A case report of cecal plasmablastic lymphoma in a HIV-negative patient

Plasmablastic lymphoma (PBL) is a unique type of diffuse proliferation of large neoplastic lymphoid cells most of which resemble B immunoblasts, but all tumor cells show the immunophenotype of plasma cells. It has a strong predilection for jaw and oral cavity in HIV-positive patients. Incidences of extraoral location of this tumor is increasingly being recognized especially in HIV-negative patients for example, stomach, jejunum, omentum, anorectum, lungs, testes, soft tissues, lymph nodes, bone marrow, skin, and central nervous system. We present a case of PBL found in cecum in an HIV-negative patient. It was accompanied by lung and lymph node involvement and presented as abdominal mass. This is only the second reported case of PBL originating in cecum.     

Inhibition of epidermal growth factor receptor-mediated signaling by "Combi-triazene" BJ2000, a new probe for Combi-Targeting postulates

The Combi-Targeting concept postulates that a molecule termed combi-molecule (C-molecule) with binary epidermal growth factor receptor (EGFR) targeting/DNA-damaging properties and with the ability to be hydrolyzed to another EGFR inhibitor should induce sustained antiproliferative activity in cells overexpressing EGFR. Because we postulate that the EGFR affinity of the C-molecule and that of its hydrolytic metabolites are critical parameters for sustained potency against EGFR-overexpressing cells, we synthesized BJ2000 (IC(50) = 0.1 microM, competitive binding at ATP site), a novel C-molecule that can decompose into a 6-amino-4-anilinoquinazoline FD105 (IC(50) = 0.2 microM). Studies using the EGFR-overexpressing A431 cells revealed that BJ2000 could damage DNA and block epidermal growth factor-stimulated EGFR autophosphorylation by a partially irreversible mechanism. Blockade of EGFR autophosphorylation subsequently induced inhibition of mitogen-activated protein kinase activation and c-fos gene expression. Enzyme-linked immunosorbent assay and growth factor-mediated stimulation of proliferation assays in the EGFR-expressing NIH3T3HER14 demonstrated the preferential EGFR-targeting properties of BJ2000, and more importantly suggest that blockade of EGFR phosphorylation by this drug translate into significant growth inhibitory effects. These properties culminated into irreversible antiproliferative effects as confirmed by a sulforhodamine B assay. Five days after a 2-h treatment, BJ2000 retained significant antiproliferative effect in A431 cells, whereas its reversible metabolite FD105 almost completely lost its activity. This result in toto lend support to the Combi-Targeting concept according to which a molecular conjugate kept small enough to interact with EGFR and designed to degrade into another inhibitor of the same target plus a DNA-damaging species may induce sustained growth inhibitory effect in EGFR-overexpressing cells.