Subcutaneous fat predicts bone metastasis in breast cancer: A novel multimodality-based deep learning model.

OBJECTIVES: This study explores a deep learning (DL) approach to predicting bone metastases in breast cancer (BC) patients using clinical information, such as the fat index, and features like Computed Tomography (CT) images. METHODS: CT imaging data and clinical information were collected from 431 BC patients who underwent radical surgical resection at Harbin Medical University Cancer Hospital. The area of muscle and adipose tissue was obtained from CT images at the level of the eleventh thoracic vertebra. The corresponding histograms of oriented gradients (HOG) and local binary pattern (LBP) features were extracted from the CT images, and the network features were derived from the LBP and HOG features as well as the CT images through deep learning (DL). The combination of network features with clinical information was utilized to predict bone metastases in BC patients using the Gradient Boosting Decision Tree (GBDT) algorithm. Regularized Cox regression models were employed to identify independent prognostic factors for bone metastasis. RESULTS: The combination of clinical information and network features extracted from LBP features, HOG features, and CT images using a convolutional neural network (CNN) yielded the best performance, achieving an AUC of 0.922 (95% confidence interval [CI]: 0.843-0.964, P< 0.01). Regularized Cox regression results indicated that the subcutaneous fat index was an independent prognostic factor for bone metastasis in breast cancer (BC). CONCLUSION: Subcutaneous fat index could predict bone metastasis in BC patients. Deep learning multimodal algorithm demonstrates superior performance in assessing bone metastases in BC patients.

Pectoralis muscle predicts distant metastases in breast cancer by deep learning radiomics.

BACKGROUND: Sarcopenia is associated with a poor prognosis in patients with breast cancer (BC). Currently, there are few quantitative assessments carried out between muscle biomarkers and distant metastasis using existing methods. PURPOSE: To assess the predictive value of the pectoralis muscle for BC distant metastasis, we developed a deep learning radiomics nomogram model (DLR-N) in this study. MATERIAL AND METHODS: A total of 493 patients with pathologically confirmed BC were registered. Image features were extracted from computed tomography (CT) images for each patient. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors for distant metastasis. The DLR-N was built based on independent prognostic factors and CT images to predict distant metastases. The model was assessed in terms of overall performance, discrimination, calibration, and clinical value. Finally, the predictive performance of the model was validated using the testing cohort. RESULTS: The developed DLR-N combined multiple radiomic features and clinicopathological factors and demonstrated excellent predictive performance. The C-index of the training cohort was 0.983 (95% confidence interval [CI] = 0.969-0.998) and the C-index of the testing cohort was 0.948 (95% CI = 0.917-0.979). Decision curve analysis (DCA) showed that patients could benefit more from incorporating multimodal radiomic features into clinicopathological models. CONCLUSIONS: DLR-N verified that there were biomarkers at the level of the fourth thoracic vertebra (T4) that affected distant metastasis. Multimodal prediction models based on deep learning could be a potential method to aid in the prediction of distant metastases in patients with BC.

IGF2BP2 promotes lncRNA DANCR stability mediated glycolysis and affects the progression of FLT3-ITD + acute myeloid leukemia.

Internal tandem duplication (ITD) is the most common type of FLT3 mutation (FLT3-ITD), accounting for about 25% of AML patients. The expression of DANCR in FLT3-ITD AML had not been paid attention to, and whether its regulatory relationship with IGF2BP2 can affect the progression of FLT3-ITD AML was unclear. Our study sought to verify the biological role of IGF2BP2 as an m6A reading protein in FLT3-ITD AML. To further explore the role and mechanism of DANCR in AML, and provide a basis for the screening of biomarkers and the development of targeted drugs. The results show that IGF2BP2 was upregulated in FLT3-ITD+ AML patients and cells. Si-IGF2BP2 could inhibit the proliferation, glycolytic and promote the apoptosis in MV4-11 cells. IGF2BP2 could promote the DANCR RNA stability. This discovery will provide new horizons for early screening and targeted therapy of FLT3-ITD+ AML.

METTL3 affects FLT3-ITD+ acute myeloid leukemia by mediating autophagy by regulating PSMA3-AS1 stability.

The study was designed to explore the role of PSMA3-AS1 in initiation and progression of acute myeloid leukemia (AML) and investigate its action mechanism. Expression of PSMA3-AS1, miR-20a-5p and ATG16L1 both in vitro and in vivo was measured by qRT-PCR. The expression of protein was detected by western blot assay. Edu staining and flow cytometry were utilized to measure cell proliferation and apoptosis. Potential target was predicted by bioinformatics and was verified by dual-luciferase report gene assay and RNA pull down assay. QRT-PCR was used to quantify autophagy (LC3, Beclin1, P62) related genes. The m6A modification test is used to verify the effect of METTL3 on PSMA3-AS1. Tumor model was used to identify the effect of PSMA3-AS1 on tumor growth in vivo, and immunohistochemistry was applied to detect expression of ki67 and TUNEL. The results indicate that PSMA3-AS1 was upregulated in FLT3-ITD+ AML patients. Si-PSMA3-AS1 could inhibit the proliferation, autophagy and promote the apoptosis in MV4-11 and Molm13 cells. METTL3 could enhance the PSMA3-AS1 RNA stability. In addition, this study revealed that PSMA3-AS1 affected FLT3-ITD+ AML by targeting expression of miR-20a-5p, and miR-20a-5p further modulated expression of ATG16L1, an mRNA that down-regulated in AML, to affect disease advancement. PSMA3-AS1 could promote FLT3-ITD+ AML progression by regulating the level of autophagy through miR-20a-5p/ATG16L1 pathway. In addition, the increase of PSMA3-AS1 may be caused by the involvement of METTL3 in regulating its stability. This discovery will provide new horizons for early screening and targeted therapy of FLT3-ITD+ AML.

Hes1 Controls Proliferation and Apoptosis in Chronic Lymphoblastic Leukemia Cells by Modulating PTEN Expression.

Hairy and enhancer of split homolog-1 (HES1), regulated by the Notch, has been reported to play important roles in the immune response and cancers, such as leukemia. In this study, we aim to explore the effect of HES1-mediated Notch1 signaling pathway in chronic lymphocytic leukemia (CLL). Reverse transcription quantitative polymerase chain reaction and Western blot assay were conducted to determine the expression of HES1, Notch1, and PTEN in B lymphocytes of peripheral blood samples of 60 CLL patients. We used lentivirus-mediated overexpression or silencing of HES1 and the Notch1 signaling pathway inhibitor, MW167, to detect the interaction among HES1, Notch1, and PTEN in CLL MEC1 and HG3 cells. MTT assay and flow cytometry were employed for detection of biological behaviors of CLL cells. HES1 and Notch1 showed high expression, but PTEN displayed low expression in B lymphocytes of peripheral blood samples of patients with CLL in association with poor prognosis. HES1 bound to the promoter region of PTEN and reduced PTEN expression. Overexpression of HES1 activated the Notch1 signaling pathway, thus promoting the proliferation of CLL cells, increasing the proportion of cells arrested at the S phase and limiting the apoptosis of CLL cells. Collectively, HES1 can promote activation of the Notch1 signaling pathway to cause PTEN transcription inhibition and the subsequent expression reduction, thereby promoting the proliferation and inhibiting the apoptosis of CLL cells.

Effect of EPA on Hsp90 and GRα protein expression in multiple myeloma drug-resistant cells.

BACKGROUND: Approximately 20% of MM patients harbor glucocorticoid (GC) resistance and are not responsive to therapeutic effect. Chaperoneheat-shock proteins Hsp90 is needed for ligand docking, The imbalance of Hsp90/GRα (glucocorticoid receptor α) may be an important cause of GC resistance. Recent studies have indicated that EPA could repress cancer cell growth by regulating critical influential factors in progression of cancer, consisting of resistance to drugs, chemosensitivity. The aim of the present study was to test the cytotoxic effects of EPA alone or EPA + Dexamethasone in dexamethasone-resistant MM cell (MM.1R) and investigate whether DHA can induce apoptosis and reverse acquired glucocorticoid resistance in dexamethasone-resistant MM cell (MM.1R). METHODS: Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of MM.1R cells after treating with EPA alone and EPA combined with DEX. Mitochondrial membrane potential was measured by flow cytometry and GRα and Hsp90 protein expression were assessed by western blot analysis. RESULTS: EPA alone was able to inhibit cell proliferation as evidenced by CCK-8 assay and the tumor growth was remarkably suppressed by EPA + Dexamethasone, Cell apoptosis after EPA treatment was obviously observed by Flow cytometry analysis of the mitochondrial membrane potential. Analysis of Hsp90 and GRα proteins in MM.1R cells incubated with EPA revealed down-regulation of Hsp90 and up-regulation of GRα. Accordingly, the Hsp90/GRα ratio was significantly decreased with the increase of EPA concentration. CONCLUSIONS: EPA might be used as a new effective treatment for reversal of glucocorticoid-resistance in multiple myeloma.

Buyang Huanwu Decoction Attenuates Infiltration of Natural Killer Cells and Protects Against Ischemic Brain Injury.

BACKGROUND/AIMS: Natural killer (NK) cells are among the first immune cells that respond to an ischemic insult in human brains. The infiltrated NK cells damage blood-brain barrier (BBB) and exacerbate brain infarction. Buyang Huanwu Decoction (BHD), a classic Chinese traditional herbal prescription, has long been used for the treatment of ischemic stroke. The present study investigated whether BHD can prevent brain infiltration of NK cells, attenuate BBB disruption and improve ischemic outcomes. METHODS: Transient focal cerebral ischemia was induced in rats by a 60-minute middle cerebral artery occlusion, and BHD was orally administrated at the onset of reperfusion, 12 hours later, then twice daily. Assessed parameters on Day 3 after ischemia were: neurological and motor functional deficits through neurological deficit score and rotarod test, respectively; brain infarction through TTC staining; BBB integrity through Evans blue extravasation; matrix metalloproteinase-2/9 activities through gelatin zymography; tight junction protein, nuclear factor-kB (NF-kB) p65 and phospho-p65 levels through Western blotting; NK cell brain infiltration and CXCR3 levels on NK cells through flow cytometry; interferon-γ production through ELISA; CXCL10 mRNA levels through real-time PCR; CXCL10 expression and p65 nuclear translocation through immunofluorescence staining. RESULTS: BHD markedly reduced brain infarction, improved rotarod performance, and attenuated BBB breakdown. Concurrently, BHD attenuated the upregulation of matrix metalloproteinase-2/9 activities and the degradation of tight junction proteins in the ischemic brain. Infiltration of NK cells was observed in the ischemic hemisphere, and this infiltration was blunted by treatment with BHD. BHD suppressed brain ischemia-induced interferon-γ and chemokine CXCL10 production. Furthermore, BHD significantly reduced the expression of CXCR3 on brain-infiltrated NK cells. Strikingly, BHD did not affect NK cell levels or its CXCR3 expression in the spleen or peripheral blood after brain ischemia. The nuclear translocation of NF-kB p65 and phospho-p65 in the ischemic brain was inhibited by BHD. CONCLUSION: Our findings suggest that BHD prevents brain infiltration of NK cells, preserves BBB integrity and eventually improves ischemic outcomes. The inhibitory effects of BHD on NK cell brain invasion may involve its ability of suppressing NF-kB-associated CXCL10-CXCR3-mediated chemotaxis. Notably, BHD only suppresses NK cells and their CXCR3 expression in the ischemic brain, but not those in periphery.

[Short-term efficacy observation on Chinese traditional medicine used after functional endoscopic sinus surgery for chronic sinusitis].

OBJECTIVE: To evaluate the efficacy of chinese traditional treatment after functional endoscopic sinus surgery (FESS) for patients with chronic sinusitis. METHOD: Eighty-eight cases of patients with chronic sinusitis were randomly divided into control group and treatment group after FESS and followed for 3 months. The control group received routine treatment. The treatment group received Chinese traditional treatment on the basis of routine treatment. VAS scores, Lund-Kennedy scores and Lund-Mackay scores were employed to conduct the subjective and objective assessment, comprehensively evaluate the clinical efficacy before and after treatment. RESULT: (1) After 3 months of treatment, the two groups of VAS scores and Lund-Mackay scores were significantly improved before treatment (P<0. 05). (2)After 3 months of treatment, the effectiveness of the control group was 81. 8%, treatment group was 97. 7%, the difference was statistically significant(P<0. 05). CONCLUSION: Chinese traditional treatment after FESS can reduce postoperative mucosal edema and promote the postoperative recovery of sinus mucosal inflammation, is effective in preventing the recurrence of postoperative.

Adiponectin signals through Adiponectin Receptor 1 to reverse imatinib resistance in K562 human chronic myeloid leukemia cells.

Adiponectin, a member of adipokines, is a functional ligand for Adiponectin Receptor-1 (AdipoR1) and Adiponectin Receptor-2 (AdipoR2), and has been found to be linked to the risk of CML. Imatinib has undoubtedly revolutionised the management and outcome of chronic myeloid leukemia (CML), however imatinib resistance has been recognized as a major problem in CML therapy. In this study, we first established imatinib-resistant K562 CML cells, and then evaluated the effect of Adiponectin in reversing imatinib resistance. The data presented here demonstrated that Adiponectin was able to reverse K562 resistance to imatinib in vitro and in vivo. Additional data with molecular approaches suggested that the reversion of Adiponectin in imatinib resistance signals through AdipoR1 but not AdipoR2 to downregulate Bcr-Abl expression and effect in imatinib-resistant K562 CML cells. Taken together, our data showed that Adiponectin can reverse imatinib resistance in CML, and to a certain extent elucidate the mechanism of Adiponectin reversing imatinib resistance that may provide a new and promising approach in imatinib resistance management in CML therapy.

Enhancing effect of ß-elemene emulsion on chemotherapy with harringtonine, aclacinomycin, and Ara-c in treatment of refractory/relapsed acute myeloid leukemia.

Objective : This study is to determine the curative effect of ß-elemene emulsion on chemotherapy in the treatment of refractory/relapsed acute myeloid leukemia (AML). Methods : In the ß-elemene emulsion plus HAA chemotherapy (harringtonine, aclacinomycin, Ara-c group) group, 120 cases received ß-elemene emulsion (400 mg) plus the HAA treatment. A 14-day treatment was a course of treatment, followed by an 8-14 day pause, and then the next course of treatment. The HAA treatment included Ara-C, 100 mg/m2, once every 12 h from day 1 to day 7; aclacinomycin, 20 mg/m2, from day 1 to day 7; and homoharringtonine, 4 mg/m2, from day 1 to day 7. The patients in the control HAA group received HAA treatment only. For both groups, effective antibiotics were given to patients when it was necessary. Results : The total effective rate in the ß-elemene emulsion plus HAA group was 80.8%. But the total effective rate in the HAA only group was 52.9%. These results suggest that the ß-elemene emulsion plus HAA treatment has a much better curative effect in comparison with the HAA only treatment (P < 0.05). Furthermore, ß-elemene emulsion has slightly adverse response, without causing blood and bone marrow depression. Conclusion : ß-elemene emulsion has a curative effect in treatment of refractory/relapsed AML in combination with harringtonine, aclacinomycin, and Ara-c.