Dermatofibrosarcoma protuberans with areas of giant cell fibroblastoma in the vulva: a case report.

OBJECTIVE: To review the clinical, morphologic, immunohistochemical, and histogenetic characteristics of dermatofibrosarcoma protuberans with areas of giant cell fibroblastoma and explore current treatment options. METHODS: We describe the case of a 38-year-old patient with a tumor measuring 5.7 cm on the right labium majus of the vulva. Serial sections stained with hematoxylin-eosin were examined and immunohistochemical staining was performed for CD34 and PDGF receptor alpha and beta (PDFGRA and PDGFRB). RESULTS: The histologic study showed spindle-cell proliferation typical of dermatofibrosarcoma protuberans and other areas containing fibrosis and giant cells lining pseudovascular spaces. Both tumor areas expressed CD34, PDGFRA, and PDGFRB. CONCLUSIONS: Only two cases of dermatofibrosarcoma protuberans with areas of giant cell fibroblastoma in the vulva have been reported to date. Both dermatofibrosarcoma protuberans and giant cell fibroblastoma are characterized by the translocation t (17;22) (q22;q13). The fact that PDGFRA and PDGFRB are overexpressed in these tumors opens new treatment options with imatinib. Surgical excision with wide margins or Mohs micrographic surgery continues to be the treatment of choice.

Mesenchymal Stem Cells for Liver Regeneration in Liver Failure: From Experimental Models to Clinical Trials.

The liver centralizes the systemic metabolism and thus controls and modulates the functions of the central and peripheral nervous systems, the immune system, and the endocrine system. In addition, the liver intervenes between the splanchnic and systemic venous circulation, determining an abdominal portal circulatory system. The liver displays a powerful regenerative potential that rebuilds the parenchyma after an injury. This regenerative mission is mainly carried out by resident liver cells. However, in many cases this regenerative capacity is insufficient and organ failure occurs. In normal livers, if the size of the liver is at least 30% of the original volume, hepatectomy can be performed safely. In cirrhotic livers, the threshold is 50% based on current practice and available data. Typically, portal vein embolization of the part of the liver that is going to be resected is employed to allow liver regeneration in two-stage liver resection after portal vein occlusion (PVO). However, hepatic resection often cannot be performed due to advanced disease progression or because it is not indicated in patients with cirrhosis. In such cases, liver transplantation is the only treatment possibility, and the need for transplantation is the common outcome of progressive liver disease. It is the only effective treatment and has high survival rates of 83% after the first year. However, donated organs are becoming less available, and mortality and the waiting lists have increased, leading to the initiation of living donor liver transplantations. This type of transplant has overall complications of 38%. In order to improve the treatment of hepatic injury, much research has been devoted to stem cells, in particular mesenchymal stem cells (MSCs), to promote liver regeneration. In this review, we will focus on the advances made using MSCs in animal models, human patients, ongoing clinical trials, and new strategies using 3D organoids.

Metabolic Reprogramming, Autophagy, and Reactive Oxygen Species Are Necessary for Primordial Germ Cell Reprogramming into Pluripotency.

Cellular reprogramming is accompanied by a metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Previous results from our laboratory showed that hypoxia alone is able to reprogram primordial germ cells (PGCs) into pluripotency and that this action is mediated by hypoxia-inducible factor 1 (HIF1). As HIF1 exerts a myriad of actions by upregulating several hundred genes, to ascertain whether the metabolic switch toward glycolysis is solely responsible for reprogramming, PGCs were cultured in the presence of a pyruvate kinase M2 isoform (PKM2) activator, or glycolysis was promoted by manipulating PPARγ. Conversely, OXPHOS was stimulated by inhibiting PDK1 activity in normoxic or in hypoxic conditions. Inhibition or promotion of autophagy and reactive oxygen species (ROS) production was performed to ascertain their role in cell reprogramming. Our results show that a metabolic shift toward glycolysis, autophagy, and mitochondrial inactivation and an early rise in ROS levels are necessary for PGC reprogramming. All of these processes are governed by HIF1/HIF2 balance and strict intermediate Oct4 levels. Histone acetylation plays a role in reprogramming and is observed under all reprogramming conditions. The pluripotent cells thus generated were unable to self-renew, probably due to insufficient Blimp1 downregulation and a lack of Klf4 and cMyc expression.