Displaying publications 1 - 20 of 69 in total

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  1. 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: Kidney Neoplasms/metabolism*
  2. Mathew A, Cheng HM, Sam CK, Joab I, Prasad U, Cochet C
    Cancer Immunol. Immunother., 1994 Jan;38(1):68-70.
    PMID: 8299121
    The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.
    Matched MeSH terms: Kidney Neoplasms/immunology
  3. 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: Kidney Neoplasms/genetics; Kidney Neoplasms/metabolism; Kidney Neoplasms/virology
  4. Hor, S.M., Mushawiahti, M.
    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: Kidney Neoplasms
  5. 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: Kidney Neoplasms
  6. Christakoudi S, Kakourou A, Markozannes G, Tzoulaki I, Weiderpass E, Brennan P, et al.
    Int. J. Cancer, 2019 Jul 18.
    PMID: 31319002 DOI: 10.1002/ijc.32576
    Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HR) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating centre and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR=1.12 (1.08-1.17) per 10mmHg higher SBP and HR=1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR=1.16 (1.07-1.26) (SBP), HR=1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR=1.08 (1.04-1.12) (SBP), HR=1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, post-menopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC, or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR=0.91 (0.82-1.00) and lymphomas: HR=0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies. This article is protected by copyright. All rights reserved.
    Matched MeSH terms: Kidney Neoplasms
  7. 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: Kidney Neoplasms/pathology; Kidney Neoplasms/therapy*
  8. Sasongko TH, Ismail NF, Zabidi-Hussin Z
    Cochrane Database Syst Rev, 2016 Jul 13;7:CD011272.
    PMID: 27409709 DOI: 10.1002/14651858.CD011272.pub2
    BACKGROUND: Previous studies have shown potential benefits of rapamycin or rapalogs for treating people with tuberous sclerosis complex. Although everolimus (a rapalog) is currently approved by the FDA (U.S. Food and Drug Administration) and the EMA (European Medicines Agency) for tuberous sclerosis complex-associated renal angiomyolipoma and subependymal giant cell astrocytoma, applications for other manifestations of tuberous sclerosis complex have not yet been established. A systematic review is necessary to establish the clinical value of rapamycin or rapalogs for various manifestations in tuberous sclerosis complex.

    OBJECTIVES: To determine the effectiveness of rapamycin or rapalogs in people with tuberous sclerosis complex for decreasing tumour size and other manifestations and to assess the safety of rapamycin or rapalogs in relation to their adverse effects.

    SEARCH METHODS: Relevant studies were identified by authors from the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and clinicaltrials.gov. Relevant resources were also searched by the authors, such as conference proceedings and abstract books of conferences, from e.g. the Tuberous Sclerosis Complex International Research Conferences, other tuberous sclerosis complex-related conferences and the Human Genome Meeting. We did not restrict the searches by language as long as English translations were available for non-English reports.Date of the last searches: 14 March 2016.

    SELECTION CRITERIA: Randomized or quasi-randomized studies of rapamycin or rapalogs in people with tuberous sclerosis complex.

    DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors using standard acquisition forms. The data collection was verified by one author. The risk of bias of each study was independently assessed by two authors and verified by one author.

    MAIN RESULTS: Three placebo-controlled studies with a total of 263 participants (age range 0.8 to 61 years old, 122 males and 141 females, with variable lengths of study duration) were included in the review. We found high-quality evidence except for response to skin lesions which was judged to be low quality due to the risk of attrition bias. Overall, there are 175 participants in the treatment arm (rapamycin or everolimus) and 88 in the placebo arm. Participants all had tuberous sclerosis complex as proven by consensus diagnostic criteria as a minimum. The quality in the description of the study methods was mixed, although we assessed most domains as having a low risk of bias. Blinding of treatment arms was successfully carried out in all of the studies. However, two studies did not report allocation concealment. Two of the included studies were funded by Novartis Pharmaceuticals.Two studies (235 participants) used oral (systemic) administration of everolimus (rapalog). These studies reported response to tumour size in terms of the number of individuals with a reduction in the total volume of tumours to 50% or more relative to baseline. Significantly more participants in the treatment arm (two studies, 162 participants, high quality evidence) achieved a 50% reduction in renal angiomyolipoma size, risk ratio 24.69 (95% confidence interval 3.51 to 173.41) (P = 0.001). For the sub-ependymal giant cell astrocytoma, our analysis of one study (117 participants, high quality evidence) showed significantly more participants in the treatment arm achieved a 50% reduction in tumour size, risk ratio 27.85 (95% confidence interval 1.74 to 444.82) (P = 0.02). The proportion of participants who showed a skin response from the two included studies analysed was significantly increased in the treatment arms, risk ratio 5.78 (95% confidence interval 2.30 to 14.52) (P = 0.0002) (two studies, 224 participants, high quality evidence). In one study (117 participants), the median change of seizure frequency was -2.9 in 24 hours (95% confidence interval -4.0 to -1.0) in the treatment group versus -4.1 in 24 hour (95% confidence interval -10.9 to 5.8) in the placebo group. In one study, one out of 79 participants in the treatment group versus three of 39 in placebo group had increased blood creatinine levels, while the median percentage change of forced expiratory volume at one second in the treatment arm was -1% compared to -4% in the placebo arm. In one study (117 participants, high quality evidence), we found that those participants who received treatment had a similar risk of experiencing adverse events compared to those who did not, risk ratio 1.07 (95% confidence interval 0.96 - 1.20) (P = 0.24). However, as seen from two studies (235 participants, high quality evidence), the treatment itself led to significantly more adverse events resulting in withdrawal, interruption of treatment, or reduction in dose level, risk ratio 3.14 (95% confidence interval 1.82 to 5.42) (P < 0.0001).One study (28 participants) used topical (skin) administration of rapamycin. This study reported response to skin lesions in terms of participants' perception towards their skin appearance following the treatment. There was a tendency of an improvement in the participants' perception of their skin appearance, although not significant, risk ratio 1.81 (95% confidence interval 0.80 to 4.06, low quality evidence) (P = 0.15). This study reported that there were no serious adverse events related to the study product and there was no detectable systemic absorption of the rapamycin during the study period.

    AUTHORS' CONCLUSIONS: We found evidence that oral everolimus significantly increased the proportion of people who achieved a 50% reduction in the size of sub-ependymal giant cell astrocytoma and renal angiomyolipoma. Although we were unable to ascertain the relationship between the reported adverse events and the treatment, participants who received treatment had a similar risk of experiencing adverse events as compared to those who did not receive treatment. Nevertheless, the treatment itself significantly increased the risk of having dose reduction, interruption or withdrawal. This supports ongoing clinical applications of oral everolimus for renal angiomyolipoma and subependymal giant cell astrocytoma. Although oral everolimus showed beneficial effect on skin lesions, topical rapamycin only showed a non-significant tendency of improvement. Efficacy on skin lesions should be further established in future research. The beneficial effects of rapamycin or rapalogs on tuberous sclerosis complex should be further studied on other manifestations of the condition.

    Matched MeSH terms: Kidney Neoplasms/drug therapy*; Kidney Neoplasms/pathology
  9. 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: Kidney Neoplasms/genetics*; Kidney Neoplasms/pathology
  10. 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: Kidney Neoplasms/drug therapy*
  11. Yap YH, Say YH
    Cell Biol. Int., 2012 Mar 1;36(3):273-7.
    PMID: 21980981 DOI: 10.1042/CBI20110088
    Since the discovery of PrPC (cellular prion protein), most studies have focused on its role in neurodegenerative diseases, whereas its function outside the nervous system remains obscure. We investigated the ability of PrPC in resisting TNFα (tumour necrosis factor α) apoptosis in three PrPC-transiently transfected cancer cell lines, renal adenocarcinoma ACHN, oral squamous cell carcinoma HSC-2 and colon adenocarcinoma LS174T. PrPC-expressing ACHN and LS174T cells had higher viabilities compared with the mock-transfected cells, while the transient overexpression of PrPC had minimal overall effect on HSC-2 cells due to its high endogenous PrPC expression. Cell cycles were also analysed, with both PrPC expressing ACHN and LS174T cells having a significantly higher proliferative index than mock-transfected cells. Flow cytometry analysis indicated a G1/S-phase cell cycle transition in both PrPC-expressing ACHN and LS174T cells. PrPC resists TNFα apoptosis due to a modest, but statistically significant, cell-specific cytoprotection compared with mock-transfected cells.
    Matched MeSH terms: Kidney Neoplasms/metabolism*
  12. Ang AH, Lambeth JT, Soo YS, Ong SC
    Med J Malaya, 1970 Sep;25(1):8-16.
    PMID: 4249503
    Matched MeSH terms: Kidney Neoplasms/radiography
  13. Poh ME, Liam CK, Pang YK, Chua KT
    Respirol Case Rep, 2013 Dec;1(2):26-7.
    PMID: 25473534 DOI: 10.1002/rcr2.16
    We report a man presenting with dyspnea, cough, and hemoptysis due to left lung collapse from an endobronchial tumor obstructing the left main bronchus. Endobronchial biopsy of the tumor showed renal cell carcinoma, identical to a previous specimen of renal cell carcinoma removed by a radical left nephrectomy five years ago. The endobronchial tumor was removed by snare diathermy through a flexible bronchoscope, following which his symptoms resolved and the left lung re-expanded. Endobronchial metastasis from renal cell carcinoma is rare and can mimic obstruction from other endobronchial etiologies, such as bronchogenic carcinoma. Total lung collapse as a result is even more uncommon, although atelectasis is well described. Endobronchial techniques, such as snare diathermy, can relieve obstruction, providing symptom palliation even in advanced disease.
    Matched MeSH terms: Kidney Neoplasms
  14. Tan BL, Norhaizan ME, Hairuszah I, Hazilawati H, Roselina K
    Oxid Med Cell Longev, 2015;2015:539798.
    PMID: 26257841 DOI: 10.1155/2015/539798
    Brewers' rice, which is known locally as temukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers' rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers' rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers' rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers' rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers' rice could be used in future applications to combat liver and kidney disease.
    Matched MeSH terms: Kidney Neoplasms/chemically induced; Kidney Neoplasms/pathology; Kidney Neoplasms/prevention & control*
  15. Ariffin H, Muthukkumaran T, Stanslas J, Sabariah AR, Veerasekaran N, Lin HP
    Leuk. Lymphoma, 2005 Aug;46(8):1233-7.
    PMID: 16085568
    We report the clinical features and in vitro chemosensitivity assay findings of a 13-year-old girl who developed secondary B-cell acute lymphoblastic leukemia (ALL) 7 years after a diagnosis of Wilms' tumor. The patient was treated using the Berlin - Frankfurt - Muenster (BFM) ALL chemotherapy protocol with poor response to initial therapy before succumbing to sepsis. An in vitro chemosensitivity assay on her peripheral blood lymphoblasts was performed while she was undergoing induction therapy and showed a high level of resistance to drugs commonly used for ALL therapy, e.g. steroids, anthracyclines, vincristine and L-asparaginase. The mechanism of chemoresistance was not elicited, but was probably not related to P-glycoprotein (P-gp) over-expression. We believe that the in vitro chemosensitivity assay is a good indicator of cellular response to chemotherapy and may provide reliable information for the basis of the selection of drugs to be used for the treatment of similarly rare patients rather than relying on "standard" protocols.
    Matched MeSH terms: Kidney Neoplasms/complications*; Kidney Neoplasms/diagnosis; Kidney Neoplasms/drug therapy
  16. Lim, Pei Shan, Ng, BK, Rozman, Z, Nirmala K, Shuhaila A, Omar MH
    MyJurnal
    Renal angiomyolipoma is a rare disease seen during pregnancy. Rupture of renal angiomyolipoma could be catastrophic and might result in maternal and even perinatal mortality. Management includes conservative vs surgical approach. A 29-year-old woman Para 2 with history of bleeding renal angiomyolipoma in her first pregnancy at 11 weeks treated with selective arterial embolisation. The pregnancy was terminated. Even though having small residual tumour, her subsequent pregnancy progressed well with conservative management. Intervention is advisable in the presence of large or symptomatic renal angiomyolipoma prior to pregnancy in order to minimise potential life-threatening haemorrhage during pregnancy. For those with small tumour of less than 4cm, perhaps conservative approaches i.e. frequent follow-up and close monitoring would assist in early identification of any rupture or bleeding.
    Matched MeSH terms: Kidney Neoplasms
  17. Kadhim Jawad Obaid, Yahya Mohammad Arpine, Nor Salmah Bakar, Marlina Tanty Ramli Hamid, Ahmed Ramzi Yusof
    MyJurnal
    Intramuscular shoulder angiomyolipomas are very rare. We report a case in a 22-year-old male with a well circumscribed lesion located on the back of the shoulder. This lesion, differs from renal angiomyolipoma in terms of non-association with tuberous sclerosis, circumscription and male predominance. Another characteristic feature is the absence of epithelioid cells. Differential diagnosis includes lipoma, angiolipoma, angioleiomyoma, hemangioma, myolipoma and liposarcoma. It is distinguished from the above mentioned entities by the presence of a combination of thick-walled blood vessels, smooth muscle and fat.
    Matched MeSH terms: Kidney Neoplasms
  18. 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: Kidney Neoplasms
  19. Bennett NC, Rajandram R, Ng KL, Gobe GC
    J Kidney Cancer VHL, 2014;1(2):17-25.
    PMID: 28326246 DOI: 10.15586/jkcvhl.2014.9
    Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC), with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.
    Matched MeSH terms: Kidney Neoplasms
  20. Ellis RJ, Ng KL, Samaratunga H, Del Vecchio SJ, Wood ST, Gobe GC
    J Kidney Cancer VHL, 2016;3(2):14-22.
    PMID: 28326280 DOI: 10.15586/jkcvhl.2016.53
    Renal cell carcinoma (RCC) is the fifth most common malignancy in kidney transplant recipients, with increased risk arising due to immunosuppression. De novo RCC occurrence in kidney allografts is much less common when compared with the native kidneys. Multifocal RCC in allograft kidneys is rarely described. In this report, we discuss two cases of de novo multifocal renal neoplasms in allograft kidneys. Case 1 had three distinct neoplastic lesions of >5 mm, and case 2 had four. Using the World Health Organization 2016 classification of adult renal tumours, case 1 had one clear-cell (cc) RCC (grade 3) and two papillary adenomas; all confined to the kidney. Case 2 had a nodular lesion classified as ccRCC (grade 4) with focal rhabdoid differentiation and some infiltration of renal sinus fat; a cc tubulopapillary RCC; a multilocular cystic renal neoplasm of low malignant potential; and a mucinous tubular and spindle cell carcinoma; the last three all confined to the kidney. This is the first report of mucinous tubular and spindle cell carcinoma in a kidney allograft. When considering multifocal RCC with discordant histology, it is likely that these represent independent tumourigenic events.
    Matched MeSH terms: Kidney Neoplasms
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