Altered glutamine metabolism in platinum resistant ovarian cancer.

Ovarian cancer is characterized by an increase in cellular energy metabolism, which is predominantly satisfied by glucose and glutamine. Targeting metabolic pathways is an attractive approach to enhance the therapeutic effectiveness and to potentially overcome drug resistance in ovarian cancer. In platinum-sensitive ovarian cancer cell lines the metabolism of both, glucose and glutamine was initially up-regulated in response to platinum treatment.

Evaluation and comparison of a new DOTA and DTPA-bombesin agonist in vitro and in vivo in low and high GRPR expressing prostate and breast tumor models.

We evaluated and compared a new bombesin analog [Tyr-Gly5, Nle(14)]-BBN(6-14) conjugated to DOTA or DTPA and radiolabeled with In-111 in low and high GRPR expressing tumor models. Both peptides were radiolabeled with high radiochemical purity and specific activity. In vitro assays on T-47D, LNCaP and PC-3 cells showed that the affinity of peptides is similar and a higher binding and internalization of DOTA-peptide to PC-3 cells was observed.

Brn-3a transcription factor blocks p53-mediated activation of proapoptotic target genes Noxa and Bax in vitro and in vivo to determine cell fate.

The Brn-3a POU transcription factor is associated with survival and the differentiation of sensory neuronal cells during development. Brn-3a mediates its effects either by the direct regulation of target genes or indirectly upon interaction with proteins such as p53. Brn-3a differentially regulates p53-mediated gene expression and modifies its effect on cell fate.

Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis.

The Brn-3a transcription factor is critical for survival and differentiation of sensory neurons derived from neural crest cells (NCC). Interaction of Brn-3a with p53 results in differential effects on target gene expression, which profoundly affects fate of neuronal cells. Here we demonstrate colocalization of p53 in a subset of Brn-3a-positive NCC-derived cells fated for the sensory neuronal lineage.

Analysis of the Fanconi anaemia complementation group A gene in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults. Around 10-15% of individuals with recessively inherited Fanconi anaemia (FA) develop AML. FA is one of a group of recessive syndromes characterized by excessive spontaneous chromosomal breakage in which heterozygote carriers appear to display an increased risk of cancer and there is some indirect evidence that FA carriers may also be at increased risk of AML.

ATM mutations are rare in familial chronic lymphocytic leukemia.

It is now recognized that a subset of B-cell chronic lymphocytic leukemia (CLL) is familial. The genetic basis of familial CLL is poorly understood, but recently germ line mutations in the Ataxia Telangiectasia (ATM) gene have been proposed to confer susceptibility to CLL. The evidence for this notion is, however, not unequivocal.