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1.
J Pediatr Endocrinol Metab ; 26(3-4): 239-46, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23327822

RESUMO

OBJECTIVE: To study bone density in healthy Greek girls going through puberty and determine the influence of developmental and hormonal factors. DESIGN: Sixty healthy female adolescents (average age of 13.88±2.53 years) were included. Bone mineral density (BMD) was measured at the hip by DXA (dual energy X-ray absorptiometry). Pubertal stage was determined by Tanner's criteria. Creatinine, calcium, phosphorus, parathyroid hormone, calcitonin and 25-OH-vitamin D levels were measured in blood samples. The European physical fitness test battery (EUROFIT) was used to assess the parameters of physical fitness that are related to strength. RESULTS: Adolescent girls had a mean (±SD) BMD value of 0.947±0.144 g/cm2 at the total hip (total hip BMD). Tanner's stage for pubic hair and body mass index (BMI) constituted significant, positive and independent predicting factors for bone density of total hip. Deficiency of 25OH-vitamin D was a negative predicting factor of bone density. Blood levels of calcium and phosphorus, the hours that adolescents devoted to sports, and handgrip strength, were independent predicting factors of bone density at the hip. CONCLUSIONS: Bone density and consequently bone health is determined by factors that can be modified in order to achieve optimal bone growth and reduce the risk of fractures and osteoporosis in later life.


Assuntos
Densidade Óssea/fisiologia , Desenvolvimento Ósseo/fisiologia , Osso e Ossos/fisiologia , Hormônios/fisiologia , Puberdade/fisiologia , Absorciometria de Fóton , Adolescente , Antropometria , Osso e Ossos/diagnóstico por imagem , Estudos Transversais , Feminino , Grécia , Força da Mão/fisiologia , Humanos , Aptidão Física/fisiologia
2.
Eur J Oral Sci ; 119 Suppl 1: 35-40, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22243224

RESUMO

Stage-specific expression of ameloblast-specific genes is controlled by differential expression of transcription factors. In addition, ameloblasts follow daily rhythms in their main activities (i.e. enamel protein secretion and enamel mineralization). This time-related control is orchestrated by oscillations of clock proteins involved in the regulation of circadian rhythms. Our aim was to identify the potential links between daily rhythms and developmental controls of ameloblast differentiation. The effects of the transcription factors distal-less homeobox 3 (Dlx3) and runt-related transcription factor 2 (Runx2), and the clock gene nuclear receptor subfamily 1, group D, member 1 (Nr1d1), on secretory and maturation ameloblasts [using stage-specific markers amelogenin (Amelx), enamelin (Enam), and kallikrein-related peptidase 4 (Klk4)] were evaluated in the HAT-7 ameloblast cell line. Amelx and Enam steady-state mRNA expression levels were down-regulated in Runx2 over-expressing cells and up-regulated in Dlx3 over-expressing cells. In contrast, Klk4 mRNA was up-regulated by both Dlx3 and Runx2. Furthermore, a temporal and spatial relationship between clock genes and ameloblast differentiation markers was detected. Of interest, clock genes not only affected rhythmic expression of ameloblast-specific genes but also influenced the expression of Runx2. Multiscale mathematical modeling is being explored to further understand the temporal and developmental controls of ameloblast differentiation. Our study provides novel insights into the regulatory mechanisms sustaining ameloblast differentiation.


Assuntos
Ameloblastos/citologia , Amelogênese/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Ritmo Circadiano/genética , Proteínas do Esmalte Dentário/biossíntese , Regulação da Expressão Gênica , Fatores de Transcrição/genética , Ameloblastos/fisiologia , Amelogenina/biossíntese , Amelogenina/genética , Animais , Proteínas CLOCK/genética , Diferenciação Celular/genética , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Proteínas do Esmalte Dentário/genética , Proteínas de Homeodomínio/genética , Calicreínas/biossíntese , Calicreínas/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Ratos , Ratos Sprague-Dawley
3.
BMC Public Health ; 8: 28, 2008 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-18215322

RESUMO

BACKGROUND: Analysis of hospital mortality helps to assess the standards of health-care delivery. METHODS: This is a retrospective cohort study evaluating the causes of deaths which occurred during the years 1995-1999 in a single hospital. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10). RESULTS: Of the 149,896 patients who were discharged the 5836 (3.4%) died. Males constituted 55% and females 45%. The median age was 75.1 years (1 day - 100 years). The seven most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 92% of the total 5836 deaths. The most common contributors of non-neoplasmatic causes of death were cerebrovascular diseases (I60-I69) at 15.8%, ischemic heart disease (I20-I25) at 10.3%, cardiac failure (I50.0-I50.9) at 7.9%, diseases of the digestive system (K00-K93) at 6.7%, diabetes mellitus (E10-E14) at 6.6%, external causes of morbidity and mortality (V01-Y98) at 6.2%, renal failure (N17-N19) at 4.5%, influenza and pneumonia (J10-J18) at 4.1% and certain infectious and parasitic diseases (A00-B99) at 3.2%, accounting for 65.3% of the total 5836 deaths. Neoplasms (C00-D48) caused 17.7% (n = 1027) of the total 5836 deaths, with leading forms being the malignant neoplasms of bronchus and lung (C34) at 3.5% and the malignant neoplasms of large intestine (C18-21.2) at 1.5%. The highest death rates occurred in the intensive care unit (23.3%), general medicine (10.7%), cardiology (6.5%) and nephrology (5.5%). Key problems related to certification of death were identified. Nearly half of the deaths (49.3%: n = 2879) occurred by the completion of the third day, which indicates the time limits for investigation and treatment. On the other hand, 6% (n = 356) died between the 29th and 262nd days after admission. Inadequacies of the emergency care service, infection control, medical oncology, rehabilitation, chronic and terminal care facilities, as well as lack of regional targets for reducing mortality related to diabetes, recruitment of organ donors, provision for the aging population and lack of prevention programs were substantiated. CONCLUSION: Several important issues were raised. Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects.


Assuntos
Causas de Morte/tendências , Mortalidade Hospitalar , Hospitais Urbanos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Grécia/epidemiologia , Hospitais Urbanos/normas , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Grupos Raciais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
4.
World J Surg Oncol ; 6: 59, 2008 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-18558015

RESUMO

The coxsackievirus and adenovirus receptor (CAR) is a crucial receptor for the entry of both coxsackie B viruses and adenoviruses into host cells. CAR expression on tumor cells was reported to be associated with their sensitivity to adenoviral infection, while it was considered as a surrogate marker for monitoring and/or predicting the outcome of adenovirus-mediated gene therapy. The aim of the present study was to evaluate the clinical significance of CAR expression in endometrial adenocarcinoma. CAR expression was assessed immunohistochemically in tumoral samples of 41 endometrial adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological parameters, tumor proliferative capacity and patient survival. CAR positivity was noted in 23 out of 41 (56%) endometrial adenocarcinoma cases, while high CAR expression in 8 out of 23 (35%) positive ones. CAR intensity of immunostaining was classified as mild in 11 (48%), moderate in 10 (43%) and intense in 2 (9%) out of the 23 positive cases. CAR positivity was significantly associated with tumor histological grade (p = 0.036), as well differentiated tumors more frequently demonstrating no CAR expression. CAR staining intensity was significantly associated with tumor histological type (p = 0.016), as tumors possessing squamous elements presented more frequently intense CAR immunostaining. High CAR expression showed a trend to be correlated with increased tumor proliferative capacity (p = 0.057). Patients with tumors presenting moderate or intense CAR staining intensity were characterized by longer survival times than those with mild one; however, this difference did not reach statistical significance. These data reveal, for the first time, the expression of CAR in clinical material obtained from patients with endometrial adenocarcinoma in relation to important clinicopathological parameters for their management. As CAR appears to modulate the proliferation and characteristics of cancer cells, its expression could be considered of possible clinical importance for future (gene) therapy applications.


Assuntos
Adenocarcinoma/metabolismo , Infecções por Adenoviridae/metabolismo , Infecções por Coxsackievirus/metabolismo , Neoplasias do Endométrio/metabolismo , Receptores Virais/metabolismo , Adenocarcinoma/patologia , Infecções por Adenoviridae/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína de Membrana Semelhante a Receptor de Coxsackie e Adenovirus , Infecções por Coxsackievirus/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Prognóstico
5.
Anticancer Res ; 35(4): 1861-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25862839

RESUMO

Kallikrein-related-peptidase-4 (KLK4), a serine protease originally discovered in developing tooth with broad target sequence specificity, serves vital functions in dental enamel formation. KLK4 is involved in degradation of extracellular matrix proteins and it is thought that this proteolytic activity could also promote tumor invasion and metastasis. Recent studies have associated KLK4 expression with tumor progression and clinical outcome, particularly in prostate and ovarian cancer. Very little is known in regard KLK4 involvement in oral squamous cell carcinomas (OSCCs). Our objective was to investigate KLK4 expression in OSCC pathogenesis and disease progression. KLK4 expression was evaluated by immunohistochemistry, western blots and zymograms in OSCC lines. Invasion assays using high versus low/undetectable KLK4-expressing OSCC cell lines were performed jointly with KLK4 siRNA inhibition. A large collection of OSCC specimens was evaluated for KLK4 expression and correlation with patients' characteristics and outcomes were determined. Our data indicate that KLK4 is differentially expressed in oral carcinomas. OSCC cell lines with high invasive and metastatic potential have the highest levels of KLK4 expression. KLK4 mRNA and protein expression correlated with enzyme activity detected by zymograms. Inhibition of KLK4 expression results in diminished invasive potential in OSCC cell lines. Consistently, KLK4 expression is stronger in primary tumors that later either recurred or developed metastases, suggesting that its preferential expression in OSCC might contribute to individual tumor biology. Therefore, this study provides supportive evidence in favor of a prognostic value for KLK4 in OSCC and suggests that KLK4 could serve as a potential therapeutic target in patients with oral cancer.


Assuntos
Carcinoma de Células Escamosas/genética , Calicreínas/genética , Neoplasias Bucais/genética , Prognóstico , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Calicreínas/biossíntese , Masculino , Neoplasias Bucais/patologia , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , RNA Mensageiro/genética , Resultado do Tratamento
6.
J Pediatr Endocrinol Metab ; 27(7-8): 685-92, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24756049

RESUMO

OBJECTIVE: The aim of this study was to assess possible associations between potential risk factors for fractures and their occurrence in otherwise healthy Greek male adolescents. SUBJECTS: A total of 63 male adolescents participated in the study, 21 males with a history of at least one fracture and 42 healthy male controls. METHODS: Each participant was assessed for physical and pubertal status, hormonal profile, bone mineral density, bone turnover indices, and dietary habits. RESULTS: The lower bone mineral density-z scores and increasing testosterone and serum collagen type 1 cross-linked C-telopeptide levels were related to fracture risk, whereas increased insulin-like growth factor-1, soluble receptor activator of nuclear factor kappa-B (factor-κB) ligand, and soluble receptor activator of nuclear factors-κB ligand/osteoprotegerin levels were protective for fractures. CONCLUSIONS: The findings indicate a potential 'added value' of hormonal parameters and bone markers to bone mineral density for evaluating fracture risk in healthy male adolescents.


Assuntos
Densidade Óssea , Osso e Ossos/metabolismo , Fraturas Ósseas/etiologia , Adolescente , Estudos de Casos e Controles , Colágeno Tipo I/metabolismo , Humanos , Masculino , Peptídeos/metabolismo , Risco
7.
Head Neck ; 35(11): 1542-50, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23322448

RESUMO

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) have devastating morbidity rates with mortality mainly because of metastasis. METHODS: Multiplex enzyme-linked immunosorbent assay (ELISA) to assay a variety of cytokine levels secreted by a panel of stage-specific and anatomic site-specific primary, and recurrent and metastatic University of Michigan-HNSCC cell lines over a 72-hour time course. RESULTS: Conditioned medium from metastatic or recurrent HNSCC showed significantly higher amounts of interleukin (IL)-6, IL-6 receptor, tumor growth factor-beta (TGF-ß) and vascular endothelial growth factor (VEGF) than nonmetastatic cells or normal oral keratinocytes. Tumor necrosis factor (TNF) was only secreted by stage IV, metastatic, or recurrence-derived cell lines. CONCLUSION: The cytokine profile of cultured HNSCC cells suggests that high levels of IL-6 and IL-6R, TGF-ß, and VEGF are significantly related with their metastatogenic potential and provide rationale for determining if serum testing for a combination of these 4 soluble factors could be of predictive value for the HNSCC tumor progression and clinical outcome.


Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/secundário , Citocinas/sangue , Neoplasias de Cabeça e Pescoço/sangue , Ensaio de Imunoadsorção Enzimática , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Técnicas In Vitro , Interleucina-6/sangue , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta1/sangue , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/metabolismo , Fator A de Crescimento do Endotélio Vascular/sangue
8.
Otolaryngol Head Neck Surg ; 149(1): 97-104, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23558285

RESUMO

OBJECTIVE: To evaluate in vitro the potential links between sialyl Lewis X (sLeX) and cancer stem cells (CSC) in head and neck squamous cell carcinoma (HNSCC). HNSCC is an aggressive malignancy with high mortality mainly due to metastasis. CSC have emerged as important players in HNSCC metastasis. sLeX is a tetrasaccharide carbohydrate known to play a key role in metastatic dissemination by promoting binding of the tumor cells to the endothelium. STUDY DESIGN: Experimental, in vitro. SETTING: Laboratory of Head and Neck Cancer Metastasis, University of Michigan. SUBJECTS AND METHODS: A panel of stage- and anatomic-site specific primary and metastatic HNSCC cell lines was assessed by flow cytometry to quantify sLeX relative expression levels. Serum-free conditioned media from the same HNSCC lines was collected over a time course of 72 hours and assessed by Western blot for secreted sLeX expression. Representative HNSCC cell lines were cultured as floating orospheres (condition that enhance CSC growth) or under normal adherent conditions and characterized by flow cytometry for CSC markers (CD44, aldehyde dehydrogenase [ALDH]) comparatively with sLeX expression. RESULTS: sLeX is predominantly expressed in carcinomas originating from the oral cavity. Secreted sLeX is also found to be high in oral carcinomas and increased over the analyzed time course. Floating orospheres were strongly positive for CD44 and ALDH, confirming CSC enrichment of the orospheres. Tumor cells grown as orospheres are 95% to 100% positive for sLeX compared to 10% to 40% of adherent counterpart. CONCLUSION: These studies provide the first evidence of sLeX relationship with CSC in HNSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Células-Tronco Neoplásicas/metabolismo , Oligossacarídeos/metabolismo , Aldeído Desidrogenase/fisiologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Humanos , Receptores de Hialuronatos/fisiologia , Células-Tronco Neoplásicas/patologia , Antígeno Sialil Lewis X
9.
Med Sci Monit ; 14(1): RA8-15, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18160950

RESUMO

DNA repair is an important defense mechanism against DNA damage and includes four distinct pathways: direct, excision, mismatch, and double-strand break repair systems. Recent evidence suggests that alterations in proteins participating in the DNA repair systems may result in cellular senescence, cell death, and neoplastic transformation. Malignancies in adulthood exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair. However, our knowledge on DNA repair defects, both in germline and somatic mutations, and their relationship with childhood malignancies remains incomplete. Mutations, gene deletions, and inversions in various DNA repair genes have been reported and special attention has recently been focused on the interaction between these abnormalities and malignant transformation in childhood. The purpose of this review is to summarize the existing clinical information concerning components of the DNA repair systems and their influence on the development of the most common pediatric malignancies, including leukemia, tumors of the central nervous system, rhabdomyosarcoma, and retinoblastoma. Such information could possibly explain the response or resistance to chemotherapy and the possible risk of relapse in childhood malignancies presenting specific DNA repair defects. Additionally, these data could be beneficial for the development of novel therapeutic strategies.


Assuntos
Reparo do DNA/genética , Neoplasias/genética , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/metabolismo , Criança , Dano ao DNA , Reparo de Erro de Pareamento de DNA , Reparo do DNA/fisiologia , Humanos , Leucemia/genética , Leucemia/metabolismo , Mutação , Neoplasias/etiologia , Neoplasias/metabolismo , Polimorfismo Genético , Neoplasias da Retina/genética , Neoplasias da Retina/metabolismo , Retinoblastoma/genética , Retinoblastoma/metabolismo , Rabdomiossarcoma/genética , Rabdomiossarcoma/metabolismo
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