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62 Publications visible to you, out of a total of 62
Myofibroblasts reduce angiogenesis and vasculogenesis in a vascularized microphysiological model of lung fibrosis

Abstract

Not specified

Authors: Elena Cambria, Adriana Blazeski, Eunkyung Clare Ko, Tran Thai, Shania Dantes, David A. Barbie, Sarah E. Shelton, Roger D. Kamm

Date Published: 2025

Publication Type: Journal

Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques

Abstract

Not specified

Authors: Shu Wang, Amy J. Myers, Edward B. Irvine, Chuangqi Wang, Pauline Maiello, Mark A. Rodgers, Jaime Tomko, Kara Kracinovsky, H. Jacob Borish, Michael C. Chao, Douaa Mugahid, Patricia A. Darrah, Robert A. Seder, Mario Roederer, Charles A. Scanga, Philana Ling Lin, Galit Alter, Sarah M. Fortune, JoAnne L. Flynn, Douglas A. Lauffenburger

Date Published: 1st Dec 2024

Publication Type: Journal

Confined cell migration along extracellular matrix space in vivo

Abstract

Not specified

Authors: Oleksandr Chepizhko, Josep-Maria Armengol-Collado, Stephanie Alexander, Esther Wagena, Bettina Weigelin, Luca Giomi, Peter Friedl, Stefano Zapperi, Caterina A. M. La Porta

Date Published: 1st Dec 2024

Publication Type: Journal

Personalized Vascularized Models of Breast Cancer Desmoplasia Reveal Biomechanical Determinants of Drug Delivery to the Tumor.

Abstract (Expand)

Desmoplasia in breast cancer leads to heterogeneity in physical properties of the tissue, resulting in disparities in drug delivery and treatment efficacy among patients, thus contributing to high … disease mortality. Personalized in vitro breast cancer models hold great promise for high-throughput testing of therapeutic strategies to normalize the aberrant microenvironment in a patient-specific manner. Here, tumoroids assembled from breast cancer cell lines (MCF7, SKBR3, and MDA-MB-468) and patient-derived breast tumor cells (TCs) cultured in microphysiological systems including perfusable microvasculature reproduce key aspects of stromal and vascular dysfunction causing impaired drug delivery. Models containing SKBR3 and MDA-MB-468 tumoroids show higher stromal hyaluronic acid (HA) deposition, vascular permeability, interstitial fluid pressure (IFP), and degradation of vascular HA relative to models containing MCF7 tumoroids or models without tumoroids. Interleukin 8 (IL8) secretion is found responsible for vascular dysfunction and loss of vascular HA. Interventions targeting IL8 or stromal HA normalize vascular permeability, perfusion, and IFP, and ultimately enhance drug delivery and TC death in response to perfusion with trastuzumab and cetuximab. Similar responses are observed in patient-derived models. These microphysiological systems can thus be personalized by using patient-derived cells and can be applied to discover new molecular therapies for the normalization of the tumor microenvironment.

Authors: G. S. Offeddu, E. Cambria, S. E. Shelton, K. Haase, Z. Wan, L. Possenti, H. T. Nguyen, M. R. Gillrie, D. Hickman, C. G. Knutson, R. D. Kamm

Date Published: 16th Oct 2024

Publication Type: Journal

Colorimetric Detection of Aqueous N-Nitrosodimethylamine via Photonitrosation of a Naphtholsulfonate Indicator.

Abstract (Expand)

N-Nitrosamines are contaminants found throughout the environment, including in drinking water, and many nitrosamines are likely potent carcinogens. Correspondingly, there is a need for rapid and … cost-effective in-field detection methods that can provide timely information about their contamination levels in water. This study details a colorimetric assay for detecting aqueous N-nitrosodimethylamine (NDMA) by photochemical nitrosation of a commercial naphtholsulfonate, to offer an attractive alternative to traditional laboratory-based analysis. The resulting naphthoquinone-oxime coordinates to aqueous iron(II) ions to form a green complex, allowing for direct visual detection. Characterization via Mossbauer and electron paramagnetic resonance (EPR) spectroscopy, alongside single-crystal structure determination, provides comprehensive structure information on the iron indicator complex. Optimization of detection conditions, including UV irradiation and response times, led to an improved colorimetric detection method with a limit of detection of 0.66 ppm for NDMA. The practical applicability and selectivity of this colorimetric detection scheme make it a promising candidate for the development of field-deployable sensors for NDMA in environmental water samples.

Authors: J. C. Beard, C. H. Wang, A. Sridharan, R. G. Croy, J. M. Essigmann, T. M. Swager

Date Published: 27th Sep 2024

Publication Type: Journal

Optical Detection of Interleukin-6 Using Liquid Janus Emulsions Using Hyperthermophilic Affinity Proteins.

Abstract (Expand)

When equal volumes of two immiscible liquids are mixed (e.g., a hydrocarbon and a fluorocarbon), Janus droplets can form in an aqueous solution. In a gravity-aligned Janus droplet, the boundary between … the two phases is flat and thus optically transparent when viewed from above. When tipped due to interactions with an analyte (i.e., agglutination), the resulting change in refraction and reflection yields an optical signal that can be detected and quantified. This study reports the detection and quantitation of interleukin-6 (IL-6) using emulsions functionalized at the hydrocarbon:aqueous interface with engineered proteins that bind IL-6 at high affinity and specificity. Hyperthermophilic affinity proteins (rcSso7d) are derived from thermophiles, giving them excellent thermal stability. Two rcSso7d affinity protein variants were synthesized with a noncanonical azide-functionalized amino acid to enable click chemistry to novel polymeric anchors embedded in the hydrocarbon phase. The two binding proteins recognize different epitopes, enabling the detection of both monomeric and dimeric IL-6 via agglutination. It is noteworthy that the rsSso7d protein variants, in addition to having superior thermal stability and facile recombinant synthesis in E. coli, show superior performance when compared to commercial antibodies for IL-6.

Authors: M. Chen, E. I. Corless, B. P. Engelward, T. M. Swager

Date Published: 3rd Sep 2024

Publication Type: Journal

Patient-specific vascularized tumor model: Blocking monocyte recruitment with multispecific antibodies targeting CCR2 and CSF-1R.

Abstract (Expand)

Tumor-associated inflammation drives cancer progression and therapy resistance, often linked to the infiltration of monocyte-derived tumor-associated macrophages (TAMs), which are associated with poor … prognosis in various cancers. To advance immunotherapies, testing on immunocompetent pre-clinical models of human tissue is crucial. We have developed an in vitro model of microvascular networks with tumor spheroids or patient tissues to assess monocyte trafficking into tumors and evaluate immunotherapies targeting the human tumor microenvironment. Our findings demonstrate that macrophages in vascularized breast and lung tumor models can enhance monocyte recruitment via CCL7 and CCL2, mediated by CSF-1R. Additionally, a multispecific antibody targeting CSF-1R, CCR2, and neutralizing TGF-beta (CSF1R/CCR2/TGF-beta Ab) repolarizes TAMs towards an anti-tumoral M1-like phenotype, reduces monocyte chemoattractant protein secretion, and blocks monocyte migration. This antibody also inhibits monocyte recruitment in patient-specific vascularized tumor models. In summary, this vascularized tumor model recapitulates the monocyte recruitment cascade, enabling functional testing of innovative therapeutic antibodies targeting TAMs in the tumor microenvironment.

Authors: H. T. Nguyen, E. L. Kan, M. Humayun, N. Gurvich, G. S. Offeddu, Z. Wan, M. F. Coughlin, D. C. Renteria, A. Loew, S. Wilson, C. Zhang, V. Vu, S. W. L. Lee, S. L. Tan, D. Barbie, J. Hsu, M. R. Gillrie, R. D. Kamm

Date Published: 3rd Sep 2024

Publication Type: Journal

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