Learning multi-view and centerline topology connectivity information for pulmonary artery-vein separation.

BACKGROUND: Automatic pulmonary artery-vein separation has considerable importance in the diagnosis and treatment of lung diseases. However, insufficient connectivity and spatial inconsistency have always been the problems of artery-vein separation. METHODS: A novel automatic method for artery-vein separation in CT images is presented in this work. Specifically, a multi-scale information aggregated network (MSIA-Net) including multi-scale fusion blocks and deep supervision, is proposed to learn the features of artery-vein and aggregate additional semantic information, respectively. The proposed method integrates nine MSIA-Net models for artery-vein separation, vessel segmentation, and centerline separation tasks along with axial, coronal, and sagittal multi-view slices. First, the preliminary artery-vein separation results are obtained by the proposed multi-view fusion strategy (MVFS). Then, centerline correction algorithm (CCA) is used to correct the preliminary results of artery-vein separation by the centerline separation results. Finally, the vessel segmentation results are utilized to reconstruct the artery-vein morphology. In addition, weighted cross-entropy and dice loss are employed to solve the class imbalance problem. RESULTS: We constructed 50 manually labeled contrast-enhanced computed CT scans for five-fold cross-validation, and experimental results demonstrated that our method achieves superior segmentation performance of 97.7%, 85.1%, and 84.9% on ACC, Pre, and DSC, respectively. Additionally, a series of ablation studies demonstrate the effectiveness of the proposed components. CONCLUSION: The proposed method can effectively solve the problem of insufficient vascular connectivity and correct the spatial inconsistency of artery-vein.

Germline and somatic mutation profile in Cancer patients revealed by a medium-sized pan-Cancer panel.

Gene mutation detection and the resulted precision-medicine therapy is transforming clinical practice. Here, we report the use of a custom-developed, medium-sized, pan-cancer probe panel for the detection of somatic and germline mutations. We used a hybridization capture-based NGS assay for targeted deep sequencing of all exons and selected introns of 181 key cancer driver genes, covering both inherited risks and somatic mutations. We performed paired-variant calling on tumor samples and their matched normal samples. We processed clinical patient samples of formalin-fixed, paraffin embedded tumors (FFPE samples) and cell-free peripheral blood (cfDNA samples). We found germline mutations of inherited cancer risk at 9%; and discovered a novel germline mutation in BRCA1. Somatic mutation rate in driver genes is at 73.1%, much higher than previously reported. On recommending precision-medicine therapeutics, we achieved 91.6% for patients with FFPE samples.

Melatonin Protects Neural Stem Cells Against Tri-Ortho-Cresyl Phosphate-Induced Autophagy.

Tri-ortho-cresyl phosphate (TOCP) is an extensively used organophosphate in industry. It has been proven to lead to toxicity in different organ systems, especially in the nervous system. Neural stem cells (NSCs) play important roles in both embryonic and adult nervous systems. However, whether TOCP induces cytotoxicity in embryonic NSCs remains unclear. In this study, mouse NSCs were exposed to different concentrations of TOCP for 24 h. The results showed that TOCP led to impaired proliferation of NSCs and induced the autophagy of NSCs by increasing the generation of intracellular reactive oxygen species (ROS) and decreasing the phosphorylation of extracellular regulated protein kinase (ERK1/2). Melatonin has been reported to exert neuroprotective effects via various mechanisms. Therefore, we further investigate whether melatonin has potential protective effects against TOCP-induced cytotoxicity on NSCs. Our data showed that melatonin pretreatment attenuated TOCP-induced autophagy by suppressing oxidative stress and restoring ERK1/2 phosphorylation consistently. Taken together, the results indicated that TOCP induced the autophagy in mouse NSCs, and melatonin may effectively protect NSCs against TOCP-induced autophagy.

Chemotherapy Resistance Molecular Mechanism in Small Cell Lung Cancer.

The malignancy of small cell lung cancer (SCLC) is the highest amongst all lung cancer types. It is characterized by rapid growth, early occurrence of distant sites metastasis, poor survival rates and is initially sensitive to chemotherapy and radiotherapy. However, most patients eventually relapse or disease progresses because of chemotherapy resistance. Because of lack of effective second-line therapies, the prognosis of SCLC patients is usually poor. For the development of novel therapies, it is necessary to understand the mechanisms of chemotherapy resistance in SCLC. The mechanism is complex, because multiple factors could lead to chemotherapy resistance. An overview of multiple events triggering the formation of chemotherapy resistance phenotypes of SCLC cells is discussed.

Resveratrol-loaded folic acid-grafted dextran stearate submicron particles exhibits enhanced antitumor efficacy in non-small cell lung cancers.

In this study, we have aimed to prepare folic acid-conjugated dextran stearate (DF) polymeric micelles to target resveratrol in lung cancers. The polymeric micelle was nanosized and exhibited a controlled drug release pattern. The resveratrol (RSV)-loaded dextran stearate (RSV-DF) micelles exhibited an enhanced cellular uptake in A549 cells due to the folic acid-based receptor interactions. We have demonstrated that RSV-DF polymeric micelles retain the cytotoxic and metabolic effects of RSV on A549 cancer cells with potencies similar to that of the free compound. Furthermore, RSV-DF showed an enhanced cellular apoptosis of cancer cells compared to that of free RSV. We have found that apoptosis induced by RSV-DF was associated with the higher expression of p53, caspase-3, and BAX than the free RSV. The higher level of BAX and caspase-3 further indicates the involvement of mitochondria-dependent apoptosis in the anticancer efficacy of formulations. Based on these results, it can be concluded that natural compound like RSV could be an interesting prospect to treat lung cancers and the fact that folic acid-conjugated dextran stearate could be a potential carrier to deliver the drug in the cancer cells.

Icaritin induces apoptotic and autophagic cell death in human glioblastoma cells.

BACKGROUND: GBM represents the most aggressive type of glioma which is featured by extremely aggressive invasion and destructive malignancy with a high proliferation rate. The aim of this study was to investigate the in vitro anti-tumor effect of icaritin in human GBM cell line U87. METHODS: The effect of icaritin on In vitro cell viability was determined by MTT assay and colony formation assay. The inducing effect of icaritin on cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation was assessed by flow cytometry. The apoptotic cell death was also confirmed by TUNEL assay. The expression levels of target or marker molecules were examined by western blot. The activity of caspase-3, -8 and -9 was detected with ELISA kit. RESULTS: Our results showed that icaritin significantly induced both caspase-dependent apoptosis and autophagy in human GBM cell line U87. Additionally, our findings revealed that icaritin exerted anti-tumor effect by modulating Stat3 through generating ROS and subsequent activation of AMPK and inhibition of mTOR. Further investigation also showed that icaritin-induced autophagy served as a pro-death function and possibly contributed to icaritin-induced apoptosis. CONCLUSION: Icaritin potently inhibit the cell growth of human GBM cell line U87 through inducing both caspase-dependent apoptosis and autophagy. Base on our findings, icaritin can be considered as a promising candidate therapeutic agent for treatment of GBM, though further studies are needed.

[Clinical value of preoperative serum VEGF, CRP and IL-6 levels in colorectal carcinoma].

OBJECTIVE: To determine the preoperative serum VEGF, IL-6, and CRP levels in colorectal carcinoma, and to explore their correlation with disease status and prognosis. METHODS: Serum VEGF and IL-6 levels were assessed using ELISA, and CRP was measured by immunoturbidimetry. They were compared between the colorectal carcinoma group and the control group. The five-year survival rate and poor prognostic factors were analyzed by Kaplan-Meier and Log-rank method, respectively. RESULTS: The serum VEGF, IL-6, and CRP levels in colorectal carcinoma were (591 ± 312) pg/ml, (13.2 ± 3.7) pg/ml, and (1.14 ± 0.87) mg/dl, respectively, higher than that in the control group. The two groups showed significant difference in VEGF and CRP (P < 0.001, P = 0.002). VEGF expression was higher in male than that in female [(638 ± 387) pg/ml vs. (552 ± 271) pg/ml, P = 0.042]. The cases with tumor size smaller than 5 cm had lower VEGF expression compared with that in cases with tumor size ≥ 5 cm [(538 ± 275) pg/ml vs. (647 ± 331) pg/ml, P = 0.009]. IL-6 expression showed significant difference in males (11.7 ± 3.2) and females (15.2 ± 4.0) pg/ml, (P = 0.011). The five-year survival rate in the group with VEGF < 591 pg/ml was 86.8% (33/38), higher than that in the ≥ 591 pg/m group. High VEGF level tended to reduce survival (χ(2) = 0.933, P = 0.344). VEGF ≥ 591 pg/ml was a factor of poor prognosis in colorectal carcinoma, assessed by Log-rank methods (P < 0.05). Tumor size and VEGF concentration were risk factors of prognosis (P = 0.032, OR = 0.985; P = 0.011, OR = 0.976). CONCLUSIONS: Serum VEGF and IL-6 expressions have gender differences. Serum VEGF can be used as a biomaker of clinical diagnosis of colorectal cancer, and has an important significance on the prognosis of patients.