Publications by authors named "Yitshak Zohar"

Prostate cancer is a disease in which cells in the prostate, a gland in the male reproductive system below the bladder, grow out of control and, among men, it is the second-most frequently diagnosed cancer (other than skin cancer). In recent years, prostate cancer death rate has stabilized and, currently, it is the second-most frequent cause of cancer death in men (after lung cancer). Most deaths occur due to metastasis, as cancer cells from the original tumor establish secondary tumors in distant organs.

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Article Synopsis
  • Androgen Receptor (AR) activity in the prostate stroma is essential for maintaining a healthy prostate by promoting epithelial cell differentiation via morphogenic factors.
  • In aggressive prostate cancer, there is a loss of AR expression in the stroma, linked to tumor-secreted factors TGFβ1 and TNFα, which suppress AR mRNA and protein levels through the NF-κB signaling pathway, as well as p38-MAPK pathways.
  • Furthermore, the absence of AR leads to decreased production of key morphogens (FGF10 and Wnt16), disrupting normal prostate cell survival and epithelial homeostasis.
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Lack of adequate models significantly hinders advances in prostate cancer treatment, where resistance to androgen-deprivation therapies and bone metastasis remain as major challenges. Current models fail to faithfully mimic the complex prostate physiology. animal models can shed light on the oncogenes involved in prostate cancer development and progression; however, the animal prostate gland is fundamentally different from that of human, and the underlying genetic mechanisms are different.

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Background: CASK-related neurodevelopmental disorders are untreatable. Affected children show variable severity, with microcephaly, intellectual disability (ID), and short stature as common features. X-linked human CASK shows dosage sensitivity with haploinsufficiency in females.

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The balance between cell quiescence and proliferation is fundamental to tissue physiology and homeostasis. Recent studies have shown that quiescence is not a passive and homogeneous state but actively maintained and heterogeneous. These cellular characteristics associated with quiescence were observed primarily in cultured cells under a static medium.

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Cancer is a disease in which cells in the body grow out of control; breast cancer is the most common cancer in women in the United States. Due to early screening and advancements in therapeutic interventions, deaths from breast cancer have declined over time, although breast cancer remains the second leading cause of cancer death among women. Most deaths are due to metastasis, as cancer cells from the primary tumor in the breast form secondary tumors in remote sites in distant organs.

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As the range of applications of organs-on-chips is broadening, the evaluation of aerosol-based therapies using a lung-on-a-chip model has become an attractive approach. Inhalation therapies are not only minimally invasive but also provide optimal pharmacokinetic conditions for drug absorption. As drug development evolves, it is likely that better screening through use of organs-on-chips can significantly save time and cost.

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Lung-on-a-chip (LoC) models hold the potential to rapidly change the landscape for pulmonary drug screening and therapy, giving patients more advanced and less invasive treatment options. Understanding the drug absorption in these microphysiological systems, modeling the lung-blood barrier is essential for increasing the role of the organ-on-a-chip technology in drug development. In this work, epithelial/endothelial barrier tissue interfaces were established in microfluidic bilayer devices and transwells, with porous membranes, for permeability characterization.

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Receptor-ligand binding has been one of the more popular approaches to specifically targeting tumour cells. In this work, targeting efficiency was quantitatively characterized using silica particles functionalized with EpCAM antibodies and EpCAM-expressing BT-20 breast cancer cells. The effects of incubation time and particle concentration on the number of functionalised particles bound to target cells were experimentally investigated.

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Microfluidic devices functionalized with EpCAM antibodies were utilized for the capture of target cancer cells representing circulating tumor cells (CTCs). The fraction of cancer cells captured from homogeneous suspensions is mainly a function of flow shear rate, and can be described by an exponential function. A characteristic shear rate emerges as the most dominant parameter affecting the cell attachment ratio.

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Self-assembled peptide/protein nanofibers are valuable 1D building blocks for creating complex structures with designed properties and functions. It is reported that the self-assembly of silk-elastin-like protein polymers into nanofibers or globular aggregates in aqueous solutions can be modulated by tuning the temperature of the protein solutions, the size of the silk blocks, and the charge of the elastin blocks. A core-sheath model is proposed for nanofiber formation, with the silk blocks in the cores and the hydrated elastin blocks in the sheaths.

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Dynamic states of cancer cells moving under shear flow in an antibody-functionalized microchannel are investigated experimentally and theoretically. The cell motion is analyzed with the aid of a simplified physical model featuring a receptor-coated rigid sphere moving above a solid surface with immobilized ligands. The motion of the sphere is described by the Langevin equation accounting for the hydrodynamic loadings, gravitational force, receptor-ligand bindings, and thermal fluctuations; the receptor-ligand bonds are modeled as linear springs.

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A unique flow field pattern in a bio-functional microchannel is utilized to significantly enhance the performance of a microsystem developed for selectively isolating circulating tumor cells from cell suspensions. For high performance of such systems, disposal of maximum non-target species is just as important as retention of maximum target species; unfortunately, most studies ignore or fail to report this aspect. Therefore, sensitivity and specificity are introduced as quantitative criteria to evaluate the system performance enabling a direct comparison among systems employing different techniques.

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A study of the influences of embedding artificial structures in a microfluidic device for CE with a free buffer solution is presented. Compared with conventional slab-gel electrophoresis, three major additional effects on the overall system performance are identified when sub-micron pillar arrays are integrated into a standard CE microsystem. Since DNA molecules have to migrate in-between and interact with the pillars, pillar geometry is first demonstrated to have a direct impact on the DNA motion pattern.

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Attachment, deformation and detachment of N-cadherin expressing prostate and breast cancer cell lines in a functionalized microchannel under hydrodynamic loading have been studied. N-cadherin antibodies are immobilized on the microchannel surface to capture the target cancer cells, PC3N and MDA-MB-231-N, from a homogeneous cell suspension. Although difficult, a significant fraction of moving cells can be captured under a low flow rate.

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A novel photolithography method to build aligned patterns of two different proteins is presented. Chessboard patterns of 125 microm x 125 microm squares are constructed on a silicon dioxide substrate, using standard photoresist chemistries in combination with low-temperature oxygen plasma etching. Low-melting-point agarose (LMPA) is used to protect underlying protein layers and, at the appropriate stage, the digestive enzyme GELase (EPICENTRE) is used to selectively remove the prophylactic LMPA layers.

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A novel self-aligned method to selectively immobilize proteins on a silicon dioxide surface is developed in conjunction with a standard lift-off patterning technique of a PEG layer. The approach is designed to photolithographically pattern regions that specifically bind target proteins and particles, surrounded by regions that suppress non-specific attachment of bio-species. The physical and biological properties of the derivatized surfaces at the end of the fabrication process are characterized.

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