Synthesis and antimicrobial and antifungal activities of cyclopentene β, β'-triketones and their methyl enol ethers

The natural cyclopentene β, β'-triketone coruscanone B and its methyl enol ether coruscanone A, metabolites of the higher plant Piper coruscans, in addition to 19 of their simple analogs have been synthesized. The antimicrobial activity of the synthesized compounds against Gram-positive (Staphylococcus aureus ATCC 21027) and Gram-negative (Escherichia coli ATCC 15034) bacteria, yeast (Sofale S-04 and Candida albicans KMM455), and fungi (Aspergillus niger KMM4634 and Fusarium oxysporum KMM4639) was studied. The nature and number of substituents at the 4- and 5-positions of the five-membered ring and also the nature of the substituent in the 2-position were found to have a profound effect on the level of activity and the spectrum of antimicrobial action of the tested compounds. Free β, β'ect. It is established that the level of activity and the spectrum of the antimicrobial action of coruscanone A and 2-(1-methoxyethylidene)-4,5-dichlorocyclopent-4-ene-1,3-dione are almost identical to those of the reference drug nitrofungin.     

Risks and Mechanisms of Oncological Disease Following Stem Cell Transplantation

Unique biological properties of stem cells make them a precious source of cell material for treatment of a number of pathological conditions. Among issues inhibiting transition of stem cell technologies to the clinics, the risk of oncological complications of stem cell-based therapies is the most critical. A massive amount of clinical and experimental data demonstrates that both hematological (including acute and chronic myeloid leukemia) and non-hematological (including teratoma and non-teratoma tumors) malignancies could arise from donor stem cells of different types. A wide spectrum of mechanisms could underlie the development of oncological disease in recipients, including: i) blast transformation of proliferating donor stem cells under persistent action of certain factors in the recipient, thus causing de novo malignancies; ii) contamination of donor cell material with malignant cells; iii) transmission of particular viral subtypes with donor stem cells, combined with immunosuppression therapy effects; iv) uncontrollable proliferation of residual undifferentiated stem cells of various plasticity; and v) karyotypic instability in stem cells following prolonged culturing/expansion in vitro. Potential preventive strategies are diverse and include i) high-throughput cell sorting-based strategies; ii) introduction of suicide genes into the donor stem cell genome; iii) application of apoptosis-inducing epigenetic factors; and some other options.     

Persistence of carcinogenic effect in intact progeny of mice treated transplacentally with 7,12-dimethylbenz[a]anthracene

Pregnant SHR mice were treated once with 7,12-dimethylbenz[a]anthracene (DMBA) on days 17-19 of gestation. F1 and F2 descendants of these mice received multiple skin applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week for 24 weeks beginning at 12 weeks of age, or applications of solvent alone. The increase in the frequency of skin tumours in F1 and F2 descendants was reported elsewhere. In addition, we report here an increase in overall numbers of tumor-bearing animals, independently of TPA treatment both in F1 and F2 groups compared to respective control groups. Separate statistical analyses were performed for lung tumours, mammary gland tumours, leukaemias and lymphomas. In both generations of descendants of DMBA-treated mothers lung tumour incidence was considerably increased and differed significantly (maximal P-value = 0.003) from control values. Local applications of TPA resulting in strong skin tumour promoting effect described in our previous paper (Napalkov et al., Carcinogenesis, 8(3) (1987) 381) did not produce any significant change in the rates of other types of tumours. The results of the present study provide additional evidence in support of the hypothesis on possibility of hereditary transmission of carcinogenic action of certain chemical compounds.     

Carcinogenesis and aging 20 years after: escaping horizon

Carcinogenesis is a multistage process: neoplastic transformation implies the engagement of a cell through sequential stages, and different agents may affect the transition between continuous stages. Multistage carcinogenesis is accompanied by disturbances in tissue homeostasis and perturbations in nervous, hormonal, and metabolic factors which may affect antitumor resistance. The development of these changes depends on the susceptibility of various systems to a carcinogen and on the dose of the carcinogen. Changes in the microenvironment may condition key carcinogenic events and determine the duration of each carcinogenic stage, and sometimes they may even reverse the process of carcinogenesis. These microenvironmental changes influence the proliferation rate of transformed cells, the total duration of carcinogenesis and, consequently, the latent period of tumor development. Aging may increase or decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer by two mechanisms: tissue accumulation of cells in late stages of carcinogenesis and alterations in internal homeostasis, in particular, alterations in immune and endocrine system. Aging is associated with number of events at molecular, cellular and physiological levels that influence carcinogenesis and subsequent cancer growth.     

Cancer risk in women: a possible connection with geographic and certain economic and social factors

The paper deals with mulivariate regression analysis of effects of latitude, economic environment and electricity consumption on breast cancer morbidity in 35 countries (1985-2007). Our data are compared with the influence of the same factors on incidence rates for ovarian carcinoma, endometrial and cervical cancer as well as those of the stomach, liver, colon and lung. It was found that rates of morbidity for breast, endometrial, colonic and lung cancer tend to increase north of the equator while cervical, gastric and hepatic cancer incidence is relatively higher in circumequatorial populations. In 1985, geographic factors made a dramatic contribution to hormone-dependent tumors incidence while economic ones--to that of gastrointestinal neoplasms. In the 2000-ies, climate-related risks of hormone-dependent tumors have gradually slumped down while those of economic and social factors have increased.     

Lighting effect on spontaneous tumor development in female rats

The investigation is concerned with effects of lighting--12hr light/12hr dark (standard), natural lighting in the Russian North-West, constant illumination and light deprivation--on life span and spontaneous tumor development in female LIO rats. Constant and North-West lighting involved premature aging, shorter mean (13.5 and 25%) and maximum life span (by 9 and 7 months, respectively) and a significant increase in spontaneous tumor development rate as compared with standard lighting. Light deprivation resulted in a longer maximum life span and significant (2.1 times) drop in tumor incidence.     

Modulation of interleukin-2-induced proliferation and nonspecific cytotoxicity of rat lymphocytes by phorbol myristate acetate and staurosporine

It is shown that a 19-h pretreatment of rat splenocytes with 1 μM phorbol 12-myristate 13-acetate followed by a 42-h incubation with human recombinant interleukin-2 inhibits nonspecific cytotoxicity of these cells toward the target YAC-1 cells. By contrast, proliferation of splenocytes and thymocytes incubated under the same conditons increases considerably. The inhibitor of protein kinase C staurosporine (0.1 μM) significantly decreases nonspecific cytotoxicity of splenocytes after a 20-min incubation, while in a dose of 0.01 μM it stimulates lytic activity of splenocytes and thymocytes following a 3-day incubation with interleukin-2 in the presence of the inhibitor. Cell proliferation under these conditions is markedly decreased. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 394–398, October, 1996