Altered lipid metabolism and aberrant protein translation are strongly associated with cancerous outgrowth; however, the inter-regulation of these key processes is still underexplored in diffuse large B-cell lymphoma (DLBCL). Although fatty acid synthase (FASN) activity is reported to positively correlate with PI3K-Akt-mTOR pathway that can modulate protein synthesis, the precise impact of FASN inhibition on this process is still unknown. Herein, we demonstrate that attenuating FASN expression or its activity significantly reduces eIF4B (eukaryotic initiation factor 4B) levels and consequently overall protein translation. Through biochemical studies, we identified eIF4B as a bonafide substrate of USP11, which stabilizes and enhances eIF4B activity. Employing both pharmacological and genetic approaches, we establish that FASN-induced PI3K-S6Kinase signaling phosphorylates USP11 enhancing its interaction with eIF4B and thereby promoting oncogenic translation.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare and aggressive B‐cell lymphoma strongly associated with human immunodeficiency virus (HIV) infection. The authors conducted a multi‐institutional, retrospective study to describe characteristics and determine prognostic factors in HIV‐associated PBL. METHODS: For this study, the investigators included consecutive, HIV‐positive patients diagnosed between the years 2000 and 2010 whose tumors had a plasmablastic morphology, were cluster of differentiation 20 (CD20)‐negative, and expressed markers of plasmacytic differentiation. RESULTS: Fifty patients from 13 institutions were evaluated. The median age was 43 years, and there was a male predominance. The median count of cells that were positive for CD4 (a glycoprotein expressed on the surface of T‐helper cells, monocytes, macrophages, and dendritic cells) was 206 cells/mm3. At presentation, 90% of patients had extranodal involvement, 69% presented with advanced stage disease, and 27% had oral involvement. Rearrangements of v‐myc myelocytomatosis viral oncogene homolog (MYC) were detected in 41% of the tested patients. Eighty‐five percent of patients received chemotherapy, with 63% receiving cyclophosphamide, doxorubicin, vincristine, and prednisone and 37% receiving more intensive regimens. The complete response (CR) rate was 66%. The median overall survival (OS) was 11 months regardless of the intensity of chemotherapy. In the survival analysis, an Eastern Cooperative Oncology Group performance status ≥2, advanced stage, and MYC rearrangements were associated significantly with a worse outcome, whereas attaining a CR with chemotherapy was associated with a better outcome. CONCLUSIONS: The prognosis of PBL in HIV‐infected individuals remains poor in the highly active antiretroviral therapy era. Intensive chemotherapy regimens do not seem to increase survival in patients with HIV‐associated PBL. Cancer 2012. © 2012 American Cancer Society.

Recent pathologic studies suggest that localized amyloidosis of the larynx is caused by a localized, nonmalignant plasma cell disorder. Because full resection is difficult, we recommend a combination of surgery and radiation therapy to cure this disease.

This is a review of several new approaches developed at or adopted by the Cooperative Prostate Cancer Tissue Resource (CPCTR) to resolve issues involved in tissue microarray (TMA) construction and use. CPCTR developed the first needle biopsy TMA, allowing researchers to obtain 200 or more consecutive cancer sections from a single biopsy core. Using radiographs of original paraffin blocks to measure tissue thickness we developed a method to produce TMAs with a larger number of usable sections. The modular approach to plan TMA construction is also a novel concept wherein TMAs of different types, such as tumor grade TMAs, metastasis TMA and hormone refractory tumors TMA can be combined to form an ensemble of TMAs with expanded research utility, such as support for tumor progression studies. We also implemented an open access TMA Data Exchange Specification that allows TMA data to be organized in a self-describing XML document annotated with well-defined common data elements. It ensures inter-laboratory reproducibility because it offers information describing the preparation of TMA blocks and slides. There are many important aspects that may be missed by both beginners and experienced investigators in areas of TMA experimental design, human subjects protection, population sample size, selection of tumor areas to sample, strategies for saving tissues, choice of antibodies for immunohistochemistry, and TMA data management.