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The current positive computed tomography (CT) contrast agents (PCTCAs) including clinical iodides, present high CT density value (CT‐DV). However, they are incapable for the accurate diagnosis of some diseases with high CT‐DV, such as osteosarcoma. Because bones and PCTCAs around osteosarcoma generate similar X‐ray attenuations. Here, an innovative strategy of negative CT contrast agents (NCTCAs) to reduce the CT‐DV of osteosarcoma is proposed, contributing to accurate detection of osteosarcoma. Hollow mesoporous silica nanoparticles, loading ammonia borane molecules and further modified by polyethylene glycol, are synthesized as NCTCAs for the diagnosis of osteosarcoma. The nanocomposites can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, resulting in nearly 20 times reduction of CT density in osteosarcoma. This helps form large CT density contrast between bones and osteosarcoma, and successfully achieves accurate diagnosis of osteosarcoma. Meanwhile, The NCTCAs strategy greatly expands the scope of CT application, and provides profound implications for the precise clinical diagnosis, treatment, and prognosis of diseases. A negative computed tomography (CT) contrast agent based on hollow mesoporous silica nanoparticles@ammonia borane@polyethylene glycol nanocomposite can produce H2 in situ at osteosarcoma areas by responding to the acidic microenvironment of osteosarcoma, and prominently reduce the CT density of osteosarcoma, which can form large CT density difference contrast between bones and osteosarcoma, and further realize accurate diagnosis of malignant osteosarcoma.

Positive computed tomography (CT) contrast nanoagent has significant applications in diagnosing tumors. However, the sensitive differentiation between hepatoma and normal liver tissue remains challenging. This challenge arises primarily because both normal liver and hepatoma tissues capture the nanoagent, resulting in similar positive CT contrasts. Here, a strategy for fusing positive and negative CT contrast nanoagent is proposed to detect hepatoma. A nanoagent Hf‐MOF@AB@PVP initially generates a positive CT contrast signal of 120.3 HU in the liver. Subsequently, it can specifically respond to the acidic microenvironment of hepatoma to generate H2, further achieving a negative contrast of −96.0 HU. More importantly, the relative position between the negative and positive signals area is helpful to determine the location of hepatoma and normal liver tissues. The distinct contrast difference of 216.3 HU and relative orientation between normal liver and tumor tissues are meaningful to sensitively distinguish hepatoma from normal liver tissue utilizing CT imaging. A strategy for fusing positive and negative CT contrast nanoagent is presented. The distinct contrast of 216.3 HU and relative orientation between positive and negative CT signals are meaningful to sensitively distinguish hepatoma from normal liver tissue utilizing CT.

Background Group IVA cytosolic phospholipase A2 (cPLA2α) plays an important role in tumorigenesis and angiogenesis. It is overexpressed in basal-like breast cancer (BLBC), which is aggressive and usually triple-negative, making it unresponsive to current targeted therapies. Here, we evaluated the anti-angiogenic effects of a specific cPLA2α inhibitor, AVX235, in a patient-derived triple-negative BLBC model. Methods Mice bearing orthotopic xenografts received i.p. injections of AVX235 or DMSO vehicle daily for 1 week and then every other day for up to 19 days. Six treated and six control mice were terminated after 2 days of treatment, and the tumors excised for high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS) and prostaglandin E2 (PGE2) enzyme immunoassay (EIA) analysis. A 1-week imaging study was performed on a separate cohort of mice. Longitudinal dynamic contrast enhanced (DCE)-MRI was performed before, after 4 days, and after 1 week of treatment. The mice were then perfused with a radiopaque vascular casting agent, and the tumors excised for micro-CT angiography. Subsequently, tumors were sectioned and stained with lectin and for Ki67 or α-smooth muscle actin to quantify endothelial cell proliferation and vessel maturity, respectively. Partial least squares discriminant analysis was performed on the multivariate HR MAS MRS data, and non-parametric univariate analyses using Mann–Whitney U tests (α = 0.05) were performed on all other data. Results Glycerophosphocholine and PGE2 levels, measured by HR MAS MRS and EIA, respectively, were lower in treated tumors after 2 days of treatment. These molecular changes are expected downstream effects of cPLA2α inhibition and were followed by significant tumor growth inhibition after 8 days of treatment. DCE-MRI revealed that AVX235 treatment caused a decrease in tumor perfusion. Concordantly, micro-CT angiography showed that vessel volume fraction, density, and caliber were reduced in treated tumors. Moreover, histology showed decreased endothelial cell proliferation and fewer immature vessels in treated tumors. Conclusions These results demonstrate that cPLA2α inhibition with AVX235 resulted in decreased vascularization and perfusion and subsequent inhibition of tumor growth. Thus, cPLA2α inhibition may be a potential new therapeutic option for triple-negative basal-like breast cancer.