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1.
Anticancer Res ; 40(2): 977-981, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014942

RESUMEN

BACKGROUND/AIM: The aim of this study was to analyze the survival of patients with brain metastases treated with best supportive care or additional whole-brain radiotherapy (WBRT), in order to confirm results from the prospective randomized QUARTZ study, which suggested prolonged survival after WBRT (5 fractions of 4 Gy) if favorable prognostic factors were present (age younger than 60 years, graded prognostic assessment score 2.5-3 points). PATIENTS AND METHODS: We performed a retrospective single institution analysis of 76 patients with favorable prognosis. In contrast to the QUARTZ trial, inclusion was not limited to patients with non-small cell lung cancer (NSCLC). Furthermore, a cohort treated with higher total doses of WBRT was included (10 fractions of 3 Gy). RESULTS: All patients were younger than 60 years or had a graded prognostic assessment score of 2.5-3. The median survival was significantly shorter after best supportive care (1.2 months; 3.2 months after WBRT with 5 fractions of 4 Gy and 3.9 months after 10 fractions of 3 Gy). Also, in multivariate analyses, survival was significantly better after WBRT. Further favorable prognostic factors included better performance status, no or limited extracranial metastases and primary tumor other than gastrointestinal. CONCLUSION: In line with the QUARTZ trial results, WBRT prolonged survival in patients with favorable prognostic features.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/patología , Irradiación Craneana , Neoplasias Pulmonares/patología , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Irradiación Craneana/métodos , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento
2.
Anticancer Res ; 40(2): 1007-1014, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014946

RESUMEN

BACKGROUND/AIM: Myeloid cell leukemia-1 (MCL-1) is a member of the B-cell lymphoma-2 (Bcl-2) family of proteins, which regulate the intrinsic (mitochondrial) apoptotic cascade. MCL-1 inhibits apoptosis, which may be associated with resistance to cancer therapy. Therefore, in this study, the clinical role of MCL-1 in non-small cell lung cancer (NSCLC) was explored. PATIENTS AND METHODS: This retrospective study included 80 patients with stage 1-3A NSCLC, who underwent surgery without preoperative treatment between 2010 and 2011. MCL-1 expression and Ki-67 index were determined via immunohistochemical staining. Apoptotic index (AI) was determined via terminal deoxynucleotidyl transferase dUTP nick end labeling. RESULTS: The receiver operating characteristic curve analysis (area under curve=0.6785) revealed that MCL-1 expression in 30.0% of the NSCLC tumor cells was a significant cut-off for predicting prognosis. Tumors were considered MCL-1-positive if staining was observed in >30% of the cells. Thirty-six tumors (45.0%) were MCL-1-positive. However, there were no significant differences between MCL-1 expression and clinical variables. AI was lower in MCL-1-positive (2.2±3.6%) than in MCL-1-negative (5.2±7.9%) tumors, although the difference was not significant (p=0.1080). The Ki-67 index was significantly higher in MCL-1-positive than in MCL-1-negative tumors (18.0% vs. 3.0%; p<0.001). Five-year survival rate was significantly worse in patients with MCL-1-positive tumors (68.3%) than in those with MCL-1-negative tumors (93.1%, p=0.0057). Univariate [hazard ratio (HR)=5.041, p=0.0013], and multivariate analyses revealed that MCL-1 expression was a significant prognostic factor (HR=3.983, p=0.0411). CONCLUSION: MCL-1 expression in NSCLC cells correlated inversely with AI and positively with Ki-67 index. MCL-1 may serve as a potential prognostic biomarker and a novel therapeutic target in NSCLC.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Adulto , Anciano , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC
3.
Zhonghua Yi Xue Za Zhi ; 100(3): 213-219, 2020 Jan 21.
Artículo en Chino | MEDLINE | ID: mdl-32008289

RESUMEN

Objective: To investigate the efficacy and safety of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope. Methods: One hundred patients undergoing radical resection of lung cancer under thoracoscope in Affiliated Cancer Hospital of Zhengzhou University from March to September in 2019, were randomly divided into control group (group C) and sugammadex group (group S). All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion of propofol and remifentanil, and intermittent intravenous injection of the neuromuscular block of rocuronium. During the operation, the bispectral index (BIS) was used to monitor the depth of anesthesia, and the neuromuscular block was assessed with TOF. Single-lung mechanical ventilation and double-lumen endotracheal intubation were carried out, and patient-controlled analgesia after operation were enforced. Patients in group C received neostigmine (2 mg) combined with atropine (0.5-1.0 mg) after thoracic closure, while patients in group S received sugammadex (2 mg/kg) at TOF count (≥2) after thoracic closure, and then double-lumen endotracheal tubes were extubated according to extubation indications. At these time points: T(0) (immediate before anesthesia induction), T(1) (immediate before tracheal intubation), T(2) (immediately after thoracic closure), T(3) (1 h after operation), T(4) (6 h after operation), T(5) (24 h after operation), T(6)(48 h after operation), the heart rate(HR) and mean arterial pressure (MAP) were recorded, QT interval (V3 ECG) were measured and calculated, indicators of liver function [alanine transaminase (ALT), aspartate transaminase(AST)], renal function [blood urea nitrogen (BUN), creatinine (Cre)] and clotting function [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The duration of operation, postoperative conditions within 48 hours after operation(the time of tracheal tube extubation, respiratory suppression/dysfunction, allergy, nausea and vomiting, itching of skin, abnormal sensation), pathological types and the postoperative hospital stay were recorded. Results: There were no significant differences of the age, sex ratio, body mass index (BMI), American Society of Anesthesiologists (ASA) grading ratio, duration of operation, pathological types and the postoperative hospital stay, HR, MAP and QT interval between two groups (all P>0.05). There were no remarkable differences of the levels of serum histamine, ALT, AST, BUN, Cre, TT, PT, APTT and FIB before and after administration of neuromuscular blockade antagonists (neostigmine or Sugammadex) in the same group patients (all P>0.05), also no significant differences between group C and group S at the same time points (all P>0.05). Average time of tracheal tube extubation in group S [(3.7±1.3) min] was sharply shorter than that in group C [(14.5±4.4) min, t=2.266, P<0.05)]. There were no patients with allergy, skin itching, sensory abnormality in these two groups. There were no significant difference of the incidence of postoperative nausea and vomiting between these two groups. There were 5 patients with respiratory depression in group C and no respiratory depression patient in group S, the difference was statistically significant between these two groups (χ(2)=5.263, P<0.05). Conclusion: Sugammadex is effective for antagonizing the neuromuscular blockade of rocuronium in patients with radical resection of lung cancer under thoracoscope, and can shorten the time of tracheal tube extubation after surgery.


Asunto(s)
Neoplasias Pulmonares/cirugía , Bloqueo Neuromuscular/métodos , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , Sugammadex/administración & dosificación , gamma-Ciclodextrinas , Androstanoles/administración & dosificación , Androstanoles/antagonistas & inhibidores , Inhibidores de la Colinesterasa , Humanos , Neoplasias Pulmonares/patología , Neostigmina/administración & dosificación , Fármacos Neuromusculares no Despolarizantes/efectos adversos , Sugammadex/efectos adversos , Toracoscopios
4.
Medicine (Baltimore) ; 99(5): e18455, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000358

RESUMEN

INTRODUCTION: Whole brain radiotherapy (WBRT) has been the mainstay treatment of brain metastases (BM) in non-small cell lung cancer (NSCLC) patients for years. Temozolomide (TMZ) could penetrate the blood-brain barrier and some studies showed that TMZ plus MBRT may improve clinical effectiveness. This meta-analysis is aim to evaluate the clinical effectiveness and safety of TMZ plus MBRT in the NSCLC patients with BM. METHODS AND ANALYSIS: We systematically searched databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database) without language restrictions from inception until July 26, 2019. Randomized controlled trials (RCTs) which compared TMZ plus WBRT with single WBRT in the advanced NSCLC patients with BM were included. The outcomes analysis reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), quality of life (QOL), and adverse effects. Two reviewers will independently extract data from the selected studies and assess the quality of studies. Statistical analyses will be performed using Review manager 5.3 software. Random-effects or fixed models were used to estimate pooled hazard ratio and relative risk. RESULTS: This systemic review and meta-analysis will evaluate the effects of TMZ plus MBRT in the NSCLC patients with BM in RCTs. CONCLUSION: Our study will provide evidence to judge if TMZ plus MBRT are effective treatment for NSCLC patients with BM.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Temozolomida/uso terapéutico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/secundario , Humanos , Neoplasias Pulmonares/patología , Metaanálisis como Asunto , Revisiones Sistemáticas como Asunto
5.
Adv Exp Med Biol ; 1225: 53-69, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32030647

RESUMEN

Tobacco smoke is a multicomponent mixture of chemical, organic, and inorganic compounds, as well as additive substances and radioactive materials. Many studies have proved the carcinogenicity of various of these compounds through the induction of DNA adducts, mutational potential, epigenetic changes, gene fusions, and chromosomal events. The tumor microenvironment plays an important role in malignant tumor formation and progression through the regulation of expression of key molecules which mediate the recruitment of immune cells to the tumor site and subsequently regulate tumor growth and metastasis. In this chapter, we discuss the effects of inhaled tobacco smoke in the tumor microenvironment of the respiratory tract. The mechanisms underlying these effects as well as their link with tumor progression are analyzed.


Asunto(s)
Neoplasias Pulmonares/patología , Humo/efectos adversos , Tabaco , Microambiente Tumoral/efectos de los fármacos , Progresión de la Enfermedad , Humanos , Tabaco/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos
6.
Life Sci ; 244: 117346, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31978448

RESUMEN

AIM: Emerging studies have shown that application of low concentration of bioactive phytomolecules can confer anti-proliferative effects on tumour cells by inducing senescence pathways. The alkaloid berberine is recognized for its anti-cancer attributes but its potential to induce senescence in tumour cells is least understood. MATERIALS AND METHODS: The present work assessed the mechanisms pertaining to dose-dependent anti-proliferative effects of berberine in the perspective of senescence and inflammation using human non-small cell lung cancer cell line (A549). KEY FINDINGS: Amongst the different tested bioactive phytomolecules, berberine treatment suppressed the proliferation of A549 cells regardless of the concentration applied. Application of low doses of berberine induced a weak SA-ß-gal activity and p21WAF1 expression but did not show evidence of SASP activation due to absence of NF-κB activation and expression of proinflammatory genes. However, treatment with higher dose of berberine showed no evidence of SA-ß-gal activity or p21WAF1 expression, but instead induced apoptosis and suppressed the expression of cell cyclins. The proliferative capacity of berberine treated cells was at par with control cells and no SA-ß-gal activity could be observed in first generation of berberine treated cells. mTOR pathway showed no distinct activation on account of berberine treatment thereby further emphasizing that low dose of berberine induced quiescence and not senescence in A549 cells. SIGNIFICANCE: Taken together, our observations indicate that despite its strong anti-proliferative effects, low dose berberine treatment may only induce transient changes akin to quiescence that needs to be considered before implying pro-senescence attributes of berberine in cancer therapeutics.


Asunto(s)
Apoptosis/efectos de los fármacos , Berberina/farmacología , Senescencia Celular/efectos de los fármacos , Ciclinas/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inflamación/tratamiento farmacológico , Neoplasias Pulmonares/patología , Serina-Treonina Quinasas TOR/metabolismo , Células A549 , Proliferación Celular/efectos de los fármacos , Ciclinas/genética , Humanos , Inflamación/metabolismo , Inflamación/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/genética
7.
Isr Med Assoc J ; 22(1): 22-26, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31927801

RESUMEN

BACKGROUND: Prophylactic cranial irradiation (PCI) exclusion in favor of brain magnetic resonance imaging (MRI) staging and surveillance in the management of small cell lung cancer (SCLC) is controversial yet accepted by some centers. The use of MRI suggests performing stereotactic radiosurgery (SRS) treatment for limited brain metastases. Data regarding SRS efficacy in this setting is limited. OBJECTIVES: To assess intracranial objective response rate (iORR), progression-free survival (iPFS), intracranial failure patterns, overall survival (OS) and time-to-whole-brain radiation therapy (WBRT)/death, whichever occurred first (TTWD) with SRS in SCLC. METHODS: The study comprised 10 consecutive SCLC patients with brain metastases treated with SRS and followed-up at Davidoff Cancer center between Aug 2012 and March 2019. Brain MRI images were reviewed by a neuro-radiology specialist. RESULTS: iORR was 57% as assessed by response assessment in neuro-oncology brain metastases. Intracranial progression developed in 8 patients. Median iPFS was 4.0 months (95% confidence interval [95%CI] 1.7-7.2). In-site, off-site and combined pattern of intracranial failure was seen in 0, 5, and 3 patients, respectively; median number of new brain lesions following SRS was 4 (range, 1-12). SRS was performed 10 additional times in 6 patients (median number of lesions irradiated per round was 1, range 1-5). WBRT was administered in 3 patients. Median TTWD was 20.9 months (95% CI, 1.9-26.8). Median OS since SRS administration was 23.2 months (95% CI, 4.2-not reached). CONCLUSIONS: MRI surveillance with multiple rounds of SRS may serve a reasonable alternative to PCI or therapeutic WBRT in SCLC.


Asunto(s)
Neoplasias Encefálicas/secundario , Neoplasias Pulmonares/patología , Radiocirugia , Carcinoma Pulmonar de Células Pequeñas/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Supervivencia sin Progresión , Radiocirugia/métodos , Resultado del Tratamiento
8.
Anticancer Res ; 40(1): 379-386, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892590

RESUMEN

BACKGROUND/AIM: We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) alone for Stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Data of 65 patients (median age=73 years) with Stage III NSCLC who underwent CIRT alone in the QST Hospital, Chiba, Japan, between 1997 and 2015 were retrospectively analysed. The median dose was 72.0 Gy (relative biological effectiveness). RESULTS: The median follow-up was 27.6 months (range=1.6-207.7 months). Two-year local control, progression-free survival (PFS), and overall survival (OS) rates were 73.9%, 38.6%, and 54.9%, respectively. Overall, 1 (2%), 4 (6%), and 1 (2%) patient developed Grade 4 (mediastinal haemorrhage), Grade 3 (radiation pneumonitis), and Grade 3 (bronchial fistula) toxicities, respectively. On univariate analysis, clinical T and N stage and CIRT timing were significant predictors of PFS and OS; clinical target volume was a significant predictor of PFS. CONCLUSION: CIRT alone is effective with acceptable toxicity for Stage III NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Radioterapia de Iones Pesados/efectos adversos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del Tratamiento
9.
Anticancer Res ; 40(1): 413-419, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892595

RESUMEN

BACKGROUND/AIM: In patients with lung cancer, there has been no study that treated 'distant metastases' as 'metastatic patterns'. This study aimed to evaluate if specific 'metastatic patterns' exist in lung cancer patients. PATIENTS AND METHODS: Data were collected from lung cancer patients between 2009 and 2018. Metastatic patterns were analyzed using cluster analysis in patients with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, those with small cell lung cancer (SCLC), and those with squamous cell lung cancer (SqCLC). RESULTS: In 313 patients (127 patients with EGFR mutation, 87 patients with SCLC, and 99 patients with SqCLC), metastatic patterns existed in each of the three subset groups, and metastatic patterns of these groups were statistically different. CONCLUSION: The knowledge of the metastatic patterns might be useful for clinical practice in the foreseeable future, as it enables a more efficient detection of metastatic disease through imaging, and a more effective treatment at predicted metastatic sites.


Asunto(s)
Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón/genética , Anciano , Anciano de 80 o más Años , Análisis por Conglomerados , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Metástasis de la Neoplasia , Probabilidad
10.
Anticancer Res ; 40(1): 421-426, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892596

RESUMEN

BACKGROUND/AIM: Distant organ metastases do not occur at random in lung cancer. A retrospective study was conducted in order to evaluate 1) what kinds of metastatic patterns exist in three different types of lung cancer, and 2) whether metastatic patterns affected prognosis in the different types of lung cancer. PATIENTS AND METHODS: Data were collected from all consecutive patients with diagnosed lung cancer between April 2009 and October 2018 in our hospitals. Cluster analysis was performed to classify patients. Kaplan-Meier analysis, log-rank test, and Cox proportional hazards model were used. RESULTS: Epidermal growth factor-mutated adenocarcinoma, small cell lung cancer, and squamous cell lung cancer had different 'metastatic patterns', survival, and unfavorable prognostic factors, respectively. CONCLUSION: There might be different metastatic patterns, survival, and unfavorable prognostic factors in each pathological and genetic type of lung cancer. It is worthwhile carrying out diagnostic imaging and treatment considering information on metastatic patterns.


Asunto(s)
Neoplasias Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación/genética , Metástasis de la Neoplasia , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia
11.
Anticancer Res ; 40(1): 261-269, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892575

RESUMEN

BACKGROUND: Pulmonary pleomorphic carcinoma (PPC) is a rare aggressive neoplasm, with dismal prognosis. Whether tumor immunity is associated with the progressive biological behavior of PPC remains unclear. The purpose of this study was to examine the prognostic significance of tumor immunity-related markers such as programmed death-1 ligand (PD-L1) and CD4+ or CD8+ tumor-infiltrating lymphocytes (TILs) in patients with surgically resected PPC. PATIENTS AND METHODS: Ninety-nine patients with surgically resected PPC were assessed by immunohistochemistry. The expression of PD-L1, CD4, and CD8 was examined in specimens of the resected tumors. RESULTS: PD-L1 was highly expressed in 61% (60/99) of lesions and high expression of CD4 and CD8 was identified in 42% (42/99) and 51% (51/99) of lesions, respectively. There was no relationship between the expression PD-L1 and the numbers of CD4+ or CD8+ TILs. The expression of PD-L1 was not identified as a significant prognostic marker; however, a low number of CD4+ TILs was identified as an independent marker for predicting a worse outcome after surgical resection of PPC, especially in patients with an epithelial component of adenocarcinoma or early stage of disease. By univariate analysis, a low number of CD8+ TILs was found to be a significant prognostic marker linked to poor overall survival in patients with non-adenocarcinoma components. CONCLUSION: A low number of CD4+ TILs is an independent marker for predicting a favorable prognosis after surgical resection in patients with PPC, especially in patients with adenocarcinoma components or early stage of disease.


Asunto(s)
Adenoma Pleomórfico/inmunología , Inmunidad , Neoplasias Pulmonares/inmunología , Adenoma Pleomórfico/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico
12.
Anticancer Res ; 40(1): 323-333, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892583

RESUMEN

BACKGROUND/AIM: Despite the Warburg effect, mitochondria play an essential role in the survival and maintenance of cancer cells. Thus, mitochondria have been considered a target for anticancer agents. Here, we identified a mitochondria-targeting anticancer agent from natural products. MATERIALS AND METHODS: Morphological and functional changes in mitochondria were determined by a fluorescence-based High Content Imaging System. Using human non-small cell lung cancer (NSCLC) cell lines (H1299, H226B, and A549), cell viability and colony formation assays, cell cycle analysis, and immunoblotting were performed to determine cytotoxic and proapoptotic effects of papuamine. RESULTS: Using a natural product chemical library, we identified papuamine as an active compound to inhibit viability and ATP production of NSCLC cells. Papuamine depleted intracellular ATP by causing mitochondrial dysfunction, as indicated by the loss of the mitochondrial membrane potential and increased mitochondrial superoxide generation. Papuamine significantly inhibited viability and colony formation of NSCLC cells by inducing apoptosis. CONCLUSION: Papuamine has a potential as a novel mitochondria-targeting anticancer agent.


Asunto(s)
Alcaloides/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Mitocondrias/patología , Células A549 , Adenosina Trifosfato/metabolismo , Adenilato Quinasa/metabolismo , Alcaloides/química , Alcaloides/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Mitocondrias/efectos de los fármacos , Ensayo de Tumor de Célula Madre , Regulación hacia Arriba/efectos de los fármacos
13.
Medicine (Baltimore) ; 99(2): e18678, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914061

RESUMEN

To investigate the correlation between the proliferating cell nuclear antigen Ki-67 and the multislice computed tomography (MSCT) signs in different subtypes of lung adenocarcinoma.Ninety-five patients with lung adenocarcinoma confirmed by surgical pathology and treated between January 2017 and December 2017 were included. MSCT was performed before the operation, and the characteristics of the high-resolution CT (HRCT) signs of the lesions were compared with the Ki-67 immunohistochemistry results.The levels of Ki-67 in the 95 lung adenocarcinoma specimens were positively correlated with the malignancy of lung adenocarcinoma. Spearman correlation coefficient was 0.615. The expression of Ki-67 was positively correlated with the nodules' diameter, density, and lobulated sign, with Spearman correlation coefficients of 0.58, 0.554, and 0.436. There was no significant correlation with spiculation and pleural retraction, with correlation coefficients of 0.319/0.381.These findings suggest that the MSCT signs of different types of lung adenocarcinoma might be associated with the expression of Ki-67. Without replacing biopsy, the imaging features of pulmonary nodules could be comprehensively analyzed to evaluate the proliferation potential of preoperative nodules, but additional studies are needed for confirmation.


Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Antígeno Ki-67/biosíntesis , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada Multidetector/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nódulos Pulmonares Múltiples/patología , Pleura/patología , Estudios Retrospectivos
14.
Anal Bioanal Chem ; 412(3): 601-609, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31897558

RESUMEN

Numerous studies have shown that exosomes are closely related to the pathogenesis of various diseases, especially cancers. Therefore, a rapid and sensitive method for exosome detection will be of great importance for the diagnosis and prognosis of diseases. We report here a method for exosome detection based on the CD63 aptamer and clustered regular interspaced short palindromic repeats (CRISPR)/Cas12a system. This method consists mainly of exosomal membrane protein recognition based on the CD63 aptamer and signal amplification based on CRISPR/Cas12a. The CD63 aptamer, as an easily adaptable nucleic acid strand, is responsible for the conversion of the amounts of exosomes into nucleic acid detection, whereas CRISPR/Cas12a is responsible for highly specific nucleic acid signal amplification. The detection range of the method was determined as 3 × 103-6 × 107 particles per microliter. Additionally, we successfully applied this method to detect exosomes in clinical samples from both healthy individuals and patients with lung cancer, and the results were highly consistent with those obtained by nanoparticle tracking analysis. In general, this method provides a highly sensitive and specific method for the detection of exosomes and offers an avenue toward future exosome-based diagnosis of diseases.


Asunto(s)
Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Exosomas/química , Tetraspanina 30/análisis , Células A549 , Sistemas CRISPR-Cas , Exosomas/patología , Humanos , Neoplasias Pulmonares/patología , Técnicas de Amplificación de Ácido Nucleico/métodos
15.
Khirurgiia (Mosk) ; (1): 61-66, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-31994501

RESUMEN

OBJECTIVE: To develop a method for analysis of lymphatic drainage pathways from the lobe of the lung affected by non-small cell lung cancer (NSCLC) using infrared fluorescence. MATERIAL AND METHODS: A study enrolled patients with NSCLC who underwent anatomic resection of the lung with systematic lymph node dissection and preliminary intraoperative peritumoral injection of indocyanine green conjugate with human albumin. Registration of fluorescence in regional lymph nodes (LN) was carried out immediately after excision of specimen using the FLUM-808 instrumental system. RESULTS: Infrared fluorescence was observed in 117 hilar and mediastinal lymph nodes from 43 patients (2.7 nodes per a patient). Comparison of localization of fluorescent LN with localization of tumor in various lobes established significant variability of lymphatic drainage pathways. CONCLUSION: The developed method of infrared fluorescent evaluation of lymphatic drainage in patients with NSCLC confirms the necessity of systematic lymph node dissection for adequate staging.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Metástasis Linfática/diagnóstico por imagen , Estadificación de Neoplasias/métodos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Colorantes , Fluorescencia , Humanos , Verde de Indocianina , Rayos Infrarrojos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/fisiopatología , Ganglios Linfáticos/cirugía , Metástasis Linfática/fisiopatología
17.
Medicine (Baltimore) ; 99(4): e18543, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31977847

RESUMEN

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer with a high mortality disease which has been positioned the first and second cancer morbidity of men and women in China, separately. Our study was to assess the prognostic meaningful of ubiquitin conjugating enzyme E2 T (UBE2T) expression in LUAD dependent on data acquired from The Cancer Genome Atlas (TCGA) and so as to increase further knowledge into the biological pathways involved in LUAD pathogenesis related to UBE2T.Information on gene expression and comparing clinical data were recognized and downloaded from TCGA. Gene set enrichment analysis (GSEA) created an arranged list of all genes s indicated by their connection with UBE2T expression.Our study cohort included 265 (54.5%) female and 221 (36.0%) male patients. The scatter plot and paired plot showed the difference of UBE2T expression between normal and tumor samples (P < .01). Overall survival (OS) analysis demonstrated that LUAD with UBE2T-high had a more terrible prognosis than that with UBE2T-low (P < .01). Multivariate analysis with the cox proportional hazards model indicated that the expression of UBE2T (hazard ratio [HR]: 1.28; 95% Confidence Interval (CI): 1.06-1.56; P = .011) and stage (HR: 2.02; 95% CI: 1.27-3.21; P = .003) were independent prognostic factors for patients with LUAD. The GSEA results showed that cell cycle, DNA replication, RNA degradation, oxidative phosphorylation, pathogenic Escherichia coli infection, citrate cycle tricarboxylic acid cycle, Alzheimer's disease, P53 signaling pathway, and purine metabolism are differentially enriched in UBE2T high expression phenotype.Our study found that the expression of UBE2T was significantly increased in LUAD patients and associated with several clinical features. UBE2T may be a potentially useful prognostic molecular biomarker of bad survival in LUAD, while further experimental ought to be performed to demonstrate the biologic effect of UBE2T.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/patología , ARN Mensajero/biosíntesis , Enzimas Ubiquitina-Conjugadoras/biosíntesis , Adenocarcinoma del Pulmón/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Ciclo Celular , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Pronóstico , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia
18.
Medicine (Baltimore) ; 99(4): e18607, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31977852

RESUMEN

Systemic inflammatory response markers are associated with poor survival in many types of malignances. This study aimed to evaluate the prognostic value of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP) in patients with non-small cell lung cancer (NSCLC).We retrospectively evaluated 254 NSCLC patients who underwent radical surgery between January 2012 and April 2014 in the Sichuan Provincial Cancer Hospital. The cut-off values of NLR, PLR, LMR, and CRP were determined according to the receiver operating characteristic curve, and the correlation of NLR, PLR, LMR, and CRP with prognosis was analyzed based on the cut-off value.The cut-off value for NLR, PLR, LMR, and CRP were 3.18, 122, 4.04, and 8.8, respectively. Univariate analysis showed that age (P = .022), tumor-node-metastasis (TNM) stage (P < .001), T stage (P = .001), and N stage (P < .001) were significantly correlated with disease-free survival (DFS), while age (P = .011), TNM stage (P < .001), T stage (P = .008), N stage (P < .001), and PLR (P = .001) were significantly correlated with overall survival (OS). In multivariate analysis, age (hazard ratio [HR]: 1.564, 95% confidence interval [CI]: 1.087-2.252, P = .016) and TNM stage (HR: 1.704, 95% CI: 1.061-2.735, P = .027) remained independent risk factors affecting DFS, while age (HR: 1.721, 95% CI: 1.153-2.567, P = .008), TNM stage (HR: 2.198, 95% CI: 1.263-3.824, P = .005), and PLR (HR: 1.850, 95% CI: 1.246-2.746, P = .002) were independent risk factors affecting OS.The preoperative PLR is superior to NLR, LMR, and CRP as a biomarker for evaluating the prognosis of patients undergoing curative surgery for NSCLC.


Asunto(s)
Plaquetas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Inflamación/metabolismo , Neoplasias Pulmonares/patología , Linfocitos/metabolismo , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Proteína C-Reactiva/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/sangre , Femenino , Humanos , Neoplasias Pulmonares/sangre , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neutrófilos/metabolismo , Análisis de Supervivencia
19.
Life Sci ; 244: 117297, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31954745

RESUMEN

As novel non-invasive tumor diagnostic biomarkers, exosomal bioactive miRNAs have received increasing attention. Herein, the aim of this study is to explore the clinical values and roles of exosomal miR106b in lung cancer. The exosomal miR-106b level was much higher in the serum of patients with lung cancer than that in healthy volunteers. Also, the exosomal miR-106b level in the lung cancer patient serum was associated with TNM stages and lymph node metastasis. Furthermore, exosomal miR-106b enhanced the migrated and invasive ability of lung cancer cells and increased the MMP-2 and MMP-9 expression. Mechanistically, exosomal miR-106b could target PTEN, and promote lung cancer cell migration and invasion. More importantly, PTEN overexpression reversed the effect of exosomal miR-106b on lung cancer cell migration and invasion. Taken together, these findings indicate that exosomal miR-106b may be a promising diagnostic biomarker and drug target for patients with lung cancer.


Asunto(s)
MicroARNs/genética , Fosfohidrolasa PTEN/metabolismo , Adulto , Anciano , Apoptosis/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Exosomas/genética , Exosomas/metabolismo , Femenino , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica/genética , Metástasis de la Neoplasia/genética , Fosfohidrolasa PTEN/genética , Pronóstico , Transducción de Señal/genética
20.
Medicine (Baltimore) ; 99(4): e19018, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31977918

RESUMEN

RATIONALE: Small cell neuroendocrine carcinoma of the salivary gland is an extremely rare condition. To the best of our knowledge, metastasis of small cell neuroendocrine lung cancer to the submandibular gland has not been reported in the literature. PATIENT CONCERN: An 87-year-old female complained of a left neck mass that enlarged from one month ago. DIAGNOSIS: The final diagnosis was diagnosed as a metastatic small cell neuroendocrine carcinoma of the submandibular gland from lung by an immunohistochemistry. INTERVENTIONS: Left submandibular resection was performed under general anesthesia. OUTCOMES: We recommended further evaluation and treatment, but the patient and patient family support team rejected further treatment of her condition. It was confirmed that 3 months after this conclusive diagnosis, the patient died as a result of this condition and disease. LESSONS: Small cell neuroendocrine carcinoma of the salivary gland is an extremely rare condition. We report a case of metastatic small cell neuroendocrine carcinoma of the submandibular gland from the lung.


Asunto(s)
Carcinoma Neuroendocrino/secundario , Neoplasias Pulmonares/patología , Carcinoma Pulmonar de Células Pequeñas/patología , Neoplasias de la Glándula Submandibular/secundario , Anciano de 80 o más Años , Carcinoma Neuroendocrino/diagnóstico por imagen , Carcinoma Neuroendocrino/patología , Resultado Fatal , Femenino , Humanos , Neoplasias de la Glándula Submandibular/diagnóstico por imagen , Neoplasias de la Glándula Submandibular/patología , Tomografía Computarizada por Rayos X
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