Background/AimsThe most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated.MethodsNinety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD).ResultsThe 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05).ConclusionsInduction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.
Rationale:
Senescent melanocytes accumulate in photoaged skin and are closely related to skin aging. A better understanding of the molecular characteristics of senescent melanocytes may be the key to controlling skin aging.
Methods:
We have developed an
in vitro
model of senescence in melanocytes using UV irradiation and investigated the functional characteristics and molecular mechanisms underlying senescence in UV-irradiated melanocytes.
Results:
We have highlighted that
in vitro
senescent melanocytes are characterized by melanosome transport dysfunction resulting in melanin accumulation. The defective melanosome transport was confirmed with the ultrastructural characterization of both
in vitro
UV-induced senescent melanocytes and
in vivo
melanocytes of hypopigmented aging skin. A single-cell transcriptomic analysis revealed that the glycolytic metabolism pathway appeared to be significantly upregulated in most senescent phenotypes. Furthermore, the inhibition of glycolysis by pharmacological compounds mitigates the pro-aging effects of melanocytes senescence, suggesting that alterations in cellular glucose metabolism act as a driving force for senescence in melanocytes.
Conclusion:
These results demonstrate that senescent melanocytes are characterized by glycolytic metabolism changes and a defective melanosome transport process, which may be related to impaired mitochondrial function, highlighting the importance of metabolic reprogramming in regulating melanocyte senescence.
Background
Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer, of which most research has been conducted in Caucasians. Therefore, the clinicopathological features and prognosis of Merkel cell carcinoma in Asians are still scarce. The aim of this study is to investigate the epidemiology and survival of MCC in South Korea and provide representative information regarding MCC in Asia.
Methods
This was a retrospective, nationwide, multicenter study conducted in 12 centers across South Korea. Patients with pathologically proven MCC were included in the study. The clinicopathological features and clinical outcomes of the patients were investigated. Overall survival (OS) was analyzed using the Kaplan–Meier method, and independent prognostic factors were identified using Cox regression analysis.
Results
A total of 161 patients with MCC were evaluated. The mean age was 71 years with a female predominance. OS was significantly different among the stages. Among clinicopathological features, multivariate Cox regression analysis demonstrated that only the stage at diagnosis was associated with poorer overall survival.
Conclusions
The results of our study suggest that the incidence of MCC was higher in females than in males and that there was a higher rate of local disease at the time of diagnosis. Among the variable clinicopathological features, disease stage at diagnosis was the only significant prognostic factor for MCC in South Korea. The findings of this nationwide, multicenter study suggest that MCC has distinct features in South Korea compared with other countries.
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