Displaying publications 41 - 55 of 55 in total

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  1. Fulltext Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma - Tissue Microarray of Human Samples
    Rajandram R, Razack AH, Ng KL, Gobe GC
    J Kidney Cancer VHL, 2016;3(1):1-11.
    PMID: 28326275 DOI: 10.15586/jkcvhl.2016.47
    Although primary localised tumours of renal cell carcinoma (RCC) can be treated relatively successfully with surgery, metastatic RCC has poor prognosis because of late diagnosis and resistance to therapies. In the present study, we were interested in profiling the protein expression of "inhibitor of caspase-activated DNase" (ICAD), an apoptosis inhibitor, in kidney cancer and its paired normal kidney. Immunohistochemistry with automated batch staining and morphometry using digital pathology were used to compare ICAD in 121 RCC specimens with their paired normal kidney tissue. Tissue microarray of formalin-fixed, paraffin-embedded archival tissue was used. Intensity and localisation of ICAD were compared between normal and cancer samples, and against grading within the cancers. The results demonstrated that, in this cohort, ICAD was highly expressed in the proximal tubular epithelium of normal kidney, and significantly decreased in clear cell RCC tissue (p < 0.05) as well as other subtypes of RCC (p < 0.01) compared with normal kidney. There was a tendency towards nuclear localisation of ICAD in clear cell RCC, but not in other subtypes of RCC. No significant association was found between ICAD intensity and grade of RCC. In summary, down-regulation of ICAD occurs in RCC. ICAD normally inhibits DNA fragmentation and apoptosis; thus, its down-regulation was unexpected in a cancer known for its resistance to apoptosis. However, these RCC samples were from primary, not metastatic, RCC sites, and down-regulated ICAD may be part of a progressive pathway that promotes RCC metastasis.
    Matched MeSH terms: Carcinoma, Renal Cell
  2. Fulltext Management of renal cell carcinoma in von hippel-lindau syndrome: case report and review of literature
    Aroona, S., Shamsuddin, O.
    Journal of Surgical Academia, 2015;5(1):75-78.
    MyJurnal
    Renal cell carcinoma (RCC) is the one of the most common type of of cancer of the kidneys affecting adults. A 35- year-old man, with Von Hippel Lindau (VHL) syndrome was referred for bilateral renal mass in a follow up CT for evaluation. Open partial left nephrectomy was performed and the final histopathological report confirmed the diagnosis. One of the most important genetic and hereditary risk factor for RCC is Von Hippel-Lindau syndrome (VHL). RCC in VHL may occur bilaterally in some cases, so preserving renal parenchymal function is a major therapeutic goal and nephron sparing surgery provides a favorable patient outcome.
    Matched MeSH terms: Carcinoma, Renal Cell
  3. Sorafenib in renal cell carcinoma
    Davoudi ET, bin-Noordin MI, Javar HA, Kadivar A, Sabeti B
    Pak J Pharm Sci, 2014 Jan;27(1):203-8.
    PMID: 24374450
    Cancer is among most important causes of death in recent decades. Whoever the renal cell carcinoma incidence is low but it seems it is more complicated than the other cancers in terms of pathophysiology and treatments. The purpose of this work is to provide an overview and also deeper insight to renal cell carcinoma and the steps which have been taken to reach more specific treatment and target therapy, in this type of cancer by developing most effective agents such as Sorafenib. To achieve this goal hundreds of research paper and published work has been overviewed and due to limitation of space in a paper just focus in most important points on renal cell carcinoma, treatment of RCC and clinical development of Sorafenib. The information presented this paper shows the advanced of human knowledge to provide more efficient drug in treatment of some complicated cancer such as RCC in promising much better future to fight killing disease.
    Matched MeSH terms: Carcinoma, Renal Cell/drug therapy*
  4. High-risk human papillomavirus infection in different histological subtypes of renal cell carcinoma
    Farhadi A, Behzad-Behbahani A, Geramizadeh B, Sekawi Z, Rahsaz M, Sharifzadeh S
    J Med Virol, 2014 Jul;86(7):1134-44.
    PMID: 24700118 DOI: 10.1002/jmv.23945
    Limited data exist regarding whether a high-risk human papillomavirus (HR-HPV) infection increases the risk of developing renal cell carcinoma. The aim of this study was to investigate whether HPV infection has a role in the pathogenesis or development of a certain histological subtype of renal cell carcinoma. Formalin-fixed paraffin-embedded (FFPE) specimens of 122 patients with histopathologically proven renal cell carcinoma and their respective peritumoral tissues were examined. The presence of HPV-DNA was determined by a combination of MY/GP+ consensus primers and HPV-16/18 type specific nested PCRs followed by direct sequencing. Catalyzed signal-amplified colorimetric in situ hybridization (CSAC-ISH) technique was applied to determine the physical status of viral genome. The expression of p16INK4a and HPV L1 capsid proteins was evaluated using immunohistochemistry. HPV genome was detected in 37 (30.3%) tumor specimens and their four (4.1%) corresponding peritumoral tissues. HPV-18 was the most common viral type identified followed by HPV-16 and 58. Immunoexpression of p16INK4a was detected in 24 (20.3%) cases. Data analysis showed a significant correlation between p16INK4a expression and the presence of HR-HPV DNA (P renal cell carcinoma. It is proposed that HPV infection in high-grade tumors might precede disease progression in a number of tumors, particularly of the papillary subtype.
    Matched MeSH terms: Carcinoma, Renal Cell/etiology*; Carcinoma, Renal Cell/virology*
  5. Fulltext Clinical characteristics of renal cancer in Malaysia : a ten year review
    Singam P, Ho C, Hong GE, Mohd A, Tamil AM, Cheok LB, et al.
    Asian Pac J Cancer Prev, 2010;11(2):503-6.
    PMID: 20843141
    Renal cancer is rare and its incidence is 1.9 per 100,000 in the Malaysian population, which consists of three major ethnic groups (Malay, Chinese and Indians). A retrospective study was her conducted to identify clinical characteristics and ethnic background influences on presentation. The study included all renal cancer patients from a single medical institution over ten years, with a total of 75 cases. Seventy-three patients underwent surgery while 2 received only radiotherapy or chemotherapy. The male to female ratio was 2.75:1. Incidence was equal among the Malay (49.3%) and Chinese ethnic groups (45.3%). Mean age of patients were 57.1 (18-93) years old. There were 26 (37.4%) patients with Stage I disease, 14 (18.7%) at Stage II, 23 (30.7%) at Stage III and 12 (16%) at Stage IV. The Chinese race presented at mean older age (p= 0.02) and later stage of disease (p= 0.046). Patients above 40 years old had more advanced stage disease (p= 0.023). Tumour histology were clear cell (72%), urothelial cell (13.3%), sarcomatoid cell and nephroblastoma each contributed 2.7%. The mean tumour size was 8.1 (2-20) cm. There was substantial agreement between the pre and post operative staging (kappa 0.691). In conclusion we observed significant influences of age and race in the clinical presentation of renal cancer in our institution based population. There was larger male to female ratio and mean tumour size as compared to previous epidemiology studies.
    Matched MeSH terms: Carcinoma, Renal Cell/secondary; Carcinoma, Renal Cell/therapy*
  6. Fulltext A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma
    Syafruddin SE, Rodrigues P, Vojtasova E, Patel SA, Zaini MN, Burge J, et al.
    Nat Commun, 2019 03 11;10(1):1152.
    PMID: 30858363 DOI: 10.1038/s41467-019-09116-x
    Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
    Matched MeSH terms: Carcinoma, Renal Cell/genetics*; Carcinoma, Renal Cell/pathology
  7. Fulltext The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling
    Ch'ng WC, Stanbridge EJ, Yusoff K, Shafee N
    J Interferon Cytokine Res, 2013 Jul;33(7):346-54.
    PMID: 23506478 DOI: 10.1089/jir.2012.0095
    Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), is active and regulates expression of many genes that contribute to aggressive malignancy, radio-, and chemo-resistance. To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2α, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used. We show that these RCC cells responded to NDV by producing only interferon (IFN)-β, but not IFN-α, and are associated with increased STAT1 phosphorylation. Restoration of wt VHL expression enhanced NDV-induced IFN-β production, leading to prolonged STAT1 phosphorylation and increased cell death. Hypoxia augmented NDV oncolytic activity regardless of the cells' HIF-2α levels. These results highlight the potential of oncolytic NDV as a potent therapeutic agent in the killing of hypoxic cancer cells.
    Matched MeSH terms: Carcinoma, Renal Cell/immunology; Carcinoma, Renal Cell/therapy*
  8. Fulltext Endogenous HIF2A reporter systems for high-throughput functional screening
    Zaini MN, Patel SA, Syafruddin SE, Rodrigues P, Vanharanta S
    Sci Rep, 2018 08 13;8(1):12063.
    PMID: 30104738 DOI: 10.1038/s41598-018-30499-2
    Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.
    Matched MeSH terms: Carcinoma, Renal Cell/genetics
  9. Robot-assisted Cavectomy Versus Thrombectomy for Level II Inferior Vena Cava Thrombus: Decision-making Scheme and Multi-institutional Analysis
    Shi T, Huang Q, Liu K, Du S, Fan Y, Yang L, et al.
    Eur Urol, 2020 10;78(4):592-602.
    PMID: 32305170 DOI: 10.1016/j.eururo.2020.03.020
    BACKGROUND: Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described.

    OBJECTIVE: To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT.

    DESIGN, SETTING, AND PARTICIPANTS: Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019.

    SURGICAL PROCEDURE: The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals.

    MEASUREMENTS: Clinicopathological, operative, and survival outcomes were collected and analyzed.

    RESULTS AND LIMITATIONS: All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p < 0.001). IVC invasion was a risk factor for progression-free and overall survival at midterm follow-up. Large-volume and long-term follow-up studies are needed.

    CONCLUSIONS: RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation.

    PATIENT SUMMARY: In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

    Matched MeSH terms: Carcinoma, Renal Cell/secondary*
  10. Human renal carcinoma cells respond to Newcastle disease virus infection through activation of the p38 MAPK/NF-κB/IκBα pathway
    Ch'ng WC, Abd-Aziz N, Ong MH, Stanbridge EJ, Shafee N
    Cell Oncol (Dordr), 2015 Aug;38(4):279-88.
    PMID: 25930675 DOI: 10.1007/s13402-015-0229-5
    Newcastle disease virus (NDV) is an oncolytic virus that is known to have a higher preference to cancer cells than to normal cells. It has been proposed that this higher preference may be due to defects in the interferon (IFN) responses of cancer cells. The exact mechanism underlying this process, however, remains to be resolved. In the present study, we examined the antiviral response towards NDV infection of clear cell renal cell carcinoma (ccRCC) cells. ccRCC is associated with mutations of the von Hippel-Lindau tumor suppressor gene VHL, whose protein product is important for eliciting cellular responses to changes in oxygen levels. The most common first line treatment strategy of ccRCC includes IFN. Unfortunately, most ccRCC cases are diagnosed at a late stage and often are resistant to IFN-based therapies. Alternative treatment approaches, including virotherapy using oncolytic viruses, are currently being investigated. The present study was designed to investigate the mechanistic pathways underlying the response of ccRCC cells to oncolytic NDV infection.
    Matched MeSH terms: Carcinoma, Renal Cell/genetics; Carcinoma, Renal Cell/metabolism; Carcinoma, Renal Cell/virology
  11. Metastatic leiomyosarcoma of the thyroid: A rare entity
    Che Jalil NA, Rama Chandran P, Samsudin AHZ, Yahya MM, Wan Abdul Rahman WF
    Malays J Pathol, 2021 Apr;43(1):69-73.
    PMID: 33903308
    Cancer metastasis to the thyroid gland from non-thyroid sites is a rare presentation in clinical practice. The most frequent primary cancers that metastasise to the thyroid are renal cell carcinoma, followed by colorectal, lung and breast. We report a case of a 64-year-old Malay lady who presented with anterior neck swelling 4 years after an initial diagnosis of uterine leiomyosarcoma. She had undergone a hysterectomy procedure four years ago. Fine needle aspiration cytology of the thyroid mass suggested undifferentiated thyroid carcinoma. After multi-disciplinary discussion, the patient underwent thyroidectomy and the final histopathological diagnosis was metastatic leiomyosarcoma of the thyroid. The diagnosis was aided by an immunohistochemistry panel of positive myogenic markers, negative epithelial markers as well as the previous medical history of uterine leiomyosarcoma. Metastatic leiomyosarcoma of the thyroid may mimic primary undifferentiated (anaplastic) thyroid carcinoma (UTC) with a sarcomatoid pattern, medullary thyroid carcinoma (MTC) with spindle cells morphology and spindle cell tumour with thymus-like differentiation (SETTLE). Hence, a multidisciplinary approach must be practised by pathologists, surgeons and radiologists to consider metastatic lesions of the thyroid gland, especially when a previous history of cancer exists or is suspected.
    Matched MeSH terms: Carcinoma, Renal Cell
  12. Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance
    Rajandram R, Yap NY, Pailoor J, Razack AH, Ng KL, Ong TA, et al.
    Pathology, 2014 Oct;46(6):518-22.
    PMID: 25158810 DOI: 10.1097/PAT.0000000000000145
    Renal cell carcinoma (RCC) generally has a poor prognosis because of late diagnosis and metastasis. We have previously described decreased tumour necrosis factor receptor-associated factor-1 (TRAF-1) in RCC compared with paired normal kidney in a patient cohort in Australia. In the present study, TRAF-1 expression in clear cell RCC (ccRCC) and normal kidney was again compared, but in a cohort from University Malaya Medical Centre. Serum TRAF-1 was also evaluated in RCC and normal samples.Immunohistochemistry with automated batch staining and Aperio ImageScope morphometry was used to compare TRAF-1 in 61 ccRCC with paired normal kidney tissue. Serum from 15 newly diagnosed and untreated ccRCC and 15 healthy people was tested for TRAF-1 using ELISA.In this cohort, TRAF-1 was highly expressed in proximal tubular epithelium of normal kidney, and significantly decreased in ccRCC tissue (p 
    Matched MeSH terms: Carcinoma, Renal Cell
  13. Fulltext Choroidal metastasis from renal cell carcinoma presenting with exudative retinal detachment
    Hor, S.M., Mushawiahti, M.
    Journal of Surgical Academia, 2017;7(1):62-65.
    MyJurnal
    A 42-year-old Chinese man, known case of renal cell carcinoma with lung metastasis, was referred to Universiti
    Kebangsaan Malaysia Medical Centre for left eye blurring of vision for one month duration, which was worse upon
    waking up in the morning and cleared up after 1-2 hours. On examination, visual acuities were 6/6 in both eyes. No
    relative afferent pupillary defect. Left fundus showed inferonasal retinal detachment without macular involvement.
    No retina break, no retinitis and no choroidal lesion seen. Right eye examination was normal. Optical coherence
    tomography (OCT) of left eye showed subretinal fluid temporal and inferior to optic disc. Fundus fluorescein
    angiography (FFA) left eye showed hypofluoresence in early phase but hyperfluorescence with pin point leakage in
    late phase over inferonasal quadrant. Indocyanine green (ICG) showed early hypofluoresence with late pin point
    hyperfluoresence in the same quadrant. A clinical diagnosis of exudative retinal detachment due to choroidal
    metastasis secondary to renal cell carcinoma was made. The patient was planned for cyber-knife radiotherapy of his
    left eye but unfortunately we lost the follow up. High index of suspicion and relevant investigation are needed for
    patients with visual complaints and history of renal cell carcinoma to diagnose choroidal metastasis.
    Matched MeSH terms: Carcinoma, Renal Cell
  14. Fulltext Prognostic biomarkers in renal cell carcinoma: is there a relationship with obesity?
    Rajandram R, Perumal K, Yap NY
    Transl Androl Urol, 2019 May;8(Suppl 2):S138-S146.
    PMID: 31236331 DOI: 10.21037/tau.2018.11.10
    Obesity is a recognized risk factor for renal cell carcinoma (RCC) the commonest form of kidney cancer. Both obesity and RCC are serious diseases with increasing incidence yearly. This review examined certain obesity associated measurements and adipokines as detection/prognostic indicators for RCC. The obesity related measurements such as body mass index (BMI), waist circumstance (WC), waist-hip ratio (WHR) in predicting RCC are valid when used in conjunction with other risk factors such as age and sex or with histological findings. The adipokine adiponectin holds promising outcomes as a predictive marker in assessing the risk of developing RCC. In addition, tissue leptin/leptin receptor may be a distinguishing marker for RCC subtypes. However, circulating leptin may not be a suitable detection or prognostic biomarker for RCC. The other less investigated adipokines; omentin, visfatin, apelin and resistin are also expressed in RCC but their prognostic capabilities are still inconclusive. BMI, WC and adipokines may be useful additions in a nomogram which includes TNM staging and pathological grading system to detect, confirm and follow-up RCC cases.
    Matched MeSH terms: Carcinoma, Renal Cell
  15. Decreased apoptosis repressor with caspase recruitment domain confers resistance to sunitinib in renal cell carcinoma through alternate angiogenesis pathways
    Gobe GC, Ng KL, Small DM, Vesey DA, Johnson DW, Samaratunga H, et al.
    Biochem Biophys Res Commun, 2016 Apr 22;473(1):47-53.
    PMID: 26995091 DOI: 10.1016/j.bbrc.2016.03.048
    Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby conferring drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC.
    Matched MeSH terms: Carcinoma, Renal Cell/metabolism*
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