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1.
Hum Mol Genet ; 31(20): 3521-3538, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-35708500

RESUMO

Recent research on familial dysautonomia (FD) has focused on the development of therapeutics that facilitate the production of the correctly spliced, exon 20-containing, transcript in cells and individuals bearing the splice-altering, FD-causing mutation in the elongator acetyltransferase complex subunit I (ELP1) gene. We report here the ability of carnosol, a diterpene present in plant species of the Lamiaceae family, including rosemary, to enhance the cellular presence of the correctly spliced ELP1 transcript in FD patient-derived fibroblasts by upregulating transcription of the ELP1 gene and correcting the aberrant splicing of the ELP1 transcript. Carnosol treatment also elevates the level of the RNA binding motif protein 24 (RBM24) and RNA binding motif protein 38 (RBM38) proteins, two multifunctional RNA-binding proteins. Transfection-mediated expression of either of these RNA binding motif (RBMs) facilitates the inclusion of exon 20 sequence into the transcript generated from a minigene-bearing ELP1 genomic sequence containing the FD-causing mutation. Suppression of the carnosol-mediated induction of either of these RBMs, using targeting siRNAs, limited the carnosol-mediated inclusion of the ELP1 exon 20 sequence. Carnosol treatment of FD patient peripheral blood mononuclear cells facilitates the inclusion of exon 20 into the ELP1 transcript. The increased levels of the ELP1 and RBM38 transcripts and the alternative splicing of the sirtuin 2 (SIRT2) transcript, a sentinel for exon 20 inclusion in the FD-derived ELP1 transcript, are observed in RNA isolated from whole blood of healthy adults following the ingestion of carnosol-containing rosemary extract. These findings and the excellent safety profile of rosemary together justify an expedited clinical study of the impact of carnosol on the FD patient population.


Assuntos
Disautonomia Familiar , Rosmarinus , Fatores de Elongação da Transcrição/metabolismo , Abietanos/farmacologia , Acetiltransferases , Adulto , Proteínas de Transporte/genética , Disautonomia Familiar/tratamento farmacológico , Disautonomia Familiar/genética , Disautonomia Familiar/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Rosmarinus/genética , Rosmarinus/metabolismo , Sirtuína 2/metabolismo , Fatores de Elongação da Transcrição/genética
2.
Ann Behav Med ; 58(3): 156-166, 2024 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-38141201

RESUMO

BACKGROUND: Risk factors for cancer-related fatigue are understudied in colorectal cancer. PURPOSE: This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. METHODS: Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. RESULTS: Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III-IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (ß = 0.26, p = .016). When stratified by cancer stage (I-II vs. III-IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, ß = 0.43, p = .035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. CONCLUSIONS: Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. TRIAL REGISTRATION: The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014.


Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced (Stages III and IV) colorectal cancer the first year after diagnosis.


Assuntos
Neoplasias Colorretais , Transtornos do Sono-Vigília , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Colorretais/complicações , Estudos Transversais , Exercício Físico , Fadiga/complicações , Qualidade de Vida , Sono , Transtornos do Sono-Vigília/complicações
3.
Mol Biol Rep ; 51(1): 260, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302762

RESUMO

Vascular diseases are the underlying pathology in many life-threatening illnesses. Human cellular and molecular mechanisms involved in angiogenesis are complex and difficult to study in current 2D in vitro and in vivo animal models. Engineered 3D in vitro models that incorporate human pluripotent stem cell (hPSC) derived endothelial cells (ECs) and supportive biomaterials within a dynamic microfluidic platform provide a less expensive, more controlled, and reproducible platform to better study angiogenic processes in response to external chemical or physical stimulus. Current studies to develop 3D in vitro angiogenesis models aim to establish single-source systems by incorporating hPSC-ECs into biomimetic extracellular matrices (ECM) and microfluidic devices to create a patient-specific, physiologically relevant platform that facilitates preclinical study of endothelial cell-ECM interactions, vascular disease pathology, and drug treatment pharmacokinetics. This review provides a detailed description of the current methods used for the directed differentiation of human stem cells to endothelial cells and their use in engineered 3D in vitro angiogenesis models that have been developed within the last 10 years.


Assuntos
Células Endoteliais , Células-Tronco Pluripotentes , Animais , Humanos , Avaliação Pré-Clínica de Medicamentos , Angiogênese , Neovascularização Fisiológica , Diferenciação Celular
4.
Support Care Cancer ; 32(4): 270, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578444

RESUMO

PURPOSE: The COVID-19 pandemic shifted the healthcare field from in-person clinic visits to virtual-based telehealth appointments. This study explored young adult (YA) hematopoietic stem cell transplantation (HSCT) patient and physician communication preferences and quality of life. METHODS: One researcher conducted semi-structured interviews with n = 10 YA HSCT patients and n = 10 healthcare providers (HPs). HPs included physicians (n = 5) and advanced practice provider (APP) (nurse practitioners and physician assistants) (n = 5). Interviews lasted approximately 10-15 min, were held over Zoom®, and were audio-recorded. Interviews were professionally transcribed verbatim, and two independent researchers conducted a thematic analysis using Dedoose®. RESULTS: Common themes included the following: (1) convenience, (2) improved communication, (3) technology issues, and (4) quality of life for patients and physicians. In general, most patients (n = 7; 70%) preferred in-person visits over telehealth for initial appointments, stating they chose the "social connection" and "engagement" associated with in-person visits. For "check-ins" and follow-up appointments (n = 5; 50%), patients preferred hybrid appointments. Physicians (n = 4; 80%) preferred telehealth stating it was "convenient," "timesaving," and improved "compliance." In contrast, all APP staff (n = 5; 100%) preferred in-person visits, stating in-person improved "relationships" with patients and was more "convenient" than using electronic devices for telehealth. CONCLUSION: Providers differed in preference. APP personnel preferred in-person visits and HSCT physicians preferred telehealth appointments. YA HSCT patients preferred in-person for initial appointments and hybrid clinic visits for follow-up appointments.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Telemedicina , Humanos , Adulto Jovem , Qualidade de Vida , Pandemias , Pessoal de Saúde
5.
Support Care Cancer ; 32(3): 184, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393418

RESUMO

PURPOSE: This study provides an updated evaluation of the prevalence and severity of acute cancer-related symptoms and quality of life (QOL) concerns among patients treated with emetogenic chemotherapy. METHODS: Patients were recruited to a larger, multi-site observational study prior to starting chemotherapy. Participants completed sociodemographic questionnaires and clinical data were abstracted via medical record review. Symptoms and QOL were assessed 5 days after starting moderately or highly emetogenic chemotherapy. Functional Assessment of Cancer Therapy - General assessed QOL concerns. Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events evaluated symptoms. Symptoms were considered severe when participants responded "severe" or "very severe." RESULTS: Participants (N = 1174) were on average 58 ± 13 years, mostly female (73%), non-Hispanic (89%), and White (87%). Most participants were diagnosed with breast (38.1%), gynecological (20%), and gastrointestinal (17.1%) cancer. The most common QOL concerns of any severity were fatigue (94%), anhedonia (89%), dissatisfaction with QOL (86%), and sleep disturbance (86%). The most common severe QOL concerns were anhedonia (44%), fatigue (40%), and inability to work (38%). Decreased appetite (74%), pain (71%), and constipation (70%) were the most common symptoms of any severity, as well as most common severe symptoms (13%, 18%, and 18%, respectively). CONCLUSION: Herein, updates are provided in regard to QOL concerns and symptoms reported by patients in the days after chemotherapy and demonstrates that concerns and symptoms have shifted in the last decade.


Assuntos
Neoplasias , Qualidade de Vida , Feminino , Humanos , Masculino , Anedonia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Pessoa de Meia-Idade , Idoso
6.
J Ethn Subst Abuse ; : 1-23, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557402

RESUMO

Community-based interventions for youth substance use prevention require high levels of capacity to organize and coordinate community resources to support youth development and create opportunities to prevent youth substance use. This project aimed to better understand what Black prevention practitioners perceive as the requirements for a successful drug-free community coalition. Black prevention practitioners, who were engaged in drug-free community funded coalitions, had discussions about coalitions as a strategy for youth substance use prevention in Black communities. These facilitated discussions resulted in consensus over a set of nine core principles regarding successful youth substance use prevention coalition building in these communities.

7.
Nutr Cancer ; 75(9): 1743-1751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37553951

RESUMO

Preoperative nutritional status is an important and modifiable risk factor of a patient's recovery and outcome after radical cystectomy. There are multiple malnutrition screening tools and treatment options. In this review, we discuss the best indicators of this condition and how to optimize nutrition status prior to radical cystectomy.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias da Bexiga Urinária , Humanos , Cistectomia/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle
8.
Inorg Chem ; 62(14): 5479-5486, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-36961751

RESUMO

Acid modulator has been the most widely employed ingredient for highly crystalline metal-organic framework (MOF) synthesis. However, the mechanistic understanding of thorium (Th)-based MOF crystallization remains a great challenge due to the intrinsic properties of fast olation and oxolation reactions of Th species in solution. Here, we constructed a series of Th-based MOFs by adding different modulators (formic acid, acetic acid, trifluoroacetic acid, and benzoic acid) to a synthetic solution along with tetratopic 1,3,5,7-adamantane tetracarboxylic acid (H4ATC), a three-dimensional (3D) ligand with a rigid aliphatic backbone. This work presents an in-depth study of the structure-modulator relationship between the H4ATC ligand and coordinating modulators in the Th-based MOF crystallization process. Crystal structures of these Th-based MOFs reveal that formic acid and acetic acid modulators can compete with the H4ATC ligand to form NU-52 and NU-54; these MOFs possess Th nodes linked by the corresponding modulator. Alternatively, usage of trifluoroacetic acid and benzoic acid modulators results in NU-53 and NU-55; these MOFs possess Th nodes coordinated by only the H4ATC ligand, regardless of the modulator amount. This work highlights that both the identity and amount of modulator play a crucial role in determining the resulting Th-based MOF structures when H4ATC is selected as the coordinated ligand.

9.
Colorectal Dis ; 25(10): 2054-2063, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37700526

RESUMO

AIM: This study sought to identify groups of colorectal cancer patients based upon trajectories of fatigue and examine how demographic, clinical and behavioural risk factors differentiate these groups. METHOD: Patients were from six cancer centres in the United States and Germany. Fatigue was measured using the fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at five time points (baseline/enrolment and 3, 6, 12 and 24 months after diagnosis). Piecewise growth mixture models identified latent trajectories of fatigue. Logistic regression models examined differences in demographic, clinical and behavioural characteristics between fatigue trajectory groups. RESULTS: Among 1615 participants (57% men, 86% non-Hispanic White, mean age 61 ± 13 years at diagnosis), three distinct groups were identified. In the high fatigue group (36%), fatigue significantly increased in the first 6 months after diagnosis and then showed statistically and clinically significant improvement from 6 to 24 months (P values < 0.01). Throughout the study period, average fatigue met or exceeded cutoffs for clinical significance. In the moderate (34%) and low (30%) fatigue groups, fatigue levels remained below or near population norms across the study period. Patients who were diagnosed with Stage II-IV disease and/or current smokers were more likely to be in the high fatigue than in the moderate fatigue group (P values < 0.05). CONCLUSION: A large proportion of colorectal cancer patients experienced sustained fatigue after initiation of cancer treatment. Patients with high fatigue at the time of diagnosis may benefit from early supportive care.


Assuntos
Neoplasias Colorretais , Qualidade de Vida , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Fadiga/etiologia , Fadiga/epidemiologia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/diagnóstico , Fatores de Risco , Alemanha/epidemiologia , Inquéritos e Questionários
10.
Support Care Cancer ; 32(1): 50, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38129689

RESUMO

PURPOSE: Hematopoietic stem cell transplantation (HSCT) recipients experience several post-HSCT complications affecting nutritional status, body mass index (BMI), and mortality that can potentially be mitigated by nutritional management. This rapid review examines the relationship between pre-HSCT nutritional status and BMI and post-HSCT survival. METHODS: Articles were identified from PubMed, Scopus, and Embase. Two researchers independently completed the title, abstract, and full-text review. Inclusion criteria included the following: (1) randomized clinical trials or observational studies; (2) human subjects diagnosed with cancer and undergoing HSCT; (3) reported pre-HSCT nutritional status (e.g., diet recall, nutritional survey, dietitian session) or BMI; and (4) reported treatment related mortality and/or survival. RESULTS: The initial search found 3036 articles, 28 were included in full-text review, and 18 met inclusion criteria. Articles had quasi-experimental (n = 2) and observational (n = 16) study designs. Of the studies, n = 5 reported nutritional intake decreased post-HSCT, and n = 2 reported nutrition intervention (i.e., controlled feeding) post-HSCT improved survival. Four studies reported having a BMI classified as underweight improved survival, while n = 5 reported having a BMI classified as overweight or obese improved survival. CONCLUSION: Current research exploring the relationship between nutritional status and BMI with HSCT survival is mixed. Further research is needed to determine how nutritional status and BMI are associated withsurvival post-HSCT to inform future intervention work.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Estado Nutricional , Humanos , Índice de Massa Corporal , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Obesidade/complicações , Sobrepeso/complicações
11.
Endocr Pract ; 29(6): 471-477, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37004872

RESUMO

OBJECTIVE: To investigate the incidence of corticotroph hyperplasia (CH) or lymphocyte infiltration in the pituitary of patients with obesity. METHODS: The pituitary and adrenal glands from 161 adult autopsies performed between 2010 and 2019 at our institution were reviewed. The clinical history, body mass index (BMI), and cause of death were recorded. Routine hematoxylin and eosin staining, reticulin staining, and immunohistochemical staining for adrenocorticotropic hormone, CD3, and CD20 were performed. The results were analyzed using the Fisher and chi-square statistics. Decedents were separated into 4 groups based on BMI (kg/m2): (1) lean (BMI, <25.0), (2) overweight (BMI, 25.0-29.9), (3) obesity class I (BMI, 30.0-34.9), and (4) obesity classes II to III (BMI, >34.9). RESULTS: CH/neoplasia was identified in 44 of 161 pituitary glands. Four (9.1%) of 53 lean patients had pituitary lesions, whereas 27.3% (12) of overweight, 22.7% (10) of obesity class I, and 40.9% (18) of obesity class II patients had hyperplasia (P < .0001). Small corticotroph tumors were identified in 15 patients; only 1 was a lean patient, and the tumor was associated with the Crooke hyaline change of nontumorous corticotrophs. The presence of CH and neoplasia was associated with adrenal cortical hyperplasia and lipid depletion. Microscopic foci of T and B lymphocytes were identified in the pituitaries of patients in each weight category; no independent association between BMI and lymphocyte inflammation was found. CONCLUSION: Our data indicate an association between CH/neoplasia and obesity. It remains unclear whether obesity is the cause or effect of adrenocorticotropic hormone and cortisol excess.


Assuntos
Obesidade Mórbida , Doenças da Hipófise , Neoplasias Hipofisárias , Adulto , Humanos , Corticotrofos/metabolismo , Corticotrofos/patologia , Obesidade Mórbida/patologia , Hiperplasia/patologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Hipófise/patologia , Hormônio Adrenocorticotrópico/metabolismo , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Obesidade/complicações , Obesidade/epidemiologia
12.
Curr Issues Mol Biol ; 44(5): 2015-2028, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35678665

RESUMO

Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different sites with very limited information on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we have analyzed the gut microbiome (both fungal and bacterial communities) in patients with metastatic GEP-NENs. Fecal samples were collected and compared with matched healthy control samples using logistic regression distances utilizing R package MatchIt (version 4.2.0, Daniel E. Ho, Stanford, CA, USA). We examined differences in microbiome profiles between GEP-NENs and control samples using small subunit (SSU) rRNA (16S), ITS1, ITS4 genomic regions for their ability to accurately characterize bacterial and fungal communities. We correlated the results with different behavioral and dietary habits, and tumor features including differentiation, grade, primary site, and therapeutic response. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Gut samples of 34 patients (12 males, 22 females, median age 64 years) with metastatic GEP-NENs (22 small bowel, 10 pancreatic, 1 gall bladder, and 1 unknown primary) were analyzed. Twenty-nine patients had well differentiated GEP-neuroendocrine tumors (GEP-NETs), (G1 = 14, G2 = 12, G3 = 3) and five patients had poorly differentiated GEP-neuroendocrine carcinomas (GEP-NECs). Patients with GEP-NENs had significantly decreased bacterial species and increased fungi (notably Candida species, Ascomycota, and species belonging to saccharomycetes) compared to controls. Patients with GEP-NECs had significantly enriched populations of specific bacteria and fungi (such as Enterobacter hormaechei, Bacteroides fragilis and Trichosporon asahii) compared to those with GEP-NETs (p = 0.048, 0.0022 and 0.034, respectively). In addition, higher grade GEP-NETs were associated with significantly higher Bacteroides fragilis (p = 0.022), and Eggerthella lenta (p = 0.00018) species compared to lower grade tumors. There were substantial differences associated with dietary habits and therapeutic responses. This is the first study to analyze the role of the microbiome environment in patients with GEP-NENs. There were significant differences between GEP-NETs and GEP-NECs, supporting the role of the gut microbiome in the pathogenesis of these two distinct entities.

13.
Cancer ; 128(3): 461-470, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34643945

RESUMO

Uncontrolled chemotherapy-induced nausea and vomiting can reduce patients' quality of life and may result in premature discontinuation of chemotherapy. Although nausea and vomiting are commonly grouped together, research has shown that antiemetics are clinically effective against chemotherapy-induced vomiting (CIV) but less so against chemotherapy-induced nausea (CIN). Nausea remains a problem for up to 68% of patients who are prescribed guideline-consistent antiemetics. Despite the high prevalence of CIN, relatively little is known regarding its etiology independent of CIV. This review summarizes a metagenomics approach to the study and treatment of CIN with the goal of encouraging future research. Metagenomics focuses on genetic risk factors and encompasses both human (ie, host) and gut microbial genetic variation. Little work to date has focused on metagenomics as a putative biological mechanism of CIN. Metagenomics has the potential to be a powerful tool in advancing scientific understanding of CIN by identifying new biological pathways and intervention targets. The investigation of metagenomics in the context of well-established demographic, clinical, and patient-reported risk factors may help to identify patients at risk and facilitate the prevention and management of CIN.


Assuntos
Antieméticos , Antineoplásicos , Neoplasias , Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Humanos , Metagenômica , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Neoplasias/induzido quimicamente , Neoplasias/tratamento farmacológico , Qualidade de Vida , Vômito/induzido quimicamente
14.
Mod Pathol ; 35(11): 1570-1577, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35676332

RESUMO

Ameloblastoma is a benign, locally aggressive odontogenic neoplasm with variable solid and cystic morphology. On account of its histologic variety, diagnostically challenging cases can bear resemblance to odontogenic keratocyst/keratocystic odontogenic tumor (KCOT) or dentigerous cyst (DC). BRAFV600E mutation has been reported to be specific for and frequent in ameloblastoma, and this study evaluated the usefulness of immunohistochemistry (IHC) using the BRAF VE1 mutant-specific antibody as a diagnostic adjunct in this setting. We investigated 46 ameloblastomas, 30 KCOTs, and 30 DCs. BRAF VE1 IHC was performed on all cases and allele-specific polymerase chain reaction (AS-PCR) for BRAFV600E mutation was performed on 30 ameloblastomas and any IHC-positive KCOT/DC. BRAF VE1 IHC was positive in 31/37 (83.8%) mandibular ameloblastomas but not in any maxillary ameloblastomas (0/9), KCOT (0/30), or DC (0/30). Equivocal staining was seen in 1/37 (3.3%) mandibular ameloblastomas. Of the 30 ameloblastomas subjected to AS-PCR, BRAFV600E mutation was identified in 19/23 (82.6%) mandibular ameloblastomas and 0/7 (0.0%) maxillary ameloblastomas. BRAFV600E mutant ameloblastomas were positive by IHC in 18/19 (94.7%) cases and equivocal in 1/19 (5.3%) cases. All 11 (100.0%) BRAF-wild type ameloblastomas were negative by IHC. BRAF VE1 is an excellent tool for the diagnosis of mandibular ameloblastoma but of limited utility in the maxilla, where it less commonly occurs and where BRAFV600E mutation is considerably less frequent.


Assuntos
Ameloblastoma , Tumores Odontogênicos , Humanos , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Ameloblastoma/patologia , Imuno-Histoquímica , Proteínas Proto-Oncogênicas B-raf/genética , Biomarcadores Tumorais/genética , Mutação
15.
Mod Pathol ; 35(6): 712-720, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35249100

RESUMO

Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Several challenges exist related to quantifying the Ki-67 proliferation index due to lack of method standardization and inter-reader variability. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. We systematically reviewed all published studies on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The most common advantages of DIA were improvement in the standardization and reliability of Ki-67 evaluation, as well as its speed and practicality, compared to the current gold standard approach of manual counts from captured images, which is cumbersome and time consuming. The main limitations were attributed to higher costs, lack of widespread availability (as of yet), operator qualification and training issues (if it is not done by pathologists), and most importantly, the drawback of image algorithms counting contaminating non-neoplastic cells and other signals like hemosiderin. However, solutions are rapidly developing for all of these challenging issues. A comparative meta-analysis for DIA versus manual counting shows very high concordance (global coefficient of concordance: 0.94, 95% CI: 0.83-0.98) between these two modalities. These findings support the widespread adoption of validated DIA methods for Ki-67 assessment in PanNENs, provided that measures are in place to ensure counting of only tumor cells either by software modifications or education of non-pathologist operators, as well as selection of standard regions of interest for analysis. NENs, being cellular and monotonous neoplasms, are naturally more amenable to Ki-67 assessment. However, lessons of this review may be applicable to other neoplasms where proliferation activity has become an integral part of theranostic evaluation including breast, brain, and hematolymphoid neoplasms.


Assuntos
Neoplasias da Mama , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Biomarcadores Tumorais/análise , Proliferação de Células , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Antígeno Ki-67/análise , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Reprodutibilidade dos Testes
16.
Neuropathol Appl Neurobiol ; 48(2): e12754, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34296770

RESUMO

We describe a rare TPIT-positive corticotroph PitNET that is admixed with SF1-positive adrenocortical cells. This dimorphous population of cells showed no colocalisation between TPIT and SF1 by immunofluorescence, and an adrenocortical choristoma was favoured. Methylation array analysis revealed a novel methylation profile in relation to other pituitary neoplasms.


Assuntos
Adenoma Hipofisário Secretor de ACT/patologia , Corticotrofos/patologia , Metilação de DNA , Hipófise/patologia , Neoplasias Hipofisárias/patologia , Adenoma Hipofisário Secretor de ACT/genética , Adenoma Hipofisário Secretor de ACT/metabolismo , Adulto , Corticotrofos/metabolismo , Humanos , Masculino , Hipófise/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo
17.
Inorg Chem ; 61(25): 9480-9492, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35700478

RESUMO

We report the synthesis, characterization, and iodine capture application of a novel thorium-organic nanotube, TSN-626, [Th6O4(OH)4(C6H4NO2)7(CHO2)5(H2O)3]·3H2O. The classification as a metal-organic nanotube (MONT) distinguishes it as a rare and reduced dimensionality subset of metal-organic frameworks (MOFs); the structure is additionally hallmarked by low node connectivity. TSN-626 is composed of hexameric thorium secondary building units and mixed O/N-donor isonicotinate ligands that demonstrate selective ditopicity, yielding both terminating and bridging moieties. Because hard Lewis acid tetravalent metals have a propensity to bind with electron donors of rival hardness (e.g., carboxylate groups), such Th-N coordination in a MOF is uncommon. However, the formation of key structural Th-N bonds in TSN-626 cap some of the square antiprismatic metal centers, a position usually occupied by terminal water ligands. TSN-626 was characterized by using complementary analytical and computational techniques: X-ray diffraction, vibrational spectroscopy, N2 physisorption isotherms, and density functional theory. TSN-626 satisfies design aspects for the chemisorption of iodine. The synergy between accessibility through pores, vacancies at the metal-oxo nodes, and pendent N-donor sites allowed a saturated iodine loading of 955 mg g-1 by vapor methods. The crystallization of TSN-626 diversifies actinide-MOF linker selection to include soft electron donors, and these Th-N linkages can be leveraged for the investigation of metal-to-ligand bonding and unconventional topological expressions.

18.
Support Care Cancer ; 30(6): 4635-4649, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35064822

RESUMO

PURPOSE: The aim was to summarize the current literature for the effectiveness of physical activity interventions on physical functioning, body composition, and quality of life (QOL) in pediatric, adolescent and young adult cancer survivors. METHODS: We conducted systematic structured searches of PubMed and Web of Science databases. Two independent researchers selected against inclusion criteria: (1) lifestyle intervention including physical activity and/or physical activity interventions for pediatric, adolescent, and young adults with any cancer diagnosis; (2) measured QOL, physical functioning (e.g., strength, activities of daily living), or body composition (e.g., changes in weight, percent body fat); and (3) randomized controlled trials. RESULTS: Searches identified 4770 studies. Following the removal of duplicates and title and abstract screening, 83 full-text articles were assessed, and 9 studies met the inclusion criteria. Childhood and adolescent cancer survivors encompassed n = 7 studies while young adult cancer survivors were included in n = 2 studies. Three studies reported using a theoretical framework and six did not. Interventions ranged from 1 week to 6 months. Across all studies reviewed, n = 2 reported improvements in physical activity, n = 5 studies reported partial improvements, and n = 2 reported no improvements. CONCLUSIONS: Interventions to improve physical activity behaviors reported mixed results. Only two physical activity interventions incorporated young adults with cancer; thus, physical activity interventions for young adult cancer survivors should be further explored. Future research should focus on personalized physical activity components encouraging behavior change techniques to maximize physical health and QOL improvements.


Assuntos
Sobreviventes de Câncer , Neoplasias , Atividades Cotidianas , Adolescente , Criança , Exercício Físico , Humanos , Estilo de Vida , Neoplasias/terapia , Qualidade de Vida , Adulto Jovem
19.
Support Care Cancer ; 31(1): 75, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36544032

RESUMO

PURPOSE: No evidence-based prevention strategies currently exist for cancer-related cognitive decline (CRCD). Although patients are often advised to engage in healthy lifestyle activities (e.g., nutritious diet), little is known about the impact of diet on preventing CRCD. This secondary analysis evaluated the association of pre-treatment diet quality indices on change in self-reported cognition during chemotherapy. METHODS: Study participants (n = 96) completed the Block Brief Food Frequency Questionnaire (FFQ) before receiving their first infusion and the PROMIS cognitive function and cognitive abilities questionnaires before infusion and again 5 days later (i.e., when symptoms were expected to be their worst). Diet quality indices included the Dietary Approaches to Stop Hypertension (DASH), Alternate Mediterranean Diet (aMED), and a low carbohydrate diet index and their components. Descriptive statistics were generated for demographic and clinical variables and diet indices. Residualized change models were computed to examine whether diet was associated with change in cognitive function and cognitive abilities, controlling for age, sex, cancer type, treatment type, depression, and fatigue. RESULTS: Study participants had a mean age of 59 ± 10.8 years and 69% were female. Although total diet index scores did not predict change in cognitive function or cognitive abilities, higher pre-treatment ratio of aMED monounsaturated/saturated fat was associated with less decline in cognitive function and cognitive abilities at 5-day post-infusion (P ≤ .001). CONCLUSIONS: Higher pre-treatment ratio of monounsaturated/saturated fat intake was associated with less CRCD early in chemotherapy. Results suggest greater monounsaturated fat and less saturated fat intake could be protective against CRCD during chemotherapy.


Assuntos
Disfunção Cognitiva , Dieta Mediterrânea , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Dieta , Cognição , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/prevenção & controle
20.
J Am Chem Soc ; 143(42): 17354-17359, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34652154

RESUMO

A Np(V) neptunyl metal-organic framework (MOF) with rod-shaped secondary building units was synthesized, characterized, and irradiated with γ rays. Single-crystal X-ray diffraction data revealed an anionic framework containing infinite helical chains of actinyl-actinyl interaction (AAI)-connected neptunyl ions linked together through tetratopic tetrahedral organic ligands (NSM). NSM exhibits an unprecedented net, demonstrating that AAIs may be exploited to give new MOFs and new topologies. To probe its radiation stability, we undertook the first irradiation study of a transuranic MOF and its organic linker building block using high doses of γ rays. Diffraction and spectroscopic data demonstrated that the radiation resistance of NSM is greater than that of its linker building block alone. Approximately 6 MGy of irradiation begins to induce notable changes in the long- and short-range order of the framework, whereas 3 MGy of irradiation induces total X-ray amorphization and changes in the local vibrational bands of the linker building block.

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