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1.
Sci Rep ; 14(1): 11486, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769368

RESUMO

The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3-4. In addition to stage, intrahepatic metastasis and Child-Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p < 0.05). The OS (14.63 pg/mL as cutoff value) and PFS (9.85 pg/mL as cutoff value) of patients with low IL-6 levels exceeded those with high levels (21.0 and 6.9, 15.8 and 10.0 months, respectively). The risks of death and disease progression were reduced by 63.0% (HR = 0.37, 95% CI: 0.19-0.72) and 43.0% (HR = 0.57, 95% CI: 0.22-1.47), respectively. Pre-treatment IL-6 levels may be a simple and effective prognostic indicator for patients with advanced HCC treated with radiotherapy combined with immunotargeted therapy.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Citocinas , Indóis , Neoplasias Hepáticas , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Idoso , Indóis/uso terapêutico , Indóis/administração & dosagem , Prognóstico , Citocinas/sangue , Adulto , Interleucina-6/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
2.
World J Gastrointest Oncol ; 16(2): 372-385, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425405

RESUMO

BACKGROUND: Circulating tumor cell (CTC) count and neutrophil-to-lymphocyte ratio (NLR) are both closely associated with the prognosis of hepatocellular carcinoma (HCC). AIM: To investigate the prognostic value of combining these two indicators in HCC. METHODS: Clinical data were collected from patients with advanced HCC who received immune therapy combined with targeted therapy at the Department of Oncology, the Affiliated Hospital of Southwest Medical University, Sichuan, China, from 2021 to 2023. The optimal cutoff values for CTC programmed death-ligand 1 (PD-L1) (+) > 1 or CTC PD-L1 (+) ≤ 1 and NLR > 3.89 or NLR ≤ 3.89 were evaluated using X-Tile software. Patients were categorized into three groups based on CTC PD-L1 (+) counts and NLR: CTC-NLR (0), CTC-NLR (1), and CTC-NLR (2). The relationship between CTC-NLR and clinical variables as well as survival rates was assessed. RESULTS: Patients with high CTC PD-L1 (+) expression or NLR at baseline had shorter median progression-free survival (mPFS) and median overall survival (mOS) than those with low levels of CTC PD-L1 (+) or NLR (P < 0.001). Meanwhile, patients in the CTC-NLR (2) group showed a significant decrease in mPFS and mOS. Cox regression analysis revealed that alpha-fetoprotein (AFP), CTC PD-L1 (+), and CTC-NLR were independent predictors of OS. The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months (0.821) and 18 months (0.821) was superior to that of AFP and CTC PD-L1 (+). CONCLUSION: HCC patients with high CTC PD-L1 (+) or NLR expression tend to exhibit poor prognosis, and a high baseline CTC-NLR score may indicate low survival. CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

3.
Front Oncol ; 13: 1238553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727206

RESUMO

Background: Anlotinib showed encouraging anti-tumor activity in metastatic colorectal cancer (mCRC). This study was designed to assess the efficacy and safety of anlotinib plus XELOX as first-line therapy in mCRC patients. Materials and Methods: Eligible patients aged ≥18 with mCRC were enrolled in this multicenter, single-arm, phase II, exploratory study. Patients received at least 6 cycles of anlotinib, oxaliplatin, and capecitabine as initial therapy. Subsequently, patients received anlotinib monotherapy as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Results: Thirty-one patients were included between December 2019 and March 2022. The median follow-up was 17.5 (95% CI, 3.0-17.5) months. The median PFS was 8.3 (95% CI, 6.3-10.0) months, with 6- and 12-month PFS rates of 82.3% (95% CI, 59.2%-93.0%) and 18.9% (95% CI, 4.8%-40.1%), respectively. Fifteen (48.4%) achieved partial response for an ORR of 48.4% (95% CI, 30.2%-66.9%). The disease control rate was 71.0% (95% CI, 52.0%-85.8%) due to 7 (22.6%) stable diseases. The median duration of response was 6.0 (95% CI, 3.6-8.0) months and 1 patient had the longest ongoing response of 17.3 months. Of 24 patients with evaluable imaging, 23 (74.2%) obtained tumor shrinkage. The median PFS (11.0 vs. 6.9 months) and ORR (66.7% vs. 60.0%) for patients with RAS/BRAF wild-type were numerically better than those with mutation. Three patients are still ongoing treatment. The grade 3 or more treatment-emergent adverse events (TEAEs) were mainly hypertension (12.9%) and decreased neutrophil count (12.9%). Four (12.9%) had serious TEAEs, primarily including abdominal pain and incomplete intestinal obstruction. Conclusion: Anlotinib plus XELOX as first-line therapy in patients with mCRC showed anti-tumor activity and safety profile, which is worth further investigation. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR1900028417.

4.
World J Gastroenterol ; 29(17): 2679-2700, 2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37213399

RESUMO

BACKGROUND: Multiple studies investigating the relationship between intake of different types of fruit and colorectal cancer (CRC) risk have yielded inconsistent results. AIM: To perform a meta-analysis of existing studies to assess the association between the intake of different kinds of fruit and the incidence of CRC. METHODS: We searched online literature databases including PubMed, Embase, WOS, and Cochrane Library for relevant articles available up to August 2022. With data extracted from observational studies, odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using random-effects models. A funnel plot and Egger's test were used to determine publication bias. Furthermore, subgroup analysis and dose-response analysis were performed. All analyses were conducted using R (version 4.1.3). RESULTS: Twenty-four eligible studies involving 1068158 participants were included in this review. The meta-analysis showed that compared to a low intake, a higher intake of citrus, apples, watermelon, and kiwi reduced the risk of CRC by 9% [OR (95%CI) = 0.91 (0.85-0.97)], 25% [OR (95%CI) = 0.75 (0.66-0.85)], 26% [OR (95%CI) = 0.74 (0.58-0.94)], 13% [OR (95%CI) = 0.87 (0.78-0.96)], respectively. No significant association was observed between the intake of other types of fruit and the risk of CRC. In the dose-response analysis, a nonlinear association was found [R (95%CI) = -0.0031 (-0.0047 to -0.0014)] between citrus intake and CRC risk (P < 0.001), with the risk minimized around 120 g/d (OR = 0.85), while no significant dose-response correlation was observed after continued increase in intake. CONCLUSION: We found that a higher intake of citrus, apples, watermelon, and kiwi was negatively associated with the risk of CRC, while the intake of other types of fruits were not significantly associated with CRC. Citrus intake showed a non-linear dose-response relationship with the risk of CRC. This meta-analysis provides further evidence that a higher intake of specific types of fruit is effective in preventing the occurrence of CRC.


Assuntos
Citrus , Neoplasias Colorretais , Frutas , Dieta/efeitos adversos , Fatores de Risco , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle
5.
Pharmacol Res ; 177: 106096, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35077844

RESUMO

Thrombocytopenia, a most common complication of radiotherapy and chemotherapy, is an important cause of morbidity and mortality in cancer patients. However, there are still no approved agents for the treatment of radiation- and chemotherapy-induced thrombocytopenia (RIT and CIT, respectively). In this study, a drug screening model for predicting compounds with activity in promoting megakaryocyte (MK) differentiation and platelet production was established based on machine learning (ML), and a natural product ingenol was predicted as a potential active compound. Then, in vitro experiments showed that ingenol significantly promoted MK differentiation in K562 and HEL cells. Furthermore, a RIT mice model and c-MPL knock-out (c-MPL-/-) mice constructed by CRISPR/Cas9 technology were used to assess the therapeutic action of ingenol on thrombocytopenia. The results showed that ingenol accelerated megakaryopoiesis and thrombopoiesis both in RIT mice and c-MPL-/- mice. Next, RNA-sequencing (RNA-seq) was carried out to analyze the gene expression profile induced by ingenol during MK differentiation. Finally, through experimental verifications, we demonstrated that the activation of PI3K/Akt signaling pathway was involved in ingenol-induced MK differentiation. Blocking PI3K/Akt signaling pathway abolished the promotion of ingenol on MK differentiation. Nevertheless, inhibition of TPO/c-MPL signaling pathway could not suppress ingenol-induced MK differentiation. In conclusion, our study builds a drug screening model to discover active compounds against thrombocytopenia, reveals the critical roles of ingenol in promoting MK differentiation and platelet production, and provides a promising avenue for the treatment of RIT.


Assuntos
Trombocitopenia , Trombopoese , Animais , Plaquetas/metabolismo , Diterpenos , Humanos , Megacariócitos/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Trombopoese/genética , Trombopoetina/genética , Trombopoetina/metabolismo , Trombopoetina/farmacologia
6.
Front Oncol ; 11: 767134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35070971

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck. The primary clinical manifestations are nasal congestion, blood-stained nasal discharge, headache, and hearing loss. It occurs frequently in Southeast Asia, North Africa, and especially in southern China. Radiotherapy is the main treatment, and currently, imaging examinations used for the diagnosis, treatment, and prognosis of NPC include computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-CT, and PET-MRI. These methods play an important role in target delineation, radiotherapy planning design, dose evaluation, and outcome prediction. However, the anatomical and metabolic information obtained at the macro level of images may not meet the increasing accuracy required for radiotherapy. As a technology used for mining deep image information, radiomics can provide further information for the diagnosis and treatment of NPC and promote individualized precision radiotherapy in the future. This paper reviews the application of radiomics in the diagnosis and treatment of nasopharyngeal carcinoma.

7.
BMC Cancer ; 20(1): 893, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942998

RESUMO

BACKGROUND: The effect of brachytherapy on lymphocytes and cytokines in the tumor microenvironment is unclear. This study aimed to analyze the relationship between the invasion of lymphocytes and cytokines in the tumor microenvironment and the interval after single brachytherapy hypofractionated radiotherapy (SBHFRT) and conventional fractionation radiotherapy (CFRT) in non-small cell lung cancer (NSCLC). METHODS: Lewis tumor-bearing mice were randomly divided into control, CFRT, and SBHFRT groups. On days 7 and 14 after radiation, the expression levels of CD86+, CD4+, CD8+, and Foxp3+ cells, and levels of Ki-67+ protein were detected by immunohistochemistry, and the tumor necrosis rate was calculated. Following this, the levels of interleukin-10 (IL-10), IL-12, and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay. The apoptosis rate was evaluated via flow cytometry. The tumor volume and tumor growth inhibition rate (TGIR) were calculated on day 14. Tumor metabolism was assessed via 18F-FDG micropositron emission tomography/computer tomography. RESULTS: The tumor volume reduced by 22.0% and TGIR increased by 92.2% (p < 0.05) in the SBHFRT group. Further, on days 7 and 14 after radiation, tumor metabolism, Ki-67+ and Foxp3+ expression levels, and IL-10 levels were lower, and tumor necrosis and apoptosis rates; CD86+, CD4+, and CD8+ expression levels; and IL-12 and IFN-γ levels were higher in the SBHFRT group than in the CFRT group, particularly on day 7. CONCLUSION: SBHFRT could lead to more accumulation of dendritic cells, anti-tumor lymphocytes, and cytokines, and further reduce the aggregation of immunosuppressive lymphocytes and cytokines in the tumor microenvironment compared with CFRT, and the difference was the most obvious on day 7 after radiation. The clinical significance of the findings remains to be further verified.


Assuntos
Braquiterapia/métodos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Linfócitos/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Microambiente Tumoral
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(2): 507-511, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32319387

RESUMO

OBJECTIVE: To analyze the survival and prognosis of patients with nasal extranodal natural killer/T-cell lymphoma (ENKL). METHODS: The clinical data of newly diagnosed 52 patients with nasal NK/T-cell lymphoma from June 2012 to June 2018 were selected. Univariate and multivariate analysis was performed on the relationship between different clinical factors and prognosis by Kaplan-Meier method and COX proportional hazard model. RESULTS: The median overall survival (OS) time of patients was 72 months. Univariate analysis showed that age, sex, IPI score, ECOG score, hemoglobin(Hb) level, clinical stage, and treatment pattern all associated with OS of nasal NK/T-cell lymphoma patients. Multivariate analysis showed that hemoglobin level, age and clinical stage were independent factors affecting OS of nasal NK/T lymphoma patients. CONCLUSION: Hemoglobin level, age and clinical stage can be used as indicators to evaluate the prognosis of nasal NK/T-cell lymphoma.


Assuntos
Linfoma Extranodal de Células T-NK , Linfoma de Células T Periférico , Intervalo Livre de Doença , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
9.
BMC Cancer ; 18(1): 967, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30305062

RESUMO

BACKGROUND: Conventional chemotherapy is commonly used to treat non-small cell lung cancer (NSCLC) however it increases therapeutic resistance. In contrast, metronomic chemotherapy (MET) is based on frequent drug administration at lower doses, resulting in inhibition of neovascularization and induction of tumor dormancy. This study aims to evaluate the inhibitory effects, adverse events, and potential mechanisms of MET Vinorelbine (NVB) combined with an angiogenesis inhibitor (Endostar). METHODS: Circulating endothelial progenitor cells (CEPs), apoptosis rate, expression of CD31, vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 (HIF-1α) were determined using flow cytometry, western blot analysis, immunofluorescence staining and Enzyme-linked immunosorbent assay (ELISA) analysis. And some animals were also observed using micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) to identify changes by comparing SUVmax values. In addition, white blood cell (WBC) counts and H&E-stained sections of liver, lungs, kidney, and heart were performed in order to monitor toxicity assessments. RESULTS: We found that treatment with MET NVB + Endo was most effective in inhibiting tumor growth, decreasing expression of CD31, VEGF, HIF-1α, and CEPs, and reducing side effects, inducing apoptosis, such as expression of Bcl-2, Bax and caspase-3. Administration with a maximum tolerated dose of NVB combined with Endostar (MTD NVB + Endo) demonstrated similar anti-tumor effects, including changes in glucose metabolism with micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) imaging, however angiogenesis was not inhibited. Compared with either agent alone, the combination of drugs resulted in better anti-tumor effects. CONCLUSION: These results indicated that MET NVB combined with Endo significantly enhanced anti-tumor and anti-angiogenic responses without overt toxicity in a xenograft model of human lung cancer.


Assuntos
Administração Metronômica , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Endostatinas , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Vinorelbina , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Lewis , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Linhagem Celular Tumoral , Endostatinas/administração & dosagem , Endostatinas/efeitos adversos , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Camundongos , Vinorelbina/administração & dosagem , Vinorelbina/efeitos adversos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Oncotarget ; 8(32): 52813-52822, 2017 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-28881773

RESUMO

Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP). The impact of treatment regimens on the growth, microvascularization, apoptosis, and metabolic response of tumors, as well as mouse survival was determined by histopathology, immunohistochemistry (VEGFR-2 and CD31), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), micro 18F-FDG PET/CT imaging and survival curves. Administration of apatinib alone inhibited tumor growth, reduced microvascular density, and facilitated the apoptosis of tumors. Tumors treated simultaneously with apatinib and cisplatin exhibited significantly-increased inhibition of tumor growth, prolonged survival time, decreased expression of VEGFR-2, reduced microvascular density, and frequency of apoptosis over standalone and sequential administration therapy. Tumors treated simultaneously with apatinib and cisplatin had the lowest uptake of FDG. Taken together, the simultaneous administration of apatinib and cisplatin improves the therapeutic efficacy over standalone treatments, which also led to improved efficacy over sequential administration regimens. VEGFR-2 is an important predictive marker for efficacy of apatinib treatment of NPC.

11.
Oncotarget ; 8(8): 13157-13165, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-28061457

RESUMO

Notch signalling is aberrantly activated in human non-small cell lung cancer (NSCLC). Nevertheless, the prognostic roles of mRNA expression of four Notch receptors in NSCLC patients remain elusive. In this report, we reported the prognostic roles of Notch receptors in a total of 1,926 NSCLC patients through "The Kaplan-Meier plotter" (KM plotter) database which is capable to assess the effect of 22,277 genes on survival of NSCLC patients. We found that mRNA high expression level of Notch1 was associated with better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 0.78 (0.69-0.89), p=0.00019, better OS in adenocarcinoma (Ade) patients, HR 0.59 (0.46-0.75), p=1.5e-05, as well as in squamous cell carcinoma (SCC) patients, HR 0.78 (0.62-0.99), p=0.044. mRNA high expression levels of Notch2 and Notch3 were associated with worsen OS for all NSCLC patients, as well as in Ade, but not in SCC patients. mRNA high expression level of Notch4 was not found to be associated with to OS for all NSCLC patients. In addition, mRNA high expression levels of Notch2, Notch3, but Notch4 are significantly associated with the NSCLC patients who have different smoking status. Our results indicate that mRNA expression of Notch receptors may have distinct prognostic values in NSCLC patients. These results will benefit for developing tools to accurately predict the prognosis of NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , RNA Mensageiro/genética , Receptores Notch/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Perfilação da Expressão Gênica/métodos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas/genética , Receptor Notch1/genética , Receptor Notch2/genética , Receptor Notch3/genética , Receptor Notch4 , Fumar
12.
Oncotarget ; 8(13): 22166-22174, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-27825140

RESUMO

Runt-related transcription factor 3 (RUNX3) methylation plays an important role in the carcinogenesis of breast cancer (BC). However, the association between RUNX3 hypermethylation and significance of BC remains under investigation. The purpose of this study is to perform a meta-analysis and literature review to evaluate the clinicopathological significance of RUNX3 hypermethylation in BC. A comprehensive literature search was performed in Medline, Web of Science, EMBASE, Cochrane Library Database, CNKI and Google scholar. A total of 10 studies and 747 patients were included for the meta-analysis. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were evaluated and summarized respectively. RUNX3 hypermethylation was significantly correlated with the risk of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), OR was 50.37, p < 0.00001 and 22.66, p < 0.00001 respectively. Interestingly, the frequency of RUNX3 hypermethylation increased in estrogen receptor (ER) positive BC, OR was 12.12, p = 0.005. High RUNX3 mRNA expression was strongly associated with better relapse-free survival (RFS) in BC patients. In summary, RUNX3 methylation could be a promising early biomarker for the diagnosis of BC. High RUNX3 mRNA expression is correlated to better RFS in BC patients. RUNX3 could be a potential therapeutic target for the development of personalized therapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Animais , Feminino , Humanos
13.
Cancer Med ; 4(11): 1633-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333429

RESUMO

The aim of the study was to assess the clinical prognostic value of serum cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) for non-small-cell lung cancer (NSCLC) patients. Literatures related to effects of serum CYFRA21-1 and CEA on the prognosis of lung cancer patients were retrieved from databases such as PubMed, Springer Link, Embase, Wanfang, and CNKI. Meta-analysis was carried out using RevMan 5.1 software. Ten literatures involving 1990 NSCLC patients were selected in this study. Total survive estimation merging hazard ratio (HR) in all NSCLC patients with high-level serum CYFRA21-1 was 1.64 (95% CI 1.46-1.84, P < 0.001) and that in all NSCLC patients with high level serum CEA was 1.46 (95% CI 1.28-1.65, P < 0.001). Serum CYFRA21-1 and CEA can be used as prognostic factors of NSCLC patients. Combinative detection of the two indices will be more reliable.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Queratina-19/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Feminino , Humanos , Masculino , Prognóstico , Modelos de Riscos Proporcionais , Viés de Publicação
14.
Med Oncol ; 32(6): 615, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25926333

RESUMO

DNA methylation analysis, an epigenetic specification, has been explored for partial determination of cancer cell phenotypes. The development of metastasis in cancerogenesis has led its feasible association with the epigenetic modulations. We generated highly aggressive non-small cell lung cancer cell lines (HTB56 and A549) by using in vivo selection approach. These were, then, subjected to DNA methylation analysis (genome-wide). We also explored the therapeutic effects of azacytidine, an epigenetic agent, on DNA methylation patterns as well as the in vivo phenotypes. During the development of highly aggressive cell lines, we observed widespread modulations in DNA methylation. Reduced representation bisulfite sequencing was used and compared with the less aggressive parental cell lines to identify the differential methylation, which was achieved up to 2.7 % of CpG-rich region. Azacytidine inhibited DNA methyltransferase and reversed the prometastatic phenotype. We found its high association with the preferential loss of DNA methylation from hypermethylated sites. After persisted exposure of azacytidine, we observed that DNA methylation affected the polycomb-binding sites. We found close association of DNA methylome modifications with metastatic capability of non-small cell lung cancer. We also concluded that epigenetic modulation could be used as a potential therapeutic approach to prevent metastasis formation as prometastatic phenotype was reversed due to inhibition of DNA methyltransferase.


Assuntos
Metilação de DNA/genética , Epigênese Genética/genética , Neoplasias Pulmonares/genética , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Epigênese Genética/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Fenótipo
15.
Zhonghua Zhong Liu Za Zhi ; 35(5): 372-6, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-24054015

RESUMO

OBJECTIVE: To compare the difference of receptor expression between primary and locally recurrent breast tumor tissues, and analyze their impact on survival of the patients. METHODS: The expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) of primary and locally recurrent breast tumor tissues of 70 breast cancer patients were analyzed by immunohistochemistry or fluorescence in situ hybridization. The impact of the differences on overall survival (OS) and post-recurrence survival (PRS) of the patients was analyzed. RESULTS: The effective discrepancy rates between primary and locally recurrent breast cancer tissues were 26.1% (18/69) for ER, 50.0% (34/68) for PR, and 10.3%(4/39) for HER-2 expressions. In the 60 cases who had complete follow-up data, 23 patients (38.3%) died and the median overall survival was 107 months (11-288 months). The 3-, 5- and 10-year overall survival rates were 84.3%, 71.6% and 45.7%, respectively. Kaplan-Meier survival analysis showed that the changes of ER expression had significant impact on the OS (P = 0.001) and PRS (P < 0.001), but PR had no significant effect on OS (P = 0.416) and PRS (P = 0.056). However, the OS and PRS for patients with PR⁺ locally recurrent tumors were better than that of PR⁻ patients regardless of the primary tumor PR status. The expression of HER-2 had no significant effect on the OS (P = 0.840) and PRS (P = 0.544) of the patients. CONCLUSIONS: An expression discrepancy of ER, PR and HER-2 exists between primary and locally recurrent breast cancer tissues, it significantly affects the survival of the patients. Re-evaluation of the expressions of ER, PR and HER-2 receptor in locally recurrent breast tumor tissue is beneficial for their therapy and prognosis.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Recidiva Local de Neoplasia/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
16.
Zhonghua Zhong Liu Za Zhi ; 34(4): 291-5, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22781043

RESUMO

OBJECTIVE: To retrospectively evaluate the mammographic imaging findings and pathologic changes of the so-called "triple-negative" breast cancer (ER(-)/PR(-)/HER-2(-) breast cancer), and to compare them with the ER(+)/PR(+)/HER-2(-) and ER(-)/PR(-)/HER-2(+) breast cancer patients. METHODS: Five hundred cases of breast cancer treated in Cancer Institute and Hospital of Tianjin University from January to June of 2010 were included in this study. There were 112 cases of triple-negative breast cancer, 310 cases of ER(+)/PR(+)/HER-2(-) breast cancer, and 78 cases of ER(-)/PR(-)/HER-2(+) breast cancer. Their pathological and mammographic data were reviewed and analyzed. The pathological and mammographic features of the three groups were compared. RESULTS: Compared with the ER(+)/PR(+)/HER-2(-) breast cancer group, the triple-negative group had a higher histological grade (P < 0.001). Compared with the ER(+)/PR(+)/HER-2(-) and ER(-)/PR(-)/HER-2(+) groups, the triple-negative group was more likely to have a tumor mass (simple mass accounted for 58.0%, and tumor mass with calcification accounted for 19.6%). Moreover, compared with the ER(+)/PR(+)/HER-2(-) group (47.1% vs. 9.8%, P = 0.032)and the ER(-)/PR(-)/HER-2(+) group (47.1% vs. 0, P = 0.028), the tumor mass of triple-negative cancer was more likely to have a smooth margin. Triple-negative breast cancer seldom represented as calcification (simple calcification only accounted for 13.4%, and a mass with calcification accounted for 19.6%), and most of them were benign calcification (70.3%), significantly higher than that in the ER(+)/PR(+)/HER-2(-) group (23.1%, P = 0.002) and ER(-)/PR(-)/HER-2(+) group (10.2%, P < 0.001). CONCLUSIONS: Different types of breast cancer have different biological characteristics and mammographic features. Analysis of the mammographic features may help us to predict the type of breast cancer and its prognosis, and to select an optimal treatment plan for patients with different types of breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Mamografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
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