RESUMO
BACKGROUNDS: Currently, family with sequence similarity 65 member A (FAM65A) is reported as a pivotal regulator in various cancers. However, the effect of FAM65A in lung squamous cell carcinoma (LSCC) is still unclear, the prime objective of this research is to explore the role of FAM65A in LSCC. METHODS: Gene expression data and correlated clinical information were downloaded from the public database and the expression of FAM65A was detected. The expression of FAM65A was also detected in our collected clinical samples and LSCC cell lines. Survival package of R language was used to determine the survival significance of FAM65A. Proteins expression level was determined via western blot assay. Cell function experiments and in vivo experiments were performed to explore the effect of FAM65A on LSCC cell biological behaviors. RESULTS: FAM65A expression was significantly increased in LSCC clinical samples and cell lines. High FAM65A expression predicted poor prognosis in LSCC patients. After silencing FAM65A, the ability of LSCC cell proliferation, invasion and migration was decreased, and LSCC cell cycle was blocked. Moreover, in vivo experiments revealed that silencing FAM65A could inhibit LSCC cell proliferation. CONCLUSIONS: High FAM65A expression could enhance proliferative, invasive and migratory abilities of LSCC. FAM65A might be a novel biomarker of LSCC.
Assuntos
Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Proliferação de Células/genética , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Camundongos , Linhagem Celular Tumoral , Masculino , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Prognóstico , Pessoa de Meia-Idade , Camundongos Nus , Invasividade NeoplásicaRESUMO
BACKGROUND: Previous observational research showed a potential link between physical activities such as walking and the risk of lung cancer. However, Mendelian randomization (MR) studies suggested there was no association between moderate to vigorous physical activity and lung cancer risk. We speculated that specific physical activities may be associated with lung cancer risk. Consequently, we conducted an MR study to examine the potential relationship between walking and the risk of lung cancer. METHODS: We collected genetic summary data from UK Biobank. After excluding SNPs with F values less than 10 and those associated with confounding factors, we conducted a MR analysis to assess the causal effects between different types of walk and lung cancer. We also performed sensitivity analysis to validate the robustness of our findings. Finally, we analyzed the possible mediators. RESULTS: MR analysis showed number of days/week walked for 10 + minutes was associated with a reduced risk of lung cancer risk (OR = 0.993, 95% CI = 0.987-0.998, P = 0.009). Additionally, usual walking pace was identified as a potentially significant factor in lowering the risk (OR = 0.989, 95% CI = 0.980-0.998, P = 0.015). However, duration of walks alone did not show a significant association with lung cancer risk (OR = 0.991, 95%CI = 0.977-1.005, P = 0.216). The sensitivity analysis confirmed the robustness of these findings. And number of days/week walked for 10 + minutes could affect fed-up feelings and then lung cancer risk. There was a bidirectional relationship between usual walking pace and sedentary behaviors (time spent watching TV). CONCLUSION: The study unveiled a genetically predicted causal relationship between number of days/week walked for 10 + minutes, usual walking pace, and the risk of lung cancer. The exploration of potential mediators of walking phenotypes and their impact on lung cancer risk suggests that specific physical activities may reduce the risk of lung cancer.
Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Análise da Randomização Mendeliana , Caminhada , Exercício Físico , Emoções , Estudo de Associação Genômica AmplaRESUMO
cfDNA fragmentomic features have been used in cancer detection models; however, the generalizability of the models needs to be tested. We proposed a type of cfDNA fragmentomic feature named chromosomal arm-level fragment size distribution (ARM-FSD), evaluated and compared its performance and generalizability for lung cancer and pan-cancer detection with existing cfDNA fragmentomic features (as reference) by using cohorts from different institutions. The ARM-FSD lung cancer model outperformed the reference model by â¼10% when being tested by two external cohorts (AUC: 0.97 vs. 0.86; 0.87 vs. 0.76). For pan-cancer detection, the performance of the ARM-FSD based model is consistently higher than the reference (AUC: 0.88 vs. 0.75, 0.98 vs. 0.63) in a pan-cancer and a lung cancer external validation cohort, indicating that ARM-FSD model produces stable performance across multiple cohorts. Our study reveals ARM-FSD based models have a higher generalizability, and highlights the necessity of cross-study validation for predictive model development.
Assuntos
Ácidos Nucleicos Livres , Transtornos Cromossômicos , Neoplasias Pulmonares , Humanos , Ácidos Nucleicos Livres/genética , Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Transtornos Cromossômicos/diagnóstico , Biomarcadores Tumorais/genéticaRESUMO
OBJECTIVE: This study aimed to enhance understanding, engagement, and learning efficiency in the course "The Care of Common Diseases of Older Adults" using a developed Immersive Virtual Reality(IVR) system. METHODS: A mixed-methods study with 32 students was conducted. The quantitative part involved a randomized controlled trial, and the qualitative part included thematic interviews with students and teachers. RESULTS: The intervention group using the IVR system showed significant improvements in positivity and performance evaluation scores (P < 0.05) compared to the control group. Negative affect scores also decreased significantly (P < 0.05). Qualitative data from interviews supported the quantitative findings, highlighting increased curiosity, learning enthusiasm, and academic performance. CONCLUSION: IVR significantly enhances learning by stimulating curiosity and active participation, making education more accessible and improving student performance. Future IVR enhancements should focus on user-friendliness and empathetic feedback in adult care.
Assuntos
Realidade Virtual , Humanos , Masculino , Feminino , Idoso , Pesquisa Qualitativa , Estudantes de Enfermagem/psicologia , Adulto , AprendizagemRESUMO
There is a shortage of personnel to provide care for older adults with dementia, and traditional teaching methods could be improved. The teaching method used in the Care for Older Adults With Dementia course is mainly theoretical, lacking real-life care scenarios and practical procedural training. In the current study, we developed a virtual reality (VR) teaching system and designed a randomized controlled trial aimed at testing the availability of the VR-assisted teaching system, filling the gap in teaching through care scenarios, enabling students majoring in intelligent health and oldage care service management to have a more positive attitude toward learning, and improving students' knowledge and course satisfaction. This study showed that the developed VR system can meet the initial needs of daily teaching, help students have a more positive attitude toward learning, and improve their academic performance and course satisfaction. [Journal of Gerontological Nursing, 49(11), 25-32.].
Assuntos
Demência , Enfermagem Geriátrica , Realidade Virtual , Humanos , Idoso , Estudantes , Competência Clínica , Demência/terapiaRESUMO
OBJECTIVE: Primary aldosteronism (PA) is a common form of secondary hypertension. Adrenal venous sampling (AVS) is the gold standard for subtyping PA. This study aimed to determine whether there is a difference between immunoassays and liquid chromatography-mass spectrometry (LC-MS/MS) methods for measuring cortisol levels that affect the judgement of AVS. DESIGN: This was a retrospective study. PATIENTS: Included 72 patients who were diagnosed with PA and had undergone AVS. MEASUREMENTS: Patients were grouped according to whether they received adrenocorticotropic hormone (ACTH) stimulation during AVS, and the cortisol results were measured using immunoassay and LC-MS/MS. RESULTS: There were 48 patients in the without ACTH stimulation group and 24 in the post-ACTH stimulation group during AVS (bilateral adrenal vein cannulation success rate, 56.25% vs. 83.33%). ACTH stimulation was beneficial for increasing the success rate of AVS (p < .001). Immunoassays were linearly correlated with LC-MS/MS when cortisol concentrations were <1750 nmol/L (r = .959, p < .001). When cortisol concentrations were >17,500 nmol/L, no correlation was found between the two methods (p = .093). The two methods were consistent for the detection of cortisol for evaluating the success of cannulation for AVS. Five percent of patients showed discordant lateralization of aldosterone production according to the cortisol LC-MS/MS and immunoassay results in the without ACTH group, and 15% showed discordant lateralization in the post-ACTH group. CONCLUSIONS: The immunoassay method can be used to determine whether cannulation is successful. The final decision for lateralization may be more appropriate based on LC-MS/MS results.
Assuntos
Hidrocortisona , Hiperaldosteronismo , Glândulas Suprarrenais/irrigação sanguínea , Aldosterona , Cromatografia Líquida , Erros de Diagnóstico , Humanos , Hidrocortisona/análise , Hiperaldosteronismo/diagnóstico , Estudos Retrospectivos , Espectrometria de Massas em TandemRESUMO
Adoptive T cell transfer is one of the most promising ways to combat solid tumors. However, the weak infiltration of T cells into tumor sites has restricted their antitumor efficacy. To overcome this obstacle, we used the lipophilic protein painting strategy to improve tumor targeting and penetrating capacity of lymphocytes for the first time. We synthesized the lipid anchor consisting of a bispecific recombinant protein iRGD-antiEGFR and DSPE-PEG derivates, then successfully inserted it into the membranes of T cells. This surface modification was non-invasive and could efficiently improve the infiltration ability of T cells into multicellular spheroids and tumor masses. The surface modified T cells also displayed superior antitumor activities in EGFR-positive tumor xenografts via systematic infusion. Moreover, the permeability and antitumor efficacy of these surface painted T cells could be remarkably enhanced when used in combination with local low-dose irradiation.
Assuntos
Membrana Celular/metabolismo , Imunoterapia Adotiva/métodos , Linfócitos do Interstício Tumoral/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Anticorpos de Domínio Único/metabolismo , Neoplasias Gástricas/terapia , Linfócitos T/metabolismo , Animais , Linhagem Celular Tumoral , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Engenharia Genética , Humanos , Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidiletanolaminas , Polietilenoglicóis , Receptores de Antígenos de Linfócitos T/genética , Anticorpos de Domínio Único/genética , Neoplasias Gástricas/imunologia , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Background: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based assays are employed in more and more clinical laboratories to quantify steroids. The steroid quantification by LC-MS/MS shows great value in screening or diagnosing endocrine disorders; however, the number of functional steroids included in the LC-MS/MS methods is still limited. Methods: Here, we describe the performance and validation of a 20-steroid plasma panel by LC-MS/MS. The panel included progestogens (including mineralocorticoids and glucocorticoids), androgens and estrogens biosynthesized in steroid metabolic pathways. The LC-MS/MS method was validated according to guidance documents, and subsequently employed to profile steroid changes in endocrine disorders. Results: Using LC-MS/MS, 20 steroids were separated and quantified in 8 min. Coefficients of variation (CVs) of the 20 analytes at the lower limit of quantification (LLoQ) were all less than 15% (ranging from 1.84% to 14.96%). The linearity of the assay was demonstrated by all the R2 values greater than 0.995. Individual plasma steroids changed significantly in patients with subclinical Cushing's syndrome (SCS) and polycystic ovary syndrome (PCOS) - 17-hydroxypregnenolone (17-OH-PR), testosterone (T) and dihydrotestosterone (DHT) were significantly decreased in SCS patients, while in PCOS patients, pregnenolone, corticosterone (CORT), androstenedione (A4) and T were significantly increased and DHT was decreased. Conclusions: The LC-MS/MS method we developed for the quantification of 20 plasma steroids is clinical practicable. The steroid profiling data using this assay indicate its screening value for endocrine disorders. To further explore the value of the assay, more investigations are however needed.
Assuntos
Cromatografia Líquida , Hipersecreção Hipofisária de ACTH/sangue , Síndrome do Ovário Policístico/sangue , Esteroides/sangue , Espectrometria de Massas em Tandem , Feminino , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BMS-986120 is a PAR4 antagonist that is being investigated as an antiplatelet agent in phase I clinical trial. An improved synthesis of BMS-986120 has been developed. Based on the novel synthetic approach to BMS-986120, a series of deuterated derivatives of BMS-986120 have been synthesized and biologically evaluated to search for more potent antiplatelet agents. The in vitro antiplatelet assay by turbidimetry demonstrated that PC-2 and PC-6 had IC50 values of 6.30â¯nM and 6.97â¯nM, respectively, versus BMS-986120 with an IC50 of 7.80â¯nM. The result of in vitro metabolic stability study showed that all of the deuterated compounds had similar half-life (T1/2) and intrinsic clearance (Clint) in comparison with BMS-986120. Further probing the metabolic profile of BMS-986120 is worth being conducted.
Assuntos
Benzofuranos/farmacologia , Imidazóis/farmacologia , Morfolinas/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Receptores de Trombina/antagonistas & inibidores , Tiazóis/farmacologia , Animais , Benzofuranos/síntese química , Benzofuranos/química , Plaquetas/efeitos dos fármacos , Deutério , Estabilidade de Medicamentos , Humanos , Imidazóis/síntese química , Imidazóis/química , Masculino , Camundongos Endogâmicos ICR , Microssomos Hepáticos/metabolismo , Morfolinas/síntese química , Morfolinas/química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Tiazóis/síntese química , Tiazóis/químicaRESUMO
AIM: Diabetic bladder dysfunction (DBD) is one of the most common and bothersome complications of diabetes mellitus (DM). This study aimed to investigate the functional, structural, and molecular changes of the bladder at 0, 3, 6, 9, and 12 weeks after DM induction by streptozotocin (STZ) in male C57BL/6 mice. METHODS: Male C57BL/6J mice were injected with STZ (130 mg/kg). Then, diabetic general characteristics, cystometry test, histomorphometry, and contractile responses to α, ß-methylene ATP, KCl, electrical-field stimulation, carbachol were performed at 0, 3, 6, 9, and 12 weeks after induction. Finally, protein and messenger RNA (mRNA) expressions of myosin Va and SLC17A9 were quantified. RESULTS: DM mice exhibited lower body weight, voiding efficiency and higher water intake, urine production, fasting blood glucose, oral glucose tolerance test, bladder wall thickness, maximum bladder capacity, residual volume, bladder compliance. In particular, nonvoiding contractions has increased more than five times at 6 weeks. And the amplitudes of spontaneous activity, contractile responses to all stimulus was about two times higher at 6 weeks but cut almost in half at 12 weeks. The protein and mRNA expressions of myosin Va and SLC17A9 were about two times higher at 6 weeks, but myosin Va was reverted nearly 40% while SLC17A9 is still higher at 12 weeks. CONCLUSIONS: DBD transitioned from a compensated state to a decompensated state in STZ-induced DM mice at 9 to 12 weeks after DM induction. Our molecular data suggest that the transition may be closely related to the alterations of myosin Va and SLC17A9 expression levels in the bladder with time.
Assuntos
Diabetes Mellitus Experimental/patologia , Doenças da Bexiga Urinária/patologia , Animais , Peso Corporal , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Ingestão de Líquidos , Estimulação Elétrica , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/efeitos dos fármacos , Cadeias Pesadas de Miosina/biossíntese , Cadeias Pesadas de Miosina/genética , Miosina Tipo V/biossíntese , Miosina Tipo V/genética , Proteínas de Transporte de Nucleotídeos/biossíntese , Proteínas de Transporte de Nucleotídeos/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Estimulação Química , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/genética , UrodinâmicaRESUMO
BACKGROUND: This study aimed to elucidate the effects and mechanisms of Radix Linderae (RL) extracts on a mouse model of diabetic bladder dysfunction (DBD), especially on later decompensated phase. METHODS: Male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) after 4 weeks of high-fat diet (HFD) feeding. DBD mouse models (later decompensated phase) were developed by 12-weeks persistent hyperglycemia and then treated with RL extracts for 4 weeks. During administration, the fasting blood glucose (FBG) test was performed once a week. Four weeks later, oral glucose tolerance test (OGTT), voided stain on paper (VSOP), and urodynamic alteration were explored. We also performed haematoxylin and eosin (H&E) and Masson's trichrome staining to observe the histology of the bladder. Then, the contractile responses to α, ß-methylene ATP, capsaicin (CAP), KCl and carbachol were measured. Moreover, qPCR assay was performed to analyse the bladder gene expression levels of M3 receptors and TRPV1. RESULTS: The diabetic mice exhibited higher FBG, OGTT and urine production, and no substantial alteration was observed after RL treatment. Urodynamic test showed the maximum bladder capacity (MBC), residual volume (RV) and bladder compliance (BC), as well as the decrement of voided efficiency (VE) and micturition volume (MV), remarkably increased in the DBD mice. Furthermore, RL treatment significant improved urodynamic urination, with lower MBC, RV, and, BC, as well as higher VE and MV, as compared with the model groups. The wall thickness of the bladder and the ratio of smooth muscle/collagen remarkably increased, and RL could effectively attenuate the pathological change. The response of bladder strips to the stimulus was also reduced in the DBD mice, and RL treatment markedly increased the contraction. Furthermore, the gene expression levels of M3 receptors and TRPV1 were down-regulated in the bladders of the diabetic mice, whereas RL treatment retrieved those gene expression levels. CONCLUSIONS: RL extracts can improve the bladder voiding functions of the DBD model mice in later decompensated phase, and underlying mechanisms was associated with mediating the gene expression of M3 receptors and TRPV1 in the bladder instead of improving blood sugar levels.
Assuntos
Diabetes Mellitus Experimental/complicações , Medicamentos de Ervas Chinesas , Lindera/química , Doenças da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Raízes de Plantas , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Doenças da Bexiga Urinária/fisiopatologiaRESUMO
Adoptive cell therapy (ACT) of autologous tumor-infiltrating lymphocytes (TILs) has shown an effect on mediating tumor regression in some patients with highly advanced, refractory metastatic malignancy. Here, the in vitro generation of TILs isolated from malignant pleural effusion and ascites was compared with which using engineered cells for costimulatory enhancement (ECCE) and 3 common γ-chain cytokines, interleukin (IL)-2, IL-7, and IL-15, alone or in combination. We showed the robust clinical-scale production of TILs with a less differentiated 'young' phenotype by expansion in the presence of ECCE combined with IL-2/7/15. Furthermore, a major fraction of the TILs generated in this fashion was shown to produce much more IFN-γ and TNF-α, and displayed cytolytic activity against target cells expressing the relevant antigens. To our knowledge, this is the first time that the combination of ECCE and IL-2/7/15 has been applied for the generation of TILs isolated from malignant pleural effusion and ascites.
Assuntos
Ascite/imunologia , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/imunologia , Derrame Pleural Maligno/imunologia , Ligante 4-1BB/genética , Ligante 4-1BB/imunologia , Ligante 4-1BB/metabolismo , Adulto , Idoso , Ascite/patologia , Divisão Celular/imunologia , Células Cultivadas , Feminino , Humanos , Imunoterapia Adotiva/métodos , Interleucina-15/genética , Interleucina-15/imunologia , Interleucina-15/metabolismo , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-2/metabolismo , Interleucina-7/genética , Interleucina-7/imunologia , Interleucina-7/metabolismo , Células K562 , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Derrame Pleural Maligno/patologiaRESUMO
Adoptive immunotherapy is a promising cancer treatment that entails infusion of immune cells manipulated to have antitumor specificity, in vitro. Antigen-specific cytotoxic T lymphocytes are the main executors of transformed cells during cancer immunotherapy. To induce antigen-specific cytotoxic T lymphocytes, we developed artificial antigen-presenting cells (aAPCs) by engineering K562 cells with electroporation to direct the stable expression of HLA-A∗0201, CD80, and 4-1BBL. Our findings demonstrate that after three stimulation cycles, the aAPCs promoted the induction of antigen-specific cytotoxic T lymphocytes with a less differentiated "young" phenotype, which enhanced immune responses with superior cytotoxicity. This novel, easy, and cost-effective approach to inducing antigen-specific cytotoxic T lymphocytes provides the possibility of improved cancer therapies.
Assuntos
Apresentação de Antígeno/imunologia , Células Apresentadoras de Antígenos/imunologia , Antígenos de Neoplasias/imunologia , Células Dendríticas/imunologia , Linfócitos T Citotóxicos/imunologia , Ligante 4-1BB/imunologia , Antígeno B7-1/imunologia , Linhagem Celular Tumoral , Antígenos HLA-A/imunologia , Humanos , Imunoterapia Adotiva/métodos , Células K562 , Ativação Linfocitária/imunologiaRESUMO
Blockade of the immune cell checkpoint inhibitors programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) has become a powerful tool in cancer treatment, which is effective across various solid cancer types and hematologic malignancies. Our previous studies showed that by reducing immune tolerance, clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) modified cytotoxic T lymphocytes (CTLs) rank highly in terms of immune responses and cytotoxicity. In this study, a genetically modified K562 cell line with surface expression of 4-1BBL was developed to expand PD-1-disrupted CTLs in vitro for further adoptive immunotherapy against cancer. Our findings demonstrate that after a long-term, up to 28days, engineered cells for costimulatory enhancement (ECCE) combined with IL-21 promote the expansion of PD-1-disrupted CTLs with a less differentiated "young" phenotype, enhanced immune response and superior cytotoxic effector characteristics. These new in vitro conditions represent a nimble and cost-effective approach to developing PD-1-disrupted CTLs with improved therapeutic potential.
Assuntos
Ligante 4-1BB/genética , Vacinas Anticâncer/imunologia , Imunoterapia Adotiva/métodos , Interleucinas/uso terapêutico , Neoplasias/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Linfócitos T Citotóxicos/imunologia , Ligante 4-1BB/metabolismo , Sistemas CRISPR-Cas , Proliferação de Células , Citotoxicidade Imunológica , Engenharia Genética , Humanos , Tolerância Imunológica , Células K562 , Ativação Linfocitária , Neoplasias/imunologia , Linfócitos T Citotóxicos/transplanteRESUMO
LncRNA SPRY4-IT1 has been shown to promote the progression of melanoma. However, the role of lncRNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to investigate the clinical significance and biological functions of SPRY4-IT1 in ESCC. The expression levels of lncRNA SPRY4-IT in 92 ESCC patients and 8 ESCC cell lines were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in ESCC cell lines. Both in vitro and in vivo assays were performed to further explore its role in tumor progression. SPRY4-IT1 levels were significantly higher in ESCC tissues and cells than in corresponding adjacent noncancerous tissues and nontumorigenic esophageal epithelial cells, and the ESCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. The multivariate analysis revealed that SPRY4-IT1 expression level is an independent prognostic factor in ESCC patients. In vitro assays demonstrated that knockdown of SPRY4-IT1 reduced cell proliferation, invasiveness, and migration. In vivo assays demonstrated that knockdown of SPRY4-IT1 decreases cell growth. SPRY4-IT1 is a novel molecule involved in ESCC progression, which may provide a potential prognostic biomarker and a potential target for therapeutic intervention.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , RNA Longo não Codificante/fisiologia , Idoso , Animais , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , RNA Longo não Codificante/genética , Regulação para CimaRESUMO
BACKGROUND: Recent studies revealed that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer. AIM: This study aimed to assess the potential role of PlncRNA-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PlncRNA-1 in 73 pairs of ESCC and their matched normal tissues. The correlation of PlncRNA-1 with clinicopathological features and clinical stages was also analyzed. Cancer cell proliferation and apoptosis were assessed following knock-down of PlncRNA-1 by MTT, colony formation assay, and flow cytometry. RESULTS: The expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8 %, p < 0.05), and the high level of PlncRNA-1 expression was significantly correlated with advanced clinical stage (p < 0.01) and lymph node metastasis (p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro. CONCLUSIONS: PlncRNA-1 plays an important role in ESCC cell proliferation. Overexpression of PlncRNA-1 is correlated with advanced tumor stage and lymph node metastasis, and may serve as a potential prognostic marker and therapeutic target for ESCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: To develop a method for determination of voglibose contents in its tablets by high-performance liquid chromatography-mass spectrometry (HPLC-MS). METHODS: The measurements were carried out on an Agilent ZORBAX Eclipse Plus C18 column (2.1×150mm 3.2µm) with a temperature of 40 degrees Celsius. A mixture of methanol and water (2:3,v/v) was used as a mobile phase at a flow rate of 0.25 ml/min. Voglibose was detected in an electrospray ionization (ESI) mode with MRM. RESULTS: The calibration curves of voglibose showed good linearity in a range of 1.5804-2.6340 µg/ml (r=0.9990). The average recovery was 100.2% with RSD of 1.37% (n=6) for m/z 268.2/74.2.Linearity was obtained with r=0.9976 and the average recovery was 99.3% with RSD of 1.78% (n=6) for m/z 268.2/92.2. CONCLUSION: HPLC-MS method is accurate,reproducible and can be used for quality control of voglibose tablets.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Inositol/análogos & derivados , Espectrometria de Massas/métodos , Inositol/análise , ComprimidosRESUMO
The personalized neoantigen nanovaccine (PNVAC) platform for patients with gastric cancer we established previously exhibited promising anti-tumor immunoreaction. However, limited by the ability of traditional neoantigen prediction tools, a portion of epitopes failed to induce specific immune response. In order to filter out more neoantigens to optimize our PNVAC platform, we develop a novel neoantigen prediction model, NUCC. This prediction tool trained through a deep learning approach exhibits better neoantigen prediction performance than other prediction tools, not only in two independent epitope datasets, but also in a totally new epitope dataset we construct from scratch, including 25 patients with advance gastric cancer and 150 candidate mutant peptides, 13 of which prove to be neoantigen by immunogenicity test in vitro. Our work lay the foundation for the improvement of our PNVAC platform for gastric cancer in the future.
Assuntos
Vacinas Anticâncer , Neoplasias Gástricas , Vacinas , Humanos , Antígenos de Neoplasias , Neoplasias Gástricas/prevenção & controle , Epitopos , Peptídeos , ImunoterapiaRESUMO
Background: Several studies have shown that surgery may improve prognosis in patients with limited-stage small cell lung cancer (LS-SCLC). This study aimed to compare the effects of different treatment modalities on lung cancer specific survival (LCSS) and overall survival (OS) in LS-SCLC patients. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed with LS-SCLC. Kaplan-Meier analysis was used to determine the effect of each factor on LCSS and OS. Multivariate analysis was used to analyze the relationship between patient characteristics and survival of different treatment modalities. Results: After a series of screening steps, this study ultimately analyzed the prognosis of patients with stage I-IIIa SCLC under different treatment modalities. The results showed that lobectomy plus postoperative chemoradiotherapy was significantly better than chemoradiotherapy or lobectomy in treatment (all P<0.05). For stage II and IIIA patients, lobectomy plus postoperative chemotherapy ± radiotherapy had similar efficacy to chemoradiotherapy in improving patients' LCSS and OS (all P>0.05), and lobectomy plus postoperative chemotherapy ± radiotherapy did not significantly improve LCSS or OS compared with lobectomy (all P>0.05). Conclusions: For stage II-IIIa SCLC patients, lobectomy might have similar efficacy to chemoradiotherapy in improving LCSS and OS, and there is no need for adjuvant chemotherapy ± radiotherapy after surgery. For stage I SCLC patients, lobectomy plus postoperative chemoradiotherapy might be superior to chemoradiotherapy or lobectomy in improving LCSS and OS; however, the conclusion might be biased. These results suggest that the effect of surgery on SCLC patients may be worthy of further study.
RESUMO
Pyrolysis holds immense potential for clean treatment of pulp and paper mill sludge (PPMS), enabling efficient energy and chemical recovery. However, current understanding of PPMS pyrolysis kinetics and product characteristics remains incomplete. This study conducted detailed modeling of pyrolysis kinetics for two typical PPMSs from a wastepaper pulp and paper mill, namely, deinking sludge (PPMS-DS) and sewage sludge (PPMS-SS), and analyzed comprehensively pyrolysis products. The results show that apparent activation energy of PPMS-DS (169.25-226.82 kJ/mol) and PPMS-SS (189.29-411.21 kJ/mol) pyrolysis undergoes significant change, with numerous parallel reactions present. A distributed activation energy model with dual logistic distributions proves to be suitable for modeling thermal decomposition kinetics of both PPMS-DS and PPMS-SS, with coefficient of determination >0.999 and relative root mean square error <1.99 %. High temperature promotes decomposition of solid organic materials in PPMS, and maximum tar yield for both PPMS-DS (53.90 wt%, daf) and PPMS-SS (56.48 wt%, daf) is achieved at around 500 °C. Higher levels of styrene (24.45 % for PPMS-DS and 14.71 % for PPMS-SS) and ethylbenzene (8.61 % for PPMS-DS and 8.33 % for PPMS-SS) are detected in tar and could be used as chemicals. This work shows great potential to propel development of PPMS pyrolysis technology, enabling green and sustainable production in pulp and paper industry.