RESUMO
OBJECTIVES: To determine the efficacy and safety of nintedanib in patients with anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5+ DM-ILD). METHODS: The study was a retrospective cohort design that evaluated patients with anti-MDA5+ DM who either received or did not receive nintedanib. Clinical symptoms, laboratory tests, and survival were compared in the two groups using a propensity score-matched analysis. The primary endpoint was mortality, while adverse events were recorded descriptively. RESULTS: After propensity score matching, 14 patients who received nintedanib (nintedanib+ group) and matched 56 patients who did not receive nintedanib (nintedanib- group) were enrolled. Compared with the nintedanib- group, the nintedanib+ group had a lower incidence of heliotrope and arthritis, higher lymphocyte counts, lower serum ferritin levels, and greater 12-month survival (all p<0.005). Although lung function, HRCT score, and lung VAS were not statistically different between the two groups, the longitudinal study showed significant improvement in HRCT scores (p=0.028) and pulmonary VAS (p=0.019) in the nintedanib+ group. Adverse events occurred in 28.6% of patients, with the most common adverse event with nintedanib being diarrhoea. CONCLUSIONS: Nintedanib may be effective for improving clinical symptoms, laboratory parameters, lung lesions, and survival in anti-MDA5+ DM. Diarrhoea was the most common adverse event associated with nintedanib, although the drug was well tolerated by most patients.
Assuntos
Dermatomiosite , Indóis , Doenças Pulmonares Intersticiais , Humanos , Prognóstico , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dermatomiosite/diagnóstico , Estudos Retrospectivos , Progressão da Doença , Estudos Longitudinais , Helicase IFIH1 Induzida por Interferon , Autoanticorpos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Diarreia/complicaçõesRESUMO
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by progressive cognitive dysfunction and an impaired ability to carry out daily life functions. Mitochondrial dysfunction and ß-amyloid (Aß) deposition are the most common causes of AD. Antioxidants have been shown to delay brain aging and AD development; however, it remains unknown whether the antioxidant peptide SS31 can protect mitochondrial and synaptic function and delay the progression of behavioral deficits in early-stage AD in vivo. Therefore, in this study we compared mitochondrial and synaptic changes, as well as the protective effects of SS31, in APP/PS1 transgenic mice and C57BL/6J control mice. The APP/PS1 transgenic mice exhibited elevated expression of Aß40/Aß42 and mitochondrial fission protein DLP1 and reduced expression of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) reductions, as well as increased levels of neuronal apoptosis and ROS in the hippocampus, and long-term treatment with SS31 reversed these effects. Furthermore, the cognitive impairments observed in APP/PS1 transgenic mice were reversed by SS31 treatment. Our findings show that SS31 lowers ROS and Aß levels, protecting mitochondrial homeostasis and synaptic integrity, and ultimately improving behavioral deficits in early-stage AD. This suggests that SS31 is a potential pharmacological agent for treating or slowing the progression of AD.
Assuntos
Doença de Alzheimer , Placa Amiloide , Camundongos , Animais , Placa Amiloide/tratamento farmacológico , Placa Amiloide/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Camundongos Transgênicos , Mitocôndrias/metabolismo , Antioxidantes/farmacologia , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Presenilina-1/metabolismoRESUMO
Cancer stem-like cells (CSCs), which play an important role in tumor initiation and progression, have been identified in many cancers. Diallyl trisulfide (DATS) is an organosulfur compound extracted from garlic with anticancer activities. Nanog is a transcription factor responsible for maintaining the stemness of CSCs, but its role in the DATS-induced attenuation of renal CSC properties is unknown. In this study, renal CSCs were enriched from human renal cancer cell lines 786-O and ACHN cultured in a serum-free medium (SFM). The properties of CSCs were analyzed by evaluating the ability of the cells in sphere formation and measuring the expression of stem cell markers. We found that downregulation of Nanog inhibited renal CSC properties. DATS suppressed renal CSC activities by reducing tumorsphere formation, decreasing stem cell markers including Nanog, CD44, ALDH1A1, and Oct4, inhibiting cell proliferation and promoting apoptosis. We further revealed that overexpression of Nanog reversed the suppressive effects of DATS on renal CSCs. Taken together, our results demonstrated that DATS inhibited renal CSCs by suppressing Nanog. These novel findings suggested that, through Nanog targeting, DATS can potentially be used as an anti-tumor agent for renal cancer.
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Compostos Alílicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Linhagem Celular Tumoral , Sulfetos/farmacologia , Compostos Alílicos/farmacologia , Carcinoma de Células Renais/patologia , Apoptose , Neoplasias Renais/patologia , Células-Tronco Neoplásicas , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Proteína Homeobox Nanog/farmacologiaRESUMO
OBJECTIVES: This study aimed to identify whether apparent diffusion coefficient (ADC) values and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters are helpful in distinguishing mesorectal tumor deposits (TD) from metastatic lymph nodes (MLN) in rectal cancer (RC). METHODS: Thirty patients (59 lesions, including 30 TD and 29 MLN) with RC who underwent pretreatment-MRI between February 2016 and August 2018 were enrolled. The morphological features, ADC values, and semi-quantitative parameters of DCE-MRI, including relative enhancement (RE), maximum enhancement (ME), maximum relative enhancement (MRE), time to peak (TTP), wash-in rates (WIR), wash-out rates (WOR), brevity of enhancement (BRE), and area under the curve (AUC) were measured on lesions (TD or MLN) and RC. The parameters were compared between TD and MLN, tumor with and without TD group by using Fisher's exact test, independent-samples t-test, and Mann-Whitney U test. The ratio (lesion-to-tumor) of the parameters was compared between TD and MLN. Receiver operating characteristic curve analysis and binary logistic regression analysis were used to assess the diagnostic ability of single and combined metrics for distinguishing TD from MLN. RESULTS: The morphological features, including size, shape, and border, were significantly different between TD and MLN. TD exhibited significantly lower RE, MRE, RE-ratio, MRE-ratio, ADCmin-ratio, and ADCmean-ratio than MLN. RE-ratio showed the highest AUC (0.749) and accuracy (77.97%) among single parameters. The combination of DCE-MRI and DWI parameters together showed higher diagnostic efficiency (AUC = 0.825). CONCLUSIONS: Morphological features, ADC values, and DCE-MRI parameters can preoperatively help distinguish TD from MLN in RC. KEY POINTS: ⢠DWI and DCE-MRI can facilitate early detection and distinguishing mesorectal TD (tumor deposits) from MLN (metastatic lymph nodes) in rectal cancer preoperatively. ⢠TD has some specific morphological features, including relatively larger size, lower short- to long-axis ratio, irregular shape, and ill-defined border on T2-weighted MR images in rectal cancer. ⢠The combination of ADC values and semi-quantitative parameters of DCE-MRI (RE, MRE) can help to improve the diagnostic efficiency of TD in rectal cancer.
Assuntos
Extensão Extranodal , Neoplasias Retais , Humanos , Meios de Contraste/farmacologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Estudos RetrospectivosRESUMO
Identification of novel markers would contribute to the individualised risk assessment and development of a risk prediction model. This study aimed to investigate the role of the C-reactive protein to albumin ratio (CAR) in predicting surgical site infection (SSI) following instrumented posterior lumbar interbody fusion (PLIF) of lumbar degenerative diseases. This study enrolled patients who underwent PLIF and instrumentation for treatment of lumbar degenerative diseases between 2015 and 2020. Electronic medical records were inquired for data collection, with follow-up register for identifying SSI cases. The optimal cut-off for CAR was determined by constructing the receiver operator characteristic (ROC) curve. Patients with high- or low-CAR value were compared using the univariate analyses, and the association between CAR and the risk of SSI was investigated using multivariate logistics regression analysis. A total of 905 patients were enrolled, twenty-nine (3.2%) had developed an SSI with 72.4% occurring during index hospitalisation, and 11 (1.2%) had deep and 18 (2.0%) superficial SSIs. An SSI was associated with additional 10.7 days of index total hospital stay (P = .001). The CAR was 0-5.43 (median, 0.05), and the optimal cut-off was 0.09 and area under the curve was 0.720 (P < .001). 336 (37.1%) patients had a CAR ≥0.09 and 22 (6.5%) developed an SSI, with a crude risk of 5.6 relative to those with a low CAR. The multivariate analyses showed CAR ≥0.09 was associated with 8.06-fold increased risk of SSI, together with diabetes (P = .018), while hypertension was identified as a protective factor (OR, 0.34; 95%CI, 0.11-1.00, P = .049). High CAR is found to significantly predict the incident SSI following instrumented PLIF of lumbar degenerative diseases, and can be considered as a useful index in practice only after it is verified by future high-level evidences.
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Fusão Vertebral , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/etiologia , Proteína C-Reativa , Fusão Vertebral/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVES: To evaluate the efficacy and safety of marking ground glass nodules (GGNs) with pulmonary nodules localization needle (PNLN) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From June 2020 to February 2021, all patients with GGNs who received CT-guided localization using PNLN before VATS were enrolled. Clinical and imaging data were retrospectively analyzed. RESULTS: A total of 352 consecutive patients with 395 GGNs were included in the study. The mean diameter of GGNs was 0.95 ± 0.48 cm, and the shortest distance from nodules to the pleura was 1.73 ± 0.96 cm. All 395 GGNs were marked using PNLNs. The time required for marking was 7.8 ± 2.2 min. The marking success rate was 99.0% (391/395). The marking failure of four nodules was all due to the unsatisfactory position of PNLNs. No marker dislocation occurred. Marking-related complications included pneumothorax in 63 cases (17.9%), hemorrhage in 34 cases (9.7%), and hemoptysis in 6 cases (1.7%). All the complications were minor and did not need special treatment. Localization and VATS were performed on the same day in 95 cases and on different days in 257 cases. All GGNs were successfully removed by VATS. No patient converted to thoracotomy. Histopathological examination revealed 74 (18.7%) benign nodules and 321 (81.3%) malignant nodules. CONCLUSIONS: It is safe and reliable to perform preoperative localization of GGNs using PNLNs, which can effectively guide VATS to remove GGNs. KEY POINTS: ⢠Preoperative localization of GGNs could effectively guide VATS to remove GGNs. ⢠PNLN was based on the marking principle of hook-wire, through the improvement of its material, specially designed to mark pulmonary nodules. ⢠The application of PNLN to mark GGNs had high success rate, good patient tolerance, and no dislocation. Meanwhile, VATS could be performed 2 to 3 days after marking GGNs with PNLN.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Cirurgia Torácica Vídeoassistida/métodosRESUMO
BACKGROUND: Endoscopic combined intrarenal surgery (ECIRS) is well established as a minimally invasive procedure for the treatment of multiple urolithiasis. The position is the key to the perfect combination of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). Galdakao-modified supine Valdivia (GMSV) and prone split-leg positions are widely used. However, both positions have their own advantages and disadvantages. This study aimed to evaluate the effect of ECIRS in the treatment of multiple urolithiasis in the modified prone split-leg position. PATIENTS AND METHODS: A total of 96 patients with multiple urolithiasis underwent ECIRS in modified prone split-leg position from September 2017 to January 2021. Relevant demographic and clinical data were analysed retrospectively. Clinical outcomes, such as the stone free rate, complications and postoperative hospital stay were evaluated. The chi-square test was used to compare categorical variables and Student's t test was applied for continuous variables of the treatment groups. RESULTS: The mean renal stone size was 32.5 ± 10.7 mm and renal stone surface area was 712.2 ± 264.8 mm2. The mean ureteral stones size was 24.8 ± 12.3 mm. The mean surgical time was 82.2 ± 38.3 min. The incidence of complications was 16.7%, and they were mainly grade 1 and grade 2. No complications occurred above grade 3. The stone was completely removed in 75 (78.1%) patients in a single operation. The risk factors affecting the stone-free rate of ECIRS were analysed, and only the number of involved calyces by stone was found to be significant (p = 0.01). CONCLUSION: ECIRS is safe and effective in the treatment of multiple renal calculi or multiple renal calculi with ipsilateral ureteral calculi in the modified prone split-leg position. The modification of the prone split-leg position makes the retrograde operation more convenient, which is conducive to the combination of RIRS and PCNL.
Assuntos
Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Posicionamento do Paciente/métodos , Idoso , Feminino , Humanos , Cálculos Renais/patologia , Masculino , Pessoa de Meia-Idade , Nefrolitotomia Percutânea/efeitos adversos , Duração da Cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: The purpose of this study was to evaluate the usefulness of intraprocedural CT and prior PET/CT fusion imaging in improving the diagnostic yield of CT-guided transthoracic core-needle biopsy (CNB) in lung masses. METHODS: In total, 145 subjects with lung masses suspicious for malignancy underwent image-guided transthoracic CNB. According to imaging modality the subjects were divided into two groups. PET/CT images obtained no more than 14 days before the biopsy were integrated with intraprocedural CT images. The integrated or fused images were then used to plan the puncture sites. The clinical characteristics, diagnostic yield of CNB, diagnostic accuracy rate, procedure-related complications and procedure duration were recorded and compared between the two groups. Final clinical diagnosis was determined by surgical pathology or at least 6-months follow-up. The diagnostic accuracy of CNB was obtained by comparing with final clinical diagnosis. RESULTS: 145 subjects underwent CNB with adequate samples, including 76 in fusion imaging group and 69 in routine group. The overall diagnostic yield and diagnostic accuracy rate were 80.3% (53/66), 82.9% (63/76) for fusion imaging group, 70.7% (41/58), 75.4% (52/69) for routine group, respectively. In addition, the diagnostic yield for malignancy in fusion imaging group (98.1%, 52/53) was higher than that in routine group (81.3%, 39/48). No serious procedure-related complications occurred in both two groups. CONCLUSION: CNB with prior PET/CT fusion imaging is particularly helpful in improving diagnostic yield and accurate rate of biopsy in lung masses, especially in heterogeneous ones, thus providing greater potential benefit for patients.
Assuntos
Biópsia Guiada por Imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Biópsia com Agulha de Grande Calibre , Humanos , Biópsia Guiada por Imagem/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
AIMS: Renal cell cancers typically exhibit high metastasis and recurrence, and this is thought to be due to renal cancer stem cells (CSCs). Meanwhile, aberrant activation of Sonic hedgehog (Shh) signaling is linked with CSCs. Resveratrol has direct or indirect impacts on the pathological activities of CSCs. However, the effects of resveratrol on renal CSCs remain to be elucidated. METHODS: We cultured renal CSCs in serum-free medium. Western blotting was used to analyze the expression levels of related proteins. The mRNA changes were detected by qRT-PCR after resveratrol treatment. The CD133+ cells were quantified by flow cytometry analysis. Immunofluorescence staining images showed the changes in CD44 and Smoothened expression in the cell spheres. RESULTS: Renal CSCs were enriched by tumorsphere formation assays of ACHN and 786-O cells. Resveratrol treatments markedly decreased the size and number of cell spheres and downregulated the expression of the Shh pathway-related proteins and CSCs markers. Moreover, we observed that resveratrol inhibited cell proliferation and induced cell apoptosis, while purmorphamine upregulated the Shh pathway and weakened the effects of resveratrol on renal CSCs. CONCLUSIONS: These results suggested that resveratrol is a potential novel therapeutic agent that targets inactivation of renal CSCs by affecting the function of the Shh pathway.
Assuntos
Proteínas Hedgehog , Neoplasias , Células-Tronco Neoplásicas/efeitos dos fármacos , Resveratrol , Transdução de Sinais , Proliferação de Células , Células Cultivadas , Humanos , Resveratrol/farmacologiaRESUMO
BACKGROUND: To evaluate the feasibility and safety of microcoil in simultaneous localization for multiple pulmonary nodules before video-assisted thoracic surgery (VATS). METHODS: Twenty-eight consecutive patients (26 two-nodule, 2 three-nodule; 58 nodules in total; Group A) underwent simultaneous CT-guided localization of multiple pulmonary nodules before VATS using microcoil. Successful targeting, localization, and VATS were defined as implantation of microcoil at the target site on CT image which was obtained immediately after the marking procedure, visualization of nodule location, and complete resection of the target nodule with adequate margin, respectively. Meanwhile, the clinical characteristics, localization procedure-related variables of the nodules and procedure-related complications in group A were also assessed and compared with those in a control group (221 single-localization procedures in 221 patients; Group B). RESULTS: Similar rates of successful targeting, localization and VATS were observed in group A and B (96.6% vs. 98.2%; 91.4% vs. 91.0%; 100% vs. 99.1%). Although the rate of overall complications (including localized pneumothorax and intrapulmonary hemorrhage) was a bit higher in group A than that in group B (32.8% vs. 30.8%, p = 0.771), only minor complications were observed in the subjects of the two groups with no need for further treatment. In addition, the duration of simultaneous localization procedures was significantly longer than that of single localization (24 ± 7.5 vs.13 ± 6 min, p < 0.001). CONCLUSIONS: CT-guided simultaneous microcoil localization for multiple pulmonary nodules before VATS was clinically feasible and safe with acceptable increase in the procedure time. Compared with localization for a single pulmonary nodule, simultaneous microcoil localizations for multiple nodules were prone to pneumothorax and hemorrhage. However, no statistically significant differences were observed between the two groups.
Assuntos
Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/cirurgia , Período Pré-Operatório , Cirurgia Torácica Vídeoassistida/efeitos adversos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Pneumotórax/etiologia , Complicações Pós-Operatórias/etiologia , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/instrumentaçãoRESUMO
AIM: Polycystic ovary syndrome (PCOS) is a complicated endocrine and metabolic abnormality diseases common in women of child-bearing age. This study aims to screen out critical miRNAs and mRNAs associated with PCOS, which may be conducive to offer novel insights and treatment for the diseases. METHODS: Three mRNA datasets and one miRNA dataset derived from granulosa cells of patients with PCOS and normal controls were downloaded to obtain the differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs). Then, DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Quantitative real time polymerase chain reaction (qRT-PCR) validation of the expression of the selected DEmRNAs and DEmiRNAs were performed. RESULTS: A total of 1643 DEmRNAs, 88 DEmiRNAs, 2406 DEmiRNA (down)-DEmRNA (up), and 2179 DEmiRNA (up)-DEmRNA (down) pairs were obtained. The functional annotation of DEmiRNA-target DEmRNAs revealed that C-type lectin receptor signaling pathway, Steroid biosynthesis and Galactose metabolism were significantly enriched KEGG pathways. CONCLUSION: These findings may provide make contribution to understanding PCOS pathogenesis, diagnosis, or treatment.
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MicroRNAs , Síndrome do Ovário Policístico , Feminino , Humanos , MicroRNAs/genética , Síndrome do Ovário Policístico/genética , RNA Mensageiro , Transdução de SinaisRESUMO
BACKGROUND: Glomus tumors are uncommon and mostly benign mesenchymal neoplasms of the perivascular family. To date, only a few cases of glomus tumors occurring in the trachea have been reported. Tracheal glomus tumors simulated low-grade neuroendocrine tumors on clinical and histomorphological examination, so the differential diagnosis between these two entities is very necessary. The latest studies showed that BRAF mutation may be associated with a malignant phenotype of glomus tumors. METHODS: We investigated the clinical, histopathologic, immunohistochemical, and BRAF V600E mutation status of four cases of tracheal glomus tumors. RESULTS: The cases showed a female predilection (male:female, 1:3) with a median age of 35.5. All of the cases had the typical morphological characteristics of glomus tumors, such as uniform round tumor cells with nest-like distribution surrounding thin-walled vessels; two of them met the malignant diagnostic criteria based on the 5th edition of WHO classification, including marked nuclear atypia and any level of mitotic activity. Immunohistochemistry showed diffusely positive for vimentin (4/4), α-SMA (4/4) and collagen IV (4/4), variably reactive for synaptophysin (3/4) and SSTR2 (2/2), and negative for AE1/AE3 (0/4) and chromogranin A (0/4). Three tested cases harbored no BRAF V600E mutation. Three follow-up cases were alive and free of disease with an average follow-up of 89.3 months. CONCLUSIONS: Tracheal glomus tumors are rare mesenchymal tumors that have overlapping morphologic and immunohistochemical features with neuroendocrine neoplasms. Our cases highlight the importance of careful histomorphological examination and comprehensive immunohistochemical study in reaching a correct diagnosis of glomus tumors of the trachea. Other than BRAF mutation, malignant glomus tumors may have a complex mutational profile.
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Tumor Glômico , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Diagnóstico Diferencial , Feminino , Tumor Glômico/diagnóstico , Tumor Glômico/genética , Tumor Glômico/metabolismo , Tumor Glômico/patologia , Humanos , Imuno-Histoquímica , Masculino , Mutação , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Proteínas Proto-Oncogênicas B-raf/análise , Proteínas Proto-Oncogênicas B-raf/genética , Receptores de Somatostatina/análise , Receptores de Somatostatina/genética , Traqueia/patologia , Adulto JovemRESUMO
BACKGROUND: The importance of mRNA methylation erased by ALKBH5 in mRNA biogenesis, decay, and translation control is an emerging research focus. Ectopically activated YAP is associated with the development of many human cancers. However, the mechanism whereby ALKBH5 regulates YAP expression and activity to inhibit NSCLC tumor growth and metastasis is not clear. METHODS: Protein and transcript interactions were analyzed in normal lung cell and NSCLC cells. Gene expression was evaluated by qPCR and reporter assays. Protein levels were determined by immunochemical approaches. Nucleic acid interactions and status were analyzed by immunoprecipitation. Cell behavior was analyzed by standard biochemical tests. The m6A modification was analyzed by MeRIP. RESULTS: Our results show that YAP expression is negatively correlated with ALKBH5 expression and plays an opposite role in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. ALKBH5 reduced m6A modification of YAP. YTHDF3 combined YAP pre-mRNA depending on m6A modification. YTHDF1 and YTHDF2 competitively interacted with YTHDF3 in an m6A-independent manner to regulate YAP expression. YTHDF2 facilitated YAP mRNA decay via the AGO2 system, whereas YTHDF1 promoted YAP mRNA translation by interacting with eIF3a; both these activities are regulated by m6A modification. Furthermore, ALKBH5 decreased YAP activity by regulating miR-107/LATS2 axis in an HuR-dependent manner. Further, ALKBH5 inhibited tumor growth and metastasis in vivo by reducing the expression and activity of YAP. CONCLUSIONS: The presented findings suggest m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Moreover, effective inhibition of m6A modification of ALKBH5 might constitute a potential treatment strategy for lung cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Homólogo AlkB 5 da RNA Desmetilase/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Proteínas de Ligação a RNA/genética , Taxa de Sobrevida , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAPRESUMO
Breast cancer has the highest incidence and mortality in the female population. Forkhead box M1 (FOXM1) known as a transcription factor is upregulated and associated with poor prognosis in a variety of cancers. However, the molecular mechanisms of FOXM1 on breast cancer progression are poorly understood. In this study, we found that FOXM1 was up-regulated in breast cancer. FOXM1 promoted cell proliferation, clonal formation, and migration capacity in triple negative breast cancer by increasing transcriptional activity of YAP1. FOXM1 also maintained cell stemness via the Hippo pathway. The YAP1-TEAD binding inhibitor Verteporfin reduced the transcription level of OCT4 and NANOG but the Hippo pathway activator XMU-MP-1 could increase the transcription level of OCT4 and NANOG. In summary, our findings indicated that FOXM1 promoted breast cancer progression through the Hippo pathway, and it was suggested a new strategy to treat breast cancer.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Movimento Celular/fisiologia , Proteína Forkhead Box M1/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proliferação de Células/fisiologia , Proteína Forkhead Box M1/genética , Técnicas de Silenciamento de Genes , Humanos , Proteína Homeobox Nanog/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Fosforilação/genética , Fatores de Transcrição/química , Regulação para Cima , Proteínas de Sinalização YAPRESUMO
OBJECTIVES: To summarize the experiences of CT-guided microcoil localization before video-assisted thoracoscopic surgery (VATS) and to investigate the risk factors associated with pleural marking failure. METHODS: Totally, 249 consecutive patients with 279 pulmonary nodules who underwent CT-guided microcoil localization prior to VATS were enrolled in this study. According to intraoperative observation, all the nodules were divided into two groups. The clinical characteristics and microcoil localization procedure-related variables of the nodules were analyzed by univariate analysis and multivariate logistic regression analysis to screen the independent factors associated with procedure results. RESULTS: Among the 279 nodules, 28 failed to observe the proximal end of the microcoil deployed on visceral pleura during VATS. The logistic regression revealed that needle-pleura angle (≤ 30°: OR = 39.022, p = 0.003), pleura-microcoil distance (≤ 10 mm: OR = 87.054, p < 0.001; 10~20 mm: OR = 10.088, p = 0.010), and presence of pleural indentation (OR = 21.623, p < 0.001) were independent risk factors for pleural marking failure. CONCLUSIONS: CT-guided microcoil localization for pulmonary nodules is a safe and effective procedure. Small needle-pleura angle (≤ 30°), pleura-microcoil distance (≤ 20 mm), and the presence of pleural indentation during the procedure are significant risk factors contributing to microcoil pleura marking failure. KEY POINTS: ⢠CT-guided microcoil localization for pulmonary nodules was a safe and effective procedure. ⢠CT-guided microcoil localization for pulmonary nodules yielded low complication rates. ⢠Small needle-pleura angle, short pleura-microcoil distance, and the presence of pleural indentation were contributing to pleura marking failure.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Cuidados Pré-Operatórios , Radiografia Intervencionista , Nódulo Pulmonar Solitário/diagnóstico por imagem , Cirurgia Torácica Vídeoassistida , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/cirurgia , Agulhas , Pleura , Estudos Retrospectivos , Fatores de Risco , Nódulo Pulmonar Solitário/cirurgiaRESUMO
OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: ⢠TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. ⢠A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. ⢠The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Micro-Ondas/uso terapêutico , Estadiamento de Neoplasias/métodos , Nomogramas , Terapia por Radiofrequência/métodos , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Lysine demethylase 5B (KDM5B) is up-regulated in many cancers, including breast cancer. However, the underlying metabolic mechanisms of KDM5B on breast cancer progression are poorly understood. Here, we showed that KDM5B expression positively correlates with metastasis in breast cancer. Cell functional analyses were demonstrated that KDM5B knockdown and KDM5B inhibitor AS-8351 inhibited breast cancer cell proliferation and migration. Furthermore, we reported that KDM5B knockdown and AS-8351 reversed epithelial-mesenchymal transition (EMT) and decreased the protein levels of fatty acid synthase (FASN) and ATP citrate lyase (ACLY) in MCF-7 and MDA-MB-231â¯cells. Interestingly, we found that activation of AMP-activated protein kinase (AMPK) signaling pathway is involved in KDM5B-mediated EMT and lipid metabolism reprogramming in breast cancer cells. As a result, silencing of KDM5B-induced activation of AMPK signaling pathway inhibited breast cancer cell proliferation and migration. Taken together, our findings indicated that KDM5B was a novel regulator of lipid metabolism reprogramming, and it was suggested a new strategy to treat breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Movimento Celular/fisiologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Metabolismo dos Lipídeos/fisiologia , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacosRESUMO
BACKGROUND: This study aims to analyze the effect of the body mass index (BMI) on E2, P and LH values in females who received intrauterine insemination (IUI) treatment on human chorionic gonadotropin (HCG) day. METHODS: A total of 2319 cycles of IUI-assisted pregnancy treatment were selected in our hospital. Based on the BMI, female infertility patients are divided into three groups: normal weight group, overweight and obese group. RESULTS: For patients with natural cycles and ≤ 35 years old, there were 440, 178 and 197 cases in the three groups, respectively. For patients with natural cycles and > 35 years old, there were 90, 83 and 81 cycles in the three groups, respectively. For patients with induced ovulation cycle and ≤ 35 years old, there were 425, 203 and 516 cases in the three groups, respectively. For patients with induced ovulation cycle and > 35 years old, there were 26, 26 and 54 cases in the three groups, respectively. CONCLUSION: When a patient is ≤35 years old, the BMI affects the E2, LH and P values on the day of artificial insemination. However, the BMI is negatively correlated with E2, LH and P in IUI on HCG day. After controlling for age and assisted pregnancy, the correlation analysis revealed that the BMI is negatively correlated with hormone E2 and LH. The higher the BMI was, the lower the levels of hormones E2, LH and P became. However, in the present study, the BMI did not significantly improve the clinical pregnancy rate of patients who received IUI.
Assuntos
Índice de Massa Corporal , Gonadotropina Coriônica/sangue , Inseminação Artificial , Indução da Ovulação/métodos , Taxa de Gravidez , Adulto , Estradiol/sangue , Feminino , Humanos , Hormônio Luteinizante , GravidezRESUMO
BACKGROUND: The most serious complication of ureter stent is long-term retention of ureteral stent and stone formation around the stent. CASE PRESENTATION: A 51-year old female patient with left ureteral stent placed 2 years before developed both pyelic and vesical stones on the two ends of the double J was admitted to our hospital. Intravesical lithotripsy, retrograde ureteroscopy, and percutaneous nephrolithotripsy were performed with the patient in the prone split-leg position. All the stones and the ureteral stent were successfully removed in a single session. CONCLUSIONS: Combined endoscopic techniques in the prone split-leg position can effectively and safely manage severely encrusted stents.
Assuntos
Cistoscopia/métodos , Cálculos Renais/terapia , Litotripsia/métodos , Nefrolitotomia Percutânea/métodos , Posicionamento do Paciente/métodos , Stents , Ureteroscopia/métodos , Cálculos da Bexiga Urinária/cirurgia , Remoção de Dispositivo/métodos , Feminino , Humanos , Pelve Renal , Pessoa de Meia-Idade , Radiografia Abdominal , Tomografia Computadorizada por Raios XRESUMO
Nanog plays an important role in the regulation of cancer stem cells (CSCs) which participate in tumorgenesis and progression. In renal cancer, tobacco smoke (TS) is considered a major risk factor. However, the molecular mechanism by which TS induces the development of renal CSC properties remains largely unknown. In this study, we showed that the level of Nanog was elevated in renal cell carcinoma (RCC) patients with a smoking history, and that Nanog overexpression promoted the traits of CSCs in renal cancer. We further demonstrated that a 8-week exposure of TS enhanced the formation of renal tumorspheres, increased the population of CD133-positive cells, and stimulated the expression of Nanog and CSC markers. In addition, TS was found to play a role in accelerating the cell growth transition from G1 to S phase in renal CSCs. Finally, we demonstrated that the TS-induced effects in renal CSCs could be reversed through the downregulation of Nanog. Our results suggested that Nanog plays a role in mediating TS-induced renal CSC properties. This study may provide new insights into the molecular mechanism of TS-related renal tumorigenesis, which can contribute to the future development of therapeutics for renal cancer.