Published ahead of print in the online edition of the journal PNAS, the study establishes using segments of genetic material called antisense oligonucleotides — ASOs — to block the buildup and selectively degrade the toxic RNA that contributes to the most common form of ALS, without affecting the normal RNA produced from the same gene. …
The researchers donned their thinking caps to explain how neural stem and progenitor cells differentiate into neurons and related cells called glia. Neurons transmit information through electrical and chemical signals; glia surround, support and protect neurons in the brain and throughout the nervous system. Glia do everything from holding neurons in place to supplying them with nutrients and oxygen to protecting them from pathogens. …
The studies involved controlling the actions of microRNAs, tiny pieces of RNA that were once considered to be "junk" but are now known to fine-tune gene activation and expression. The researchers showed that treating mice with short RNA strands that precisely target and inhibit microRNAs ("antimicroRNAs") can stop the aberrant growth of blood vessels ("neovascularization"). It is this abnormal proliferation of vessels that exacerbates vision loss in neovascular eye diseases like "wet" macular degeneration and diabetic retinopathy, two of the leading causes of blindness. Described in the cover story of the November issue of the Journal of Clinical Investigation, the microRNA treatments blocked aberrant vessel growth without damaging existing vasculature or neurons in three separate models of neovascular eye disease — a proof-of-principle that suggests future treatment based on the same approach may be effective in humans…
Published online in Cell Metabolism, the Ludwig Cancer Research study also reveals how the aggressive brain cancer glioblastoma harnesses the mechanism to resist targeted therapies that should disrupt this capability — known as the Warburg effect — and suggests how such resistance might be overcome. In detailing the molecular circuitry of the phenomenon, the researchers uncover several possible targets for new drugs that might disrupt cancer cell metabolism to destroy tumors. "Cancer and other fast-growing cells extract energy from glucose using a process that ordinarily kicks in only when oxygen is in short supply," explains Ludwig scientist Paul Mischel, MD, who is based at the University of California, San Diego School of Medicine…
The investigators identified STAG2 as one of the most commonly mutated genes in bladder cancer, particularly in tumors that do not spread. The finding suggests that checking the status of the gene may help identify patients who might do unusually well following cancer treatment, says the study’s senior investigator, cancer geneticist Todd Waldman, MD, PhD, a professor of oncology at Georgetown Lombardi. "Most bladder cancers are superficial tumors that have not spread to other parts of the body, and can therefore be easily treated and cured. However, a small fraction of these superficial tumors will recur and metastasize even after treatment," he says. …
The journal includes a comment by David A. Brenner, from the University of California, who is a leader in the field of gastroenterological research, specializing in diseases of the liver. …
Writing in the October 7 Early Edition of PNAS, Lars Eckmann, MD, professor of medicine, and colleagues describe creating more than 650 new compounds by slightly altering structural elements of metronidazole and other 5-nitromidazoles (5-NI), a half-century-old class of antimicrobial drugs used to combat everything from an ulcer-causing stomach bacterium to a gut-churning protozoan found in contaminated water. "The basic building blocks of 5-NI drugs are the same for all. We decorated around them, adding extra molecular pieces to change their shapes and sizes," said Eckmann, who published the paper with colleagues at UC San Diego, The Scripps Research Institute and the Queensland Institute of Medical Research in Australia…
During the four-year Ella Binational Breast Cancer Study, scientists assessed the association between reproductive factors and tumors subtypes in 1,041 Mexican and Mexican-American female cancer patients. …
The scientists’ findings, suggesting that potentially lethal castration-resistant prostate carcinoma cells already exist in some cancer patients at the very early stages of their disease, will be published by PLOS ONE on September 25, 2013. The work describes the isolation and propagation of the earliest prostate cancer cells yet identified in human prostate cancer biopsy samples, allowing the detailed molecular characterization of these very early-stage cancer cells, including analysis of gene expression and mutations. …
"These structural details should help us understand more precisely how HIV infects cells, and how we can do better at blocking that process with next-generation drugs," said Beili Wu, PhD, professor at the Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences. Wu was the senior investigator for the study, which was published in Science Express on September 12, 2013. The study, which focused on the CCR5 receptor, was supported by both US and Chinese research funding agencies. "International collaborations like this one are increasingly needed to solve big problems in science," said study co-author Raymond C…