Browsing by Author "Chinnaiyan, Arul M."

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    Clinical Utility and Concordance of Upper Urinary Tract Cytology and Biopsy in Predicting Clinicopathologic Features of Upper Urinary Tract Urothelial Carcinoma
    (Elsevier, 2019) Talsma Simon, Caroline; Skala, Stephanie L.; Weizer, Alon Z.; Ambani, Sapan N.; Chinnaiyan, Arul M.; Palapattu, Ganesh; Hafez, Khaled; Magers, Martin J.; Kaffenberger, Samuel D.; Spratt, Daniel E.; Montgomery, Jeffrey S.; Morgan, Todd M.; Udager, Aaron M.; Lew, Madelyn; Mehra, Rohit; Pathology and Laboratory Medicine, School of Medicine
    5% of urothelial carcinoma occurs in the upper urinary tract (UUT), a challenging location to biopsy. We aim to evaluate concordance between biopsy, cytology, and resection specimens in a large upper tract urothelial carcinoma (UTUC) cohort.117 UTUC resections with UUT biopsy and/or cytology specimens from 2000–2016 were retrieved; pathologic material was re-reviewed, evaluated for concordance, and correlated with clinical information. 14% pre-operative biopsies, including 8 from renal pelvis and 6 from ureter, lacked neoplastic diagnoses. 77% diagnostic biopsies included subepithelial tissue; 11% demonstrated reclassification of grade and 30% demonstrated reclassification of invasion status. 26% of renal pelvis UTUC and 36% ureter UTUC were invasive only on resection. Of 18 UTUC reclassified from noninvasive high-grade papillary urothelial carcinoma (HGPUC) to invasive HGPUC, 39% had prior radical cystectomy (versus 8% invasive UTUC and 11% noninvasive UTUC with concordant biopsies). Most high-grade UTUC (88%) and some low-grade UTUC (58%) resections had abnormal cytology results. Biopsy-resection pairs with concordant invasion status and pairs with discordant invasion status showed similar rates of recurrence (38% versus 38%) and metastasis (25% versus 27%). 14% of UUT biopsies lacked diagnostic neoplastic material. Grade concordance between biopsy and resection was high (89%), but 30% of cases showed invasion only on resection. Subepithelial tissue was less commonly present in ureter biopsies, particularly from mid or proximal ureter. UTUC in patients with prior cystectomy were more likely to show invasion on resection but not biopsy.
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    RNA-seq of Human T Cells after Hematopoietic Stem Cell Transplantation Identifies Linc00402 as a Regulator of T-Cell Alloimmunity
    (American Association for the Advancement of Science, 2021) Peltier, Daniel; Radosevich, Molly; Ravikumar, Visweswaran; Pitchiaya, Sethuramasundaram; Decoville, Thomas; Wood, Sherri C.; Hou, Guoqing; Zajac, Cynthia; Oravecz-Wilson, Katherine; Sokol, David; Henig, Israel; Wu, Julia; Kim, Stephanie; Taylor, Austin; Fujiwara, Hideaki; Sun, Yaping; Rao, Arvind; Chinnaiyan, Arul M.; Goldstein, Daniel R.; Reddy, Pavan; Pediatrics, School of Medicine
    Mechanisms governing allogeneic T cell responses after solid organ and allogeneic hematopoietic stem cell transplantation (HSCT) are incompletely understood. To identify lncRNAs that regulate human donor T cells after clinical HSCT, we performed RNA sequencing on T cells from healthy individuals and donor T cells from three different groups of HSCT recipients that differed in their degree of major histocompatibility complex (MHC) mismatch. We found that lncRNA differential expression was greatest in T cells after MHC-mismatched HSCT relative to T cells after either MHC-matched or autologous HSCT. Differential expression was validated in an independent patient cohort and in mixed lymphocyte reactions using ex vivo healthy human T cells. We identified Linc00402, an uncharacterized lncRNA, among the lncRNAs differentially expressed between the mismatched unrelated and matched unrelated donor T cells. We found that Linc00402 was conserved and exhibited an 88-fold increase in human T cells relative to all other samples in the FANTOM5 database. Linc00402 was also increased in donor T cells from patients who underwent allogeneic cardiac transplantation and in murine T cells. Linc00402 was reduced in patients who subsequently developed acute graft-versus-host disease. Linc00402 enhanced the activity of ERK1 and ERK2, increased FOS nuclear accumulation, and augmented expression of interleukin-2 and Egr-1 after T cell receptor engagement. Functionally, Linc00402 augmented the T cell proliferative response to an allogeneic stimulus but not to a nominal ovalbumin peptide antigen or polyclonal anti-CD3/CD28 stimulus. Thus, our studies identified Linc00402 as a regulator of allogeneic T cell function.