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BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is receiving increased attention, frequently due to growing requirements for cosmetic incisions. Here, we report our initial experience and discuss the safety and efficacy of the innovative surgical working space suspension system for gasless TOETVA. METHODS: We retrospectively analyzed 75 consecutive patients for whom gasless TOETVA with our novel working space suspension system was used. This suspension system included self-developed retractors, a sterile bandage, and an anesthesia stand. We also improved some main surgical instruments in gasless TOETVA. RESULTS: The study included 75 patients who successfully underwent thyroidectomy and central neck dissection via gasless TOETVA. The mean operating time was 143.27 ± 34.60 min. The mean number of retrieved lymph nodes was 8.00 ± 5.39. Conversion to open surgery did not occur, nor did patients exhibit serious postoperative complications. Postoperative complications included 4 cases of transient recurrent laryngeal nerve (RLN) palsy, 9 of transient hypoparathyroidism, and 3 of transient mental nerve injury. One patient with subcutaneous fluid after surgery recovered after aspiration. Another patient with submental minor perforation recovered well after suturing. There was no evidence of specific complications related to self-designed retractors. CONCLUSION: The innovative working space suspension system for gasless TOETVA provided enough and stable working space and optimized the clarity of the surgical field without CO2-related complications.
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Hipoparatireoidismo , Cirurgia Endoscópica por Orifício Natural , Neoplasias da Glândula Tireoide , Paralisia das Pregas Vocais , Humanos , Tireoidectomia/efeitos adversos , Estudos Retrospectivos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Hipoparatireoidismo/complicações , Hipoparatireoidismo/cirurgia , Paralisia das Pregas Vocais/etiologia , Complicações Pós-Operatórias/etiologia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
As the first-generation targeted therapy, sorafenib remains an effective single-drug treatment for advanced hepatocellular carcinoma (HCC). Unfortunately, the existence of resistance restricts the long-term benefit of patients. UDP-glucose 6-dehydrogenase (UGDH) is the key enzyme of glucuronic acid metabolism which was largely reported in mediating drug systemic elimination. In this study, we explore its critical role in regulating sorafenib sensitivity. Here we find sorafenib exposure could activate glucuronic acid metabolism, accompanied with the elevated expression of UGDH. Interference with the route by silencing UGDH could boost HCC cells sensitivity to sorafenib. Meanwhile, the analysis of HCC patients with sorafenib treatment displayed that low UGDH expression predicted superior prognosis. Further screening assay suggested that unfolded protein response (UPR) involves in UGDH silencing-mediated apoptosis. Xenograft model confirmed that combined UGDH intervention could significantly improve sorafenib efficacy. Our results reveal the impact of sorafenib exposure on glucuronic acid metabolism reprogramming and provide UGDH as a promising target to improve sorafenib efficacy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Resposta a Proteínas não Dobradas , Uridina Difosfato Glucose Desidrogenase , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Ácido Glucurônico/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Uridina Difosfato Glucose Desidrogenase/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Some surgeons believe that dissection posterior to the right recurrent laryngeal nerve lymph node (PRRLN-LN) is unnecessary for the low metastasis rate and high complication risk. However, persistent metastatic lymph nodes may have a higher recurrence rate, surgical risk, and complications. Thus, it is important to distinguish patients who require PRRLN-LN dissection. To identify the risk factors for lymph nodes posterior to the right recurrent laryngeal nerve metastasis (LN-prRLN) and establish a scoring system to help determine whether PRRLN-LN dissection is required in patients with papillary thyroid carcinoma. METHODS: 821 participants were randomly allocated to the development and validation cohorts in a 2:1 ratio. A nomogram-based predictive model for LN-prRLN was established based on the risk factors identified in the development cohort. RESULTS: LN-prRLN was diagnosed pathologically in 124 of 821 patients (15.1%) from the entire cohort. Multivariate analysis identified age (odds ratio [OR], 0.964; 95% CI, 0.945-0.983; P < .001), tumor size (OR, 1.536; 95% CI, 1.135-2.079; P = .005), extrathyroidal extension (OR 2.271, 95% CI, 1.368-3.770; P = .002), clinically involved right central compartment lymph node metastasis (OR 1.643, 95% CI, 1.055-2.559; P = .028), and right lateral lymph node metastasis (OR 4.271, 95% CI, 2.325-7.844; P < .001) as the predictors of LN-prRLN. A risk model was established and well validated. Calibration curves to evaluate the nomogram in both the development and validation cohorts revealed a concordance index of 0.756 ± 0.058 and 0.745 ± 0.042, respectively. CONCLUSION: Our scoring system may be useful for helping the surgeons decide which patients should undergo the dissection of PRRLN-LN.
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Carcinoma Papilar , Carcinoma , Neoplasias da Glândula Tireoide , Carcinoma/cirurgia , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/cirurgia , Humanos , Linfonodos , Esvaziamento Cervical , Recidiva Local de Neoplasia , Nervo Laríngeo Recorrente , Estudos Retrospectivos , Câncer Papilífero da Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
BACKGROUND: The level VI lymph nodes are anatomically connected to the level VII lymph nodes and papillary thyroid carcinoma (PTC) can metastasis to both regions. The aim of this study was to identify clinicopathologic factors associated with level VII lymph node metastasis. METHODS: Between March 2015 and September 2016, a total of 275 consecutive patients were operated on for PTC with prophylactic level VII dissection at the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, ZheJiang, China. Patients with PTC were performed via video-assisted approach. Multivariate logistic regression analysis was performed to evaluate the associations between clinicopathologic factors. RESULTS: Of the 275 subjects enrolled in this study, 79 patients (28.73%) showed lymph node metastasis to the level VII. The multivariate logistic regression analysis showed ultrasonography-positive lymph nodes (p < 0.001), the location of primary carcinoma (p = 0.002) and hashimoto thyroiditis (HT) (p = 0.04) were associated with level VII lymph node metastasis. CONCLUSIONS: Based on the results of our study, we considered central-compartment lymph node dissection (CLND) as an integral strategy. On the basis of surgery safety, transcervical level VII lymph node dissection could be considered for PTC patients with high risk factors such as ultrasonography-positive lymph nodes, tumor located in middle and lower thirds of the thyroid lobe and the patients without HT. In future, prognostic significance of level VII lymph node dissection should be evaluated through long-term surveillance.
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Linfonodos/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , China , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Prognóstico , Fatores de Risco , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
The ETS family of transcription factors exemplifies current uncertainty in how eukaryotic genetic regulators with overlapping DNA sequence preferences achieve target site specificity. PU.1 and Ets-1 represent archetypes for studying site discrimination by ETS proteins because their DNA-binding domains are the most divergent in sequence, yet they share remarkably superimposable DNA-bound structures. To gain insight into the contrasting thermodynamics and kinetics of DNA recognition by these two proteins, we investigated the structure and dynamics of site discrimination by their DNA-binding domains. Electrophoretic mobilities of complexes formed by the two homologs with circularly permuted binding sites showed significant dynamic differences only for DNA complexes of PU.1. Free solution measurements by dynamic light scattering showed PU.1 to be more dynamic than Ets-1; moreover, dynamic changes are strongly coupled to site discrimination by PU.1, but not Ets-1. Interrogation of the protein/DNA interface by DNA footprinting showed similar accessibility to dimethyl sulfate for PU.1/DNA and Ets-1/DNA complexes, indicating that the dynamics of PU.1/DNA complexes reside primarily outside that interface. An information-based analysis of the two homologs' binding motifs suggests a role for dynamic coupling in PU.1's ability to enforce a more stringent sequence preference than Ets-1 and its proximal sequence homologs.
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DNA/química , Proteína Proto-Oncogênica c-ets-1/química , Proteínas Proto-Oncogênicas/química , Transativadores/química , Sítios de Ligação , DNA/metabolismo , Modelos Moleculares , Ligação Proteica , Estrutura Terciária de Proteína , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Transativadores/metabolismoRESUMO
PURPOSE: Video-assisted lateral neck dissection (VALND) for papillary thyroid carcinoma (PTC) with lateral neck lymph node metastases (LNM) has been described previously, however, the advantages and drawbacks of VALND have not been demonstrated in previous studies. The aim of this study was to compare the surgical outcomes of video-assisted and open lateral neck dissection for PTC with lateral neck LNM. MATERIALS AND METHODS: Between May 2013 and November 2014, 92 consecutive patients with PTC and lateral neck lymph node metastases underwent total thyroidectomy with central compartment neck dissection and unilateral lateral neck dissection. These included 54 individuals who underwent video-assisted surgery, and 38 in whom an open approach was used. The two groups were retrospectively compared with respect to their clinicopathological characteristics, surgical outcomes and oncological completeness. RESULTS: The mean follow-up period was 18.6months. The mean tumor size, tumor stage, mean numbers of retrieved lymph nodes, mean postoperative serum thyroglobulin levels, complication rates, and mean postoperative hospital stay were similar between the two groups. The mean operation time was longer (p=0.0001) and mean age was lower (p=0.0354) in the video-assisted group. The cosmetic results, evaluated by numerical scale and verbal response scale, were in favor of the video-assisted group (p=0.0003 and p<0.0001, respectively). CONCLUSIONS: The safety and oncological completeness of VALND was similar to that of open procedures, but the VALND resulted in improved cosmetic results. VALND is an effective treatment for the selected cases of PTC with lateral neck LNM.
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Carcinoma Papilar/cirurgia , Esvaziamento Cervical/métodos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Cirurgia Vídeoassistida/métodos , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Carcinoma Papilar/patologia , Estética , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
Papillary thyroid cancer (PTC) is an endocrine malignant tumor with a rapidly increasing incidence in recent years. Although the disease prognosis is good in general, there are still some patients with local invasion, distant metastasis and recurrence, which make treatment difficult. This study aimed to investigate the effect of a novel circRNA, circPCNXL2, on the progression of PTC and to explore its underlying mechanism in PTC. In this study, we found that the expression of circPCNXL2 was upregulated in PTC, which was positively correlated with the proliferation of PTC, and knockdown of circPCNXL2 enhanced the cell cycle arrest of PTC and promoted cell apoptosis. Further research revealed that circPCNXL2 can interact with ACC1, a key enzyme of cellular lipid metabolism, and then promote cell growth by affecting the de novo synthesis of fatty acids. Mechanistically, circPCNXL2 enhances the protein activity of ACC1 by reducing ACC1 phosphorylation of ser 79, thereby promoting the formation of fatty acids such as free fatty acids and triglycerides in cells to meet the energy metabolism needs of cells and promote cell growth. In a nude mouse subcutaneous tumorigenesis model, knockdown of circPCNXL2 inhibited the growth of PTC tumors while high levels of circPCNXL2 expression promoted tumor proliferation. This study revealed that circPCNXL2 regulates PTC lipid metabolism by enhancing the protein activity of ACC1 and identified a novel signaling pathway, the circPCNXL2-ACC1 axis, that can be targeted for the treatment of PTC.
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Acetil-CoA Carboxilase , Proliferação de Células , Progressão da Doença , Ácidos Graxos , Camundongos Nus , RNA Circular , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Animais , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Camundongos , Acetil-CoA Carboxilase/metabolismo , Acetil-CoA Carboxilase/genética , Ácidos Graxos/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Linhagem Celular Tumoral , Masculino , Regulação Neoplásica da Expressão Gênica , Feminino , Apoptose , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Camundongos Endogâmicos BALB CRESUMO
The mapping of DNA footprints and affinity cleavage sites for small DNA ligands is affected by the choice of sequencing chemistry and end label, and the potential for indexing errors can be significant when mapping small ligand-DNA interactions. Described here is a mechanism for avoiding such errors based on a summary of standard labeling, cleavage, and indexing chemistries and a comparison among them for analysis of these interactions by capillary electrophoresis. The length dependence of the difference between Sanger and Maxam-Gilbert indexing is examined for a number of duplexes of mixed sequence.
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Cromatografia de Afinidade/métodos , Pegada de DNA/métodos , Eletroforese Capilar/métodos , Hidróxidos , LigantesRESUMO
Parathyroid gland transplantation into the sternocleidomastoid muscle is effective, but it is not possible to confirm transplant survival with this method. In this study, we evaluated parathyroid autotransplantation into the brachioradialis muscle and its survival rate. OBJECTIVES: To evaluate autologous parathyroid gland left forearm brachioradial muscle transplantation and its survival rate. SUMMARY BACKGROUND DATA: The most commonly used transplantation site is the sternocleidomastoid muscle, but transplant survival cannot be confirmed using this method. Autologous parathyroid gland left forearm brachioradial muscle transplantation solves this problem, and we evaluate the transplant survival using this method. METHODS: We followed-up patients who underwent thyroidectomy and autologous parathyroid left forearm brachioradial muscle transplantation in our center from September 2013 to January 2018. The last follow-up date was January 2021; all enrolled patients underwent at least 3 years of follow-up. We calculated the transplant survival rate at several time points. RESULTS: We evaluated 238 transplanted cases, for which the long-term survival rate was 85.7% (204/238), and the short-term survival rate was 86.1% (205/238). Sixty-five cases had two parathyroid glands transplanted into the left forearm brachioradialis muscle. The long-term survival rate was 92.3% (60/65), and the short-term survival rate was 95.4% (62/65). CONCLUSIONS: Autologous parathyroid gland left brachioradialis transplantation is a reliable, measurable method with good survival rate, and we recommend this method for consideration for transplanting parathyroid glands in thyroidectomy.
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Hipoparatireoidismo , Glândulas Paratireoides , Humanos , Glândulas Paratireoides/transplante , Seguimentos , Antebraço/cirurgia , Transplante Autólogo/métodos , Tireoidectomia/métodosRESUMO
Background: The development of transoral endoscopic vestibular approach thyroidectomy (TOETVA) has been limited by inherent defects, such as mental nerve injury and carbon dioxide (CO2)-related complications. Herein, we proposed a new technique without CO2 called gasless submental-transoral combined approach endoscopic thyroidectomy (STET) to solve the problems in TOETVA. Methods: We reviewed 75 patients who successfully underwent gasless STET using novel instruments at our institution from November 2020 to November 2021. A main incision of approximately 2 cm was made in the natural submental crease line and then combined with two vestibule incisions to complete the procedure. Demographic data, surgical technique and perioperative outcomes were retrospectively recorded. Results: Thirteen male and sixty-two female patients with a mean age of 34.0 ± 8.1 years were enrolled in this study. Sixty-eight patients had papillary thyroid carcinomas and seven had benign nodules. We successfully performed all gasless STET without conversion to open surgery. The average postoperative hospital stay was 4.2 ± 1.8 days. One transient recurrent laryngeal nerve injury and two transient hypoparathyroidisms were observed. Three patients complained of slight lower lip numbness on the first postoperative day. One case of lymphatic fistula, subcutaneous effusion, and incision swelling occurred each, all of which were conservatively cured. One patient developed a recurrence six months after surgery. Conclusions: Gasless STET using our own designed suspension system is technically safe and feasible with reasonable operative and oncologic results.
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Purpose: The aim of this study was to investigate the value of S-Detect for predicting the malignant risk of cytologically indeterminate thyroid nodules (CITNs). Methods: The preoperative prediction of 159 CITNs (Bethesda III, IV and V) were performed using S-Detect, Thyroid Imaging Reporting and Data System of American College of Radiology (ACR TI-RADS) and Chinese TI-RADS (C-TIRADS). First, Linear-by-Linear Association test and chi-square test were used to analyze the malignant risk of CITNs. McNemar's test and receiver operating characteristic curve were used to compare the diagnostic efficacy of S-Detect and the two TI-RADS classifications for CITNs. In addition, the McNemar's test was used to compare the diagnostic accuracy of the above three methods for different pathological types of nodules. Results: The maximum diameter of the benign nodules was significantly larger than that of malignant nodules [0.88(0.57-1.42) vs 0.57(0.46-0.81), P=0.002]. The risk of malignant CITNs in Bethesda system and the two TI-RADS classifications increased with grade (all P for trend<0.001). In all the enrolled CITNs, the diagnostic results of S-Detect were significantly different from those of ACR TI-RADS and C-TIRADS, respectively (P=0.021 and P=0.007). The sensitivity and accuracy of S-Detect [95.9%(90.1%-98.5%) and 88.1%(81.7%-92.5%)] were higher than those of ACR TI-RADS [87.6%(80.1%-92.7%) and 81.8%(74.7%-87.3%)] (P=0.006 and P=0.021) and C-TIRADS [84.3%(76.3%-90.0%) and 78.6%(71.3%-84.5%)] (P=0.001 and P=0.001). Moreover, the negative predictive value and the area under curve value of S-Detect [82.8% (63.5%-93.5%) and 0.795%(0.724%-0.855%)] was higher than that of C-TIRADS [54.8%(38.8%-69.8%) and 0.724%(0.648%-0.792%] (P=0.024 and P=0.035). However, the specificity and positive predictive value of S-Detect were similar to those of ACR TI-RADS (P=1.000 and P=0.154) and C-TIRADS (P=1.000 and P=0.072). There was no significant difference in all the evaluated indicators between ACR TI-RADS and C-TIRADS (all P>0.05). The diagnostic accuracy of S-Detect (97.4%) for papillary thyroid carcinoma (PTC) was higher than that of ACR TI-RADS (90.4%) and C-TIRADS (87.8%) (P=0.021 and P=0.003). Conclusion: The diagnostic performance of S-Detect in differentiating CITNs was similar to ACR TI-RADS and superior to C-TIRADS, especially for PTC.
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Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia/métodos , Estudos RetrospectivosRESUMO
Polyamides (PAs) are distamycin-type ligands of DNA that bind the minor groove and are capable of sequence selective recognition. This capability provides a viable route to their development as therapeutics. Presented here is a simple and convenient fluorescence assay for PA-DNA binding. PAs are titrated into a sample of a hairpin DNA featuring a TAMRA dye attached to an internal dU near the PA binding site. In a study of 6 PAs, PA binding leads to a steady reproducible decrease in fluorescence intensity that can be used to generate binding isotherms. The assay works equally well with both short (6- to 8-ring) and long (14-ring) PAs, and K(d) values ranging from approximately 1 nM to at least 140 nM were readily obtained using a simple monochromator or filter configuration. Competition assays provide a means to assessing possible dye interference, which can be negligible. The assay can also be used to determine PA extinction coefficients and to measure binding kinetics; thus, it is an accessible and versatile tool for the study of PA properties and PA-DNA interactions.
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Bioensaio/métodos , DNA/metabolismo , Nylons/metabolismo , Espectrometria de Fluorescência , Sequência de Bases , DNA/química , Cinética , Nylons/síntese química , Nylons/química , Rodaminas/químicaRESUMO
PURPOSE: To compare the clinical efficacy and safety of pre-indwelling double-J stents versus ureteral catheters for artificial hydronephrosis in percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: We retrospectively analyzed the data of 1,258 patients who underwent PCNL for kidney stones from August 2017 to July 2020 in our hospital. Among them, 682 patients had double-J stents inserted (DJ group) and 576 patients had ureteral catheters (UC group). We analyzed baseline patient characteristics, perioperative outcomes, and complications in both groups. RESULTS: The puncture success rate was 97.9% and 97.4% in the DJ and UC groups, respectively (p>0.05). The operation time was 74.5±37.8 minutes in the DJ group compared with 80.8±38.5 minutes in the UC group (p=0.004). The total stone-free rate in the DJ and UC groups was 80.5% and 78.7%, respectively (p>0.05). The incidence of perioperative complications was relatively low in both groups and showed no obvious differences. In the subgroup analysis, the operation time for patients with no obvious or mild hydronephrosis preoperatively was significantly shorter in the DJ group than in the UC group (p<0.05). However, there were no significant differences among patients who had moderate or severe hydronephrosis preoperatively. CONCLUSIONS: It is feasible, safe, and effective to create artificial hydronephrosis by insertion of pre-indwelling double-J stents in PCNL surgery. Furthermore, the operation time was significantly shorter in the DJ group than in the group with pre-indwelling ureteral catheters, especially in patients who had no obvious or mild hydronephrosis preoperatively.
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Hidronefrose , Cálculos Renais , Nefrolitotomia Percutânea , Humanos , Hidronefrose/etiologia , Hidronefrose/cirurgia , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/efeitos adversos , Estudos Retrospectivos , Stents/efeitos adversos , Cateteres Urinários/efeitos adversosRESUMO
Papillary thyroid cancer (PTC) is a common endocrine tumor with a rapidly increasing incidence in recent years. Although the majority of PTCs are relatively indolent and have a good prognosis, a certain proportion is highly aggressive with lymphatic metastasis, iodine resistance, and easy recurrence. Circular RNAs (circRNAs) are a class of noncoding RNAs that are linked to a variety of tumor processes in several cancers, including PTC. In the current study, circRNA high-throughput sequencing was performed to identify alterations in circRNA expression levels in PTC tissues. circTIAM1 was then selected because of its increased expression in PTC and association with apoptosis, proliferation, and migration of PTC cells in vitro and in vivo. Mechanistically, circTIAM1 acted as a sponge of microRNA-646 and functioned in PTC by targeting miR-646 and heterogeneous ribonucleoprotein A1. Fluorescence in situ hybridization and dual-luciferase reporter assays further confirmed these connections. Overall, our results reveal an important oncogenic role of circTIAM1 in PTC and may represent a potentially therapeutic target against PTC progression.
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Autophagy is a highly conserved catabolic process to maintain cellular homeostasis. However, dysfunctional autophagy contributes to a context-dependent role in cancer. Here, we clarified the exact role of autophagy modulated by the scavenger receptor lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in esophageal cancer (EC). A comprehensive analysis in various cancers displayed that LOX-1 was upregulated the most in EC tissues and associated with poor prognosis of patients. Deletion of LOX-1 ex vivo and in vivo suppresses EC development by inducing autophagic cell death. Receptor for activated C kinase 1 (RACK1) was identified as a signal adapter of LOX-1, which incented RAS/MEK/ERK pathway and TFEB nuclear export signal and safeguarded tumorigenesis. A sulfated polysaccharide fucoidan extracted from brown seaweed was found to bind with LOX-1 and mediate its proteasomal degradation but not the lysosome pathway, leading to autophagy-related cell death in EC. These results reveal a central contribution of LOX-1 to EC development and provide genetic ablation or bioactive polysaccharide as an effective intervention for EC therapy.
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Neoplasias Esofágicas , Receptores Depuradores Classe E/metabolismo , Autofagia , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Lipoproteínas LDL/metabolismo , Lisossomos/metabolismo , Receptores Depuradores Classe E/genéticaRESUMO
Papillary thyroid cancer (PTC) has a continuously increasing incidence and imposes a heavy medical burden to individuals and society due to its high proportion of lymph node metastasis and recurrence in recent years. Circular RNAs, a class of noncoding RNAs, participate in the progression of many cancers, but the role of circRNAs in PTC is still rarely reported. In this study, circRNA deep sequencing was performed to identify differentially expressed circRNAs in PTC. CircRUNX1 was selected for its high expression in PTC, and circRUNX1 silencing was directly associated with the week potential for migration, invasion and proliferation of PTC in vivo and in vitro. Fluorescence in situ hybridization (FISH) was further used to confirm the cytoplasmic localization of circRUNX1, indicating the possible function of circRUNX1 as a ceRNAs in PTC progression through miRNA binding. MiR-296-3p was then confirmed to be regulated by circRUNX1 and to target DDHD domain containing 2 (DDHD2) by luciferase reporter assays. The strong antitumor effect of miR-296-3p and the tumor-promoting effect of DDHD2 were further investigated in PTC, indicating that circRUNX1 modulates PTC progression through the miR-296-3p/DDHD2 pathway. Overall, circRUNX1 plays an oncogenic role in PTC and provides a potentially effective therapeutic strategy for PTC progression.
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Subunidade alfa 2 de Fator de Ligação ao Core/genética , MicroRNAs/metabolismo , Fosfolipases/biossíntese , RNA Circular/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Progressão da Doença , Humanos , MicroRNAs/genética , Metástase Neoplásica , Fosfolipases/genética , Fosfolipases/metabolismo , RNA Circular/genética , Câncer Papilífero da Tireoide/genética , TransfecçãoRESUMO
Nephrolithiasis is a very common disease in which cell-crystal adhesion is an essential mechanism for kidney stone formation. This study has explored the anti-adhesion function of the microRNA, miR-34a, by targeting CD44, a cell surface receptor, in human renal epithelial (HK-2) cells. The expression of CD44 was monitored by qPCR and western blot. A luciferase assay validated the target of miR-34a in CD44 3' UTR. Immunofluorescence staining under confocal microscopy was used to detect the cell-crystal adhesion effects in vitro. Pizzolato staining was performed to examine the adhesion role of miR-34a in vivo. In HK-2 cells, miR-34a was down-regulated and CD44 was up-regulated when exposed to calcium oxalate monohydrate crystals. Moreover, miR-34a negatively regulated the expression of CD44. According to the luciferase report assay, miR-34a direct targeted a binding site in the CD44 3'UTR. In vitro experiments, miR-34a overexpression inhibited CD44 expression and cell-crystals adhesion; whereas CD44 overexpression showed reversed results. Furthermore, miR-34a suppressed cell-crystals adhesion and stone formation in vivo. These findings indicate that miR-34a targets CD44 in HK-2 cells and inhibits cell-crystal adhesion both in vitro and in vivo. Based on these results, miR-34a may be a potential therapeutic target for renal stone disease.
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Adesão Celular/genética , Células Epiteliais/patologia , Receptores de Hialuronatos/genética , Cálculos Renais/genética , MicroRNAs/metabolismo , Oxalato de Cálcio/metabolismo , Linhagem Celular , Regulação para Baixo , Células Epiteliais/metabolismo , Perfilação da Expressão Gênica , Humanos , Cálculos Renais/tratamento farmacológico , Cálculos Renais/patologia , MicroRNAs/agonistas , Reação em Cadeia da Polimerase em Tempo RealRESUMO
N6-methyladenosine (m6A) is the most prevalent modification of RNA in mammals. m6A RNA methylation levels are dynamically regulated by m6A RNA methylation regulators. While increasing evidence has suggested that m6A RNA methylation is vital in the initiation and progression of human carcinoma, little is known about the expression and effect of m6A RNA methylation regulators in differentiated thyroid carcinoma (DTC). Herein, we demonstrate that most of the thirteen main m6A RNA methylation regulators are differentially expressed in DTC tissues and normal thyroid tissues. Based on consensus clustering of m6A RNA methylation regulators, DTC cases were divided into two subgroups (TC1 and TC2). Compared with the TC1 subgroup, the TC2 subgroup was associated with a poorer prognosis, older age, higher T grade, higher N grade and higher TNM stage. The results indicated that alteration of m6A RNA methylation regulators was closely related to DTC. We further established a risk signature of four m6A RNA methylation regulators that could evaluate prognosis and clinicopathological features in DTC. Finally, the results of the TCGA analysis were verified by other cohorts from Gene Expression Omnibus (GEO) database. In conclusion, m6A RNA methylation regulators play a crucial part in the progression of DTC and are potentially useful for evaluating the prognosis and providing potential novel insights into treatment strategies.
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BACKGROUND: Transurethral resection of the prostate (TURP) was considered the golden standard to treat benign prostatic hyperplasia (BPH) for decades. However, TURP was associated with low efficiency to alleviate the lower urinary tract symptoms (LUTS) and a significantly higher risk of bladder neck contracture (BNC) for patients with small-volume BPH. Our study aims to compare the therapeutic effect of a transurethral split of the prostate (TUSP) with TURP for patients with small-volume BPH (<30 mL). METHODS: In this study, 101 small-volume BPH patients were randomly divided into two groups (TUSP and TURP group). The patient's baseline characteristics and perioperative outcomes were recorded. The follow-up was done at six months, one year and two years after surgical treatment. RESULTS: No significant differences were observed between the two groups for the baseline characteristics, including age, prostate volume, prostate-specific antigen (PSA) level, concurrent disease, post-void residual (PVR), maximum urinary flow rate (Qmax), international prostate symptoms score (IPSS), and quality of life (QoL) score. The operative time and hemoglobin decrease were significantly lower in the TUSP group compared to the TURP group. However, no significant differences were observed between both groups for catheterization time, postoperative hospital stay, and incidence of transurethral resection syndrome (TURS). However, of the late complications, the incidence of BNC in the TUSP group was significantly lower than the TURP group. No significant differences were found between both groups for other complications, including postoperative bleeding, micturition urgency, micturition frequency, micturition pain, urinary tract infection, recatheterization, transient incontinence, and continuous incontinence. Follow-up results showed that the IPSS of the TUSP group was significantly lower than the TURP group, while the Qmax of the TUSP group was significantly higher than the TURP group. CONCLUSIONS: This study shows that TUSP may be an efficient and safe treatment for small-volume BPH (<30 mL) with a lower incidence of postoperative BNC and better longtime clinical outcomes than TURP. It suggested that TUSP could be an ideal treatment choice for small-volume BPH.
RESUMO
PURPOSE: To explore the efficacy and safety of flexible ureteroscopic incision and drainage and flexible ureteroscopic lithotripsy for treatment of parapelvic renal cyst combined with secondary renal stone. MATERIALS AND METHODS: 28 patients with parapelvic renal cyst combined with renal stone were treated with flexible ureteroscopic incision and drainage and flexible ureteroscopic lithotripsy simultaneously from May 2010 to December 2016. The follow-up was made 1, 3, 6?12 months and 2 years after surgical treatment in our outpatient department. Ultrasonic examination and CT were used to detect the residual stone and recurrence of renal cyst. RESULTS: The mean age of the patients was 45.3 ± 18.6 years. The average size of the parapelvic renal cysts was 4.3 ± 1.6 cm, including 27 with Bosniak category I and 1 patient with Bosniak II renal cysts. The mean size of the renal stones was 14.3 ± 3.9 mm. The mean operative time was 53.4 ± 20.7 minutes and the mean blood loss was 10.8 ± 5.6 ml. The mean hospitalization time was 3.2 ± 0.7 days. No severe complications were encountered. The complications included transient fever ( > 38°C) in 3 patients and significant hemorrhage in 1 patient. The stone-free rates one month and three months after operation were 89.3% and 96.4%, respectively. During the 2 years follow-up, the cyst recurrence rate was 14.3% and the stone recurrence rate was 7.1%. CONCLUSION: In this study, we firstly demonstrated that it is safe and effective to treat both renal stone and parapelvic renal cyst simultaneously by flexible ureteroscopic lithotripsy and flexible ureteroscopic incision and drainage, with satisfactory stone free rate and low cyst recurrence rate.