Drug news & perspectives最新文献

Advances in the understanding of the intriguing properties of stem cells are prompting the development of new therapeutic approaches in oncology. Stemness is a crucial condition for the homeostasis of the human body. Nevertheless, pathways that regulate self-renewal and cell fate of normal stem cells, such as Wnt and hedgehog, are also involved in the regulation of cancer stem cells and tumor growth and progression, and may thus represent novel therapeutic targets in cancer treatment. In addition, the ability of stem cells to self-renew, migrate to tumor sites and differentiate into multiple cell types makes them perfect candidates for being used as tools for delivering therapeutic genes and proteins and as drug vectors to eliminate malignant cells.

With the images of the earthquake in Haiti still fresh in the memory, and a similar disaster just occurring in Chile, coming again to New Orleans brought back vivid images of the Hurricane Katrina disaster. The city has for the most part recovered from that experience, although molds persist in many historical and ancient buildings, putting allergy sufferers at risk as they breathe in allergens. The city of New Orleans is almost fully restored to its former glory, however, and music again pours out through doors and windows of the French Quarter, calling people in to share drinks and food while clearly stating which specific products contain or may contain traces of nuts, so that people with allergies do not need to run to their epinephrine autoinjector to treat life-threatening anaphylactic attacks. Against this background, and under heavy, rainy and windy skies, the American Academy of Asthma, Allergy and Immunology (AAAAI) held its 2010 annual meeting in the Ernst E. Memorial Convention Center, where 4 days packed with presentations and discussions displaced most other thoughts from the attendees' minds. Indeed, nights on Bourbon Street had never been so uncrowded as they were during the meeting, suggesting that attendees were perhaps sequestered in their hotel rooms, working with new information obtained at the meeting.

There is a constant need for discovering novel sources of compounds with antimicrobial properties, and recent studies support that symbiotic associations involving chemically mediated interactions may be a prominent source of novel compound discovery. Here I review a particularly promising natural system involving such interactions, the multipartite fungus-growing ant symbiosis. This includes a review of the ancient symbiosis involving intricate interactions between at least six symbionts, a review of the efforts that have been made in examining host-symbiont and symbiont-symbiont interactions, as well as the efforts made in identifying and characterizing chemical compounds mediating these interactions. Finally, I outline the prospects for future natural product discoveries from the system, touching on how advances in chemical analyses and whole-genome sequencing techniques will facilitate the process of natural product discovery of biomedical interest.

Prostate cancer is a major health problem with an incompletely understood pathogenesis and etiology. The advent of the prostate-specific antigen (PSA) test in the 1980s caused a revolution in how the disease was detected, but the evidence for PSA as a screening test is deficient. Biomarkers have been investigated, both for detection and discrimination of indolent from aggressive cancers. Refinements to the PSA test have been proposed but for practical and evidence-based reasons none have translated through to widespread clinical use. Of the novel biomarkers, the most promising is the prostate cancer antigen 3 (PCA3) test. New biomarkers to predict aggressive disease are even more contentious. The pathological grade of tumor remains the most powerful biomarker of prognosis. Other proven variables include tumor extent on biopsy and serum PSA. Tissue biomarkers have proven unhelpful due to a variable and biased literature with multiple methodological flaws, but Ki-67 probably shows more promise than any other current tissue biomarker. The recent discovery of a family of fusion genes in the prostate has led to considerable discussion on their prognostic role. Dissection of the genetic basis of the disease may lead to discoveries that will enhance our understanding and aid the search for prognostically valuable biomarkers.

There exists a substantial need to identify new neuropharmacological targets to treat alcohol-dependent individuals. Ghrelin represents a gut-brain peptide, initially discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The existing literature clearly demonstrates that ghrelin affects appetite and food intake. Both animal and human studies provide evidence that ghrelin not only influences hunger but also has a role in the search for rewarding substances, such as alcohol. Animal studies provide evidence that ghrelin stimulates the reward system, acting on specific brain reward nodes, and that ghrelin signaling is required for stimulation of the reward system by alcohol. Human studies show that ethanol acutely affects ghrelin levels. Interestingly, human studies with alcohol-dependent individuals suggest that higher ghrelin levels are associated with higher self-reported measurements of alcohol craving. Altogether, these findings suggest that the ghrelin system plays a role in alcohol dependence. Ghrelin antagonists (i.e., GHS-R1a antagonists and/or inverse agonists) might affect alcohol-seeking behavior, thus having therapeutic potential in alcohol use disorders. Future laboratory and clinical studies testing this hypothesis are warranted.

The emerging increase of antibiotic resistance constitutes an important risk to human health. Two million patients acquire nosocomial infections in U.S. hospitals each year. Of these infections, 60% involve resistant bacteria. In the last decade, only a few new antibiotics with new mechanisms of action were approved by the FDA, but additional costs for preventing the spread of bacteria, side effects and resistance may limit their long-term usefulness. Therefore, the number of therapeutic options is limited and necessitates exploration of novel antibacterial agents/approaches to treat hospital- and community-acquired infections. The challenge in antibacterial research is to find appropriate structurally novel antibacterial agents inhibiting bacterial targets. The XF drug series, having a dicationic porphyrin structure, which is distinct from all other known antibiotic classes, are rapidly active against a broad range of bacteria. Another new strategy is called photodynamic inactivation of bacteria (PDIB), which utilizes visible light in combination with photosensitizing molecules to efficiently kill bacteria via reactive oxygen species. The XF drugs act additionally as photosensitizers to inactivate bacteria upon light activation. This review summarizes the efficacy of the XF series and describes it as a new class of antibacterial agents or as new photo-sensitizers.

Selective antagonism of centrally localized histamine H(3) receptors has been shown to enhance the release of a wide spectrum of important neurotransmitters including acetylcholine, gamma-aminobutyric acid, dopamine and noradrenalin, among others, which play fundamental roles in cognitive processes, in an output-dependent manner. The cognitive-enhancing effects of H(3) receptor antagonists across multiple cognitive domains in a wide number of preclinical cognition models also endow confidence in this therapeutic strategy for the treatment of Alzheimer's disease, attention deficit hyperactivity disorder and the cognitive deficits often expressed in schizophrenia. Recent positive clinical reports are beginning to reinforce this optimism.