24 research outputs found
Glioblastoma Models Reveal the Connection between Adult Glial Progenitors and the Proneural Phenotype
Tumor heterogeneity is a major obstacle for finding effective treatment of
Glioblastoma (GBM). Based on global expression analysis, GBM can be
classified into distinct subtypes: Proneural, Neural, Classical and
Mesenchymal. The signatures of these different tumor subtypes may reflect
the phenotypes of cells giving rise to them. However, the experimental
evidence connecting any specific subtype of GBM to particular cells of
origin is lacking. In addition, it is unclear how different genetic
alterations interact with cells of origin in determining tumor
heterogeneity. This issue cannot be addressed by studying end-stage human
tumors.To address this issue, we used retroviruses to deliver transforming genetic
lesions to glial progenitors in adult mouse brain. We compared the resulting
tumors to human GBM. We found that different initiating genetic lesions gave
rise to tumors with different growth rates. However all mouse tumors closely
resembled the human Proneural GBM. Comparative analysis of these mouse
tumors allowed us to identify a set of genes whose expression in humans with
Proneural GBM correlates with survival.This study offers insights into the relationship between adult glial
progenitors and Proneural GBM, and allows us to identify molecular
alterations that lead to more aggressive tumor growth. In addition, we
present a new preclinical model that can be used to test treatments directed
at a specific type of GBM in future studies
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Cytogenetic analysis of adult T-Cell leukemia/ lymphoma: evaluation of a Caribbean cohort
Adult T-cell leukemia/lymphoma (ATLL) is a rare and highly aggressive type of peripheral T-cell lymphoma associated with human T-lymphotropic virus, type I (HTLV-I) infection. ATLL has a long latency and only a small percentage of HTLV-I infected individuals develop ATLL, suggesting the requirement of additional genetic events for neoplastic transformation of HTLV-I infected lymphocytes. The disease is endemic in several regions of the world, in particular, southwestern Japan and the Caribbean basin. The clinical features of Caribbean ATLL have been reported to differ from Japanese cases, includ- ing a younger age at diagnosis, higher frequency of the lymphomatous subtype, and a more aggressive clinical course [1β7]. A number of publications have described the cytogenetic profile of Japanese ATLL [8β11]; however, cytogenetic data on Caribbean ATLL are limited [5,6]. In this study, we assessed the cytogenetic alterations in a large series of Caribbean ATLL cases to investigate whether the differences in the types and frequencies of karyotype abnormalities account for the reported differ- ences in clinical presentation and outcome between Japanese and Caribbean patients
Indolent T- and NK-Cell Lymphoproliferative Disorders of the Gastrointestinal Tract: Current Understanding and Outstanding Questions
Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract are uncommon clonal neoplasms that have a protracted clinical course and limited response to therapy. In recent years, advances in the immunophenotypic, genetic, and clinical characterization of these disorders have led to increased awareness and a better understanding of disease pathogenesis. However, many questions remain unanswered, including those concerning the cell(s) of origin, inciting immune or environmental factors, and the molecular pathways underlying disease progression and transformation. In this review, we discuss recent findings regarding the immunophenotypic and genomic spectrum of these lymphoproliferative disorders and highlight unresolved issues
Author response for "Cancer Testis Antigen Expression Across TβCell Lymphoma Subtypes"
Targeting CD38 with Daratumumab Plus Chemotherapy for Patients with Advanced-Stage Plasmablastoid Large B-Cell Lymphoma
Plasmablastic lymphoma (PBL) is a rare and aggressive form of large B-cell lymphoma (LBCL) most commonly seen in the setting of chronic immunosuppression or autoimmune disease. The prognosis is poor and CHOP-like regimens often fail to produce durable remission; therefore, there is no established standard of care treatment. However, PBL demonstrates substantial morphologic and immunophenotypic overlap with multiple myeloma (MM), suggesting that MM therapeutics might prove useful in treating PBL. We studied the effects of treatment using the first-in-class monoclonal antibody directed against CD38, daratumumab, in combination with chemotherapy in seven patients with advanced-stage LBCL with plasmablastic features. Treatment was safe and well-tolerated. Among six evaluable patients, six patients had complete response after treatment, and four patients who met strict WHO criteria for PBL had durable response (12–31 months and ongoing)
Refractory celiac disease type II: An atypical case highlighting limitations of the current classification system
Speciation for analysis of organotin compounds by GC AA and GC MS after ethylation by sodium tetraethylborate
Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract.
Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of ten indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD