Recurrence of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits with a Striated Ultrastructure

This is the peer-reviewed but unedited manuscript version of the following article: Nephron 2020;144(suppl 1):43–48 (DOI: 10.1159/000512330)]. The final, published version is available at http://www.karger.com/?doi=10.1159/000512330

Morphological Changes, Cadherin Switching, and Growth Suppression in Pancreatic Cancer by GALNT6 Knockdown

Pancreatic cancer reveals the worst prognosis among human cancers with little improvement in its clinical outcome in the last three decades. We previously suggested that polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6), which catalyzes O-type glycosylation of Mucin 1, might be a promising molecular target for drug development for breast cancer. In this study, we report upregulation of GALNT6 in pancreatic cancer cells where Mucin proteins are highly O-glycosylated. We found that knockdown of GALNT6 with small interfering RNA in pancreatic cancer cells decreased the amount of Mucin 4 protein as well as that of its transcript, reduced the levels of human epidermal growth factor receptor 2 and extracellular signal–regulated kinase, and significantly reduced pancreatic cancer cell viability. Interestingly, knockdown of GALNT6 caused drastic morphological changes of pancreatic cells, accompanied with the cadherin switching from P-cadherin to E-cadherin. Considering important roles of Mucin 4 in growth and invasion, our findings imply that targeting GALNT6 is a very promising therapeutic strategy for treatment of pancreatic cancer patients who still have very limited treatment modalities

Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation