Background. Disulfiram, an alcohol aversion agent, has been in use for .50 years. Numerous authors have reported an anticancer effect of this drug in vitro and in mouse models. More recently, several reports have claimed that disulfiram also possesses anti-stem cell activity. We set out to obtain initial data regarding the safety of combining this drug with chemotherapy and the possible effectiveness of disulfiram in a combination regimen in non-small cell lung cancer (NSCLC). Methods. This phase II, multicenter, randomized, doubleblinded study assessed the safety and efficacy of adding of disulfiram to cisplatin and vinorelbine for six cycles. Newly diagnosed NSCLC patients were recruited. Patients with either stage IV or what was considered at the time "wet IIIb" (since 2009, these patients have been considered stage IV) were recruited. The patients were treated with only chemotherapy, and none were treated with either surgery or chemoradiation. Disulfiram was administered at a dose of 40 mg three times daily. Results. Forty patients were treated for more than two cycles, half with and half without disulfiram, which was well tolerated. An increase in survival was noted for the experimental group (10 vs. 7.1 months). Interestingly, there were only two longterm survivors, both in the disulfiram group. Conclusion. The addition of disulfiram to a combination regimen of cisplatin and vinorelbine was well tolerated and appeared to prolong survival in patients with newly diagnosed non-small cell lung cancer. The results from this small study seem encouraging enough forassessment inlarger trials.Disulfiramis an inexpensive and safe drug; if its addition to chemotherapy could be shown to
Short-duration pazopanib was generally well tolerated and demonstrated single-agent activity in patients with early-stage NSCLC. Several target genes were dysregulated after pazopanib treatment, validating target-specific response and indicating a persistent pazopanib effect on lung cancer tissue. Further clinical evaluation of pazopanib in NSCLC is planned.
Vav1 is a signal transducer protein expressed exclusively in the haematopoietic system, where it plays a pivotal role in growth factor-induced differentiation and proliferation. Vav1 couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, leading to cell differentiation and/or proliferation. Vav1 was originally detected as an oncogene, but its involvement in human malignancies has not been reported thus far. We report here that Vav1 is expressed in a neuroblastoma cell line, SK-N-MC. Molecular analysis indicated that there are no gross rearrangements or mutations in the Vav1 gene in SK-N-MC cells. Vav1 protein from SK-N-MC cells was similar to wild-type Vav1 in apparent molecular weight, phosphorylation state, and ability to associate with active EGFR. We also analysed the expression of Vav1 in 42 specimens of human neuroblastoma. Vav1 was expressed in the majority of these tumours. Our results suggest that Vav1 may play a role in the neoplastic process in a subset of neuroblastomas.
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