Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 351
Filtrar
1.
Cancer ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167594

RESUMO

BACKGROUND: Inpatient supportive care programs often target patients with advanced solid tumors. To the authors' knowledge, few studies to date have characterized symptom burden in hospitalized patients with potentially curable cancers. The objective of the current study was to compare symptom burden, palliative care consultation, and readmission rates in hospitalized patients by cancer type and treatment intent. METHODS: The authors conducted a single-center study of hospitalized patients with cancer between 2014 and 2017. They assessed physical symptoms using the Edmonton Symptom Assessment System and psychological distress using the Patient Health Questionnaire-4 and the Primary Care PTSD (Posttraumatic Stress Disorder) Screen. Multivariate linear regression models were used to assess symptom burden, logistic regression was used to assess palliative care use, and competing risk regression was used to compare 90-day readmission risk. RESULTS: A total of 1549 patients were enrolled and surveyed. The majority of patients reported moderate to severe fatigue, poor well-being, and drowsiness with no significant differences noted by cancer type and treatment intent. Compared with other groups, patients with incurable solid cancer reported higher physical symptoms (beta coefficient [B], 4.73; P < .01) and symptoms of depression (B, 0.44; P < .01) and anxiety (B, 0.39; P < .01), but no difference in posttraumatic stress disorder. Among patients in the top quartile symptom burden according to the Edmonton Symptom Assessment System, the palliative care service was consulted in 14.7%, 7.9%, 25.0%, and 49.6%, respectively, of patients with potentially curable hematologic, potentially curable solid, incurable hematologic, and incurable solid cancers (P < .001). Compared with patients with potentially curable solid cancer, patients in each group experienced a higher risk of readmission within 90 days. CONCLUSIONS: Hospitalized patients with cancer experience substantial physical and psychological symptoms. Palliative care rarely is consulted for highly symptomatic patients with potentially curable cancers. Supportive care interventions should target the needs of symptomatic patients regardless of treatment intent.

2.
Invest New Drugs ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898183

RESUMO

Subsets of esophagogastric (EG) cancers harbor genetic abnormalities, including amplification of HER2, MET, or FGFR2 or mutations in PIK3CA, EGFR, or BRAF. Ganetespib which is a novel triazolone heterocyclic inhibitor of HSP90, is a potentially biologically rational treatment strategy for advanced EG cancers with these gene amplification. This multicenter, single-arm phase 2 trial enrolled patients with histologically confirmed advanced EG cancer with progression on at least one line of systemic therapy. Patients received Ganetespib 200 mg/m2 IV on Days 1, 8, and 15 of a 28-day cycle. The primary endpoint was overall response rate (ORR). Secondary endpoints included: Progression Free Survival (PFS); to correlate the presence of HSP clients with ORR and PFS; evaluating the safety, tolerability and adverse events profile. In this study 26 eligible patients mainly: male 77%, median age 64 years were enrolled. The most common drug-related adverse events were diarrhea (77%), fatigue (65%), elevated ALKP (42%), and elevated AST (38%). The most common grade 3/4 AEs included: leucopenia (12%), fatigue (12%), diarrhea (8%), and elevated ALKP (8%). The ORR of 4% reflects the single patient of 26 who had a complete response and stayed on treatment for more than seventy (70) months. Median PFS and OS was 61 days (2.0 months), 94 days (3.1 months) respectively. Ganetespib showed manageable toxicity. While the study was terminated early due to insufficient evidence of single-agent activity, the durable CR and 2 minor responses suggest that there may be a subset of EG patients who could benefit from this drug.

3.
Clin Cancer Res ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941831

RESUMO

PURPOSE: ctDNA offers a promising, noninvasive approach to monitor therapeutic efficacy in real-time. We explored whether the quantitative percent change in ctDNA early after therapy initiation can predict treatment response and progression-free survival (PFS) in patients with metastatic gastrointestinal cancer. EXPERIMENTAL DESIGN: A total of 138 patients with metastatic gastrointestinal cancers and tumor profiling by next-generation sequencing had serial blood draws pretreatment and at scheduled intervals during therapy. ctDNA was assessed using individualized droplet digital PCR measuring the mutant allele fraction in plasma of mutations identified in tumor biopsies. ctDNA changes were correlated with tumor markers and radiographic response. RESULTS: A total of 138 patients enrolled. A total of 101 patients were evaluable for ctDNA and 68 for tumor markers at 4 weeks. Percent change of ctDNA by 4 weeks predicted partial response (PR, P < 0.0001) and clinical benefit [CB: PR and stable disease (SD), P < 0.0001]. ctDNA decreased by 98% (median) and >30% for all PR patients. ctDNA change at 8 weeks, but not 2 weeks, also predicted CB (P < 0.0001). Four-week change in tumor markers also predicted response (P = 0.0026) and CB (P = 0.022). However, at a clinically relevant specificity threshold of 90%, 4-week ctDNA change more effectively predicted CB versus tumor markers, with a sensitivity of 60% versus 24%, respectively (P = 0.0109). Patients whose 4-week ctDNA decreased beyond this threshold (≥30% decrease) had a median PFS of 175 days versus 59.5 days (HR, 3.29; 95% CI, 1.55-7.00; P < 0.0001). CONCLUSIONS: Serial ctDNA monitoring may provide early indication of response to systemic therapy in patients with metastatic gastrointestinal cancer prior to radiographic assessments and may outperform standard tumor markers, warranting further evaluation.

4.
Chem Commun (Camb) ; 56(3): 482-485, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31829388

RESUMO

A simple Co(ii)-based amine-borane dehydropolymerisation catalyst system is reported that operates at low loadings, to selectively give (H2BNMeH)n polymer on scale, with catalyst control over Mn, narrow dispersities and low residual metal content.

5.
J Gastrointest Cancer ; 51(1): 204-210, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30980294

RESUMO

PURPOSE/OBJECTIVE(S): Definitive chemoradiation (CRT) results in high cure rates of anal cancer, with advanced radiation (RT) techniques improving toxicity. However, there is limited data regarding these patients' sexual function (SF), quality of life (QOL), and mood. We hypothesized that anal cancer treatment would result in detrimental effects on SF, QOL, and mood. MATERIALS/METHODS: We prospectively surveyed patients with anal cancer treated with definitive CRT. We assessed SF for women with the Female Sexual Function Index (FSFI) and for men with the International Index of Erectile Function (IIEF). For all patients, we assessed QOL using EORTC QLQ-C30 and CR29 and mood using the Hospital Anxiety and Depression Scale (HADS). We reported descriptive statistics for SF, QOL, and mood and used univariate analysis to evaluate predictors of SF for women. RESULTS: Of 50 eligible patients, 84% completed the surveys. Median time from RT until survey was 36 months (1-97 months). Women (n = 34) reported poor SF overall (mean FSFI score = 15, scale 2-36, standard deviation (SD) 10.4). Most women reported poor SF related to satisfaction, desire, orgasm, arousal, pain, and lubrication. Men (n = 8) also had poor overall satisfaction (mean IIEF score = 6.1, scale 2-10, SD 3.6). Men reported poor erectile function and lower satisfaction with intercourse. Mean QLQ-C30 QOL score was 86.5 (SD 16.3). Results from EORTC QLQ-CR-20 demonstrated patients experienced poor sexual interest. Per HADS, 2.5% reported depression and 18% anxiety. CONCLUSION: Patients with anal cancer experience sexual dysfunction after RT, with QOL and mood symptoms similar to patients with other cancers. Our data support the need for ongoing efforts to understand and address issues with SF, QOL, and mood following RT for these patients.

6.
Ann Surg Oncol ; 27(4): 1122-1129, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31873931

RESUMO

OBJECTIVE: The aim of this study was to evaluate outcomes for patients with unresectable intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT). METHODS: We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008 to 2018. Median age at RT was 76 years (range 30-92), including 27 patients (41%) aged ≥ 80 years. Median RT dose was 58.05 Gy (range 37.5-67.5), all delivered in 15 daily fractions. Thirty-two patients received proton RT and 34 patients received photon RT. RESULTS: Median follow-up times from diagnosis and RT start were 21 months and 14 months, respectively. In total, five patients (7.6%) developed local failure. The 2-year outcomes were 84% local control (LC) and 58% OS. Among the 51 patients treated with definitive intent, the 2-year LC rate was 93% and the OS rate was 62%. On multivariate analysis for LC, older age was associated with a lower risk of local failure [hazard ratio (HR) 0.91; p = 0.02], while prior surgery (HR 16.5; p = 0.04) and macrovascular invasion (HR 123.93; p = 0.02) were independently associated with an increased risk of local failure. On multivariate analysis for OS, female sex (HR 0.33; p = 0.001) and prior chemotherapy (HR 0.38; p = 0.003) remained significantly associated with OS. On multivariate analysis for OS, compared with photon RT, there was a trend towards improved survival with proton RT (HR 0.50; p = 0.05). The rate of overall grade 3 + toxicity was 11%. One patient developed radiation-induced liver disease and was treated with corticosteroids. CONCLUSIONS: HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent ICC.

7.
Oncologist ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31876321

RESUMO

Every year millions of pulmonary nodules are discovered incidentally and through lung cancer screening programs. Management of these nodules is often suboptimal, with low follow-up rates and poor provider understanding of management approaches. There is an emerging body of literature about how to optimize management of pulmonary nodules. The Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) at Massachusetts General Hospital was founded in 2012 to manage pulmonary nodules via a multidisciplinary approach with optimized support staff. Recommendations from clinic providers and treatment details were recorded for all patients seen at the PNLCSC. Adherence to recommendations and outcomes were also tracked and reviewed. From October 2012 to September 2019, 1,136 patients were seen at the PNLCSC, each for a mean of 1.8 appointments (range, 1-10). A total of 356 procedures were recommended by the clinic and 271 patients were referred for surgery and/or radiation. The majority of interventions (74%) were recommended at the initial PNLCSC appointment. In total, 211 patients (19%) evaluated at the PNLCSC had pathologically confirmed pulmonary malignancies or were treated empirically with radiation. Among patients followed by the clinic, the adherence rate to clinic recommendations was 95%. This study shows how a multidisciplinary approach to pulmonary nodule management can streamline care and optimize follow-up. The PNLCSC provides a template that can be replicated in other health systems. It also provides an example of how multidisciplinary approaches can be applied to other complex conditions. IMPLICATIONS FOR PRACTICE: This work demonstrates how an integrated, multidisciplinary approach to management of pulmonary nodules can streamline patient care and improve adherence to provider recommendations. This approach has the potential to improve patient outcomes and reduce health care costs.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31843922

RESUMO

Transcriptional profiling has defined pancreatic ductal adenocarcinoma (PDAC) into distinct subtypes with the majority being classical epithelial (E) or quasi-mesenchymal (QM). Despite clear differences in clinical behavior, growing evidence indicates these subtypes exist on a continuum with features of both subtypes present and suggestive of interconverting cell states. Here, we investigated the impact of different therapies being evaluated in PDAC on the phenotypic spectrum of the E/QM state. We demonstrate using RNA-sequencing and RNA-in situ hybridization (RNA-ISH) that FOLFIRINOX combination chemotherapy induces a common shift of both E and QM PDAC toward a more QM state in cell lines and patient tumors. In contrast, Vitamin D, another drug under clinical investigation in PDAC, induces distinct transcriptional responses in each PDAC subtype, with augmentation of the baseline E and QM state. Importantly, this translates to functional changes that increase metastatic propensity in QM PDAC, but decrease dissemination in E PDAC in vivo models. These data exemplify the importance of both the initial E/QM subtype and the plasticity of E/QM states in PDAC in influencing response to therapy, which highlights their relevance in guiding clinical trials.

10.
EMBO Rep ; 20(11): e47967, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31566294

RESUMO

Dystroglycan, an extracellular matrix receptor, has essential functions in various tissues. Loss of α-dystroglycan-laminin interaction due to defective glycosylation of α-dystroglycan underlies a group of congenital muscular dystrophies often associated with brain malformations, referred to as dystroglycanopathies. The lack of isogenic human dystroglycanopathy cell models has limited our ability to test potential drugs in a human- and neural-specific context. Here, we generated induced pluripotent stem cells (iPSCs) from a severe dystroglycanopathy patient with homozygous FKRP (fukutin-related protein gene) mutation. We showed that CRISPR/Cas9-mediated gene correction of FKRP restored glycosylation of α-dystroglycan in iPSC-derived cortical neurons, whereas targeted gene mutation of FKRP in wild-type cells disrupted this glycosylation. In parallel, we screened 31,954 small molecule compounds using a mouse myoblast line for increased glycosylation of α-dystroglycan. Using human FKRP-iPSC-derived neural cells for hit validation, we demonstrated that compound 4-(4-bromophenyl)-6-ethylsulfanyl-2-oxo-3,4-dihydro-1H-pyridine-5-carbonitrile (4BPPNit) significantly augmented glycosylation of α-dystroglycan, in part through upregulation of LARGE1 glycosyltransferase gene expression. Together, isogenic human iPSC-derived cells represent a valuable platform for facilitating dystroglycanopathy drug discovery and therapeutic development.

11.
Tob Induc Dis ; 17: 04, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582916

RESUMO

INTRODUCTION: Adolescents use electronic nicotine delivery systems (ENDS, or e-cigarettes) more than other tobacco products. Among adults, some data indicate that motivations for use vary by sociodemographic group. This study sought to examine how adolescents' motivations for ENDS use vary by sociodemographic characteristics, including age, gender, race/ethnicity and household income. METHODS: The current study used data from Wave 2 of the Population Assessment of Tobacco and Health (PATH) study. Youth who used ENDS in the past 30 days were asked to report their motivations for product use. Rates of reporting each reason for use were compared across sociodemographic groups. RESULTS: Appealing flavors was the most commonly reported motivation for using ENDS, and was mentioned more often among females (89.23%) than males (74.00%). Females were also more likely than males to report using ENDS because the product feels like smoking cigarettes (AOR=1.761) and people who are important to the participant smoke them (AOR=1.895). Older teens were more likely to report using ENDS because the product does not smell bad (56.45%, 15-17 years old; 42.83%, 12-14 years old). CONCLUSIONS: Motivations for ENDS use vary by sociodemographic group. Understanding the motivations for use among sociodemographic subgroups is an initial step towards informing the development of policies and interventions with equally distributed benefits.

12.
Nat Med ; 25(9): 1415-1421, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501609

RESUMO

During cancer therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms in an individual patient1-3. Previous case reports and small case series have suggested that liquid biopsy (specifically, cell-free DNA (cfDNA)) may better capture the heterogeneity of acquired resistance4-8. However, the effectiveness of cfDNA versus standard single-lesion tumor biopsies has not been directly compared in larger-scale prospective cohorts of patients following progression on targeted therapy. Here, in a prospective cohort of 42 patients with molecularly defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of postprogression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cfDNA, tumor biopsies and rapid autopsy specimens elucidated substantial geographic and evolutionary differences across lesions. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity, and that the emergence of multiple resistance alterations in an individual patient may represent the 'rule' rather than the 'exception'. These findings have profound therapeutic implications and highlight the potential advantages of cfDNA over tissue biopsy in the setting of acquired resistance.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA de Neoplasias/sangue , Neoplasias Gastrointestinais/sangue , Biópsia Líquida , Autopsia , Ácidos Nucleicos Livres/genética , Estudos de Coortes , DNA de Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Heterogeneidade Genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Sequenciamento Completo do Exoma
13.
Ergonomics ; 62(11): 1415-1425, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478466

RESUMO

It is not currently known if biomechanical factors contribute to low back pain (LBP) during prolonged sitting. Thus, this study recruited 90 participants (61 with no history of LBP, and 29 with) to sit for 1 hour where back electromyography, spine posture, and perceived pain ratings (PPR) were collected. Participants were classified as Pain Developers (PD) or Non-Pain Developers (NPD) based on their maximum PPR. PDs had significantly higher PPR (p = 0.000) and lower number of spine fidgets (p = 0.004) than NPDs. There was a significant interaction between clinical health history and pain group (p = 0.037) for PPR. Besides fidget frequency, there were no biomechanical differences between pain groups. Therefore, sitting-induced back pain does not appear to be due to posture or muscle activity; however, it may be related to micro-movement strategies. Future work should explore fidgeting further and whether healthy PDs are at risk for clinical LBP in the future. Practitioner summary: We have replicated the differential transient sitting-induced pain response observed in previous studies. Pain developers do not sit differently than non-pain developers, although they do appear to move less. More research is warranted to better understand these groups and the relationship between pain developers and future cases of back pain. Abbreviations: LBP: low back pain; PG: pain group; PD: pain developer; NPD: non-pain developer; +veHx: positive clinical history for low back pain; -veHx: negative clinical history for low back pain; RTS: right thoracic erector spinae; LTS: left thoracic erector spine; RLM: right lumbar multifidus; LLM: left lumbar multifidus; MVC: maximum voluntary contraction; Pelvic N: normalized pelvic angle; ANOVA: analysis of variance; SD: standard deviation.


Assuntos
Músculos do Dorso/fisiologia , Desenho de Equipamento , Dor Lombar/fisiopatologia , Postura/fisiologia , Postura Sentada , Coluna Vertebral/fisiologia , Acelerometria , Adulto , Fenômenos Biomecânicos , Estudos de Casos e Controles , Eletromiografia , Feminino , Humanos , Masculino , Adulto Jovem
14.
Invest New Drugs ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31297636

RESUMO

Background In pancreatic ductal adenocarcinoma (PDAC), the chemokine (C-C motif) ligand 2 (CCL2)/chemokine (C-C motif) receptor 2 (CCR2) axis plays a key role in immunosuppressive properties of the tumor microenvironment, patient prognosis, and chemoresistance. This phase Ib study assessed the effects of the orally administered CCR2 inhibitor PF-04136309 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic PDAC. Methods Patients received PF-04136309 twice daily (BID) continuously plus nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) administered on days 1, 8, and 15 of each 28-day cycle. The primary objectives were to evaluate safety and tolerability, characterize dose-limiting toxicities (DLTs), and determine the recommended phase II dose (RP2D) of PF-04136309. Results In all, 21 patients received PF-04136309 at a starting dose of 500 mg or 750 mg BID. The RP2D was identified to be 500 mg BID. Of 17 patients treated at the 500 mg BID starting dose, three (17.6%) experienced a total of four DLTs, including grade 3 dysesthesia, diarrhea, and hypokalemia and one event of grade 4 hypoxia. Relative to the small number of patients (n = 21), a high incidence (24%) of pulmonary toxicity was observed in this study. The objective response rate for 21 patients was 23.8% (95% confidence interval: 8.2-47.2%). Levels of CD14 + CCR2+ inflammatory monocytes (IM) decreased in the peripheral blood, but did not accumulate in the bone marrow. Conclusions PF-04136309 in combination with nab-paclitaxel plus gemcitabine had a safety profile that raises concern for synergistic pulmonary toxicity and did not show an efficacy signal above nab-paclitaxel and gemcitabine. ClinicalTrials.gov identifier: NCT02732938.

15.
Exp Hematol ; 76: 1-12.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31326613

RESUMO

Pluripotent stem cell (PSC) differentiation in vitro represents a powerful and tractable model to study mammalian development and an unlimited source of cells for regenerative medicine. Within hematology, in vitro PSC hematopoiesis affords novel insights into blood formation and represents an exciting potential approach to generate hematopoietic and immune cell types for transplantation and transfusion. Most studies to date have focused on in vitro hematopoiesis from mouse PSCs and human PSCs. However, differences in mouse and human PSC culture protocols have complicated the translation of discoveries between these systems. We recently developed a novel chemical media formulation, expanded potential stem cell medium (EPSCM), that maintains mouse PSCs in a unique cellular state and extraembryonic differentiation capacity. Herein, we describe how EPSCM can be directly used to stably maintain human PSCs. We further demonstrate that human PSCs maintained in EPSCM can spontaneously form embryoid bodies and undergo in vitro hematopoiesis using a simple differentiation protocol, similar to mouse PSC differentiation. EPSCM-maintained human PSCs generated at least two hematopoietic cell populations, which displayed distinct transcriptional profiles by RNA-sequencing (RNA-seq) analysis. EPSCM also supports gene targeting using homologous recombination, affording generation of an SPI1 (PU.1) reporter PSC line to study and track in vitro hematopoiesis. EPSCM therefore provides a useful tool not only to study pluripotency but also hematopoietic cell specification and developmental-lineage commitment.


Assuntos
Meios de Cultura/farmacologia , Hematopoese/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Células-Tronco Pluripotentes/efeitos dos fármacos , Animais , Técnicas de Cultura de Células/métodos , Ciclo Celular , Linhagem da Célula , Células Cultivadas , Técnicas de Reprogramação Celular , Corpos Embrioides/efeitos dos fármacos , Fibroblastos/citologia , Genes Reporter , Células-Tronco Embrionárias Humanas/citologia , Humanos , Camundongos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/transplante , Análise de Sequência de RNA , Especificidade da Espécie , Transplante de Células-Tronco/efeitos adversos , Teratoma/etiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31328626

RESUMO

Four low-cost materials, oyster shells, pumice stone, sand and zeolite were employed as adsorbents in an adsorption batch assays investigating the removal of ammonia, phosphate and nitrate from an aqueous solution. These compounds were chosen as they represent typical compounds found in landfill leachate (LFL). Assay performance was evaluated by the Langmuir and Freundlich adsorption isotherms. The top two materials, oyster shells and pumice stone, were employed as adsorbents in a fixed-bed column trial examining the effect of bed height and flow rate on the treatment of a synthetic LFL. The trial concluded that the highest rates of adsorption were achieved using bed heights of 20 cm with a flow rate of 5 mL min-1. After optimization, the system was employed for the treatment of LFL from Powerstown landfill, Carlow, Ireland. Ammonia and nitrate were effectively removed by both adsorption materials resulting in a reduction of influent ammonia and nitrate concentrations to below the national discharge limits set for these compounds of ≤4 mg L-1 and ≤50 mg L-1, respectively. In contrast, although similar high removal efficiencies were observed for phosphate, these rates were not maintained during the test period with overall results indicating reduced phosphate adsorption in comparison to the other compounds tested.


Assuntos
Amônia/isolamento & purificação , Nitratos/isolamento & purificação , Fosfatos/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Amônia/química , Exoesqueleto/química , Animais , Irlanda , Nitratos/química , Fosfatos/química , Silicatos/química , Eliminação de Resíduos Líquidos/economia , Poluentes Químicos da Água/química , Poluentes Químicos da Água/economia
17.
Eur J Nucl Med Mol Imaging ; 46(11): 2260-2269, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359108

RESUMO

PURPOSE: The primary aim of the present study was to evaluate if PET/MR induced management changes versus standard of care imaging (SCI) in treated colorectal cancer patients. The secondary aim was to assess the staging performance of PET/MR and of SCI versus the final oncologic stage. METHODS: Treated CRC patients who underwent PET/MR with 18F-FDG and SCI between January 2016 and October 2018 were enrolled in this retrospective study. Their medical records were evaluated to ascertain if PET/MR had impacted on their clinical management versus SCI. The final oncologic stage, as reported in the electronic medical record, was considered the true stage of disease. RESULTS: A total of 39 patients who underwent 42 PET/MR studies were included, mean age 56.7 years (range 39-75 years), 26 males, and 13 females. PET/MR changed clinical management 15/42 times (35.7%, standard error ± 7.4%); these 15 changes in management were due to upstaging in 9/42 (21.5%) and downstaging in 6/42 (14.2%). The differences in management prompted by SCI versus PET/MR were statistically significant, and PET/MR outperformed SCI (P value < 0.001; odds ratio = 2.8). In relation to the secondary outcome, PET/MR outperformed the SCI in accuracy of oncologic staging (P value = 0.016; odds ratio = 4.6). CONCLUSIONS: PET/MR is a promising imaging tool in the evaluation of treated CRC and might change the management in these patients. However, multicenter prospective studies with larger patient samples are required in order to confirm these preliminary results.

18.
Nat Cell Biol ; 21(6): 687-699, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31160711

RESUMO

We recently derived mouse expanded potential stem cells (EPSCs) from individual blastomeres by inhibiting the critical molecular pathways that predispose their differentiation. EPSCs had enriched molecular signatures of blastomeres and possessed developmental potency for all embryonic and extra-embryonic cell lineages. Here, we report the derivation of porcine EPSCs, which express key pluripotency genes, are genetically stable, permit genome editing, differentiate to derivatives of the three germ layers in chimeras and produce primordial germ cell-like cells in vitro. Under similar conditions, human embryonic stem cells and induced pluripotent stem cells can be converted, or somatic cells directly reprogrammed, to EPSCs that display the molecular and functional attributes reminiscent of porcine EPSCs. Importantly, trophoblast stem-cell-like cells can be generated from both human and porcine EPSCs. Our pathway-inhibition paradigm thus opens an avenue for generating mammalian pluripotent stem cells, and EPSCs present a unique cellular platform for translational research in biotechnology and regenerative medicine.


Assuntos
Diferenciação Celular/genética , Reprogramação Celular/genética , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes/citologia , Animais , Blastômeros/citologia , Blastômeros/metabolismo , Linhagem da Célula/genética , Células-Tronco Embrionárias/citologia , Camadas Germinativas/crescimento & desenvolvimento , Camadas Germinativas/metabolismo , Humanos , Camundongos , Medicina Regenerativa , Transdução de Sinais/genética , Suínos , Trofoblastos/citologia , Trofoblastos/metabolismo
19.
Case Rep Oncol ; 12(1): 311-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123457

RESUMO

Leptomeningeal carcinomatosis (LC) is a rare leptomeningeal spread of diffusely metastatic tumors. It occurs more commonly with hematologic tumors, less commonly with solid tumors, and is exceedingly rare in prostate cancer. Due to its scarcity, it has traditionally been difficult to diagnose LC but advancement of MRI has helped considerably. However, even with technological improvements, pre-mortem diagnosis of LC remains difficult and controversial. Our case is a 71-year-old male with prostate cancer with bone metastases who presented to our facility with altered mental status (AMS), lower extremity weakness, and worsening diarrhea. The diarrhea was responsive to antibiotic therapy, but his AMS did not resolve. A head CT without contrast was negative but follow-up brain MRI revealed leptomeningeal enhancement highly suggestive of LC. Cerebrospinal fluid (CSF) cytology results were negative and other CSF studies were inconclusive. Although further studies were planned, the patient continued to deteriorate, and the family elected to withdraw care. He passed away without beginning treatment for the LC. Despite advances in cancer therapies, LC remains difficult to diagnose and treat. Imaging may be suggestive of the condition but the confirmatory tests such as repeated CSF cytology or meningeal biopsy are not only invasive but also usually occur postmortem. Additional methods of CSF testing have been studied to evaluate their role in accurately diagnosing LC but low specificity for LC has somewhat limited their use. Although treatment options are mainly palliative in nature, prompt recognition and early treatment could grant valuable time for patients and families.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31117215

RESUMO

Chromium contamination of drinking water has become a global problem due to its extensive use in industry. The most commonly used methods for chromium detection in water are laboratory-based methods, such as atomic absorption spectroscopy and mass spectroscopy. Although these methods are highly selective and sensitive, they require expensive maintenance and highly trained staff. Therefore, there is a growing demand for cost effective and portable detection methods that would meet the demand for mass monitoring. Microfluidic detection systems based on optical detection have great potential for onsite monitoring applications. Furthermore, their small size enables rapid sample throughput and minimises both reagent consumption and waste generation. In contrast to standard laboratory methods, there is also no requirement for sample transport and storage. The aim of this study is to optimise a colorimetric method based on 1,5-diphenylcarbazide dye for incorporation into a microfluidic detection system. Rapid colour development was observed after the addition of the dye and samples were measured at 543 nm. Beer's law was obeyed in the range between 0.03-3 mg·L-1. The detection limit and quantitation limit were found to be 0.023 and 0.076 mg·L-1, respectively.


Assuntos
Cromo/análise , Colorimetria/métodos , Difenilcarbazida/química , Poluentes Químicos da Água/análise , Água Potável/química , Monitoramento Ambiental/métodos , Humanos , Limite de Detecção
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA