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1.
Int J Biol Sci ; 18(1): 214-228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34975328

RESUMO

Resistance to radiotherapy is frequently observed in the clinic and leads to poor prognosis of non-small cell lung cancer (NSCLC). How to overcome resistance to radiotherapy is a challenge in the treatment of NSCLC. In this study, PPDPF was found to be upregulated in NSCLC tissues and cell lines, and its expression negatively correlated with the overall survival of patients with NSCLC. PPDPF promoted the growth, colony formation and invasion of lung cancer cells. Moreover, knockout of PPDPF inhibited tumorigenesis in the KL (KrasG12D; LKB1f/f) mouse model of lung cancer. Additionally, overexpression of PPDPF led to radioresistance in lung cancer cells, and knockdown of PPDPF sensitized lung cancer cells to radiotherapy. Mechanistically, PPDPF interacted with BABAM2 (an antiapoptotic protein) and blocked its ubiquitination by MDM2, thus stabilizing BABAM2 and promoting the radioresistance of lung cancer cells. Our present study suggested PPDPF as a therapeutic target in NSCLC.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Animais , Carcinogênese , Linhagem Celular Tumoral , Progressão da Doença , Regulação para Baixo , Humanos , Camundongos , Camundongos Nus , Prognóstico , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Hum Reprod ; 34(8): 1479-1484, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310320

RESUMO

STUDY QUESTION: Does oestrogen dose tapering during the luteal phase affect the clinical outcome after hormone replacement treatment-frozen-thawed embryo transfer (HRT-FET) cycles? SUMMARY ANSWER: Our results suggest that tapering oestrogen doses during the luteal phase results in similar clinical outcomes to those obtained with the traditional luteal phase support (LPS). WHAT IS KNOWN ALREADY: Traditional LPS with oestrogen and progesterone is considered necessary in HRT-FET cycles. However, case reports have shown successful clinical pregnancies and live births in the absence of oestrogen administration after embryo transfers. STUDY DESIGN, SIZE, DURATION: This was a retrospective study on 6035 HRT-FET cycles extending over 7 years from January 2011 to June 2018 at the reproductive medicine centre of Xiangya Hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: We compared the clinical outcomes of 1632 HRT-FET cycles with tapered oestrogen doses from 12 days after embryo transfer (study group) to those of 4403 HRT-FET cycles maintained on constant oestrogen doses during the luteal phase (control group) in the case of positive serum HCG test. MAIN RESULTS AND THE ROLE OF CHANCE: We found similar biochemical pregnancy rates (52.1% vs. 51.9, P = 0.864), clinical pregnancy rates (44.9% vs. 43.2%, P = 0.249), implantation rates (29.8% vs. 29.3%, P = 0.591) and miscarriage rates (16.0% vs. 14.6%, P = 0.379) between the studied groups. LIMITATIONS, REASONS FOR CAUTION: Retrospective, design-associated biases are possible. In addition, some baseline characteristics differed between groups. Finally, we did not compare live birth rates between groups. WIDER IMPLICATIONS OF THE FINDINGS: Our study showing similar outcomes between traditional LPS and oestrogen tapering during the luteal phase indicates that oestrogen may be cautiously tapered during the luteal phase after HRT-FET cycles. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant no. 81401269) and the class General Financial Grant from the China Postdoctoral Science Foundation (grant no. 2017M620360). The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Transferência Embrionária , Estrogênios/administração & dosagem , Indução da Ovulação/métodos , Adulto , Implantação do Embrião , Feminino , Humanos , Nascido Vivo , Fase Luteal , Gravidez , Taxa de Gravidez , Progesterona/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-355250

RESUMO

<p><b>OBJECTIVE</b>To study the changes in quantitative kinetic parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during radiotherapy and their value for efficacy evaluation in patients with nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Twenty-four patients with NPC that had been pathologically confirmed as poorly differentiated squamous cell carcinoma underwent conventional MRI and DCE-MRI scans 1-2 days before radiotherapy (Pre-RT), during radiotherapy (RT 50 Gy), and upon completion of radiotherapy (RT 70 Gy). Based on the two-compartment model and using the arterial input function deconvolution technique, we calculated the quantitative kinetic parameters of DCE-MRI (K(trans), kep, and Ve) of the tumor tissues, examined the correlation between the tumor regression rate (RS0-50) and the parameters on Pre-RT and RT 50 Gy, and compared the parameters for RT 70 Gy among the groups with different prognosis.</p><p><b>RESULTS</b>The K(trans) value of the tumor tissue decreased after radiotherapy and showed a significant difference between Pre-RT and RT 70 Gy, but not between Pre-RT and RT 50 Gy. The kep value decreased and Ve value increased after radiotherapy. The tumor regression rate was found to be positively correlated with the K(trans) value for Pre-RT (P=0.005) but negatively with the K(trans) value for RT 50 Gy (P=0.001). During the follow-up for 3 years, 5 patients died and 3 patients had distant metastases. No statistical differences in K(trans), kep, or Ve were found between the groups with different prognosis.</p><p><b>CONCLUSIONS</b>The kinetic parameters in DCE-MRI, which vary significantly during radiotherapy, allow monitoring of tumor angiogenesis and vascular permeability and quantitative assessment of treatment efficacy for NPC. K(trans) value for Pre-RT and RT 50 Gy can serve as an indicator for early efficacy assessment of radiotherapy and for treatment adjustment, but its relation with the long-term outcomes awaits further study.</p>


Assuntos
Humanos , Algoritmos , Permeabilidade Capilar , Carcinoma , Carcinoma de Células Escamosas , Diagnóstico , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas , Radioterapia , Neovascularização Patológica , Prognóstico , Resultado do Tratamento
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