Lee J.,Korea Advanced Institute of Science and Technology |
Chung D.,Korea Advanced Institute of Science and Technology |
Chang S.,Discovery Laboratory |
Jeong J.,Korea Advanced Institute of Science and Technology
Brain Imaging and Behavior | Year: 2012
Gender differences in temporo-spectral EEG patterns during verbal cognitive performance are poorly understood. The aim of the present study was to examine whether the event-related dynamics of EEG differ between genders during the performance of Navon letter identification tasks (NLITs). To this end, the EEG patterns of 40 subjects were recorded during the NLIT performance. We compared behavioral outcomes, event-related temporo-spectral dynamics, and source distribution of neural oscillations within cortical regions of male and female subjects. We found that male subjects exhibited greater induced neural activities than female subjects in right temporo-parietal areas at theta and alpha frequency bands. Source imaging for the time ranges at which maximal gender differences were observed revealed gender-dependent estimated current densities in the right posterior temporal regions. These gender differences can be explained by the existence of distinct, gender-specific hemispheric specialization. Thus, gender differences should be considered during behavioral tasks and electrophysiological measurements. © 2012 Springer Science+Business Media, LLC.
News Article | January 7, 2016
UCLA scientists have developed a promising novel method to treat gynecologic tumors. The approach focuses on a protein called p53, which is commonly mutated in women who have high-grade serous ovarian cancer, the deadliest form of reproductive cancer. In many women with the disease, the cancer is very advanced by the time it is diagnosed and is therefore difficult to treat. The discovery was the result of a three-year study co-led by David Eisenberg and Dr. Sanaz Memarzadeh, members of the UCLA Jonsson Comprehensive Cancer Center. The findings, which were published online in the journal Cancer Cell, could ultimately lead to new targeted therapies for many other types of cancer carrying similar p53 mutations. P53 is known as the “guardian of the genome.” It prevents damaged cells from reproducing by stopping their growth until the damage is repaired or, if the damage cannot be reversed, promotes cell death. But mutations, which are found in 96 percent of patients with high-grade serous ovarian tumors, can cause p53 to form clumps, or “aggregates,” which impair the protein’s normal function. As a result, the damaged cells are able to multiply uncontrollably, which can lead to cancer. The UCLA scientists developed and tested a peptide called ReACp53, which penetrates cancer cells and prevents mutated p53 from clumping together. The technique restores normal p53 function, causing death of the ovarian cancer cells. “Our lab has worked for 15 years on the protein aggregates that cause amyloid diseases such as Alzheimer’s and Parkinson’s disease,” said Eisenberg, who also is a professor of biological chemistry and a member of UCLA–DOE Institute. “These aggregates are organized as fibers that are 500 times smaller than the width of a hair, which is quite a challenge.” “This approach was originally developed for neurodegenerative diseases and we are now applying it to cancer therapy,” said Alice Soragni, a UCLA postdoctoral scholar in Eisenberg’s lab and first author of the study. “We identified the sticky segments of p53 that cause the protein to clump by using a computer algorithm, determined their structure and then designed ReACp53 to block this process,” Soragni added. “This can keep the protein from clumping so it can do its job and kill cancer cells.” The researchers isolated tumor cells from patients and grew them to reproduce small tumors in the lab dish. The “mini-tumors” are extremely useful for drug development because they faithfully replicate several features of the original cancer. “The results were remarkable, with significant shrinkage in patient-derived tumors,” said Memarzadeh, who also is a UCLA associate professor of obstetrics and gynecology the director of the G.O. Discovery Laboratory at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. She added that the approach produced no obvious side effects in a physiological model and that ReACp53 was very well tolerated. More than 80 percent of women with advanced stage high-grade serous ovarian cancer experience relapses even after repeated surgeries and multiple rounds of chemotherapy, and this effective new approach to treat the disease could be a major step forward in preventing cancer from returning. More than 15,000 women a year in the U.S. die from all types of ovarian cancer. The study was funded by the UCLA Jonsson Cancer Center Foundation, the Elsa U. Pardee Foundation, the Howard Hughes Medical Institute and the National Institutes of Health. UCLA has licensed ReACp53 and the technology used to develop it to ADRx, Inc., a biopharmaceutical company co-founded by Eisenberg.
Proof of Concept Study Published in Clinical Microbiology and Infection Reports the Benefit of PathoQuest NGS Based Metagenomics Test to Identify Clinically Relevant Pathogens in Immunocompromised Patients Suspected of Infection
News Article | February 22, 2017
PARIS--(BUSINESS WIRE)--PathoQuest, a biotechnology company spun out from Institut Pasteur, announced today the on-line publication of results from the PATHOQUEST-1 study. The full manuscript, titled Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study, is available in Clinical Microbiology and Infection. PATHOQUEST-1 (NCT02007642) is an observational proof-of-concept study conducted in 2 reference hospitals -Necker-Enfants Malades and Européen-Georges Pompidou hospitals- (Paris, France). It enrolled 101 immunocompromised patients suspected of infection, and compared the performance of PathoQuest’s NGS-based metagenomics test and the conventional diagnostic pipeline to identify pathogens. PATHOQUEST-1 was run with a prototype version of the CE-IVD iDTECT Blood™ test. The 3 key components of the test -i.e. sample preparation, sequencing and data analysis- have been improved to reach the level of performance and validation required for CE marking. Specific steps of the test process have been patented or copyrighted and are proprietary. “This study demonstrates that the metagenomic test identified a relevant pathogen in more patients in a difficult-to-diagnose population than the conventional pipeline,” said Marc Eloit, PhD, Pathogen Discovery Laboratory at Institut Pasteur, Paris, France, a study investigator and founder and scientific advisor for PathoQuest. “These data underscore the potential of NGS to improve detection and identification of pathogens in routine diagnostic testing of biological samples including blood which is technically challenging.” “With the broader availability of sequencing platforms in clinical microbiology laboratories, metagenomics-based testing will increase our chances of identifying pathogens in infected patients and allow a better management of infectious diseases, especially in immunocompromised patients where the current diagnostic pipeline frequently fails to identify a responsible pathogen.” added Xavier Nassif, MD, PhD, Head of the Clinical Microbiology Laboratory, Necker-Enfants Malades Hospital, Paris, France, and a study investigator. “These study results should pave the way for such developments”. Immunocompromised patients have an impaired or weakened immune system resulting in an increased susceptibility to infection and reduced ability to efficiently respond to such situations. This inability to fight infections can be caused by a number of diseases (such as cancer or leukemia), or drugs (such as anti-cancer therapies or long term immune-suppressants used to prevent organ rejection). Prevalence of these conditions is increasing. Identifying the causative pathogen(s) in immunocompromised patients suspected of infection can be challenging. For instance, only 20 to 30% of blood cultures, the conventional diagnostic test in this clinical situation, are positive for a pathogen in patients developing febrile neutropenia following chemotherapy or stem cell transplantation (1,2,3). In most other cases, the infection remains of unknown origin, leading to the systematic use of broad spectrum instead of targeted antibiotics. Moreover, these patients are more susceptible to viruses or other microorganisms which have limited or no pathogenicity for non-immunocompromised subjects. Many also receive prophylactic or recurrent courses of antibiotics, making their pathogens difficult to grow in the lab. 1 Gyamarti et al, Scientific Reports, 2016 2 Freifeld et al, CID 2011 3 Gea-Banacloche, Hematology Am Soc Hematol Educ Program. 2013 PathoQuest, a spin out of Institut Pasteur, is a biotechnology company offering a game changing metagenomics approach to improving pathogen detection in biological samples that overcomes the current limitation associated with pathogen detection. PathoQuest’s technology combines a Next-Generation Sequencing (NGS) platform and a proprietary sample preparation process which is applicable to several types of samples with a proprietary pathogen genome sequence database and automated analysis pipeline. The company’s solution provides microbiologists and clinicians with a comprehensive analysis covering all known clinically relevant human pathogens. PathoQuest has developed iDTECT™ Blood Test, the first and only clinical CE IVD metagenomic test in infectious disease. Using a single blood sample, the test provides clinicians and microbiologists with an improved method for detecting pathogens, particularly for immunocompromised patients with suspected infections. This new molecular diagnostic test should improve antibiotic stewardship and lead to better patient care through precision medicine. Based on the company’s technological platform, PathoQuest also offers biopharmaceutical companies a disruptive approach to secure production of biologics like vaccines and recombinant proteins. PathoQuest’s solution is currently being utilized by several major biopharma companies for this purpose. To learn more about PathoQuest, visit www.pathoquest.com
Rajesh A.,Discovery Laboratory |
Sharma G.V.M.,Discovery Laboratory |
Damera K.,Discovery Laboratory
Tetrahedron Letters | Year: 2014
An efficient synthesis of C1-C12 fragment of amphotericin B is described. The synthesis is based on asymmetric dihydroxylation and cross-metathesis reactions. © 2014 Elsevier Ltd. All rights reserved.
Rao R.N.,Discovery Laboratory |
Prasad K.G.,Discovery Laboratory |
Naidu C.G.,Discovery Laboratory |
Saida S.,Discovery Laboratory |
Agwane S.B.,Indian Institute of Chemical Technology
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013
A rapid and highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of doxofylline on rat dried blood spots and urine was developed and validated. The chromatographic separation was achieved on a reverse phase C18 column (250mm×4.6mm, 5μm), using 20mM ammonium acetate (pH adjusted to 3.5 with trifluoroacetic acid) and acetonitrile (75:25 v/v) as a mobile phase at 25°C. LC-MS detection was performed with selective ion monitoring using target ions at m/z 267 and m/z 195 for doxofylline and caffeine used as internal standard respectively. The calibration curve showed a good linearity in the concentration range of 1-5000ng/mL. The effect of hematocrit on extraction of doxofylline from DBS was evaluated. The mean recoveries of doxofylline from DBS and urine were 93.46 and 89.86% respectively. The intra and inter-day precisions were less than 4.28% in DBS as well as urine. The limit of detection and quantification were 0.24 and 0.84ng/mL in DBS and 0.28 and 1.00ng/mL in urine samples respectively. The method was validated as per ICH guidelines and successfully applied to a pharmacokinetic study of doxofylline in rats. © 2013 Elsevier B.V.
PubMed | Discovery Laboratory
Type: | Journal: Journal of pharmaceutical and biomedical analysis | Year: 2013
A rapid and highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of doxofylline on rat dried blood spots and urine was developed and validated. The chromatographic separation was achieved on a reverse phase C18 column (250 mm 4.6 mm, 5 m), using 20 mM ammonium acetate (pH adjusted to 3.5 with trifluoroacetic acid) and acetonitrile (75:25 v/v) as a mobile phase at 25 C. LC-MS detection was performed with selective ion monitoring using target ions at m/z 267 and m/z 195 for doxofylline and caffeine used as internal standard respectively. The calibration curve showed a good linearity in the concentration range of 1-5000 ng/mL. The effect of hematocrit on extraction of doxofylline from DBS was evaluated. The mean recoveries of doxofylline from DBS and urine were 93.46 and 89.86% respectively. The intra and inter-day precisions were less than 4.28% in DBS as well as urine. The limit of detection and quantification were 0.24 and 0.84 ng/mL in DBS and 0.28 and 1.00 ng/mL in urine samples respectively. The method was validated as per ICH guidelines and successfully applied to a pharmacokinetic study of doxofylline in rats.