RESUMO
OBJECTIVE: We aimed at exploring the feasibility of noninvasive late arterial phase enhanced CT imaging in evaluating tumor angiogenesis, ischemic necrosis, and glucose metabolism, thereby providing pathological information for the comprehensive treatment plan in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: 52 cases of NSCLC were enrolled in this study. The mean ischemia necrosis CT quantitative value (INCTQ) and CT enhanced value (CTe) of the tumor were determined, and the immunohistochemical staining of factors relating to tumor angiogenesis, ischemic necrosis and glucose metabolism, including VEGF, VEGFR-2, HIF-1α, CAIX, GLUT1, and GLUT3, were conducted. RESULTS: The mean INCTQ values of different expression grades of VEGF, VEGFR-2, HIF-1α, and CAIX have no significant difference, but the mean INCTQ values of different expression grades of GLUT1 or GLUT3 have significant differences (p < 0.001), respectively. However, INCTQ value has a positive correlation with CAIX expression. In addition, CTe value was positively correlated with VEGF. CONCLUSIONS: To sum up, late arterial phase CT enhanced images of NSCLC not only can assess the tumor angiogenesis, but also can reflect the degree of ischemic necrosis, effectively reflecting the level of glucose metabolism in tumor and tumor angiogenesis, for the comprehensive treatment program.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Neovascularização Patológica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Porphyromonas gingivalis is a bacterial species that causes destruction of periodontal tissues. Additionally, previous evidence indicates that GroEL from P. gingivalis may possess biological activities involved in systemic inflammation, especially inflammation involved in the progression of periodontal diseases. The literature has established a relationship between periodontal disease and cancer. However, it is unclear whether P. gingivalis GroEL enhances tumor growth. Here, we investigated the effects of P. gingivalis GroEL on neovasculogenesis in C26 carcinoma cell-carrying BALB/c mice and chick eggs in vivo as well as its effect on human endothelial progenitor cells (EPC) in vitro. We found that GroEL treatment accelerated tumor growth (tumor volume and weight) and increased the mortality rate in C26 cell-carrying BALB/c mice. GroEL promoted neovasculogenesis in chicken embryonic allantois and increased the circulating EPC level in BALB/c mice. Furthermore, GroEL effectively stimulated EPC migration and tube formation and increased E-selectin expression, which is mediated by eNOS production and p38 mitogen-activated protein kinase activation. Additionally, GroEL may enhance resistance against paclitaxel-induced cell cytotoxicity and senescence in EPC. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to the neovasculogenesis of tumor cells and resulting in accelerated tumor growth.
Assuntos
Proteínas de Bactérias/metabolismo , Chaperonina 60/metabolismo , Neoplasias do Colo/microbiologia , Células Progenitoras Endoteliais/metabolismo , Porphyromonas gingivalis/patogenicidade , Alantoide/irrigação sanguínea , Animais , Linhagem Celular Tumoral , Embrião de Galinha , Selectina E/metabolismo , Células Progenitoras Endoteliais/citologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Porphyromonas gingivalis/genética , Proteínas Recombinantes/metabolismo , Fatores de Virulência/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Suppressor of cytokine signalling 3 is thought to be associated with insulin resistance in patients with chronic hepatitis C. We evaluated the role of suppressor of cytokine signalling 3 polymorphisms in determining insulin resistance in patients with chronic hepatitis C. Two hundred and ninety untreated hepatitis C virus-infected patients without diabetes and cirrhosis were genotyped for the SNPs rs4969168, rs4969170 and rs12952093 of suppressor of cytokine signalling 3 using the TaqMan Genotyping Assay. We found that the rs4969170 AA genotype and rs4969170 A allele frequency were significantly more common in the insulin-resistant group than the non-insulin-resistant group (89.5% vs 76.1%, OR = 2.693, 95% CI: 1.221-5.939, P = 0.012 and 94.8% vs 88.0%, OR = 2.463, 95% CI: 1.151-5.271, P = 0.017, respectively). Haplotype G-C was likely associated with non-insulin resistance (adjusted P = 0.011). Multiple logistic regression analysis indicates that the independent risk factors for insulin resistance are the SNP rs4969170 AA genotype (OR = 3.005, 95% CI: 1.194-7.560, P = 0.019), HCV genotype 1 (OR = 2.524, 95% CI: 1.099-5.794, P = 0.029) and BMI (OR = 0.514, 95% CI: 0.265-0.999, P = 0.05).
Assuntos
Hepatite C Crônica/complicações , Hepatite C Crônica/genética , Resistência à Insulina/genética , Polimorfismo de Nucleotídeo Único , Proteínas Supressoras da Sinalização de Citocina/genética , Adulto , Idoso , Índice de Massa Corporal , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 3 Supressora da Sinalização de CitocinasRESUMO
The in silico mapping (ISM) technique and its extension represent major advances for novel gene discovery in germplasm resources of inbred lines. However, the techniques suffer from a relatively high false-positive rate (FPR) and they do not consider the effect of linkage disequilibrium (LD) markers around the identified quantitative trait locus (QTL). In addition, it has not yet been established whether it is optimal to use absolute trait differences as the response variable. To address these problems, this article presents the multiple loci ISM (MLISM) approach, which uses all markers on the entire genome, along with a penalized maximum likelihood. The method proposed here was verified by a series of simulation experiments with a maize pedigree population of inbred lines of known ancestry. Results from the simulated studies show that the best response variable is the trait product. The MLISM FPR is substantially decreased and the proportion of the number of false QTL to the number of LD markers around the identified QTL is adequately reduced. The MLISM method, with the trait product as the response variable, is an improvement on the existing methods for novel QTL mapping in germplasm resources of inbred lines.
Assuntos
Mapeamento Cromossômico/métodos , Locos de Características Quantitativas , Zea mays/genética , Endogamia , Desequilíbrio de Ligação , Modelos GenéticosRESUMO
Connective tissues are biological composites comprising of collagen fibrils embedded in (and reinforcing) the hydrated proteoglycan-rich (PG) gel within the extracellular matrices (ECMs). Age-related changes to the mechanical properties of tissues are often associated with changes to the structure of the ECM, namely, fibril diameter. However, quantitative attempts to correlate fibril diameter to mechanical properties have yielded inconclusive evidence. Here, we described a novel approach that was based on the rule of mixtures for fiber composites to evaluate the dependence of age-related changes in tendon tensile strength (sigma) and stiffness (E) on the collagen fibril cross-sectional area fraction (rho), which is related to the fibril volume fraction. Tail tendons from C57BL6 mice from age groups 1.6-35.3 months old were stretched to failure to determine sigma and E. Parallel measurements of rho as a function of age were made using transmission electron microscopy. Mathematical models (rule of mixtures) of fibrils reinforcing a PG gel in tendons were used to investigate the influence of rho on ageing changes in sigma and E. The magnitudes of sigma, E, and rho increased rapidly from 1.6 months to 4.0 months (P-values <0.05) before reaching a constant (age independent) from 4.0 months to 29.0 months (P-values >0.05); this trend continued for E and rho (P-values >0.05) from 29.0 months to 35.3 months, but not for sigma, which decreased gradually (P-values <0.05). Linear regression analysis revealed that age-related changes in sigma and E correlated positively to rho (P-values <0.05). Collagen fibril cross-sectional area fraction rho is a significant predictor of ageing changes in sigma and E in the tail tendons of C57BL6 mice.
Assuntos
Colágeno/fisiologia , Modelos Teóricos , Tendões/fisiologia , Animais , Fenômenos Biomecânicos , Colágeno/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Estresse Mecânico , Tendões/ultraestrutura , Resistência à TraçãoRESUMO
PURPOSE: To evaluate the safety and efficacy of injections with botulinum toxin type A (BTTA,Botox), given transcutaneously, in the treatment of upper lid retraction associated with thyroid eye disease (TED). METHODS: A total of 15 patients (21 eyes) with a stable (TED) condition, and a euthyroid state, were enrolled into the study. There were 12 females and three males from ages 23 to 52 years. A single injection, at the centrally superior tarsal border transcutaneously, aiming at the levator aponeurosis and Müller muscle, was administered into each eyelid with 5-6 U of Botox. All patients were followed regularly for 4-6 months. Any complications, such as ptosis, diplopia, pain,or lid ecchymosis were recorded. RESULTS: All patients, except one, experienced much reduction of palpebral fissure. The mean difference of MRD1 between pre- and postinjections of Botox at the first week was -3.1 mm, and the effect remained, at least, for 2 months. There were temporary complications of ptosis in three patients and vertical diplopia in two patients, lasting 3-4 weeks. CONCLUSIONS: A single transcutaneous injection with Botox for the treatment of thyroid lid retraction is safe and effective. Some minor complications may occur, such as ptosis and diplopia; however, it may offer an alternative and temporary method for patients with dysthyroid lid retraction, who are waiting for a staged operation of either an orbital decompression or a strabismus surgery or both.