Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our laboratory has recently discovered a novel candidate oncogene, MCT-1, amplified in human T-cell lymphoma and mapped to chromosome Xq22-24. This region is amplified in a subset of primary B-cell non-Hodgkin lymphoma (NHL), suggesting that increased copy number of a gene(s) located in this region confers a growth advantage to some primary human lymphomas. We examined a diverse panel of lymphoid malignancies for the expression of MCT-1. We demonstrated that there are significantly increased levels of MCT-1 protein in a panel of T-cell lymphoid cell lines and in non-Hodgkin lymphoma cell lines. Furthermore, we identified a subset of primary diffuse large B-cell lymphomas that exhibited elevated levels of MCT-1 protein. Interestingly, all transformed follicular lymphomas in our study demonstrated elevated protein levels of MCT-1. There was no detectable MCT-1 protein in leukemic cells from patients with chronic lymphocytic leukemia or in any healthy lymphoid tissue examined. Lymphoid cell lines overexpressing MCT-1 exhibited increased growth rates and displayed increased protection against apoptosis induced by serum starvation when compared with matched controls. We found that MCT-1-overexpressing cells show constitutively higher levels of phosphorylated PKB/Akt protein, especially under serum starvation. Activation of survival pathways may be an additional function of the MCT-1 gene. Our data suggest that high levels of MCT-1 protein may be associated with a high-risk subset of lymphoid neoplasms and may further support the potential role of MCT-1 in promoting human lymphoid tumor development.
 ...
PMID:Expression of the candidate MCT-1 oncogene in B- and T-cell lymphoid malignancies. 1263 15

New therapies that challenge existing paradigms are needed for the treatment of cancer. We report a nanoparticle-enabled therapeutic approach to B-cell lymphoma using synthetic high density lipoprotein nanoparticles (HDL-NPs). HDL-NPs are synthesized using a gold nanoparticle template to control conjugate size and ensure a spherical shape. Like natural HDLs, biomimetic HDL-NPs target scavenger receptor type B-1, a high-affinity HDL receptor expressed by lymphoma cells. Functionally, compared with natural HDL, the gold NP template enables differential manipulation of cellular cholesterol flux in lymphoma cells, promoting cellular cholesterol efflux and limiting cholesterol delivery. This combination of scavenger receptor type B-1 binding and relative cholesterol starvation selectively induces apoptosis. HDL-NP treatment of mice bearing B-cell lymphoma xenografts selectively inhibits B-cell lymphoma growth. As such, HDL-NPs are biofunctional therapeutic agents, whose mechanism of action is enabled by the presence of a synthetic nanotemplate. HDL-NPs are active in B-cell lymphomas and potentially, other malignancies or diseases of pathologic cholesterol accumulation.
 ...
PMID:Biomimetic, synthetic HDL nanostructures for lymphoma. 2334 42

We have previously reported that LITAF is silenced by promoter hypermethylation in germinal centre-derived B-cell lymphomas, but beyond these data the regulation and function of lipopolysaccharide-induced tumour necrosis factor (TNF) factor (LITAF) in B cells are unknown. Gene expression and immunohistochemical studies revealed that LITAF and BCL6 show opposite expression in tonsil B-cell subpopulations and B-cell lymphomas, suggesting that BCL6 may regulate LITAF expression. Accordingly, BCL6 silencing increased LITAF expression, and chromatin immunoprecipitation and luciferase reporter assays demonstrated a direct transcriptional repression of LITAF by BCL6. Gain- and loss-of-function experiments in different B-cell lymphoma cell lines revealed that, in contrast to its function in monocytes, LITAF does not induce lipopolysaccharide-mediated TNF secretion in B cells. However, gene expression microarrays defined a LITAF-related transcriptional signature containing genes regulating autophagy, including MAP1LC3B (LC3B). In addition, immunofluorescence analysis co-localized LITAF with autophagosomes, further suggesting a possible role in autophagy modulation. Accordingly, ectopic LITAF expression in B-cell lymphoma cells enhanced autophagy responses to starvation, which were impaired upon LITAF silencing. Our results indicate that the BCL6-mediated transcriptional repression of LITAF may inhibit autophagy in B cells during the germinal centre reaction, and suggest that the constitutive repression of autophagy responses in BCL6-driven lymphomas may contribute to lymphomagenesis.
...
PMID:LITAF, a BCL6 target gene, regulates autophagy in mature B-cell lymphomas. 2379 61