Kidney Clear Cell Carcinoma

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DNA CpGs-Pairs-Based Classification and Identification of Kidney Clear Cell Carcinoma Prognosis-Associated Subgroups

DNA CpGs-Pairs-Based Classification and Identification of Kidney Clear Cell Carcinoma Prognosis-Associated Subgroups

Renal cell carcinoma is one of the commonest and most lethal urologic malignancies. Kidney Clear Cell Carcinoma (KIRC) subtype is the most common and aggressive form of kidney tumors[1-3]. Recent genomic researches of clear cell carcinoma have revealed high molecular heterogeneity in these tumors, which is necessary to further classify these tumors for improving diagnosis and treatment strategies[3-5].

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Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study

Tumor-targeted Dual-modality Imaging to Improve Intraoperative Visualization of Clear Cell Renal Cell Carcinoma: A First in Man Study

In the current study, dual-modality imaging devices were not integrated in the standard set of surgical instruments and therefore switching between standard surgery and dual-modality image-guided surgery took additional time. After introducing the standard surgical instruments and opening the retroperitoneum, the laparoscopic gamma probe was used to localize the tumor. After exposure of the tumor, the fluorescence camera was introduced. Subsequently, surgery was continued with the standard surgical instruments. Therefore, dual- modality imaging could only be performed before resection and after terminating the critical period of kidney ischemia and haemostasis, making deep surgical margins less accessible for NIRF. Integration of imaging devices into the standard surgical instruments would increase the convenient use of dual-modality imaging. Except for its use during NSS, the specific accumulation of 111 In-DOTA-giren-
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Abnormal expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma based on data mining

Abnormal expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma based on data mining

Methods: In this study, we collected the mRNA expression of EPB41L1 in KIRC through the Oncomine platform, and used the HPA database to perform the pathological tissue immunohistochemistry in patients. Then, the sub- groups and prognosis of KIRC were performed by UALCAN and GEPIA web-tool, respectively. Further, the mutation of EPB41L1 in KIRC was analyzed by c-Bioportal. The co-expression genes of EPB41L1 in KIRC were displayed from the LinkedOmics database, and function enrichment analysis was used by LinkFinder module in LinkedOmics. The func- tion of EPB41L1 in cell adhesion and migration was confirmed by wound healing assay using 786-O cells in vitro. Co- expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them was visualized by Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in TCGA by using the UCSC Xena browser.
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Downregulation of CLDN7 due to promoter hypermethylation is associated with human clear cell renal cell carcinoma progression and poor prognosis

Downregulation of CLDN7 due to promoter hypermethylation is associated with human clear cell renal cell carcinoma progression and poor prognosis

Renal cell carcinoma (RCC) accounts for up to 85% to 90% of all kidney cancers [1, 2]. According to the most recent pathological classification by the International Society of Urological Pathology (ISUP), RCC mainly in- cludes clear cell (ccRCC), papillary (pRCC) and chro- mophobe (chRCC) subtypes [3], with ccRCC being the most common subtype [4]. The 5-year survival rate of patients with kidney cancer increased approximately 30% in recent years. This improvement is largely due to low-stage and low-grade tumors being incidentally de- tected by improved early-detection techniques [2, 5, 6]. However, one third of patients with kidney cancer present with metastatic disease [5], and 20%~ 30% of the patients who undergo curative surgery relapse in distant sites during follow-up [7]. Although there has been considerable progress in the systemic treatment of metastatic renal cell carcinoma in the past 20 years [2], metastatic RCC remains an incurable condition for the majority of patients.
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Review Article Clear cell papillary renal cell carcinoma: a review

Review Article Clear cell papillary renal cell carcinoma: a review

plasms [5-9]. CCP-RCC is considered to be the fourth most common histologic type of RCC in one study, but the diagnostic criteria should be steadily established in order to exclude mimick- ers of CCP-RCC [9]. CCP-RCC comprises 9.3% of all renal tumors occurring in young adults [11]. The age of patients with CCP-RCC range from 18 to 88 years with a mean age of 70 years [5]. There is no sex predilection [4, 5, 9]. CCP-RCC can occur in normal kidney (sporadic, non familial setting), non-cystic end-stage renal disease (ESRD) and acquired cystic disease (ACD) [1, 6-9, 12-14]. Two cases with CCP-RCC occurred within less than 10 years of hemodi- alysis [15]. Some cases associated with von Hippel-Lindau disease have been reported [4, 6, 9, 10]. The association with other renal tumors has been described including clear cell RCC, papillary RCC, chromophobe RCC, multi- locular cystic RCC, acquired cystic disease- associated RCC (ACD-RCC) and renal oncocy- toma [6-9].
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Changes in the expression and subcellular distribution of galectin-3 in clear cell renal cell carcinoma

Changes in the expression and subcellular distribution of galectin-3 in clear cell renal cell carcinoma

from nephrectomy surgeries. The intersection zone between tumor and normal tissue was defined as inter- mediate tissue. The study was positively evaluated by the local ethic commission. The patients gave a written informed consent for this study and were not followed clinically. After nephrectomy the specimens were stored in ice-cold PBS containing a protease inhibitor cocktail and samples were immediately processed for Western blotting, immunohistochemistry or nuclear matrix isola- tion. Epithelial kidney cells (RC-124) and cells of clear cell renal cell carcinoma (RCC-FG1) (Cell Lines Service, Germany) were cultivated in McCoy’s 5a medium/10% FCS (PAA, Pasching, Austria). Western blot analysis was performed essentially as described before [13]. Protein concentrations were established by Bradford protein assay (BioRad DC Protein Assay, Munich, Germany). Equal amounts of 60 μg/slot were separated by SDS- PAGE and transferred to nitrocellulose membranes. Membranes were blocked for 1 h in 5% skimmed milk powder in PBS. Following immunostaining, bands were detected and quantified using Gel-Pro Software (Kapelan Bio-Imaging, Leipzig, Germany) and normalized to the sum or to tubulin quantities of the same sample.
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NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498

NDRG2 suppresses the proliferation of clear cell renal cell carcinoma cell A-498

Renal cell carcinoma (RCC) accounts for 3% of all malignant tumors and 90% of neoplasms arising from the kidney. The incidence rates vary more than 10-fold around the world; rates are higher in Western countries than in Asia. In the United States, renal cancer is the 7th leading malignant condition among men and the 12th among women [1]. Clear cell renal cell carcinoma (CCRCC) originates from proximal tubule cells and is the most common pathological type of renal cell carci- noma. Multiple genetic changes have been found in CCRCC, but little is known about major tumor suppres- sor genes involved in the tumorigenesis of the disease.
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Surgery for metastatic tumors of the pancreas

Surgery for metastatic tumors of the pancreas

Nine patients underwent pancreatic resection for meta- static malignant disease from 2000 to 2015 at the Depart- ment of Gastroenterological Surgery of the Kumamoto University Hospital. The patients included 5 males and 4 females, with a median age of 66 years (range, 52 – 83) at the pancreatic surgery (Table 1). The primary lesion, clear cell renal cell carcinoma (RCC) (right kidney in 3, left in 3, and bilateral in 1), 1 rectal cancer (tubular adenocarcin- oma), and 1 oral malignant melanoma (MM), was resected in all cases.

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Case Report Synchronous renal neoplasms: clear cell renal cell carcinoma, papillary renal cell carcinoma, and multilocular cystic renal cell neoplasm of low malignant potential in the same kidney

Case Report Synchronous renal neoplasms: clear cell renal cell carcinoma, papillary renal cell carcinoma, and multilocular cystic renal cell neoplasm of low malignant potential in the same kidney

In conclusion, we presented an additional case of three or more concurrent, different subtypes of RCC in the same kidney. According to our PubMed searching results, this is the first case report to date which has described CCRCC, PRCC, and mcCCRCNLMP synchronously aris- ing in a single kidney. To the best of our knowl- edge, there is no sufficient data to compare the different types of renal malignant neoplasms in the same kidney in terms of survival or onco- logic survey. Larger numbers of studies are needed to elucidate the etiology of coexisting renal tumors with different histological fea- tures.
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Case Report Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature

Case Report Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature

ric adenoma. Small cell carcinoma exhibits high grade cellular atypia and high mitotic/prolifera- tive indices. Tumor necrosis is often extensive [14]. Renal PNETs are rare and they have more of a monotonous proliferation of small rounds in sheets, associated with which is a prominent ramifying capillary network. Variable mitotic fig- ures and pseudorosettes can be seen. They are characteristically positive for CD99 and EWS- FLI1 fusion transcription, and are usually nega- tive for pancytokeratin, synaptophysin and chromagranin, unlike renal carcinoid tumors [15]. Metanephric adenoma shows very small cells with very little cytoplasm forming very small tubules in an acellular stroma. In contrast to renal carcinoid tumors, metanephric adeno- mas lack well-developed neuroendocrine fea- tures with lack of immunoreactivity for neuro- endocrine markers but positive for WT1 [16].
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Identification of a three-long noncoding RNA prognostic model involved competitive endogenous RNA in kidney renal clear cell carcinoma

Identification of a three-long noncoding RNA prognostic model involved competitive endogenous RNA in kidney renal clear cell carcinoma

Long noncoding RNA (lncRNA), broadly defined as noncoding RNA molecules longer than 200 nucleotides, has gained emerging attention in cancer biology due to their direct and indirect regulatory roles [7]. It has been reported to be aberrantly expressed in a broad spec- trum of tumors, leading to tumor initiation and pro- gression [8]. Hence, they may serve as promising a new type of biomarkers for tumor diagnosis, prognosis, even in targeted gene therapy [9]. More recently, extensive research has explored the lncRNA expression profiling in the KIRC with the development of sequencing technol- ogy [10–12]. The determination of their interaction with other molecules and functional analysis is also widely investigated in recent years [13]. Notably, the subcellu- lar localization of lncRNAs holds valuable clues to their molecular function [14]. In the cell nucleus, lncRNA could modulate nuclear functions, such as transcription, chromatin regulation, and variable splicing [15]. While in the cytoplasm, lncRNA could modulate mRNA mainly
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Maxillary Clear Cell Odontogenic Carcinoma-ARare Entity

Maxillary Clear Cell Odontogenic Carcinoma - A Rare Entity

The term clear cell odontogenic tumor was coined by Hansen et al. [2]. Clear cell odontogenic carcinoma (CCOC) is a rare neoplasm with only few cases reported in the literarure [6]. Clear cell lesions in the head and neck region have a wide range of differential diagnosis that includes odontogenic tumors such as ameloblastoma, calcifying epithelial odontogenic tumor, odontogenic carcinoma, and salivary gland tumors like mucoepidermoid carcinoma or hyalinizing clear cell carcinoma. Also included are intraosseous melanocytic tumors, and metastatic tumors from kidney, thyroid, and prostate [2].
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Identification of clear cell renal cell carcinoma and oncocytoma using a three gene promoter methylation panel

Identification of clear cell renal cell carcinoma and oncocytoma using a three gene promoter methylation panel

The frequency of methylated samples was determined for each RCT type, considering the highest value determined in the normal kidney tissue as cutoff. Median and inter- quartile range of methylation levels were also computed. Kruskal–Wallis non-parametric ANOVA followed by Mann–Whitney U test (with Bonferroni’s correction) for pair-wise comparisons were used to identify significant differences in methylation levels among RCT subtypes and association with standard clinicopathological vari- ables. Spearman’s test was performed to ascertain corre- lation between age and methylation levels.
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Original Article Expressions of miR-193b and miR-338-3p in renal clear-cell carcinoma cells and their effects on biological function

Original Article Expressions of miR-193b and miR-338-3p in renal clear-cell carcinoma cells and their effects on biological function

[2] Aron M, Chang E, Herrera L, Hes O, Hirsch MS, Comperat E, Camparo P, Rao P, Picken M, Mi- chal M, Montironi R, Tamboli P, Monzon F, Amin MB. Clear cell-papillary renal cell carcinoma of the kidney not associated with end-stage renal disease. Am J Surg Pathol 2015; 39: 873-888. [3] Deml KF, Schildhaus HU, Compérat E, von Tei- chman A, Storz M, Schraml P, Bonventre JV, Fend F, Fleige B, Nerlich A, Gabbert HE, GaBler N, Grobholz R, Hailemariam S, Hinze R, Knüchel R, Lhermitte B, Nesi G, Rüdiger T, Sau- ter G, Moch H. Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor-two variants of a morphologic, immuno- histochemical and genetic distinct entity of re- nal cell carcinoma. Am J Surg Pathol 2015; 39: 889-901.
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Case Report Clear cell changes in mucinous tubular and spindle cell carcinoma: cytoplasmic pallor/clearing within tubules, vacuoles or hybrid conventional clear cell carcinoma of kidney?

Case Report Clear cell changes in mucinous tubular and spindle cell carcinoma: cytoplasmic pallor/clearing within tubules, vacuoles or hybrid conventional clear cell carcinoma of kidney?

ment. Meanwhile, there is no biomarkers or imagining tools but pathological examination can confirm the diagnosis of MTSCC. Therefore, we used to follow the guideline of RCCs to deal with this kind of tumor in clinical practice [23]. Partial nephrectomy or radical nephrectomy is mostly performed via open approach, few cases are done with laparoscopic or coelio- scopic robot-assisted approaches. Herein, we present two cases of MTSCC resected by open radical nephrectomy (Case 1) or by laparoscop- ic radical nephrectomy (Case 2), respectively. Case 1 is still well and alive without any evi- dence of recurrence or metastasis when follow- ing for 8.5 years which may rank first related to followups reported in the literature since 2004, while Case 2 is well after 8 months of resection of tumor. Although Case 2 has not given any medical intervention except active surveillance, Case 1 had received Proleukin (a recombinant human IL-2) for three months. As is indicted in the ESMO guideline of RCCs [23], partial nephrectomy can be performed via open, lapa- roscopic or coelioscopic robot assisted appr- oaches, especially for patients with compro- mised renal function, solitary kidney or bilateral tumors, with no tumor size limitation (impera- tive indication). MacLennan S and colleagues [24] declared that laparoscopic radical nephrec- tomy is recommended if partial nephrectomy is not technically feasible. The two patients in our research were fully informed consent and received the strategy, which took the guideline [23], the general condition of patients and patients’ will into consideration. Simon RA and colleagues [14] report one case of MTSCC with two other identified lesions in the thoracic ver- tebral bodies, which received high-dose ste- roids with minimal neurological response and underwent a CT-guided biopsy of the mass. Then, the patient received radiotherapy fol- lowed by tumor embolization and a radical nephrectomy with vertebral body resection. However, follow-up imaging studies showed additional vertebral body lesions, a parietal bone lesion, liver lesions, and possible malig- nant pleural effusions and the patient died three weeks after surgery. Radio frequency or cryoablative treatments are alternative appr- oaches for RCC, which have not been reported for MTSCC in literatures. Meanwhile, Larkin J and colleagues [25] founded that tumor shrink- age occurred in response to sunitinib in the biopsy-proven MSTCC retroperitoneal lymph node lesion.
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Original Article SIRT4 protein levels are downregulated in kidney renal clear cell carcinoma

Original Article SIRT4 protein levels are downregulated in kidney renal clear cell carcinoma

To the best of our knowledge, our study is the first to analyze the relationship between SIRT4 expression levels and clinicopathological par- ameters in human KIRC specimens, especially at the protein level. Moreover, for the first time,we found that the average survival time of KIRC patients with low expression of SIRT4 was lower than that of patients with high expres- sion, especially in patients older than 60 years andwith pathological grade III-IV. Although the differences were not statistically significant, our results indicate the necessity for further study on the role of SIRT4 in renal cell carcino- ma. Thus, the next step will be to use a larger sample size from various tumor types to further determine the relationship between SIRT4 lev- els and the prognosis of KIRC patients. This approach will allow us to further study the effect of SIRT4 on the biological behavior of KIRC cells. In summary, our results suggest that SIRT4 may participant in the development of KIRC.
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Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

with bevacizumab in metastatic RCC patients, and whether this would assist in patient selection for cytoreductive nephrec- tomy. 50 patients with clear cell carcinoma received either bevacizumab plus erlotinib (n = 23) or bevacizumab alone (n = 27) for 8 weeks followed by restaging. 42/50 patients underwent nephrectomy. Median PFS was 11.0 months (95% CI 5.5–15.6 months), and median OS 25.4 months (95% CI 11.4 months to not evaluated). Wound dehiscence required treatment discontinuation for three and treatment delay for two other patients. The investigators concluded presurgical treat- ment with bevacizumab yields clinical outcomes comparable to postsurgical treatment, but it may result in wound-healing delays. Prospective, randomized trials are now required to test the value of neoadjuvant bevacizumab.
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Ovarian metastasis of clear cell renal cell carcinoma: A case report

Ovarian metastasis of clear cell renal cell carcinoma: A case report

We report on a 61-year-old woman with a history of right-sided nephrectomy for clear cell renal cell carcinoma (RCC) occurring 21 years ago; she currently presented with a bilateral ovarian tumour. Histologically, the tumour of both ovaries was clear cell carci- noma. Immunohistochemically, the tumour cells were positive for vimentin, RCC marker, epithelial membrane antigen, cytokeratin AE1/3 and CD10. Cytokeratin 7, CA125, HMWCK, estrogen and progesterone receptors were all negative. Based on the morphology and immunophenotype of the tumour, we established a diagnosis of late metastasis of RCC in the ovaries. A postoperative abdominal computed tomography scan, however, revealed a tumour mass solely in the left kidney, which had not been visible in the preop- erative ultrasound. The patient underwent nephron-sparing surgery and a biopsy showed the tumour to be clear cell RCC. Metastasis of RCC to the ovaries is rare, and to the best of our knowledge, only 24 cases have been reported to date. However, due to the differ- ent treatments and prognosis, the distinction between a primary ovarian tumour and metastasis of RCC is important.
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Original Article The effects of LOXL2 in clear cell renal cell carcinoma: a

Original Article The effects of LOXL2 in clear cell renal cell carcinoma: a

In China, about 66,800 people are newly diag- nosed with kidney cancer, and 23,400 patients die of the disease each year [1]. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, accounting for 75%- 85% of kidney cancer cases [2-4]. Currently, surgical resection and targeted therapy are the main therapeutic approaches for ccRCC [5]. Novel molecule-targeted drugs and immuno- therapy agents are under development, and some have been approved with significant activity in ccRCC patients [6, 7]. Despite these advances, a large number of patients still die of the disease. Developing novel biomarkers and alternative therapeutic targets is still valuable. Lysyl oxidase-like 2 (LOXL2), a copper-depen- dent enzyme, is a member of the lysyl oxidase family which oxidizes primary amine substrates
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Metastatic renal cell carcinoma in the head and neck region

Metastatic renal cell carcinoma in the head and neck region

examination, 3×2 cms diffuse bulge present in the left temporal region. Swelling was firm in consistency and nontender. Patient had history of clear cell carcinoma of left kidney and underwent left nephrectomy one year prior to the presentation of the swelling in the temporal region. Six month’s post nephrectomy status, follow-up imaging showed right adrenal mass lesion. Patient underwent right adrenal tumour excision. Histopathological examination showed metastatic renal cell carcinoma. 1 year post nephrectomy patient had developed bulge in the left temporal region. MRI was done which showed 4×2 cms intensely enhancing mass in the muscular plane of left temporal fossa. Ultrasound guided biopsy from the left temporal bulge was done. Histopathological examination showed metastatic renal cell carcinoma (Figure 7). Tumour cells are positive for CD 10 & PAX 8 and negative for CK-7. Case was discussed in our tumour board meeting and the decision of hypofractionation radiotherapy was taken.
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