Biomechanical microenvironment regulates fusogenicity of breast cancer cells

Fusion of cancer cells is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have demonstrated that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive area of the patterned substrates, reducing cytoskeletal tensions pharmacologically, altering matrix stiffness, and modulating pattern curvature all supported the spontaneous fusion and stability of these multinucleated giant cells. These observations highlight that the biomechanical microenvironment of cancer cells, including the matrix rigidity and interfacial curvature, can directly modulate their fusogenicity, an unexplored mechanism through which biophysical cues regulate tumor progression

Synthesis and structure-activity relationship studies of novel 3,9-substituted α-carboline derivatives with high cytotoxic activity against colorectal cancer cells

In our continued focus on 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) analogs, we synthesized a novel series of 3,9-substituted α-carboline derivatives and evaluated the new compounds for antiproliferactive effects. Structure activity relationships revealed that a COOCH or CHOH group at position-3 and substituted benzyl group at position-9 of the α-carboline nucleus were crucial for maximal activity. The most active compound, , showed high levels of cytotoxicity against HL-60, COLO 205, Hep 3B, and H460 cells with IC values of 0.3, 0.49, 0.7, and 0.8 μM, respectively. The effect of compound on the cell cycle distribution demonstrated G2/M arrest in COLO 205 cells. Furthermore, mechanistic studies indicated that compound induced apoptosis by activating death receptor and mitochondria dependent apoptotic signaling pathways in COLO 205 cells. The new 3,9-substituted α-carboline derivatives exhibited excellent anti-proliferative activities, and compound can be used as a promising pro-apoptotic agent for future development of new antitumor agents

EXTRACELLULAR MATRIX STIFFNESS AS A CUE TO SHAPE PHENOTYPIC EVOLUTION OF TRIPLE NEGATIVE BREAST CANCER

Accumulation of epigenetic and genetic changes results in oncogenic transformation of epithelial cells. During breast cancer metastasis, while the extracellular matrix (ECM) becomes stiffer, breast cancer cells transmit mechanical forces into intracellular tension and activate signaling pathways influencing growth, migration, and metastasis. Once cancer cells detach from the primary tumor, they intravasate into the vasculature, survive in the circulation, extravasate and adapt to a new microenvironment of a secondary site. Throughout the process, only a very small population of cancer cells survive, and they are likely to reside at the metastatic sites for several years. The most frequent metastatic sites for breast cancer are brain, lung, liver, and bone. Each has distinct mechanical and biochemical properties. To recapitulate this selection process, we grew triple negative breast cancer (TNBC) on soft and stiff biomaterials in addition to the widely used cell culture platform, tissue culture polystyrene over time. Alterations in phenotypes and gene expressions were captured. Since TNBC is heterogeneous, we were interested in investigating the phenotypes of their subclonal compositions. By isolating subclones from the established TNBC cell lines, we were able to measure variations in growth, motility, response to ECM stiffness and proteins, and drug response, etc

Visualization 1: Direct visualization of functional heterogeneity in hepatobiliary metabolism using 6-CFDA as model compound

Movie Originally published in Biomedical Optics Express on 01 September 2016 (boe-7-9-3574

Congenital Stationary Night Blindness: Clinical and Genetic Features

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert–Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype–phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype–phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed

Roadmap on biomaterials for women's health

The application of engineering tools and techniques to studying women's health, including biomaterials-based approaches, is a research field experiencing robust growth. Biomaterials are natural or synthetic materials used to repair or replace damaged tissues or organs or replicate an organ's physiological function. However, in addition to in vivo applications, there has been substantial recent interest in biomaterials for in vitro systems. Such artificial tissues and organs are employed in drug discovery, functional cell biological investigations, and basic research that would be ethically impossible to conduct in living women. This Roadmap is a collection of 11 sections written by leading and up-and-coming experts in this field who review and discuss four aspects of biomaterials for women's health. These include conditions that disproportionately but not exclusively affect women (e.g. breast cancer), conditions unique to female reproductive organs, in both non-pregnant and pregnant states, and sex differences in non-reproductive tissues (e.g. the cardiovascular system). There is a strong need to develop this exciting field, with the potential to materially influence women's lives worldwide.This article is published as Fogg, Kaitlin, Ning-Hsuan Tseng, Shelly R. Peyton, Pieper Holeman, Shannon Mc Loughlin, John P. Fisher, Allison Sutton et al. "Roadmap on biomaterials for women’s health." Journal of Physics: Materials 6 (2022): 012501. DOI: 10.1088/2515-7639/ac90ee. Copyright 2022 The Author(s). Attribution 4.0 International (CC BY 4.0). Posted with permission

Roadmap on biomaterials for women’s health

The application of engineering tools and techniques to studying women’s health, including biomaterials-based approaches, is a research field experiencing robust growth. Biomaterials are natural or synthetic materials used to repair or replace damaged tissues or organs or replicate an organ’s physiological function. However, in addition to in vivo applications, there has been substantial recent interest in biomaterials for in vitro systems. Such artificial tissues and organs are employed in drug discovery, functional cell biological investigations, and basic research that would be ethically impossible to conduct in living women. This Roadmap is a collection of 11 sections written by leading and up-and-coming experts in this field who review and discuss four aspects of biomaterials for women’s health. These include conditions that disproportionately but not exclusively affect women (e.g. breast cancer), conditions unique to female reproductive organs, in both non-pregnant and pregnant states, and sex differences in non-reproductive tissues (e.g. the cardiovascular system). There is a strong need to develop this exciting field, with the potential to materially influence women’s lives worldwide