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1.
Colorectal Dis ; 18(1): O10-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26530997

RESUMO

AIM: The frequent presence of acellular mucin in specimens showing pathological complete response to preoperative chemoradiotherapy (CRT) and the poor response to preoperative CRT in mucinous rectal cancer have been reported. However, the prevalence and prognostic significance of cellular and acellular mucin have not been evaluated in resected specimens from patients with mucinous rectal cancer who undergo preoperative CRT. METHOD: We retrospectively evaluated the clinicopathological features and prognostic significance of mucin in resected specimens from 59 consecutive patients with mucinous rectal cancer who underwent long-course CRT followed by resection between January 2000 and December 2009. Patients were categorized according to the presence of mucin, as identified by pathological analysis. The clinicopathological findings and oncological results were compared. RESULTS: Mucin was identified in 25 of 59 patients with mucinous rectal cancer (42.4%). Mucin was more frequent in men (hazard ratio = 23.94, 95% confidence interval = 1.875-305.504, P = 0.015) and in specimens showing a good tumour response grade (hazard ratio = 64.26, 95% confidence interval = 6.940-595.045, P < 0.001). With a median follow-up of 67.7 (range 8.6-133.2) months, the 5-year overall survival (60.7% without mucin vs 51.4% with mucin, P = 0.898) and disease-free survival (59.9% without mucin vs 56.9% with mucin, P = 0.813) did not differ between the groups. CONCLUSION: The presence of mucin in rectal cancer with mucinous differentiation after preoperative CRT and resection is associated with male gender and a good tumour response grade, without significant impact on oncological outcome.


Assuntos
Adenocarcinoma Mucinoso/metabolismo , Quimiorradioterapia , Mucinas/metabolismo , Terapia Neoadjuvante , Neoplasias Retais/metabolismo , Reto/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Fatores Sexuais , Taxa de Sobrevida , Resultado do Tratamento
2.
J Comput Electron ; 15: 939-958, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27610051

RESUMO

The Boltzmann transport equation is commonly considered to be the best semi-classical description of carrier transport in semiconductors, providing precise information about the distribution of carriers with respect to time (one dimension), location (three dimensions), and momentum (three dimensions). However, numerical solutions for the seven-dimensional carrier distribution functions are very demanding. The most common solution approach is the stochastic Monte Carlo method, because the gigabytes of memory requirements of deterministic direct solution approaches has not been available until recently. As a remedy, the higher accuracy provided by solutions of the Boltzmann transport equation is often exchanged for lower computational expense by using simpler models based on macroscopic quantities such as carrier density and mean carrier velocity. Recent developments for the deterministic spherical harmonics expansion method have reduced the computational cost for solving the Boltzmann transport equation, enabling the computation of carrier distribution functions even for spatially three-dimensional device simulations within minutes to hours. We summarize recent progress for the spherical harmonics expansion method and show that small currents, reasonable execution times, and rare events such as low-frequency noise, which are all hard or even impossible to simulate with the established Monte Carlo method, can be handled in a straight-forward manner. The applicability of the method for important practical applications is demonstrated for noise simulation, small-signal analysis, hot-carrier degradation, and avalanche breakdown.

3.
Colorectal Dis ; 17(8): O161-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26095997

RESUMO

AIM: Colorectal cancer (CRC) with microsatellite instability (MSI) is characterized by frequent poor differentiation or mucinous histology. The purpose of this study was to evaluate the association of MSI with clinicopathological features and the oncological outcome in patients with a mucinous component. METHOD: CRC tissue samples were analysed for histology and MSI. Patients were grouped according to the mucinous content of the tumour, as follows: > 50%, mucinous adenocarcinoma (MA); ≤ 50%, adenocarcinoma with mucinous component (AMC); none, nonmucinous adenocarcinoma (NMA). Clinicopathological parameters and survival were compared between patient groups. RESULTS: Of 2025 patients, 84 (4%) had MA and 124 (6%) had AMC. In addition, 202 (10%) had MSI. Patients with MA and AMC tended to have a younger age of onset, right-colon predilection, large-sized tumour and high frequency of MSI compared with those with NMA (P < 0.001). MA and AMC patients with MSI showed a trend towards right-colon predilection and infrequent lymph-node metastasis compared with those with microsatellite stability (MSS; P = 0.005-0.03). There were no survival differences between the three groups, but patients with MSI-MA demonstrated lower 4-year recurrence and better overall survival rates than those with MSS-MA (P = 0.018 and P = 0.046, respectively). CONCLUSION: Clinicopathological features of AMC and MA were similar and closely associated with MSI status. Although the prognoses of AMC and MA were no different from that of NMA, survival of patients with an MSI-MA tumour was significantly better than for those with MSS-MA tumours.


Assuntos
Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/secundário , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Recidiva Local de Neoplasia/genética , Adenocarcinoma Mucinoso/mortalidade , Idade de Início , Colo Ascendente , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
4.
Asian-Australas J Anim Sci ; 25(10): 1451-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25049502

RESUMO

A total of 144 ((Duroc×Yorkshire)×Landrace)) pigs with an average initial BW of 28.85±0.63 kg were used in this 6-wk growth trial. Pigs were randomly allotted to 1 of 4 treatments in a completely random block design. Each dietary treatment consisted of 9 replicate pens, with 4 pigs per replicate. Dietary treatments included: i) NC (basal diet), ii) PC (NC+apramycin 0.5 g/kg), iii) BPT1 (NC+bacteriophage 0.25 g/kg) and iv) BPT2 (NC+bacteriophage 0.5 g/kg). The inclusion of antibiotics and bacteriophages did not affect the (p>0.05) ADG, ADFI and G:F compared with the basal diet. Dietary antibiotics and bacteriophages supplementation led to a higher (p<0.05) DM digestibility than the NC treatment. Pigs fed the bacteriophage supplemented diet increased (p<0.05) the N digestibility compared with those fed NC treatment. Supplementation of antibiotics led to a higher (p<0.05) energy digestibility than the NC treatment. No difference (p>0.05) was observed in the RBC, WBC, lymphocyte concentration and fecal moisture among treatments. Pigs fed PC and BPT2 treatments reduced (p<0.05) the E. coli concentration compared with those fed NC treatment. The inclusion of BPT2 treatment led to a higher (p<0.05) lactobacillus concentration compared with NC and PC treatment. Dietary antibiotic and bacteriophage supplementation reduced (p<0.05) the Salmonella concentration compared with NC treatment. In conclusion, our study suggested that bacteriophage at the level of 0.5 g/kg could be used as an antibiotics alternative for growing pigs.

5.
Asian-Australas J Anim Sci ; 25(7): 1003-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25049656

RESUMO

One hundred and twenty weanling pigs in experiment 1 (Exp. 1) (6.91±0.99 kg; 21 d of age) and Exp. 2 (10.20±1.09 kg; 28 d of age) were used in two 42-d and 35-d experiments to evaluate the effect of medium-chain-triglyceride (MCT) on growth performance, apparent total tract digestibility (ATTD) of nutrients and blood profile. In both of Exp. 1 and Exp. 2, the same dietary treatments were utilized as follows : i) negative control (NC), ii) positive control (PC), NC+antibiotics (40 mg/kg Tiamulin, 110 mg/kg Tylosin, and 10 mg/kg Enramycin, iii) MCT3, NC+0.32% (phase 1, 2 and 3) MCT, and iv) MCT5, NC+0.55% (phase 1), 0.32% (phase 2 and 3) MCT. In Exp. 1, the pigs fed MCT5 diets had higher (p<0.05) ADG compared to NC treatment during the first 2 wk. From d 15 to 28, the ATTD of energy was improved (p<0.05) by MCT3 compared to the PC treatment. No effect has been observed on the blood profiles [red blood cell (RBC), white blood cell (WBC), immunoglobulin-G (IgG), lymphocyte concentration] measured in this study. In Exp. 2, the ADG were increased (p<0.05) by the MCT5 treatment than the PC treatment from d 0 to 14. Pigs fed PC treatment diet had lower ADFI (p<0.05) and better FCR (p<0.05) than NC treatment, whereas no differences were shown between MCT treatments and NC or PC treatment from d 15 to 35 and overall phase. The ATTD of DM and nitrogen were improved (p<0.05) by the effect of MCT5 related to the NC and PC treatment at the end of 2nd and 5th wk. The pigs fed MCT3 had higher (p<0.05) energy digestibility than PC treatment. No effects were seen in the blood profiles we measured (WBC, RBC, lymphocyte and immunoglobulin-G). In conclusion, the addition of MCT in the weanling pigs diet can improve the ADG and digestibility during the earlier period (first 2 wks), but had little effect on the blood characteristics.

6.
Asian-Australas J Anim Sci ; 25(9): 1294-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25049693

RESUMO

A total of 96 pigs (49.23±3.20 kg) were used in an 11 wk growth trial to evaluate the effect of fermentable carbohydrate (FC) content on growth performance, apparent total tract digestibility (ATTD) of nutrient, blood profile, and meat quality. The dietary treatments were: i) negative control (NC), basal diet, ii) positive control (PC), NC+antibiotics (positive control diet with 5 ppm flavomycin), iii) PCL, PC-13% lower FC, and iv) NCL, NC-13% lower FC. The growth performance (average daily gain, average daily feed intake, and gain/feed) didn't differ among treatments through the whole experiment. These pigs fed the PCL diet had the greater (p<0.05) apparent total tract digestibility (ATTD) of dry matter than those from PC and NC treatment at the end of the experiment. No differences were observed in white blood cell (WBC), red blood cell (RBC), and lymphocyte concentration among different treatments. After the feeding period, meat samples were collected from the pigs at slaughter. The pigs in NCL and PCL treatments had greater (p<0.05) backfat thickness and lower lean percentage. The color value of loin was higher (p<0.05) in NCL treatment compared to PCL treatment. Also, the NCL treatment had higher (p<0.05) marbling value than PC treatment. The drip loss was depressed by PCL and NCL treatment comapared to NC treatments. The water holding capacity (WHC) was higher (p<0.05) in NC and PCL treatment. In conclusion, the low FC can improve digestibility and meat quality of finishing pigs.

7.
Br J Cancer ; 104(8): 1296-302, 2011 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-21448168

RESUMO

PURPOSE: Tumour epithelial vimentin expression is a marker of mesenchymal differentiation and may be a useful marker of carcinomas with more aggressive behaviour. The aim of this study was to determine the extent and prognostic significance of vimentin expression in pancreatic ductal adenocarcinomas. METHODS: Vimentin expression was detected by immunohistochemistry on tissue microarrays of surgically resected pancreatic ductal adenocarcinomas from 387 patients. The percentage of vimentin-immunolabelled neoplastic cells was correlated with outcome and with clinico-pathological factors using the Kaplan-Meier method and Cox multivariate survival models. RESULTS: In all, 45% of primary pancreatic adenocarcinomas contained neoplastic cells that expressed vimentin, and in 27.5% of the cancers >10% of cells expressed vimentin. Vimentin expression was correlated with poor histological differentiation. By both uni- and multivariate survival analysis, neoplastic vimentin expression (P<0.01, HR 1.52, 95% confidence interval 1.14-2.04) was an indicator of a shorter postsurgical survival independent of other clinico-pathological variables. CONCLUSION: The presence of vimentin-expressing tumour epithelial cells in surgically resected pancreatic adenocarcinomas independently predicted a shorter postsurgical survival.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Vimentina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Epitélio/metabolismo , Epitélio/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos
8.
ESMO Open ; 6(3): 100119, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33901869

RESUMO

BACKGROUND: Grade 3 neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) origin with Ki-67 indices <55% do not respond well to platinum-based chemotherapy. The combination of capecitabine and temozolomide (CAPTEM) has shown favorable responses in grade 1-2 NENs, but has rarely been studied in patients with grade 3 NENs. PATIENTS AND METHODS: This open-label, single-arm phase II trial included patients with unresectable or metastatic grade 3 NENs of GEP origin with Ki-67 indices <55% enrolled between June 2017 and July 2020. Patients received oral capecitabine 750 mg/m2 twice daily on days 1 to 14 and oral temozolomide 200 mg/m2 once daily on days 10 to 14 every 4 weeks. Histologic findings were centrally reviewed after the completion of enrollment. The primary endpoint was overall response rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Of the 30 patients included in the full analysis set, 1 (3.3%) achieved complete response, 8 (26.7%) had partial responses, and 14 (46.7%) had stable disease, making the overall response rate 30.0%. At a median follow-up of 19.2 months, the median PFS was 5.9 months and the median OS was not reached. Patients with well-differentiated NENs showed significantly better median PFS (9.3 months versus 3.5 months, P = 0.005) and median OS (not reached versus 6.2 months, P = 0.004) than patients with poorly differentiated tumors. Expression of O6-methyl-guanine methyltransferase protein did not correlate with clinical outcomes. The most common grade 3-4 adverse events were thrombocytopenia (10%), anemia (6.7%), and nausea (6.7%). CONCLUSIONS: CAPTEM was effective and well tolerated in patients with grade 3 GEP-NENs with Ki-67 indices <55%, with superior efficacy outcomes compared with the historical controls receiving platinum-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Tumores Neuroendócrinos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Humanos , Antígeno Ki-67 , Tumores Neuroendócrinos/tratamento farmacológico , Temozolomida/uso terapêutico
9.
J Psychopharmacol ; 22(5): 522-31, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18308779

RESUMO

We investigated the effect and mechanism of exercise and chlorpromazine (CPZ), a conventional anti-psychotic drug, on beta-cell function and mass in 90% pancreatectomized (Px) male rats. The diabetic Px rats were divided into two groups, one of which was provided with exercise whereas the other was not. Both groups were subdivided into the three groups and administered with 0, 5 or 50 mg CPZ per kg body weight (control, low dosage of chlorpromazine (LCPZ), high dosage chlorpromazine (HCPZ)) for 8 weeks. LCPZ did not modulate glucose homeostasis. HCPZ impaired acute phase and second phase insulin secretion during hyperglycemic clamp. Apoptosis of pancreatic beta-cells increased in the HCPZ group, and proliferation decreased, contributing to reduced beta-cell mass. Exercise partially improved glucose-stimulated insulin secretion and beta-cell mass in HCPZ-treated rats. Interestingly, insulin receptor substrate-2 (IRS2) protein levels in islets decreased by increased degradation in the HCPZ group, whereas exercise partially reversed this trend by induction of IRS2 expression. In isolated islets, 50 microM CPZ decreased IRS2 expression by promoting ubiquitin-proteasome degradation, which had been prevented by proteasome inhibitors. Furthermore, similar to the effect of HCPZ treatment, a high dosage of rottlerin, a protein kinase C-delta inhibitor, reduced IRS2 levels in the islets. In conclusion, exercise partially recovered the diabetic symptoms exacerbated by HCPZ through enhancement of beta-cell function and mass in diabetic rats. This modulation by HCPZ and exercise was associated with increasing intracellular IRS2 protein levels in independent pathways.


Assuntos
Antipsicóticos/efeitos adversos , Clorpromazina/efeitos adversos , Proteínas Substratos do Receptor de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Acetofenonas/farmacologia , Animais , Antipsicóticos/administração & dosagem , Benzopiranos/farmacologia , Clorpromazina/administração & dosagem , Diabetes Mellitus Experimental/metabolismo , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica , Glucose/metabolismo , Técnica Clamp de Glucose , Homeostase/efeitos dos fármacos , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Condicionamento Físico Animal , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Ratos Sprague-Dawley , Ubiquitina/efeitos dos fármacos , Ubiquitina/metabolismo
10.
Hum Exp Toxicol ; 37(4): 350-357, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28441892

RESUMO

The aim of this study was to assess changes in bone mineral density (BMD) and cadmium (Cd) levels in blood and urine in individuals living in a Cd-contaminated area according to the type of osteoporosis medication over a three-year period. This follow-up study included 204 residents living in the vicinity of a closed copper refinery, who had been found to have elevated urinary or blood Cd levels. Cd levels in the blood and urine, as well as BMD, were measured every 6 months. After the first BMD measurement, individuals were prescribed antiresorptives such as alendronate or vitamin D and calcium, according to their BMD. Subjects were classified according to the type of medicine provided over the previous 6 months. General linear models controlling for other factors were used to evaluate the effects of each type of medication on the participants' Cd levels and BMD. Spinal BMD showed a significant increase in the antiresorptive group compared to the nontreatment group. Significant decreases in blood Cd levels were found in the vitamin D and calcium group, in comparison to the nontreatment group, as well as a marginally significant decrease in the antiresorptive group. The vitamin D and calcium group showed a significantly greater decrease in urinary Cd levels than the nontreatment group. In contrast, antiresorptive medication was found to have a negative effect on urinary Cd excretion. These results suggest that vitamin D and calcium treatment for osteoporosis lowers blood Cd levels more effectively and improves urinary Cd excretion.


Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Cádmio/sangue , Cádmio/urina , Cálcio/uso terapêutico , Suplementos Nutricionais , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Osteoporose/tratamento farmacológico , Vitamina D/uso terapêutico , Absorciometria de Fóton , Idoso , Carga Corporal (Radioterapia) , Cobre , Feminino , Humanos , Masculino , Metalurgia , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/fisiopatologia , Eliminação Renal , República da Coreia , Fatores de Tempo , Resultado do Tratamento
11.
J Colloid Interface Sci ; 304(2): 505-11, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17046778

RESUMO

In this paper we develop a method for the determination of the zeta potential zeta and the dielectric constant epsilon by exploiting velocity measurements of the electroosmotic flow in microchannels. The inverse problem is solved through the minimization of a performance function utilizing the conjugate gradient method. The present method is found to estimate zeta and epsilon with reasonable accuracy even with noisy velocity measurements.

12.
Phys Med Biol ; 61(5): 1947-67, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26878653

RESUMO

The prediction as well as the gating of respiratory motion have received much attention over the last two decades for reducing the targeting error of the radiation treatment beam due to respiratory motion. In this article, we present a real-time algorithm for predicting respiratory motion in 3D space and realizing a gating function without pre-specifying a particular phase of the patient's breathing cycle. The algorithm, named EKF-GPRN(+) , first employs an extended Kalman filter (EKF) independently along each coordinate to predict the respiratory motion and then uses a Gaussian process regression network (GPRN) to correct the prediction error of the EKF in 3D space. The GPRN is a nonparametric Bayesian algorithm for modeling input-dependent correlations between the output variables in multi-output regression. Inference in GPRN is intractable and we employ variational inference with mean field approximation to compute an approximate predictive mean and predictive covariance matrix. The approximate predictive mean is used to correct the prediction error of the EKF. The trace of the approximate predictive covariance matrix is utilized to capture the uncertainty in EKF-GPRN(+) prediction error and systematically identify breathing points with a higher probability of large prediction error in advance. This identification enables us to pause the treatment beam over such instances. EKF-GPRN(+) implements a gating function by using simple calculations based on the trace of the predictive covariance matrix. Extensive numerical experiments are performed based on a large database of 304 respiratory motion traces to evaluate EKF-GPRN(+) . The experimental results show that the EKF-GPRN(+) algorithm reduces the patient-wise prediction error to 38%, 40% and 40% in root-mean-square, compared to no prediction, at lookahead lengths of 192 ms, 384 ms and 576 ms, respectively. The EKF-GPRN(+) algorithm can further reduce the prediction error by employing the gating function, albeit at the cost of reduced duty cycle. The error reduction allows the clinical target volume to planning target volume (CTV-PTV) margin to be reduced, leading to decreased normal-tissue toxicity and possible dose escalation. The CTV-PTV margin is also evaluated to quantify clinical benefits of EKF-GPRN(+) prediction.


Assuntos
Algoritmos , Imageamento Tridimensional/métodos , Modelos Teóricos , Movimento/fisiologia , Neoplasias/radioterapia , Radioterapia Assistida por Computador/métodos , Respiração , Teorema de Bayes , Humanos , Neoplasias/fisiopatologia , Distribuição Normal , Interpretação de Imagem Radiográfica Assistida por Computador , Mecânica Respiratória
13.
Oncogene ; 35(27): 3544-54, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-26568303

RESUMO

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme involved in NAD+ biosynthesis. Although NAMPT has emerged as a critical regulator of metabolic stress, the underlying mechanisms by which it regulates metabolic stress in cancer cells have not been completely elucidated. In this study, we determined that breast cancer cells expressing a high level of NAMPT were resistant to cell death induced by glucose depletion. Furthermore, NAMPT inhibition suppressed tumor growth in vivo in a xenograft model. Under glucose deprivation conditions, NAMPT inhibition was found to increase the mitochondrial reactive oxygen species (ROS) level, leading to cell death. This cell death was rescued by treatment with antioxidants or NAD+. Finally, we showed that NAMPT increased the pool of NAD+ that could be converted to NADPH through the pentose phosphate pathway and inhibited the depletion of reduced glutathione under glucose deprivation. Collectively, our results suggest a novel mechanism by which tumor cells protect themselves against glucose deprivation-induced oxidative stress by utilizing NAMPT to maintain NADPH levels.


Assuntos
Neoplasias da Mama/metabolismo , Citocinas/metabolismo , Glucose/metabolismo , NADP/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Acrilamidas/farmacologia , Animais , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Hipóxia Celular , Linhagem Celular , Linhagem Celular Tumoral , Citocinas/antagonistas & inibidores , Citocinas/genética , Feminino , Células HCT116 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , NAD/metabolismo , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/genética , Piperidinas/farmacologia , Interferência de RNA , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
14.
Chemosphere ; 59(7): 929-37, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15823326

RESUMO

The concentrations of three different size fractions of particulate matter (PM) including PM2.5, PM10, and TSP were determined continuously at hourly intervals from four different sites in Seoul, Korea during the spring of 2001. To learn the effects of wind speed change on PM fractionation, the entire data sets were initially sorted into three particle fractions such as: fine (F: PM2.5), coarse (C: PM10-PM2.5), and giant (G: TSP-PM10). The inter-fraction relationships of PM were then explored by linear regression analysis of the data divided into four wind speed regimes. The results of this analysis, when examined in terms of either relative dominance between different PM fractions (i.e., in terms of their slope values) or strength of correlations, indicate the existence of diverse inter-fraction patterns. Most importantly, the physical influence of wind speed is seen to be reflected most efficiently between fine and coarse particle fractions, as the relative contribution of coarse fraction to the mass concentration of total particles (e.g., PM10) changes proportionally with changes in wind speed. However, such systematic patterns decrease noticeably between fine and giant fractions, as they can be affected more sensitively by such factors as the nature of their sources or the surrounding environmental conditions. The results of our comparative analysis thus confirm that wind speed is a useful barometer to distinguish and predict the behavior of different particle fractions in relation to each other.


Assuntos
Poluentes Atmosféricos/análise , Meio Ambiente , Monitoramento Ambiental/estatística & dados numéricos , Vento , Coreia (Geográfico) , Modelos Lineares , Tamanho da Partícula
15.
Phys Med Biol ; 60(1): 233-52, 2015 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-25489980

RESUMO

Motion-adaptive radiotherapy aims to deliver a conformal dose to the target tumour with minimal normal tissue exposure by compensating for tumour motion in real time. The prediction as well as the gating of respiratory motion have received much attention over the last two decades for reducing the targeting error of the treatment beam due to respiratory motion. In this article, we present a real-time algorithm for predicting and gating respiratory motion that utilizes a model-based and a model-free Bayesian framework by combining them in a cascade structure. The algorithm, named EKF-GPR(+), implements a gating function without pre-specifying a particular region of the patient's breathing cycle. The algorithm first employs an extended Kalman filter (LCM-EKF) to predict the respiratory motion and then uses a model-free Gaussian process regression (GPR) to correct the error of the LCM-EKF prediction. The GPR is a non-parametric Bayesian algorithm that yields predictive variance under Gaussian assumptions. The EKF-GPR(+) algorithm utilizes the predictive variance from the GPR component to capture the uncertainty in the LCM-EKF prediction error and systematically identify breathing points with a higher probability of large prediction error in advance. This identification allows us to pause the treatment beam over such instances. EKF-GPR(+) implements the gating function by using simple calculations based on the predictive variance with no additional detection mechanism. A sparse approximation of the GPR algorithm is employed to realize EKF-GPR(+) in real time. Extensive numerical experiments are performed based on a large database of 304 respiratory motion traces to evaluate EKF-GPR(+). The experimental results show that the EKF-GPR(+) algorithm effectively reduces the prediction error in a root-mean-square (RMS) sense by employing the gating function, albeit at the cost of a reduced duty cycle. As an example, EKF-GPR(+) reduces the patient-wise RMS error to 37%, 39% and 42% in percent ratios relative to no prediction for a duty cycle of 80% at lookahead lengths of 192 ms, 384 ms and 576 ms, respectively. The experiments also confirm that EKF-GPR(+) controls the duty cycle with reasonable accuracy.


Assuntos
Algoritmos , Modelos Teóricos , Movimento , Neoplasias/radioterapia , Radioterapia Assistida por Computador/métodos , Mecânica Respiratória , Teorema de Bayes , Humanos , Neoplasias/fisiopatologia , Redes Neurais de Computação , Distribuição Normal , Interpretação de Imagem Radiográfica Assistida por Computador , Análise de Regressão , Respiração , Máquina de Vetores de Suporte
16.
Int J Radiat Oncol Biol Phys ; 50(2): 335-41, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11380219

RESUMO

OBJECTIVE: To determine the rectal tolerance for developing Grade 2 radiation proctitis after 125I prostate implantation based on the rectal dose-volume histogram. METHODS AND MATERIALS: Two hundred twelve patients with T1-T2 prostate cancer underwent 125I implantation without external beam irradiation. One month after the procedure, all patients underwent CT-based postimplant dosimetry (3-mm abutting slices). The rectal volumes, defined by an inner and outer wall, were determined from 9 mm above the seminal vesicles to 9 mm below the prostate apex. All doses were calculated by TG43 formalism. The prostate prescription dose was 160 Gy. A dose response analysis was undertaken for volumes of rectal tissue receiving a given dose. Dose levels examined were 80 Gy, 100 Gy, 120 Gy, 140 Gy, 160 Gy, 180 Gy, 200 Gy, 220 Gy, and 240 Gy. Grade 2 proctitis was defined as rectal bleeding occurring at least once a week for a minimum period of one month. The risk of proctitis was calculated using actuarial methods. For each dose level, a critical volume cutpoint was chosen to define a low and high volume group of patients. The cutpoint was determined based on two goals: minimizing thep value and finding a < or =5% risk of proctitis in the low volume group. Patients were followed from 12 to 61 months (median: 28 months) after implantation. RESULTS: Twenty-two patients developed Grade 2 proctitis: 14% within the first year, 72% between the first and second year, and 14% during the third year after the implant date. After the third year postimplantation, no cases of proctitis were reported. Proctitis was found to be significantly volume dependent for a given dose. The prescription dose (160 Gy) delivered to < or =1.3 cc of rectal tissue resulted in a 5% rate of proctitis at 5 years vs. 18% for volumes >1.3 cc (p = 0.001). Similar results were found for all doses examined. As the rectal volume receiving the prescription dose (160 Gy) increased, so did the proctitis rate: 0% for < or =0.8 cc, 7% for >0.8-1.3 cc, 8% for >1.3-1.8 cc, 24% for >1.8-2.3 cc, and 25.5% for >2.3cc (p = 0.002). CONCLUSIONS: Rectal dose-volume histogram analysis is a practical and predictive method of assessing the risk of developing Grade 2 proctitis after 125I prostate implantation. Delivered dose should be kept below defined rectal volume thresholds to minimize this risk. This information can allow one to decrease rectal morbidity by modifying prostate implant technique.


Assuntos
Braquiterapia/efeitos adversos , Proctite/etiologia , Lesões por Radiação/etiologia , Idoso , Análise de Variância , Braquiterapia/normas , Relação Dose-Resposta à Radiação , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Proctite/prevenção & controle , Neoplasias da Próstata/radioterapia , Lesões por Radiação/prevenção & controle , Radiometria , Reto/efeitos da radiação
17.
Am J Surg Pathol ; 24(5): 660-7, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10800984

RESUMO

The distribution of smooth muscle fibers in the extrahepatic bile duct (EBD) wall is not well characterized. We analyzed 101 consecutive Whipple's operation specimens and 21 autopsy specimens for the pattern of smooth muscle distribution in EBD using the Masson-trichrome stain and the desmin immunohistochemical stain. The patterns were categorized as continuous, interrupted, scattered, and no muscle layer. EBDs were divided into lower, middle, and upper portions, and the distribution pattern of smooth muscle fibers was analyzed separately in each portion. Because most surgically resected specimens contained the middle and lower EBDs with only a portion of the upper EBD, only the length of the middle and lower EBDs (common bile duct, CBD) was measured. The mean length of CBD in surgically resected specimens was 6.4 +/- 1.4 cm (men, 6.6 +/- 1.3 cm; women, 6.1 +/- 1.5 cm). The mean length of CBD in autopsy specimens was 6.8 +/- 1.0 cm. The predominant patterns of the lower third of the EBD were interrupted (49%) and continuous (43%). The predominant patterns of the middle third of the EBD were scattered (63%) and interrupted (23%). Those of the upper third of the EBD were no muscle fiber (58%) and scattered (39%). In conclusion, different patterns of smooth muscle distribution were observed in different portions of the EBD. Because scattered muscle fibers or no muscle fibers were the main features of the upper third of the EBD, understanding of this pattern may be helpful for assessment of the depth of invasion or staging of carcinoma of the upper third of the EBD.


Assuntos
Ductos Biliares Extra-Hepáticos/anatomia & histologia , Músculo Liso/anatomia & histologia , Ductos Biliares Extra-Hepáticos/metabolismo , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Extra-Hepáticos/cirurgia , Cadáver , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Músculo Liso/metabolismo , Músculo Liso/patologia , Músculo Liso/cirurgia , Doença de Whipple/metabolismo , Doença de Whipple/patologia , Doença de Whipple/cirurgia
18.
J Dermatol ; 27(2): 123-6, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10721662

RESUMO

Keratosis lichenoides chronica (KCL) is a rare dermatosis characterized by a distinctive seborrheic dermatitis-like facial eruption, together with violaceous, papular, and nodular lesions on the extremities and trunk, typically arranged in a linear and reticulate pattern. KLC is resistant to therapy, although spontaneous remission has been reported. We describe a 35-year-old woman with KLC who had the typical features of widespread violaceous, reticulate, and striae-like eruptions with a prominent keratotic component over a nine-year period and who responded well to treatment with calcipotriol ointment. The immunohistochemical profiles are presented in addition to typical histopathologic features.


Assuntos
Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Ceratose/tratamento farmacológico , Erupções Liquenoides/tratamento farmacológico , Administração Cutânea , Adulto , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Doença Crônica , Dermatite Seborreica/patologia , Fármacos Dermatológicos/administração & dosagem , Dermatoses Faciais/patologia , Feminino , Humanos , Ceratose/patologia , Erupções Liquenoides/patologia , Pomadas , Transtornos da Pigmentação/patologia , Remissão Espontânea
19.
Arch Pharm Res ; 21(4): 378-84, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9875463

RESUMO

The processing pathway of G-proteins and Ras family proteins includes the isoprenylation of the cysteine residue, followed by proteolysis of three terminal residues and alpha-carboxyl methyl esterification of the cysteine residue. Farnesylcysteine methyltransferase (FCMT) activity is responsible for the methylation reaction which play a role in the membrane attachment of a variety of cellular proteins. Four kinds of Ras protein (c-Ha-ras, c-N-Ras, c-Ki-Ras, pan-Ras) expression were detected in adenocarcinoma of human tissue by immunohistochemical method, and hematoxylin and eosin staining. The level of Ras protein in human stomach tumor tissues was much higher than in normal and peritumoral regions of the same biopsy samples. The FCMT activities of each cellular fractions were high in mitochondrial fraction followed by microsomal fraction, whole homogenate and cytosolic fraction. The inhibitory effect on FCMT activity on stomach tumor tissue was determined after treatment with 0.25 microM of S-adenosyl-L-homocysteine. S-adenosyl-L-homocysteine inhibited FCMT activity from 11.2% to 30.5%. These results suggested that FCMT might be involved in Ras proteins activity.


Assuntos
Cisteína/análogos & derivados , Proteínas Metiltransferases/metabolismo , Neoplasias Gástricas/enzimologia , Proteínas ras/biossíntese , Adenocarcinoma/enzimologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Cisteína/metabolismo , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Proteínas Metiltransferases/antagonistas & inibidores , S-Adenosil-Homocisteína/farmacologia , Estômago/enzimologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteínas ras/análise , Proteínas ras/metabolismo
20.
J Soc Psychol ; 134(2): 223-8, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8201818

RESUMO

A self-report, attitudinal questionnaire was administered to 1,717 adult Australians between 18 and 40 years old to examine the effects of age and gender on psychological reactance. Analysis yielded a significant age effect: As age increased, the level of reactance tended to decrease. No significant differences in reactance emerged in relation to gender. A significant interaction between age and gender was found.


Assuntos
Envelhecimento/psicologia , Mecanismos de Defesa , Identidade de Gênero , Individualidade , Controle Interno-Externo , Adolescente , Adulto , Austrália , Feminino , Humanos , Masculino , Inventário de Personalidade
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