium iodide and detecting the cell population. The level of the cell surface MHC class I molecules was analysed with indirect immunofluorescence on cytofluorimeter using a monoclonal antibody to the non-polymorphic region of the human MHC class I. MSC stimulated tyrosine phosphorylation of intracellular proteins and the influx of extracellular Ca2+ resulted in elevation of intracellular Ca2+ concentration. Prominent apoptosis of 20-40% was detected upon 24 h of MSC treatment of the cell lines. As a result of the MSC treatment, the amount of the cell surface MHC class I proteins was downregulated by 70-85% compared to the non-stimulated control. MSC did not induce a similar degree of apoptosis in healthy peripheral blood mononuclear cells. Inhibition of the cellular tyrosine phosphatase activity or Ca2+ influx resulted in the opposite effect increasing or diminishing the Avemar induced apoptosis as well as the MHC class I downregulation, respectively. A benzoquinone component (2,6-dimethoxi-p-benzoquinone) in MSC induced similar apoptosis and downregulation of the MHC class I molecules in the tumor T and B cell lines to that of MSC. These results suggest that MSC acts on lymphoid tumor cells by reducing MHC class I expression and selectively promoting apoptosis of tumor cells on a tyrosine phosphorylation and Ca2+ influx dependent way. One of the components in MSC, 2,6-dimethoxi-p-benzoquinone was shown to be an important factor in MSC mediated cell response. 

 p) Boros LG, Lapis K, Szende B, Tömösközi-Farkas R, Balogh A, Boren J, Marin S, Cascante M, Hidvégi M., Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells, Pancreas. 2001 Aug;23(2):141-7. 

 The fermented wheat germ extract with standardized benzoquinone composition has potent tumor propagation inhibitory properties. The authors show that this extract induces profound metabolic changes in cultured MIA pancreatic adenocarcinoma cells when the [1,2-13C2]glucose isotope is used as the single tracer with biologic gas chromatography-mass spectrometry. MIA cells treated with 0.1, 1, and 10 mg/mL wheat germ extract showed a dose-dependent decrease in cell glucose consumption. uptake of isotope into ribosomal RNA (2.4%, 9.4%, and 28.0%), and release of 13CO2. Conversely, direct glucose oxidation and ribose recycling in the pentose cycle showed a dose-dependent increase of 1.2%, 20.7%, and 93.4%. The newly synthesized fraction of cell palmitate and the 13C enrichment of acetyl units were also significantly increased with all doses of wheat germ extract. The fermented wheat germ extract controls tumor propagation primarily by regulating glucose carbon redistribution between cell proliferation-related and cell differentiation-related macromolecules. Wheat germ extract treatment is likely associated with the phosphorylation and transcriptional regulation of metabolic enzymes that are involved in glucose carbon redistribution between cell proliferation-related structural and functional macromolecules (RNA, DNA) and the direct oxidative degradation of glucose, which have devastating consequences for the proliferation and survival of pancreatic adenocarcinoma cells in culture.