47 results on '"Alexandrov VA"'
Search Results
2. Climate variation and crop production in Georgia, USA, during the twentieth century
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Alexandrov, VA, primary and Hoogenboom, G, additional
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- 2001
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3. On the Monte Carlo Matrix Computations on Intel MIC Architecture
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Karaivanova Aneta, Alexandrov Vassil, Gurov Todor, and Ivanovska Sofiya
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monte carlo ,matrix computations ,intel mic ,high performance computing (hpc) scalability ,Cybernetics ,Q300-390 - Abstract
The tightened energy requirements when designing state-of-the-art high performance computing systems lead to the increased use of computational accelerators. Intel introduced the Many Integrated Core (MIC) architecture for their line of accelerators and successfully competes with NVIDIA on basis of price/performance and ease of development. Although some codes may be ported successfully to Intel MIC architecture without significant modifications, in order to achieve optimal performance one has to make the best use of the vector processing capabilities of the architecture. In this work we present our implementation of Quasi-Monte Carlo methods for matrix computations specifically optimised for the Intel Xeon Phi accelerators. To achieve optimal parallel efficiency we make use of both MPI and OpenMP.
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- 2017
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4. Cooperative research sought by the Prof. N.N. Petrov Research Institute of Oncology, St. Petersburg.
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Alexandrov VA, Anisimov VN, Berstein LM, Likhachev AJ, Okulov VB, Pozharisski KM, Alexandrov, V A, Anisimov, V N, Berstein, L M, Likhachev, A J, Okulov, V B, and Pozharisski, K M
- Published
- 1995
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5. Using 3D Hidden Markov Models that explicitly represent spatial coordinates to model and compare protein structures
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Gerstein Mark and Alexandrov Vadim
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Hidden Markov Models (HMMs) have proven very useful in computational biology for such applications as sequence pattern matching, gene-finding, and structure prediction. Thus far, however, they have been confined to representing 1D sequence (or the aspects of structure that could be represented by character strings). Results We develop an HMM formalism that explicitly uses 3D coordinates in its match states. The match states are modeled by 3D Gaussian distributions centered on the mean coordinate position of each alpha carbon in a large structural alignment. The transition probabilities depend on the spread of the neighboring match states and on the number of gaps found in the structural alignment. We also develop methods for aligning query structures against 3D HMMs and scoring the result probabilistically. For 1D HMMs these tasks are accomplished by the Viterbi and forward algorithms. However, these will not work in unmodified form for the 3D problem, due to non-local quality of structural alignment, so we develop extensions of these algorithms for the 3D case. Several applications of 3D HMMs for protein structure classification are reported. A good separation of scores for different fold families suggests that the described construct is quite useful for protein structure analysis. Conclusion We have created a rigorous 3D HMM representation for protein structures and implemented a complete set of routines for building 3D HMMs in C and Perl. The code is freely available from http://www.molmovdb.org/geometry/3dHMM, and at this site we also have a simple prototype server to demonstrate the features of the described approach.
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- 2004
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6. Therapeutic effect of iodised serum milk protein, lycopene and their combination on benign prostatic hyperplasia induced in rats.
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Alexandrov VA, Tochilnikov GV, Zhilinskaya NT, Gubareva EA, Romanov VA, Ermakova ED, Dorofeeva AA, Zmitrichenko YG, Tumanyan IA, and Semenov AL
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- Animals, Humans, Lycopene, Male, Milk Proteins, Plant Extracts, Rats, Rats, Wistar, Testosterone, Prostatic Hyperplasia chemically induced, Prostatic Hyperplasia drug therapy
- Abstract
Benign prostatic hyperplasia (BPH) is a common chronic disease in ageing men. Synthetic inhibitors of 5α-reductase commonly used in BPH treatment have limited effectiveness and may cause side effects. Evaluation of iodised serum milk protein and lycopene therapeutic effect in rat BPH model was the aim of the present study. BPH was induced in male Wistar rats by surgical castration and subsequent testosterone administrations (25 mg/kg, 7 injections). Rats with induced BPH received lycopene (5 mg/kg), iodised serum milk protein (200 µg/kg) or their combination for 1 month daily. The efficacy of the treatment was evaluated by the prostate weight, prostatic index and ventral lobe epithelium thickness. In lycopene and iodised serum milk protein-treated rats, prostate weight and prostatic index were significantly reduced compared to control group; and lycopene and iodised serum milk protein used in combination yielded an additive effect. Thus, further investigation of combined supplementation with micronutrients and plant-derived substances in BPH models may help to find new opportunities or its safe and effective treatment., (© 2021 Wiley-VCH GmbH.)
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- 2021
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7. Cisplatin effect on digital cytomorphometric and bioinformatic tumor cell characteristics in rat ovarian cancer model-a preliminary study.
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Zhilinskaya NT, Bespalov VG, Semenov AL, Ermakova ED, Tochilnikov GV, Barakova NV, Alexandrov VA, and Baranenko DA
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- Animals, Ascitic Fluid cytology, Computational Biology, Drug Resistance, Neoplasm, Female, Neoplasm Transplantation, Ovarian Neoplasms pathology, Rats, Rats, Wistar, Antineoplastic Agents pharmacology, Cisplatin pharmacology, Ovarian Neoplasms drug therapy
- Abstract
Background: Ovarian cancer is one of the most common diseases of the female reproductive system. The aim of this study was the investigation of the antitumor cisplatin effect on ascitic fluid tumor cells in the ovarian cancer experimental model by digital cytomorphometry and cell bioinformatic analysis., Methods: Female Wistar rats were inoculated by ovarian cancer strain. After ovarian cancer transplantation rats were divided into two groups: control group-without cisplatin treatment, the experimental group-under cisplatin treatment. The ascitic fluid was taken on the 9-th day after tumor cell inoculation. Digital cytomorphometric and cytobioinformatic analysis were used to study ascitic fluid cancer cell morphofunctional changes under cisplatin treatment., Results: Digital cytomorphometric characteristics of rat ovarian cancer ascitic cells were obtained. Tumor cells were classified into four groups according to their geometric size: small, medium, large, "gigantic". The algorithm and the computer program based on tumor cell morphometric characteristics were created to calculate such cell bioinformatic characteristic as information redundancy coefficient R. Three parameters were determined as the criteria of cisplatin effect on cancer cells: cell number, nuclear/cytoplasmic ratio, R-value., Conclusions: Data obtained suggest that cisplatin reduces the total cell number, the nuclear/cytoplasmic ratio and R-value thus indicates a decrease in cellular resistance and adaptive potential. The digital cytomorphometry and bioinformatics could be recommended as a testing system in the experimental or clinical study.
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- 2021
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8. Old Rats Are More Susceptible to Induction of Benign Prostatic Hyperplasia (BPH) at Comparative to Young Mature.
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Bespalov VG, Alexandrov VA, Semenov AL, Tochilnikov GV, Ermakova ED, Zmitrichenko YG, Vasilyeva IN, Ivantsov AO, and Zhilinskaya NT
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- Animals, Male, Prostate, Rats, Rats, Wistar, Testosterone, Prostatic Hyperplasia etiology
- Abstract
Aims: The aim of the experiments was to find out the factors on which age-related sensitivity to the occurrence of BPH depends., Methods: 45 Male Wistar rats aged 3 and 24 months were used. In each age group, there were intact rats and animals with induced BPH (by surgical castration + testosterone injections, 25 mg/kg x 7). On the 36th day of the experiment, blood was taken from rats to determine serum testosterone, cholesterol, triglycerides and glucose; then, the animals were autopsied, their prostates were weighed, and their morphology was studied., Results: Young mature intact rats had much higher testosterone levels (6.2±0.93 nmol/l) than old intact (3.8±0.55 nmol/l), while the ratio of prostate weight was inverse. The weight of the prostate and prostatic index in old rats with induced BPH was significantly higher not only in comparison with the old intact rats but also with young animals after BPH induction. Morphologically, the inflammatory foci were determined not only in the prostates of old rats, which induced BPH, but also in intact animals. Besides, in old intact rats, the foci of prostate hyperplasia were often noted., Conclusion: Our experimental model indicates the important role of non-bacterial prostatitis in the pathogenesis of BPH. No metabolic disorders in BPH induction were revealed. The sensitivity of the prostate of old rats to BPH development is increasing despite the low concentrations of testosterone in the body. Age sensitivity to BPH is probably determined by a higher expression of androgen receptors in old animals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2021
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9. Efficacy of Gemcitabine on Intracranial Erlich Tumor and its Determinants.
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Stukov AN, Bespalov VG, Alexandrov VA, Semenov AL, Kireeva GS, Semiglazova TY, Filatova LV, and Baranenko DA
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- Animals, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents pharmacology, Blood-Brain Barrier metabolism, Brain Neoplasms pathology, Carcinoma, Ehrlich Tumor pathology, Deoxycytidine administration & dosage, Deoxycytidine pharmacokinetics, Deoxycytidine pharmacology, Dose-Response Relationship, Drug, Male, Mice, Mice, Inbred BALB C, Permeability, Tissue Distribution, Gemcitabine, Antineoplastic Agents administration & dosage, Brain Neoplasms drug therapy, Carcinoma, Ehrlich Tumor drug therapy, Deoxycytidine analogs & derivatives
- Abstract
Gemcitabine is quite effective in the treatment of brain tumors, although this drug has a limited ability to overcome the blood-brain barrier (BBB). Aim of study is to assess the therapeutic efficacy of gemcitabine and other drugs with different permeability of BBB in the model of intracranial tumor. The therapeutic activity of gemcitabine, carmustine, cyclophosphamide and cisplatin was studied in mice with intracranially implanted Ehrlich tumor, and also gemcitabine in various doses - with intramuscularly implanted tumor. On intracranial tumor model gemcitabine (25 mg/kg) increased the life span (ILS) by 60-89% (p<0.001), despite the fact that its permeability of the BBB is about 10%. Therapeutic activity of carmustine, cyclophosphamide and cisplatin (ILS were 44, 22 and 11%, respectively) corresponds with the BBB permeability for these drugs (90, 20 and 8%, respectively). On intramuscular tumor model, gemcitabine showed significant antitumor effect at both 25 and 2.5 mg/kg, indicating a wide range of therapeutic doses of this drug. Pronounced therapeutic effect of gemcitabine on intracranial tumor most likely is due to the small but sufficient concentration of the drug that overcomes the BBB., Competing Interests: The authors declare that there is no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)
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- 2020
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10. Enchancement of Toremifene Anti-Tumor Action by Metformin and Unusual Side Effect of Toremifene in Male Transgenic Mice with HER2-Positive Breast Tumor.
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Stukov AN, Osipov MA, Semiglazova TY, Filatova LV, Alexandrov VA, Bespalov VG, Semenov AL, Tyndyk ML, Yurova MN, Panchenko AV, and Baranenko DA
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- Animals, Female, Male, Mice, Disease Models, Animal, Mice, Transgenic, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Metformin pharmacology, Receptor, ErbB-2 metabolism, Toremifene pharmacology
- Abstract
HER2-positive breast tumors are found in 25-30% of patients with breast cancer and are characterized by aggressive course and reduced sensitivity to both chemotherapy and hormone therapy. The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse. Male FBV/N mice with intramuscularly transplanted HER2-positive mammary gland tumor from a female mouse of the same strain have been given toremifene (30 mg/kg, orally daily) or metformin (100 mg/kg, orally daily) that had a moderate antitumor effect (decrease the area under the kinetic curve of tumor growth by 1.6 and 1.5 times, respectively, when compared with intact control). Co-administration of these drugs in the same doses had a more pronounced effect (the area under the kinetic curve of tumor growth decreased by 3.1 times compared to intact control; p<0.05). After 10 days, in group receiving toremifene all 10 mice developed inguinal-scrotal hernias, and in group that received toremifene plus metformin - only 5 of 10 (p=0.0325). By the 15
th day after the start of treatment, the hernias was also determined in all mice treated with the combination of toremifene and metformin, but the size of the hernial sac was significantly smaller than in those receiving only toremifene - 537 ± 96 mm3 and 1309 ± 120 mm3 , respectively (p=0.0001). A possible explanation is the manifestation of collagen-degrading effect of toremifene., Competing Interests: The authors declare that there is no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)- Published
- 2019
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11. Iodine Bonded with Milk Protein Inhibits Benign Prostatic Hyperplasia Development in Rats.
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Bespalov VG, Alexandrov VA, Tochilnikov GV, Lukin DЕ, Zhilinskaya NT, Semenov AL, Vasilyeva IN, Romanov VA, Tumanyan IA, Ermakova ED, Kovalevskaya EI, Barakova NV, and Baranenko DA
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- Androgen Antagonists administration & dosage, Animals, Finasteride administration & dosage, Male, Milk Proteins administration & dosage, Rats, Rats, Wistar, Iodine chemistry, Milk Proteins chemistry, Prostatic Hyperplasia prevention & control
- Abstract
Background: There is some evidence that Benign Prostatic Hyperplasia (BPH) may increase the risk of developing prostate cancer, so conducting research on effective BPH inhibitors is important., Objective: This research studied the inhibitory effect of Iodized Serum Milk Protein (ISMP) on BPH in rats. ISMP is a concentrate of lactic protein containing 2.2% iodine., Methods: Male Wistar rats, aged 18 months, were used. In the intact control group, sunflower oil was administered intragastrically by gavage. In 36 rats, BPH was induced by surgical castration, followed by subcutaneous injections of prolonged testosterone - omnadren, 25mg/kg every other day (7 administrations). One group of rats served as BPH-control. ISMP and finasteride (positive control), dissolved in sunflower oil, were administered to rats intragastrically daily at a dose of 200μg/kg and 5mg/kg, respectively, for 4 weeks starting immediately after castration., Results: ISMP inhibited the development of BPH in rats, significantly reducing the mass of the prostate and its parts (except for the anterior lobes) by 1.1-1.3 times and the prostatic index (the ratio of prostate weight to the body weight) - by 1.3-1.4 times. Finasteride inhibited the development of BPH, and its activity was higher (by 1.1-1.3 times) than in ISMP. Histological analysis of the prostate showed fewer pronounced morphological hyperplasia signs in animals treated with ISMP or finasteride., Conclusion: The iodine-containing preparation ISMP has the ability to inhibit the development of BPH in rats although its activity is somewhat lower than that of finasteride., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2019
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12. The inhibitory effect of Filipendula ulmaria (L.) Maxim. on colorectal carcinogenesis induced in rats by methylnitrosourea.
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Bespalov VG, Alexandrov VA, Semenov AL, Vysochina GI, Kostikova VA, and Baranenko DA
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- Adenocarcinoma chemically induced, Adenocarcinoma pathology, Animals, Colorectal Neoplasms chemically induced, Colorectal Neoplasms pathology, Female, Flowers, Methylnitrosourea, Phytotherapy, Rats, Adenocarcinoma drug therapy, Antineoplastic Agents therapeutic use, Colorectal Neoplasms drug therapy, Filipendula, Plant Extracts therapeutic use
- Abstract
Ethnopharmacological Relevance: Meadowsweet (Filipendula ulmaria (L.) Maxim.) is a medicinal plant with a variety of therapeutic properties, traditionally used in various diseases including treatment and prevention of tumors. The aim of this study was to present an ethnomedicinal justification that a meadowsweet decoction is able to inhibit colorectal carcinogenesis induced by the methylnitrosourea (MNU) in rats., Materials and Methods: The chemical composition of meadowsweet extracts was studied by traditional methods. In animal experiments adult outbred female rats received four intrarectal instillations of MNU, one per week, at dose 4 mg in 0.5 ml saline (the total dose of MNU during the 4-week exposure was 16 mg/rat). After carcinogenic exposure one group (MNU) of rats continued to receive standard feed and tap water throughout life. In another group (MNU+meadowsweet), rats were given daily a decoction of the meadowsweet instead of drinking water and standard feed., Results: Meadowsweet extracts showed a sufficiently high content of flavonoids and tannins and also some individual phenolic compounds and salicylic acid. In rats after administration of MNU the overall incidence of tumors was 91% with tumor multiplicity of 3.5. The majority of rats (86%) developed multiple tumors of large intestine (most often adenocarcinomas:88 from 107; index of multiplicity - 2.0). In rats from the group MNU+meadowsweet there was a statistically significant decrease of the overall tumor incidence and multiplicity-by 1.4 and 2.9 times, respectively, and the incidence and multiplicity of colon tumors - by 2.0 and 2.8 times, respectively; the incidence and multiplicity of malignant tumors of other localizations was also reduced-by 2.2 and 3.0 times, respectively., Conclusions: Meadowsweet extract is an effective inhibitor of colorectal carcinogenesis in experiment, that provides support for the traditional use of this plant in the oncology., (Copyright © 2018 Elsevier B.V. All rights reserved.)
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- 2018
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13. Comparative efficacy evaluation of catheter intraperitoneal chemotherapy, normothermic and hyperthermic chemoperfusion in a rat model of ascitic ovarian cancer.
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Bespalov VG, Alvovsky IK, Tochilnikov GV, Stukov AN, Vyshinskaya EA, Semenov AL, Vasilyeva IN, Belyaeva OA, Kireeva GS, Senchik KY, Zhilinskaya NT, Von JD, Krasilnikova LA, Alexandrov VA, Khromov-Borisov NN, Baranenko DA, and Belyaev AM
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- Animals, Ascites pathology, Chemotherapy, Cancer, Regional Perfusion methods, Disease Models, Animal, Female, Humans, Hyperthermia, Induced, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Rats, Rats, Wistar, Survival Analysis, Ascites drug therapy, Infusions, Parenteral methods, Ovarian Neoplasms drug therapy
- Abstract
Objectives: The choice of an optimal administration route for intraperitoneal (IP) chemotherapy and a suitable chemotherapeutic regime in the treatment of ovarian cancer remains a controversy. We investigated survival outcomes according to catheter intraperitoneal chemotherapy (CIPC), normothermic and hyperthermic chemoperfusion (NIPEC and HIPEC) with cytostatic drugs dioxadet and cisplatin in rats with transplantable ascitic ovarian cancer., Methods: Ascitic liquid containing 1 × 10
7 tumour cells was inoculated to female Wistar rats and 48 hours after rats received dioxadet and cisplatin at the maximum tolerated doses. Dioxadet at doses 1.5, 30 and 15 mg/kg and cisplatin at doses 4, 40 and 20 mg/kg body weight were administered for CIPC, NIPEC and HIPEC, respectively. Rats in the control groups received physiological saline and CIPC with physiological saline was regarded as the untreated control. The antitumor activity of the drugs was evaluated as an increase in average life expectancy (ALE). Analysis of the data was based primarily on Bayesian statistics and included Kaplan-Meier method, log-rank test and hazard ratio (HR) estimation., Results: Compared to the untreated control CIPC, NIPEC and HIPEC with dioxadet significantly increased ALE by10 1316 ,6 1524 and1.7 1735 days, whereas with cisplatin by6 1013 ,12 2437 and-13 523 days, respectively., Conclusions: Dioxadet and cisplatin show similar efficacy in the CIPC route. Compared with CIPC IP chemotherapy by chemoperfusions is more effective for both the drugs. Dioxadet in HIPEC showed highest survival benefit whereas largest effect during NIPEC is achieved with cisplatin.- Published
- 2018
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14. Inhibitory Effect of Filipendula ulmaria on Mammary Carcinogenesis Induced by Local Administration of Methylnitrosourea to Target Organ in Rats.
- Author
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Bespalov VG, Alexandrov VA, Vysochina GI, Kostikova VA, Semenov AL, and Baranenko DA
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- Animals, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Female, Flavonoids chemistry, Flavonoids isolation & purification, Mammary Neoplasms, Experimental chemically induced, Mammary Neoplasms, Experimental pathology, Methylnitrosourea administration & dosage, Molecular Structure, Phenols chemistry, Phenols isolation & purification, Plant Extracts chemistry, Rats, Rats, Wistar, Structure-Activity Relationship, Tannins chemistry, Tannins isolation & purification, Filipendula chemistry, Flavonoids pharmacology, Mammary Neoplasms, Experimental drug therapy, Phenols pharmacology, Tannins pharmacology
- Abstract
Background: The meadowsweet (Filipendula ulmaria (L.) Maxim.) may have a cancer prophylactic activity, since its extracts exhibit antioxidant, anti-inflammatory and other effects. We investigated the ability of a meadowsweet decoction to inhibit mammary carcinogenesis induced by intramammary injections of Methylnitrosourea (MNU) to the target organ in rats., Materials and Methods: The chemical composition of meadowsweet extracts was studied by traditional methods. In animal experiments, adult outbred female rats received single injections of MNU at a dose 1mg directly into the tissue of each mammary gland. After carcinogenic exposure one group (MNU) of rats continued to receive standard feed and tap water throughout life. In another group (MNU+meadowsweet), rats were given daily a decoction of the meadowsweet instead of drinking water and standard feed., Results: Meadowsweet extracts showed a sufficiently high content of flavonoids and tannins and also some individual phenolic compounds. In rats after injections of MNU the overall incidence of tumors was 90% with tumor multiplicity of 3.1. The majority of rats (86%) developed multiple malignant tumors of the mammary gland (most often adenocarcinomas). In rats from the group MNU+meadowsweet, there was a statistically significant decrease of the overall tumor multiplicity-by 1.5 times, and the incidence and multiplicity of breast tumors-by 1.6 and 2.2 times, respectively., Conclusions: Meadowsweet extract can be considered an effective inhibitor of breast carcinogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2018
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15. The inhibitory effect of meadowsweet (Filipendula ulmaria) on radiation-induced carcinogenesis in rats.
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Bespalov VG, Alexandrov VA, Semenov AL, Kovan'ko EG, Ivanov SD, Vysochina GI, Kostikova VA, and Baranenko DA
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- Animals, Carcinogenesis drug effects, Carcinogenesis radiation effects, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Female, Flowers chemistry, Neoplasms, Radiation-Induced etiology, Radiation Dosage, Rats, Survival Rate, Treatment Outcome, Whole-Body Irradiation adverse effects, Filipendula chemistry, Neoplasms, Radiation-Induced pathology, Neoplasms, Radiation-Induced prevention & control, Plant Extracts administration & dosage, Radiation-Protective Agents administration & dosage
- Abstract
Purpose: To examine the ability of the meadowsweet preparation to inhibit carcinogenesis induced by ionizing radiation in female rats., Materials and Methods: The chemical composition of meadowsweet (Filipendula ulmaria) raw material (ethanol and aqueous extracts of meadowsweet flowers) has been studied for the presence of flavonoids, tannins and catechins. Adult female LIO strain rats were subjected to a single whole body γ-irradiation at a dose of 4 Gy in animal experiments. One group of irradiated rats served as control while the other group, starting from the 10th day after irradiation and until the end of the experiment, was given meadowsweet as a decoction of the flowers instead of drinking water. The average daily intake of meadowsweet (dry raw material) was 1 g/kg body weight. Rats were observed for 16 months., Results: The analyzed meadowsweet extracts showed a sufficiently high content of flavonoids and tannins. In irradiated rats after 16 months the overall incidence of tumors was 79.6% (in 82 of 103 rats), the incidence of malignant tumors was 43.7% and the overall tumor multiplicity was 1.48. Most tumors were localized in the mammary gland - 57.3%. In rats that received meadowsweet, the incidence of all malignant tumors and overall multiplicity of tumors were significantly decreased by 1.5 and 1.3 times, respectively. The greatest reduction of many parameters has been identified for breast tumors: the overall incidence was decreased by 1.5 (p = 0.0174) and the overall multiplicity and multiplicity of malignant tumors - by 1.6 (p = 0.0002) and 2.2 (p = 0.0383) times, respectively., Conclusions: Meadowsweet preparation showed inhibiting activity on radiation carcinogenesis.
- Published
- 2017
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16. The inhibiting activity of meadowsweet extract on neurocarcinogenesis induced transplacentally in rats by ethylnitrosourea.
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Bespalov VG, Alexandrov VA, Vysochina GI, Kostikova VА, and Baranenko DA
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- Animals, Central Nervous System Neoplasms chemically induced, Central Nervous System Neoplasms pathology, Disease Models, Animal, Female, Kidney Neoplasms chemically induced, Kidney Neoplasms drug therapy, Kidney Neoplasms pathology, Male, Maternal-Fetal Exchange, Plant Extracts therapeutic use, Pregnancy, Prenatal Exposure Delayed Effects, Central Nervous System Neoplasms drug therapy, Ethylnitrosourea toxicity, Filipendula, Plant Extracts administration & dosage
- Abstract
Inhibitory activity of a decoction of meadowsweet, given postnatally, was studied in rats at risk for neurogenic and renal tumors initiated by transplacental exposure to ethylnitrosourea (ENU). Chemical analysis of ethanol and aqueous extracts of meadowsweet has shown high content of biologically active flavonoids and tannins. Pregnant rats of LIO strain were given a single i.v. injection of ENU, 75 mg/kg, оn the 21st day of gestation. After weaning at 3 weeks after birth, the offspring were divided into two groups: the first was a positive control (ENU), while rats in the second group (ENU + meadowsweet) were given daily a decoction of meadowsweet as drinking water throughout their lifetime. All rats of the first group (ENU) developed multiple malignant tumors, which occurred in brain (86%), spinal cord (43%), peripheral and cranial nerves (29%) and in kidney (31%). More than one-third of CNS tumors were oligodendrogliomas. Mixed gliomas (oligoastrocytomas) occurred less frequently. All other types including astrocytomas, glioblastomas, and ependymomas were rare. All PNS tumors were neurinomas (schwannomas). The spectrum of tumors was similar in rats of the second group. Postnatal consumption of meadowsweet significantly reduced number of tumor-bearing rats (by 1.2 times), the incidence and multiplicity of CNS tumors (brain-by 2.0 and 2.1 times, respectively; spinal cord-by 3.1 and 3.0 times, respectively) and significantly increased latency period, compared to rats of the first group. No significant reduction in PNS or renal tumors was seen in rats given meadowsweet. Meadowsweet extract can be considered an effective cancer preventive agent especially as a neurocarcinogenesis inhibitor.
- Published
- 2017
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17. Phenozan, a Synthetic Phenolic Antioxidant, Inhibits the Development of Spontaneous Tumors in Rats and Mice.
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Bespalov VG, Alexandrov VA, Korman DB, and Baranenko DA
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- Animals, Female, Kaplan-Meier Estimate, Male, Mice, Rats, Antioxidants pharmacology, Neoplasms prevention & control, Phenylpropionates pharmacology
- Abstract
Synthetic phenolic antioxidant β-(4-hydroxy-3,5-di-tert-butylphenyl) propionic acid, named phenozan, is a potential antiepileptic drug. In pre-clinical trials this substance did not manifest any toxicity, and also inhibited the development of some spontaneous tumors in animals. The purpose of this study was to evaluate inhibiting effect of phenozan on spontaneous carcinogenesis in rats and mice. In experiments with rats LIO and mice SHR of local breeding, with high spontaneous tumor incidence, phenozan was dissolved in sunflower oil and administered by gavage in therapeutic dose 5 mg/kg 3 times per week for 18 months. There were no any signs of toxicity and differences in weight of animals during the phenozan treatment compared with the control (sunflower oil). Phenozan significantly reduced the overall incidence and multiplicity of all tumors but only multiplicity of malignant tumors, compared with the control. Moreover a significant decrease of overall incidence and multiplicity was observed in pituitary and breast tumors in females and only overall multiplicity of tumors of pituitary and lymphoid tissue in males. In mice phenozan reduced overall incidence and multiplicity of lung tumors (in females) and also overall multiplicity of all tumors (in females) and only malignant tumors (in males). These findings allow us to classify phenozan as anticarcinogenic agent. Anticarcinogenic activity of phenozan is important because clinical study of this drug as the possible antiepileptic drug goes along and it is known that such drugs are designed for long-term use., (© Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2016
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18. [Relationship between benign prostatic hyperplasia and prostate cancer: new opportunities for prostate cancer chemoprevention].
- Author
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Bespalov VG, Kuzhanov AA, Vasilieva IN, Semenov AL, and Alexandrov VA
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- Humans, Male, Risk Factors, Antineoplastic Agents therapeutic use, Prostatic Hyperplasia metabolism, Prostatic Hyperplasia pathology, Prostatic Hyperplasia prevention & control, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Prostatic Neoplasms prevention & control
- Abstract
In a review article the relationship between benign prostatic hyperplasia (BPH) and prostate cancer (PC) has been conducted. Epidemiological data on increasing the risk of PC in patients with BPH are presented. There are discussed common for BPH and PC constitutional, food, and life style etiologic factors and also common for the both diseases pathogenetic factors such as androgens, inflammation, metabolic syndrome. Pharmaceutical drugs and natural agents that have unidirectional therapeutic and preventive effect on BPH and PC are presented. Results of experimental studies of the authors to prove the link between BPH and PC are presented. It is concluded that BPH is a risk factor for PC and, ideally, drugs for the treatment of BPH should have a chemo preventive effect on PC.
- Published
- 2016
19. [Therapeutic activity of gemcitabine in intracranial tumors].
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Stukov AN, Filatova LV, Latipova DKh, Bespalov VG, Belyaeva OA, Kireeva GS, Vasilieva IN, Alexandrov VA, Maidin MA, Semenov AL, Vershinina SF, Markochev AB, Abduloeva NKh, Chubenko VA, and Semiglazova TY
- Subjects
- Animals, Antimetabolites, Antineoplastic administration & dosage, Brain Neoplasms etiology, Carmustine administration & dosage, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Deoxycytidine administration & dosage, Deoxycytidine pharmacology, Injections, Intraperitoneal, Male, Mice, Neoplasm Transplantation, Gemcitabine, Antimetabolites, Antineoplastic pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Brain Neoplasms drug therapy, Carcinoma, Ehrlich Tumor drug therapy, Deoxycytidine analogs & derivatives
- Abstract
Gemcitabine is known to exert a therapeutic effect on brain tumors despite the limited permeability of the blood-brain barrier (BBB). In our experimental research single intraperitoneal (i.p.) injection of gemcitabine 25 mg/kg provided increase in median survival of mice with intracranially transplanted Ehrlich carcinoma by 41-89% (p < 0.001). In this experimental model i.p. administration of gemcitabine (permeability of the BBB of less than 10%), carmustine (good permeability of the BBB), cyclophosphamide (poor permeability of the BBB) and cisplatin (doesn't penetrate through the BBB) increased median survival of mice by 88% (p < 0.001), 59% (p = 0.001), 35% (p = 0.005) and 18% (p = 0.302) respectively. Considering strong correlation between antitumor activity of the drugs (carmustine, cyclophosphamide and cisplatin) and their permeability of the BBB, efficacy of gemcitabine in intracranial tumors could be due to its wide range of therapeutic doses.
- Published
- 2015
20. [Intraperitoneal chemotherapy--a method of improving treatment effectiveness in ovarian cancer].
- Author
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Bespalov VG, Vyshinskaya EA, Vasilieva IN, Maidin MA, Semenov AL, Stukov AN, Kireeva GS, Belyaeva OA, Kopteva OS, Krasilnikova LA, Alexandrov VA, and Belyaev AM
- Subjects
- Animals, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Female, Infusions, Intravenous, Maximum Tolerated Dose, Melphalan administration & dosage, Mitomycin administration & dosage, Ovarian Neoplasms pathology, Paclitaxel administration & dosage, Peritoneal Neoplasms drug therapy, Peritoneal Neoplasms secondary, Rats, Rats, Wistar, Triazines administration & dosage, Gemcitabine, Antineoplastic Agents administration & dosage, Infusions, Parenteral, Ovarian Neoplasms drug therapy
- Abstract
The study or antitumor effects of dioxadet, cisplatin, melphalan, paclitaxel, mitomycin C, cyclophosphamide and gemcitabine at intraperitoneal (i.p.) and intravenous (i.v.) administration as monochemotherapy and polychemotherapy in a rat model of ascitic ovarian cancer was carried out in 244 female Wistar rats. Ovarian cancer was transplanted i.p. at a number of 1 x 10(7) tumor cells. The drugs were administered once in 48 hours after ovarian cancer transplantation i.p. or i.v. for monotherapy--in maximum tolerated doses, for i.p. polychemotherapy--in half doses from maximum tolerated doses. Antitumor effects of the treatment were estimated in increase in median survival time (MST) compared to control rats who were administered saline i.p. At i.p. administration dioxadet, cisplatin and melphalan increased MST by 79%, 88% and 144%, respectively, while at i.v. administration these drugs didn't affect MST. Mitomycin C and paclitaxel had stronger antitumor action at i.v. administration increasing MST by 152% and 81%, respectively, while at i.p. administration these drugs increased MST by 35 and 45%, respectively. Combinations dioxadet + cisplatin, dioxadet + cyclophosphamide and dioxadet + paclitaxel at i.p. administration increased MST by 305%, 277% and 133%, respectively, and had additive antitumor action compared to mono-effects of these drugs. Gemcitabine and combination dioxadet + gemcitabine at i.p. administration didn't significantly affect survival of rats with ovarian cancer. Intraperitoneal monochemotherapy and polychemotherapy could be more effective in the treatment of peritoneal carcinomatosis from ovarian cancer compared to systemic administration of the drugs.
- Published
- 2015
21. Anticarcinogenic activity of alpha-difluoromethylornithine, ginseng, eleutherococcus, and leuzea on radiation-induced carcinogenesis in female rats.
- Author
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Bespalov VG, Alexandrov VA, Semenov AL, Kovan'Ko EG, and Ivanov SD
- Subjects
- Animals, Female, Gamma Rays adverse effects, Rats, Survival Analysis, Whole-Body Irradiation adverse effects, Anticarcinogenic Agents pharmacology, Carcinogenesis drug effects, Carcinogenesis radiation effects, Eflornithine pharmacology, Eleutherococcus chemistry, Leuzea chemistry, Panax chemistry
- Abstract
Purpose: To carry out a comparative study of inhibition of radiation carcinogenesis using alpha-difluoromethylornithine (DFMO), tinctures of ginseng, eleutherococcus and leuzea in female rats., Materials and Methods: Locally bred female LIO-strain rats were subjected to a single whole body γ-irradiation dose of 4 Gy at 12 weeks of age. Modifying drugs were given with drinking water from the 10th day after irradiation until the end of the experiment (for 16 months)., Results: Irradiated rats developed tumors 70.0-79.6% (malignant tumors: 43.7-45.0%) with a multiplicity of 1.48-1.75 (malignant: 0.5-0.58), while in unirradiated animals the incidence of all/malignant tumors was 21.9%/7.7% with multiplicity of 0.22/0.08. In exposed rats tumors most often developed in the mammary gland - 57.3%, reproductive and endocrine organs - 27.2%, and other localizations - 29.1%. All drugs, except leuzea, significantly reduced incidence and multiplicity of tumors, overall or at some localizations in irradiated rats. Highest, and practically equal inhibition, was shown by ginseng and DFMO, while eleutherococcus was clearly inferior. Ginseng reduced overall tumor incidence and multiplicity by 1.5 and 2.4 times, malignant tumor incidence and multiplicity - by 2.5 and 2.9 times, respectively., Conclusions: The ginseng extract is the most promising radiation carcinogenesis inhibitor tested.
- Published
- 2014
- Full Text
- View/download PDF
22. Rodent models for the preclinical evaluation of drugs suitable for pharmacological intervention in aging.
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Anisimov VN, Zabezhinski MA, Popovich IG, Pliss GB, Bespalov VG, Alexandrov VA, Stukov AN, Anikin IV, Alimova IN, Egormin PА, Panchenko AV, Piskunova TS, Semenchenko AV, Tyndyk ML, and Yurova MN
- Subjects
- Aging physiology, Animals, Anticarcinogenic Agents adverse effects, Anticarcinogenic Agents pharmacology, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacology, Disease Models, Animal, Humans, Longevity, Mice, Rats, Aging drug effects, Drug Design, Drug Evaluation, Preclinical methods
- Abstract
Introduction: There is a growing scientific and public interest in the development of new antiaging drugs for the purposes of extending mean and/or maximum life span, maintaining normal physiological function, and alleviating the onset and severity of age-associated diseases. This review looks at the current screening approaches used to evaluate the efficacy of such compounds, with a particular focus on those that extend life span., Areas Covered: This article reviews the current preclinical approaches for assessing longevity therapy including the assessment of antiaging drugs (aging reversal) and geroprotectors (drugs that prevent premature aging and/or slowdown or postpone aging). This article also discusses the methods and the importance in evaluating the anticarcinogenic potential and safety of antitumor drugs., Expert Opinion: Based on more than 30 years of experience in the field, the authors believe that the standard testing protocols for antiaging drugs should include the simultaneous evaluation of the drug's safety, as well as its antitumor and anticarcinogenic activity potential. The authors also believe that the principles of international programs for the expert critical evaluation of pharmacological interventions should be created to improve the range of antiaging interventions available for human studies.
- Published
- 2012
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23. Residual dysplasia after successful Pavlik harness treatment: early ultrasound predictors.
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Alexiev VA, Harcke HT, and Kumar SJ
- Subjects
- Acetabulum diagnostic imaging, Chi-Square Distribution, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Infant, Male, Predictive Value of Tests, Probability, Radiography, Range of Motion, Articular physiology, Recurrence, Risk Assessment, Severity of Illness Index, Treatment Outcome, Ultrasonography, Doppler, Acetabulum growth & development, Hip Dislocation, Congenital diagnostic imaging, Hip Dislocation, Congenital therapy, Orthotic Devices
- Abstract
The purpose of this study was to evaluate a group of children treated with Pavlik harness for developmental dysplasia of the hip (DDH) to determine early ultrasound characteristics that predict poor acetabular development after walking age. From a group of 487 infants with DDH, 55 met inclusion criteria of (1) ultrasound documentation of major neonatal hip instability, (2) treatment with Pavlik harness, and (3) a minimum of 4 years of follow-up. These 55 infants had 100 abnormal hips. Harness treatment alone was successful in treating 87 of 100 hips. Persistent or late acetabular dysplasia was defined from serial radiographs. At a mean follow-up of 5.3 years, 5 of the 87 (6%) were found to have sequelae (late acetabular dysplasia, avascular necrosis of the femoral head, or both). Three sonographic findings present on the initial ultrasound predicted late sequelae: (1) dynamic coverage index of 22% or less, (2) alpha angle less than 43 degrees, and (3) abnormal echogenicity of the cartilaginous roof on initial ultrasound. Abnormal echogenicity was the most specific single predictor of residual dysplasia (sensitivity 100% and specificity 88%). The structurally normal cartilaginous roof is non-echogenic except for a short triangular fibrous tip (the labrum). Pathologic cartilage becomes echogenic beyond the tip as hyaline cartilage becomes fibrous and deformed. In unstable hips that respond well to Pavlik harness treatment, it would appear that midterm acetabular development can be affected when early transformation of roof cartilage accompanies displacement and instability.
- Published
- 2006
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24. Effects of glucose on cloning efficiency and mutagenesis of fetal rat cells.
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Donovan PJ, Smith GT, Riggs CW, and Alexandrov VA
- Subjects
- Animals, Cell Division, Cells, Cultured, Methylnitrosourea pharmacology, Mutation, Rats, Rats, Inbred F344, Time Factors, Cloning, Organism, Embryo, Mammalian cytology, Glucose pharmacology, Mutagenesis
- Abstract
In a previous study, treatment of rats with 10% glucose in the drinking water, as fetuses during gestation and for 1.5 months after delivery, significantly enhanced tumor incidence that resulted from N-methyl-N-nitrosourea (MNU, 20 mg/kg) given transplacentally on gestation day 21, with a 1.6-fold increase in overall tumor incidence. We investigated whether glucose would have an effect on MNU-induced mutation in fetal F-344 rat somatic cells as measured in an in vivo/in vitro assay. Rat fetuses were exposed transplacentally to MNU on gestation day 16 and to a 10% glucose solution from gestation day 7 to day 17. Cells were isolated on gestation day 17 for determination of cloning efficiency and for selection of 6-thioguanine (6-TG)-resistant HGPRT mutants. Cloning efficiency of the fetal cells exposed to MNU alone was 22.6+/-2.3% S.E., while that for cells from fetuses exposed to MNU+glucose was 27.5+/-1.6% S.E., which was a significant difference (P=0.018). This indicates an effect of glucose on cell proliferation and survival. MNU treatment significantly increased the mutation frequency of fetal cells from a spontaneous value of 0.4 x 10(-6) per viable cell to (8.8+/-1.8 S.E.,) x 10(-6) (P=0.0087). The coexposure to MNU and glucose yielded a mutant frequency per plate of 0.62+/-0.05 S.E., which was a 1.5-fold increase compared to MNU alone (0.43+/-0.11 S.E., P=0.075. In summary, the data indicate that glucose during pregnancy increases proliferation/survival of fetal cells and possibly also mutation rate.
- Published
- 2002
- Full Text
- View/download PDF
25. Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.
- Author
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Bespalov VG, Alexandrov VA, Limarenko AY, Voytenkov BO, Okulov VB, Kabulov MK, Peresunko AP, Slepyan LI, and Davydov VV
- Subjects
- Adenocarcinoma chemically induced, Adenocarcinoma prevention & control, Adult, Animals, Cells, Cultured, Clinical Trials as Topic, Culture Techniques, Cytotoxicity Tests, Immunologic, Disease Models, Animal, Endometrial Neoplasms pathology, Endometrial Neoplasms prevention & control, Endometrium pathology, Esophageal Neoplasms pathology, Esophageal Neoplasms prevention & control, Esophagus pathology, Estradiol blood, Female, Fibroadenoma chemically induced, Fibroadenoma prevention & control, Humans, Macrophages, Peritoneal cytology, Macrophages, Peritoneal immunology, Male, Mammary Neoplasms, Experimental chemically induced, Mammary Neoplasms, Experimental prevention & control, Mice, Mice, Inbred C57BL, Neoplasms, Experimental chemically induced, Nervous System Neoplasms chemically induced, Nervous System Neoplasms prevention & control, Precancerous Conditions pathology, Rats, Uterine Cervical Neoplasms chemically induced, Uterine Cervical Neoplasms prevention & control, Uterine Neoplasms chemically induced, Uterine Neoplasms prevention & control, Vaginal Neoplasms chemically induced, Vaginal Neoplasms prevention & control, Antineoplastic Agents, Phytogenic therapeutic use, Neoplasms, Experimental prevention & control, Panax metabolism, Precancerous Conditions prevention & control
- Abstract
The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.
- Published
- 2001
- Full Text
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26. Study of post-natal effect of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. III. Inhibitory action of indomethacin, voltaren, theophylline and epsilon-aminocaproic acid.
- Author
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Alexandrov VA, Bespalov VG, Petrov AS, Troyan DN, and Lidaks MYu
- Subjects
- Animals, Brain Neoplasms prevention & control, Carcinogens, Central Nervous System Neoplasms chemically induced, Central Nervous System Neoplasms pathology, Ethylnitrosourea, Female, Kidney Neoplasms chemically induced, Kidney Neoplasms pathology, Maternal-Fetal Exchange, Neoplasms, Experimental chemically induced, Neoplasms, Experimental pathology, Peripheral Nervous System Neoplasms chemically induced, Peripheral Nervous System Neoplasms pathology, Pregnancy, Rats, Spinal Cord Neoplasms prevention & control, Aminocaproic Acid pharmacology, Anticarcinogenic Agents pharmacology, Central Nervous System Neoplasms prevention & control, Diclofenac pharmacology, Indomethacin pharmacology, Kidney Neoplasms prevention & control, Neoplasms, Experimental prevention & control, Peripheral Nervous System Neoplasms prevention & control, Prenatal Exposure Delayed Effects, Theophylline pharmacology
- Abstract
The influence of the arachidonic acid metabolism inhibitors, indomethacin and voltaren; an inhibitor of phosphodiesterase activity, theophylline and the protease inhibitor epsilonaminocaproic acid (EACA) on N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was studied in rats. ENU was given to pregnant rats as a single i.v. exposure at a dose of 75 mg/kg body weight on the 21st day after conception. Indomethacin and voltaren (20 p.p.m. in drinking water), theophylline (0.01% in diet) and EACA (1000 p.p.m. in drinking water) were given to the offspring throughout their post-natal life until all survivors were killed at 12 months. In the ENU-only control groups, 100% of the offspring developed tumors of brain, spinal cord, peripheral nervous system or kidneys, with a total average number of 3.1 tumors per rat. The most marked inhibitory effect was exerted by theophylline, which significantly decreased the incidence and multiplicity of total tumors, and at all main sites selectively (brain, spinal cord, peripheral nerves and kidneys). It also prolonged average survival time of the offspring. Indomethacin and voltaren significantly decreased total tumor incidence and multiplicity and brain tumor incidence and multiplicity. Indomethacin also decreased kidney tumor multiplicity and voltaren diminished spinal cord tumor multiplicity. EACA decreased multiplicities of total, brain, peripheral nerve and kidney tumors, and diminished the incidence of brain tumors. These chemopreventive agents decreased tumor incidences 20-33% and tumor multiplicities 1.4-2.7 times, compared with the ENU-only controls.
- Published
- 1996
- Full Text
- View/download PDF
27. Study of the post-natal effects of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. II. Influence of low-molecular-weight polypeptide factors from the thymus, pineal gland, bone marrow, anterior hypothalamus, brain cortex and brain white substance.
- Author
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Alexandrov VA, Bespalov VG, Morozov VG, Khavinson VKh, and Anisimov VN
- Subjects
- Animals, Brain Neoplasms prevention & control, Carcinogens, Central Nervous System Neoplasms chemically induced, Central Nervous System Neoplasms pathology, Cerebral Cortex physiology, Ethylnitrosourea, Female, Kidney Neoplasms chemically induced, Kidney Neoplasms pathology, Maternal-Fetal Exchange, Neoplasms, Experimental chemically induced, Neoplasms, Experimental pathology, Peripheral Nervous System Neoplasms chemically induced, Peripheral Nervous System Neoplasms pathology, Pregnancy, Rats, Rats, Inbred Strains, Spinal Cord Neoplasms prevention & control, Anticarcinogenic Agents pharmacology, Bone Marrow physiology, Brain physiology, Central Nervous System Neoplasms prevention & control, Hypothalamus, Anterior physiology, Kidney Neoplasms prevention & control, Neoplasms, Experimental prevention & control, Peptides pharmacology, Peripheral Nervous System Neoplasms prevention & control, Pineal Gland physiology, Prenatal Exposure Delayed Effects, Thymus Gland physiology, Tissue Extracts
- Abstract
The influence of the polypeptide factors extracted from thymus, pineal gland, bone marrow, anterior hypothalamus, brain cortex or brain white substance on N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was studied in rats. ENU was given to pregnant rats as a single i.v. exposure at a dose of 75 mg/kg body weight on the 21st day of gestation. The polypeptide factors were given to the offspring as a series of s.c. injections, at a dose of 0.5 mg/rat/day, starting at one or 2.5 months of age and continuing throughout the whole of post-natal life. ENU induced tumors of the brain, spinal cord, peripheral nerves and kidneys in 94-98% of the offspring exposed to the carcinogen, with an average number of 2.3-2.6 tumors per rat, and an average survival time of 294 days. Post-natal thymus factor or pineal gland factor administration was followed by an increase in mean lifespan of approximately 2 months and a significant decrease (P < 0.05) in the total tumor number per tumor-bearing rat, as well as the incidence and multiplicity of spinal cord tumors. Pineal gland factor also decreased the incidence of peripheral nerve and kidney tumors and their number per tumor-bearing rat. Brain cortex factor and brain white substance factor treatment was followed by a decrease in total tumor multiplicity of 1.2- to 3.3-fold, and a decrease in incidence of brain tumors of 10 to 33% per rat in comparison to the controls. Brain cortex factor also decreased the total tumor incidence. At the same time, brain white substance factor administration increased the incidence of peripheral nerve tumors and decreased the mean lifespan. Both bone marrow factor and anterior hypothalamus factor did not have any modifying effects on any of the ENU-induced tumors and mean lifespan. Thus, our results show the possibility of attenuation of transplacental ENU-induced carcinogenesis with post-natal administration of some polypeptide substances.
- Published
- 1996
- Full Text
- View/download PDF
28. Focusing of submicron beams for TeV-scale e+e- linear colliders.
- Author
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Balakin V V, Alexandrov VA, Mikhailichenko A, Flöttmann K, Peters F, Voss G, Bharadwaj V V, Halling M, Holt JA, Buon J, Jeanjean J, LeDiberder F, Lepeltier V V, Puzo P, Heimlinger G, Settles R, Stierlin U, Hayano H, Ishihara N, Nakayama H, Oide K, Shintake T, Takeuchi Y, Yamamoto N, Bulos F, Burke D, Field R, Hartman S, Helm R, Irwin J, Iverson R, Rokni S, Roy G, Spence W, Tenenbaum P, Wagner SR, Walz D, and Williams S
- Published
- 1995
- Full Text
- View/download PDF
29. Study of postnatal effects of chemopreventive agents on offspring of ethylnitrosourea-induced transplacental carcinogenesis in rats. I. Influence of retinol acetate, alpha-tocopherol acetate, thiamine chloride, sodium selenite, and alpha-difluoromethylornithine.
- Author
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Alexandrov VA, Bespalov VG, Boone CW, Kelloff GJ, and Malone WF
- Subjects
- Animals, Diterpenes, Ethylnitrosourea, Female, Kidney Neoplasms chemically induced, Maternal-Fetal Exchange, Nervous System Neoplasms chemically induced, Pregnancy, Rats, Retinyl Esters, Sodium Selenite, Thiamine pharmacology, Tocopherols, Vitamin A administration & dosage, Vitamin A analogs & derivatives, Vitamin A pharmacology, Vitamin E administration & dosage, Vitamin E analogs & derivatives, Vitamin E pharmacology, Antioxidants pharmacology, Eflornithine pharmacology, Neoplasms, Experimental prevention & control, Selenium pharmacology, Vitamins pharmacology, alpha-Tocopherol analogs & derivatives
- Abstract
We studied the influence of the vitamins retinol acetate, alpha-tocopherol acetate and thiamine chloride; the antioxidant sodium selenite and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine, on the offspring of transplacental carcinogenesis by ethylnitrosourea in rats. Ethylnitrosourea was given to pregnant rats as a single i.v. injection, at a dose of 75 mg/kg body wt. or 5.5 mg/kg body wt., on the 21st day after conception. Retinol, tocopherol or thiamine was added to the diet, and selenite and alpha-difluoromethylornithine to drinking water of the offspring throughout their postnatal life at moderate doses. In control groups, ethylnitrosourea induced tumors of brain, spinal cord, peripheral nervous system and kidneys in the offspring. alpha-Difluoromethylornithine exerted a slight inhibitory effect; this agent decreased the total tumor multiplicity and the multiplicity of peripheral nervous system tumors and also prolonged survival time. Retinol, tocopherol, thiamine and selenite did not influence the development of the transplacentally-induced tumors.
- Published
- 1991
- Full Text
- View/download PDF
30. Glucose consumption, newborn weight and nitrosomethylurea transplacental carcinogenesis in rats.
- Author
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Berstein LM and Alexandrov VA
- Subjects
- Animals, Drug Interactions, Female, Fetus drug effects, Pregnancy, Rats, Animals, Newborn, Glucose pharmacology, Maternal-Fetal Exchange, Methylnitrosourea toxicity, Neoplasms, Experimental chemically induced, Nitrosourea Compounds toxicity
- Abstract
This study used rats bred at the Petrov Research Institute of Oncology. On the 21st day of pregnancy N-nitrosomethylurea (NMU) (20 mg/kg) was administered to the animals intraperitoneally. From the 7th day of pregnancy experimental rats were treated with 10% glucose solution instead of drinking water, and during 1.5 months after delivery the rats of this group and their progeny received 5% glucose solution. The present work has revealed an increase of fetal weight in pregnant rats treated with glucose. A significant increase of tumor frequency was detected in the progeny of these rats. In the male progeny, tumors of the nervous system and kidneys, typical for NMU, predominated and in females, tumors of other organs and tissues, particularly the mammary gland, pituitary body and hemopoietic system, predominated. This paper discusses a possible mechanism of the modifying effect of glucose on transplacental carcinogenic action of NMU.
- Published
- 1984
- Full Text
- View/download PDF
31. The inhibition of the transplacental blastomogenic effect of nitrosomethylurea by postnatal administration of buformin to rats.
- Author
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Alexandrov VA, Anisimov VN, Belous NM, Vasilyeva IA, and Mazon VB
- Subjects
- Animals, Buformin administration & dosage, Buformin pharmacology, Cholesterol blood, Dietary Carbohydrates pharmacokinetics, Diethylstilbestrol pharmacology, Energy Metabolism drug effects, Female, Glucose Tolerance Test, Hypertrophy, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents pharmacology, Hypothalamo-Hypophyseal System physiopathology, Insulin blood, Kidney Neoplasms chemically induced, Kidney Neoplasms embryology, Kidney Neoplasms prevention & control, Male, Maternal-Fetal Exchange, Neoplasms, Experimental chemically induced, Neoplasms, Experimental embryology, Neoplasms, Nerve Tissue chemically induced, Neoplasms, Nerve Tissue embryology, Neoplasms, Nerve Tissue prevention & control, Nervous System Neoplasms chemically induced, Nervous System Neoplasms embryology, Nervous System Neoplasms prevention & control, Ovariectomy, Ovary drug effects, Ovary pathology, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Somatomedins deficiency, Buformin therapeutic use, Diethylstilbestrol analogs & derivatives, Hypoglycemic Agents therapeutic use, Methylnitrosourea toxicity, Neoplasms, Experimental prevention & control
- Abstract
N-Nitrosomethylurea (NMU) (20 mg/kg) was i.p. administered to rats on the 21st day of pregnancy. A decrease of glucose utilisation in the oral glucose tolerance test was found in 3 month old female progeny of NMU-treated rats. The serum insulin level did not differ from control, but serum cholesterol level was higher in offspring of NMU-treated rats. The ability of diethylstilboestrol to inhibit compensatory ovarian hypertrophy was decreased in female hemicastrated 3 month old rats whose mothers were treated with NMU. Postnatal administration of the antidiabetic drug buformin decreased the malignant neurogenic tumor incidence 3.5 times (to rats transplacentally treated with NMU).
- Published
- 1980
- Full Text
- View/download PDF
32. Role of the maternal organism in transplacental carcinogenesis.
- Author
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Alexandrov VA
- Subjects
- Animals, Carcinogens metabolism, Cell Differentiation, Drug Interactions, Female, Fetus metabolism, Gestational Age, Mice, Neoplasms, Experimental embryology, Neoplasms, Experimental metabolism, Pharmaceutical Preparations metabolism, Placenta metabolism, Pregnancy, Rats, Species Specificity, Carcinogens toxicity, Maternal-Fetal Exchange, Neoplasms, Experimental chemically induced
- Abstract
The maternal organism plays a highly important role in transplacental carcinogenesis, since for carcinogens in the bloodstream of the mother to reach the fetus, they must cross several barriers, the first of which is the placenta. Some types of compounds require metabolic activation in the maternal organism, in the fetus and even sometimes in the placenta. Thus, four main pathways can be hypothesized by which substances exert a carcinogenic effect on the fetus. Most carcinogens can cross the placenta; data confirm that this process consists of simple diffusion or - in the case of high doses - facilitated diffusion. That carcinogens may be detoxified in the maternal organism is confirmed by experiments on activation of enzyme systems and on caesarean deliveries. Species and strain specificities are characteristic of transplacental carcinogenesis and are manifested in organotropism. Organotropism in transplacental carcinogenesis is determined by genetic predisposition, cell differentiation and proliferative activity in the target tissues. For indirect carcinogens, the level of metabolizing enzymes is also important.
- Published
- 1983
33. Nephroblastoma and renal mesenchymal tumor induced in rats by N-nitrosoethyl- and N-nitrosomethylurea.
- Author
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Turusov VS, Alexandrov VA, and Timoshenko IV
- Subjects
- Animals, Female, Kidney Neoplasms pathology, Mesenchymoma pathology, Neoplasms, Experimental chemically induced, Neoplasms, Experimental pathology, Rats, Wilms Tumor pathology, Ethylnitrosourea, Kidney Neoplasms chemically induced, Mesenchymoma chemically induced, Methylnitrosourea, Nitrosourea Compounds, Wilms Tumor chemically induced
- Abstract
Rats treated prenatally with N-nitrosoethylurea or with N-nitrosomethylurea developed nephroblastomas, renal mesenchymal tumors and epithelial tumors (adenomas and carcinomas) of the kidneys. 15 nephroblastomas and 59 mesenchymal tumors were examined histologically. Nephroblastomas were encapsulated growths composed of dark cells, forming primitive tubules similar to those seen in the rat embryonal kidney and in human Wilms' tumor. Mesenchymal renal tumors showed an infiltrative growth and consisted of fibroblast-like cells, smooth muscles and angiomatous areas with the engulfed pre-existing tubules. These growths are similar to the mesenchymal renal tumors induced in the rat by N-nitrosodimethylamine. Nephroblastoma and mesenchymal renal tumor are considered to be separated entities, the first corresponsing to the epithelial variant of human Wilms' tumor and the second to congenital mesoblastic nephroma.
- Published
- 1980
34. Neurotropic effect of 7,12-dimethylbenz(a)anthracene in transplacental carcinogenesis.
- Author
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Napalkov NP and Alexandrov VA
- Subjects
- Animals, Female, Gestational Age, Pregnancy, Rats, Benz(a)Anthracenes, Fetus drug effects, Maternal-Fetal Exchange, Neoplasms, Experimental chemically induced, Neoplasms, Nerve Tissue chemically induced
- Published
- 1974
- Full Text
- View/download PDF
35. Influence of hormonal disturbances on transplacental and multigeneration carcinogenesis in rats.
- Author
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Alexandrov VA, Popovich IG, Anisimov VN, and Napalkov NP
- Subjects
- Animals, Female, Male, Methylthiouracil, Neoplasms, Experimental genetics, Pregnancy, Rats, Thyroidectomy, Thyroxine, 9,10-Dimethyl-1,2-benzanthracene toxicity, Estrus physiology, Methylnitrosourea toxicity, Neoplasms, Experimental chemically induced, Prenatal Exposure Delayed Effects, Thyroid Hormones physiology
- Abstract
Thyroid dysfunction (induced by thyroidectomy or administration of thyroxin and methylthiouracil) during the postnatal period was tested as a modifying factor on carcinogenesis induced transplacentally by N-methyl-N-nitrosourea (MNU). It resulted mainly in inhibition of tumours of the nervous system and kidney in rats of two subsequent generations, but thyroid carcinogenesis was increased. Postnatal disturbance of oestrous function (induction of persistent oestrus syndrome) in female rats increased the incidence of tumours of the central nervous system induced transplacentally by MNU or 7,12-dimethylbenz[a]anthracene. No such effect was seen in animals of the F2 generation.
- Published
- 1989
36. Transplacental carcinogenic effect of n-nitrosoethylurea in dogs.
- Author
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Napalkov NP, Alexandrov VA, and Anisimov VN
- Subjects
- Animals, Brain Neoplasms chemically induced, Dogs, Female, Kidney Neoplasms chemically induced, Male, Neoplasms pathology, Neoplasms, Experimental chemically induced, Pregnancy, Splenic Neoplasms chemically induced, Thyroid Neoplasms chemically induced, Ethylnitrosourea toxicity, Fetus drug effects, Neoplasms chemically induced, Nitrosourea Compounds toxicity
- Abstract
During the late period of pregnancy (on the 50th and 53rd days post coitum) 2 dogs were injected intraperitoneally with 100 mg/kg (a single administration) of nitrosoethylurea. Nine puppies were born. During the 9 year period of observation no tumours were detected in mother-dogs. Three of 9 offspring developed the following tumours: brain haemangioblastoma (on the 526th day after administration), nephroblastoma and spleen angioleiomyoma (on the 845th day after administration) and adenoma of thyroid gland (after 7 years). Among other lesions 3 offspring-dogs developed polycystic kidneys. The revealed tumours of brain, kidney and spleen could be connected with transplacental carcinogenic effect of N-nitrosoethylurea (NEU), while neoplasms of these localizations and types rarely occur in dogs spontaneously.
- Published
- 1981
- Full Text
- View/download PDF
37. Some results and prospects of transplacental carcinogenesis studies.
- Author
-
Alexandrov VA
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene metabolism, Abnormalities, Drug-Induced pathology, Animals, Brain abnormalities, Disease Models, Animal, Female, Fetus metabolism, Neoplasms, Experimental chemically induced, Nervous System Diseases chemically induced, Organ Specificity, Placenta metabolism, Pregnancy, Rats, Brain Neoplasms chemically induced, Ethylnitrosourea, Maternal-Fetal Exchange, Methylnitrosourea, Nitrosourea Compounds
- Abstract
Analysis of literary data and the author's findings have shown that the transplacental action of most of the compounds tested in experiments on rats manifested itself by a neurotropic carcinogenic effect. A marked neurotropism in transplacental carcinogenesis in rats is characteristic even for such drugs (e.g. dimethylbenzathracene) that have never induced neurogenic neoplasms in adult animals. To elucidate the relationship between teratogenesis and carcinogenesis the peculiarities of tumor development in brain against the background of malformations induced by combined transplacental treatment by methylnitrosourea (MNU) and ethylnitrosourea (ENU) in rats have been studied. Tumorigenesis was sharply inhibited by administration of ENU (on the 13th day) prior to MNU treatment (on the 15th day). There is reason to believe that the cytotoxic effect of MNU for microephaly results in the death of a considerable part of the cell population already transformed by ENU. In a special series of experiments characteristics of the permeability of polycyclic aromatic hydrocarbons through the placenta in rats have been specified.
- Published
- 1976
38. Fetal macrosomia and sex differences in the influence of modifying factors on transplacental carcinogenesis.
- Author
-
Berstein LM and Alexandrov VA
- Subjects
- Animals, Female, Fetal Macrosomia chemically induced, Glucose, Male, Methylnitrosourea, Neoplasms, Experimental chemically induced, Neoplasms, Experimental embryology, Pregnancy, Sex Factors, Fetal Macrosomia complications, Neoplasms, Experimental etiology, Prenatal Exposure Delayed Effects
- Abstract
Differences in cancer frequency between men and women are well known. Sexual dimorphism is also observed in the development of some experimental tumours, including those induced transplacentally. Differences in the production and binding of sex hormones by target tissues are evidently not the only cause of sexual dichotomy in the action of modifying factors on transplacental carcinogenesis. In our experiments, the average weight of newborn rats treated with glucose during intrauterine life from day 7 to 20 of gestation exceeded that of control animals, and rats exposed transplacentally to N-methyl-N-nitrosourea (MNU) on day 21 of gestation in combination with glucose (beginning from day 7 of prenatal life to 1.5 months after delivery) had a significantly increased tumour frequency. In males, there was an increased frequency of neoplasms of the nervous system and kidneys, which are typical transplacental carcinogenic effects of MNU; however, in females, neoplasms were induced in other organs and tissues, mainly the mammary gland and pituitary body. Thus, fetal macrosomia acts as a modifying factor in transplacental carcinogenesis also by determining the tumour spectrum in females and males and not only in increasing tumour frequency. The possible causes of these differences and perspectives for further research are discussed.
- Published
- 1989
39. Carcinogenic effect of N-nitrosotriethylurea in single administration to female rats.
- Author
-
Anisimov VN, Alexandrov VA, Petrov AS, and Lijinsky W
- Subjects
- Animals, Female, Mammary Neoplasms, Experimental chemically induced, Neoplasms, Experimental pathology, Ovarian Neoplasms chemically induced, Rats, Rats, Inbred Strains, Uterine Neoplasms chemically induced, Neoplasms, Experimental chemically induced, Nitrosourea Compounds toxicity
- Abstract
N-Nitrosotriethylurea (NTEU) was administered once into the stomach or intravenously to outbred female rats. The rats given NTEU by oral administration developed malignant tumours of the mammary gland, uterus and liver. The rats exposed to NTEU by i.v. administration developed tumours of the mammary gland and ovaries. NTEU accelerated the appearance of tumours which are normally characteristic of the rat stock used (tumours of the pituitary, thyroid, adrenal cortex, fibroadenoma of the mammary gland, endometrial polyps.
- Published
- 1988
- Full Text
- View/download PDF
40. The stimulating effect of acetic acid, alcohol and thermal burn injury on esophagus and forestomach carcinogenesis induced by N-nitrososarcosin ethyl ester in rats.
- Author
-
Alexandrov VA, Novikov AI, Zabezhinsky MA, Stolyarov VI, and Petrov AS
- Subjects
- Acetic Acid, Animals, Carcinoma in Situ pathology, Carcinoma, Squamous Cell pathology, Cocarcinogenesis, Male, Papilloma pathology, Precancerous Conditions pathology, Rats, Acetates pharmacology, Carcinoma in Situ chemically induced, Carcinoma, Squamous Cell chemically induced, Esophageal Neoplasms chemically induced, Ethanol pharmacology, Hot Temperature, Nitrosamines, Papilloma chemically induced, Precancerous Conditions chemically induced, Stomach Neoplasms chemically induced
- Abstract
Five groups of outbred white male rats were given N-nitrososarcosin ethyl ester (NSEE) i.g. for 4 or 6 months at a daily dose of 50 mg/kg of body wt. 5 days/week. Some groups of animals were given a 3% water solution of acetic acid or a 40% solution of ethanol i.g. for 8 months from the beginning of the experiment. The remaining groups of these rats received controlled local thermal burn injury of the esophageal mucosa 15 days before the beginning of the experiment. Acetic acid solution increased the multiplicity of benign and malignant tumors as well as carcinoma incidence in the esophagus. Ethanol in combination with NSEE did not influence carcinogenesis in the esophagus but increased the incidence of leukokeratosis and the multiplicity of forestomach papillomas. In rats treated with NSEE after thermal burn injury, a significant increase in the frequency and multiplicity of papillomas was found in the burn zone.
- Published
- 1989
- Full Text
- View/download PDF
41. Inhibition of DMBA-induced carcinogenesis by phenformin in the mammary gland of rats.
- Author
-
Dilman VM, Berstein LM, Zabezhinski MA, Alexandrov VA, Bobrov JF, and Pliss GB
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene, Animals, Blood Glucose analysis, Cholesterol blood, Fatty Acids, Nonesterified blood, Insulin blood, Rats, Mammary Neoplasms, Experimental prevention & control, Phenformin therapeutic use
- Abstract
It is shown that daily oral administration of 5--10 mg of an antidiabetic biguanide-phenformin (phenethyl-biguanide) for 2.5--5 months suppressed DMBA-induced mammary tumour development in rats considerably. Phenformin-treated rats revealed-a tendency towards a decrease in blood insulin level (radioimmunoassay). The obtained data are regarded as additional evidence for the proposed existence of the same metabolic background of diseases of compensation, i.e. adult-onset diabetes, artherosclerosis and cancer, and suggest studies on possible antitumour effect of phenformin in man.
- Published
- 1978
42. [Teratogenic effect of ethylurea and nitrite in rats].
- Author
-
Alexandrov VA and Jänisch W
- Subjects
- Anencephaly chemically induced, Animals, Female, Hernia, Ventral chemically induced, Hydrocephalus chemically induced, Maternal-Fetal Exchange, Nitrosourea Compounds toxicity, Pregnancy, Rats, Abnormalities, Drug-Induced, Embryo, Mammalian drug effects, Nitrites toxicity, Urea toxicity
- Published
- 1971
- Full Text
- View/download PDF
43. Uterine, vaginal and mammary tumours induced by nitrosoureas in pregnant rats.
- Author
-
Alexandrov VA
- Subjects
- Animals, Female, Injections, Intraperitoneal, Injections, Intravenous, Pregnancy, Rats, Mammary Neoplasms, Experimental chemically induced, Nitroso Compounds, Pregnancy, Animal, Urea, Uterine Neoplasms chemically induced, Vaginal Neoplasms chemically induced
- Published
- 1969
- Full Text
- View/download PDF
44. Analysis of the lethal effect of "Myleran" on rat embryos.
- Author
-
Alexandrov VA
- Subjects
- Animals, Female, Palmitic Acids pharmacology, Pregnancy, Rats, Busulfan toxicity, Embryo, Mammalian drug effects, Pregnancy, Animal drug effects
- Published
- 1966
- Full Text
- View/download PDF
45. On the effects of blastomogenic substances on the organism during embryogenesis.
- Author
-
Napalkov NP and Alexandrov VA
- Subjects
- Aniline Compounds, Animals, Benz(a)Anthracenes, Carcinoma chemically induced, Carcinoma, Squamous Cell chemically induced, Female, Gestational Age, Hydrocephalus chemically induced, Kidney Neoplasms chemically induced, Maternal-Fetal Exchange, Methylthiouracil pharmacology, Microcephaly chemically induced, Pregnancy, Rats, Thyroid Neoplasms chemically induced, Urea, Urethane, Abnormalities, Drug-Induced, Neoplasms, Germ Cell and Embryonal chemically induced, Nitroso Compounds, Pregnancy, Animal
- Published
- 1968
- Full Text
- View/download PDF
46. Balneologic treatment of chronic osteomyelitis.
- Author
-
ALEXANDROV VA
- Subjects
- Humans, Balneology, Chronic Disease, Osteomyelitis
- Published
- 1946
47. Blastomogenic effect of dimethylnitrosamine on pregnant rats and their offspring.
- Author
-
Alexandrov VA
- Subjects
- Adenocarcinoma chemically induced, Adenoma chemically induced, Animals, Female, Kidney Neoplasms chemically induced, Rats, Sarcoma chemically induced, Wilms Tumor chemically induced, Carcinogens, Neoplasms, Experimental chemically induced, Nitrosamines, Pregnancy
- Published
- 1968
- Full Text
- View/download PDF
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