Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Open J Blood Dis ; 11(4): 120-132, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34984108

ABSTRACT

Primary cardiac lymphoma (PCL) is a rare entity that comprises only 1-2% of all cardiac tumors. Due to their scarcity and variable clinical presentation, early diagnosis is challenging. In this series, three cases of PCL from a single institution are described, which highlight the spectrum of presenting features and emphasize common principles. In the first case, a 73-year-old male who presented with dyspnea was found to have a 12.1 cm mass in the right ventricle. Biopsy via cardiac catheterization revealed diffuse large B cell lymphoma (DLBCL). He was treated with chemoimmunotherapy and survived for two months. The second case describes a 55-year-old female who presented with chest pain. Imaging revealed a 3.1 cm right atrial mass and bilateral pleural effusions, with cytology from the latter demonstrating DLBCL. She was lost to follow up after three cycles of chemoimmunotherapy. In the last case, an 80-year-old female presented with weakness. A 4.0 cm mass was discovered in the right atrium and the patient expired shortly after admission. Autopsy confirmed the diagnosis of DLBCL. These case summaries are followed by a review of the clinical presentation, diagnostic approach, and treatment outcomes of PCL.

2.
Mol Cancer ; 14: 93, 2015 Apr 24.
Article in English | MEDLINE | ID: mdl-25907958

ABSTRACT

BACKGROUND: Rb1 is the most frequently mutated gene in the pediatric cancer retinoblastoma, and its loss causes E2F transcription factors to induce proliferation related genes. However, high E2F levels following pRB loss also induce apoptosis-promoting genes as a safeguard mechanism to suppress emergent tumors. Although p53 accumulation and apoptosis induction is believed to be a primary mechanism to eliminate cells with excess E2F activity, p53 deletion doesn't suppress RB/E2F induced apoptosis in vivo in the retina. This prompted us to test the PTEN/PI3K/AKT signaling pathway on RB/E2F apoptosis suppression in vivo, to ascertain if the PI3K pathway may provide a potential avenue for retinoblastoma therapy. METHODS: We developed a mouse model in which Rb1 and Pten were conditionally deleted from retinal progenitor cells using Chx10-Cre, whereas Rbl1 (p107) was constitutively deleted. Pathway components were also tested individually by in vivo electroporation into newborn retinas for an effect on apoptosis and tumor initiation. Mouse retinal tissues were analyzed by immunohistochemistry (IHC) for proliferation, apoptosis, and pathway activation. ShRNAs were used in vitro to assess effects on apoptosis and gene expression. RESULTS: Co-deleting Pten with Rb1 and Rbl1 in mouse retinal progenitor cells (RPCs) causes fully penetrant bilateral retinoblastomas by 30 days and strongly suppresses Rb/E2F-induced apoptosis. In vivo electroporation of constitutively active (ca)-Pik3ca, ca-Akt, or dominant-negative (dn)-Foxo1 into apoptosis prone newborn murine retina with deleted Rb/p107 eliminate Rb/E2F induced apoptosis and induce retinoblastoma emergence. Retinal deletion of Pten activates p-AKT and p-FOXO1 signaling in incipient retinoblastoma. An unbiased shRNA screen focusing on Akt phosphorylation targets identified FOXOs as critical mediators of Rb/E2F induced apoptosis and expression of Bim and p73 pro-apoptotic genes. CONCLUSIONS: These data indicate that we defined a key molecular trigger involving E2F/FOXO functioning to control retinal progenitor cell homeostasis and retinoblastoma tumor initiation. We anticipate that our findings could provide contextual understanding of the proliferation of other progenitor cells, considering the high frequency of co-altered signaling from RB/E2F and PTEN/PI3K/AKT pathways in a wide variety of normal and malignant settings.


Subject(s)
Cell Transformation, Neoplastic/genetics , Gene Deletion , PTEN Phosphohydrolase/genetics , Penetrance , Retinoblastoma Protein/genetics , Retinoblastoma/genetics , Stem Cells/metabolism , Animals , Apoptosis , Class I Phosphatidylinositol 3-Kinases , Disease Models, Animal , Forkhead Box Protein O1 , Forkhead Transcription Factors/metabolism , Mice , Mice, Knockout , Models, Biological , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Retina/cytology , Retinoblastoma/metabolism , Retinoblastoma/pathology , Retinoblastoma Protein/metabolism , Retinoblastoma-Like Protein p107/genetics , Retinoblastoma-Like Protein p107/metabolism , Signal Transduction
SELECTION OF CITATIONS
SEARCH DETAIL
...