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1.
World J Gastroenterol ; 23(14): 2601-2612, 2017 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-28465645

RESUMO

AIM: To investigate the expression and clinical pathological significance of ROR2 and WNT5a in gallbladder squamous/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC). METHODS: EnVision immunohistochemistry was used to stain for ROR2 and WNT5a in 46 SC/ASC patients and 80 AC patients. RESULTS: Poorly differentiated AC among AC patients aged > 45 years were significantly more frequent compared with SC/ASC patients, while tumors with a maximal diameter > 3 cm in the SC/ASC group were significantly more frequent compared with the AC group. Positive ROR2 and WNT5a expression was significantly lower in SC/ASC or AC with a maximal mass diameter ≤ 3 cm, a TNM stage of I + II, no lymph node metastasis, no surrounding invasion, and radical resection than in patients with a maximal mass diameter > 3 cm, TNM stage IV, lymph node metastasis, surrounding invasion, and no resection. Positive ROR2 expression in patients with highly differentiated SC/ASC was significantly lower than in patients with poorly differentiated SC/ASC. Positive ROR2 and WNT5a expression levels in highly differentiated AC were significantly lower than in poorly differentiated AC. Kaplan-Meier survival analysis showed that differentiation degree, maximal mass diameter, TNM stage, lymph node metastasis, surrounding invasion, surgical procedure and the ROR2 and WNT5a expression levels were closely related to average survival of SC/ASC or AC. The survival of SC/ASC or AC patients with positive expression of ROR2 and WNT5a was significantly shorter than that of patients with negative expression results. Cox multivariate analysis revealed that poor differentiation, a maximal diameter of the mass ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, unresected surgery and positive ROR2 or WNT5a expression in the SC/ASC or AC patients were negatively correlated with the postoperative survival rate and positively correlated with mortality, which are risk factors and independent prognostic predictors. CONCLUSION: SC/ASC or AC patients with positive ROR2 or WNT5a expression generally have a poor prognosis.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Carcinoma Adenoescamoso/química , Neoplasias da Vesícula Biliar/química , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/análise , Proteína Wnt-5a/análise , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Diferenciação Celular , Distribuição de Qui-Quadrado , China , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
2.
PLoS One ; 12(5): e0176927, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28467477

RESUMO

Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 µg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 µg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 µg/L BPS-treated groups. After exposure to BPS, the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 µg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 µg/L of BPS treatment group. Moreover, exposure to 10 µg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 µg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trß) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSH concentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption.


Assuntos
Fenóis/efeitos adversos , Sulfonas/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiologia , Larva/efeitos dos fármacos , Larva/fisiologia , Glândula Tireoide/embriologia , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Poluentes Químicos da Água/efeitos adversos , Peixe-Zebra/fisiologia
3.
Tumori ; 103(6): 557-565, 2017 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-27174628

RESUMO

PURPOSE: Gallbladder cancers (GBCs) are highly aggressive gastrointestinal cancers with high mortality. Biological markers for the diagnosis, prognosis, and targeted therapy of GBCs have not been established. METHODS: The protein expression of Jagged1 and DLL4 in 80 adenocarcinomas (AC) and 46 squamous cell/adenosquamous carcinomas (SC/ASCs) was measured using immunohistochemistry. RESULTS: Positive Jagged1 and DLL4 expression in both SC/ASC and AC was significantly associated with poor differentiation, large tumor size, invasion, metastasis, and low surgical curability. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expression was significantly associated with mean survival of SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expression, as well as poor differentiation, large tumor size, high TNM stage, invasion, lymph node metastasis, and low surgical curability are independent poor prognostic factors in both SC/ASC and AC patients. CONCLUSIONS: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with SC/ASC and patients with AC.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Vesícula Biliar/patologia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Proteína Jagged-1/biossíntese , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Proteína Jagged-1/análise , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico
4.
Hepatobiliary Pancreat Dis Int ; 15(6): 640-646, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27919854

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC. METHODS: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals. Thirteen normal pancreatic tissues and 55 benign pancreatic specimens were collected at the same period. Immunohistochemical staining was used to measure Jagged1 and DLL4 protein expressions in these tissues. RESULTS: The percentage of positive Jagged1 and DLL4 was significantly higher in PDAC than in normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P<0.01). The higher Jagged1 and DLL4 expressions in PDAC were significantly associated with poor differentiation, maximum tumor size >5 cm, invasion, regional lymph node metastasis, and TNM III/IV disease (P<0.05). In PDAC, Jagged1 expression positively correlated with DLL4 expression. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expressions were significantly associated with shorter survival in patients with PDAC. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expressions were independent prognostic factors for poor prognosis of patients with PDAC. CONCLUSION: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with PDAC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/química , Peptídeos e Proteínas de Sinalização Intercelular/análise , Proteína Jagged-1/análise , Neoplasias Pancreáticas/química , Adulto , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Regulação para Cima
5.
Cancer Invest ; 34(6): 255-64, 2016 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-27389087

RESUMO

Biomarkers for the diagnosis, prognosis, and targeting therapy of gallbladder cancers are not clinically available. This study demonstrated that the percentage of cases with positive SHP2 and UGP2 expression significantly correlated with the percentage of cases with positive vimentin, ß-catenin, MMP2, MMP9, and Ki-67 expression, large tumor size, high TNM stage, lymph node metastasis, and survival in patients with adenocarcinomas and squamous cell/adenosquamous carcinomas. Positive SHP2 and UGP2 expression are independent poor-prognostic factors in both types of tumors. Our study suggested that positive SHP2 and UGP2 expression correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , UTP-Glucose-1-Fosfato Uridililtransferase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/terapia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
6.
Appl Immunohistochem Mol Morphol ; 24(4): 275-82, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26200836

RESUMO

PURPOSE: To study the expression of breast cancer metastasis suppressor 1 (BRMS1) and heparanase (HPA) and evaluate their clinicopathologic significance and relationship in benign and malignant lesions of the gallbladder. MATERIALS AND METHODS: EnVision immunohistochemical method for determining the expression of BRMS1 and HPA was used in routinely paraffin-embedded sections of surgical resected specimens from gallbladder adenocarcinoma, peritumoral tissues, polyp, and chronic cholecystitis. RESULTS: The positive rate of BRMS1 expression was significantly lower in gallbladder adenocarcinoma than that in peritumoral tissues (P<0.01), polyp (P<0.01), and chronic cholecystitis (P<0.01). The positive rate of HPA expression was significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues (P<0.01), polyp (P<0.05), and chronic cholecystitis (P<0.01). The positive expression of BRMS1 and negative expression of HPA were significantly associated with differentiation, lymph node metastasis, and invasion of adenocarcinoma (P<0.05 or P<0.01). Unitivariate Kaplan-Meier analysis showed that decreased expression of BRMS1 (P=0.008) or increased expression of HPA (P=0.016) was associated with decreased overall survival. Multivariate Cox regression analysis showed that decreased expression of BRMS1 (P=0.011) and/or increased expression of HPA (P=0.019) was an independent bad prognostic predictor in gallbladder adenocarcinoma. CONCLUSION: The expression of BRMS1 and/or HPA might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Glucuronidase/metabolismo , Proteínas Repressoras/metabolismo , Adenocarcinoma/patologia , Progressão da Doença , Neoplasias da Vesícula Biliar/patologia , Humanos , Prognóstico , Análise de Sobrevida
7.
Pathol Oncol Res ; 22(3): 483-92, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26634853

RESUMO

Gallbladder cancers (GBCs) are highly malignant gastrointestinal cancers. The biological makers for the prognosis and targeting therapy of GBCs have not been established. The protein expression of Notch 1 and Notch 3 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (AC) was measured using immunohistochemistry. Positive Notch 1 and Notch 3 expression in both SC/ASC and AC was significantly associated with large tumor size, invasion, metastasis, and low surgical curability (P < 0.05 or P < 0.01). Univariate Kaplan-Meier analysis showed that positive Notch 1 and Notch 3 expression was significantly associated with mean survival of SC/ASC and AC patients (P < 0.01 or P < 0.001). Multivariate Cox regression analysis showed that positive Notch 1 and Notch 3 expression, as well as low differentiation, large tumor size, high TNM stage, invasion, lymph node metastasis, and surgical curability are independent poor-prognostic factors in both SC/ASC and AC patients. Positive Notch 1 and Notch 3 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in both SC/ASC and AC patients.


Assuntos
Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Receptor Notch1/metabolismo , Receptor Notch3/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Diferenciação Celular/fisiologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico
8.
Oncol Lett ; 12(6): 5136-5144, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28105220

RESUMO

Gallbladder cancer (GBC) is a rare but highly aggressive cancer for which no well-accepted prognostic biomarkers have been identified. Thymus cell antigen 1 (Thy1), also known as cluster of differentiation (CD)90, and integrin α6 (ITGA6), also known as CD49f, are important molecules in cancer and putative markers of various stem cell types. However, their role in GBC remains to be elucidated. In the present study, Thy1 and ITGA6 expression status in clinical GBC samples, which comprised squamous cell/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC) subtypes, was investigated. The associations between Thy1 and ITGA6 expression and clinical parameters and survival rate were analyzed separately. The THY1 and ITGA6 messenger RNA levels were significantly higher in both SC/ASC and AC tissues than in adjacent non-tumor tissues (all P<0.001). These results were subsequently confirmed by immunohistochemical analyses. Overexpression of Thy1 and ITGA6 was correlated with poor differentiation, large tumor size, lymph node metastasis and great invasiveness in SC/ASC (Thy1, P=0.045, P=0.005, P=0.003 and P=0.009, respectively, and ITGA6, P=0.029, P=0.011, P=0.009 and P=0.004, respectively) and AC (Thy1, P=0.027, P<0.001, P=0.003 and P 0.004, respectively, and ITGA6, P=0.002, P=0.003, P=0.006 and P=0.006, respectively). Both Thy1 and ITGA6 were expressed at higher levels in AC with advanced tumor-node-metastasis stage (TNM) than in AC with low TNM stage (P=0.001 and P=0.018, respectively). In addition, patients with elevated Thy1 or ITGA6 expression had shorter overall survival than those with negative Thy1 or ITGA6 expression. Multivariate Cox regression analysis demonstrated that Thy1 (SC/ASC, P=0.001 and AC, P=0.005) and ITGA6 (both P=0.003) were independent predictors of poor prognosis in both SC/ASC and AC patients. In conclusion, Thy1 and ITGA6 could be clinical prognostic markers for GBC.

9.
J Mol Histol ; 46(1): 57-65, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25311765

RESUMO

The differences in clinical, pathological, and biological characteristics between adenocarcinoma (AC) and squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented. This study investigates the clinical and pathological associations of ATP5B and ß2M with benign and malignant lesions of the gallbladder. In this study, ATP5B and ß2M expression in 46 SC/ASCs and 80 ACs were examined using immunohistochemistry. The rate of ATP5B positive expression was significantly lower, while the rate of ß2M expression was significantly higher, in AC and SC/ASC than in gallbladder adenomas, gallbladder polyps, or gallbladder epithelium with stone (P < 0.01). More SC/ASCs had larger tumor mass and good differentiation compared to ACs. Positive ß2M and negative ATP5B expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis, and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that positive ß2M (P < 0.05 or P < 0.001) expression and negative ATP5B (P < 0.001) expression were significantly associated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that negative ATP5B expression is an independent-prognostic factor for poor prognosis in both SC/ASC (P < 0.01) and AC (P < 0.001) patients. Positive ß2M expression is an independent-prognostic factor for poor prognosis in AC (P < 0.05) patients. Our study suggested that positive ß2M expression or loss of ATP5B expression in tumor tissues is closely related to the metastasis, invasion, and poor-prognosis of gallbladder cancer.


Assuntos
Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Microglobulina beta-2/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , ATPases Mitocondriais Próton-Translocadoras/genética , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral , Microglobulina beta-2/genética
10.
Appl Immunohistochem Mol Morphol ; 22(10): 741-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25046228

RESUMO

Gall bladder cancers (GBCs) are highly resistant to radiotherapy and chemotherapy. Unfortunately, the key molecular mechanisms responsible for therapeutic resistance have not been identified. In this study, the expression of DNA-PKcs and Ku70 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (ACs) were examined by immunohistochemical analysis. Positive DNA-PKcs and Ku70 expression were significantly associated with less lymph node metastasis, invasion, and low TNM stage of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that loss of DNA-PKcs and Ku70 expression significantly correlated with decreased survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that loss of DNA-PKcs and Ku70 expression was an independent poor prognostic predictor in both SC/ASC and AC patients. Our study suggested that DNA-PKcs and Ku70 are tumor suppressors, and loss of DNA-PKcs and Ku70 expression is an important biological marker for metastasis, invasion, and prognosis of GBC. Currently, there is no implication of DNA-PKcs and Ku70 expression in chemoresistance or radioresistance in GBC.


Assuntos
Adenocarcinoma/patologia , Antígenos Nucleares/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Proteína Quinase Ativada por DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias da Vesícula Biliar/patologia , Proteínas Nucleares/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Autoantígeno Ku , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
11.
Asian Pac J Cancer Prev ; 15(3): 1441-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24606480

RESUMO

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there are few clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASC and 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined using immunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1 and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than 3 cm in diameter, stage I or II (TNM stage), with no lymph node metastases, with no local invasion and treated with radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in well differentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degree of differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expression rate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01). Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC (P SC/ASC =0.000) or AC (P AC =0.000 or P AC =0.002) had longer survival than those negative expression. Cox multivariate analysis indicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1 and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers for SC/ASC and AC of gallbladder.


Assuntos
Efrina-B1/biossíntese , Neoplasias da Vesícula Biliar/diagnóstico , Receptor EphB1/biossíntese , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Imuno-Histoquímica , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
12.
Pathol Res Pract ; 210(6): 363-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24636838

RESUMO

Gallbladder cancer (GBC) is a rare, but highly aggressive cancer. The most common type of gallbladder cancer is adenocarcinoma (AC), while squamous cell/adenosquamous carcinoma (SC/ASC) is a rare type of gallbladder cancer. The clinicopathologic and biological characteristics of SC/ASC have not been well documented. In this study, the protein expression of N-cadherin and P-cadherin in 46 SC/ASCs and 80 ACs was measured using immunohistochemistry. We demonstrated that positive N-cadherin and P-cadherin expression were significantly associated with large tumor size, invasion, and lymph node metastasis of both SC/ASC and AC. In contrast, positive N-cadherin and P-cadherin expression were significantly associated with differentiation and TNM stage in only AC. Univariate Kaplan-Meier analysis showed that positive N-cadherin and P-cadherin expression, differentiation, tumor size, TNM stage, invasion, lymph node metastasis, and surgical curability were significantly associated with overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive N-cadherin and P-cadherin expression are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive N-cadherin and P-cadherin expression closely correlated with clinicopathological and biological behaviors, and poor-prognosis of gallbladder cancer.


Assuntos
Adenocarcinoma/química , Antígenos CD/análise , Biomarcadores Tumorais/análise , Caderinas/análise , Carcinoma Adenoescamoso/química , Neoplasias da Vesícula Biliar/química , Adenocarcinoma/secundário , Adulto , Idoso , Carcinoma Adenoescamoso/secundário , Diferenciação Celular , Feminino , Neoplasias da Vesícula Biliar/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Carga Tumoral
13.
World J Surg Oncol ; 12: 32, 2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24502441

RESUMO

BACKGROUND: To establish a model of pancreatic cancer induced by 7,12-dimethylbenzantracene (DMBA) in Sprague-Dawley (SD) rats, and detect the expression of DNA-repair proteins (MGMT, ERCC1, hMSH2, and hMLH1) and their significance in pancreatic cancer and non-cancerous pancreatic tissues of SD rats. METHODS: DMBA was directly implanted into the parenchyma of rat pancreas (group A and group B), and group B rats were then treated with trichostatin A (TSA). The rats in both groups were executed within 3 to 5 months, and their pancreatic tissues were observed by macrography and under microscopy. Meanwhile, the rats in the control group (group C) were executed at 5 months. Immunohistochemistry was used to assay the expression of MGMT, ERCC1, hMSH2, and hMLH1. RESULTS: The incidence of pancreatic cancer in group A within 3 to 5 months was 48.7% (18/37), including 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3% (12/36), including 1 case of fibrosarcoma. The mean of maximal diameters of tumors in group A was higher than that in group B (P <0.05). No pathological changes were found in pancreas of group C and other main organs (except pancreas) of group A and group B. No statistical differences were found among the positive rates of MGMT, ERCC1, hMSH2, and hMLH1 in ductal adenocarcinoma and non-cancerous pancreatic tissues of group A (P >0.05). The positive rates of MGMT, ERCC1, hMSH2, and hMLH1 were significantly lower in ductal adenocarcinoma than those in non-cancerous tissues of group B (P ≤0.05). All pancreas of group C had positive expression of MGMT, ERCC1, hMSH2, and hMLH1 and two cases of fibrosarcoma showed a negative expression. CONCLUSIONS: DMBA, directly implanted into the parenchyma of pancreas, creates an ideal pancreatic cancer model within a short time. TSA might restrain DNA damage related to the genesis and growth of pancreatic cancer in rats. The DNA-repair proteins, including MGMT, ERCC1, hMSH2, and hMLH1, might play an important role in the genesis of pancreatic cancer induced by DMBA in rats.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Animais , Carcinoma Ductal Pancreático/patologia , Técnicas Imunoenzimáticas , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Ratos , Ratos Sprague-Dawley
14.
Tumori ; 100(6): 667-74, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25688501

RESUMO

AIMS AND BACKGROUND: Over 90% of patients with gallbladder cancer have invasion and/or metastasis when they are diagnosed at the clinic. Such patients usually have an extremely poor prognosis. The molecular mechanism responsible for the high prevalence of invasion and metastasis remains unknown. METHODS: We investigated the expression of two metastasis-suppression genes--KAI-1 and KiSS-1--and a metastasis-associated gene--MTA1--in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using in situ hybridization or immunohistochemistry. RESULTS: We demonstrated that positive MTA1 expression was significantly higher whereas positive expressions of KAI-1 and KiSS-1 genes were significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, polyps, and chronic cholecystitis. Positive MTA1 expression was significantly lower, but positive KAI-1 and KiSS-1 expressions were significantly higher in cases with well-differentiated adenocarcinoma, smaller tumor mass, no metastasis of lymph node, and no invasion of regional tissues than in cases having poorly differentiated adenocarcinoma, larger tumor mass, metastasis and invasion. Univariate Kaplan-Meier analysis showed that increased expression of MTA1 and lowered expression of KAI-1 and KiSS-1 were significantly associated with decreased overall survival. Cox regression analysis showed that tumor mass, lymph node metastasis, invasion, and MTA1 expression levels negatively correlated with survival. CONCLUSIONS: Our study suggested that KAI-1, KiSS-1, and MTA1 might be important biological markers involved in the carcinogenesis, metastasis, and invasion of gallbladder adenocarcinoma, but MTA1 is an independent factor of prognosis.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Histona Desacetilases/metabolismo , Proteína Kangai-1/metabolismo , Kisspeptinas/metabolismo , Proteínas Repressoras/metabolismo , Adenocarcinoma/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Colecistite/metabolismo , Regulação para Baixo , Detecção Precoce de Câncer , Feminino , Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/diagnóstico , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Proteína Kangai-1/genética , Estimativa de Kaplan-Meier , Kisspeptinas/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Pólipos/metabolismo , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Regulação para Cima
15.
Hepatogastroenterology ; 61(131): 574-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-26176038

RESUMO

BACKGROUND/AIMS: To investigate the expressions and prognostic value of stem cell markers, EpCAM and CD133, in benign and malignant lesions of gallbladder. METHODOLOGY: Expression of EpCAM and CD133 was assessed in gallbladder adenocarcinoma (n = 100), peritumoral tissues (n = 46), adenoma (n = 30), polyp (n = 15), and chronic cholecystitis (n = 35) by using immunohistochemistry. RESULTS: The positive rates of EpCAM and CD133 expression were significantly higher in gallbladder adenocarcinoma than that in peritumoral tissues (χ2(EpCAM7) = 15.36, χ2(CD133) =16.05; Ps < 0.01), adenoma (χ2 (EpCAM) =10.92, χ2(CD133) = 11.09; Ps < 0.01), polyp (χ2(EpCAM) = 8.88, χ2(CD133) = 10.43; Ps < 0.01) and chronic cholecystitism (χ2(EpCAM) = 28.58, χ2(CD133) =25.57; Ps < 0.01). In adenocarcinoma, the positive expression of EpCAM and CD133 was significanctly associated with differentiation, tumor mass, lymph node metastasis, invasion and overall survival. Notably, the benign lesions with positive EpCAM or /and CD133 expression showed moderately or severely atypical hyperplasia in gallbladder epithelium. The high consistence was found between the expressive levels of EpCAM and CD133 in gallbladder adenocarcinoma (χ2 = 10.02, P < 0.01). Unitivariate Kaplan-Meier analysis showed that high level of EpCAM (P = 0.004) and CD133 (P = 0.012) were associated with poor overall survival. CONCLUSIONS: The elevated expression of EpCAM and/or CD133 is closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.


Assuntos
Adenocarcinoma/química , Antígenos CD/análise , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Moléculas de Adesão Celular/análise , Neoplasias da Vesícula Biliar/química , Glicoproteínas/análise , Células-Tronco Neoplásicas/química , Peptídeos/análise , Antígeno AC133 , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenoma/química , Adenoma/patologia , Adulto , Idoso , Distribuição de Qui-Quadrado , Colecistite/metabolismo , Colecistite/patologia , Doença Crônica , Progressão da Doença , Molécula de Adesão da Célula Epitelial , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Células-Tronco Neoplásicas/patologia , Pólipos/química , Pólipos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Regulação para Cima
16.
J Mol Histol ; 45(1): 47-57, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23921915

RESUMO

The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented, and no prognosis marker has been identified because of the rare occurrence of this gallbladder cancer subtype. In this study, we examined ACE2 and FZD1 expression in 46 SC/ASCs and 80 adenocarcinomas using immunohistochemistry and further analyzed their correlations with clinicopathological characteristics. We demonstrated that positive FZD1 and negative ACE2 expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis and invasion of SC/ASC and AC. Univariate Kaplan-Meier analysis showed that positive FZD1 and negative ACE2 expression as well as differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability were closely associated with decreased overall survival in both SC/ASC (p < 0.001) and AC (p < 0.001) patients. The average survival time in SC/ASC and AC patients with FZD1(-)ACE2(+) expression was significantly longer than that in patients with FZD1(+)ACE2(-) or FZD1(+)ACE2(+) (p < 0.01). Multivariate Cox regression analysis showed that positive FZD1 and negative ACE2 expression are independent poor-prognostic factors for both SC/ASC and AC patients. In addition, FZD1 expression positively, but ACE2 expression negatively correlated with the expression of CA19-9 in SC/ASC and AC. Our study suggested that positive FZD1 and negative ACE2 expression are closely related to the expression of CA19-9; clinical, pathological, and biological behaviors; as well as poor-prognosis of gallbladder cancer.


Assuntos
Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Receptores Frizzled/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Peptidil Dipeptidase A/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
17.
Pathol Oncol Res ; 20(2): 285-92, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24078426

RESUMO

Gallbladder cancers (GBCs) are highly aggressive and lethal diseases. However, the key molecular mechanisms responsible for the progression and prognosis of GBCs have not been identified. No biological markers for effectively identifying GBC subtypes have been reported. In this study the expression of keratin 19 (KRT19) and human achaete-scute homolog 1 (hASH1) proteins in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined using immunohistochemistry. Negative KRT19 or positive hASH1 expression were significantly associated with lymph node metastasis, invasion and TNM stage of SC/ASC patients. In contrast, positive KRT19 and hASH1 expression were significantly associated with large tumor size, lymph metastasis, invasion, and TNM stage in AC patients. Univariate Kaplan-Meier analysis showed that loss of KRT19 or elevated hASH1 expression significantly correlated with decreased survival in SC/ASC patients. In contrast, positive KRT19 and hASH1 expression correlated with a shorter survival time in AC patients. Multivariate Cox regression analysis showed that negative KRT19 expression or positive hASH1 expression was an independent poor-prognostic predictor in SC/ASC, but positive KRT19 and hASH1 expression were poor-prognostic factors in AC patients. Our study suggested that hASH1 can be used to determine the malignancy of SC/ASC and AC tumors and is associated with poor prognosis. In contrast, KRT19 is a protective factor in AC patients but a sign of malignancy in SC/ASC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Queratina-19/metabolismo , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Dis Markers ; 35(3): 163-72, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24167362

RESUMO

BACKGROUND: Gallbladder cancers (GBCs) are highly aggressive cancers with high mortality. However, biological markers for the progression and prognosis of GBC are currently unavailable in the clinic. OBJECTIVE: To identify biomarkers for predicting GBC metastasis and prognosis. METHODS: We examined ALDH1A3 and GPX3 expressions in 46 squamous cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) by using immunohistochemistry. RESULTS: Positive ALDH1A3 and negative GPX3 expressions were significantly associated with lymph node metastasis and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that either positive ALDH1A3 (P < 0.001) or negative GPX3 (P < 0.001) expression significantly correlated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that positive ALDH1A3 expression or negative GPX3 expression was an independent poor-prognostic predictor in both SC/ASC and AC patients. CONCLUSIONS: Our study suggested that positive ALDH1A3 and negative GPX3 expressions are closely associated with clinical pathological behaviors and poor prognosis of gallbladder cancer.


Assuntos
Aldeído Oxirredutases/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Glutationa Peroxidase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldeído Oxirredutases/genética , Biomarcadores Tumorais/genética , Carcinoma/genética , Carcinoma/metabolismo , Feminino , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Regulação Neoplásica da Expressão Gênica , Glutationa Peroxidase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico , Prognóstico
19.
World J Surg Oncol ; 11: 143, 2013 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-23782473

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC. METHODS: We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes. RESULTS: We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality. CONCLUSIONS: Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC.


Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/secundário , Carcinoma de Células Escamosas/secundário , Chaperonina com TCP-1/metabolismo , Neoplasias da Vesícula Biliar/patologia , Isomerases de Dissulfetos de Proteínas/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/mortalidade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
20.
Pol J Pathol ; 64(1): 44-51, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23625600

RESUMO

Gallbladder cancer (GBC) is one of the most aggressive tumors; we examined the expression level of DNA fragmentation factor 45 (DFF45) and thyroid transcription factor 1 (TTF-1) in benign and malignant lesions of the gallbladder by immunohistochemistry. The results were correlated with clinicopathological features and prognosis. DNA fragmentation factor 45 and TTF-1 expression was significantly higher in gallbladder adenocarcinomas than in the corresponding peritumoral tissues (χ²DFF45 = 6.92, χ²TTF-1 = 8.68, ps < 0.01), polyps (χ²DFF45 = 4.49, χ²TTF-1 = 5.35, ps < 0.05), and chronic cholecystitis (χ²DFF45 = 12.98, χ²TTF-1 = 17.74, ps < 0.01). Negative expression of DFF45 and TTF-1 was significantly associated with tumor differentiation, tumor mass, lymph node metastasis and invasion of adenocarcinomas (p < 0.05). Univariate Kaplan-Meier analysis showed that elevated expression levels of DFF45 and TTF-1 (p < 0.05) were closely associated with increased overall survival. In addition, the average survival time of patients with DFF45(+) TTF-1(+) tumors was significantly higher than those with DFF45(-) TTF-1(-) tumors (p < 0.05). Finally, multivariate Cox regression analysis showed that negative expression of DFF45 and TTF-1 was an independent prognostic predictor in gallbladder adenocarcinoma (p < 0.05). The expression of DFF45 and/or TTF-1 is closely related to the carcinogenesis, progression, clinical behavior and prognosis of gallbladder adenocarcinomas. DNA fragmentation factor 45 and TTF-1 could be progression-associated genes correlating with good prognosis in GBC.


Assuntos
Adenocarcinoma/metabolismo , Pólipos Adenomatosos/metabolismo , Colecistite/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Proteínas Nucleares/metabolismo , Proteínas/metabolismo , Fatores de Transcrição/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Pólipos Adenomatosos/mortalidade , Pólipos Adenomatosos/patologia , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/metabolismo , Colecistite/mortalidade , Colecistite/patologia , Progressão da Doença , Feminino , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Fator Nuclear 1 de Tireoide
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