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1.
Gynecol Oncol ; 159(1): 23-29, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32718729

RESUMO

OBJECTIVES: A pooled analysis of PORTEC-1 & 2 identified substantial lymphovascular space invasion (LVSI) in 4.8% of patients, which predicted for pelvic recurrence, distant metastasis, and overall survival. Our institution implemented the PORTEC three-tier system of LVSI reporting (absent, focal, or substantial). We aimed to quantify the incidence of substantial LVSI in a North American population and to correlate extent of LVSI with lymph node (LN) involvement. METHODS: A retrospective review was conducted on patients with clinically uterine-confined, endometrioid type endometrial cancer who underwent surgical staging and were found to have pT1a-b disease. Binary logistic regression was used to assess predictors of LN involvement (defined as ITC, micrometastases, or macrometastases). RESULTS: In total, 438 patients with pT1a-b disease were identified. In the overall cohort and in the subset meeting PORTEC-1 inclusion criteria (n = 195), no LVSI was present in 67.4% and 50.8%; focal LVSI was present in 16.7% and 24.1%; and substantial LVSI was present in 16.0% and 25.1%, respectively. Among patients who underwent surgical LN assessment (79.2%, n = 347), LNs were involved in 3.3% without LVSI, 7.5% with focal LVSI (OR 2.4), and 15.2% with substantial LVSI (OR 5.3) (p = .005), with a similar trend in the PORTEC-1 cohort. Extent of LVSI correlated with disease burden in LN metastases. CONCLUSION: Our incidence of substantial LVSI was three to five times higher than reported by PORTEC and correlated with LN involvement. This questions the reproducibility of the three-tier LVSI reporting system and emphasizes the need for multi-institutional data outside PORTEC for confirmation of our findings.


Assuntos
Neoplasias do Endométrio/patologia , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Recidiva Local de Neoplasia/epidemiologia , Idoso , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Incidência , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Metástase Linfática/terapia , Vasos Linfáticos/cirurgia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Estados Unidos/epidemiologia
2.
Scand J Med Sci Sports ; 23(3): 271-80, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22093055

RESUMO

This study sought to determine if knowledge regarding the risk for knee injuries and the potential for their prevention is being translated to female adolescent soccer players (13-18 years), their parents, and coaches. Eligible participants in the 2007 indoor soccer season were surveyed to determine their knowledge of the risk for and the potential to prevent knee injuries, and their knowledge of effective prevention strategies, if they felt that injury prevention was possible. Team selection was stratified to be representative of both competitive and recreational level play and age group distributions within the selected soccer association. Of the study subjects, 773/1396 (55.4%) responded to the survey: 408 (53%) players, 292 (38%) parents, and 73 (9%) coaches. Most respondents (538 [71%]) were aware of the risk for knee injury. Coaches and parents were more likely than players to view knee injuries as preventable; however, appropriate prevention strategies were often not identified. Four hundred eighty-four (63.8%) respondents reported that they had never received information on knee injuries. Substantial knowledge gaps regarding knee injury prevention and effective preventative strategies were identified. Given the predominance of knee injuries in female adolescent soccer players, there is an urgent need for knowledge translation of prevention strategies to decrease both incidence and long-term consequences of knee injuries.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Traumatismos do Joelho/prevenção & controle , Futebol/lesões , Adolescente , Coleta de Dados , Feminino , Humanos , Disseminação de Informação , Traumatismos do Joelho/etiologia , Pais , Fatores de Risco
3.
Aust Vet J ; 100(6): 230-235, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35156193

RESUMO

The causative agent of Q fever, Coxiella burnetii, is endemic to Queensland and is one of the most important notifiable zoonotic diseases in Australia. The reservoir species for C. burnetii are classically ruminants, including sheep, cattle and goats. There is increasing evidence of C. burnetii exposure in dogs across eastern and central Australia. The present study aimed to determine if pig-hunting dogs above the Tropic of Capricorn in Queensland had similar rates of C. burnetii exposure to previous serosurveys of companion dogs in rural north-west New South Wales. A total of 104 pig-hunting dogs had serum IgG antibody titres to phase I and phase 2 C. burnetii determined using an indirect immunofluorescence assay test. Almost one in five dogs (18.3%; 19/104; 95% confidence interval 9.6%-35.5%) were seropositive to C. burnetii, with neutered dogs more likely to test positive compared to entire dogs (P = 0.0497). Seropositivity of the sampled pig-hunting dogs was one of the highest recorded in Australia. Thirty-nine owners of the pig-hunting dogs completed a survey, revealing 12.8% (5/39) had been vaccinated against Q fever and 90% (35/39) were aware that both feral pigs and dogs could potentially be sources of C. burnetii. Our findings indicate that pig hunters should be aware of the risk of exposure to Q fever during hunts and the sentinel role their dogs may play in C. burnetii exposure.


Assuntos
Doenças dos Bovinos , Coxiella burnetii , Doenças do Cão , Doenças das Cabras , Febre Q , Doenças dos Ovinos , Doenças dos Suínos , Animais , Bovinos , Cães , Anticorpos Antibacterianos , Austrália , Doenças dos Bovinos/epidemiologia , Doenças do Cão/epidemiologia , Cabras , Febre Q/epidemiologia , Febre Q/veterinária , Queensland/epidemiologia , Estudos Soroepidemiológicos , Ovinos , Suínos , Cães Trabalhadores
4.
Aust Vet J ; 100(8): 360-366, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35607254

RESUMO

Brucellosis is a zoonotic disease with worldwide distribution. Brucella suis serotype 1 is thought to be maintained in the Australian feral pig population, with disease prevalence higher in Queensland (Qld) than New South Wales (NSW). Pig hunting is a popular recreational activity in rural Qld and NSW, with feral pigs in these states thought to carry B. suis. Brucellosis associated with B. suis has been diagnosed in dogs engaged in pig hunting in some of these areas. A total of 431 dogs from northern Qld and north-west NSW were recruited. Two distinct cohorts of clinically healthy dogs were tested - (1) 96 dogs from central, north and far north Queensland actively engaged in pig-hunting and (2) 335 dogs from rural and remote north-west NSW that were primarily companion (non-pig hunting) animals. Serum samples were tested for antibodies to Brucella spp. using the Rose Bengal test (RBT) test followed by complement fixation testing (CFT) for RBT-positive samples. A subset of samples was retested using RBT and CFT. Seven dogs were considered seropositive for B. suis from Qld and remote NSW, including 4/96 (4.2%; 95% CI 3.5% to 4.3%) from the pig-hunting cohort and 3/335 (0.9%) from the regional pet dog cohort. The use of RBT and CFT in dogs to detect anti-Brucella antibodies requires validation. Veterinarians treating pig-hunting dogs and physicians treating pig hunters in central, north and far north Qld need to be aware of the zoonotic risk posed by B. suis to these groups.


Assuntos
Brucella suis , Brucelose , Doenças do Cão , Animais , Animais Selvagens , Austrália , Brucelose/epidemiologia , Brucelose/veterinária , Doenças do Cão/epidemiologia , Cães , Humanos , Caça
5.
J Environ Radioact ; 255: 106968, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36148707

RESUMO

In 2015 and 2016, atmospheric transport modeling challenges were conducted in the context of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) verification, however, with a more limited scope with respect to emission inventories, simulation period and number of relevant samples (i.e., those above the Minimum Detectable Concentration (MDC)) involved. Therefore, a more comprehensive atmospheric transport modeling challenge was organized in 2019. Stack release data of Xe-133 were provided by the Institut National des Radioéléments/IRE (Belgium) and the Canadian Nuclear Laboratories/CNL (Canada) and accounted for in the simulations over a three (mandatory) or six (optional) months period. Best estimate emissions of additional facilities (radiopharmaceutical production and nuclear research facilities, commercial reactors or relevant research reactors) of the Northern Hemisphere were included as well. Model results were compared with observed atmospheric activity concentrations at four International Monitoring System (IMS) stations located in Europe and North America with overall considerable influence of IRE and/or CNL emissions for evaluation of the participants' runs. Participants were prompted to work with controlled and harmonized model set-ups to make runs more comparable, but also to increase diversity. It was found that using the stack emissions of IRE and CNL with daily resolution does not lead to better results than disaggregating annual emissions of these two facilities taken from the literature if an overall score for all stations covering all valid observed samples is considered. A moderate benefit of roughly 10% is visible in statistical scores for samples influenced by IRE and/or CNL to at least 50% and there can be considerable benefit for individual samples. Effects of transport errors, not properly characterized remaining emitters and long IMS sampling times (12-24 h) undoubtedly are in contrast to and reduce the benefit of high-quality IRE and CNL stack data. Complementary best estimates for remaining emitters push the scores up by 18% compared to just considering IRE and CNL emissions alone. Despite the efforts undertaken the full multi-model ensemble built is highly redundant. An ensemble based on a few arbitrary runs is sufficient to model the Xe-133 background at the stations investigated. The effective ensemble size is below five. An optimized ensemble at each station has on average slightly higher skill compared to the full ensemble. However, the improvement (maximum of 20% and minimum of 3% in RMSE) in skill is likely being too small for being exploited for an independent period.


Assuntos
Poluentes Radioativos do Ar , Monitoramento de Radiação , Humanos , Radioisótopos de Xenônio/análise , Poluentes Radioativos do Ar/análise , Monitoramento de Radiação/métodos , Canadá , Cooperação Internacional
6.
Brachytherapy ; 20(1): 104-111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32952053

RESUMO

PURPOSE: The Vienna and Venezia (Elekta) are hybrid intracavitary/interstitial brachytherapy (BT) applicators for cervical cancers unsuitable for intracavitary BT alone to improve target coverage or reduce critical organ dose. There is limited outcome data with the use of these applicators outside published experience of the EMBRACE group. We report feasibility and early outcomes with the use of these hybrid applicators at our institution. METHODS AND MATERIALS: Hybrid applicators were used to treat 61 patients with cervical cancer from November 2011 to December 2019. Indications for hybrid applicator use were involvement of the vagina in 10 patients (16%), residual central or parametrial disease in 46 patients (75%), and a narrow introitus in 5 patients (9%). Toxicities were graded using the CTCAE v4.0. Outcomes were assessed with the Kaplan-Meier method. RESULTS: Median follow-up was 16 months (IQR 9-32 mos). Median HRCTV volume was 31.6 cm3 (IQR 25-48 cm3). Median HRCTV D90 was 86.1 Gy (IQR 84.3-88.0 Gy). In 54 patients with follow-up PET/CT at 3 months, complete initial imaging response locally was seen in 46 patients.Estimated 12-month Kaplan-Meier overall survival, locoregional control, distant control, and recurrence-free survival estimates were 86.9%, 80.6%, 73.8%, and 65.9%, respectively. The 12-month incidence of Grade 3+ GI/GU chronic toxicities was 5.7%, consisting of vesicovaginal fistula, rectovaginal fistula, and ureterovesical fistula. CONCLUSIONS: Our single-institution data support the use of the hybrid applicators, as an alternative to traditional BT applicators when clinically warranted. Use of hybrid applicators is feasible with adequate coverage of disease in the vagina and parametrium.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Braquiterapia/métodos , Quimiorradioterapia , Feminino , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/radioterapia
7.
Clin Oncol (R Coll Radiol) ; 33(3): e110-e117, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32919862

RESUMO

AIMS: There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy. MATERIALS AND METHODS: Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm. RESULTS: Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%). CONCLUSION: This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes.


Assuntos
Quimiorradioterapia , Neoplasias do Endométrio , Neoplasias do Endométrio/cirurgia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Histerectomia , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia
8.
Science ; 293(5538): 2224-7, 2001 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-11567131

RESUMO

We combined coherent nonlinear optical spectroscopy with nano-electron volt energy resolution and low-temperature near-field microscopy with subwavelength resolution (

9.
Curr Oncol ; 26(2): e266-e269, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31043836

RESUMO

Charcot-Marie-Tooth (cmt) disease is the most common form of inherited neuropathy. Core features include peripheral neuropathy and secondary axonal degeneration, with a noted distal predominance of limb-muscle wasting, weakness, and sensory loss. Given the significant prevalence of cmt, superimposed neoplastic disease can be encountered within this patient population. Malignancies that are treated with vincristine (a microtubule-targeting agent), even at low doses as part of standard treatment, pose a significant challenge for patients with cmt. Here, we present the case of a child with cmt who was successfully treated for medulloblastoma without vincristine, a standard drug used for treatment of that disease, to avoid the risk of severe debilitating neuropathy. This report is the first of a patient successfully treated for medulloblastoma without vincristine.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Cerebelares/terapia , Doença de Charcot-Marie-Tooth/tratamento farmacológico , Quimiorradioterapia , Meduloblastoma/tratamento farmacológico , Carboplatina/uso terapêutico , Pré-Escolar , Cisplatino/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Lomustina/uso terapêutico , Indução de Remissão
10.
Aust Vet J ; 96(12): 475-480, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30478844

RESUMO

OBJECTIVE: To evaluate the extent, costs, demands and expectations of Australian veterinary practices in the treatment of wildlife, to identify potential risks to animal welfare based on the current situation and to propose recommendations for improvements. METHODS: A survey was sent to all veterinary practices across Australia identified through the website Yellow Pages®. The survey was designed as a cross-sectional study. Data were collected using an online self-completed questionnaire and analysed using IBM SPSS 19.0. RESULTS: Of the 902 veterinary practices contacted, 132 (14.6%) completed the questionnaire. Most practices (82%) saw less than 10 wildlife patients per week, with birds and marsupials most commonly admitted. Vehicular trauma, trauma (other) and predation made up the majority (82%) of presentations. However, wildlife cases were only examined immediately upon presentation in 20% of practices, with 74% reporting they only attended to wildlife whenever they had spare time. The majority (90%) of veterinary practices never or rarely received reimbursement for their wildlife work, indicating most is performed pro bono. Several barriers to treatment were highlighted, including time and a lack of knowledge/skills. CONCLUSION: Private veterinary practices play a more significant role in wildlife treatment than has been previously thought. The effect of perceived barriers on willingness to treat wildlife requires further research. Further investigation into educational resources to aid veterinary assessment of wildlife should also be considered.


Assuntos
Animais Selvagens , Medicina Veterinária/estatística & dados numéricos , Ferimentos e Lesões/veterinária , Adolescente , Adulto , Idoso , Bem-Estar do Animal , Animais , Animais Selvagens/lesões , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Médicos Veterinários , Medicina Veterinária/economia , Ferimentos e Lesões/economia , Ferimentos e Lesões/epidemiologia , Adulto Jovem
11.
Am J Trop Med Hyg ; 50(6 Suppl): 97-115, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7912908

RESUMO

An integrated approach for the control of mosquitoes and the diseases they transmit will better enable sustainable control while helping to circumvent some of the problems associated with the use of conventional insecticides. Environmental methods and biological control are alternatives to chemical control and are key components of the integrated strategy. The use of vertebrate and invertebrate predators and entomopathogens as biological control agents and their role in integrated control programs is reviewed with emphasis on fish, Toxorhynchites mosquitoes, Notonecta species, predatory copepods, entomopathogenic bacteria, and the fungus Lagenidium giganteum. The successful implementation of these organisms will depend on an in-depth understanding of the ecology of both the targeted species and the biological control agents to be used. Thorough geographic reconnaissance will also be essential for the successful abatement of pest and vector mosquitoes. The success and sustainability of future programs, especially in developing countries, will rely not only on the use of the most appropriate technologies but also on the direct participation of the affected communities. Possible undesirable effects of biological control are also reviewed.


Assuntos
Controle de Doenças Transmissíveis/métodos , Culicidae , Insetos Vetores , Controle Biológico de Vetores , Animais , Artrópodes/fisiologia , Bacillus/fisiologia , Serviços de Saúde Comunitária , Crustáceos/fisiologia , Humanos , Oomicetos/fisiologia
12.
J Dent Res ; 82(6): 443-8, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12766196

RESUMO

This investigation sets out to mimic protein-crystal interaction during biomineralization with the use of artificial proteins (dendrimers). It is hypothesized that these interactions depend on the surface charge of hydroxyapatite crystals. This was investigated with the use of dendrimers with capped surfaces of different charges to probe the surface. We used AFM images of crystal-bound dendrimers to determine the distribution of the surface charge, and its magnitude was correlated to the binding capacity of the dendrimers to the surface. The binding capacity of the dendrimers in ascending order at pH 7.4 was: acetamide-capped, -NHC(O)CH3, neutral charge; carboxylic-acid-capped, -COOH, negative charge; and amine-capped, -NH2, positive charge. AFM images of the crystals showed dendrimers spaced equally along the crystal. The results suggest that the crystal surface has alternating bands of positive and negative charge or a differential charge array, i.e., alternating bands of either more or less positive or negative charge.


Assuntos
Materiais Biocompatíveis/química , Durapatita/química , Poliaminas/química , Acetamidas/química , Aminas/química , Sítios de Ligação , Materiais Biomiméticos/química , Ácidos Carboxílicos/química , Cristalização , Cristalografia , Dendrímeros , Eletroquímica , Humanos , Concentração de Íons de Hidrogênio , Propriedades de Superfície
13.
Oecologia ; 90(4): 474-482, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28313566

RESUMO

The surface cover produced by aquatic macrophytes is the primary habitat for immature stages (eggs, larvae, and pupae) ofAnopheles mosquitoes. We hypothesized that both the abundance of immatureAnopheles and the recruitment ofAnopheles (from oviposition or larval movement) is positively related to the amount of surface cover present. Field sampling documented a positive correlation betweenAnopheles egg and larval abundance and the amount of vegetative cover present (measured as the number of emergent stems m-2) in monospecific beds ofMyriophyllum aquaticum in a California, USA, wetland. Experiments conducted to determine the influence ofMyriophyllum stem density on selection of oviposition sites by adultAnopheles females clearly indicate that oviposition rate (eggs m-2 d-1) increases as stem density increases from 0 to 1000 stems m-2 but decreases as stem density approaches 2000 stems m-2. In selecting microhabitats,Anopheles larvae preferred patches with high stem densities over patches with few or no plant stems; this preference correlates with differences in habitat quality (e.g., increased refuge from predation and enriched food sources). The optimal habitat for anopheline mosquitoes apparently occurs above a threshold plant density of approximately 500Myriophyllum stems m-2. Habitat heterogeneity produced by variability in the distribution and structure of aquatic vegetation strongly influences the local distribution and abundance of anopheline mosquitoes.

14.
Talanta ; 33(11): 875-82, 1986 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18964219

RESUMO

A low-power helium microwave-induced plasma, sustained in a cylindrical TM(010) cavity, has been used with sample introduction from a graphite furnace. An end-on optical configuration was employed to monitor both atomic and ionic emission from Cl, I, S and P. The operating parameters were optimized with respect to the nature of the plasma background response, the limits of detection, and the shapes and linearity ranges of the log-log analytical working curves. Possible applications were evaluated by determining iodine in milk and analysing a multi-component mixture of sulphur compounds.

15.
J Am Mosq Control Assoc ; 5(4): 579-85, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2614408

RESUMO

Emergent or submergent macrophytes can enhance the survival of Anopheles larvae by providing favorable microhabitat and refuge from predation. The relationships among the amount of aquatic macrophyte cover, the density of Gambusia affinis, and survivorship of Anopheles freeborni larvae were tested experimentally. Larval survivorship was positively related to amount of plant cover and negatively related to Gambusia density. Larval survivorship was lowest in treatments with low plant cover and high fish density (0-15% survivorship) and highest in treatments with high plant cover and no fish (41-76% survivorship). Similar patterns of larval survivorship were found in enclosure experiments conducted at 3 sites, using 3 species of aquatic macrophytes (Potamogeton pectinatus, Myriophyllum aquaticum and M. spicatum).


Assuntos
Anopheles , Ecologia , Animais , California , Ciprinodontiformes , Larva , Plantas , Densidade Demográfica , Comportamento Predatório , Água
16.
J Am Acad Psychiatry Law ; 25(2): 173-81, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9213289

RESUMO

The advent of novel antipsychotic medications has raised treatment expectations for patients with severe mental illness. In this regard, clozapine has been particularly effective in reducing aggressive behavior in patients with schizophrenia. This study compared the efficacy of risperidone and conventional antipsychotic medications in the management of hostile patients. Improvements in the level of aggression were evident over time in both treatment groups, and a similar response between risperidone and typical antipsychotics was observed. Future studies should address the relative role of typical antipsychotics, adjunctive agents, and novel antipsychotic medications in the pharmacological management of persistent aggression in patients with schizophrenia.


Assuntos
Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Adulto , Análise de Variância , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ohio , Psicofarmacologia , Restrição Física , Estudos Retrospectivos , Isolamento Social , Resultado do Tratamento
17.
Oncogene ; 33(35): 4433-41, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24077291

RESUMO

Hypoxic regions are frequent in glioblastoma (GBM), the most common type of malignant adult brain tumor, and increased levels of tumor hypoxia have been associated with worse clinical outcomes. To unmask genes important in hypoxia, we treated GBM neurospheres in hypoxia and identified monocarboxylate transporter-4 (MCT4) as one of the most upregulated genes. To investigate the clinical importance of MCT4 in GBM, we examined clinical outcomes and found that MCT4 overexpression is associated with shorter patient survival. Consistent with this, MCT4 upregulation correlated with the aggressive mesenchymal subset of GBM, and MCT4 downregulation correlated with the less aggressive G-CIMP (Glioma CpG Methylator Phenotype) subset of GBM. Immunohistochemical analysis of tissue microarrays confirmed that MCT4 protein levels were increased in high-grade as compared with lower-grade astrocytomas, further suggesting that MCT4 is a clinically relevant target. To test the requirement for MCT4 in vitro, we transduced neurospheres with lentiviruses encoding short-hairpin RNAs (shRNAs) against MCT4, resulting in growth inhibition of 50-80% under hypoxia in two lines. MCT4 knockdown was associated with a decreased percentage of cells expressing the stem-cell marker CD133 and increased apoptotic fraction. We also found that flow-sorted CD133-positive cells had almost sixfold higher MCT4 levels than CD133-negative cells, suggesting that the stem-like population might have a greater requirement for MCT4. Most importantly, MCT4 silencing also slowed GBM intracranial xenograft growth in vivo. Interestingly, whereas MCT4 is a well-characterized lactate exporter, we found that both intracellular and extracellular lactate levels did not change following MCT4 silencing, suggesting a novel lactate export-independent mechanism for growth inhibition in GBMs. To identify this potential mechanism, we performed microarray analysis on control and shMCT4-expressing neurospheres and found a dramatic reduction in the expression of multiple Hypoxia-Inducible Factor (HIF)-regulated genes following MCT4 knockdown. The overall reduction in HIF transcriptional response was further validated using a hypoxia response element (HRE)-dependent green-fluorescent protein (GFP) reporter line.


Assuntos
Hipóxia Celular , Glioblastoma/patologia , Fator 1 Induzível por Hipóxia/metabolismo , Ácido Láctico/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioblastoma/metabolismo , Humanos , Fator 1 Induzível por Hipóxia/genética , Camundongos Nus , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Musculares/genética , Neoplasias Experimentais , Células-Tronco Neoplásicas/imunologia , Prognóstico
18.
Oncogenesis ; 3: e96, 2014 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-24686726

RESUMO

Dysregulation of Sonic hedgehog (Shh) signaling has been implicated in glioma pathogenesis. Yet, the role of this pathway in gliomagenesis remains controversial because of the lack of relevant animal models. Using the cytokeratin 5 promoter, we ectopically expressed a constitutively active zebrafish Smoothened (Smoa1) in neural progenitor cells and analyzed tumorigenic capacity of activated Shh signaling in both transient and stable transgenic fish. Transient transgenic fish overexpressing Smoa1 developed retinal and brain tumors, suggesting smoa1 is oncogenic in the zebrafish central nervous system (CNS). We further established stable transgenic lines that simultaneously developed optic pathway glioma (OPG) and various retinal tumors. In one of these lines, up to 80% of F1 and F2 fish developed tumors within 1 year of age. Microarray analysis of tumor samples showed upregulated expression of genes involved in the cell cycle, cancer signaling and Shh downstream targets ptc1, gli1 and gli2a. Tumors also exhibited specific gene signatures characteristic of radial glia and progenitor cells as transcriptions of radial glia genes cyp19a1b, s100ß, blbp, gfap and the stem/progenitor genes nestin and sox2 were significantly upregulated. Overexpression of GFAP, S100ß, BLBP and Sox2 was confirmed by immunofluorescence. We also detected overexpression of Mdm2 throughout the optic pathway in fish with OPG, therefore implicating the Mdm2-Tp53 pathway in glioma pathogenesis. In conclusion, we demonstrate that activated Shh signaling initiates tumorigenesis in the zebrafish CNS and provide the first OPG model not associated with neurofibromatosis 1.

19.
J Environ Radioact ; 126: 1-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23917155

RESUMO

The verification of the Comprehensive Nuclear-Test Ban Treaty (CTBT) relies amongst other things on the continuous and worldwide monitoring of radioxenon. The characterization of the existing and legitimate background, which is produced mainly by nuclear power plants and isotope production facilities, is of high interest to improve the capabilities of the monitoring network. However, the emissions from legitimate sources can usually only be estimated. For this paper historic source terms of (133)Xe emissions from the isotope production facility at ANSTO, Sydney, Australia, have been made available in a daily resolution. Based on these high resolution data, different source term sets with weekly, monthly and yearly time resolution have been compiled. These different sets are then applied together with atmospheric transport modelling (ATM) to predict the concentration time series at two radioxenon monitoring stations. The results are compared with each other in order to examine the improvement of the prediction capability depending on the used time resolution of the most dominant source term in the region.


Assuntos
Poluentes Radioativos do Ar/análise , Centrais Nucleares , Monitoramento de Radiação , Radioisótopos de Xenônio/análise , Modelos Teóricos
20.
Oncogene ; 31(9): 1130-42, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21804603

RESUMO

The stromal microenvironment has key roles in prostate development and cancer, and cancer-associated fibroblasts (CAFs) stimulate tumourigenesis via several mechanisms including the expression of pro-tumourigenic factors. Mesenchyme (embryonic stroma) controls prostate organogenesis, and in some circumstances can re-differentiate prostate tumours. We have applied next-generation Tag profiling to fetal human prostate, normal human prostate fibroblasts (NPFs) and CAFs to identify molecules expressed in prostatic stroma. Comparison of gene expression profiles of a patient-matched pair of NPFs vs CAFs identified 671 transcripts that were enriched in CAFs and 356 transcripts whose levels were decreased, relative to NPFs. Gene ontology analysis revealed that CAF-enriched transcripts were associated with prostate morphogenesis and CAF-depleted transcripts were associated with cell cycle. We selected mRNAs to follow-up by comparison of our data sets with published prostate cancer fibroblast microarray profiles as well as by focusing on transcripts encoding secreted and peripheral membrane proteins, as well as mesenchymal transcripts identified in a previous study from our group. We confirmed differential transcript expression between CAFs and NPFs using QrtPCR, and defined protein localization using immunohistochemistry in fetal prostate, adult prostate and prostate cancer. We demonstrated that ASPN, CAV1, CFH, CTSK, DCN, FBLN1, FHL1, FN, NKTR, OGN, PARVA, S100A6, SPARC, STC1 and ZEB1 proteins showed specific and varied expression patterns in fetal human prostate and in prostate cancer. Colocalization studies suggested that some stromally expressed molecules were also expressed in subsets of tumour epithelia, indicating that they may be novel markers of EMT. Additionally, two molecules (ASPN and STC1) marked overlapping and distinct subregions of stroma associated with tumour epithelia and may represent new CAF markers.


Assuntos
Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Próstata/metabolismo , Neoplasias da Próstata/genética , Adulto , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Feto , Regulação da Expressão Gênica , Humanos , Masculino , Próstata/citologia , Neoplasias da Próstata/metabolismo , Transporte Proteico , Proteoma/metabolismo , Reprodutibilidade dos Testes , Células Estromais/metabolismo , Antígenos Thy-1/metabolismo , Transcriptoma , Microambiente Tumoral/genética
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