Omics Screening for Pharmaceutical Efficacy and Safety in Clinical Practice.
Omics Screening for Pharmaceutical Efficacy and Safety in Clinical Practice.
Filed under: Drug and Alcohol Rehabilitation
J Pharmacogenomics Pharmacoproteomics. 2012 Mar 16; S5:
Monte AA, Vasiliou V, Heard KJ
As molecular techniques have improved, investigators have attempted to improve pharmaceutical efficacy and safety by making trait associations with genomic, epigenomic, transcriptomic, proteomic, and metabolomic polymorphisms. The ‘omics era has seen screening assays for pharmaceutical efficacy and safety translated into clinical practice. This manuscript will discuss each ‘omic field and the screening assays available to the clinician. While success has been demonstrated in each ‘omic field, many challenges remain. Assays need wider availability, predictive values remain low, and costs remain high. In order for clinicians to realize improved efficacy and safety due ‘omic screens, development of improved techniques, combining of ‘omic assays, and increased clinical utilization is necessary. This is an exciting time for investigators and clinicians that desire improved pharmaceutical therapy.
HubMed – drug
Syntheses of Siderophore-Drug Conjugates Using a Convergent Thiol-Maleimide System.
Filed under: Drug and Alcohol Rehabilitation
ACS Med Chem Lett. 2012 Oct 11; 3(10): 799-803
Juárez-Hernández RE, Miller PA, Miller MJ
Three siderophore-drug conjugates (sideromycins) were synthesized by preparation of a maleimide linked derivative of the siderophore desferrioxamine B and reacting the corresponding Ga(3+)-complex with freshly prepared thiol-containing antibiotics: loracarbef, ciprofloxacin and nadifloxacin. The conjugates and their synthetic precursors were tested against a broad panel of bacteria and were found to display Gram-positive selective, growth inhibitory activity (µM) indicating that this approach is suitable for the convergent synthesis and screening of novel sideromycins.
HubMed – drug
The STAT5 Inhibitor Pimozide Displays Efficacy in Models of Acute Myelogenous Leukemia Driven by FLT3 Mutations.
Filed under: Drug and Alcohol Rehabilitation
Genes Cancer. 2012 Jul; 3(7-8): 503-11
Nelson EA, Walker SR, Xiang M, Weisberg E, Bar-Natan M, Barrett R, Liu S, Kharbanda S, Christie AL, Nicolais M, Griffin JD, Stone RM, Kung AL, Frank DA
Activation of the transcription factor STAT5 is essential for the pathogenesis of acute myelogenous leukemia (AML) containing the FLT3 internal tandem duplication (ITD) mutation. FLT3 ITD is a constitutively active tyrosine kinase that drives the activation of STAT5, leading to the growth and survival of AML cells. Although there has been some success in identifying tyrosine kinase inhibitors that block the function of FLT3 ITD, there remains a continued need for effective treatment of this disease. We have identified the psychotropic drug pimozide as an effective inhibitor of STAT5 function. Pimozide inhibits the tyrosine phosphorylation of STAT5, leading to the death of AML cells through the induction of apoptosis. Pimozide shows a combinatorial effect with the tyrosine kinase inhibitors midostaurin (PKC412) and sunitinib in the inhibition of STAT5 tyrosine phosphorylation and the induction of apoptosis. Significantly, pimozide reduces the tumor burden in a mouse model of FLT3-driven AML. Therefore, identifying STAT5 inhibitors may provide a new avenue for the treatment of AML, and these may be effective alone or in combination with tyrosine kinase inhibitors.
HubMed – drug
Cancer genes in lung cancer: racial disparities: are there any?
Filed under: Drug and Alcohol Rehabilitation
Genes Cancer. 2012 Jul; 3(7-8): 467-80
El-Telbany A, Ma PC
Cancer is now known as a disease of genomic alterations. Mutational analysis and genomics profiling in recent years have advanced the field of lung cancer genetics/genomics significantly. It is becoming more accepted now that the identification of genomic alterations in lung cancer can impact therapeutics, especially when the alterations represent “oncogenic drivers” in the processes of tumorigenesis and progression. In this review, we will highlight the key driver oncogenic gene mutations and fusions identified in lung cancer. The review will summarize and report the available demographic and clinicopathological data as well as molecular details behind various lung cancer gene alterations in the context of race. We hope to shed some light into the disparities in the incidence of various genetic mutations among lung cancer patients of different racial backgrounds. As molecularly targeted therapy continues to advance in lung cancer, racial differences in specific genetic/genomic alterations can have an important impact in the choices of therapeutics and in our understanding of the drug sensitivity/resistance profile. The most relevant genes in lung cancer described in this review include the following: EGFR, KRAS, MET, LKB1, BRAF, PIK3CA, ALK, RET, and ROS1. Commonly identified genetic/genomic alterations such as missense or nonsense mutations, small insertions or deletions, alternative splicing, and chromosomal fusion rearrangements were discussed. Relevance in current targeted therapeutic drugs was mentioned when appropriate. We also highlighted various targeted therapeutics that are currently under clinical development, such as the MET inhibitors and antibodies. With the advent of next-generation sequencing, the landscape of genomic alterations in lung cancer is expected to be much transformed and detailed in upcoming years. These genomic landscape differences in the context of racial disparities should be emphasized both in tumorigenesis and in drug sensitivity/resistance. It is hoped that such effort will help to diminish racial disparities in lung cancer outcome in the future.
HubMed – drug
Punches Salvation Army worker in the face – FLORISSANT, MO (KMOV)– A man who allegedly punched and stole over 00 from a female employee outside a Salvation Army thrift store in Florissant on Tuesday has been arrested and charged for the crime. Edward J. Mitchell, 25, was arrested on Wednesday and charged with second-degree robbery. Police said the incident happened at the Salvation Army store in the Paddock Hills Plaza shopping center around 8:30 pm According to reports, a female employee was heading towards a vehicle to deposit money in a bank when a regular customer approached and asked for a ride. Authorities said after they got in the car, the suspect punched the woman and grabbed 00 in store receipts before fleeing the scene. Store officials said the money was intended to fund drug and alcohol rehabilitation programs. The administrator of the Salvation Army’s adult rehabilitation center, Major Kendall Mathews, said a criminal could not get much lower than to steal from them. He said they will be soliciting donations soon to pay for surveillance cameras to be installed at all seven of their thrift stores. Officials did not say if the stolen money was recovered after the suspect was arrested.
Find More Drug And Alcohol Rehabilitation Information…