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1.
Environ Sci Pollut Res Int ; 31(19): 28578-28593, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38558333

RESUMO

The application of perovskite lanthanum ferrite (LaFeO3) as a photocatalyst has shown significant potential in the removal of persistent organic and inorganic contaminants. In the present research, LaFeO3 and various composites consisting of LaFeO3 and TiO2 were prepared. The photocatalytic efficiency of the produced catalysts was assessed by measuring their effectiveness in degrading thiamethoxam, a pesticide belonging to the second generation of neonicotinoids. Experimental investigations were carried out to examine the impact of various factors on the degradation process, including variables like concentration of thiamethoxam, catalyst amount, and pH level. The produced catalysts were characterized by various techniques, including field emission scanning electron microscopy (FESEM), Brunauer-Emmett-Teller (BET) analysis, X-ray diffraction (XRD), ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS), photoluminescence (PL), and X-ray photoelectron spectroscopy (XPS). The highest degradation rates were observed when using the synthesized catalyst, 1% LaFeO3/TiO2 (LFTO1), under both UV-C and direct sunlight conditions. This performance outperformed TiO2 and bare LaFeO3. When exposed to ultraviolet (UV-C) radiation at an intensity of 15 W m-2 and under neutral pH conditions, LFTO1 achieved approximately 97% degradation, while under direct sunlight, the LFTO1 photocatalyst exhibited a degradation rate of 79% within a 120-min reaction period. The enhanced activity of LFTO1 could be attributed to its increased surface area, reduced bandgap, and lower electron-hole recombination. The investigation of reaction kinetics showed that the degradation of thiamethoxam followed a pseudo-first-order rate law. Furthermore, LFTO1 can be employed up to 5 times without experiencing any loss in its catalytic activity, thus confirming its long-term utility.


Assuntos
Tiametoxam , Titânio , Titânio/química , Tiametoxam/química , Catálise , Compostos Férricos/química , Lantânio/química , Neonicotinoides/química , Compostos de Cálcio/química
2.
Clin Chem ; 70(1): 206-219, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175602

RESUMO

BACKGROUND: Cancer is a dynamic process and thus requires highly informative and reliable biomarkers to help guide patient care. Liquid-based biopsies have emerged as a clinical tool for tracking cancer dynamics. Extracellular vesicles (EVs), lipid bilayer delimited particles secreted by cells, are a new class of liquid-based biomarkers. EVs are rich in selectively sorted biomolecule cargos, which provide a spatiotemporal fingerprint of the cell of origin, including cancer cells. CONTENT: This review summarizes the performance characteristics of EV-based biomarkers at different stages of cancer progression, from early malignancy to recurrence, while emphasizing their potential as diagnostic, prognostic, and screening biomarkers. We discuss the characteristics of effective biomarkers, consider challenges associated with the EV biomarker field, and report guidelines based on the biomarker discovery pipeline. SUMMARY: Basic science and clinical trial studies have shown the potential of EVs as precision-based biomarkers for tracking cancer status, with promising applications for diagnosing disease, predicting response to therapy, and tracking disease burden. The multi-analyte cargos of EVs enhance the performance characteristics of biomarkers. Recent technological advances in ultrasensitive detection of EVs have shown promise with high specificity and sensitivity to differentiate early-cancer cases vs healthy individuals, potentially outperforming current gold-standard imaging-based cancer diagnosis. Ultimately, clinical translation will be dictated by how these new EV biomarker-based platforms perform in larger sample cohorts. Applying ultrasensitive, scalable, and reproducible EV detection platforms with better design considerations based upon the biomarker discovery pipeline should guide the field towards clinically useful liquid biopsy biomarkers.


Assuntos
Vesículas Extracelulares , Neoplasias , Humanos , Detecção Precoce de Câncer , Neoplasias/diagnóstico , Biópsia Líquida , Biomarcadores
3.
Int J Mol Sci ; 24(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37511077

RESUMO

Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates the at-risk population. Ample research has elucidated the pathogenesis of BE and its progression from metaplasia to invasive carcinoma; and multiple molecular pathways have been implicated in this process, presenting several points of cancer interception. Here, we explore the mechanisms of action of various agents, including proton pump inhibitors, non-steroidal anti-inflammatory drugs, metformin, and statins, and explain their roles in cancer interception. Data from the recent AspECT trial are discussed to determine how viable a multipronged approach to cancer chemoprevention would be. Further, novel concepts, such as the repurposing of chemotherapeutic drugs like dasatinib and the prevention of post-ablation BE recurrence using itraconazole, are discussed.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Humanos , Esôfago de Barrett/metabolismo , Neoplasias Esofágicas/patologia , Adenocarcinoma/metabolismo , Fatores de Risco , Metaplasia
4.
Clin Cancer Res ; 29(9): 1678-1688, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36892581

RESUMO

PURPOSE: To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation. PATIENTS AND METHODS: Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0. RESULTS: Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9-17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P < 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60-1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15-1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events. CONCLUSIONS: An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection.


Assuntos
Adenoma , Neoplasias do Colo , Neoplasias Colorretais , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adenoma/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Imunoglobulina G , Vacinas de Subunidades Antigênicas
5.
J Clin Gastroenterol ; 57(3): 246-252, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730670

RESUMO

Colorectal cancer (CRC) continues to be a significant public health problem worldwide. CRC screening programs have reduced the incidence rates of CRCs but still suffer from the problems of missed lesions and interval cancers. Chemopreventive strategies against CRC would benefit high-risk populations but trials testing synthetic and naturally occurring compounds have not yielded a front runner. Immune mechanisms promoting cancer have been modulated to develop immunotherapy for cancer treatment that has revolutionized cancer management, but could also be applied to cancer interception, that is, cancer immunoprevention. Cancer immunoprevention refers to approaches that can enhance the immune system, either directly or by removing natural breaks such as immune checkpoints, to survey and destroy tumor cells. In this primer, we aim to explain the concepts behind vaccine-based cancer immunoprevention. Multiple cancer vaccines have been tried in advanced cancer populations, but most have failed primarily because of an immunosuppressive environment that accompanies advanced cancers. Preventive vaccines in immunocompetent hosts may have a better clinical response compared with therapeutic vaccines in immunosuppressed hosts. The first randomized controlled trial testing the mucin1 vaccine against CRC in the prevention setting has been successfully completed. For the benefit of the clinician, we briefly discuss important concepts related to the workings of preventive vaccines. Prevention with vaccines is a highly attractive approach because of the potential for highly targeted therapy with minimal side effects that could theoretically provide lifelong protection.


Assuntos
Vacinas Anticâncer , Neoplasias Colorretais , Humanos , Vacinas Anticâncer/uso terapêutico , Imunoterapia , Neoplasias Colorretais/prevenção & controle , Imunossupressores , Vacinação
6.
Am J Gastroenterol ; 117(11): 1877-1879, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36087100

RESUMO

INTRODUCTION: Germline variants in CDH1 are associated with elevated risks of diffuse gastric cancer and lobular breast cancer. It is uncertain whether there is an increased risk of colorectal neoplasia. METHODS: This was a retrospective analysis of colonoscopy outcomes in patients with germline CDH1 pathogenic/likely pathogenic variants. RESULTS: Eighty-five patients were included with a mean age of 46.9 years. Initial colonoscopy found adenomatous polyps in 30 patients (35.3%), including advanced adenomas in 9 (10.6%). No colorectal cancers were identified on index or subsequent colonoscopies (when available). DISCUSSION: CDH1 carriers have colorectal neoplasia identified at similar rates as in the general population. Despite potential difficulties after gastrectomy, colorectal cancer screening remains important in this population.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Mutação em Linhagem Germinativa , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/diagnóstico , Colonoscopia , Antígenos CD/genética , Caderinas/genética
7.
Cancer Prev Res (Phila) ; 15(9): 557-559, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047056

RESUMO

The CAPP2 investigators report on the long-term effects of resistant starch (RS) on the incidence of colorectal cancer and other Lynch syndrome-related tumors in the trial population of the CAPP-2 study. RS has no effect on colorectal cancer incidence, but it reduced the numbers of other Lynch syndrome-related tumors, mainly driven by upper gastrointestinal cancers. Although the study has limitations related to secondary analysis, it fills an important void in the field of cancer interception of non-colorectal Lynch syndrome-related tumors and should form the basis for future trials of RS in Lynch syndrome. See related article, p. 623.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Musa , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Seguimentos , Humanos , Incidência , Amido Resistente
8.
Am J Physiol Gastrointest Liver Physiol ; 322(6): G598-G614, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35380457

RESUMO

The pathogenesis of subsquamous intestinal metaplasia (SSIM), in which glands of Barrett's esophagus (BE) are buried under esophageal squamous epithelium, is unknown. In a rat model of reflux esophagitis, we found that columnar-lined esophagus developed via a wound-healing process involving epithelial-mesenchymal plasticity (EMP) that buried glands under ulcerated squamous epithelium. To explore a role for reflux-induced EMP in BE, we established and characterized human Barrett's organoids and sought evidence of EMP after treatment with acidic bile salts (AB). We optimized media to grow human BE organoids from immortalized human Barrett's cells and from BE biopsies from seven patients, and we characterized histological, morphological, and molecular features of organoid development. Features and markers of EMP were explored following organoid exposure to AB, with and without a collagen I (COL1) matrix to simulate a wound-healing environment. All media successfully initiated organoid growth, but advanced DMEM/F12 (aDMEM) was best at sustaining organoid viability. Using aDMEM, organoids comprising nongoblet and goblet columnar cells that expressed gastric and intestinal cell markers were generated from BE biopsies of all seven patients. After AB treatment, early-stage Barrett's organoids exhibited EMP with loss of membranous E-cadherin and increased protrusive cell migration, events significantly enhanced by COL1. Using human BE biopsies, we have established Barrett's organoids that recapitulate key histological and molecular features of BE to serve as high-fidelity BE models. Our findings suggest that reflux can induce EMP in human BE, potentially enabling Barrett's cells to migrate under adjacent squamous epithelium to form SSIM.NEW & NOTEWORTHY Using Barrett's esophagus (BE) biopsies, we established organoids recapitulating key BE features. During early stages of organoid development, a GERD-like wound environment-induced features of epithelial-mesenchymal plasticity (EMP) in Barrett's progenitor cells, suggesting that reflux-induced EMP can enable Barrett's cells to migrate underneath squamous epithelium to form subsquamous intestinal metaplasia, a condition that may underlie Barrett's cancers that escape detection by endoscopic surveillance, and recurrences of Barrett's metaplasia following endoscopic eradication therapy.


Assuntos
Esôfago de Barrett , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Esofagite Péptica , Refluxo Gastroesofágico , Animais , Esôfago de Barrett/patologia , Ácidos e Sais Biliares/farmacologia , Carcinoma de Células Escamosas/complicações , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/patologia , Refluxo Gastroesofágico/complicações , Humanos , Metaplasia , Organoides/patologia , Ratos
9.
J Environ Manage ; 306: 114516, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35051823

RESUMO

The sludge yield minimization from advanced biological treatment for industrial wastewater could be considered a poorly explored area, therefore, seeks serious attention of the scientific community. Up to best of the knowledge, the extracellular polymeric substances (EPS) profile underlying an upgraded activated sludge treatment (as MANODOX system) for real tannery wastewater has not been addressed in a desired manner. This study covers the elucidation of EPS degradation mechanism and floc morphology underlying MANODOX system for the treatment of real tannery influent. For this purpose, a modified heat extraction method was followed for the estimation of EPS fractions like protein (PN), polysaccharides (PS) and humic contents from the sludge. For the present investigation, the variation in floc characteristics including PN/PS ratio, sludge hydrophobicity, sludge volume index, and facultative microbiota at corresponding change in hydrodynamic sludge retention time (SRT) of 08-40 days was emphasized. The strict maintenance of adapted operational strategies including favoring range of SRT (24 days) for MANODOX implementation succeeded an outstanding in-situ sludge yield minimization lowered up to 0.39 gMLSS/gTCOD that attributed to three times lowered accumulation of PN and PS, comparably lower PN/PS ratio, higher salinity of the mixed liquid, weakened cell-to-cell attachment compared with a parallel run identical aerobic treatment. Here, the reason for improved hydrophobicity and corresponding decline in floc aggregation was attributed to change in sludge PN/PS ratio, carbon to nitrogen ratio of feed influent. The observations confirmed that the sludge yield minimization from MANODOX like systems could be effectively controlled by maintaining aforementioned operational tactics.


Assuntos
Esgotos , Águas Residuárias , Reatores Biológicos , Floculação , Nitrogênio , Eliminação de Resíduos Líquidos
10.
Chemosphere ; 286(Pt 3): 131837, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34399266

RESUMO

The presence of highly toxic and persistent pesticides in water bodies causes serious problems to human beings as well as aquatic life. Quinalphos is one such widely used organophosphorus pesticide in agricultural fields. Herein, for degradation and mineralization of quinalphos, ZnO nanoflowers and their hybrid nanocomposite with graphene oxide have been synthesized. FESEM analysis confirmed the formation of ZnO nanoflowers over nanosheets of graphene oxide having a thickness of 20 ± 10 nm. GO-ZnO composite exhibited remarkable photocatalytic activity in comparison to pure ZnO. 98 % degradation of quinalphos was achieved using GO-ZnO nano-catalyst at 6 pH within 45 min of irradiations, whereas it was 80 % for bare ZnO nanoflowers. Higher degradation with hybrid nanocomposite was attributed to improved surface area (36 m2 g-1), a substantial reduction in bandgap energy from 3.10 to 2.90 eV and enhanced charge separation (e-/h+ pairs) after the addition of GO. Reaction kinetics study followed pseudo-first-order behaviour. Further, mineralization to the extent of 90 % in 90 min was confirmed by TOC analysis. Based on identified intermediates, using LCMS analysis, degradation pathways were proposed. The plausible pathways confirmed the presence of smaller and safer reaction intermediates supported by excitation of e- from nanocomposite followed by oxidation of quinalphos with huge free radicals. Overall, this study is significant in terms of using photocatalysis as a tertiary treatment of quinalphos pesticide wastewater at pH 6 in a short duration.


Assuntos
Praguicidas , Óxido de Zinco , Catálise , Humanos , Cinética , Compostos Organofosforados , Compostos Organotiofosforados
11.
Anticancer Res ; 42(1): 59-66, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969709

RESUMO

BACKGROUND/AIM: This study aimed to compare the efficacy and tolerability of pre-operative platinum/5-fluorouracil (P5F) and carboplatin/paclitaxel (CP), in combination with radiation therapy in older adults with locally advanced, stage I-III esophageal cancer. PATIENTS AND METHODS: We retrospectively reviewed 51 patients aged ≥70 years who underwent chemoradiotherapy followed by esophagectomy for stage I-III esophageal cancer between 2008 and 2018. Pathological complete response (pCR) and survival rates were compared across the two chemotherapy regimen arms. RESULTS: Treatment completion (p=0.28), pCR (p=0.89), and partial response rates were similar across both chemotherapy groups. Overall survival (OS) and disease-free survival (DFS) were similar across both groups with HR=0.80 (p=0.62) and HR=0.72 (p=0.72) respectively. CONCLUSION: The lesser toxic CP regimen may be used in older patients with locally advanced esophageal cancer, with tumor response and survival rates similar to P5F chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/uso terapêutico , Paclitaxel/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/farmacologia , Fluoruracila/farmacologia , Humanos , Paclitaxel/farmacologia , Estudos Retrospectivos
12.
Int J Oncol ; 59(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34396449

RESUMO

Microsatellite instability­high/deficient mismatch repair colorectal cancer (MSI­H/dMMR CRC) is a molecular subtype characterized by high­frequency mutations within DNA mismatch repair genes. Defects in the DNA mismatch repair machinery lead to subsequent frame­shift mutations, resulting in the generation of frame­shift peptides that serve as neoantigens. This has translated into exquisite sensitivity to immune checkpoint inhibitors (ICIs) and a significant clinical benefit from immune therapies in this patient population. The present article provides a comprehensive review of the advances in the field of immune therapies for MSI­H/dMMR metastatic CRC, with a focus on the major randomized clinical trials that led to Food and Drug Administration approval of specific ICIs for this population, a detailed review of the molecular background responsible for tumor response, as well as the mechanisms of resistance to ICI therapy. Finally, ongoing investigations of other immunotherapeutic strategies to address and overcome the challenges that currently limit response and long­term response to ICIs were presented.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/uso terapêutico , Instabilidade de Microssatélites/efeitos dos fármacos , Ensaios Clínicos como Assunto , Neoplasias Colorretais/genética , Aprovação de Drogas/organização & administração , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Metástase Neoplásica , Estados Unidos , United States Food and Drug Administration
13.
PLoS One ; 16(8): e0255809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34403452

RESUMO

Colorectal cancer (CRC) is one of the most common types of cancer with a high mortality rate. Colonoscopy is the preferred procedure for CRC screening and has proven to be effective in reducing CRC mortality. Thus, a reliable computer-aided polyp detection and classification system can significantly increase the effectiveness of colonoscopy. In this paper, we create an endoscopic dataset collected from various sources and annotate the ground truth of polyp location and classification results with the help of experienced gastroenterologists. The dataset can serve as a benchmark platform to train and evaluate the machine learning models for polyp classification. We have also compared the performance of eight state-of-the-art deep learning-based object detection models. The results demonstrate that deep CNN models are promising in CRC screening. This work can serve as a baseline for future research in polyp detection and classification.


Assuntos
Pólipos do Colo/classificação , Colonoscopia , Pólipos do Colo/patologia , Neoplasias Colorretais/diagnóstico , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
14.
Bioresour Technol ; 341: 125748, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34416656

RESUMO

An advanced operational configuration of anoxic-aerobic moving bed biofilm reactors (AMOMOX process) was experimentally demonstrated to achieve simultaneous sludge yield minimization, pollution and nitrogen removal. The AMOMOX experimentation witnessed considerable variation in process parameters while feed operation changed from synthetic wastewater to real tannery influent. The strict maintenance of operational strategies resulted prominent removal of TCOD, SCOD, ammonia nitrogen and total nitrogen higher upto 93.5%, 94.8%, 95.2% and 88.7% respectively. The nourishment of filamentous microbiota and purposeful promotion of cell-lysis effectively sustained sludge yield restriction. Here, the sludge yield (Yobs) lowering upto 0.51 gVSS/gCOD ultimately turned an overall sludge minimization of 46.8% compared with a parallel-run conventional activated sludge treatment. The observations were further supported by sophisticated instrumental imaging, thermogravimetric analysis and batch digestion test of the sludge pool. The experimental Yobs and corresponding solids retention showed consensus with the reported correlation model and, thus, a modified correlation was tested.


Assuntos
Poluentes Ambientais , Purificação da Água , Biofilmes , Reatores Biológicos , Desnitrificação , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos
15.
Environ Sci Pollut Res Int ; 28(40): 57009-57029, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34080119

RESUMO

Nanoflowers and nanorods of ZnO were synthesized via hydrothermal route. These morphologies of zinc oxide (ZnO) were then decorated over graphene oxide (GO) to yield hybrid nanocomposites, namely, GO-ZnOnR and GO-ZnOnF. The decoration of ZnO nanorods and nanoflowers on GO layers was confirmed through FESEM images. The synthesized nanocomposites were subjected to degrade the Orange G under identical conditions. The band gap energies determined using diffused reflectance spectra were 2.87, 2.89 eV for GO-ZnOnR, and GO-ZnOnF, whereas, for both ZnOnR and ZnOnF, it was 3.14 eV. For 50 min of UV irradiations (at 6 pH), 100% degradation was achieved corresponding to GO-ZnOnR (44.1 m2 g-1) followed by 90.1%, 70.2%, and 68.3% with GO-ZnOnF (35.9 m2 g-1), ZnOnR (20 m2 g-1), and ZnOnF (15.1 m2 g-1), respectively. Significant boost in the degradation of Orange G, with GO-ZnOnR, was attributed to its reduced band gap, higher surface area, and enhanced charge separation. Kinetic study confirms the pseudo-first-order reaction rate. Mineralization efficiency of 91% in 120 min indicated the efficient reduction of Orange G and its intermediates. Further, reactive species trapping experiments revealed that photo-induced •OH are dominant radicals for the degradation followed by •O2- and h+. Liquid chromatography mass spectra data has been used to predict the plausible reaction pathways. Reusability studies indicated that GO-ZnOnR can be used for four successive degradation cycles, without any significant activity loss.


Assuntos
Nanocompostos , Nanotubos , Óxido de Zinco , Compostos Azo , Grafite
16.
Curr Opin Gastroenterol ; 37(4): 378-383, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33883421

RESUMO

PURPOSE OF REVIEW: This review will focus on how the extent of Barrett's metaplasia influences the risk of esophageal adenocarcinoma (EAC). More specifically, this review will discuss the concepts of long and short-segment Barrett's metaplasia and irregular Z line as they relate to EAC risk. RECENT FINDINGS: The Prague classification can standardize reporting of Barrett's metaplasia. Recent literature has found significant associations between the length of Barrett's metaplasia and increased progression risk to EAC in multiple geographically distinct populations. Length of Barrett's metaplasia has been incorporated into the Progression of Barrett's esophagus (PIB) model that can predict individualized life-time risks of progression. The risk of malignant transformation appears to be very low in patients with irregular Z line. SUMMARY: Length of Barrett's metaplasia has emerged as an important predictor that can influence the risk of EAC and should be reported using the Prague classification. The PIB model, if further validated, could help a practicing gastroenterologist to inform patients with Barrett's metaplasia about their personal risk of progression to tailor surveillance intervals. Current guidelines do not recommend surveillance in patients with irregular Z line, but careful examination is recommended.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Adenocarcinoma/etiologia , Transformação Celular Neoplásica , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Humanos , Metaplasia
17.
Lab Invest ; 101(6): 745-759, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33495575

RESUMO

Multiple genome-wide association studies (GWAS) have linked Forkhead Box F1 (FOXF1) to Barrett's esophagus (BE). Understanding whether FOXF1 is involved in initiation of Barrett's metaplasia could allow FOXF1 to be used for risk stratification and for therapy. Two-dimensional cell cultures and three-dimensional organoid cultures and well-annotated human biopsies were used to determine the role of FOXF1 in BE pathogenesis. Multiple established esophageal squamous and BE cell lines were tested in gain- and loss-of-function studies. Initiation of a BE-like metaplastic change was evaluated by measuring characteristic cytokeratins and global gene expression profiling and by culturing organoids. Epithelial-mesenchymal transition (EMT) was evaluated by immunostaining for E-cadherin, vimentin and Snail, and by cell motility assay. Columnar esophageal epithelium of BE patients exhibited higher expression of FOXF1 compared to normal squamous esophageal epithelium of GERD patients (P < 0.001). Acidic bile salts induced nuclear FOXF1 in esophageal squamous cells. FOXF1 overexpression in normal esophageal squamous cells: (a) increased columnar cytokeratins and decreased squamous cytokeratins, (b) converted squamous organoids to glandular organoids, and (c) switched global gene profiles to resemble that of human BE epithelium (P = 2.1685e - 06 for upregulated genes and P = 8.3378e - 09 for downregulated genes). FOXF1 inhibition in BE cell lines led to loss of BE differentiation markers, CK7, and mucin 2. Also, FOXF1 induced EMT and promoted cell motility in normal esophageal squamous epithelial cells. FOXF1-induced genes mapped to pathways such as Cancer, Cellular Assembly and Organization, DNA Replication, Recombination, and Repair. In conclusion, FOXF1 promotes a BE-like columnar phenotype and cell motility in esophageal squamous epithelial cells, which may have a critical role in BE development. FOXF1 should be studied further as a biomarker for BE and as a target for BE treatment.


Assuntos
Esôfago de Barrett/etiologia , Transição Epitelial-Mesenquimal , Fatores de Transcrição Forkhead/metabolismo , Idoso , Esôfago de Barrett/metabolismo , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Esôfago/citologia , Esôfago/metabolismo , Humanos , Pessoa de Meia-Idade
18.
J Clin Gastroenterol ; 55(4): 321-326, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32379085

RESUMO

BACKGROUND AND AIMS: Men are at a higher risk for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), but little is known about BE progression to dysplasia and EAC in women. We performed a retrospective, multicenter cohort study to assess risk of BE progression to dysplasia and EAC in women compared with men. We also investigated comorbidities, medication use, and endoscopic features that contribute to sex differences in risk of BE progression. METHODS: We collected data from large cohort of patients with BE seen at 6 centers in the United States and Europe, followed for a median 5.7 years. We obtained demographic information (age, sex, ethnicity), clinical history (tobacco use, body mass index, comorbidities), endoscopy results (procedure date, BE segment length), and histopathology findings. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Rates of disease progression between women and men were compared using χ2 analysis and the Student t test. Multivariable logistic regression was used to assess the association between sex and disease progression after adjusting for possible confounding variables. RESULTS: Of the total 4263 patients in the cohort, 2145 met the inclusion criteria, including 324 (15%) women. There was a total of 34 (1.6%) incident EACs, with an overall annual incidence of 0.3% (95% confidence interval: 0.2%-0.4%). We found significant differences between women and men in annual incidence rates of EAC (0.05% for women vs. 0.3% in men; P=0.04) and in the combined endpoint of HGD or EAC (0.1% for women vs. 1.1% for men; P<0.001). Female gender was an independent predictor for reduced progression to HGD or EAC when rates of progression were adjusted for body mass index, smoking history, race, use of aspirin, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, or statins, hypertriglyceridemia, BE length, and histology findings at baseline (hazard ratio: 0.11; 95% confidence interval: 0.03-0.45; P=0.002). CONCLUSIONS: In a multicenter study of men versus women with BE, we found a significantly lower risk of disease progression to cancer and HGD in women. The extremely low risk of EAC in women with BE (0.05%/y) indicates that surveillance endoscopy may not be necessary for this subgroup of patients with BE.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Lesões Pré-Cancerosas , Esôfago de Barrett/epidemiologia , Estudos de Coortes , Progressão da Doença , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/etiologia , Europa (Continente) , Feminino , Humanos , Masculino , Lesões Pré-Cancerosas/epidemiologia , Estudos Retrospectivos , Medição de Risco , Estados Unidos/epidemiologia
19.
Dig Dis Sci ; 66(3): 705-713, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32277372

RESUMO

Esophageal adenocarcinoma (EAC) continues to be a significant public health problem with survival rates that have remained stagnant. Although the population at the highest risk for EAC, i.e., patients with Barrett's esophagus (BE) has been clearly defined, patients with EAC continue to do poorly due to advanced stage at diagnosis. The field of extracellular vesicles (EV) could have huge application for the management of patients with BE and EAC by allowing timely diagnosis, serial monitoring, and improved understanding of disease biology. EV are actively packaged and actively secreted vesicles and contain microRNAs, proteins, lipids, and DNA. The contents of EV have been shown to provide useful insights into cellular transformation and pro-oncogenic processes. Early work shows promise but suffers from a high degree of technical and biological variation. The current review not only summarizes the current knowledge about EV as diagnostic biomarkers and their role in disease progression of BE and EAC but also provides the reader practical guidance to devise future experiments to perform well-designed studies.


Assuntos
Esôfago de Barrett/diagnóstico , Esôfago de Barrett/patologia , Vesículas Extracelulares , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Esôfago de Barrett/complicações , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/metabolismo , Progressão da Doença , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/patologia , Humanos
20.
Curr Colorectal Cancer Rep ; 16(5): 97-106, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32905465

RESUMO

PURPOSE OF REVIEW: Molecular pathways in colorectal carcinogenesis involve several complex genetic and epigenetic modulations that cause normal colonic mucosa to metamorphose into a benign polyp and subsequently into a malignant tumor. Our purpose is to recapitulate historical and recent genomic research in order to augment the understanding of colorectal cancer pathogenesis. RECENT FINDINGS: In 2015, the molecular classification for colorectal cancers was unified into one system with four distinct groups, also called as consensus molecular subtypes. This led to an enhanced understanding of molecular and immune signatures which has implications on predicting the clinical behavior as well as response to different therapeutic agents. SUMMARY: In this review, we expound on the current literature as well as draw on our own experience to present the important molecular pathogenesis pathways, key genetic mutations, differences in pathogenesis of left versus right sided tumors as well as the molecular classification of colorectal cancers.

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