• BMB Reports
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• 제55권1호
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• pp.3-10
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• 2022

Extracellular vesicles (EVs) released from different types of kidney cells under physiologic conditions contribute to homeostasis maintenance, immune-modulation, and cell-to-cell communications. EVs can also negatively affect the progression of renal diseases through their pro-inflammatory, pro-fibrotic, and tumorigenic potential. Inhibiting EVs by blocking their production, release, and uptake has been suggested as a potential therapeutic mechanism based on the significant implication of exosomes in various renal diseases. On the other hand, stem cell-derived EVs can ameliorate tissue injury and mediate tissue repair by ameliorating apoptosis, inflammation, and fibrosis while promoting angiogenesis and tubular cell proliferation. Recent advancement in biomedical engineering technique has made it feasible to modulate the composition of exosomes with diverse biologic functions, making EV one of the most popular drug delivery tools. The objective of this review was to provide updates of recent clinical and experimental findings on the therapeutic potential of EVs in renal diseases and discuss the clinical applicability of EVs in various renal diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제20권2호
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• pp.161-168
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• 2016

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor effects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory effects of S109 on CRM1 is reversible. Our data demonstrated that S109 significantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the effects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9113-9116
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• 2014

Purpose: : To assess the clinic value of application of laparospic ultrasonography (LU) in partial nephrectomy of small renal cell carcinoma. Materials and Methods: From 2007 to 2011, 28 small renal cell carcinoma patients in ou clinic underwent laparoscopic partial nephrectomy with LU. For comparison with preoperative conventional ultrasound and CT, we collected ultrasonic performance of the affected side kidney, renal tumor location, size, echo change, blood supply situation and the relationship with the surrounding tissue. Results: LU could more clearly show the tumor interior structure and blood supply, as well as the relationship with the surrounding tissue. It also can provided doctor assistance with real-time tumor resection, reducing operative complications. Conclusions: LU can clearly show tumor internal structure and blood supply, which is helpful for explicit diagnosis. Moreover, it supplies accurate information for surgeons and assists surgery. Therefore LU has an important guiding value in partial nephrectomy for small renal cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8419-8423
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• 2016

Purpose: Anti-cancer activity evaluation of aqueous extract of CRUEL (herbomineral formulation) capsules on renal cell carcinoma cell lines, and exploration of mechanisms of cell death. Materials and Methods: To detect the cytotoxic dose concentration in renal cell carcinoma (RCC) cells, MTT assays were performed and morphological changes after treatment were observed by inverted microscopy. Drug effects against RCC cell lines were assessed with reference to cell cycle distribution (flow cytometry), anti-metastatic potential (wound healing assay) and autophagy(RT-PCR). Results: CRUEL showed anti-proliferative effects against RCC tumor cell lines with an IC50 value of ${\approx}4mg/mL$ in vitro., while inducing cell cycle arrest at S-phase of cell cycle and inhibiting wound healing. LC3 was found to be up-regulated after drug treatment in RT-PCR resulting in an autophagy mode of cell death. Conclusions: This study provides the experimental validation for antitumor activity of CRUEL.

• 한국임상수의학회지
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• 제37권4호
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• pp.204-207
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• 2020

A 12-year-old dog was evaluated for depression and anorexia. The results of complete blood count and serum biochemistry were normal. Survey radiographs revealed markedly enlarged right kidney and abdominal ultrasound showed a renomegaly and hydronephrosis filled with mixed echogenic fluid. Primary renal tumor was suspected in this dog. Nephroureterectomy of the right kidney was performed, and no regional metastases have been identified. Transitional cell carcinoma (TCC) arising from renal pelvis accompanied hydronephrosis of the right kidney was diagnosed on histology. TCC usually affects trigone of the bladder, and renal origin of TCC is a very rare finding in dogs. This is the first case report to present the clinical features, diagnostic imaging findings and histopathological characteristics of a dog with TCC originating from the renal pelvis in Korea.

• Toxicological Research
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• 제11권1호
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• pp.127-131
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• 1995

Sequential changes in cell proliferation during the development of epitherial kidney tumors induced in rats were investigated by autoradiographic determination of the $^3H$-thymidine-labeling index. Renal cell tumors were induced in male Sprague-Dawley rats by oral administration of N-nitrosomorpholine at the concentration of 120 mg/l in the drinking water for 7 weeks. At different times between 12 and 34 weeks after withdrawal of the carcinogen (stop model) animals were sacrificed. According to cytological criteria, neoplastic lesions were classified into clear cell, acidophilic cell, basophilic cell and oncocytic tumors. The labeling index was found to be increased in all types of preneoplastic tubules as compared to their corresponding original tubules. A much stronger elevation of cell proliferation was ocurred during the development of renal cell tumors from preneoplastic tubules. Of four tumor types, acidophilic cell tumor showed the highest labeling index while oncocytoma exhibited the lowest proliferative activity. These findings are in good accordance with the clinical observations that acidophilic cell tumors have a worse prognosis than oncocytoma. The data presented in this study suggest that the individual proliferation rates may be an objective biological marker of kidney tumor aggressiveness.

• Journal of Korean Neurosurgical Society
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• 제48권3호
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• pp.263-267
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• 2010

Although cerebellar hemangioblastomas are histopathologically benign, they yield a degree of malignant clinical behavior in long-term follow-up. We present two cases of long-term progression of renal cell carcinoma, which had been diagnosed as renal cysts during treatment for cerebellar hemangioblastoma. A 14-year-old male with von Hippel-Lindau disease was admitted for a cerebellar hemangioblastoma with multiple spinal hemangioblastomas and a renal cyst. After primary total resection of the cerebellar hemangioblastoma, the patient required two further surgeries after 111 and 209 months for a recurrent cerebellar hemangioblastoma. Furthermore, he underwent radical nephrectomy as his renal cyst had progressed to renal cell carcinoma 209 months after initial diagnosis. A 26-year-old male presented with multiple cerebellar hemangioblastomas associated with von Hippel-Lindau disease and accompanied by multiple spinal hemangioblastomas and multiple cystic lesions in the liver, kidney, and pancreas. He underwent primary resect'lon of the cerebellar hemangioblastoma in association with craniospinal radiation for multiple intracranial/spinal masses. Unexpectedly, a malignant glioma developed 83 months after discovery of the cerebellar hemangioblastoma. At the same time, renal cell carcinoma, which had developed from an initial renal cyst, was diagnosed, and a radical nephrectomy was performed. In the view of long term clinical course, cerebellar hemangioblastoma associated with von Hipple-Lindau disease may redevelop even after primary total resection. In addition, associated lesions such as renal cysts may also progress to malignancy after the passing of a sufficient length of time.

• International Journal of Stem Cells
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• 제16권2호
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• pp.168-179
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• 2023

Background and Objectives: We evaluated the effect of adipose-derived stem cell-derived conditioned medium (ADSC-CM) on the renal function of rats with renal ischemia-reperfusion injury (IRI)-induced acute kidney injury. Methods and Results: Forty male Sprague-Dawley rats were randomly divided into four groups: sham, nephrectomy control, IRI control, ADSC-CM. The ADSC-CM was prepared using the three-dimensional spheroid culture system and injected into renal parenchyme. The renal function of the rats was evaluated 28 days before and 1, 2, 3, 4, 7, and 14 days after surgical procedures. The rats were sacrificed 14 days after surgical procedures, and kidney tissues were collected for histological examination. The renal parenchymal injection of ADSC-CM significantly reduced the serum blood urea nitrogen and creatinine levels compared with the IRI control group on days 1, 2, 3, and 4 after IRI. The renal parenchymal injection of ADSC-CM significantly increased the level of creatinine clearance compared with the IRI control group 1 day after IRI. Collagen content was significantly lower in the ADSC-CM group than in the IRI control group in the cortex and medulla. Apoptosis was significantly decreased, and proliferation was significantly increased in the ADSC-CM group compared to the IRI control group in the cortex and medulla. The expressions of anti-oxidative makers were higher in the ADSC-CM group than in the IRI control group in the cortex and medulla. Conclusions: The renal function was effectively rescued through the renal parenchymal injection of ADSC-CM prepared using a three-dimensional spheroid culture system.

• 대한의생명과학회지
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• 제11권4호
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• pp.441-446
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• 2005

The molecular mechanism of ischemia/reperfusion injury remains unclear. Reactive oxygen species (ROS) are implicated in cell death caused by ischemia/reperfusion in vivo or hypoxia in vitro. Poly (ADP-ribose) polymerase (PARP) activation has been reported to be involved in hydrogen peroxide-induced cell death in renal epithelial cells. This study was therefore undertaken to evaluate the role of P ARP activation in chemical hypoxia in opossum kidney (OK) cells. Chemical hypoxia was induced by incubating cells with antimycin A, an inhibitor of mitochondrial electron transport. Exposure of OK cells to chemical hypoxia resulted in a time-dependent cell death. In OK cells subjected to chemical hypoxia, the generation of ROS was increased, and this increase was prevented by the $H_2O_2$ scavenger catalase. Chemical hypoxia increased P ARP activity and chemical hypoxia-induced cell death was prevented by the inhibitor of PARP activation 3-aminobenzamide. Catalase prevented OK cell death induced by chemical hypoxia. $H_2O_2$ caused PARP activation and $H_2O_2-induced$ cell death was prevented by 3-aminobenzamide. Taken together, these results indicate that chemical hypoxia-induced cell injury is mediated by PARP activation through H202 generation in renal epithelial cells.

• 대한의생명과학회지
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• 제10권4호
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• pp.341-346
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• 2004

Tumor necrosis factor-α (TNF-α) or its mRNA expression are increased in acute nephrosis of various types including ischemia/reperfusion injury. This study was undertaken to determine whether pentoxifylline (PTX), an inhibitor of TNF-α production, provides a protective effect against hypoxia-induced cell injury in rabbit renal cortical slices. To induce hypoxia-induced cell injury, renal cortical slices were exposed to 100% N₂ atmosphere. Control slices were exposed to 100% O₂ atmosphere. The cell injury was estimated by measuring lactate dehydrogenase (LDH) release and p-aminohippurate (PAH) uptake. Exposure of slices to hypoxia increased the LDH release in a time-dependent manner. However, when slices were exposed to hypoxia in the presence of PTX, the LDH release was decreased. The protective effect of PTX was dose-dependent over the concentrations of 0.05∼1 mM. Hypoxia did not increase lipid peroxidation, whereas an organic hydroperoxide t-butylhydroperoxide (tBHP) resulted in a significant increase in lipid peroxidation. PTX did not affect tBHP-induced lipid peroxidation. Hypoxia decreased PAH uptake, which was significantly attenuated by PTX and glycine. tBHP-induced inhibition of PAH uptake was not altered by PTX, although it was prevented by antioxidant deferoxarnine. The PAH uptake by slices in rabbits with ischemic acute renal failure was prevented by PTX pretreatment. These results suggest that PTX may exert a protective effect against hypoxia-induced cell injury and its effect may due to inhibition of the TNF-α production, but not by its antioxidant action.