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1.
Cell Biochem Funct ; 38(2): 158-166, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989658

RESUMO

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti-oncogene associated with PTC. By RT-qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss-function experiments in TC cell lines (KTC-1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future. SIGNIFICANCE OF THE STUDY: Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial anti-oncogene associated with PTC. Furthermore, knocking-down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelial-mesenchymal transition-related proteins.


Assuntos
Transição Epitelial-Mesenquimal , Receptores Depuradores Classe A/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Genoma Humano , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Interferência de RNA , Estudos Retrospectivos
2.
J Cell Mol Med ; 23(12): 7974-7984, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31568662

RESUMO

Thyroid cancer is maintaining at a high incidence level and its carcinogenesis is mainly affected by a complex gene interaction. By analysis of the next-generation resequencing of paired papillary thyroid cancer (PTC) and adjacent thyroid tissues, we found that Growth Associated Protein 43 (GAP43), a phosphoprotein activated by protein kinase C, might be novel markers associated with PTC. However, its function in thyroid carcinoma has been poorly understood. We discovered that GAP43 was significantly overexpressed in thyroid carcinoma and these results were consistent with that in The Cancer Genome Atlas (TCGA) cohort. In addition, some clinicopathological features of GAP43 in TCGA database showed that up-regulated GAP43 is significantly connected to lymph node metastasis (P < 0.001) and tumour size (P = 0.038). In vitro experiments, loss of function experiments was performed to investigate GAP43 in PTC cell lines (TPC-1 and BCPAP). The results proved that GAP43 knockdown in PTC cell significantly decreased the function of cell proliferation, colony formation, migration, and invasion and induced cell apoptosis. Furthermore, we also indicated that GAP43 could modulate the expression of epithelial-mesenchymal transition-related proteins, which could influence invasion and migration. Put those results together, GAP43 is a gene which was associated with PTC and might be a potential therapeutic target.


Assuntos
Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Proteína GAP-43/metabolismo , Metástase Linfática , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Estudos de Coortes , Bases de Dados Genéticas , Feminino , Proteína GAP-43/genética , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , RNA Interferente Pequeno , Fatores de Risco , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/secundário
3.
Clin Genet ; 96(5): 418-428, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31334828

RESUMO

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA/genética , Proteínas de Ligação a Fosfato/genética , Câncer Papilífero da Tireoide/genética , Proliferação de Células/genética , Feminino , Mutação com Ganho de Função/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , RNA-Seq , Câncer Papilífero da Tireoide/patologia
4.
Med Sci Monit ; 24: 2744-2749, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29722351

RESUMO

BACKGROUND Skip metastasis is defined as metastasis incident to the lateral compartment without involvement of the central compartment, and is generally unpredictable in papillary thyroid cancer (PTC). The present study aimed to investigate the frequency and predictor value of skip metastasis in PTC patients. MATERIAL AND METHODS A total of 355 patients diagnosed with thyroid cancer who had received a prior complete thyroidectomy with bilateral central neck and ipsilateral lateral neck lymph node dissection were enrolled in this study. The clinicopathological and ultrasound features were analyzed. A univariate and multivariate analysis were performed to identify the risk factors of skip metastasis. RESULTS The frequency of skip metastasis was 12.4% (44/355). The PTC patients with skip metastasis exhibited fewer lymph node metastasis, which was more commonly detected in tumor size ≤1 cm (OR 9.354; p=0.001; 95% confidence interval (CI) 1.865-26.735), tumors located in upper pole (OR 3.822; p<0.001; 95% CI 1.935-7.549), without a well-defined margin (OR 2.528; p=0.016; CI 1.191-5.367), and extrathyroidal extension (OR 2.406; p=0.013; CI 1.691-4.367). CONCLUSIONS Skip metastasis was common in PTC. The PTC patients with a tumor size ≤1.0 cm, located in the upper pole, without a well-defined margin and extrathyroidal extension should be carefully evaluated for skip metastasis.


Assuntos
Carcinoma Papilar/patologia , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Câncer Papilífero da Tireoide , Adulto Jovem
5.
Biochem Biophys Res Commun ; 470(3): 479-483, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26820525

RESUMO

Breast cancer is diverse in their natural history and in their responsiveness to treatments. It is urgent to generate candidate biomarkers for the stratification of patients and personalization of therapy to avoid overtreatment or inadequate treatment. Long noncoding RNAs (lncRNAs) have been found to be pervasively transcribed in the genome and played critical roles in cancer progression. A lot of lncRNAs have been reported as potential prognostic biomarkers and therapeutic targets in multiple cancers. In this study, we demonstrated that FGF14 antisense RNA 2 (FGF14-AS2), a novel long non-coding RNA, was significantly down-regulated in breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Reduced expression of FGF14-AS2 was correlated with larger tumor size, more lymph node metastasis and advanced clinical stage in both cohorts. Kaplan-Meier analysis indicated that patients with lower FGF14-AS2 expression had a worse overall survival. Moreover, multivariate analysis revealed that decreased expression of FGF14-AS2 was an independent predictor of overall survival. Together, these results suggested that FGF14-AS2 involved in the progress of breast cancer and might act as a tumor suppressor gene. To the best of our knowledge, it was firstly reported that FGF14-AS2 was involved in cancer. This study provided a potential new marker and a target for gene therapy in breast cancer treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Fatores de Crescimento de Fibroblastos/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , China/epidemiologia , Regulação para Baixo/genética , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Estatística como Assunto , Taxa de Sobrevida
6.
World J Surg Oncol ; 13: 249, 2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26271634

RESUMO

BACKGROUND: Gene expression profiling of breast cancers identifies distinct molecular subtypes that affect prognosis. The aim of this study was to determine whether features of tumors especially the risks of lymph node (LN) metastases differ among molecular subtypes. METHODS: Subtypes were classified by immunohistochemical surrogates as luminal A, luminalHer2-, luminalHer2+, TNBC, and HER-2+. Data were obtained from an established, registered database of patients with invasive breast cancer treated at our hospital between July 2012 and October 2014. A total of 929 tumors were classifiable into molecular subtypes. RESULTS: The distribution of subtypes was luminal A (24.2%), luminalHer2- (27.8%), luminalHer2+ (9.1%), TNBC (21.3%), and HER-2+ (17.5%). Marked differences in age, tumor size, extent of lymph node involvement, and grade were observed among subtypes. On univariate analysis, the LN positivity varied across subtypes with 33.6% in luminal A, 40.3% in luminalHer2-, 37.3% in luminalHer2+, 37.6% in TNBC, and 47.4 % in HER-2+ (p=0.201). There was no significant difference in LN positivity among subtypes. On multivariable analysis, grade and tumor size were independent predictors of LN positivity. CONCLUSIONS: Predictors of LN metastases include higher grade and larger tumor size. Even though breast cancer subtype is not a statistically significant predictor of LN positivity, this information may still be useful in selecting the appropriate therapy in clinical practice.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Humanos , Linfonodos/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
7.
World J Surg Oncol ; 10: 67, 2012 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-22540396

RESUMO

BACKGROUND: The optimal resection extent for papillary thyroid microcarcinoma (PTMC) remains controversial. The objective of the study was to investigate risk factors of bilateral PTMC and central lymph node metastasis (CLNM) to guide surgical strategies for PTMC patients. METHODS: We retrospectively reviewed 211 PTMC patients who underwent total thyroidectomy (TT) and 122 clinical lymph node-negative (cN0) cases that underwent prophylactic central lymph node dissection (CLND) between 2010 and 2011. The frequency, pattern, and predictive factors for bilateral PTMC and CLNM in these patients were studied using univariate and multivariate analysis with respect to the following variables: age, gender, extrathyroidal extension (ETE), T stage, with Hashimoto thyroiditis (HT), tumor size and multifocality based on final pathology, and preoperative evaluation using ultrasonography (US). RESULTS: Fifty-four of 211 (25.6%) patients had bilateral PTMC. In multivariate analysis, multifocality (P < 0.001, OR = 23.900) and tumor size ≥7 mm (P = 0.014, OR = 2.398) based on US were independent predictive factors for bilateral PTMC which was also independently associated with multifocality (P < 0.001, OR = 29.657) and tumor size ≥7 mm (P = 0.005, OR = 2.863) based on final pathology. Among 122 cN0 patients who underwent prophylactic CLND, we found 49.2% of patients had CLNM. CLNM was independently associated with men, age <50 years and tumor size ≥7 mm based on final pathology or preoperative US. CONCLUSIONS: TT should be considered for PTMC patients who are found multifocality and tumor size ≥7 mm based on preoperative US. CLND need be considered in cN0 patients who are men, aged <50 years or tumor size ≥7 mm based on preoperative US.


Assuntos
Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Biópsia por Agulha Fina , Carcinoma , Carcinoma Papilar , Feminino , Humanos , Modelos Logísticos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Estatística como Assunto , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/cirurgia , Adulto Jovem
8.
Ann Surg Oncol ; 17(12): 3294-300, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20953721

RESUMO

BACKGROUND: This study analyzed the utility of BRAF mutation screening of ultrasonography-guided fine-needle aspiration biopsy (FNAB) specimens for predicting aggressive clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC). METHODS: We assessed the T1799A BRAF mutation status in FNAB specimens obtained from 61 PTMC patients before undergoing operations for PTMC. We examined whether the BRAF mutation was associated with clinicopathologic characteristics in PTMC. Additionally, we reviewed the BRAF mutation status, and clinical, ultrasound (US), hematological, and pathology records of the patients and analyzed the associations between these characteristics and lateral lymph node metastasis (LNM). RESULTS: Analysis of the preoperative FNABs accurately reflected the BRAF status of the resected tissues in 19 of the 20 paired samples (95% concordance). We observed that the BRAF mutation was statistically significantly associated with multifocality, extrathyroidal invasion, lateral LNM, and advanced tumor stages III and IV. The BRAF mutation, pathologic features (central LNM), and US features (upper pole location) were independent predictive factors for lateral LNM in a multivariate analysis with odds ratios of 18.144 (95% confidence interval [95% CI], 1.999-164.664; P = 0.01), 8.582 (95% CI, 1.014-76.662; P = 0.049) and 9.576 (95% CI, 1.374-66.728; P = 0.023), respectively. CONCLUSIONS: BRAF mutation-positive PTMCs were more likely to manifest aggressive characteristics (extrathyroidal extension and LNM). The BRAF mutation screening of FNAB specimens can be used to predict aggressive clinicopathological characteristics of PTMC. Lateral neck nodes should be meticulously analyzed for cases of PTMC demonstrating the following three characteristics: BRAF mutation, central LNM, and US features in the upper pole location.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Biópsia por Agulha Fina , Carcinoma Papilar/patologia , DNA de Neoplasias/genética , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Adulto Jovem
9.
Zhonghua Wai Ke Za Zhi ; 48(3): 205-8, 2010 Feb 01.
Artigo em Zh | MEDLINE | ID: mdl-20388420

RESUMO

OBJECTIVE: To investigate the expression of the miR-155 in human primary breast cancer and its clinical significance. METHODS: From February to June 2009, 45 pairs of specimens of human primary breast cancer and matched nontumor breast tissues were collected from the patients who received operation for breast cancer. Real-time polymerase chain reaction (RT-PCR) was used to detect the miR-155 expression in those specimens. RESULTS: The stem-loop RT-PCR was sensitive and specific enough to detect the expression of the miR-155. The median relative expression of miR-155 was 0.360 in tumor samples, and it was 0.135 in matched nontumor breast tissues, the difference was statistically significant (P < 0.05). It's indicated that the up-regulation of miR-155 expression was associated with advanced TNM clinical stage (median 0.316, 0.358 and 0.417 respectively for stage I, II and III tumor, P = 0.002), lymph node metastasis (median 0.383 and 0.355 respectively for cases with positive and negative lymph nodes, P = 0.034), higher proliferation index [median 0.387 and 0.353 respectively for cases with high proliferation index (Ki67 > 10%) and low proliferation index (Ki67 ≤ 10%), P = 0.019], estrogen receptor-positive (0.367 and 0.318 respectively for cases with positive estrogen receptor and negative group, P = 0.041) and progesterone receptor-positive (0.398 and 0.335 respectively for cases with positive progesterone receptor and negative group, P = 0.029) in patients with breast cancer. CONCLUSIONS: The expression of miR-155 is up-regulated in primary breast cancer, especially in patients with positive estrogen and progesterone receptor. miR-155 may play an important role in the proliferation, invasion and metastasis of human primary breast cancer, and it could be a indicator in the diagnosis and prognosis of primary breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , MicroRNAs/metabolismo , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Receptores de Progesterona/metabolismo
10.
Cancer Manag Res ; 12: 12557-12567, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324100

RESUMO

BACKGROUND: Microfibril-associated protein 2 (MFAP2) is a protein coding gene that exerts important phenotypic effects on cell motility, and increasing research has indicated that MFAP2 was correlated with many cancers. However, the functional and potential clinical role of MFAP2 in papillary thyroid cancer (PTC) has not yet been verified. MATERIALS AND METHODS: We performed whole transcriptome sequencing on 78 paired PTC tissues and corresponding adjacent normal tissues and found that MFAP2 was highly expressed in PTC tissues. Then, we analyzed the expression of MFAP2 and its relation with the clinicopathological features of PTC in The Cancer Genome Atlas (TCGA) PTC genomic dataset. We detected MFAP2 expression in 40 paired PTC tissues and corresponding adjacent normal tissues through RT-qPCR (real time-quantitative polymerase chain reaction) to validate the sequencing data and TCGA cohort. Cell functional assays were performed to elucidate the function of MFAP2 in PTC cells, Western blot assay was performed to explore the correlation between MFAP2 and EMT (epithelial-mesenchymal transition)-related proteins. RESULTS: Statistical analysis showed that MFAP2 was obviously upregulated in PTC tissues compared to matched normal tissues, and the expression levels of MFAP2 in PTC tissues were strongly related with lymph node metastasis (p=0.016). The results of RT-qPCR of our own tissue specimens showed the same conclusions as that in TCGA dataset. The results of functional assays in PTC cell lines showed that MFAP2 could promote proliferation, colony formation, migration and invasion abilities and decrease the apoptotic rate in PTC cells. Western Blot assay showed that MFAP2 could regulate the expression of EMT-related proteins. CONCLUSION: MFAP2 increases the proliferation, motility and decreases the apoptosis of PTC cells, and might be a potential therapeutic target for papillary thyroid cancer.

11.
Am Surg ; 86(5): 450-457, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32684022

RESUMO

This study analyzed the characteristics of BRAFV600E mutation in papillary thyroid carcinoma (PTC) in Chinese coastal areas. We intended to identify noninvasive methods to determine BRAFV600E status in thyroid nodules prior to surgery. BRAFV600E mutation and the sonographic characteristics of thyroid nodules were investigated in 670 PTC patients in our hospital. We aimed to determine the relationship between BRAFV600E mutation and the clinicopathological and sonographic imaging characteristics of PTC. The mutation rate of the BRAFV600E was 78.2%. BRAFV600E mutation was significantly associated with central node (univariate analyses, P = .005; multivariate analyses, P < .001, odds ratio [OR] = 10.255) and lateral node metastases (univariate analyses, P = .001; multivariate analyses, P < .001, OR = 22). It was less frequent in PTC coexisting with Hashimoto's thyroiditis (univariate analyses, P = .016; multivariate analyses, P < .001, OR = .034). Nodules without blood flow had a significantly higher mutation rate of BRAFV600E in PTC patients (univariate analyses, P = .026). BRAFV600E mutation was significantly associated with high suspicion in the Thyroid Imaging Reporting and Data System 5 (univariate analyses, P = .004; multivariate analyses, P = .014, OR = 6.456). Our results strongly suggest that BRAFV600E mutation plays a potential role in lymph node metastasis (central node metastasis, OR = 10.225; lateral node metastasis, OR = 22). Some sonographic imaging features might be helpful in estimating the status of BRAFV600E preoperatively.


Assuntos
Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/genética , Adulto , China , Correlação de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia
12.
BMC Cancer ; 9: 134, 2009 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-19419554

RESUMO

BACKGROUND: Emerging evidence has demonstrated that Neutrophil gelatinase-associated lipocalin (NGAL) is up-regulated in multiple malignancies, including oesophagus cancer, and plays a critical role in tumorigenesis and progression. However, till now, little is known about the role of NGAL in human rectal cancer. Its association with clinicopathologic characteristics and expression of MMP-9, one of its target genes, has not been reported systematically in rectal cancer. Therefore, to further determine the potential involvement of NGAL in rectal cancer, we have evaluated the expression level of NGAL mRNA by real time RT-PCR, and further elucidated the correlation of NGAL mRNA expression with clinicopathologic features and MMP-9 in rectal cancer. METHODS: 100 paired samples of rectal cancer and adjacent normal tissues obtained from inpatients undergoing surgical operation were allocated into two groups (cancer group and control group). The mRNA expression of NGAL and MMP-9 was determined by real-time RT-PCR. The association between their expression and clinicopathological characteristics of rectal cancer were analysised. RESULTS: Among the 100 rectal cancers, 69 cases of NGAL mRNA up-regulation were observed. NGAL mRNA up-regulation was positively correlated with MMP-9 (rs = 0.393, p < 0.001). In rectal cancer, NGAL mRNA overexpression was significantly associated with depth of invasion (p = 0.028), lymph node metastasis (p = 0.009), venous involvement (p = 0.023) and advanced pTNM stage (p = 0.011). CONCLUSION: In human rectal cancer, NGAL mRNA expression was elevated. NGAL mRNA up-regulation was correlated significantly with tumor progression and MMP-9 mRNA overexpression in rectal cancer, suggesting a more aggressive phenotype. NGAL could be used for rectal cancer characterization.


Assuntos
Proteínas de Fase Aguda/genética , Regulação Neoplásica da Expressão Gênica , Lipocalinas/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias Retais/genética , Proteínas de Fase Aguda/metabolismo , Progressão da Doença , Humanos , Lipocalina-2 , Lipocalinas/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia , Regulação para Cima
13.
Ann Clin Lab Sci ; 49(4): 481-487, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31471337

RESUMO

BACKGROUND: Chemotherapy resistance reduces the effectiveness of chemotherapeutic drugs greatly, resulting in treatment failure. Therefore, exploring chemoresistance-related genes and the corresponding mechanism is extremely important. The central role of CD44v6 in colorectal cancer has been previously reported. However, the effects of CD44v6 gene knockdown on the chemosensitivity of colorectal cancer cells are not conclusive. MATERIAL AND METHODS: A stable CD44v6 knockdown cell model in HT29 cells (HT29-KD) was established via lentiviral transduction. A quantitative real-time polymerase chain reaction (PCR) was carried out to confirm the knockdown efficiency. The chemosensitivity of cells to 5-fluorouracil (5-FU) was determined by a cell counting kit (CCK)-8 assay. Cell apoptosis and the cell cycle were assessed by flow cytometry. RESULTS: The CD44v6 knockdown cell model was successfully constructed by using lentiviral transduction. Upon treatment with 5-FU, the inhibitory rate for cell activity of HT29-KD cells was significantly higher than that of the control group (HT29-NC). CD44v6 gene knockdown did not significantly affect HT-29 cell proliferation, according to the CCK-8 assay and cell cycle analysis. The cell apoptosis assay revealed that CD44v6 gene knockdown promoted HT-29 cell apoptosis. Without 5-FU treatment, there was no significant difference in terms of the relative expression level of the autophagy-related gene BECN1 between the two groups. However, with 5-FU treatment, the relative expression level of BECN1 in HT29-KD cells was much lower than that in HT29-NC cells. CONCLUSION: Our study confirms that CD44v6 gene knockdown can enhance chemosensitivity in HT29 cells by promoting apoptosis and inhibiting autophagy, thus affirming the effects of CD44v6 on the chemosensitivity of colorectal cancer.


Assuntos
Apoptose , Autofagia , Neoplasias Colorretais/genética , Regulação para Baixo/genética , Receptores de Hialuronatos/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Células HT29 , Humanos , Modelos Biológicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
J Cancer ; 10(15): 3543-3552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293659

RESUMO

Purpose: Aldo-keto reductase family 1, member C2 (AKR1C2) gene encodes for a member of the AKR superfamily and participates in the metabolism of various drugs. Moreover, tumor and normal tissues exhibit an evident difference in the expression level of this gene. Methods: We downloaded and analyzed AKR1C2 expression level and the data consisting of the clinicopathological features of 490 papillary thyroid carcinoma (PTC) tumor tissues and 59 normal thyroid tissues from The Cancer Genome Atlas (TCGA) cohort. Diverse statistical methods, such Chi-square test, univariate and multivariate Cox regression analyses, and Kaplan-Meier survival curves were used. We down-/up-regulated the expression of AKR1C2 and explored its specific role in thyroid cancer cell lines by utilizing the si-RNA and plasmid. Results: We divided all patients who were collected in TCGA data sets into under-expressed (n = 245) and over-expressed groups (n = 245). We subsequently analyzed the data and obtained the following findings: (a) AKR1C2 is down-regulated in papillary thyroid carcinoma (PTC) (p<0.001), (b) Kaplan-Meier result revealed that high expression level of AKR1C2 are correlated with favorable survival in PTC (p = 0.043), and (c) factors independently associated with recurrence-free survival are AKR1C2 expression (hazard ratio (HR 0.819) and American Joint Committee on Cancer (AJCC) stage (HR 1.534). We also analysed the relationship between AKR1C2 expression and clinicopathological features in the validated cohort. AKR12C under-expression correlated with lymph node metastasis (p = 0.009) and AJCC stage (p= 0.001) which might indicate AKR12C as a prognostic factor in PTC. The cell line experiment results showed that the knockdown and overexpression of AKR1C2 significantly enhance and weaken the abilities of migration and invasion in papillary thyroid carcinoma cell. Conclusion: Our results indicated that AKR1C2 exerts inhibitory effects on PTC oncogenesis and elevated AKR1C2 expression is associated with the favorable prognostic factors and recurrence free survival.

15.
Cancer Manag Res ; 10: 3237-3243, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233240

RESUMO

BACKGROUND: Preoperative diagnosis of central lymph node metastasis (CLNM) poses to be a challenge in clinical node-negative papillary thyroid microcarcinoma (PTMC). This research work aims at investigating the association existing between BRAF mutation, clinicopathological factors, ultrasound characteristics, and CLNM, in addition to establishing a predictive model for CLNM in PTMC. MATERIALS AND METHODS: The study included 673 PTMC patients, already undergone total thyroidectomy or lobectomy with prophylactic central lymph node dissection. The predictor factors were identified through univariate and multivariate analyses. The support vector machine was put to use to develop statistical models, which could predict CLNM on the basis of independent predictors. RESULTS: Tumor size (>5 mm), lower location, no well-defined margin, contact of >25% with the adjacent capsule, display of enlarged lymph nodes, and BRAF mutation were independent predictors of CLNM. Through the use of the predictive model, 79.6% of the patients were classified accurately, the sensitivity and specificity amounted to be 85.1% and 75.8%, respectively, and the positive predictive value and negative predictive value stood at 71.6% and 87.6%, respectively. CONCLUSIONS: We established a predictive model in order to predict CLNM preoperatively in PTMC when preoperative diagnosis of CLNM was not clear.

16.
Cancer Manag Res ; 10: 1351-1358, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29881305

RESUMO

AIM: To investigate the clinical effects of MUC1 on papillary thyroid cancer (PTC) and explore the relationship between MUC1 expression and BRAF mutation. METHODS: The data of 69 patients subjected to fine-needle aspiration biopsy in our hospital and 486 patient data downloaded from The Cancer Genome Atlas (TCGA) database were used. Univariate and multivariate analyses were performed. RESULTS: The results on the 486 patients recorded in the TCGA indicated that high MUC1 expression was independently related to BRAF mutation, lymph node metastasis (LNM), and unifocal type. In the 69 fine-needle aspiration biopsy patients with PTC, high MUC1 expression was significantly related to LNM and extrathyroid extension (ETE). The result of Pearson's correlation coefficient showed that BRAF mutation and MUC1 expression were moderately correlated. Moreover, in the subgroup with low MUC1 expression, the patients with BRAF mutation had higher ETE frequency and LNM than those without BRAF mutation. In the subgroup with BRAF mutation, patients with high MUC1 expression exhibited higher ETE frequency than those with low MUC1 expression, and high MUC1 expression occurred in older patients. In the subgroup with BRAF wild-type mutation, patients with high MUC1 expression had a higher incidence of ETE and LNM than those with low expression. CONCLUSION: We demonstrated that the MUC1 is an important oncogene in PTC and may have great significance on therapeutic cancer vaccine development.

17.
Zhonghua Nan Ke Xue ; 13(2): 130-3, 2007 Feb.
Artigo em Zh | MEDLINE | ID: mdl-17345768

RESUMO

OBJECTIVE: To analyze the expression of DD3 mRNA in the prostate tissues. METHODS: DD3 mRNA was detected by realtime fluorescent quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) based on the Taqman technique in the tissues of 27 patients with non-prostate cancer( NPCa), 21 prostate cancer( PCa), 39 benign prostatic hyperplasia (BPH) and 15 normal prostate (NP). The ROC curve was used to evaluate the diagnostic value of DD3 mRNA. RESULTS: DD3 mRNA expression was not detected in the NPCa tissues. The median expressions of DD3 mRNA in PCa, BPH and NP tissues were 7. 2 x 10(6), 2. 5 x 10(4) and 1.5 x 10(4) copies/mg tissue, respectively. The DD3 mRNA expression levels were significantly different between nonmalignant and malignant tissues (P < 0.01). No significant differences in DD3 mRNA expression were detected between the NP and BPH tissues and no significant correlation was found between the DD3 mRNA expression and clinical pathological parameters. The AUC-ROC was 0.937 (95% CI: 0.879 - 0.995) at cutoff value 1.4 x 10(5) copies/mg tissue. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio for DD3 were 90.5%, 85.0%, 86.7%, 76.0%, 94.3%, 6.03 and 0.11 respectively. CONCLUSION: The DD3 mRNA expression is confined to prostate tissues and highly upregulated in PCa tissues. It has a potential application value in the early diagnosis of prostate cancer and the follow-up of the patient.


Assuntos
Antígenos de Neoplasias/biossíntese , Neoplasias da Próstata/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Onco Targets Ther ; 10: 4997-5004, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29081662

RESUMO

BACKGROUND: Tracheal and bronchial stenosis is a life-threatening condition causing difficulty in breathing and even severe respiratory distress. The silicone tracheobronchial stents were placed using the rigid bronchoscopy into the trachea of severe dyspneic patients and they exhibited symptomatic improvement as well as a rise in the saturation of oxygen. The bronchial stents were applicable to many extensive malignant airway stenosis patients, such as those with esophageal cancer, lung cancer, and laryngeal cancer. But the effectiveness of bronchial stents for thyroid cancer is not certain. CASE PRESENTATION: Here, we report 3 emergency patients with a thyroid mass referred to our hospital because of grade 4 dyspnea according to the American Thoracic Society shortness of breath guidelines. The main clinical symptoms were severe dyspnea and stridor. The radiographic examination and tomographic examination showed the narrowing and displacement of the trachea. To the best of our knowledge, ideal airway management for the massive thyroid mass was considered to be temporary tracheobronchial stent placement pre-operation. CONCLUSION: In our study, we applied the tracheobronchial stent to massive thyroid mass patients with dyspnea and aimed to not only improve preoperative airway obstruction but also to protect the potential airway collapse from post-operative tracheomalacia following extubation. We found that application of tracheobronchial stents may provide a new strategy to dyspneic patients with huge thyroid mass.

19.
Oncol Lett ; 14(4): 4122-4134, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28943919

RESUMO

The association between central lymph node metastasis (LNM) and risk factors, including the presence of the BRAF mutation, BRAFV600E, in patients with papillary thyroid cancer (PTC) requires further investigation. A potent risk factor that can indicate LNM in different histological subtypes of PTC and in different preoperative central lymph node statuses also requires further research. A total of 287 patients with PTC who accepted thyroidectomy were included in the present study. Clinicopathological data of these patients were reviewed to examine the risk factors for central LNM through univariate and multivariate analyses. Overall, BRAFV600E in patients with cN0 (subclinical nodal disease) and cN1 (other than cN0) PTC was associated with central LNM. However, multivariate analyses demonstrated that BRAFV600E was not an independent risk factor in patients with cN1 or cN0 PTC. For patients with classical variant PTC (CVPTC), BRAFV600E was independently associated with central LNM. However, on further analysis, the association was only significant in patients with cN0 CVPTC. For patients with follicular variant PTC (FVPTC) or aggressive variant PTC (AVPTC), the BRAFV600E mutation rate was not significantly different between patients with and without central LNM. In conclusion, BRAFV600E was an independent risk factor for central LNM overall in patients with PTC and in patients with CVPTC, particularly in patients with cN0 CVPTC. However, BRAFV600E was not an independent risk factor for patients with FVPTC and AVPTC. Therefore, BRAFV600E provides varied clinical significance in different histological subtypes and preoperative central lymph node status.

20.
Zhonghua Zhong Liu Za Zhi ; 28(5): 389-92, 2006 May.
Artigo em Zh | MEDLINE | ID: mdl-17045009

RESUMO

OBJECTIVE: To investigate the indications, safety and difficulties of one stage thyroidectomy and bilateral neck lymph node dissection for well-differentiated thyroid carcinoma. METHODS: A retrospective review was carried out in 36 well-differentiated thyroid carcinoma patients so treated from 1990 to 2004. Various incisions including H, L and modified Kocher types were selected according to the location of primary tumor and status of cervical lymph node metastasis. Either total thyroidectomy or sub-total thyroidectomy combined with bilateral neck lymph node dissection according to the principles of modified radical neck lymph node dissection: preserving the internal jugular vein, spinal accessory nerve and sternocleidomastoid muscles. RESULTS: There was no operative death in this group. Postoperative complications included: 2 wound bleeding, 3 recurrent laryngeal nerve resection due to tumor involvement, 1 recurrent laryngeal nerve injury, 2 unilateral internal branch of superior laryngeal nerve injury, 9 unilateral external branch of superior laryngeal nerve injury, 3 unilateral accessory nerve injury, 5 unilateral sympathetic nerve injury, 2 unilateral phrenic nerve injury, 6 chylus fistula, 13 temporary hypoparathyroidism, 2 permanent hypoparathyroidism. The dissected lymph nodes were found to be positive from 0 to 21 in each patient with a mean of 8.3. Of the 36 patients: 31 had bilateral positive lymph nodes; 3 unilateral positive; 2 bilateral negative lymph nodes. The follow up period ranged from 1 to 13 years, Three patients died of distant metastasis, 1 died of cerebral vascular accident. 7 patients lost in follow-up. Totally, 25 patients are still alive, 3 patients had local relapse and were surgically treated again. CONCLUSION: The procedure of one-stage thyroidectomy and bilateral neck lymph node dissection for well-differentiated thyroid carcinoma is safe, as it is mandatory that at least one unilateral internal jugular vein should be preserved; one unilateral recurrent laryngeal nerves and accessory nerves should not be injured. Well-differentiated thyroid carcinoma patients whose bilateral cervical lymph nodes are clinically suspected to be positive (obviously enlarged, hard, purplish grapelike lymph node) or are confirmed pathologically to be positive are indications for one-stage thyroidectomy and bilateral neck lymph node dissection. Total or sub-total thyroidectomy should be undertaken with emphasis that at least one parathyroid with blood supply should be preserved. It is of utmost importance that not only the cancer be completely resected but the function of the organs be preserved.


Assuntos
Carcinoma Papilar/cirurgia , Linfonodos/patologia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adenocarcinoma Folicular/secundário , Adenocarcinoma Folicular/cirurgia , Adulto , Carcinoma Papilar/secundário , Feminino , Seguimentos , Humanos , Hipotireoidismo/etiologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Complicações Pós-Operatórias , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia
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