Defining the landscape of metabolic dysregulations in cancer metastasis

Metastasis is the primary cause of cancer related deaths due to the limited number of efficient druggable targets. Signatures of dysregulated cancer metabolism could serve as a roadmap for the determination of new treatment strategies. However, the metabolic signatures of metastatic cells remain vastly elusive. Our aim was to determine metabolic dysregulations associated with high metastatic potential in breast cancer cell lines. We have selected 5 triple negative breast cancer (TNBC) cell lines including three with high metastatic potential (HMP) (MDA-MB-231, MDA-MB-436, MDA-MB-468) and two with low metastatic potential (LMP) (BT549, HCC1143). The normal epithelial breast cell line (hTERT-HME1) was also investigated. The untargeted metabolic profiling of cells and growth media was conducted and total of 479 metabolites were quantified. First we characterized metabolic features differentiating TNBC cell lines from normal cells as well as identified cell line specific metabolic fingerprints. Next, we determined 92 metabolites in cells and 22 in growth medium that display significant differences between LMP and HMP. The HMP cell lines had elevated level of molecules involved in glycolysis, TCA cycle and lipid metabolism. We identified metabolic advantages of cell lines with HMP beyond enhanced glycolysis by pinpointing the role of branched chain amino acids (BCAA) catabolism as well as molecules supporting coagulation and platelet activation as important contributors to the metastatic cascade. The landscape of metabolic dysregulations, characterized in our study, could serve as a roadmap for the identification of treatment strategies targeting cancer cells with enhanced metastatic potential.

Semantic Segmentation of Urinary Bladder Cancer Masses From CT Images: A Transfer Learning Approach

Urinary bladder cancer is one of the most common cancers of the urinary tract. This cancer is characterized by its high metastatic potential and recurrence rate. Due to the high metastatic potential and recurrence rate, correct and timely diagnosis is crucial for successful treatment and care. With the aim of increasing diagnosis accuracy, artificial intelligence algorithms are introduced to clinical decision making and diagnostics. One of the standard procedures for bladder cancer diagnosis is computer tomography (CT) scanning. In this research, a transfer learning approach to the semantic segmentation of urinary bladder cancer masses from CT images is presented. The initial data set is divided into three sub-sets according to image planes: frontal (4413 images), axial (4993 images), and sagittal (996 images). First, AlexNet is utilized for the design of a plane recognition system, and it achieved high classification and generalization performances with an AUCmicro¯ of 0.9999 and σ(AUCmicro) of 0.0006. Furthermore, by applying the transfer learning approach, significant improvements in both semantic segmentation and generalization performances were achieved. For the case of the frontal plane, the highest performances were achieved if pre-trained ResNet101 architecture was used as a backbone for U-net with DSC¯ up to 0.9587 and σ(DSC) of 0.0059. When U-net was used for the semantic segmentation of urinary bladder cancer masses from images in the axial plane, the best results were achieved if pre-trained ResNet50 was used as a backbone, with a DSC¯ up to 0.9372 and σ(DSC) of 0.0147. Finally, in the case of images in the sagittal plane, the highest results were achieved with VGG-16 as a backbone. In this case, DSC¯ values up to 0.9660 with a σ(DSC) of 0.0486 were achieved. From the listed results, the proposed semantic segmentation system worked with high performance both from the semantic segmentation and generalization standpoints. The presented results indicate that there is the possibility for the utilization of the semantic segmentation system in clinical practice.

Nail Mélanoma

Melanoma is originating from melanocytes, it is a malignant tumor with high metastatic potential. It is the leading cause of moratlity from skin cancer, Nail melanoma is a rare form of malignant melanoma. we report a new case of this rare localization