• Title, Summary, Keyword: renal cancer

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CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells

  • Liu, Xuejiao;Chong, Yulong;Liu, Huize;Han, Yan;Niu, Mingshan
    • 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.

Review on Targeted Treatment of Patients with Advanced-Stage Renal Cell Carcinoma: A Medical Oncologist's Perspective

  • Tanriverdi, Ozgur
    • 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.

Awareness of Cancer Screening During Treatment of Patients with Renal Failure: A Physician Survey in Turkey

  • Uysal-Sonmez, Ozlem;Tanriverdi, Ozgur;Uyeturk, Ummugul;Budakoglu, Isil Irem;Kazancioglu, Rumeyza;Turker, Ibrahim;Budakoglu, Burcin;Yalcintas-Arslan, Ulku;Oksuzoglu, Berna
    • 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.

Incidence of Cisplatin-Induced Nephrotoxicity and Associated Factors among Cancer Patients in Indonesia

  • Prasaja, Yenny;Sutandyo, Noorwati;Andrajati, Retnosari
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1117-1122
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    • 2015
  • Background: Cisplatin is still used as a first-line medication for solid tumors. Nephrotoxicity is a serious side effect that can decrease renal function and restrict applicable doses. This research aimed to obtain the profile of cisplatin-induced nephrotoxicity and its associated factors in adult cancer patients at Dharmais National Cancer Hospital (DNCH). Materials and Methods: The design was cross-sectional with data obtained from patient medical records. We retrospectively reviewed adult cancer patients treated with cisplatin ${\geq}60mg/m^2$ for at least four consecutive chemotherapy cycles from August 2011 to November 2013. The nephrotoxicity criterion was renal function decline characterized by creatinine clearance <60 ml/min using the Cockroft-Gault (CG) equation. Results: Eighty-eight subjects received at least four chemotherapy cycles of cisplatin. The prevalence of cisplatin nephrotoxicity was 34.1%. Symptoms could be observed after the first cycle of chemotherapy, and the degree of renal impairment was higher with increased numbers of cycles (r=-0.946, $r^2=89.5%$). Factors that affected the decline of renal function were patient age (p=0.008, OR=3.433, 95%CI= 1.363-8.645) and hypertension (p=0.026, OR=2.931, 95%CI=1.120-7.670). Conclusions: Cisplatin nephrotoxicity occurred in more than one-third of patients after the fourth cycle of chemotherapy and worsened after each cycle despite preventive strategies such as hydration. The decline of renal function induced by cisplatin ${\geq}60mg/m^2$ was affected by age and hypertension.

MicroRNA-122 Promotes Proliferation, Invasion and Migration of Renal Cell Carcinoma Cells Through the PI3K/Akt Signaling Pathway

  • Lian, Ji-Hu;Wang, Wei-Hua;Wang, Jia-Qiang;Zhang, Yu-Hong;Li, Yi
    • 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.

RNA Interference-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth, Induces Apoptosis, and Increases the Chemosensitivity to 5-Fluorouracil in Renal Cancer Caki-1 Cells

  • Wang, Peng;Yin, Bo;Shan, Liping;Zhang, Hui;Cui, Jun;Zhang, Mo;Song, Yongsheng
    • 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.

Clinicopathologic Patterns of Adult Renal Tumors in Pakistan

  • Hashmi, Atif Ali;Ali, Rabia;Hussain, Zubaida Fida;Faridi, Naveen
    • 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.

Honokiol Suppresses Renal Cancer Cells' Metastasis via Dual-Blocking Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties through Modulating miR-141/ZEB2 Signaling

  • Li, Weidong;Wang, Qian;Su, Qiaozhen;Ma, Dandan;An, Chang;Ma, Lei;Liang, Hongfeng
    • 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.

Nature of Lesions Undergoing Radical Nephrectomy for Renal Cancer

  • Mustafa, Gunes;Ilhan, Gecit;Necip, Pirincci;Kerem, Taken;Kadir, Ceylan
    • 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.

Serum Levels of CA15-3, AFP, CA19-9 and CEA Tumor Markers in Cancer Care and Treatment of Patients with Impaired Renal Function on Hemodialysis

  • Estakhri, Rasoul;Ghahramanzade, Ali;Vahedi, Amir;Nourazarian, Alireza
    • 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.