• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1077-1082
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• 2013

Background: Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. We aimed to explore whether the expression of Long Non-Coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5) is associated with RCC genesis. Methods: We selected twelve clinical samples diagnosed for renal clear cell carcinoma and found that the LncRNA GAS5 transcript levels were significantly reduced relative to those in adjacent unaffected normal renal tissues. Results: In addition, expression of GAS5 was lower in the RCC cell line A498 than that in normal renal cell line HK-2. Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. At the same time, the migration and invasion potential of A498 cells were inhibited compared to control groups. Conclusion: Our study provided the first evidence that a decrease in GAS5 expression is associated with RCC genesis and progression and overexpression of GAS5 can act as a tumor suppressor for RCC, providing a potential attractive therapeutic approach for this malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3703-3708
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• 2015

Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). Materials and Methods: Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. Results: The NLR of 327 patients was $2.72{\pm}2.25$. NLR <1.7 and NLR ${\geq}1.7$ were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). Conclusions: Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5017-5021
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• 2013

Objective: MicroRNAs (miRNAs) are a small class of non-coding, single-stranded RNAs with a critical role in genesis and maintenance of renal cancer mainly through binding to 3'-untranslated regions (3'UTR) of target mRNAs, which causes a block of translation and/or mRNA degradation. The aim of the present study was to investigate the potential effects of miR-122 in human renal cell carcinomas. Methods: The expression level of miR-122 was quantified by qRT-PCR. MTT, colony formation, invasion and migration assays were used to explore the potential functions of miR-122 in human renal cell carcinoma cells. Results: Cellular growth, invasion and migration in two A498 and 786-O cells were significantly increased after miR-122 transfection. Further experiments demonstrated that overexpression of miR-122 resulted in the increase of phospho-Akt (Ser473) and phospho-mTOR (Ser2448), then activation of mTOR targets, p70S6K and 4E-BP1. Conclusions: The up-regulation of miR-122 may play an important role in the progress of renal cancer through activating PI3K/Akt signal pathway and could be a potential molecular target for anti-cancer therapeutics.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3993-3996
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• 2014

Background: Diabetes is a chronic disease characterized by impaired fasting blood glucose that leads to disturbances in various organs. In this study, we evaluated relationships between tumor size and grade in a population of diabetic and non-diabetic patients with renal cell carcinoma. Materials and Methods: Between 2007-2013, in our clinic radical nephrectomy performed to 310 patients for renal tumors and pathology reported renal cell carcinoma cases were enrolled in the study. Patients with and without a history of diabetes regarding fasting glucose and HgA1c levels were evaluated during surgery for tumor size and Fuhrman grade. Results: Diabetes was found in 95 patients. The mean age of the patients with and without diabetes mellitus was 64.3 (40-79) and 58.4 (31-87) years, respectively. In the diabetes group 51% of patients had a tumor size over 7 cm and 54% a tumor grade over Fuhrman 3. The respective figures in the non-diabetes group were 35% and 30% (p<0.05 in both cases). Conclusions: Renal cancer appears more aggressive in patients with diabetes. In this study lifestyle and risk factors with diabetes regulation were observed to be important for renal cancer patients. Multicenter studies are needed in larger series for more accurate results.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7351-7354
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• 2013

Background: Metabolic syndrome (MetS) is a multifactorial disease characterized by impaired glucose tolerance/diabetes, obesity, high triglyceride levels, low HDL levels, and hypertension. In this study we evaluate the relationship between tumor size and grade, and presence of the metabolic syndrome in patients with renal cell carcinoma. Materials and Methods: Between 2007-2013, radical nephrectomy was performed for 310 patients with renal tumors in our clinic and those with pathology reported renal cell carcinoma were enrolled and divided into two groups, with and without metabolic syndrome diagnosed on the basis of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria. The relationship between tumor size and grade of the two groups (Fuhrman nuclear degree) was evaluated statistically. Results: The metabolic syndrome was found in 70 patients, with a mean age of 65.5 (40-87), as compared to 58.8 (31-84) years in the non-metabolic syndrome group. Tumor size over 7 cm was found in 54% and 33%, respectively, and tumor grade over Fuhrman 3 in 56% and 32% of patients. Patients with metabolic syndrome had significantly higher tumor size and grade (p<0.05). In the presence of hypertension, diabetes and high triglyceride levels, significant assocations were again observed (p<0.05). Tumor size and degree also increased with increasing body mass index but this was not statistically significant (p>0.05). Conclusions: Renal cancer is more aggressive in patients with metabolic syndrome. Lifestyle and risk factors were revealed to be significant influences in renal cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8947-8950
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• 2014

Immunological functions of heat shock proteins (HSPs) have long been recognized. In this study we aimed to efficiently purify HSP70 from renal cell carcinoma and test it as a tumor antigen for pulsing dendritic cells in vitro. HSP70 was purified from renal cell carcinoma specimens by serial column chromatography on Con A-sepharose, PD-10, ADP-agarose and DEAE-cellulose, and finally subjected to fast protein liquid chromatography (FPLC). Dendritic cells derived from the adherent fraction of peripheral blood mononuclear cells were cultured in the presence of IL-4 and GM-CSF and exposed to tumor HSP70. After 24 hours, dendritic cells were phenotypically characterized by flow cytometry. T cells obtained from the non-adherent fraction of peripheral blood mononuclear cells were then co-cultured with HSP70-pulsed dendritic cells and after 3 days T cell cytotoxicity towards primary cultured renal cell carcinoma cells was examined by Cell Counting Kit-8 assay. Dendritic cells pulsed in vitro with tumor-derived HSP70 expressed higher levels of CD83, CD80, CD86 and HLA-DR maturation markers than those pulsed with tumor cell lysate and comparable to that of dendritic cells pulsed with tumor cell lysate plus TNF-${\alpha}$. Concomitantly, cytotoxic T-lymphocytes induced by HSP70-pulsed dendritic cells presented the highest cytotoxic activity. There were no significant differences when using homologous or autologous HSP70 as the tumor antigen. HSP70 can be efficiently purified by chromatography and induces in vitro dendritic cell maturation in the absence of TNF-${\alpha}$. Conspecific HSP70 may effectively be used as a tumor antigen to pulse dendritic cells in vitro.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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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.

• Korean Journal of Head & Neck Oncology
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• v.29 no.2
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• pp.62-64
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• 2013

The distant metastasis is found out in about 25-57% of the patients with renal cell carcinoma at the time of diagnosis. But, the incidence of metastases to the head and neck region, especially to the thyroid gland, is rare. Most of patients with metastatic renal cell carcinoma to the thyroid gland are asymptomatic at presentation as patients with primary thyroid carcinoma. In the presence of clear cell tumor of the thyroid gland, the diagnostic considerations must include metastatic renal cell carcinoma. We report a case of thyroid metastasis from renal cell carcinoma at the time of diagnosis.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.499-502
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• 2013

Trace elements which are essential components of biological structures may also be toxic when present at levels above the amounts required for biological function. In our study, trace element levels were measured with furnace atomic absorption spectrophotometry in 33 newly diagnosed renal cell carcinoma cases (preoperative) and 32 healthy controls. When compared with the control group, it was found that the levels of cadmium (Cd), lead (Pb) were higher and the levels of zinc (Zn), iron (Fe) and manganese (Mn) were lower in the patient group. These changes may be important in the formation of renal cell carcinoma, a question which should be explored with postoperative comparative studies.