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renal cell carcinoma carbonic anhydrase

Oleksandr N Kryvenko
There have been no recurrences or metastases of clear cell papillary renal cell carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language literature. We identified all our cases of CCPRCC (1990-2013), reviewing all cases that preceded the formal designation of the entity. Immunohistochemical stains were performed on 32 cases during their initial workup. In addition, stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one with atypical follow-up and the other with a more compact morphology, although not performed initially...
April 13, 2017: Urologic Oncology
Sean R Williamson, David J Grignon, Liang Cheng, Laura Favazza, Dibson D Gondim, Shannon Carskadon, Nilesh S Gupta, Dhananjay A Chitale, Shanker Kalyana-Sundaram, Nallasivam Palanisamy
Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K...
March 2017: American Journal of Surgical Pathology
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
Small molecule-drug conjugates (SMDCs) are increasingly being considered as an alternative to antibody-drug conjugates (ADCs) for the selective delivery of anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of renal cell carcinomas and which can be efficiently targeted in vivo, using charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here, we show that SMDC products, obtained by the coupling of acetazolamide with monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti-tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas...
January 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Sean R Williamson, John N Eble, Nallasivam Palanisamy
Renal cell carcinoma with TFEB rearrangement (t[6;11][p21;q13]) was initially recognized to be composed of dual populations of large cells with clear cytoplasm and small cells forming rosettes around hyaline material. With increasing awareness, however, the spectrum of described morphology has been found to be more heterogeneous. We report a 54-year-old woman who underwent partial nephrectomy for a 2.4-cm renal mass, composed of fibrosis, hyalinization, calcification, and ossification and a smaller component of epithelioid cells...
April 2017: Human Pathology
Karim Chamie, Nicholas M Donin, Pia Klöpfer, Paul Bevan, Barbara Fall, Olaf Wilhelm, Stephan Störkel, Jonathan Said, Michael Gambla, Robert E Hawkins, Gustavo Jankilevich, Anil Kapoor, Evgeny Kopyltsov, Michael Staehler, Kimmo Taari, Alberto J A Wainstein, Allan J Pantuck, Arie S Belldegrun
Importance: Girentuximab is a chimeric monoclonal antibody that binds carbonic anhydrase IX, a cell surface glycoprotein ubiquitously expressed in clear cell renal cell carcinoma (ccRCC). Its safety and activity in phase 2 studies prompted investigation into its use as adjuvant monotherapy in participants with high-risk ccRCC. Objective: To evaluate the safety and efficacy of adjuvant girentuximab on disease-free survival (DFS) and overall survival (OS) in patients with localized completely resected high-risk ccRCC...
October 27, 2016: JAMA Oncology
S Chow, V Galvis, M Pillai, R Leach, E Keene, A Spencer-Shaw, A Shablak, J Shanks, T Liptrot, F Thistlethwaite, R E Hawkins
BACKGROUND: VEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report...
2016: Journal for Immunotherapy of Cancer
Oystein S Eikrem, Philipp Strauss, Christian Beisland, Andreas Scherer, Lea Landolt, Arnar Flatberg, Sabine Leh, Vidar Beisvag, Trude Skogstrand, Karin Hjelle, Anjana Shresta, Hans-Peter Marti
OBJECTIVE: A previous study by this group demonstrated the feasibility of RNA sequencing (RNAseq) technology for capturing disease biology of clear cell renal cell carcinoma (ccRCC), and presented initial results for carbonic anhydrase-9 (CA9) and tumor necrosis factor-α-induced protein-6 (TNFAIP6) as possible biomarkers of ccRCC (discovery set) [Eikrem et al. PLoS One 2016;11:e0149743]. To confirm these results, the previous study is expanded, and RNAseq data from additional matched ccRCC and normal renal biopsies are analyzed (confirmation set)...
December 2016: Scandinavian Journal of Urology
Xiaoqi Lin
BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) shares some morphologic and immunohistochemical markers with clear cell RCC and papillary RCC. To the author's knowledge, its cytomorphology on fine-needle aspiration (FNA) or touch preparations (TPs) of core needle biopsy specimens has not been well delineated in the English language literature. METHODS: The FNA/TP cytomorphology of 7 retrieved cases was studied. RESULTS: The tumor cells were arranged in small nests (100%), 3-dimensional clusters (71%), papillary/tubular/acinar arrays (43%), and as single cells (57%)...
January 2017: Cancer
Samuele Cazzamalli, Alberto Dal Corso, Dario Neri
In most cases, cytotoxic drugs do not preferentially accumulate at the tumor site, causing unwanted toxicities and preventing dose escalation to therapeutically active regimens. Here, we show that acetazolamide derivatives, which bind to carbonic anhydrase IX (CAIX) on the surface of kidney cancer cells, selectively deliver payloads at the site of disease, sparing normal organs. Biodistribution studies, performed in tumor-bearing mice with acetazolamide derivatives bearing a technetium-99m chelator complex or a red fluorophore as payload, revealed a preferential tumor accumulation of the compound at doses up to 560 nmol/kg...
December 2016: Molecular Cancer Therapeutics
Javad Garousi, Hadis Honarvar, Ken G Andersson, Bogdan Mitran, Anna Orlova, Jos Buijs, John Löfblom, Fredrik Y Frejd, Vladimir Tolmachev
Overexpression of the enzyme carbonic anhydrase IX (CAIX) is documented for chronically hypoxic malignant tumors as well as for normoxic renal cell carcinoma. Radionuclide molecular imaging of CAIX would be useful for detection of hypoxic areas in malignant tumors, for patients' stratification for CAIX-targeted therapies, and for discrimination of primary malignant and benign renal tumors. Earlier, we have reported feasibility of in vivo radionuclide based imaging of CAIX expressing tumors using Affibody molecules, small affinity proteins based on a nonimmunoglobulin scaffold...
November 7, 2016: Molecular Pharmaceutics
Chuanyong Lu, Anthony Nicastri, Charles Shao
Here we report a rare case of coexisting renal cell carcinoma (RCC) with leiomyomatous stroma and a ruptured adrenal aneurysm. The patient was a 75-year-old woman with acute abdominal pain. Imaging studies showed a left peri-renal hematoma and a mass in the left kidney. Left nephrectomy and adrenalectomy were performed. Pathological examination showed a ruptured aneurysm in the left adrenal gland. The renal mass was composed of tubules and acini of epithelial cells and a prominent leiomyomatous stroma. The tumor cells were positive for carbonic anhydrase IX, cytokeratin 7, and negative for AMACR, consistent with clear cell (tubulo) papillary RCC...
September 2016: Urology Case Reports
Shijie Liu, Zuhong Tian, Lei Zhang, Shuang Hou, Sijun Hu, Junshen Wu, Yuming Jing, Huimin Sun, Fei Yu, Libo Zhao, Ruoxiang Wang, Hsian-Rong Tseng, Haiyen E Zhau, Leland W K Chung, Kaichun Wu, Hao Wang, Jason Boyang Wu, Yongzhan Nie, Chen Shao
Circulating tumor cells (CTCs) have emerged as promising tools for noninvasive cancer detection and prognosis. Most conventional approaches for capturing CTCs use an EpCAM-based enrichment strategy, which does not work well in cancers that show low or no expression of EpCAM, such as renal cell carcinoma (RCC). In this study, we developed a new set of cell surface markers including CA9 and CD147 as alternative CTC-capture antigens specifically designed for RCC patients. We showed that the expression of both CA9 and CD147 was prevalent in a RCC patient cohort (n=70) by immunohistochemical analysis, with both molecules in combination covering 97...
September 13, 2016: Oncotarget
Il Minn, Soo Min Koo, Hye Soo Lee, Mary Brummet, Steven P Rowe, Michael A Gorin, Polina Sysa-Shah, William D Lewis, Hye-Hyun Ahn, Yuchuan Wang, Sangeeta Ray Banerjee, Ronnie C Mease, Sridhar Nimmagadda, Mohamad E Allaf, Martin G Pomper, Xing Yang
Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of cases of clear cell renal cell carcinoma (ccRCC), the most common renal cancer. We synthesized and performed in vitro and in vivo evaluation of a dual-motif ligand, [64Cu]XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu]XYIMSR-06 was generated in yields of 51.0 ± 4.5% (n=5) and specific activities of 4.1 - 8.9 GBq/μmol (110-240 Ci/mmol). Tumor was visualized on PET images by 1 h post-injection with high tumor-to-background levels (>100 tumor-to-blood and -muscle) achieved within 24 h...
August 30, 2016: Oncotarget
Nazleen C Lobo, Craig Gedye, Anthony J Apostoli, Kevin R Brown, Joshua Paterson, Natalie Stickle, Michael Robinette, Neil Fleshner, Robert J Hamilton, Girish Kulkarni, Alexandre Zlotta, Andrew Evans, Antonio Finelli, Jason Moffat, Michael A S Jewett, Laurie Ailles
BACKGROUND: Patients with clear cell renal cell carcinoma (ccRCC) have few therapeutic options, as ccRCC is unresponsive to chemotherapy and is highly resistant to radiation. Recently targeted therapies have extended progression-free survival, but responses are variable and no significant overall survival benefit has been achieved. Commercial ccRCC cell lines are often used as model systems to develop novel therapeutic approaches, but these do not accurately recapitulate primary ccRCC tumors at the genomic and transcriptional levels...
2016: BMC Cancer
Necip Pirinççi, Tacettin Yekta Kaya, Mehmet Kaba, Tunç Ozan, İlhan Geçit, Hüseyin Özveren, Hüseyin Eren, Kadir Ceylan
OBJECTIVES: To determine whether serum levels of adenosine deaminase (AD), catalase (CAT), and carbonic anhydrase (CA) enzymes may be useful biomarkers in the diagnosis of renal tumors and may lead to early diagnosis of renal tumors. MATERIAL AND METHODS: The study included 33 patients with renal cell carcinoma (RCC) and 31 healthy controls. The activity of serum AD, CA, and CAT was determined and analyzed using the Giusti spectrophotometric method, H2O2 substrate, and C02 hydration, respectively...
July 14, 2016: Redox Report: Communications in Free Radical Research
Xiang-Hui Ning, Teng Li, Yan-Qing Gong, Qun He, Q I Shen, Shuang-He Peng, Jiang-Yi Wang, Jin-Chao Chen, Ying-Lu Guo, Kan Gong
Fructose-1,6-bisphosphatase 1 (FBP1) is a rate-limiting enzyme in gluconeogenesis. Recently, the catalytic activity-independent function of FBP1, hypoxia-induced factor (HIF) repression in the nucleus, was identified. The aim of the present study was to investigate the association between FBP1 and hypoxia-related gene expression in clear cell renal cell carcinoma (ccRCC). The protein expression levels of FBP1, HIF-1α, HIF-2α, erythropoietin (EPO) and carbonic anhydrase IX (CA9) were assessed by immunohistochemical staining of ccRCC paraffin blocks from 123 patients using the tissue microarray technique...
June 2016: Oncology Letters
A Ingels, M Hew, F Algaba, O J de Boer, R J A van Moorselaar, S Horenblas, P Zondervan, J J M C H de la Rosette, M Pilar Laguna Pes
PURPOSE: Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging. MATERIALS AND METHODS: This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN...
May 20, 2016: World Journal of Urology
Eloah Rabello Suarez, De Kuan Chang, Jiusong Sun, Jianhua Sui, Gordon J Freeman, Sabina Signoretti, Quan Zhu, Wayne A Marasco
Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site...
June 7, 2016: Oncotarget
Ofer N Gofrit, Marina Orevi
PURPOSE: Positron emission tomography-computerized tomography is a leading imaging modality for many types of solid tumors. The ability to characterize molecular processes noninvasively during a relatively fast whole-body scan is the major advantage of this technology. We reviewed the literature in an attempt to clarify the usefulness of positron emission tomography-computerized tomography in patients with a renal mass. MATERIALS AND METHODS: We searched PubMed® for articles published from 2004 through September 2015 using the keywords "renal," "kidney," "mass," "tumor," "cancer," and "PET/CT...
September 2016: Journal of Urology
Marlène C H Hekman, Otto C Boerman, Mirjam de Weijert, Desirée L Bos, Egbert Oosterwijk, Hans F Langenhuijsen, Peter F A Mulders, Mark Rijpkema
PURPOSE: Antibodies labeled with both a near-infrared fluorescent dye and a radionuclide can be used for tumor-targeted intraoperative dual-modality imaging. Girentuximab is a chimeric monoclonal antibody against carbonic anhydrase IX (CAIX), an antigen expressed in 95% of clear cell renal cell carcinoma (ccRCC). This study aimed to assess the feasibility of targeted dual-modality imaging with (111)In-girentuximab-IRDye800CW using ex vivo perfusion of human tumorous kidneys. EXPERIMENTAL DESIGN: Seven radical nephrectomy specimens from patients with ccRCC were perfused during 11 to 15 hours with dual-labeled girentuximab and subsequently rinsed during 2...
September 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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