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1.
Environ Health Prev Med ; 23(1): 36, 2018 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-30092754

RESUMEN

Cancerous tissue transformation developing usually over years or even decades of life is a highly complex process involving strong stressors damaging DNA, chronic inflammation, comprehensive interaction between relevant molecular pathways, and cellular cross-talk within the neighboring tissues. Only the minor part of all cancer cases are caused by inborn predisposition; the absolute majority carry a sporadic character based on modifiable risk factors which play a central role in cancer prevention. Amongst most promising candidates for dietary supplements are bioactive phytochemicals demonstrating strong anticancer effects. Abundant evidence has been collected for beneficial effects of flavonoids, carotenoids, phenolic acids, and organosulfur compounds affecting a number of cancer-related pathways. Phytochemicals may positively affect processes of cell signaling, cell cycle regulation, oxidative stress response, and inflammation. They can modulate non-coding RNAs, upregulate tumor suppressive miRNAs, and downregulate oncogenic miRNAs that synergically inhibits cancer cell growth and cancer stem cell self-renewal. Potential clinical utility of the phytochemicals is discussed providing examples for chemoprevention against and therapy for human breast cancer. Expert recommendations are provided in the context of preventive medicine.


Asunto(s)
Anticarcinógenos/farmacología , Neoplasias de la Mama/prevención & control , Fitoquímicos/farmacología , Animales , Apoptosis/efectos de los fármacos , Carotenoides/farmacología , Proliferación Celular/efectos de los fármacos , Humanos , Mediadores de Inflamación/metabolismo , Metástasis de la Neoplasia/prevención & control , Células Madre Neoplásicas/efectos de los fármacos , Neovascularización Patológica/prevención & control , Fenoles/farmacología , ARN no Traducido/efectos de los fármacos , Compuestos de Azufre/farmacología
2.
Adv Exp Med Biol ; 911: 1-8, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26987328

RESUMEN

MicroRNAs (miRNAs) are a class of small single-stranded non-protein-coding RNAs that play important regulatory roles in many cellular processes including cell proliferation, differentiation, growth control, and apoptosis. They regulate gene expression on the posttranscriptional level by translational repression, mRNA cleavage, or mRNA degradation in various physiological and pathological processes. In addition, some miRNAs can function as oncogenes or tumor suppressors, so they can regulate several genes that play important roles in tumorigenesis. It was found that miRNAs are directly involved in many types of cancer, including lung cancer. Lung cancer is the leading cause of cancer mortality worldwide with a substantially low survival rate. In this work, we summarize recent findings related to miRNAs mechanisms of action and the role of their dysregulated expression in lung tumorigenesis. We describe the most important miRNAs involved in lung cancer development and targets of their activity. The understanding of the miRNA regulation in cancer may help better understand the molecular mechanisms of tumorigenesis and their importance in cancerous transformation.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Neoplasias/genética , Neoplasias/patología , Oncogenes/genética , Humanos
3.
Adv Exp Med Biol ; 911: 17-22, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26987333

RESUMEN

Chromium is a well-known mutagen and carcinogen involved in lung cancer development. DNA repair genes play an important role in the elimination of genetic changes caused by chromium exposure. In the present study, we investigated the polymorphisms of the following DNA repair genes: XRCC3, participating in the homologous recombination repair, and hMLH1 and hMSH2, functioning in the mismatch repair. We focused on the risk the polymorphisms present in the development of lung cancer regarding the exposure to chromium. We analyzed 106 individuals; 45 patients exposed to chromium with diagnosed lung cancer and 61 healthy controls. Genotypes were determined by a PCR-RFLP method. We unravelled a potential for increased risk of lung cancer development in the hMLH1 (rs1800734) AA genotype in the recessive model. In conclusion, gene polymorphisms in the DNA repair genes underscores the risk of lung cancer development in chromium exposed individuals.


Asunto(s)
Cromo/efectos adversos , Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/genética , Homólogo 1 de la Proteína MutL/genética , Proteína 2 Homóloga a MutS/genética , Exposición Profesional/efectos adversos , Polimorfismo Genético/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Reparación del ADN , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Tasa de Supervivencia
4.
Eur Cell Mater ; 25: 351-65; discussion 365, 2013 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-23832688

RESUMEN

Full-thickness articular cartilage damage does not resolve spontaneously. Studies with growth factors, implantation of autologous chondrocytes and mesenchymal stem cells have led to variable, to some extent inconsistent, results. This work compares osteochondral knee-defect repair in rabbits upon implantation of a previously described alginate/(poly(lactic-co-glycolic) acid (PLGA) osteochondral scaffold in distinct conditions. Systems were either in vitro pre-cultured with a small number of allogeneic chondrocytes under fibroblast growth factor (FGF)-2 stimulation or the same amount of allogeneic, marrow derived, mesenchymal stem cells (without any pre-differentiation), or loaded with microsphere-encapsulated bone morphogenetic protein (BMP)-2 within the alginate layer, or holding combinations of one or the other cell type with BMP-2. The experimental limit was 12 weeks, because a foregoing study with this release system had shown a maintained tissue response for at least 24 weeks post-operation. After only 6 weeks, histological analyses revealed newly formed cartilage-like tissue, which resembled the adjacent, normal cartilage in cell as well as BMP-2 treated defects, but cell therapy gave higher histological scores. This advantage evened out until 12 weeks. Combinations of cells and BMP-2 did not result in any additive or synergistic effect. Equally efficient osteochondral defect repair was achieved with chondrocyte, stem cell, and BMP-2 treatment. Expression of collagen X and collagen I, signs of ongoing ossification, were histologically undetectable, and the presence of aggrecan protein indicated cartilage-like tissue. In conclusion, further work should demonstrate whether spatiotemporally controlled, on-site BMP-2 release alone could become a feasible therapeutic approach to repair large osteochondral defects.


Asunto(s)
Proteína Morfogenética Ósea 2/farmacología , Cartílago Articular/patología , Condrocitos/citología , Trasplante de Células Madre , Células Madre/citología , Cicatrización de Heridas/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Cartílago Articular/efectos de los fármacos , Cartílago Articular/metabolismo , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Ácido Láctico/química , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Implantación de Prótesis , Conejos , Regeneración/efectos de los fármacos , Células Madre/efectos de los fármacos , Andamios del Tejido/química
5.
Neoplasma ; 60(1): 46-55, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23067216

RESUMEN

Peroral antidiabetics from thiazolidinedione (glitazone) group showed oncostatic effects in preclinical models. This study evaluated chemopreventive effects of rosiglitazone in N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. N-methyl-N-nitrosourea was administered in two intraperitoneal doses each per 50 mg/kg b.w. between 40th and 51st postnatal days. Rosiglitazone was administered in a diet at a concentration of 10 ppm and 100 ppm, respectively, 9 days before the first carcinogen dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors and estimation of latency period, tumor frequency per group and animal, and tumor volume were recorded. The experiment was terminated 16 weeks after the first carcinogen dose, basic tumor growth parameters and selected metabolic and hormonal variables were evaluated. Chemoprevention with higher rosiglitazone dose decreased tumor frequency per group by 44%, other tumor parameters (incidence, tumor frequency per animal) were decreased insignificantly (at both doses), latency period was not changed. Rosiglitazone administration decreased cumulative tumor volume, more efficiently at lower dose. Glycaemia and insulinaemia decreased after lower rosigitazone dose administration but glycaemia did not exceed normal values. Higher rosiglitazone dose alleviated some metabolic alterations resulting from cancer progression more effectively but induced a prominent cardiac hypertrophy.


Asunto(s)
Transformación Celular Neoplásica/efectos de los fármacos , Hipoglucemiantes/farmacología , Neoplasias Mamarias Animales/tratamiento farmacológico , Tiazolidinedionas/farmacología , Animales , Carcinógenos/toxicidad , Femenino , Índice Glucémico , Insulina/metabolismo , Neoplasias Mamarias Animales/inducido químicamente , Neoplasias Mamarias Animales/patología , Metilnitrosourea/toxicidad , Ratas , Ratas Sprague-Dawley , Rosiglitazona
6.
Neoplasma ; 59(5): 516-23, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22668016

RESUMEN

The results of experimental studies have indicated the pleiotropic effects of statins in organism, e.g. the influence on cell cycle, apoptosis or angiogenesis. In this study, the effects of simvastatin on selected parameters of apoptosis and proliferation in chemocarcinogen-induced mammary tumorigenesis in female rats were determined. Simvastatin was administered dietary at a dose of 18 mg/kg and highly effective dose of 180 mg/kg the entire experiment (18 weeks). At autopsy mammary tumors were removed and prepared for immunohistochemical and histomorphological analysis. In treated animals (simvastatin 180 mg/kg), significant decrease by 12% in Bcl-2 protein expression and non-significant decrease by 27% of Ki67 protein expression in tumor cells compared to tumor cells in control animals were observed after semiquantitative evaluation. Morphometrical analysis has shown significant proapototic shift in Bcl-2/Bax ratio in tumor cells. In high grade control carcinoma cells, the expression of Ki67 increased by 37% (non-significantly) in comparison with control low grade carcinomas. A histomorphological analysis of malignant tumors has revealed a shift from high grade to low grade carcinomas after simvastatin treatment. The noticeable decrease of mammary tumor frequency and incidence in rats after simvastatin treatment was accompanied with antiapoptotic Blc-2 protein decrease and proapoptotic Bax protein increase in this experiment.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Animales/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Simvastatina/uso terapéutico , Proteína X Asociada a bcl-2/metabolismo , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Técnicas para Inmunoenzimas , Neoplasias Mamarias Animales/metabolismo , Ratas , Ratas Sprague-Dawley
7.
Neoplasma ; 59(4): 469-74, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22489703

RESUMEN

The aim of this paper was to test lower, safe bexarotene dose administered alone and in combination with melatonin to improve its efficacy. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea in female Sprague-Dawley rats, administered in two doses intraperitoneally between 42.-54. postnatal days and chemoprevention was initiated 7 days prior to first N-methyl-N-nitrosourea injection and lasted 15 weeks. Bexarotene, particularly in combination with melatonin decreased mammary tumor incidence and frequency with a shift from poorly to well differentiated carcinomas. Bexarotene alleviated glycaemia and liver/heart muscle glycogen concentration decreased as well as liver/thymus malondialdehyde increased in comparison with control group. The combination of bexarotene and melatonin is therefore beneficial in preventive-curative model of experimental mammary carcinogenesis and may be applied in oncological practice as such.


Asunto(s)
Anticarcinógenos/uso terapéutico , Antioxidantes/uso terapéutico , Neoplasias Mamarias Experimentales/prevención & control , Melatonina/uso terapéutico , Tetrahidronaftalenos/uso terapéutico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Bexaroteno , Carcinógenos/toxicidad , Femenino , Neoplasias Mamarias Experimentales/inducido químicamente , Metilnitrosourea/toxicidad , Ratas , Ratas Sprague-Dawley , Resultado del Tratamiento
8.
Bratisl Lek Listy ; 113(10): 624-7, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23094905

RESUMEN

Basal cell carcinoma (BCC) is recently the most common cancer in humans characterized by several histopathological subtypes. Fibroepithelioma of Pinkus (FEP) is traditionally classified as a very rare variant of BCC, however, it manifests clinical and morphological differences that distinguish it from most other types BCCs. This study was performed to evaluate the incidence of FEP and clinical-pathological characteristics of patients diagnosed with this tumor. Four cases of primary FEP (3 females, 1 male, mean age 53.4 y) were analyzed retrospectively. The prevalence of FEP was 0.7 % of all diagnosed BCCs. Topographically, tumors were localized on the right brachium, right gluteal region, left mesogastrium, and right side of the abdomen. Histological examination showed typical anastomosing cords of basaloid cells extending from the overlying epidermis into the loose fibrous stroma in the dermis. Mitotic activity or significant cellular atypia, as well as sign of solar dermatosis were absent. Mean horizontal and vertical diameter of the lesions were 7.7 and 2.8 mm, retrospectively. We did not observe infiltration of deeper skin structures. All lesions were removed completely and classified as pathological stage pT1. Three cases manifested typical picture of a "pure" FEP, one lesion had partially a feature of nodular type BCC, too. Although FEP is conventionally considered as indolent BCC variant with a favorable clinical outcome, recent evidences also favors its classification as a form of trichoblastoma. This is appropriate example how some types of cutaneous tumors can overlap in terms of dignity and clinical-morphological characteristics. This should be taken into account in differential diagnosis and in predicting of biological behaviour of the individual tumors of the skin (Tab. 2, Fig. 3, Ref. 26).


Asunto(s)
Carcinoma Basocelular/patología , Neoplasias Fibroepiteliales/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
9.
Klin Onkol ; 25(4): 262-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22920166

RESUMEN

BACKGROUND: Basal cell carcinoma (BCC) recurrences are relatively frequent event in a routine dermatologic practice. One of the most important factor which impacts risk of their development is a histomorphological appearance of tumor. DESIGN: The purpose of our study was to compare histological types of primary and corresponding relapsing BCCs of the skin. MATERIAL AND METHODS: The study included 36 cases of BCC recurrences from 34 patients, 17 women and 17 men. The patients ranged in age from 32 to 97 years, with a mean age of 67.1 years at the time of (the first) recurrence. RESULTS: Both tumor groups generally exhibited the same proportion of indolent and aggressive histological phenotype. In 21 cases (58.4%), we found an identical histological BCC type in primary and subsequent relapsing lesion. In 3 cases (8.3%), primary lesion showed indolent histological features without aggressive--growth component, while recurrent tumor already manifested it. Conversely, in next 3 cases (8.3%) primary tumor exhibited focal infiltrative-growth features and corresponding relapsing lesion did not. Of the remaining 9 cases (25%), histomorphological phenotype was not identical, but it showed the same prognostic histological tumor variant. CONCLUSION: Based on the results of our study it can be assumed that a BCC recurrence is a dynamic histogenetic process, during which the phenotypic transformation and the changes in histomorphological picture of lesions occur, probably as a result of the interactions between cancer cells and re-modulated surrounding stroma.


Asunto(s)
Carcinoma Basocelular/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
10.
Klin Onkol ; 25(5): 359-63, 2012.
Artículo en Sk | MEDLINE | ID: mdl-23102197

RESUMEN

BACKGROUND: High levels of prostaglandins found in many neoplastic tissues, especially in colon cancer and breast cancer, suggest a role of cyclooxygenase in the process of carcinogenesis. MATERIAL AND METHODS: The aim of this study was to analyse the chemopreventive potential of non-steroidal inflammatory drug indomethacin and its combination with pineal hormone melatonin in rat mammary carcinogenesis induced by N-methyl-N-nitrosourea. Indomethacin was administered 3 times a week and melatonin 4 times a week, both substances in a concentration of 20 µg/ml of drinking water. Chemoprevention began approximately 2 weeks before carcinogen administration and lasted until the end of the experiment 25 weeks later. RESULTS: Indomethacin administered alone and in combination with melatonin stimulated the growth of mammary tumors. We found a significant increase in the average tumor volume caused by indomethacin alone by 126%, and in combination with melatonin by 104% compared to the control group. Indomethacin administered alone increased the incidence of tumors by 21.5% (also in combination with melatonin) and reduced the tumor latency by 17 days compared to controls. Melatonin alone significantly reduced tumor volume in comparison with control animals. During the long-term administration, both substances were well tolerated by animals. CONCLUSION: Indomethacin, a predominant cyclooxygenase inhibitor-1, showed significant neoplastic effects in the prevention of N-methyl-N-nitrosourea induced rat mammary carcinogenesis. This finding is in strong contrast to our previous experiment, where indomethacin in 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis revealed marked antineoplastic effects.


Asunto(s)
Anticarcinógenos/uso terapéutico , Quimioprevención , Indometacina/uso terapéutico , Neoplasias Mamarias Experimentales/prevención & control , Melatonina/uso terapéutico , Animales , Femenino , Neoplasias Mamarias Experimentales/inducido químicamente , Metilnitrosourea , Ratas , Ratas Sprague-Dawley
11.
Klin Onkol ; 25(2): 124-9, 2012.
Artículo en Sk | MEDLINE | ID: mdl-22533887

RESUMEN

AIM: Increasing prevalence of non-malignant thyroid disorders in women with breast cancer has been known for several decades; it is said to be associated with a better prognosis of the cancerous disease. The aim of this work was to analyse associations between thyropathies found in women with breast cancer and particular prognostic factors. PATIENTS AND METHODS: A group of 110 women with breast cancer were tested for autoimmune thyroiditis (AIT) and functional changes of the thyroid gland. Presence of thyroid-peroxidase autoantibodies (TPOAb), serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT3, FT4) were determined after the surgery but before adjuvant cancer treatment (radiotherapy, chemotherapy or hormone therapy) initiation. Conventionally evaluated prognostic factors of breast cancer, including histological grading and molecular predictive factors (i.e. the status of the hormone receptors and the human epidermal growth factor receptor) were assessed - these were divided into four basic categories. RESULTS AND CONCLUSIONS: The incidence of AIT and subclinical hypothyroidism in the study group was 37.3% and 20%, respectively, i.e. higher than in the general population. The only correlation found was between thyropathies and the specific prognostic factors was that with G1 breast cancer grading.


Asunto(s)
Neoplasias de la Mama/complicaciones , Hipotiroidismo/complicaciones , Tiroiditis Autoinmune/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Pronóstico
12.
Cesk Patol ; 47(4): 178-82, 2011 Oct.
Artículo en Sk | MEDLINE | ID: mdl-22145219

RESUMEN

Basal cell carcinoma (BCC) of the skin is generally characterised by a favourable clinical outcome. The slow and mostly local character of growth helps in its early recognition, thus the vast majority of cases are diagnosed in the early phase of disease. However, in cases of long-term neglect of clinical symptoms, certain cancers may reach huge proportions and may significantly destroy surrounding tissue. BCCs larger than 5 cm are called giant BCCs. The authors of the article present a case report of woman suffering from a giant BCC of the head with a history of 15 years of lasting growth, during which she had refused a medical examination. Finally, she was forced to go into hospital due to episodes of unconsciousness and convulsions. Clinical investigations revealed a huge ulcerating tumour in the fronto-parietal region infiltrating the skull and penetrating into the cranial cavity with compression of the brain. A surgical extirpation of the tumor-affected soft tissue and the calva was performed with plastic reconstruction of dura mater and skin. Microscopic examination of biopsy specimens confirmed a diagnosis of mixed BCC with nodular, infiltrative and metatypical features, which had completely infiltrated calva and dura mater. It was not possible to surgically remove a part of the tumour-affected bones of the left orbita, thus the patient is going to undergo local radiotherapy. This case report emphasizes the fact that BCC, in spite of its usually "benign" biological behaviour, should never be underestimated because it may progress to the advanced stage of the disease, for which treatment is much more difficult with a larger negative impact and a significantly worse prognosis for the patient.


Asunto(s)
Carcinoma Basocelular/patología , Neoplasias de Cabeza y Cuello/patología , Cuero Cabelludo , Neoplasias Cutáneas/patología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Carcinoma Basocelular/cirugía , Femenino , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Cutáneas/cirugía , Neoplasias Craneales/patología , Neoplasias Craneales/cirugía
13.
Klin Onkol ; 24(1): 8-17, 2011.
Artículo en Sk | MEDLINE | ID: mdl-21542271

RESUMEN

Basal cell carcinoma of the skin is currently the most frequent malignancy in human population. Basal cell carcinoma represents a heterogeneous group of tumors with a variable clinical and morphological picture. Based on its biological behaviour, we generally differentiate between indolent (superficial and nodular) and aggressive type (infiltrative, micronodular, and metatypical) of basal cell carcinoma. Because of the different biological characteristics of these tumors, it is questionable whether they are a part of a continuous spectrum of carcinogenesis, starting with indolent and ending with aggressive forms, or they represent separate developmental lines. In the current clinical practice, there is an increasing demand for identification of tumors that are prognostically more adverse and their impact on the overall health status of patients is more serious. Recent advances in pathology and molecular medicine allow identification of various biomarkers from tumor tissue that are significantly involved in the mechanisms of malignant cell transformation. Detection of these biomarkers is of great importance in predicting further clinical behaviour of the cancer. The authors of the paper present basic information about biological behaviour of cutaneous basal cell carcinoma and provide an overview of the most important biomarkers that influence the clinical outcome and disease progression and are detectable through a routine biopsy tissue examination. It is now necessary to search for novel histological and molecular parameters that, in the future, could have a prognostic value in diagnostic and therapeutic process of this disorder.


Asunto(s)
Carcinoma Basocelular/patología , Neoplasias Cutáneas/patología , Carcinoma Basocelular/genética , Carcinoma Basocelular/secundario , Progresión de la Enfermedad , Genes Supresores de Tumor , Humanos , Pronóstico , Neoplasias Cutáneas/genética
14.
Klin Onkol ; 24(1): 41-5, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21539141

RESUMEN

BACKGROUNDS: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have proven therapeutic and preventive effects on cardiovascular diseases. Preclinical evidence demonstrates tumor-suppressive effects of statins in several human neoplasias, including breast cancer. MATERIALS AND METHODS: In this study, antineoplastic effects of simvastatin in chemoprevention of N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats were evaluated. The drug was dietary administered at two concentrations--18 mg/kg (SIMVA 18) and 180 mg/kg (SIMVA 180). RESULTS: Basic parameters of experimental carcinogenesis after long-term simvastatin treatment in animals were assessed. In the SIMVA 180 group, simvastatin significantly suppressed tumour frequency by 80.5% and tumour incidence by 58.5% in comparison to the controls. Higher dose simvastatin non-significantly decreased the mean tumor volume by 23.5%, as well as non-significantly lengthened the latency period by 14.5 days compared to the control animals. Simvastatin, administered at a lower dose did not change parameters of mammary carcinogenesis in comparison to the control group. Simvastatin in both treated groups significantly decreased serum levels of triacylglycerols and VLDL-cholesterol in comparison to the control animals. Compared to the controls, a significant increase in food intake by the animals was recorded in the SIMVA 18 and SIMVA 180 groups. No significant differences in the final body weight gain between the simvastatin-administered and the control group were found. CONCLUSION: This study represents the first report of simvastatin use in experimental mammary carcinogenesis in vivo.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Simvastatina/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Femenino , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/prevención & control , Ratas , Ratas Sprague-Dawley
15.
Eur Cell Mater ; 20: 282-93; discussion 293-4, 2010 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-20927712

RESUMEN

Diverse carbon materials have been used for tissue engineering and clinical implant applications with varying success. In this study, commercially available reticulated vitreous carbon (RVC) foams were tested in vitro and in vivo for compatibility with primary cell adhesion and tissue repair. Pores sizes were determined as 279 ± 98 µm. No hydroxyapatite deposition was detected after immersion of the foams in simulated body fluid. Nonetheless, RVC provided an excellent support for adhesion of mesenchymal stem cells (MSCs) as well as primary chondrocytes without any surface pre-treatment. Live cell quantification revealed neutral behaviour of the material with plastic adhered chondrocytes but moderate cytotoxicity with MSCs. Yet, rabbit implanted foams exhibited good integration in subcutaneous pockets and most importantly, total defect repair in bone. Probably due to the stiffness of the material, incompatibility with cartilage regeneration was found. Interestingly and in contrast to several other carbon materials, we observed a total lack of foreign body reactions. Our results and its outstanding porous interconnectivity and availability within a wide range of pore sizes convert RVC into an attractive candidate for tissue engineering applications in a variety of bone models and for ex vivo cell expansion for regenerative medical applications.


Asunto(s)
Materiales Biocompatibles/química , Carbono/química , Animales , Carbono/metabolismo , Adhesión Celular , Condrocitos/citología , Condrocitos/metabolismo , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Porosidad , Conejos , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos
16.
Bratisl Lek Listy ; 111(6): 353-6, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20635683

RESUMEN

Cystic renal disorders generally comprise a heterogeneous group of conditions. The most common genetic form is a polycystic kidney disease. This nosologic entity can be inherited as either an autosomal recessive or autosomal dominant trait. Among all cystic renal disorders, autosomal recessive polycystic kidney disease is the most frequent heritable disease manifesting in infancy and childhood and is among those that come to clinical attention early. The characteristic pathologic changes occur in the kidneys and the liver, however, several other organ systems can be affected secondarily. Both kidneys are enlarged because of multiple progressive cystic dilatation of the renal tubules that results to renal failure. The liver is characterized by periportal fibrosis with bile ducts abnormalities. The renal and hepatic manifestations are more or less inversely proportional in individual patients. Therefore, the morphological features and clinical presentation of this disorder can vary substantially. Moreover, there is also a great variability in the severity and manifestations even between individuals from the same family who carry the identical mutations. The authors present a case report of a fatal clinical course of the perinatal congenital polycystic kidney disease in one of the twins (Fig. 4, Ref. 19).


Asunto(s)
Enfermedades en Gemelos , Riñón Poliquístico Autosómico Recesivo/genética , Adulto , Femenino , Humanos , Recién Nacido , Masculino , Riñón Poliquístico Autosómico Recesivo/patología , Embarazo
17.
Klin Onkol ; 23(2): 104-10, 2010.
Artículo en Sk | MEDLINE | ID: mdl-20465089

RESUMEN

BACKGROUNDS: To evaluate the analgesic effect of low-dose radiotherapy in the treatment of plantar fasciitis and to analyse prognostic factors. PATIENTS AND METHODS: Retrospective analysis was used in the assessment of the analgesic effect after the 1st and 2nd series of low-dose radiotherapy. The treatment regime of 273 patients included total dose of 4.0 Gy, with fraction dose 1.0 Gy, received 2-3 times a week. Recommended follow-up was 3 months. In 323 cases of plantar fasciitis, prognostic factors (age, sex and pain duration before treatment) were evaluated. RESULTS: Analgesic effect of total dose of 4.0 Gy was 55.7% after the 1st series and 74.8% after the 2nd series. The results are comparable to published results. Pain duration before treatment shorter than 6 months had a significant effect on the treatment. Age was also a significant prognostic factor, with benefits in the group of patients younger than 50 years. CONCLUSION: Results confirm the advantageous analgesic effect of the dose regime received by our group of 273 patients. Analysis of prognostic factors shows greater benefit of treatment in the acute stage of plantar fasciitis. When treating young patients, however, the possible risks of radiotherapy should be considered compared to other treatment modalities.


Asunto(s)
Fascitis Plantar/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Pronóstico , Dosificación Radioterapéutica
18.
Rev Sci Instrum ; 91(8): 085117, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32872942

RESUMEN

Inelastic deformation of minerals and rocks is associated with activation of various defects such as fractures, twins, and dislocations. Active and passive ultrasound probes are potential tools to examine the nature of these defects under a broad range of pressure and temperature conditions. Here, we report on the development of an ultrasound probe array that allows us to monitor deforming samples in a high-pressure, high-temperature solid medium apparatus (a modified Griggs rig). We utilize several broadband miniature piezoelectric sensors that are placed above and below the sample to record acoustic emissions accompanying deformation and determine their locations in 1D. The emissions are recorded at 50 MS/s with a 12 bit resolution. Proper grounding and electric insulation of the sensors, together with optimized power delivery from the heating system, tremendously reduces electromagnetic interference and allows for a background noise level of ≈90 mV at a full range of ±2 V and 60 dB amplification. The system is capable of recording acoustic waves from 80 kHz to 2.5 MHz at sample temperatures up to 1100 °C and confining pressure up to 2.5 GPa.

19.
Physiol Res ; 69(Suppl 3): S443-S454, 2020 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-33471544

RESUMEN

Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases that degrades extracellular matrix (ECM) components. MMPs are associated with venous wall remodelling, proliferation, migration, phenotypic and functional transformation of vascular smooth muscle cells and ECM organization under the physiological and pathophysiological conditions. We investigated possible association of genetic promoter polymorphisms of MMP2 (rs243866), MMP8 (rs11225395), MMP9 (rs3918242) and TIMP2 (rs8179090) to varicose veins development in the Slovak population. Genomic DNA from 276 Slovak individuals (138 cases, 138 controls) was genotyped for selected SNPs (rs243866, rs11225395, rs3918242 and rs8179090) using the PCR-RFLP analysis. The data were analysed by chi-squared (chi2) test, logistic regression, and Mann-Whitney test. The risk of varicose veins development was evaluated in dominant, codominant and recessive genetic models. The statistical evaluation of selected polymorphisms in patients in all three genetic models has not shown a significant risk of varicose veins development. Our study has not shown the association between selected polymorphisms and increased risk of varicose veins development in Slovak population. More evidence with broaden sample size is needed.


Asunto(s)
Metaloproteinasas de la Matriz/genética , Inhibidor Tisular de Metaloproteinasa-2/genética , Várices/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 8 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Persona de Mediana Edad , Proyectos Piloto , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Eslovaquia/epidemiología , Várices/epidemiología , Várices/patología , Adulto Joven
20.
Neoplasma ; 56(2): 130-5, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19239327

RESUMEN

UNLABELLED: The anti-apoptotic protein survivin was detected in a panel of 27 dysplastic nevi. From each representative paraffin block 4 mm sections were cut and stained with anti-survivin antibody (DAKO, Clone 12C4). In each section, the labeling intensity, the subcellular location of survivin antigen, the percentage of labeled cells and the degree of dysplasia were assessed. Survivin was present in 23 out of 27 cases (85.2%), but absent in 4/27 cases (14.8%). Positive staining was confined to the cytoplasm (C) of nevus cells only in 18 cases (66.7%), while cytoplasmic as well as nuclear positivity (NC) was found in 5 cases (18.5%). In no case solely nuclear staining could be seen. Furthermore, in 4 out of 5 cases (80%) with NC staining, severe dysplasia was found. Our data point at usefulness of survivin staining, otherwise rarely performed in dysplastic nevi. We confirm the importance of nuclear location of the survivin antigen, which may be helpful for assessing the possible progression to melanoma. KEYWORDS: survivin, immunohistochemistry, nevi, dysplasia, melanoma.


Asunto(s)
Síndrome del Nevo Displásico/metabolismo , Proteínas Asociadas a Microtúbulos/análisis , Núcleo Celular/química , Citoplasma/química , Síndrome del Nevo Displásico/patología , Humanos , Inmunohistoquímica , Proteínas Inhibidoras de la Apoptosis , Survivin
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