RESUMO
The rich morphology of 2D materials grown through chemical vapor deposition (CVD), is a distinctive feature. However, understanding the complex growth of 2D crystals under practical CVD conditions remains a challenge due to various intertwined factors. Real-time monitoring is crucial to providing essential data and enabling the use of advanced tools like machine learning for unraveling these complexities. In this study, we present a custom-built miniaturized CVD system capable of observing and recording 2D MoS2 crystal growth in real time. Image processing converts the real-time footage into digital data, and machine learning algorithms (ML) unveil the significant factors influencing growth. The machine learning model successfully predicts CVD growth parameters for synthesizing ultralarge monolayer MoS2 crystals. It also demonstrates the potential to reverse engineer CVD growth parameters by analyzing the as-grown 2D crystal morphology. This interdisciplinary approach can be integrated to enhance our understanding of controlled 2D crystal synthesis through CVD.
RESUMO
Clinically relevant animal models of mammary carcinogenesis are crucial for the development and evaluation of new breast cancer chemopreventive agents. The neu-induced retroviral rat mammary carcinogenesis model is based on the direct in situ transfer of the activated neu oncogene into the mammary epithelium using a replication-defective retroviral vector. The resulting mammary carcinomas in intact Wistar-Furth rats exhibit a mixed hormonal response in the same proportion as has been observed in women. In intact rats, approximately 50% of mammary carcinomas can be prevented by tamoxifen treatment. In ovariectomized animals, the mammary carcinomas are hormonally nonresponsive and cannot be prevented by tamoxifen. We evaluated the efficacy of retinoic X receptor-selective retinoids (rexinoids) in this novel model of mammary carcinogenesis. The rexinoids LG100268 and bexarotene (LG1069, Targretin) were highly efficacious in the prevention of neu-induced mammary carcinomas. Dietary LG100268 at 100 mg/kg diet decreased tumor multiplicity by 32% (P = 0.0114) in intact rats and 50% (P < 0.0001) in ovariectomized rats. Bexarotene treatment at a dose of 250 mg/kg diet was associated with reductions in tumor multiplicity of 84% (P < 0.0001) and 86% (P < 0.0001) in intact and ovariectomized animals, respectively. In addition to tumor multiplicity, proliferation and apoptosis were modulated by bexarotene treatment independently of estrogen signaling. The neu-induced retroviral rat mammary carcinogenesis model represents a valuable addition to existing rodent chemoprevention models. The model is useful for assessing the efficacy of chemopreventive agents, specifically those compounds that target hormonally nonresponsive tumors.
Assuntos
Anticarcinógenos/farmacologia , Modelos Animais de Doenças , Genes erbB-2 , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/prevenção & controle , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/prevenção & controle , Animais , Bexaroteno , Peso Corporal/efeitos dos fármacos , Feminino , Vetores Genéticos/genética , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/virologia , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/virologia , Ácidos Nicotínicos/farmacologia , Ratos , Ratos Endogâmicos WF , Retroviridae/genética , Tamoxifeno/farmacologia , Tetra-Hidronaftalenos/farmacologiaRESUMO
The rat is a widely used model in biomedical research and is often the preferred rodent model in many areas of physiological and pathobiological research. Although many genetic tools are available for the rat, methods to produce gene-disrupted knockout rats are greatly needed. In this study, we developed protocols for creating N-ethyl-N-nitrosourea (ENU)-induced germline mutations in several rat strains. F1 preweanling pups from mutagenized Sprague Dawley (SD) male rats were then screened for functional mutations in Brca1 and Brca2 using a yeast gap-repair, ADE2-reporter truncation assay. We produced knockout rats for each of these two breast cancer suppressor genes.
Assuntos
Etilnitrosoureia/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Marcação de Genes/métodos , Mutagênese Sítio-Dirigida , Ratos Mutantes/genética , Animais , Proteína BRCA1/deficiência , Proteína BRCA1/genética , Proteína BRCA2/deficiência , Proteína BRCA2/genética , Células Cultivadas , Masculino , Engenharia de Proteínas/métodos , Ratos , Ratos Mutantes/metabolismo , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Leveduras/efeitos dos fármacos , Leveduras/isolamento & purificaçãoRESUMO
Tumor-induced skeletal muscle wasting involves tumor necrosis factor (TNF) and the ubiquitin-proteasome pathway of muscle protein degradation. In this study, growth of the colon-26 adenocarcinoma in mice was associated with diminished gastrocnemius muscle mass and increased muscle levels of actin, ubiquitin-conjugated proteins, free ubiquitin, E3 ubiquitin ligases, and the type 1 TNF receptor (TNFR1). Indomethacin at 1 or 5 mg/kg/day reduced tumor growth and muscle levels of TNFR1. However, only the 5 mg dose of indomethacin reduced muscle wasting and muscle levels of the E3 ligases and actin. These data suggest that the beneficial effects of indomethacin in the treatment of tumor-induced skeletal muscle wasting may involve inhibition of TNF- and ubiquitin-mediated pathways of muscle protein degradation. These data also demonstrate that E3 ligases, which are involved in disuse atrophy, also are associated with tumor-induced skeletal muscle wasting.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Caquexia/tratamento farmacológico , Indometacina/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Análise de Variância , Animais , Western Blotting , Peso Corporal/efeitos dos fármacos , Caquexia/etiologia , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Camundongos , Neoplasias Experimentais/complicações , Neoplasias Experimentais/patologiaRESUMO
Cancer cachexia is a syndrome of weight loss, muscle wasting, fatigue, and anorexia that occurs in patients with advanced or recurrent solid tumor disease. Tumor necrosis factor-alpha (TNFalpha) and prostaglandin E2 (PGE2) have been implicated in the biology of cachexia and serve as possible targets for treatment of this condition. Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid that alters the synthesis of PGE2 and reduces the negative effects of TNF on body weight of healthy mice. We hypothesized that a diet supplemented with .5% CLA might reduce muscle wasting in mice bearing the colon-26 adenocarcinoma, an animal model of cancer cachexia. CLA preserved gastrocnemius muscle mass and reduced TNF receptors in muscle of tumor-bearing mice. These data suggest that CLA may preserve muscle mass by reducing the catabolic effects of TNF on skeletal muscle.
Assuntos
Peso Corporal/efeitos dos fármacos , Caquexia/tratamento farmacológico , Ácidos Linoleicos Conjugados/farmacologia , Músculo Esquelético/efeitos dos fármacos , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Animais , Caquexia/etiologia , Neoplasias do Colo/complicações , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Camundongos , Músculo Esquelético/metabolismo , Neoplasias Experimentais/complicações , Neoplasias Experimentais/patologia , Células Tumorais CultivadasRESUMO
Skeletal muscle wasting is a prominent feature of cancer cachexia and involves decreased muscle protein synthesis and increased activity of the ubiquitin-proteasome pathway of protein degradation. We report that both indomethacin and ibuprofen improved body weight and weight of the gastrocnemius muscle in tumor-bearing mice. Ibuprofen increased the soluble protein content of the muscle without affecting muscle levels of phosphorylated p70 S6 kinase, a ribosomal kinase involved in protein synthesis. Paradoxically, indomethacin increased levels of ubiquitin-conjugated proteins. Further study is needed to understand the mechanism of action by which indomethacin and ibuprofen preserve body weight and muscle mass in the tumor-bearing mice. The data suggest that ibuprofen may have beneficial effects in the treatment of cancer cachexia.