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1.
Int J Hyperthermia ; 40(1): 2223369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37344382

RESUMO

PURPOSE: To investigate the feasibility of percutaneous intrauterine instillation of chilled saline to protect the endometrium during microwave ablation (MWA) treating types 1-3 uterine fibroids. MATERIALS AND METHODS: Twenty-six patients with types 1-3 uterine fibroids were prospectively enrolled in an intrauterine saline instillation group (study group). The same number of patients with types 1-3 uterine fibroids who previously received MWA without endometrial protection were retrospectively included in a control group. Endometrial impairment was evaluated by hysteroscopy and magnetic resonance imaging (MRI). RESULTS: In the study group, hysteroscopy revealed an intact endometrium in 17 patients, congestion and reddening of the endometrium due to heat in 8 patients, and a burnt necrosis with a size < 1 cm on the functional layer of the endometrium in 1 patient. On MRI, in the study group, there were 17 (65.4%), 6 (23.1%), and 3 (11.5%) patients with grades 0, 1, and 2 endometrial impairment, respectively, but no grade 3 endometrial impairment. In the control group, there were 8 (30.8%), 8 (30.8%), 7 (26.9%), and 3 (11.5%) patients with grades 0, 1, 2, and 3 endometrial impairment, respectively. Endometrial impairment in the study group was significantly better than that in the control group (p = 0.006). One patient had puncture tunnel bleeding and no other complications occurred in the study group. CONCLUSION: Intraoperative percutaneous intrauterine instillation of chilled saline may be effective and safe in reducing the thermal damage to the endometrium caused by MWA for treating types 1-3 uterine fibroids.


Assuntos
Leiomioma , Neoplasias Uterinas , Feminino , Gravidez , Humanos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Endométrio/diagnóstico por imagem , Endométrio/cirurgia , Endométrio/patologia , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Leiomioma/complicações , Histeroscopia , Neoplasias Uterinas/cirurgia
2.
Front Vet Sci ; 9: 1053701, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36478946

RESUMO

A protein of Eimeria tenella (encoded by the locus ETH_00028350) homologous to Toxoplasma gondii dense granule protein 9, designated as EtHGRA9 hereafter, was reported to be expressed in all life cycle stages of E. tenella. However, no data are currently available regarding its functional properties. In the present study, a recombinant vector harboring a 741 bp gene segment encoding the mature form of EtHGRA9 was constructed and transfected into leghorn male hepatoma (LMH) cells. Then, transcriptomic analysis of the transfected LMH cells was carried out by using a high-throughput RNA-seq technology. The LMH cells overexpressing EtHGRA9 was validated by means of Western blotting as well as indirect immunofluorescence staining. The results demonstrated that the expression of 547 genes (275 upregulated genes and 272 downregulated genes) was altered by EtHGRA9. The quantitative real-time polymerase chain reaction (qRT-PCR) validation of the ten genes with differential expression between the two groups was consistent with the transcriptome analysis. According to pathway enrichment analysis for the obtained differentially expressed genes, seven pathways were significantly affected by EtHGRA9, such as cytokine-cytokine receptor interaction, MAPK signaling pathway, and protein processing in endoplasmic reticulum. Our data reveal several possible roles of EtHGRA9 in immune or inflammatory responses, which paves the way for a better understanding of the molecular interplay between E. tenella and its host.

3.
BMC Genomics ; 23(1): 847, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36544082

RESUMO

BACKGROUND: Toxocara canis is distributed worldwide, posing a serious threat to both human and dog health; however, the pathogenesis of T. canis infection in dogs remains unclear. In this study, the changes in microRNA (miRNA) expression profiles in the bone marrow of Beagle dogs were investigated by RNA-seq and bioinformatics analysis. RESULTS: Thirty-nine differentially expressed (DE) miRNAs (DEmiRNAs) were identified in this study. Among these, four DEmiRNAs were identified at 24 h post-infection (hpi) and all were up-regulated; eight DEmiRNAs were identified with two up-regulated miRNAs and six down-regulated miRNAs at 96 hpi; 27 DEmiRNAs were identified with 13 up-regulated miRNAs and 14 down-regulated miRNAs at 36 days post-infection (dpi). Among these DEmiRNAs, cfa-miR-193b participates in the immune response by regulating the target gene cd22 at 24 hpi. The novel_328 could participate in the inflammatory and immune responses through regulating the target genes tgfb1 and tespa1, enhancing the immune response of the host and inhibiting the infection of T. canis at 96 hpi. In addition, cfa-miR-331 and novel_129 were associated with immune response and self-protection mechanisms at 36 dpi. 20 pathways were significantly enriched by KEGG pathway analysis, most of which were related to inflammatory response, immune response and cell differentiation, such as Cell adhesion molecules (CAMs), ECM-receptor interaction and Focal adhesion. CONCLUSIONS: These findings suggested that miRNAs of Beagle dog bone marrow play important roles in the pathogenesis of T. canis infection in dogs and provided useful resources to better understand the interaction between T. canis and the hosts.


Assuntos
MicroRNAs , Toxocaríase , Animais , Cães , Medula Óssea/metabolismo , Medula Óssea/parasitologia , Doenças do Cão/genética , Doenças do Cão/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Toxocara canis/genética , Toxocaríase/genética , Toxocaríase/metabolismo
4.
Poult Sci ; 101(11): 102109, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36067577

RESUMO

Though genome sequencing of Eimeria tenella predicts more than 8,000 genes, the molecular functions of many proteins remain unknown. In this study, the coding region corresponding to the mature peptide of a hypothetical protein of E. tenella (ETH_00023950) was amplified and expressed in a bacterial system. Following preparation of polyclonal antibody that recognizes ETH_00023950, the expression of ETH_00023950 in merozoites was examined. Meanwhile, we determined the transcriptomic responses of the leghorn male hepatoma (LMH) cells to its expression. Sequencing analysis showed that one single nucleotide polymorphism and one indel of ETH_00023950 of E. tenella SD-01 strain were found compared with that of the UK reference Houghton strain, leading to a frame shift and a premature stop codon. The expression of ETH_00023950 in E. tenella merozoites was confirmed by indirect immunofluorescence and Western blot analysis. Transcriptomic analysis showed that ETH_00023950 altered the expression of 2,680 genes (321 downregulated genes and 2,359 upregulated genes) in LMH cells. The RNA-sequencing data were consistent with the results of the quantitative real-time polymerase chain reaction (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that differentially expressed transcripts were significantly related to 8 pathways, including oxidative phosphorylation and TGF-beta signaling pathway. These findings contribute to understanding host-pathogen interaction and secondary bacterial infections related to E. tenella.


Assuntos
Coccidiose , Eimeria tenella , Animais , Masculino , Eimeria tenella/genética , Galinhas/genética , Transcriptoma , Merozoítos/genética , Perfilação da Expressão Gênica/veterinária , Coccidiose/veterinária , Coccidiose/metabolismo
5.
Infect Dis Poverty ; 11(1): 96, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104766

RESUMO

BACKGROUND: Toxoplasma gondii is a protozoan parasite which can infect almost all warm-blooded animals and humans. Understanding the differential expression of proteins and transcripts associated with T. gondii infection in its definitive host (cat) may improve our knowledge of how the parasite manipulates the molecular microenvironment of its definitive host. The aim of this study was to explore the global proteomic alterations in the major organs of cats during acute T. gondii infection. METHODS: iTRAQ-based quantitative proteomic profiling was performed on six organs (brain, liver, lung, spleen, heart and small intestine) of cats on day 7 post-infection by cysts of T. gondii PRU strain (Genotype II). Mascot software was used to conduct the student's t-test. Proteins with P values < 0.05 and fold change > 1.2 or < 0.83 were considered as differentially expressed proteins (DEPs). RESULTS: A total of 32,657 proteins were identified in the six organs, including 2556 DEPs; of which 1325 were up-regulated and 1231 were down-regulated. The brain, liver, lung, spleen, heart and small intestine exhibited 125 DEPs, 463 DEPs, 255 DEPs, 283 DEPs, 855 DEPs and 575 DEPs, respectively. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of all proteins and DEPs in all organs showed that many proteins were enriched in binding, cell part, cell growth and death, signal transduction, translation, sorting and degradation, extracellular matrix remodeling, tryptophan catabolism, and immune system. Correlations between differentially expressed proteins and transcripts were detected in the liver (n = 19), small intestine (n = 17), heart (n = 9), lung (n = 9) and spleen (n = 3). CONCLUSIONS: The present study identified 2556 DEPs in six cat tissues on day 7 after infection by T. gondii PRU strain, and functional enrichment analyses showed that these DEPs were associated with various cellular and metabolic processes. These findings provide a solid base for further in-depth investigation of the complex proteotranscriptomic reprogramming that mediates the dynamic interplays between T. gondii and the different feline tissues.


Assuntos
Proteoma , Animais , Animais Domésticos , Doenças do Gato/genética , Gatos , Proteoma/análise , Proteômica , Toxoplasma , Toxoplasmose Animal/genética , Transcriptoma
6.
Front Vet Sci ; 9: 956040, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016802

RESUMO

Though a number of Eimeria tenella rhoptry kinase family proteins have been identified, little is known about their molecular functions. In the present study, the gene fragment encoding the matured peptide of E. tenella rhoptry kinase family protein 17 (EtROP17) was used to construct a recombinant vector, followed by transfection into leghorn male hepatoma (LMH) cells. Then, the transcriptional changes in the transfected cells were determined by RNA-seq. The expression of EtROP17 in LMH cells was validated by both Western blot and indirect immunofluorescence analysis. Our analysis showed that EtROP17 altered the expression of 309 genes (114 downregulated genes and 195 upregulated genes) in LMH cells. The quantitative real-time polymerase chain reaction (qRT-PCR) results of the selected differentially expressed genes (DEGs) were consistent with the RNA-seq data. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in nine pathways, such as toll-like receptor signaling pathway, ECM-receptor interaction, intestinal immune network for IgA production and focal adhesion. These findings reveal several potential roles of EtROP17, which contribute to understanding the molecular mechanisms underlying the host-parasite interplay.

7.
Int J Ophthalmol ; 15(4): 591-597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450171

RESUMO

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.

8.
Calcif Tissue Int ; 110(4): 451-463, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34988594

RESUMO

Hyperplastic callus (HPC) is the most conspicuous features of osteogenesis imperfecta (OI) type V, of which accurate diagnosis and treatment are facing challenges. We investigate the clinical features, and impact factors of HPC in OI type V patients. In this retrospective single-center study, a total of 21 patients with type V OI confirmed by IFITM5 mutation were included. Radiological characteristics of bone were evaluated by X-rays, dual-energy X-ray absorptiometry, and computed tomography scan. Bone biopsy specimens were performed and stained by routine hematoxylin-eosin. The effects of bisphosphonates on HPC were investigated. Eleven patients (52.3%) had HPCs at 19 skeletal sites, 11 of which affected the femur. Three patients developed four (21.1%) HPCs after fractures, and 15 (78.9%) HPCs occurred in absence of bone fracture. The progress of HPCs was variable, of which most HPCs enlarged in the initial phase and remained stable, and only one HPC dwindled in size. One patient had a rapidly growing mass on the right humerus, and biopsy showed irregular trabeculae of woven bone and immature bone and cartilage in the loose and edematous collagenous network without signs of tumor. Bisphosphonates treatment had no significant effects on HPC of OI patients. HPC is the specific characteristic of OI type V patients, and its location, shape, size, and progression are variable, and the femur is the most frequently involved site. It is very important to make a diagnosis of HPC through detecting IFITM5 mutation and completing pathological diagnosis if necessary. The treatment of HPC is worth further exploration.


Assuntos
Osteogênese Imperfeita , Difosfonatos/uso terapêutico , Humanos , Proteínas de Membrana/genética , Osteogênese Imperfeita/tratamento farmacológico , Estudos Retrospectivos
9.
Front Cell Dev Biol ; 9: 688128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277631

RESUMO

Bone marrow is the main hematopoietic organ that produces red blood cells, granulocytes, monocyte/macrophages, megakaryocytes, lymphocytes, and myeloid dendritic cells. Many of these cells play roles in the pathogenesis of Toxocara canis infection, and understanding how infection alters the dynamics of transcription regulation in bone marrow is therefore critical for deciphering the global changes in the dog transcriptional signatures during T. canis infection. In this study, long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in the bone marrow of Beagle dogs infected with T. canis were determined at 12 h post-infection (hpi), 24 hpi, 96 hpi, and 36 days post-infection (dpi). RNA-sequencing and bioinformatics analysis identified 1,098, 984, 1,120, and 1,305 differentially expressed lncRNAs (DElncRNAs), and 196, 253, 223, and 328 differentially expressed mRNAs (DEmRNAs) at 12 h, 24 h, 96 h, and 36 days after infection, respectively. We also identified 29, 36, 38, and 68 DEmRNAs potentially cis-regulated by 44, 44, 51, and 80 DElncRNAs at 12 hpi, 24 hpi, 96 hpi, and 36 dpi, respectively. To validate the sequencing findings, qRT-PCR was performed on 10 randomly selected transcripts. Many altered genes were involved in the differentiation of bone marrow cells. GO of DElncRNAs and GO and KEGG pathway analyses of DEmRNAs revealed alterations in several signaling pathways, including pathways involved in energy metabolism, amino acid biosynthesis and metabolism, Wnt signaling pathway, Huntington's disease, HIF-1 signaling pathway, cGMP-PKG signaling pathway, dilated cardiomyopathy, and adrenergic signaling in cardiomyocytes. These findings revealed that bone marrow of T. canis-infected dogs exhibits distinct lncRNA and mRNA expression patterns compared to healthy control dogs. Our data provide novel insights into T. canis interaction with the definitive host and shed light on the significance of the non-coding portion of the dog genome in the pathogenesis of toxocariasis.

10.
Mol Med Rep ; 22(2): 1285-1294, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32627016

RESUMO

Autoimmune polyendocrine syndrome type 1 (APS­1) is a rare inherited autoimmune disease, characterized by a classic triad, including chronic mucocutaneous candidiasis, primary adrenocortical insufficiency and hypoparathyroidism. The present study investigated phenotypes and pathogenic variants in a Chinese woman with non­classical APS­1. Disease­associated variants in a patient with APS­1 were identified via targeted next generation sequencing and the variant was confirmed via Sanger sequencing. Serum levels of calcium, phosphorus, parathyroid hormone (PTH), follicle­stimulating hormone (FSH), luteinizing hormone (LH), estradiol and urinary levels of calcium were measured. Blood count assays and bone marrow morphology were investigated. The patient was a 32­year­old woman who had suffered from typical carpopedal spasms since she was 7 years old. She developed syncope, primary amenorrhea, intermittent diarrhea and general fatigue in subsequent years. Hypocalcemia, hyperphosphatemia, low levels of PTH and estradiol, elevated levels of FSH and LH, and absence of erythroblasts were observed, which indicated hypoparathyroidism, primary ovarian insufficiency and pure red cell aplasia. A novel heterozygous missense variant (NM_000383.2: c.623G>T, NP_000374.1: p.Gly208Val) in exon 5 of autoimmune regulator and a reported variant (NM_000383.2: c.371C>T, NP_000374.1: p.Pro124Leu) in exon 3 were detected, of which the c.623G>T variant may be a pathogenic variation that induces APS­1. Under a regular follow­up and therapeutic adjustment of calcium, calcitriol, hormone replacement therapy and methylprednisolone, the endocrine function and clinical symptoms of the patient were notably improved. The results of the present study expand the known genetic and phenotypical spectra of APS­1.


Assuntos
Poliendocrinopatias Autoimunes , Fatores de Transcrição/genética , Adulto , Cálcio/sangue , Cálcio/metabolismo , Cálcio/urina , Terapia de Reposição de Estrogênios , Feminino , Hormônios/sangue , Humanos , Metilprednisolona/uso terapêutico , Mutação , Fenótipo , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/genética , Proteína AIRE
11.
Mol Genet Genomic Med ; 8(3): e1139, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31972903

RESUMO

BACKGROUND: Spondyloepiphyseal dysplasia congenita (SEDC) is an extremely rare inherited chondrodysplasia characterized by abnormal epiphyses, short stature, and flattened vertebral bodies. We investigate the phenotypes and the disease-associated variants of SEDC in two unrelated Chinese families. METHODS: We identified disease-associated variants in two nonconsanguineous families with SEDC using targeted next-generation sequencing and confirmed the variants using Sanger sequencing. We investigated the phenotypes of the patients, including clinical manifestations, bone turnover biomarkers, bone mineral density and skeletal radiographic features. RESULTS: Two probands were diagnosed as SEDC according to the phenotypes of disproportionately short-trunk stature, kyphosis, lumbar lordosis and adduction deformity of hips. Radiographs revealed kyphosis and lumbar lordosis, flattened vertebral bodies, compressed femoral heads and shortening of the femurs. Bone mineral density of the probands was lower than that of age- and gender-matched normal children, but bone turnover biomarker levels were within normal range. Two novel heterozygous missense variants (NM_001844.5: c.1654 G>A, NP_001835.3: p.Gly552Arg; NM_001844.5: c.3518G>T, NP_001835.3: p.Gly1173Val) in collagen type II alpha 1 chain (COL2A1) were detected in the two families, which would impair the formation of stable triple-helical type II collagen. CONCLUSIONS: We identified two novel disease-associated variants in COL2A1, which led to severe SEDC. Our findings expanded the gene variant spectrum and phenotypic spectrum of extremely rare type II collagenopathies.


Assuntos
Colágeno Tipo II/genética , Osteocondrodisplasias/genética , Adulto , Pré-Escolar , Colágeno Tipo II/química , Feminino , Humanos , Masculino , Mutação , Osteocondrodisplasias/patologia , Linhagem , Fenótipo , Domínios Proteicos
12.
Biomed Res Int ; 2016: 9170167, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27340671

RESUMO

Enzootic bovine leukosis (EBL) is a chronic lymphosarcoma disease of cattle caused by bovine leukemia virus (BLV). No information is available concerning the epidemiology of BLV infection in yaks (Bos mutus). One thousand five hundred and eighty-four serum samples from 610 black yaks and 974 white yaks from Gansu province, northwest China, were collected between April 2013 and March 2014 and tested for BLV antibodies using a commercially available ELISA kit. The overall BLV seroprevalence in yaks was 21.09% (334/1584), with 24.26% (148/610) black yaks and 19.10% (186/974) white yaks yielding positive results. Risk factor analysis indicated that with the exception of breed (OR = 1.36, 95% CI = 1.06-1.73, P < 0.05), the age, region, gender, farm, and the numbers of pregnancies were not considered as risk factors for the presence of BLV in yaks included in this study. This is the first report of BLV infection in yaks in China, which provides information for controlling BLV infection in yaks.


Assuntos
Bovinos/virologia , Leucose Enzoótica Bovina/epidemiologia , Leucose Enzoótica Bovina/virologia , Vírus da Leucemia Bovina/fisiologia , Animais , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Razão de Chances , Fatores de Risco , Estudos Soroepidemiológicos
13.
Zhong Xi Yi Jie He Xue Bao ; 7(8): 736-40, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19671411

RESUMO

BACKGROUND: Chronic microinflammatory state is common in the patients undergoing maintenance hemodialysis (MHD), which seriously affects the long-term survival rate of MHD patients. It is important to improve the microinflammatory state in MHD patients. OBJECTIVE: To investigate the effects of oxymatrine on microinflammatory state in patients undergoing continuous hemodialysis. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty MHD patients in Blood Purification Center, Wuhan No.1 Hospital, from June to September 2008, were randomized into treatment group (30 cases) and control group (30 cases). Oxymatrine Capsule was orally administered to the patients in the treatment group 0.4 g once a day for 3 months, while the patients in the control group were not given oxymatrine. MAIN OUTCOME MEASURES: The serum concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), albumin (Alb), pre-albumin (PAB), total cholesterol (TC) and triglyceride (TG) were detected before and after 3-month treatment. RESULTS: Three patients in the treatment group had a stomachache on the first day of treatment, and two out of the three quitted the trial. The stomachache disappeared in one patient after stopping taking the drug, and did not recur after continuing to receive the intervention. Two patients in the treatment group had skin rash with pruritus on the second day of treatment. The rash disappeared after the patients stopped taking the drug, and did not recur after continuing to receive the intervention. A total of 58 cases accessed to the statistical analysis, while 2 cases were excluded. In the treatment group, the concentrations of hs-CRP, IL-1beta and TNF-alpha significantly decreased (P<0.01) and the mean values of Alb, PAB, TC and TG significantly increased after the treatment as compared with those before the treatment (P<0.01), but there were no significant differences in all parameters between before and after treatment in the control group. There were significant differences in all parameters between the treatment group and the control group after treatment (P<0.01, P<0.05). CONCLUSION: Oxymatrine can improve the microinflammatory state in the patients undergoing continuous hemodialysis.


Assuntos
Alcaloides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Quinolizinas/uso terapêutico , Diálise Renal , Adulto , Idoso , Proteína C-Reativa/metabolismo , Feminino , Humanos , Inflamação/etiologia , Interleucina-1beta/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
14.
J Dig Dis ; 10(2): 91-8, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19426390

RESUMO

OBJECTIVE: To investigate the effects of the non-cytotoxic drug (cyclooxygenase-2 (COX-2) inhibitor and octreotide) on growth of the multidrug-resistant human gastric carcinoma cell line SGC-7901/ADR. METHODS: The effects of non-cytotoxic drug on the growth of SGC-7901 and SGC-7901/ADR cells were evaluated by (3)H-thymidine incorporation assay. The apoptosis of cells was measured by the TdT-mediated dUTP nick end-labeling assay (TUNEL) and flow cytometric assay. Western blotting was used to analysis the expression of cyclooxygenase (COX-2) protein in SGC-7901 cells and SGC-7901/ADR cells and P-glycoprotein (P-gp) from SGC-7901/ADR cells with variable treatments. Activator protein-1 binding activity was examined by electrophoretic mobility shift assay. RESULTS: (3)H-thymidine incorporation into SGC-7901/ADR cells treated with celecoxib was significantly lower than that of control group (471.3 +/- 79.7 cpm vs 917.5 +/- 130.8 cpm, P < 0.05). When combined with octreotide, celecoxib presented lower (3)H-thymidine incorporations than its used alone and decreased to 53.3% of that amount original. Either celecoxib or the combination group markedly induced apoptosis in SGC-7901/ADR cells. COX-2 protein in the SGC-7901/ADR cells was higher than in that of the SGC-7901 cells (1.543 +/- 0.052 vs 0.564 +/- 0.021, P < 0.05). The inhibition of P-gp could be achieved with celecoxib alone and combination with octreotide (0.486 +/- 0.012, 0.252 +/- 0.014 vs 0.941 +/- 0.033, P < 0.05). Moreover, AP-1 binding activity could be suppressed by non-cytotoxic drug and showed a synergistic effect. CONCLUSION: The combination of non-cytotoxic drug significantly improved the inhibitive effects on the growth of multidrug-resistant human gastric cancer cells.


Assuntos
Octreotida/farmacologia , Pirazóis/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Sulfonamidas/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Apoptose/efeitos dos fármacos , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2/análise , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Octreotida/administração & dosagem , Antígeno Nuclear de Célula em Proliferação/análise , Pirazóis/administração & dosagem , Neoplasias Gástricas/patologia , Sulfonamidas/administração & dosagem , Fator de Transcrição AP-1/metabolismo
15.
Ai Zheng ; 23(12): 1628-32, 2004 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-15601550

RESUMO

BACKGROUND & OBJECTIVE: Both cyclooxygenase-2 (COX-2) inhibitor and octreotide can inhibit growth of tumor cells. This study was to investigate inhibitory effects of COX-2 inhibitor celecoxib alone, and celecoxib combined with octreotide on growth of multidrug resistant human gastric cancer cell line SGC7901/ADR. METHODS: Experimental groups:(1)celecoxib (1 x 10(-4)-1 x 10(-8) mol/L); (2)octreotide (1 x 10(-5)-1 x 10(-9) mol/L); (3)celecoxib (1 x 10(-4)-1 x 10(-8) mol/L) combined with octreotide (1 x 10-6 mol/L);(4)control group (RPMI-1640 medium without serum). The effects of all treatments on SGC7901 cells, and SGC7901/ADR cells were observed. Cell proliferation was measured by (3)H-thymidine incorporation into DNA. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunocytochemistry. Cell apoptosis was measured by TdT-mediated dUTP nick end-labeling assay (TUNEL) and flow cytometry. RESULTS: (3)H-thymidine incorporation into SGC7901/ADR cells treated with celecoxib [(471.3+/-79.7) cpm] was significantly lower than that of control group [(917.5+/-130.8) cpm](P< 0.05). When combined with octreotide, celecoxib presented lower (3)H-thymidine incorporation [(220.0+/-19.7)cpm] than it alone with a 53.3% decrease. The concentration of celecoxib in combination group negatively related to synthesis of DNA in SGC7901/ADR cells (r=0.996,P< 0.001). The expression of PCNA in either celecoxib group or combination group markedly decreased. The apoptosis rates of SGC7901/ADR cells induced by celecoxib alone, and combination treatment were 32.9%, and 52.5%. CONCLUSION: Celecoxib combined with octreotide may enhance inhibition of growth of multidrug resistant human gastric cancer cells. The mechanism may be related with inhibiting DNA synthesis, and inducing apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Octreotida/farmacologia , Pirazóis/farmacologia , Neoplasias Gástricas/patologia , Sulfonamidas/farmacologia , Antineoplásicos Hormonais/farmacologia , Celecoxib , Linhagem Celular Tumoral , Inibidores de Ciclo-Oxigenase/farmacologia , DNA de Neoplasias/biossíntese , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Neoplasias Gástricas/metabolismo
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