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1.
BMC Endocr Disord ; 24(1): 87, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867258

RESUMO

BACKGROUND: Anaplastic thyroid carcinoma(ATC) is a rare pathological type of thyroid malignancy. Primary squamous cell carcinoma of thyroid(PSCCT) is now considered as a subtype of ATC, hereinafter referred to as ATC-SCC subtype. ATC-SCC subtype combined with follicular thyroid carcinoma is exceedingly rare, with fewer cases reported. The ATC-SCC subtype is a highly invasive tumor with a poor prognosis for patients after metastasis occurs, and current treatment of this type of tumor is tricky. CASE PRESENTATION: A 68-year-old female patient presented with a gradually growing swelling of right cervical region. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of ATC-SCC subtype with follicular thyroid carcinoma, and the metastasis squamous cell carcinoma of the right cervical lymph nodes originates from ATC-SCC subtype. The patient received chemoradiotherapy postoperative. However, the residual cervical lymph nodes metastasis with squamous cell carcinoma still infiltrated surrounding structures in the neck extensively after palliative resection. The patient died 7 months after surgery. CONCLUSION: Our case highlights that cervical lymph node metastasis may be a significant factor in the poor prognosis of ATC-SCC subtype. This malignancy should be detected and treated early.


Assuntos
Adenocarcinoma Folicular , Metástase Linfática , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Feminino , Idoso , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/patologia , Adenocarcinoma Folicular/secundário , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/diagnóstico , Carcinoma Anaplásico da Tireoide/terapia , Prognóstico , Evolução Fatal , Pescoço/patologia , Linfonodos/patologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico
2.
Environ Toxicol ; 37(5): 1081-1092, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35048507

RESUMO

Triple-negative breast cancer (TNBC) is a breast cancer subtype without targeted treatment options. Accumulating evidence has demonstrated the roles of circular RNAs in cancer. This study aimed to investigate the expression and function of circFAM64A in TNBC. The GSE101124 dataset from the GEO database was examined to identify the differentially expressed circular RNAs in TNBC. RT-qPCR and western blot analyses were performed to measure gene expression. TNBC cell proliferation, migration, invasion, and cell cycle were assessed using cell counting kit-8, EdU, flow cytometry, wound healing, and transwell invasion experiments. Bioinformatics analysis, RIP, RNA pulldown, and luciferase reporter assays were used to investigate the regulatory mechanism of circFAM64A. In this study, CircFAM64A expression was significantly upregulated in TNBC tissues and cells compared with normal tissues and cells. Overexpression of circFAM64A increased the proliferative, migratory, and invasive capacities of TNBC cells and promoted cell cycle progression. Mechanistically, circFAM64A acted as a molecular sponge for miR-149-5p, and miR-149-5p directly targeted the Cdc10-dependent transcript 1 (CDT1) 3'UTR. Moreover, the high expression of CDT1 is associated with a poor prognosis in patients with breast cancer. Rescue experiments demonstrated that circFAM64A sponged miR-149-5p to increase CDT1 expression, thereby promoting cellular processes in TNBC. Overall, CircFAM64A plays an oncogenic role in TNBC by interacting with miR-149-5p to increase CDT1 expression.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs , Proteínas Nucleares/genética , Neoplasias de Mama Triplo Negativas , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/genética
3.
BMC Gastroenterol ; 21(1): 86, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622273

RESUMO

BACKGROUND: Esophageal cancer is one of the most aggressive malignancies, and is associated with multiple genetic mutations. At present, the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation has been observed in esophageal cancer and is associated with poor prognosis. This study aimed to investigate the protein expression of BRAF in esophageal cancer and determine its effect on patient outcomes. METHODS: We used immunohistochemistry to detect the expression of BRAF via tissue microarrays in esophageal cancer samples, the Kaplan-Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the risk factors of esophageal cancer. The role of BRAF in the proliferation, invasion, and metastasis of esophageal cancer was studied by clone formation, scratch test, Transwell invasion and migration test. The tumor-bearing model of BRAF inhibitor was established using TE-1 cells, and corresponding negative control was set up to observe the growth rate of the two models. RESULTS: The results revealed that BRAF overexpression was significantly correlated with Ki67 (P < 0.05). Survival analysis showed that BRAF overexpression contributed to a shorter overall survival (P = 0.014) in patients with esophageal cancer. Univariate and multivariate regression analyses demonstrated that BRAF was a prognostic factor for poor esophageal cancer outcomes (P < 0.05). Small interfering RNA knockdown of BRAF significantly reduced the cell clone formation rate compared to the control group. Transwell assay analysis showed that the migration and invasion of cells in the experimental group were significantly inhibited relative to the control group, and the inhibition rates of the small interfering RNA group were 67% and 60%, respectively. In the scratch test, the wound healing ability of the BRAF knockdown group was significantly weaker than that of the control group. There were significant differences in tumor growth volume and weight between the two groups in nude mice. CONCLUSION: BRAF overexpression may serve as an effective predictive factor for poor prognosis.


Assuntos
Neoplasias Colorretais , Neoplasias Esofágicas , Animais , Biomarcadores , Neoplasias Colorretais/genética , Neoplasias Esofágicas/genética , Humanos , Camundongos , Camundongos Nus , Mutação , Oncogenes , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética
4.
BMC Gastroenterol ; 18(1): 12, 2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29338701

RESUMO

BACKGROUND: Slingshot homolog-1 (SSH1) plays an important role in pathological processes, including in the occurrence and development of tumours. The purpose of this study was to determine whether SSH1 is a key biomarker with prognostic value for survival in patients with gastric cancer. METHODS: We performed immunohistochemistry (IHC) on tissue microarrays containing 100 gastric cancer specimens to evaluate SSH1 protein expression. The association of pathological characteristics with cumulative survival was determined by Kaplan-Meier analysis. A Cox proportional hazards model was generated in the multi-factorial survival analysis to identify univariate prognostic factors of GC. RESULTS: SSH1 expression level in gastric cancer tissues was significantly associated with lymph node metastasis (P = 0.032). Additionally, multivariate regression analysis clearly indicated that SSH1 expression was significantly correlated with poor clinical outcomes of patients with gastric cancer (P = 0.016). Multivariate analyses showed that SSH1 was the best predictor of poor prognosis in patients with gastric cancer (P = 0.030). CONCLUSIONS: SSH1 expression is associated with gastric cancer progression and predicts a poor prognosis. SSH1 may play an important role in the development of gastric cancer, and it is a promising target for prevention and/or treatment of gastric cancer.


Assuntos
Fosfoproteínas Fosfatases/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/patologia
5.
World J Surg Oncol ; 15(1): 32, 2017 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28125992

RESUMO

BACKGROUND: Whether sonography is an appropriate imaging modality for cervical lymph nodes in patients with papillary thyroid microcarcinoma (PTMC) remains unclear. Hence, this study aimed to evaluate the diagnostic value of ultrasonography (US) features for lymph node metastasis in PTMC. METHODS: Seven hundred twelve patients with PTMC who underwent conventional ultrasonography examinations of the cervical lymph nodes were included. All included cases underwent total thyroidectomy plus prophylactic central lymph node dissection. The included lymph nodes were marked superficially, and the corresponding lymph nodes were completely removed and sent for pathological examination. The US features of lymph nodes with and without metastasis were compared, and the odds ratios of the suspicious US features were determined with univariate and multivariate analyses. RESULTS: Round shape, loss of an echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were significantly more common in metastatic than nonmetastatic lymph nodes, whereas the boundary and echo did not significantly differ. Multivariate logistic regression analysis showed that round shape, loss of echogenic fatty hilum, cystic change, calcification, and abnormal vascularity were independent predictive factors for the assessment of metastatic lymph nodes. Round shape had the highest sensitivity of all variables, while loss of an echogenic fatty hilum had the highest specificity and accuracy. The area under the receiver operating characteristic curve, which was calculated to verify the relationship between the various US features and metastatic lymph nodes, was 0.793. CONCLUSIONS: Our study found that the US features of round shape, cystic change, calcification, loss of echogenic fatty hilum, and abnormal vascularity were useful sonographic criteria for differentiating between cervical lymph nodes with and without metastasis.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/secundário , Linfonodos/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/secundário , Ultrassonografia/estatística & dados numéricos , Carcinoma Papilar/cirurgia , Seguimentos , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
6.
Biochem Biophys Res Commun ; 473(1): 212-218, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27003257

RESUMO

Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.


Assuntos
Aurora Quinase A/metabolismo , Cofilina 1/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias da Glândula Tireoide/metabolismo , Idoso , Animais , Carcinoma/metabolismo , Carcinoma Papilar , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Piperazinas/química , RNA Interferente Pequeno/metabolismo , Análise de Regressão , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Análise Serial de Tecidos
7.
Biochem Biophys Res Commun ; 469(3): 679-85, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26707881

RESUMO

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine (131)I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from (131)I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells by JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced (131)I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer.


Assuntos
Radioisótopos do Iodo/farmacocinética , Proteínas Nucleares/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Fatores de Transcrição/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Radioisótopos do Iodo/uso terapêutico , Taxa de Depuração Metabólica , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Regulação para Cima
8.
AME Case Rep ; 8: 47, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711906

RESUMO

Background: Papillary thyroid carcinoma (PTC) accounts for about 60% of adult thyroid carcinoma and generally has an excellent prognosis. Primary squamous cell carcinoma of thyroid (PSCCT) is a rare thyroid tumor with high malignancy and poor prognosis. In 2022, the 5th edition of World Health Organization (WHO) has classified it as a subtype of anaplastic thyroid carcinoma (ATC), abbreviated as ATC-squamous cell carcinoma (SCC) subtype. Poorly differentiated thyroid carcinoma (PDTC) is a kind of follicular-derived malignancy, which is prone to recurrence and distant metastasis. Here, we report a rare case of the coexistence of PTC, ATC-SCC subtype and PDTC. Case Description: We herein report a case of 69-year-old female who initially presented with a history of left neck mass for one month. Comprehensive auxiliary examinations and postoperative pathology confirmed the diagnosis of PTC combined with ATC-SCC subtype, and PDTC. Total thyroidectomy with radical left cervical lymph node dissection was performed, followed by thyroid-stimulating hormone (TSH) suppressive therapy, 131I, radiotherapy and chemotherapy. The patient showed no tumor recurrence or metastasis after a 5-month postoperative follow-up. Conclusions: The simultaneous occurrence of PTC, ATC-SCC subtype, and PDTC is extremely rare in clinical terms or literature reports. The treatment has not been standardized, and early radical surgery is the first choice. In addition, the combination of adjuvant therapies such as TSH suppressive therapy, radiotherapy, chemotherapy and 131I may further improve the prognosis of the patient.

9.
Cancer Rep (Hoboken) ; 7(4): e2047, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577726

RESUMO

BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia. CASE: A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient's PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range. CONCLUSION: The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.


Assuntos
Fraturas Espontâneas , Hipercalcemia , Hipocalcemia , Neoplasias das Paratireoides , Masculino , Humanos , Pessoa de Meia-Idade , Hipocalcemia/etiologia , Hipocalcemia/complicações , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/cirurgia , Cálcio , Hipercalcemia/complicações , Fraturas Espontâneas/complicações , Fósforo , Atrofia Muscular/complicações , Dor
10.
Gland Surg ; 10(8): 2414-2427, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34527553

RESUMO

BACKGROUND: Recently, low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) has been the focus of molecular targeted therapy for breast cancer; however, its role in breast cancer is still controversial. The purpose of this study was to investigate the effect of LRP6 overexpression on the prognosis of breast cancer. METHODS: We used immunohistochemistry to detect the expression of LRP6 via tissue microarrays in breast cancer samples, Chi-square test analyze the relationship between LRP6 expression and clinicopathological features of breast cancer, the Kaplan-Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the potential risk factors of breast cancer. The role of LRP6 in the proliferation, invasion, and metastasis of breast cancer was studied by colony formation, Transwell migration and invasion assay and scratch assay. The tumor-bearing model of LRP6 knockdown was established using MCF-7 cells, and corresponding negative control was set up to observe the growth rate of the two models. RESULTS: High expression of LRP6 was observed in 89 out of 150 (59.3%) breast cancer cases, as detected by microarray of breast cancer tissue. Chi-square tests showed no significant correlation between LRP6 expression and tumor size, lymph node staging, or mitosis. Survival analysis showed that the overall survival rate of tumor patients with high LRP6 expression was significantly lower than that of patients with low LRP6 expression. Univariate and multivariate regression analyses revealed that LRP6 was an independent risk factor for breast cancer and was negatively correlated with the prognosis of breast cancer. Compared with the control group, small interference RNA (si-RNA) knockdown of LRP6 significantly reduced the clonogenic rate as well as the migration and invasion abilities of MCF-7 cells. In the scratch experiment, the wound healing ability of the LRP6 knockdown was significantly weaker than that of the control group. There were significant differences in tumor growth weight and volume between lentivirus transfected LRP6 knockdown MCF-7 cell line and control MCF-7 cell line in nude mice. CONCLUSIONS: LRP6 could be a useful biomarker of poor prognosis of breast cancer, as it plays an important role in tumor growth, migration, and invasion.

11.
Appl Immunohistochem Mol Morphol ; 27(1): 59-64, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-28682834

RESUMO

CONTEXT: The Hippo signal transduction pathway is highly conserved in mammals. It plays a critical role in tissue and organ size by regulating the balance between cell proliferation and apoptosis. However, there have been few reports concerning Yes-activated protein-1 (YAP-1) elevation in papillary thyroid cancer (PTC). OBJECTIVE: The objective of this study was to determine whether YAP-1 expression is a biomarker and high-risk clinicopathologic prognosticator in PTC. DESIGN: A large series of patients of PTC with a long follow-up were investigated for YAP-1 expression. SETTING: Our study was carried out in the laboratory of breast and thyroid and Department of pathology. PATIENTS OR OTHER PARTICIPANTS: Immunohistochemical staining was performed on 240 patient-derived PTC specimens to analyze the correlation of YAP-1 expression with clinicopathologic features and prognosis in patients with PTC. INTERVENTION: The 240 PTC patients were immunohistochemically assessed for YAP-1 expression. OUTCOME MEASURES: Kaplan-Meier analysis was conducted to assess recurrence-free survival (RFS). Univariate and multivariate analyses were conducted to determine prognosticators of RFS. RESULTS: YAP-1 expression was observed in 62.1% of PTC tumors. There were significant positive correlations between YAP-1 expression and tumor size, lymph node metastases, extrathyroidal extension, and tissue infiltration. YAP-1 expression was significantly associated with RFS. Univariate analysis revealed that YAP-1 expression significantly affects RFS. YAP-1 and extrathyroidal extension were significant independent prognosticators for RFS. CONCLUSIONS: YAP-1 expression was significantly correlated with high-risk clinicopathologic features and inferior RFS in patients with PTC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Fatores de Transcrição/metabolismo , Apoptose , Proliferação de Células , Progressão da Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais , Análise de Sobrevida , Câncer Papilífero da Tireoide/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Proteínas de Sinalização YAP
13.
Onco Targets Ther ; 11: 2051-2061, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29695913

RESUMO

OBJECTIVES: 1) Analyze the correlation of SIRT1 and Src with human breast cancer (BC) prognosis; 2) explore the roles of SIRT1 and Src in BC cell proliferation, tumor invasion, and metastasis; and 3) analyze the correlation and interaction between SIRT1 and Src. MATERIALS AND METHODS: 1) Tissue microarray was used to analyze the expression of SIRT1 and Src in human BC tissues and the correlation between protein expression and cancer prognosis; 2) CCK8 assay was used to determine the influence of SIRT1 and Src inhibitors on BC cell proliferation; 3) Transwell migration assay and wound healing assay were used to determine the effect of SIRT1 and Src inhibitors on BC cell migration and invasion; and 4) Western blotting was used to analyze the correlation and interaction between SIRT1 and Src. RESULTS: 1) Combination of SIRT1 and/or Src positivity is a prognosis factor in BC, especially in luminal type; 2) MCF-7 cell proliferation is suppressed by SIRT1 inhibitor Ex527, and cell migration and invasion were inhibited by Src inhibitor bosutinib; 3) combined with Ex527, bosutinib has a significantly increased effect on MCF-7 cell migration suppression; and 4) there is a positive association between SIRT1 and Src both in BC tissues and in MCF-7 cells. CONCLUSION: 1) SIRT1 and Src overexpression are both correlated with poor prognosis in human BC; 2) SIRT1 + Src (SIRT1 and/or Src positivity) is a fine prognosis model for luminal-type BC; 3) SIRT1 is a copromotor of Src in BC migration and invasion, but not in cell proliferation; and 4) our results suggest a potential interaction or a common regulation pathway between SIRT1 and Src expression and activity.

14.
Cancer Biomark ; 19(4): 411-418, 2017 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-28582840

RESUMO

BACKGROUND: Bcl-2 interacting mediator of cell death (Bim) appears to have contradictory roles in cancer. It is uncertain whether Bim show prognostic significance in patients with breast cancer. OBJECTIVE: To investigate the correlation between Bim expression and clinicopathological characteristics of breast cancer and to evaluate Bim's effect on overall survival (OS). METHODS: We used immunohistochemistry (IHC) technique to detect the expression of Bim via tissue microarray in 275 breast cancer samples, Kaplan-Meier analysis to perform survival analysis, and Cox proportional hazards regression model to explore the risk factors of breast cancer. RESULTS: The results revealed that Bim expression was significantly correlated with age, estrogen receptor (ER) and/or progesterone receptor (PR), human epidermal growth factor receptor (HER2) and Ki67 expression (P< 0.05). Bim expression was significantly different in the four molecular subtypes (P= 0.000). Survival analysis showed that Bim positive expression contributed to a shorter OS (P= 0.034), especially in patients with luminal A tumors (P= 0.039). Univariate and multivariate regression analysis showed that Bim was an independent prognostic factor for breast cancer (P< 0.05). CONCLUSION: Bim may serve as an effective predictive factor for lower OS in breast cancer patients, especially in those with luminal A tumors.


Assuntos
Proteína 11 Semelhante a Bcl-2/biossíntese , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inclusão em Parafina , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Análise Serial de Tecidos
15.
Oncol Lett ; 14(2): 2288-2294, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28781665

RESUMO

Cofilin, a key regulator of actin cytoskeleton dynamics, is considered to be involved in cellular migration, tumor invasion and mitosis, and its activity is increased in cancer cells. To address the association between cofilin and breast cancer prognosis, which is unclear at present, cofilin expression was analyzed in tissue microarrays of tumors from 310 patients with breast cancer via immunohistochemistry. In a multivariate Cox regression analysis, a high expression of cofilin in tumor cells correlated significantly with shorter overall survival (hazard ratio, 2.22; 95% confidence interval, 1.35-3.66, P=0.002, and with the Nottingham histologic grade, Ki-67 status and human epidermal growth factor receptor 2 status (P=0.031, 0.001, and 0.001, respectively). Cofilin expression was not observed as correlated with estrogen or progesterone receptor expression, tumor size or lymph node status. These data demonstrate that cofilin is associated with poor outcome, thereby suggesting that it is a potential prognostic factor in breast cancer.

16.
Oncotarget ; 8(39): 66195-66203, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029503

RESUMO

Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that plays a critical role in cell membrane protrusion and migration by transforming inactive phosphorylated cofilin to an active form. SSH-like protein 1 (SSH-1L) expression is detected in various types of tumors; insulin induces the phosphatases activity of SSH-1L in a phosphoinositide 3-kinase-dependent manner. However, little is known about the expression and role of SSH-1L in breast cancer. Here, we analyzed 295 human breast cancer tissue specimens for SSH-1L expression by immunohistochemistry. The correlation between SSH-1L level and patients' clinical characteristics was analyzed with Pearson's χ2 test. The function of SSH-1L was evaluated by gene knockdown and quantitative real-time polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7, and SK-BR-3 human breast cancer cell lines. SSH-1L expression was detected in 88.1% of tissue specimens by immunohistochemistry and was strongly associated with increased metastasis and mortality. Loss of SSH-1L expression decreased the nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines, which was associated with reduced cell motility. Accordingly, SSH-1L/cofilin signaling played a critical role in primary breast cancer metastasis and was a potential therapeutic target for breast cancer treatment.

17.
PLoS One ; 12(4): e0174843, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28394898

RESUMO

The potential prognostic value of GATA binding protein 3 (GATA3) in breast cancer has recently increased, although the evidence is inconclusive. This meta-analysis of 10 articles involving 5,080 breast cancer patients explored the prognostic and clinicopathological value of GATA3 in breast cancer. Time to tumor progression (TTP) and overall survival (OS) were primary endpoints. Pooled hazard ratio (HR), pooled risk ratio (RR), and 95% confidence interval (CI) were calculated to evaluate the association between GATA3, prognosis, and clinicopathological parameters. High GATA3 expression predicts breast cancer, with a HR (HR = 0.671; 95% CI = 0.475-0.947; P = 0.023) of TTP, but is not associated with OS (HR = 0.889; 95% CI = 0.789-1.001; P = 0.052). GATA3 overexpression is associated with positive ER (RR = 3.155; 95% CI = 1.680-5.923; P = 0.000), positive PR (RR = 3.949; 95% CI = 1.567-9.954, P = 0.004), lower nuclear grade (RR = 0.435; 95% CI = 0.369-0.514; P = 0.000), and smaller tumor size (RR = 0.816; 95% CI = 0.709-0.940; P = 0.005). High GATA3 expression may predict TTP in breast cancer, and such patients may show better clinicopathological features.


Assuntos
Neoplasias da Mama/metabolismo , Fator de Transcrição GATA3/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico
18.
Medicine (Baltimore) ; 95(40): e5067, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27749574

RESUMO

The increasing detection of papillary thyroid microcarcinoma (PTMC) has created management dilemmas. To clarify the clinical significance of postsurgery stimulated thyroglobulin (ps-Tg) in PTMC who undergo thyroidectomy and radioactive iodine (RAI), we retrospectively reviewed the 358 PTMC patients who were treated with RAI and followed up in our hospital. Those with an excessive anti-Tg antibody, ultrasound-detected residual were excluded, thereby resulting in the inclusion of 280 cases. Their clinical and histopathological information and clinical outcomes were collected and summarized. Tumor stages were classified according to the tumor, node, metastasis (TNM) staging system and the consensus of the European Thyroid Association (ETA) risk stratification system, respectively. Kaplan-Meier curves were constructed to compare the disease-free survival (DFS) rates of different risk-staging systems. By the end of follow-up, none of the patients died of the disease or relapsed. The 8-year DFS rate was 76.9%. Kaplan-Meier curves showed different DFS rates in TNM stages I versus IV, III versus IV, very low risk versus high risk, low risk versus high risk, respectively (P < 0.05), while they were not significantly different in stage I versus stage III, very low risk versus low risk (P > 0.05). Finally, 40 (14.3%) cases got a persistent disease. Five variables (male sex, nonconcurrent benign pathology, initial tumor size >5 mm, lymph node metastasis, and ps-Tg ≥ 10 µg/L) were associated with disease persistence by univariate regression analysis. Ps-Tg ≥ 10 µg/L was the only independent prognostic variable that predicted disease persistence by multivariate regression analysis (odds ratio: 36.057, P = 0.000). Therefore, PTMC with a small size of ≤1 cm does not always act as an indolent tumor. In conclusion, ps-Tg ≥ 10 µg/L is associated with increased odds of disease persistence. ETA risk stratification is more effective in predicting disease persistence than the TNM classification system.


Assuntos
Carcinoma Papilar/radioterapia , Radioisótopos do Iodo/uso terapêutico , Estadiamento de Neoplasias , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Biópsia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/mortalidade , China/epidemiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/mortalidade , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
PLoS One ; 11(5): e0156323, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27227453

RESUMO

Recently, the interest in programmed death ligand-1 (PD-L1) as a prognostic marker in several types of malignant tumors has increased. In the present meta-analysis, we aimed to explore the prognostic and clinicopathological value of PD-L1 in breast cancer. We searched Medline/PubMed, Web of Science, EMBASE, the Cochrane Library databases, and grey literature from inception until January 20, 2016. Studies concerning breast cancer that focused on PD-L1 expression and studies reporting survival data were included; two authors independently performed the data extraction. The pooled risk ratio (RR) and 95% confidence interval (CI) were assessed to determine the association between the clinicopathological parameters of patients and PD-L1 expression. Five studies involving 2061 patients were included in this meta-analysis. The results indicated that positive/higher PD-L1 expression was a negative predictor for breast cancer, with an RR of 1.64 (95% CI, 1.14-2.34) for the total mortality risk and an RR of 2.53 (95% CI, 1.78-3.59) for the mortality risk 10 years after surgery. Moreover, positive/higher PD-L1 expression was significantly associated with positive lymph node metastasis (RR, 1.33; 95% CI, 1.04-1.70), poor nuclear grade (RR, 1.24; 95% CI, 1.07-1.43), and negative estrogen receptor status (RR, 2.45; 95% CI, 1.31-4.60) in breast cancer patients. Our findings suggest that PD-L1 can serve as a significant biomarker for poor prognosis and the adverse clinicopathologic features of breast cancer and could facilitate the better management of individual patients.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Prognóstico
20.
Onco Targets Ther ; 9: 6461-6466, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27799793

RESUMO

BACKGROUND: Proteins in the cofilin pathway regulate actin dynamics and may be involved in cancer cell migration and invasion. However, there are no direct data that suggest that dephosphorylated cofilin can affect breast cancer prognosis. METHODS: We assessed the expressions of cofilin and phosphorylated cofilin (P-cofilin) in breast cancer tissue microarrays (290 patients, mean follow-up: 95.7±2.49 months) to evaluate dephosphorylated cofilin and its relationship with breast cancer prognosis. The associations of pathological characteristics with cumulative survival were evaluated using Kaplan-Meier analysis. RESULTS: Univariate analyses revealed that overall survival was associated with cofilin levels, N category, TNM stage, estrogen receptor status, progesterone receptor status, and molecular subtypes. Cofilin status and TNM stage independently affected overall survival, although P-cofilin expression was not associated with patient survival. In the P-cofilin-negative subgroup, cofilin expression was significantly associated with patient survival, although cofilin expression was not significantly associated with patient survival in the P-cofilin-positive subgroup. We further analyzed the P-cofilin-negative cases and found that Ki-67 expression was significantly elevated in the subgroup that was strongly positive for cofilin (P=0.002). CONCLUSION: Among P-cofilin-negative patients with breast cancer, cofilin expression defines a population of patients with lower overall survival, which suggests that dephosphorylated cofilin expression might predict the prognosis in cases of P-cofilin-negative breast cancer. Furthermore, our results suggest that inhibitors of dephosphorylated cofilin expression may provide therapeutic benefits in patients with breast cancer.

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