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1.
Maedica (Bucur) ; 17(3): 726-729, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36540589

RESUMO

Background: We present the case of a patient with a Merkel cell carcinoma (MCC) of the left preauricular area. Case presentation:A 84-year-old Greek man was examined at the outpatient ENT Department of our clinic with a lesion in the preauricular area that had appeared four months ago. The patient history included antihypertensive and antihyperlipidemic therapy as well as treatment for dementia. The excision of the skin lesion was performed under local anesthesia. The histological examination revealed a Merkel cell carcinoma. The patient underwent a computed tomography (CT) scan that showed a lesion with clear limits in the left parotid gland and lymph nodes. Under general anesthesia, he underwent a left superficial parotidectomy, left submandibular gland excision and radical neck dissection. Histological preparations were analyzed using an intraoperative flow cytometry (iFC) protocol. A radiation therapy concluded the patient's treatment. Conclusion:Even if MCC appears as a less common and more aggressive skin cancer type, a clinician always has to include it in the differential diagnosis of a skin lesion. We found the use of iFC very useful for the diagnosis of this skin cancer.

3.
J BUON ; 26(2): 620-625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34077014

RESUMO

PURPOSE: To evaluate the impact of psychiatric co-morbidities on the quality of life-36 (QoL36) and tolerance to mental pain scale (TMPS) questionnaire of cancer patients administered in the Laboratory of Nuclear Medicine prior to a bone scan to rule out metastatic disease. METHODS: A group of 40 consecutive cancer patients (24 prostate, 12 breast and 4 with other cancers) were subjected to bone scan (BS) to rule out metastatic disease. Each patient received QoL36 and TMPS questionnaire prior to BS. RESULTS: There were low QoL and TMPS scores in all patient groups. The average QoL36 questionnaire score was 43,71 (23-70) (normal values considered >90). The average TMPS scores for prostate cancer patients was 55.42 (21-96), for breast cancer patients 63.42 (44-83) and for the other cancer patients 58.25 (48-68). Female patients with breast cancer had statistically higher tolerance to mental pain compared to patients with prostate cancer. Both tests were independently important for evaluation of the psychological status of the patients. There was no significant correlation of either QoL or TMPS with age, sex or disease duration. CONCLUSIONS: Cancer patients exhibited low QoL and TMPS, independent of sex, age, cancer type and disease duration. Multi-modality psychological support may be needed for these patients.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Dor/psicologia , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
J Inorg Biochem ; 208: 111074, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32497827

RESUMO

Novel vitamin E chelate derivatives and their VIV/V complexes have been synthesized and characterized, and their anticancer properties have been evaluated. The new complexes have been designed to exhibit enhanced cytotoxicity by combining high lipophilicity with the properties of vanadium to induce the formation of reactive oxygen species (ROS). In particular, the ß-tocopherol derivatives with iminodiethanol (ß-tocDEA) and dipicolylamine (ß-tocDPA) as well their VV and VIV complexes, [VVO(ß-tocDEA] and [VIVO(ß-tocDPA] have been synthesized and characterized by Nuclear Magnetic Resonance (NMR), Ultra Violet-Visible (UV-Vis) and Electron Paramagnetic Resonance (EPR) spectroscopies. Although the ß-tocopherol compounds exhibit antioxidant activity their complexes induce formation of radicals. In addition, two vanadium amphiphilic complexes of 2,2'-((2-hydroxyoctadecyl)azanediyl)bis(ethan-1-ol) (C18DEA) and 1-(bis(pyridin-2-ylmethyl)amino)octadecan-2-ol (C18DPA) known to activate O2 and produce ROS were synthesized and characterized (C. Drouza, A. Dieronitou, I. Hadjiadamou, M. Stylianou, J. Agric. Food. Chem., vol. 65, 2017, pp. 4942-4951). The four amphiphilic vanadium complexes exhibit enhanced hydrolytic stability. All compounds found to be cytotoxic for cancer cells exhibiting activity similar or higher to cis-platin.


Assuntos
Complexos de Coordenação , Citotoxinas , Lipídeos , Neoplasias , Vanádio , Vitamina E , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , Complexos de Coordenação/farmacologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacologia , Células HEK293 , Células HeLa , Humanos , Lipídeos/síntese química , Lipídeos/química , Lipídeos/farmacocinética , Lipídeos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Vanádio/química , Vanádio/farmacocinética , Vanádio/farmacologia , Vitamina E/síntese química , Vitamina E/química , Vitamina E/farmacocinética , Vitamina E/farmacologia
5.
J BUON ; 24(5): 2107-2113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31786882

RESUMO

PURPOSE: To evaluate the potential of prostate cancer detection on the basis of prostate-specific antigen (PSA)-level and percent free PSA (% fPSA) according to the outcome of prostate needle biopsy. METHODS: This was a retrospective study of 1040 patients that underwent a prostate biopsy in the Urologic Clinic of the University Hospital of Ioannina, Greece. The patients underwent needle biopsy after abnormal finding in digital rectal examination (DRE). Tissue samples were extracted using a 12-core TRUS-GB. The patients were divided into four groups according to the biopsy outcome. Total serum and free PSA were measured. RESULTS: The mean PSA concentration of cancer versus noncancer groups was significantly higher (p<0.05). The positive predictive value (PPV) of PSA for serum concentration >10 ng/ml was 47% while the negative predictive value (NPV) in patients with PSA levels <4 ng/ml was 81%. The diagnostic accuracy of % fPSA for patients with PSA level between 4-10 ng/ml was 0.651 (95% CI, 0.549-0.754) (p<0.05). A statistically significant difference in mean PSA concentration was recorded between prostate cancers classified as grade 2 (3+4=7) and 3 (4+3=7) and grade 4 (8) and 5 (9-10) (p<0.05). CONCLUSIONS: Though informative and suggestive, PSA and % fPSA are not definitive for cancer or non-cancer determination. The differentiation of PSA level between tumours classified as grade 2 (3+4=7) and grade 3 (4+3=7) could support the determination of treatment by backing pathologist's interpretation of the histological diagnosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Antígeno Prostático Específico/sangue , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Idoso , Biópsia , Exame Retal Digital , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos
6.
Med Hypotheses ; 133: 109393, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563097

RESUMO

The aim of this article is to investigate the potential cytotoxic and antitumor effects of the resonant electromagnetic fields (rEMFs) derived from the 1H NMR spectrum of the Ph3Sn(Mercaptonicotinic)SnPh3 complex (SnMNA). The ability of the complex's rEMFs to induce leiomyosarcoma (LMS) cell death and to recess tumor (leiomyosarcoma) development in Wistar rats was evaluated. The effects of the simultaneous administration of the SnMNA complex at extremely low concentrations and exposure to its rEMFs was also investigated. The emission of the 1H NMR spectrum of the complex alone or in a combination with low ineffective doses of the complex decreased LMS cell viability mainly through apoptosis. Moreover, the results from the in vivo experiments showed a significant prolongation of life expectancy in tumor-bearing rats exposed to the rEMFs alongside a deceleration in tumor growth rate. We speculate that the rEMFs of a biologically active substance could exert similar biological effects as the substance itself, mainly when is combined with extremely low ineffective concentrations of the substance.


Assuntos
Antineoplásicos/uso terapêutico , Leiomiossarcoma/radioterapia , Compostos Orgânicos de Estanho/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Terapia por Radiofrequência/métodos , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Campos Eletromagnéticos , Feminino , Humanos , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/toxicidade , Distribuição Aleatória , Ratos , Ratos Wistar , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Integr Cancer Ther ; 18: 1534735419872811, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31441361

RESUMO

Background. Cisplatin (cis-diamminedichloroplatinum) is a widely used chemotherapeutic agent for the treatment of various cancers. Although it represents an effective regimen, its application is accompanied by side effects to normal tissues, especially to the kidneys. Cisplatin generates free radicals and impairs the function of antioxidant enzymes. Modulation of cisplatin-induced oxidative stress by specific antioxidant molecules represents an attractive approach to minimize side effects. Methods. We studied the ability of curcumin to sensitize leiomyosarcoma (LMS) cells to cisplatin. Assays for cell proliferation, mitochondrial function, induction of apoptosis, and cell cycle arrest were performed using various concentrations of cisplatin and a concentration of curcumin that caused a nonsignificant reduction in cell viability. Moreover, the effect of curcumin was examined against cisplatin-induced experimental nephrotoxicity. Renal injury was assessed by measuring serum creatinine, blood urea nitrogen (BUN), and the kidney's relative weight. Oxidative stress was measured by means of enzymatic activities of superoxide dismutase and glutathione peroxidase in the rats' blood and malondialdehyde levels in rats' urine. Results. In our study, we found that curcumin sensitizes LMS cells to cisplatin by enhancing apoptosis and impairing mitochondrial function. In an in vivo model of cisplatin-induced experimental nephrotoxicity, intraperitoneal administration of curcumin failed to preserve blood's antioxidant enzyme activity and decrease lipid peroxidation. Nevertheless, curcumin was able to protect nephrons' histology from cisplatin's toxic effect. Conclusion. Our results showed that curcumin can act as chemosensitizer, but its role as an adjunctive cisplatin-induced oxidative stress inhibitor requires further dose-finding studies to maximize the effectiveness of chemotherapy.


Assuntos
Antioxidantes/metabolismo , Cisplatino/farmacologia , Curcumina/farmacologia , Nefropatias/tratamento farmacológico , Leiomiossarcoma/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Linhagem Celular , Creatinina/metabolismo , Feminino , Glutationa/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Leiomiossarcoma/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
9.
J BUON ; 23(5): 1242-1248, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30570843

RESUMO

Prostate specific antigen (PSA) is the most widely known screening test to detect prostate cancer (PCa). However, PSA testing has been recently put under the microscope mainly due to its weak correlation with prostate malignancy. In several clinical trials the PSA-screening validity for the diagnosis of PCa was evaluated. PSA lacks the ability to define the progression potential of the disease usually resulting in overdiagnosis and overtreatment of patients. Therefore, the development of new "multivariate" prediction models for PCa that would combine the PSA screening marker (and probably PSA metrics) with better biomarkers and imaging techniques has become an evolving field. New screening tests and/or methods with increased specificity could reduce the number of men undergoing prostate biopsy - thus alleviating patients from the anxiety and the distress experienced by an unnecessary (negative) biopsy- and minimizes the healthcare cost. Herein, we reviewed the information on PSA and other novel tests that can assist in diagnosing clinically meaningful prostate cancer.


Assuntos
Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/diagnóstico , Progressão da Doença , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/prevenção & controle
10.
J Med Food ; 21(12): 1197-1203, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30311825

RESUMO

Type 2 diabetes mellitus (T2DM) is evolving to an epidemic of the modern world. T2DM is associated with a number of pathological complications, including cardiovascular disease that is mostly promoted by the increased oxidative stress in type 2 diabetic patients. We performed a randomized double-blind placebo-controlled trial to investigate the effectiveness of an individualized oral supplementation with α-lipoic acid (ALA), carnosine, and thiamine. For that purpose, 82 obese type 2 diabetic patients were randomly assigned to 2 groups, and were either supplemented daily with 7 mg ALA/kg body weight, 6 mg carnosine/kg body weight, and 1 mg thiamine/kg body weight or placebo for 8 weeks. An array of biochemical tests including the estimation of oxidative stress and platelet aggregation were performed at baseline and at follow-up. Moreover, the antiplatelet activity of each of the supplement's components was determined ex vivo at human and washed rabbit platelets. Glucose and HbA1c levels were significantly reduced after supplementation (135.7 ± 19.5 mg/dL vs. 126.5 ± 16.8 mg/dL and 8.3% ± 0.3% vs. 6.03% ± 0.58%, respectively, P < .05); however, insulin was significantly increased (3.6 ± 0.7 µIU/mL vs. 6.8 ± 0.2 µIU/mL, P < .05). The patients treated with the supplement recorded higher follow-up values for HOMA-IR and HOMA-ß, and a significant drop in serum hydroperoxide level. Only ALA inhibited platelets aggregation ex vivo through ADP, platelet activating factor, arachidonic acid, epinephrine, collagen, and thrombin pathways. Daily supplementation with an individualized ALA, carnosine, and thiamine supplement effectively reduced glucose concentration in type 2 diabetic patients, probably by increasing insulin production from the pancreas. In addition to that, the reduction of oxidative stress and inhibition of platelet aggregation could potentially provide greater cardiovascular protection. Further studies are needed to fine-tune the supplementation dose-response effects in T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Obesidade Mórbida , Administração Oral , Glicemia/metabolismo , Carnosina/administração & dosagem , Carnosina/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Tiamina/administração & dosagem , Tiamina/uso terapêutico , Ácido Tióctico/administração & dosagem , Ácido Tióctico/uso terapêutico , Resultado do Tratamento
11.
Nucl Med Rev Cent East Eur ; 21(2): 100-103, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30070350

RESUMO

BACKGROUND: Heterotopic ossification (HO) is a potential complication in patients hospitalized in an intensive care unit (ICU). In this study we examined the association of HO diagnosed with three-phase bone scan (3pBS) in association with various parameters in patients previously hospitalized in ICU. MATERIAL AND METHODS: We retrieved patient records of the last 12 years subjected to 3pBS and diagnosed with HO from the Department of Nuclear Medicine (2004 up to 2016) and searched for a name match from ICU records. RESULTS: We found 61 patients that had a positive 3pBS for HO of whom 17 patients were hospitalized in the ICU. Among the 17 patients, twelve fulfilled the study criteria and were included in the study. The mean age was 38 years and 92% were males. HO was unilateral in 7 and bilateral in 5 patients. Patients with unilateral HO had up to 2 joints with HO, while those with bilateral had up to 4 joints. HO was most frequently observed in lower limbs, with hip being the most common joint affected. In the upper limbs, HO occurred predominantly in bilateral joints with elbow being the most frequently involved joint. Patients with longer duration of ICU stay had more joints affected. CONCLUSION: HO is a potential complication in patients with ICU hospitalization. Since 3pBS is an imaging method for early detection of HO, patients hospitalized in ICU should be screened with 3pBS for appropriate management.


Assuntos
Hospitalização , Unidades de Terapia Intensiva , Ossificação Heterotópica/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Nat Prod Res ; 32(11): 1337-1342, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28641455

RESUMO

The aim of this study was to investigate the cytotoxic effect cisplatin in combination with epigallocatechin-3-gallate (EGCG) on leiomyosarcoma cells (LMS cells) in order to identify a less toxic but equally effective alternative. Assays for cell proliferation, colony formation efficiency, induction of apoptosis and cell cycle arrest were performed using the IC50 of cisplatin (8.6 µΜ) as a reference value and a concentration of EGCG (30 µΜ) that caused a non-significant reduction in cell proliferation. Pre-treatment of cells with EGCG for 24 h before the addition of cisplatin increased cytotoxicity up to 8.5% (p < 0.05) and the number of apoptotic cells by 40%. Epigallocatechin-3-gallate failed to alter S-phase cell cycle arrest induced by cisplatin and to modulate cisplatin effects on mitochondrial function. These results indicate that pre-treatment with EGCG could be used as an adjunctive therapy to maximise effectiveness of chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Leiomiossarcoma/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Catequina/administração & dosagem , Catequina/análogos & derivados , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Concentração Inibidora 50 , Leiomiossarcoma/patologia , Mitocôndrias/efeitos dos fármacos , Ratos Wistar
13.
Ren Fail ; 38(5): 738-43, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26983797

RESUMO

Chronic kidney disease is a condition that promotes oxidative stress. There are conflicting evidence about the role of hemodialysis on oxidative stress, that are mostly related with the various types of membrane materials used, the quality and type of dialysate, the method used, etc. The phase angle (PhA), which is determined with bioelectrical impedance analysis (BIA), measures the functionality of cell membranes. In this study, the correlation of the PhA with parameters of oxidative stress is attempted for the first time. We evaluated parameters of oxidative status as total antioxidant capacity (TAC) in erythrocytes (RBCs) and plasma of patients with ESRD undergoing hemodialysis with low flux synthetic polysulfone membranes. Measurements were recorded from 30 patients (16 men and 14 women) aged 64 ± 14 years before, during, and after dialysis, and in 15 healthy volunteers aged 56 ± 12 years The PhA was obtained by BIA. The plasma TAC increased significantly (41%, p < 0.05). Intracellular TAC noted a non-significant increase. Total antioxidant capacity of the patients before and after hemodialysis was significantly lower from the healthy volunteers (p < 0.05) showing that ESRD patients are at the state of increased oxidative stress. The PhA increased in significantly positive correlation with plasma TAC at the end of hemodialysis. The process of hemodialysis with biocompatible synthetic membranes and bicarbonate dialysate improved plasma TAC. The positive correlation of PhA with extracellular TAC could evolve to a method of oxidative stress estimation by BIA but further research is needed.


Assuntos
Antioxidantes/metabolismo , Soluções para Diálise/farmacologia , Impedância Elétrica , Falência Renal Crônica , Polímeros/farmacologia , Diálise Renal , Sulfonas/farmacologia , Idoso , Materiais Biocompatíveis/farmacologia , Feminino , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Estresse Oxidativo , Diálise Renal/efeitos adversos , Diálise Renal/instrumentação , Diálise Renal/métodos , Estatística como Assunto
14.
In Vivo ; 29(1): 55-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25600531

RESUMO

AIM: This study was carried-out to investigate the effect of four different silver substances (S1, S2, S3, and S4) on burn wound healing in a rat model. MATERIALS AND METHODS: One hundred and eighty Wistar rats were used. Animals were randomized into six groups to receive no treatment (CG, control group), and local application of the solvent of silver substances (SG, solvent group), as well as of the four silver substances (EG1-EG4 groups for substances S1-S4, respectively). On days 0, 3, 6, 12, 21, and 31 following burn wound infliction, the size and healing progress of each wound were recorded and evaluated by means of clinical evaluation, planimetry and histological examination. RESULTS: According to our findings lower infection rates, as well as significantly accelerated wound healing and faster re-epithelialization were recorded in EG1, EG2, and EG4 compared to the other groups. DISCUSSION: The use of S1, S2, and S4 substances proved to be an effective treatment of burn wounds that ensured better outcomes compared to the control and solvent groups, as well as with the use of S3 substance. Nevertheless, they failed to produce short-term healing of the full-thickness burn. Further research is required to examine the possibility of speeding the treatment of full-thickness burns by these complexes in order to reduce healing time to acceptable limits and prevent the need for surgery.


Assuntos
Queimaduras/tratamento farmacológico , Compostos de Prata/farmacologia , Compostos de Prata/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Cicatrização/efeitos dos fármacos , Animais , Queimaduras/etiologia , Modelos Animais de Doenças , Feminino , Estrutura Molecular , Ratos , Compostos de Prata/química , Fatores de Tempo
15.
Turk Neurosurg ; 24(5): 745-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25269047

RESUMO

AIM: Heat shock proteins (HSP) are an evolutionary conserved family of proteins that serve as molecular chaperones, preventing the formation of nonspecific protein aggregates and assisting proteins in the acquisition of their native structures. Furthermore, HSPs have anti-apoptotic properties and have been found to be elevated in many human cancers; their overexpression has been associated with poor survival and response to therapy. In the present study we assessed the HSP expression in brain tumors. MATERIAL AND METHODS: Simultaneous detection of HSP27, HSP40, HSP60, HSP70, HSP90a, total Akt and phospho- Akt in 19 brain tumor specimens was performed using the multiplex bead array assay. RESULTS: There was expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90a, total-Akt and phospho- Akt in both gliomas and meningiomas. Significantly higher levels of HSP70 and a trend towards higher levels of HSP40 were found in meningiomas compared to gliomas. There was a significant correlation between HSP27 (pSer82) and HSP27 (pSer15) expression and between HSP90a and both total-AKT and phospho- AKT. A significant correlation between HSP27 and total-AKT was observed. CONCLUSION: Since HSPss are an attractive target for anticancer therapy, further studies are needed in order to better assess their relationship with tumor aggressiveness and patient prognosis.


Assuntos
Neoplasias Encefálicas/metabolismo , Proteínas de Choque Térmico/metabolismo , Adulto , Idoso , Astrocitoma/metabolismo , Chaperonina 60/metabolismo , Feminino , Glioblastoma/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Masculino , Meningioma/metabolismo , Pessoa de Meia-Idade , Neuroma/metabolismo
16.
Anticancer Res ; 33(9): 4033-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24023347

RESUMO

It is well-known that there is an interplay between hemostasis, thrombosis and cancer. Functional DNA polymorphisms in genes encoding factors related to thrombosis have been associated with increased risk for oral squamous cell carcinoma (OSCC). The present study investigated the possible combinatory effect of 10 such polymorphisms as primary risk predictors for OSCC in a European population. Two groups including 160 patients with OSCC and 168 healthy controls of Greek and German origin were studied. The patient and control groups were comparable regarding ethnicity, age and gender. For all studied individuals, 10 genotypes of functional polymorphisms were investigated: 5,10-methylene tetrahydrofolate reductase (MTHFR) C677T, coagulation factor V (F5) Leiden, coagulation factor II (F2, also known as prothrombin) G20210A, coagulation factor XII (F12) C46T, coagulation factor XIII A1 subunit (F13A1) Val34Leu, serpine1 (SERPINE1, also known as plasminogen activator inhibitor-1) 4G/5G, protein Z (PROZ) -A13G, angiotensin I-converting enzyme (ACE) I/D, angiotensinogen (AGT) Met325Thr, and carboxypeptidase B2 (CPB2, also known as thrombin-activatable fibrinolysis inhibitor) C1040T. Multivariate logistic regression models were used in order to evaluate the relation and contribution of homozygous and heterozygous variant polymorphisms upon overall, early and advanced stages of OSCC. Five out of the studied polymorphisms, influencing the expression of SERPINE1 and ACE genes, as well as the activity of CPB2, F12 and F13 proteins, were recognized as significant predictive factors for OSCC. The 'mode of inheritance' regression model, in particular, revealed the low expression I allele of ACE to be a primary predictor in overall, early and advanced stages of oral cancer. Comparing the present findings with previous knowledge, possible interactions of these factors and their relation to the risk for OSCC development are discussed.


Assuntos
Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Neoplasias Bucais/genética , Polimorfismo Genético , Trombose/genética , Carcinoma de Células Escamosas/complicações , Estudos de Casos e Controles , Genótipo , Humanos , Neoplasias Bucais/complicações , Análise de Regressão , Estudos Retrospectivos , Trombose/complicações
17.
Int Urol Nephrol ; 45(4): 1137-44, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23212145

RESUMO

PURPOSE: Chronic renal failure patients undergoing peritoneal dialysis (PD) are characterized by increased oxidative stress (OS), which is associated with enhanced cardiovascular risk. Moreover, oxidative stress also contributes to peritoneal membrane changes and ultrafiltration failure. The aim of this study was to evaluate OS in PD patients and the effect of treatment with ascorbic acid and α-tocopherol. METHODS: Plasma, erythrocyte, urine, and peritoneal effluent samples from 20 patients on PD were evaluated for glutathione peroxidase and superoxide dismutase activity, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as protein carbonyl formation, before and after administration of vitamin C, alone or in combination with vitamin E, in comparison with 10 apparently healthy control individuals. RESULTS: All studied markers showed enhanced OS in the PD group, compared to controls. The supplementation of vitamin C and E resulted in improvements of all the OS markers, as indicated by increased erythrocyte antioxidant enzymes activity and TAC levels, as well as decreased MDA concentration and carbonyl compound formation. CONCLUSIONS: The oral supplementation of antioxidant vitamins C and E, in combination, can lead to decreased OS, thus providing a useful and cost-effective therapeutic option in PD patients.


Assuntos
Ácido Ascórbico/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Falência Renal Crônica/terapia , Estresse Oxidativo/efeitos dos fármacos , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Vitamina E/uso terapêutico , Idoso , Análise de Variância , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Seguimentos , Glutationa Peroxidase/análise , Glutationa Peroxidase/metabolismo , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Diálise Peritoneal Ambulatorial Contínua/métodos , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Resultado do Tratamento
18.
Biol Trace Elem Res ; 150(1-3): 460-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22983773

RESUMO

Zinc (Zn), a cell-protective metal against various toxic compounds, is the key agent for neutral endopeptidase (NEP) functional structure. NEP is a zinc metalloenzyme which degrades endogenous opioids and is expressed in human keratinocytes (HaCaT). Ropivacaine, a widely used opiate local anaesthetic, exerts cell toxic and apoptotic effects against HaCaT cells. The aim of the present study is to investigate whether zinc modulates the effects of ropivacaine on proliferation, viability, apoptosis and NEP expression in HaCaT cells. To investigate the role of ropivacaine in NEP function, HaCaT cells overexpressing NEP were generated via cell transfection with plasmids carrying NEP cDNA. Ropivacaine's anti-proliferative effect was tested by Neubauer's chamber cell counting, and induction of cell death was demonstrated by trypan blue exclusion assay. Apoptosis due to ropivacaine was tested via DNA fragmentation and poly-ADP-ribose-polymerase (PARP) cleavage. NEP and PARP expression was performed by western blot analysis. Results showed that zinc (15 µΜ) inhibited proliferation and cell death induction by ropivacaine (0.5, 1 and 2 mM) (p < 0.05) as well as apoptosis induced by the drug (0.5 and 1 mM) in HaCaT cells. Ropivacaine (1.0, 2.0 and 5.0 mM) downregulated NEP expression in the presence of zinc (15 µΜ) while NEP overexpression enhanced ropivacaine's apoptotic effect. In conclusion, the abilities of zinc to inhibit the toxic and apoptotic effects of ropivacaine, to maintain NEP downregulation induced by the drug and, consequently, to enhance its anaesthetic result suggest that zinc may have a significant role in pain management and tissue protection.


Assuntos
Amidas/farmacologia , Analgésicos Opioides/farmacologia , Apoptose/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Neprilisina/metabolismo , Zinco/metabolismo , Amidas/efeitos adversos , Analgésicos Opioides/efeitos adversos , Anestésicos Locais/efeitos adversos , Anestésicos Locais/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Suplementos Nutricionais , Resistência a Medicamentos , Humanos , Queratinócitos/enzimologia , Queratinócitos/metabolismo , Neprilisina/antagonistas & inibidores , Neprilisina/genética , Nitratos/metabolismo , Concentração Osmolar , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Substâncias Protetoras/metabolismo , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/metabolismo , Ropivacaina , Compostos de Zinco/metabolismo
19.
Eur J Pharm Sci ; 47(2): 490-6, 2012 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-22841513

RESUMO

Since the initial success of cisplatin, metal complexes and organometallic compounds have been gaining growing interest in cancer therapy. It is well known that organotin(IV) compounds display strong biological activity. The triorganotin compound [(C(6)H(5))(3)Sn(cmbzt)] (cmbzt=5-chloro-2-mercaptobenzothiazole) (SnCMB), was tested for its antiproliferative and antitumour activities. Two sets of experimental procedures were followed: (1) In vitro and ex vivo procedures included the study of the cytotoxic activity of the complex against leiomyosarcoma cells (LMS) and on a normal human fibroblast line (MRC5) by the MTT assay (cell proliferation), colony formation efficiency and flow cytometric analysis with Annexin V-FITC. The anticoagulation properties of the complex were also studied. (2) In vivo procedures included acute toxicity studies and finally administration of the complex to tumour bearing Wistar rats. The results showed that the complex exhibited potent cytotoxic activity (LMS IC(50)=155 nM) and induced significant apoptosis against LMS cells. Acute toxicity studies on Wistar rats presented kidney and liver toxicity at a single dose of 40 mg/kg body wt. Furthermore, antitumour activity studies on sarcoma bearing Wistar rats revealed that SnCMB complex, administrated in two different therapeutic schemes (treated with 4 × 2 mg/kg body wt every 5 days and 3 × 2.67 mg/kg body wt every 10 days of SnCMB complex), prolonged mean survival time (by 50% and 70% respectively), but failed to decrease the mean tumour growth rate (MTGR) compared to the control group (p<0.01). In conclusion, the organic complex SnCMB possess potent cytotoxic and antimetastatic effects, and low toxicity introducing it as possible successor of organometallic compounds used nowadays in chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Orgânicos de Estanho/uso terapêutico , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Compostos Orgânicos de Estanho/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Wistar , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Radiat Oncol ; 6: 151, 2011 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-22067743

RESUMO

PURPOSE: To evaluate the cardiac toxicity of radiotherapy (RT) in breast cancer (BC) patients employing myocardial perfusion imaging (MPI) with Tc-99 m Tetrofosmin-single photon emission computer tomography (T-SPECT). MATERIALS AND METHODS: We studied 46 BC female patients (28 patients with left and 18 patients with right BC) treated with postoperative RT compared to a control group of 85 age-matched females. The median time of RT to SPECT was 40 months (6-263). RESULTS: Abnormalities in the summed stress score (SSS) were found in 54% of left BC patients, 44.4% of right BC patients, and 32.9% of controls. In left BC patients there were significantly more SSS abnormalities compared to controls (4.0 ± 3.5 vs 2.6 ± 2.0, p = 0.05) and possible trend of increased abnormalities of right BC patients (3.7 ± 3.0 vs 2.6 ± 2.0, p = 0.14). Multiple regression analysis showed more abnormalities in the MPI of left BC patients compared to controls (SSS, p = 0.0001); Marginal toxicity was also noted in right BC patients (SSS, p = 0.045). No additional toxicity was found in patients that received adjuvant cardiotoxic chemotherapy. All T-SPECT abnormalities were clinically silent. CONCLUSION: The study suggests that radiation therapy to BC patients result in MPI abnormalities but without apparent clinical consequences.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Compostos Organofosforados/farmacologia , Compostos de Organotecnécio/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Radioterapia/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Fatores de Risco , Resultado do Tratamento
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