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Browsing by Author "Zhang, Chao"
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Item On-Clamp vs. Off-Clamp Robot-Assisted Partial Nephrectomy for cT2 Renal Tumors: Retrospective Propensity-Score-Matched Multicenter Outcome Analysis(MDPI, 2022-09-13) Brassetti, Aldo; Cacciamani, Giovanni E.; Mari, Andrea; Garisto, Juan D.; Bertolo, Riccardo; Sundaram, Chandru P.; Derweesh, Ithaar; Bindayi, Ahmet; Dasgupta, Prokar; Porter, James; Mottrie, Alexander; Schips, Luigi; Rah, Koon Ho; Chen, David Y. T.; Zhang, Chao; Jacobsohn, Kenneth; Anceschi, Umberto; Bove, Alfredo M.; Costantini, Manuela; Ferriero, Mariaconsiglia; Mastroianni, Riccardo; Misuraca, Leonardo; Tuderti, Gabriele; Kutikov, Alexander; White, Wesley M.; Ryan, Stephen T.; Porpiglia, Francesco; Kaouk, Jihad; Minervini, Andrea; Gill, Inderbir; Autorino, Riccardo; Simone, Giuseppe; Urology, School of MedicineWe compared perioperative outcomes after on-clamp versus off-clamp robot-assisted partial nephrectomy (RAPN) for >7 cm renal masses. A multicenter dataset was queried for patients who had undergone RAPN for a cT2cN0cM0 kidney tumor from July 2007 to February 2022. The Trifecta achievement (negative surgical margins, no severe complications, and ≤ 30% postoperative estimated glomerular filtration rate (eGFR) reduction) was considered a surrogate of surgical quality. Overall, 316 cases were included in the analysis, and 58% achieved the Trifecta. A propensity-score-matched analysis generated two cohorts of 89 patients homogeneous for age, ASA score, preoperative eGFR, and RENAL score (all p > 0.21). Compared to the on-clamp approach, OT was significantly shorter in the off-clamp group (80 vs. 190 min; p < 0.001), the incidence of sRFD was lower (22% vs. 40%; p = 0.01), and the Trifecta rate higher (66% vs. 46%; p = 0.01). In a crude analysis, >20 min of hilar clamping was associated with a significantly higher risk of sRFD (OR: 2.30; 95%CI: 1.13−4.64; p = 0.02) and with reduced probabilities of achieving the Trifecta (OR: 0.46; 95%CI: 0.27−0.79; p = 0.004). Purely off-clamp RAPN seems to be a safe and viable option to treat cT2 renal masses and may outperform the on-clamp approach regarding perioperative surgical outcomes.Item USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer(Springer Nature, 2022-09-26) Shi, Dongni; Wu, Xianqiu; Jian, Yunting; Wang, Junye; Huang, Chengmei; Mo, Shuang; Li, Yue; Li, Fengtian; Zhang, Chao; Zhang, Dongsheng; Zhang, Huizhong; Huang, Huilin; Chen, Xin; Wang, Y. Alan; Lin, Chuyong; Liu, Guozhen; Song, Libing; Liao, Wenting; Medicine, School of MedicineIndoleamine 2,3 dioxygenase 1 (IDO1) is an attractive target for cancer immunotherapy. However, IDO1 inhibitors have shown disappointing therapeutic efficacy in clinical trials, mainly because of the activation of the aryl hydrocarbon receptor (AhR). Here, we show a post-transcriptional regulatory mechanism of IDO1 regulated by a proteasome-associated deubiquitinating enzyme, USP14, in colorectal cancer (CRC). Overexpression of USP14 promotes tryptophan metabolism and T-cell dysfunction by stabilizing the IDO1 protein. Knockdown of USP14 or pharmacological targeting of USP14 decreases IDO1 expression, reverses suppression of cytotoxic T cells, and increases responsiveness to anti-PD-1 in a MC38 syngeneic mouse model. Importantly, suppression of USP14 has no effects on AhR activation induced by the IDO1 inhibitor. These findings highlight a relevant role of USP14 in post-translational regulation of IDO1 and in the suppression of antitumor immunity, suggesting that inhibition of USP14 may represent a promising strategy for CRC immunotherapy.