Cancer

Objective: The fermented wheat germ extract (FWGE) nutraceutical (FWGE™), manufactured under “good manufacturing practice” conditions and, fulfilling the self-affirmed “generally recognized as safe” status in the United States, has been approved as a “dietary food for special medical purposes for cancer patients” in Europe. In this paper, we report the adjuvant use of this nutraceutical in the treatment of high-risk skin melanoma patients. Methods: In a randomized, pilot, phase II clinical trial, the efficacy of dacarbazine (DTIC)-based adjuvant chemotherapy on survival parameters of melanoma patients was compared to that of the same treatment supplemented with a 1-year long administration of FWGE. Results: At the end of an additional 7-year-long follow-up period, log-rank analyses (Kaplan-Meier estimates) showed significant differences in both progression-free (PFS) and overall survival (OS) in favor of the FWGE group. Mean PFS: 55.8 months (FWGE group) versus 29.9 months (control group), p 0.0137. Mean OS: 66.2 months (FWGE group) versus 44.7 months (control group), p 0.0298. Conclusions: The inclusion of FWGE into the adjuvant protocols of high-risk skin melanoma patients is highly recommended.

Background and aim Anorexia/cachexia syndrome is frequently correlated with increased oxidative stress (OS). A fermented wheat-germ extract with a standardized benzoquinone content (brand name FWGE) has been shown to exert an intense antioxidant activity with no side effects. The aim of this study was to investigate the effects of FWGE in patients affected by head and neck cancer, correlating the variations with OS with the quality of life as assessed by the Spitzer’s index. Patients and methods A cohort of 60 patients affected by head and neck tumours (stage IIIa, IIIb, IV) were enrolled in the study following an open-label protocol. The patients were assigned to two subgroups, A or B. Group A was treated with conventional oncological therapy alone, and group B was treated with FWGE in addition to standard therapy. After 2 months only 55 patients survived and could be evaluated (29 in the control group and 26 in the FWGE group). Each patient was checked for circulating concentrations of hydroperoxides using the FRAS III test. Results The levels of OS significantly decreased after 2 months in the group receiving FWGE (group). The value of Spitzer’s index was significantly higher in group B, attesting to an improved quality of life. Conclusion Although the specific active substance in FWGE has not yet been identified, the reduction in free oxygen radicals induced by it is correlated with a clinically significant improvement in the quality of life in patients with advanced cancer. 

The Hungarian Association of Oral and Maxillofacial Surgeons (Magyar Arc-, Állcsont- és Szájsebészeti Társaság) has reviewed the research results related to FWGE and issued its opinion as follows: For patients suffering from head- and neck tumors - primarily malignant tumorous diseases of the oral cavity, the progression of the disease can be slowed significantly, the five-year survival rate increased considerably, the quality of life improved, and the oxidative stress on the patients reduced by the long-term application of the supplementary formula FWGE . The Association considers the supportive treatment with the formula FWGE as an important part of the complex therapeutic protocols applied in stages II, III and IV of malignant tumorous diseases of the oral cavity. 

Objective. To investigate the effect of the fermented wheat germ extract (FWGE ®) in patients with severe rheumatoid arthritis (RA). Methods. Fifteen female RA (Steinbrocker II-III) patients, who had unsuccesfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received FWGE ® as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used. Results. At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of FWGE ® were observed. Conclusion. Supplementation of standard therapies with a continuous administration of FWGE ® is beneficial for RA patients.

The hypothesis that oxidative stress favours flogistic and immune processes inducing autoimmune rheumatic diseases (ARDs) and their complications is still under discussion. In this review we take into consideration both the aetiopathological role of the diet in such diseases and the possible efficacy of dietary supports as adjuvants for the usual specific therapies. Moreover, we shall examine the hypothetical pathophysiological role of oxidative stress on ARDs and their complications, the methods for its evaluation and the possibility of intervening on oxidative pathways by means of nutritional modulation. It is possible that in the future we will be able to control connective pathology by associating an immuno-modulating therapy (‘re-educating’) with naturalproducts having an anti-oxidant activity to current immunosuppressive treatment (which has potentially toxic effects).
2003 Elsevier B.V. All rights reserved.

Purpose: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (FWGE ) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. Methods: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. Results: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). Conclusions: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.

MSC (FWGE) 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%, Po0.01; new metastases: 7.6 vs 23.1%, Po0.01; deaths: 12.1 vs 31.7%, Po0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P ¼ 0.0184) and overall survivals (P ¼ 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. 

FWGE pulvis” is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 µg/g of the natural constituent 2,6-dimethoxy-p-benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United States. FWGE pulvis has been used in Hungary since 1998 and is approved in that country, as well as in the Czech Republic, Bulgaria, and Romania, as a “medical nutriment for cancer patients.” Acute and subacute toxicity studies using rodents orally administered FWGE pulvis showed that dose levels (2000 to 3000 mg/kg body weight [bw]/day) exceeding the normal recommended oral dosage (8.5 g/day or 121 mg/kg bw/day for a 70-kg individual) by up to approximately 25-fold caused no adverse effects. The test substance showed no evidence of mutagenicity or genotoxicity in vitro or in vivo. Clinical studies using FWGE pulvis as a supplement to drug therapy in cancer patients at doses of 8.5 g/day not only showed no evidence of toxicity, but also showed a reduction in the side effects of chemotherapy. Overall, it was concluded that FWGE pulvis would not be expected to cause adverse effects under the conditions of its intended use as an ingredient in dietary supplements.

ACCREDITATION InnoVision Communications is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. CREDIT DESIGNATION STATEMENT InnoVision Communications designates this educational activity for a maximum of 1.5 AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity. STATEMENT OF PURPOSE Natural products are being used as supplements by cancer patients, with or without the knowledge of their cancer treatment team. It is important to know which of these products show efficacy against diseases such as cancer, and which are ineffective. It is also essential to define the mechanism(s) of action of natural products, especially as relevant to cancer prevention or treatment. The purpose of this article is to review the use of one such natural product, a fermented wheat germ extract (FWGE ), in the treatment regimen of cancer patients. FWGE has shown efficacy in both animal cancer models and human clinical trials with cancer patients, but more well-controlled trials in humans are necessary to assess the full potential of FWGE in cancer treatment. FWGE exerts its anticancer effect via an array of mechanisms, likely because there are many undefined components in this product that modulate numerous biological systems in cancer patients. 

In this study, the protective effect of a fermented wheat germ extract (FWGE) against LPS-induced inflammation and oxidative stress in IPEC-J2 porcine intestinal epithelial cells was studied. Enterocytes were treated with LPS derived from Salmonella enterica ser. Typhimurium and Escherichia coli O55:B5, O111:B4, and O127:B8 strains. Intracellular ROS level and extracellular H2O2 level were followed up by two fluorescent assays (DCFH-DA and Amplex Red). The effect of FWGE on the intestinal barrier integrity was determined by transepithelial electric resistance measurements and using a FD4 fluorescent tracer dye. IL-6 concentration of supernatants was also measured by the ELISA method. Our data revealed that FWGE had a significant lowering effect on the inflammatory response especially related to oxidative stress. Treatment with FWGE (1-2%) significantly decreased the level of intracellular ROS compared to LPS-treated cells. Furthermore, LPS-triggered partial disruption of epithelial integrity was reduced after FWGE application.

Abstract--The acute and subacute toxicity of five biogenic amines--tyramine, spermidine, spermine, putrescine and cadaverine--were examined in Wistar rats. Tyramine and cadaverine had a low acute oral toxicity of more than 2000 mg/kg body weight. Putrescine had an acute oral toxicity of 2000 mg/kg body weight and spermidine and spermine each of 600 mg/kg body weight. All amines investigated caused a dose-related decrease in blood pressure after intravenous administration, except for tyramine, where an increase was h~und. In 6-wk studies the biogenic amines were administered in the diet to groups of 10 male and 10 female rats. Tyramine and cadaverine were given at levels of 0, 200, 2000 or 10,000 ppm, spermine and putrescine at levels of 0, 200, 2000 or 5000 ppm and spermidine at levels of 0, 20, 200 or 500/1000 ppm in the first study and at levels of 0 or 10,000 ppm in a second study. Spermine was the most toxic. The high dose level showed a great number of changes, such as emaciation, aggressiveness, convulsions and paralysis of the hind legs. Growth, food intake and water intake were considerably decreased. Slight anaemia (males) and changes in plasma clinical chemistry occurred. The relative weights of the thyroid, adrenals, spleen and heart were increased and that of the liver decreased. Impaired kidney function, together with renal histopathological changes and changes in plasma electrolytes and urea, occurred with ,;permine. Histopathological examinations also revealed decreased glycogen content in the liver, reduction of spermatogenesis, severe depletion of splenic white pulp, acute involution of the thymus and moderate myocardial degeneration in the heart. 

Supplementation of spermidine, an autophagy‐inducing agent, has been shown to protect against neurodegeneration and cognitive decline in aged animal models. The present translational study aimed to determine safety and tolerability of a wheat germ extract containing enhanced spermidine concentrations. In a preclinical toxicity study, supplementation of spermidine using this extract did not result in morbidities or changes in behavior in BALBc/Rj mice during the 28‐days repeated‐dose tolerance study. Post mortem examination of the mice organs showed no increase in tumorigenic and fibrotic events. In the human cohort (participants with subjective cognitive decline, n=30, 60 to 80 years of age), a 3‐month randomized, placebo‐ controlled, double‐blind Phase II trial was conducted with supplementation of the spermidine‐rich plant extract (dosage: 1.2 mg/day). No differences were observed between spermidine and placebo‐treated groups in vital signs, weight, clinical chemistry and hematological parameters of safety, as well as in self‐reported health status at the end of intervention. Compliance rates above 85% indicated excellent tolerability. The data demonstrate that spermidine supplementation using a spermidine‐rich plant extract is safe and well‐tolerated in mice and older adults. These findings allow for longer‐term intervention studies in humans to investigate the impact of spermidine treatment on cognition and brain integrity.

FWGE pulvis” is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 µg/g of the natural constituent 2,6-dimethoxy-p-benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United States. FWGE pulvis has been used in Hungary since 1998 and is approved in that country, as well as in the Czech Republic, Bulgaria, and Romania, as a “medical nutriment for cancer patients.” Acute and subacute toxicity studies using rodents orally administered FWGE pulvis showed that dose levels (2000 to 3000 mg/kg body weight [bw]/day) exceeding the normal recommended oral dosage (8.5 g/day or 121 mg/kg bw/day for a 70-kg individual) by up to approximately 25-fold caused no adverse effects. The test substance showed no evidence of mutagenicity or genotoxicity in vitro or in vivo. Clinical studies using FWGE pulvis as a supplement to drug therapy in cancer patients at doses of 8.5 g/day not only showed no evidence of toxicity, but also showed a reduction in the side effects of chemotherapy. Overall, it was concluded that FWGE pulvis would not be expected to cause adverse effects under the conditions of its intended use as an ingredient in dietary supplements.

abstract

 2,6-Dimethoxy-1,4-benzoquinone (2,6-DMBQ) is the major bioactive compound found in fermented

wheat germ extract. Although fermented wheat germ extract has been reported to show antiproliferative and anti-metabolic effects in various cancers, the anticancer potential and molecular

mechanisms exerted by 2,6-DMBQ have not been investigated in non-small cell lung cancer (NSCLC)

cells. Here, we report that 2,6-DMBQ suppresses NSCLC cell growth and migration through inhibiting

activation of AKT and p38 MAPK. 2,6-DMBQ significantly suppressed anchorage-dependent and independent cell growth. Additionally, 2,6-DMBQ induced G2 phase cell cycle arrest through inhibiting the

expression and phosphorylation of cyclin B1 and CDC2, respectively. Furthermore, 2,6-DMBQ strongly

suppressed NSCLC cell migration through induction of E-cadherin expression. To determine the molecular mechanism(s) exerted by 2,6-DMBQ upon NSCLC cell lines, various signaling kinases were

screened; the results indicate that 2,6-DMBQ strongly inhibits the phosphorylation of AKT and p38

MAPK. Additionally, the growth kinetics of cells treated with an AKT or p38 MAPK inhibitor in combination with 2,6-DMBQ indicate that 2,6-DMBQ suppresses NSCLC cell growth and migration through

inhibition of AKT and p38 MAPK. Taken together, our results suggest that 2,6-DMBQ is a potential

anticancer reagent against NSCLC cells and could be useful for treating lung cancer patients.

ÖSSZEFOGLALÁS

Az AIDS kórfejlődésének vizsgálatára alkalmas modellállat a macska. Az ember

és a macska immundeficienciáját okozó vírusok (HIV és FIV) hasonlóak, egyéb

vírusaik, mint a macska-adenovírus, elősegítik a betegség progresszióját, együttes kezelésük nehéz. A szerzők vizsgálataiban a fermentált búzacsíra-alapú Avemar granulátum daganatellenes készítmény gátolta az akut és krónikus fertőzési modellekben a FIV szaporodását, apoptosis révén pusztította a FIV-termelő

sejteket. Az Avemar a macska-adenovírus replikációját normál sejtekben igen,

daganatos sejtekben minimálisan gátolta. A daganatos sejtekben és a vírusszaporodásban egyaránt szerepet játszó ribonukleotid reduktáz gátlása lehet a

közös pont a gátlási folyamatokban.

Abstract

Background:  Fermented wheat germ extract has been reported to exert various pharmacological activities,

including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-

benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its

anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated.

Methods: Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis.

Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell

lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed

using gastric cancer patient-derived xenograft models.

Results: 2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric

cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is

dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived

xenograft gastric tumor growth in an in vivo mouse model.

Conclusions: 2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic

implications for gastric cancer patients.

Keywords:  2,6-DMBQ, mTOR, p70S6K, Gastric cancer, Patient-derived xenograft

Bioactive compounds such as benzoquinone derivates presented in fermented wheat germ extract (FWGE) have several positive

effects on overall health status of humans and animals alike. Since available data regarding the antioxidant activity of FWGE are

limited, the aim of our study was to investigate its effects on the cellular redox homeostasis applying primary hepatocyte cell

cultures of rat origin. Cultures were challenged to lipopolysaccharide (LPS) treatment for 2 or 8 hours to trigger inflammatory

response. Further, culture media were concomitantly supplemented with or without FWGE (Immunovet®, 0.1% and 1%). In

order to monitor the metabolic activity of the cell cultures, CCK-8 test was applied, while reactive oxygen species (ROS)

production was measured using Amplex Red method. Malondialdehyde concentration of culture media as a specific marker of

lipid peroxidation and the activity of glutathione peroxidase in cell lysates were also determined to monitor the redox status of

the cultures. Based on our findings, it can be concluded that FWGE did not show cytotoxic effects in any applied concentration

in cell cultures. Furthermore, FWGE efficiently decreased cellular ROS production and lipid peroxidation rate in case of LPSinduced inflammatory response. However, without LPS treatment, higher concentration of FWGE increased the rate of both

ROS and malondialdehyde synthesis. This observation may refer to the prooxidant activity of high dose FWGE, which is an

important beneficial effect regarding tumor cells. 

Summary

Preliminary studies which may be of signicance for research against

coronaviruses, including SARS-CoV-2, which has caused an epidemic

in China, are presented. An analysis was made of publicly available

data that contain information about important metabolites neutralizing

coronaviruses. Preliminary studies show that especially Ficus, barley,

thistle and sundew should be additionally tested with the aim of producing

medicines for coronavirus.

Key words: coronavirus, meta-analysis, avonoids, rhoifolin, pectolinarin,

herbacetin, ANOVA, Tukey's HSD test, barley, Ficus, thistle, sundew,

wheat, soybean, Brachypodium distachyon

The effect of fermented wheat germ extract (FWGE) (Immunovet®) was evaluated with cotreatments with deoxynivalenol (DON)

and T-2 toxin (T-2). These mycotoxins are produced by Fusarium mold species. The effects of FWGE on IPEC-J2 with DON and T2 have not been studied until now. The IPEC-J2 porcine, nontumorigenic cell line was selected to investigate the outcome of the

individually and simultaneously added compounds, as it has in vivo-like properties. The cells were treated for 24 h with the

selected solutions; then, the IPEC-J2 cells were allowed to regenerate in a culture medium for an additional 24 h. In our results,

DON and T-2 significantly increased the adverse impacts on cell viability and integrity of the cell monolayer. To elucidate the

extent of oxidative stress, extracellular H2O2 concentrations and intracellular reactive oxygen species (ROS) were measured.

FWGE appeared to be beneficial to IPEC-J2 cells given the separately and significantly decreased ROS levels. 1% and 2% FWGE

could significantly reduce mycotoxin-induced oxidative stress. In conclusion, the results demonstrate that FWGE exerted

protective effects to counteract the oxidative stress-provoking properties of applied fusariotoxins in the nontumorigenic IPEC-J2

cell line.

Abstract

Introduction:  Glioblastoma (GBM) has poor survival with standard treatment. Experimental data suggest potential

for metabolic treatment with low carbohydrate ketogenic diet (KD). Few human studies of KD in GBM have been

done, limited by difficulty and variability of the diet, compliance, and feasibility issues. We have developed a novel

KD approach of total meal replacement (TMR) program using standardized recipes with ready-made meals. This

pilot study evaluated feasibility, safety, tolerability, and efficacy of GBM treatment using TMR program with “classic”

4:1 KD.

Method:  GBM patients were treated in an open-label study for 6 months with 4:1 [fat]:[protein + carbohydrate]

ratio by weight, 10 g CH/day, 1600 kcal/day TMR. Patients were either newly diagnosed (group 1) and treated

adjunctively to radiation and temozolomide or had recurrent GBM (group 2). Patients checked blood glucose and

blood and urine ketone levels twice daily and had regular MRIs. Primary outcome measures included retention,

treatment-emergent adverse events (TEAEs), and TEAE-related discontinuation. Secondary outcome measures were

survival time from treatment initiation and time to MRI progression

Abstract

The global cancer burden has increased, and about 9.6 million cancer-related deaths were recorded in 2018. Genetic makeup,

unhealthy lifestyle, urbanization, obesity, and dietary preferences are key risk factors associated with cancer incidence and

development. Next to lung cancer, colorectal cancer is the most perilous cancer type in terms of mortality rate. Diet plays a

major role in colorectal cancer risk. The consumption of vegetables, unprocessed cereals, fish product, and fermented foods are

associated with lower cancer risk, while raw and processed red meats and refined foods are associated with increased cancer

risk. The anti-cancer properties of fermented foods and their possible mechanisms are summarized in this review. Some studies

indicated that the consumption of fermented foods reduced the risk of cancer and improved the health status of cancer patients.

However, some other research findings suggested that the intake of fermented foods was not associated with reduced cancer

risk. Several signaling pathways (p38 MAPK, ERK1/2, energy deprivation, and death-receptor mediated pathways) are involved

in the anti-proliferative and growth suppressive properties of fermented foods. Overall, the literature survey suggested that the

consumption of fermented foods might reduce cancer risk and improve health status in association with other factors, such as

genetics and healthy lifestyle.

Keywords:  fermented foods; anticancer; apoptosis; inflammation; diet.

Practical Application: The manuscript summarizes the anti-cancer properties and possible mechanism of fermented foods,

which highlights the benefits of fermented foods.

Abstract  

This systematic review and meta-analysis aim to

evaluate the association of wheat germ interventions and

metabolic markers. An electronic search was performed by

mid-May 2019 in the PubMed, Google Scholar, and Web

of Science databases. Quality was evaluated using the risk

of bias assessment tools. Thirty-three randomized controlled trials (RCTs) were identified, among which ten were

suitable and systematically reviewed based on biomarkers

(cholesterol, triglycerides, glucose, and oxidative stress).

Three biomarkers in five eligible studies were investigated

by meta-analysis. Total cholesterol showed non-significant

results (p = 0.98), with standard mean difference (SMD) of

- 0.01 (95% confidence interval; - 0.17, 0.16). The SMD

was - 0.06 (95% CI - 0.41, 0.29, n = 4) for triglycerides

and - 0.09 (95% CI - 0.62, 0.45, n = 2) for glucose. No

biomarkers showed heterogeneity (0%). This review

revealed non-significant association between wheat germ

interventions and metabolic markers. Sensitive analysis

with high-quality RCTs may be worth trying.

Keywords 

Wheat germ  Metabolic markers

Cholesterol  Triglycerides  Glucose

ABSTRACT

2,6-Dimethoxy-1,4-benzoquinone is a natural phytochemical

present in fermented wheat germ. It has been reported to exhibit anti-inflammatory, antitumor, and antibacterial activities. However, the anti-adipogenic effects of 2,6-dimethoxy1,4-benzoquinone and the mechanisms responsible have not

previously been elucidated. Such findings may have ramifications for the treatment of obesity. 2,6-Dimethoxy-1,4-benzoquinone (5 and 7.5 µM) significantly reduced the expression of

various adipogenic transcription factors, including peroxisome

proliferator-activated receptor-γ and CCAAT/enhancer binding protein α as well as adipocyte protein 2 and fatty acid synthase. 2,6-Dimethoxy-1,4-benzoquinone upregulated AMPdependent protein kinase phosphorylation and inhibited the

mature form of sterol regulatory element-binding protein 1c.

Notably, 2,6-dimethoxy-1,4-benzoquinone attenuated mammalian target of rapamycin complex 1 activity in 3T3-L1 and

mouse embryonic fibroblast cells. These findings highlight a

potential role for 2,6-dimethoxy-1,4-benzoquinone in the

suppression of adipogenesis. Further studies to determine the

anti-obesity effects of 2,6-dimethoxy-1,4-benzoquinone in

animal models appear warranted.

ABSTRACT

Goldnanoparticles (AuNPs) have well applied in imaging and carriers of drugs and/or biomolecules for diseases

and cancers therapeutics, due to their tunable physicochemical properties, easy functionalized with biomolecules and biocompatibility. AuNPs conjugated with biopolymer such as collagen has been demonstrated that

increased the cell proliferation, migration and cell differentiation. Avemar (Ave) is a nutraceutical from natural

components and dietary supplement for healthcare of tumor related anorexia/cachexia. Moreover, Ave has revealed the excellent bio-efficacy of anti-proliferation, cell cycle disturbing and apoptosis induction in numerous

types of tumor cells in in vivo and in vitro. However, the effects of Ave on cellular uptake mechanisms still

unclear. In this study, we fabricate the Ave-deposited AuNP-collagen nanocarrier (AuNP-Col-Ave) and investigate their endocytic mechanisms in transformed SCC oral cancer cells and non-transformed BAEC and HSF

cell lines. By using DLS assay, Ave-deposited AuNP-Col have shown a particle size of 303 ± 35.2 nm. Both

UV–vis absorption assay and FTIR spectrum analysis were also demonstrated that the Ave conjugated onto

AuNP-Col. Further, both MTT assay and Calcein AM assay were revealed that AuNP-Col-Ave induced a significant cytotoxicity in cancerous SCC cells and showed nontoxicity and biocompatibility for non-transformed

BAEC and HFS cells. In addition, AuNP-Col-Ave has showed an excellent uptake capacity in all these cell lines as

compared to AuNP-Col group. 

Cereals are one of the major food sources in human diet and a large quantity of by-products is generated throughout their processing chain. These by-products mostly consist of the germ and outer layers (bran), deriving from dry and wet milling of grains, brewers' spent grain originating from brewing industry, or others originating during bread-making and starch production. Cereal industry by-products are rich in nutrients, but still they end up as feed, fuel, substrates for biorefinery, or waste. The above uses, however, only provide a partial recycle. Although cereal processing industry side streams can potentially provide essential compounds for the diet, their use in food production is limited by their challenging technological properties. For this reason, the development of innovative biotechnologies is essential to upgrade these by-products, potentially leading to the design of novel and commercially competitive functional foods. Fermentation has been proven as a very feasible option to enhance the technological, sensory, and especially nutritional and functional features of the cereal industry by-products. Through the increase of minerals, phenolics and vitamins bioavailability, proteins digestibility, and the degradation of antinutritional compounds as phytic acid, fermentation can lead to improved nutritional quality of the matrix. In some cases, more compelling benefits have been discovered, such as the synthesis of bioactive compounds acting as antimicrobial, antitumoral, antioxidant agents. When used for baked-goods manufacturing, fermented cereal by-products have enhanced their nutritional profile.

Abstract:  Wheat germ is rich in quinones that exist as glycosides. In this study, we used Celluclast

1.5L to release the hydroxyquinones, which turn into benzoquinone, and prepared the water extract

from enzyme-treated wheat germ (EWG). We investigated whether enzyme treatment altered

the anti-inflammatory activity compared to the water extract of untreated wheat germ (UWG).

UWG inhibited the production of inducible nitric oxide synthase (iNOS) and interleukin (IL)-12 and

induced the production of IL-10 and heme oxygenase (HO)-1 in lipopolysaccharide (LPS)-stimulated

macrophages. Enzyme treatment resulted in greater inhibition of iNOS and IL-10 and induction of

HO-1 compared to UWG, possibly involving the modulation of nuclear factor (NF)-κB, activator protein

1 (AP-1) and nuclear factor erythroid 2-related factor (Nrf2). Mice fed UWG or EWG had decreased

serum tumor necrosis factor (TNF)-α and increased serum IL-10 levels after intraperitoneal injection

of LPS, with UWG being more effective for IL-10 and EWG more effective for TNF-α. Hepatic HO-1

gene was only expressed in mice fed EWG. We provide evidence that enzyme treatment is a useful

biotechnology tool for extracting active compounds from wheat germ.

Keywords: wheat germ; enzyme; benzoquinone; inflammation; macrophages

Abstract

The diagnosis of cancer in a child leaves parents and families devastated and vulnerable. In an effort to do

everything possible, families often choose an integrative medicine approach to their child’s care. Surveys have

found that 31%–84% of children with cancer use complementary and alternative medicine and most often as

supportive care agents. Several systematic reviews have demonstrated a clinical benefit for some select therapies;

however, the safety and efficacy of the combination of biological therapies with conventional treatment remain

largely unknown and garner concern due to the potential for interactions with conventional therapy. Given the

sustained use and potential benefit of integrative medicine, additional research is warranted in pediatric oncology.

Utilizing the available literature, clinical providers should aim to conduct open and nonjudgmental discussions

with families about the use of integrative medicine so as to guide the safe integration of the two modalities.

Keywords:  integrative medicine, nutrition, complementary/alternative medicine, pediatrics, cancer

Abstract.  Avemar, a derivative of fermented wheat germ

extract, is a non-toxic and natural compound that is used as

a dietary supplement by cancer patients undergoing chemotherapy and radiotherapy. Avemar has numerous biological

activities, and several recent studies have reported that it

may also have metastatic and anti-angiogenic effects. In the

present study, the mechanism of the anti-angiogenic effect of

Avemar on human cancer cells was investigated. The human

cell lines NCI-N87 (gastric tubular adenocarcinoma), PC3

(prostate carcinoma), HeLa (endocervical adenocarcinoma)

and A549 (lung adenocarcinoma) were treated with various

doses (400, 800, 1,600 and 3,200 µg/ml) of Avemar, and the

changes in mRNA and protein levels of two important markers

of angiogenesis, vascular endothelial growth factor (VEGF)

and cyclooxygenase-2 (Cox-2), were assessed by reverse transcription-quantitative polymerase chain reaction and ELISA.

VEGF and Cox‑2 protein and mRNA levels were significantly

lower in Avemar-treated cells than in untreated cells. The

data suggest that Avemar may exert an anti-angiogenic effect

on cancer cells. Thus, it is suggested to medical doctors as a

potential agent for the anti-angiogenic treatment of cancer.

Abstract  – Recent scientific researches proved a strong link between the diet adapted and the prevalence

of some diseases (cardiovascular diseases, diabetes, obesity…). The use of functional products may

contribute in solving this problem. Wheat is a cereal quite present in Mediterranean diet as it has an

energetic and nutritional interest (proteins, carbohydrate, fibers, vitamins…). Consumers in occidental

countries become more and more interested by mini-processed, without chemicals, natural, safe food

products. Sprouts are in agreement with this trend. Sprouting is a physiological event where a complex

nutrients transfer occurs. The aim of this review was to describe sprouting process and its impact on

nutritional properties of wheat seeds. During germination, storage molecules (proteins, starch) are

degraded under enzymatic action. Added to, some bioactive compounds such as polyphenols,

vitamins… are newly synthesized. Altogether, contribute in improving wheat nutritional quality.

Sprouting affects also functional and sensory properties of wheat. All modifications occurring during

sprouting make sprouted wheat seeds a functional ingredient, naturally enhanced by bioactive

molecules. Its use in food industry would provide an added value. 

Keywords: Wheat, Sprouting, Functional ingredient, Bioactive compounds, Wheat Technology

Abstract

Non-Hodgkin lymphoma (NHL) affects over 400,000 people in the United States; its incidence increases with age. Treatment options are numerous and expanding, yet efficacy is

often limited by toxicity, particularly in the elderly. Nearly 70% patients eventually die of the

disease. Many patients explore less toxic alternative therapeutics proposed to boost antitumor immunity, despite a paucity of rigorous scientific data. Here we evaluate the lymphomacidal and immunomodulatory activities of a protein fraction isolated from fermented

wheat germ. Fermented wheat germ extract was produced by fermenting wheat germ with

Saccharomyces cerevisiae. A protein fraction was tested for lymphomacidal activity in vitro

using NHL cell lines and in vivo using mouse xenografts. Mechanisms of action were

explored in vitro by evaluating apoptosis and cell cycle and in vivo by immunophenotyping

and measurement of NK cell activity. Potent lymphomacidal activity was observed in a panel

of NHL cell lines and mice bearing NHL xenografts. This activity was not dependent on

wheat germ agglutinin or benzoquinones. Fermented wheat germ proteins induced apoptosis in NHL cells, and augmented immune effector mechanisms, as measured by NK cell killing activity, degranulation and production of IFNγ. Fermented wheat germ extract can be

easily produced and is efficacious in a human lymphoma xenograft model. The protein fraction is quantifiable and more potent, shows direct pro-apoptotic properties, and enhances

immune-mediated tumor eradication. The results presented herein support the novel concept that proteins in fermented wheat germ have direct pro-apoptotic activity on lymphoma

cells and augment host immune effector mechanisms.

Abstract:  Fermented wheat germ extract (FWGE; trade name AVEMAR) is a natural compound

derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged

from recent studies. The aim of this systematic review is to summarize the data available in the

scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review

of English articles in electronic databases has been performed. The primary outcomes of the review

regarded types of cancer cell lines subjected to the investigation and the main results concerning cell

viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in

the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed,

showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of

apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro

and in vivo studies are necessary to prove its effectiveness and safety in humans.

Keywords: FWGE; AVEMAR; fermented wheat germ extract; nutraceuticals; cancer treatment

Abstract

Wheat grains and its fractions contain significant level of antioxidant activity and many

phytochemicals, such as phenolic acids (ferulic and vanillic acids), carotenoids, and

tocopherol are beneficial in curing many disorders. The beneficial phytochemicals

are mostly present in aleurone fraction of wheat bran. The phytochemicals and antioxidants present in wheat have several health benefits, such as their ability to act as

antioxidants, immunoenhancers, and inhibitors of certain lesions, which have been

demonstrated for phenolic. Many wheat antioxidants are similar to the antioxidants

present in wheat, but their characteristics are also unique in nature. The regular consumption of these antioxidant compounds in whole grains is associated with a reduced

risk of many heart diseases and several forms of cancers and improves the regulation of

blood glucose. Wheat antioxidants play a vital role in bakery industry mostly in bread

industry. People are getting aware to use the bakery products that are prepared from

the white flour due to proper nutrition, healthy lifestyle, improved nutritional composition, and functional properties. In nutshell, wheat antioxidants including phytochemicals synergistically improve the health status of consumers by consuming the products

having complete nutrition.

Keywords:  wheat antioxidants, phytochemicals, bakery products, health perspectives

Background: Fermented wheat germ extract (FWGE) is a multisubstance composition and, besides others, contains 2-methoxy benzoquinone and 2, 6-dimethoxy benzoquinone which are likely to exert some of its biological effects. FWGE interferes with anaerobic glycolysis, pentose cycle and ribonucleotide reductase. It has significant antiproliferative effects and kills tumor cells by the induction of apoptosis via the caspase-poly [ADP-ribose] polymerase-pathway. FWGE interacts synergistically with a variety of different anticancer drugs and exerted antimetastatic properties in mouse models. In addition, FWGE modulates immune response by downregulation of MHC-I complex and the induction of TNF-a and various interleukins. Data in the F-344 rat model provide evidence for a colon cancer preventing effect of FWGE. Clinical data from a randomized phase II trial in melanoma patients indicate a significant benefit for patients treated with dacarbazine in combination with FWGE in terms of progression free survival (PFS) and overall survival (OS). Similarly, data from studies in colorectal cancer suggested a benefit of FWGE treatment. Besides extension of OS and PFS, FWGE improved the quality of life in several studies. 

Conclusion: In conclusion, available data so far, justify the use of FWGE as a non-prescription medical nutriment for cancer patients. Further randomized, controlled and large scale clinical studies are mandatory, to further clarify the value of FWGE as a drug component of future chemotherapy regimens.

 Keywords: Fermented wheat germ extract, in vitro effects, in vivo effects, clinical activity

FWGE, the product of industrial fermentation of wheat germ, possesses unique cancer-fighting characteristics. Taken orally, FWGEcan inhibit metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation. Benefits of FWGEtreatment have been shown in various human cancers, in cultures of in vitro grown cancer cells, in the prevention of chemical carcinogenesis, and also in some autoimmune conditions. This document reviews the clinical and experimental results obtained with this extract so far. Special references are made for its safety, including its coadministration with anticancer drugs, as well as for its immunomodulatory activity, its molecular targets, and its use in cancer clinical trials.

Fermented wheat germ extract (FWGE; trade name FWGE ) is a natural compound derived from industrial fermentation of wheat germ. Its potential anticancer properties has emerged from recent studies. The aim of this systematic review is to summarize the data available in the scientific literature concerning the in vitro activity of FWGE on malignant cells. A systematic review of English articles in electronic databases has been performed. The primary outcomes of the review regarded types of cancer cell lines subjected to the investigation and the main results concerning cell viability, proliferation, and apoptosis observed within the studies. Sixteen articles were included in the final qualitative analysis. Various types of cancer cells treated with FWGE have been analyzed, showing mainly cytotoxic effects, alteration of the cell cycle, antiproliferative effects, and induction of apoptosis. FWGE can be a promising drug component in cancer treatment; however, further in vitro and in vivo studies are necessary to prove its effectiveness and safety in humans.

MSC (FWGE ) 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%, Po0.01; new metastases: 7.6 vs 23.1%, Po0.01; deaths: 12.1 vs 31.7%, Po0.01). Survival analysis showed significant improvements in the MSC group regarding progression-free (P ¼ 0.0184) and overall survivals (P ¼ 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.

Background and aim Anorexia/cachexia syndrome is frequently correlated with increased oxidative stress (OS). A fermented wheat-germ extract with a standardized benzoquinone content (brand name FWGE ) has been shown to exert an intense antioxidant activity with no side effects. The aim of this study was to investigate the effects of FWGE in patients affected by head and neck cancer, correlating the variations with OS with the quality of life as assessed by the Spitzer’s index. Patients and methods A cohort of 60 patients affected by head and neck tumours (stage IIIa, IIIb, IV) were enrolled in the study following an open-label protocol. The patients were assigned to two subgroups, A or B. Group A was treated with conventional oncological therapy alone, and group B was treated with FWGE in addition to standard therapy. After 2 months only 55 patients survived and could be evaluated (29 in the control group and 26 in the FWGE group). Each patient was checked for circulating concentrations of hydroperoxides using the FRAS III test. Results The levels of OS significantly decreased after 2 months in the group receiving FWGE (group). The value of Spitzer’s index was significantly higher in group B, attesting to an improved quality of life. Conclusion Although the specific active substance in FWGE has not yet been identified, the reduction in free oxygen radicals induced by it is correlated with a clinically significant improvement in the quality of life in patients with advanced cancer.

Objective: The fermented wheat germ extract (FWGE) nutraceutical (FWGE ™), manufactured under “good manufacturing practice” conditions and, fulfilling the self-affirmed “generally recognized as safe” status in the United States, has been approved as a “dietary food for special medical purposes for cancer patients” in Europe. In this paper, we report the adjuvant use of this nutraceutical in the treatment of high-risk skin melanoma patients. Methods: In a randomized, pilot, phase II clinical trial, the efficacy of dacarbazine (DTIC)-based adjuvant chemotherapy on survival parameters of melanoma patients was compared to that of the same treatment supplemented with a 1-year long administration of FWGE. Results: At the end of an additional 7-year-long follow-up period, log-rank analyses (Kaplan-Meier estimates) showed significant differences in both progression-free (PFS) and overall survival (OS) in favor of the FWGE group. Mean PFS: 55.8 months (FWGE group) versus 29.9 months (control group), p 0.0137. Mean OS: 66.2 months (FWGE group) versus 44.7 months (control group), p 0.0298. Conclusions: The inclusion of FWGE into the adjuvant protocols of high-risk skin melanoma patients is highly recommended.

Objective: Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists. Methods: In this study, we investigated the activity of FWGE , a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level. Results: We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate G 0.2) representing 27 biologic pathways (P G 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity. Conclusions: Our findings confirm the value of FWGE as a natural product with anticancer properties that may also enhance the activity of existing therapeutic agents. 

The fermented extract of wheat germ, trade name FWGE , is a complex mixture of biologically active molecules with potent anti-metastatic activities in various human malignancies. Here we report the effect of FWGE on Jurkat leukemia cell viability, proliferation, cell cycle distribution, apoptosis, and the activity of key glycolytic/pentose cycle enzymes that control carbon flow for nucleic acid synthesis. The cytotoxic IC50 concentration of FWGE for Jurkat tumor cells is 0.2 mg/ml, and increasing doses of the crude powder inhibit Jurkat cell proliferation in a dose-dependent fashion. At concentrations higher than 0.2 mg/ml, FWGE inhibits cell growth by more than 50% (72 h of incubation), which is preceded by the appearance of a sub-G1 peak on flow histograms at 48 h. Laser scanning cytometry of propidium iodideand annexin V-stained cells indicated that the growthinhibiting effect of FWGE was consistent with a strong induction of apoptosis. Inhibition by benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone of apoptosis but increased proteolysis of poly(ADP-ribose) indicate caspases mediate the cellular effects of AvFWGE emar. Activities of glucose-6-phosphate dehydrogenase and transketolase were inhibited in a dose-dependent fashion, which correlated with decreased 13C incorporation and pentose cycle substrate flow into RNA ribose. 

Purpose: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (FWGE ) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. 

Methods: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. 

Results: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). 

Conclusions: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.

The Hungarian Association of Oral and Maxillofacial Surgeons (Magyar Arc-, Állcsont- és Szájsebészeti Társaság) has reviewed the research results related to FWGE and issued its opinion as follows: For patients suffering from head- and neck tumors - primarily malignant tumorous diseases of the oral cavity, the progression of the disease can be slowed significantly, the five-year survival rate increased considerably, the quality of life improved, and the oxidative stress on the patients reduced by the long-term application of the supplementary formula FWGE . The Association considers the supportive treatment with the formula FWGE as an important part of the complex therapeutic protocols applied in stages II, III and IV of malignant tumorous diseases of the oral cavity. 

Autophagy is primordial for the maintenance of metabolic and genetic homeostasis in all eukaryotic organisms. Owing to its cell-intrinsic effects, autophagy robustly inhibits malignant transformation, yet can support the progression of established neoplasms as well as their resistance to conventional treatments. The notion that autophagy inhibition sensitizes neoplastic cells to chemotherapy and radiation therapy rivals with the capacity of autophagy to contribute to natural and therapy-driven anticancer immunosurveillance via a multitude of mechanisms. Indeed, autophagy ensures an optimal release of immunostimulatory signals by dying cancer cells and hence boosts their capacity to initiate an immune response. Moreover, autophagy is important for the activity of several components of the immune system involved in tumor recognition and elimination, including antigen-presenting cells and CD8C cytotoxic T lymphocytes. In this review, we discuss how cancer cells disable autophagy to bypass immune control and how strategies aiming to enhance autophagy can be envisaged to improve the efficacy of immunogenic cancer therapies.

Cancer can be viewed in 2 rather distinct ways, namely (i) as a cell-autonomous disease in which malignant cells have escaped control from cell-intrinsic barriers against proliferation and dissemination or (ii) as a systemic disease that involves failing immune control of aberrant cells. Since macroautophagy/autophagy generally increases the fitness of cells as well as their resistance against endogenous or iatrogenic (i.e., relating to illness due to medical intervention) stress, it has been widely proposed that inhibition of autophagy would constitute a valid strategy for sensitizing cancer cells to chemotherapy or radiotherapy. Colliding with this cell-autonomous vision, however, we found that immunosurveillance against transplantable, carcinogen-induced or genetically engineered cancers can be improved by pharmacologically inducing autophagy with caloric restriction mimetics. This positive effect depends on autophagy induction in cancer cells and is mediated by alterations in extracellular ATP metabolism, namely increased release of immunostimulatory ATP and reduced adenosine-dependent recruitment of immunosuppressive regulatory T cells into the tumor bed. The combination of autophagy inducers and chemotherapeutic agents is particularly efficient in reducing cancer growth through the stimulation of CD8+ T lymphocyte-dependent anticancer immune responses.

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.

 Background: The positive effect of the wheat germ extract FWGE 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. FWGE 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 FWGE 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 FWGE (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 FWGE for 48 hours. To determine the kinase expression pattern Kinase OpenArrayTM 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). 

This review will discuss some issues related to the risk/benefit profile of the use of dietary antioxidants. Thus, recent progress regarding the potential benefit of dietary antioxidants in the treatment of chronic diseases with a special focus on immune system and neurodegenerative disorders will be discussed here. It is well established that reactive oxygen species (ROS) play an important role in the etiology of numerous diseases, such as atherosclerosis, diabetes and cancer. Among the physiological defense system of the cell, the relevance of antioxidant molecules, such as glutathione and vitamins is quite well established. Recently, the interest of researchers has, for example, been conveyed on antioxidant enzyme systems, such as the heme oxygenase/biliverdin reductase system, which appears modulated by dietary antioxidant molecules, including polyphenols and beta-carotene. These systems possibly counteract oxidative damage very efficiently and finally modulate the activity of oxidative phenomena occurring, for instance, during pathophysiological processes. Although evidence shows that antioxidant treatment results in cytoprotection, the potential clinical benefit deriving from both nutritional and supplemental antioxidants is still under wide debate. In this line, the inappropriate assumption of some lipophylic vitamins has been associated with increased incidence of cancer rather than with beneficial effects

Objective: The fermented wheat germ extract (FWGE) nutraceutical (FWGE ™), manufactured under “good manufacturing practice” conditions and, fulfilling the self-affirmed “generally recognized as safe” status in the United States, has been approved as a “dietary food for special medical purposes for cancer patients” in Europe. In this paper, we report the adjuvant use of this nutraceutical in the treatment of high-risk skin melanoma patients. Methods: In a randomized, pilot, phase II clinical trial, the efficacy of dacarbazine (DTIC)-based adjuvant chemotherapy on survival parameters of melanoma patients was compared to that of the same treatment supplemented with a 1-year long administration of FWGE. Results: At the end of an additional 7-year-long follow-up period, log-rank analyses (Kaplan-Meier estimates) showed significant differences in both progression-free (PFS) and overall survival (OS) in favor of the FWGE group. Mean PFS: 55.8 months (FWGE group) versus 29.9 months (control group), p 0.0137. Mean OS: 66.2 months (FWGE group) versus 44.7 months (control group), p 0.0298. Conclusions: The inclusion of FWGE into the adjuvant protocols of high-risk skin melanoma patients is highly recommended

A búzacsírával a Műegyetemen találkozott először. De valahogy úgy, mint mikor Salamon Bélától egy színpadi tréfában megkérdezték, látott-e már nyulat. Hát persze, felelte a legendás színész, az a barna, amit szósszal leöntenek. - Biológus-mérnökként kerültem a Gabona Tröszthöz, s professzorom, Lásztity Radomir hatására elköteleztem magam a gabonakémia mellett. Kikerültem ösztöndíjasként Kanadába, Winnipegbe. Az ajánlóm Holló János volt, a magyar biotechnológia atyja. Az első szabadalmaztatott gyógyhatású készítményemet, az Esterint lucernából kivont anyagokból állítottuk elő. Csak gyanítható, hogy azért fordultam végül a gyógyszerkutatás felé, mert nálunk a családban majd mindenki a gyógyszerészet területén tüsténkedett. Anyai nagyapját említi elsőként a sorban. 

Background and aim Anorexia/cachexia syndrome is frequently correlated with increased oxidative stress (OS). A fermented wheat-germ extract with a standardized benzoquinone content (brand name FWGE ) has been shown to exert an intense antioxidant activity with no side effects. The aim of this study was to investigate the effects of FWGE in patients affected by head and neck cancer, correlating the variations with OS with the quality of life as assessed by the Spitzer’s index. Patients and methods A cohort of 60 patients affected by head and neck tumours (stage IIIa, IIIb, IV) were enrolled in the study following an open-label protocol. The patients were assigned to two subgroups, A or B. Group A was treated with conventional oncological therapy alone, and group B was treated with FWGE in addition to standard therapy. After 2 months only 55 patients survived and could be evaluated (29 in the control group and 26 in the FWGE group). Each patient was checked for circulating concentrations of hydroperoxides using the FRAS III test. Results The levels of OS significantly decreased after 2 months in the group receiving FWGE (group). The value of Spitzer’s index was significantly higher in group B, attesting to an improved quality of life. Conclusion Although the specific active substance in FWGE has not yet been identified, the reduction in free oxygen radicals induced by it is correlated with a clinically significant improvement in the quality of life in patients with advanced cancer.

INTRODUCTION 

Dr. Otto Warburg was awarded the Nobel Prize more than 70 years ago for his discovery that cancer cells use glucose at a rate 10 to 50 times higher than healthy cells through direct glycolysis via non-oxidative pathways.' Called "the Warburg Effect," this characteristic hypermetabolic activity fuels the explosive growth o f cancer, steals glucose from healthy tissue and produces metabolic byproducts that contribute to systemic illness. Warburg theorized that if t he uptake of glucose into cancer cells could be inhibited, their energy supply could be choked off, slowing or stopping cancer growth and fo rcing cancer cells to die.

FWGE , a product of industrial fermentation of wheat germ with a standardized content of benzoquinone and plant flavonoids, has been tested as an anti-cancer and immunomodulatory dietary supplement. Proposed mechanisms include anti-oxidant and anti-inflammatory actions. This study has determined whether these actions of FWGE may also be useful in the treatment of cardiovascular diseases. Two experimental rat models of cardiovascular remodeling were used in this project: the deoxycorticosterone acetate (DOCA)-salt-induced model of chronic hypertension (study I) and a high-carbohydrate/high-fat dietinduced model producing chronic symptoms of the metabolic syndrome and its associated cardiovascular complications (study II). Our results in these rat models of hypertension and diet-induced obesity show that treatment with FWGE improved cardiac function, decreased macrophage infiltration resulting in decreased collagen deposition in the ventricular myocardium, reversed an increased stiffness of the left ventricle in the diseased hearts and attenuated increased plasma malondialdehyde concentrations. In addition to the changes in the heart, FWGE reversed glucose intolerance, normalized systolic blood pressure and decreased visceral fat deposition in rats fed a high-fat/high-carbohydrate diet. In conclusion, the fermented wheat germ extract FWGE has a potential role in attenuating chronic hypertension, diabetes or metabolic syndrome-induced cardiovascular symptoms along with metabolic abnormalities such as glucose tolerance and obesity.

Many healthy foods are derived from wheat germ. The molecular composition of these products, however, greatly differs as shown by normal-phase HPLC-mass spectrometry analysis; thus, experimental data obtained by one of them is not necessarily true for the other. FWGE is a nontoxic wheat germ extract registered as a special nutriment for cancer patients in Hungary. It shows potent anticancer activity on cell lines by deeply interfering with glucose metabolism and affecting expressions of several kinases. In in vivo experimental models, FWGE is also effective by enhancing the activity of the immune system such as stimulating NK cell activity (by reducing MHC I molecule expression), enhancing TNF secretion of the macrophages, increasing ICAM 1 molecule expression on the vascular endothelial cells. All of these lead to apoptosis of tumor cells. The wide range of biological activity of FWGE probably cannot be explained by only one active ingredient. Since there are numerous experimental data and the clinical benefit repeatedly confirmed FWGE can be one of the most potent and best researched food supplements available for cancer patients

FWGE (MSC) is a nontoxic fermented wheat germ extract, which has been shown to significantly improve the survival rate in patients suffering from various malignancies. We investigated its effects in sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells. After 48 and 72 h of incubation, FWGE inhibited the growth of sensitive H9 cells with IC50 values of 290 and 200 μg/ml, whereas the growth of 5-FdUrd/Ara-C cross-resistant H9 cells was attenuated with IC50 values of 180 and 145 μg/ml, respectively. Treatment with 300 μg/ml MSC for 48 h caused dosedependent induction of apoptosis in 48% of sensitive H9 cells. In cross-resistant H9 cells, incubation with 200 μg/ml FWGE for 48 h led to 41% of apoptotic tumor cells. Growth arrest of sensitive H9 cells after exposure to various concentrations of MSC occurred mainly in the S phase of the cell cycle, thereby increasing the cell population from 54 to 73% while depleting cells in the G0-G1 phase from 40 to 19%. Growth arrest in cross-resistant H9 cells occurred also mainly in the S phase, increasing the cell population from 45 to 68% while depleting cells in the G0-G1 phase from 45 to 31%. As MSC treatment likely overcomes 5-FdUrd/Ara-C resistance, further investigations to elucidate the exact mechanisms are warranted. We conclude that FWGE exerts a number of beneficial effects which could support conventional chemotherapy of human malignancies.

Worldwide medical literature supports the notion that environmental and nutritional factors play a role in the development of cancer. Nutritional recommendations to the public to help prevent cancer are available from the USA’s National Cancer Institute, the American Cancer Society and other organizations. However, when it comes to treating patients who have been diagnosed with cancer, the vast majority of oncologists fail to deal with nutritional and lifestyle factors to help their patients manage their cancers. Evidence continues to mount that some of the same recommendations designed to prevent cancer should also be applied to patients who already have cancer. Implementing such a program of lifestyle modi!cations, improvement in diet, exercise, stress management, optimal exposure to sunlight, improving energy "ow and nutritional supplements should improve cancer patients’ survival statistics and the quality of life of these patients, including signi!cantly reducing the side e#ects of conventional treatments. $is article focuses on dietary changes and nutritional supplements to help clinicians educate cancer patients, so that they may better deal with their illness. Highlighted are principles involving an optimal diet, avoidance of harmful chemicals and use of nutritional supplements. Some of the controversies surrounding nutritional supplements are reviewed. Speci!c topics covered include a broad range supplement program, vitamin C, amygdalin, iodine, and fermented wheat germ extract. Finally, there is a discussion about paradigms in health care and the e#ects of politics and economics on how health care is practiced today.

Worldwide medical literature supports the notion that environmental and nutritional factors play a role in the development of cancer. Nutritional recommendations to the public to help prevent cancer are available from the USA’s National Cancer Institute, the American Cancer Society and other organizations. However, when it comes to treating patients who have been diagnosed with cancer, the vast majority of oncologists fail to deal with nutritional and lifestyle factors to help their patients manage their cancers. Evidence continues to mount that some of the same recommendations designed to prevent cancer should also be applied to patients who already have cancer. Implementing such a program of lifestyle modi!cations, improvement in diet, exercise, stress management, optimal exposure to sunlight, improving energy "ow and nutritional supplements should improve cancer patients’ survival statistics and the quality of life of these patients, including signi!cantly reducing the side e#ects of conventional treatments. $is article focuses on dietary changes and nutritional supplements to help clinicians educate cancer patients, so that they may better deal with their illness. Highlighted are principles involving an optimal diet, avoidance of harmful chemicals and use of nutritional supplements. Some of the controversies surrounding nutritional supplements are reviewed. Speci!c topics covered include a broad range supplement program, vitamin C, amygdalin, iodine, and fermented wheat germ extract. Finally, there is a discussion about paradigms in health care and the e#ects of politics and economics on how health care is practiced today.

n the present study on effect of feeding raw wheat germ, microwave treated wheat germ, gamma irradiated wheat germ and fermented wheat germ on Interferon gamma (IFN-γ ) and Interleukin 10 (IL-10) in serum of rats were investigated. The data indicated that treated and untreated wheat germ had significant increase in (IFNγ ) level in the serum of rats . Fermented wheat germ recorded the highest significant increase in this concept in comparison to control group. Wheat germ supplementation indicated significant changes of (IL-10) level in serum of rats in comparison to control group. Fermented wheat germ recorded the least significant decrease in (IL-10) level in serum of rats in comparison to control group. Treated and untreated wheat germ specially fermented wheat germ raised the immune system of experimental rats .On the other hand, the present study included the vitamins content (vitamins A, E, and C ) of raw ,microwave treated, gamma irradiated, and fermented wheat germ clarifying the role of each vitamin in raising the immune system.

INTRODUCTION

Health is considered as a fundamental human right and a worldwide social goal. It encompasses all humans disregard of age. Geographical conditions, culture, economic status and life style of people have major impact on their health. Thanks to scientific advancements that the life style of the people is tremendously metamorphosing and their physical activities are getting minimal. The food style is not in conformity to the accustomed geographical or cultural conditions. This results in a wide range of health issues visibly seen as obesity, diabetes and related diseases. If this is the scenario midst the affluent population, malnutrition and low immunity - perpetuating secondary diseases are abounding with the poorest of the poor of the population. In such a context, there arises an essentiality for a study addressing the entire gamut of issue through one single medium. With this as the setting to the research problem, the investigator chose to unravel the utility of wheat as the medium, fine tuning to the questions of addressing the health issues of Indian population, of both the affluent and the have-nots. Much not known components of wheat produce such as wheat bran, wheat germ and wheat grass are the subjective components of study as the investigator came across astounding facts of their nutritive values and medicinal potentials in the researcher’s pilot studies conducted. 

Lactobacillus plantarum LB1 and Lactobacillus rossiae LB5, isolated from wheat germ and selected based on the kinetics of acidification, were used as starters for the manufacture of sourdough fermented wheat germ. A bread containing sourdough fermented wheat germ as an ingredient (SFWGB) was compared to breads made with (raw wheat germ bread, RWGB) or without (wheat flour bread, WFB) raw wheat germ. The higher concentration of free amino acids mainly differentiated SFWGB from WFB and RWGB. The in vitro protein digestibility of WFB was the highest, even if sourdough fermentation of wheat germ attenuated the difference. Phytase and antioxidant activities of SFWGB were highest. The specific volume and celltotal areas were also the highest for SFWGB. As determined by texture profile analysis, the values of hardness, resilience and fracturability of breads containing wheat germ were lower than those found in WFB. The crust lightness showed a decrease from WFB to SFWGB. As determined by sensory analysis, SFWGB had mainly acid taste and flavour and resulted more salty. Sourdough fermented wheat germ is an ingredient able to enhance nutritional, texture and sensory properties of bread. 

The biochemical effects of ethylacetate extract of wheat (FWGE ) on some serum and liver enzymes were evaluated in T. brucei infected rats. The results show significant increase in specific activities of serum aspartate transaminase (AST) in infected untreated rats when compared with infected treated rats. However, there were no significant difference in serum and liver alanine transaminase (ALT). Liver Alkaline phosphatase (ALP) activities were significantly increased in infected untreated when compared with the infected treated rats. Results also show significant increase in specific activities of serum catalase (CAT) and Superoxide dismutase (SOD) in infected treated rats when compared with infected untreated rats. Whereas, there was no significant difference in specific activities of liver catalase, (CAT) and Superoxide dismutase (SOD) in infected treated rats when compared with infected untreated rats. We hereby conclude that ethylacetate extract of wheat has no toxic effect and can ameliorate the effect caused by T. brucei infection.

We evaluated the antibacterial activities of selected edible Korean plant seeds against the food-borne pathogens Staphylococcus aureus KCTC1927, Escherichia coli KCTC2593, Salmonella typhimurium KCTC2054, and Bacillus cereus KCTC1014. While screening for antibacterial agents, we discovered that wheat germ extract contains 2,6-dimethoxy-1,4-benzoquinone (DMBQ) and is highly inhibitory to S. aureus and B. cereus. This is the first report of the antibacterial activity of wheat germ extract. We also investigated the antibacterial activities of the 1,4- benzoquinone standards 1,4-benzoquinone (BQ), hydroquinone (HQ), methoxybenzoquinone (MBQ), and 2,6-dimethoxy1,4-benzoquinone (DMBQ). DMBQ and BQ were the most highly inhibitory to S. aureus and S. typhimurium, followed by MBQ and HQ. MICs for DMBQ and BQ ranged between 8 and 64 µg/ml against the four foodborne pathogens tested. DMBQ and BQ showed significant antibacterial activity; the most sensitive organism was S. aureus with an MIC of 8 µg/ml. BQ exhibited good activity against S. typhimurium (32 µg/ml) and B. cereus (32 µg/ml). The results suggest that wheat germ extract has potential for the development of natural antimicrobials and food preservatives for controlling foodborne pathogens.

Praise be to ALLAH, the most gracious, the most merciful. He (alone) we worship and he alone we seek for help. The almighty that is never weary of protecting me from childhood to this present stage of life. I wish to express my sincere and unreserved appreciation to my supervisor Prof. Clement O. Bewaji. Thank you for the painstaking and scholarly guidance. I want to particularly acknowledge Dr J.T Ekanem for his support and encouragement throughout these past years. I pray that almighty God will grant him good health and abundant blessing in this world and hereafter. Likewise my appreciation goes to the Ag. Head of Department, Dr. (Mrs.) A. T. Oladiji and other members of staff (teaching and non- teaching) for the assiatance and contribution towards the success of this work. My profound gratitude goes to my parents, brothers and sisters for their love, care, support and encouragement not only in this course of this work. I love you all. At this juncture, l acknowledge everyone that contributed immensely in one way or the other to the successfully completion of this work. Although, I cannot mention everybody’s name, Almighty God knows you and equally appreciates you all. Finally to my beloved one Mr Olanrewaju Ibrahim Shittu, l pray Allah reward you accordingly.

Ethyl acetate extract of wheat (Triticum aestivum) and methanolic extract of garlic (Allium sativum) were obtained by fermenting powdered wheat germ and garlic bulbs. The extracts were assessed for their active constituents. The result of the quantitative phytochemical analysis shows that the plant contain secondary metabolite with high percentage of glycoside (19.513%), alkaloids (4.017%) and saponins (7.992%) for wheat extract and glycoside (21.088%), alkaloids (3.570%) and saponins (0.696%) for garlic extract. The extract exhibit antit-rypanosomal activity by showing decrease in the proliferation of parasite and extension of surviving days of Trypanosoma brucei - infected rats from 8 days of the control (infected-untreated) to 14 days of infected treated with wheat and 17 days for infected treated with garlic extract. This study scientifically demonstrates the potential of fermented wheat germ ethylacetate extract and garlic bulbs methanolic extract in the management of Africa trypanosomiasis. 

A recent prospective epidemiological study suggested that an increase in the nutritional uptake of the natural polyamine spermidine is associated with reduced overall and cancer-specific mortality. Here, we speculate through which mechanisms spermidine might exert such oncopreventive effects.

Spermidine, as a natural component from polyamine members, is originally isolated from semen and also existed in many natural plants, and can be responsible for cell growth and development in eukaryotes. The supplementation of spermidine can extend health and lifespan across species. Although the elevated levels of polyamines and the regulation of rate-limiting enzymes for polyamine metabolism have been identified as the biomarkers in many cancers, recent epidemiological data support that an increased uptake of spermidine as a caloric restriction mimic can reduce overall mortality associated with cancers. The possible mechanisms between spermidine and cancer development may be related to the precise regulation of polyamine metabolism, anticancer immunosurveillance, autophagy, and apoptosis. Increased intake of polyamine seems to suppress tumorigenesis, but appears to accelerate the growth of established tumors. Based on these observations and the absolute requirement for polyamines in tumor growth, spermidine could be a rational target for chemoprevention and clinical therapeutics of cancers.

Prostate cancer is the second leading cancer in men. A large amount of polyamines are synthesised in the human prostate and are involved in prostate cell growth and its physiological functions. The content of intracellular polyamines is closely related to cell growth. An increase in cell growth is accompanied by a rise of intracellular polyamine content, and a depletion of intracellular polyamine pools can cause growth arrest or cell death. Therefore, maintaining polyamine concentrations is critical to the cell. Spermidine/spermine N1 -acetyltransferase (SSAT) is the first and rate-limiting enzyme in the polyamine catabolic pathway. SSAT gene is highly inducible, with many stimuli including polyamine analogues and some anticancer drugs producing dramatic increases in activity. Many studies have focussed on polyamine analogues as inducers of SSAT activity as increases in SSAT are associated with a growth inhibition in many tumour cells. However, the mechanisms of this inhibition are not fully understood with respect to polyamine content. Additionally, in vivo results in SSAT transgenic mice studies are contradictory. For example, prostate carcinogenesis is reduced in TRAMP mice but Apcmin/+ mice show a promoted intestinal tumorigenesis. It is thus necessary to characterise the regulation of polyamine content and metabolism by SSAT in prostate cancer cells. The aim of the present study was to characterise the role of SSAT in both the growth of LNCaP prostate carcinoma cells and the response of these cells to anticancer drugs.

Background: Putrescine, spermidine, and spermine (i.e., polyamines) are small cationic amines synthesized by cells or acquired from the diet or gut bacteria. Polyamines are required for both normal and colorectal cancer (CRC) cell growth. 

Objective: We investigated the association between dietary polyamines and risk of CRC incidence and mortality.

 Design: The study was a prospective analysis in 87,602 postmenopausal women in the Women’s Health Initiative Observational Study. Multivariate Cox regression was used to calculate HRs and 95% CIs. 

Results: Total dietary polyamine intake (mean 6 SD: 289.2 6 127.4 mmol/d) was not positively associated with CRC in fully adjusted models. Instead, intake $179.67 mmol/d was associated with reduced risk of CRC [HR (95% CI): 0.82 (0.68, 1.00), 0.81 (0.66, 0.99), 0.91 (0.74, 1.12), and 0.80 (0.62, 1.02) for quintiles 2–5, respectively, compared with quintile 1]. Reduced risk was not significant across all quintiles. Polyamines were not significantly associated with CRCspecific mortality in fully adjusted models. When stratified by risk factors for CRC, only body mass index (BMI) and fiber intake significantly modified the association between polyamine intake and CRC. In women with BMI (in kg/m2 ) #25 or fiber consumption above the median, polyamine intake was associated with significantly lower risk of CRC.

 Conclusions: No positive association between dietary polyamines and CRC or CRC-specific mortality risk in women was observed. Instead, a protective effect of dietary polyamines was suggested in women with some CRC risk-lowering behaviors in particular. These results are consistent with emerging evidence that exogenous polyamines may be beneficial in colon health and warrant additional study

Liver fibrosis and hepatocellular carcinoma (HCC) have worldwide impact but continue to lack safe, low cost and effective treatments. In this study, we show how the simple polyamine spermidine can relieve cancer cell defects in autophagy which trigger oxidative stress-induced cell death and promote liver fibrosis and HCC. We found that the autophagic marker protein LC3 interacted with the microtubule-associated protein MAP1S which positively regulated autophagy flux in cells. MAP1S stability was regulated in turn by its interaction with the histone deacetylase HDAC4. Notably, MAP1S-deficient mice exhibited a 20% reduction in median survival and developed severe liver fibrosis and HCC under stress. Wild-type mice or cells treated with spermidine exhibited a relative increase in MAP1S stability and autophagy signaling via depletion of cytosolic HDAC4. Extending recent evidence that orally administered spermidine can extend lifespan in mice, we determined that life extension of up to 25% can be produced by lifelong administration which also reduced liver fibrosis and HCC foci as induced by chemical insults. Genetic investigations established that these observed impacts of oral spermidine administration relied upon MAP1S-mediated autophagy. Our findings offer a preclinical proof of concept for the administration of oral spermidine to prevent liver fibrosis and HCC and potentially extend lifespan. 

Response to an online chat question. On Thursday, June 10 we held an online chat about diet and cancer myths. One question was about a dietary supplement (FWGE) for cancer treatment, rather than about food, weight and physical activity. So, we turned to for help with answering this question. Suzanne Dixon, MPH, RD Suzanne developed and taught nutrition science coursework at University of Michigan Medical School. At the university's Comprehensive Cancer Center, Suzanne counseled thousands of cancer patients and represented the school as an appointed member to the National Comprehensive Cancer Network (NCCN) nutrition sub-committee. She has also written numerous articles for both scholarly and popular publications. Suzanne is the recipient of the American Dietetic Association Awards for Distinguished Practice in Oncology (cancer) Nutrition and Innovative Nutrition Education Programs for the Public. Please note the following information is from Ms. Dixon and does not represent views or opinions of AICR. Any decisions you make regarding treatment should be in consultation with your physician or health care provider. 

Case repart:

 The patient is a 46-yearold male of Chinese decent diagnosed with stage IV colon cancer with l0 + metastases to the liver on October 12,2009 (Figure l). His CEA at the time of discovFigure l. MRI of the liver at the time of diagnosis. efy WaS 4,030ng/ml. FOLFOX (s-FU, folinic acid, oxaloplatin) chemotherapy every two weeks was started on October 28, 2OO9. Alternative therapy included fermented wheat germ extract (FWGE ) and high-dose IV Vitamin C (3,0OOmg IV 3 times per week) beginning in the same month and 8glday of fucoidan from Fucus vesiculosis beginning in early December 2009. The patient had minimal side effects from the FOLFOX chemotherapy regimen, reported no GI discomforts, and had no noticeable hair loss during his l2 weeks of FOLFOX. Unfortunately, the patient's tumors did not respond to the chemo regimen, and his CEA reached 7,9oong/ml by fanuary 2010. His oncologist switched his chemo regimen to cetuximab + FOLFIRI (5-FU, folinic acid, irinotecan) while his alternative therapies remained the same.

Wheat germ contains the glycosylated forms of 2-methoxy-p-benzoquinone (2-MBQ) and 2,6-dimethoxy-p-benzoquinone (2,6-DMBQ), both of which have antimicrobial and immunostimulatory effects. Conversion of glycosylated 2-MBQ and 2,6-DMBQ to their more functional unglycosylated forms requires enzymatic action of β-glucosidase. We investigated the applications of lactic acid bacteria and yeast that produce β-glucosidase as starters for production of unglycosylated 2-MBQ and 2,6-DMBQ from wheat germ. Lactobacillus zeae and Pichia pijperi were selected through β-glucosidase enzyme assays for 37 yeast strains and five strains of lactic acid bacteria. Lb. zeae was more efficient than P. pijperi at producing 2-MBQ and 2,6-DMBQ from wheat germ. After 48 hr of fermentation with a mixed culture of Lb. zeae and P. pijperi, the concentration of 2-MBQ was 0.46±0.07 mg/g, indicating an approximately 1.6-fold higher concentration than that obtained by pure culture of Lb. zeae. However, the concentration of 2,6-DMBQ was not significantly enhanced by fermentation with a mixed culture of Lb. zeae and P. pijperi

Nuruk, a traditional Korean fermentation starter, contains 2,6-dimethoxy-ρ-benzoquinoe (2,6- DMBQ), also found in fermented wheat germ extract, and has anti-cancer and immune supporting effects. The presence of 2,6-DMBQ was confirmed by high performance liquid chromatography and mass spectrometry. Among the five traditional nuruks tested, the highest 2,6-DMBQ content of 1.16±0.07 mg/50 g was obtained from nuruk purchased in Hwaseong. The results of this study may explain the health-promoting functions of traditional Korean alcoholic beverages that employ nuruk as a fermentation starter.

Chloropyrifos (CPF) is an organophosphate insecticide is widely used for a variety of agricultural and public health applications. The purpose of this study was to assess the biochemical role of the fermented wheat germ (FWGE ) on the liver and kidney function tests and the oxidative stress induced by chlorpyrifos in rats; moreover the heamatological measurements and histological investigation were studied. Chloropyrifos was added to the different experimental tested diets at two levels of low and high doses (25 and 50 mg/kg diet, respectively). The fermented wheat germ was added at a level of 3g/kg diet. The results demonstrated that there were significant decrease in the total counts of RBC's, WBC's, erythrocyte indices, hemoglobin concentration and hematocrit level in experimental rats fed diets containing low and high levels of CPF. Liver functions is impaired in rats administrated only chlorpyrifos either low or high dose and the results showed a significant increase in enzyme activities such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γGT), while total proteins, albumin, and globulin showed a significant decrease at high and low doses of CPF treated groups but kidney functions results showed a significant increase in serum creatinine and urea levels. Administration of CPF caused a significant increase in lipid peroxidation level, lipid profile while the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-stransferase (GST) were decreased significantly. So FWGE supplementation caused significant improvement in all results in comparison with those groups administrated CPF.

Fermented wheat germ extract (FWGE) is currently used as nutrition supplement for cancer patients. Limited recent data suggest antiproliferative, antimetastatic and immunological effects which were at least in part exerted by two quinones, 2-methoxy benzoquinone and 2,6-dimethoxybenzquinone as ingredients of FWGE. These activity data prompted us to further evaluate the in vitro antiproliferative activity of FWGE alone or in combination with the commonly used cytotoxic drugs 5-FU, oxaliplatin or irinotecan in a broad spectrum of human tumor cell lines. We used the sulforhodamine B assay to determine dose response relationships and IC50-values were calculated using the Hill equation. Drug interaction of simultaneous and sequential drug exposure was estimated using the model of Drewinko and potential clinical activity was assessed by the model of relative antitumor activity (RAA). Apoptosis was detected by DNA gel electrophoresis. FWGE induced apoptosis and exerted significant antitumor activity in a broad spectrum of 32 human cancer cell lines. The highest activity was found in neuroblastoma cell lines with an average IC50 of 0.042 mg/ml. Furthermore, IC50-range was very narrow ranging from 0.3 mg/ml to 0.54 mg/ml in 8 colon cancer cell lines.

170 broilers have been infected with Salmonella infantis and vaccinated against IBD,(infectious bursal disease) IB, (infectious bronchitis) ND. (Newcastle disease)Feed of 85 broilers has been completed with FWGE (fermented wheat germ extract) Shedding-characteristics of Salmonella infantis and immune reactions after vaccinations were investigated with both broiler groups. Intensity and dynamics of shedding of bacteria by cloacal swabs proved to be equal with both groups and stopped between 18- 19th day after infection, but cecal content remained positive even on 31-33 days after infection. FWGE increased the IBD VN GMT (virusneutralization geometric mean titers) 7 days after vaccination by 26%, but 21 days after immunization there was no difference in the titres. IB ELISA MMT (mathematical mean titers) 28 and 42 days after vaccination have been increased with the FWGE treated group by 820 and 180% compared to the control. ND HI GMT (haemagglutination inhibition geometric mean titers) proved to be 100% higher with the FWGE treated group on the 42nd day of rearing.

Fermented wheat germ extract (FWGE) is a multisubstance composition and, besides others, contains 2-methoxy benzoquinone and 2, 6-dimethoxy benzoquinone which are likely to exert some of its biological effects. FWGE interferes with anaerobic glycolysis, pentose cycle and ribonucleotide reductase. It has significant antiproliferative effects and kills tumor cells by the induction of apoptosis via the caspase-poly [ADP-ribose] polymerase-pathway. FWGE interacts synergistically with a variety of different anticancer drugs and exerted antimetastatic properties in mouse models. In addition, FWGE modulates immune response by downregulation of MHC-I complex and the induction of TNF-a and various interleukins. Data in the F-344 rat model provide evidence for a colon cancer preventing effect of FWGE. Clinical data from a randomized phase II trial in melanoma patients indicate a significant benefit for patients treated with dacarbazine in combination with FWGE in terms of progression free survival (PFS) and overall survival (OS). Similarly, data from studies in colorectal cancer suggested a benefit of FWGE treatment. Besides extension of OS and PFS, FWGE improved the quality of life in several studies.

Cancer cells possess unique metabolic signatures compared to normal cells, including shifts in aerobic glycolysis, glutaminolysis, and de novo biosynthesis of macromolecules. Targeting these changes with agents (drugs and dietary components) has been employed as strategies to reduce the complications associated with tumorigenesis. This paper highlights the ability of several food components to suppress tumor-specific metabolic pathways, including increased expression of glucose transporters, oncogenic tyrosine kinase, tumor-specific M2-type pyruvate kinase, and fatty acid synthase, and the detection of such effects using various metabonomic technologies, including liquid chromatography/mass spectrometry (LC/MS) and stable isotope-labeled MS. Stable isotope-mediated tracing technologies offer exciting opportunities for defining specific target(s) for food components. Exposures, especially during the early transition phase from normal to cancer, are critical for the translation of knowledge about food components into effective prevention strategies. Although appropriate dietary exposures needed to alter cellular metabolism remain inconsistent and/or ill-defined, validated metabonomic biomarkers for dietary components hold promise for establishing effective strategies for cancer prevention.

Model experiment was conducted with growing pigs fed diets containing zero or two levels (1 or 2 g/kg) of fermented wheat germ extract (FWGE). In the first part of the experiment (19 days between 49 and 68 days of age) weight gain and feed conversion were tested. The 2nd part of the experiment (21 days between 68 and 89 days of age) served to measure the effect of FWGE on some compartments of the immune system. In the first part of the experiment supplementation of the starters’ diet with FWGE yielded 7.8 and 14.2% additional daily weight gain in the 1st and 2nd experimental groups, respectively (P<0.05). Humoral immune response to purified horse globulin (PHG) antigen was unaffected by the treatment. The blastogenic response of lymphocytes to non specific mitogens (PHA, Con-A, PWM), phagocytic activity and phagocytic index as well as the intradermal PHA test was consistently and significantly enhanced by the treatments.

Wheat has been used as food and folk medicine. We have earlier reported that the administration of ethyl acetate extract of ferrmented wheat at 300 mg/kg body weight have anti-trypanosomal activity. To better understand the active constituent for anti-trypanosomal properties, the crude extract was partially purified using column chromatography to give fractions A, B and C, which were further characterized by gas chromatographic – mass spectral (GC/MS) analysis. The fractions identified 12, 14 and 23 compounds respectively. The major volatile compounds were classified into oxygenated hydrocarbon (manool, hexadecyl acetate and butyl dodecanoate) and n-hydrocarbon (1- eicosene).

Objective: The fermented wheat germ extract, which is the active ingredient of nutraceuticals widely used by cancer patients in Europe, Korea and the United States, possesses cytotoxic and anti-metastatic effects in various human malignancies. In estrogen responsive MCF-7 breast cancer cells, it has been shown to potentiate the induction of apoptosis by tamoxifen. However, its effects in triple-negative and Her2-overexpressing breast cancer cells and interactions with chemotherapy have not been investigated until now. Methods: Cytotoxicity of FWGE lyophilisate alone and in combination with docetaxel was assessed by MTT and clonogenic assays in MCF-7 estrogen responsive, HCC-38 triple-negative and SKBR-3 Her2/neu overexpressing cells. Cell cycle phase distribution was determined by FACS. Apoptosisassociated activaton of caspase-3/7 was measured by Caspase-Glo Assay. Inhibition of tumor cell invasion was quantified using the ORIS Cell Invasion kit. Results: FWGE lyophilisate exhibited highest cytotoxic activity against triple negative HCC-38 cells in MTT and clonogenic assays with IC50 values of 180 and 15 lg/ml, respectively, indicating likely clinical activity.

Over the years, I have read about dozens of alternative treatments that have been promoted for controlling or reversing cancer, including, but by no means limited to, laetrile, macrobiotics, Hoxsey, Gerson, and Krebiozen.While conventional treatments (surgery, chemotherapy, and radiation) are often brutal—and serious questions remain about their long-term effectiveness—a certain skepticism is warranted when it comes to claims of alternative therapies for cancer. In the late 1960s, I was convinced that laetrile had real merit—until a study funded by the drug’s advocates found that vitamin A was more effective. I do believe that some alternative therapies for cancer have been of exceptional value, such as a 1950s-era immune-enhancing therapy known as Krebiozen (and a later variation known as Carcalon), although it faded into history with the death of its chief researcher and clinician, Andrew Ivy, MD, in 1978. Likewise, considerable research now supports the use of high-dose intravenous vitamin C as an adjunct treatment for cancer.1,2 Many alternative therapies have grown out of personal or anecdotal reports—that is, by sharing the knowledge of an unexpected benefit.

We all know someone who has been touched by cancer. This disease is personal, no matter who you are. And unfortunately, it’s only getting worse… President Nixon declared a “War on Cancer” when he signed the National Cancer Act in 1971. Since then, many health authorities have pointed to statistics that supposedly illustrate our progress. Most often, they cite an increasing survival rate. But they’re missing the full picture. Modern technology and aggressive screening programs detect cancer at a much earlier stage. Plus, researchers include nonthreatening cancers in the survival statistics. So if your cousin Harry is still alive five years after he had that mole removed from his hand… he’s counted as a “survivor.” Regardless of how the numbers are presented, cancer continues to increase. Since the 1970s, the incidence rate, the mortality rate, and the number of diagnoses have all gone up. A hundred years ago, one out of every 33 people was diagnosed with cancer in their lifetime. 

Background & objectives: Nutritional compounds which display anti-inflammatory and antioxidant effects have specific applications in preventing oxidative stress and endothelial dysfunction. In this study we evaluated the effect of Lisosan G (powder of Triticum sativum grains) on human microvascular endothelial cells (HMEC-1) exposed to oxidized low density lipoprotein (ox-LDL). Methods: The protective effects of Lisosan G were evaluated on human microvascular endothelial cells exposed to ox-LDL. Intercellular adhesion molecular-1 (ICAM-1), endothelin-1 (ET-1), and interleukin-6 (IL-6) concentrations and the expression of the respective genes were evaluated in response to incubation with ox-LDL, after co-incubation with ox-LDL and Lisosan G or exposed to Lisosan G alone. The analysis of LOX-1 gene was performed with RT-PCR semi quantitative method. The degree of oxidation induced in relation to control, was established by measurement of malondialdehyde (MDA) production. Results: The incubation with ox-LDL induced a significant increase in ICAM-1, IL-6 and ET-1 levels compared to the basal condition (P<0.01, P<0.05, and P<0.01, respectively), while in presence of Lisosan G, ICAM-1 levels showed a significant reduction both compared to the cultures treated with ox-LDL and control (P<0.01). 

Objective: Most women with advanced-stage epithelial ovarian cancer (OVCA) ultimately develop chemoresistant recurrent disease. Therefore, a great need to develop new, more active, and less toxic agents and/or to optimize the efficacy of existing agents exists. Methods: In this study, we investigated the activity of FWGE , a natural, nontoxic, fermented wheat germ extract (FWGE), against a range of OVCA cell lines, both alone and in combination with cisplatin chemotherapy and delineated the molecular signaling pathways that underlie FWGE activity at a genome-wide level. Results: We found that FWGE exhibited significant antiproliferative effects against 12 human OVCA cell lines and potentiated cisplatin-induced apoptosis. Pearson correlation of FWGE sensitivity and gene expression data identified 2142 genes (false discovery rate G 0.2) representing 27 biologic pathways (P G 0.05) to be significantly associated with FWGE sensitivity. A parallel analysis of genomic data for 59 human cancer cell lines matched to chemosensitivity data for 2,6-dimethoxy-p-benzoquinone, a proposed active component of FWGE, identified representation of 13 pathways common to both FWGE and 2,6-dimethoxy-p-benzoquinone sensitivity. Conclusions:

To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment as outpatients of those with fever and neutropenia. Methods A literature search identified relevant studies published in English. Primary outcomes included: development of fever and/or infections in afebrile neutropenic outpatients and recovery without complications and overall mortality in febrile neutropenic outpatients. Secondary outcomes included: in afebrile neutropenic outpatients, infection-related mortality; in outpatients with fever and neutropenia, defervescence without regimen change, time to defervescence, infectious complications, and recurrent fever; and in both groups, hospital admissions, duration, and adverse effects of antimicrobials. An Expert Panel developed guidelines based on extracted data and informal consensus. Results Forty-seven articles from 43 studies met selection criteria. Recommendations Antibacterial and antifungal prophylaxis are only recommended for patients expected to have
100 neutrophils/
L for 7 days, unless other factors increase risks for complications or mortality to similar levels. Inpatient treatment is standard to manage febrile neutropenic episodes, although carefully selected patients may be managed as outpatients after systematic assessment beginning with a validated risk index (eg, Multinational Association for Supportive Care in Cancer [MASCC] score or Talcott’s rules). 

Az FWGE , amely a rákos megbetegedésekben szenvedő betegek részére az FDA által jóváhagyott kiegészítő készítmény, serkenti a sejtszintű immunitást, javítja a hematológiai paramétereket, apoptózist indukál malignus sejtekben, valamint mérsékli az autoimmun reakciókat. Ezen hatások arra utalnak, hogy az FWGE gátló hatást fejthet ki a humán/állati immunszuppresszív vírusokra. Célok: A vizsgálat célja az FWGE által az etiológiai ágensre (macska immundeficiencia vírus, FIV) és annak tranzaktivációs kofaktorára (macska adenovírus, FeADV) kifejtett gátló hatásának in vitro tanulmányozása macska AIDS-modellben. Módszerek: Macska limfoid (MBM) és vese (CrFK) sejtkultúrákat amerikai (FIV-Pet) és európai (FIVPisa/M2) FIV izolátumokkal fertőztünk meg és tenyésztettünk a FIV-et folyamatosan termelő FL-4 limfoid sejtekkel egyetemben. Emellett humán méhnyakrák sejtvonalat (HeLa) és CrFK sejteket fertőztünk meg FeAdV-vel. A fertőzött és a nem fertőzött sejteket FWGE hígítási sorral kezeltük, majd a szer toxikus hatását (fotometriás assay segítségével), valamint a virális citopátiás hatást és a vírusterhelést (p24 antigén ELISA) monitoroztuk.

Fermented wheat germ extract (FWGE) is a multi-substance composition and currently used as nutrition supplement for cancer patients. Nanotechnology holds promise for medication and nutrition because materials at the nanometer dimension exhibit novel properties different from those of both isolated atom and bulk material. Selenium nano particle (Nano-Se) is a novel Se species with novel biological activities and low toxicity. The aim of our study is to evaluate antitumor activity of fermented wheat germ extract and fermented wheat germ extract in combination with selenium nanoparticles (FWGE-nano-Se mixture). The two prepared materials were applied on an experimental carcinogenesis model in order to evaluate their in vitro and in vivo antitumor potential; against animal carcinogenesis "Ehrlich carcinoma". Cytotoicity assay of different concentrations of FWGE and FWGE-nano-Se mixture on EAC cells was evaluated by trypan blue exclusion method. In vivo studies were done by induction of solid tumors produced by intramuscular inoculation of EAC in the right thigh of the lower limb of each mouse and treating Erlich tumor bearing mice orally with FWGE and FWGE-nano-Se mixture for 6 weeks. Tumor volume was determined all over the experimental period. Blood, liver and tumor tissue samples were collected after 2 and 6 weeks from the beginning of treatment.

Chemotherapie in der Onkologie Krebs stellt nach kardiovaskulären Erkrankungen die häufigste Todesursache in den Industrienationen dar. Die Weltgesundheitsorganisation WHO rechnet mit einem massiven Anstieg der Krebsinzidenz in den nächsten Jahrzehnten. Betrug die Zahl neuer Krebsfälle im Jahr 2007 weltweit noch ca. 11 Millionen, so werden für das Jahr 2030 mehr als 15 Millionen Neuerkrankungen prognostiziert (http://www.who.int/features/qa/15/en/index.html). Fortschritte in der onkologischen Forschung haben dazu geführt, dass heute effektive und nebenwirkungsärmere Medikamente für die Krebstherapie zur Verfügung stehen (Deininger et al. 2005; Kawai und Akaza 2010). Das Konzept, Krebserkrankungen chemotherapeutisch zu behandeln, fand ihren Anfang in der ersten Hälfte des 20. Jahrhunderts. Der deutsche Chemiker und Nobelpreisträger Paul Ehrlich führte erstmals chemische Modifizierungen an bekannten Arsenverbindungen durch, um ihre Nebenwirkung („Giftigkeit“) zu mindern, aber ihre Wirksamkeit zu erhalten. Dieses systematische Vorgehen führte 1909 zur Entdeckung von Salvarsan, einem arsenhaltigen Medikament zur Therapie der Syphilis. Ehrlichs Anstrengungen, mit der Strategie der gezielten chemischen Synthese auch Medikamente zur Krebsbehandlung zu entwickeln, blieben dagegen erfolglos.

Many plants exhibit antioxidant properties which may be useful in the prevention of oxidative stress reactions, such as those mediated by the formation of free radical species in different pathological situations. In recent years a number of studies have shown that whole grain products in particular have strong antioxidant activity. Primary cultures of rat hepatocytes were used to investigate whether and how a fermented powder of wheat (Lisosan G) is able to modulate antioxidant and detoxifying enzymes, and whether or not it can activate Nrf2 transcription factor or inhibit NF-kB activation. All of the antioxidant and detoxifying enzymes studied were significantly up-regulated by 0.7 mg/ml Lisosan G treatment. In particular, NAD(P)H:quinone oxidoreductase and heme oxygenase-1 were induced, although to different degrees, at the transcriptional, protein and/or activity levels by the treatment. As for the Nrf2 transcription factor, a partial translocation of its protein from the cytosol to the nucleus after 1 h of Lisosan G treatment was revealed by immunoblotting. Lisosan G was also observed to decrease H2O2-induced toxicity Taken together, these results show that this powder of wheat is an effective inducer of ARE/Nrf2-regulated antioxidant and detoxifying genes and has the potential to inhibit the translocation of NF-kB into the nucleus.

Millions of Americans will be eating out at restaurants or at loved one’s homes this holiday season. But be careful, you may be gobbling down more than just turkey dinner! More on that dinner-time disaster later, but first let’s talk tummy troubles. Sam, a pleasant forty-five year old attorney sought my help for a decade old struggle with irritable bowel syndrome (IBS). His problem was bloating, gas, and an uneasy sensation in his abdomen. These symptoms were a source of stress for him in an already stressful environment—the courtroom. I explained to Sam that IBS is a very common condition. It affects approximately 30 percent of the US adult population. 

There is growing evidence that tumor-associated immune imbalance is an important prognostic factor in several types of malignancy. Results from basic research as well as several case reports on sarcoma patients suggest that immune function may be improved by plant immunomodulators. Such treatments hold promise to partially restore the impaired balance along the regulatory access of the innate immune system that may be critical for clinical outcomes. There is also some evidence that combined therapy with plant preparations such as mistletoe extract injections with fixed Viscum album lectin content (0.5 to 1.0 ng/kg twice a week), rice bran preparation with a fixed dose of arabinoxylan (12 to 45 mg/kg twice a week) and wheat germ extract with a fixed dose of 2.6-dimethoxy-p-benzoquinone (50 to 80 mg/kg four times a week) on top of conventional oncotherapy may result in complete remission of hepatic metastases. These results suggest that the combination of these plant immunomodulators with conventional oncologic treatments can render possible complete remissions which are rarely attainable by oncologic therapies only. Studies using SF-36 questionnaires reported improved quality of life in advanced stages of various malignancies with plant-derived lectin immunomodulator. Combined therapy with plant immunomodulators, which are able to bind pattern recognition receptors on effector cells of innate immune system, may improve outcomes compared to conventional oncotherapy. However, further studies are required to provide additional evidence. 

Abstract Defatted wheat germ peptides (DWGPs) were prepared by fermentation with Bacillus Subtilis B1 and the antioxidant activities of DWGPs were investigated. The fermentation condition was optimized by response surface method (RSM) with three factors and three levels according to Box-Behnken theory. A maximal yield of DWGPs was achieved 8.69 mg/mL under optimal conditions: inoculum size 8%, fermentation temperature 31 °C and time 48 h. The main portion in the hydrolysates after fermentation was not free amino acid but peptide. The main molecular weight distribution of DWGPs was lower than 1000 Da. A positive correlation (R2 =0.9911) was found between concentration of DWGPs and total antioxidant capacity (T-AOC). DWGPs presented a significant does-dependent on scavenging activities of DPPH, hydroxyl and superoxide anion radicals. The EC50 values for the scavenging rates of DPPH, hydroxyl and superoxide anion radicals were 3.16 mg/mL, 6.04 mg/mL and 7.46 mg/mL, respectively. The results suggested that DWGPs produced by fermentation could be used as a promising antioxidant ingredient.

Abstract: Background: Metastatic hepatocellular carcinoma often has a multifocal tumor pattern with markedly depressed hepatic function. Hepatic resection in many cases results in no long-term benefit. After a chemotherapy hepatic tumors rarely disappear completely and the duration of responses is short. In the last decades growing evidence suggested that a disturbed balance in the innate system can also play a role in the poor prognosis of hepatic tumors. Objectives: The aim of this article is to present and discuss several favorable clinical responses of patients with hepatic metastases who parallel to conventional oncologic therapy, were treated with immunologically effective and standardized plant extracts. Course of Therapy and Results: In accordance with the bell-shaped dose-response relationship of mistletoe lectins (MLs), the patients were treated with a fermented mistletoe extract (ME) preparation, standardized for the active sugarbinding lectin contents. Thus, an optimal dose between 0.5 and 1.0ng/kg MLs was given twice a week subcutaneously. In addition to ML therapy, a heteropolysaccharide rice bran preparation standardized for arabinoxylan (12-45mg/kg MGN-3/BiobranR twice a week) and wheat germ extract (WGE) standardized for 2, 6-dimethoxy-p-benzoquinone (50- 80mg/kg FWGE four times a week) was also given. In these case reports the clinical progress of seven patients showed a complete or nearly complete remission of hepatic metastases. 

Abstract Background: In the last decade, several studies described the promising cytotoxic activity of fermented wheat germ towards cancer cell lines and during in vivo clinical trials. Recent data suggested that the antiproliferative, antimetastatic and immunological effects of this preparation are mainly attributed to quinones. This study aimed at exploiting the potential of sourdough lactic acid bacteria fermentation to release 2-methoxy benzoquinone, and 2,6-dimethoxybenzoquinone, which are naturally present in wheat germ as glycosylated and non-physiologically active form. Results: Preliminarily, forty strains of lactic acid bacteria, previously isolated from wheat germ, were in vitro screened based on β-glucosidase activity. Lactobacillus plantarum LB1 and Lactobacillus rossiae LB5 were selected based on the highest enzyme activity and on technology features. These strains were used in combination to ferment wheat germ. Raw wheat germ, without bacterial inoculum, was subjected to the same incubation and used as the control. 

Professor Hidvegi, how did you come up with the idea of working on the wheat germ and the original fermentation process? Drug research has always been fundamental in my family. My Transylvanian­Armenian grandfather, Professor Lajos David was the organizer of the Department of Pharmacy of the University of Szeged in the 1920’s. He was elected as the Dean of the Faculty of Medicine, the first and only pharmacist who has reached this highest position at the University since. My grandfather was a devout Roman catholic, who publicly opposed Nazi persecution of Jews during the Holocaust. One of his colleagues and, perhaps his best friend, was Albert Szent­Gyorgyi, the Nobel laureate who discovered vitamin C. After II. World War Szent­Gyorgyi moved to the United States where he made significant contributions to muscle biochemistry. In his later years he turned to cancer research with the goal to find a cure for cancer.

Colorectal cancer is the leading cause of cancer-related mortality in the western world. It is also the third most common cancer diagnosed in both men and women in the United States with a recent estimate for new cases of colorectal cancer in the year 2012 being around 103,170. Various risk factors for colorectal cancer include life-style, diet, age, personal and family history, and racial and ethnic background. While a few cancers are certainly preventable but this does not hold true for colon cancer as it is often detected in its advanced stage and generally not diagnosed until symptoms become apparent. Despite the fact that several options are available for treating this cancer through surgery, chemotherapy, radiation therapy, immunotherapy, and nutritionalsupplement therapy, but the success rates are not very encouraging when used alone where secondary complications appear in almost all these therapies. To maximize the therapeutic-effects in patients, combinatorial approaches are essential. In this review we have discussed the therapies previously and currently available to patients diagnosed with colorectal-cancer, focus on some recent developments in basic research that has shaded lights on new therapeutic-concepts utilizing macrophages/dendritic cells, natural killer cells, gene delivery, siRNA-, and microRNAtechnology, and specific-targeting of tyrosine kinases that are either mutated or over-expressed in the cancerous cell to treat these cancer. Potential strategies are discussed where these concepts could be applied to the existing therapies under a comprehensive approach to enhance the therapeutic effects. 

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. Due to the difficulties of early diagnosis, curative treatments are not available for most patients. Palliative treatments such as chemotherapy are often associated with low response rate, strong adverse effects and limited clinical benefits for patients. The alternative approaches such as fermented wheat germ extract (FWGE) with anti-tumor efficacy may provide improvements in the clinical outcome of current therapy for HCC. This study aimed to clarify antitumor efficacy of FWGE and the combination drug effect of FWGE with chemotherapeutic agents, cisplatin and 5-fluorouracil (5-Fu) in human HCC cells, HepG2, Hep3B, and HepJ5. The present study indicated that FWGE exhibited potential to suppress HepG2, Hep3B, and HepJ5 cells, with the half maximal inhibitory concentrations (IC50) of FWGE were 0.494, 0.371 and 1.524 mg/mL, respectively. FWGE also induced Poly (Adenosine diphosphate ribose) polymerase (PARP) associated cell death in Hep3B cells. Moreover, the FWGE treatment further enhanced the cytotoxicity of cisplatin in all tested HCC cells, and cytotoxicity of 5-Fu in a synergistic manner in HepJ5 cells. Collectively, the results identified the anti-tumor efficacy of FWGE in HCC cells and suggested that FWGE can be used as a supplement to effectively improve the tumor suppression efficiency of cisplatin and 5-Fu in HCC cells.

Abstract Designer foods are normal foods fortified with health promoting ingredients. These foods are similar in appearance to normal foods and are consumed regularly as a part of diet. In this article we have reviewed the global regulatory status and benefits of available designer foods such as designer egg, designer milk, designer grains, probiotics, designer foods enriched with micro and macronutrients and designer proteins. Designer foods are produced by the process of fortification or nutrification. With the advances in the biotechnology, biofortification of foods using technologies such as recombinant DNA technology and fermentation procedures are gaining advantage in the industry. The ultimate acceptability and extensive use of designer foods depend on proper regulation in the market by the regulatory authorities of the country and by creating consumer awareness about their health benefits through various nationwide programs.

The aim of this experiment was to determine whether wheat germ extract has an increasing cytotoxic activity or any cytotoxic activity on the malignant glioblastoma cancer cells. Thus, this paper includes the comparison of cell viability after the exposition to different concentrations of Wheat Germ Extract (WGE) in medium. My research question was: “How does the cytotoxic activity measured by the percentage of remaining living cells found in Methylthiazol Tetrazolium Assay test (MTT) of glioblastoma multiforme cells differ according to their exposition to different concentrations of wheat germ extract?” My hypothesis was: “As the concentration of applied WGE increases, the cytotoxic activity in glioblastoma cells will also increase. It is expected that the rapidly proliferating cells will be slowed down and largely killed as the WGE concentration increases.” To answer the research question, WGE was produced and given to glioblastoma cells in 6 different concentrations starting from 10% to 35%, increasing 5 by 5 in growth medium. Distilled water was given to the control group at the same concentrations in medium as distilled water was used during the production of WGE and it was important to check whether WGE or distilled water had the cytotoxic effect on cells. The cells were left in a CO2 incubator for 48 hours. After 48 hours, the medium, distilled water, WGE were extracted from the cells and were replaced with MTT. An MTT test was applied and viability was calculated with the results. It was clear that the cytotoxic activity increased as the WGE concentration increased and more than half of the cells went through apoptosis at 35% WGE exposure. Such a conclusion gives hope towards the future of curing of cancer and raises new questions about the usage of WGE.

Abstract: A wide range of health benefits have been attributed to wheatgrass, the young grass of the common wheat plant Triticum aestivum. Its components include chlorophyll, flavonoids, and vitamins C and E. Forms of wheatgrass include fresh juice, frozen juice, tablets, and powders, with compositions varying according to their production processes, as well as to the growing conditions of the wheatgrass. Laboratory in vitro studies, mostly using the fermented wheat germ extract, have demonstrated anticancer potential and have identified apoptosis as a possible mechanism. In animal experiments, wheatgrass demonstrated benefits in cancer prevention and as an adjunct to cancer treatment, as well as benefits to immunological activity and oxidative stress. Clinical trials show that wheatgrass may induce synergistic benefits to chemotherapy and may attenuate chemotherapy-related side effects, as well as benefit rheumatoid arthritis, ulcerative colitis, hematological diseases, diabetes, obesity, and oxidative stress. However, all the trials were small and a number of methodological problems arose. No adverse events of wheatgrass have been reported, although some forms pose problems of tolerability. The popularity of wheatgrass continues to grow. Nevertheless, the advantages seen in the clinical trials need to be proved in larger studies before clinical recommendations for the public can be given.

2,6-Dimethoxy-1,4-benzoquinone (2,6-DMBQ) is the major bioactive compound found in fermented wheat germ extract. Although fermented wheat germ extract has been reported to show antiproliferative and anti-metabolic effects in various cancers, the anticancer potential and molecular mechanisms exerted by 2,6-DMBQ have not been investigated in non-small cell lung cancer (NSCLC) cells. Here, we report that 2,6-DMBQ suppresses NSCLC cell growth and migration through inhibiting activation of AKT and p38 MAPK. 2,6-DMBQ significantly suppressed anchorage-dependent and independent cell growth. Additionally, 2,6-DMBQ induced G2 phase cell cycle arrest through inhibiting the expression and phosphorylation of cyclin B1 and CDC2, respectively. Furthermore, 2,6-DMBQ strongly suppressed NSCLC cell migration through induction of E-cadherin expression. To determine the molecular mechanism(s) exerted by 2,6-DMBQ upon NSCLC cell lines, various signaling kinases were screened; the results indicate that 2,6-DMBQ strongly inhibits the phosphorylation of AKT and p38 MAPK. Additionally, the growth kinetics of cells treated with an AKT or p38 MAPK inhibitor in combination with 2,6-DMBQ indicate that 2,6-DMBQ suppresses NSCLC cell growth and migration through inhibition of AKT and p38 MAPK. Taken together, our results suggest that 2,6-DMBQ is a potential anticancer reagent against NSCLC cells and could be useful for treating lung cancer patients. © 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society

Abstract

Background:  Fermented wheat germ extract has been reported to exert various pharmacological activities,

including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-

benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its

anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated.

Methods: Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis.

Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell

lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed

using gastric cancer patient-derived xenograft models.

Results: 2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric

cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is

dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived

xenograft gastric tumor growth in an in vivo mouse model.

Conclusions: 2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic

implications for gastric cancer patients.

Keywords:  2,6-DMBQ, mTOR, p70S6K, Gastric cancer, Patient-derived xenograft