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1.
Medicine (Baltimore) ; 99(2): e18678, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914061

RESUMO

To investigate the correlation between the proliferating cell nuclear antigen Ki-67 and the multislice computed tomography (MSCT) signs in different subtypes of lung adenocarcinoma.Ninety-five patients with lung adenocarcinoma confirmed by surgical pathology and treated between January 2017 and December 2017 were included. MSCT was performed before the operation, and the characteristics of the high-resolution CT (HRCT) signs of the lesions were compared with the Ki-67 immunohistochemistry results.The levels of Ki-67 in the 95 lung adenocarcinoma specimens were positively correlated with the malignancy of lung adenocarcinoma. Spearman correlation coefficient was 0.615. The expression of Ki-67 was positively correlated with the nodules' diameter, density, and lobulated sign, with Spearman correlation coefficients of 0.58, 0.554, and 0.436. There was no significant correlation with spiculation and pleural retraction, with correlation coefficients of 0.319/0.381.These findings suggest that the MSCT signs of different types of lung adenocarcinoma might be associated with the expression of Ki-67. Without replacing biopsy, the imaging features of pulmonary nodules could be comprehensively analyzed to evaluate the proliferation potential of preoperative nodules, but additional studies are needed for confirmation.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Antígeno Ki-67/biossíntese , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada Multidetectores/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/patologia , Pleura/patologia , Estudos Retrospectivos
2.
Medicine (Baltimore) ; 98(46): e17921, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725643

RESUMO

The aim of the study was to investigate the molecular mechanisms in childhood adrenocortical tumors (ACTs), which is still unclear.A total of 9 girls and 4 boys with ACTs were enrolled. Relevant clinical features were obtained from records. Immunohistochemistry of vimentin, chromogranin A, S100, synaptophysin, cytokeratin (CK), type 2 3ß-hydroxysteroid dehydrogenase (3ßHSD), cytochrome P45017α, p53, p21, p27, cyclin D1, Ki-67, insulin growth facter-2 (IGF-2), and ß-catenin were undertaken for 13 tumors and 3 adjacent normal tissues. TP53 mutations in exon 2-11 were analyzed for 6 tumors and 3 blood samples.Virilization was the most common presentation (8/13, 61.5%). Immunohistochemically, p53 was positive in 8 of 13 ACTs and none in controls while p21 was positive in 12 of 13 ACTs and none in controls (P = .0036). Ki-67 was positive in 10 of 13 ACTs, but not in normal tissues (P = .0089). Although the expression of p27, cyclin D1, IGF-2 and ß-catenin were similar between the ACTs and controls, ß-catenin was noted in nuclear of 3 ACTs but not in controls. The difference of type 2 3ßHSD and P450c17α was not significant (P > .05, respectively). Four variants of TP53 were identified in the 6 tumors. C215G variant was found in 5 of 6 while A701G and G743A variants were found in 1 case, respectively. A novel C680G variant was also noted in 1 case. It was notable that C215G variant was found in the blood mononuclear cell of 3 patients.In conclusion, p53 variant and p21 overexpression, and abnormal ß-catenin distribution may be involved in the etiology and mechanism of childhood ACTs.


Assuntos
Neoplasias do Córtex Suprarrenal/epidemiologia , Neoplasias do Córtex Suprarrenal/patologia , Virilismo/epidemiologia , 3-Hidroxiesteroide Desidrogenases/biossíntese , Neoplasias do Córtex Suprarrenal/cirurgia , Fatores Etários , Criança , Pré-Escolar , Cromogranina A/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Lactente , Fator de Crescimento Insulin-Like II/biossíntese , Queratinas/biossíntese , Antígeno Ki-67/biossíntese , Masculino , Proteínas de Ligação a Poli-ADP-Ribose/biossíntese , Fatores Sexuais , Sinaptofisina/biossíntese , Vimentina/biossíntese
3.
Medicine (Baltimore) ; 98(20): e15607, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096466

RESUMO

Lack of effective biomarkers is one of the challenges in current neoadjuvant chemotherapy to predict drug response and sensitivity of cervical squamous cell carcinoma (CSCC). The present study was designed to investigate the correlation of the expression of survivin, an inhibitor of apoptosis with the prognosis of CSCC patients undergoing neoadjuvant chemotherapy.A total of 117 CSCC patients treated with paclitaxel and carboplatin between May 2015 and April 2017 in the Second Hospital of Lanzhou University were retrospectively analyzed. The pathologic diagnosis and classification of CSCC were based on the Guidelines of the International Federation of Gynaecology and Obstetrics (FIGO). The efficacy was defined as complete remission (CR), partial remission (PR), and stability disease (SD). The expressions of survivin, vascular endothelial growth factor (VEGF), and Ki67 were determined with immunohistochemistry. Data were analyzed with SPSS software.Univariate analysis showed that survivin expression had no correlation with ages, FIGO stage, macroscopic type, lymphovascular invasion, depth of lymphovascular invasion, lymph node metastasis, and tumor size among 117 CSCC patients. However, survivin expression was positively correlated with pathological grade (R = 0.691, P < .001). Multivariate analysis revealed that survivin expression was independently correlated with grades (P < .001). In addition, the analysis of correlation indicated that survivin expression is positively correlated with VEGF expression (R = 0.820, P < .001) and Ki67 expression (R = 0.673, P < .001). The numbers (percentages) of complete remission (CR), partial remission (PR), and stability disease (SD) were 11 (9.4%), 91 (77.8%), and 15 (12.8%) respectively after the treatment of paclitaxel and carboplatin. Univariate analysis showed that efficacy of treatment was negatively correlated with pathological grade (R = 0.513, P < .001), Ki67 expression (R = 0.586, P < .001), VEGF expression (R = 0.476, P < .001) and survivin expression (R = 0.519, P < .001). Multivariate analysis revealed that efficacy of treatment was independently correlated with grades (P = .028), Ki67 (P < .001), and survivin expression (P = .015).The results suggested that survivin expression is negatively correlated with the prognosis of CSCC patients treated with paclitaxel and carboplatin. Therefore, survivin expression might be a marker for prognosis in CSCC following neoadjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/patologia , Survivina/biossíntese , Neoplasias do Colo do Útero/patologia , Adulto , Carboplatina/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Quimioterapia Adjuvante , China/epidemiologia , Feminino , Humanos , Antígeno Ki-67/biossíntese , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Carga Tumoral , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade , Fator A de Crescimento do Endotélio Vascular/biossíntese
4.
Med Sci Monit ; 25: 2368-2376, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30933965

RESUMO

BACKGROUND At present, there is no effective targeted therapy for esophageal squamous cell carcinoma (ESCC), and it is urgent to find new targets for the treatment of ESCC. TRAF4 has been regarded as a cause of carcinogenesis due to overexpression in many cancer types and participation in multiple signaling pathways. However, there are few studies on TRAF4 in ESCC worldwide. Its expression in ESCC and whether it affects the prognosis of patients still remain unclear. MATERIAL AND METHODS We detected the expressions of TRAF4, ki-67, and p53 in 100 cases of ESCC and 80 cases of adjacent normal esophageal squamous epithelium tissues by immunohistochemical technique. We further explored the relationship between TRAF4 and ESCC and its prognosis through statistical analysis. RESULTS TRAF4 was highly expressed in ESCC tissues and was mainly expressed in the cytoplasm. Overexpression of TRAF4 in ESCC was also associated with high expression of ki-67 and p53 (P<0.05). We also found that patients with high expression of TRAF4 had significantly lower OS than in patients with low TRAF4 expression (P<0.05). Overexpression of TRAF4 was an independent risk factor affecting the prognosis of patients (P<0.05). CONCLUSIONS We found that TRAF4 was highly expressed in ESCC tissues and was mainly expressed in the cytoplasm of cancer cells. Overexpression of TRAF4 was an independent risk factor affecting the overall prognosis of patients. The results indicated that TRAF4 may become a new target for the treatment of ESCC in the future.


Assuntos
Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Fator 4 Associado a Receptor de TNF/biossíntese , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Antígeno Ki-67/biossíntese , Antígeno Ki-67/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais , Fator 4 Associado a Receptor de TNF/genética , Transcriptoma , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética
5.
Arch Oral Biol ; 99: 177-182, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30721793

RESUMO

OBJECTIVE: To evaluate the association of cyclin D1 overexpression with clinicopathological parameters classically considered of prognostic value in OSCC (T, N, M, clinical stage, degree of differentiation, invasive morphology and, cellular proliferation index). DESIGN: A retrospective immunohistochemical study was conducted of cyclin D1 and ki-67 expression in 68 OSCCs from 54 patients. Cases were scanned using a digital pathology system. The tumor expression of markers was assessed in four randomly selected fields (40x), and a semi-automatized count was conducted of cyclin D1-positive and -negative cells. RESULTS: Cyclin D1 overexpression was found in 28.7% of the cases of OSCC. It was significantly and positively associated with the following clinicopathological parameters: low tumor differentiation degree (p = 0.030), invasive morphology (p = 0.045), and proliferative phenotype according to tumor cell ki-67 expression (p = 0.018). CONCLUSIONS: Cyclin D1 overexpression is an event of oral carcinogenesis associated with clinicopathological parameters classically associated with a poor prognosis in patients with OSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclina D1/biossíntese , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinogênese , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Espanha
6.
BMC Cancer ; 19(1): 94, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30665389

RESUMO

BACKGROUND: Stress has been suggested as a promoter of tumor growth and development. Glucocorticoids (GCs) are the main stress hormones and widely prescribed as drugs. However, the effect of GCs on the development and progression of colorectal carcinoma (CRC) is unclear. METHODS: We evaluated the effect of corticosterone (CORT) on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in the colorectum of C57BL/6 strain mice. Plasma level of CORT was detected by radioimmunoassay. The expression of proliferation markers (Ki-67 and PCNA), nuclear factor (NF)-κB p65 and phosphoto-p65 (P-p65), as well as cyclooxygenase (COX)-2 were determined by immunohistochemistry. Inflammation in colorectum was evaluated by histopathology. RESULTS: CORT feeding in drinking water of mice not only significantly elevated plasma CORT concentration, but also significantly increased the incidence and neoplasms burden (number and size of neoplasms) in colorectum. CORT also significant enhanced the expression of cell proliferation marker (Ki-67 and PCNA), NF-κB p65 and P-p65 as well as COX-2 in colorectal neoplasm of AOM/DSS-treated mice. CONCLUSION: In this study, we have found for the first time that CORT at stress level potentially promotes the growth and development of AOM/DSS-induced colorectal adenoma and carcinoma in mice. Up-regulation of NF-κB and COX-2 may be involved in the promoting effect of CORT.


Assuntos
Azoximetano/toxicidade , Neoplasias Colorretais/induzido quimicamente , Sulfato de Dextrana/toxicidade , Glucocorticoides/toxicidade , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/metabolismo , Ciclo-Oxigenase 2/biossíntese , Sinergismo Farmacológico , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Masculino , Camundongos Endogâmicos C57BL , Antígeno Nuclear de Célula em Proliferação/biossíntese , Fator de Transcrição RelA/biossíntese
7.
J Cutan Pathol ; 46(1): 33-43, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30328119

RESUMO

INTRODUCTION: Mycosis fungoides (MF) with large cell transformation (LCT) is an advanced stage of cutaneous lymphoma with a poor prognosis. Identification of LCT is critical and especially challenging when the number of large abnormal lymphocytes is near but below 25%. We propose that Ki-67 and p53 may be useful in making this diagnosis. METHODS: We identified 17 patients with advanced stage (T3 or T4) MF without LCT and 38 patients with a biopsy-confirmed new diagnosis of MF with LCT treated at our institution's cutaneous lymphoma clinic from 2012 to 2016. Seventeen patients underwent 22 biopsies with advanced stage MF (control), and 38 patients with 46 biopsies of MF with LCT were included in this study. RESULTS: The MF cohort had an average CD30 expression of 4%, while the MF-LCT cohort had an average CD30 expression of 22% (P < 0.05). The MF cohort had an average Ki-67 staining of 13%, while the MF-LCT group had an average Ki-67 staining of 57% (P < 0.05). Forty-seven percent of the MF-LCT group was positive for p53; on the other hand, none of the MF control group showed increased p53 expression (P < 0.05). DISCUSSION: While CD30 shows some value in delineating large cell transformation, Ki-67 and p53 appear to be useful immunohistochemical markers in the diagnosis of LCT.


Assuntos
Transformação Celular Neoplásica , Antígeno Ki-1/biossíntese , Antígeno Ki-67/biossíntese , Micose Fungoide , Neoplasias Cutâneas , Proteína Supressora de Tumor p53/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/diagnóstico , Micose Fungoide/metabolismo , Micose Fungoide/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
8.
World Neurosurg ; 122: e1047-e1051, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30415039

RESUMO

BACKGROUND: Immunohistochemistry is a basic diagnostic technique. Immunohistochemical examination results reflect mainly qualitative and less quantitative characteristics of proteomic status of cells. A combined approach with complex quantitative evaluation of marker expression using colorimetric analysis and computer technologies can expand the diagnostic capabilities of immunohistochemistry. We studied such an approach developed by using expression of the proliferative marker Ki-67 in pituitary adenomas. METHODS: A retrospective, blind, randomized, comparative study was performed of Ki-67 expression activity in pituitary adenomas using the traditional Ki-67 labeling index and a simple immunohistochemical cytocolorimetric analysis developed by us with immunohistochemical cytocolorimetric index (ICI) estimation as predictors of relapse, assessing the relationships of these indicators with the time before relapse. RESULTS: Mean Ki-67 labeling index was 3.87% ± 0.29% in the relapse-free group and 4.01% ± 0.29% in the relapse group; the difference was not statistically significant. The average Ki-67 ICI was 24.16% ± 0.51% in the relapse-free group and 30.68% ± 0.64% in the relapse group; the difference was statistically significant. The correlation coefficient of ICI values and time before relapse was -0.302, indicating the presence of a weak negative correlation. CONCLUSIONS: We successfully tested an ICI estimation method developed by us to assess Ki-67 expression in pituitary adenomas. The ICI technique can be used both as a prognostic factor for relapse and, in combination with other modern proteomic and genetic methods, as the basis for creation of new multimodal analyzing systems for functional state assessment of cells and tissues.


Assuntos
Adenoma/diagnóstico , Adenoma/metabolismo , Biomarcadores Tumorais/biossíntese , Antígeno Ki-67/biossíntese , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/metabolismo , Adulto , Colorimetria/normas , Feminino , Humanos , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Método Simples-Cego
9.
J Clin Invest ; 129(1): 209-214, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30352048

RESUMO

The loss of insulin-secreting ß cells is characteristic among type I and type II diabetes. Stimulating proliferation to expand sources of ß cells for transplantation remains a challenge because adult ß cells do not proliferate readily. The cell cycle inhibitor p57 has been shown to control cell division in human ß cells. Expression of p57 is regulated by the DNA methylation status of the imprinting control region 2 (ICR2), which is commonly hypomethylated in Beckwith-Wiedemann syndrome patients who exhibit massive ß cell proliferation. We hypothesized that targeted demethylation of the ICR2 using a transcription activator-like effector protein fused to the catalytic domain of TET1 (ICR2-TET1) would repress p57 expression and promote cell proliferation. We report here that overexpression of ICR2-TET1 in human fibroblasts reduces p57 expression levels and increases proliferation. Furthermore, human islets overexpressing ICR2-TET1 exhibit repression of p57 with concomitant upregulation of Ki-67 while maintaining glucose-sensing functionality. When transplanted into diabetic, immunodeficient mice, the epigenetically edited islets show increased ß cell replication compared with control islets. These findings demonstrate that epigenetic editing is a promising tool for inducing ß cell proliferation, which may one day alleviate the scarcity of transplantable ß cells for the treatment of diabetes.


Assuntos
Síndrome de Beckwith-Wiedemann/metabolismo , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p57/biossíntese , Desmetilação do DNA , Loci Gênicos , Células Secretoras de Insulina/metabolismo , Regulação para Cima , Síndrome de Beckwith-Wiedemann/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Células Secretoras de Insulina/patologia , Antígeno Ki-67/biossíntese
10.
Pathol Res Pract ; 215(3): 446-452, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30558966

RESUMO

Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21WAF1/CIP1 and p63 tumor suppressor proteins and Ki-67 cell proliferation marker in HM. We conducted a retrospective study of 220 gestational products, including 39 hydropic abortions (HA), 41 partial HM (PHM) and 140 complete HM (CHM). The expression of c-erbB-2, Bcl-2, p53, p21WAF1/CIP1, p63 and Ki-67 was investigated by immunohistochemistry on archival tissues. c-erbB-2 expression was observed in three PHM and 10 CHM. Bcl-2 immunostaining was significantly higher in PHM (61%) and CHM (70.7%) compared with HA (7.7%, p = 0.001 and p < 0.0001, respectively). p53 expression was stronger in CHM (73.6%) compared with PHM (24.4%, p < 0.0001) and HA (12.8%, p < 0.0001). p21WAF1/CIP1 staining was observed as well in molar and non-molar gestations (p > 0.05). p63 immunoexpression was significantly described in CHM (85.7%) and PHM (78%) compared with HA (10.2%, p < 0.0001 and p = 0.0001, respectively). Ki-67 was significantly expressed in CHM (72.1%) compared with HA (46.2%, p = 0.005). Altered expression of Bcl-2, p53, p63 and Ki-67 reflects the HM pathological development. Immunohistochemical analysis is beneficial to recognize the HM molecular and pathogenic mechanisms. Furthermore, it could serve as a useful adjunct to conventional methods for refining HM diagnosis.


Assuntos
Biomarcadores Tumorais/análise , Mola Hidatiforme/patologia , Neoplasias Uterinas/patologia , Adolescente , Adulto , Inibidor de Quinase Dependente de Ciclina p21/análise , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Feminino , Humanos , Mola Hidatiforme/metabolismo , Imuno-Histoquímica , Antígeno Ki-67/análise , Antígeno Ki-67/biossíntese , Proteínas de Membrana/análise , Proteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Gravidez , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Receptor ErbB-2/análise , Receptor ErbB-2/biossíntese , Estudos Retrospectivos , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/biossíntese , Neoplasias Uterinas/metabolismo , Adulto Jovem
11.
Pathol Oncol Res ; 25(2): 477-486, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29442221

RESUMO

Several biomarkers are in use to improve the sensitivity and specificity of cervical cancer screening. Previously, increased expression of tight junction protein claudin-1 (CLDN1) was detected in premalignant and malignant cervical lesions and applied for cytology screening. To improve the specificity, a double immunoreaction with CLDN1/Ki67 was developed in the recent study. Parallel p16/Ki67 (CINtec® PLUS) and CLDN1/Ki67 dual-stained cytology and histology were performed and compared. p16/Ki67 immunoreaction showed positivity in 317 out of 1596 smears with negativity in 1072 and unacceptable reactions in 207 samples. CLDN1/Ki67 dual staining was positive in 200 of 1358 samples, negative in 962, whereas 196 smears could not be evaluated due to technical reasons. Considering the high-grade squamous intraepithelial lesion cytology as gold standard, sensitivity of CLDN1/Ki67 reaction was 76%, specificity was 85.67%, while for p16/Ki67 sensitivity was 74% and specificity was 81.38%. Comparison of CLDN1/Ki67 and p16/Ki67 dual stainings showed the results of the two tests not to be significantly different. Analysing histological slides from 63 cases, the results of the two tests agreed perfectly. As conclusion the sensitivity and specificity proved to be similar using p16/Ki67 and CLDN1/Ki67 double immunoreactions both on LBC samples and on histological slides.


Assuntos
Biomarcadores Tumorais/análise , Claudina-1/biossíntese , Imuno-Histoquímica/métodos , Antígeno Ki-67/biossíntese , Neoplasias do Colo do Útero/diagnóstico , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Citodiagnóstico/métodos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Sensibilidade e Especificidade , Esfregaço Vaginal
12.
Oncogene ; 38(4): 549-563, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30158672

RESUMO

Ionizing radiation (IR) is a conventional cancer therapeutic, to which cancer cells develop radioresistance with exposure. The residual cancer cells after radiation treatment also have increased metastatic potential. The mechanisms by which cancer cells develop radioresistance and gain metastatic potential are still unknown. In this study acute IR exposure induced cancer cell senescence and apoptosis, but after long-term IR exposure, cancer cells exhibited radioresistance. The proliferation of radioresistant cells was retarded, and most cells were arrested in G0/G1 phase. The radioresistant cells simultaneously showed resistance to further IR-induced apoptosis, premature senescence, and epithelial to mesenchymal transformation (EMT). Acute IR exposure steadily elevated CDC6 protein levels due to the attenuation of ubiquitination, while CDC6 overexpression was observed in the radioresistant cells because the insufficiency of CDC6 phosphorylation blocked protein translocation from nucleus to cytoplasm, resulting in subcellular protein accumulation when the cells were arrested in G0/G1 phase. CDC6 ectopic overexpression in CNE2 cells resulted in apoptosis resistance, G0/G1 cell cycle arrest, premature senescence, and EMT, similar to the characteristics of radioresistant CNE2-R cells. Targeting CDC6 with siRNA promoted IR-induced senescence, sensitized cancer cells to IR-induced apoptosis, and reversed EMT. Furthermore, CDC6 depletion synergistically repressed the growth of CNE2-R xenografts when combined with IR. The study describes for the first time cell models for IR-induced senescence, apoptosis resistance, and EMT, three major mechanisms by which radioresistance develops. CDC6 is a novel radioresistance switch regulating senescence, apoptosis, and EMT. These studies suggest that CDC6highKI67low represents a new diagnostic marker of radiosensitivity, and CDC6 represents a new therapeutic target for cancer radiosensitization.


Assuntos
Antígenos CD/fisiologia , Antígenos de Diferenciação de Linfócitos T/fisiologia , Apoptose/efeitos da radiação , Carcinoma/patologia , Senescência Celular/fisiologia , Transição Epitelial-Mesenquimal/efeitos da radiação , Neoplasias Nasofaríngeas/patologia , Proteínas de Neoplasias/fisiologia , Processamento de Proteína Pós-Traducional/efeitos da radiação , Tolerância a Radiação/fisiologia , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos T/biossíntese , Antígenos de Diferenciação de Linfócitos T/genética , Carcinoma/radioterapia , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Antígeno Ki-67/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Nasofaríngeas/radioterapia , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Fosforilação/efeitos da radiação , Estabilidade Proteica , Transporte Proteico/efeitos da radiação , Interferência de RNA , RNA Interferente Pequeno/genética , Ubiquitinação/efeitos da radiação , Raios X
13.
Histopathology ; 74(3): 424-429, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30326145

RESUMO

AIMS: Well-differentiated small intestinal neuroendocrine tumours (SI-NETs) are often multifocal, and this has been suggested to impart worse disease-free survival. Practice guidelines have not been established for World Health Organisation (WHO) grading of multiple primary lesions. METHODS AND RESULTS: We identified 68 patients with ileal/jejunal SI-NET for a combined total of 207 primary lesions. Each case was evaluated for patient age and sex; size of all tumours; presence of lymph node metastases, mesenteric tumour deposits or distant metastases; and disease-specific outcome. Ki67 staining was performed on all 207 primary lesions. The relationship between multifocality and clinicopathological factors was compared using Fisher's exact test. Outcome was tested using Cox proportional hazard regression. Forty-two patients had unifocal disease, and 26 had multifocal disease (median five lesions, range = 2-32). Most tumours were WHO grade 1 (201 of 207, 97%). Of the five patients with grades 2/3 tumours, three patients had unifocal disease, one patient had two subcentimetre grade 2 lesions (including the largest) and eight subcentimetre grade 1 lesions, and one patient had one 1.6-cm grade 3 lesion and one subcentimetre grade 1 lesion. There was a positive correlation between tumour size and Ki67 index (coefficient 0.28; 95% confidence interval 0.05-0.52, P = 0.017). There was no significant association between multifocality and nodal metastases, mesenteric tumour deposits, distant metastases or disease-specific survival. CONCLUSIONS: In patients with multifocal SI-NET, unless a particular lesion has a high mitotic rate, only staining the largest lesion for Ki67 should serve to grade almost all cases accurately. Multifocality does not appear to significantly impact patient survival.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Intestinais/patologia , Antígeno Ki-67/análise , Tumores Neuroendócrinos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Intestino Delgado/patologia , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais
14.
Cancer Biother Radiopharm ; 34(2): 85-90, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30585764

RESUMO

OBJECTIVE: Breast cancer (BC) is a common malignant tumor in females. The combined assay of multiple molecular markers benefits the diagnosis and prognostic prediction. Human epidermal growth factor receptor 2 (HER2) facilitates the proliferation and differentiation of cancer cells through ligand binding. Ki67 is a tumor proliferation-related gene, whereas GSTP1 is a DNA repair-related gene. This study thus investigated the significance of HER2 and Ki67/GSTP1 gene combined assay in the diagnosis and prognosis of BC. MATERIALS AND METHODS: A total of 86 breast tumor tissues and adjacent tissues were collected. Gene expression and protein levels of HER2 and Ki67 were quantified by real-time polymerase chain reaction (PCR) and Western blot, respectively. Methylation frequency of GSTP1 was analyzed by methylation-specific PCR. The correlation between HER2 and Ki67/GSTP1 and clinical/pathological features of BC was analyzed. RESULTS: Gene and protein expression levels of HER2 and Ki67 in tumor tissues were increased (p < 0.05 compared with adjacent tissues). Methylation frequency of GSTP1 gene was 37.2%, which was significantly higher in breast tumor tissues than in adjacent tissues (12.79%, p < 0.05). HER2 expression was positively correlated with TNM stage, tumor size, and lymph node metastasis, and negatively correlated with tissue grade and estrogen receptor (ER)/progesterone receptor (PR) expression (p < 0.05). GSTP1 methylation was positively correlated with TNM stage and tumor size, and negatively correlated with ER/PR expression (p < 0.05). CONCLUSIONS: HER2, Ki67, and GSTP1 methylation were correlated with clinical and pathological features of BC. The combined assay benefits the early diagnosis and prognostic prediction of cancer.


Assuntos
Neoplasias da Mama/genética , Glutationa S-Transferase pi/genética , Antígeno Ki-67/genética , Receptor ErbB-2/genética , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Metilação de DNA , Feminino , Glutationa S-Transferase pi/biossíntese , Humanos , Antígeno Ki-67/biossíntese , Prognóstico , Receptor ErbB-2/biossíntese
15.
Medicina (Kaunas) ; 54(5)2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30463213

RESUMO

Background and objectives: Energy drinks are popular non-alcoholic beverages. They are consumed in large amounts, mainly by active, young people. Although they are easily accessible and marketed as safe, numerous cases of adverse effects have been published, including cardiac arrest, arrythmias, acute hepatitis, and renal failure. The aim of the current study is the assessment of energy drink influence on the histological structure of adrenal cortex in rats. Material and Methods: 15 male young Wistar rats were equally divided into three groups: control (C), experimental (E) and reversibility control (RC). C group received water and standard rodent food ad libitum while both E and RC groups had additionally unlimited access to energy drinks. C and E groups were decapitated after 8 weeks and RC was given another 8 weeks without energy drinks. Adrenal glands were embedded in paraffin blocks and 5 µm slides were prepared and stained according to standard H&E and Masson's trichrome protocols. Additionally, immunohistochemical stainings against Ki-67, p53, CTGF and caspase-3 were prepared. Results: Decreased vacuolization and numerous pyknotic nuclei were noted in E and RC groups. Overexpression of caspase-3 was noted both subcapsular in zona glomerulosa and along sinusoids in zona fasciculata. Increased collagen deposition in zona glomerulosa and zona fasciculata of E and RC was observed. Insular and irregular overexpression of CTGF was noted. The overall picture of CTGF expression matched the Masson's trichrome. No significant difference was observed in Ki-67 expression. Conclusions: The results of the current study suggest that the stimulation is so intense that it causes significant damage to adrenal cortical cells, resulting in their apoptosis. It seems, however, that the observed effects are at least partially reversible.


Assuntos
Cafeína/efeitos adversos , Bebidas Energéticas/efeitos adversos , Gotículas Lipídicas , Taurina/efeitos adversos , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia , Zona Glomerulosa/metabolismo , Zona Glomerulosa/patologia , Animais , Apoptose , Caspase 3/biossíntese , Colágeno/biossíntese , Fator de Crescimento do Tecido Conjuntivo/biossíntese , Antígeno Ki-67/biossíntese , Masculino , Ratos , Ratos Wistar , Zona Fasciculada/citologia , Zona Glomerulosa/citologia
16.
Am J Clin Pathol ; 150(6): 512-521, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30169728

RESUMO

Objectives: While cervical cytology is accepted triage for human papillomavirus (HPV)-positive women, the efficiency of cervical screening could be improved by exploiting disease markers with higher specificity. Methods: CINtec PLUS triage alone and combined with HPV 16/18 genotyping was performed on ThinPrep samples from HPV-positive women. Clinical performance and the potential to reduce or expedite colposcopy referrals were evaluated. Results: The 2-year sensitivity and specificity for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) were 90% and 42%, respectively. Specificity was improved over HPV testing in equivocal cytology and could cut the referral rate by about 40%. When combined with HPV 16/18 genotyping, CINtec PLUS triage of the 12 other high-risk HPV genotypes generally demonstrated better sensitivity for CIN3+ than separate triage of non-type-specific HPV-positive women. This strategy could reduce colposcopy referrals by 31%. Conclusions: These findings highlight the potential of CINtec PLUS to improve management pathways in HPV-positive women. CINtec PLUS cytology represents a sensitive and efficient triage in HPV-positive women. The clinical performance of the dual-stain was most notable in women younger than 25 years and could potentially improve management pathways.


Assuntos
Biomarcadores Tumorais/análise , Neoplasia Intraepitelial Cervical/diagnóstico , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Neoplasia Intraepitelial Cervical/virologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Antígeno Ki-67/análise , Antígeno Ki-67/biossíntese , Pessoa de Meia-Idade , Estudos Retrospectivos , Triagem/métodos , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
17.
Eur Rev Med Pharmacol Sci ; 22(16): 5149-5155, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30178835

RESUMO

OBJECTIVE: The purposes of this study were to examine the therapeutic response of advanced cervical cancer to Ki-67 proliferative index (Ki-67 PI) dependent cisplatin chemotherapy, and to determine Ki-67 PI referential value that is expected to provide a satisfactory therapeutic response of cervical cancer to cisplatin chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 59 patients treated for cervical cancer at Clinic for Oncology, Clinical Center Nis, Serbia. According to the obtained Ki-67 PI values, patients were divided into three groups, and all the patients received the same cytostatic, cisplatin. Therapeutic response to chemotherapy was evaluated in relation to disease progression presence or absence and progression-free survival after a year follow-up since the first chemotherapy. RESULTS: Survival rate increases with an increase of Ki-67 PI by Kaplan-Meier survival analysis, meaning that survival rate is statistically significantly shorter in the group of patients with Ki-67 PI < 40% in comparison to patients from other two groups (p=0.010). Mann-Whitney test confirmed a statistically significant increase in survival rate among the groups of patients formed according to Ki-67 PI (p<0.05). Kaplan-Meier survival analysis confirmed that the mean survival rate in the group of patients with Ki-67 PI values over 60% is statistically significantly longer in comparison to patients with Ki-67 PI values below or equal 60% (p<0.001). CONCLUSIONS: Advanced cervical cancer with a high Ki-67 PI expression responds better to cisplatin-based chemotherapy, thus resulting in a longer survival rate. The values of Ki-67 PI were determined: high Ki-67 PI (≥ 60%), moderate Ki-67 PI (40-60%), and low Ki-67 PI (≤ 40%).


Assuntos
Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Antígeno Ki-67/biossíntese , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/mortalidade , Estudos Prospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade
18.
Respir Res ; 19(1): 150, 2018 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-30103737

RESUMO

BACKGROUND: Lung cancer ranks as the leading cause of cancer-related deaths worldwide and we performed this meta-analysis to investigate eligible studies and determine the prognostic effect of Ki-67. METHODS: In total, 108 studies in 95 articles with 14,732 patients were found to be eligible, of which 96 studies reported on overall survival (OS) and 19 studies reported on disease-free survival (DFS) with relation to Ki-67 expression in lung cancer patients. RESULTS: The pooled hazard ratio (HR) indicated that a high Ki-67 level could be a valuable prognostic factor for lung cancer (HR = 1.122 for OS, P < 0.001 and HR = 1.894 for DFS, P < 0.001). Subsequently, the results revealed that a high Ki-67 level was significantly associated with clinical parameters of lung cancer including age (odd ratio, OR = 1.246 for older patients, P = 0.018), gender (OR = 1.874 for males, P < 0.001) and smoking status (OR = 3.087 for smokers, P < 0.001). Additionally, significant positive correlations were found between Ki-67 overexpression and poorer differentiation (OR = 1.993, P = 0.003), larger tumor size (OR = 1.436, P = 0.003), and higher pathologic stages (OR = 1.867 for III-IV, P < 0.001). Furthermore, high expression of Ki-67 was found to be a valuable predictive factor for lymph node metastasis positive (OR = 1.653, P < 0.001) and advanced TNM stages (OR = 1.497 for stage III-IV, P = 0.024). Finally, no publication bias was detected in any of the analyses. CONCLUSIONS: This study highlights that the high expression of Ki-67 is clinically relevant in terms of the prognostic and clinicopathological characteristics for lung cancer. Nevertheless, more prospective well-designed studies are warranted to validate these findings.


Assuntos
Biomarcadores Tumorais/biossíntese , Regulação Neoplásica da Expressão Gênica , Antígeno Ki-67/biossíntese , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais/genética , Humanos , Antígeno Ki-67/genética , Prognóstico , Estudos Prospectivos
19.
Sci Rep ; 8(1): 11844, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087428

RESUMO

To investigate the ability of CT texture analysis to assess and predict the expression statuses of E-cadherin, Ki67, VEGFR2 and EGFR in gastric cancers, the enhanced CT images of 139 patients with gastric cancer were retrospectively reviewed. The region of interest was manually drawn along the margin of the lesion on the largest slice in the arterial and venous phases, which yielded a series of texture parameters. Our results showed that the standard deviation, width, entropy, entropy (H), correlation and contrast from the arterial and venous phases were significantly correlated with the E-cadherin expression level in gastric cancers (all P < 0.05). The skewness from the arterial phase and the mean and autocorrelation from the venous phase were negatively correlated with the Ki67 expression level in gastric cancers (all P < 0.05). The width, entropy and contrast from the venous phase were positively correlated with the VEGFR2 expression level in gastric cancers (all P < 0.05). No significant correlation was found between the texture features and EGFR expression level. CT texture analysis, which had areas under the receiver operating characteristic curve (AUCs) ranging from 0.612 to 0.715, holds promise in predicting E-cadherin, Ki67 and VEGFR2 expression levels in gastric cancers.


Assuntos
Biomarcadores/metabolismo , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/metabolismo , Tomografia Computadorizada por Raios X/métodos , Caderinas/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese
20.
Mol Oncol ; 12(9): 1608-1622, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30117261

RESUMO

Breast and prostate cancer research to date has largely been predicated on the use of cell lines in vitro or in vivo. These limitations have led to the development of more clinically relevant models, such as organoids or murine xenografts that utilize patient-derived material; however, issues related to low take rate, long duration of establishment, and the associated costs constrain use of these models. This study demonstrates that ex vivo culture of freshly resected breast and prostate tumor specimens obtained from surgery, termed patient-derived explants (PDEs), provides a high-throughput and cost-effective model that retains the native tissue architecture, microenvironment, cell viability, and key oncogenic drivers. The PDE model provides a unique approach for direct evaluation of drug responses on an individual patient's tumor, which is amenable to analysis using contemporary genomic technologies. The ability to rapidly evaluate drug efficacy in patient-derived material has high potential to facilitate implementation of personalized medicine approaches.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Modelagem Computacional Específica para o Paciente , Medicina de Precisão/métodos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Células Epiteliais , Receptor alfa de Estrogênio/metabolismo , Feminino , Esponja de Gelatina Absorvível , Xenoenxertos , Humanos , Antígeno Ki-67/biossíntese , Masculino , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Organoides , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Transdução de Sinais , Pesquisa Médica Translacional , Células Tumorais Cultivadas , Microambiente Tumoral
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