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Man H.B.,Northwestern University | Ho D.,Northwestern University | Ho D.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology
Journal of Laboratory Automation | Year: 2013

Nanoparticles possess a wide range of exceptional properties applicable to biology and medicine. In particular, nanodiamonds (NDs) are being studied extensively because they possess unique characteristics that make them suitable as platforms for diagnostics and therapeutics. This carbon-based material (2-8 nm) is medically relevant because it unites several key properties necessary for clinical applications, such as stability and compatibility in biological environments, and scalability in production. Research by the Ho group and others has yielded ND particles with a variety of capabilities ranging from delivery of chemotherapeutic drugs to targeted labeling and uptake studies. In addition, encouraging new findings have demonstrated the ability for NDs to effectively treat chemoresistant tumors in vivo. In this review, we highlight the progress made toward bringing nanodiamonds from the bench to the bedside. © 2013 Society for Laboratory Automation and Screening. Source


Ueno T.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology
Journal of biomedical materials research. Part B, Applied biomaterials | Year: 2012

The time-dependent degradation of titanium bioactivity (i.e., the biological aging of titanium) has been reported in previous studies. This phenomenon is caused by the loss of hydrophilicity and the inevitable occurrence of progressive contamination of titanium surfaces by hydrocarbons. In this study, we tested the hypothesis that gamma ray treatment, owing to its high energy to decompose and remove organic contaminants, enhances the bioactivity and osteoconductivity of titanium. Titanium disks were acid-etched and stored for 4 weeks. Rat bone marrow-derived osteoblasts (BMOs) were cultured on titanium disks with or without gamma ray treatment (30 kGy) immediately before experiments. The cell density at day 2 increased by 50% on gamma-treated surfaces, which reflected the 25% higher rate of cell proliferation. Osteoblasts on gamma-treated surfaces showed 30% higher alkaline phosphatase activity at day 5 and 60% higher calcium deposition at day 20. The strength of in vivo bone-implant integration increased by 40% at the early healing stage of week 2 for gamma-treated implants. Gamma ray-treated surfaces regained hydrophilicity and showed a lower percentage of carbon (35%) as opposed to 48% on untreated aged surfaces. The data indicated that gamma ray pretreatment of titanium substantially enhances its bioactivity and osteoconductivity, in association with the significant reduction in surface carbon and the recovery of hydrophilicity. The results suggest that gamma ray treatment could be an effective surface enhancement technology to overcome biological aging of titanium and improve the biological properties of titanium implants. Copyright © 2012 Wiley Periodicals, Inc. Source


Kozlowska A.K.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | Kozlowska A.K.,Poznan University of Medical Sciences | Kaur K.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | Topchyan P.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | And 2 more authors.
Cancer Immunology, Immunotherapy | Year: 2016

Based on data obtained from oral, pancreatic and lung cancers, glioblastoma, and melanoma, we have established that natural killer (NK) cells target cancer stem-like cells (CSCs). CSCs displaying low MHC class I, CD54, and PD-L1 are killed by cytotoxic NK cells and are differentiated by split anergized NK cells through both membrane bound and secreted forms of TNF-α and IFN-γ. NK cells select and differentiate both healthy and transformed stem-like cells, resulting in target cell maturation and shaping of their microenvironment. In our recent studies, we have observed that oral, pancreatic, and melanoma CSCs were capable of forming large tumors in humanized bone marrow, liver, thymus (hu-BLT) mice with fully reconstituted human immune system. In addition, major human immune subsets including NK cells, T cells, B cells, and monocytes were present in the spleen, bone marrow, peripheral blood, and tumor microenvironment. Similar to our previously published in vitro data, CSCs differentiated with split anergized NK cells prior to implantation in mice formed smaller tumors. Intravenous injection of functionally potent osteoclast-expanded NK cells inhibited tumor growth through differentiation of CSCs in humanized mice. In this review, we present current approaches, advances, and existing limitations in studying interactions of the immune system with the tumor, in particular NK cells with CSCs, using in vivo preclinical hu-BLT mouse model. In addition, we discuss the use of osteoclast-expanded NK cells in targeting cancer stem-like tumors in humanized mice—a strategy that provides a much-needed platform to develop effective cancer immunotherapies. © 2016 Springer-Verlag Berlin Heidelberg Source


Tseng H.-C.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | Inagaki A.,University of Miami | Bui V.T.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | Cacalano N.,The Jonsson Comprehensive Cancer Center | And 5 more authors.
Journal of Cancer | Year: 2015

We have recently shown that Natural Killer (NK) cells control survival and differentiation of Cancer Stem-like Cells (CSCs) through two distinct phenotypes of cytotoxic and anergic NK cells, respectively. In this report, brain CSCs and their serum and NK cell differentiated counterparts were studied. Serum-differentiated brain CSCs were significantly less susceptible to NK cells and CTL direct cytotoxicity as well as NK cell mediated Antibody Dependent Cellular Cytotoxicity (ADCC), whereas their CSCs were highly susceptible. The levels of CD44 and EGFR were higher in brain tumor CSCs when compared to the serum-differentiated tumors. No differences could be observed for the expression of MHC class I between brain tumor stem cells and their serum- differentiated counterparts. Moreover, supernatants from the combination of IL-2 and anti- CD16mAb treated NK cells (anergized NK cells) induced resistance of brain tumor CSCs to NK cell mediated cytotoxicity. Unlike serum-differentiated CSCs, NK supernatant induced differentiation and resistance to cytotoxicity in brain CSCs correlated with the increased expression of CD54 and MHC class I. The addition of anti-MHC class I antibody moderately inhibited NK mediated cytotoxicity against untreated or serum-differentiated CSCs, whereas it increased cytotoxicity against NK supernatant differentiated tumors. Therefore, two distinct mechanisms govern serum and NK supernatant mediated differentiation of brain tumors. © 2015 Ivyspring International Publisher. Source


Kozlowska A.K.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | Kozlowska A.K.,Poznan University of Medical Sciences | Tseng H.-C.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | Kaur K.,The Jane and Jerry Weintraub Center for Reconstructive Biotechnology | And 9 more authors.
Cancer Immunology, Immunotherapy | Year: 2016

Natural killer (NK) cells are functionally suppressed in the glioblastoma multiforme (GBM) tumor microenvironment. We have recently shown that survival and differentiation of cancer stem-like cells (CSCs)/poorly differentiated tumors are controlled through two distinct phenotypes of cytotoxic and non-cytotoxic/split anergized NK cells, respectively. In this paper, we studied the function of NK cells against brain CSCs/poorly differentiated GBM and their NK cell-differentiated counterparts. Brain CSCs/poorly differentiated GBM, differentiated by split anergized NK supernatants (supernatants from NK cells treated with IL-2 + anti-CD16mAb) expressed higher levels of CD54, B7H1 and MHC-I and were killed less by the NK cells, whereas their CSCs/poorly differentiated counterparts were highly susceptible to NK cell lysis. Resistance to NK cells and differentiation of brain CSCs/poorly differentiated GBM by split anergized NK cells were mediated by interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Brain CSCs/poorly differentiated GBM expressed low levels of TNFRs and IFN-γRs, and when differentiated and cultured with IL-2-treated NK cells, they induced increased secretion of pro-inflammatory cytokine interleukin (IL)-6 and chemokine IL-8 in the presence of decreased IFN-γ secretion. NK-induced differentiation of brain CSCs/poorly differentiated GBM cells was independent of the function of IL-6 and/or IL-8. The inability of NK cells to lyse GBM tumors and the presence of a sustained release of pro-inflammatory cytokines IL-6 and chemokine IL-8 in the presence of a decreased IFN-γ secretion may lead to the inadequacy of NK cells to differentiate GBM CSCs/poorly differentiated tumors, thus failing to control tumor growth. © 2016 Springer-Verlag Berlin Heidelberg Source

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