Citations

Abstract Acute eosinophilic pneumonia is characterized by acute respiratory insufficiency, hypoxemia, fever, diffuse radiographic infiltrates, and eosinophilia in bronchoalveolar lavage fluid (BALF) or lung biopsies in the absence of infection, atopy, or asthma. A rapid response to corticosteroids is characteristic. We reviewed our experience with nine cases of acute lung disease with histologic features of acute and organizing diffuse alveolar damage and prominent interstitial and alveolar eosinophils in order to determine whether this pathology was characteristic of acute eosinophilic pneumonia. The mean age of the patients (four men and five women) was 53 yr (range: 33 to 71 yr). They presented with 2 to 21 d of dyspnea, cough, myalgias, and fever. All were hypoxic and had bilateral infiltrates on chest radiographs. Peripheral blood eosinophilia was present in four of eight patients (peripheral blood count unavailable for one patient). All patients were treated with high-dose corticosteroids with a mean time to symptomatic and radiographic improvement of 4 d. Seven of the nine patients enrolled in the study are alive without relapse; one patient has a mild deficit in diffusing capacity, and one patient died of a myocardial infarct while improving on therapy. The presence of eosinophils in cases of acute respiratory insufficiency due to diffuse alveolar damage (DAD) should suggest the diagnostic possibility of acute eosinophilic pneumonia. Acute eosinophilic pneumonia should be distinguished from other causes of DAD because of important differences in natural history.

Abstract We previously utilized a whole genome tiling array to identify novel transcripts which had altered expression in response to the genotoxic effects of the tobacco carcinogen NNK. Our goal was to identify novel long stress-induced non-coding transcripts that could play important regulatory roles within cells and be important targets of alteration during cancer formation. Utilizing very stringent criteria, we examined all transcriptionally active regions that had altered expression in response to NNK treatment and identified a group of 12 transcripts, termed long stress-induced noncoding trancripts (LSINCTs). These novel long non-coding transcripts are between 2 and 4 Kb in length and do not contain any open reading frames or have homology to any mRNAs. 11 LSINCTs are intergenically located and one LSINCT is intragenically located within the genome. We found LSINCTs to be more highly expressed in more proliferative normal human tissues and to be frequently over-expressed in a number of different cancers including breast cancer. We studied one of these transcripts in greater detail, LSINCT5. We found LSINCT5 to be a polyadenylated nuclear transcript of exactly 2,647 base pairs. It is highly over-expressed in both breast and ovarian cancers and knocking down its' expression in either a breast or ovarian cancer cell line resulted in decreased cellular proliferation. We further compared gene expression in the breast cancer cell line, MCF7, before and after knocking down LSINCT5 expression and identified a number of genes whose expression changed more than 2-fold in response. Two of the genes identified were the gene for the major paraspeckle protein PSPC1, and another long non-coding transcript NEAT1. Paraspeckles are irregularly shaped compartments found in the nucleus' interchromatin space. Paraspeckles are RNA-protein structures formed by the interaction of NEAT1 and members of the Drosophila Behavior Human Splicing family of proteins including PSPC1. Paraspeckles appear to be critical to the control of gene expression through the nuclear retention of certain species of RNA. It is though that paraspeckles and their components play a role in controlling gene expression during a number of different cellular processes including differentiation, viral infection and stress responses. Using RNA fluorescent in situ hybridization, we found LSINCT5 to co-localize with NEAT1 within the nucleus. Hence, this novel stress-induced transcript may be another important long non-coding transcript that is involved in the normal cellular function of the paraspeckles. Citation Format: David I. Smith, Silva M. Jessica. Long stress-induced non-coding transcripts (LSINCTs) and Cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A1.

Key Points Lenalidomide consolidation repairs T-cell immune synapses in CLL patients. Lenalidomide consolidation improved the quality of response in CLL patients treated with chemoimmunotherapy.