Incidence of isolated heparin-induced thrombocytopenia and risk of thrombosis by IgG-specific anti-PF4/heparin ELISA.

UNLABELLED: Heparin-induced thrombocytopenia (HIT) antibodies are screened by an enzyme-linked immunosorbent assay (ELISA). Polyspecific ELISA detects anti-PF4/heparin IgG, IgA, and IgM. Recently, anti-PF4/heparin IgG ELISA has been shown to be more specific. However, the impact of using the IgG-ELISA on the incidence of isolated HIT (thrombocytopenia alone without clinically evident thrombosis) and the risk of developing subsequent thrombosis are still unknown. METHODS: A total of 492 consecutive patients with clinically suspected HIT at The University of Texas Southwestern Medical Center and affiliated hospitals were retrospectively reviewed from December 2008 to May 2010. RESULTS: 29 patients (6%) were diagnosed with HIT based on clinical findings and positive ELISA. 19 of the 29 patients (65%) had thrombosis at the time of diagnosis; whereas 10 of the 29 (35%) had only isolated HIT. The ten patients with isolated HIT had serial follow up for at least 3 months. 3 of 10 were treated with direct thrombin inhibitors and 5 of 10 were treated with Warfarin for at least 1 month upon discharge. None of them developed symptoms or signs of thrombosis during 3 months of follow up. CONCLUSION: The incidence of isolated HIT in this study was 35%, which is significantly lower than previously reported in the literature. It is possible that some patients previously thought to have HIT by the poly-specific ELISA assay had false positive results. The improved specificity of the IgG- ELISA appears to reduce the incidence of isolated HIT which may have lower risk of subsequent thrombosis.

Cells lacking IKKα show nuclear cyclin D1 overexpression and a neoplastic phenotype: role of IKKα as a tumor suppressor.

The catalytic subunits of IκB kinase (IKK) complex, IKKα and IKKß, are involved in activation of NF-κB and in mediating a variety of other biological functions. Though these proteins have a high-sequence homology, IKKα exhibits different functional characteristics as compared with IKKß. Earlier, we have shown that cyclin D1 is overexpressed and predominantly localized in the nucleus of IKKα(-/-) cells, indicating that IKKα regulates turnover and subcellular distribution of cyclin D1, which is mediated by IKKα-induced phosphorylation of cyclin D1. Because cyclin D nuclear localization is implicated in tumor development, we examined whether the absence of IKKα leads to tumor development as well. In the current study, we show that IKKα plays a critical role in tumorigenesis. Though IKKα(-/-) MEF cells show a slower anchorage-dependent growth, they are clonogenic in soft agar. These cells are tumorigenic in nude mice. Microarray analysis of IKKα(-/-) cells indicates a differential expression of genes involved in proliferation and apoptosis. Furthermore, analysis of microarray data of human lung cancer cell lines revealed decreased IKKα RNA expression level as compared with cell lines derived from normal bronchial epithelium. These results suggest that IKKα may function as a tumor suppressor gene. Absence of IKKα may induce tumorigenicity by nuclear localization of cyclin D1 and modulating the expression of genes involved in neoplastic transformation.

Taxane vs. taxane: is the duel at an end? A commentary on a phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study.

Taxanes (paclitaxel and docetaxel) comprise a class of mitotic inhibitors which considered highly active chemotherapeutic agents against cancer cells, and have become a cornerstone in the treatment of patients with early and advanced breast cancer. Following the initial generation of trials conducted to prove their efficacy, investigators turned to explore which taxane is superior in terms of efficacy, side effects, and quality of life based on head-to-head comparisons of paclitaxel versus docetaxel containing regimens. Moreover, many trials conducted to evaluate the optimal taxane dosing and schedule. This commentary discusses the ERASME 3 trial which compared the quality of life after four courses of doxorubicin combination with either paclitaxel or docetaxel, and also, it reviews all trials compared paclitaxel to docetaxel in both early and metastatic disease settings, in terms of efficacy, dosing, schedule, and toxicity profile.