Browsing by Author "Kauffman, Eric"

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    Development and Validation of an Objective Scoring Tool for Robot-Assisted Partial Nephrectomy: Scoring for Partial Nephrectomy
    (Mary Ann Liebert, 2021) Iqbal, Umar; Jing, Zhe; Ahmed, Youssef; Elsayed, Ahmed S.; Rogers, Craig G.; Boris, Ronald S.; Porter, James Robert; Allaf, Mohamad E.; Badani, Ketan K.; Stifelman, Michael D.; Kaouk, Jihad; Terakawa, Tomoaki; Hinata, Nobuyuki; Aboumohamed, Ahmed; Kauffman, Eric; Li, Qiang; Abaza, Ronney; Guru, Khurshid A.; Hussein, Ahmed; Eun, Daniel; Urology, School of Medicine
    Objective: To develop a structured and objective scoring tool for assessment of robot-assisted partial nephrectomy (RAPN): Scoring for Partial Nephrectomy (SPaN). Materials and Methods:Content development: RAPN was deconstructed into 6 domains by a multi-institutional panel of 10 expert robotic surgeons. Performance on each domain was represented on a Likert scale of 1 to 5, with specific descriptions of anchors 1, 3, and 5. Content validation: The Delphi methodology was utilized to achieve consensus about the description of each anchor for each domain in terms of appropriateness of the skill assessed, objectiveness, clarity, and unambiguous wording. The content validity index (CVI) of ≥0.75 was set as cutoff for consensus. Reliability: 15 de-identified videos of RAPN were utilized to determine the inter-rater reliability using linearly weighted percent agreement, and Construct validation of SPaN was described in terms of median scores and odds ratios. Results: The expert panel reached consensus (CVI ≥0.75) after 2 rounds. Consensus was achieved for 36 (67%) statements in the first round and 18 (33%) after the second round. The final six-domain SPaN included Exposure of the kidney; Identification and dissection of the ureter and gonadal vessels; Dissection of the hilum; Tumor localization and exposure; Clamping and tumor resection; and Renorrhaphy. The linearly weighted percent agreement was >0.75 for all domains. There was no difference between median scores for any domain between attendings and trainees. Conclusion: Despite the lack of significant construct validity, SPaN is a structured, reliable, and procedure-specific tool that can objectively assesses technical proficiency for RAPN.
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    Therapeutic Targeting of TFE3/IRS-1/PI3K/mTOR Axis in Translocation Renal Cell Carcinoma
    (American Association for Cancer Research, 2018-12) Damayanti, Nur P.; Budka, Justin A.; Khella, Heba W. Z.; Ferris, Mary W.; Ku, Sheng Yu; Kauffman, Eric; Wood, Anthony C.; Ahmed, Khunsha; Chintala, Venkata Nithinsai; Adelaiye-Ogala, Remi; Elbanna, May; Orillion, Ashley; Chintala, Sreenivasulu; Kao, Chinghai; Linehan, W. Marston; Yousef, George M.; Hollenhorst, Peter C.; Pili, Roberto; Medicine, School of Medicine
    Purpose: Translocation renal cell carcinoma (tRCC) represents a rare subtype of kidney cancer associated with various TFE3, TFEB, or MITF gene fusions that are not responsive to standard treatments for RCC. Therefore, the identification of new therapeutic targets represents an unmet need for this disease. Experimental Design: We have established and characterized a tRCC patient-derived xenograft, RP-R07, as a novel preclinical model for drug development by using next-generation sequencing and bioinformatics analysis. We then assessed the therapeutic potential of inhibiting the identified pathway using in vitro and in vivo models. Results: The presence of a SFPQ-TFE3 fusion [t(X;1) (p11.2; p34)] with chromosomal break-points was identified by RNA-seq and validated by RT-PCR. TFE3 chromatin immunoprecipitation followed by deep sequencing analysis indicated a strong enrichment for the PI3K/AKT/mTOR pathway. Consistently, miRNA microarray analysis also identified PI3K/AKT/mTOR as a highly enriched pathway in RP-R07. Upregulation of PI3/AKT/mTOR pathway in additional TFE3–tRCC models was confirmed by significantly higher expression of phospho-S6 (P < 0.0001) and phospho-4EBP1 (P < 0.0001) in established tRCC cell lines compared with clear cell RCC cells. Simultaneous vertical targeting of both PI3K/AKT and mTOR axis provided a greater antiproliferative effect both in vitro (P < 0.0001) and in vivo (P < 0.01) compared with single-node inhibition. Knockdown of TFE3 in RP-R07 resulted in decreased expression of IRS-1 and inhibited cell proliferation. Conclusions: These results identify TFE3/IRS-1/PI3K/AKT/mTOR as a potential dysregulated pathway in TFE3–tRCC, and suggest a therapeutic potential of vertical inhibition of this axis by using a dual PI3K/mTOR inhibitor for patients with TFE3–tRCC.