Ruihan Zhang^1,2, Junhao Yang¹, Chunxiao Chen^1,*

Molecular & Cellular Biomechanics, Vol.15, No.3, pp. 177-187, 2018, DOI: 10.3970/mcb.2018.04292

Abstract The proportion of cells staining for the nuclear antigen Ki-67 is an important predictive indicator for assessment of tumor cell proliferation and growth in routine pathological investigation. Instead of traditional scoring methods based on the experience of a trained laboratory scientist, deep learning approach can be automatically used to analyze the expression of Ki-67 as well. Deep learning based on convolutional neural networks (CNN) for image classification and single shot multibox detector (SSD) for object detection are used to investigate the expression of Ki-67 for assessment of biopsies from patients with breast cancer in this study. The results focus on… More >

R. M. Ardito Marretta^*, F. Ales^†

Molecular & Cellular Biomechanics, Vol.7, No.4, pp. 225-266, 2010, DOI:10.3970/mcb.2010.007.225

Abstract In this paper, cell cycle in higher eukaryotes and their molecular networks signals both inG1/SandG2/Mtransitions are replicatedin silico. Biochemical kinetics, converted into a set of differential equations, and system control theory are employed to design multi-nested digital layers to simulate protein-to-protein activation and inhibition for cell cycle dynamics in the presence of damaged genomes. Sequencing and controlling the digital process of four micro-scale species networks (p53/Mdm2/DNA damage, p21mRNA/cyclin-CDK complex, CDK/CDC25/wee1/ SKP2/APC/CKI and apoptosis target genes system) not only allows the comprehension of the mechanisms of these molecule interactions but paves the way for unraveling the participants and their by-products, until… More >

R. M. Ardito Marretta^∗,†, G. Barbaraci^‡

Molecular & Cellular Biomechanics, Vol.7, No.3, pp. 135-164, 2010, DOI:10.3970/mcb.2010.007.135

Abstract Upon severe DNA damage, p21 acts in a dual mode; on the one hand, it inhibits the cyclin-CDK complex for arresting the G2/M transition and on the other hand, it indirectly becomes an apoptotic factor by activating - in sequence - the retinoblastoma protein, E2F1 and APAF1 expressions. But, in a cancer cells proliferation, the mechanisms of, and participants in, the apoptosis failure remain unclear. Since the p21/p53/Mdm2 proteins network normally involves a digital response in a cancer cell, through an original design of a cell signalling-protein simulator, we demonstrate,in silico, that apoptosis phase instability is fully reciprocated by p21mRNA… More >

Shile Liang^†, Meghan Hoskins^†, Cheng Dong^‡

Molecular & Cellular Biomechanics, Vol.7, No.2, pp. 77-91, 2010, DOI:10.3970/mcb.2010.007.077

Abstract To complete the metastatic journey, cancer cells have to disseminate through the circulation and extravasate to distal organs. However, the extravasation process, by which tumor cells leave a blood vessel and invade the surrounding tissue from the microcirculation, remains poorly understood at the molecular level. In this study, tumor cell adhesion to the endothelium (EC) and subsequent extravasation were investigated under various flow conditions. Results have shown polymorphonuclear neutrophils (PMNs) facilitate melanoma cell adhesion to the EC and subsequent extravasation by a shear-rate dependent mechanism. Melanoma cell-PMN interactions are mediated by the binding between intercellular adhesion molecule-1 (ICAM-1) on melanoma… More >

R. M. Ardito Marretta^*, G. Barbaraci^†

Molecular & Cellular Biomechanics, Vol.6, No.3, pp. 175-190, 2009, DOI:10.3970/mcb.2009.006.175

Abstract This study, through a typical aerospace systems architecture, suggests an engineering design of a human cancer cell circuitry in which a digital optimal control matrix is assigned to repair the DNA damage level and/or to trigger its apoptosis.
Here, the conceived machinery is proposed taking into account the state of the art in cancer investigation. However, it could be further generalized. The most recent studies on cancer pathologies give a predominant role to the oncosuppressor protein p53 and its antagonist, the oncogene Mdm2.
Experimental and theoretical approaches are in agreement in deducing a “digital” response of the p53 when genomic… More >

Cheng Dong^1,2,3, Margaret J. Slattery^2,3, Shile Liang³, Hsin-Hsin Peng²

Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 145-160, 2005, DOI:10.3970/mcb.2005.002.145

Abstract Attachment of tumor cells to the endothelium (EC) under flow conditions is critical for the migration of tumor cells out of the vascular system to establish metastases. Innate immune system processes can potentially promote tumor progression through inflammation dependant mechanisms.\nobreakspace {} White blood cells, neutrophils (PMN) in particular, are being studied to better understand how the host immune system affects cancer cell adhesion and subsequent migration and metastasis. Melanoma cell interaction with the EC is distinct from PMN-EC adhesion in the circulation. We found PMN increased melanoma cell extravasation, which involved initial PMN tethering on the EC, subsequent PMN capture… More >