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1.
J Bone Miner Metab ; 42(1): 90-98, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38157037

RESUMEN

INTRODUCTION: Previous research has confirmed that patients with type 2 diabetes mellitus tend to have higher bone mineral density (BMD), but it is unknown whether this pattern holds true for individuals without diabetes. This Mendelian randomization (MR) study aims to investigate the potential causal relationship between various glycemic trait (including fasting glucose, fasting insulin, 2-h postprandial glucose, and glycated hemoglobin) and BMD in non-diabetic individuals. The investigation focuses on different age groups (15-30, 30-45, 45-60, and 60 + years) and various skeletal sites (forearm, lumbar spine, and hip). MATERIALS AND METHODS: We utilized genome-wide association study data from large population-based cohorts to identify robust instrumental variables for each glycemic traits parameter. Our primary analysis employed the inverse-variance weighted method, with sensitivity analyses conducted using MR-Egger, weighted median, MR-PRESSO, and multivariable MR methods to assess the robustness and potential horizontal pleiotropy of the study results. RESULTS: Fasting insulin showed a negative modulating relationship on both lumbar spine and forearm. However, these associations were only nominally significant. No significant causal association was observed between blood glucose traits and BMD across the different age groups. The direction of fasting insulin's causal effects on BMD showed inconsistency between genders, with potentially decreased BMD in women with high fasting insulin levels and an increasing trend in BMD in men. CONCLUSIONS: In the non-diabetic population, currently available evidence does not support a causal relationship between glycemic traits and BMD. However, further investigation is warranted considering the observed gender differences.


Asunto(s)
Diabetes Mellitus Tipo 2 , Análisis de la Aleatorización Mendeliana , Humanos , Femenino , Masculino , Adolescente , Densidad Ósea/genética , Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo , Insulina , Glucosa , Polimorfismo de Nucleótido Simple
2.
Environ Sci Technol ; 57(40): 15004-15013, 2023 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-37782146

RESUMEN

Growing evidence indicates that rivers are hotspots of greenhouse gas (GHG) emissions and play multiple roles in the global carbon budget. However, the roles of terrestrial carbon from land use in river GHG emissions remain largely unknown. We studied the microbial composition, dissolved organic matter (DOM) properties, and GHG emission responses to different landcovers in rivers (n = 100). The bacterial community was mainly constrained by land-use intensity, whereas the fungal community was mainly controlled by DOM chemical composition (e.g., terrestrial DOM with high photoreactivity). Anthropogenic stressors (e.g., land-use intensity, gross regional domestic product, and total population) were the main factors affecting chromophoric DOM (CDOM). DOM biodegradability exhibited a positive correlation with CDOM and contributed to microbial activity for DOM transformation. Variations in CO2 and CH4 emissions were governed by the biodegradation or photomineralization of dissolved organic carbon derived from autotrophic DOM and were indirectly affected by land use via changes in DOM properties and water chemistry. Because the GHG emissions of rivers offset some of the climatic benefits of terrestrial carbon (or ocean) sinks, intensified urban land use inevitably alters carbon cycling and changes the regional microclimate.


Asunto(s)
Materia Orgánica Disuelta , Gases de Efecto Invernadero , Ríos , Carbono , Materia Orgánica Disuelta/análisis , Gases de Efecto Invernadero/análisis , Ríos/química , China
3.
Pharm Biol ; 52(8): 978-82, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25017652

RESUMEN

CONTEXT: Polymeric nanoparticles (NPs) have been used frequently as drug delivery vehicles. Surface modification of polymeric NPs with specific ligands defines a new biological identity, which assists in targeting of the nanocarriers to specific cancers cells. OBJECTIVE: The aim of this study is to develop a kind of modified vector which could target the cancer cells through receptor-mediated pathways to increase the uptake of doxorubicin (DOX). METHODS: Folate (FA)-conjugated PEG-PE (FA-PEG-PE) ligands were used to modify the polymeric NPs. The modification rate was optimized and the physical-chemical characteristics, in vitro release, and cytotoxicity of the vehicle were evaluated. The in vivo therapeutic effect of the vectors was evaluated in human nasopharyngeal carcinoma KB cells baring mice by giving each mouse 100 µl of 10 mg/kg different solutions. RESULTS: FA-PEG-PE-modified NPs/DOX (FA-NPs/DOX) have a particle size of 229 nm, and 86% of drug loading quantity. FA-NPs/DOX displayed remarkably higher cytotoxicity (812 mm(3) tumor volume after 13 d of injection) than non-modified NPs/DOX (1290 mm(3)) and free DOX solution (1832 mm(3)) in vivo. CONCLUSION: The results demonstrate that the modified drug delivery system (DDS) could function comprehensively to improve the efficacy of cancer therapy. Consequently, the system was shown to be a promising carrier for delivery of DOX, leading to the efficiency of antitumor therapy.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Ácido Fólico/administración & dosificación , Nanopartículas/administración & dosificación , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Antibióticos Antineoplásicos/química , Doxorrubicina/química , Ácido Fólico/química , Humanos , Células KB , Ratones , Ratones Endogámicos BALB C , Nanopartículas/química
4.
Zhonghua Bing Li Xue Za Zhi ; 43(8): 533-6, 2014 Aug.
Artículo en Zh | MEDLINE | ID: mdl-25346123

RESUMEN

OBJECTIVE: To investigate the frequency of USP6 gene rearrangement in nodular fasciitis (NF) and to evaluate its clinical application. METHODS: Twenty nine cases of previously diagnosed NF were screened for the presence of the USP6 gene rearrangement by interphase fluorescence-in-situ hybridization (FISH) on formalin-fixed paraffin-embedded tissue. Fifteen of these cases, which had available tissue, were also analysed for MYH9-USP6 fusion transcripts by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Twenty four of the 29 cases (83%) were positive for the USP6 gene rearrangement by interphase FISH. The 15 cases with RT-PCR showed the following results: 11 positive, one deletion and three negative for USP6 gene rearrangement. Of these 15 cases, eight (8/15) showed MYH9-USP6 fusion transcript by RT-PCR. Of these eight cases, seven were positive for USP6 gene rearrangement and one showed USP6 deletion by FISH. CONCLUSIONS: USP6 gene rearrangement is a recurrent genetic event in NF. It is a valuable ancillary tool for the pathological diagnosis of these lesions.


Asunto(s)
Fascitis/genética , Reordenamiento Génico , Proteínas Proto-Oncogénicas/genética , Translocación Genética , Ubiquitina Tiolesterasa/genética , Humanos , Hibridación Fluorescente in Situ , Interfase , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
5.
J Cancer ; 15(7): 1966-1982, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38434972

RESUMEN

Background: Hepatocellular carcinoma (HCC) is one of the common primary cancers of the liver worldwide and leading cause of mortality. Gasdermins (GSDMs) family genes play an important role in the regulation of the normal physiological processes and have been implicated in multiple diseases. However, little is known about the relationship between different GSDMs proteins and HCC. The aim of this study was to explore the potential relationship between the expression, prognosis, genetic variation and immune infiltration of GSDMs family genes and HCC. Methods: We used different bioinformatics common public databases such as GSCA, GEPIA, UALCAN, HPA, Kaplan-Meier Plotter, LinkedOmics, GeneMANIA, STRING, cBioPortal, TIMER and TISIDB to analyze the differential expression of the different GSDMs, prognostic value, genetic alterations, immune cell infiltration and their functional networks in HCC patients. Results: All the members of the GSDMs family exhibited elevated mRNA expression levels in LIHC compared to the normal tissues, while only GSDMB, GSDMD and GSDME showed enhanced protein expression. The mRNA expression of most GSDMs members was found to be elevated in HCC patients at stages I-III (clinical stage) compared to the normal subjects. The expression of GSDMD was correlated with OS and DSS of patients, whereas GSDME was correlated with OS, DSS and RFS of patients. Gene amplification was observed to be main mode of variation in members of the GSDMs family. KEGG pathway analysis showed that genes associated with different members of the GSDMs family were enriched in the pathways of S. aureus infection, intestinal immunity, ribosome and protein assembly, oxidative phosphorylation, osteoclast differentiation and Fc gamma (γ) R-mediated phagocytosis. In addition, expression of both GSDMA and GSDME were found to be correlated most significantly with infiltration of immune cells, while GSDMA and GSDME somatic cell copy number alteration (CAN) were correlated significantly with the infiltration of immune cells. All GSDMs were noted to be associated with distinct subtypes of immune cells, except GSDMC. Conclusions: Our findings have provided useful insights to better understand the roles and functions of GSDMs in HCC that can provide novel direction for developing therapeutic modalities for HCC, including immunotherapy.

6.
Front Med (Lausanne) ; 9: 833822, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35669919

RESUMEN

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade malignant soft tissue tumor. Most of the previously reported cases about this tumor were diagnosed within the soft tissues. Here, we report a unique case of MIFS of the right parotid gland in a 39-year-old Chinese male. The tumor primarily consisted of an inflammatory area and a mucus-like area in a migratory distribution. A number of lymphocytes, neutrophils, viral-like cells with large nucleoli, and eosinophilic cytoplasm or Reed-Sternberg-like cells, as well as spindle cells and epithelial-like aberrant cells, were observed within the tumor. They were found to express Vimentin and CD10 protein and no other specific immunohistochemical markers. The various cytomorphology and immunohistochemical features of this tumor were highly consistent with MIFS found in other sites. Therefore, several leading pathologists ultimately confirmed the final diagnosis of MIFS in the right parotid gland after repeated deliberation. To our knowledge, this is the first case of MIFS occurring in the parotid gland. Thus, our study provides a novel basis for identifying the biological behavior of the tumor in MIFS and also allows us to better understand the pathology of this rare tumor.

7.
Front Med (Lausanne) ; 9: 833864, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35836959

RESUMEN

Sclerosing epithelioid fibrosarcoma (SEF) is a rare subtype of soft tissue tumors, and SEF originating from the side of the spine is even rarer. We report that a 28-year-old young woman suffered from chest pain and back pain for 3 years, and thereafter she went to see a doctor because her condition deteriorated. Enhanced CT showed that the right posterior upper chest wall mass invaded the adjacent bone, and the boundary between the lesion and the surrounding tissues was relatively clear. She then underwent posterior tumor removal surgery. The pathological examination confirmed the diagnosis of SEF. In histomorphology, the tumor displayed a typical epithelioid clear cell morphology, accompanied by extensive vitrification and fibrosis, which better helped to differentiate the tumor from low grade fibromyxoid sarcoma, solitary fibrous tumor and other entities. The immunohistochemical analysis showed a diffuse positive reaction to MUC4, a highly specific marker of SEF, which was detected by Immunohistochemistry (IHC), and fluorescence in-situ hybridization (FISH) confirmed that the EWSR1 gene was rearranged, while the FUS gene was not rearranged. This is the first time that we have encountered such this rare case and thus report this case with updated literature related to this tumor.

8.
Front Pharmacol ; 13: 1003812, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36532750

RESUMEN

Methotrexate (MTX) is a folic acid antagonist, the mechanism of action is to inhibit DNA synthesis, repair and cell proliferation by decreasing the activities of several folate-dependent enzymes. It is widely used as a chemotherapy drug for children and adults with malignant tumors. High-dose methotrexate (HD-MTX) is an effective treatment for extramedullary infiltration and systemic consolidation in children with acute lymphoblastic leukemia (ALL). However, significant toxicity results in most patients treated with HD-MTX, which limits its use. HD-MTX-induced toxicity is heterogeneous, and this heterogeneity may be related to gene polymorphisms in related enzymes of the MTX intracellular metabolic pathway. To gain a deeper understanding of the differences in toxicity induced by HD-MTX in individuals, the present review examines the correlation between HD-MTX-induced toxicity and the gene polymorphisms of related enzymes in the MTX metabolic pathway in ALL. In this review, we conclude that only the association of SLCO1B1 and ARID5B gene polymorphisms with plasma levels of MTX and MTX-related toxicity is clearly described. These results suggest that SLCO1B1 and ARID5B gene polymorphisms should be evaluated before HD-MTX treatment. In addition, considering factors such as age and race, the other exact predictor of MTX induced toxicity in ALL needs to be further determined.

9.
Sci Adv ; 7(22)2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-34039604

RESUMEN

The development of machine learning provides solutions for predicting the complicated immune responses and pharmacokinetics of nanoparticles (NPs) in vivo. However, highly heterogeneous data in NP studies remain challenging because of the low interpretability of machine learning. Here, we propose a tree-based random forest feature importance and feature interaction network analysis framework (TBRFA) and accurately predict the pulmonary immune responses and lung burden of NPs, with the correlation coefficient of all training sets >0.9 and half of the test sets >0.75. This framework overcomes the feature importance bias brought by small datasets through a multiway importance analysis. TBRFA also builds feature interaction networks, boosts model interpretability, and reveals hidden interactional factors (e.g., various NP properties and exposure conditions). TBRFA provides guidance for the design and application of ideal NPs and discovers the feature interaction networks that contribute to complex systems with small-size data in various fields.

10.
Front Oncol ; 11: 698811, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34381721

RESUMEN

The way of cell death can be roughly divided into two categories: cell necrosis and PCD(programmed cell death). Pyroptosis is a kind of PCD, its occurrence depends on the gasdermin protein family and it will produce inflammatory response. With constant research in recent years, more and more evidences show that pyroptosis is closely related to the occurrence and development of tumors. The treatment of tumors is a big problem worldwide. We focus on whether we can discover new potential tumor markers and new therapeutic targets from the mechanism. If we can understand the mechanism of pyroptosis and clear the relationship between pyroptosis and the development of tumors, this may provide a new reference for clinical cancer treatment.

11.
Environ Int ; 146: 106302, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395945

RESUMEN

Both gut microbes and environmental contamination may cause metabolic disorders and obesity. However, the relationships among gut microbes, environmental contamination and obesity remain obscure. The drinking water on a national scale (31 cities in China) contained nanocolloid-pattern contamination at the mg/L level, a concentration that is 10- to 100-fold higher than commonly reported pollutants. Exposure to nanocolloids (environmentally related dose, 0.15 mg/kg) for three weeks increased the body weight and leptin levels of mice and decreased the expression of adiponectin. Nanocolloids increased the ratio of Firmicutes to Bacteroidetes, a typical obesity-related phenomenon, in the obese individuals. Oral administration of resveratrol verified the role of gut microbes in the tendency toward obesity induced by nanocolloids. The ratio of Firmicutes to Bacteroidetes is positively correlated with body weight and leptin levels. Compared to the control, the levels of triglycerides and high-density lipoprotein cholesterol were up- and downregulated by the tested nanocolloids at 0.15 mg/kg, respectively. Long-chain fatty acids, lipid metabolites and the expression of lipid synthesis-related genes (Fas, Srebp-1 and ACC-1) were also significantly increased by nanocolloids. The present study provides new insights that improve our understanding the risks of obesity associated with drinking water contamination that are mediated by gut microbes.


Asunto(s)
Agua Potable , Microbioma Gastrointestinal , Animales , Peso Corporal , China , Ratones , Obesidad
12.
Nat Commun ; 12(1): 493, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33479209

RESUMEN

Biofilms contribute to bacterial infection and drug resistance and are a serious threat to global human health. Antibacterial nanomaterials have attracted considerable attention, but the inhibition of biofilms remains a major challenge. Herein, we propose a nanohole-boosted electron transport (NBET) antibiofilm concept. Unlike known antibacterial mechanisms (e.g., reactive oxygen species production and cell membrane damage), nanoholes with atomic vacancies and biofilms serve as electronic donors and receptors, respectively, and thus boost the high electron transport capacity between nanomaterials and biofilms. Electron transport effectively destroys the critical components (proteins, intercellularly adhered polysaccharides and extracellular DNA) of biofilms, and the nanoholes also significantly downregulate the expression of genes related to biofilm formation. The anti-infection capacity is thoroughly verified both in vitro (human cells) and in vivo (rat ocular and mouse intestinal infection models), and the nanohole-enabled nanomaterials are found to be highly biocompatible. Importantly, compared with typical antibiotics, nanomaterials are nonresistant and thereby exhibit high potential for use in various applications. As a proof-of-principle demonstration, these findings hold promise for the use of NBET in treatments for pathogenic bacterial infection and antibiotic drug resistance.


Asunto(s)
Antibacterianos/administración & dosificación , Biopelículas/efectos de los fármacos , Nanoestructuras/administración & dosificación , Staphylococcus aureus/efectos de los fármacos , Animales , Células CACO-2 , Transporte de Electrón/efectos de los fármacos , Humanos , Ratones Endogámicos ICR , Pruebas de Sensibilidad Microbiana , Ratas Sprague-Dawley , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/fisiología
13.
ACS Appl Bio Mater ; 4(7): 5503-5519, 2021 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-35006747

RESUMEN

Many engineered nanomaterials (ENMs) and drugs have been fabricated to improve memory and promote neuroprotection, but their use remains challenging due to their high cost, poor ability to penetrate the blood-brain barrier (BBB), and many side effects. Herein, we found that nanoparticles with multiple enzymatic activities purified from groundwater (NMEGs) can efficiently cross the BBB and present memory-enhancing and neuroprotective effects in vitro and in vivo. In contrast to the adverse effects of chemicals and ENMs, NMEGs are able to cross the BBB by endocytosis without damaging the BBB and even possibly promote BBB integrity. NMEGs-treated normal mice were smarter and better behaved than saline-treated normal mice in the open-field test and Morris water maze test. NMEGs can enhance synaptic transmission by increasing neurotransmitter production and activating nicotinic acetylcholine receptors (nAChRs), activate the antioxidant enzyme system, and increase the number of mitochondria and ribosomes in cells. Intravenous NMEGs injection also rescued memory deficits and increased antioxidant capacity in Parkinson's disease (PD) mice due to the antioxidant activity caused by the presence of conjugated double bonds and abundant phenolic -OH groups. This study is a proof-of-principle demonstration that natural products are less expensive, more easily available, safer, and more effective ways to improve memory and promote neuroprotection than ENMs and reported drugs. Our article also shows the potential of NMEGs as a PD treatment in patients via intravenous injection, as they avoid the complex modifications of ENMs. In the future, it will be possible to treat PD by intravenously injecting NMEGs in patients.


Asunto(s)
Agua Subterránea , Nanopartículas , Enfermedad de Parkinson , Animales , Antioxidantes/farmacología , Barrera Hematoencefálica , Humanos , Ratones , Nanopartículas/química , Neuroprotección
14.
Front Mol Biosci ; 8: 799060, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35047559

RESUMEN

Object: This study aims to clarify the expression of plasma miRNA in CRC patients, and to clarify the potential use of these miRNAs in diagnosis and prognosis, and to establish a prognostic model to initially explore its clinical value. Methods: We detected the expression of 6 miRNAs in normal colon epithelial cell lines and colorectal cancer cell lines by qRT-PCR and they were validated in the tissues of three subtypes: 20 healthy subjects, 41 pCRC and 49 mCRC patients. COX regression and ROC analyses use to evaluate the diagnostic and prognostic efficacy of candidate miRNAs. Subsequently, we initially established a nomogram prognostic model. MiRNA is also used to construct miRNA-mRNA interaction network and PPI network modules. Results: Five miRNAs showed significant differential expression in pCRC, mCRC patients and normal groups. ROC analysis showed that CEA, miR-96, miR-99b and miR-96/miR-99b are distinguishable from pCRC and mCRC patients, with AUC ranging from 0.65 to 0.91; among them, the ratio of miR-96/miR-99b is stronger than any diagnostic indicators, such as CEA and CA125. Multivariate survival analysis identified miR-96, miR-99b, N stage, M stage and clinical stage as independent prognostic indicators of mCRC. The nomogram based on these 5 characteristics has satisfactory prognostic values. Conclusion: Our data indicate that plasma miR-96/miR-99b can be used as a promising biomarker for early detection of mCRC patients; our nomogram has a promising evaluation value.

15.
Environ Pollut ; 267: 115434, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32841907

RESUMEN

Predicting the biological responses to engineered nanoparticles (ENPs) is critical to their environmental health assessment. The disturbances of metabolic pathways reflect the global profile of biological responses to ENPs but are difficult to predict due to the highly heterogeneous data from complicated biological systems and various ENP properties. Herein, integrating multiple machine learning models and metabolomics enabled accurate prediction of the disturbance of metabolic pathways induced by 33 ENPs. Screening nine typical properties of ENPs identified type and size as the top features determining the effects on metabolic pathways. Similarity network analysis and decision tree models overcame the highly heterogeneous data sources to visualize and judge the occurrence of metabolic pathways depending on the sorting priority features. The model accuracy was verified by animal experiments and reached 75%-100%, even for the prediction of ENPs outside of databases. The models also predicted metabolic pathway-related histopathology. This work provides an approach for the quick assessment of environmental health risks induced by known and unknown ENPs.


Asunto(s)
Nanopartículas , Animales , Aprendizaje Automático , Redes y Vías Metabólicas , Metabolómica
16.
Biomaterials ; 243: 119937, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32172032

RESUMEN

We report a heterojunction Bi2WO6/WS2-x with sulfur vacancies as a broad-spectrum bactericide to efficiently kill Gram-positive and Gram-negative bacteria in vitro and in vivo under visible-light irradiation. Sulfur vacancies in single-layer WS2 make the surface electron-rich. Integration of Bi2WO6 with WS2 enhances the photoelectric activity under visible-light irradiation. Sulfur vacancies promote the generation of radicals and the extraction of membrane phospholipids from bacterial cells. Density functional theory verifies that S vacancies strengthen the interactions between the Bi2WO6/WS2-x surface and H2O, enhancing the generation of ·OH. Two-dimensional correlation spectroscopy analysis reveals that perturbation of ß-sheet proteins and formation of outer-sphere surface complexes contribute to the high antibacterial capacity. Bi2WO6/WS2-x accelerates the re-epithelialization and healing of infected wounds in an animal model. Uncommonly, Bi2WO6/WS2-x does not exhibit drug resistance and is biocompatible with human cells. Our results indicate that vacancy-functionalized heterojunctions are potentially promising antibacterial agents by regulating the interface interaction between biology and nanomaterials.


Asunto(s)
Antibacterianos , Nanoestructuras , Animales , Antibacterianos/farmacología , Biología , Bacterias Gramnegativas , Bacterias Grampositivas , Humanos , Azufre
17.
Cancer Manag Res ; 11: 4461-4469, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31191008

RESUMEN

Background: Perineural invasion (PNI) is closely associated with poor survival in several types of malignant tumours, but whether this is true in vulvar squamous cell carcinoma (VSCC) is unclear. The aims of this study were to determine the prognostic significance of PNI in patients with VSCC. Patients and methods: We retrospectively analysed clinico-pathological data on 105 patients with VSCC (stages IB-IV) treated surgically at our medical center between 2005 and 2015. Results: PNI was detected in 30 (28.6%) patients, and it was significantly associated with well-known clinical risk factors: large tumour size, depth of invasion, lymphatic vascular space invasion (LVSI), and intra- or extra-nodal spread. Significantly greater proportions of patients with PNI received adjuvant therapy after surgery (P=0.001) or showed local recurrence (P=0.002). Multivariable analysis indicated that risk factors for disease-free survival were tumour size (HR 3.02, 95%CI 1.75-7.75), LVSI (HR 4.82, 95%CI 1.36-17.07), depth of invasion (HR 3.11, 95%CI 1.50-6.44), lymph node metastasis (HR 3.15, 95%CI 1.14-8.96) and positive or close surgical margins (HR 4.86, 95%CI 1.67-14.19). The latter three variables were also risk factors for overall survival. PNI was associated with significantly shorter disease-free survival (DFS) (P=0.020) and overall survival (OS) (P=0.017) based on the log-rank test. Among patients who received adjuvant treatment, Kaplan-Meier curves indicated no significant differences between PNI-positive or -negative subgroups in disease-free survival (P=0.085) or overall survival (P=0.061). Based on multivariable analysis of all patients, PNI was not a significant risk factor for either type of survival . Conclusion: PNI in VSCC is associated with significantly shorter disease-free and overall survival, though it appears to be a weak independent predictor of worse prognosis. Combining PNI with other risk factors may be useful for predicting whether postoperative adjuvant therapy will be needed.

18.
PLoS One ; 11(12): e0168795, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27992557

RESUMEN

An association between epidermal growth factor receptor (EGFR) and clinical characteristics of non-small cell lung cancer (NSCLC) was reported ten years ago. In addition, a different type of relationship was seen in different ethic races. However, the relationship between these factors is not well understood in the Guangxi province. Up to now, there are only very limited data on the association of TTF1/EGFR protein positivity and EGFR mutation status in NSCLC. This study aims to investigate the role of EGFR gene mutation status on the clinical characteristics and the relationship with TTF-1/EGFR protein positivity of patients with NSCLC in Guangxi, China. 1506 samples from different patients with NSCLC were detected by amplification refractory mutation system for 29 hotspot mutations. Analysis of the relationship between clinical characteristics and EGFR mutation status was performed by using the crosstabs Chi-square and SPSS 21.0 software. Of 1506 samples, 537 (35.7%) revealed tyrosine kinase inhibitor (TKI) sensitive EGFR mutations with 27 (1.8%) cases harboring TKI resistant EGFR mutations or union co-existing EGFR-TKIs sensitive mutations. EGFR-TKIs sensitive mutations were not significantly associated with age and TNM-M stage (P = 0.863; P = 0.572, respectively). However, they were significantly associated with p-stage, TNM-T stage and TNM-N stage (P = 0.011, P < 0.001, P = 0.036, respectively). Immunohistochemical studies revealed that TTF-1 and EGFR protein expression level were all associated with EGFR mutation status (P < 0.001, P = 0.002, respectively). Of the 537 EGFR-TKIs sensitive mutation cases, the rates of exon 19-del, 18 G719X point, exon 21 L858R and L861Q points were 54.6, 0.9, 42.3 and 0.9%, respectively. EGFR TKI-sensitive mutations commonly occur in female, non-smoking and adenocarcinoma patients. The p-stage, TNM-T stage, TNM-N stage, EGFR and TTF-1 protein expression levels have close relationships with EGFR mutation status.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos/genética , Receptores ErbB , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Mutación Missense , Adulto , Anciano , Anciano de 80 o más Años , Sustitución de Aminoácidos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , China , Análisis Mutacional de ADN , Resistencia a Antineoplásicos/efectos de los fármacos , Receptores ErbB/biosíntesis , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Nucleares/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Factor Nuclear Tiroideo 1 , Factores de Transcripción/metabolismo
19.
Int J Clin Exp Pathol ; 7(12): 8740-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25674240

RESUMEN

The overexpressed HER2 (human epidermal growth factor receptor 2) is a valuable therapeutic target. Precise assessment of HER2 status is thus crucial in the treatment of breast cancer. In this study, formalin-fixed, paraffin-embedded samples of tumors from 304 breast cancer patients who underwent curative surgery procedures between 2011 and 2014 were tested by immunohistochemistry (IHC) as a primary estimate of HER2 status, followed by fluorescence in situ hybridization (FISH). Concordance rate between IHC and FISH was evaluated. The Χ(2) test was used to evaluate the correlation between HER2 gene amplification status and different clinical pathological features including: (estrogen receptor) ER and (progesterone receptor) PR expression, age, menopausal status and tumor size. The results show that 84.8% of IHC score 3+ cases and 6.2% of IHC score 0/1+ cases were amplified by FISH. After exclusion of group IHC 2+, the concordance rate between FISH and IHC was 87.4%. There was a significant inverse association between expression of hormone receptors (ER and PR) and HER2 amplification (P < 0.001) among the patients studied. However, no relationship was observed between HER2 amplification and age, menopausal status and tumor size (P > 0.05). The data demonstrate a relatively high level of concordance rate for HER2 testing between FISH and IHC, and HER2 overexpression was associated with the levels of ER and PR.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Receptor ErbB-2/análisis , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Femenino , Amplificación de Genes , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Receptor ErbB-2/biosíntesis , Receptor ErbB-2/genética , Receptores de Estrógenos/análisis , Receptores de Estrógenos/biosíntesis , Receptores de Progesterona/análisis , Receptores de Progesterona/biosíntesis , Reproducibilidad de los Resultados
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