Real-Life Experience of mTOR Inhibitors in Liver Transplant Recipients in a Region Where Living Donation Is Predominant

Sung, Pil Soo; Han, Ji Won; Seo, Changho; Ahn, Joseph; Lee, Soon Kyu; Nam, Hee Chul; Choi, Ho Joong; You, Young Kyoung; Jang, Jeong Won; Choi, Jong Young; Yoon, Seung Kew

doi:10.3389/fphar.2021.685176

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…To examine the mechanism by which LncTUG1 may promote HCC progression, we first selected genes related with LncTUG1 and make GO enrichment analysis in StarBase ( http://starbase.sysu.edu.cn ) and Metascape ( http://metascape.org/gp/index ). On account of it remarkably affects the evolement of HCC 23 – 25 , the mTOR/S6K pathway was selected for study (Fig. 2 a).…”

Section: Resultsmentioning

confidence: 99%

LncTUG1 contributes to the progression of hepatocellular carcinoma via the miR-144-3p/RRAGD axis and mTOR/S6K pathway

Chen

Bai

et al. 2023

Sci Rep

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Hepatocellular carcinoma (HCC) is a symptomatic disease involed multi-stage program. Here, we elucidated the molecular mechanism of LncTUG1 in the regulation of HCC evolvement. And that may in all likelyhood supply a innovative latent target for HCC’s diagnoses and prognosis. LncRNA TUG1, miR-144-3p, RRAGD and mTOR signaling pathway were screened as target genes in the database, and their expression levels at the cytological level were verified utilized qRT-PCR, Western Blot and immunohistochemistry. Then, we adopted CCK-8, Transwell and flow cytometry assays to estimate cell proliferation, invasion and apoptosis. By use of luciferase reporter assay, the relationships of LncRNA TUG1, miR-144-3p and RRAGD was confirmed. In addition, the LncRNA TUG1-miR-144-3p-RRAGD-mTOR signaling pathway in HCC cells was verified adopted rescue experiment and confirmed by xenotransplantation animal experiment. LncTUG1 in HCC tissues from three databases were identified and further verified through qRT-PCR in HCC cells (Huh7, Hep3B). Knockdown the LncTUG1 could increase apoptosis and inhibite invasion and proliferation in HCC cells. Using inhibitors and activators of the mTOR/S6K pathway, LncTUG1 was confirmed to regulate HCC progression by the mTOR/S6K pathway. Luciferase reporter assay demonstrated that TUG1 negatively regulates miR-144-3p. Furthermore, miR-144-3p negativly regulates RRAGD by way of interacting with the 3′UTR of the RRAGD mRNA in HCC utilized luciferase reporter assay. In vivo, we also discovered that neoplasm weight and tumor volume reduced significantly in subcutaneous xenograft nude mouse models derived from sh-LncTUG1-expressing Huh7 cells. And the expressions of p-mTOR, p-S6K and RRAGD were decreased obviously while the miR144-3p increased in subcutaneous xenograft nude mouse models. In a word, the research suggests that LncTUG1 targets miR-144-3p while miR-144-3p binds to RRAGD mRNA, which induces mTOR/S6K pathway activation and promotes the progression of HCC.

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Section: Resultsmentioning

confidence: 99%

LncTUG1 contributes to the progression of hepatocellular carcinoma via the miR-144-3p/RRAGD axis and mTOR/S6K pathway

Chen

Bai

et al. 2023

Sci Rep

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“…The findings from this follow-up study in the LDLT setting further demonstrated that early conversion to an EVR-based regimen improves/preserves renal function, both immediately and long-term. A recent retrospective real-world study showed that patients with renal impairment experienced significant improvement in renal function after conversion to mTOR inhibitor [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipients with Hepatocellular Carcinoma

et al. 2022

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Background The study objective was to evaluate the effect of everolimus (EVR) in combination with reduced tacrolimus (rTAC) compared with a standard TAC (sTAC) regimen on hepatocellular carcinoma (HCC) recurrence in de novo living-donor liver transplantation recipients (LDLTRs) with primary HCC at liver transplantation through 5 years after transplantation. Material/Methods In this multicenter, non-interventional study, LDLTRs with primary HCC, who were previously randomized to either everolimus plus reduced tacrolimus (EVR+rTAC) or standard tacrolimus (sTAC), and who completed the 2-year core H2307 study, were followed up. Data were collected retrospectively (end of core to the start of follow-up study), and prospectively (during the 3-year follow-up study). Results Of 117 LDLTRs with HCC at LT in the core H2307 study (EVR+rTAC, N=56; sTAC, N=61), 86 patients (EVR+rTAC, N=41; sTAC, N=45) entered the follow-up study. Overall HCC recurrence was lower but statistically non-significant in the EVR+rTAC group (3.6% vs 11.5% in sTAC; P =0.136) at 5 years after LT. There was no graft loss or chronic rejection. Acute rejection and death were comparable between treatment groups. Higher mean estimated glomerular filtration rate in the EVR+rTAC group (76.8 vs 65.8 mL/min/1.73 m 2 in sTAC) was maintained up to 5 years. Reported adverse events were numerically lower in the EVR+rTAC group (41.0% vs 53.5% sTAC) but not statistically significant. Conclusions Although statistically not significant, early EVR initiation reduced HCC recurrence, with comparable efficacy and safety, and better long-term renal function, than that of sTAC treatment.

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“…In a retrospective study, Sung et al [ 19 ] found that individuals with impaired renal function improved significantly after 12 mo of using mTOR inhibitors. The median eGFR values at 1, 3, 6, and 12 mo after switching to mTOR inhibitors were 90, 75.5, 74.5, and 76.8 mL/min.…”

Section: To the Editormentioning

confidence: 99%

Sirolimus vs tacrolimus: Which one is the best therapeutic option for patients undergoing liver transplantation for hepatocellular carcinoma?

Ahmed¹,

Zakaria²,

Nya³

et al. 2022

WJGS

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Liver transplantation (LT) withstands as the most preferred therapeutic option for patients afflicted with hepatocellular carcinoma (HCC) and cirrhosis. To improve prognosis post-transplant, as well as to prevent the occurrence of rejection, a life-long immunosuppression strategy is implemented. The following letter to the editor highlights and provides novel evidence from recently published literature on topics discussed within the review article titled “Trends of rapamycin in survival benefits of liver transplantation for hepatocellular carcinoma” in World J Gastrointest Surg 2021; 13: 953-966. In the recent manuscript, the authors compared immunosuppressive drugs such as the newer option first-generation mammalian target of rapamycin inhibitor, also known as sirolimus, with the most widely used first-generation calcineurin inhibitors, such as tacrolimus (TAC). TAC is commonly known as the most effective immunosuppressive drug after LT, but it has been reported to cause intolerable side effects such as nephrotoxicity, neurotoxicity, diabetes, hypertension, gastrointestinal disturbances, increased risk of infections, and malignancies. It is necessary for physicians to be aware of recent advances in tacrolimus and sirolimus therapies to compare and understand distinctly the effectiveness and tolerability of these drugs. This will assist clinicians in making the best treatment decisions and improve the clinical prognosis of LT recipients with HCC.

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Real-Life Experience of mTOR Inhibitors in Liver Transplant Recipients in a Region Where Living Donation Is Predominant

Cited by 7 publications

References 36 publications

LncTUG1 contributes to the progression of hepatocellular carcinoma via the miR-144-3p/RRAGD axis and mTOR/S6K pathway

LncTUG1 contributes to the progression of hepatocellular carcinoma via the miR-144-3p/RRAGD axis and mTOR/S6K pathway

Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipients with Hepatocellular Carcinoma

Sirolimus vs tacrolimus: Which one is the best therapeutic option for patients undergoing liver transplantation for hepatocellular carcinoma?

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