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.
ConclusionsThe results pointed out that the high expression of miR-106b-5p serves as an independent factor for predicting the worse prognosis of RCC patients.
Abstract A 73-year-old man presented with a red papule on the posterior aspect of his neck (Figure 1). The growth had first been noted approximately 1 month before his visit. The patient complained of irritation from his collar but had no other symptoms. He had hypertension controlled by medication and denied recent weight loss, malaise, or swollen glands. Examination of the lesion revealed a firm, bright red papule 4 mm in diameter on a slightly indurated flesh-color base. (SKINmed. 2019;17:65-66). PMID: 30888953 [PubMed - in process]
Michael Atkins, MD, Deputy Director, Georgetown-Lombardi Comprehensive Cancer Center, Scholl Professor and Vice Chair Department of Oncology, Georgetown University Medical Center, Discusses KEYNOTE 42... Author: obr Added: 03/20/2019
Conclusion: Image-guided FNAC is highly sensitive and specific for early diagnosis of an otherwise silent retroperitoneal mass. It saves patient from meticulous surgical procedures for diagnostic reasons and allows more rational planning of management. Knowledge of the distribution of tumors by age group helps to narrow down differential diagnoses.Acta Cytologica
We report a case of ureteral stump carcinoma following a radical nephrectomy for renal cell carcinoma. A 76-year-old man was diagnosed as having ascending colon cancer and a right renal carcinoma. He was treated with partial colon resection and radical nephrectomy without lymphadenectomy. The histology was renal cell carcinoma. Three years after that surgery, he complained of intermittent macrohematuria. Abdominal computed tomography (CT) suggested a solid mass in the pelvis. We then performed a biopsy with CT guidance. An epithelial tumor was suspected by immunohistochemistry. A total excision of ureter was then performed...
Junlong Wu, Shengming Jin, Weijie Gu, Fangning Wan, Hailiang Zhang, Guohai Shi, Yuanyuan Qu, Dingwei Ye
Authors: Azuma T, Sugihara T, Honda S, Yoshizaki U, Niimi F, Tsuru I, Kume H Abstract Sequential therapy using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors is the mainstay of treatment for metastatic renal cell carcinoma. Recently, anti-programmed death-1 (PD-1) antibody, a type of immune checkpoint inhibitor, was approved for use against metastatic renal cell carcinoma. In the present report, two cases of TKI-refractory metastatic renal cell carcinoma which regained sensitivity to TKI after immunotherapy with nivolumab were described. In one case, a third challenge with axitinib a...
Authors: Naito S, Ichiyanagi O, Ito H, Kabasawa T, Kanno H, Narisawa T, Fukuhara H, Yagi M, Kurota Y, Yamagishi A, Sakurai T, Nishida H, Kawazoe H, Yamanobe T, Kato T, Makhov P, Kolenko VM, Yamakawa M, Tsuchiya N Abstract Eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) is phosphorylated and activated by mammalian target of rapamycin complex 1, which serves as a regulator of cell growth, cell survival, metastasis and angiogenesis in many types of cancer. The aim of this study was to evaluate the role of phosphorylated 4EBP1 (p4EBP1) in primary renal cell carcinoma (RCC) as a biomarker in metast...
In conclusion, the present study demonstrated that Wnt10a may have an oncogenic role during carcinogenesis of CRC through activation of Wnt/β-catenin signaling. PMID: 30881490 [PubMed]