Purpose
To develop a fast, sub‐millimeter 3D magnetic resonance fingerprinting (MRF) technique for whole‐brain quantitative scans.
Methods
An acquisition trajectory based on multi‐axis spiral ...projection imaging (maSPI) was implemented for 3D MRF with steady‐state precession and slab excitation. By appropriately assigning the in‐plane and through‐plane rotations of spiral interleaves in a novel acquisition scheme, an maSPI‐based acquisition was implemented, and the total acquisition time was reduced by up to a factor of 8 compared to stack‐of‐spiral (SOS)‐based acquisition. A sliding‐window method was also used to further reduce the required number of time points for a faster acquisition. The experiments were conducted both on a phantom and in vivo.
Results
The results from the phantom measurements with the proposed and gold standard methods were consistent with a good linear correlation and an R2 value approaching 0.99. The in vivo experiments achieved whole‐brain parametric maps with isotropic resolutions of 1 mm and 0.8 mm in 5.0 and 6.0 min, respectively, with potential for further acceleration. An in vivo experiment with intentionally moving subjects demonstrated that the maSPI scheme largely outperforms the SOS scheme in terms of robustness to head motion.
Conclusion
3D MRF with an maSPI acquisition scheme enables fast and robust scans for high‐resolution parametric mapping.
Programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) blockade has been unsuccessful in prostate cancer, with poor immunogenicity and subsequent low PD-L1 expression in prostate ...cancer being proposed as an explanation. However, recent studies indicate that a subset of prostate cancer may express significant levels of PD-L1. Furthermore, the androgen antagonist enzalutamide has been shown to upregulate PD-L1 expression in prostate cancer preclinical models. In this study, we evaluated the effect of neoadjuvant androgen deprivation therapy with abiraterone acetate plus prednisone and leuprolide (Neo-AAPL) on PD-L1 expression in prostate cancer.
Radical prostatectomy (RP) tissues were collected from 44 patients with intermediate- to high-risk prostate cancer who underwent RP after Neo-AAPL treatment. Untreated prostate cancer tissues were collected from 130 patients, including 44 matched controls for the Neo-AAPL cases. Tumor PD-L1 expression was detected by IHC using validated anti-PD-L1 antibodies. Tumor-infiltrating CD8
cells were analyzed in trial cases and matched controls. Expression of DNA mismatch repair genes was examined in PD-L1-positive tumors.
Neo-AAPL-treated tumors showed a trend toward decreased PD-L1 positivity compared with matched controls (7% vs. 21% having ≥1% positive tumor cells;
= 0.062). Treated tumors also harbored significantly fewer tumor-infiltrating CD8
cells (
= 0.029). In 130 untreated prostate cancers, African American ethnicity, elevated serum PSA, and small prostate independently predicted tumor PD-L1 positivity. Loss of MSH2 expression was observed in 1 of 21 PD-L1-positive tumors.
A subset of prostate cancer expresses PD-L1, which is not increased by Neo-AAPL treatment, indicating that combining Neo-AAPL treatment with PD-L1/PD-1 blockade may not be synergistic.
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The low light absorption efficiency has seriously hindered the application of two-dimensional transition metal dichalcogenide (TMDC) nanosheets in the field of optoelectronic devices. Various ...approaches have been used to improve the performance of TMDC nanosheets. Preparation of one-dimensional TMDC nanoscrolls in combination with photoactive materials has been a promising method to improve their properties recently. In this work, we report a facile method to enhance the optoelectronic performance of TMDC nanoscrolls by wrapping the photoactive organic dye rhodamine (R6G) into them. After R6G molecules were deposited on monolayer TMDC nanosheets by the solution method, the R6G/MoS2 nanoscrolls with lengths up to hundreds of microns were prepared in a short time by dropping a mixture of ammonia and ethanol solution on the R6G/MoS2 nanosheets. The as-obtained R6G/MoS2 nanoscrolls were well characterized by optical microscopy, atomic force microscopy, Raman spectroscopy, and transmission electron microscopy to prove the encapsulation of R6G. There are multiple type II heterojunction interfaces in the R6G/MoS2 nanoscrolls, which can promote the generation of photo-induced carriers and the following electron–hole separation. The separated electrons were transported rapidly along the axial direction of the R6G/MoS2 nanoscrolls, which greatly improves the efficiency of light absorption and photoresponse. Under the irradiation of an incident 405 nm laser, the photoresponsivity, carrier mobility, external quantum efficiency, and detectivity of R6G/MoS2 nanoscrolls were enhanced to 66.07 A/W, 132.93 cm2V−1s−1, 20,261%, and 1.25 × 1012 cm·Hz1/2W−1, which are four orders of magnitude higher than those of monolayer MoS2 nanosheets. Our work indicates that the R6G/TMDC hybrid nanoscrolls could be promising materials for high-performance optoelectronic devices.
The transcription factor SOX9 is critical for prostate development, and dysregulation of SOX9 is implicated in prostate cancer (PCa). However, the SOX9-dependent genes and pathways involved in both ...normal and neoplastic prostate epithelium are largely unknown. Here, we performed SOX9 ChIP sequencing analysis and transcriptome profiling of PCa cells and determined that SOX9 positively regulates multiple WNT pathway genes, including those encoding WNT receptors (frizzled FZD and lipoprotein receptor-related protein LRP family members) and the downstream β-catenin effector TCF4. Analyses of PCa xenografts and clinical samples both revealed an association between the expression of SOX9 and WNT pathway components in PCa. Finally, treatment of SOX9-expressing PCa cells with a WNT synthesis inhibitor (LGK974) reduced WNT pathway signaling in vitro and tumor growth in murine xenograft models. Together, our data indicate that SOX9 expression drives PCa by reactivating the WNT/β-catenin signaling that mediates ductal morphogenesis in fetal prostate and define a subgroup of patients who would benefit from WNT-targeted therapy.
In this study we have tested the efficacy of citrate therapy in various cancer models. We found that citrate administration inhibited A549 lung cancer growth and additional benefit accrued in ...combination with cisplatin. Interestingly, citrate regressed Ras-driven lung tumors. Further studies indicated that citrate induced tumor cell differentiation. Additionally, citrate treated tumor samples showed significantly higher infiltrating T-cells and increased blood levels of numerous cytokines. Moreover, we found that citrate inhibited IGF-1R phosphorylation. In vitro studies suggested that citrate treatment inhibited AKT phosphorylation, activated PTEN and increased expression of p-eIF2a. We also found that p-eIF2a was decreased when PTEN was depleted. These data suggest that citrate acts on the IGF-1R-AKT-PTEN-eIF2a pathway. Additionally, metabolic profiling suggested that both glycolysis and the tricarboxylic acid cycle were suppressed in a similar manner in vitro in tumor cells and in vivo but only in tumor tissue. We reproduced many of these observations in an inducible Her2/Neu-driven breast cancer model and in syngeneic pancreatic tumor (Pan02) xenografts. Our data suggests that citrate can inhibit tumor growth in diverse tumor types and via multiple mechanisms. Dietary supplementation with citrate may be beneficial as a cancer therapy.
Localized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of ...whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen deprivation therapy. A patient was diagnosed with a large semi-contiguous tumor by imaging, histologically composed of a large Gleason score 9 tumor with an adjacent Gleason score 7 nodule. DNA sequencing demonstrates these are two independent tumors, as only the Gleason 9 tumor harbors single-copy losses of PTEN and TP53. The PTEN/TP53-deficient tumor demonstrates treatment resistance, selecting for subclones with mutations to the remaining copies of PTEN and TP53, while the Gleason 7 PTEN-intact tumor is almost entirely ablated. These findings indicate that spatiogenetic variability is a major confounder for personalized treatment of patients with prostate cancer.
The CYP17A1 inhibitor abiraterone markedly reduces androgen precursors and is thereby effective in castration-resistant prostate cancer (CRPC). However, abiraterone increases progesterone, which can ...activate certain mutant androgen receptors (AR) identified previously in flutamide-resistant tumors. Therefore, we sought to determine if CYP17A1 inhibitor treatment selects for progesterone-activated mutant ARs.
AR was examined by targeted sequencing in metastatic tumor biopsies from 18 patients with CRPC who were progressing on a CYP17A1 inhibitor (17 on abiraterone, 1 on ketoconazole), alone or in combination with dutasteride, and by whole-exome sequencing in residual tumor in one patient treated with neoadjuvant leuprolide plus abiraterone.
The progesterone-activated T878A-mutant AR was present at high allele frequency in 3 of the 18 CRPC cases. It was also present in one focus of resistant tumor in the neoadjuvant-treated patient, but not in a second clonally related resistant focus that instead had lost one copy of PTEN and both copies of CHD1. The T878A mutation appeared to be less common in the subset of patients with CRPC treated with abiraterone plus dutasteride, and transfection studies showed that dutasteride was a more potent direct antagonist of the T878A versus the wild-type AR.
These findings indicate that selection for tumor cells expressing progesterone-activated mutant ARs is a mechanism of resistance to CYP17A1 inhibition.
High-quality and fast reconstructions are essential for the clinical application of positron emission tomography (PET) imaging. Herein, a deep-learning-based framework is proposed for PET image ...reconstruction directly from the sinogram domain to achieve high-quality and high-speed reconstruction at the same time. In this framework, conditional generative adversarial networks are constructed to learn a mapping from sinogram data to a reconstructed image and to generate a well-trained model. The network consists of a generator that utilizes the U-net structure and a whole-image strategy discriminator, which are alternately trained. Simulation experiments are conducted to validate the performance of the algorithm in terms of reconstruction accuracy, reconstruction efficiency, and robustness. Real patient data and Sprague Dawley rat data were used to verify the performance of the proposed method under complex conditions. The experimental results demonstrate the superior performance of the proposed method in terms of image quality, reconstruction speed, and robustness.
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