Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 213
Filtrar
1.
Toxicol Sci ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730829

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is a major deleterious health effect of chronic arsenic (iAs) exposure. The molecular mechanism of arsenic-induced cSCC remains poorly understood. We recently demonstrated that chronic iAs exposure leads to temporally regulated genome-wide changes in profiles of differentially expressed mRNAs and miRNAs at each stage of carcinogenesis (7, 19 and 28 weeks) employing a well-established passage-matched HaCaT cell line model of arsenic-induced cSCC. Here, we performed longitudinal differential expression analysis (miRNA and mRNA) between the different time points (7 vs. 19 weeks and 19 vs. 28 weeks) within unexposed and exposed groups, coupled to expression pairing and pathway analyses to differentiate the relative effects of long-term passaging and chronic iAs exposure. Data showed that 66-105 miRNA [p < 0.05; log2(Fold Change)>I1I] and 2826-4079 mRNA [p < 0.001; log2(Fold Change)>I1I] molecules were differentially expressed depending on the longitudinal comparison. Several mRNA molecules differentially expressed as a function of time, independent of iAs exposure were being targeted by miRNA molecules which were also differentially expressed in a time dependent manner. Distinct pathways were predicted to be modulated as a function of time or iAs exposure. Some pathways were also modulated both by time and exposure. Thus, the HaCaT model can distinguish between the effects of passaging and chronic iAs exposure individually and corroborate our previously published data on effects of iAs exposure compared to unexposed passage matched HaCaT cells. In addition, this work provides a template for cell line based longitudinal chronic exposure studies to follow for optimal efficacy.

2.
Asian J Neurosurg ; 16(3): 512-517, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660362

RESUMO

Study Design: This was a retrospective study. Purpose: The purpose was to retrospectively evaluate long-term outcome of anterior stabilization in three-column injury of the subaxial cervical spine. Overview of Literature: Literature shows varied results regarding the approach to be chosen. Most studies prefer a combined approach since biomechanically forms more stable construct. The isolated posterior approach is preferred by many as it is easy to reduce and fix three-column injuries. There are very few studies which show the isolated anterior approach to be better than the other two. Materials and Methods: Seventy-eight patients of three-column injury operated by anterior approach with follow-up of atleast 2 years were included and retrospectively analyzed. Clinical data included age, sex, time to surgery, methods of reduction, postoperative mobilization, and neurological evaluation using the ASIA scale. Radiological data included pre- and postreduction X-ray, computed tomography, and magnetic resonance imaging (MRI). X-rays taken post-operatively at 1,3, 6 months, 1yr and 2yrs. Variables like fracture type (AO Classification), overall alignment, localized kyphosis, time for fusion and grade of fusion mass were noted. Results: Of 78 patients, 61 had bifacetal dislocation and 17 unifacetal. The most common site was C5-6, followed by C3-4 and C6-7. The mean patient age was 35.98 years with 60 males and 18 females. The mean time to surgery was 4.4 days. Forty dislocations were reduced by closed method and 38 by open anterior approach. Fifty-six percent of patients had traumatic disc injury on MRI. All are managed by single-level anterior cervical discectomy and fusion with iliac crest autograft for fusion. The mean preoperative lordosis: 4.44° (range -13.4° to 25°) and mean postoperative lordosis: 28.57° (P < 0.0001) mean loss of alignment: 2.59° by 2 years, 100% fusion with mean time - 22.82 weeks, neurological recovery in 34.6% with atleast one grade improvement in ASIA scale. No neurological worsening or need for revision surgery was observed. Conclusion: The goal of surgery in cervical injury is bony stabilization and fusion using a least morbid approach and one with good long-term outcome. Above study concludes that only anterior stabilization after reduction of three-column injury would suffice with good long-term outcome, thereby obviating need for global fusion.

3.
J Proteome Res ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670092

RESUMO

The 2021 Metrics of the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 357 (92.8%) of the 19 778 predicted proteins coded in the human genome, a gain of 483 since 2020 from reports throughout the world reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 478 to 1421. This represents remarkable progress on the proteome parts list. The utilization of proteomics in a broad array of biological and clinical studies likewise continues to expand with many important findings and effective integration with other omics platforms. We present highlights from the Immunopeptidomics, Glycoproteomics, Infectious Disease, Cardiovascular, Musculo-Skeletal, Liver, and Cancers B/D-HPP teams and from the Knowledgebase, Mass Spectrometry, Antibody Profiling, and Pathology resource pillars, as well as ethical considerations important to the clinical utilization of proteomics and protein biomarkers.

4.
Pancreas ; 50(7): 916-922, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34629446

RESUMO

ABSTRACT: The potential of artificial intelligence (AI) applied to clinical data from electronic health records (EHRs) to improve early detection for pancreatic and other cancers remains underexplored. The Kenner Family Research Fund, in collaboration with the Cancer Biomarker Research Group at the National Cancer Institute, organized the workshop entitled: "Early Detection of Pancreatic Cancer: Opportunities and Challenges in Utilizing Electronic Health Records (EHR)" in March 2021. The workshop included a select group of panelists with expertise in pancreatic cancer, EHR data mining, and AI-based modeling. This review article reflects the findings from the workshop and assesses the feasibility of AI-based data extraction and modeling applied to EHRs. It highlights the increasing role of data sharing networks and common data models in improving the secondary use of EHR data. Current efforts using EHR data for AI-based modeling to enhance early detection of pancreatic cancer show promise. Specific challenges (biology, limited data, standards, compatibility, legal, quality, AI chasm, incentives) are identified, with mitigation strategies summarized and next steps identified.

5.
Nat Rev Cancer ; 21(10): 655-668, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34489588

RESUMO

Detection of cancer at an early stage when it is still localized improves patient response to medical interventions for most cancer types. The success of screening tools such as cervical cytology to reduce mortality has spurred significant interest in new methods for early detection (for example, using non-invasive blood-based or biofluid-based biomarkers). Yet biomarkers shed from early lesions are limited by fundamental biological and mass transport barriers - such as short circulation times and blood dilution - that limit early detection. To address this issue, synthetic biomarkers are being developed. These represent an emerging class of diagnostics that deploy bioengineered sensors inside the body to query early-stage tumours and amplify disease signals to levels that could potentially exceed those of shed biomarkers. These strategies leverage design principles and advances from chemistry, synthetic biology and cell engineering. In this Review, we discuss the rationale for development of biofluid-based synthetic biomarkers. We examine how these strategies harness dysregulated features of tumours to amplify detection signals, use tumour-selective activation to increase specificity and leverage natural processing of bodily fluids (for example, blood, urine and proximal fluids) for easy detection. Finally, we highlight the challenges that exist for preclinical development and clinical translation of synthetic biomarker diagnostics.

6.
Global Spine J ; 11(7): 1070-1075, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34343039

RESUMO

STUDY DESIGN: Retrospective observational analysis. OBJECTIVES: Spinal tuberculosis accounts for about 50% of cases among extra pulmonary osteoarticular tuberculosis. Resistance to drugs in spinal tuberculosis patients is on a rise and there is inadequate literature concentrating on the precise pattern of resistance in Indian subcontinent which harbors 24% of global prevalence. The aim was to study the pattern of drug resistance in spinal tuberculosis among first- and second-line drugs. Drug resistance is common in spinal tuberculosis and we intended to find the prevalence of various drug resistance patterns. METHODS: Patients with spinal tuberculosis visiting a tertiary center were assessed. Samples were taken from the affected vertebrae and sent for BACTEC mycobacterium growth indicator tube (MGIT) 960 culture. Patients with a positive growth in MGIT were included in the study. All previously treated patients (relapse, treatment after failure, treatment after loss to follow-up and other previously treated patients) were excluded. RESULTS: A total of 150 patients with a positive growth in MGIT report were included in the study, of whom 43 patients had some kind of drug resistance. Seven were multidrug resistant (MDR), 9 had preextensive drug resistance (pre-XDR), and 4 had extensive drug resistance (XDR). Seventeen patients had mono-drug resistance, which was most frequently for isoniazid. Resistance among second-line drugs was common in the fluoroquinolone group. CONCLUSION: Drug resistance in spinal tuberculosis was found to be 28.6%. Of these, MDR was in 16.2%, pre-XDR in 20.9%, and XDR in 9.3% patients.

7.
Asian J Neurosurg ; 16(1): 187-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211892

RESUMO

Non penetrating trauma to vertebral artery is a known complication in craniovertebral trauma. They are mainly reported with facet dislocations or injuries involving the foramen transversarium. Such a type of injury is rarely seen with flexion injuries. We report such a case leading to cerebellar stroke in a young male presenting to us with hemiparesis. A 43-year-old male presented to us 1 month post trauma after a motor vehicular accident with complaint of weakness of right half of the body since the trauma. He suffered blunt trauma to head and neck and complained of a flail right upper limb since trauma and weakness of the right lower limb which had partly improved. He was conservatively managed elsewhere. Radiographic investigations revealed complete occlusion of the right vertebral injury above the level of 6th cervical vertebra and flexion teardrop fracture of 5th cervical vertebra. He was managed conservatively for the vertebral artery injury (VAI) and corpectomy of C5 vertebra with anterior cervical plating and fusion. Such a rare type of injury can present with unexplained neurodeficit which needs appropriate radiological investigations for diagnosis before ascribing the cause to cord trauma. Hence, all high velocity motor vehicular accidents with associated fractures and neurodeficit should be screened for blunt VAIs.

8.
Arch Toxicol ; 95(7): 2351-2365, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34032870

RESUMO

Chronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.

9.
Dis Colon Rectum ; 64(9): 1083-1095, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33990498

RESUMO

BACKGROUND: Colon cancer survival is dependent on metastatic potential and treatment. Large RNA-sequencing data sets may assist in identifying colon cancer-specific biomarkers to improve patient outcomes. OBJECTIVE: This study aimed to identify a highly specific biomarker for overall survival in colon adenocarcinoma by using an RNA-sequencing data set. DESIGN: Raw RNA-sequencing and clinical data for patients with colon adenocarcinoma (n = 271) were downloaded from The Cancer Genome Atlas. A binomial regression model was used to calculate differential RNA expression between paired colon cancer and normal epithelium samples (n = 40). Highly differentially expressed RNAs were examined. SETTINGS: This study was conducted at the University of Louisville using data acquired by The Cancer Genome Atlas. PATIENTS: Patients from US accredited cancer centers between 1998 and 2013 were analyzed. MAIN OUTCOME MEASURES: The primary outcome measures were recurrence-free and overall survival. RESULTS: The median age was 66 years (147/271 men, 180/271 White patients). Thirty RNAs were differentially expressed in colon adenocarcinoma compared with paired normal epithelium, using a log-fold change cutoff of ±6. Using median expression as a cutoff, 4 RNAs were associated with worse overall survival: decreased ZG16 (log-rank = 0.023), aquaporin 8 (log-rank = 0.023), and SLC26A3 (log-rank = 0.098), and increased COL1A1 (log-rank = 0.105). On multivariable analysis, low aquaporin 8 expression (HR, 1.748; 95% CI, 1.016-3.008; p = 0.044) was a risk factor for worse overall survival. Our final aquaporin 8 model had an area under the curve of 0.85 for overall survival. On subgroup analysis, low aquaporin 8 was associated with worse overall survival in patients with high microsatellite instability and in patients with stage II disease. Low aquaporin 8 expression was associated with KRAS and BRAF mutations. Aquaporin 8 immunohistochemistry was optimized for clinical application. LIMITATIONS: This was a retrospective study. CONCLUSION: Aquaporin 8 is a water channel selectively expressed in normal colon tissue. Low aquaporin 8 expression is a risk factor for worse overall survival in patients who have colon cancer. Aquaporin 8 measurement may have a role as a colon-specific prognostic biomarker and help in patient risk stratification for increased surveillance. See Video Abstract at http://links.lww.com/DCR/B603. LA DISMINUCIN DE LA EXPRESIN TUMORAL DE LA ACUAPORINA DEL CANAL DE AGUA ESPECFICO DEL COLON SE ASOCIA CON UNA REDUCCIN DE LA SUPERVIVENCIA GENERAL EN EL ADENOCARCINOMA DE COLON: ANTECEDENTES:La supervivencia del cáncer de colon depende del potencial metastásico y del tratamiento. Grandes conjuntos de datos de secuenciación de ARN pueden ayudar a identificar biomarcadores específicos del cáncer de colon para mejorar los resultados de los pacientes.OBJETIVO:Identificar un biomarcador altamente específico para la supervivencia general en el adenocarcinoma de colon utilizando un conjunto de datos de secuenciación de ARN.DISEÑO:La secuenciación de ARN sin procesar y los datos clínicos para pacientes con adenocarcinoma de colon (n = 271) se descargaron de The Cancer Genome Atlas. Se utilizó un modelo de regresión binomial para calcular la expresión diferencial de ARN entre muestras de cáncer de colon emparejadas y muestras de epitelio normal (n = 40). Se examinaron los ARN expresados de forma altamente diferencial.ENTORNO CLINICO:Este estudio se realizó en la Universidad de Louisville utilizando datos adquiridos por The Cancer Genome Atlas.PACIENTES:Se analizaron pacientes de centros oncológicos acreditados en Estados Unidos entre 1998-2013.PRINCIPALES MEDIDAS DE VALORACION:Las principales medidas de valoración fueron la supervivencia general y libre de recurrencia.RESULTADOS:La mediana de edad fue de 66 años (147/271 hombres, 180/271 caucásicos). Treinta ARN se expresaron diferencialmente en el adenocarcinoma de colon en comparación con el epitelio normal emparejado, utilizando un límite de cambio logarítmico de ± 6. Utilizando la expresión mediana como punto de corte, cuatro ARN se asociaron con una peor supervivencia general: disminución de ZG16 (rango logarítmico = 0,023), acuaporina8 (rango logarítmico = 0,023) y SLC26A3 (rango logarítmico = 0,098) y aumento de COL1A1 (log -rango = 0,105). En el análisis multivariable, la baja expresión de acuaporina8 (HR = 1,748, IC del 95%: 1,016-3,008, p = 0,044) fue un factor de riesgo para una peor supervivencia global. Nuestro modelo de aquaporin8 final tuvo un AUC de 0,85 para la supervivencia global. En el análisis de subgrupos, la acuaporina8 baja se asoció con una peor supervivencia general en pacientes con MSI-H y en pacientes en estadio II. La baja expresión de acuaporina8 se asoció con mutaciones de KRAS y BRAF. La inmunohistoquímica de aquaporina8 se optimizó para su aplicación clínica.LIMITACIONES:Este fue un estudio retrospectivo.CONCLUSIÓN:La acuaporina8 es un canal de agua expresado selectivamente en el tejido normal del colon. La baja expresión de AQP8 es un factor de riesgo de peor supervivencia global en pacientes con cáncer de colon. La medición de aquaporina8 puede tener un papel como un biomarcador de pronóstico específico del colon y ayudar en la estratificación del riesgo del paciente para una mayor vigilancia. Consulte Video Resumen en http://links.lww.com/DCR/B603.

10.
Curr Opin Gastroenterol ; 37(5): 480-485, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039875

RESUMO

PURPOSE OF REVIEW: Diseases of the pancreas are a broad spectrum of conditions resulting from metabolic, inflammatory, and neoplastic processes (pancreatitis, pancreatogenic diabetes, and pancreatic cancers). Pancreatic diseases cause significant morbidity, mortality, and cost. RECENT FINDINGS: Research progress in diseases of the exocrine pancreas (chronic pancreatitis [CP], pancreatogenic diabetes mellitus, and pancreatic cancer) has been hampered by the disorders' heterogeneity, the limitations of previous small cross-sectional studies, the inability to safely obtain pancreatic tissue for study, and the lack of structured epidemiology tools, genetic testing, and biomarker development. SUMMARY: Given the increasing incidence and prevalence of CP and its complications, high mortality rate, and associated healthcare cost, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute funded the Consortium for the study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC) to identify research gaps and foster multidisciplinary collaborations to better diagnose, characterize and manage CP and its sequelae and to understand the diabetes/pancreatic cancer association.The studies undertaken by the CPDPC are described in other articles in this journal's issue.


Assuntos
Diabetes Mellitus , Neoplasias Pancreáticas , Pancreatite Crônica , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Detecção Precoce de Câncer , Humanos , National Institutes of Health (U.S.) , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/terapia , Estados Unidos/epidemiologia
11.
Pancreas ; 50(3): 251-279, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33835956

RESUMO

ABSTRACT: Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.

12.
Int J Spine Surg ; 15(1): 18-25, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33900953

RESUMO

BACKGROUND: Though spinal tuberculosis has a predilection for the dorsal and lumbar spine, a high percentage of morbidity and mortality is associated with cervical tuberculosis. Cervical tuberculosis accounts for about 10% of cases, with the major concerns being quadriparesis/quadriplegia and kyphotic deformity. Herein we describe our experience with the use of anterior instrumentation with titanium implants in 46 patients with subaxial tuberculosis. MATERIALS AND METHODS: Included in the study were a total of 46 patients with subaxial cervical (C3-C7) and upper dorsal (D1-D3) tuberculosis who underwent operations with anterior debridement, decompression, bone grafting, and anterior instrumentation by a single surgeon at our institute between January 2007 and December 2014. A review of the demographic data, medical records, and x-rays before and after surgery and at subsequent follow-ups was performed retrospectively from the departmental database. RESULTS: Neurological involvement in the postoperative period was seen in 29 of the 30 patients, 26 of whom showed complete neurological recovery. The Cobb angle at presentation ranged from 2°-58° of kyphosis with an average kyphosis of 15.4°. The average lordosis after surgery was found to be 17.5° (ie, a mean correction of 32.9°). CONCLUSIONS: Anterior instrumentation of subaxial cervical tuberculosis with titanium implants provides good correction of kyphosis and provides reasonable neurologic recovery in patients and ensures a long-lasting functional outcome. LEVEL OF EVIDENCE: 4.

13.
Commun Biol ; 4(1): 265, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649493

RESUMO

Large numbers of cells are generally required for quantitative global proteome profiling due to surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs)). Here we report a surfactant-assisted one-pot sample preparation coupled with mass spectrometry (MS) method termed SOP-MS for label-free global single-cell proteomics. SOP-MS capitalizes on the combination of a MS-compatible nonionic surfactant, n-Dodecyl-ß-D-maltoside, and hydrophobic surface-based low-bind tubes or multi-well plates for 'all-in-one' one-pot sample preparation. This 'all-in-one' method including elimination of all sample transfer steps maximally reduces surface adsorption losses for effective processing of single cells, thus improving detection sensitivity for single-cell proteomics. This method allows convenient label-free quantification of hundreds of proteins from single human cells and ~1200 proteins from small tissue sections (close to ~20 cells). When applied to a patient CTC-derived xenograft (PCDX) model at the single-cell resolution, SOP-MS can reveal distinct protein signatures between primary tumor cells and early metastatic lung cells, which are related to the selection pressure of anti-tumor immunity during breast cancer metastasis. The approach paves the way for routine, precise, quantitative single-cell proteomics.


Assuntos
Neoplasias da Mama/metabolismo , Glucosídeos/química , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Células Neoplásicas Circulantes/metabolismo , Proteoma , Proteômica , Análise de Célula Única , Tensoativos/química , Animais , Neoplasias da Mama/patologia , Cromatografia Líquida , Feminino , Humanos , Neoplasias Pulmonares/secundário , Células MCF-7 , Camundongos , Micrometástase de Neoplasia , Células Neoplásicas Circulantes/patologia , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
14.
Cell Death Discov ; 7(1): 61, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771981

RESUMO

Colon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found to be principally located in the cellular cytoplasm. ZFAS1 knockdown was associated with decreased cellular proliferation, migration, and invasion in two colon cancer cell lines (HT29 and SW480). MicroRNA-200b and microRNA-200c (miR-200b and miR-200c) are experimentally validated targets of ZFAS1, and this interaction was confirmed using reciprocal gene knockdown. ZFAS1 knockdown regulated ZEB1 gene expression and downstream targets E-cadherin and vimentin. Knockdown of miR-200b or miR-200c reversed the effect of ZFAS1 knockdown in the ZEB1/E-cadherin, vimentin signaling cascade, and the effects of cellular migration and invasion, but not cellular proliferation. ZFAS1 knockdown was also associated with decreased tumor growth in an in vivo mouse model. These results demonstrate the critical importance of ZFAS1 as a regulator of the miR-200/ZEB1/E-cadherin, vimentin signaling cascade.

16.
Trends Cancer ; 7(2): 122-133, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008796

RESUMO

Early cancer diagnosis is critical for improving patient survival and mortality rates, but most diagnostics on solid tumors rely on imaging tests with limited sensitivity and specificity to identify potential cases, which are then confirmed by tissue biopsies. However, this process is usually not suitable for cancer screening or evaluation of tumor responses to treatment. Liquid biopsies have the potential to bridge this gap, but few such assays have been approved for cancer applications. Extracellular vesicles hold particular promise for liquid biopsy diagnostics but are currently limited by the lack of robust methods for isolation and analysis. New isolation and analysis techniques, however, show promise to improve the clinical utility of extracellular vesicle-based cancer diagnosis.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Vesículas Extracelulares/patologia , Neoplasias/diagnóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Humanos , Biópsia Líquida/métodos , Neoplasias/sangue , Neoplasias/genética , Neoplasias/patologia
17.
J Urol ; 205(2): 420-425, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32945736

RESUMO

PURPOSE: Prostate cancer is predominantly indolent at diagnosis with a small fraction (15% to 25%) representing aggressive subtype (Gleason score 7-10), which is prone to metastatic progression. It is critical to explore noninvasive assays for the early detection of this aggressive subtype, when it still can be treated effectively. Additionally, there is an emerging need to develop markers that perform equally well across races, as racial differences in the prevalence and mortality of prostate cancer has become evident. MATERIALS AND METHODS: First catch, nondigital rectal examination urine specimens were collected from patients undergoing diagnostic biopsy. Total RNA was extracted from urinary exosomes and a quantitative expression assay protocol using droplet digital polymerase chain reaction was developed for detection of candidate genes in exosomal mRNAs from urine. Clinical performance for the gene expression assay was evaluated to predict high grade cancer (Gleason score 7-10) from low grade cancer (Gleason score 6) and cancer negative cases at biopsy. Assay performance was examined in combination with standard of care to determine improvement in model prediction. RESULTS: In a racially diverse patient cohort a 2-gene panel (PCA3, PCGEM1), in combination with standard of care variables, significantly improved the prediction of high grade cancer at diagnosis compared to standard of care variables alone (AUC 0.88 vs 0.80, respectively, p=0.016). Decision curve analysis showed that there is a benefit of adopting the gene panel for detection of high grade cancer compared to standard of care alone. CONCLUSIONS: This study highlights the potential for developing broadly applicable prostate cancer diagnostic biomarker panels for aggressive prostate cancer using our novel gene expression assay platform.


Assuntos
Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Coortes , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/urina
19.
Global Spine J ; : 2192568220973615, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33327790

RESUMO

STUDY DESIGN: Retrospective analysis of case series. OBJECTIVE: The aim is to study the recovery of neurological deficit in pediatric spinal tuberculosis cases presenting to us more than 6 months after onset of motor weakness in lower limbs. METHODS: This is a retrospective analysis of 13 consecutive patients of pediatric spinal tuberculosis presenting to us at least 6 months after the onset of neurologic deficit. All these patients underwent surgical intervention at our center and their neurological recovery was noted in terms of improvement in Frankel grading and spasticity improvement by modified Ashworth scale. All the patients were followed up to at least 18 months post op and final neurologic status was assessed at that time. RESULTS: The mean age of the patients at presentation was 8.5 years. The mean duration of neurologic deficit at the time of presentation was 10.23 months (6-24 months). Seven patients had a Frankel grade B at presentation out of which 6 improved to Frankel grade D and one improved to Frankel C at final follow up. Out of the other 3 patients with Frankel A at presentation, 2 improved to Frankel grade D and 1 to Frankel grade C. The remaining 3 patients presented with Frankel grade C at presentation, 2 improved to Frankel D and one improved to Frankel E at the time of final follow up. CONCLUSION: Neurologic recovery in patients with neurological deficit is possible even in cases of long standing deficit more than 6 months and in some cases upto 24 months as shown in our study.

20.
Asian J Neurosurg ; 15(3): 648-652, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33145221

RESUMO

Introduction: Tricortical iliac bone is the gold standard as an autograft for the reconstruction of the anterior column in tuberculosis (TB) of the thoracic spine. However, the quantity of graft needed is significant. It creates a considerable defect in the pelvic bone, causing graft site complications, including pain, pelvic instability, fractured ilium, herniated muscle, or abdominal contents. To prevent these donor site morbidities, ribs that were removed during the versatile approach were used for anterior reconstruction. The aim of this study was to assess the clinical and radiological results of the reconstruction of the anterior column of the spine with the help of an excised rib during the versatile approach. Subjects and Methods: This retrospective study was undertaken at a tertiary care center with a study duration of 14 years. Between January 2004 and December 2016, 52 patients with thoracic Koch's spine had anterior column reconstructed with multiple rib grafts. A single surgeon performed all operations. Indications for the surgery in these patients were the presence of neurologic deficit (49 patients) and vertebral column instability (3 patients). The preoperative kyphosis angle and visual analog scale (VAS) score were compared with postoperative values using a paired t-test. Results: All patients underwent a minimum follow-up of 18 months and were evaluated clinicoradiologically. Good bony fusion with neurological recovery was achieved in all cases. The VAS score for back pain improved significantly postsurgery. There was one case of graft buckling treated conservatively. Discussion: Appropriate anterior reconstruction forms the cornerstone of successful surgical management of spinal TB. The "Versatile approach" used offers anterior and posterior access in the lateral position. In these patients, we obviated the need for iliac crest graft using multiple segments of the rib for anterior column reconstruction. This meticulous rib grafting technique gives good functional outcome in terms of solid bony fusion. Conclusion: Meticulous rib grafting technique gives 360° bony fusion and good functional outcome in surgery for thoracic spinal TB. It has the advantage of avoiding the complications associated with a tricortical iliac crest graft.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...