RESUMO
The prevalence of cannabis use for recreational and medicinal purposes has steadily increased. While it is commonly used to alleviate pain, its use is also associated with many acute and chronic adverse effects. There are cases reported on the negative impact of cannabis use on gastrointestinal (GI) disorders; however, there have been few reported cases linking cannabis use to acute pancreatitis. This case report discusses a 37-year-old female presenting to the emergency department for cannabis-induced acute pancreatitis. The purpose of this case report is to educate on the importance of recognizing the potential GI complications resulting from marijuana use.
RESUMO
Constitutively activated tyrosine kinase JAK3 is implicated in the pathogenesis of cutaneous T-cell lymphomas (CTCL). The mechanisms of constitutive JAK3 activation are unknown although a JAK3 mutation was reported in a small portion of CTCL patients. In this study, we assessed the oncogenic roles of a newly identified JAK3-INSL3 fusion transcript in CTCL. Total RNA from malignant T-cells in 33 patients with Sézary syndrome (SS), a leukemic form of CTCL, was examined for the new JAK3-INSL3 fusion transcript by RT-PCR followed by Sanger sequencing. The expression levels were assessed by qPCR and correlated with patient survivals. Knockdown and/or knockout assays were conducted in two CTCL cell lines (MJ cells and HH cells) by RNA interference and/or CRISPR/Cas9 gene editing. SS patients expressed heterogeneous levels of a new JAK3-INSL3 fusion transcript. Patients with high-level expression of JAK3-INSL3 showed poorer 5-year survival (n = 19, 42.1%) than patients with low-level expression (n = 14, 78.6%). CTCL cells transduced with specific shRNAs or sgRNAs had decreased new JAK3-INSL3 fusion transcript expression, reduced cell proliferation, and decreased colony formation. In NSG xenograft mice, smaller tumor sizes were observed in MJ cells transduced with specific shRNAs than cells transduced with controls. Our results suggest that the newly identified JAK3-INSL3 fusion transcript confers an oncogenic event in CTCL.
Assuntos
Linfoma Cutâneo de Células T , Proteínas de Fusão Oncogênica , Síndrome de Sézary , Neoplasias Cutâneas , Animais , Humanos , Camundongos , Janus Quinase 3/genética , Janus Quinase 3/metabolismo , Linfoma Cutâneo de Células T/metabolismo , RNA Guia de Sistemas CRISPR-Cas , RNA Interferente Pequeno , Síndrome de Sézary/genética , Neoplasias Cutâneas/patologia , Proteínas de Fusão Oncogênica/genéticaRESUMO
BACKGROUND/PURPOSE: We previously reported that myeloid dendritic cells (mDC) were increased in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) following extracorporeal photopheresis (ECP) using the Therakos UVAR XTS™ system. We now assessed monocyte-derived mDCs (Mo-DCs) in L-CTCL patients treated with the CELLEXTM photopheresis system. CD209, a transmembrane receptor, was used to define Mo-DCs. METHODS: Peripheral blood samples from baseline pre-ECP and at Day 2, 1 month, 3 months, and 6 months post-ECP were analyzed by flow cytometry for Lin- HLA-DR+ CD123+ plasmacytoid dendritic cells (pDCs), Lin- HLA-DR+ CD11c+ mDCs, and CD209+ mDCs. The expression of CD209 mRNA was assessed by real-time PCR. RESULTS: At baseline, 7 of 19 patients had lower than normal mDCs, and all patients had lower than normal CD209+ mDCs in peripheral blood mononuclear cells (0.005% in patients, n = 19, vs 0.50% in healthy donors, n = 7, P < .0001). The CD209+ mDC numbers only accounted for 3.28% out of total mDCs in patients compared with 66.51% in healthy donors. After treatment, the CD209+ mDC numbers showed increasing trends in patients. The average absolute numbers of CD209+ mDCs went up by 4.8-fold at 3 months (n = 10, P = .103) and by 6.4-fold at 6 months (n = 9, P = .100). CD209 mRNA expression went up in two patients responsive to therapy, parallel to CD209+ mDC numbers. L-CTCL patients achieved 70% overall clinical response rate (7/10) following ECP therapy with the CELLEXTM system. CONCLUSIONS: Our results suggest that the CELLEXTM photopheresis system is effective for treating L-CTCL patients like the UVAR XTS™ system, and in vivo-generated Mo-DCs increase following ECP.