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AIM: To investigate imaging features and differentiating qualities of type 1 and type 2 papillary renal cell carcinoma (pRCC) by different imaging techniques. MATERIALS AND METHODS: From 2007 to 2019, 107 patients with type 1 pRCC (T1-pRCC) and 147 with type 2 pRCC (T2-pRCC) were included in this retrospective study. All patients underwent conventional ultrasound (US); some also underwent contrast-enhanced ultrasound (CEUS), contrast-enhanced computed tomography (CECT), or contrast-enhanced magnetic resonance imaging (CE-MRI). Tumour Fuhrman grade or World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (after June 2016) and invasive ranges were recorded. The two types of pRCC were analysed and compared for imaging features including tumour position, size, margin, echo type, and colour Doppler flow imaging (CDFI) using US as well as enhanced features from CEUS, CECT, or CE-MRI. RESULTS: T2-pRCC showed a higher Fuhrman grade (p<0.001) and greater propensity to invade extrarenal tissue (p<0.001) than T1-pRCC. On US imaging, T2-pRCC was more likely to be a cystic-solid lesion (p<0.001), and colour flow with a higher resistance index (RI; p=0.014) was more easily detected (p=0.001) in T2-pRCC than in T1-pRCC. Within contrast-enhanced examinations, more T2-pRCC lesions had blurred tumour borders (p=0.003), hypervascular characteristics (p=0.003), and heterogeneous enhancement (p<0.001) than those of T1-pRCC. CONCLUSIONS: T2-pRCC manifests more aggressively than T1-pRCC. T2-pRCC has a higher proportion of hypervascular and heterogeneous enhancement than T1-RCC.
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Carcinoma de Células Renais/diagnóstico por imagem , Meios de Contraste , Diagnóstico por Imagem/métodos , Aumento da Imagem/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: To analyse the correlation between imaging features using multiple techniques and extracellular mucus content in pure mucinous breast carcinoma (PMBC). MATERIALS AND METHODS: A retrospective review of available images from 25 patients with 25 PMBC tumours was conducted, with ultrasonography (US), ultrasonic elastography (USE), mammography, and breast-specific gamma imaging (BSGI) available for 25, 15, 11, and eight patients, respectively. Microscopic slides from each tumour were evaluated for extracellular mucus content. The correlation between imaging features and mucus content was analysed using linear-by-linear association chi-square tests or Spearman's rank correlation analyses. RESULTS: On US images, a significant correlation was found between mucus content and echo pattern (p=0.042) and colour Doppler blood flow (p=0.032), with a trend that the lower mucus content present in tumours, the more likely they were detected with isoechoic echo and high blood flow. On USE images, a moderate negative correlation (r=-0.60, p=0.029) was observed between mucus content and tumour stiffness. On BSGI images, a strong negative correlation (r=-0.92, p=0.001) was shown between mucus content and lesion to non-lesion ratio (L/N) values of radioactivity counts. No significant correlation was found between mucus content and mammography imaging features (all p>0.05). CONCLUSION: Imaging features at US, USE, and BSGI correlated with extracellular mucus content in PMBC tumours, among which the L/N value using BSGI imaging is the most relevant feature.
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Adenocarcinoma Mucinoso/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Muco , Ultrassonografia Mamária/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/diagnóstico por imagem , Técnicas de Imagem por Elasticidade , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Vasculogenic mimicry (VM) is the formation of vascular channels by tumor cells or tumor cell-derived, trans-differentiated cells in highly aggressive, solid tumors. However, the disease features and prognostic value of VM for overall survival of cancer patients remain controversial. METHOD: To systematically investigate the roles of VM in cancer progression and its prognostic values, we performed a meta-analysis based on 36 studies (33 eligible articles) including 3609 patients. The pooled hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were used to assess the relationship between VM and overall survival in cancer patients. RESULTS: Vasculogenic mimicry was significantly associated with cancer differentiation, lymph node metastasis, distant metastasis, and TNM stage. The prognostic value of VM was significant in overall survival (HR 2.16; 95 % CI 1.98-2.38; P < 0.001). Analyses stratified by confounders, such as cancer type, ethnicity, VM detection methods, sample size, and Newcastle-Ottawa quality score, found similar significant results. CONCLUSIONS: The presence of VM predicts poorer survival outcomes in cancer patients.
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Neoplasias/irrigação sanguínea , Neoplasias/diagnóstico , Neovascularização Patológica/patologia , Heterogeneidade Genética , Humanos , Prognóstico , Viés de Publicação , Análise de SobrevidaRESUMO
OBJECTIVE: The application of cell-based therapies in regenerative medicine is hindered by the difficulty of acquiring adequate numbers of competent cells. For the knee meniscus in particular, this may be solved by harvesting tissue from neighboring tendons and ligaments. In this study, we have investigated the potential of cells from tendon and ligament, as compared to meniscus cells, to engineer scaffold-free self-assembling fibrocartilage. METHOD: Self-assembling meniscus-shaped constructs engineered from a co-culture of articular chondrocytes and either meniscus, tendon, or ligament cells were cultured for 4 weeks with TGF-ß1 in serum-free media. After culture, constructs were assessed for their mechanical properties, histological staining, gross appearance, and biochemical composition including cross-link content. Correlations were performed to evaluate relationships between biochemical content and mechanical properties. RESULTS: In terms of mechanical properties as well as biochemical content, constructs engineered using tenocytes and ligament fibrocytes were found to be equivalent or superior to constructs engineered using meniscus cells. Furthermore, cross-link content was found to be correlated with engineered tissue tensile properties. CONCLUSION: Tenocytes and ligament fibrocytes represent viable cell sources for engineering meniscus fibrocartilage using the self-assembling process. Due to greater cross-link content, fibrocartilage engineered with tenocytes and ligament fibrocytes may maintain greater tensile properties than fibrocartilage engineered with meniscus cells.
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Ligamentos , Tendões , Células Cultivadas , Condrócitos , Humanos , Menisco , Engenharia TecidualRESUMO
A novel design of decorating microsphere surface with concentric rings to modulate the photonic nanojet (PNJ) is investigated. By introducing the concentric ring structures into the illumination side of the microspheres, a reduction of the full width at half maximum (FWHM) intensity of the PNJ by 29.1%, compared to that without the decoration, can be achieved numerically. Key design parameters, such as ring number and depth, are analyzed. Engineered microsphere with four uniformly distributed rings etched at a depth of 1.2 µm and width of 0.25 µm can generate PNJ at a FWHM of 0.485 λ (λ = 400nm). Experiments were carried out by direct observation of the PNJ with an optical microscope under 405 nm laser illumination. As a result, shrinking of PNJ beam size of 28.0% compared to the case without the rings has been achieved experimentally. Sharp FWHM of this design can be beneficial to micro/nanoscale fabrication, optical super-resolution imaging, and sensing.
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AIM: To evaluate potential value of Virtual Touch quantification (VTQ) of acoustic radiation force impulse (ARFI) imaging for characterising focal solid renal lesions. MATERIALS AND METHODS: Two independent operators performed 10 and five measurements of each lesion and adjacent renal cortex, respectively. Mean shear wave velocity (SWV) and shear wave velocity ratio (SWR) of histotypes were compared. RESULTS: One hundred and ninety-seven renal lesions were evaluated, including 155 renal cell carcinomas (RCCs; 129 clear-cell RCCs [ccRCCs], 14 papillary RCCs [pRCCs], and 12 chromophobe RCCs [cRCCs]) and 42 angiomyolipomas (AMLs). The interoperator reproducibility of SWV of renal tumours and renal cortex were good (ICC=0.852, and 0.903, respectively). SWV of the renal cortex at a depth of <4 cm was significant higher than that at a depth of >4 cm. Regardless of the subtypes of RCC, SWV and SWR of RCCs differed significantly from those of AMLs (2.28±0.85 versus 1.98±0.85; 1.09±0.56 versus 0.78±0.34; p=0.045 and p<0.001, respectively). At cut-off points of SWV >1.87 m/s or SWR >0.84 to differentiate RCCs from AMLs, the sensitivity and specificity were 47.5%, 33.2% or 47.5%, 30.2%, respectively. When the subtypes of RCCs were taken into account, SWV and SWR of ccRCCs were significantly higher than those of pRCCs, cRCCs, and AMLs, while there was no significant difference among the latter. With SWV >1.98 m/s or SWR >0.80 as the cut-off point to differentiate ccRCCs from other renal tumours, the sensitivity and specificity were 69.8%, 65% or 76.8%, 73.4%, respectively. CONCLUSION: The ARFI technique offers additional information regarding renal tumour elasticity with good reproducibility. SWV and SWR are potential biomarkers in this setting, helping to differentiate ccRCC from other renal tumour histotypes.
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Técnicas de Imagem por Elasticidade/métodos , Neoplasias Renais/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
AIM: To evaluate whether contrast-enhanced ultrasound (CEUS)-guided radiofrequency ablation (RFA) can be performed effectively in small hepatic malignancies that are invisible or poorly visualized at traditional grey-scale ultrasonography (US). MATERIALS AND METHODS: The institutional ethics committee approved the study, and all patients provided written informed consent before their enrolment. The study focused on 55 patients (43 men, 12 women, age 57.4 ± 10.9 years) with 60 hepatic lesions from May 2010 to March 2011. All lesions were treated with multipolar radiofrequency ablation (RFA). During the RFA procedure, with the injection of ultrasound contrast agent (sulphur hexafluoride; SonoVue, Bracco Imaging Spa, Milan, Italy), RFA was conducted under CEUS guidance when the optimal depiction of a lesion was obtained. Artificial pleural effusions were used in those cases obstructed by the lungs. Twenty-four hours after RFA, contrast-enhanced MRI was used as the reference standard to evaluate the primary effectiveness rate and complete tumour necrosis. The follow-up time was 12-24 months (median 15 months). RESULTS: Among 60 hepatic malignancies, CEUS detected 57 lesions (95%), which was higher than that at US (26.6%). Artificial pleural effusions were performed in three cases, resulting in the detection of three additional lesions. The insertion of RFA electrodes was monitored by CEUS in all lesions. Immediately after RFA, complete tumour necrosis were achieved in all 60 lesions as apparent at MRI, for a primary effectiveness rate of 100%. CONCLUSION: CEUS-guided RFA is a promising technique for targeting and improving the efficiency of treatment of hepatic malignancies.
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Ablação por Cateter/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Ultrassonografia de Intervenção , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fosfolipídeos , Ondas de Rádio , Hexafluoreto de Enxofre , Resultado do TratamentoRESUMO
Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.
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COVID-19 , Fístula , Obstrução Intestinal , Exenteração Pélvica , Lesões por Radiação , Humanos , Feminino , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Qualidade de Vida , Estudos Retrospectivos , COVID-19/etiologia , Pelve , Reto , Lesões por Radiação/cirurgia , Lesões por Radiação/etiologia , Complicações Pós-Operatórias/etiologia , Obstrução Intestinal/etiologia , Fístula/etiologiaRESUMO
BACKGROUND: Previous studies indicate that N-ratio has significant superiority in minimizing 'stage migration' for patients with >15 lymph nodes retrieved. Whether the result is applicable to patients with < or =15 lymph nodes retrieved is still in question. PATIENTS AND METHODS: Overall survival rates of 2159 gastric cancer patients who underwent radical resection were compared between patients with different number and level of lymph nodes retrieved according to pN [International Union Against Cancer (Union Internationale Contre le Cancer)/AJCC N stage], n (JGCA N stage) and rN (N-ratio) staging system. RESULTS: Patient number was significantly different between insufficient and sufficient number or level retrieved group in pN and n system, respectively, but not in rN system, while overall survival rates were not significantly different between those groups. The 5-year survival rates of patients with insufficient nodes retrieved were significantly lower than those with sufficient nodes retrieved in pN and n system, but not in rN system. The hazard risk for patients with insufficient nodes retrieved was significantly higher than that for patients with sufficient nodes retrieved in pN and n system, but not in rN system. CONCLUSION: The rN stage has more potential advantages in minimizing stage migration phenomenon for patients with insufficient number or level of lymph nodes retrieved.
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Gastrectomia , Excisão de Linfonodo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , China , Humanos , Estimativa de Kaplan-Meier , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Neoplasias Gástricas/mortalidade , Fatores de Tempo , Resultado do TratamentoRESUMO
Using the level-spacing (LS) statistics, we have investigated the localization-delocalization transitions (LDTs) in Hessian matrices of a simple fluid with short-ranged interactions. The model fluid is a prototype of topologically disordered systems and its Hessian matrices are recognized as an ensemble of Euclidean random matrices with elements subject to several kinds of constraints. Two LDTs in the Hessian matrices are found, with one in the positive-eigenvalue branch and the other in the negative-eigenvalue one. The locations and the critical exponents of the two LDTs are estimated by the finite-size scaling for the second moments of the nearest-neighbor LS distributions. Within numerical errors, the two estimated critical exponents are almost coincident with each other and close to that of the Anderson model (AM) in three dimensions. The nearest-neighbor LS distribution at each LDT is examined to be in a good agreement with that of the AM at the critical disorder. We conclude that the LDTs in the Hessian matrices of topologically disordered systems exhibit the critical behaviors of orthogonal universality class.
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Objective: To investigate the safety and efficacy of surgical treatment for chronic radiation intestinal injury. Methods: A descriptive cohort study was performed. Clinical data of 73 patients with definite radiation history and diagnosed clinically as chronic radiation intestinal injury, undergoing operation at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to February 28, 2019, were reviewed and analyzed retrospectively. Patients did not undergo operation or only received adhesiolysis were excluded. All the patients had preoperative examination and overall evaluation of the disease. According to severity of intestinal obstruction and patients' diet, corresponding nutritional support and conservative treatment were given. Surgical methods: The one-stage bowel resection and anastomosis was the first choice for surgical treatment of chronic radiation intestinal injury. Patients with poor nutritional condition were given enterostomy and postoperative enteral nutrition and second-stage stoma closure and intestinal anastomosis if nutritional condition improved. For those who were unable to perform stoma closure, a permanent stoma should be performed. Patients with severe abdominal adhesion which was difficult to separate, enterostomy or bypass surgery after adhesiolysis would be the surgical choice. For patients with tumor metastasis or recurrence, enterostomy or bypass surgery should be selected. Observation parameters: the overall and major (Clavien-Dindo grades III to V) postoperative complication within 30 days after surgery or during hospitalization; mortality within postoperative 30 days; postoperative hospital stay; time to postoperative recovery of enteral nutrition; time to removal of drainage tube. Results: Of the 73 patients who had been enrolled in this study, 10 were male and 63 were female with median age of 54 (range, 34-80) years. Preoperative evaluation showed that 61 patients had intestinal stenosis, 63 had intestinal obstruction, 11 had intestinal perforation, 20 had intestinal fistula, 3 had intestinal bleeding, and 6 had abdominal abscess, of whom 64(87.7%) patients had multiple complications. Tumor recurrence or metastasis was found in 15 patients. A total of 65(89.0%) patients received preoperative nutritional support, of whom 35 received total parenteral nutrition and 30 received partial parenteral nutrition. The median preoperative nutritional support duration was 8.5 (range, 6.0-16.2) days. The rate of one-stage intestine resection was 69.9% (51/73), and one-stage enterostomy was 23.3% (17/73). In the 51 patients undergoing bowel resection, the average length of resected bowel was (50.3±49.1) cm. Among the 45 patients with intestinal anastomosis, 4 underwent manual anastomosis and 41 underwent stapled anastomosis; 36 underwent side-to-side anastomosis, 5 underwent end-to-side anastomosis, and 4 underwent end-to-end anastomosis. Eighty postoperative complications occurred in 39 patients and the overall postoperative complication rate was 53.4% (39/73), including 39 moderate to severe complications (Clavien-Dindo grade III-V) in 20 patients (27.4%, 20/73) and postoperative anastomotic leakage in 2 patients (2.7%, 2/73). The mortality within postoperative 30 days was 2.7% (2/73); both patients died of abdominal infection, septic shock, and multiple organ failure caused by anastomotic leakage. The median postoperative hospital stay was 13 (11, 23) days, the postoperative enteral nutrition time was (7.2±6.9) days and the postoperative drainage tube removal time was (6.3±4.2) days. Conclusions: Surgical treatment, especially one-stage anastomosis, is safe and feasible for chronic radiation intestine injury. Defining the extent of bowel resection, rational selection of the anatomic position of the anastomosis and perioperative nutritional support treatment are the key to reduce postoperative complications.
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Enteropatias/cirurgia , Lesões por Radiação/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Doença Crônica , Enterostomia , Feminino , Humanos , Enteropatias/etiologia , Intestinos/efeitos da radiação , Intestinos/cirurgia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Lesões por Radiação/complicações , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Tumor necrosis factor (TNF) administration produces an increase in plasma triglycerides that may be due to inhibition of adipose lipoprotein lipase activity and/or a stimulation of hepatic lipogenesis. We now report that TNF administration to insulinopenic diabetic rats increases serum triglycerides (2 h, 2.4-fold; 17 h, 4.3-fold). Adipose tissue lipoprotein lipase activity was markedly decreased in diabetic animals compared with controls and was not further inhibited by TNF. Incorporation of tritiated water into fatty acids in the liver was increased 45% 1-2 h after TNF and 87% at 16-17 h. These results indicate that the TNF-induced increase in circulating lipid levels can occur in the absence of a TNF-induced inhibition of adipose tissue lipoprotein lipase activity. Moreover, the clearance from the circulation of triglycerides in chylomicrons was similar in control and TNF-treated animals; these results provide further evidence that the removal of triglyceride-rich lipoproteins is not altered in the TNF-treated animals. Our data suggest that the TNF-induced stimulation of hepatic lipid synthesis may play an important role in the increase in serum triglycerides. In addition, TNF administration to diabetic animals leads to an elevation in serum glucose levels (73% at 17 h) without a change in serum insulin levels. Thus, TNF stimulation of hepatic lipogenesis is independent of changes in insulin.
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Diabetes Mellitus Experimental/metabolismo , Metabolismo dos Lipídeos , Fator de Necrose Tumoral alfa/farmacocinética , Tecido Adiposo/enzimologia , Animais , Glicemia/análise , Quilomícrons/metabolismo , Diabetes Mellitus Experimental/sangue , Jejum , Feminino , Lipídeos/biossíntese , Lipídeos/sangue , Lipase Lipoproteica/metabolismo , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid (GC) resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs as well as in a subset of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 (IL7) stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.
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Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Glucocorticoides/farmacologia , Interleucina-7/metabolismo , Janus Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Proteína 11 Semelhante a Bcl-2/metabolismo , Linhagem Celular Tumoral , Dexametasona/farmacologia , Modelos Animais de Doenças , Humanos , Inibidores de Janus Quinases/farmacologia , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44(+/High) stem-like cells in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, which subsequently stimulated expression of CSC markers, development of side population and tumor sphere formation. This suggests that PI3K/AKT pathway has an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44(+/High) cells. In addition, LMP1 greatly increased expression of miR-21 and downregulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by an miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and upregulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to the development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC.
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Neoplasias Nasofaríngeas/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas da Matriz Viral/metabolismo , Adulto , Idoso , Animais , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Immunoblotting , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Transplante Heterólogo , Proteínas da Matriz Viral/genéticaRESUMO
BACKGROUND: Analysis using publicly available algorithms has found that high mobility group AT-hook 2 (HMGA2), a key transcriptional regulatory factor, is a potential target of microRNA-204 (miR-204). Some studies have shown that both miR-204 and HMGA2 are associated with cancer development. OBJECTIVE: We examined the possible relationship between miR-204 and HMGA2 in the development of thyroid cancer. METHODS: We assessed miR-204 expression in thyroid cancer specimens and cell lines using real-time polymerase chain reaction (PCR). Luciferase reporter assay was used to confirm the target associations. The effect of miR-204 on cell proliferation was confirmed with tetrazolium and colony formation assays. Gene and protein expression were examined using real-time PCR and western blotting, respectively. RESULTS: MiR-204 was downregulated in the thyroid cancer specimens and cell lines, and targeted the 3^\prime untranslated region of HMGA2 directly. MiR-204 overexpression decreased cyclin D1 and Ki67 expression and increased P21 expression, which subsequently inhibited thyroid cancer cell proliferation. CONCLUSIONS: Our findings suggest that miR-204 plays a protective role by inhibiting thyroid cancer cell proliferation, and may identify new targets for anti-cancer treatment.
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Biomarcadores Tumorais/genética , Proteína HMGA2/biossíntese , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteína HMGA2/genética , Humanos , MicroRNAs/biossíntese , Neoplasias da Glândula Tireoide/patologiaRESUMO
An antibody was raised against a synthetic peptide corresponding to the carboxyl-terminal amino acids of the human insulin receptor (Anti-R beta C). Immunoprecipitation of the human insulin receptor and immunoblotting to the beta-subunit by Anti-R beta C could be inhibited by competition with the corresponding peptide. However, even at saturating concentrations, anti-R beta C could not completely immunoprecipitate or immunodeplete insulin receptors compared to a human autoantibody (anti-R B2). Using receptor labeled directly by 125I, evidence of multiple forms of the beta-subunit was found. When the receptor could be immunoprecipitated by anti-R beta C, the beta-subunit migrated with an apparent mol wt (MW) of 96,000 (at or above the phosphorylase b MW marker). However, in preparations where anti-R beta C was not able to immunoprecipitate the insulin receptor, the beta-subunit migrated at a significantly lower MW of 91,000 (below phosphorylase b), as detected by immunoprecipitation with Anti-R B2. Intermediate forms could also be detected. Phosphorylation of partially purified insulin receptor did not affect is ability to be immunoprecipitated by anti-R beta C, although insulin-stimulated phosphorylation increased the apparent MW of the beta-subunit. However, insulin receptor that was phosphorylated in solubilized extracts of whole cells had a beta-subunit that migrated at lower MW and was not immunoprecipitated by anti-R beta C. One possible explanation for this is that the beta-subunit may be degraded during preparation. When the MW of insulin receptor that has been purified to homogeneity from human placenta is compared to our data, it is clear that many of these insulin receptor preparations contain lower MW beta-subunits. These results must be taken into account when the sites of phosphorylation and kinase activity of purified insulin receptor preparations are studied.
Assuntos
Anticorpos , Fragmentos de Peptídeos/imunologia , Receptor de Insulina/análise , Sequência de Aminoácidos , Especificidade de Anticorpos , Eletroforese em Gel de Poliacrilamida , Imunoensaio , Técnicas de Imunoadsorção , Radioisótopos do Iodo , Peso Molecular , Radioisótopos de Fósforo , FosforilaçãoRESUMO
POPULATION-BASED DATA ON HYPERTENSION IN HAWAII are limited. Two groups for which data from the 1980s exist are Japanese-American men ages 60 to 81 in the Honolulu Heart Program (HHP) and native Hawaiians ages 20 to 59 in the Molokai Heart Study (MHS). In the elderly HHP men, the mean systolic blood pressure (SBP) was higher and the mean diastolic blood pressure (DBP) was lower in the older age groups. In the MHS, both the mean SBP and the mean DBP were higher with increasing age in both sexes. Among Japanese-American men, 53% of those ages 60 to 64 were hypertensive (SBP greater than or equal to 140 mmHg or DBP greater than or equal to 90 mmHg, or taking antihypertensive medications), as were 59% of those ages 65 to 74, and 67% of those ages 75 to 81. Among native Hawaiians, 6% of men and 8% of women ages 20 to 24 were hypertensive, as were 37% of men and 41% of women ages 45 to 54. At ages 55 to 59 the prevalence for men was 31%; and for women, 33%. These data indicate that hypertension is relatively common in both ethnic groups; however, native Hawaiians appear to be at greater risk of cardiovascular disease overall.
Assuntos
Asiático , Hipertensão/etnologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Estudos de Coortes , Feminino , Havaí/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
To investigate the frequency of HER-2 oncogene amplification in primary hepatocellular carcinoma (HCCs) and its relationships with clinicopathological parameters and prognosis, 42 surgical samples from patients with primary HCCs were detected for their HER-2 oncogene amplification by dual FISH technique, and then the correlations between HER-2 amplification and clinicopathological characteristics and prognosis were analyzed statistically. HER-2 oncogene amplification was detected in 9 of 42 (21.4%) primary HCCs, including 4 (9.5%) cases with high copy (HC) and 5 (11.9%) ones with low copy (LC). HER-2 amplification was associated significantly with postoperative survival time of HCC patients examined (P = 0.046) and the presence of HER-2 gene amplification showed a trend toward a correlation with tumor size (P = 0.085), but wasn't relative to sex, age, AFP level, HBV infection, postoperative relapse and clinical staging of HCC patients tested (P > 0.05). On the other hand, gain of the HER-2 oncogene copy was examined in 31 of 42(73.8%) primary HCCs, consisting of 9 (21.4%) cases with HER-2 amplification and 22(52.4%) ones with aneusomy 17/polysomy 17. There weren't significant relationships between gain of HER-2 oncogene copy and, HCC patient's sex, tumor size, clinical staging, postoperative relapse and survival time (P > 0.05), but gain of HER-2 oncogene copy correlated significantly to patients' age, AFP level and HBV infection (P < 0.05). The study indicated that there were a lower frequency of HER-2 oncogene amplification and a higher frequency of aneusomy 17/polysomy 17 in primary HCCs and that HER-2 oncogene amplification activation might be involved in the development and progression of a subset of HCCs, and seemed to be a valuably independent prognosis factor predicting postoperative poorer survival for patients with HCC.
Assuntos
Carcinoma Hepatocelular/genética , Amplificação de Genes , Genes erbB-2 , Hibridização in Situ Fluorescente , Neoplasias Hepáticas/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
In terms of the multifractal analysis, we investigate the characteristics of the instantaneous normal modes (INMs) at two mobility edges (MEs) of a simple fluid, where the locations of the MEs in the INM spectrum were identified in a previous work [B. J. Huang and T. M. Wu, Phys. Rev. E 79, 041105 (2009)]. The mass exponents and the singularity spectrum of the INMs are obtained by the box-size and system-size scalings under the typical average. The INM eigenvectors at a ME exhibit a multifractal nature and the multifractal INMs at each ME yield the same results in generalized fractal dimensions and singularity spectrum. Our results indicate that the singularity spectrum of the multifractal INMs agrees well with that of the Anderson model at the critical disorder. This good agreement provides numerical evidence for the universal multifractality at the localization-delocalization transition. For the multifractal INMs, the probability density function and the spatial correlation function of the squared vibrational amplitudes are also calculated. The relation between the probability density function and the singularity spectrum is examined numerically, so are the relations between the critical exponents of the spatial correlation function and the mass exponents of the multifractal INMs.