Ashish Aggarwal

Amisulpride is an atypical antipsychotic used for the management of schizophrenia and other conditions like dysthymia. It has also been used for the management of bipolar disorders as an add on therapy. Here, we report a patient of schizophrenia who developed a manic episode while on amisulpride.

To the Editors: Schizophrenia is often first diagnosed in early adulthood, but in about one third of the cases, the disorder already developed during adolescence.1 Adolescent-onset schizophrenia is considered to be associ-ated with a particularly poor prognosis,2 which underscores ...

The work presented here was initiated to explore the mechanisms underlying vinorelbine resistance in two previously established murine leukemia P388 cell lines (N.63 and N2.5). IC50 measurements demonstrated that the vinorelbine-resistant cell line N.63 was sensitive to both vinblastine and vinflunine. In addition, vinorelbine-resistant cell line N2.5 retained sensitivity to vinflunine. We used flow cytometry with propidium iodide to measure G2/M arrest in response to drug treatment. Annexin V labeling was used as a marker of apoptosis and JC-1 dye labeling as a marker of mitochondrial membrane depolarization to explore differential responses that might help explain the absence of cross resistance to vinflunine. At equipotent (10X IC50) doses, after 8 h of drug treatment, vinflunine induced G2/M arrest in a significantly larger fraction of vinorelbine- resistant cells compared to vinorelbine. At the same drug doses, at 16 h after initiation of drug treatment, vinflunine induced a statistically significant greater apoptotic response and mitochondrial depolarization. The mitochondrial depolarization at 16 h was confirmed by Western blotting that showed release of cytochrome c. Comparison of apoptotic and mitochondrial depolarization responses in vinorelbine-resistant cells upon exposure to vinorelbine, vinblastine and vinflunine demonstrated the following pattern of drug activity: vinflunine > vinblastine > vinorelbine, confirming the importance of a antimitotic-induced mitochondria-mediated pathways in these P388 cell lines. We conclude that vinflunine may be preferred for treatment of specific cancers compared to other vinca alkaloids due to its enhanced effects on apoptotic pathways that follow G2/M arrest.

Antimitotic drugs are chemotherapeutic agents that bind tubulin and microtubules. Resistance to these drugs is a major clinical problem. One hypothesis is that the cellular composition of tubulin isotypes may predict the sensitivity of a tumor to antimitotics. Reliable and sensitive methods for measuring tubulin isotype levels in cells and tissues are needed to address this hypothesis. Quantitative measurements of tubulin isotypes have frequently relied upon inferring protein amounts from mRNA levels. To determine whether this approach is justified, protein and mRNA levels of β-tubulin isotypes from 12 human cancer cell lines were measured. This work focused on only β-tubulin isotypes because we had readily available monoclonal antibodies for quantitative immunoblots. The percentage of β-tubulin isotype classes I, II, III, and IVa + IVb mRNA and protein were compared. For β-tubulin class I that comprises >50% of the β-tubulin protein in 10 of the 12 cell lines, there was good agreement between mRNA and protein percentages. Agreement between mRNA and protein was also found for β-tubulin class III. For β-tubulin classes IVa + IVb, we observed higher protein levels compared to mRNA levels. β-Tubulin class II protein was found in only four cell lines and in very low abundance. We conclude that quantitative Western blotting is a reliable method for measuring tubulin isotype levels in human cancer cell lines. Inferring protein amounts from mRNA levels should be done with caution, since the correspondence is not one-to-one for all tubulin isotypes. Cell Motil. Cytoskeleton 2006. © 2005 Wiley-Liss, Inc.