Hounsfield units on abdominal computed tomography: a new tool for predicting osteoporosis.

BACKGROUND: Osteoporosis can cause bone fractures and disability, but early diagnosis faces challenges. Our proposed diagnostic indicators offer a new approach for early detection, which benefits early identification. PURPOSE: To determine the most appropriate threshold for predicting osteoporosis in patients with each section of vertebral body. MATERIAL AND METHODS: A retrospective analysis of 210 patients, including 646 vertebrae, who had both abdominal computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) within six months. The correlation between DXA T-score and CT Hounsfield units (HU) values was tested by Pearson. The area under the curve (AUC) was calculated using the threshold obtained from the regression equation. RESULTS: The thresholds matching the T-score of -2.5 were 85, 95, 85, and 90 HU for the upper axial plane of the vertebral body (Lau), the middle axial plane of the vertebral body (Lam), the lower axial plane of the vertebral body (Lad), and the mid-sagittal plane of the vertebral body (Lsm), respectively. Defining osteoporosis using CT as Lau ≤ 85, Lam ≤ 95, Lad ≤ 85, or Lsm ≤ 90 HU had a specificity of 88.1% (116/134) and sensitivity of 90.8% (69/76) for distinguishing DXA osteoporosis of the lumbar spine in 210 patients. T-score ≤-2.5 defined as Lau ≤85 or Lam ≤95 or Lad ≤85 or Lsm ≤90 HU had a specificity of 85.9% (275/320) and sensitivity of 82.8% (270/326) for DXA T-score ≤-2.5 in 646 lumbar vertebrae. CONCLUSION: CT HU values obtained based on different sections of the vertebral body in abdominal CT can be used as a supplementary measure to assess osteoporosis.

Routine chest CT combined with the osteoporosis self-assessment tool for Asians (OSTA): a screening tool for patients with osteoporosis.

INTRODUCTION: The osteoporosis self-assessment tool for Asians (OSTA) is a common screening tool for osteoporosis. The seventh thoracic CT (CT-T7) Hounsfield unit (HU) measured by chest CT correlates with osteoporosis. This study aimed to investigate the diagnostic value of OSTA alone, CT-T7 alone, or the combination of OSTA and CT-T7 in osteoporosis. MATERIALS AND METHODS: In this study, 1268 participants were grouped into 586 men and 682 women. We established multiple linear regression models by combining CT-T7 and OSTA. Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose osteoporosis. RESULTS: In the male group, the mean age was 59.02 years, and 108 patients (18.4%) had osteoporosis. In the female group, the mean age was 63.23 years, and 308 patients (45.2%) had osteoporosis. By ROC curve comparison, the CT-T7 (male, AUC = 0.789, 95% CI 0.745-0.832; female, AUC = 0.835, 95% CI 0.805-0.864) in the diagnosis of osteoporosis was greater than the OSTA (male, AUC = 0.673, 95% CI 0.620-0.726; female, AUC = 0.775, 95% CI 0.741-0.810) in both the male and female groups (p < 0.001). When OSTA was combined with CT, the equation of multiple linear regression (MLR) was obtained as follows: female = 3.020-0.028*OSTA-0.004*CT-T7. In the female group, it was found that the AUC of MLR (AUC = 0.853, 95% CI 0.825-0.880) in the diagnosis of osteoporosis was larger than that of CT-T7 (p < 0.01). When the MLR was 2.65, the sensitivity and specificity were 53.9% and 90%, respectively. CONCLUSION: For a patient who has completed chest CT, CT-T7 (HU) combined with OSTA is recommended to identify the high-risk population of osteoporosis, and it has a higher diagnostic value than OSTA alone or CT-T7 alone, especially among females. For a female with MLR greater than 2.65, further DXA examination is needed.

Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML.

Cytarabine (Ara-C) is the first-line drug for the treatment of acute myelogenous leukemia (AML). However, resistance eventually develops, decreasing the efficacy of Ara-C in AML patients. The expression of SAMHD1, a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, has been reported to be elevated in Ara-C-resistant AML patients and to play a crucial role in mediating Ara-C resistance in AML. However, the mechanism by which SAMHD1 is upregulated in resistant AML remains unknown. In this study, NONO interacted with and stabilized SAMHD1 by inhibiting DCAF1-mediated ubiquitination/degradation of SAMHD1. Overexpression of NONO increased SAMHD1 expression and reduced the sensitivity of AML cells to Ara-C, and downregulation of NONO had the opposite effects. In addition, the DNA-damaging agents DDP and adriamycin (ADM) reduced NONO/SAMHD1 expression and sensitized AML cells to Ara-C. More importantly, NONO was upregulated in Ara-C-resistant AML cells, resulting in increased SAMHD1 expression in resistant AML cells, and DDP and ADM treatment resensitized resistant AML cells to Ara-C. This study revealed the mechanism by which SAMHD1 is upregulated in Ara-C-resistant AML cells and provided novel therapeutic strategies for Ara-C-resistant AML.

The synergistic anticancer effect of the bromodomain inhibitor OTX015 and histone deacetylase 6 inhibitor WT-161 in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a tumour with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extraterminal domain (BET) and histone deacetylases (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. METHODS: Cell proliferation, migration, invasion, colony formation, and sphere-forming assays were performed with the two inhibitors alone or in combination to evaluate their suppressive effect on the malignant properties of OS cells. Apoptosis and the cell cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumours was also examined in a nude mouse xenograft model. RESULTS: The combined therapy of OTX015/WT-161 synergistically inhibited growth, migration, and invasion and induced apoptosis, resulting in G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibited the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration revealed that the synergistic downregulation of ß-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be critical for the synergistic effect. Finally, the results of an in vivo assay showed that tumour xenografts were significantly decreased after treatment with the OTX015/WT-161 combination compared with OTX015 or WT-161 alone. CONCLUSIONS: Our findings in this study demonstrated that OTX015 and WT-161 had synergistic anticancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

Serglycin promotes proliferation, migration, and invasion via the JAK/STAT signaling pathway in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a common disease in the world, and its pathogenesis is still unclear. This study aims to identify the key genes that promote the proliferation, invasion, and metastasis of osteosarcoma cells. METHOD: GSE124768 and GSE126209 were downloaded from the Gene Expression Omnibus (GEO) database. The gene ontology and enrichment pathway were analyzed by FunRich software. qPCR and Western blot were used to detect the gene expression. After gene knockdown, Transwell and wound healing assays were conducted on osteosarcoma cells to detect whether the genes were defined before enhancing the invasion of osteosarcoma. RESULTS: Totally, 341 mRNAs were found to be regulated differentially in osteosarcoma cells compared to osteoblasts. In addition, the expression level of Serglycin (SRGN) in osteosarcoma cells was higher than that in human osteoblasts. The invasion and proliferation ability of osteosarcoma cells with upregulated Serglycin was significantly increased, and on the contrary, decreased after Serglycin knockdown. Moreover, we preliminarily found that Serglycin may associate with the JAK/STAT signaling pathway. CONCLUSIONS: By using microarray and bioinformatics analyses, differently expressed mRNAs were identified and a complete gene network was constructed. To our knowledge, we describe for the first time Serglycin as a potential biomarker.

Role of LncRNAs in regulating cancer amino acid metabolism.

The metabolic change of tumor cells is an extremely complicated process that involves the intersection and integration of various signal pathways. Compared with normal tissues, cancer cells show distinguished metabolic characteristics called metabolic reprogramming, which has been considered as a sign of cancer occurrence. With the deepening of tumor research in recent years, people gradually found that amino acid metabolism played crucial roles in cancer progression. Long non-coding RNAs (lncRNAs), which are implicated in many important biological processes, were firstly discovered dysregulating in cancer tissues and participating in extensive regulation of tumorigenesis. This review focuses on the reprogramming of amino acid metabolism in cancers and how lncRNAs participate in the regulatory network by interacting with other macromolecular substances. Understanding the functions of lncRNA in amino acid reprogramming in tumors might provide a new vision on the mechanisms of tumorigenesis and the development of new approaches for cancer therapy.