RESUMO
OBJECTIVES: To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. RESULTS: Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p < 0.0001) in the validation cohort. The 2D corrected radiomics model yielded the optimal performance and was used to build the nomogram. The calibration curve of the radiomics model demonstrated good agreement between prediction and observation and the decision curve analysis confirmed the clinical utility. CONCLUSIONS: The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Inibidores de Checkpoint Imunológico/uso terapêutico , Máquina de Vetores de Suporte , Anticorpos Monoclonais Humanizados/administração & dosagem , Viés , Biomarcadores Tumorais , Carboplatina/administração & dosagem , Terapia Combinada/métodos , Docetaxel/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
A neutral chiral receptor based on TPE cyclohexylbisurea was synthesized and could discriminate the enantiomers of many different kinds of chiral reagents, including chiral acidic compounds, basic compounds, amino acids, and even neutral alcohols. The (1)H NMR spectra disclosed that the ability of chiral recognition could be ascribed to the multiple hydrogen bonds and CH-π interactions between the TPE urea receptor and the enantiomer of the chiral guest, which led to the selective aggregation of the receptor with one of the two enantiomers. This result exhibited a great potential in enantiomer discernment and high-throughput analysis of enantiomer composition of these chiral analytes by one chiral AIE molecule.
RESUMO
INTRODUCTION: This meta-analysis aimed to compare the postoperative analgesic effects of patient-controlled epidural analgesia (PCEA) and patient-controlled intravenous analgesia (PCIA) for patients undergoing spinal fusion surgeries. METHOD: Relevant articles were identified using computerized and manual search strategies. Statistical analyses were undertaken by the CMA 2.0 statistical software. RESULTS: Nine cohort studies with a total of 436 patients undergoing spinal fusion surgeries were incorporated in the present meta-analysis. There were significant differences between the PCEA and PCIA groups in the visual analogue scale score of patients undergoing spinal fusion [standardized mean difference = 0.27, 95 % confidence interval (95 % CI) = 0.070-0.470, P = 0.008]. However, no obvious difference was observed in the rate of side effects between the PCIA and PCEA groups (side effects: odds ratio = 0.957, 95 % CI = 0.536-1.708, P = 0.882). CONCLUSION: Our findings suggested that PCEA may be more effective in relieving pain than PCIA for patients undergoing spinal fusion surgeries.
Assuntos
Analgesia Controlada pelo Paciente/métodos , Dor Pós-Operatória/prevenção & controle , Fusão Vertebral , Analgesia Epidural , Humanos , Infusões Intravenosas , Escala Visual AnalógicaRESUMO
The association between clinical characteristics, prognosis, and the ABO blood group of esophageal squamous cell carcinoma (ESCC) is rarely discussed. The aims of the current study were to investigate the correlation of the ABO blood group with the clinicopathological characteristics in a consecutive cohort of patients with ESCC and to assess whether the ABO blood group was associated with prognosis. A total of 511 patients with locoregional ESCC who underwent curative treatment were retrospectively analyzed at a single institution between January 2007 and December 2008. The relationship between the ABO blood group and clinicopathological variables was assessed by chi-squared analysis. The Kaplan-Meier method was used to estimate the 5-year overall survival (OS). The Cox proportional hazards model was used in univariate and multivariate analyses of OS. There were no significant differences in the clinicopathological characteristics among patients with different ABO blood groups. The 5-year OS rates were 50.0 % for patients with blood type A, 45.4 % for type B, 50.8 % for type O, and 60.7 % for type AB. In a subgroup analysis of 321 patients who ever smoked, the B/O group had a poorer OS compared with the A/AB group (p = 0.0245). Multivariate analysis revealed an unfavorable and independent impact of the B/O group on patient survival with ESCC who ever smoked (p = 0.011). Findings suggest the B/O blood type as a predictor of mortality in ESCC patients who ever smoked. Future studies conducted prospectively are warranted to confirm this work and to better understand the underlying biological mechanisms.
Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , China , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fumar/efeitos adversos , Taxa de SobrevidaRESUMO
RATIONALE AND OBJECTIVES: This study explored the intratumor heterogeneity (ITH) of esophageal squamous cell carcinoma (ESCC) using computed tomography (CT) and investigated the value of CT-based ITH in predicting the response to immune checkpoint inhibitor (ICI) plus chemotherapy in patients with ESCC. MATERIALS AND METHODS: This retrospective study included 416 patients with ESCC who received ICI plus chemotherapy at two independent hospitals between January 2019 and July 2022. Multiparametric CT features were extracted from ESCC lesions and screened using hierarchical clustering and dimensionality reduction algorithms. Logistic regression and machine learning models based on selected features were developed to predict treatment response and validated in separate datasets. ITH was quantified using the score calculated by the best-performing model and visualized through feature clustering and feature contribution heatmaps. A gene set enrichment analysis (GSEA) was performed to identify the biological pathways underlying the CT-based ITH. RESULTS: The extreme gradient boosting model based on CT-derived ITH had higher discriminative power, with areas under the receiver operating characteristic curve of 0.864 (95% confidence interval [CI]: 0.774-0.954) and 0.796 (95% CI: 0.698-0.893) in the internal and external validation sets. The CT-based ITH pattern differed significantly between responding and non-responding patients. The GSEA indicated that CT-based ITH was associated with immunity-, keratinization-, and epidermal cell differentiation-related pathways. CONCLUSION: CT-based ITH is an effective biomarker for identifying patients with ESCC who could benefit from ICI plus chemotherapy. Immunity-, keratinization-, and epidermal cell differentiation-related pathways may influence the patient's response to ICI plus chemotherapy.
RESUMO
BACKGROUND: The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. METHODS: A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). FINDINGS: Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5-80·0) in low-risk, 58·3% (48·9-66·6) in intermediate-risk, and 49·2% (42·2-55·8) in high-risk patients (p(trend)=0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0-80·6) in low-risk, 57·4% (48·3-65·5) in intermediate-risk, and 44·6% (40·2-48·9) in high-risk patients (p(trend)<0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. INTERPRETATION: Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. FUNDING: UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Reação em Cadeia da Polimerase , Adulto , Idoso , California/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Cooperação Internacional , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Medição de RiscoRESUMO
The purpose of this study was to investigate the effect of Raf kinase inhibitor protein (RKIP) on the growth, proliferation, invasion and metastasis of triple-negative breast cancer (TNBC) cells to provide experimental evidence for developing future therapies against human TNBC. The pcDNA3.1-RKIP eukaryotic expression vector was constructed and transfected into the TNBC cell line MDA-MB-231. The alterations of the biological characteristics of RKIP-transfected MDA-MB-231 cells were analyzed using the following approaches: a growth curve, a 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, bromodeoxyuridine (BrdU) staining and a cell migration assay. The effects of the RKIP gene on MMP-1 and MMP-2 expression were also examined. The pcDNA3.1 empty vector-transfected and mock-transfected MDA-MB-231 cells were used as control groups. Compared with the empty vector-transfected and mock-transfected cells, the cell growth of RKIP-transfected MDA-MB-231 cells was significantly reduced. The empty vector-transfected group was not significantly different compared with the mock-transfected MDA-MB-231 cells. The results of the MTT and BrdU assays demonstrated that the proliferation of pcDNA3.1-RKIP-transfected cells was significantly reduced compared to the control cells (P < 0.05). The result of the cell migration assay suggested that the cross-membrane migration rate of the pcDNA3.1-RKIP-transfected cells was significantly lower than that of the control MDA-MB-231 cells (P < 0.05). We also demonstrated that RKIP may inhibit MMP-1 and MMP-2 expression in MDA-MB-231 cells. The RKIP gene may play a role in inhibiting cellular proliferation. The RKIP gene may also have some inhibitory effects on the invasiveness and metastatic capability of human TNBC cells.
Assuntos
Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteína de Ligação a Fosfatidiletanolamina/genética , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Humanos , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , TransfecçãoRESUMO
This study aimed to investigate the expression of Twist in gastric cancer tissues and its correlation between Twist and the epithelial-mesenchymal transition (EMT). By means of RT-PCR and Western blot, the mRNA and protein expressions of Twist, E-cadherin, and Vimentin in 61 gastric cancer tissues and adjacent normal tissues were detected. The positive rates of Twist, E-cadherin, and Vimentin mRNA expression in gastric cancer tissues were 73.9. 40.6, and 60.9 %, respectively; compared to the expression of these genes in adjacent normal tissues (2.9, 75.4, and 27.5 %), the differences were significant (p < 0.05). The E-cadherin protein expression level in gastric cancer tissues was significantly lower than that in the adjacent normal tissues (p < 0.05). After the transfection of Twist siRNA into the MKN45 cells, the protein expression of Twist was significantly reduced (p < 0.05), the protein expression of E-cadherin was significantly increased, and the number of cells that passed through the Transwell chamber was significantly lower than that in the non-transfected control group as well as the transfected control group (p < 0.05). Twist may be associated with the epithelial-mesenchymal transition in gastric cancer and the tumorigenesis, invasion, and metastasis of gastric cancer.
Assuntos
Transição Epitelial-Mesenquimal , Expressão Gênica , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Adulto , Idoso , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transformação Celular Neoplásica , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Neoplasias Gástricas/patologia , Proteína 1 Relacionada a Twist/genética , Vimentina/metabolismoRESUMO
BACKGROUND: The purposes of this study were to measure both the mRNA and protein expression levels of high-temperature requirement serine peptidase 1 (HtrA1) in human esophageal cancer tissues and their adjacent, comparatively normal esophageal tissues. METHODS: The expression levels of HtrA1 mRNA and protein in both tissue types were measured by semi-quantitative RT-PCR (reverse transcription-polymerase chain reaction) and Western blotting. The clinical and pathological correlation between HtrA1 expression levels and the occurrence and development of esophageal cancer was analyzed. RESULTS: The expression levels of HtrA1 mRNA and protein in esophageal carcinoma were significantly lower than the levels expressed in their adjacent normal esophageal tissue (p < 0.05). The more highly undifferentiated esophageal tumor cells expressed lower HtrA1 mRNA and protein expression levels (p < 0.05). Patients with tumors in early pathological stages (I-II) had significantly higher HtrA1 mRNA and protein expression levels than did patients with tumors in mid-to-late pathological stages (III-IV) (p < 0.05). Patients with positive lymph node metastasis had significantly lower HtrA1 mRNA and protein expression levels than did patients with lymph node-negative disease (p < 0.05). CONCLUSIONS: HtrA1 expression is associated with the occurrence and development of esophageal cancer.
Assuntos
Neoplasias Esofágicas/etiologia , Serina Endopeptidases/fisiologia , Idoso , Western Blotting , Linhagem Celular Tumoral , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Mensageiro/análise , Serina Endopeptidases/análise , Serina Endopeptidases/genéticaRESUMO
Land resources are indispensable for the development of a country, especially for a country such as China with a very high population relative to its land area. Since reforms were introduced and liberalization was adopted, many policies have been promulgated for the protection and utilization of land resources. In the present study, more than 2000 land policies that have been formulated and promulgated in China from 1980 to 2019 were examined and statistically analyzed to qualitatively and quantitatively introduce the evolution of these policies in China. This paper mainly studies land policy of China from three perspectives as follows: policy intensity, policy tools, and policy targets, and three principal observations emerged from these investigations. First, during the past 40 years, the quantity of land policies introduced showed an increasing trend, while policy intensity became increasingly stabilized. Second, compared with regulatory policies and stimulative policies, it seems that China prefers to adopt guiding policies to manage land resources. Third, the main purpose of land policies issued during 1980-2019 is land market regulation, with subordinate policies for land resources protection.
Assuntos
Conservação dos Recursos Naturais , Políticas , ChinaRESUMO
The asymmetric unit of the title compound, C(9)H(9)N(2) (+)·0.5C(8)H(4)O(4) (-)·H(2)O, contains one 2-phenyl-imidazolium cation, half a benzene-1,3-dicarboxyl-ate anion and one water mol-ecule. In the crystal, components are connected by N-Hâ¯O and O-Hâ¯O hydrogen-bonding inter-actions into a three-dimensional network.
RESUMO
OBJECTIVE: The aim of this study was to evaluate if factors associated with dissected lymph nodes affect the outcome of completely resected stage II (T1-2N1) non-small cell lung cancer (NSCLC). METHODS: Clinical data of 121 patients with complete resection of stage II NSCLC in Sun Yat-sen University Cancer center from January 1998 to December 2004 were reviewed retrospectively and the effect of factors of dissected lymph nodes on overall survival (OS) and disease-free survival (DFS) of NSCLC was analyzed. RESULTS: The univariate analysis demonstrated that the total number of removed lymph nodes, the number of involved N1 lymph nodes, the ratio of involved N1 lymph nodes and the total number of removed N2 lymph nodes were significant prognostic factors for OS. In the multivariate analysis, the total number of removed lymph nodes and the number of involved N1 lymph nodes were independent prognostic factors for OS. In both of univariate and multivariate analyses, tumor size, the total number of removed lymph nodes and the number of involved N1 lymph nodes were independent prognostic factors for DFS. CONCLUSION: For patients with completely resectable stage II NSCLC, 10 or more lymph nodes should be removed at the surgical resection. Total number of removed lymph nodes >or= 10 is a favorable prognostic factor and involved N1 >or= 3 is an adverse one.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVE: Most patients with esophageal carcinoma have disease in the locally late stage (stage III) when first diagnosed, with surgery as the first treatment of choice. This study analyzed the clinical data of patients with esophageal squamous carcinoma after radical esophagectomy and investigated prognostic factors. METHODS: The data of 361 patients with esophageal squamous carcinoma who underwent radical esophagectomy and were hospitalized at Sun Yat-sen University Cancer Center between January 1997 and March 2004 were analyzed. The Kaplan-Meier method was used to analyze prognosis, log-rank test was used to compare the groups, and the Cox proportional hazards model was used for multivariate analysis. RESULTS: The 1-, 2-, 3-, 4-, and 5-year survival rates were 67.7%, 40.6%, 27.5%, 23.4%, and 20.1%, respectively. Based on univariate analysis, the degree of invasion, rate of lymph node metastasis, number of metastatic regions, number of metastatic lymph nodes, postoperative complications, and duration of surgery were prognostic factors. Based on multivariate analysis, the degree of invasion, rate of lymph node metastasis, and postoperative complications were independent factors for the prognosis. CONCLUSIONS: Of all clinical and pathologic factors, the degree of invasion, rate of lymph node metastasis, and postoperative complications were independent prognostic factors for the patients with stage-III esophageal squamous carcinoma after radical esophagectomy.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND AND OBJECTIVE: Surgery is the main therapy for patients with stage II non small cell lung cancer (NSCLC), but patients still have an unsatisfactory prognosis even though complete resection is usually possible. Adjuvant chemotherapy provides low rates of clinical benefit as well. We retrospectively analyzed prognostic factors of patients with completely resected stage II NSCLC to find patients with unfavorable factors for proper management. METHODS: Clinical data of 220 patients with complete resections of stage II NSCLC at the Sun Yat sen University Cancer Center between January 1998 and December 2004 were retrospectively analyzed. Cumulative survival was analyzed by the Kaplan Meier method and compared by log rank test. Prognosis was analyzed by the Cox proportional hazards model. RESULTS: The overall 3 and 5 year survival rates were 58.8% and 47.9%, respectively. The 3 and 5 year disease free survival rates were 45.8% and 37.0%, respectively. Of the 220 patients, 86 (39.1%) had recurrence or metastasis. A univariate analysis demonstrated that age (> 55 years), blood type, the presence of symptoms, chest pain, tumor volume (> 20 cm3), total number of removed lymph nodes (> or = 10), number of involved N1 lymph nodes (> or =3 ), total number of removed N2 lymph nodes (> 6), and the ratio of involved N1 lymph nodes (> or = 35%) were significant prognostic factors for 5 year survival. In the multivariate analysis, age (> 55 years), chest pain, tumor volume (> 20 cm3), total number of removed lymph nodes (> or = 10), and number of involved N1 lymph nodes (> or = 3) were independent prognostic factors for 5 year survival. CONCLUSIONS: For patients with completely resectable stage II NSCLC, having > 55 years, presenting chest pain, tumor volumes > 20 cm3, and > or = 3 involved N1 lymph nodes were adverse prognostic factors, and > or = 10 removed lymph nodes was a favorable one. Patients with poor prognoses might be treated by individual adjuvant therapy for better survival.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimioterapia Adjuvante , Dor no Peito/etiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/métodos , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Carga TumoralRESUMO
OBJECTIVE: To detect DNA copy number abnormality and LOH and explore the profile of chromosomal imbalances in esophageal atypical hyperplasia and early stage esophageal squamous cell carcinoma using SNP array. METHODS: The DNA copy number abnormality and LOH in pathological change esophageal tissue and matched normal esophageal tissue of one case of primary esophageal high atypical hyperplasia and four cases of primary early stage esophageal squamous cell carcinoma were detected by using Affymetrix GeneChip Human Mapping 250K Nsp Array. RESULTS: Amplification was found in a few DNA fragment and no deletion or LOH was found in esophageal high atypical hyperplasia. In early stage esophageal squamous cell carcinoma, DNA amplification occurred in 1p, 1q, 2p, 2q, 3q, 4q, 5p, 6p, 6q, 7q, 8q, 11p, 11q, 12p, 12q, 14q, 17q, 18p, 19q, 20q, 22q and X chromosome. DNA deletion occurred in 1p, 2q, 3p, 3q, 4p, 4q, 8p, 9p, 9q, 10q, 11p, 13q, 16p, 18q, 19p, 19q and 22q chromosome. LOH occurred in 3q and 9q chromosome. The amplification in 1p, 19q, 4q, 11p chromosome and the deletion in 3q, 11p, 2q, 16p chromosome were rarely reported. CONCLUSION: DNA abnormality was rare in esophageal high atypical hyperplasia. The obvious amplification and deletion in DNA have been found in early stage esophageal squamous cell carcinoma, but LOH was rarely found. 250K SNP array could effectively detect DNA copy number change and LOH in whole-wide genes in esophageal atypical hyperplasia and early stage esophageal squamous cell carcinoma with high distinguishability and precise location. The results would provide important academic information for detection and location of related genes in early stage esophageal squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Lesões Pré-Cancerosas/genética , Carcinoma de Células Escamosas/patologia , Replicação do DNA , Neoplasias Esofágicas/patologia , Esôfago/patologia , Genoma Humano , Humanos , Hiperplasia , Perda de Heterozigosidade/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Lesões Pré-Cancerosas/patologiaRESUMO
OBJECTIVE: To analyze the prognostic factors of thoracic esophageal squamous cell carcinoma (ESCC) after esophagectomy. METHODS: The clinicopathologic data of 716 patients with thoracic ESCC from January 1990 to December 1998 were analyzed retrospectively. There were 538 male and 178 female patients aged from 24 to 78 years old with a median of 57 years old. Cumulative survival rate was analyzed by the Kaplan-Meier method and compared by the Log-rank test. COX regression model was used for multivariate prognostic analysis. RESULTS: The overall 1-, 3-, 5- and 10-year survival rates were 82.9%, 44.3%, 34.2% and 25.7% respectively. The 5-year survival rates was 80.0%, 51.2%, 19.7% and 13.3% for stage I, stage IIA, stage IIB and stage III respectively. Of the 716 patients, 151 (21.1%) patients recurred, including 48 (84.2%) of stage IIA recurrence, 22 (91.7%) of stage IIB recurrence and 63 (90.0%) of stage III recurrence occurred within 3 years postoperatively. Univariate analysis revealed that the factors impacting the prognosis were gender, depth of invasion, lymph node metastasis, pathologic stage, number of lymph node metastatic field, differentiation, surgical margin and tumor relapse. Multivariate analysis showed that depth of invasion, lymph node metastasis, pathologic stage and tumor relapse were independently associated to poor prognosis. CONCLUSIONS: Depth of invasion, lymph node metastasis, pathologic stage and tumor relapse are the independent factors of ESCC. Surgery is still the primary treatment for stage I-IIA esophageal cancer; but it is suggested to adopt surgical treatment as primary modality combined with other therapies for stage IIB-III esophageal cancer.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Two cyclopeptides, celogentin L (1) and its epimer lyciumin A (2) were firstly isolated from Celosia argentea L.. The planar structures of the two compounds were fully determined by spectroscopic data, including 1D-, 2D-NMR, and HR-ESI/MS. The absolute configurations of amino acid components were assigned via chiral-phase HPLC analyses after acid hydrolysis. Furthermore, the configuration of C-N linkage at the glycine Cα was elucidated by extensive analyses of 2D-NMR and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cytotoxicity of the two compounds against human alveolar epithelial A549, hepatocellular carcinoma HepG2, and cervical cancer Hela cell lines was assayed. Although both of them were inactive in these cells, the present findings add new facets for the chemistry of Celosia argentea.
Assuntos
Celosia/química , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Sementes/química , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Analítica , Células HeLa , Células Hep G2 , Humanos , Conformação Molecular , Estrutura Molecular , Peptídeos Cíclicos/toxicidade , EstereoisomerismoRESUMO
BACKGROUND: Over-expression of inhibitor of differentiation or DNA binding 1 (Id-1) is associated with poor prognosis in esophageal squamous cell carcinoma (ESCC). However, some biomarkers discordant expression in metastasis has been reported previously. We aimed to confirm possible differential expression and prognostic value of Id-1 in paired metastatic lymph node (PMLN). METHODS: Expression of Id-1 in primary tumors (PT) and paired regional metastatic lymph nodes of ESCC were evaluated with immunohistochemical (IHC) analysis. Statistical analysis of Kaplan-Meier method was performed to test the prognostic significance of Id-1 expression. RESULTS: The expression of Id-1 was down-regulated in metastatic lymph nodes compared with primary esophageal tumors (P<0.001). Patients with 1 to 2 lymph nodes involved had significantly higher Id-1 expression in metastatic lymph nodes (P=0.028). The similar association was observed between a ratio of involved to examined lymph nodes ≤0.2 and high level Id-1 expression in lymphatic metastases (P=0.011). Better overall survival with statistical significance was observed in patients with higher level Id-1 expression in metastatic lymph nodes (P=0.015). The results of Id-1 expression in metastatic lymph node and paired PT was to predict prognosis effective in out cohort (P=0.035). CONCLUSIONS: The level of Id-1 protein expression was down-regulated from PT to metastatic lymph node. It was contrary to previous studies that strong expression of Id-1 in metastatic lymph nodes was associated with better clinical outcomes in patients with stage T3N1-3M0 ESCC.
RESUMO
Simple regulation of c-Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase (MAPK) pathways is not enough to trigger cell apoptosis. However, activation of the stress activated pathway (JNK/p38 MAPK) together with inhibition of the growth factor activated extracellular signal-regulated kinase (ERK) pathway can promote cell apoptosis. We hypothesized that inhibition of the JNK or p38 pro-apoptotic pathway and activating the ERK pathway could be the mechanism of anti-apoptosis following cerebral ischemia/reperfusion injury. To investigate the mechanism of the protective effect of electroacupuncture on cerebral ischemia/reperfusion injury in JNK knockout mice, mouse models of cerebral ischemia/reperfusion injury were established by Longa's method. Electroacupuncture was conducted at acupoints Chize (LU5), Hegu (LI4), Sanyinjiao (SP6) and Zusanli (ST36) 1.5 hours after ischemia/reperfusion injury for 20 minutes, once a day. The neurological function was evaluated using neurological deficit scores. The expression of phospho-extracellular signal-regulated kinase (p-ERK) and phospho-p38 (p-p38) in JNK knockout mice was detected using double-labeling immunofluorescence and western blot assay. The mRNA expression of ERK and p38 was measured by quantitative real-time polymerase chain reaction. Electroacupuncture improved neurological function, increased the immunoreactivity and relative expression of p-ERK and reduced that of p-p38 in the cerebral cortex and hippocampus on the injured side. Electroacupuncture increased mRNA expression of ERK, but decreased that of p38 in the cerebral cortex and hippocampus on the injured side. In conclusion, electroacupuncture upregulated the protective ERK pathway and inhibited the pro-apoptotic p38 pathway, thereby exerting a neuroprotective effect and improving the neurological function in JNK knockout mice.
RESUMO
OBJECTIVE: The purpose of this study was to investigate the clinical characteristics of lymph node metastasis in the contralateral mediastinum and scalene in patients with potentially operable nonsmall cell lung cancer (NSCLC). METHODS: Cervical mediastinoscopy was performed for 89 patients with clinical stage I-III A non-small cell lung cancer prior to thoracotomy. Of these, 12 underwent cervical medistinoscopy combined with right scalene lymph node biopsy and 10 with anterior para-mediastinal small incision. RESULTS: A total of 9 patients were found have N3 disease on mediastinosopy, with cancer-cell-positive lymph nodes in the contralateral mediastinum in 6 and 3 in the right scalene. Statistical analysis revealed that the incidence of N3 disease in adenocarcinoma group was higher than that in patients with nonadenocarcinoma (P < 0.05), which was also higher in the patients with serum CEA >5 ng/ml than that in the patients with CEA <5 ng/ml (P < 0.05), and it was higher in the patients with ipsilateral mediastinal multi-station lymph node metastasis than that in the patients with uni-station lymph node metastasis (P < 0.05). CONCLUSION: Biopsy of contralateral mediastinal lymph nodes or scalene lymph node should be performed in order to exclude N3 disease for potentially operable NSCLC patients with adenocarcinoma, serum CEA >5 ng/ml or ipsilateral multi-station mediastinal lymph node metastasis.