RESUMEN

Objective: This retrospective study aimed to establish ultrasound radiomics models to predict central lymph node metastasis (CLNM) based on preoperative multimodal ultrasound imaging features fusion of primary papillary thyroid carcinoma (PTC). Methods: In total, 498 cases of unifocal PTC were randomly divided into two sets which comprised 348 cases (training set) and 150 cases (validition set). In addition, the testing set contained 120 cases of PTC at different times. Post-operative histopathology was the gold standard for CLNM. The following steps were used to build models: the regions of interest were segmented in PTC ultrasound images, multimodal ultrasound image features were then extracted by the deep learning residual neural network with 50-layer network, followed by feature selection and fusion; subsequently, classification was performed using three classical classifiers-adaptive boosting (AB), linear discriminant analysis (LDA), and support vector machine (SVM). The performances of the unimodal models (Unimodal-AB, Unimodal-LDA, and Unimodal-SVM) and the multimodal models (Multimodal-AB, Multimodal-LDA, and Multimodal-SVM) were evaluated and compared. Results: The Multimodal-SVM model achieved the best predictive performance than the other models (P < 0.05). For the Multimodal-SVM model validation and testing sets, the areas under the receiver operating characteristic curves (AUCs) were 0.910 (95% CI, 0.894-0.926) and 0.851 (95% CI, 0.833-0.869), respectively. The AUCs of the Multimodal-SVM model were 0.920 (95% CI, 0.881-0.959) in the cN0 subgroup-1 cases and 0.828 (95% CI, 0.769-0.887) in the cN0 subgroup-2 cases. Conclusion: The ultrasound radiomics model only based on the PTC multimodal ultrasound image have high clinical value in predicting CLNM and can provide a reference for treatment decisions.

RESUMEN

Papillary thyroid carcinoma (PTC), a common thyroid cancer (TC) subtype, rapidly increases in occurrence. MicroRNAs (miRNAs), which are non-coding small RNAs, have been demonstrated to play a role in cancer pathogenic mechanisms. Although miR-143 is involved in suppressing certain malignant tumor progression, its biological role is unknown in PTC. The present study found that miR-143 levels were strongly lower in PTC patient samples and cell lines, implying that miR-143 may play a biological role in PTC. Down-regulation of miR-143 resulted in the increased expression of HMGA2. Furthermore, HMGA2 was found to be a direct target of miR-143. A dual-luciferase assay confirmed a direct binding site for miR-143 was confirmed on HMGA2 using a dual-luciferase assay. Next, over-expression of miR-143 suppressed PTC cell growth as analyzed by MTT, clone formation, and Ki-67 immunofluorescence staining assays. miR-143 mimics transfection downregulated the expression of PCNA, CDK4, CDK1, and Cyclin E1. In addition, wound healing and trans-well assays revealed that miR-143 up-regulation inhibited PTC cells invasion and migration. Co-transfection of HMGA2 expression vector restored HMGA2 expression and rescued PTC cells proliferation capability in miR-143 mimics transfected PTC cells, indicating that miR-143 inhibited PTC cells proliferation via HMGA2. These observations were also obtained in xenografts experiments in nude mice. Altogether, our study shed light on miR-143's anti-cancer biological functions in PTC progression through targeting HMGA2, suggesting that restoration of miR-143 could be a potential therapeutic approach for PTC treatment.

Asunto(s)

Proteína HMGA2/genética , MicroARNs/genética , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Adulto , Anciano , Animales , Línea Celular Tumoral , Progresión de la Enfermedad , Proteína HMGA2/metabolismo , Humanos , Ratones , Ratones Desnudos , MicroARNs/metabolismo , Persona de Mediana Edad , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patología , Glándula Tiroides/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología

RESUMEN

BACKGROUND: Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. It is reported that the activity of pyruvate kinase is increased in cancers. Phosphoribosyl amidotransferase (PPAT) is reported to be a crucial regulator for pyruvate kinase activity in lung cancer. However, its role in thyroid cancer remains largely unknown. MATERIALS AND METHODS: Immunohistochemical analysis and qRT-PCR were used to detect the expression of PPAT in thyroid cancer samples. Both gain-of-function and loss-of-function models were constructed in thyroid cancer cell lines and the biological functions of PPAT on cellular phenotypes were studied using CCK-8 assay and transwell assay in vitro, respectively. Then, Western blot was used to evaluate the change of PKM2 and downstream signal pathways after PPAT was overexpressed or knocked down. RESULTS: Immunohistochemical analysis showed increased expression of PPAT in thyroid cancer tissues, and it was associated with unfavorable pathological characteristics. Knockdown and overexpression assays suggested that altering PPAT expression modulated cell proliferation, migration, and invasion. In terms of mechanism, PPAT could positively regulate the expression of PKM2 and activate ERK and STAT3 signaling pathways. CONCLUSION: PPAT plays crucial roles in regulating proliferation, migration, and invasion of thyroid cancer cells via activating PKM2, ERK, and STAT3.

RESUMEN

BACKGROUND: The incidence of thyroid cancer is increasing worldwide. This study investigated the association of B-type RAF kinase (BRAF)V600E mutation status, the expression of BRAF-activated long non-coding RNA (BANCR) and microRNA miR-9, and the clinicopathological features of papillary thyroid carcinoma (PTC). METHODS: Clinicopathological data for PTC patients (n = 51) diagnosed and treated between 2018 and 2019 were collected. Carcinoma and adjacent normal tissue samples were analyzed for the presence of the BRAFV600E mutation and/or expression of BANCR and miR-9. RESULTS: Larger tumor, higher rate of bilateral tumors and multifocality, extracapsular invasion, and lateral lymph node metastasis (LNM) were observed in PTC patients with BRAF V600E mutation. Patients with higher BANCR expression had a higher rate of extracapsular invasion and lateral LNM in carcinoma tissue and a lower frequency of bilateral tumors and multifocality in normal adjacent tissue. Patients with higher miR-9 expression had a lower rate of central and lateral LNM in carcinoma tissue and higher rates of bilateral tumor location and multifocality in normal adjacent tissue. Patients with BRAFV600E mutation have a higher rate of BANCR overexpression and tended to have a lower rate of miR-9 overexpression (P = 0.057), and a negative association was observed between BANCR and miR-9 expression in carcinoma tissue. CONCLUSIONS: BRAFV600E mutation and the BANCR and miR-9 expression were closely associated with the tumor size, bilateral tumor location, multifocality, extracapsular invasion, and lateral LNM. PTC patients with these clinicopathological characteristics, BRAFV600E mutation, and high BANCR expression and low miR-9 expression needed earlier surgical treatment and are recommended for total thyroidectomy in primary surgery for reducing the risk of recurrence. These findings provide new insight into the molecular basis for PTC and can inform strategies for the management of PTC.

Asunto(s)

MicroARNs/genética , Mutación , Recurrencia Local de Neoplasia/patología , Proteínas Proto-Oncogénicas B-raf/genética , ARN Largo no Codificante/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas B-raf/metabolismo , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Tiroidectomía/métodos , Adulto Joven

RESUMEN

The long noncoding RNA (lncRNA) LINC00520 is an important modulator of the oncogenicity of multiple human cancers. However, whether LINC00520 is involved in the malignancy of papillary thyroid carcinoma (PTC) has not been extensively studied until recently. Therefore, the present study aimed to detect LINC00520 expression and evaluate its clinical significance in PTC. Functional experiments were conducted to test the biological role(s) and underlying mechanisms of LINC00520 in PTC progression. Reverse transcription quantitative polymerase chain reaction was performed to detect LINC00520 expression in PTC. A series of functional experiments, including Cell Counting Kit-8 assay, flow cytometry, Transwell migration assay, and tumor xenograft assay, was employed to investigate the biological roles of LINC00520 in PTC cells. High LINC00520 expression was verified in PTC tissues and cell lines, and this high expression was associated with the unfavorable clinicopathological parameters and short overall survival of patients. Functionally, LINC00520 interference resulted in a significant decrease in PTC cell proliferation, migration, and in vitro invasion and an increase in cell apoptosis. Further, its downregulation impaired tumor growth in vivo. Mechanistically, LINC00520 functioned as a competing endogenous RNA by sponging microRNA-577 (miR-577) and thereby increasing sphingosine kinase 2 (Sphk2) expression. Rescue experiments revealed that inhibiting miR-577 or restoring Sphk2 could abrogate the effects of LINC00520 silencing on the malignant phenotypes of PTC. LINC00520 functioned as an oncogenic lncRNA in PTC, and it facilitated PTC progression by regulating the miR-577/Sphk2 axis, suggesting that the LINC00520/miR-577/Sphk2 axis is an effective target in anticancer management.

Asunto(s)

Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , MicroARNs/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , ARN Largo no Codificante/metabolismo , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Adulto , Animales , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Silenciador del Gen , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Persona de Mediana Edad , Fenotipo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Pronóstico , ARN Largo no Codificante/genética , Cáncer Papilar Tiroideo/enzimología , Regulación hacia Arriba/genética

RESUMEN

Thyroid cancer keeps rapidly increasing worldwide and the most frequent type is papillary thyroid carcinoma (PTC). MicroRNAs (miRNAs) are proved dysregulated in many types of malignancies, including thyroid cancer. Although miR-let-7e has been implicated in several types of cancer regulation, relatively little is known about the function of miR-let-7e in PTC. In this study, we showed that the overexpression of miR-let-7e or knockdown of high mobility group box 1 (HMGB1) inhibited cell migration and invasion. MiR-let-7e downregulates HMGB1 expression by directly targeting the HMGB1 3'-UTR. Furthermore, HMGB1 reintroduction reversed the anti-proliferation, anti-migration, and anti-invasion roles of miR-let-7e. miR-let-7e might function as a tumor suppressor in papillary thyroid carcinoma through HMGB1. Therefore, our study demonstrates that miR-let-7e plays an important role in papillary thyroid carcinoma progression and might represent a new potential therapeutic target for treatment.

Asunto(s)

Movimiento Celular/fisiología , Regulación Neoplásica de la Expresión Génica , Proteína HMGB1/biosíntesis , MicroARNs/biosíntesis , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/metabolismo , Animales , Línea Celular Tumoral , Proteína HMGB1/antagonistas & inhibidores , Proteína HMGB1/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología

RESUMEN

Anaplastic thyroid carcinoma (ATC) is one of the most lethal carcinoma with a poor prognosis; however, molecular mechanisms underlying the aggressiveness of ATC remain unclear. Our goal was to examine the expression of X-linked inhibitor of apoptosis protein (XIAP) in ATC, as well as its role in ATC tumorigenesis. This is a retrospective study of ATC patients from the Second Affiliated Hospital of Harbin Medical University during June 2003 to October 2013. The expression of XIAP in tumor specimens of ATC patients was examined by immunohistochemical staining. The roles of XIAP in proliferation, migration, invasion, and chemoresistance were investigated by shRNA mediated-knockdown of XIAP in human ATC cell lines. The effect of XIAP on tumorigenesis was evaluated using a xenograft tumor model with nude mice. XIAP expression was significantly higher in the invasive area of ATC samples, whereas XIAP expression was negative in either normal thyroid follicular epithelial cells or the differentiated papillary thyroid carcinoma. XIAP-depleted ATC cells showed a remarkable decrease in the proliferation, migration, and invasion compared with the scramble group. Knockdown of XIAP expression significantly enhanced the chemosensitivity of WRO and SW1736 cells to docetaxel or taxane. Moreover, knockdown of XIAP significantly suppressed ATC tumorigenesis in vivo. XIAP is highly expressed in ATC cells and tumors. XIAP play important roles in tumor behaviors and chemosensitivity of ATC cells. XIAP may function in ATC aggressiveness and may serve as a potential therapeutic target for ATC treatment.

RESUMEN

Chemotherapy is one of the most effective forms of cancer treatment and has been used in the treatment of various malignant tumors. We have gained significant insight into the mechanisms of chemoresistance but the details of the molecular mechanisms remain unclear. In the present study, we found that tripartite motif 8 (TRIM8) expression was downregulated in anaplastic thyroid cancer (ATC) tissues and cell lines. This downregulation of TRIM8 was significantly correlated with the upregulation of miR-182 in human ATC tissues. Bioinformatic analysis and luciferase reporter assays identified TRIM8 as a direct target of miR-182 in ATC. A functional assay using an MTT assay and colony formation showed that miR-182 induced cellular growth by repressing TRIM8 expression. Additionally, overexpressed miR-182 contributed to the chemoresistance of ATC cells by the repression of TRIM8 expression. In conclusion, these results demonstrate that miR-182/TRIM8 may be a therapeutic target for the treatment of chemoresistant human thyroid papillary cancer.

RESUMEN

We compared the clinical effects and prognosis of patients receiving lymph node dissection after surgical removal of the thyroid tissues and those not receiving it after the removal. A total of 80 patients diagnosed with differentiated thyroid carcinoma (DTC) by our hospital from March 2012 to March 2014 were successively included in the study. The cases were divided into the control group (n=36 cases) and observation group (n=44 cases), and the two groups underwent total or subtotal resection of the thyroid. In the control group, patients underwent preoperative high-frequency color ultrasonography, and the most suspicious lymph node was removed. In the observation group, patients underwent preoperative high-frequency color ultrasonography, and the surgeons cleared the lymph node of the widest range. Difference in clinical effects and prognosis of the two groups were compared. After nearly a year's follow-up observation, the tumor recurrence rate of the observation group was significantly lower than that of the control group and the survival rate of the observation group was significantly higher than that of the control group (P<0.05). The rate of surgery complications and comparative difference of the two patient groups had no statistical significance (P>0.05). When comparing the data of lymphatic metastasis tested by preoperative high-frequency color ultrasonography with intraoperative diagnosed figures, sensitivity was 97.4%, specificity 33.3%, positive predictive value 90.2% and the negative predictive value 66.7%. In conclusion, removal of the lymph node for DTC patients having undergone thyroid tissue excision with preoperative high-frequency color ultrasonography can be beneficial to improve the effects along with reduction in the recurrence rate.

RESUMEN

BACKGROUND: Metabotropic glutamate could contribute to the development of neuropathic pain-related behaviors. Previously, we have confirmed that the glutamic acid and dizocilpine maleate in the hippocampal CA3 region are involved in the modulation of noxious stimulation. However, whether the metabotropic glutamate receptor 7 (mGluR7) can modulate the pain-evoked electrical activities of pain-excited neurons and pain-inhibited neurons in the hippocampal CA3 region is not clear. OBJECTIVE: The study aimed to examine the effects of mGluR7 allosteric agonist N,N'-dibenzhydrylethane- 1,2-diamine dihydrochloride (AMN082) and antagonist 6-(4-methoxyphenyl)-5-methyl-3- pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) on the pain-evoked electrical activities of pain-excited neurons and pain-inhibited neurons in the CA3 region of rats. METHOD: A train of electric impulses applied to the sciatic nerve were used for noxious stimulation. The bio-electrical activities of pain-excited neuron or pain-inhibited neuron in the CA3 region were recorded by a glass microelectrode. RESULTS: Our results exhibited that intra-CA3 region administration of the glutamic acid or AMN082 increased the pain-evoked discharged frequency and shortened the latency of pain-excited neuron, while decreased the pain-evoked discharged frequency and prolonged the inhibitory duration of paininhibited neuron in the CA3 region. The intra-CA3 region microinjection of MMPIP produced the opposite response. CONCLUSION: These findings demonstrated that the glutamic acid and mGluR7 in hippocampal CA3 region are involved in the modulation of nociceptive information transmission by regulating pain-evoked electric activities of pain-excited neurons and pain-inhibited neurons.

Asunto(s)

Región CA3 Hipocampal/metabolismo , Neuralgia/metabolismo , Neuronas/metabolismo , Dolor Nociceptivo/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Analgésicos no Narcóticos/farmacología , Animales , Compuestos de Bencidrilo/farmacología , Región CA3 Hipocampal/efectos de los fármacos , Fármacos actuantes sobre Aminoácidos Excitadores/farmacología , Ácido Glutámico/metabolismo , Masculino , Microelectrodos , Neuralgia/tratamiento farmacológico , Neuronas/efectos de los fármacos , Dolor Nociceptivo/tratamiento farmacológico , Piridonas/farmacología , Ratas Wistar , Receptores de Glutamato Metabotrópico/agonistas , Nervio Ciático/fisiopatología , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología

RESUMEN

OBJECTIVE: To investigate the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC) for surgery by comparing the difference between PTMC and larger papillary thyroid carcinoma (LPTC). METHODS: We analyzed the differences in the clinicopathological characteristics, prognosis, B-type RAF kinase (BRAF)V600E mutational status and expression of angiogenic factors, including pigment epithelium-derived factor (PEDF), Vascular Endothelial Growth Factor (VEGF), and hypoxia-inducible factor alpha subunit (HIF-1α), between PTMC and LPTC by retrospectively reviewing the records of 251 patients with papillary thyroid carcinoma, 169 with PTMC, and 82 with LPTC (diameter >1 cm). RESULTS: There were no significant differences in the gender, age, multifocality, Hashimoto's thyroiditis, TNM stage, PEDF protein expression, rate of recurrence, or mean follow-up duration between patients with PTMC or LPTC. The prevalence of extrathyroidal invasion (EI), lymph node metastasis (LNM), and BRAF mutation in patients with PTMC was significantly lower than in patients with LPTC. In addition, in PTMC patients with EI and/or LNM and/or positive BRAF (high-risk PTMC patients), the prevalence of extrathyroidal invasion, Hashimoto's disease, lymph node metastasis, tumor TNM stage, PEDF positive protein expression, the rate of recurrent disease, and the mRNA expression of anti-angiogenic factors was almost as high as in patients with larger PTC, but with no significant difference. CONCLUSIONS: Extrathyroid invasion, lymph node metastases, and BRAFV600E mutation were the high risk factors of PTMC. PTMC should be considered for the same treatment strategy as LPTC when any of these factors is found. Particularly, PTMC with BRAFV600E gene mutations needed earlier surgical treatment. In addition, the high cell subtype of PTMC with BRAFV600E gene mutation is recommended for total thyroidectomy in primary surgery to reduce the risk of recurrence.

Asunto(s)

Carcinoma Papilar/diagnóstico , Carcinoma/patología , Regulación Neoplásica de la Expresión Génica , Mutación Puntual , Proteínas Proto-Oncogénicas B-raf/genética , Glándula Tiroides/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Adulto , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma/cirugía , Carcinoma Papilar/genética , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Proteínas del Ojo/genética , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Metástasis Linfática/diagnóstico , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Factores de Crecimiento Nervioso/genética , Pronóstico , Serpinas/genética , Cáncer Papilar Tiroideo , Glándula Tiroides/metabolismo , Glándula Tiroides/cirugía , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Factor A de Crecimiento Endotelial Vascular/genética

RESUMEN

The aim of this study was to determine the effects of nanocarbon particles in combination with meticulous capsular dissection on enhancing the identification and protecting the function of parathyroid glands in thyroid cancer surgery.The data of 97 patients with papillary thyroid tumors diagnosed and treated at the Second Affiliated Hospital, Harbin Medical University between January 2014 and February 2015 were reviewed. Data regarding the sex, age, calcium and parathyroid hormone (PTH) levels, tumor size, multifocality, T stage, and extrathyroid invasion were collected. The incidence of surgeries in which the parathyroid glands were cut mistakenly, the concentration of serum calcium and parathyroid hormone before surgery (baseline) and after surgery on days 1, 3, and 7, and 1 and 6 months in the patients of the two groups (the nanocarbon and control groups) were analyzed.Fifty-two patients underwent meticulous capsular dissection combined with nanocarbon treatment (nanocarbon group), and 45 underwent meticulous capsular dissection alone (control group). The nanocarbon group showed a significantly higher total and average number of revealed parathyroid glands (average number is the mean for different individuals have different number) and a lower incidence of the parathyroid glands being mistakenly cut, in addition to a lower level of hypoparathyroidism than control group following surgery (P < 0.05). Serum calcium and PTH levels were significantly lower in patients from both groups after surgery on days 1, 3, and 7 and after 1 month, compared with the preoperative levels (P < 0.05). Compared with the control group, the serum calcium and PTH levels were significantly higher in the nanocarbon group after surgery on days 1, 3, 7, than in the control group.Treatment with nanocarbon in combination with meticulous capsular dissection can significantly facilitate the identification of the parathyroid in thyroid cancer surgery, reduce the risk of mistakenly cutting the parathyroid, and reduce the incidence of postoperative hypoparathyroidism.

Asunto(s)

Carbono , Complicaciones Intraoperatorias/prevención & control , Nanopartículas , Glándulas Paratiroides , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glándulas Paratiroides/anatomía & histología , Glándulas Paratiroides/fisiología , Estudios Retrospectivos , Adulto Joven

RESUMEN

The progression mechanism of papillary thyroid carcinoma (PTC) remains largely unknown. Accumulating evidence has suggested that various targets of pigment epithelium-derived factor (PEDF) are able to inhibit cancer progression. The aim of the present study was to examine PEDF expression in PTC patients and to investigate its relationship with aggressive clinicopathological features, as well as to explore whether PEDF affects the progression of PTC via the hypoxia-inducible factor 1α (HIF1α)-vascular endothelial growth factor (VEGF) pathway. A total of 271 patients with PTC, including 24 men and 247 women, were enrolled in the present study. Relevant patient data, including demographic features, preoperative clinical features and pathological features, were collected for analysis. The protein expression levels of PEDF in PTC tissues were detected using immunohistochemical staining, and the mRNA expression levels of PEDF, VEGF and HIF1α in 15 PTC tissues with lymph node metastasis (LNM) and 10 tissues without LNM were detected using reverse transcription-quantitative polymerase chain reaction. Immunohistochemical staining with an anti-PEDF antibody detected PEDF expression in 74.5% of the PTC tissues. PEDF expression levels were significantly correlated with LNM, extrathyroid invasion, a high TNM stage, the presence of the BRAFV600E mutation and tumor size. PEDF mRNA expression levels were significantly decreased in PTC tissues with LNM, as compared with PTC tissues without LNM, while the mRNA expression levels of HIF1α and VEGF were markedly increased in PTC tissues with LNM. Taken together, the results of the present study suggested that PEDF plays a role in the progression of PTC, and that PEDF may exert an anti-angiogenesis role by affecting the HIF1α-VEGF pathway, eventually inhibiting the metastasis of PTC.

RESUMEN

OBJECTIVE: To investigate the association of concomitant BRAFV600E mutation with central lymph node metastases in papillary thyroid carcinoma (PTC). METHODS: The clinicopathological data of 126 PTC patients who underwent surgical treatment within a period of 2 years were retrospectively analyzed. The BRAF V600E gene mutation was detected by quantitative fluorescence PCR. RESULTS: The BRAF mutation rate was 69.0% (87/126). The univariate analysis showed that BRAF mutation status was significantly associated with central lymph node metastasis (P<0.05), while the gender, multiple lesions, tumor size, extra-thyroidal invasion, Hashimoto's thyroiditis and tumor stage were not significantly associated with the BRAF mutation (P>0.05 for all). The multivariate analysis showed that only central lymph node metastasis was significantly correlated with BRAF mutation (P<0.05). When the diameter of tumor was ≤10 mm, BRAF mutation was statistically not significantly correlated to central lymph node metastasis (P>0.05). When the diameter of tumor was >10 mm, the central lymph node metastasis rate was significantly higher in patients with positive BRAF mutation than that in patients with a negative BRAF mutation (P<0.05). CONCLUSIONS: The presence of BRAF mutation is an independent predictive factor for central lymph node metastasis. When PTC is with preoperative positive BRAF mutation, the cervical dissection should be routinely performed. The larger the tumor diameter is, the more important is the central lymph node dissection. There should be re-evaluated the necessity of preventative central lymph node dissection when the tumor diameter was ≤5 mm in patients with negative BRAF mutation.

Asunto(s)

Carcinoma/genética , Metástasis Linfática/diagnóstico , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/genética , Carcinoma/epidemiología , Carcinoma/metabolismo , Carcinoma Papilar , Enfermedad de Hashimoto , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática/genética , Mutación , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/metabolismo

RESUMEN

OBJECTIVE: To evaluate the relationship between BRAF mutation and factors influencing the prognosis of papillary thyroid microcarcinoma (PTMC). METHODS: Clinical data from patients with PTMC were subjected to retrospective analysis. A total of 86 patients were included, and the BRAF(V600E) mutation was identified in surgically dissected tissues. RESULTS: The incidence of BRAF mutation in patients with PTMC was 65.1% (56/86). Both univariate and multivariate analyses indicated a correlation between BRAF mutation and lymph node metastasis (P = 0.057). For patients with tumors ≤ 10 mm in diameter, BRAF mutation had no effect on lymph node metastasis (P > 0.05). No lymph node metastasis was found in patients with tumors ≤ 5 mm in diameter. CONCLUSION: BRAF gene mutation is an independent predictive risk factor for central lymph node metastasis in patients with PTMC. For patients with preoperative BRAF mutation positivity, it is important to perform central lymph node dissection (CLND) and lymphatic and adipose tissues should be routinely removed. However, in patients without BRAF mutation and tumors ≤ 5 mm in diameter, the necessity of prophylactic CLND should be reevaluated.

RESUMEN

Glutamic acid (Glu) participates in pain modulation of the central nervous system. The CA3 region of the hippocampal formation has been suggested to be involved in nociceptive perception. However, it is unknown whether Glu could modulate the electrical activities of pain-related neurons in the hippocampal CA3 region. The present study aimed to determine the effects of Glu and its receptor antagonist MK-801 in the pain-evoked response of both pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the hippocampal CA3 region of normal rats. We used a train of electric impulses applied to the sciatic nerve as noxious stimulation. The electrical activities of either PENs or PINs in the hippocampal CA3 region were recorded by a glass microelectrode. The results revealed that intra-CA3 region microinjection of Glu (0.5 µg/1 µl) increased the evoked firing frequency and shortened the firing latency of PEN, while decreased the evoked firing frequency and prolonged the inhibitory duration of PIN in the hippocampal CA3 region of rat evoked by the noxious stimulation. Intra-CA3 region administration of MK-801 (0.25 µg/1 µl) produced the opposite response. These results suggest that Glu and its receptors in hippocampal CA3 region are involved in the modulation of nociceptive information transmission by affecting the electric activities of PENs and PINs.

Asunto(s)

Región CA3 Hipocampal/citología , Región CA3 Hipocampal/fisiopatología , Fenómenos Electrofisiológicos/fisiología , Ácido Glutámico/farmacología , Neuronas/fisiología , Dolor/fisiopatología , Animales , Maleato de Dizocilpina/farmacología , Estimulación Eléctrica , Antagonistas de Aminoácidos Excitadores/farmacología , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/fisiología , Microelectrodos , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Técnicas Estereotáxicas

RESUMEN

BACKGROUND: Heme oxygenase (HO)-1 protects transplanted organs from ischemia reperfusion injury and immune rejection. This study sought to investigate whether persistent overexpression of HO-1 in donor livers could improve the survival by expanding T regulatory cells in a rat model of orthotopic liver transplantation. METHODS: Livers of Dark Agouti rats were intraportally perfused with an AAV expression vector encoding rat HO-1 (AAV-HO-1), and then transplanted into Lewis rats. The survival, HO-1 activity, Banff rejection activity index, serum levels of IL-2 and TNF-α, infiltration of CD4(+), CD8(+), and T(reg) (CD4(+)CD25(+)Foxp3(+)) cells into donor livers, and expression of Foxp3, TGF-ß, and IL-10 were examined. A mixed lymphocyte reaction (MLR) was performed. RESULTS: Intraportal delivery of AAV-HO-1 resulted in persistent expression of HO-1 and increased activity of HO-1 in transplanted livers, leading to prolonged survival of recipients. Overexpression of HO-1 reduced the Banff rejection activity index, and production of IL-2 and TNF-α, inhibited infiltration of CD4(+) and CD8(+) cells, and increased infiltration of T(reg) cells, into donor livers. The spleens of recipients expressed higher levels of Foxp3, TGF-ß, and IL-10 than those of control rats, and the transplanted livers expressed higher levels of Foxp3 and TGF-ß. Splenocytes from the tolerant recipients had higher percentages of T(reg) cells, and responded poorly to the allogeneic donor splenocytes. CONCLUSIONS: Persistent expression of HO-1 in donor livers by intraportal delivery of AAV-HO-1 improves the survival by expanding T(reg) cells. HO-1-based therapies, as described herein, promise new strategies to prevent the rejection of liver transplants.

Asunto(s)

Terapia Genética/métodos , Supervivencia de Injerto/inmunología , Hemo Oxigenasa (Desciclizante)/genética , Trasplante de Hígado , Daño por Reperfusión/terapia , Linfocitos T Reguladores/citología , Adenoviridae/genética , Animales , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Factores de Transcripción Forkhead/genética , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Rechazo de Injerto/terapia , Hemo Oxigenasa (Desciclizante)/inmunología , Interleucina-10/genética , Hígado/enzimología , Hígado/inmunología , Hígado/cirugía , Masculino , Ratas , Ratas Endogámicas Lew , Ratas Wistar , Daño por Reperfusión/inmunología , Daño por Reperfusión/prevención & control , Bazo/fisiología , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta/genética , Acondicionamiento Pretrasplante , Trasplante Homólogo

RESUMEN

BACKGROUND/AIMS: Studies investigating the association between p53 codon 72 polymorphism and colorectal cancer risk report conflicting results. In order to clarify this, we carried out a meta-analysis using published data to obtain more precise estimates of risk. METHODOLOGY: Electronic searches of PubMed and EMBASE were conducted to select studies for this meta- analysis. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of colorectal cancer associated with p53 codon 72 genotype. RESULTS: We identified seven epidemiological studies, which included 1964 colorectal cancer cases and 2943 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [Arg/Arg (OR=0.86, 95% CI=0.68, 1.08); Pro/Pro (OR=1.27, 95% CI=0.96, 1.68); Pro/Arg (OR=1.04, 95% CI=0.92, 1.17)] between colorectal cancer and non-cancer patients. When stratifying for race, we found that patients with colorectal cancer had a significantly higher frequency of Pro/ Pro (OR=1.79, 95% CI=1.37, 2.35) and lower frequency of Arg/Arg (OR=0.66, 95% CI=0.44, 0.98) than controls among Asians. No statistical association was found between this genotype and alcohol, tobacco, stage, histological differentiation, lymph node metastasis of colorectal cancer. CONCLUSIONS: Our meta-analysis suggests that the p53 codon 72 polymorphism may be associated with colorectal cancer among Asians.

Asunto(s)

Codón , Neoplasias Colorrectales/genética , Genes p53 , Polimorfismo Genético , Neoplasias Colorrectales/patología , Genotipo , Humanos , Metástasis Linfática

RESUMEN

Dizocilpine maleate (MK-801) causes the blockage of the glutamic acid (Glu) receptors in the central nervous system that are involved in pain transmission. However, the mechanism of action of MK-801 in pain-related neurons is not clear, and it is still unknown whether Glu is involved in the modulation of this processing. This study examines the effect of MK-801, Glu on the pain-evoked response of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the nucleus accumbens (NAc) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The electrical activities of PENs or PINs in NAc were recorded by a glass microelectrode. Our results revealed that the lateral ventricle injection of Glu increased the discharged frequency and shortened the discharged latency of PEN, and decreased the discharged frequency and prolonged the discharged inhibitory duration (ID) of PIN in NAc of rats evoked by the noxious stimulation, while intra-NAc administration of MK-801 produced the opposite response. On the basis of above findings we can deduce that Glu, MK-801 and N-methyl-D-aspartate (NMDA) receptor are involved in the modulation of nociceptive information transmission in NAc.

Asunto(s)

Analgésicos/farmacología , Maleato de Dizocilpina/farmacología , Ácido Glutámico/fisiología , Núcleo Accumbens/efectos de los fármacos , Dolor/fisiopatología , Receptores de N-Metil-D-Aspartato/fisiología , Transmisión Sináptica/efectos de los fármacos , Animales , Masculino , Neuronas/efectos de los fármacos , Neuronas/fisiología , Núcleo Accumbens/citología , Núcleo Accumbens/fisiología , Ratas , Ratas Wistar

RESUMEN

OBJECTIVES: The analgesic effect of electroacupuncture (EA) stimulation has been proved. However, its mechanism of action is not clear. It has been well-known that cholecystokinin-8 (CCK-8) is a neuropeptide which is mainly related to the mediation of pain. The caudate nucleus was selected to determine if the release of CCK and the neural activity in this nucleus were involved in producing EA analgesia. MATERIALS AND METHODS: Radiant heat focused on the rat-tail was used as the noxious stimulus. The pain threshold of rats was measured by tail-flick latency (TFL). EA stimulation at the bilateral Zusanli (ST 36) acupoints of rats was used to investigate the effects of EA analgesia. The electrical activities of pain-excited neurons (PEN) and pain-inhibited neurons (PIN) in the caudate nucleus were recorded with a glass microelectrode. The present study examined the antagonistic effects of the intracerebral ventricular injection of CCK-8 on EA analgesia and reversing effects of CCK-B receptor antagonist (L-365,260) injection into the caudate nucleus on CCK-8. RESULTS: The radiant heat focused on the tail of rats caused an increase in the evoked discharge of PEN and a reduction in the evoked discharge of PIN. EA stimulation at the bilateral ST 36 acupoints of rats resulted in the inhibition of PEN, the potentiation of PIN, and prolongation of TFL. The analgesic effect of EA was antagonized when CCK-8 was injected into the intracerebral ventricle of rats. The antagonistic effect of CCK-8 on EA analgesia was reversed by injection of CCK-B receptor antagonist (L-365,260) into the caudate nucleus of rats. CONCLUSIONS: Our results suggest that CCK-8 antagonize EA analgesia through its B receptor.