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The homeobox gene NKX6.1 was recently identified in cervical tumors. This study was designed to explore the clinical and prognostic significance of NKX6.1 further in patients with primary hepatocellular carcinoma (HCC). The expression levels of NKX6.1 were examined using real-time PCR, Western blotting, and immunohistochemistry in HCC cell lines and HCC tissues. The invasion capability of cell lines following silencing or overexpression of NKX6.1 was investigated by Transwell assay. Cells proliferation was tested by MTT assays. Epithelial-mesenchymal transition (EMT) marker expression levels were detected in relation to NKX6.1 expression. Correlation between NKX6.1 immunohistochemical staining, clinicopathologic parameters, and follow-up data of HCC patients was analyzed statistically. NKX6.1 expression was higher in HCC tissues compared to the adjacent noncancerous tissue. NKX6.1 overexpression was significantly correlated with tumor size, tumor differentiation, clinical stage, metastasis, and relapse. Kaplan-Meier analysis revealed that NKX6.1 overexpression was related to unfavorable 5-year disease-free survival and overall survival. Importantly, multivariate analysis indicated that NKX6.1 overexpression was an independent unfavorable marker for overall survival. Moreover, a significant relationship was observed between NKX6.1 and EMT marker expression levels, and NKX6.1 knockdown inhibited cell invasion, and overexpression of NKX6.1 promotes cell proliferation in vitro. NKX6.1 is upregulated in HCC and is a reliable prognostic marker for patients with HCC.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Proteínas de Homeodomínio/genética , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Proteínas de Homeodomínio/biossíntese , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Recidiva Local de Neoplasia/patologia , PrognósticoRESUMO
AIM: The homeobox gene Barx2 was recently identified as a regulator of ovarian and breast cancer; however, the expression level of BARX2 and its significance in hepatocellular carcinoma (HCC) remain unknown. METHODS: Protein and mRNA expression levels of Barx2 were examined using Western blotting and real-time PCR respectively, in paired HCC tissue and matched adjacent non-cancerous tissue from 12 patients. The expression levels of epithelial-mesenchymal transition (EMT) markers were also detected in relation to BARX2 expression. Lastly, immunohistochemistry for BARX2 was also performed on a tissue microarray containing 231 HCC tissue samples. RESULTS: We observed that BARX2 expression was lower in HCC tissues compared to matching adjacent non-cancerous tissue. The low expression level of BARX2 was significantly correlated with metrics of tumor size, tumor differentiation, clinical stage, metastasis and relapse. Furthermore, the patients with low BARX2 expression had adverse survival outcomes. Importantly, multivariate Cox regression analysis revealed that low BARX2 expression was an independent marker for lower overall survival (P = 0.007). Moreover, a significant negative relationship was observed between the expression of BARX2 and markers of EMT. CONCLUSION: These findings provide evidence that the low expression level of BARX2 in HCC is significantly correlated with tumor metastasis, and that BARX2 may be an independent prognostic biomarker for patients with HCC.
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OBJECTIVE: To explore a precise association between tumor location and lymph node (LN) biopsy algorithm in uterine confined endometrial cancer (EC). MATERIALS AND METHODS: Patients with EC treated in the Department of Obstetrics and Gynecology, South Branch of Fujian Provincial Hospital were included in this observational retrospective study. Based on the procedure of treatment, patients were separated to stage I (2015.07-2019.09) and stage II (2019.09-2021.9). In each stage, patients were separated to high and low-risk group by the predicted results. Patients in the high-risk group received systematic lymphadenectomy in stage I and sentinel lymph node (SLN) dissection in stage II. The efficiency of lymph node metastasis (LNM) detection rates was compared between stage I and stage II cases. Precise lymph node biopsy algorithm was also constructed based on the outcomes of stage II. RESULTS: Overall, 43 patients, 28 in stage I and 15 in stage II, were included in the study. No recurrence or death cases had been found within follow-up terms. Based on the difference in the detection efficiency of LNM (p > 0.05), there was no difference between two stages. Thus, systematic lymphadenectomy and SLN biopsy provided similar success rates. The location of tumor site was also important for deciding whether pelvic or para-aortic SLN should be sampled for LNM. CONCLUSIONS: Precise SLN biopsy for EC confined to the uterus showed comparable LNM detection rate as systematic lymphadenectomy. EC location may be used to determine whether pelvic or para-aortic SLN sampling should be conducted for treatment.
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Neoplasias do Endométrio , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Estadiamento de Neoplasias , Biópsia de Linfonodo Sentinela , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Excisão de Linfonodo/métodos , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos , Idoso , Linfonodos/patologia , Adulto , AlgoritmosRESUMO
Intrinsic resistance to CDK4/6 inhibitors hinders their clinical utility in cancer treatment. Furthermore, the predictive markers of CDK4/6 inhibitors in gastric cancer (GC) remain incompletely described. Here, we found that PAX6 expression was negatively correlated with the response to palbociclib in vitro and in vivo in GC. We observed that the PAX6 expression level was negatively correlated with the overall survival of GC patients and further showed that PAX6 can promote GC cell proliferation and the cell cycle. The cell cycle is regulated by the interaction of cyclins with their partner serine/threonine cyclin-dependent kinases (CDKs), and the G1/S-phase transition is the main target of CDK4/6 inhibitors. Therefore, we tested whether PAX6 expression was correlated with the GC response to palbociclib. We found that PAX6 hypermethylates the promoter of LATS2 and inactivates the Hippo pathway, which upregulates cyclin D1 (CCND1) expression. This results in a suppressed response to palbociclib in GC. Furthermore, we found that the induction of the Hippo signaling pathway or treatment with a DNA methylation inhibitor could overcome PAX6-induced palbociclib resistance in GC. These findings uncover a tumor promoter function of PAX6 in GC and establish overexpressed PAX6 as a mechanism of resistance to palbociclib.
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Quinase 4 Dependente de Ciclina/efeitos dos fármacos , Quinase 6 Dependente de Ciclina/efeitos dos fármacos , Via de Sinalização Hippo/efeitos dos fármacos , Fator de Transcrição PAX6/efeitos dos fármacos , Piperazinas/farmacologia , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Piridinas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Proteínas Supressoras de Tumor/efeitos dos fármacos , Idoso , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , China , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/genética , Modelos Animais de Doenças , Feminino , Via de Sinalização Hippo/genética , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Oncogenes/efeitos dos fármacos , Oncogenes/genética , Fator de Transcrição PAX6/genética , Proteínas Serina-Treonina Quinases/genética , Neoplasias Gástricas/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
OBJECTIVE: Immune checkpoint inhibitors (ICIs) have shown a significant efficacy for patients with non-small cell lung cancer (NSCLC). However, checkpoint inhibitor pneumonitis (CIP) is a rare but severe and life-threatening adverse event. Hence, we performed a systematic review and meta-analysis to evaluate the incidence and risk of CIP in patients with NSCLC. METHODS: Pubmed, Embase, Cochrane Library and ClinicalTrials.gov (http://clinicaltrials.gov/) were searched up to December 15, 2020. Studies regarding all-grade and high-grade pneumonitis were included. The data was analyzed using meta-packages of R 3.6.0. RESULTS: A total of sixteen randomized controlled trials including 9500 patients were identified for further evaluation. The overall incidence of all-grade and high-grade CIP was 4.17% and 2.02%, respectively. Compared with conventional chemotherapy, patients treated with ICIs significantly increased risk of all-grade (RR: 4.11, p < 0.0001) and high-grade (RR: 3.16, p < 0.0001) pneumonitis. Subgroup analysis showed the ICIs combined with chemotherapy was associated with a higher incidence of CIP than monotherapy alone (6.03% vs 3.32%, p = 0.01). And the rate of death owing to CIP was higher than chemotherapy-mediated pneumonitis. CONCLUSION: There were a higher incidence and risk of pneumonitis with the application of ICIs when compared with chemotherapy. Higher mortality rate of pneumonitis was more frequent in ICIs group. Thus, early detection, proper administration and optimal management are needed for physicians prevent potentially CIP deterioration.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Pneumonia/epidemiologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Estadiamento de Neoplasias , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco/estatística & dados numéricosRESUMO
The emission of CO2 from major sectors and key industries are the predominant sources of regional CO2 emissions. It is the prerequisite to promote sectoral carbon emissions reduction, to cla-rify their influencing factors and investigate their relationship with regional economic growth. It is also of great significance for the implementation of regional total carbon emissions control. Using the Logarithmic mean Divisia index method (LMDI) and the Tapio decoupling model, we analyzed the driving factors, and decoupling status with economic growth of 13 major carbon emissions industries in Fujian Province from 1997 to 2017. The results showed that the electricity and heat production and supply industry was the major source of CO2 emissions in Fujian Province, with an increase of 101.74 Mt (from 18.89 Mt to 120.63 Mt) during the period 1997 to 2017. The top three industries with the fastest annual growth rate in CO2 emissions were non-ferrous metal smelting and rolling processing industry (18.1%), textile industry (12.1%), and ferrous metal smelting and rolling processing industry (12.1%). Among the influence factors for the changes in carbon emissions in 13 major industries, economic growth effect and population scale effect were the main positive driving factors, while the restraining effects of energy structure, energy intensity, and industrial structure were continuously increasing. In terms of decoupling relationship, the decoupling index between economic growth and industry-related CO2 emissions showed a downward trend on the whole. Since the 11th Five-Year-Plan period, some industries had begun to show strong decoupling to some extent. The farming, forestry, animal husbandry, fishery and water conservancy industry exhibited expansive negative decoupling, whereas the electricity and heat production and supply industry exhibited weak negative decoupling during 13th Five-Year Plan period. The effects of energy structure and energy intensity had substantial impacts on the decoupling with economic growth for various industries. The industrial structure effect had a smaller impact on the decoupling with economic growth, while the population scale effect had almost no impact.
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Dióxido de Carbono , Desenvolvimento Econômico , Carbono/análise , Dióxido de Carbono/análise , China , IndústriasRESUMO
Ascites is the pathologic accumulation of fluid within the peritoneal cavity. Because many diseases can cause ascites, in particular cirrhosis, samples of ascitic fluid are commonly analyzed in order to develop a differential diagnosis. The concept of transudate versus exudate, as determined by total protein measurements, is outdated and the use of serum-ascites albumin gradient as an indicator of portal hypertension is more accurate. Lactate dehydrogenase (LDH), vascular endothelial growth factor (VEGF), and other tumor markers can be helpful in distinguishing between malignant and benign conditions. Glucose and adenosine deaminase levels may support a diagnosis of tuberculous disease, and amylase level may indicate a diagnosis of pancreatitis. Given the specificity and sensitivity of laboratory results, accurate diagnosis should be based on both laboratory data and clinical judgment.
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Silk fibroin is a kind of polypeptide with functional amino acids in its structure. The electric charges in its molecular chains originating from the dissociation of acidic groups, i.e., hydroxyl, phenol and carboxyl, provide vast potentials for the retention of metal species of interest. In this study, the selective retention of Cu(2+) with silk fibroin at pH 6.0 was investigated and a novel on-line procedure for separation/preconcentration of Cu(2+) from complex sample matrices was thus developed by using a sequential injection system with an electrothermal atomic absorption spectrometry. A novel concept of enrichment index (EI), i.e., defined as enrichment factor (EF) obtained by consuming unity of sample volume (ml), was proposed for evaluating the enrichment efficiency of a flow-based preconcentration procedure. With a sampling volume of 900 microl, an EI of 30.3 (EF=27.3) was achieved, which was much improved as compared to that of reported procedures. A detection limit of 8.0 ng l(-1) was achieved within a linear range of 0.025-1.5 microg l(-1) along with a precision of 2.2% R.S.D. at 0.5 microg l(-1). The practical applicability of this procedure was validated by analyzing a certified reference material of riverine water (GBW08608) and a certified reference material of seawater (NASS-5) achieving satisfactory agreements between the certified and the obtained values. A spiking recovery was also performed by using a cave water sample.