ABSTRACT
Introduction: Clear cell renal cell carcinoma (ccRCC) is characterized by a predominant metabolic reprogramming triggering energy production by anaerobic glycolysis at the expense of oxydative phosphorylation. Ketogenic diet (KD), which consists of high fat and low carbohydrate intake, could bring required energy substrates to healthy cells while depriving tumor cells of glucose. Our objective was to evaluate the effect of KD on renal cancer cell tumor metabolism and growth proliferation. Methods: Growth cell proliferation and mitochondrial metabolism of ACHN and Renca renal carcinoma cells were evaluated under ketone bodies (KB) exposure. In vivo studies were performed with mice (nude or Balb/c) receiving a xenograft of ACHN cells or Renca cells, respectively, and were then split into 2 feeding groups, fed either with standard diet or a 2:1 KD ad libitum. To test the effect of KD associated to immunotherapy, Balb/c mice were treated with anti-PDL1 mAb. Tumor growth was monitored. Results: In vitro, KB exposure was associated with a significant reduction of ACHN and Renca cell proliferation and viability, while increasing mitochondrial metabolism. In mice, KD was associated with tumor growth reduction and PDL-1 gene expression up-regulation. In Balb/c mice adjuvant KD was associated to a better response to anti-PDL-1 mAb treatment. Conclusion: KB reduced the renal tumor cell growth proliferation and improved mitochondrial respiration and biogenesis. KD also slowed down tumor growth of ACHN and Renca in vivo. We observed that PDL-1 was significantly overexpressed in tumor in mice under KD. Response to anti-PDL-1 mAb was improved in mice under KD. Further studies are needed to confirm the therapeutic benefit of adjuvant KD combined with immunotherapy in patients with kidney cancer.
Subject(s)
B7-H1 Antigen , Carcinoma, Renal Cell , Cell Proliferation , Diet, Ketogenic , Kidney Neoplasms , Mice, Inbred BALB C , Animals , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/diet therapy , Mice , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Humans , Mice, Nude , Xenograft Model Antitumor Assays , Cell Line, Tumor , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , FemaleABSTRACT
BACKGROUND: Partial nephrectomy (PN) is the standard treatment for localized renal tumors. Laparoscopic PN (LPN) after selective embolization of tumor (LPNE) in a hybrid operating room has been developed to make LPN easier and safer. The aim of this study was to compare outcomes of LPNE and robot-assisted PN (RAPN). PATIENTS AND METHODS: All patients who underwent an LPNE at Angers University Hospital between May 2015 and April 2017, and a RAPN at Diaconesses Croix Saint Simon hospital between October 2014 and April 2017 were prospectively included. The functional outcomes were evaluated using the change of estimated glomerular filtration rate (eGFR) at 1 month, and the oncological outcomes were evaluated using the positive surgical margin (PSM) rate. RESULTS: Fifty-seven patients underwent LPNE and 48 underwent RAPN. There was no difference between oncological and functional outcomes, with 2 PSM (4.4%) in the LPNE group and 4 PSM (10.3%) in the RAPN group (P = .32), and a mean change in eGFR at 1 month of -5.5% for LPNE and -8.3% for RAPN (P = .17). The mean surgical time was shorter in the LPNE group (150 vs. 195 minutes; P < .001), and mean estimated blood loss was less in the LPNE group (185 vs. 345 mL; P = .04). CONCLUSION: The short-term oncological and functional outcomes for LPNE were comparable with those for RAPN. A longer follow-up and a larger cohort of patients would be necessary to verify the benefits of LPNE, which appears to be a very interesting alternative to RAPN.
