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1.
Zhongguo Gu Shang ; 37(3): 319-26, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38515423

RESUMO

Acetabular quadrilateral plate injury has become a hot spot and focus in the field of orthopaedic trauma and pelvic floor function in recent years. Although there are five fracture types,they are all based on fracture morphology,without considering the pulling force of ligaments,joint capsular and muscles. A perfect classification needs to describe the displacement of bone mass in three-dimensional space to better guide reduction and fixation. The seven incision and exposure methods are still the traditional open-eye surgery,and how to protect the criss-crossing vascular neural network and pelvic organs is still the focus. Quadrilateral defect causes dislocation of artificial hip joint,and quantitative evaluation of quadrilateral defect volume and revision techniques are still a hot topic. In this paper,the viewpoints of three-dimensional network structure of acetabular pelvic vascular anatomy,anatomical surgical target channel and fixation anchor point of acetabular fracture reduction are proposed to design new techniques for accurate and minimally invasive surgical operations,in order to realize the requirements of rapid orthopedic rehabilitation.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Fraturas da Coluna Vertebral , Humanos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Acetábulo/cirurgia , Acetábulo/lesões , Fraturas do Quadril/cirurgia , Placas Ósseas
2.
Front Pharmacol ; 14: 1291194, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38249348

RESUMO

Introduction: Carnosol exhibited ameliorating effects on muscle atrophy of mice developed cancer cachexia in our previous research. Method: Here, the ameliorating effects of carnosol on the C2C12 myotube atrophy result from simulated cancer cachexia injury, the conditioned medium of the C26 tumor cells or the LLC tumor cells, were observed. To clarify the mechanisms of carnosol, the possible direct target proteins of carnosol were searched using DARTS (drug affinity responsive target stability) assay and then confirmed using CETSA (cellular thermal shift assay). Furthermore, proteomic analysis was used to search its possible indirect target proteins by comparing the protein expression profiles of C2C12 myotubes under treatment of C26 medium, with or without the presence of carnosol. The signal network between the direct and indirect target proteins of carnosol was then constructed. Results: Our results showed that, Delta-1-pyrroline-5-carboxylate synthase (P5CS) might be the direct target protein of carnosol in myotubes. The influence of carnosol on amino acid metabolism downstream of P5CS was confirmed. Carnosol could upregulate the expression of proteins related to glutathione metabolism, anti-oxidant system, and heat shock response. Knockdown of P5CS could also ameliorate myotube atrophy and further enhance the ameliorating effects of carnosol. Discussion: These results suggested that carnosol might ameliorate cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

3.
BMC Urol ; 20(1): 161, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059661

RESUMO

BACKGROUND: Tubularized incised plate (TIP) urethroplasty is the most commonly performed procedure for hypospadias. Several flap procedures have been recommended to decrease the postoperative complication rate in TIP repair, but no single flap procedure is ideal. This study aimed to compare the outcomes of dartos fascia (DF) and tunica vaginalis fascia (TVF) as intermediate layers in TIP urethroplasty. METHODS: We searched PubMed, EMBASE, the Cochrane Library, Web of Science, clinicaltrials.gov, and other sources for comparative studies up to April 16, 2020. Studies were selected by the predesigned inclusion criteria. The primary outcomes were postoperative complications. The secondary outcomes were functional and cosmetic outcomes. RESULTS: The pooled RR with 95% CI were calculated. We extracted the relevant information from the included studies. Only 6 comparative studies were included. No secondary outcomes were reported. The RR of the total complications rate for DF was 2.41 (95% CI 1.42-4.07, P = 0.0001) compared with TVF in TIP repair. For each postoperative complication, the RRs were 6.48 (2.20-19.12, P = 0.0007), 5.95 (1.13-31.30, P = 0.04), 0.62 (0.25-1.52, P = 0.29), and 0.75 (0.23-2.46, P = 0.64) for urethrocutaneous fistula, prepuce-related complications, meatal/urethral stenosis, and wound-related complications, respectively. CONCLUSIONS: This meta-analysis reveals that compared to DF, TVF is a better option in TIP repair in terms of decreasing the incidence of the total postoperative complications, urethrocutaneous fistula, and prepuce-related complications. However there is limited evidence for functional and cosmetic outcomes. Overall, larger prospective studies and long-term follow-up data are required to further demonstrate the superiority of TVF over DF. TRIAL REGISTRATION: PROSPERO CRD42019148554.


Assuntos
Hipospadia/cirurgia , Uretra/cirurgia , Criança , Pré-Escolar , Fasciotomia , Humanos , Lactente , Masculino , Testículo/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/métodos
4.
Oncol Lett ; 20(5): 233, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32968455

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, with the second highest mortality rate among all cancer types. Growing evidence has demonstrated the notable effects of intratumor heterogeneity (ITH) and tumor immune microenvironment heterogeneity (TIMH) on the biological processes involved in HCC. However, the interactive mechanisms between ITH and TIMH is still unclear. The present study systematically screened the mRNA expression, simple nucleotide variation data and clinical data of samples from The Cancer Genome Atlas (TCGA). The mutant-allele tumor heterogeneity (MATH) score was used to represent ITH, and TCGA cohort was divided into two groups according to the MATH score. Next, different immune-related signaling pathways and enriched immune-related genes were identified using Gene Set Enrichment Analysis of these two groups, and the results revealed that interleukin-1α (IL1A) and serine/threonine-protein kinase PAK4 were associated with prognosis. Furthermore, CIBERSORT was utilized to calculate the fractions of 22 types of leukocytes to represent TIMH, and the fractions of M1 and M2 macrophages were confirmed to be associated with prognosis. Therefore, PAK4, interleukin-1α (IL1A), and M1/M2 ratio were selected as the key factors involved in the interaction between ITH and TIMH. Afterwards, microRNAs (miRNAs) that were linearly related to the M1/M2 ratio and the potential target genes of the miRNAs were screened. Finally, the regulatory network between PAK4, IL1A, and the M1/M2 ratio was established, bridged by the above miRNAs and the target genes. In addition, PAK4, heat shock protein 105 kDa and miRNA-1911 were demonstrated to be a key factor involved in immune response via Weighted Correlation Network Analysis in HCC.

5.
Chin J Traumatol ; 23(4): 196-201, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32674856

RESUMO

Outbreak of COVID-19 is ongoing all over the world. Spine trauma is one of the most common types of trauma and will probably be encountered during the fight against COVID-19 and resumption of work and production. Patients with unstable spine fractures or continuous deterioration of neurological function require emergency surgery. The COVID-19 epidemic has brought tremendous challenges to the diagnosis and treatment of such patients. To coordinate the diagnosis and treatment of infectious disease prevention and spine trauma so as to formulate a rigorous diagnosis and treatment plan and to reduce the disability and mortality of the disease, multidisciplinary collaboration is needed. This expert consensus is formulated in order to (1) prevent and control the epidemic, (2) diagnose and treat patients with spine trauma reasonably, and (3) reduce the risk of cross-infection between patients and medical personnel during the treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Traumatismos da Coluna Vertebral/diagnóstico , Traumatismos da Coluna Vertebral/terapia , COVID-19 , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/prevenção & controle , Serviço Hospitalar de Emergência , Humanos , Pandemias/prevenção & controle , Equipe de Assistência ao Paciente , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Transporte de Pacientes
6.
Int J Dermatol ; 59(11): 1320-1331, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32662887

RESUMO

Whether infantile hemangiomas (IHs) need to be treated and which treatment should be preferred are still controversial. We aimed to compare and rank the treatments and identify the optimal treatment for IHs. We searched PubMed, EMBASE, the Cochrane Library, Web of Science, and other sources for randomized controlled trials up to August 2019. We included trials comparingdifferent treatments and reported response or adverse events rate in IH patients. Two reviewers independently evaluated studies by specific criteria and extracted data. We assessed the risk of bias with the Cochrane risk of bias tool. Random-effects were performed for pair-to-pair and Bayesian framework network meta-analyses. The primary outcomes were efficacy and safety. We deemed 20 studies eligible, including 1149 participants and eight interventions. For efficacy, oral propranolol and topical propranolol/timolol were better than observation/placebo (OR, 95% CrI: 17.05, 4.02-94.94; 9.72, 1.91-59.08). For safety, topical propranolol/timolol was significantly better tolerated than oral propranolol (0.05, 0.001-0.66). Cluster analysis demonstrated oral propranolol was the most effective treatment for IHs, while topical propranolol/timolol showed high efficacy and the highest safety. Laser, intralesional propranolol or glucocorticoid, oral glucocorticoid, or captopril had significantly lower priority than oral propranolol or topical propranolol/timolol considering both efficacy and safety. The quality of evidence was rated as moderate or low in most comparisons. This network meta-analysis found topical beta-blockers had the potential to be the most preferable and beneficial option for IHs in consideration of both efficacy and safety.


Assuntos
Hemangioma Capilar , Teorema de Bayes , Humanos , Metanálise em Rede , Propranolol/efeitos adversos , Timolol
10.
Acta Pharmacol Sin ; 41(2): 237-248, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31341256

RESUMO

Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%-80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg-1per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.


Assuntos
Caquexia/tratamento farmacológico , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Esplenopatias/tratamento farmacológico , Adenocarcinoma/complicações , Animais , Caquexia/etiologia , Neoplasias do Colo/complicações , Modelos Animais de Doenças , Lactonas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sesquiterpenos/administração & dosagem , Baço/patologia , Esplenopatias/patologia , Síndrome
11.
World J Pediatr ; 15(6): 546-558, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31342465

RESUMO

BACKGROUND: A number of clinical trials evaluated the efficacy and adverse effects of oral propranolol in the treatment of infantile hemangioma (IH), but the treatment has not yet been standardized. This meta-analysis aims to reevaluate the efficacy and adverse effects of oral propranolol in comparative studies and to provide a reliable basis for clinical administration in the therapy for IH. METHODS: Data were obtained from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang database, from inception to December 1st, 2018. The pooled risk ratios (RR) with 95% confidence intervals (95% CI) were calculated and used to evaluate the effect size. The meta-analysis was performed using the random-effects model due to heterogeneity between the studies. The Cochrane Collaboration 6 aspects of bias, methodological index for non-randomized studies and the Newcastle-Ottawa Scale were used to assess the risk for bias. Sensitivity analysis, publication bias and subgroup analysis were performed. RESULTS: Eighteen unique studies involving 2701 unique children were included in the analysis. The response rate was reported in 18 trials, which compared oral propranolol with other treatments. The heterogeneity was statistically significant (P < 0.00001, I2 = 95%). The difference in the response rate was statistically significant (RR = 1.40, 95% CI 1.13-1.75) while compared with the controls. However, no significant difference in the adverse events rate (RR = 0.78, 95% CI 0.45-1.34) and relapse rate (RR = 1.45, 95% CI 0.66-3.16) were found. Otherwise, the subgroup analysis indicated that the RR was 1.64 (95% CI 0.24-11.36) for low-dose propranolol (1 mg/kg/day), 1.42 (95% CI 1.12-1.80) for medium dose (2 mg/kg/day) and 1.46 (95% CI 1.17-1.82) for high dose (3 mg/kg/day), but the high dose had higher adverse events rate than medium dose, with 3.60% and 86.22%, respectively. The effectiveness of propranolol therapy among cases of treatment duration less than 6 months (RR = 1.24, 95% CI 1.05-1.47) was inferior to that of treatment duration greater than or equal to 6 months (RR = 1.46, 95% CI 1.11-1.92). CONCLUSIONS: This meta-analysis reveals that oral propranolol is superior to other treatments in improving response rate of IH and can be used as the first-line therapy for IH children. A dosage of 2 mg/kg/day propranolol orally may be a good choice for IH. However, further studies are essential.


Assuntos
Hemangioma Capilar/tratamento farmacológico , Propranolol/administração & dosagem , Administração Oral , Criança , Humanos , Propranolol/efeitos adversos , Resultado do Tratamento
12.
Orthop Surg ; 11(1): 91-96, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30729708

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of using acromioclavicular joint hook plates for the treatment of anterior sternoclavicular joint dislocation. METHODS: Ten patients who suffered anterior sternoclavicular joint dislocation were retrospectively analyzed, and underwent acromioclavicular joint hook plate surgeries from January 2015 to May 2017. There were 7 male and 3 female patients, with a mean age of 43.6 years. According to the American Shoulder and Elbow Society (ASES) scoring system, the preoperative physical function had a mean of 83.5. RESULTS: Reduction and fixation were performed with hook plates in all 10 patients. All patients were followed up, with a mean duration of 16.9 months. There were no complications, no wound infections, and no plate or screw breakages. Movement of the shoulder girdle was improved in all patients. According to the ASES scoring system, the postoperative physical function had a mean of 94.8. CONCLUSION: The acromioclavicular joint hook plate demonstrates safety and efficacy for the treatment of anterior sternoclavicular joint dislocation. However, there are still some deficiencies that need to be improved.


Assuntos
Articulação Acromioclavicular/cirurgia , Placas Ósseas , Luxações Articulares/cirurgia , Articulação Esternoclavicular/cirurgia , Articulação Acromioclavicular/diagnóstico por imagem , Adulto , Feminino , Seguimentos , Humanos , Luxações Articulares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Articulação Esternoclavicular/diagnóstico por imagem , Articulação Esternoclavicular/lesões , Resultado do Tratamento
13.
Yi Chuan ; 41(1): 76-84, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30686787

RESUMO

Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein that induces proliferation and migration of vascular endothelial cells as well as regulation of capillary formation around hair follicles which affects the growth and development of hair follicles. cgVEGF164 is a major splice variant of the cashmere goat VEGF-A gene, but its regulation on hair follicles is rarely known. In order to investigate the role of cgVEGF164 on the growth of murine hair follicles, we produced keratin 14 promoter-driven cgVEGF164 transgenic mice via pronuclear microinjection. Firstly, the diameter and density of hair follicles of transgenic mice were compared with non-transgenic control mice in paraffin sections stained by hematoxylin-eosin (H&E). Then, protein expression levels and the phosphorylation of ERK1/2, AKT1 and LEF1 were examined by Western blot. There are five positive individuals among the neonatal mice (positive rate is 8.5%). Compared with non-transgenic control mice, the diameter and density of hair follicles in transgenic mice are both obviously increased. The expression levels of P-ERK1/2/ERK1/2, P-AKT1/AKT1 and P-LEF1/LEF1 are significantly higher in transgenic mice than those in non-transgenic control mice. Based on these results, we conclude that cgVEGF164 as a growth factor can improve the growth of hair follicles which might be mediated by increasing the levels of ERK1/2, AKT1, and LEF1 protein phosphorylation.


Assuntos
Folículo Piloso/crescimento & desenvolvimento , Isoformas de Proteínas/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Animais , Cabras , Camundongos , Camundongos Transgênicos , Fosforilação
14.
BMC Musculoskelet Disord ; 19(1): 397, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424773

RESUMO

BACKGROUND: Iliosacral screw fixation is a popular method for the management of posterior pelvic ring fractures or dislocations, providing adequate biomechanical stability. Our aim in this study was to describe the use of a new patient-specific external template to guide the insertion of iliosacral screws and to evaluate the efficacy and safety of this technique compared with the conventional fluoroscopy-guided technique. METHODS: This was a retrospective study of patients with incomplete or complete posterior pelvic ring disruptions who required iliosacral screw fixation. For analysis, patients were divided into two groups: the external template group (37 screws in 22 patients) and the conventional group (28 screws in 18 patients). The operative time per screw, radiation exposure time and the rate of screw perforation (accuracy) were compared between groups. In the external template group, the difference between the actual and planned iliosacral screw position was also compared. RESULTS: In the conventional group, the average operative time per screw was 39.7 ± 10.6 min, with an average radiation exposure dose of 1904.0 ± 844.5 cGy/cm2, with 4 cases of screw perforation. In the external template group, the average operative time per screw was 17.9 ± 4.7 min, with an average radiation exposure dose of 742.8 ± 230.6 cGy/cm2 and 1 case of screw perforation. In the template group, the mean deviation distance between the actual and planned screw position was 2.75 ± 1.0 mm at the tip, 1.83 ± 0.67 mm in the nerve root tunnel zone and 1.52 ± 0.48 mm at the entry point, with a mean deviation angle of 1.73 ± 0.80°. CONCLUSIONS: The external template provides an accurate and safe navigation tool for percutaneous iliosacral screw insertion that could decrease the operative time and radiation exposure.


Assuntos
Parafusos Ósseos , Fixadores Externos , Fraturas Ósseas/diagnóstico por imagem , Ílio/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagem , Impressão Tridimensional , Sacro/diagnóstico por imagem , Adulto , Idoso , Feminino , Fraturas Ósseas/cirurgia , Humanos , Ílio/cirurgia , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/cirurgia , Estudos Retrospectivos , Sacro/cirurgia
15.
Oncotarget ; 8(31): 50724-50730, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881598

RESUMO

Giant cell tumor of bone (GCT), which frequently occurs in the patients' spine, is relatively prevalent in Chinese population. A group of GCT invades into vessels and appears to be circulating tumor cells (CTCs) responsible for the distal metastasis of the primary tumor. So far the cell surface markers of GCT have not been determined. In the current study, we aimed to identify a novel CTC marker with higher specificity in GCT. TRAIL-R1+ cells were purified from GCT cell lines. The TRAIL-R1+ cells were compared with total GCT cells for tumor sphere formation, chemo-resistance, tumor formation in nude mice, and frequency of developing distal metastases. We found that TRAIL-R1+ GCT cells appeared to be highly enriched for CTCs in GCT. Compared to total GCT cells, TRAIL-R1+ GCT cells generated significantly more tumor spheres in culture, were higher chemo-resistant, and had a higher frequency of being detected in the circulation after subcutaneous transplantation as well as development of distal metastases. Thus, we conclude that TRAIL-R1+ may be a novel CTC marker in GCT. Selective elimination of TRAIL-R1+ GCT cells may improve the current GCT therapy.

16.
Medicine (Baltimore) ; 96(27): e7245, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28682874

RESUMO

BACKGROUND: The aim of the study was to explore the effects of microRNA-107 (miR-107) by targeting Dkk-1 on osteosarcoma (OS) via the Wnt/ß-catenin signaling pathway. METHODS: OS and adjacent tissues were collected from 67 patients diagnosed with OS. Expressions of miR-107, Dkk-1, LRP5, ß-catenin, and c-Myc were detected by the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The dual-luciferase reporter gene assay was performed to observe the relationship between miR-107 and Dkk-1.Transfected cells were divided into different investigating groups designated as Inhibitor, Mimic, siRNA, Inhibitor + siRNA, negative control (NC), and blank groups. qRT-PCR and Western blotting were used to detect expressions of miR-107, Dkk-1, ß-catenin, Bcl-2, c-Myc, Caspase-3, and PARP. Cell counting kit-8 (CCK-8), flow cytometry (FCM), colony-formation efficiency (CFE), and subcutaneous tumorigenicity assays were all utilized for to determine cell proliferation, apoptosis, colony-forming, and tumorigenic abilities. RESULTS: Dkk-1 is the target gene of miR-107. Decreased expressions of miR-107, LRP5, ß-catenin, and c-Myc, and increased expressions of Dkk-1 were found in OS tissues. The Mimic and siRNA groups exhibited decreased proliferation rates, colony-forming abilities, and tumorigenicity and increased apoptosis rates, whereas the inhibitor group showed opposite trends when compared to the blank group. On the other hand, expressions of miR-107, LRP5, ß-catenin, c-Myc, Caspase-3, and PARP were all elevated in the mimic group, whereas expressions of Dkk-1 and Bcl-2 were reduced; opposite trends were observed in the inhibitor group. CONCLUSION: We conclude that miR-107 is likely to inhibit the occurrence and development of OS by down-regulating Dkk-1 via the Wnt/ß-catenin signaling pathway, providing us with a new therapeutic target for the treatment of OS.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Apoptose/fisiologia , Caspase 3/metabolismo , Proliferação de Células/fisiologia , Células Cultivadas , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Transplante de Neoplasias , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Interferente Pequeno , Distribuição Aleatória , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
17.
Cancer Med ; 5(10): 2861-2871, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27682863

RESUMO

The purpose of this study was to screen for changes in chemokine and chemokine-related genes that are expressed in hepatocellular carcinoma (HCC) as potential markers of HCC progression. Total RNA was extracted from tumor and peritumor tissues from mice with HCC and analyzed using a PCR microarray comprising 98 genes. Changes in gene expression of threefold or more were screened and subsequently confirmed by immunohistochemical analyses and western blotting. Furthermore, whether chemokine knockdown by RNA interference (RNAi) could significantly suppress tumor growth in vivo was also evaluated. Finally, total serum samples were collected from HCC patients with HBV/cirrhosis (n = 16) or liver cirrhosis (n = 16) and from healthy controls (n = 16). The serum mRNA and protein expression levels of CXCL1 in primary liver cancer patients were detected by qRT-PCR and western blot analysis, respectively. Several genes were up-regulated in tumor tissues during the progression period, including CXCL1, CXCL2, CXCL3, and IL-1ß, while CXCR1 expression was down-regulated. CBRH-7919 cells carrying CXCL1 siRNA resulted in decreased tumor growth in nude mice. The differences in serum CXCL1 mRNA and protein levels among the HCC, hepatic sclerosis (HS), and control groups were significant (P < 0.001). The mRNA and protein levels of CXCL1 in the HCC group were up-regulated compared with the HS group or the control group (P < 0.001). Several chemokine genes were identified that might play important roles in the tumor microenvironment of HCC. These results provide new insights into human HCC and may ultimately facilitate early HCC diagnosis and lead to the discovery of innovative therapeutic approaches for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Quimiocinas/genética , Perfilação da Expressão Gênica/métodos , Interleucina-1beta/genética , Neoplasias Hepáticas/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/genética , Quimiocina CXCL2/metabolismo , Quimiocinas/metabolismo , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-1beta/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Transplante de Neoplasias
18.
Int J Oncol ; 47(6): 2131-40, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26499374

RESUMO

Hepatocellular carcinoma (HCC) is an aggressive malignancy and a major cause of cancer-related mortality worldwide. Our previous study shows that chemokine (C-X-C motif) ligand 1 (CXCL1) was upregulated and CXCR1 was downregulated in tumor tissues as compared to peritumor tissues by chemotaxis assay. As the status of CXCL subgroups and their receptors affect progression of HCC, we evaluated potential mechanisms of CXCL1 associated with anticancer effects in HCC based on our previous study. The effects of targeting CXCL1 by RNA interference (RNAi) on the proliferation and apoptosis of CBRH-7919 cells were observed in vitro and in vivo. Additionally, whether CXCL1 knockdown significantly reduce the activity of STAT3, NF-κB and HIF-1 or not were also estimated. RNAi of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice by inhibited cells proliferation and induced apoptosis. In conclusion, these findings suggest that CXCL1 plays critical roles in the growth and apoptosis of HCC. RNAi of CXCL1 inhibits the growth and apoptosis of tumor cells, which indicates that CXCL1 may be a potential molecular target for use in HCC therapy.


Assuntos
Apoptose , Carcinoma Hepatocelular/patologia , Quimiocina CXCL1/antagonistas & inibidores , Neoplasias Hepáticas/patologia , RNA Interferente Pequeno/farmacologia , Animais , Apoptose/fisiologia , Western Blotting , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Reação em Cadeia da Polimerase em Tempo Real
19.
World J Gastroenterol ; 21(16): 4864-74, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25944999

RESUMO

AIM: To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma (HCC) in nude mice. METHODS: CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice. Beginning two weeks after the challenge, tumor growth was measured every week for six weeks. The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples, and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme. A chemokine PCR array, comprised of 98 genes, was used to screen differential gene expressions, which were validated by Western blotting. Additionally, expression of identified chemokines was knocked-down by RNA interference, and the effect on tumor growth was assessed. RESULTS: Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage, neutrophil, and T cell (specifically helper and activated subsets) infiltration. Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase, suggestive of a proinflammatory phenotype. Fifty-one genes were identified in tumor tissues during the progression period, including 50 that were overexpressed (including CXCL1, CXCL2 and CXCL3) and three that were underexpressed (CXCR1, Ifg and Actb). RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2, CXCL3 and interleukin-1ß protein. CONCLUSION: These findings suggest that CXCL1 plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.


Assuntos
Carcinoma Hepatocelular/metabolismo , Quimiocinas/metabolismo , Inflamação/metabolismo , Neoplasias Hepáticas/metabolismo , Microambiente Tumoral , Animais , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Linhagem Celular Tumoral , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL1/metabolismo , Quimiocinas/genética , Quimiocinas/imunologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Inflamação/genética , Inflamação/imunologia , Inflamação/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapêutica com RNAi , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Medicine (Baltimore) ; 93(28): e194, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25526436

RESUMO

Hepatic angiomyolipoma (HAML) is a rare mesenchymal tumor of the liver with marked histological diversity. The present study was to review the magnetic resonance imaging (MRI) and clinical pathological features of HAML resembling hepatocellular carcinoma (HCC). Nine patients who underwent surgical resection and had pathological diagnosis of HAML were retrospectively analyzed. All of 9 patients (5 males and 4 females) had a solitary hepatic mass with a median size of 4 cm (from 1.4 cm to 15.3 cm). Seven cases were identified as incidental liver tumors during health screening and 2 patients were diagnosed for hepatic mass when visited hospitals with unspecific abdominal discomfort. Before resection, 6 cases were diagnosed as HCC on MRI. MRI on chemical shift imagings showed a large amount of lipids in 5 cases. The enhancement pattern of MRI was classified into 2 types: in 2 cases, lesions with small or no vessels that demonstrated prolonged enhancement (1 mixed subtype and 1 myomatous subtype) and in 7 cases, lesions with abundant central vessels that show rapid washout (3 mixed subtypes and 4 myomatous subtypes) in the portal venous/delayed phase. All patients underwent resection of hepatic tumor and no recurrence was observed during follow-up (range: 2-24 months) of median 10 months. By immunohistochemistry, the tumor cells demonstrated positive immunostaining for human melanoma black-45, smooth muscle actin, and CD34. In conclusion, all of 9 patients with HAML presented with none or nonspecific clinical manifestations. The diagnosis of HAML relies on disease and immunohistochemistry, but not MRI due to its resemblance to HCC.


Assuntos
Angiomiolipoma/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Angiomiolipoma/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Hepatectomia , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
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