An Exploratory Study on the Stable Radiomics Features of Metastatic Small Pulmonary Nodules in Colorectal Cancer Patients.

OBJECTIVES: To identify the relatively invariable radiomics features as essential characteristics during the growth process of metastatic pulmonary nodules with a diameter of 1 cm or smaller from colorectal cancer (CRC). METHODS: Three hundred and twenty lung nodules were enrolled in this study (200 CRC metastatic nodules in the training cohort, 60 benign nodules in the verification cohort 1, 60 CRC metastatic nodules in the verification cohort 2). All the nodules were divided into four groups according to the maximum diameter: 0 to 0.25 cm, 0.26 to 0.50 cm, 0.51 to 0.75 cm, 0.76 to 1.0 cm. These pulmonary nodules were manually outlined in computed tomography (CT) images with ITK-SNAP software, and 1724 radiomics features were extracted. Kruskal-Wallis test was performed to compare the four different levels of nodules. Cross-validation was used to verify the results. The Spearman rank correlation coefficient is calculated to evaluate the correlation between features. RESULTS: In training cohort, 90 features remained stable during the growth process of metastasis nodules. In verification cohort 1, 293 features remained stable during the growth process of benign nodules. In verification cohort 2, 118 features remained stable during the growth process of metastasis nodules. It is concluded that 20 features remained stable in metastatic nodules (training cohort and verification cohort 2) but not stable in benign nodules (verification cohort 1). Through the cross-validation (n=100), 11 features remained stable more than 90 times. CONCLUSIONS: This study suggests that a small number of radiomics features from CRC metastatic pulmonary nodules remain relatively stable from small to large, and they do not remain stable in benign nodules. These stable features may reflect the essential characteristics of metastatic nodules and become a valuable point for identifying metastatic pulmonary nodules from benign nodules.

Protein tyrosine phosphatase receptor type D (PTPRD)-mediated signaling pathways for the potential treatment of hepatocellular carcinoma: a narrative review.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide, and the methods for its treatment have shown limited efficacy. There is an urgent need to explore the underlying mechanism that are involved in hepatocarcinogenesis, contributing to find various signal molecular targets for HCC diagnosis, prevention and therapy. Recently, Various studies have illustrated protein tyrosine phosphatase receptor type D (PTPRD) is an important tumor-suppressor gene that is down-regulated in HCC and this downregulation occurs through its promoter hypermethylation. PTPRD is involved in the progression, migration, apoptosis, invasion and immune suppression of HCC. Also, PTPRD participates in several vital cellular signaling pathways, including PTPRD, signal transduction and activation of transcription 3 (STAT3), JAK, PTPRD, ß-catenin, TCF, along with the PTPRD-CXCL8 axis, the PTPRD/phosphatidylinositol3-kinase (PI3K)/mammalian target of rapamycin (mTOR), and the PTPRD/PD-1/programmed death receptor ligand-1 (PD-L1) axis, thus playing an essential role in HCC. Therefore, PTPRD can be considered as a novel therapeutic target for HCC, and PTPRD-targeted therapeutics in combination with methylation inhibitors, immune checkpoint inhibitors and alternative targeted drugs maybe an innovative treatment method for HCC. However, clinical research of PTPRD-targeted therapies in HCC is greatly limited and tremendous efforts are strongly urged to evaluate its clinical performance in HCC. In this review, we summarized the physiological function and the significant effects of PTPRD and performed a comprehensive analysis of PTPRD-targeted strategies for HCC.

Protein tyrosine phosphatase receptor type delta (PTPRD) suppresses the expression of PD-L1 in human hepatocellular carcinoma by down-regulating STAT3.

BACKGROUND: Protein tyrosine phosphatase receptor type delta (PTPRD) is a tumor suppressor that is often inactivated in hepatocellular carcinoma (HCC). However, the mechanisms of how PTPRD inhibits HCC are not well understood. Programmed cell death ligand 1 (PD-L1), an immune checkpoint, plays a seminal role in the regulation of carcinogenesis of HCC. The sustained activation of STAT3 is closely related to PTPRD deletion and PD-L1 overexpression; however, whether there is a relationship between PTPRD and PD-L1 expression in HCC has not been investigated. This study aims to investigate the relationship between PTPRD and PD-L1 in HCC samples and illuminate potential new molecular mechanisms of PTPRD effects on PD-L1 in HepG2 cells. METHODS: We collected 16 pairs of tumorous tissues and adjacent normal tissues from HCC patients. The mRNA and protein expression levels of PTPRD and PD-L1 in the HCC tissues were detected by RT-PCR and Western blot analysis. Next, Spearman's correlation analysis was performed to evaluate the relationship between PTPRD and PD-L1. Then, we transfected the overexpressed or knocked-down PTPRD genes into the HepG2 cell line, and the effects of PTPRD on PD-L1 in HCC cells were evaluated. The activity from the STAT3 and p-STAT3 in the HepG2 cells transfected with PTPRD gene overexpression and knockdown was determined by Western blotting tests. RESULTS: The expression of PTPRD was significantly down-regulated in the HCC tissues compared with the adjacent control tissues; however, PD-L1 was significantly higher in the HCC tissues. There was a negative correlation between PTPRD and PD-L1 expression in the HCC tissues. PTPRD over-expression significantly inhibited PD-L1 expression; meanwhile, PTPRD depletion promoted PD-L1 expression in the HepG2 cells. Furthermore, PTPRD over-expression significantly inhibited the expression of STAT3 and p-STAT3, while PTPRD depletion promoted these cytokines. Our studies revealed that PTPRD repressed PD-L1 expression in the HepG2 cells, which might occur via the STAT3 pathway. CONCLUSIONS: The results from our study show that PTPRD and PD-L1 are negatively correlated in HCC tissues. PTPRD suppresses PD-L1 expression in HepG2 cells by down-regulating STAT3. These findings are expected to become a new target for the immunotherapy of HCC.

Magnetic Resonance Imaging and Pathologic Findings of 26 Cases With Uterine Adenomatoid Tumors.

OBJECTIVE: To analyze the magnetic resonance imaging (MRI) features and pathologic findings of uterine adenomatoid tumors (ATs) for improved diagnostic accuracy and facilitating differential diagnosis of the tumors. METHODS: We investigated retrospectively 26 patients with uterine ATs confirmed by pathology. Before operation, all patients accepted multiple MRI scans, including T1-weighted image (T1WI), T2-weighted image (T2WI), T2WI/spectrally adiabatic inversion recovery, and T1-weighted enhanced imaging. Two radiologists reviewed all the MRI sequences on PACS workstations for all patients to evaluate the location, shape, size, margin, intensity, and enhancement of ATs. RESULTS: All uterine ATs exhibited either single round solid (n = 24) or predominantly cystic (n = 2) masses with either well-defined (n = 23) or ill-defined margin (n = 3). The diameter range of the tumors was 1.0 to 7.0 cm (mean, 3.8 cm). Solid masses were isointensive on T1WI and hypointensive on T2WI with moderate enhancement. The degree of enhancement in solid tumors was either lower than (18/24 [75%]) or equal to (6/24 [25%]) that of the myometrium. Predominantly cystic masses presented as cystic lesions with a little irregular solid nodule inside. The cystic parts were hypointensive on T1WI and hyperintensive on T2WI without enhancement, whereas the solid nodules were isointensive on both T1WI and T2WI with moderate enhancement. A large part of the uterine ATs (69.2% [18/26]) coexisted with other uterine diseases. On pathology, uterine ATs were characterized as gland-like structures with irregular expansion of tubular cavities, which might be correlated with low enhancement of tumors. The tumors were lined with flat or cuboidal mesothelial cells and residue of smooth muscle component, which might contribute to their hypointensive appearance on T2WI. CONCLUSIONS: Small solid uterine masses with homogeneous hypointensity on T2WI and lower enhancement or cystic lesions with inner irregular solid nodule may indicate the diagnosis of uterine ATs, and final diagnosis can be determined with pathology.

Efficient labeling in vitro with non-ionic gadolinium magnetic resonance imaging contrast agent and fluorescent transfection agent in bone marrow stromal cells of neonatal rats.

Although studies have been undertaken on gadolinium labeling-based molecular imaging in magnetic resonance imaging (MRI), the use of non-ionic gadolinium in the tracking of stem cells remains uncommon. To investigate the efficiency in tracking of stem cells with non-ionic gadolinium as an MRI contrast agent, a rhodamine-conjugated fluorescent reagent was used to label bone marrow stromal cells (BMSCs) of neonatal rats in vitro, and MRI scanning was undertaken. The fluorescent-conjugated cell uptake reagents were able to deliver gadodiamide into BMSCs, and cell uptake was verified using flow cytometry. In addition, the labeled stem cells with paramagnetic contrast medium remained detectable by an MRI monitor for a minimum of 28 days. The present study suggested that this method can be applied efficiently and safely for the labeling and tracking of bone marrow stromal cells in neonatal rats.