The charged particle transverse momentum (
p
T
) spectra measured by the ATLAS and CMS collaborations for proton–proton collisions at
s
=
0.9
and 7 TeV have been studied using Tsallis thermodynamics. ...A thermodynamically consistent form of the Tsallis distribution is used for fitting the transverse momentum spectra at mid-rapidity. It is found that the fits based on the proposed distribution are working over 14 orders of magnitude with
p
T
values up to 200 GeV/c and this gives a value of
χ
2
/
N
D
F
of 0.52/24 for the CMS data at 7 TeV. The values for
d
N
d
y
|
y
=
0
as a function of center-of-mass energy obtained using a Tsallis distribution for both ATLAS and CMS data sets are presented and discussed.
Nonlamellar liquid crystalline phases are attractive platforms for drug solubilization and targeted delivery. The attractiveness of this formulation principle is linked to the nanostructural ...versatility, compatiblity, digestiblity and bioadhesive properties of their lipid constituents, and the capability of solubilizing and sustaining the release of amphiphilic, hydrophobic and hydrophilic drugs. Nonlamellar liquid crystalline phases offer two distinct promising strategies in the development of drug delivery systems. These comprise formation of ISAsomes (internally self-assembled 'somes' or particles) such as cubosomes and hexosomes, and in situ formation of parenteral dosage forms with tunable nanostructures at the site of administration. This review outlines the unique features of cubosomes and hexosomes and their potential utilization as promising platforms for drug delivery.
Non-lamellar liquid crystalline aqueous nanodispersions, known also as ISAsomes (internally self-assembled ‘somes’ or nanoparticles), are gaining increasing interest in drug solubilisation and ...bio-imaging, but they often exhibit poor hemocompatibility and induce cytotoxicity. This limits their applications in intravenous drug delivery and targeting. Using a binary mixture of citrem and soy phosphatidylcholine (SPC) at different weight ratios, we describe a library of colloidally stable aqueous and hemocompatible nanodispersions of diverse nanoarchitectures (internal self-assembled nanostructures). This engineered library is structurally stable in human plasma as well as being hemocompatible (non-hemolytic, and poor activator of the complement system). By varying citrem to lipid weight ratio, the nanodispersion susceptibility to macrophage uptake could also be modulated. Finally, the formation of nanodispersions comprising internally V2 (inverse bicontinuous cubic) and H2 (inverse hexagonal) nanoarchitectures was achieved without the use of an organic solvent, a secondary emulsifier, or high-energy input. The tunable binary citrem/SPC nanoplatform holds promise for future development of hemocompatible and immune-safe nanopharmaceuticals.
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Lipid exchange among citrem nanoparticles and an ethanol micellar solution containing soy phosphatidylcholine was investigated in situ by coupling small angle X-ray scattering with a microfluidic ...device. The produced soy phosphatidylcholine/citrem nanoparticles have great potential in the development of hemocompatible nanocarriers for drug delivery.
The charged particle transverse momentum (pT) spectra measured by the ATLAS and CMS collaborations in proton - proton collisions at √s = 0.9 and 7 TeV have been studied using Tsallis thermodynamics. ...A thermodynamically consistent form of the Tsallis distribution is used for fitting the transverse momentum spectra at mid-rapidity. It is found that the fits based on the proposed distribution provide an excellent description over 14 orders of magnitude with pT values up to 200 GeV c.
Gastric Cancer Heterogeneity and Clinical Outcomes Sexton, Rachel E.; Hallak, Mohammed Najeeb Al; Uddin, Md. Hafiz ...
Technology in Cancer Research & Treatment,
2020, Volume:
19
Book Review, Journal Article
Peer reviewed
Open access
Gastric adenocarcinoma is a highly aggressive disease with poor overall survival. The aggressive nature of this disease is in part due to the high intra and inter tumoral heterogeneity and also due ...to the late diagnosis at presentation. Once progression occurs, treatment is more difficult due to the adaptation of tumors, which acquires resistance to commonly used chemotherapeutics. In this report, using publicly available data sets and pathway analysis, we highlight the vast heterogeneity of gastric cancer by investigating genes found to be significantly perturbed. We found several upregulated genes in the diffuse gastric cancer subtypes share similarity to gastric cancer as a whole which can be explained by the increase in this subtype of gastric cancer throughout the world. We report significant downregulation of genes that are underrepresented within the literature, such as ADH7, GCNT2, and LIF1, while other genes have not been explored within gastric cancer to the best of our knowledge such as METTL7A, MAL, CWD43, and SLC2A12. We identified gender to be another heterogeneous component of this disease and suggested targeted treatment strategies specific to this heterogeneity. In this study, we provide an in-depth exploration of the molecular landscape of gastric cancer in order to shed light onto novel areas of gastric cancer research and explore potential new therapeutic targets.
Local tumor progression is a cause of significant morbidity and mortality in patients with pancreatic ductal adenocarcinoma (PDAC) with surgically unresectable disease. Novel and effective approaches ...to accomplish durable local control are urgently needed. We tested whether CPI-613 (devimistat), a first-in-class investigational small molecule inhibitor of mitochondrial metabolism, was capable of altering cancer cell energy metabolism and sensitizing PDAC cells to radiation therapy (RT).
The effect of a combined treatment of RT with CPI-613 on the viability of, clonogenic potential of, and cell death induction in PDAC cells (MiaPaCa-2 and Panc-1) was determined using a trypan blue dye exclusion assay, a colony formation assay, and a 7–amino-actinomycin D assay, respectively. The synergistic effects of CPI-613-RT and chemotherapeutic agents (gemcitabine or 5-fluorouracil) were measured in MiaPaCa-2 cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and spheroid formation assay. Changes in energy metabolism were determined by profiling metabolites treated with either RT, CPI-613, or both using liquid chromatography-mass spectrometry.
This study demonstrates that a combination of single-fraction RT (2 and 10 Gy) with CPI-613 significantly inhibits PDAC cell growth compared with RT alone. Molecular analysis revealed inhibition of α-ketoglutarate dehydrogenase at the protein level. In addition, we demonstrate enhanced cell death of PDAC cells when treated with RT-CPI-613 combination. Targeted metabolomic analysis on PDAC cells post–CPI-613-RT treatment revealed alterations in key mitochondrial metabolites, with broader target engagement by the combination treatment, indicating the sensitization of CPI-613–treated PDAC cells to RT. Furthermore, a combination treatment of CPI-613 with either gemcitabine or 5-fluorouracil in the presence of 2 Gy RT synergistically inhibits PDAC cell proliferation.
Our results support a novel combination of CPI-613-RT that warrants further preclinical and early-phase clinical investigations. A phase 1 trial designed to identify the maximum tolerated dose of CPI-613 in combination with chemo-RT in patients with PDAC was recently initiated (NCT05325281).
Cryo-transmission electron microscopy (Cryo-TEM), and its technological variations thereof, have become a powerful tool for detailed morphological characterization and 3D tomography of soft lipid and ...polymeric nanoparticles as well as biological materials such as viruses and DNA without chemical fixation. Here, we review and discuss recent advances in Cryo-TEM analysis of lipid-based drug nanocarriers with particular emphasis on morphological and internal nanostructure characterization of lyotropic liquid crystalline nanoparticles such as cubosomes and hexosomes.
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