The Lymphatic System In The Brain Clearance Mechanisms - New Therapeutic Perspectives For Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Pathological deposits of neurotoxic proteins within the brain, such as amyloid-ß and hyperphosphorylated tau tangles, are the prominent features in AD. According to recent studies, the newly discovered brain lymphatic system was demonstrated to be crucial in the clearance of metabolic macromolecules from the brain. Meningeal lymphatic vessels located in the dura mater drain the fluid, macromolecules, and immune cells from cerebrospinal fluid (CSF) and transport them, as lymph, to the deep cervical lymph nodes. The lymphatic system provides the perivascular exchange of CSF with interstitial fluid (ISF) and ensures the homeostasis of neuronal interstitial space. In this review, we aim to summarize recent findings on the role of the lymphatic system in AD pathophysiology and discuss possible therapeutic perspectives, targeting the lymphatic clearance mechanisms within the brain.

Impact of NMDA receptor activation on DNA damage in PC12 neuron-like cell cultures in the presence of ß-amyloid peptides.

OBJECTIVE: This study aimed to investigate the effect of low nanomolar concentrations of Aß1-40 and Aß25-35 on DNA double-strand breaks following NMDA activation of cells. MATERIALS AND METHODS: After incubating the differentiated PC12 cells with Aß25-35, Aß1-40 or Aß1-42 for 24 h, the culture was washed and stimulated for 15 min with NMDA. Then, tests were performed at four-time intervals from stimulation to assess the viability of the culture, the level of oxygen free radicals, and the γH2AX and pATM kinase. NMDAR1 expression was also evaluated by performing immunocytochemical staining. RESULTS: It was found that amyloid peptides in nanomolar concentrations reduce double-stranded DNA breaks after NMDA neuron activation. A slight antioxidant effect was also demonstrated when measured 120 min after NMDA cell activation. CONCLUSION: The NMDA stimulation of PC12 cells led to a rapid increase in the number of double-stranded DNA breaks in the cells and is assumed to be the initial step in IEG activation and LTP induction. The effect of Aß on the reduction of double-strand breaks after NMDA cell stimulation indicates that at concentrations similar to physiological amyloid peptides, it may reduce the mobilization of the neuronal response to stimuli, leading to inhibition of LTP induction and decreasing synaptic plasticity in the early stages of Alzheimer's disease.

Lysosomal Exocytosis of Olivacine on the Way to Explain Drug Resistance in Cancer Cells.

Ellipticine is an indole alkaloid with proven antitumor activity against various tumors in vitro and a diverse mechanism of action, which includes topoisomerase II inhibition, intercalation, and cell cycle impact. Olivacine-ellipticine's isomer-shows similar properties. The objectives of this work were as follows: (a) to find a new path of olivacine synthesis, (b) to study the cytotoxic properties of olivacine and ellipticine in comparison to doxorubicin as well as their impact on the cell cycle, and (c) to investigate the cellular pharmacokinetics of the tested compounds to understand drug resistance in cancer cells better. SRB and MTT assays were used to study the anticancer activity of olivacine and ellipticine in vitro. Both compounds showed a cytotoxic effect on various cell lines, most notably on the doxorubicin-resistant LoVo/DX model, with olivacine's cytotoxicity approximately three times higher than doxorubicin. Olivacine proved to be less effective against cancer cells and less cytotoxic to normal cells than ellipticine. Olivacine proved to have fluorescent properties. Microscopic observation of cells treated with olivacine showed the difference in sensitivity depending on the cell line, with A549 cells visibly affected by a much lower concentration of olivacine than normal NHDF cells. An increased percentage of cells in G0/G1 was observed after treatment with olivacine and ellipticine, suggesting an impact on cell cycle progression, potentially via higher p53 protein expression, which blocks the transition from G0/G1 to the S phase. Ellipticine induced apoptosis at a concentration as low as 1 µM. It has been proved that the tested compounds (ellipticine and olivacine) undergo lysosomal exocytosis. Reducing exocytosis is possible through the use of compounds that inhibit the activity of the proton pump. Olivacine and ellipticine exhibited diverse cytotoxicity against a panel of cancer cells. Analysis of the lysosomal exocytosis of olivacine and ellipticine shows the need to look for derivatives with comparable anticancer activity but reduced weak base character.

Celastrol and Resveratrol Modulate SIRT Genes Expression and Exert Anticancer Activity in Colon Cancer Cells and Cancer Stem-like Cells.

Metastatic colorectal cancer (CRC) remains a hard-to-cure neoplasm worldwide. Its curability declines with successive lines of treatment due to the development of various cancer resistance mechanisms and the presence of colorectal cancer stem cells (CSCs). Celastrol and resveratrol are very promising phytochemicals for colon cancer therapy, owing to their pleiotropic activity that enables them to interact with various biological targets. In the present study, the anticancer activities of both compounds were investigated in metastatic colon cancer cells (LoVo cells) and cancer stem-like cells (LoVo/DX). We showed that celastrol is a very potent anti-tumor compound against metastatic colon cancer, capable of attenuating CSC-like cells at the molecular and cellular levels. In contrast, resveratrol has a much greater effect on colon cancer cells that are expressing standard sensitivity to anticancer drugs, than on CSC-like cells. In addition, both polyphenols have different influences on the expression of SIRT genes, which seems to be at least partly related to their anti-tumor activity.

Current and Near-Future Treatment of Alzheimer's Disease.

Recent findings have improved our understanding of the multifactorial nature of AD. While in early asymptomatic stages of AD, increased amyloid-ß synthesis and tau hyperphosphorylation play a key role, while in the latter stages of the disease, numerous dysfunctions of homeostatic mechanisms in neurons, glial cells, and cerebrovascular endothelium determine the rate of progression of clinical symptoms. The main driving forces of advanced neurodegeneration include increased inflammatory reactions in neurons and glial cells, oxidative stress, deficiencies in neurotrophic growth and regenerative capacity of neurons, brain insulin resistance with disturbed metabolism in neurons, or reduction of the activity of the Wnt-ß catenin pathway, which should integrate the homeostatic mechanisms of brain tissue. In order to more effectively inhibit the progress of neurodegeneration, combination therapies consisting of drugs that rectify several above-mentioned dysfunctions should be used. It should be noted that many widely-used drugs from various pharmacological groups, "in addition" to the main therapeutic indications, have a beneficial effect on neurodegeneration and may be introduced into clinical practice in combination therapy of AD. There is hope that complex treatment will effectively inhibit the progression of AD and turn it into a slowly progressing chronic disease. Moreover, as the mechanisms of bidirectional communication between the brain and microbiota are better understood, it is expected that these pathways will be harnessed to provide novel methods to enhance health and treat AD.

Interactions of Amyloid-ß with Membrane Proteins.

In developing and developed countries, an increasing elderly population is observed. This affects the growing percentage of people struggling with neurodegenerative diseases, including Alzheimer's disease. Nevertheless, the pathomechanism of this disease is still unknown. This contributes to problems with early diagnosis of the disease as well as with treatment. One of the most popular hypotheses of Alzheimer's disease is related to the pathological deposition of amyloid-ß (Aß) in the brain of ill people. In this paper, we discuss issues related to Aß and its relationship in the development of Alzheimer's disease. The structure of Aß and its interaction with the cell membrane are discussed. Not only do the extracellular plaques affect nerve cells, but other forms of this peptide as well.

Colorectal Adenocarcinoma Cell Culture in a Microfluidically Controlled Environment with a Static Molecular Gradient of Polyphenol.

To study the simultaneous effect of the molecular gradient of polyphenols (curcumin, trans-resveratrol, and wogonin) and biological factors released from tumor cells on apoptosis of adjacent cells, a novel microfluidic system was designed and manufactured. The small height/volume of microfluidic culture chambers and static conditions allowed for establishing the local microenvironment and maintaining undisturbed concentration profiles of naturally secreted from cells biochemical factors. In all trials, we observe that these conditions significantly affect cell viability by stimulating cell apoptosis at lower concentrations of polyphenols than in traditional multiwell cultures. The observed difference varied between 20.4-87.8% for curcumin, 11.0-37.5% for resveratrol, and 21.7-62.2% for wogonin. At low concentrations of polyphenols, the proapoptotic substances released from adjacent cells, like protein degradation products, significantly influence cell viability. The mean increase in cell mortality was 38.3% for microfluidic cultures. Our research has also confirmed that the gradient microsystem is useful in routine laboratory tests in the same way as a multiwell plate and may be treated as its replacement in the future. We elaborated the new repetitive procedures for cell culture and tests in static gradient conditions, which may become a gold standard of new drug investigations in the future.

Nuclear Envelope and Nuclear Pore Complexes in Neurodegenerative Diseases-New Perspectives for Therapeutic Interventions.

Transport of proteins, transcription factors, and other signaling molecules between the nucleus and cytoplasm is necessary for signal transduction. The study of these transport phenomena is particularly challenging in neurons because of their highly polarized structure. The bidirectional exchange of molecular cargoes across the nuclear envelope (NE) occurs through nuclear pore complexes (NPCs), which are aqueous channels embedded in the nuclear envelope. The NE and NPCs regulate nuclear transport but are also emerging as relevant regulators of chromatin organization and gene expression. The alterations in nuclear transport are regularly identified in affected neurons associated with human neurodegenerative diseases. This review presents insights into the roles played by nuclear transport defects in neurodegenerative disease, focusing primarily on NE proteins and NPCs. The subcellular mislocalization of proteins might be a very desirable means of therapeutic intervention in neurodegenerative disorders.

Were our Ancestors Right in Using Flax Dressings? Research on the Properties of Flax Fibre and Its Usefulness in Wound Healing.

BACKGROUND: Despite the wide range of medical dressings available commercially, there is still a search for better biomaterials for use in the treatment of especially difficult-to-heal wounds. For several years, attention has been paid to the use of substances, compounds, and even whole plants in medicine. Flax is a plant that has been used as a dressing for thousands of years. Therefore, we decided to test flax fibres that had previously been genetically modified as a potential wound dressing. MATERIALS AND METHODS: In this study, two modified flax fibres and their combinations were tested on cell lines (mice fibroblast, normal human dermal fibroblast, normal human epidermal keratinocytes, human dermal microvascular endothelial cell, epidermal carcinoma cancer cells, monocyte cells). In the tests, fibres of the traditional flax (Nike) were used as a control. Several experiments were performed to assess cell proliferation and viability, the number of apoptotic cells, the cell cycle, genotoxicity, the level of free oxygen radicals, and determination of the number of cells after 48 hours of incubation of cell cultures with the tested flax fibres. RESULTS: The obtained results confirm the positive influence of flax on the used cell lines. Both traditional fibres (Nike) and genetically modified fibres increased the proliferation of fibroblast cells and keratinocytes, reduced the level of free oxygen radicals, and influenced the repair of DNA damage. At the same time, the tested flax fibres did not have a proproliferative effect on the neoplastic cell line. Interestingly, genetic modifications had a stronger impact on the proliferative activity of fibroblasts, keratinocytes, and microvascular endothelium compared to the traditional flax fibre used. CONCLUSIONS: In this study, the positive properties of the tested flax fibres on cell lines were proved. In the next stage, it is worth carrying out in vivo tests of tested genetically modified flax fibres.

Effect of Novel Pyrrolo[3,4-d]pyridazinone Derivatives on Lipopolysaccharide-Induced Neuroinflammation.

Neuroinflammation is considered to be one of the potential causes for the development of neurodegenerative diseases, including Alzheimer's disease. In this study, we evaluated the effect of four newly synthesized pyrrolo[3,4-d]pyridazinone derivatives on the neuron-like PC12 cells under simulated inflammation conditions by preincubation with lipopolysaccharide (LPS). Our novel derivatives are selective cyclooxygenase-2 (COX-2) inhibitors and have similar effects to nonsteroidal anti-inflammatory drugs (NSAIDs). We assessed viability (LDH assay), metabolic activity (MTT assay), DNA damage (number of double-strand breaks measured by fast halo assay), and the neuronal features of cells (average neurite length and neurite outgrowth measured spectrofluorimetrically). DCF-DA and Griess assays were also performed, which allowed determining the impact of the tested compounds on the level of oxygen free radicals and nitrites. LPS administration significantly negatively affected the results in all tests performed, and treatment with the tested derivatives in most cases significantly reduced this negative impact. Multiple-criteria decision analysis indicated that overall, the best results were observed for compounds 2a and 2b at a concentration of 10 µM. The new derivatives showed intense activity against free oxygen radicals and nitrites. Reduced reactive oxygen species level also correlated with a decrease in the number of DNA damage. The compounds improved neuronal features, such as neurite length and outgrowth, and they also increased cell viability and mitochondrial activity. Our results suggest that derivatives 2a and 2b may also act additionally on mechanisms other than 3a and 3b.

Effect of new olivacine derivatives on p53 protein level.

BACKGROUND: The p53 protein is a transcription factor for many genes, including genes involved in inhibiting cell proliferation and inducing apoptosis in genotoxically damaged and tumor-transformed cells. In more than 55% of cases of human cancers, loss of the essential function of p53 protein is found. In numerous reports, it has been shown that small molecules (chemical compounds) can restore the suppressor function of the mutant p53 protein in tumor cells. The aim of this study was to evaluate the potential anticancer activity of three newly synthesized olivacine derivatives. METHODS: The study was performed using two cell lines-CCRF/CEM (containing the mutant p53 protein) and A549 (containing a non-mutant, wild-type p53 protein). The cells were incubated with olivacine derivatives for 18 h and then assays were carried out: measurement of the amount of p53 and p21 proteins, detection of apoptosis, cell cycle analysis, and rhodamine 123 accumulation assay (evaluation of P-glycoprotein inhibition). Multiple-criteria decision analysis was used to compare the anticancer activity of the tested compounds. RESULTS: Each tested compound caused the reconstitution of suppressor activity of the p53 protein in cells with the mutant protein. In addition, one of the compounds showed significant antitumor activity in both wild-type and mutant cells. For all compounds, a stronger effect on the level of the p53 protein was observed than for the reference compound-ellipticine. CONCLUSIONS: The observed effects of the tested new olivacine derivatives (pyridocarbazoles) suggest that they are good candidates for new anticancer drugs.

Impact of fabrics from transgenic flax on cultures of skin cells.

BACKGROUND: The development of a new type of wound dressing material that can support skin regeneration is an important challenge to improve treatment of chronic, non-healing wounds. OBJECTIVES: The objective of this study was to compare the impact of flax fabrics from transgenic plants overexpressing phenolic acids and flavonoids (W92) and polyhydroxybutyrate (M48), as well as fabric from non-transgenic plant (Nike) on cultures of human skin cells. MATERIAL AND METHODS: Flax fabric pieces as well as water extracts from the fabrics were co-cultured with human skin cells: keratinocytes, fibroblasts, dermal microvascular endothelial cells, and with monocytoid cell line (THP1) for 48 h. Cell viability and proliferation were assessed with the sulforhodamine B colorimetric assay. Intracellular reactive oxygen species (ROS) was estimated with the 2'7 dichlorodihydrofluorescein diacetate (DCFH-DA) oxidation method. Endothelial cell migration was measured with the scratch assay. The results were compared with the multi-criteria analysis (MCA) procedure. RESULTS: Tested flax fabrics released flavonoids and polyhydroxybutyrate to cell culture media, as it was determined by means of the high performance liquid chromatography (HPLC) method. Fabrics from transgenic plants W92 and M48 promoted proliferation of keratinocytes and fibroblasts. Water extracts from flax fabric diminished the proliferation of monocytoid cells, decreased oxidative burst in activated THP1 cells and accelerated the velocity of dermal microvascular cell migration. The MCA proved that the sum of beneficial effects estimated in human skin cell cultures was higher (by 47% and by 34% with W92 and M48, respectively) than that of non-transgenic flax fabric (Nike). CONCLUSIONS: The W92 and M48 fabrics should be further studied as candidates for elaboration of new types of bandages, able to improve skin wound healing.

Alzheimer's Disease - Future Therapy Based on Dendrimers.

Alzheimer's disease (AD) is characterized by the loss of neurons. It is the most common cause of dementia in the elderly population accompanied by pathological degeneration of neurofibrillary tangles. Senile plaques are formed with beta-amyloid, hyperphosphoryled tau protein, apolipoprotein E and presenilin associated with protease activity [amyloid beta (Aß), gamma-secretase (γS)]. The molecular mechanisms of neurodegeneration include apoptosis, oxidative stress (free radical generation), inflammation, immune activation, and others. The lack of effective treatments for AD stems mainly from the incomplete understanding the causes of AD. Currently, there are several hypotheses explaining the early mechanisms of AD pathogenesis. Recent years witnessed an unprecedented research growth in the area of nanotechnology, which uses atomic, molecular and macromolecular methods to create products in microscale (nanoscale) dimensions. In this article, we have discussed the role of nanotechnology in the development and improvement of techniques for early diagnosis and effective treatment of AD. Since AD pathology is practically irreversible, applications of disease-modifying treatments could be successful only if early diagnosis of AD is available. This review highlights various possibilities for the early diagnosis and therapy of AD and investigates potential adaptation of nanoparticles-dendrimers as a class of well-defined branched polymers that are chemically synthesized with a well-defined shape, size and nanoscopic physicochemical properties reminiscent of the proteins for the treatment of neurodegenerative diseases.

Chemopreventive activity of celastrol in drug-resistant human colon carcinoma cell cultures.

Celastrol (tripterine) a pentacyclic triterpenoid extracted from the roots of Tripterygium wilfordii Hook f., exhibits potent antioxidant and anti-inflammatory activity and also exerts important anti-cancer effects, as induction of apoptosis and lowering the level of drug resistance of several cancers. Increased level of cellular resistance to cytostatic drugs is typical for colorectal cancers, and largely determines the failure of chemotherapy for this tumor. The purpose of our research was to evaluate the chemopreventive effect of celastrol on cultures of colon cancer cells resistant to doxorubicin (LOVO/DX). With the use of flow cytometry we have shown that celastrol reduces the cell size of the SP (side population; subpopulation of cancer cells enriched with cancer stem cells), increases frequency of apoptosis and binds to Pgp protein in cell membranes inhibiting its transport function. The inhibition of the Pgp transport function has been shown to increase the accumulation of rhodamine-123 and standard cytostatic- doxorubicin in LOVO/DX cells. Our results prove that celastrol exhibits significant chemopreventive and chemosensitizing activities on drug resistant colon cancer cells. Celastrol appears to be a good candidate for adjuvant medicine that can improve the effectiveness of standard cytostatic therapy in humans.

RAGE-TLR Crosstalk Sustains Chronic Inflammation in Neurodegeneration.

Chronic inflammatory reactions are consistenly present in neurodegeneration of Alzheimer type and are considered important factors that accelerate progression of the disease. Receptors of innate immunity participate in triggering and driving inflammatory reactions. For example, Toll-like receptors (TLRs) and receptor for advanced glycation end product (RAGE), major receptors of innate immunity, play a central role in perpetuation of inflammation. RAGE activation should be perceived as a primary mechanism which determines self-perpetuated chronic inflammation, and RAGE cooperation with TLRs amplifies inflammatory signaling. In this review, we highlight and discuss that RAGE-TLR crosstalk emerges as an important driving force of chronic inflammation in Alzheimer's disease.

V79 Fibroblasts Are Protected Against Reactive Oxygen Species by Flax Fabric.

Chinese hamster pulmonary fibroblasts (V79 cells) pre-treated with flax fabrics derived from non-modified or genetically engineered flax fibres and treated with H2O2 revealed a markedly lower level of intracellular reactive oxygen species (ROS) than control, non-pre-treated cells. The fabrics were prepared from fibres derived from two kinds of transgenic plants: W92 plants, which overproduce flavonoids, and M type plants, which produce hydroxybutyrate polymer in their vascular bundles and thus in fibres. Incubating the V79 cells with the flax fabrics prior to H2O2 treatment also reduced the amount of DNA damage, as established using the comet assay (also known as alkaline single-cell gel electrophoresis) and pulsed-field electrophoresis of intact cellular DNA. Selected gene expression analysis revealed the activator impact of fabrics on the apoptotic (BCL2 family, caspases) gene expression. This promoting activity was also detected for histone acetyltransferase (HAT; MYST2) gene expression. The flax fabric derived from both GM flax plants exhibited a protective effect against oxidative stress and ROS-mediated genotoxic damage, but the W92 fabric was the strongest. It is thus suggested that these fabrics might be useful as a basis for new biomedical products (e.g. wound dressings) that actively protect cells against inflammation and degeneration.

Nanotechnology for Alzheimer Disease.

BACKGROUND: Alzheimer disease (AD) typically affects behavior, memory and thinking. The change in brain have been reported to begin approx. 10-20 years before the appearance of actual symptoms and diagnosis of AD. An early stage diagnosis and treatment of this lethal disease is the prime challenge, which is mainly halted by the lack of validated biomarkers. METHOD: Recent nanotechnological advancements have the potential to offer large scale effective diagnostic and therapeutic options. Targeted drug (e.g. Rivastigmine) delivery with the help of nanoparticles (NPs) in the range of 1-100 nm diameters can effectively cross the blood brain barrier with minimized side effects. Moreover, biocompatible nanomaterials with increased magnetic and optical properties can act as excellent alternative agents for an early diagnosis. With the high volume of research coming in support of the effective usage of NP based drug delivery in critical environment of CNS, it is quite likely that this approach can end up providing remarkable breakthroughs in early stage diagnosis and therapy of AD. CONCLUSION: In the current review, we have presented a comprehensive outlook on the current challenges in diagnosis and therapy of AD, with an emphasis on the effective options provided by biocompatible NPs as imaging contrast agents and drug carriers.

Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players.

Glucose homeostasis is crucial for neuronal survival, synaptic plasticity, and is indispensable for learning and memory. Reduced sensitivity of cells to insulin and impaired insulin signaling in brain neurons participate in the pathogenesis of Alzheimer disease (AD). The tumor suppressor protein p53 coordinates with multiple cellular pathways in response to DNA damage and cellular stresses. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic metabolites (e.g. ceramide and products of advanced glycation) and ROS-modified cellular components, together with the activation of proapoptotic genes, could finally induce a suicide death program of autophagy/apoptosis in neurons. Recent studies reveal the impact of p53 on expression and processing of several microRNAs (miRs) under DNA damage-inducing conditions. Additionally, the role of miRs in promotion of insulin resistance and type 2 diabetes mellitus has been well documented. Detailed recognition of the role of p53/miRs crosstalk in driving insulin resistance in AD brains could improve the disease diagnostics and aid future therapy.

IMPACT OF FABRICS FROM TRANSGENIC FLAX PLANT ON HUMAN DERMAL FIBROBLASTS IN VITRO PROLIFERATION.

Previously it was documented that transgenic flax plants, which contained an increased level of polyphenolic compounds, significantly improved healing of skin wounds lesions. In order to recognize mechanisms of beneficial action of transgenic flax fabrics on wound healing, in the present study the impact of flax fabric pieces/cuts from three types of transgenic flax on normal human dermal fibroblasts primary culture (NHDF) was investigated. NHDF cell cultures were exposed for 48 h to specific area of flax fabric cuts, made from M50, B 14 and M50+B14 (intertwined fibers of M and B), or parallely, extracts from fibers of the tested flax materials to cell culture medium. Cultures were inspected for cell viability, proliferation, cell cycle changes and for their resistance to oxidative stress (consecutive addition of H2,O2, to harvested cell cultures). None of the tested flax fabrics were cytotoxic to fibroblast cultures and also did not increase significantly a frequency of apoptotic cells in cultures. In the comet assay, the tested flax fabrics revealed significant protective effect on DNA damage ciused by addition of H202 to the cultures at the end of incubation time. Fabrics from transgenic flax significantly enhanced fibroblasts proliferation in vitro estimated with the SRB test. Flow cytometric analysis revealed higher frequency of cells in the S phase, in the presence of transgenic flax fabrics. Fabrics from B14 and M50+B14 flax are the most potent activators of NHDF cells in applied in vityo tests, hence they could be recommended for elaboration of new type bandage, able to improve skin wound healing.

FLAX OIL FROM TRANSGENIC LINUM USITATISSIMUM SELECTIVELY INHIBITS IN VITRO PROLIFERATION OF HUMAN CANCER CELL LINES.

Emulsions made of oils from transgenic flaxseeds significantly decreased in vitro proliferation of six tested human cancer cell lines in 48-h cultures, as assessed with the standard sulforhodamine assay. However, the emulsions also increased proliferation rate of normal human dermal fibroblasts and, to a lower extend, of keratinocytes. Both inhibition of in vitro proliferation of human cancer cell lines and stimulation of proliferation of normal dermal fibroblasts and keratinocytes were especially strong with the emulsion type B and with emulsion type M. Oils from seeds of transgenic flax type B and M should be considered as valuable adjunct to standard cytostatic therapy of human cancers and also could be applied to improve the treatment of skin lesions in wound healing.