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1.
Biochim Biophys Acta Gen Subj ; 1868(3): 130547, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38143011

RESUMO

Tumor suppressor p53 is frequently null or mutated in human cancers. Here in this study, DHX33 protein was found to be induced in p53 null cells in vitro, and in p53 mutant lung tumorigenesis in vivo. Cholesterol metabolism through mevalonate pathway is pivotal for cell proliferation and is frequently altered in human cancers. Mice carrying mutant p53 and KrasG12D alleles showed upregulation of mevalonate pathway gene expression. However upon DHX33 loss, their upregulation was significantly debilitated. Additionally, in many human cancer cells, DHX33 knockdown caused inhibition of mavelonate pathway gene transcription. We propose DHX33 locates downstream of mutant p53 and Ras to regulate mevalonate pathway gene transcription and thereby supports cancer development in vivo.


Assuntos
Ácido Mevalônico , Proteína Supressora de Tumor p53 , Humanos , Camundongos , Animais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Pulmão/metabolismo , Carcinogênese , Transcrição Gênica , RNA Helicases DEAD-box/genética
2.
Curr Med Sci ; 42(6): 1267-1272, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36462133

RESUMO

OBJECTIVE: The aim of this study was to examine the effects of photodynamic therapy (PDT) on the expression of Nav1.7 in spinal dorsal root ganglion (DRG) neurons. METHODS: The primary DRG neurons from newborn SD rats were cultured. The cells were identified by neuron-specific enolase immunofluorescence staining. DRG neurons were divided into four groups: control group, photosensitizer group, laser group, and PDT group. The cell viability was detected by a cell counting kit-8 (CCK8) assay. qRT-PCR and Western blotting were used to determine the mRNA and protein expression levels of Nav1.7 in DRG neurons. RESULTS: The purity of the cultured primary DRG neurons was greater than 90%. Compared with the control group, no significant change was found in the cell viability of the photosensitizer group, while the viability in the laser group and the PDT group was significantly reduced. The mRNA and protein expression levels of Nav1.7 were significantly greater in the laser group and the PDT group than in the control group. At the same time, the mRNA and protein expression levels of Nav1.7 were greater in the laser group than in the PDT group. CONCLUSION: Both laser and PDT could upregulate the expression of Nav1.7 in DRG neurons, and the promoting effect might be related to the pain induced by clinical treatment. This study provides a research basis for the use of laser and PDT to treat pain. A better understanding of the relationship between Nav1.7 and PDT can help clinicians better manage PDT-related pain.


Assuntos
Gânglios Espinais , Fotoquimioterapia , Ratos , Animais , Gânglios Espinais/metabolismo , Ratos Sprague-Dawley , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/metabolismo , Dor , Neurônios/metabolismo , RNA Mensageiro/metabolismo
3.
Photodiagnosis Photodyn Ther ; 30: 101761, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32283311

RESUMO

Xeroderma pigmentosum (XP) is a rare autosomal recessive dermatosis that is often complicated by multiple skin tumours at exposed locations, which are difficult to treat. We report a case of a 12-year-old girl with XP treated with oral retinoic acid and photodynamic therapy (PDT) with good clinical results. She had an 8-year history of multiple skin lesions that first appeared on her nasal dorsum, but gradually increased in size and spread to her entire face, neck, and upper limbs. Notably, the lesions became evidently aggravated after sun exposure. When she was 6 years old, sesame-seed-sized papules and plaques appeared, which were fragile and irregular in shape and would self-rupture, accompanied with slight itchiness and bloody exudate. Examination revealed multiple basal cell carcinomas. The tumours were treated with local carbon dioxide laser therapy combined with PDT. On the follow-up visit 2 months after the surgery, most of the skin lesions on her face had subsided. In cases of multiple tumours, PDT can be the treatment method of choice because it is less invasive, has less side effects, and does not damage the surrounding normal tissues.


Assuntos
Carcinoma Basocelular/tratamento farmacológico , Lasers de Gás/uso terapêutico , Fotoquimioterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Tretinoína/uso terapêutico , Xeroderma Pigmentoso/tratamento farmacológico , Carcinoma Basocelular/complicações , Criança , Quimioterapia Combinada , Face , Feminino , Hematoporfirinas/uso terapêutico , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/complicações , Xeroderma Pigmentoso/complicações , Xeroderma Pigmentoso/patologia
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