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1.
Cell Death Dis ; 15(2): 125, 2024 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336839

RESUMEN

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.


Asunto(s)
Nitrilos , Pirazoles , Pirimidinas , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/genética , Carcinoma Anaplásico de Tiroides/metabolismo , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Dinámicas Mitocondriales , Piroptosis , Caspasa 9/metabolismo , Proliferación Celular , Línea Celular Tumoral , Apoptosis
2.
Asian J Surg ; 47(4): 1734-1739, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38185563

RESUMEN

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.


Asunto(s)
Neoplasias de la Tiroides , Tiroidectomía , Humanos , Deglución , Músculos del Cuello/patología , Endoscopía , Disección del Cuello , Neoplasias de la Tiroides/cirugía
3.
Head Neck ; 45(9): 2394-2412, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37417818

RESUMEN

BACKGROUND: This paper aims to analyze the time trend of OCs incidence in 43 countries (1988-2012) and predict the incidence trend of OCs (2012-2030). METHODS: In the database for Cancer Incidence in Five Continents, the annual data on OCs incidence grouped by age and gender were obtained from 108 cancer registries in 43 countries. The age-standardized incidence rates were calculated, and the Bayesian age-period-cohort model was used to predict the incidence in 2030. RESULTS: South Asia and Oceania had the highest ASR in 1988 (9.24/100 000) and 2012 (6.74/100 000). It was predicted that India, Thailand, the United Kingdom, the Czech Republic, Austria, and Japan would be the countries with an increased incidence of OCs in 2030. CONCLUSION: Regional custom is an important factor affecting the incidence of OCs. According to our predictions., it is necessary to control risk factors according to local conditions and enhance screening and education.


Asunto(s)
Neoplasias de la Boca , Humanos , Incidencia , Teorema de Bayes , Neoplasias de la Boca/epidemiología , Japón/epidemiología , Factores de Riesgo , Sistema de Registros
4.
Asian J Surg ; 46(10): 4290-4295, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37085417

RESUMEN

BACKGROUND: For N1b papillary thyroid carcinoma (PTC) patients, lateral neck dissection encompassing levels Ⅱ-Ⅴ is generally recommended. However, routine level Ⅱ dissection is controversial given the low incidence of metastasis, and potential complications such as increased shoulder syndrome. METHODS: Retrospective analysis of consecutive patients with papillary thyroid carcinoma who underwent lateral neck dissection at a single institution from January 2019 to April 2021 was performed. Clinicopathological features such as age, gender, tumor location, tumor size, TgAb and TPOAb levels, capsular invasion, multifocality and lymph node metastases were examined to evaluate the occurrence of metastatic Level Ⅱ lymph nodes. RESULTS: Overall and occult level Ⅱ metastases were observed in 51.83% and 34.84% of cN1b PTC patients. Multivariant analysis showed that primary tumor, location of primary tumor and positive level Ⅴ can serve as independent risk factors of metastasis in level Ⅱ. For cN1b PTC patients not suspected of level Ⅱ lymph nodes preoperatively, independent risk factors for predicting occult level Ⅱ metastases may include the location of primary tumor, positive level Ⅲ and positive level Ⅴ. CONCLUSION: A significant number of patients with PTC and lateral neck disease experienced Level Ⅱ metastasis, with the location of primary tumor and multilevel lymph node involvement being the independent risk factors. If the tumor is less than 1 cm and located at lower 2/3 lobe, there is minimal possibility of level Ⅱ lymph node metastasis.


Asunto(s)
Carcinoma Papilar , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Disección del Cuello , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Carcinoma Papilar/cirugía , Carcinoma Papilar/patología , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Tiroidectomía
5.
Front Surg ; 9: 962463, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36338640

RESUMEN

Objectives: To investigate the safety and feasibility of gasless axillary parathyroid surgery in the treatment of primary hyperparathyroidism. Methods: A total of 12 patients who received gasless axillary parathyroidectomy (endoscope group) and 14 patients who received traditional open parathyroidectomy (open group) from January 2019 to April 2022 were screened and included. The differences in baseline characteristics, surgical efficiency, incidence rate of complications, changes in biochemical indicators, and incision satisfaction between the two groups were analyzed and compared. Results: The proportion of young patients was higher in the endoscopic group than in the open group, and the difference was statistically significant [(41.33 ± 13.65) years vs. (58.00 ± 9.44) years, P < 0.01]. The differences in operation time, intra-operative blood loss, post-operative drainage volume, hospital stay, and surgical efficiency between the two groups yielded no statistical significance (P > 0.05). Patients in the open group had more significant neck pain 3 days after surgery (P = 0.046), but the degree of pain 3 months after surgery was the same in the 2 groups (P = 0.432). Evaluation of post-operative mature stage scar and incision satisfaction regarding aesthetics in the endoscope group were significantly superior to that in the open group [(1.92 ± 0.92) points vs. (0.92 ± 1.00) points, P = 0.017 and (1.57 ± 0.51) points vs. (1.00 ± 0.013) points, P = 0.013, respectively]. No statistical significance was found in terms of incidence rate of post-operative fever (P > 0.05). No temporary recurrent laryngeal nerve injury, post-operative bleeding, incision hematoma infection, or other complications were observed. Comparing the two groups, the extent of the level decrease of PTH was similar to that of serum calcium and phosphorus (P < 0.05), where most patients experienced transient hypocalcemia after operation yielding no significant difference in incidence (P = 0.225). During a follow-up period of 3 to 36 months, a total of 1 patient in the open group experienced recurrence at 10 months after surgery and was treated non-surgically. Conclusion: Gasless axillary approach to parathyroid surgery for primary hyperparathyroidism possesses good safety and patient satisfaction in terms of aesthetics.

7.
Front Oncol ; 12: 947422, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36212471

RESUMEN

Parathyroid adenoma (PA), one of the most common causes of hyperparathyroidism, generally involves a single parathyroid gland and is manifested as hyperparathyroidism. Bronchogenic cysts are rare congenital cystic lesions caused by a development malformation in bronchi during the embryonic period, which mostly occur in the lung and mediastinum, with an extremely low morbidity rate in the neck. A 27-year-old young female was found to suffer from hyperparathyroidism on routine physical examination, and further examination suggested a cystic lesion in the right inferior parathyroid area combined with a tracheal diverticulum. Therefore, she was initially diagnosed with cystic hyperplasia of the parathyroid glands complicated by a tracheal diverticulum. Gasless endoscopic resection of neck masses via an axillary approach was performed because of the high requirements for the surgical cosmetic effect of the patient. During the surgery, we observed that the preoperatively diagnosed cystic lesion was a combination of two masses, which were successfully resected under endoscopy. Based on the postoperative pathology and clinical features, the patient was eventually diagnosed with a rare case of triple diseases including PA, cervical bronchial cyst, and tracheal diverticulum. Now, the patient recovered well as per the follow-up with no signs of recurrence and was extremely satisfied with the cosmetic effect of the surgery.

8.
Blood Cancer Discov ; 2(4): 388-401, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34661159

RESUMEN

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein-associated cancers by hyperthermia. SIGNIFICANCE: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.See related commentary by Wu et al., p. 300.


Asunto(s)
Hipertermia Inducida , Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Proteínas de Fusión Oncogénica/genética , Tretinoina/uso terapéutico
9.
Gland Surg ; 10(8): 2445-2454, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34527556

RESUMEN

BACKGROUND: prognosis, identify clinicopathological characteristics, and determine optimal modalities for cT1N0M0 solitary papillary thyroid carcinoma in the isthmus (PTCI). METHODS: The clinical data of 124 patients with cT1N0M0 solitary PTCI from 3 medical centers were analyzed retrospectively. Of these, 32 participants had undergone total thyroidectomy plus unilateral central neck dissection, 36 had received total thyroidectomy plus bilateral central neck dissection, 24 had less-than-total thyroidectomy plus unilateral central neck dissection, and 32 had less-than-total thyroidectomy plus bilateral central neck dissection. We compared the effects of different surgical modalities and clinicopathological characteristics on the prognosis of cT1N0M0 solitary PTCI. RESULTS: There was no significant difference in postoperative recurrence-free survival between participants who received different extents of central region lymph node dissection and thyroidectomies (P>0.05). Temporary hypocalcemia occurred in participants who underwent total thyroidectomy plus bilateral central neck dissection [chi-square (χ2) =7.87, P=0.005]. Tumors with primary lesions ≥0.55 cm were prone to have central lymph node metastasis [95% confidence interval (CI): 0.51 to 0.71, P=0.047]. Multiple logistic analysis suggested that age over 55 years [odds ratio (OR) =11.90, 95% CI: 1.36 to 104.03, P=0.025], tumor size greater than 0.55 cm (OR =4.16, 95% CI: 1.28 to 13.52, P=0.018), and absence of nodular goiter (OR =2.57, 95% CI: 1.05 to 6.32, P=0.04) were risk factors for central lymph node metastasis of patients with cT1N0M0 solitary PTCI. CONCLUSIONS: Less-than-total thyroidectomy is recommended for patients with cT1N0M0 solitary PTCI. Central lymph node dissection is recommended for patients who are prone to have central occult lymph node metastases with tumor size ≥55 cm, older than 55 years, and without nodular goiter.

10.
J Cancer ; 12(7): 1978-1989, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33753996

RESUMEN

Patient-consistent xenograft model is a challenge for all cancers but particularly for thyroid cancer, which shows some of the greatest genetic divergence between human tumors and cell lines. In this study, proteomic profiles of tumor tissues from patients, included anaplastic thyroid carcinoma (ATC) and papillary thyroid carcinoma, and xenografts (8305C, 8505C, FRO, BAPAP and IHH4) were obtained using HPLC-tandem mass spectrometry and compared based on all proteins detected (3,961), cancer-related proteins and druggable proteins using pairwise Pearson's correlation analysis. The human tissue showed low proteomic similarity to the ATC cell lines (8305C, r = 0.344-0.416; 8505C, 0.47-0.579; FRO, 0.267-0.307) and to PTC cell lines (BCPAP, 0.303-0.468; IHH4, 0.262-0.509). Human tissue showed the following similarity to cell lines at the level of 135 cancer-related pathways. The ATC cell lines contained 47.4% of the cancer-related pathways (19.26%-33.33%), while the PTC cell lines contained 40% (BCPAP, 25.93%; IHH4, 28.89%). In patient tumor tissues, 44-60 of 76 and 52-53 of 93 druggable proteins were identified in ATC and PTC tumors, respectively. Ten and 29 druggable proteins were not identified in any of the ATC and PTC xenografts, respectively. We provide a reference for CDX selecting in in vivo studies of thyroid cancer.

11.
Biomater Sci ; 9(4): 1313-1324, 2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33350399

RESUMEN

Anaplastic thyroid cancer (ATC) is an undifferentiated and highly aggressive type of thyroid cancer and is extremely resistant to standard therapies such as surgical resection and radioactive iodine therapy. Although targeted therapeutic agents including small molecule drugs and monoclonal antibodies are rapidly developed in recent years, no ATC targeted drugs are available to date; thereby, novel targeted therapies are needed to improve the outcomes of ATC patients. Aptamers are single-stranded DNA (or RNA) molecules that can selectively bind to cancer specific antigens, and aptamer-based targeted therapy has certain advantages over that based on antibodies due to its high binding affinity and low immunogenicity. Here, we identified that CD133, a cancer stem cell marker, was specifically expressed in ATC tumor tissues and cells, implying that CD133 is a potential drug target for ATC therapy. Additionally, we successfully obtained a CD133 targeted aptamer AP-1 by paired cell-based SELEX, which can precisely recognize CD133 antigen in vitro. Furthermore, the truncated AP-1-M aptamer from its precursor AP-1 has shown higher binding affinity for CD133, and specifically accumulated in anaplastic thyroid cancer FRO cell derived tumor in vivo. Conjugation of truncated AP-1-M with doxorubicin could dramatically inhibit CD133 positive FRO cell proliferation, induce cell apoptosis in vitro, and also suppress tumor growth in FRO cell xenograft mice in vivo. Our results clearly demonstrated that the CD133 targeted aptamer AP-1-M conjugated with anticancer drugs has potential to become a promising therapeutic approach against ATC in the near future.


Asunto(s)
Preparaciones Farmacéuticas , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Animales , Línea Celular Tumoral , Proliferación Celular , Humanos , Radioisótopos de Yodo , Ratones , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico
12.
Mol Cell Endocrinol ; 523: 111144, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33383107

RESUMEN

In this study, we aimed to clarify the role of PIM-1 in papillary thyroid carcinoma (PTC) in vitro and investigate the relationship between PIM-1 and redox proteins (NOX4, SOD2, and GPX2) at the tissue and cellular levels. As a PIM-1 inhibitor, SGI-1776 inhibited cell proliferation, colony formation, migration and induced an increase in apoptosis and reactive oxygen species in two PTC cell lines (BCPAP and TPC-1). The expressions of PIM-1, SOD2 and GPX2 were downregulated after siNOX4 exposure. Immunohistochemistry in 120 PTC patients showed that all four proteins exhibited higher expression levels in PTC tissues than in adjacent normal tissues. PIM-1 expression was related to NOX4, SOD2, and GPX2 expressions. The Cancer Genome Atlas database analysis showed the significant correlation between the expression of NOX4 and PIM-1. Our results demonstrated that PIM-1 played an important oncogenic role in PTC carcinogenesis that may be related to oxidative stress.


Asunto(s)
Carcinogénesis/patología , Progresión de la Enfermedad , Oncogenes , Estrés Oxidativo , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Apoptosis/efectos de los fármacos , Apoptosis/genética , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Imidazoles/farmacología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Proteínas Proto-Oncogénicas c-pim-1/genética , Piridazinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Ensayo de Tumor de Célula Madre
13.
Sci Rep ; 10(1): 710, 2020 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-31959758

RESUMEN

There are about half of papillary thyroid carcinoma (PTC) patients with the experience of central lymph node metastasis (CLNM), while the model to predict high-risk groups of CLNM from PTC patients is uncertain. The aim of this study was to evaluate candidate risk factors of CLNM and identify risk factors of recurrence to guide the postoperative therapeutic decision and follow-up for physicians and patients.A total of 4107 patients(4884 lesions) who underwent lymph node dissection in two hospitals from 2005 to 2014 were evaluated. CLNM risk was stratified and a risk-scoring model was developed on the basis of the identified independent risk factors for CLNM. Cox's proportional hazards regression model was used to investigate the risk factors for recurrence.CLNM was proved in 37.96% (1559/4107) of patients and 33.96% (1659/4884) of lesions. In the multivariate analysis, Male, Age ≤35 years, Tumor size >0.5 cm,Lobe dissemination (+), Psammoma body (+), Multifocality and Capsule invasion (+) were independent risk predictors of CLNM (P < 0.01). A 14-point risk-scoring model was built to predict the stratified CLNM in PTC patients and the area under receiver operating characteristic curve of the model for the prediction of CLNM was 0.672 (95% CI: 0.656-0.688) (P < 0.01). COX regression model showed that Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM were significant risk factors associated with poor outcomes. The research suggested that prophylactic CLN dissection could be performed in patients with total score ≥4 according to the risk-scoring model, and more aggressive treatment and more frequent follow-up should be considered for patients with Tumor size >0.5 cm, Lobe dissemination (+), Multifocality and CLNM.


Asunto(s)
Metástasis Linfática , Recurrencia Local de Neoplasia , Modelos de Riesgos Proporcionales , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/cirugía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Predicción , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Factores de Riesgo , Resultado del Tratamiento
14.
Endocr J ; 67(2): 113-123, 2020 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-31723088

RESUMEN

Thyroglobulin measurement in the needle washout after fine-needle aspiration (FNA-Tg) served as an important measurement for suspicious recurrent or metastatic lesions. We conducted a pooled analysis to evaluate the diagnostic accuracy of FNA-Tg and searched electronic databases for original articles in English from 1993 through 2017. Finally, a total of 22 studies containing 2,670 lymph nodes (LNs) that enrolled participants with suspicious neck LNs during thyroid nodule workup or papillary thyroid cancer (PTC) follow-up were included. In our analysis, the overall pooled sensitivity for FNA-Tg was 0.91 (95%CI: 0.87-0.93), specificity was 0.94 (95% CI: 0.91-0.96). Meta regression revealed that the cutoff value and status of serum Tg were sources of heterogeneity for sensitivity, and the cutoff value was source of heterogeneity for specificity. Additionally, the cutoff value and status of serum Tg were sources of heterogeneity in the joint model. Subgroup analysis about cut-off value showed that the choice of 1 ng/mL had highest sensitivity, 40 ng/mL had highest specificity. At last, we arrived at the conclusion that FNA-Tg measurement had high specificity and sensitivity in the early detection of LNs metastases from PTC by our meta-analysis. The technique was simple and could be recommended to apply in any FNA facility, especially when LN were small-sized. Significantly, a better standardization of criteria for FNA-Tg detection and cutoff value was required to provide useful data and to improve management of PTC patients in the future.


Asunto(s)
Ganglios Linfáticos/metabolismo , Tiroglobulina/metabolismo , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/metabolismo , Biopsia con Aguja Fina , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Cuello , Sensibilidad y Especificidad , Cáncer Papilar Tiroideo/diagnóstico , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Ultrasonografía
15.
Biomater Sci ; 7(3): 938-950, 2019 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-30519686

RESUMEN

Aptamers are short single-stranded DNA or RNA molecules, which have recently been developed for potential broad applications such as clinical therapeutics, diagnosis and tumor-targeted drug delivery. However, the selection of specific aptamers is often unsatisfactory using the classical protein or cell-based SELEX. Herein, we modified the paired cell line approach to identify aptamers targeting leukemia cells expressing the CD33 antigen. Our strategy artfully used the same cells for negative (HEK293T cells) and positive (CD33 transfected-HEK293T cells) aptamer selections, and the negative selections were performed adequately before the positive selection to remove unspecific sequences. The advantages of this strategy are that it is fast and accurate, where only a few rounds of selection together with PCR amplifications are sufficient to obtain high binding affinity antigen-targeted aptamers. By using our modified approach, we successfully obtained the CD33-targeting aptamer S30, which could highly recognize the C2 domain of the CD33 antigen in vitro and in vivo. Moreover, the optimized aptamer S30-T1 (i.e., core region of S30) was conjugated with doxorubicin (Dox) to synthesize S30-T1-Dox conjugates, which could specifically inhibit CD33 positive acute myeloid leukemia HL-60 cell proliferation by arresting the cell cycle at the G2 phase. Thus, our modified approach can rapidly screen reliable, stable and high binding affinity aptamers for precise cancer treatment.


Asunto(s)
Aptámeros de Nucleótidos/metabolismo , Lectina 3 Similar a Ig de Unión al Ácido Siálico/metabolismo , Animales , Aptámeros de Nucleótidos/química , Carbocianinas/química , Proliferación Celular/efectos de los fármacos , ADN de Cadena Simple/química , ADN de Cadena Simple/metabolismo , Doxorrubicina/química , Doxorrubicina/farmacología , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Células HEK293 , Células HL-60 , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Microscopía Confocal , Imagen Óptica , Lectina 3 Similar a Ig de Unión al Ácido Siálico/genética , Distribución Tisular , Trasplante Heterólogo
16.
Oncol Lett ; 16(3): 3715-3725, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30127982

RESUMEN

The objective of the present study was to investigate the long non-coding RNA (lncRNA) and mRNA expression profiles that are associated with the invasion and metastasis of papillary thyroid carcinoma (PTC). Transwell invasion assays were used to screen three highly invasive sub-strains of the human PTC IHH4 cell line: IHH4-M1, IHH4-M2 and IHH4-M3. In addition, tumor-bearing nude mice were used to identify the invasive and metastatic capacity of the three sub-strains. Agilent lncRNA microarray chips were used to screen 795 differentially expressed lncRNAs and 788 differentially expressed mRNAs. A total of 10 lncRNAs and 10 mRNAs were randomly selected for RT-qPCR validation to confirm that the results were consistent with the microarray chips, suggesting that the results of the microarray chip analysis were relatively accurate. Gene ontology enrichment-based cluster analysis revealed that the differentially expressed genes were mainly associated with steroid biosynthesis, bioadhesion, intercellular adhesion and other metastasis-associated biological processes. The results of the pathway cluster analysis identified that the differentially expressed genes were associated with tumor metastasis-associated signaling pathways, including the cholesterol metabolic signaling pathway, the sterol regulatory element-binding protein signaling pathway and the integrin signaling pathway, suggesting that lncRNA may regulate PTC metastasis through various signaling pathways. The present study screened and constructed PTC metastasis-associated lncRNA and mRNA expression profiles, and it provides a molecular basis for the future study of high-risk molecular markers of PTC.

17.
Hum Pathol ; 81: 105-112, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29953894

RESUMEN

Some thyroid carcinomas (TCs) have an aggressive biological behavior and poor prognosis, and lacking of effective molecular markers is still the main obstacle for clinical stratified diagnosis and treatment of TC. The aim of the study was to discover the clinicopathological and prognostic implications of Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) and Hook microtubule tethering protein 1 (Hook1) expression in TC. The expression of SHP2 and Hook1 was detected by immunohistochemistry on tissue microarrays from 313 primary TCs who underwent surgery in January 2006 and January 2010 in Zhejiang Cancer Hospital. The χ2 test, Kaplan-Meier method, and Cox proportional-hazards regression models were used to analyze the associations between their expressions and clinicopathological features and prognosis. The expression rates of SHP2 and Hook1 in TC were 57.5% (180/313) and 22.0% (69/313), respectively. SHP2 was positively correlated with Hook1 in TC. SHP2 expression differed significantly by age, histologic variants, maximal tumor diameter, intrathyroidal dissemination, metastases, and disease stage (P < .05). Moreover, patients with high SHP2 expression had reduced risk for death of disease compared with those with low SHP2 expression (hazard ratio, 0.267; 95% confidence interval, 0.105-0.684; P = .006) in univariate analysis, but that multivariate analysis failed to suggest that SHP2 was an independent prognostic factor. Hook1 expression differed significantly by histologic variants, maximal tumor diameter, and intrathyroidal dissemination (P < .05). However, there was no significant correlation between Hook1 expression and outcome in TC (P > .05). Our results suggested that SHP2 may be a favorable indicator of prognosis in TC.


Asunto(s)
Biomarcadores de Tumor/análisis , Proteínas Asociadas a Microtúbulos/análisis , Proteína Tirosina Fosfatasa no Receptora Tipo 11/análisis , Cáncer Papilar Tiroideo/química , Neoplasias de la Tiroides/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Bases de Datos Factuales , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Cáncer Papilar Tiroideo/mortalidad , Cáncer Papilar Tiroideo/secundario , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Factores de Tiempo , Análisis de Matrices Tisulares , Carga Tumoral , Adulto Joven
19.
Int J Clin Exp Pathol ; 11(6): 3076-3083, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-31938434

RESUMEN

The simultaneous occurrence of papillary thyroid carcinoma (PTC) and mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is extremely rare, and many questions about their diagnosis and treatment remain unsolved. We report three cases of patients with both PTC and MALT thyroid lymphoma in the setting of Hashimoto thyroiditis (HT). Patient characteristics, pre-operative examination, histological findings, treatments, and follow-up were reviewed. In addition, we searched PubMed, Embase, and ISI Web of Science databases for articles published in the English language using the key words "lymphoma" and "thyroid", and we reviewed almost all the reports about simultaneous occurrence of PTC and MALT thyroid lymphoma. In conclusion, PTC and MALT thyroid lymphoma can exist concomitantly, especially in patients with longstanding HT. These rare cases highlight the importance of close communication between clinicians, histopathologists, and radiologists to ensure that such rare cases are not missed; a multidisciplinary approach and careful surveillance are also needed.

20.
Int J Clin Exp Pathol ; 11(11): 5359-5369, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-31949617

RESUMEN

This study sought to investigate minichromosome maintenance protein 3 (MCM3) and minichromosome maintenance protein 7 (MCM7) expression in salivary adenoid cystic carcinoma (SACC) samples, and to evaluate the relationship between clinicopathological characteristics and prognosis. The expressions of MCM3 and MCM7 were evaluated using immunohistochemistry of tissue sections from SACC patients, and statistical analyses were performed to evaluate the associations between MCM expression and clinicopathological variables and to analyze the disease-free survival (DFS) and prognostic factors. The positive expression rates of MCM3 and MCM7 in SACC were 98.8% and 96.6%, respectively. MCM3 expression correlated with T-stage and nerve invasion. MCM7 expression correlated with T-stage, adjacent tissue invasion, nerve invasion, and prognosis, and was negatively associated with DFS. However, there was no significant correlation between MCM3 expression and DFS. A kappa analysis demonstrated that MCM3 was closely associated with MCM7. MCM7 may be a favorable prognosis indicator in SACC.

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