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1.
Viruses ; 14(12)2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36560601

RESUMEN

The avian immunosuppressive and neoplastic diseases caused by Marek's disease virus (MDV), avian leucosis virus (ALV), and reticuloendotheliosis virus (REV) are seriously harmful to the global poultry industry. In recent years, particularly in 2020-2022, outbreaks of such diseases in chicken flocks frequently occurred in China. Herein, we collected live diseased birds from 30 poultry farms, out of 42 farms with tumour-bearing chicken flocks distributed in central China, to investigate the current epidemiology and co-infections of these viruses. The results showed that in individual diseased birds, the positive infection rates of MDV, ALV, and REV were 69.5% (203/292), 14.4% (42/292), and 4.7% (13/277), respectively, while for the flocks, the positive infection rates were 96.7% (29/30), 36.7% (11/30), and 20% (6/30), respectively. For chicken flocks, monoinfection of MDV, ALV, or REV was 53.3% (16/30), 3.3% (1/30), and 0% (0/30), respectively, but a total of 43.3% (13/30) co-infections was observed, which includes 23.3% (7/30) of MDV+ALV, 10.0% (3/30) of MDV+REV, and 10.0% (3/30) of MDV+ALV+REV co-infections. Interestingly, no ALV+REV co-infection or REV monoinfection was observed in the selected poultry farms. Our data indicate that the prevalence of virulent MDV strains, partially accompanied with ALV and/or REV co-infections, is the main reason for current outbreaks of avian neoplastic diseases in central China, providing an important reference for the future control of disease.


Asunto(s)
Virus de la Leucosis Aviar , Leucosis Aviar , Coinfección , Herpesvirus Gallináceo 2 , Enfermedad de Marek , Neoplasias , Enfermedades de las Aves de Corral , Virus de la Reticuloendoteliosis , Animales , Pollos , Coinfección/epidemiología , Coinfección/veterinaria , Coinfección/complicaciones , Leucosis Aviar/epidemiología , Neoplasias/epidemiología , Neoplasias/veterinaria , China/epidemiología , Enfermedades de las Aves de Corral/epidemiología , Virus de la Leucosis Aviar/genética , Enfermedad de Marek/epidemiología
2.
J Hepatol ; 74(1): 96-108, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32738450

RESUMEN

BACKGROUND & AIMS: p53 mutations occur frequently in human HCC. Activation of the mammalian target of rapamycin (mTOR) pathway is also associated with HCC. However, it is still unknown whether these changes together initiate HCC and can be targeted as a potential therapeutic strategy. METHODS: We generated mouse models in which mTOR was hyperactivated by loss of tuberous sclerosis complex 1 (Tsc1) with or without p53 haplodeficiency. Primary cells were isolated from mouse livers. Oncogenic signalling was assessed in vitro and in vivo, with or without targeted inhibition of a single molecule or multiple molecules. Transcriptional profiling was used to identify biomarkers predictive of HCC. Human HCC materials were used to corroborate the findings from mouse models. RESULTS: p53 haploinsufficiency facilitates mTOR signalling via the PTEN/PI3K/Akt axis, promoting HCC tumorigenesis and lung metastasis. Inhibition of PI3K/Akt reduced mTOR activity, which effectively enhanced the anticancer effort of an mTOR inhibitor. ATP-binding cassette subfamily C member 4 (Abcc4) was found to be responsible for p53 haploinsufficiency- and Tsc1 loss-driven HCC tumorigenesis. Moreover, in clinical HCC samples, Abcc4 was specifically identified an aggressive subtype. The mTOR inhibitor rapamycin significantly reduced hepatocarcinogenesis triggered by Tsc1 loss and p53 haploinsufficiency in vivo, as well as the biomarker Abcc4. CONCLUSIONS: Our data advance the current understanding of the activation of the PTEN/PI3K/Akt/mTOR axis and its downstream target Abcc4 in hepatocarcinogenesis driven by p53 reduction and Tsc1 loss. Targeting mTOR, an unexpected vulnerability in p53 (haplo)deficiency HCC, can be exploited therapeutically to treat Abcc4-positive patients with HCC. LAY SUMMARY: Tsc1 loss facilitates the p53 (haplo)insufficiency-mediated activation of the PTEN/Akt/mTOR axis, leading to the elevated expression of Abcc4 to drive HCC tumorigenesis and metastasis in mice. Inhibition of mTOR protects against p53 haploinsufficiency and Tsc1 loss-triggered tumour-promoting activity, providing a new approach for treating an aggressive subtype of HCC exhibiting high Abcc4 expression.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Pirazoles/farmacología , Pirimidinas/farmacología , Serina-Treonina Quinasas TOR/genética , Proteína p53 Supresora de Tumor/genética , Animales , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Haploinsuficiencia/efectos de los fármacos , Haploinsuficiencia/genética , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Inhibidores mTOR/farmacología , Ratones , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Proteína 1 del Complejo de la Esclerosis Tuberosa/genética
3.
Nat Commun ; 10(1): 2707, 2019 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-31222004

RESUMEN

Bone metastases occur in most advanced breast cancer patients and cause serious skeletal-related complications. The mechanisms by which bone metastasis seeds develop in primary tumors and specifically colonize the bone remain to be elucidated. Here, we show that forkhead box F2 (FOXF2) functions as a master transcription factor for reprogramming cancer cells into an osteomimetic phenotype by pleiotropic transactivation of the BMP4/SMAD1 signaling pathway and bone-related genes that are expressed at early stages of bone differentiation. The epithelial-to-osteomimicry transition regulated by FOXF2 confers a tendency on cancer cells to metastasize to bone which leads to osteolytic bone lesions. The BMP antagonist Noggin significantly inhibits FOXF2-driven osteolytic bone metastasis of breast cancer cells. Thus, targeting the FOXF2-BMP/SMAD axis might be a promising therapeutic strategy to manage bone metastasis. The role of FOXF2 in transactivating bone-related genes implies a biological function of FOXF2 in regulating bone development and remodeling.


Asunto(s)
Neoplasias Óseas/patología , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Animales , Proteína Morfogenética Ósea 4/metabolismo , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/secundario , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Reprogramación Celular/genética , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Ratones , Ratones Desnudos , Osteoblastos , Transducción de Señal/genética , Proteína Smad1/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Oncotarget ; 7(48): 79688-79705, 2016 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-27806311

RESUMEN

Bone is one of the most common organs of breast cancer metastasis. Cancer cells that mimic osteoblasts by expressing bone matrix proteins and factors have a higher likelihood of metastasizing to bone. However, the molecular mechanisms of osteomimicry formation of cancer cells remain undefined. Herein, we identified a set of bone-related genes (BRGs) that are ectopically co-expressed in primary breast cancer tissues and determined that osteomimetic feature is obtained due to the osteoblast-like transformation of epithelial breast cancer cells that have undergone epithelial-mesenchymal transition (EMT) followed by bone morphogenetic protein-2 (BMP2) stimulation. Furthermore, we demonstrated that breast cancer cells that transformed into osteoblast-like cells with high expression of BRGs showed enhanced chemotaxis, adhesion, proliferation and multidrug resistance in an osteoblast-mimic bone microenvironment in vitro. During these processes, runt-related transcription factor 2 (RUNX2) functioned as a master mediator by suppressing or activating the transcription of BRGs that underlie the dynamic antagonism between the TGF-ß/SMAD and BMP/SMAD signaling pathways in breast cancer cells. Our findings suggest a novel mechanism of osteomimicry formation that arises in primary breast tumors, which may explain the propensity of breast cancer to metastasize to the skeleton and contribute to potential strategies for predicting and targeting breast cancer bone metastasis and multidrug resistance.


Asunto(s)
Mimetismo Biológico , Proteína Morfogenética Ósea 2/farmacología , Neoplasias Óseas/metabolismo , Neoplasias de la Mama/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Antineoplásicos/farmacología , Neoplasias Óseas/genética , Neoplasias Óseas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Osteoblastos/metabolismo , Osteoblastos/patología , Fenotipo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Transcripción Genética , Microambiente Tumoral , Regulación hacia Arriba
5.
Biomed Environ Sci ; 26(12): 1003-7, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24393512

RESUMEN

The class 1 integron and complex gene cassettes among different species of clinical isolates in northern China were characterized in this study. 383 clinical isolates were obtained from northern China, and class 1 integrons containing gene cassettes widely distributed among gram negative clinical isolates was observed. We find that the class 1 integron showed positive correlation with multidrug resistance phenotype of gram negative bacteria. In addition, we find that isolates belonged to one species harbored different types of gene cassette arrays, while same types of gene cassette arrays were observed in different species of isolates. The diversity of gene cassette arrays among the isolates indicated the complexity of multidrug resistance in clinical isolates in northern China.


Asunto(s)
Bacterias/genética , Bacterias/aislamiento & purificación , Hospitales Públicos , Integrones/genética , Bacterias/clasificación , China , Humanos
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