Obstetrical prevention of human cancers. Review article

Cancer appears in the new form of cell life as a direct consequence of self-organising pre-cancer cells (dissipathogenic systems), whose further existence is disabled by extreme impairment of their metabolism. Life itself is the highest value, since instead of necrosis or apoptosis, the cellular system in an unfavourable environment can change its genetic identity provided that the improvement in its own metabolism leads to increased chaos by higher dissipation of matter and energy in its environment. Prolongation of human life has resulted by a longer period of old age which is favourable for self-organisation of dissipative neoplastic cells. Modern medicine has explained the relation of the cervical cancer to preterm births and to inadequate use of oral contraceptives and/or replacement, instead of supplementary, neurohormonal therapy. Therefore, as early as in the period of pregnancy reproductive cells should be protected due to their prime importance in the intergenerational passage of life. Disturbance of systemic autoregulation causes development of dissipathogenic state of cells. A single zygote, whose environment is also important for the future development of the next two generations that are initiated with its formation, defines the unique identity of each person, whose life is determined by free will and neoplasms.     

Cytotoxic lignans from Podophyllum, and the nomenclature of aryltetralin lignans

Roots of Podophyllum hexandrum and P. peltatum both contain (1R,2R,3R)-desoxypodophyllotoxin [(1α,2α,3β)- desoxypodophyllotoxin] and the previously unreported (1R,2R,3R)-podophyllotoxone [(1α,2α,3α)-podophyllotoxone]. Thermal isomerization of (loc,2ct,3fl)-podophyllotoxone readily occurs to yield (1α,2α,3α)-podophyllotoxone (isopicropodophyllone) with traces of (1α,2β,3β)-podophyllotoxone (picropodophyllone). Small amounts of (1α,2α,3α)-podophyllotoxone were also present in dried roots of P. hexandrum and P. peltatum. A more systematic nomenclature for podophyllotoxin derivatives and other aryltetralin lignans using α,β conventions is proposed.     

The role of vitamin D in the prevention and the additional therapy of cancers

The active metabolite of vitamin D apart from a crucial role in maintaining mineral homeostasis and skeletal functions, has antiproliferative, apoptosis and differentiation inducing as well as immunomodulatory effects in cancer. It is well known that with increasing sunshine exposure the incidence of breast, prostate and colorectal cancer is decreasing. A number of in vitro and in vivo experiments documented the effects of vitamin D in the inhibition of the tumorigenesis. In studying the role of vitamin D in cancer, it is imperative to examine the potential pathways that control local tissue levels of vitamin D. The enzyme 24-hydroxylase converts the active vitamin D to inactive metabolite. Extra-renal production of this enzyme is observed and has been increasingly recognized as present in cancer cells. This enzyme is rate limiting for the amount of local vitamin D in cancer tissues and elevated expression is associated with an adverse prognosis. 24-hydroxylase may be a predictive marker of vitamin D efficacy in patients with cancer as an adjunctive therapy. There are many vitamin D analogs with no pronounced hypercalcemizing effects. Some analogs are in phase 1 and 2 clinical test, and they might have a role in the therapy of several types of cancer. At present our main task is to make an effort to decrease the vitamin D deficiency in Hungary. Speer G. The D-day. The role of vitamin D in the prevention and the additional therapy of cancers.     

Patterns of treatment failure in salivary gland cancers

Aim

The purpose of the study was to publish our experience of salivary gland cancer treatment with large number of patients treated at a single institution.

Cardiovascular disease prevention and treatment

The incidence of fatal and non-fatal cardiovascular disease (sudden cardiac death (SCD), myocardial infarction, others) varies, depending on conventional risk factors. However, in Western countries, like the US or Germany, incidences of fatal and non-fatal cardiovascular disease are far higher than in countries like Japan. In the present article, these differences are discussed and related to eicosapentaenoic acid (C20:5omega-3 or C20:5n-3; EPA) and docosahexaenoic acid (C22:6omega-3; DHA). Dietary intake of EPA and DHA and a number of other factors determine levels of EPA and DHA in an individual—best assessed as the omega-3 index, defined as the percentage of EPA and DHA in red cells, and analyzed in a standardized fashion. A review of the literature, expanded by measurements of the omega-3 index, indicates that the risk of sudden cardiac death correlates inversely with the omega-3 index. For persons with an omega-3 index <4%, risk is tenfold, as compared to persons with an omega-3 index >8%. A similar, less-pronounced, correlation exists for non-fatal cardiovascular disease. EPA and DHA have anti-arrhythmic and anti-atherosclerotic mechanisms of action. In large-scale intervention studies, intake of EPA and DHA has been demonstrated to reduce SCD and non-fatal cardiovascular events. Assessing or recommending dietary intake of EPA and DHA does not predict the resulting omega-3 index. Taken together, the omega-3 index is a biomarker to assess a person's content of omega-3 fatty acids, and thus the risk for sudden cardiac death, as well as non-fatal cardiovascular events. EPA and DHA prevent fatal and non-fatal cardiovascular disease and complications of congestive heart failure.     

Statins in prevention and treatment of ischemic stroke

Based on the published data, including the results of large-scale, randomized, placebo-controlled trials, the article presents current strategies for the use of statins in primary and secondary prevention of ischemic stroke. Special attention is paid to the efficacy and advanced applications of statins in acute stroke. Based on the gross data, recommendations for the use of statins in prevention and treatment of ischemic stroke are presented.     

Phenols and lignans from Chenopodium album

Cinnamic acid, 4-hydroxy-cinnamic acid, ferulic acid, methyl ferulate, sinapic acid, methyl 3-(4-hydroxy-3-methoxyphenyl)propanoate, 4-(1-hydroxyethyl)-2-methoxyphenol, vanillyl alcohol, 4-(hydroxymethyl)-2-methoxyphenol, 4-hydroxy-3-methoxybenzoic acid, 4-vinylphenol, 4-methylbenzaldehyde, N-[2-(1H-indol-3-yl)ethyl]acetamide, pinoresinol, syringaresinol, lariciresinol, 5,5'-dimethoxy-lariciresinol, threo-guaiacylglycerol-3-beta-4-syringaresinol ether and two new sesquilignans, namely, threo-guaiacylglycerol-alpha-O-methyl-beta-O-4-syringaresinol ether and threo-syringylglycerol-alpha-O-methyl-beta-O-4-syringaresinol ether, were isolated and identified as components of Chenopodium album. Constitutions were established on the basis of spectroscopic data, including two-dimensional NMR analyses.     

Aporphine alkaloids and lignans in heartwood of Liriodendron tulipifera

The following compounds were isolated from heartwood of Liriodendron tulipifera: glaucine, dehydroglaucine, asimilobine, N-acetylnornuciferine, norushinsunine, liriodenine, O-methylatheroline, (+)-syringaresinol, (+)-syringaresinol dimethyl ether and syringaldehyde. The occurrence of 1-benzyltetrahydroisoquinoline alkaloids also has been indicated by mass spectroscopy. Some characteristic spectral properties of these aporphine alkaloids and their probable biosynthetic pathways are discussed.     

Diet and urinary excretion of lignans in female subjects

Lignans, a class of compounds having a 2,3-dibenzylbutane skeleton, have recently been identified for the first time in humans and animals and evidence indicating their formation by intestinal microflora has previously been established in rats and humans. In the present report the influence of diet on the biosynthesis of this new group of compounds was investigated by comparing the urinary excretion of the principal lignan, trans-2,3-bis-(3-hydroxybenzyl) -butyrolactone (enterolactone, HBBL), in 12 omnivoric and 14 vegetarian women. Young vegetarian women were found to excrete significantly greater amounts of enterolactone than omnivores, while old vegetarians excreted comparable amounts to the omnivore group. A statistically significant (P less than 0.01-0.001) correlation was found between the amount of fibre in the diet and the urinary enterolactone excretion.     

Chemoinduction of cytotoxic selectivity in Podophyllotoxin-related lignans

Lignans are widely distributed in the plant kingdom, and display a variety of biological activities which have attracted the attention of the scientific community for decades. Several representative compounds of the cyclolignan class, such as podophyllotoxin and its semisynthetic derivative, etoposide, are currently used for the clinical treatment of warts and malign neoplasms. Other cyclolignans are involved in antineoplastic and antiarthritic clinical trials. Numerous podophyllotoxin-related compounds have been prepared through modification of nearly all the positions on the cyclolignan skeleton in the search of new, more selective and less toxic anticancer drugs. Our group has been interested in the chemoinduction of drug selectivity for several years, and we have designed and prepared new podophyllotoxin derivatives by modification mainly on the C and D-rings of the podophyllotoxin skeleton. Those derivatives, bearing an electrophilic functionality at C-9, have shown, both in vitro and in vivo, a high degree of selectivity against colon carcinoma, and less cytotoxicity for other neoplastic systems and normal kidney fibroblasts. The main structural modifications found in the literature for the podophyllotoxin skeleton in the past decade, including those from our research group, are presented in this article.     

Synthesis and antioxidant activity of olivil-type lignans

Olivil-type lignans, an enantiomeric type of natural olivil, were synthesized for the first time to evaluate the relationship between the structure of olivil and its antioxidant activity. A comparison of the antioxidant activity with that of other synthesized tetrahydrofuran lignans indicated reduced activity with the tertiary hydroxy group. A different effect of the two phenolic groups of olivil on the antioxidant activity was also observed.     

Nortriterpenoids and lignans from Schisandra sphenanthera

Nortriterpenoids, sphenadilactone C (1) and sphenasin A (2), together with four known lignans (3-6), were isolated from the leaves and stems of Schisandra sphenanthera. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and compound 2 was further confirmed by single-crystal X-ray diffraction. Compound 1 features a partial enol moiety and an acetamide group in its structure. In addition, compounds 1, 3-6 showed weak anti-HIV-1 activity with EC₅₀ values in the range of 15.5-29.5 μg/mL.     

Minor lignans of Piper clusii

Further investigations on the petrol extract of Piper clusii have afforded four more new lignans.These are 2S,3R,4R,2-ethoxy-3-(3,4,5-trimethoxyphenyl)methyl 4-(1,3-benzodioxol-5-yl) methyl tetrahydrofuranol; 3R,4R,bis-3,4-(3,4,5-trimethoxyphenyl) methyl tetrahydrofuran-2-one; 2R,3R,2-(7-methoxy-1,3-benzodioxol-5-yl) methyl 3-(3,4,5-trimethoxyphenyl)methyl butan-1,4-diol and 2R,3R,2-(1,3-benzodioxol-5-yl)methyl 3-(3,4,5-trimethoxyphenyl) methyl butan-1,4-diol. This is the first report of these compounds from a natural source.