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1.
Medicine (Baltimore) ; 98(40): e17472, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577779

RESUMO

BACKGROUND: FDG-PET might be able to reflect histopathology features of tumors. Ki 67 in head and neck carcinomas (HNSCC). The present study sought to elucidate the association between Ki 67 index and SUVmax based upon a large patient sample. METHODS: PubMed database was screened for studies analyzed the relationship between Ki 67 and SUV in HNSCC. Nine studies comprising 211 patients were suitable for analysis. RESULTS: SUVmax increased with tumor grade and was statistically significant different between G1, G2, and G3 tumors. The ROC analysis for discrimination between G1/G2 and G3 tumors revealed an area under curve of 0.71. In the overall patient sample, SUVmax correlated statistically significant with Ki 67 index (r = 0.154, P = .032). CONCLUSION: The present study identified a weak correlation between SUV values and proliferation index Ki 67 index in HNSCC in a large patient sample. Therefore, SUVmax cannot be used as surrogate parameter for proliferation activity in HNSCC.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/metabolismo , Antígeno Ki-67/metabolismo , Tomografia por Emissão de Pósitrons , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fluordesoxiglucose F18 , Humanos
2.
Pol J Pathol ; 70(2): 91-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556559

RESUMO

Currently, breast cancer chemotherapy response can be predicted based on various parameters, with common reporting of tumour grade and Ki67 proliferation index. We analysed their association with pathological complete response (pCR) in a multivariate approach. The study was carried out in a group of 353 patients, treated by preoperative chemotherapy and prospectively observed. In selected patients, parallel to routing core needle biopsy assessment, gene expression profile of tumour was analysed by oligonucleotide microarrays. Tumour parameters associated with pCR in univariate analysis were: tumour grade, nuclear grade, mitotic index, Ki67, oestrogen and progesterone receptor (all p < 0.0001), and triple-negative status (p = 0.0032). The highest increase of pCR chance was observed in patients with high-grade tumours and with Ki67 ≥ 20%. In multivariate analysis, only tumour grade and oestrogen receptor status were predictive for pCR independently of other variables, with high grade increasing the odds of pCR 2.42 fold, and high ER decreasing the chance of pCR 0.41 fold. Tumour grading reflects important biological features of breast cancer and is not inferior to proliferation markers, including Ki67. It should be taken into account in decision-making for preoperative chemotherapy in parallel to breast cancer biologic subtypes, because grade 3 tumours exhibit a higher proportion of pCR.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Gradação de Tumores , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/cirurgia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Estudos Prospectivos , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Resultado do Tratamento
3.
Zhonghua Zhong Liu Za Zhi ; 41(9): 681-685, 2019 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-31550858

RESUMO

Objective: To investigate the expression discordances of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor2 (HER-2) and Ki-67 in primary and metastatic breast cancer specimens and explore the clinical significances. Methods: Biopsies of metastatic lesions were performed in 203 patients with breast cancer recurrence and metastasis indicated by physical examination and/or imaging examination. We confirmed pathological properties and assessed the expressions of ER, PR, HER-2 and Ki-67 in primary and metastatic lesions, their relationships with prognosis were also analyzed. Results: Biopsy failed in 3 patients, the pathology and immunohistochemitry results of metastatic lesions were not obtained. One person was diagnosed as tuberculosis and another was primary lung cancer. Among the 198 cases of primary and metastatic lesions, the discordance rates of ER, PR, HER-2 and Ki-67 were 27.3%, 34.3%, 11.8% and 15.1%, respectively.The expressions of ER, HER-2 and Ki-67 were not significantly different between the primary and metastatic lesions, however, the expressions of PR were more likely to turn negative in the metastases (P<0.001). The disease-free survival (DFS) of patients with ER, PR positive, HER-2 negative and low expression of Ki-67 in metastatic lesion was much longer (P<0.05). Conclusions: The expressions of ER, PR, HER-2 and Ki-67 in metastatic lesions are associated with the prognosis of breast cancer patients.Their expression discordances between primary and metastatic lesions can guide the treatment and evaluate the risks of recurrence and prognosis.


Assuntos
Neoplasias da Mama/metabolismo , Antígeno Ki-67/metabolismo , Recidiva Local de Neoplasia/metabolismo , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Biópsia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Taxa de Sobrevida
4.
Acta Cir Bras ; 34(6): e201900606, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31432997

RESUMO

PURPOSE: To investigate the effects of pine needle extract (PNE) on the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 during liver regeneration induced by 70% partial hepatectomy (PH) in rat. METHODS: Forty-eight male rats (SD, 7 weeks) had surgery (70% PH). They were randomly divided into two groups. PH + PNE group was only provided PNE diluted in water (10%) for drinking and PH group was provided water from 5 days before surgery to the time of sacrifice. PNE was made by pressing and filtering. Animals were sacrificed at 12h, 24h, 36h, 60h, 84h, 168h after PH, respectively. The expressions of PCNA and Ki-67 were determined as proliferation indices. RESULTS: Immunohistochemistry turned out to increase the expression of PCNA and Ki-67. PCNA expression of PH+PNE group increased up to twice of that of PH group. Western blot also seemed to increase the PCNA expression. These results indicated the promotion of cell proliferation in liver tissue and hepatic regeneration. CONCLUSIONS: Pine needle extract stimulates the expression of some mitotic proteins during liver regeneration induced by 70% PH in rats. It suggests that administration of pine needle extract could accelerate the liver regeneration after partial hepatectomy.


Assuntos
Hepatectomia/métodos , Antígeno Ki-67/efeitos dos fármacos , Regeneração Hepática/efeitos dos fármacos , Pinus/química , Extratos Vegetais/farmacologia , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Animais , Proliferação de Células , Antígeno Ki-67/metabolismo , Masculino , Índice Mitótico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
5.
Int J Nanomedicine ; 14: 5109-5123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371950

RESUMO

Background: Renal cell carcinoma (RCC) is notorious for its resistance towards chemotherapy and radiation therapy in general. Combination therapy is often helpful in alleviating the resistance mechanisms by targeting multiple signaling pathways but is usually more toxic than monotherapy. Co-encapsulation of multiple therapeutic agents in a tumor-targeted drug delivery platform is a promising strategy to mitigate these limitations. Methods: A tumor-targeted liposomal formulation was prepared using phospholipids, cholesterol, DSPE-(PEG)2000-OMe and a proprietary tumor-targeting-peptide (TTP)-conjugated lipopeptide. An efficient method was optimized to encapsulate everolimus and vinorelbine in this liposomal formulation. Single drug-loaded liposomes were also prepared for comparison. Finally, the drug-loaded liposomes were tested in vitro and in vivo in two different RCC cell lines. Results: The tumor-targeted liposomal formulation demonstrated excellent tumor-specific uptake. The dual drug-loaded liposomes exhibited significantly higher growth inhibition in vitro compared to the single drug-loaded liposomes in two different RCC cell lines. Similarly, the dual drug-loaded liposomes demonstrated significantly higher suppression of tumor growth compared to the single drug-loaded liposomes in two different subcutaneous RCC xenografts. In addition, the dual drug-loaded liposomes instigated significant reduction in lung metastasis in those experiments. Conclusion: Taken together, this study demonstrates that co-delivery of everolimus and vinorelbine with a tumor-targeted liposomal formulation is an effective approach to achieve improved therapeutic outcome in RCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Everolimo/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Vinorelbina/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Antígeno Ki-67/metabolismo , Lipossomos , Neoplasias Pulmonares/secundário , Camundongos SCID , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Br J Radiol ; 92(1103): 20190324, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31386559

RESUMO

OBJECTIVE: This study was to investigate the relationship of diffusion features with molecule information, and then predict grade and survival in lower-grade gliomas. METHODS: 65 patients with primary lower-grade gliomas (WHO Grade II & III) who underwent conventional MRI and diffusion tensor imaging were retrospectively studied. The tumor region was automatically segmented into contrast-enhancing tumor, non-enhancing tumor, edematous and necrotic volumes. Diffusion features, including fractional anisotropy (FA), axial diffusivity, radial diffusivity and apparent diffusion coefficient (ADC), were extracted from each volume using histogram analysis. To estimate molecule biomarkers and predict clinical characteristics of grade and survival, support vector machine, generalized linear model, logistic regression and Cox regression were performed on the related features. RESULTS: The diffusion features in non-enhancing tumor volume showed differences between isocitrate dehydrogenase mutant and wild-type gliomas. And the mean accuracy of support vector machine classifiers was 0.79. Ki-67 labeling index was correlated with these features, which were combined to significantly estimate Ki-67 expression level (r = 0.657, p < 0.001). These features also showed differences between Grade II and III gliomas. A combination of them for grade classification resulted in an area under the curve of 0.914 (0.857-0.971). Mean FA and fifth percentile of ADC were independently associated with overall survival, with lower FA and higher ADC showing better survival outcome. CONCLUSION: In lower-grade gliomas, multiparametric and multiregional diffusion features could help predict molecule information, histological grade and survival. ADVANCES IN KNOWLEDGE: The multi parametric diffusion features in non-enhancing tumor were associated with molecule information, grade and survival in lower-grade gliomas.


Assuntos
Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Oligodendroglioma/patologia , Adulto , Idoso , Anisotropia , Astrocitoma/mortalidade , Neoplasias Encefálicas/mortalidade , Imagem de Tensor de Difusão/métodos , Estudos de Viabilidade , Feminino , Humanos , Antígeno Ki-67/metabolismo , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/mortalidade , Estudos Retrospectivos , Carga Tumoral , Adulto Jovem
7.
Virchows Arch ; 475(3): 313-323, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31267199

RESUMO

Breast cancer is a highly heterogeneous disease. The efficacy of tailored therapeutic strategies relies on the precise detection of diagnostic biomarkers by immunohistochemistry (IHC). Therefore, considering the increasing incidence of breast cancer cases, a concomitantly time-efficient and accurate diagnosis is clinically highly relevant. Microfluidics is a promising innovative technology in the field of tissue diagnostic, enabling for rapid, reliable, and automated immunostaining. We previously reported the microfluidic-based HER2 (human epidermal growth factor receptor 2) detection in breast carcinomas to greatly correlate with the HER2 gene amplification level. Here, we aimed to develop a panel of microfluidic-based IHC protocols for prognostic and therapeutic markers routinely assessed for breast cancer diagnosis, namely HER2, estrogen/progesterone receptor (ER/PR), and Ki67 proliferation factor. The microfluidic IHC protocol for each marker was optimized to reach high staining quality comparable to the standard procedure, while concomitantly shortening the staining time to 16 min-excluding deparaffinization and antigen retrieval step-with a turnaround time reduction up to 7 folds. Comparison of the diagnostic score on 50 formaldehyde-fixed paraffin-embedded breast tumor resections by microfluidic versus standard staining showed high concordance (overall agreement: HER2 94%, ER 95.9%, PR 93.6%, Ki67 93.7%) and strong correlation (ρ coefficient: ER 0.89, PR 0.88, Ki67 0.87; p < 0.0001) for all the analyzed markers. Importantly, HER2 genetic reflex test for all discordant cases confirmed the scores obtained by the microfluidic technique. Overall, the microfluidic-based IHC represents a clinically validated equivalent approach to the standard chromogenic staining for rapid, accurate, and automated breast cancer diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/métodos , Biomarcadores Tumorais/metabolismo , Mama/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente , Antígeno Ki-67/metabolismo , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
9.
BMC Complement Altern Med ; 19(1): 113, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159797

RESUMO

BACKGROUND: Embryonic neural stem cells (eNSCs) are immature precursors of the central nervous system (CNS), with self-renewal and multipotential differentiation capacities. These are regulated by endogenous and exogenous factors such as alpha-linolenic acid (ALA), a plant-based essential omega-3 polyunsaturated fatty acid. METHODS: In this study, we investigated the effects of various concentrations of Alyssum homolocarpum seed oil (AHSO), containing natural ALA, stearic acid (SA), myristic acid (MA), and ß-sitosterol, on proliferation and differentiation of eNSCs, in comparison to controls and to synthetic pure ALA. RESULTS: Treatment with natural AHSO (25 to 75 µM), similar to synthetic ALA, caused a significant ~ 2-fold increase in eNCSs viability, in comparison to controls. To confirm this proliferative activity, treatment of NSCs with 50 or 75 µM AHSO resulted in a significant increase in mRNA levels of notch1, hes-1 and Ki-67and NICD protein expression, in comparison to controls. Moreover, AHSO administration significantly increased the differentiation of eNSCs toward astrocytes (GFAP+) and oligodendrocytes (MBP+) in a dose dependent manner and was more potent than ALA, at similar concentrations, in comparison to controls. Indeed, only high concentrations of 100 µM AHSO, but not ALA, caused a significant increase in the frequency of neurons (ß-III Tubulin+). CONCLUSION: Our data demonstrated that AHSO, a rich source of ALA containing also other beneficial fatty acids, increased the proliferation and stimulated the differentiation of eNSCs. We suggest that AHSO's effects are caused by ß-sitosterol, SA and MA, present within this oil. AHSO could be used in diet to prevent neurodevelopmental syndromes, cognitive decline during aging, and various psychiatric disorders.


Assuntos
Brassicaceae/química , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Óleos Vegetais/farmacologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Antígeno Ki-67/metabolismo , Camundongos , Ácido Mirístico/análise , Células-Tronco Neurais/metabolismo , Óleos Vegetais/química , Sementes/química , Sitosteroides/análise , Ácidos Esteáricos/análise , Ácido alfa-Linoleico/análise
10.
Radiat Res ; 192(2): 200-207, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31237817

RESUMO

p53BP1 forms discrete foci within minutes of radiation exposure, at sites of DNA double-strand breaks, which ordinarily decay to background levels within 24 h of induction. Longer lived, persisting 53BP1 foci are thought to mark unrepaired or misrepaired damage and potentially, to be associated with genomic instability. It is known that repair of DNA damage is impaired in senescent (permanently arrested) and aged cells. We examined this further by measuring the induction and persistence of 53BP1 foci in proliferating and non-proliferating mid-passage (non-aged) and late-passage (in vitro aged) normal human bronchial epithelial cells. Our results showed background levels of 53BP1 foci to be elevated in in vitro aged cultures as expected and induction of 53BP1 foci after radiation exposure to be independent of culture age or proliferative status. In terms of 53BP1 decay, more cells with persisting foci were seen in in vitro aged cultures compared to non-aged populations; furthermore, this was observed in both non-cycling (nominally senescent) cells, as well as in actively proliferating cells. In conclusion, perturbation in radiation-induced damage processing is a function of increasing chronological cellular age per se and should be considered when extrapolating experimental data for radiation risk modeling.


Assuntos
Senescência Celular/genética , Senescência Celular/efeitos da radiação , Dano ao DNA , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Humanos , Antígeno Ki-67/metabolismo , beta-Galactosidase/metabolismo
11.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 23-28, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078148

RESUMO

In recent years, most related studies have found that chronic hepatitis B virus infection is the main cause of hepatocellular carcinoma (HCC), but the specific pathogenesis is still unclear. To investigate the function of HDAC in hepatocellular carcinoma (HCC), this study used qRT-PCR to determine the expression levels of miR-376a and HDAC9 mNRA in HCC and para-cancerous tissues. The clinical significance of HDAC9 in HCC was assessed in a study cohort containing 37 patients with HCC using immunohistochemistry. The expression level of miR-376a in liver cancer tissues was significantly lower than that in para-cancerous tissues, while the expression level of HDAC9 mRNA in liver cancer tissue was significantly higher than that in para-cancerous tissues. The expression of HDAC9 occurred mainly in the nucleus. There was a significant correlation between tumor differentiation and HDAC9. Survival analysis showed that HCC patients with higher HDAC9 expression had poorer prognosis, and subsequent multivariate analysis showed that HDAC9 expression level was an independent predictor. There was a definite correlation between HDAC9 and the expressions of AFP and Ki67. These results suggest that the expression level of HDAC9 in HCC is abnormally high while the expression level of miR-376a is significantly decreased, indicating that HDAC9 may be a potential prognostic indicator of HCC.


Assuntos
Carcinoma Hepatocelular/enzimologia , Histona Desacetilases/metabolismo , Neoplasias Hepáticas/enzimologia , Proteínas Repressoras/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/genética , Humanos , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Proteínas Repressoras/genética , Análise de Sobrevida , alfa-Fetoproteínas/metabolismo
12.
Cell Physiol Biochem ; 52(6): 1339-1360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31050282

RESUMO

BACKGROUND/AIMS: Melanocortin receptors (MCRs) belong to a hormonal signalling pathway with multiple homeostatic and protective actions. Microvascular and umbilical vein endothelial cells (ECs) express components of the melanocortin system, including the type 1 receptor (MC1R), playing a role in modulating inflammation and vascular tone. Since ECs exhibit a remarkable heterogeneity, we investigated whether human artery ECs express any functional MCR and whether its activation affects cell migration. METHODS: We used reverse transcription real-time PCR to examine the expression of melanocortin system components in primary human artery ECs. We assessed MC1R protein expression and activity by western blot, immunohistochemistry, cAMP production, and intracellular Ca²âº mobilization assays. We performed gap closure and scratch tests to examine cell migration after stimulation with alpha-melanocyte-stimulating hormone (α-MSH), the receptor highest-affinity natural ligand. We assessed differential time-dependent transcriptional changes in migrating cells by microarray analysis. RESULTS: We showed that human aortic ECs (HAoECs) express a functionally active MC1R. Unlike microvascular ECs, arterial cells did not express the α-MSH precursor proopiomelanocortin, nor produced the hormone. MC1R engagement with a single pulse of α-MSH accelerated HAoEC migration both in the directional migration assay and in the scratch wound healing test. This was associated with an enhancement in Ca²âº signalling and inhibition of cAMP elevation. Time-course genome-wide expression analysis in HAoECs undergoing directional migration allowed identifying dynamic co-regulation of genes involved in extracellular matrix-receptor interaction, vesicle-mediated trafficking, and metal sensing - which have all well-established influences on EC motility -, without affecting the balance between pro- and anticoagulant genes. CONCLUSION: Our work broadens the knowledge on peripherally expressed MC1R. These results indicate that the receptor is constitutively expressed by arterial ECs and provide evidence of a novel homeostatic function for MC1R, whose activation may participate in preventing/healing endothelial dysfunction or denudation in macrovascular arteries.


Assuntos
Receptor Tipo 1 de Melanocortina/metabolismo , Aorta/citologia , Sinalização do Cálcio/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , AMP Cíclico/metabolismo , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Antígeno Ki-67/metabolismo , Oligopeptídeos/farmacologia , Receptor Tipo 1 de Melanocortina/genética , alfa-MSH/farmacologia
13.
J Med Life ; 12(1): 30-33, 2019 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31123522

RESUMO

Glomus tumors are frequently associated with pain, tenderness and cold sensitivity. We report the diagnosis and successful surgical management of a case of a classic glomus tumor in a young woman. The clinical diagnosis was made on the basis of medical history and MRI findings. The lesion was excised via a dorsolateral subungual approach, leading to the complete resolution of symptoms. Histology confirmed the lesion to be a glomus tumor. Glomus tumors are painful subungual lesions. They produce a throbbing or lancinating local discomfort, cold-sensitivity, and severe pain following minor trauma. The diagnosis is confirmed by histology, but the clinical diagnosis is highly suggestive. Complete excision will usually relieve pain. Recurrence is common following incomplete resection.


Assuntos
Dedos/patologia , Tumor Glômico/patologia , Dor/etiologia , Adulto , Antígenos CD34/metabolismo , Proliferação de Células , Feminino , Tumor Glômico/diagnóstico por imagem , Tumor Glômico/cirurgia , Humanos , Antígeno Ki-67/metabolismo , Imagem por Ressonância Magnética , Mitose , Polegar/diagnóstico por imagem , Polegar/cirurgia
14.
Bull Exp Biol Med ; 166(6): 797-801, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028589

RESUMO

We studied the intensity of age-specific changes in the dermis (number and proliferative activity of fibroblasts) in mice with normal and experimentally changed level of thyroid hormones. Receptors of thyroid hormones, TR-α and TR-ß, in mouse dermal fibroblasts were identified by immunohistochemical methods. The relative expression of Thra, Thrb, and Dio2 genes was assessed by real-time PCR analysis. From the second to fifth month of life, the number of fibroblasts in the connective tissue layer of mouse skin decreased by 42.3%. The number of fibroblasts in the dermis of 5-month-old mice treated with Thyrozol significantly decreases by 25.9% (p<0.05), and vice versa, in mice receiving thyroxin this parameter increased by 4.7% in comparison with the control (p>0.05). TR-α and TR-ß were identified in dermal fibroblasts in all groups of mice. No differences in the content TR-α and Thra gene expression in 2- and 5-month-old mice of the control and experimental were revealed. TR-ß content in dermal fibroblasts of 2-month-old animals was maximum and exceeded this value in 5-month-old control mice by 25%. The number of these receptors decreased by 33.3% in mice treated with Thyrozol and increased by 25% in animals receiving thyroxin injection in comparison with the control. Relative expression of Thrb gene significantly increased only in mice treated with thyroxin. Comparative analysis of the relative expression of Dio2 gene revealed no differences between the experimental and control groups. Changes in the level of thyroid hormones, content of TR-ß, and relative Thrb gene expression contribute to agerelated shifts in the number and proliferative activity of mouse dermal fibroblasts.


Assuntos
Envelhecimento/genética , Fibroblastos/metabolismo , Iodeto Peroxidase/genética , Glândula Tireoide/metabolismo , Receptores alfa dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/genética , Envelhecimento/metabolismo , Animais , Antitireóideos/farmacologia , Proliferação de Células , Derme/citologia , Derme/efeitos dos fármacos , Derme/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Expressão Gênica , Iodeto Peroxidase/metabolismo , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Metimazol/farmacologia , Camundongos , Camundongos Endogâmicos , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Receptores alfa dos Hormônios Tireóideos/metabolismo , Receptores beta dos Hormônios Tireóideos/metabolismo , Tiroxina/farmacologia
15.
Int J Pediatr Otorhinolaryngol ; 122: 111-116, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30999159

RESUMO

AIMS: Immunohistochemical analysis of retraction pocket pars tensa of tympanic membrane in children. Identification of signs typical for cholesteatoma and support of retraction theory of cholesteatoma. STUDY DESIGN: a prospective study analysing 31 surgically removed retraction pockets. DEPARTMENT: University Hospital, Children's Medical Centre Methods: Retraction pockets processed by a standard process for immunohistochemical analysis. The observed findings were specified using antibodies CD45 LCA (leukocyte common antigen), CD31 (platelet endothelial cell adhesion molecule), D2-40 (marker of lymphatic endothelium), MMP9 (marker of degradation of connective tissue extracellular matrix) and Ki67 (cellular marker of proliferation). RESULTS: All observed parameters except for MMP9 had a significantly higher incidence in retraction pocket stage III compared to stage II according to Charachon. CONCLUSION: We described immunohistochemical signs of retraction pocket pars tensa of tympanic membrane in children resulting in cholesteatoma. All the observed signs occur in the structure of matrix and perimatrix of cholesteatoma. A significantly higher incidence of all observed parameters except from MMP9 was proved in retraction pocket stage III, unlike in stage II. This observation proves the fact that retraction pocket is a progressive disease and is a procholesteatoma stage.


Assuntos
Colesteatoma da Orelha Média/metabolismo , Antígeno Ki-67/metabolismo , Antígenos Comuns de Leucócito/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Membrana Timpânica/metabolismo , Biomarcadores/metabolismo , Criança , Humanos , Imuno-Histoquímica , Estudos Prospectivos
16.
J Korean Med Sci ; 34(13): e107, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30950252

RESUMO

BACKGROUND: Chordomas are aggressive bone tumors that have a predilection for the axial skeleton including the skull base and spinal/sacral bones. However, the histopathological and clinical differences between skull base chordoma (SBC) and sacral/spinal chordoma (SC) are unclear as previous studies have been focused on patient prognosis and treatment outcome. This study aimed to evaluate the clinicopathologic features and prognosis of chordoma according to its location. METHODS: Patients with chordomas were enrolled, and the histopathologic features were compared according to the tumor location. RESULTS: A total of 52 patients were enrolled. SBCs had more abundant chondroid matrix and diffuse growth pattern, while SCs had non-chondroid, myxoid matrix and a lobulating pattern, typical of chordoma. Old age and residual tumors were risk factors for shorter overall survival in SBCs. The chondroid matrix was an independent risk factor for shorter disease-free survival in the overall population. CONCLUSION: Chordomas have different histopathologic features depending on the anatomical location.


Assuntos
Cordoma/patologia , Neoplasias da Base do Crânio/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cordoma/mortalidade , Fossa Craniana Posterior/patologia , Intervalo Livre de Doença , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Sacro/patologia , Neoplasias da Base do Crânio/mortalidade , Taxa de Sobrevida , Adulto Jovem
17.
Int J Mol Sci ; 20(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987108

RESUMO

The aim of this study is to assess if an adhesive biopolymer, sodium hyaluronate (NaHA), has synergistic effects with s-PRGF (a serum derived from plasma rich in growth factors and a blood derivative that has already shown efficacy in corneal epithelial wound healing), to reduce time of healing or posology. In vitro proliferation and migration studies, both in human corneal epithelial (HCE) cells and in rabbit primary corneal epithelial (RPCE) cultures, were carried out. In addition, we performed studies of corneal wound healing in vivo in rabbits treated with s-PRGF, NaHA, or the combination of both. We performed immunohistochemistry techniques (CK3, CK15, Ki67, ß4 integrin, ZO-1, α-SMA) in rabbit corneas 7 and 30 days after a surgically induced epithelial defect. In vitro results show that the combination of NaHA and s-PRGF offers the worst proliferation rates in both HCE and RPCE cells. Addition of NaHA to s-PRGF diminishes the re-epithelializing capability of s-PRGF. In vivo, all treatments, given twice a day, showed equivalent efficacy in corneal epithelial healing. We conclude that the combined use of s-PRGF and HaNA as an adhesive biopolymer does not improve the efficacy of s-PRGF alone in the wound healing of corneal epithelial defects.


Assuntos
Epitélio Anterior/patologia , Ácido Hialurônico/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Soro/química , Animais , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Epitélio Anterior/efeitos dos fármacos , Fibrose , Humanos , Integrina beta4/metabolismo , Antígeno Ki-67/metabolismo , Coelhos , Reepitelização/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/metabolismo
18.
J Neuroinflammation ; 16(1): 79, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971251

RESUMO

BACKGROUND: Microglia play crucial roles in the maintenance of brain homeostasis. Activated microglia show a biphasic influence, promoting beneficial repair and causing harmful damage via M2 and M1 microglia, respectively. It is well-known that microglia are initially activated to the M2 state and subsequently switch to the M1 state, called M2-to-M1 class switching in acute ischemic models. However, the activation process of microglia in chronic and sporadic hypertension remains poorly understood. We aimed to clarify the process using a chronic hypertension model, the deoxycorticosterone acetate (DOCA)-salt-treated Wistar rats. METHODS: After unilateral nephrectomy, the rats were randomly divided into DOCA-salt, placebo, and control groups. DOCA-salt rats received a weekly subcutaneous injection of DOCA (40 mg/kg) and were continuously provided with 1% NaCl in drinking water. Placebo rats received a weekly subcutaneous injection of vehicle and were provided with tap water. Control rats received no administration of DOCA or NaCl. To investigate the temporal expression profiles of M1- and M2-specific markers for microglia, the animals were subjected to the immunohistochemical and biochemical studies after 2, 3, or 4 weeks DOCA-salt treatment. RESULTS: Hypertension occurred after 2 weeks of DOCA and salt administration, when round-shaped microglia with slightly shortened processes were observed juxtaposed to the vessels, although the histopathological findings were normal. After 3 weeks of DOCA and salt administration, M1-state perivascular and parenchyma microglia significantly increased, when local histopathological findings began to be observed but cerebrovascular destruction did not occur. On the other hand, M2-state microglia were never observed around the vessels at this period. Interestingly, prior to M1 activation, about 55% of perivascular microglia transiently expressed Ki-67, one of the cell proliferation markers. CONCLUSIONS: We concluded that the resting perivascular microglia directly switched to the pro-inflammatory M1 state via a transient proliferative state in DOCA-salt rats. Our results suggest that the activation machinery of microglia in chronic hypertension differs from acute ischemic models. Proliferative microglia are possible initial key players in the development of hypertension-induced cerebral vessel damage. Fine-tuning of microglia proliferation and activation could constitute an innovative therapeutic strategy to prevent its development.


Assuntos
Encéfalo/patologia , Proliferação de Células/fisiologia , Hipertensão/complicações , Hipertensão/patologia , Microglia/classificação , Microglia/patologia , Animais , Antígenos CD/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Carboximetilcelulose Sódica/farmacologia , Proliferação de Células/efeitos dos fármacos , Acetato de Desoxicorticosterona/toxicidade , Modelos Animais de Doenças , Lateralidade Funcional , Hipertensão/diagnóstico por imagem , Hipertensão/etiologia , Antígeno Ki-67/metabolismo , Imagem por Ressonância Magnética , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Mineralocorticoides/toxicidade , Nefrectomia/efeitos adversos , Ratos , Ratos Wistar , Cloreto de Sódio/toxicidade , Fatores de Tempo
19.
J Laryngol Otol ; 133(3): 205-207, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30983565

RESUMO

BACKGROUND: Ki-67 is a monoclonal antibody that provides a means of evaluating the growth fraction of normal and neoplastic human cell populations. A Ki-67 index of less than 3 per cent is expected for a typical schwannoma. Vestibular schwannomas with an index of greater than 3 per cent are presumed to be actively proliferating and pose a theoretically higher risk for regrowth or recurrence. METHODS: A retrospective chart review was conducted. Ki-67 staining was performed and specimens were divided into two groups according to Ki-67 activity: less than 3 per cent (low index), and 3 per cent or greater (elevated index). RESULTS: Eight patients (53.3 per cent) with elevated Ki-67 had recurrence or regrowth, versus five (8.5 per cent) in the low Ki-67 group. Among the 13 patients with recurrence or regrowth, the average Ki-67 value was 4.3 per cent. Among the 61 patients without recurrence or regrowth, the average Ki-67 value was 1.0 per cent. CONCLUSION: The Ki-67 labelling index reliably identifies vestibular schwannomas with an elevated potential for recurrence or regrowth in subtotal or total resection cases. In patients with a Ki-67 index greater than 3 per cent, more frequent clinical examination and radiological follow up are recommended.


Assuntos
Antígeno Ki-67/metabolismo , Neuroma Acústico/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neuroma Acústico/metabolismo , Neuroma Acústico/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos
20.
Br J Radiol ; 92(1098): 20180847, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31017448

RESUMO

OBJECTIVE: The microcirculatory hemodynamic changes of small-for-size syndrome (SFSS) are still unclear. In this study, they were investigated by four-dimensional CT perfusion (4D-CTP) technique. METHODS: The sham group, 50, 60, 70 and 80 % partial hepatectomy (PH) rat groups were established. At 1 hour (1 h), 1 day (1 d), 3 days (3 d) and 7 days (7 d) post-operation, serological examination, 4D-CTP scan and histopathological examination were performed. One-way analysis of variance and the Kruskal-Wallis test were used for the comparison. RESULTS: Based on the diagnostic criteria of SFSS, the 80 % group was considered to be a successful model. In all the PH groups, portal vein perfusion and total liver perfusion peaked at 1 h and declined at 1d and 3d. Both portal vein perfusion and total liver perfusion were significantly higher in the 80 % group than the sham group, 50 and 60% groups at 1 h (p < 0.05), and 80 % group at 3d and 7d (p < 0.05). In the 50 and 60 % groups, hepatic artery perfusion decreased at 1 h and maintained at a lower level until at 7 d; whereas, in the 70 and 80% groups, it increased at 1 h, then decreased and reached the lowest level at 7 d. No significant difference appeared in hepatic artery perfusion between any two groups at any time points. At all time points, hepatic perfusion index was lower in all the PH groups than the sham group. Significant differences in hepatic perfusion index appeared between the 80% group and the sham group at 1 h and 1 d (p < 0.05). CONCLUSIONS: The CTP parameters quantitatively revealed the microcirculatory hemodynamic changes in SFSS, which were further confirmed to be associated with histopathological injury. It is suggested that the hemodynamic changes in SFSS remnant liver can provide useful information for further revealing the mechanism of SFSS and may help for guiding the treatments. ADVANCES IN KNOWLEDGE: By using the 4D-CTP technique, the hepatic microcirculatory hemodynamic changes could be quantitatively measured in vivo for small animal research.


Assuntos
Hemodinâmica/fisiologia , Hepatectomia , Animais , Biomarcadores/metabolismo , Proliferação de Células/fisiologia , Feminino , Tomografia Computadorizada Quadridimensional , Artéria Hepática/fisiologia , Hepatócitos/citologia , Antígeno Ki-67/metabolismo , Fígado/irrigação sanguínea , Masculino , Microcirculação/fisiologia , Veia Porta/fisiologia , Ratos Sprague-Dawley , Síndrome , Fator de Necrose Tumoral alfa/metabolismo
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