Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway.

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes.

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.

A High-Performance Deep Neural Network Model for BI-RADS Classification of Screening Mammography.

Globally, the incidence rate for breast cancer ranks first. Treatment for early-stage breast cancer is highly cost effective. Five-year survival rate for stage 0-2 breast cancer exceeds 90%. Screening mammography has been acknowledged as the most reliable way to diagnose breast cancer at an early stage. Taiwan government has been urging women without any symptoms, aged between 45 and 69, to have a screening mammogram bi-yearly. This brings about a large workload for radiologists. In light of this, this paper presents a deep neural network (DNN)-based model as an efficient and reliable tool to assist radiologists with mammographic interpretation. For the first time in the literature, mammograms are completely classified into BI-RADS categories 0, 1, 2, 3, 4A, 4B, 4C and 5. The proposed model was trained using block-based images segmented from a mammogram dataset of our own. A block-based image was applied to the model as an input, and a BI-RADS category was predicted as an output. At the end of this paper, the outperformance of this work is demonstrated by an overall accuracy of 94.22%, an average sensitivity of 95.31%, an average specificity of 99.15% and an area under curve (AUC) of 0.9723. When applied to breast cancer screening for Asian women who are more likely to have dense breasts, this model is expected to give a higher accuracy than others in the literature, since it was trained using mammograms taken from Taiwanese women.

Automatic segmentation of paravertebral muscles in abdominal CT scan by U-Net: The application of data augmentation technique to increase the Jaccard ratio of deep learning.

ABSTRACT: Sarcopenia, characterized by a decline of skeletal muscle mass, has emerged as an important prognostic factor for cancer patients. Trunk computed tomography (CT) is a commonly used modality for assessment of cancer disease extent and treatment outcome. CT images can also be used to analyze the skeletal muscle mass filtered by the appropriate range of Hounsfield scale. However, a manual depiction of skeletal muscle in CT scan images for assessing skeletal muscle mass is labor-intensive and unrealistic in clinical practice. In this paper, we propose a novel U-Net based segmentation system for CT scan of paravertebral muscles in the third and fourth lumbar spines. Since the number of training samples is limited (i.e., 1024 CT images only), it is well-known that the performance of the deep learning approach is restricted due to overfitting. A data augmentation strategy to enlarge the diversity of the training set to boost the performance further is employed. On the other hand, we also discuss how the number of features in our U-Net affects the performance of the semantic segmentation. The efficacies of the proposed methodology based on w/ and w/o data augmentation and different feature maps are compared in the experiments. We show that the Jaccard score is approximately 95.0% based on the proposed data augmentation method with only 16 feature maps used in U-Net. The stability and efficiency of the proposed U-Net are verified in the experiments in a cross-validation manner.

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway.

Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in Taraxacum officinale extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.

NF-κB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-Associated gastric cancer.

Helicobacter pylori infection is an important pathogenic risk factor for gastric cancer, but it is still unclear what tumor markers for gastric cancer induced by H. pylori can be consistently detected. Using an miRNA microarray, we found that miR-18a-3p (6.02-fold) and miR-4286 (5.73-fold) were significantly increased in H. pylori- associated gastric cancer. In a cohort of gastric cancer patients (N = 104), serum expression of miR-18a-3p and miR-4286 was positively and significantly correlated with H. pylori; furthermore, miR-18a-3p was positively correlated with invasion (P = 0.029), and miR-4286 was positively correlated with tumor stage (P = 0.033), tumor size (P = 0.041), and lymph node metastasis (P = 0.009). Overexpression of miR-18a-3p and miR-4286 also increased cancer cell proliferation and motility and both inhibited expression of BZRAP1, resulting in tumor progression in vitro. In addition, lipopolysaccharide co-mediated the expression of miR-18a-3p and miR-4286 by activating the NF-κB transcription factor, but TAK-242 (TLR4 inhibitor) blocked this effect. These results demonstrate that serum miR-18a-3p and miR-4286 levels in H. pylori-associated gastric cancer may be useful prognostic biomarkers and suggest a novel signaling pathway of targeting BZRAP1 in gastric cancer.

Cecal lipoma with subclinical appendicitis: A case report.

BACKGROUND: Colonic lipomas are rare, slow-growing benign tumors. Colonic lipomas are generally asymptomatic and are found incidentally. Although cases of cecal lipoma have been sporadically reported in the literature, the disease has not been systematically reviewed. CASE SUMMARY: We present a 44-year-old man who underwent a routine physical check-up during which colonoscopic examination revealed an asymptomatic 1.5-cm cecal mass at the appendiceal orifice. Laparoscopic exploration was performed that also demonstrated a congested and erythematous appendix. En bloc resection of both the cecum and vermiform appendix was performed because of the suspicion of malignancy. Histopathological examination revealed a cecal lipoma composed of mature adipose tissue, and the appendix showed subclinical inflammation. Our procedures and findings were discussed, along with relevant English literature that was retrieved from the PubMed database from 2000 to 2017. Twenty-six cases, including ours, were reported. Consistent with the findings of the literature, it is difficult to obtain a definitive diagnosis by colonoscopic biopsy. CONCLUSION: Surgery remains the treatment of choice for this condition. Intraoperative frozen pathological sectioning helped the surgeon decide the extent of surgery, and radical surgery was avoided. Excision of benign lesions occupying the appendiceal orifice may be indicated for the prevention of later development of acute appendicitis. The prognosis is generally good, with only one of the 26 reported patients complicated with acute appendicitis, who subsequently succumbed due to severe comorbidities and sepsis.