MELK is Upregulated in Advanced Clear Cell Renal Cell Carcinoma and Promotes Disease Progression by Phosphorylating PRAS40.

In this study, in order to screen differentially expressed genes (DEGs) between stage IV and stage I ccRCC specimens, we initially analyzed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GSE73731). We found that maternal and embryonic leucine zipper kinase (MELK) is upregulated in stage IV ccRCC samples and that upregulation of MELK is significantly correlated with advanced disease status. Furthermore, both loss and gain-of-function assays strengthen the evidence that MELK enforces the malignant phenotype of ccRCC cells through over-activating the mammalian target of rapamycin complex 1 (mTORC1) pathway. Mechanistically, we verified that the oncogenic effect of MELK occurs through phosphorylating PRAS40, an inhibitory subunit of mTORC1, and through disrupting the interaction between PRAS40 and raptor. In summary, these results elucidate the important role of MELK in the progression of ccRCC and indicate that MELK may be a novel regulator of ccRCC progression by over-activating the mTORC1. PMID: 31813279 [PubMed - as supplied by publisher]
Source: Cell Transplantation - Category: Cytology Authors: Tags: Cell Transplant Source Type: research

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Abstract OBJECTIVES: In the Asian population, patterns and risk factors for de novo malignancies after solid-organ transplant are not well understood. MATERIALS AND METHODS: Insurance claims from Taiwan's National Health Institute Research Database from 1997 to 2011 revealed 687 deceased-donor heart transplant recipients, 5038 kidney transplant recipients (50% living related-donor, 50% deceased-donor transplants), and 2127 liver transplant recipients (mainly living related-donor transplants, 30% deceased-donor transplants). During the follow-up period, rates of malignancy incidence were calculated with standa...
Source: Experimental and Clinical Transplantation : official journal of the Middle East Society for Organ Transplantation - Category: Transplant Surgery Authors: Tags: Exp Clin Transplant Source Type: research
The United States Public Health Service Flag Promotion ceremony for Rear Admiral (RADM) Richard W. Childs, promoted to RADM Upper Half O-8 in January 2020, is being webcast live on 3/27/2020 from Masur Auditorium. Richard Childs, MD serves as the Clinical Director of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH). He was commissioned in the USPHS Commissioned Corps as a Lieutenant in 1995 when joined the NCI as an Oncology Fellow. Following fellowship training, he was appointed a tenure-track investigator in the Hematology Branch of the NHLBI where he continues to conduct r...
Source: Videocast - All Events - Category: General Medicine Tags: Upcoming Events Source Type: video
AbstractPurpose of ReviewRenal masses in the kidney graft pose an important clinical dilemma, balancing graft function against the need for cancer control.Recent FindingsDonor origin cancers in the renal graft can be classified as ‘donor transmitted’ or ‘donor derived’. The landmark TracerX Renal changed our understanding of renal cell carcinoma oncogenesis, demonstrating that key mutations in childhood lead to clinically apparent tumours in later life. Identified pre-operatively, contemporary evidence suggests that m asses excised prior to transplantation result in acceptable oncologic safety and g...
Source: Current Urology Reports - Category: Urology & Nephrology Source Type: research
We present our single centre experience in transplanted patients and future candidates for transplantation. Methods: Retrospective analysis from an anonymised database of bilateral nephrectomies for ADPKD patients. Results were reported as median, range, and percentage. Differences between groups were tested using ANOVA and t-test. Surgery was performed between January 2012 and July 2018. Results: Thirty-three patients underwent bilateral native nephrectomy for APKD. 18 had a functioning kidney transplant (transplant group, 55%) while 15 patients were on dialysis (dialysis group, 45%) at the time of surgery; 8 pa...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
We describe the clinicopathologic features of BKPyV-associated urologic carcinomas in a single-institution cohort. RESULTS: Among 4,772 kidney recipients during 1994 to 2014, 26 (0.5%) and 26 (0.5%) developed posttransplantation urothelial carcinomas (UCs) and renal cell carcinomas (RCCs), respectively, as of 2017. Six (27%) UCs but none of the RCCs expressed large T antigen (TAg). TAg-expressing UCs were high grade with p16 and p53 overexpression (P
Source: American Journal of Clinical Pathology - Category: Pathology Authors: Tags: Am J Clin Pathol Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
The authors report 27 patients rendered surgically (N  = 23) or functionally (N = 4) anephric after kidney cancer operations. Sixteen patients had renal cell carcinoma (RCC, histologic subtype not specified) and 9 transitional cell carcinoma. No partial nephrectomies were done in the 7 T1 patients (5 due to severe preexisting chronic kidney dis ease (CKD) and 2 due to anatomic complexity). Only 4 patients underwent renal transplantation, all T1a RCC (
Source: Urology - Category: Urology & Nephrology Authors: Source Type: research
We present a case of a 22-year-old man with history of allogenic renal transplantation on immunosuppression, who underwent 18F-FDG-PET/CT to characterize a lesion in the transplanted kidney on ultrasonogram and contrast-enhanced computed tomography imaging. PET/CT revealed FDG avid lesion in the transplanted kidney and mural thickening involving the distal ileum, ileocecal junction, and ileocolic lymph nodes. Subsequent histopathological examination from the renal lesion revealed renal cell carcinoma in the transplanted kidney. Additionally, endoscopic biopsy from the ileal thickening revealed granulomatous inflammation, s...
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Interesting Images Source Type: research
ConclusionsThe role of the microbiome in genitourinary cancer is an emerging field that merits further studies. Translating microbiome research into clinical action will require incorporation of microbiome surveillance into ongoing and future clinical trials as well as expansion of studies to include metagenomic sequencing and metabolomics.Patient summaryThis review covers recent evidence that microbial populations that reside in the genitourinary tract—and were previously not known to exist—may influence the development of genitourinary malignancies including bladder, kidney, and prostate cancers. Furthermore,...
Source: European Urology - Category: Urology & Nephrology Source Type: research
rta C Abstract Due to the increasing occurrence of renal cell carcinoma (RCC) in the general population and the high prevalence of chronic kidney disease among cancer patients, many people with a previous RCC may eventually require renal replacement therapy including kidney transplantation. They should accordingly be evaluated to assess their life expectancy and the risk that the chronic immunosuppressive therapy needed after grafting might impair their long-term outcome. Current guidelines on listing patients for renal transplantation suggest that no delay is required for subjects with small or incidentally disco...
Source: Journal of Nephrology - Category: Urology & Nephrology Authors: Tags: J Nephrol Source Type: research
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