RESUMO
OBJECTIVE: Thyroid cancer is one of the most frequently reported endocrine system malignancies. It is difficult to distinguish follicular thyroid cancer (FTC) from follicular thyroid adenoma (FTA) during pathological diagnosis in patients without lymph nodes or distant metastases. Therefore, we conducted a retrospective study to investigate the significance of SLC5A8 methylation and expression in the diagnosis and prognosis of FTC. METHODS: We used 165 tissue samples, including FTC (n = 58), thyroid tumors of uncertain malignant potential (TT-UMP, n = 40), and FTA (n = 67), to explore the differences in SLC5A8 methylation and mRNA transcription in different pathological types. Survival analysis was conducted to evaluate the recurrence rate at a 5-year follow-up. RESULTS: The SLC5A8 methylation positive rate was higher in patients with thyroglobulin ≥ 40 µg/l and Chol ≥ 5.17 mmol/l, and it was higher in patients with FTC (n = 42, 72.4%) than those with FTA (n = 27, 40.3%) and TT-UMP (n = 23, 57.5%). The relative concentration of SLC5A8 mRNA was lower in patients with FTC than in those with FTA (p < 0.05). At 5-year follow-ups, patients who were SLC5A8 methylation-positive had a higher recurrence rate than those who were methylation-negative. CONCLUSIONS: Our current study indicates that SLC5A8 gene methylation occurs more commonly in patients with FTC than in those with FTA. The differences in SLC5A8 methylation and expression among FTA, FTC, and TT-UMP provide an important basis for further exploration of epigenetic changes in the occurrence, development, and prognosis of thyroid cancer. Our findings need to be further validated in larger populations with long-term follow-up in the future.
Assuntos
Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Prognóstico , RNA Mensageiro , Transportadores de Ácidos MonocarboxílicosRESUMO
Pristine SnO2, Fe-doped SnO2 and Ni-doped SnO2 were synthesized using facile hydrothermal method. Analysis based on XRD, TEM and UV-Vis DRS measurements demonstrated the successful insertion of Fe and Ni dopants into SnO2 crystal. Formaldehyde-detection measurements revealed that transition metal-doped SnO2 exhibited improved formaldehyde-sensing properties compared with that of pristine SnO2. When the amount of incorporated dopant (Fe or Ni) was 4 at.%, the most effective enhancement on sensing performance of SnO2 was obtained. At 160 °C, the 4 at.% Fe-SnO2 and 4 at.% Ni-SnO2 exhibited higher response values of 7.52 and 4.37 with exposure to low-concentration formaldehyde, respectively, which were 2.4 and 1.4 times higher than that of pristine SnO2. The change of electronic structure and crystal structure as well as catalytic effect of transition metals are chiefly responsible for the enhanced sensing properties.
RESUMO
Common chromophobe renal cell carcinoma (chRCC) has a good prognosis when cured by surgery. However, clinical practice shows that a small number of patients with chRCC will produce metastasis, and the prognosis after metastasis is poor. In this regard, we try to find potential biological targets to prevent CRCC metastasis. In this experiment, we analyzed the clinical traits and gene expression data of chRCC samples which were provided by the TCGA database by the WGCNA method. On this basis, we selected MEtan, a module with a significant positive correlation with the M phase of chRCC, for subsequent analysis. The MEtan module genes in the biological process of chRCC were mainly related to steroid metabolic process, cholesterol metabolic process and STEM cell differentiation. KEGG analysis showed that these genes were mainly enriched in cancer-related signaling pathways, such as Neuroactive Ligand-receptor interaction, cAMP signaling pathway, and Wnt signaling pathway. Subsequently, we mapped the PPI interaction network and screened the key gene beta-arrestin 2 (ARRB2). Expression analysis showed that there was a significantly increased expression of ARRB2 in chRCC patients in comparison to the normal group. Expression survival analysis indicated that ARRB2 was inversely associated with overall survival. We firmly believe that the key genes identified in this study would be able to provide new clues and research basis for the treatment of chRCC.
RESUMO
PURPOSE: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. For better understanding the application of olanzapine in antiemetic strategies for breast cancer patients who suffered anthracycline plus cyclophosphamide-induced nausea and vomiting, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled-analyzed the results to confirm the efficacy and safety of olanzapine in breast cancer. METHODS: PubMed, Web of Science, EMBASE, and Cochrane CENTRAL databases were searched from inception through Sep 15, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate, and the secondary outcome was treatment-related adverse events. RESULTS: Four studies with 466 breast cancer patients were identified in the pooled analysis. In the acute period (0-24 h), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group, while in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. CONCLUSION: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.
Assuntos
Antieméticos , Antineoplásicos , Neoplasias da Mama , Antraciclinas/efeitos adversos , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Dexametasona/uso terapêutico , Feminino , Humanos , Olanzapina/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Vômito/induzido quimicamente , Vômito/tratamento farmacológicoRESUMO
BACKGROUND: Patients with lung cancer (LC) have a poor quality of life (QoL) and easily suffer from psychological diseases. Previous studies focused less on the relationship between genetic factors and QoL, depression, and anxiety status in LC patients. The current study is intended to explore the relationship between SNPs and haplotypes of ERCC1 and ERCC2 and the QoL, depression and anxiety status of patients with LC. METHODS: QoL, depression and anxiety status were assessed in 291 LC patients using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), SDS and SAS. Nine tag SNPs of ERCC1 and ERCC2 were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The association between SNPs or haplotypes and QoL or depression or anxiety in LC patients was analyzed by regression analysis. RESULTS: ERCC1 rs11615 was associated with emotional functioning (P = 0.027), and ERCC1 rs3212986 was associated with anxiety scores (P = 0.018). ERCC1 rs762562-rs3212986 haplotype was associated with cognitive function (P = 0.029), somatic function (P = 0.014) and dysphagia (OR = 3.32, P = 0.044). Patients with ERCC1 rs3212986-rs11615 AG haplotype had worse cognitive function (adjusted Beta = - 5.42) and somatic function (adjusted Beta = - 6.55) and had severer symptoms of loss of appetite (adjusted OR = 1.67) and dysphagia (adjusted OR = 4.43) (All adjusted P < 0.05). ERCC2 rs13181-rs3916874-rs238416 haplotype was associated with emotional functioning (P = 0.035), pain at other sites (OR 1.88, P = 0.014), chest pain (OR 0.42, P = 0.02), dysphagia (OR 2.82, P = 0.048), and anxiety status (OR 0.23, P = 0.009). CONCLUSION: After adjustment for environmental factors, SNPs and haplotypes of ERCC1 and ERCC2 were associated with different domains of QoL, depression and anxiety in LC patients.
Assuntos
Ansiedade/genética , Proteínas de Ligação a DNA/genética , Depressão/genética , Endonucleases/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/psicologia , Proteína Grupo D do Xeroderma Pigmentoso/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: The health burden of breast cancer is rising in China. The effect of informed diagnosis on long-term survival is not fully understood. This retrospective cohort study aims to explore the association between early informed diagnosis and survival time in breast cancer patients. METHODS: A total of 12,327 breast cancer patients were enrolled between October 2002 and December 2016. Potential factors, including knowing the cancer diagnosis status, sex, age, clinical stage, surgery history, grade of reporting hospital and diagnostic year were, analyzed. We followed up all participants every 6 months until June 2017. Propensity score matching (PSM) was used to balance the clinicopathologic characteristics between patients who knew their diagnosis and those who did not. RESULTS: By June 2017, 18.04% of the participants died of breast cancer. Before PSM, both the 3-year and 5-year survival rates of patients who knew their cancer diagnosis were longer (P < 0.001). After PSM, the above conclusion was still established. By stratified analysis, except for the subgroups of male patients and stage III patients, patients who knew their diagnosis showed a better prognosis in all the other subgroups (P < 0.05). Cox regression analysis showed that knowing a cancer diagnosis was an independent risk factor for survival in breast cancer patients (P < 0.001). CONCLUSIONS: Being aware of their cancer diagnosis plays a protective role in extending the survival time of breast cancer patients, which suggests that medical staff and patients' families should disclose the cancer diagnosis to patients in a timely manner. Further prospective studies need to be made to validate our findings.
Assuntos
Neoplasias da Mama/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Differentiated thyroid cancer (DTC) is the most common thyroid tumor, and the cells of DTC patients can lose the ability to differentiate in their natural state or during treatment and develop radioiodine-refractory DTC (RAI-R DTC), resulting in increased malignancy. Monocarboxylate transporter-1 (MCT1 ) is positively correlated with the level of malignant of various tumors, and its expression in RAI-R DTC cells is correlated with their biological cell traits. METHODS: Data from 14 iodine-refractory thyroid carcinoma patients were collected, and the effective radioiodine treatment group was used as the control group. The expression of MCT1 in iodine-refractory thyroid carcinoma and its effect on biological behaviors was observed and the molecular mechanism underlying RAI-R DTC was investigated to determine the cause of the loss of sensitivity of DTC to radioactive iodine using Immunohistochemical staining, Western blot, transwell assay, wound healing assay, flow cytogram assay. RESULTS: Compared to radioiodine-sensitive DTC (RAI-DTC), which was responded to iodine treatment, MCT1 was highly expressed in RAI-R DTC cells. The overexpression or inhibition of MCT1 altered the biological characteristics of papillary thyroid carcinoma (TPC-1) cells. The overexpression of MCT1 in TPC-1 cells increased the invasive, proliferative, and migratory abilities of the cells. Conversely, the downregulation of MCT1 decreased the invasive, proliferative and migratory abilities of the cells. CONCLUSIONS: The expression of MCT1 was enhanced in RAI-R DTC cells. MCT1 appears to be closely related to the invasive metastasis of RAI-R DTC cells, and it may be the cause of the loss of the iodine uptake ability of RAI-R DTC.
RESUMO
Ewing sarcoma (ES) is a type of highly aggressive pediatric tumor in bones and soft tissues and its metastatic spread remains the most powerful predictor of poor outcome. We previously identified that the transcription factor hepatoma-derived growth factor (HDGF) promotes ES tumorigenesis. However, the mechanisms underlying ES metastasis remain unclear. Here, we show that HDGF drives ES metastasis in vitro and in vivo, and HDGF reduces metastasis-free survival (MFS) in two independent large cohorts of human ES patients. Integrative analyses of HDGF ChIP-seq and gene expression profiling in ES cells reveal that HDGF regulates multiple metastasis-associated genes, among which activated leukocyte cell adhesion molecule (ALCAM) emerges as a major HDGF target and a novel metastasis-suppressor in ES. HDGF down-regulates ALCAM, induces expression and activation of the downstream effectors Rho-GTPase Rac1 and Cdc42, and promotes actin cytoskeleton remodeling and cell-matrix adhesion. In addition, repression of ALCAM and activation of Rac1 and Cdc42 are required for the pro-metastatic functions of HDGF in vitro. Moreover, analyses in murine models with ES tumor orthotopic implantation and experimental metastasis, as well as in human ES samples, demonstrate the associations among HDGF, ALCAM, and GTPases expression levels. Furthermore, high HDGF/low ALCAM expression define a subgroup of patients harboring the worst MFS. These findings suggest that the HDGF/ALCAM/GTPases axis represents a promising therapeutic target for limiting ES metastasis.
Assuntos
Antígenos CD/fisiologia , Neoplasias Ósseas/patologia , Moléculas de Adesão Celular Neuronais/fisiologia , Proteínas Fetais/fisiologia , GTP Fosfo-Hidrolases/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Sarcoma de Ewing/patologia , Citoesqueleto de Actina/química , Adolescente , Adulto , Animais , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Transdução de Sinais/fisiologia , Adulto JovemRESUMO
PURPOSE: Quality of life (QoL) and prognosis of lung cancer (LC) patients are poor. Previous studies focused less on the relationship between genetic factors and the QoL of LC patients. The current study is intended to explore the association of SNPs and haplotypes of BRCA1 and the QoL and survival of patients with LC. METHODS: QOL of 291 non-small-cell LC patients was measured by EORTC Core Quality of Life Questionnaire (QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) before discharge. Three tag SNPs of the BRCA1 gene (rs1799966, rs3737559, rs8067269) were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The patients' survival was followed up every six months until March 2019. RESULTS: rs8067269 was associated with physical functioning (ß = 7.97, p = 0.024) and diarrhea (Odds ratios (OR) 0.32, p = 0.042). rs1799966-rs3737559-rs8067269 haplotype was associated with several domains of QoL, including physical functioning (TCG vs. CCA: ß = 6.21, p = 0.010), worse dyspnea (TCG vs. CTA: OR 2.05, p = 0.031) and peripheral neuropathy (TCG vs. CTA: OR 3.91, p = 0.030). BRCA1 rs1799966 CC genotype, rs8067269 AA genotype and CCA haplotype were associated with longer survival time of LC patients (p < 0.05). CONCLUSION: SNPs and haplotypes of BRCA1 gene were associated with the QoL and survival of patients with LC. Patients with certain genotypes and haplotypes (i.e., rs8067269 AA genotype, or CCA haplotype) had better QoL and prognosis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Genes BRCA1/fisiologia , Haplótipos/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético/genética , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1 , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Adulto JovemRESUMO
OBJECTIVE: As a malignant tumor with high mortality, lung cancer (LC) often causes great trauma to patients, and a series of negative emotions and a heavy psychological burden accompanies poor prognosis. Whether or not to inform the patients of their condition has always been a controversial topic in the medical community. This retrospective cohort study investigated the association between early informed diagnosis and survival time in patients with LC. METHODS: A total of 29 825 patients with LC were enrolled between October 2002 and December 2016. The potential factors influencing LC survival were registered, including knowing their cancer diagnosis status, age, gender, pathological type, clinical stage, surgical history, hospital grade, and patient occupation. All participants were followed up every 6 months until June 2017. RESULTS: In June 2017, 23.1% of the participants still survived. Their median survival time (MST) was 11.20 months (95% confidence interval [CI], 10.98-11.43). Generally, patients that knew their cancer diagnosis had longer MST than those who did not (18.33 months vs 8.77 months, P < .001). By stratified analysis, patients that knew their cancer diagnosis had longer survival time in each subgroup (P < .001, all subgroups). Cox regression analysis showed that knowing their cancer diagnosis was an independent influencing factor for survival in patients with LC (hazard ratio, 0.826; 95% CI, 0.802-0.851; P < .001). CONCLUSIONS: Knowing their cancer diagnosis contributed to longer survival time in patients with LC, providing clear evidence that medical staff and patients' families should fully disclose cancer diagnoses to patients.
Assuntos
Conscientização , Detecção Precoce de Câncer/psicologia , Neoplasias Pulmonares/mortalidade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Adulto , Idoso , Atitude Frente a Saúde , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
There is a great need for identification and development of new anti-tuberculosis drugs with novel targets. Recent drug-discovery efforts typically focus on identifying inhibitors but not activators that perturb metabolic enzymes' functions as a means to kill Mycobacterium tuberculosis (Mtb). Here, we describe a class of quinoline compounds, Z0933/Z0930, which kill Mtb by acting as activators of glutamate kinase (GK), a previously untargeted enzyme catalyzing the first step of proline biosynthesis. We further show that Z0933/Z0930 augment proline production and induce Mtb killing via proline-derived redox imbalance and production of reactive oxygen species. This work highlights the effectiveness of gain-of-function probes against Mtb and provides a framework for the discovery of next-generation allosteric activators of GK.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Fosfotransferases (Aceptor do Grupo Carboxila)/metabolismo , Quinolinas/farmacologia , Animais , Antituberculosos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Cinética , Macrófagos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/enzimologia , Fosfotransferases (Aceptor do Grupo Carboxila)/genética , Estabilidade Proteica , Quinolinas/química , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
A series of small molecules with novel pyrrolo[1,2-a]quinoxaline-based scaffold was designed via molecular hybridization of privileged agents active against Mycobacterium tuberculosis. Twenty-three compounds were synthesized and investigated for their antitubercular activities in vitro where ten compounds showed appreciable activities and moderate cytotoxicity. Compound 12g with MIC values of 5⯵g/ml as a representative may possess better oral bioavailability and indicated high permeability by the parallel artificial membrane permeation assay of the blood-brain barrier (PAMPA-BBB). Further, the determination of enzyme inhibition and molecular docking study indicated that InhA may be the biological target of the active compounds. The results suggest the pyrrolo[1,2-a]quinoxaline hybrids as potential antitubercular leads for the development of new antitubercular agents.
Assuntos
Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Descoberta de Drogas , Mycobacterium tuberculosis/efeitos dos fármacos , Pirróis/farmacologia , Quinoxalinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antituberculosos/síntese química , Antituberculosos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirróis/síntese química , Pirróis/química , Quinoxalinas/síntese química , Quinoxalinas/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Nicotine may improve schizophrenia patient's cognitive deficit symptoms. This study was to explore the chronic effects of smoking on prepulse inhibition of the startle reflex (PPI) and P50 in the patients with first-episode schizophrenia (FES). METHODS: The event-related potentials (ERP) recording and analysis instrument made by Brain Products, Germany, was used to detect PPI and P50 in 49 male FES patients (FES group, n = 21 for smokers and n = 28 for non-smokers) and 43 normal male controls (control group, n = 19 for smokers and n = 24 for non-smokers). RESULTS: Compared with normal controls, the FES group had prolonged PPI latency when elicited by single stronger stimulus (P < 0.05); the FES group had prolonged PPI latency and increased PPI amplitude (P < 0.05, 0.01) when elicited by weak and strong stimuli. The FES group had lower PPI inhibition rate than normal controls (P < 0.05). Compared with normal controls, the FES group had increased P50-S2 amplitude and increased amplitude ratio S2/S1 (both P <0.05). In the control group, the smokers had a tendency of increase in P50-S2 amplitude (P > 0.05) and shorter P50-S2 latency (P < 0.05) than the non-smokers. The smokers had higher PPI amplitude than the non-smokers (P < 0.05). In the FES group, the smokers had higher P50-S1 amplitude, shorter P50-S2 latency, and higher amplitude ratio S2/S1 than the non-smokers (P < 0.05, 0.01). The smokers had higher PPI amplitude than the non-smokers (P < 0.05). CONCLUSIONS: There is obvious PPI and P50 deficits in schizophrenic patients. However, these deficits are relatively preserved in the smokers compared with the non-smokers, which suggests that long-term smoking might partially improve the sensory gating in schizophrenic patients. Whether this conclusion can be deduced to female patients requires further follow-ups.