1.LDHA inhibitor combined with targeted drugs synergistically inhibit the proliferation of fumarate hydratase-deficient renal cell carcinoma cells
Yilun HONG ; Jianfeng WANG ; Jin ZHANG
Journal of Modern Urology 2023;28(10):900-905
【Objective】 To explore the therapeutic effects of lactate dehydrogenase A (LDHA) inhibitor and targeted drugs on fumarate-hydratase-deficient renal cell carcinoma (FH-d RCC). 【Methods】 RNA-sequencing was used to detect the mRNA expression in FH-d RCC tissues, which was further validated with real-time fluorescence quantitative PCR and immunohistochemistry. Human-derived FH-d RCC cell line UOK262 and murine-derived FH-d RCC cell line FH1-/-CL19 (CL19) were treated with LDHA inhibitor [(R)-GNE-140] and listed kidney cancer targeted drugs (Axitinib, Cabozantinib, Sunitinib, Sorafenib, Pazopanib, Everolimus) respectively, and then treated with LHDA inhibitor in combination with the targeted drugs to observe the alteration of cell proliferation. The combination index (CI) of different dose groups of the combination drugs were analyzed with CompuSyn software to determine the optimal combination regimen. 【Results】 LDHA inhibitor and targeted drugs, including Cabozantinib, Sorafenib and Sunitinib, had a significant inhibitory effect on the proliferation of FH-d RCC cells, and the combination of Cabozantinib and Sorafenib or Pazopanib had a significant anti-tumor effect. 【Conclusion】 LDHA inhibitor combined with targeted drugs can significantly inhibit the growth of FH-d RCC cells, indicating that LDHA may be a potential therapeutic target of FH-d RCC.
2.Vitamin D insufficiency and deficiency in chronic kidney disease patients
Yilun LV ; Ying LIN ; Hao SHI ; Wen ZHANG ; Hong REN ; Nan CHEN
Chinese Journal of Nephrology 2009;25(9):668-672
Objective To elucidate the prevalence of vitamin D insufficiency and deficiency in chronic kidney diseases (CKD) patients and provide the evidence for treatment of these patients. Methods Clinical data of 358 inpatients with CKD from stage 1 to stage 5 were analyzed retrospectively. Level of 25 (OH)D3 in these inpatients, as well as the levels of intact parathyroid hormone (iPTH), hemoglobin (Hb), serum creatinine (Scr), urea nitrogen (BUN), carbon dioxide combining power (CO2CP), alhumin (Alb), serum calcium (Ca) and blood serum (P) were examined. Correlation between 25 (OH)D3 and parameters was analyzed. Results The mean level of 25 (OH)D3 in these CKD patients was (18.58±11.7) μg/L, which was significantly lower than that of normal reference (P<0.01). The 25(OH )D3 levels of CKD patients from stage 1 to stage 5 were (25.84±9.71) μg/L, (20.76±6.99) μg/L, (20.40±17.02) μg/L, (19.49±11.29) μg/L, and (14.16±7.98) μg/L respectively. The prevalence of vitamin D defieiency was 39.66%, and from CKD stage 1 to stage 5 was 5.00%, 17.50%, 37.21%, 42.37% and 57.14%. The prevalence of vitamin D insufficiency was 44.97%, and from CKD stage 1 to stage 5 was 72,50%, 47.50%, 45.35%, 33.90% and 40.60%. The prevalence of decreased vitamin D level was 84.63%, and from CKD stage 1 to stage 5 was 77.50%, 65.00%, 82.56%, 76.27% and 97.74%. Single factor correlation analysis showed 25 (OH)D3 was correlated with Hb, Alb, Scr, eGRF and iPTH. Regression analysis indicated that 25 (OH)D3 was negatively correlated with iPTH and Scr, and positively correlated with Alb. According to K/DOQI, percentage of CKD patients from stage 3 to stage 5 who were consistent with vitamin D treatment was 87.20%, 83.05% and 26.31% based on 25 (OH)3 and iPTH levels, but such percentage was 16.28%, 35.59% and 26.31% based on iPTH level only. Conclusions The prevalence of vitamin D insufficiency and deficiency in patients with CKD is quite high. Alia, iPTH and Scr are key factors influencing vitamin D level. Vitamin D level should be measured among CKD patients in order to carry out corresponding treatment.
3.Grafting and characterization of poly (ethylene glycol) on polysulfone sheets.
Lu SUN ; Shudong SUN ; Hong XIE ; Xiaohua HUANG ; Yilun YUE
Journal of Biomedical Engineering 2006;23(2):370-374
Grafting of poly (ethylene glycol) (PEG) on the surface of polysulfone (PSF) sheets by simultaneous or sequential UV irradiation with 4-azidobenzoic acid as the photocoupler was carried out. Water contact angle measurements showed that there was a great improvement of hydrophilicity on the grafted surface. X-ray photoelectron spectroscopy suggested that the area covered by PEG be 77.3% and 41.9% respectively after grafting by simultaneous and sequential pathways. With atomic force microscope (AFM), obvious difference in the shape and the phase mode was observed between surfaces of PEG-g-PSF sheets made by these two pathways. Evidences implied that simultaneous pathway would produce a branched PEG layer on the surface, while sequential pathway was coupled with a "pan-cake" PEG layer on it. This study provides the foundation for further advancement in tethering brush-like PEG on PSF hollow fiber membranes.
Azides
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chemistry
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Biocompatible Materials
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chemistry
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Coated Materials, Biocompatible
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chemistry
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Membranes, Artificial
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Microscopy, Atomic Force
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Polyethylene Glycols
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chemistry
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Polymers
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chemistry
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Sulfones
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chemistry
;
Ultraviolet Rays

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