25 research outputs found
Adjuvant Cancer Biotherapy by Viscum Album Extract Isorel: Overview of Evidence Based Medicine Findings
Within the integrative medicine one of the most frequently used adjuvant cancer biotherapies is based on aqueous mistletoe (Viscum album) extracts. Tumor growth inhibition, stimulation of host immune response and improvement of the quality of life are the positive effects of mistletoe therapy described in several preclinical and clinical studies. However, cumulative results of the evidence based medicine findings on such treatments are rarely given. Therefore, this paper evaluates the evidence based findings describing effects of the Viscum album extract Isorel in cancer therapy with respect to the type of therapy, stage and type of illness. This study presents cumulated data for 74 patients with different types and stages of cancer treated by Viscum album extract as adjuvant treatment to different conventional therapies, mostly combined surgery and radiotherapy. The biotherapy effectiveness was evaluated according to the outcome as 1) no major therapeutic improvement (15% of patients), 2) prevention of tumor recurrence (47% of patients) and 3) regression of cancer (38% of patients). Notably, there was no obvious health worsening during the follow up period at all. Thus, the results obtained for conventional anticancer therapies combined with adjuvant biotherapy based on Viscum album extract seem to be beneficial for the majority of cancer patients (85%) without serious side effects
Adjuvant Cancer Biotherapy by Viscum Album Extract Isorel: Overview of Evidence Based Medicine Findings
Within the integrative medicine one of the most frequently used adjuvant cancer biotherapies is based on aqueous mistletoe (Viscum album) extracts. Tumor growth inhibition, stimulation of host immune response and improvement of the quality of life are the positive effects of mistletoe therapy described in several preclinical and clinical studies. However, cumulative results of the evidence based medicine findings on such treatments are rarely given. Therefore, this paper evaluates the evidence based findings describing effects of the Viscum album extract Isorel in cancer therapy with respect to the type of therapy, stage and type of illness. This study presents cumulated data for 74 patients with different types and stages of cancer treated by Viscum album extract as adjuvant treatment to different conventional therapies, mostly combined surgery and radiotherapy. The biotherapy effectiveness was evaluated according to the outcome as 1) no major therapeutic improvement (15% of patients), 2) prevention of tumor recurrence (47% of patients) and 3) regression of cancer (38% of patients). Notably, there was no obvious health worsening during the follow up period at all. Thus, the results obtained for conventional anticancer therapies combined with adjuvant biotherapy based on Viscum album extract seem to be beneficial for the majority of cancer patients (85%) without serious side effects
Growth Modulation of Human Cells in Vitro by Mild Oxidative Stress and 1,4-Dihydropyridine Derivative Antioxidants
Reactive oxygen species and lipid peroxidation products are not only cytotoxic but may also modulate signal transduction
in cells. Accordingly, antioxidants may be considered as modifiers of cellular redox signaling. Therefore, the effects
of two novel synthetic antioxidants, analogues of 1,4-dihydropyridine derivatives, cerebrocrast and Z41-74 were
analysed in vitro on human osteosarcoma cell line HOS, the growth of which can be modulated by lipid peroxidation.
The cells were pretreated with either cerebrocrast or Z41-74 and afterwards exposed to mild, copper induced lipid peroxidation
or to 4-hydroxynonenal (HNE), the end product of lipid peroxidation. The results obtained have shown that
both antioxidants exert growth modulating effects interfering with the lipid peroxidation. Namely, cells treated with antioxidants
showed increased metabolic rate and cell growth, thereby attenuating the effects of lipid peroxidation. Such
biomodulating effects of cerebrocrast and Z41-74 resembled growth modulating effects of HNE, suggesting that the antioxidants
could eventually promote cellular adaptation to oxidative stress interacting with redox signaling and hydroxynonenal
HNE-signal transduction pathways. This may be of particular relevance for better understanding the beneficial
role of hydroxynonenal HNE in cell growth control. Therefore, cerebrocrast and Z41-74 could be convenient to study further
oxidative homeostasis involving lipid peroxidation
Growth Modulation of Human Cells in Vitro by Mild Oxidative Stress and 1,4-Dihydropyridine Derivative Antioxidants
Reactive oxygen species and lipid peroxidation products are not only cytotoxic but may also modulate signal transduction
in cells. Accordingly, antioxidants may be considered as modifiers of cellular redox signaling. Therefore, the effects
of two novel synthetic antioxidants, analogues of 1,4-dihydropyridine derivatives, cerebrocrast and Z41-74 were
analysed in vitro on human osteosarcoma cell line HOS, the growth of which can be modulated by lipid peroxidation.
The cells were pretreated with either cerebrocrast or Z41-74 and afterwards exposed to mild, copper induced lipid peroxidation
or to 4-hydroxynonenal (HNE), the end product of lipid peroxidation. The results obtained have shown that
both antioxidants exert growth modulating effects interfering with the lipid peroxidation. Namely, cells treated with antioxidants
showed increased metabolic rate and cell growth, thereby attenuating the effects of lipid peroxidation. Such
biomodulating effects of cerebrocrast and Z41-74 resembled growth modulating effects of HNE, suggesting that the antioxidants
could eventually promote cellular adaptation to oxidative stress interacting with redox signaling and hydroxynonenal
HNE-signal transduction pathways. This may be of particular relevance for better understanding the beneficial
role of hydroxynonenal HNE in cell growth control. Therefore, cerebrocrast and Z41-74 could be convenient to study further
oxidative homeostasis involving lipid peroxidation
Double-edged sword behaviour of gallic acid and its interaction with peroxidases in human microvascular endothelial cell culture (HMEC-1). Antioxidant and pro-oxidant effects*
A previous report from our group had shown in vitro a
direct interaction between peroxidases and dietary antioxidants
at physiological concentrations, where in the
absence of H2O2, the antioxidants could serve as oxidizing
substrates for the peroxidases. However, the physiological
relevance of those findings had not been evaluated.
The main objective of this study was to determine
whether the oxidizing products produced in the interaction
between peroxidase and gallic acid at a physiological
concentration of 1 μM may promote cell death or
survival in a human microvascular endothelial cell line
(HMEC-1). Our findings suggested that gallic acid may
show a double-edged sword behaviour, since in the absence
of H2O2 it may have a pro-oxidant effect which
may promote cell injury (evidenced by LDH, Crystal Violet
and calcein AM viability/citotoxicity assays), while in
the presence of H2O2, gallic acid may act as an antioxidant
inhibiting oxidative species produced in the peroxidase
cycle of peroxidases. These observations were confirmed
with several oxidative stress biomarkers and the
evaluation of the activation of cell survival pathways like
AKT and MAPK/ERK.This study was supported by grants from the Spanish Ministry of Science and Innovation (CENIT METDEV- FUN) to M. Portero-Otín, the Spanish Instituto de Salud Carlos III (FIS PI081238) to J. Boada and (FIS PI081843) to M. Portero-Otin and by the COST action B35
Clinical relevance of biomarkers of oxidative stress
SIGNIFICANCE
Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance.
CRITICAL ISSUES
The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use.
FUTURE DIRECTIONS
Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000
Metabolic control in type 2 diabetes is associated with sulfonylurea receptor-1 (SUR-1) but not with KCNJ11 polymorphisms
Background ----- The sulfonylureas are hypoglycemic agents used for promotion of insulin secretion in type 2 diabetics. They bind to sulfonylurea receptor-1 (SUR-1), which is a functional subunit of the ATP-sensitive potassium channel (KATP). The other component of potassium channel is Kir6.2, encoded by gene KCNJ11. Polymorphisms in these genes may lead to modulated response to sulfonylurea therapy. Aim ----- Aim of this study was to determine a relationship between SUR-1 [exon 16 (-3C/T), exon 31 (Arg1273Arg; AGG→AGA) and exon 33 (S1369A)] and KCNJ11 (E23K) polymorphisms and following parameters of metabolic control in type 2 diabetes: fasting plasma glucose (FPG), postprandial glucose (PPG) and HbA1c in Caucasian type 2 diabetics of the European origin. Methods ----- A total of 228 unrelated patients with type 2 diabetes on sulfonylurea therapy were included in the study. Genotyping of all polymorphisms was performed by PCR-RFLP method; biochemical parameters were determined using standard laboratory methods. Results ----- There was no difference in FPG and PPG concentration in any of the genotype subgroups. However, diabetics with wild type C/C genotype of the SUR-1 exon 16 polymorphism had significantly lower HbA1c concentration compared to the patients with variant T/T genotype [6.9 (6.2-7.7) mmol/L vs. 8.1 (6.7-8.8) mmol/L; p = 0.009]. Also, patients with wild type G/G genotype of the SUR-1 exon 31 polymorphism had significantly higher HbA1c concentration compared to the patients with variant A/A genotype [7.8 (6.9-8.8) mmol/L vs. 6.3 (5.7-6.8) mmol/L; p < 0.001]. Conclusion ----- SUR-1 exon 16 and exon 31 polymorphisms are significantly associated with HbA1c concentration
Induction of CMV-1 promoter by 4-hydroxy-2-nonenal in human embryonic kidney cells
Oxidative stress, i.e., excessive production of oxygen free radicals and reactive oxygen species, leads to lipid peroxidation and to formation of reactive aldehydes which act as second messengers of free radicals. It has previously been shown that oxidative stress may be involved in the transcriptional regulation of cytomegalovirus (CMV) immediate early promoter, involved in viral reactivation from latency. In the current study we used a plasmid containing the yellow fluorescent protein (YFP) gene under the control of CMV-1 promoter to monitor the influence of hydrogen peroxide and reactive aldehydes, 4-hydroxy-2-nonenal (HNE) and acrolein, on CMV-1 promoter activation in human embryonic kidney cells (HEK293). While acrolein was ineffective, hydrogen peroxide slightly (50 %) stimulated the CMV promoter. In contrast, HNE had a strong, up to 3-fold, enhancing effect on the CMV-1 promoter within four as well as after 24h of treatment. The most effective was the treatment with 24 µM HNE. This effect of HNE suggests that stressful conditions associated with lipid peroxidation could lead to CMV activation