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1.
J Psychiatr Res ; 169: 126-133, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38016394

RESUMO

Individuals with opioid use disorder (OUD) have been reported to show abnormal brain metabolism and impaired coupling among brain networks such as the default mode network (DMN), salience network (SN), and executive control network (ECN). However, the characteristics of brain glucose metabolism and its related functions in the brain networks in individuals with OUD remain unknown. Thirty-six individuals with OUD and thirty matched healthy controls (HCs) were recruited in this integrated positron emission tomography/magnetic resonance imaging (PET/MRI) study. Differences in glucose metabolism were analyzed by using 18F-fluorodeoxyglucose (18F-FDG), and the corresponding coupling characteristics of the individuals with OUD were also analyzed. The individuals with OUD showed widespread bilateral hypometabolism in the middle temporal gyrus (MTG), superior temporal gyrus, angular gyrus, supramarginal gyrus, inferior parietal lobe, Rolandic operculum, and left insula, but obvious hypermetabolism in the brainstem and left cerebellum. Meanwhile, in individuals with OUD, the hypometabolism of right MTG which is included in the DMN was accompanied by decreased coupling with the left superior frontal gyrus and right superior parietal gyrus which are included in the ECN. Furthermore, individuals with OUD showed a positive correlation between the duration of heroin use and glucose metabolism of the left MTG. The individuals with OUD were characterized by widespread bilateral hypometabolism in the temporal and parietal regions but obvious hypermetabolism in the brainstem and left cerebellum. The results suggest that the hypometabolism in the temporal and parietal regions might be related to DMN dysfunction and the hypermetabolism in the brainstem and left cerebellum may be compensate for other brain regions showing hypometabolism. In particular, hypometabolism in the self-referential-related DMN regions in OUD might attenuate their relationships with the inhibitory-control-related ECN regions. These findings highlight the importance of evaluating the metabolic and functional profiles of the right MTG in future studies on the treatment of OUD.


Assuntos
Imageamento por Ressonância Magnética , Transtornos Relacionados ao Uso de Opioides , Humanos , Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons , Glucose/metabolismo , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem
2.
J Psychiatry Neurosci ; 48(4): E295-E304, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37437921

RESUMO

BACKGROUND: Increasing evidence suggests that heroin addiction may be related to the dysfunction among the triple brain network (default mode network [DMN], salience network [SN] and executive control network [ECN]). However, the characteristics of glucose metabolism and metabolic connectivity among core regions of the triple brain network remain unknown. Therefore, we hypothesized that individuals with heroin dependence would show abnormal glucose metabolism and accompanied abnormal metabolic connectivity within the triple brain network. METHODS: Individuals with heroin dependence and healthy controls matched for age and sex underwent integrated positron emission tomography/magnetic resonance imaging (PET/MRI). Differences in glucose metabolism and metabolic connectivity among the DMN, SN and ECN were analyzed based on 18F-fluorodeoxyglucose PET and resting-state fMRI data. RESULTS: We included 36 individuals with heroin dependence and 30 matched healthy controls in our study. The heroin dependence group showed a significant reduction of glucose metabolism in the bilateral anterior insula (AI) and inferior parietal lobule (IPL), and a significantly decreased metabolic connectivity between the right AI and the left dorsolateral prefrontal cortex (DLPFC). The daily dose of methadone was negatively correlated with glucose metabolism of the right AI and right IPL. LIMITATIONS: The results revealed the glucose metabolism alterations and metabolic connectivity only within the triple brain network in individuals with heroin dependence; additional brain networks should be investigated in future studies. Although methadone is an opioid with a similar neurophysiological mechanism as heroin, the specific chronic effects of methadone on cerebral metabolism and metabolic connectivity should also be investigated in future studies. CONCLUSION: Our findings suggest that long-term opioid use might, to some extent, be associated with reduced synergistic ability between the SN and ECN, which may be associated with the dysfunction of cognitive control. In particular, the right AI, which showed hypometabolism and related reduction in SN-ECN metabolic connectivity, should receive increasing attention in future studies.


Assuntos
Dependência de Heroína , Imageamento por Ressonância Magnética , Humanos , Dependência de Heroína/diagnóstico por imagem , Analgésicos Opioides , Glucose , Metadona , Tomografia por Emissão de Pósitrons
3.
Brain Imaging Behav ; 17(1): 54-65, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36418675

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been shown to reduce cravings in heroin-dependent (HD) individuals, but the mechanisms underlying the anti-craving effects of rTMS are unknown. Abnormalities in the default mode network (DMN) are known to be consistent findings in HD individuals and are involved in cravings. We assessed the effect of rTMS on DMN activity and its relationship to the treatment response. Thirty HD individuals were included in this self-controlled study, and all HD participants received 10-Hz rTMS 7-session during a week. Data for cravings and withdrawal symptoms and resting-state functional magnetic resonance imaging data were collected before and after rTMS treatment. Thirty demographically matched healthy individuals who did not receive rTMS were included as controls. We focused on changes in coupling seeded from the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and bilateral inferior parietal lobe (IPL), which are the core regions of the DMN. The craving and withdrawal symptom score of HD individuals decreased significantly after rTMS treatment. The left IPL-left middle frontal gyrus coupling and the left IPL-right inferior occipital gyrus coupling decreased significantly, and the changes in the left IPL-left middle frontal gyrus coupling were positively correlated with changes in drug-cue induced cravings. rTMS could modulate the coupling between the DMN and executive control network (ECN). Alterations of the left IPL-left middle frontal gyrus coupling may play an important mechanistic role in reducing drug cue-induced cravings.


Assuntos
Dependência de Heroína , Estimulação Magnética Transcraniana , Humanos , Estimulação Magnética Transcraniana/métodos , Dependência de Heroína/terapia , Rede de Modo Padrão , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/fisiologia
4.
IUBMB Life ; 74(5): 433-445, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35112451

RESUMO

Bovine serum albumin (BSA) has been employed as a mild biological template in nanoscale particles. Copper sulfide (CuS) has been used for photothermal therapy (PTT) in several studies. In this study, we aimed to synthesize the 131 I-labeled BSA-modified CuS nanoparticles (131 I-BSA@CuS), with attributes of both radiotherapy and PTT, as a therapeutic agent against anaplastic thyroid carcinoma (ATC). BSA@CuS nanoparticles were prepared using the solvothermal reaction and then labeled with Na131 I by the chloramine-T method. The products were characterized and their cytotoxicity was investigated in vitro and in vivo. The therapeutic efficacy of 131 I-BSA@CuS was evaluated in ARO cell (an ATC cell line) subcutaneous tumors. The nanoparticles showed good biocompatibility and low toxicity in vitro and in vivo. BSA@CuS rapidly and effectively converted the light energy from an 808 nm laser into thermal energy with a conversion efficiency of 28.07%. SPECT/CT imaging demonstrated that the accumulation of radioactivity peaked within 24 hr and resided in the tumors for 5 days post intratumoral injection. In vivo assays indicated that, compared to monotherapy, the synthesized nanoparticles employing both PTT and radiotherapy possess better therapeutic efficacy against tumors. The synthesized nanomaterial showed uniform dispersion, good stability and aqueous solubility, excellent photothermal properties, and long-term retention in ATC. Hence, combined radiotherapy and PTT can significantly inhibit tumor growth compared to monotherapy, and can be applied in clinical settings.


Assuntos
Nanopartículas , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Cobre , Humanos , Fototerapia/métodos , Terapia Fototérmica , Soroalbumina Bovina , Carcinoma Anaplásico da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/radioterapia
5.
Addict Biol ; 27(2): e13121, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34841633

RESUMO

The abnormal interactions of three key large-scale brain networks (default mode [DMN], salience and executive control [ECN]) were showed underlie dysfunctions in heroin addiction. Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a potential treatment for heroin addiction. It is unclear whether impaired coupling among the large-scale brain networks would be improved by rTMS in treated heroin-dependent individuals. Thirty-five heroin-dependent individuals were included in this sham-controlled, randomized study. The patients received either active or sham rTMS for 1 week. The craving for heroin and resting-state functional magnetic resonance imaging data were collected before and after 1-week rTMS. Twenty-two healthy subjects were included as controls not receiving rTMS. After 1-week rTMS, only the active rTMS group showed a significant decrease in spontaneous and heroin cue-induced craving. The coupling between left DLPFC (a key node of left ECN) and left parahippocampal gyrus (PHG, included in DMN) significantly increased for the active group with a tendency towards that of controls. The coupling between the right precentral gyrus and three key regions included in DMN (posterior cingulate cortex/precuneus and bilateral inferior parietal cortex) significantly decreased for the active group with a tendency towards that of healthy controls. For the active rTMS individuals, the left DLPFC-PHG coupling negatively correlated with the spontaneous craving and the drug cue-induced craving. It suggested that the rTMS could reduce heroin craving, which might be related to the modulation of ECN-DMN coupling. This finding might shed light on the mechanism of rTMS for heroin addiction treatment.


Assuntos
Heroína , Estimulação Magnética Transcraniana , Encéfalo/diagnóstico por imagem , Fissura/fisiologia , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Magnética Transcraniana/métodos
6.
Int J Neurosci ; 131(2): 128-134, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32098541

RESUMO

OBJECTIVES: To assess the clinical value of voxel-based automatic quantitative analysis using a normal brain glucose metabolism database in the preoperative localization of focal intractable temporal lobe epilepsy patients. METHODS: Patients with refractory temporal lobe epilepsy who underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging were retrospectively enrolled from January to June 2017. Visual analysis was performed by two nuclear medicine radiologists, and the automatic quantitative analysis was carried out using MIMneuro software based the age- and gender-stratified normal brain glucose metabolism database. Setting postoperative outcomes as reference, the consistency between visual analysis and automatic quantitative analysis was tested by Cohen's kappa coefficient, and differences in localization of epileptic foci of the two methods were compared by Chi-square test. RESULTS: A total of 32 patients intractable temporal lobe epilepsy were included in this study. There was a moderate agreement between the automatic quantitative analysis based on MIMneuro software and visual analysis (kappa coefficient = 0.472, p = 0.002). In terms of the efficiency of focus localization, the voxel-based automatic quantitative analysis was higher than that of visual analysis (Chi-square value = 6.969, p = 0.008). CONCLUSIONS: The voxel-based automatic quantitative analysis combined with normal brain glucose metabolism database had a certain clinical application value for detection temporal lobe epilepsy.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/metabolismo , Glucose/metabolismo , Adolescente , Adulto , Proteínas de Arabidopsis , Bases de Dados Factuais , Humanos , Liases Intramoleculares , Masculino , Pessoa de Meia-Idade , Álcool Feniletílico/análogos & derivados , Tomografia por Emissão de Pósitrons , Adulto Jovem
7.
Neurol Sci ; 41(11): 3219-3226, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32372198

RESUMO

OBJECTIVES: This study aimed to measure the global brain glucose metabolism of patients with temporal lobe epilepsy (TLE) using MIMneuro software based on the normal brain glucose metabolism database. METHODS: In this cross-sectional study, 23 patients (11 males and 12 females, mean age 25.6 ± 10.1 years) with TLE who underwent 18F-labeled fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET) were enrolled. 18F-FDG PET images were then imported into MIMneuro software, which can automatically analyze the differences in regional brain glucose metabolism between patients and a normal database, and the results of different brain regions were presented by values of Z-score. RESULTS: In patients with TLE, 18F-FDG PET imaging showed that in addition to the presence of temporal lobe hypometabolism, there was hypometabolism in the ipsilateral hippocampus, parahippocampal gyrus, insula, amygdala, temporal operculum, and bilateral cerebellar hemisphere, while hypermetabolism was found in the contralateral temporal lobe, frontal lobe, parietal lobe, parietal lobule, angular gyrus, and precentral gyrus. There was no significant difference in brain areas between the left and the right temporal lobe seizures (P > 0.05). CONCLUSIONS: We found that TLE has a specific characteristic in terms of brain glucose metabolism, and the underlying mechanism needs to be further studied that may be helpful to localize seizure focus.


Assuntos
Epilepsia do Lobo Temporal , Fluordesoxiglucose F18 , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Estudos Transversais , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Glucose , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
ACS Omega ; 4(18): 17735-17740, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31681879

RESUMO

Controlling the surface is necessary to adjust the essential properties and desired functions of nanomaterials and devices. For nanostructured multivalent vanadium oxides, unwanted surface oxidation occurs at ambient atmosphere generally and needs to be suppressed or avoided. We describe the suppressed surface oxidation of VO2 nanostructures through blocking oxygen adsorption. During an enhanced photoinduced surface oxidation process, the increased oxidation states of vanadium in VO2 nanostructures are suppressed by the use of an inert atmosphere or coating. Intermediate oxidation states are observed, and an ALD-TiO2 coating has a good antioxidant capacity for preventing the formation of oxygen-enriched components. Such oxidation suppression is beneficial to improving the stability of VO2 nanostructures. Controllable surface oxidation helps us to understand the physical essentials of surface chemical reactions and achieve better control of surface functions and performances on correlated vanadium oxide nanostructures.

9.
Int J Neurosci ; 129(5): 417-422, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30375250

RESUMO

PURPOSE: To create a standard Western Chinese normal functional brain database for quantitative analysis using 2-deoxy-2-[18F] fluoro-d-glucose (18F-FDG) positron emission tomography (PET) images and MIMneuro software. METHODS: 78 healthy right-handed Chinese volunteers from Tangdu Hospital were scanned using 18F-FDG PET to evaluate brain metabolism between March and October 2016. All PET images were processed using MIMneuro software to create a normal database platform. The platform included anatomical optimization to facilitate spatial localization of abnormalities and a statistical comparison with normal cases utilizing the Z-scores, which represent the number of standard deviations from the mean of the normal controls in the database. RESULTS: The novel Chinese brain metabolism database platform including 78 healthy volunteers (male: female 40:38; age 3-78 years, mean age, 45 years) was constructed based on the MIMneuro software, which increased the diagnostic confidence in the test patient by quantifying and emphasizing the abnormality. The BrainAlignTM deformation algorithm of MIMneuro matched the size, shape, and orientation of the patient's brain scan to a template brain for comparison against a database of normal controls. The quantitative analysis performed on a voxel and regional level was useful in assessing the areas of abnormalities. CONCLUSIONS: A novel Chinese 18F-FDG PET-based normal brain function database was created to highlight the local regions of abnormal metabolic activity through quantitative comparisons against the normal database. The Z-scores obtained by MIMneuro potentially aid in visualizing and quantifying the subtle lesions on 18FDG-PET scan images as observed in a patient diagnosed with epilepsy.


Assuntos
Encéfalo/diagnóstico por imagem , Bases de Dados Factuais , Epilepsia/diagnóstico por imagem , Fluordesoxiglucose F18 , Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Idoso , Encéfalo/metabolismo , Criança , Pré-Escolar , China , Bases de Dados Factuais/estatística & dados numéricos , Epilepsia/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Adulto Jovem
10.
Oncol Lett ; 14(6): 7431-7436, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29344184

RESUMO

Thyroid cancer is the most common type of malignant endocrine tumor diagnosed. Previous studies have indicated that gene therapy is the most promising and effective therapeutic method for thyroid cancer. Therefore, in the present study, Na131I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The present study explored the combined cytotoxic effects of adenovirus-mediated CD and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad-PEG-3-CD-NIS) with Na131I/5-FC against the human thyroid cancer TT cell line in vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed using XbaI. TT cells were transfected by recombinant adenovirus. The method of reverse transcription-quantitative PCR was performed to test the expression of CD and NIS at the level of transcription. The morphological change was assessed by fluorescence microscopy and investigated by western blot analysis. An MTT assay was used to determine the number of living cells inhibited by single or combination therapies on TT cells. The results indicated that the PEG-3 was successfully cloned, and was also positively regulated in 293 cells. CDA and SLC5A5 genes were highly expressed in TT cells. Na131I combined with 5-FC significantly decreased the human thyroid cancer cells. In conclusion, combination therapy of Ad-PEG3-CDA-SLC5A5 and Na131I/5-FC induces significantly more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA-SLC5A5 or Na131I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the cytotoxic effects.

11.
Mol Neurobiol ; 53(3): 2029-2035, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25862376

RESUMO

Multiple sclerosis (MS) is an autoimmune/inflammatory neurodegenerative disease which mainly affects the central nervous system in young adults. Fc-receptor-like-3 (FCRL3) gene, which involved in immune cell regulation, has drawn lots of attentions. This study aims to investigate the association between common polymorphisms of FCRL3 gene and MS risk in a Chinese Han population. Nine single nucleotide polymorphisms (SNPs) were genotyped in 120 patients and 240 healthy controls through PCR assay. t test and chi-square test was conducted to find a possible association between FCRL3 genetic mutations and risk of MS. This analysis results performed that four SNPs, rs7528684 (FCRL3_3), rs945635 (FCRL3_5), rs3761959 (FCRL3_6), and rs2282284 (FCRL3_8), were significantly associated with the risk of MS. Further haplotype analysis showed two haplotypes of FCRL3_3, 5, 6, 8, CCAG and CGAG, presented the significant associations with the susceptibility to MS. Four SNPs in FCRL3 gene could possibly associate with the susceptibility of MS in a Chinese Han population. Moreover, the haplotype analysis confirmed that the linkage disequilibrium exists in polymorphisms in FCRL3. Based on the supporting evidence, we deduced that FCRL3_3C, FCRL3_5C, FCRL3_6A, and FCRL3_8G caused increased risk of MS. Nevertheless, large cohort studies are required in the future to validate the autoimmune function.


Assuntos
Predisposição Genética para Doença , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Imunológicos/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Haplótipos/genética , Humanos , Masculino , Modelos Biológicos
12.
J Cardiovasc Pharmacol ; 65(4): 357-63, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25850725

RESUMO

Cardiac hypertrophy is a primary pathological change associated with cardiovascular diseases. Dysregulated microRNAs are frequent in cardiovascular diseases and contribute to cardiac hypertrophy by regulating a series of targeted genes. In this study, a rat model of cardiac hypertrophy was created by transverse abdominal aortic constriction, and cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes was induced using angiotensin II (AngII) to investigate the role of miR-101 in myocardial hypertrophy. We demonstrated that miR-101 was downregulated in both the transverse abdominal aortic constriction rat model and hypertrophic cardiac myocytes. The overexpression of miR-101 in neonatal rat cardiomyocytes, which was accompanied by a reduced Rab1a level, inhibits 3 cardinal features of cardiomyocyte hypertrophy: fetal gene expression, protein synthesis, and cell enlargement. Conversely, the downregulation of miR-101 reverses these effects. Furthermore, the luciferase reporter system demonstrated that Rab1a is a target gene of miR-101, and the ectopic expression of Rab1a can reverse the cardiomyocyte hypertrophy inhibitory activity of miR-101. Taken together, our findings identify miR-101 as an important regulator in cardiac hypertrophy and implicate the potential application of miR-101 in the therapy of cardiac hypertrophy.


Assuntos
Cardiomegalia , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Proteínas rab1 de Ligação ao GTP/metabolismo , Animais , Cardiomegalia/genética , Cardiomegalia/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Expressão Ectópica do Gene , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Ratos , Regulação para Cima
13.
Tumour Biol ; 35(3): 2391-5, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24163084

RESUMO

The aim of this study was to detect stress-induced phosphoprotein 1 (STIP1) expression in papillary thyroid carcinoma (PTC) and to analyze its association with prognosis of PTC patients. Immunohistochemistry was performed to detect the expression of STIP1 in 113 PTC tissues and paired adjacent noncancerous tissues. The χ2 test was used to analyze the relationship between STIP1 expression and clinicopathological characteristics. Survival curves were plotted by the Kaplan-Meier method and compared using the log-rank test. Survival data was evaluated using univariate and multivariate Cox regression analysis. We identified abnormally elevated expression of STIP1 protein in PTC tissues compared to paired adjacent noncancerous tissues. Clinicopathological analysis showed that STIP1 expression was significantly correlated with tumor size (P = 0.017), lymph node metastasis (P = 0.007), and TNM stage (P = 0.026). Patients with higher STIP1 expression had shorter overall survival time, whereas those with lower STIP1 expression had longer survival time. Multivariate analysis suggested that STIP1 expression might be an independent prognostic indicator (P < 0.05) for the survival of patients with PTC. In conclusion, our findings provide evidences that positive expression of STIP1 in PTC may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with PTC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Proteínas de Choque Térmico/biossíntese , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Carcinoma Papilar , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Câncer Papilífero da Tireoide
14.
Tumour Biol ; 34(4): 2451-7, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23605323

RESUMO

The aim of this study was to introduce human somatostatin receptors subtype-2 (hsstr2) gene into A549 lung carcinoma cells in order to investigate the role of these receptors, and to observe the lethal effect of (131)I-RC-160 (RC-160, vapreotide, an analog of somatostatin) on transfected cells through tumor scintigraphy. Clones overexpressing SSTR2 were selected for radioligand-receptor binding assay and assessment of (125)I-RC-160 internalization. The methylthiazolyl tetrazolium test was used to observe the lethal effect of (131)I-RC-160, Na(131)I, and RC-160 on hSSTR2-transfected A549 cells (A549-hSSTR2). Planar imaging was performed with a gamma camera equipped with pinhole collimator in nude mice bearing both A549-hSSTR2 tumors overexpressing SSTR2 and A549-pcDNA3 (pcDNA3-transfected A549 cells) tumors as control. Images were obtained at 0.5, 6, and 24 h after injection of 3.7 × 10(6) Bq (99m)Tc-RC-160 via the tail vein. The inhibitory effects of (131)I-RC-160, RC-160, and Na(131)I on the tumors were recorded by measuring the tumor volumes. At the end of the study, the tumors were excised and HE staining was performed. The binding radioactivity (sum of membrane-bound and internalized radioligand) of A549-hSSTR2 cells was 18.24 ± 1.9 % of total counts added after 1 h of incubation, and was higher than that of A549-pcDNA3 cells 5.7 ± 1.4 % (P < 0.05). The inhibition ratio of A549-hSSTR2 cells was 78.8 ± 5.9 %. Clear images of tumor lesions in nude mice were achieved at 0.5 h post injection. In the A549-hSSTR2 xenograft tumor group, the growth of the tumors treated with (131)I-RC-160 was significantly inhibited as compared to tumors in the group treated with RC-160 (P < 0.01). This study demonstrated that it was possible to introduce hsstr2 to non-expressing tumor cell lines and treat tumors with radiolabeled somatostatin analogs.


Assuntos
Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Receptores de Somatostatina/genética , Somatostatina/análogos & derivados , Animais , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Transferência de Genes , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Compostos Radiofarmacêuticos , Somatostatina/farmacologia , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Tumour Biol ; 34(2): 941-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23264086

RESUMO

The aim of this study was to detect FOXC1 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Expressional levels of FOXC1 mRNA and protein in 30 cases of NSCLC and corresponding non-tumor tissue samples were examined by quantitative real-time PCR and Western blotting. Immunohistochemistry was performed to detect the expression of FOXC1 in 125 NSCLC tissues. We found that the expression levels of FOXC1 mRNA and protein in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level FOXC1 expression was correlated with poor tumor differentiation, tumor-node-metastasis stage, and lymph node metastasis. Patients with high expression levels of FOXC1 showed lower overall survival rate than those with low expression levels. Multivariate analysis showed that high FOXC1 protein expression was an independent prognostic factor for NSCLC patients. Our study suggests that over-expression of FOXC1 may play an important role in the progression of NSCLC, and FOXC1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.


Assuntos
Adenocarcinoma/mortalidade , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Pulmonares/mortalidade , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Humanos , Técnicas Imunoenzimáticas , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida
16.
Nucl Med Biol ; 37(3): 317-26, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20346871

RESUMO

BACKGROUND AND AIM: We investigated the anti-tumor effect induced by the combination of the radiotherapeutic agent (131)I-RC-160 and the prodrug 5-FC in human non-small cell lung cancer (NSCLC) A549 cells that were co-expressing the human somatostatin receptor 2 gene (hSSTR2) and E. coli cytosine deaminase gene (CD). METHODS: We cloned both hSSTR2 and CD into a bicistronic mammalian expression plasmid and stably transfected it into A549 cells (pCIS-A549 cells). After antibiotic selection, SSTR expression in stable clones was determined by reverse transcription and polymerase chain reaction (RT-PCR), Western blot, flow cytometry and immunofluorescence analyses. To assess the in vivo targeting efficiency of the "engineered" A549 cells, the cells were subcutaneously injected into nude mice and the biodistribution of (99m)Tc-RC-160 was assessed at different time points. The tumor inhibitory effects of (131)I-RC-160 and/or 5-FC were evaluated by measurement of tumor growth and immunohistochemical analysis. RESULTS: Multiple analyses demonstrated the successful expression of hSSTR2 in A549 cells. In vivo radioimaging revealed specific targeting of RC-160 to the tumors derived from pCIS-A549 cells when compared to those from control A549 cells. The tumor inhibitory rate of pCIS-A549 tumors in the (131)I-RC-160 plus 5-FC-treated group was significantly higher than that in the single agent-treated group, control group and control tumors. CONCLUSION: Co-expression of the hSSTR2 and CD genes in tumor cells can selectively sensitize these cells to the infra-additive effects of radioisotope-labeled RC-160 and 5-FC in vivo. This approach offers a potential therapeutic strategy for the treatment of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Flucitosina/administração & dosagem , Radioisótopos do Iodo/administração & dosagem , Neoplasias Pulmonares/terapia , Somatostatina/análogos & derivados , Animais , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Linhagem Celular Tumoral , Terapia Combinada/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Radiofarmacêuticos/administração & dosagem , Somatostatina/administração & dosagem , Resultado do Tratamento
17.
Zhonghua Jie He He Hu Xi Za Zhi ; 28(2): 108-11, 2005 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-15854393

RESUMO

OBJECTIVE: To study the clinical value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the diagnosis and staging of lung cancer. METHODS: Ninety-four patients with lung nodular changes were examined by CT, 18F-FDG PET and pathology, cytology. 18F-FDG PET images were analyzed by semi-quantitative standard uptake value (SUV) only and (or) SUV plus visual observation. Focuses with a SUV > 2.5 were judged as malignant changes, while SUV < or = 2.5 was judged as benign. SUV plus visual analysis, based on the focal SUV, the nodular size and shape, and clinical data, was carried out by two nuclear doctors. CT imaging was interpreted by two radiological doctors. The sensitivity, specificity, accuracy, positive predictive and negative predictive values of 18F-FDG PET and CT in the diagnosis, and in the evaluation of lymphatic metastasis and remote metastasis of lung lesions were calculated. The diagnostic efficiency of the two methods (SUV or visual plus SUV method) was compared. RESULTS: (1) 58 cases were confirmed to be malignant by surgery or pathological examination, while 36 cases were proved benign by pathology or empirical therapy. (2) The sensitivity, specificity, accuracy, positive and negative predictive values were 69%, 65%, 68%, 82% and 49% respectively for CT; and 91%, 89%, 90%, 93% and 87% respectively for SUV analysis; and 95%, 94%, 95%, 97% and 92% respectively for visual plus SUV methods. (3) Among 34 patients with mediastinal lymph node involvement confirmed by pathology, 18F-FDG PET detected 30 cases, while CT detected only 18 cases (P < 0.01). (4) 18F-FDG PET revealed 19 cases with distant metastases, while CT only discovered 8 cases with distant metastases. As a result, the therapy was modified by PET examination in 14 patients. CONCLUSION: 18F-FDG PET imaging is of important clinical value in the diagnosis of lung lesions and the staging of malignancy.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
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