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1.
Exp Oncol ; 45(1): 70-78, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37417280

RESUMO

BACKGROUND: Familial non-medullary thyroid carcinoma (FNMTC) is defined as cancer developing in two or more first-degree relatives if predisposing factors, for example, radiation, are absent. The disease can be either syndromic, when it is a component of complex genetic syndromes, or non-syndromic (95% cases). The genetic basis of non-syndromic FNMTC is unknown; the clinical behavior of tumorsis unclear and, at times, contradictory. AIM: To analyze clinical manifestations of FNMTC and compare them with the data for sporadic papillary thyroid carcinomas in patients of the same age groups. MATERIALS AND METHODS: We examined 22 patients (a "parents" group and a "children" group) suffering from the non-syndromic FNMTC. For comparison, two groups of sporadic papillary carcinomas patients of the same age were drawn up("adult" and "young"). We analyzed tumor size and frequency of the distributionby the categoryof TNM system, invasiveness, multifocality, metastases to lymph nodes, type and extent of surgical and radioiodine treatment, and prognosis according to the MACIS criterion. RESULTS: Whether sporadic or familial, the tumor size, metastatic potential, and invasive potential are higher in young people, asalready known. There was no significant difference between the "parents" and "adult" groups of patients in terms of tumor parameters. One exception was the higher frequency of multifocal tumors in the FNMTC patients. Meanwhile, compared to the "young" sporadic papillary carcinomas patients, the FNMTC "children" had a higher frequency of T2 tumors, metastasizing (N1a-N1ab), and multifocal tumors, but a lower frequency of carcinomas with intrathyroidal invasions.In the FNMTC "children" compared to FNMTC "parents" was a higher frequency of T2 tumors, metastasizing carcinomas, and tumors with capsular invasion. CONCLUSION: FNMTC carcinomas are more aggressive than sporadic ones, especially in patients who are first-degree relatives in a family with parents already diagnosed with the disease.


Assuntos
Carcinoma Papilar , Carcinoma , Neoplasias da Glândula Tireoide , Humanos , Adolescente , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Radioisótopos do Iodo , Tireoidectomia , Neoplasias da Glândula Tireoide/patologia , Predisposição Genética para Doença
2.
Cytol Genet ; 55(6): 519-523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34898734

RESUMO

The COVID-19 infection is associated with dyslipidemia and cardiovascular complications. The aim of the study was to determine the content of ApoA1, ApoB, and oxidized low-density lipoproteins (oxLDL) in the plasma of patients (n = 81) with COVID-19, diabetes, and cardiovascular disease (CVD). ApoA1, ApoB, and oxLDL were determined using enzyme-linked immunosorbent assay kits (Elabscience, United States). The measurements were performed at an optical wavelength of 450 nm. It was shown that the level of ApoA1 in the blood of patients with type 2 diabetes and especially with COVID-19 was significantly lower than in the blood of healthy people. Blood ApoA1 levels did not show a further decrease in patients with both COVID-19 and diabetes or CVD compared to patients with COVID-19 without concomitant diseases. It was found that the level of ApoB in the blood of patients with diabetes and, especially, with COVID-19 is significantly higher than in the blood of healthy people. Blood levels of ApoB and oxLDL are higher in patients with both COVID-19 and diabetes or CVD compared to patients with COVID-19 without comorbidities. Thus, levels of ApoA1, ApoB, and oxLDL may be promising markers of COVID-19.

3.
Ukr Biochem J ; 88(5): 90-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29235817

RESUMO

We studied the expression and activation of the main effector protein kinase of phosphatidylinositol-3-kinase cascade (PI3K) ­ Akt in conventionally normal tissues, benign and highly differentiated (with and without metastases) human thyroid tumors. There was a difference in the Akt1 amount in tumor tissue compared with normal tissue in papillary carcinomas and tissue of multinodular goiter. Akt expression both in tumor and conventionally normal tissues of follicular adenoma was significantly lower than in follicular carcinoma. The lowest level of Akt expression was observed in tissues of multinodular goiter. Total activity of all three isoforms of Akt1/2/3 was lower in tumors compared to conventionally normal tissue. Thus, Akt activity (according to Thr308 phosphorylation) is not associated with proliferative processes in the tumor tissue of the thyroid. Apoptosis level detected in these tissues was not associated with the protein kinase activity either. Possible mechanisms of signaling cascade PI3K/Akt inhibition in thyroid tumors are discussed.


Assuntos
Adenocarcinoma Folicular/genética , Adenoma/genética , Carcinoma Papilar/genética , Bócio Nodular/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/enzimologia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/cirurgia , Adenoma/enzimologia , Adenoma/patologia , Adenoma/cirurgia , Apoptose , Carcinoma Papilar/enzimologia , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Regulação Neoplásica da Expressão Gênica , Bócio Nodular/enzimologia , Bócio Nodular/patologia , Bócio Nodular/cirurgia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Glândula Tireoide/enzimologia , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
4.
Ukr Biochem J ; 87(3): 63-74, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26502701

RESUMO

Anticancer drug paclitaxel (Ptx) effect on biochemical mechanisms, regulating apoptosis in anaplas- tic thyroid carcinoma cells, was studied. It was shown that in addition to apoptotic cell death, Ptx induces signaling cascades that ensure cell survival. Paclitaxel-induced activation of nuclear factor kappa B (NF-κB) leads to an increase of some antiapoptotic proteins expression such as survivin, cIAP, XIAP. A novel NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), was found to enhance cytotoxic effect of Ptx in anaplastic thyroid carcinoma cells. An enhancement of caspase-3 and -9 activation and PARP cleavage as well as the decreased levels of proteins-inhibitors of apoptosis were observed when cells were treated with a combination of both drugs. Mitochondria transmembrane potential (Δψ (m)) loss was observed at higher concentrations of Ptx and DHMEQ. NF-κB inhibition also potentiates paclitaxel effect at tumors formed by xenotransplantation of FRO cells into mice. Tumor mass reduction, significantly different from the effects of each of the compounds alone, was observed in animals, treated with paclitaxel and NF-κB inhibitor. Thus, the combined use of paclitaxel and NF-κB inhibitor inhibits biochemical processes that contribute to the resistance of anaplastic thyroid carcinoma cells to paclitaxel action.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Benzamidas/farmacologia , Cicloexanonas/farmacologia , NF-kappa B/antagonistas & inibidores , Paclitaxel/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzamidas/administração & dosagem , Benzamidas/uso terapêutico , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cicloexanonas/administração & dosagem , Cicloexanonas/uso terapêutico , Sinergismo Farmacológico , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Nus , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Br J Cancer ; 109(8): 2286-94, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24045656

RESUMO

BACKGROUND: A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. METHODS: We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. RESULTS: Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. CONCLUSION: The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.


Assuntos
Acidente Nuclear de Chernobyl , Expressão Gênica/efeitos da radiação , Radioisótopos do Iodo/administração & dosagem , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/genética , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Criança , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Transcriptoma/efeitos da radiação , Adulto Jovem
6.
Ukr Biokhim Zh (1999) ; 85(1): 51-61, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23534290

RESUMO

The aim of the paper was to describe the biochemical effects of Paclitaxel (Ptx), gamma-irradiation (IR) and their combination in undifferentiated thyroid cancer cells (ATC). IR activated common DNA damage-induced signaling and manifested certain mitogenic effect by inactivation of retinoblastoma protein (pRb). There was clear antagonism between Ptx and IR relative to cell cycle regulators--tumor suppressor p53, pRb, CHK2 and c-Abl as well as proapoptotic Bax expression, but combined action of both agents enhanced caspase-3 and, especially, caspase-8 activation. The Ptx at low (1-25 nM) concentrations caused noticeable radioprotective effect. Thus, in ATC cells the ionizing radiation and Ptx exhibited competitive effects upon phosphorylation of cell cycle controllers: p53, pRb, CHK2, cAbl and expression of Bax. At the same time, the combined effect of radiation and Ptx enhanced antiapoptotic Bcl-2 phosphorylation, caspases activation and survivin expression. The net effect of these events during the first 48-72 h of cells incubation can be considered as antiapoptotic--Ptx attenuated cytotoxic effect of IR.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Raios gama , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Paclitaxel/farmacologia , Neoplasias da Glândula Tireoide/genética , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Linhagem Celular Tumoral , Quinase do Ponto de Checagem 2 , Terapia Combinada/efeitos adversos , Relação Dose-Resposta a Droga , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Survivina , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
7.
ISRN Biochem ; 2012: 826305, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-25969761

RESUMO

Aim. To study the significance of cyclin-dependent kinases (Cdks) in paclitaxel-dependent apoptosis in colon and undifferentiated thyroid cancer cells. Materials and Methods. Experiments were performed on undifferentiated thyroid carcinoma (KTC-2) and colon carcinoma (ARO) cell lines. Cells were treated with paclitaxel (Ptx) and inhibitor of Cdk, roscovitine. Cell survival test and Western blotting were used for characterization of the effects of paclitaxel and roscovitine on cancer cells. Results. It was shown that not c-Jun N-terminal kinase, but cyclin-dependent kinases are responsible for antiapoptotic Bcl-2 phosphorylation. Cdk inhibition enhanced the cytotoxic effects of Ptx at low drug concentrations. There was antagonism between Ptx and roscovitine at higher (25 nM) paclitaxel concentrations. Conclusion. Using of paclitaxel at low (2.5 to 5 nM) concentrations and roscovitine is a promising combination for further preclinical trials for the development of new therapeutic approaches to the treatment of colon and anaplastic thyroid cancer.

9.
Exp Oncol ; 33(1): 24-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21423091

RESUMO

AIM: To study the effects of Paclitaxel (Ptx), γ-irradiation (IR) and their combination on the growth of xenografted tumors derived from undifferentiated thyroid cancer cells. MATERIALS AND METHODS: Experiments were performed in nude mice with tumors developing from implanted undifferentiated thyroid carcinoma cells (FRO). Animals were treated with Ptx i.p. and exposed locally to a single dose of 5 Gy of IR. Apoptosis in situ was detected using ApopTag Peroxidase Kit. RESULTS: In the in vivo experiments, IR significantly inhibited but did not abrogate tumor growth. Ptx effect was stronger, and the combination therapy with Ptx and IR led to the decrease of tumor volume to 0-0.3% of the control (P < 0.01). The systemic administration of Ptx to the animals with advanced tumors resulted in a profound tumor growth suppression and in apoptosis in tumor tissues in time-dependent manner. CONCLUSION: The combination of Ptx and IR is a promising strategy for further preclinical and clinical trials aimed at the development of new therapeutic approaches to the treatment of undifferentiated thyroid cancer.


Assuntos
Antineoplásicos , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Paclitaxel , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Clin Oncol (R Coll Radiol) ; 23(4): 268-75, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21324656

RESUMO

Over the last 20 years, nearly 5000 cases of differentiated thyroid cancer have been diagnosed and treated in the regions of Russia, Ukraine and Belarus in young people previously exposed to the Chernobyl radioactive fallout during childhood. At diagnosis, 60-70% of the Chernobyl-related paediatric thyroid cancers had clinically evident cervical lymph node metastases (N1) and 10-15% had distant metastases (M1). Despite early reports suggesting that the paediatric thyroid cancer cases that developed after exposure to Chernobyl fallout were particularly aggressive, it now seems that the initial presentation and early clinical course of most of these cases are very similar to both non-radiation-associated paediatric thyroid cancers and thyroid cancers that arise after exposure to external beam irradiation. Over an average clinical follow-up period of about 10 years, the disease-specific mortality rate in these paediatric thyroid cancer cases that developed after the Chernobyl accident is quite low (1% or less). As would be expected in paediatric thyroid cancer, short-term recurrence rates range from 7 to 28% in published reports (mean 17%). However, long-term studies of paediatric thyroid cancer suggest that although the 30 year disease-specific mortality rate should be about 1%, the risk of developing structural disease recurrence is nearly 30% (of which 80% are expected to be locoregional recurrences and 20% are probably new distant metastases). Projected over 30 years of follow-up, a 1% disease-specific mortality in this cohort of 5000 patients would equate to about 50 deaths directly attributable to thyroid cancer. However, a 30% recurrence rate would also mean that about 1500 patients may develop a clinically meaningful recurrence that would need to be diagnosed and treated. It is imperative that we continue to work with our colleagues in Belarus, Ukraine and Russia to ensure that this large volume of patients destined to develop clinically significant recurrences are diagnosed and treated in a timely manner. Ready access to modern disease detection tools (serum thyroglobulin, postoperative neck ultrasonography, cytology/pathology support, and radioactive iodine scanning) and treatments (surgery for recurrent disease, radioactive iodine therapy) in their major academic centres are mandatory if we expect to achieve the excellent clinical outcomes that should be seen when paediatric thyroid cancer recurrence is diagnosed early and treated appropriately.


Assuntos
Carcinoma Papilar/diagnóstico , Acidente Nuclear de Chernobyl , Neoplasias Induzidas por Radiação/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Criança , Feminino , Humanos , Metástase Linfática , Masculino , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/terapia , Prognóstico , Liberação Nociva de Radioativos , República de Belarus , Federação Russa , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Resultado do Tratamento , Ucrânia
11.
Exp Oncol ; 32(4): 269-72, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21270757

RESUMO

AIM: The aim of this work was to assess caspase-3 activity in the tissue of papillary thyroid carcinomas of patients and analyze the peculiarities of changes in this activity depending upon a number of pathomorphological and clinical features of tumoral process. METHODS: Caspase-3 activity was determined by spectrophotometry with regard to acetyl-asp-glu-val-asp-paranitroanilide. RESULTS: At initial stages of tumor development, in the absence of metastases to lymph nodes, blood and lymphatic vessel invasion by tumor cells, extrathyroid spreading of tumor, sclerotic and fibrous changes in tumor stroma, and in the presence of tumor capsule, caspase-3 activity in papillary carcinoma tissue was higher compared to unchanged thyroid tissue of normofollicular structure. In case of a more aggressive behaviour of tumor, enzyme activity in carcinoma tissue did not differ significantly or (in case of extrathyroid spreading of tumor) was decreased compared to that in extratumoral tissue. In combination, this was expressed by a progressive decrease in caspase-3 activity in tumor tissue with increasing T category. Сaspase 3 activity was found to be much higher in the tissue of papillary carcinomas of follicular-papillary structure and lower in the tissue of tumors of mixed structure with solid areas, compared to that in the tissue of papillary carcinomas of typical papillary structure. CONCLUSIONS: The data obtainеd in assessing caspase-3 activity suggest that the intensity of spontaneous apoptosis of human papillary thyroid carcinoma cells depends upon the stage and aggressiveness of tumoral process.


Assuntos
Adenocarcinoma Papilar/enzimologia , Caspase 3/metabolismo , Adenocarcinoma Papilar/patologia , Adulto , Apoptose/fisiologia , Carcinoma , Carcinoma Papilar , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/patologia
13.
Exp Oncol ; 31(1): 16-21, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19300411

RESUMO

AIM: To study the changes of cell cycle, mitochondrial membrane potential and caspase activation in response to an antitumour drug Taxol in ARO and KTC-2 cell lines of anaplastic thyroid carcinoma. METHODS: Experiments were done on thyroid anaplastic cancer cell lines ARO and KTC-2 using Western blotting, flow cytometry, light and fluorescent microscopy. RESULTS: Taxol significantly activated caspases in ARO cells starting from drug concentration of 5 nM. Maximum activation was observed at 25 nM and further increase of Taxol concentration to 100 nM resulted in a reduction of caspase activation. Concomitant to caspase activation, a loss of mitochondrial membrane potential was observed. At Taxol concentration of 100 nM, most cells lost their mitochondrial membrane potential. Low Taxol concentrations (10 nM) caused changes in the cell cycle that are typical for apoptosis without cell cycle arrest. Higher drug doses starting from 50 nM arrested cell cycle in G2/M phase. In KTC-2 cell line Taxol concentration as low as 1 nM induced apoptosis. 6-15 nM of the drug caused massive (75-83%) cell death. Upon Taxol action, the increase in the number of cells displaying manifestations of accelerated senescence was insignificant. CONCLUSION: Taxol induces bona fide apoptosis in thyroid cancer cell cultures at low (1-25 nM) concentrations. Higher drug doses cause the loss of mitochondrial membrane potential and possibly lead to other types of cell death. No accelerated senescence at different Taxol concentrations was observed. The significance of subG1 and G2/M cell populations at low and high doses of Taxol is discussed.


Assuntos
Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Paclitaxel/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Apoptose/efeitos dos fármacos , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
14.
Exp Oncol ; 30(3): 190-4, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18806740

RESUMO

AIM: To study the molecular mechanisms of dose-dependent effects of an anticancer drug, Taxol, on the cell cycle machinery and apoptosis-related proteins in thyroid anaplastic cancer cell lines ARO and KTC-2. MATERIALS AND METHODS: Western blot analysis was used for the detection of various proteins and of their phosphorylated forms. RESULTS: Low dose of Taxol that cause apoptosis (25 nM) enhanced Rb protein phosphorylation, decreased the expression of cyclin-dependent kinase inhibitors p27(KIP1) and p21(WAF1) , and potentiated the accumulation of phosphorylated p53 and of the prolyl isomerase Pin1. High Taxol doses (100 and 1000 nM) that cause necrosis-like cell death drastically decreased Pin1 level in both cell lines. CONCLUSION: Low doses of Taxol promoted G(1)/S transition, thus exhibiting mitogen-like effect. Drug-induced Pin1 accumulation could probably facilitate this transition and in parallel contribute to apoptosis via the p53/p73-dependent mechanism. At higher doses of Taxol, there was a dramatic decrease of Pin1 levels which may be a reason for G(2)/M cell cycle arrest.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma/tratamento farmacológico , Paclitaxel/administração & dosagem , Peptidilprolil Isomerase/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma/metabolismo , Carcinoma/patologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Relação Dose-Resposta a Droga , Humanos , Peptidilprolil Isomerase de Interação com NIMA , Necrose , Fosforilação/efeitos dos fármacos , Proteína do Retinoblastoma/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo
15.
Exp Oncol ; 30(1): 6-21, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18438336

RESUMO

The proapoptotic and antineoplastic properties of cannabinoids with emphasis on effects of N-acylethanolamines were analyzed. Cannabinoids enhanced apoptotic and necrotic processes in many types of tumour cells and tissues. Involvement of different types of receptors and signaling pathways in mediating the proapoptotic effects of cannabinoids are discussed. The evidences in favour of both proapoptotic, pronecrotic and protective, antiapoptotic effects of cannabinoids and, especially N-acylethanolamines, are evaluated. The hypothesis is suggested that N-acylethanolamines, formed in some tissues under strong stress conditions, can be not a consequence of tissue damage but cause such damage. The conclusion is made on promising of cannabinoids as potential anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Canabinoides/farmacologia , Etanolaminas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Moduladores de Receptores de Canabinoides/farmacologia , Moduladores de Receptores de Canabinoides/fisiologia , Canabinoides/biossíntese , Canabinoides/metabolismo , Canabinoides/uso terapêutico , Etanolaminas/metabolismo , Etanolaminas/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica/prevenção & controle , Receptores de Canabinoides/fisiologia , Canais de Cátion TRPV/fisiologia
16.
Diabetologia ; 50(1): 32-5, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17093948

RESUMO

AIMS/HYPOTHESIS: Numerous epidemiological studies have shown differences in seasonality of birth patterns between the general population and the group who develop type 1 diabetes mellitus. This finding indicates that environmental factors operating during pre- and/or postnatal development could be aetiologically important. We examined whether the pattern of month of birth for type 1 diabetes patients in Ukraine differs from that for total live births. METHODS: Data consist of prevalent cases of type 1 diabetes in Ukraine by the end of 2003. Cases are restricted to persons born after 1 January 1960, diagnosed with type 1 diabetes before the age of 30 years (n = 20,117). People born during the same time in the general population (n = 29,105,560) were the reference standard. Seasonal patterns were estimated using logistic regression with harmonic terms. RESULTS: We found a strongly significant seasonal pattern of type 1 diabetes incidence rates (p < 0.001), with the lowest rates in December and the highest in April. The rate ratio between the extremes was 1.32 (95% CI 1.27-1.39). Tests for seasonal patterns in subgroups defined by sex and age or by sex and date of birth were all significant with p values less than 0.02. We found no interactions with sex (p = 0.142) or age at diagnosis (p = 0.207), but found a strong interaction with period of birth (p < 0.0001). CONCLUSIONS/INTERPRETATION: The results obtained indicate that early-life factors linked to seasons may influence type 1 diabetes risk later in life.


Assuntos
Coeficiente de Natalidade/tendências , Diabetes Mellitus Tipo 1/epidemiologia , Estações do Ano , Adolescente , Adulto , Declaração de Nascimento , Coeficiente de Natalidade/etnologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/etnologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Fatores de Risco , Ucrânia
17.
J Clin Endocrinol Metab ; 91(11): 4344-51, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16912122

RESUMO

CONTEXT: Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive. OBJECTIVE: The objective of the study was to quantify risk of AIT after 131I exposure. DESIGN/SETTING/PARTICIPANTS: Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident. OUTCOMES: AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity. RESULTS: No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals. CONCLUSIONS: Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.


Assuntos
Carcinoma/epidemiologia , Acidente Nuclear de Chernobyl , Radioisótopos do Iodo/efeitos adversos , Neoplasias Induzidas por Radiação/epidemiologia , Doenças da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Tireoidite Autoimune/epidemiologia , Adolescente , Autoanticorpos/sangue , Autoantígenos/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Masculino , Programas de Rastreamento/métodos , Doses de Radiação , Ucrânia/epidemiologia
18.
J Radiol Prot ; 26(1): 51-67, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16522944

RESUMO

Our objective is to assess the regional and temporal dependences of the baseline cases contributing to thyroid cancer incidence among those exposed in childhood or during adolescence in Belarus and Ukraine after the Chernobyl accident. Data are analysed for Kyiv and Sevastopol City and the 25 oblasts (regions) in Ukraine, and for Minsk and Gomel City and the 6 oblasts in Belarus. Average thyroid doses due to the Chernobyl accident were assessed for every birth year in the period from 1968 to 1985. Case data pertain to people who underwent surgical removal of thyroid cancers during the period 1986 to 2001 and who were allocated to their place of residence at the time of the accident. The 35 oblasts/cities were subdivided into an upper, middle and lower group of baseline thyroid cancer incidence. Poisson regressions were performed to estimate age, time and gender dependences of the baseline incidence rates in the three groups. The majority of oblasts/cities with high average doses and the majority of Belarusian oblasts/cities belong to the upper group of baseline thyroid cancer incidence. The baseline in the upper group is estimated to be larger than in the middle group by a factor of 2.3, and by a factor of 4.0 when compared to the lower group. The baseline incidence increases with age and with time since exposure. Estimated baseline incidence rates were found to increase from 1988 to 1999 by factors of three and two for the upper and the two lower groups respectively. The estimated thyroid cancer incidence rates in Belarus and Ukraine, and their dependences on gender and age, are consistent with observed rates found in the larger cancer registries of other countries. In conclusion, the baseline cases are found to contribute about 70% to the thyroid cancer incidence in Ukraine, and about 40% to the incidence in Belarus.


Assuntos
Acidente Nuclear de Chernobyl , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Criança , Feminino , Humanos , Incidência , Masculino , Centrais Elétricas , Doses de Radiação , Sistema de Registros , República de Belarus/epidemiologia , Ucrânia/epidemiologia
19.
Radiat Res ; 165(1): 1-8, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16392956

RESUMO

The purpose of the present study was to analyze the thyroid cancer incidence risk after the Chernobyl accident and its degree of dependence on time and age. Data were analyzed for 1034 settlements in Ukraine and Belarus, in which more than 10 measurements of the (131)I content in human thyroids had been performed in May/June 1986. Thyroid doses due to the Chernobyl accident were assessed for the birth years 1968-1985 and related to thyroid cancers that were surgically removed during the period 1990-2001. The central estimate for the linear coefficient of the EAR dose response was 2.66 (95% CI: 2.19; 3.13) cases per 10(4) PY-Gy; for the quadratic coefficient, it was -0.145 (95% CI: -0.171; -0.119) cases per 10(4) PY-Gy(2). The EAR was found to be higher for females than for males by a factor of 1.4. It decreased with age at exposure and increased with age attained. The central estimate for the linear coefficient of the ERR dose response was 18.9 (95% CI: 11.1; 26.7) Gy(-1); for the quadratic coefficient, it was -1.03 (95% CI: -1.46; -0.60) Gy(-2). The ERR was found to be smaller for females than for males by a factor of 3.8 and decreased strongly with age at exposure. Both EAR and ERR were higher in the Belarusian settlements than in the Ukrainian settlements. In contrast to ERR, EAR increases with time after exposure. At the end of the observation period, excess risk estimates were found to be close to those observed in a major pooled analysis of seven studies of childhood thyroid cancer after external exposures.


Assuntos
Poluentes Radioativos do Ar/toxicidade , Acidente Nuclear de Chernobyl , Exposição Ambiental/análise , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carga Corporal (Radioterapia) , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta à Radiação , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Centrais Elétricas , Prevalência , Doses de Radiação , Monitoramento de Radiação/métodos , Liberação Nociva de Radioativos , Sistema de Registros , República de Belarus/epidemiologia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Distribuição por Sexo , Fatores de Tempo , Ucrânia/epidemiologia
20.
Br J Cancer ; 92(8): 1545-52, 2005 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-15812549

RESUMO

Thyroid cancers have been the main medical consequence of the Chernobyl accident. On the basis of their pathological features and of the fact that a large proportion of them demonstrate RET-PTC translocations, these cancers are considered as similar to classical sporadic papillary carcinomas, although molecular alterations differ between both tumours. We analysed gene expression in post-Chernobyl cancers, sporadic papillary carcinomas and compared to autonomous adenomas used as controls. Unsupervised clustering of these data did not distinguish between the cancers, but separates both cancers from adenomas. No gene signature separating sporadic from post-Chernobyl PTC (chPTC) could be found using supervised and unsupervised classification methods although such a signature is demonstrated for cancers and adenomas. Furthermore, we demonstrate that pooled RNA from sporadic and chPTC are as strongly correlated as two independent sporadic PTC pools, one from Europe, one from the US involving patients not exposed to Chernobyl radiations. This result relies on cDNA and Affymetrix microarrays. Thus, platform-specific artifacts are controlled for. Our findings suggest the absence of a radiation fingerprint in the chPTC and support the concept that post-Chernobyl cancer data, for which the cancer-causing event and its date are known, are a unique source of information to study naturally occurring papillary carcinomas.


Assuntos
Carcinoma Papilar/genética , Acidente Nuclear de Chernobyl , Expressão Gênica/efeitos da radiação , Neoplasias Induzidas por Radiação/genética , Neoplasias da Glândula Tireoide/genética , Adenoma/classificação , Adenoma/genética , Adolescente , Adulto , Algoritmos , Carcinoma Papilar/classificação , Criança , Feminino , Perfilação da Expressão Gênica , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/classificação
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