Fulminant hyperpyrexia induced by bleomycin

Mild and self-limiting fever following bleomycin use is common, and a fatal hyperpyrexial response occurs rarely. In previously reported cases, such hyperpyrexia occurred either after the initial administration of the drug or during subsequent therapy following an initial pyrexial response. We describe a fatal hyperpyrexial reaction after bleomycin in a patient with T-cell lymphoma who had had no febrile response when she received her initial injection 3 weeks earlier. Since the occurrence of this hyperpyrexial response is unpredictable, health care workers as well as patients and relatives should always be alert to this potentially lethal complication and prompt measures should be taken in any patient who develops fever after bleomycin use.published_or_final_versio

A Brief History, Status, and Perspective of Modified Oligonucleotides for Chemotherapeutic Applications

The advent of rapid and efficient methods of oligonucleotide synthesis has allowed the design of modified oligonucleotides that are complementary to specific nucleotide sequences in mRNA targets. Such modified oligonucleotides can be used to disrupt the flow of genetic information from transcribed mRNAs to proteins. This antisense strategy has been used to develop therapeutic oligonucleotides against cancer and various infectious diseases in humans. This overview reports recent advances in the application of oligonucleotides as drug candidates, describes the relationship between oligonucleotide modifications and their therapeutic profiles, and provides general guidelines for enhancing oligonucleotide drug properties.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143788/1/cpnc0401.pd

Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies

Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20-30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150-300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides