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1.
Int J Mol Sci ; 24(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36982943

RESUMO

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual's cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.


Assuntos
Anti-Hipertensivos , Neoplasias Colorretais , Humanos , Irbesartana/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Linfócitos T CD8-Positivos/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia
2.
ESMO Open ; 7(6): 100647, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36455506

RESUMO

BACKGROUND: We analyzed the FGF/FGFR and co-alteration cancer landscape, hypothesizing that combination therapy might be useful in the presence of co-drivers. MATERIALS AND METHODS: We describe FGF/FGFR-altered pathways, prognosis, and co-alterations [cBioPortal (N = 7574)] and therapeutic outcomes [University of California San Diego Molecular Tumor Board (MTB) (N = 16)]. RESULTS: Patients whose cancers harbored FGF/FGFR alterations (N = 1074) versus those without them (N = 6500) had shorter overall survival (OS) (median: 23.1 versus 26.4 months, P = 0.038) (cBioPortal). Only 6.1% (65/1074 patients) had no pathogenic co-alterations accompanying FGF/FGFR axis abnormalities. The most frequently co-altered pathways/genes involved: TP53 (70%); cell cycle (58%); PI3K (55%); and receptor tyrosine kinases and mitogen-activated protein kinase (MAPK) (65%). Harboring alterations in both FGF/FGFR and in the TP53 pathway or in the cell cycle pathway correlated with shorter OS (versus FGF/FGFR-altered without those co-altered signals) (P = 0.0001 and 0.0065). Four of 16 fibroblast growth factor receptor (FGFR) inhibitor-treated patients presented at MTB attained durable partial responses (PRs) (9, 12, 22+, and 52+ months); an additional two, stable disease (SD) of ≥6 months (13+ and 15 months) [clinical benefit rate (SD ≥ 6 months/PR) = 38%]. Importantly, six patients with cyclin pathway co-alterations received the CDK4/6 inhibitor palbociclib (75 mg p.o. 3 weeks on, 1 week off) and the multikinase FGFR inhibitor lenvatinib (10 mg p.o. daily); three (50%) achieved a PR [9 (ovarian), 12 (biliary), and 52+ months (osteosarcoma)]. Palbociclib and lenvatinib were tolerated well. CONCLUSIONS: FGF/FGFR alterations portend a poor prognosis and are frequently accompanied by pathogenic co-aberrations. Malignancies harboring co-alterations that activate both cyclin and FGFR pathways can be co-targeted by CDK4/6 and FGFR inhibitors.


Assuntos
Neoplasias , Quinolinas , Humanos , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Compostos de Fenilureia , Neoplasias/tratamento farmacológico , Neoplasias/genética
3.
Curr Oncol ; 27(Suppl 3): S144-S151, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33343208

RESUMO

Locoregional therapies (lrts) play an important role in the treatment of hepatocellular carcinoma (hcc), with the aim of increasing overall survival while preserving liver function. Various forms of lrt are available, and choosing the best one depends on technical aspects, liver morphology, tumour biology, and the patient's symptoms. The purpose of the present review article is to provide an overview of the current evidence relating to the use of percutaneous ablation, transarterial chemoembolization, and transarterial radioembolization for the curative or palliative treatment of hcc. Special situations are also reviewed, including the combined use of systemic therapy and lrt, indications and techniques for bridging to transplant and downstaging, and the use of lrt to treat patients with hcc and macrovascular invasion.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Terapia Combinada , Humanos , Neoplasias Hepáticas/cirurgia
4.
Br J Oral Maxillofac Surg ; 57(3): 268-270, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30898454

RESUMO

Cemento-osseous dysplasia is a well-known condition in which healthy bone becomes sclerotic. Hypovascularity of the lesion (caused by cementum-like deposits) increases the risk of secondary infection and osteomyelitis, which can also be induced by the placement of implants.


Assuntos
Implantes Dentários , Displasia Fibrosa Óssea , Tumores Odontogênicos , Osteomielite , Osso e Ossos , Implantes Dentários/efeitos adversos , Humanos , Tumores Odontogênicos/cirurgia , Osteomielite/etiologia
5.
Psychooncology ; 27(1): 53-60, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28075038

RESUMO

BACKGROUND: Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof-of-concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors. METHODS: Women, aged 40 to 65 years, postmenopausal, stages I to IIIA breast cancer, and who self-reported cognitive dysfunction following chemotherapy treatment, were recruited and randomized to a 24-week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self-report measures of the impact of cognitive issues on quality of life (Functional Assessment of Cancer Therapy-Cognitive version 3), objective neuropsychological testing, and functional magnetic resonance imaging at baseline and 24 weeks. RESULTS: Compared to CON, EX had a reduced time to complete a processing speed test (trail making test-A) (-14.2 seconds, P < .01; effect size 0.35). Compared to CON, there was no improvement in self-reported cognitive function and effect sizes were small. Interestingly, lack of between-group differences in Stroop behavioral performance was accompanied by functional changes in several brain regions of interest in EX compared to CON at 24 weeks. CONCLUSION: These findings provide preliminary proof-of-concept results for the potential of aerobic exercise to improve cancer-related cognitive impairment and will serve to inform the development of future trials.


Assuntos
Disfunção Cognitiva/terapia , Exercício Físico , Pós-Menopausa , Sobreviventes , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/psicologia , Terapia por Exercício , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudo de Prova de Conceito , Qualidade de Vida , Autorrelato , Resultado do Tratamento
6.
Int J Tuberc Lung Dis ; 21(10): 1169-1175, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28911363

RESUMO

BACKGROUND: The nodular bronchiectatic (NB) form of non-tuberculous mycobacteria (NTM) lung disease usually involves the right middle lobe (RML) and the left upper lobe lingular segment. However, the reason underlying this preference is not known. METHODS: Fifty patients with NB NTM lung disease who had both positive NTM culture(s) and NB lesions in the RML or lingular segment on computed tomography (CT) of the chest, and 100 healthy subjects matched for sex, age, height and body weight with normal chest CT, were randomly selected. Using reconstructed curved multiplanar reformation (MPR) images, the lengths, diameters and angles of the RML and lingular bronchi were measured. RESULTS: Of the 150 individuals, 64% were female; the mean age was 55 years. The angles of the bronchi were significantly more acute in patients than in healthy subjects, both in the RML (patients, mean 46.75° ± standard deviation 8.87° vs. healthy subjects, mean 51.73° ± 7.76°; P = 0.001) and in the lingular segments (patients, mean 26.94° ± 8.16° vs. healthy subjects, mean 34.65° ± 9.75°; P < 0.001). In addition, the angles of the bronchi in the involved segments were more acute than those in the non-involved segments, both in the RML and the lingular segments. There were no differences in the lengths and bronchi diameters between groups. CONCLUSIONS: An acute angle (obtuse slope) of RML/lingular bronchi could be an anatomical risk factor for NB NTM lung disease.


Assuntos
Brônquios/diagnóstico por imagem , Bronquiectasia/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Adulto , Idoso , Brônquios/microbiologia , Bronquiectasia/microbiologia , Estudos de Casos e Controles , Feminino , Humanos , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/isolamento & purificação , Fatores de Risco , Tomografia Computadorizada por Raios X
7.
Curr Oncol ; 23(5): 329-333, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27803597

RESUMO

BACKGROUND: Therapy with anti-epidermal growth factor receptor (egfr) monoclonal antibody improves outcomes for patients with metastatic colorectal cancer (mcrc) in the first-, second-, and third-line trial settings. In British Columbia, the use of egfr inhibitors (egfris) is confined to third-line therapy, which might lower the proportion of patients who receive this therapy. The objective of the present study was to describe egfri treatment patterns when those agents are limited to the third-line setting. The results will inform decisions about optimal use of egfri agents, including earlier in the course of therapy for metastatic disease. METHODS: All patients with newly diagnosed mcrc who were referred to BC Cancer Agency clinics in 2009 were included in the study. Prognostic and treatment information was prospectively collected; KRAS test results were determined by chart review. RESULTS: The study included 443 patients with a median age of 66 years. For the 321 patients who received systemic therapy, median survival was 22.3 months. Of the 117 patients who were treated with 5-fluorouracil, oxaliplatin, and irinotecan, and who were potentially eligible for egfri therapy, 90% (105 patients) were tested for KRAS status. Of the 60 patients with KRAS wild-type tumours, 82% (49 patients) received egfri therapy. CONCLUSIONS: When egfri therapy is limited to the third-line setting, only a small proportion of patients receive such therapy, with death and poor performance status preventing its use in the rest. Availability of egfri in earlier lines of therapy could increase the proportion of patients treated with all active systemic agents.

8.
Transplant Proc ; 48(7): 2407-2411, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27742310

RESUMO

BACKGROUND: Donor shortage for kidney transplantation may increase the number of expanded-criteria living donors (ECLDs). We investigated recent trends for ECLD use and the long-term outcomes of living kidney donors. METHODS: We retrospectively analyzed medical records of 1,144 living kidney donors who donated at the Seoul National University Hospital from 1993 to 2015. The expanded criteria for living donation allow the following: age ≥60 years, body mass index >30 kg/m2, history of hypertension, estimated glomerular filtration rate <80 mL/min, proteinuria or microscopic hematuria, and fasting glucose >100 mg/dL. RESULTS: The mean age of donors was 40.7 ± 10.8 years, and there were 600 women (52.4%). A total of 466 donors (40.7%) met the ECLD criteria, and the proportion of ECLDs increased over time. Only 5 donors died after donation over a median follow-up of 7 years. No donor developed end-stage renal disease (ESRD). A urine protein-creatinine ratio ≥0.3 g/gCr was found in 14 patients and was more common in the ECLDs than in the standard-criteria living donors. The follow-up loss rate of donors was 59.3% at 5 years. CONCLUSIONS: Both mortality and ESRD were very rare in carefully selected living kidney donors. However, living donors should be followed more carefully, because the follow-up loss rate was very high and ECLDs are increasingly used.


Assuntos
Taxa de Filtração Glomerular , Falência Renal Crônica/epidemiologia , Transplante de Rim , Doadores Vivos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto , Glicemia , Definição da Elegibilidade , Feminino , Seguimentos , Intolerância à Glucose/epidemiologia , Hematúria/epidemiologia , Humanos , Hipertensão/epidemiologia , Falência Renal Crônica/etiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Mortalidade , Obesidade/epidemiologia , Complicações Pós-Operatórias/etiologia , Proteinúria/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos
10.
11.
Transplant Proc ; 48(3): 844-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27234749

RESUMO

BACKGROUND: As patient and graft survival rates have been improving after kidney transplantation, health-related quality of life (HR-QOL) has become an important indicator of effective treatment. This study aimed to evaluate changes in HR-QOL after kidney transplantation. MATERIALS AND METHODS: The KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) is a multicenter, observational, 9-year, cohort study. The HR-QOL of patients in the KNOW-KT study was assessed before transplantation and 2 years after transplantation using the Kidney Disease Quality of Life Short Form (KDQOL-SF) including chronic kidney disease targeted area and the Medical Outcome Study 36-item Short Form Health Survey (SF-36). Multivariate linear regression was used to identify significant factors associated with follow-up QOL scores. RESULTS: A total of 175 patients from 8 centers were analyzed. All QOL scores including the total QOL score, chronic kidney disease targeted score, and SF-36 at the 2-year follow-up were significantly increased compared to baseline values. Both physical and mental scale scores were improved after transplantation. CONCLUSION: The QOL scores for both the mental and physical scales were improved at 2 years after kidney transplantation. High glomerular filtration rate at 2 years, high baseline QOL score, and low body mass index were associated with good follow-up QOL scores. Kidney transplantation for an Asian population with end-stage renal disease can result in better QOL as well as better patient and graft survival.


Assuntos
Seguimentos , Transplante de Rim , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , República da Coreia , Adulto Jovem
12.
Ann Oncol ; 27(5): 801-6, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27022066

RESUMO

BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer. RESULTS: Integrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin-angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response. CONCLUSIONS: This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.


Assuntos
Compostos de Bifenilo/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Medicina de Precisão , Tetrazóis/administração & dosagem , Fator de Transcrição AP-1/genética , Idoso , Antagonistas de Receptores de Angiotensina/administração & dosagem , Angiotensinas/antagonistas & inibidores , Angiotensinas/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Biologia Computacional , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Irbesartana , Metástase Neoplásica , Sistema Renina-Angiotensina/efeitos dos fármacos , Transcriptoma/genética
13.
Curr Oncol ; 23(6): e571-e575, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28050146

RESUMO

BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. RESULTS: In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation; and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. SUMMARY: We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.

14.
J Med Econ ; 19(2): 135-47, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26442575

RESUMO

OBJECTIVE: Clinical practice guidelines support the use of the epidermal growth factor receptor (EGFR) inhibitors panitumumab and cetuximab for the treatment of metastatic colorectal cancer (mCRC) after failure of other chemotherapy regimens, based on significant clinical benefits in patients with wild-type KRAS. The purpose of the analysis was to compare provincial hospital costs when using panitumumab vs cetuximab with or without irinotecan in this patient population using a Net Impact Analysis (NIA) approach. METHODS: The NIA determined the total per patient cost of the reimbursed regimens of panitumumab vs cetuximab in British Columbia, Alberta, Manitoba, Ontario, and Québec. Utilization of healthcare resources related to EGFR inhibitor infusions, follow-up monitoring, and treatment of adverse events (AEs) were also included. Healthcare resource use including drugs, medical supplies, laboratory testing, oncology infusion time, and healthcare professionals' time was obtained through expert consultation and the use was then multiplied by the province-specific cost of each resource. Numerous sensitivity analyses were conducted. RESULTS: Based on the dosing regimens in place in each province, the total annual per patient cost of panitumumab ranged from $22,203-$32,600, while the total annual per patient cost of cetuximab treatment varied from $30,321-$40,908. Treatment with panitumumab resulted in lower costs in all cost categories including drug acquisition, infusion preparation/administration, patient monitoring, and AE management. Per patient savings with panitumumab ranged from a low of $3815 in British Columbia to a high of $10,603 in Ontario. In sensitivity analyses, panitumumab remained cost saving in all scenarios where the savings ranged from $150-$16,006 per patient. CONCLUSIONS: Treating chemorefractory mCRC patients with panitumumab rather than cetuximab reduced healthcare resource costs. Provincial healthcare savings achieved with the use of panitumumab could potentially be re-allocated to other cancer treatments, although further study would be needed to validate this assumption.


Assuntos
Anticorpos Monoclonais/economia , Antineoplásicos/economia , Cetuximab/economia , Neoplasias Colorretais/tratamento farmacológico , Análise Custo-Benefício , Metástase Neoplásica/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Canadá , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Panitumumabe
15.
Brain Behav Immun ; 52: 11-17, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26318411

RESUMO

Stress-induced impairments of mucosal immunity may increase susceptibility to infectious diseases. The present study investigated the association of perceived stress, depressive symptoms, and loneliness with salivary levels of secretory immunoglobulin A (S-IgA), the subclasses S-IgA1, S-IgA2, and their transporter molecule Secretory Component (SC). S-IgA/SC, IgA1/SC and IgA2/SC ratios were calculated to assess the differential effects of stress on immunoglobulin transport versus availability. This study involved 113 university students, in part selected on high scores on the UCLA Loneliness Scale and/or the Beck Depression Inventory. Stress levels were assessed using the Perceived Stress Scale. Unstimulated saliva was collected and analysed for total S-IgA and its subclasses, as well as SC and total salivary protein. Multiple linear regression analyses, adjusted for gender, age, health behaviours, and concentration effects (total protein) revealed that higher perceived stress was associated with lower levels of IgA1 but not IgA2. Perceived stress, loneliness and depressive symptoms were all associated with lower IgA1/SC ratios. Surprisingly, higher SC levels were associated with loneliness and depressive symptoms, indicative of enhanced transport activity, which explained a lower IgA1/SC ratio (loneliness and depression) and IgA2/SC ratio (depression). This is the first study to investigate the effects of protracted psychological stress across S-IgA subclasses and its transporter SC. Psychological stress was negatively associated with secretory immunity, specifically IgA1. The lower immunoglobulin/transporter ratio that was associated with higher loneliness and depression suggested a relative immunoglobulin depletion, whereby availability was not keeping up with enhanced transport demand.


Assuntos
Imunoglobulina A Secretora/imunologia , Estresse Psicológico/imunologia , Adulto , Estudos de Coortes , Suscetibilidade a Doenças , Feminino , Humanos , Imunidade nas Mucosas/imunologia , Infecções/imunologia , Masculino , Saliva/imunologia , Componente Secretório/metabolismo , Adulto Jovem
16.
Clin Neurophysiol ; 127(1): 369-378, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25868929

RESUMO

OBJECTIVE: Many breast cancer survivors (BCS) report cognitive problems following chemotherapy, yet controversy remains concerning which cognitive domains are affected. This study investigated a domain crucial to daily function: the ability to maintain attention over time. METHODS: We examined whether BCS who self-reported cognitive problems up to 3 years following cancer treatment (n=19) performed differently from healthy controls (HC, n=12) in a task that required sustained attention. Participants performed a target detection task while periodically being asked to report their attentional state. Electroencephalogram was recorded during this task and at rest. RESULTS: BCS were less likely to maintain sustained attention during the task compared to HC. Further, the P3 event-related potential component elicited by visual targets during the task was smaller in BCS relative to HC. BCS also displayed greater neural activity at rest. CONCLUSIONS: BCS demonstrated an abnormal pattern of sustained attention and resource allocation compared to HC, suggesting that attentional deficits can be objectively observed in breast cancer survivors who self-report concentration problems. SIGNIFICANCE: These data underscore the value of EEG combined with a less traditional measure of sustained attention, or attentional states, as objective laboratory tools that are sensitive to subjective complaints of chemotherapy-related attentional impairments.


Assuntos
Antineoplásicos/efeitos adversos , Atenção/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/fisiopatologia , Eletroencefalografia/efeitos dos fármacos , Adulto , Idoso , Atenção/fisiologia , Transtornos Cognitivos/diagnóstico , Eletroencefalografia/tendências , Potenciais Evocados P300/efeitos dos fármacos , Potenciais Evocados P300/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Autorrelato , Fatores de Tempo
17.
J Appl Microbiol ; 120(2): 379-87, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26606545

RESUMO

AIMS: To demonstrate and characterize a portable lysis apparatus for rapid single-step bacterial DNA extraction. METHODS AND RESULTS: Our portable lysis apparatus employed a novel design consisting of an annular piezo-element with perforated diaphragm. Using Bacillus subtilis as target bacteria, our portable lysis apparatus was able to achieve a normalized percent lysis as high as 66% within 30 s. This is comparable to that by microprobe ultrasonication and almost 7 times higher than that by conventional bead beating. The effect from adding glass beads was predictable. However, the results from the addition of sodium dodecyl sulphate (SDS) were counter-intuitive because a further increase from 0·5 to 1% concentration reduced the lysis performance. The portable lysis apparatus is also at least 1·5-5 times more power efficient than microprobe ultrasonication. CONCLUSIONS: Our portable lysis apparatus is capable of rapidly extracting bacterial DNA and is more power efficient than microprobe ultrasonication. The addition of glass beads or SDS concentration (up to 0·5%) improves its performance. SIGNIFICANCE AND IMPACT OF THE STUDY: The portable lysis apparatus provides a standalone, rapid, low cost and power efficient way of obtaining genomic constituents prior to a variety of bioassays used in the field of environmental, biomedical and other applied microbiology.


Assuntos
Métodos Analíticos de Preparação de Amostras/métodos , Bacillus subtilis/química , DNA Bacteriano/isolamento & purificação , Métodos Analíticos de Preparação de Amostras/instrumentação , Bacillus subtilis/genética , Bacillus subtilis/isolamento & purificação , DNA Bacteriano/genética
18.
Curr Oncol ; 22(2): 133-43, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25908912

RESUMO

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.

19.
Curr Oncol ; 22(2): 144-55, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25908913

RESUMO

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti-factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

20.
Cell Death Differ ; 22(6): 912-20, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25633194

RESUMO

The positive roles of the Wnt/ß-catenin pathway in osteoblast differentiation and bone mineral density (BMD) maintenance have been clearly demonstrated in both animal experiments and clinical investigations. CXXC finger protein 5 (CXXC5), a recently identified negative regulator of the Wnt/ß-catenin pathway, showed altered cellular localization and function, which were dependent on the cell type in previous studies. However, the in vivo function of CXXC5 has not been clearly investigated yet. Here, we characterized CXXC5 as a negative regulator of osteoblast differentiation and bone formation. Deficiency of CXXC5 resulted in elevated BMD in mice without any severe gross developmental abnormalities. CXXC5 exerted a negative-feedback effect on the Wnt/ß-catenin pathway via Wnt-dependent binding to Dishevelled (Dvl) during osteoblast differentiation. Suppression of the Dvl-CXXC5 interaction using a competitor peptide resulted in the activation of the Wnt/ß-catenin pathway and osteoblast differentiation, and accelerated thickness growth of ex vivo-cultured calvariae. Overall, CXXC5 is a negative-feedback regulator induced by Wnt/ß-catenin signaling that inhibits osteoblast differentiation and bone formation via interaction with Dvl.


Assuntos
Osteoblastos/citologia , Osteoblastos/metabolismo , Receptores CXCR5/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular , Humanos , Camundongos , Camundongos Knockout , Receptores CXCR5/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismo
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