Novel second-generation rexinoid induces growth arrest and reduces cancer cell stemness in human neuroblastoma patient-derived xenografts

IntroductionThe poor therapeutic efficacy seen with current treatments for neuroblastoma may be attributed to stem cell-like cancer cells (SCLCCs), a subpopulation of cancer cells associated with poor prognosis and disease recurrence. Retinoic acid (RA) is a differentiating agent used as maintenance therapy for high-risk neuroblastoma but nearly half of children treated with RA relapse. We hypothesized that 6-Methyl-UAB30 (6-Me), a second-generation rexinoid recently developed with a favorable toxicity profile compared to RA, would reduce cancer cell stemness in human neuroblastoma patient-derived xenografts (PDXs).MethodsCells from three neuroblastoma PDXs were treated with 6-Me and proliferation, viability, motility, and cell-cycle progression were assessed. CD133 expression, sphere formation, and mRNA abundance of stemness and differentiation markers were evaluated using flow cytometry, in vitro extreme limiting dilution analysis, and real-time PCR, respectively.ResultsTreatment with 6-Me decreased proliferation, viability, and motility, and induced cell-cycle arrest and differentiation in all three neuroblastoma PDXs. In addition, 6-Me treatment led to decreased CD133 expression, decreased sphere-forming ability, and decreased mRNA abundance of Oct4, Nanog, and Sox2, indicating decreased cancer cell stemness.Conclusions6-Me decreased oncogenicity and reduced cancer cell stemness of neuroblastoma PDXs, warranting further exploration of 6-Me as potential novel therapy for neuroblastoma.     

Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.     

Single-Center Experience of Living Donor Liver Transplantation for Patients With Secondary Biliary Cirrhosis

BackgroundSecondary biliary cirrhosis (SBC) represents a unique form of cirrhosis that develops in the liver secondary to persistent biliary obstruction. This study aimed to review the living donor liver transplants (LDLTs) performed at our center for patients with SBC and end-stage liver disease and to share the perioperative strategies undertaken to achieve satisfactory outcomes.MethodsThe medical records of 29 patients who underwent LDLT for SBC between December 1994 and July 2018 at the Asan Medical Center (Seoul, South Korea) were retrospectively reviewed. Their clinical data were extracted and statistically analyzed. Survival curves were computed.ResultsThe perioperative and in-hospital morbidity rates were 72.4% and 10.3%, respectively. The overall mean recipient follow-up was 80.0 (SD, 66.4) months (range, 0.8-246.8 months). Patient survival rates after 1, 3, 5, and 10 years after transplant were 82.8%, 79.3%, 79.3%, and 79.3%, respectively. For liver grafts, the survival rates were 82.8%, 75.8%, 75.8%, and 75.8% at 1, 3, 5, and 10 years, respectively.ConclusionsLDLT is potentially a final lifesaving resort for patients with SBC with portal hypertension. However, considering the difficulty of surgery and perioperative management, LDLT should be performed by experienced transplant surgeons in a center where a multidisciplinary approach is possible.     

ASO Visual Abstract: Association of Obesity with Worse Operative and Oncologic Outcomes Among Patients Undergoing Gastric Cancer Resection

Annals of Surgical Oncology -