ABSTRACT
Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target.
Subject(s)
Gene Expression Regulation, Neoplastic , Lymphoma, Large B-Cell, Diffuse/diagnosis , Receptors, Lysosphingolipid/analysis , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Female , Germinal Center , Humans , Immunohistochemistry , Lymphoma, Large B-Cell, Diffuse/chemistry , Lysophospholipids , Male , Middle Aged , Phosphorylation , Prognosis , RNA, Messenger/analysis , Receptors, Lysosphingolipid/genetics , STAT3 Transcription Factor/metabolism , Sphingosine/analogs & derivatives , Testicular NeoplasmsABSTRACT
Amenamevir is an oral once-daily antiherpesvirus drug that can be administered without dose adjustment in patients with impaired renal function. There are currently no clinical data on immunocompromised patients with herpes zoster treated with amenamevir. Therefore, an exploratory study of the efficacy and safety of amenamevir against herpes zoster in patients with immunosuppression was conducted. Inclusion criteria included patients with acute herpes zoster receiving immunosuppressive drugs or those with malignant tumors or autoimmune diseases. Twenty-four patients were included and received amenamevir (400 mg once daily after meals) for up to 14 days. The primary end point of overall improvement in skin symptoms 7 days after treatment initiation (day 7) was 58.3% for "markedly improved" and 20.8% for "improved." The combined improvement rate was 79.2% (95% confidence interval, 57.8-92.9), and 20.8% of patients experienced "worsened" symptoms. The secondary end points of overall improvement in skin symptoms on day 14 and day 28 were 95.7% and 100%, respectively. The skin symptoms progressed during treatment, peaking on day 7, and then began to heal. By Kaplan-Meier estimation, the median periods to complete crusting and healing were both day 14. There were five adverse events with a possible causal relationship to amenamevir (bacterial skin infection, anemia, hyponatremia, headache, and abnormal liver function) in one of the 24 patients. Although the bacterial skin infection was severe, all events in this patient were reported to be either recovered or recovering. These findings indicate that amenamevir can be effective and safe in immunocompromised patients with herpes zoster. However, as worsening can happen around day 7, it is necessary to carefully monitor such patients and switch to other therapies such as intravenous acyclovir if necessary. Clinical trial identifier: Japan Registry of Clinical Trials jRCTs031190208.
Subject(s)
Antiviral Agents , Herpes Zoster , Immunocompromised Host , Immunosuppressive Agents , Humans , Herpes Zoster/drug therapy , Herpes Zoster/immunology , Male , Female , Middle Aged , Aged , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Treatment Outcome , Aged, 80 and over , Adult , Administration, Oral , OxadiazolesABSTRACT
Acute lymphoblastic leukemia (ALL) with chromosome aberration t(8;14)(q11.2;q32) mostly affects patients younger than 20 years old. One third of patients with this translocation have been reported to have Down syndrome. This translocation has been reported rarely in patients over the age of 50. Here we report a 71-year-old male ALL patient who carried t(8;14)(q11.2;q32). Fluorescence in situ hybridization (FISH) analysis revealed the involvement of CCAAT enhancer-binding protein delta (CEBPD) gene on chromosome 8, and IgH gene on chromosome 14. This case provides a new aspect for considering this clinical entity.