VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor B activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
Source: ScienceNOW - Category: Science Authors: Tags: Cell Biology, Medicine, Diseases reports Source Type: news

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Publication date: November 2018Source: European Journal of Surgical Oncology, Volume 44, Issue 11Author(s): Abdullah Malik, Aditya Kanwar, Clara Munro, David Rix, Colin Wilson, Steven White, Derek Manas, Gourab Sen
Source: European Journal of Surgical Oncology (EJSO) - Category: Surgery Source Type: research
While the somatic mutation profiles of renal cell carcinoma (RCC) have been revealed by several studies worldwide, the overwhelming majority of those were not derived from Chinese patients. The landscape of so...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
A heightened understanding of hereditary renal cancer syndromes and their molecular basis has led to an increased awareness and recognition of these renal neoplasms by pathologists. Because a diagnosis of hereditary renal cell carcinoma has a profound impact on the patient and family members, when and how to raise such a suspicion via pathologic assessment has become an important yet very challenging task. This review discusses key clinicopathologic, immunohistochemical, and genetic characteristics of hereditary renal cancer syndromes, and important differential diagnostic challenges, emphasizing recent pathologic and molecular advances.
Source: Surgical Pathology Clinics - Category: Pathology Authors: Source Type: research
The most important prognostic parameter in renal cell carcinoma is tumor stage. Although pathologic primary tumor (pT) categories are influenced by tumor size (pT1 –pT2), critical elements (≥pT3) are dictated by invasion of structures, including renal sinus, perinephric fat, and the renal vein or segmental branches. Because this invasion can be subtle, awareness of the unique characteristics of renal cell carcinoma is critical for the pathologist to aid in clinical decision making. This review addresses challenges in pathologic stage and grade reporting and updates to the World Health Organization and American Joi...
Source: Surgical Pathology Clinics - Category: Pathology Authors: Source Type: research
ConclusionBrain was the most common site of PD in patients treated with nivolumab, and only half of patients progressing on nivolumab were able to initiate subsequent treatment. The risk of PD increased with a higher baseline NLR and reduced with a higher baseline eosinophil count.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Combination VEGFR/immune checkpoint inhibitor therapy: a promising new treatment for renal cell carcinoma, Published online: 17 October 2018; doi:10.1038/s41416-018-0175-xCombination VEGFR/immune checkpoint inhibitor therapy: a promising new treatment for renal cell carcinoma
Source: British Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
AbstractThe analysis of cell characteristics from high-resolution digital histopathological images is the standard clinical practice for the diagnosis and prognosis of cancer. Yet, it is a rather exhausting process for pathologists to examine the cellular structures manually in this way. Automating this tedious and time-consuming process is an emerging topic of the histopathological image-processing studies in the literature. This paper presents a two-stage segmentation method to obtain cellular structures in high-dimensional histopathological images of renal cell carcinoma. First, the image is segmented to superpixels wit...
Source: Medical and Biological Engineering and Computing - Category: Biomedical Engineering Source Type: research
International Journal of Urology, EarlyView.
Source: International Journal of Urology - Category: Urology & Nephrology Authors: Source Type: research
AbstractBackgroundSarcopenia is a state of degenerative skeletal muscle wasting induced by cancer cachexia.ObjectiveTo evaluate the prognostic impact of changes in skeletal muscle mass (SMM) during first-line sunitinib therapy on oncological outcomes in metastatic renal cell carcinoma (mRCC).Patients and MethodsSixty-nine patients were evaluated retrospectively. The skeletal muscle index (SMI) was calculated based on computed tomography images obtained before the initiation (pre-treatment SMI) and after two cycles of sunitinib treatment (post-treatment SMI). The change in SMM was evaluated based on the value of ΔSMI,...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
Boiling histotripsy (BH) is an experimental focused ultrasound technique that produces non-thermal mechanical ablation. We evaluated the feasibility, short-term histologic effects and the resulting acute inflammatory response to BH ablation of renal cell carcinoma (RCC) in the Eker rat. Genotyped Eker rats were monitored for de novo RCCs with serial ultrasound (US) imaging. When tumors were ≥8mm, rats underwent ultrasound-guided extracorporeal ablation of the tumor with BH, a pulsed focused US technique that produces non-thermal mechanical ablation of targeted tissues, or a sham US procedure.
Source: Ultrasound in Medicine and Biology - Category: Radiology Authors: Tags: Original Contribution Source Type: research
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