• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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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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• v.15 no.5
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• pp.2165-2168
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• 2014

Background: Today, survival rate of patients with chronic renal failure/hemodialysis has increased so that chronic illnesses are more likely to occur. Cancer is the main cause of morbidity and mortality in such patients. Aim: In this study, physician attitudes were examined about cancer screening in patients with renal failure. Materials and Methods: This study was done by face to face questionnaire in the $27^{th}$ National Nephrology Congress to determine if the physicians dealing with chronic renal failure, hemodialysis or renal transplanted patients, recommend cancer screening or not and the methods of screening for cervix, prostate, breast and colon cancer. Results: One hundred and fifty six physicians were included in the survey. A total of 105 (67%) participants were male and the age of responders was $48{\pm}9$ years. About 29% were specialists in nephrology, 28% internal medicine, and 5% were other areas of expertise. Some 48% of participants were hemodialysis certified general practitioners. Patients were grouped as compensated chronic renal failure, hemodialysis or renal transplanted. Of the 156 responders, 128 (82%) physicians recommended breast cancer screening and the most recommended subgroup was hemodialysis patients (15%). The most preferred methods of screening were combinations of mammography, self breast examination and physicianbreast examination. 112 (72%) physicians recommended cervix cancer screening, and the most preferred method of screening was pap-smear. Colon cancer screening was recommended by 102 (65%) physicians and prostate screening by 109 (70%) physicians. The most preferred methods of screening were fecal occult blood test and PSA plus rectal digital test, respectively. Conclusions: It is not obvious whether cancer screening in renal failure patients is different from the rest of society. There is a variety of screening methods. An answer can be found to these questions as a result of studies by a common follow-up protocol and cooperation of nephrologists and oncologists.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.609-617
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• 2013

Renal cell carcinomas make up 3% of all cancers and one in four patients is metastatic at time of diagnosis. This cancer is one of the most resistant to cytotoxic chemotherapy. Studies have shown that the efficiency of interferon-alpha and/or interleukin-2 based immune therapies is limited in patients with metastatic renal cell carcinoma but latest advances in molecular biology and genetic science have resulted in better understanding of its biology. Tumor angiogenesis, tumor proliferation and metastasis develop by the activation of signal message pathways playing a role in the development of renal cell carcinomas. Better definition of these pathways has caused an increase in preclinic and clinical studies into target directed treatment of renal cell carcinoma. Many recent studies have shown that numerous anti-angiogenic agents have marked clinical activity. In this article, the focus is on general characteristics of molecular pathways playing a major role in renal cell carcinoma, reviewing clinical information onagents used in the target directed treatment of metastatic lesions.

• Molecules and Cells
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• v.37 no.12
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• pp.857-864
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• 2014

Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the antiapoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADPribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.

• Molecules and Cells
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• v.37 no.5
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• pp.383-388
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• 2014

Renal cell carcinoma (RCC) is associated with a high frequency of metastasis and only few therapies substantially prolong survival. Honokiol, isolated from Magnolia spp. bark, has been shown to exhibit pleiotropic anticancer effects in many cancer types. However, whether honokiol could suppress RCC metastasis has not been fully elucidated. In the present study, we found that honokiol suppressed renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. In addition, honokiol inhibited tumor growth in vivo. It was found that honokiol could upregulate miR-141, which targeted ZEB2 and modulated ZEB2 expression. Honokiol reversed EMT and suppressed CSC properties partly through the miR-141/ZEB2 axis. Our study suggested that honokiol may be a suitable therapeutic strategy for RCC treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2303-2307
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• 2014

Background: Renal cancer is a serious public health problem which may be under reported and registered in our setup, since the Karachi cancer registry documented only 43 cases out of 4,268 incident cancer cases over 3 year duration. Therefore we aimed to determine the clinicopathologic characteristics of adult renal tumors in our setup. Materials and Methods: The study was conducted in histopathology department, Liaquat National Hospital and included total of 68 cases of adult renal tumors over 4 years. Detailed histopathologic characteristics of tumors were analyzed. Results: Mean age of patients was 56.4 (18-84) years. Renal cell carcinoma (RCC) was the most common cell type (78%) cases; followed by transitional/urothelial carcinoma (12.5%), leiomyosarcoma (4.7%), oncocytoma (1.6%), squamous cell carcinoma (1.6%) and high grade pleomorphic undifferentiated sarcoma (1.6%). Among 50 RCC cases; 62% were conventional/clear cell RCC (CCRCC) type followed by papillary RCC(PRCC), 24%; chromophobe RCC(CRCC), 6% and sarcomatoid RCC(SRCC), 8%. Mean tumor size for RCC was 7.2 cm. Most RCCs were intermediate to high grade (60% and 40% respectively). Capsular invasion, renal sinus invasion, adrenal gland involvement and renal vein invasion was seen in 40%, 18%, 2% and 10% of cases respectively. Conclusions: We found that RCC presents at an earlier age in our setup compared to Western populations. Tumor size was significantly larger and most of the tumors were of intermediate to high grade. This reflects late presentation of patients after disease progression which necessitates effective measures to be taken in primary care setup to diagnose this disease at an early stage.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4431-4433
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• 2012

Aim: The aim of the present study was to evaluate retrospectively histopathologically-diagnosed lesions that were detected in the kidney after radical nephrectomy for a preoperative diagnosis of kidney cancer. Methods: The medical records of 83 patients (51 male, 32 female) were included. Preoperative staging was accomplished by various methods including physical examination, blood hemography and biochemistry, abdominal ultrasonography (US), chest x-ray, abdominal computed tomography (CT) and abdominal magnetic resonance imaging (MRI). Results: Totals of 70 patients underwent radical nephrectomy and 13 nephron sparing surgery. Of the 83 patients, 70 had malignant lesions (renal cell carcinoma, squamous cell carcinoma or other malignancies) 13 had a variety of benign lesions, the most frequently detected being oncoytoma (6), angiomyolipoma (3), xanthogranulamatous pyelonephritis (2), cortical cyst (1) and chronic pyelonephritic change (1). Conclusion: It was concluded that in spite of great technological developments regarding radiological imaging modalities such as US, CT and MRI, benign lesions might still be detected pathologically in patients who undergo radical nephrectomy with the preoperative diagnosis of renal cancer. But, all renal masses should be regarded as malignant and should be managed surgically otherwise proven benign.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1597-1599
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• 2013

Since renal failure causes decrease in tumor marker excretion, use of these markers in cancer care and treatment in patients with renal insufficiency or hemodialysis is controversial. The aim of this study was to investigate differences of serum levels of tumor markers CA15-3, AFP, CA19-9 and CEA in patients with impaired renal function. A total of 100 patients referred to the Tabriz Immam Reza and Amiralmomenin hospital from June 2010 to November 2011 were selected for study. Subjects were divided to 3 groups of healthy, dialysis and renal failure but non hemodialysis cases, the last category being re-grouped based on creatinine clearance. No significant relationship between different groups in serum levels of CEA (P=0.99) and CA19-9 (P=0.29) tumor markers was found. A significant correlation was observed between serum levels of AFP (P<0.001) and CA15-3 (P<0.001) and also a tendency between creatinine clearance and CEA (r=0.05, P=0.625). Creatinine clearance significantly correlated with AFP (P<0.001, r=0.53) and CA15-3 (p=0.00, r=-0.412), but not CA19-9 (P=0.089, r=-0.171). According to results of this study it appears that use of tumor markers in patients with impaired renal function should be performed with special precautions.

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.83-91
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• 2017

Background: Piperacillin/tazobactam (TZP) is an antibiotic against a broad spectrum of gram-positive, gram-negative, and aerobic and anaerobic strains of bacteria. Due to changes in its pharmacokinetic and pharmacodynamic parameters by TZP-treated patients' renal functions and obesity, it is important to administrate and monitor TZP based on their renal functions and Body Mass Index (BMI) levels. The purpose of this study was to determine the appropriateness of administration doses of TZP based on renal functions of obese cancer patients in a tertiary hospital. Methods: This study was retrospectively conducted with obese cancer patients with $BMI{\geq}30kg/m^2$ in a tertiary hospital, Korea from September 2004 to August 2014. Data were collected through Electronic Medical Record (EMR) which contained laboratory data and TZP dosing of each patient. Results: Among 7,058 patients during the study period, 102 prescriptions were selected based on inclusion and exclusion criteria and classified by their renal functions. Although TZP should be used based on patients' renal functions to adjust its dose, its initial dose and dosing interval were consistently used without considering patients' renal functions on a regular basis. Especially, in the comparison with FDA dosing standard of TZP, approximately twice patients with $20mL/min{\leq}CrCl{\leq}40mL/min$ received domestically 4.5 g instead of 2.25 g as the TZP starting dose. Conclusion: The appropriate doses of TZP were administered to almost all of obese cancer patients; however, the recommended TZP dose was different between Korea and other countries by twice the amount. Further related studies are necessary to clearly determine the results, to optimize TZP treatment for obese patients with cancer in clinical practice, and to design and develop new TZP formulations for them in pharmaceutical industry.

• Journal of Digestive Cancer Research
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• v.4 no.1
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• pp.36-38
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• 2016

Biliary tract cancer, a relatively rare disease, is usually found in an unresectable stage. Weekly cisplatin plus gemcitabine has been applied as a standard first-line therapy for advanced biliary tract cancer, but almost up to 3-5% patients experience drug induced renal impairment. Many anticancer medication guidelines recommend drug adjustment when kidneys are damaged, but weekly cisplatin is somewhat low dose so that there is a controversy on reducing the dose. And it is known that the cumulative dose of cisplatin is the most important factor contributing to renal impairment. Therefore, clinicians face troubles whether or not to maintain the chemotherapy. Here, we reported a patient whose renal function (eGFR) had been decreased as the number of chemotherapy increased, so her chemotherapy should be stopped. Since we held the chemotherapy on her, the disease progressed aggressively. Weekly cisplatin regimen is just 25 mg/m², so it may be meaningless to reduce this dose, and it is well known that cumulative dose of cisplatin is the most important factor contributing to renal impairment, it is better not to use cisplatin anymore. Therefore, we recommend that if the patient responds well to weekly cisplatin plus gemcitabine regimen, it would be beneficial to use gemcitabine alone.