Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking cancerous growths to maximize treatment options and improve patient outcomes. This goal of early ...detection remains unfulfilled by current clinical imaging techniques that fail to detect lesions due to their small size and suborgan localization. With proper probes, optical imaging techniques can overcome this by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, the first use of nanophotonic short wave infrared technology is proposed to molecularly phenotype small lesions for more sensitive detection. Here, human serum albumin encapsulated rare‐earth nanoparticles (ReANCs) with ligands for targeted lesion imaging are designed. AMD3100, an antagonist to CXCR4 (a classic marker of cancer metastasis) is adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). fReANCs are able to preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. fReANCs can also target subtissue microlesions at a maximum depth of 10.5 mm in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs are 2.25 times smaller than those detected with ReANCs. Thus, an integrated nanoprobe detection platform is presented, which allows target‐specific identification of subtissue cancerous lesions.
Optical imaging using targeted rare‐earth‐doped albumin nanocomposites provides a method for subsurface detection of microscale breast cancer metastasis. Particles functionalized to common metastatic receptors molecularly discriminate between cellular populations, which enables minimally invasive determination of tumor phenotype. Improved particle localization to tumor sites allows for detection of microscale tumors in vivo ≈1 cm from the imaging surface.
In this study, the effects of long-term nitrogen deficiency (N 0.1
mM for 4 months) on growth, phenolic content and activity of phenylalanine ammonia lyase (PAL; EC 4.3.1.5) were investigated in the ...leaves, inflorescences and roots of yarrow (
Achillea collina Becker ex Rchb.) grown in hydroponics. The antioxidant capacity of methanol extracts was also evaluated. Nitrogen starvation decreased plant growth and the leaves’ total nitrogen, amino acids, proteins, chlorophylls and carotenoids contents indicating that the primary metabolism was severely limited by low nitrogen availability. The amount of total phenolics and the antioxidant capacity were higher in leaves and roots of nitrogen-starved compared to control plants. The most abundant phenolic acids identified in yarrow were 5-
O-caffeoylquinic acid (chlorogenic acid), and 3,5 and 4,5-di-
O-caffeoylquinic acids. Nitrogen starvation significantly increased the contents of all these compounds and the PAL activity in leaf and root tissues. Results suggest that hydroponics, with proper manipulation of nutritional factors, might be a suitable system for the production of compounds with health benefits, such as caffeic acid derivatives, in yarrow.
Abstract
Metastatic cancer is the leading cause of almost 90% of cancer-related deaths. Early detection of metastatic lesions in breast cancer would lead to judicious therapeutic choices in the ...management of the disease. Current clinical imaging techniques are unable to detect micro-metastases due to limited resolution. Optical imaging technologies are challenged by high tissue scattering and absorption of visible light, limiting resolution of deeper tissue lesions. While optical imaging modalities have the potential for real-time in vivo monitoring, poor penetration through biological mediums limits their application to subcutaneous lesions. Our approach utilizes rare earth (RE) nanoprobes that absorb near infrared (NIR) radiation and emit in the shortwave infrared (SWIR) spectrum (1000-3000 nm), allowing for greater depth of detection.
In this study, we demonstrate the ability of CXCR4-targeting Rare Earth Albumin NanoComposites (ReANCs) to preferentially accumulate in receptor positive tumor lesions and image lesion dynamics in an in vivo MDA-MB-231 derived lung metastatic model. ReANCs or AMD3100 (small molecule inhibitor of CXCR4) functionalized ReANCs (fReANCs) were injected via the tail vein once a week and SWIR imaging was performed up to 48 hours post injection. Tumor burden in the lungs was assessed by MRI and compared to the SWIR signal from the nanoprobes. Longitudinal in vivo imaging confirmed improved accumulation of functionalized nanoprobes in tumor lesions compared to control ReANCs. This improved accumulation at early lesion stages allowed for earlier and more sensitive detection of internal tumors. We also observed control ReANCs cleared faster through the liver as evidenced by increased SWIR signal in the liver of these animals.
In addition to the targeted imaging effect of fReANCs, we were able to demonstrate the ability of ReANCs to image micro-metastatic lesions in long bones and spine of animals prior to their detection via conventional imaging techniques such as MRI and CT. This was confirmed by ex-vivo SWIR imaging of the skeleton and micro-CT of the long bones. This advancement is exciting due to the paucity of imaging modalities capable of detecting micro-metastasis of breast cancer to bone. Histological analysis was performed to validate the presence of micro-lesions in the bones. Furthermore, immunohistochemical analysis of bone sections using markers over-expressed by MDA-MB-231 cells, namely Vimentin and pan-Cytokeratin confirmed the presence of tumors in the regions of interest.. Findings from this study support the promise of the “new window” imaging platform and suggest future clinical translatability for nanomedicine. Given the multifunctional nature of ANCs as drug delivery vehicles, our imaging probes can also be adapted for pre-clinical pharmacogenomic screening, an emerging component of precision medicine.
Citation Format: Margot Zevon, Vidya Ganapathy, Harini Kantamneni, Marco Mingozzi, Paul Kim, Derek Adler, Mark Pierce, Richard Riman, Charles Roth, Prabhas Moghe. Early detection and longitudinal imaging of breast cancer metastatic microlesions using short-wave infrared light emitting rare-earth nanoprobes. abstract. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1482. doi:10.1158/1538-7445.AM2015-1482
Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking of cancerous growths in order to maximize treatment options and improve patient outcomes. However, ...this goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect diseased lesions, due to their small size and sub-organ localization. With proper probes, optical imaging techniques can overcome this limitation by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, we propose the first use of nanophotonic short wave infrared technology to molecularly phenotype small sub-surface lesions for more sensitive detection and improved patient outcomes. To this end, we designed human serum albumin encapsulated rare-earth (RE) nanoparticles (ReANCs)
1
,
2
with ligands for targeted lesion imaging. AMD3100, an antagonist to CXCR4 (a chemokine receptor involved in cell motility and a classic marker of cancer metastasis) was adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). Functionalized nanoparticles were able to discriminate and preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. Additionally, fReANCs, administered intravenously, were able to target sub-tissue tumor micro-lesions, at a maximum depth of 10.5 mm, in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs were 2.25 times smaller than those detected with unfunctionalized ReANCs (
p
< .01) with the smallest tumor being 18.9 mm
3
. Thus, we present an integrated nanoprobe detection platform that allows target-specific identification of sub-tissue cancerous lesions.
Effects of photoautotrophic and photomixotrophic growth conditions on adventitious shoot regeneration from leaf explants of eastern cottonwood (Populus deltoides Bartr. ex Marsh.) were investigated. ...Rooting and proliferating shoot cultures (Stage I) were grown in either an elevated (1500 ppm) CO2 concentration (CO2) at high photosynthetic photon flux (PPF; approximately 150 μmol m⁻² s⁻¹) (photoautotrophic condition) with 0, 10 or 30 g l⁻¹ sucrose or under standard conditions (ambient (360 ppm) CO2 at low PPF (approximately 60 μmol m⁻² s⁻¹) with 30 g l⁻¹ sucrose). Leaves harvested from these cultures were analyzed for soluble sugars and were used as explants for adventitious shoot regeneration (Stage II), which was also carried out under photoautotrophic and standard conditions. Photoautotrophic conditions during Stage I promoted growth of rooting shoots but inhibited axillary shoot proliferation. Photoautotrophic conditions during Stage II suppressed callus and adventitious bud production from leaf explants compared with standard conditions. The regeneration environment appeared to be more important in controlling bud formation than the conditions under which the donor shoots were grown. Regardless of Stage I treatment, bud production was up to 100-fold higher for leaves cultured under standard conditions than under photoautotrophic conditions. Once adventitious buds were differentiated from the leaf tissues, however, their elongation was faster under photoautotrophic conditions than that under standard conditions, with some shoots reaching 10 mm in length on leaf explants cultured under photoautotrophic conditions. Because total leaf soluble sugar concentration was always lowest in shoots under standard conditions, which also yielded the highest bud production, the results suggest that endogenous starvation enhanced shoot production.
In this long-term follow-up study, men with hemophilia B had steady production of functional factor IX after gene transfer with an adeno-associated viral vector. Patients had a marked reduction in ...bleeding episodes and factor IX replacement with minimal toxicity.
Hemophilia B, an X-linked recessive bleeding disorder, results from a defect in the gene encoding coagulation factor IX, a serine protease that is critical for blood clotting. Patients with functional plasma levels of factor IX that are less than 1% of the normal value (1 IU per deciliter) have a severe phenotype characterized by frequent spontaneous bleeding episodes that result in chronic, debilitating arthropathy and occasionally death.
1
Current treatment to prevent these bleeding episodes entails lifelong intravenous injections of factor IX every 2 or 3 days. Although this treatment is effective in preventing spontaneous bleeding episodes, it is not curative . . .
This study analyses the specific neuropsychological profiles of children with dyslexia and/or dyscalculia, in particular concerning phonological awareness, lexical access, working memory and ...numerical processing. Four groups were selected, through a screening process that used strict criteria, from 1568 7-10-year-old children: 90 with typical development, 61 with dyslexia, 13 with dyscalculia, and 14 with dyslexia + dyscalculia. Children with dyslexia show a deficit in phonological processing, lexical access, and verbal working memory, especially with alphabetic stimuli. Children with developmental dyscalculia show a deficit of phonological processing, verbal working memory with digits and visual-spatial working memory. They also show an impairment in spatial representation of numbers and in the automatic access to numerical semantics to a greater extent than those with double disturbance. Children with dyslexia + dyscalculia show a profile generally characterized by the summation of the deficits of the two disorders, although they have a lower deficit in access to numerical semantics and mental representation of numbers.
Abstract
Growing evidence in support of a connection between active galactic nuclei (AGN) activity and the ram pressure stripping (RPS) phenomenon has been found both observationally and ...theoretically in the past decades. In this work, we further explore the impact of RPS on the AGN activity by estimating the gas-phase metallicity of nuclear regions and the mass–metallicity relation of galaxies at
z
≤ 0.07 and with stellar masses
log
M
*
/
M
⊙
≥
9.0
, either experiencing RPS or not. To measure oxygen abundances, we exploit Integral Field Spectroscopy data from the GASP and MaNGA surveys, photoionization models generated with the code
Cloudy
and the code
Nebulabayes
to compare models and observations. In particular, we build
Cloudy
models to reproduce line ratios induced by photoionization from stars, AGN, or a contribution of both. We find that the distributions of metallicity and O
iii
λ
5007 luminosity of galaxies undergoing RPS are similar to the ones of undisturbed galaxies. Independently of the RPS, we do not find a correlation between stellar mass and AGN metallicity in the mass range
log
M
*
/
M
⊙
≥
10.4
, while for the star-forming galaxies we observe the well-known mass–metallicity relation between
9.0
≤
log
M
*
/
M
⊙
≤
10.8
with a scatter mainly driven by the star formation rate and a plateau around
log
M
*
/
M
⊙
∼
10.5
. The gas-phase metallicity in the nuclei of AGN hosts is enhanced with respect to those of star-forming galaxies by a factor of ∼ 0.05 dex regardless of the RPS.
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