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1.
Curr Aging Sci ; 14(2): 124-132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33535964

RESUMO

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.


Assuntos
Hiperplasia Prostática , Animais , Masculino , Próstata , Hiperplasia Prostática/etiologia , Ratos , Ratos Wistar , Testosterona
2.
Pharmacol Rep ; 73(2): 642-649, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33604796

RESUMO

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.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Animais , Líquido Ascítico/citologia , Biologia Computacional , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Neoplasias , Neoplasias Ovarianas/patologia , Ratos , Ratos Wistar
3.
Drug Res (Stuttg) ; 70(2-03): 86-90, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31556073

RESUMO

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.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma de Ehrlich/tratamento farmacológico , Desoxicitidina/análogos & derivados , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/patologia , Carcinoma de Ehrlich/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacocinética , Desoxicitidina/farmacologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Permeabilidade , Distribuição Tecidual , Gencitabina
4.
Drug Res (Stuttg) ; 69(12): 683-687, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31550733

RESUMO

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 15th 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.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Metformina/farmacologia , Receptor ErbB-2/metabolismo , Toremifeno/farmacologia , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama Masculina/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Transgênicos
5.
Anticancer Agents Med Chem ; 19(13): 1627-1632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31284874

RESUMO

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.


Assuntos
Iodo/química , Proteínas do Leite/química , Hiperplasia Prostática/prevenção & controle , Antagonistas de Androgênios/administração & dosagem , Animais , Finasterida/administração & dosagem , Masculino , Proteínas do Leite/administração & dosagem , Ratos , Ratos Wistar
6.
J Ethnopharmacol ; 227: 1-7, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30114518

RESUMO

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.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Filipendula , Extratos Vegetais/uso terapêutico , Adenocarcinoma/induzido quimicamente , Adenocarcinoma/patologia , Animais , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/patologia , Feminino , Flores , Metilnitrosoureia , Fitoterapia , Ratos
7.
Anticancer Agents Med Chem ; 18(8): 1177-1183, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29607788

RESUMO

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.


Assuntos
Filipendula/química , Flavonoides/farmacologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Fenóis/farmacologia , Taninos/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Flavonoides/química , Flavonoides/isolamento & purificação , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Metilnitrosoureia/administração & dosagem , Estrutura Molecular , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Taninos/química , Taninos/isolamento & purificação
8.
Int J Hyperthermia ; 34(5): 545-550, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28893108

RESUMO

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 × 107 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 by 101316, 61524 and 1.71735 days, whereas with cisplatin by 61013, 122437 and -13523 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.


Assuntos
Ascite/tratamento farmacológico , Infusões Parenterais/métodos , Neoplasias Ovarianas/tratamento farmacológico , Animais , Ascite/patologia , Quimioterapia do Câncer por Perfusão Regional/métodos , Modelos Animais de Doenças , Feminino , Humanos , Hipertermia Induzida , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ratos , Ratos Wistar , Análise de Sobrevida
9.
Noise Health ; 19(87): 79-83, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29192617

RESUMO

OBJECTIVES: Evaluation of the effect of low-frequency noise (LFN) on the frequency of chromosomal aberrations in the bone marrow cells and on the content of low-molecular-weight DNA (lmwDNA) in the blood plasma of rats. MATERIALS AND METHODS: A total of 96 male Wistar rats were exposed to either single (17 min session) or multiple (17 min session repeated five times a week for 13 weeks) LFN, with the maximum range below 250 Hz and the sound pressure levels (SPLs) at 120 and 150 dB, respectively. The rats in the control groups were not subjected to any impact. The frequency of chromosomal aberrations in the bone marrow cells and the levels of lmwDNA in the blood plasma were measured afterwards. RESULTS: It has been detected that a single LFN exposure with either corresponding SPLs had a significant increase in the frequency of chromosomal aberrations (more than 10-fold) compared to the controls (0.9 ± 0.3%) and resulted in the appearance of dicentric chromosomes in the aberration spectrum, both of which are evident for the occurrence of deoxyribonucleic acid double strand breaks triggered by the exposure. Furthermore, the lmwDNA levels in the blood plasma measured the following day after a single LFN exposure were significantly higher (7.7- and 7.6-fold, respectively) than that in the control group (11.0 ± 5.4 ng/ml), and such levels were maintained higher (4.8- and 2.1-fold, respectively) in the week after a single LFN exposure for the SPL of 120 and 150 dB, respectively, compared to the control group (18.8 ± 1.6 ng/ml). Similar results were obtained from the group with multiple LFN exposures (36.4- and 22.4-fold, respectively) compared to the control (17.7 ± 1.7 ng/ml) and suggest the enhancement of cellular apoptosis as a result of the LFN impact. CONCLUSION: Presumably, the LFN may have possible mutagenic effects and cause massive cell death.


Assuntos
Células da Medula Óssea/patologia , Aberrações Cromossômicas , DNA/sangue , Ruído/efeitos adversos , Animais , Masculino , Peso Molecular , Ratos , Ratos Wistar
10.
J Neurooncol ; 131(3): 459-467, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27838807

RESUMO

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.


Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Etilnitrosoureia/toxicidade , Filipendula , Extratos Vegetais/administração & dosagem , Animais , Neoplasias do Sistema Nervoso Central/induzido quimicamente , Neoplasias do Sistema Nervoso Central/patologia , Modelos Animais de Doenças , Feminino , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Troca Materno-Fetal , Extratos Vegetais/uso terapêutico , Gravidez , Efeitos Tardios da Exposição Pré-Natal
11.
Int J Radiat Biol ; 93(4): 394-401, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27827272

RESUMO

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.


Assuntos
Filipendula/química , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/prevenção & controle , Extratos Vegetais/administração & dosagem , Protetores contra Radiação/administração & dosagem , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/efeitos da radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Feminino , Flores/química , Neoplasias Induzidas por Radiação/etiologia , Doses de Radiação , Ratos , Taxa de Sobrevida , Resultado do Tratamento , Irradiação Corporal Total/efeitos adversos
12.
Adv Exp Med Biol ; 924: 79-84, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27753023

RESUMO

Exposure to either to low-frequency noise or ionizing radiation causes an increase in the number of chromosomal aberrations in the bone marrow cells and the level of low-molecular-weight DNA in the blood plasma of experimental animals. The dynamics of the content of low-molecular-weight DNA increasing after exposure to low-frequency noise and ionizing radiation differs significantly. Both exposures are able to provide a direct damaging effect on DNA.


Assuntos
Células da Medula Óssea/metabolismo , Aberrações Cromossômicas , Dano ao DNA , DNA/genética , Ruído , Radiação Ionizante , Animais , Células da Medula Óssea/efeitos da radiação , DNA/sangue , Pulmão/metabolismo , Pulmão/patologia , Pulmão/efeitos da radiação , Masculino , Modelos Genéticos , Ratos Wistar
13.
Adv Exp Med Biol ; 924: 85-89, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27753024

RESUMO

Only limited sequencing data of the normal extracellular DNA (ecDNA) are currently available. The uptake of the ecDNA by cultured cells and its integration into the host chromatin have been demonstrated. A number of membrane-bearing vesicles in plasma and serum have been shown to carry nucleic acids. The presence of Tandem Repeat (TR) in both apoptotic DNA of HUVEC culture medium and membrane-associated DNA is shown. The existence and successful application of CREST serum also show the presence of fragments of the centromeric heterochromatin together with their TR and specific proteins in blood. Apparently, pericentromeric and centromeric DNA (TR) should be part of ecDNA in all cases.


Assuntos
Centrômero/genética , DNA/genética , Heterocromatina/genética , Sequências de Repetição em Tandem/genética , Células Cultivadas , DNA/metabolismo , Espaço Extracelular/genética , Humanos , Hibridização in Situ Fluorescente , Análise de Sequência de DNA/métodos
14.
J Surg Oncol ; 113(4): 438-42, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26710749

RESUMO

BACKGROUND AND OBJECTIVES: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the time of Cytoreductive Surgery (CRS) is an actively researched treatment in patients with advanced ovarian cancer. Relative contribution of heat and chemotherapeutic agents during HIPEC as well as efficacy of a new agent dioxadet for regional chemotherapy in a rat model of ovarian cancer was studied. METHODS: Sixty rats were divided into three groups: no treatment control group (n = 19), hyperthermia without chemotherapy (HIPEP) (n = 14), HIPEC + cisplatin (n = 14), HIPEC + dioxadet (n = 13). The intra-abdominal tumor was not resected. End points were: median survival (primary), cause of death (secondary). RESULTS: The median survival of the animals in the control group, HIPEP group, HIPEC + cisplatin, HIPEC + dioxadet were 9 (CI; 8-23), 22.5 (CI; 12-43), 25.5 (CI; 13-62), 49 (Cl; 28-70) days, respectively. The P-values control versus HIPEP, HIPEC + cisplatin versus HIPEC + dioxadet were 0.006, 0.002, and 0.001, respectively. CONCLUSION: During HIPEC both the heat and the cytotoxic drug had antitumor effects in a rat ovarian cancer model. Dioxadet showed potential as a drug for regional chemotherapy. J. Surg. Oncol. 2016;113:438-442. © 2015 Wiley Periodicals, Inc.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Hipertermia Induzida/métodos , Neoplasias Ovarianas/terapia , Triazinas/administração & dosagem , Animais , Quimioterapia do Câncer por Perfusão Regional/métodos , Cisplatino/administração & dosagem , Terapia Combinada , Modelos Animais de Doenças , Feminino , Infusões Parenterais , Neoplasias Ovarianas/tratamento farmacológico , Distribuição Aleatória , Ratos
15.
Int J Radiat Biol ; 90(12): 1191-200, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24913295

RESUMO

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.


Assuntos
Anticarcinógenos/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/efeitos da radiação , Eflornitina/farmacologia , Eleutherococcus/química , Leuzea/química , Panax/química , Animais , Feminino , Raios gama/efeitos adversos , Ratos , Análise de Sobrevida , Irradiação Corporal Total/efeitos adversos
16.
Expert Opin Drug Discov ; 7(1): 85-95, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22468896

RESUMO

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.


Assuntos
Envelhecimento/efeitos dos fármacos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Envelhecimento/fisiologia , Animais , Anticarcinógenos/efeitos adversos , Anticarcinógenos/farmacologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Modelos Animais de Doenças , Humanos , Longevidade , Camundongos , Ratos
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