54 research outputs found
In Vivo Fluorescence-Based Endoscopic Detection of Colon Dysplasia in the Mouse Using a Novel Peptide Probe
Colorectal cancer (CRC) is a major cause of cancer-related deaths in much of the
world. Most CRCs arise from pre-malignant (dysplastic) lesions, such as
adenomatous polyps, and current endoscopic screening approaches with white light
do not detect all dysplastic lesions. Thus, new strategies to identify such
lesions, including non-polypoid lesions, are needed. We aim to identify and
validate novel peptides that specifically target dysplastic colonic epithelium
in vivo. We used phage display to identify a novel peptide
that binds to dysplastic colonic mucosa in vivo in a
genetically engineered mouse model of colo-rectal tumorigenesis, based on
somatic Apc (adenomatous polyposis coli) gene
inactivation. Binding was confirmed using confocal microscopy on biopsied
adenomas and excised adenomas incubated with peptide ex vivo.
Studies of mice where a mutant Kras allele was somatically
activated in the colon to generate hyperplastic epithelium were also performed
for comparison. Several rounds of in vivo T7 library biopanning
isolated a peptide, QPIHPNNM.
The fluorescent-labeled peptide bound to dysplastic lesions on endoscopic
analysis. Quantitative assessment revealed the fluorescent-labeled peptide
(target/background: 2.17±0.61) binds ∼2-fold greater to the colonic
adenomas when compared to the control peptide (target/background:
1.14±0.15), p<0.01. The peptide did not bind to the non-dysplastic
(hyperplastic) epithelium of the Kras mice. This work is first
to image fluorescence-labeled peptide binding in vivo that is
specific towards colonic dysplasia on wide-area surveillance. This finding
highlights an innovative strategy for targeted detection to localize
pre-malignant lesions that can be generalized to the epithelium of hollow
organs
Influenza B virus: Need for heightened surveillance and epidemiologic case studies
Recent report of increased influenza B virus infection, particularly theclinical profiles and treatment challenges imposed like that of influenza A,underscores the importance of continuing influenza B virus surveillance.This is, especially in resource limited country, early detection of influenzavirus, its clinical presentation and complications would be vital in minimizingthe public heath burden imposed by this virus.Keywords: chronic obstructive pulmonary disease, influenza B, severe acutepulmonary infection
Whole-Genome Sequence of Sungri/96 Vaccine Strain of Peste des Petits Ruminants Virus
We report the complete genome sequence of the Sungri/96 vaccine strain of peste des petits ruminants virus (PPRV). The whole-genome nucleotide sequence has 89 to 99% identity with the available PPRV genome sequences in the NCBI database. This study helps to understand the epidemiological and molecular characteristics of the Sungri/96 strain
Advancing the translation of optical imaging agents for clinical imaging
Despite the development of a large number of promising candidates, few contrast agents for established medical imaging modalities have successfully been translated over the past decade. The emergence of new imaging contrast agents that employ biomedical optics is further complicated by the relative infancy of the field and the lack of approved imaging devices compared to more established clinical modalities such as nuclear medicine. Herein, we propose a navigational approach (as opposed to a fixed “roadmap”) for translation of optical imaging agents that is (i) proposed through consensus by four academic research programs that are part of the cooperative U54 NCI Network for Translational Research, (ii) developed through early experiences for translating optical imaging agents in order to meet distinctly varied needs in cancer diagnostics, and (iii) adaptable to the rapidly changing environment of academic medicine. We describe the pathways by which optical imaging agents are synthesized, qualified, and validated for preclinical testing, and ultimately translated for “first-in-humans” studies using investigational optical imaging devices. By identifying and adopting consensus approaches for seemingly disparate optical imaging modalities and clinical indications, we seek to establish a systematic method for navigating the ever-changing “roadmap” to most efficiently arrive at the destination of clinical adoption and improved outcome and survivorship for cancer patients
Variation in grain zinc and iron concentrations, grain yield and associated traits of biofortified bread wheat genotypes in Nepal
Wheat (Triticum aestivum L.) is one of the major staples in Nepal providing the bulk of food calories and at least 30% of Fe and Zn intake and 20% of dietary energy and protein consumption; thus, it is essential to improve its nutritional quality. To select high-yielding genotypes with elevated grain zinc and iron concentration, the sixth, seventh, eighth, and ninth HarvestPlus Yield Trials (HPYTs) were conducted across diverse locations in Nepal for four consecutive years: 2015–16, 2016–17, 2017–18, and 2018–19, using 47 biofortified and 3 non-biofortified CIMMYT-bred, bread wheat genotypes: Baj#1, Kachu#1, and WK1204 (local check). Genotypic and spatial variations were found in agro-morphological traits; grain yield and its components; and the grain zinc and iron concentration of tested genotypes. Grain zinc concentration was highest in Khumaltar and lowest in Kabre. Likewise, grain iron concentration was highest in Doti and lowest in Surkhet. Most of the biofortified genotypes were superior for grain yield and for grain zinc and iron concentration to the non-biofortified checks. Combined analyses across environments showed moderate to high heritability for both Zn (0.48–0.81) and Fe (0.46–0.79) except a low heritability for Fe observed for 7th HPYT (0.15). Grain yield was positively correlated with the number of tillers per m2, while negatively correlated with days to heading and maturity, grain iron, grain weight per spike, and thousand grain weight. The grain zinc and iron concentration were positively correlated, suggesting that the simultaneous improvement of both micronutrients is possible through wheat breeding. Extensive testing of CIMMYT derived high Zn wheat lines in Nepal led to the release of five biofortified wheat varieties in 2020 with superior yield, better disease resistance, and 30–40% increased grain Zn and adaptable to a range of wheat growing regions in the country – from the hotter lowland, or Terai, regions to the dry mid- and high-elevation areas
Targeted Optical Imaging Agents in Cancer: Focus on Clinical Applications
Molecular imaging is an emerging strategy for in vivo visualization of cancer over time based on biological mechanisms of disease activity. Optical imaging methods offer a number of advantages for real-time cancer detection, particularly in the epithelium of hollow organs and ducts, by using a broad spectral range of light that spans from visible to near-infrared. Targeted ligands are being developed for improved molecular specificity. These platforms include small molecule, peptide, affibody, activatable probes, lectin, and antibody. Fluorescence labeling is used to provide high image contrast. This emerging methodology is clinically useful for early cancer detection by identifying and localizing suspicious lesions that may not otherwise be seen and serves as a guide for tissue biopsy and surgical resection. Visualizing molecular expression patterns may also be useful to determine the best choice of therapy and to monitor efficacy. A number of these imaging agents are overcoming key challenges for clinical translation and are being validated in vivo for a wide range of human cancers
In vivo targeting of colonic dysplasia on fluorescence endoscopy with near-infrared octapeptide
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