Non-invasive conductivity method for detection of dynamic body fluid changes: in vitro and in vivo validation

AbstractThe tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.

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In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging

Nature Materials ◽

10.1038/nmat3095 ◽

2011 ◽

Vol 10 (9) ◽

pp. 890-890 ◽

Cited By ~ 124

Author(s):

Natalie Artzi ◽

Nuria Oliva ◽

Cristina Puron ◽

Sagi Shitreet ◽

Shay Artzi ◽

...

Keyword(s):

Fluorescence Imaging ◽

Biodegradable Materials ◽

Non Invasive

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Non-invasive, real-time reporting drug release in vitro and in vivo

Chemical Communications ◽

10.1039/c4cc09920f ◽

2015 ◽

Vol 51 (32) ◽

pp. 6948-6951 ◽

Cited By ~ 31

Author(s):

Yanfeng Zhang ◽

Qian Yin ◽

Jonathan Yen ◽

Joanne Li ◽

Hanze Ying ◽

...

Keyword(s):

Drug Release ◽

Real Time ◽

Near Infrared ◽

Reporting System ◽

Real Time Monitoring ◽

Near Infrared Fluorescence ◽

Non Invasive ◽

Fluorescence Dye

Anin vitroandin vivodrug-reporting system is developed for real-time monitoring of drug release via the analysis of the concurrently released near-infrared fluorescence dye.

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Menstrual flow as a non-invasive source of endometrial organoids

Communications Biology ◽

10.1038/s42003-021-02194-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Tereza Cindrova-Davies ◽

Xiaohui Zhao ◽

Kay Elder ◽

Carolyn J. P. Jones ◽

Ashley Moffett ◽

...

Keyword(s):

Early Pregnancy ◽

Recurrent Miscarriage ◽

Milk Proteins ◽

Receptor Expression ◽

In Vitro Fertilisation ◽

Non Invasive ◽

Menstrual Flow ◽

Pregnancy Hormones

AbstractAssessment of the endometrium often necessitates a biopsy, which currently involves an invasive, transcervical procedure. Here, we present an alternative technique based on deriving organoids from menstrual flow. We demonstrate that organoids can be derived from gland fragments recovered from menstrual flow. To confirm they faithfully reflect the in vivo state we compared organoids derived from paired scratch biopsies and ensuing menstrual flow from patients undergoing in vitro fertilisation (IVF). We demonstrate that the two sets of organoids share the same transcriptome signature, derivation efficiency and proliferation rate. Furthermore, they respond similarly to sex steroids and early-pregnancy hormones, with changes in morphology, receptor expression, and production of ‘uterine milk’ proteins that mimic those during the late-secretory phase and early pregnancy. This technique has wide-ranging impact for non-invasive investigation and personalised approaches to treatment of common gynaecological conditions, such as endometriosis, and reproductive disorders, including failed implantation after IVF and recurrent miscarriage.

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In Vitro and In Vivo Degradation, Mechanical Properties, and Histocompatibility of Weft-Knitted Silk Mesh-Like Grafts

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2022.2911 ◽

2022 ◽

Vol 12 (2) ◽

pp. 411-416

Author(s):

Liang Tang ◽

Si-Yu Zhao ◽

Ya-Dong Yang ◽

Geng Yang ◽

Wen-Yuan Zhang ◽

...

Keyword(s):

Mechanical Properties ◽

Simulated Body Fluid ◽

Body Fluid ◽

Degradation Rate ◽

Maximum Load ◽

Artificial Ligament ◽

In Vivo Degradation

To investigate the degradation, mechanical properties, and histocompatibility of weft-knitted silk mesh-like grafts, we carried out the In Vitro and In Vivo silk grafts degradation assay. The In Vitro degradation experiment was performed by immersing the silk grafts in simulated body fluid for 1 year, and the results showed that the degradation rate of the silk mesh-like grafts was very slow, and there were few changes in the mechanical properties and quality of the silk mesh-like graft. In Vivo degradation assay was taken by implantation of the silk mesh-like grafts into the subcutaneous muscles of rabbits. At 3, 6, and 12 months postoperation, the rate of mass loss was 19.36%, 31.84%, and 58.77%, respectively, and the maximum load was 63.85%, 34.63%, and 10.76%, respectively of that prior to degradation. The results showed that the degradation rate of the silk graft and the loss of mechanical properties In Vivo were faster than the results obtained in the In Vitro experiments. In addition, there were no significant differences in secretion of serum IL-6 and TNF-α between the experimental and normal rabbits (P >0.05), suggesting no obvious inflammatory reaction. The findings suggest that the weft-knitted silk mesh-like grafts have good mechanical properties, histocompatibility, and In Vivo degradation rate, and therefore represent a candidate material for artificial ligament

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Porphyrins to restrict progression of pancreatic cancer by stabilizing KRAS G-quadruplex: In silico, in vitro and in vivo validation of anticancer strategy

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2018.09.011 ◽

2018 ◽

Vol 125 ◽

pp. 39-53 ◽

Cited By ~ 9

Author(s):

Rudradip Pattanayak ◽

Atish Barua ◽

Amlan Das ◽

Tanima Chatterjee ◽

Adrija Pathak ◽

...

Keyword(s):

Pancreatic Cancer ◽

In Silico ◽

G Quadruplex ◽

In Vivo Validation

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OMRT-11. The effect of microenvironment on glioblastoma stem cells therapeutic resistance

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab070.035 ◽

2021 ◽

Vol 3 (Supplement_2) ◽

pp. ii9-ii9

Author(s):

Tamara Lah Turnsek ◽

Barbara Breznik ◽

Bernarda Majc ◽

Metka Novak ◽

Andrej Porčnik ◽

...

Keyword(s):

Stem Cells ◽

Epithelial To Mesenchymal Transition ◽

Combined Treatment ◽

Cell Plasticity ◽

Glioblastoma Stem Cells ◽

Mesenchymal Transition ◽

Non Invasive ◽

Differential Gene

Abstract Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process in physiologic processes and invasion of various types of carcinoma and glioblastoma (GBM) cells. EMT is activated and regulated by specific endogenous triggers in complex network of intercellular interactions and signaling pathways. The hallmark of cancer-linked EMT are intermediate states that show notable cell plasticity, characteristic of cancer stem cells (CSCs), including glioblastoma stem cells – GSCs. GSCs resistance to irradiation (IR) and temozolomide (TMZ) chemotherapy is responsible for early relapses, even at distant brain sites. As GSCs are mostly homing to their “niches” as slowly-dividing GSC-subtype, mimicking a proneural-like non- invasive phenotype PN-genotype, we assume that this, by undergoing an EMT-like transition, GSCs are-reprogrammed to an invasive mesenchymal (MES) GBs/GSCs phenotype in a processes, called PMT (1). However, it is not known, if and by which environmental cues within the niche, this transition of GSCs is induced in vivo. In this work, we are presenting the transriptome data obtained when we exposed GSC spheroids to irradiation alone, TMZ alone and to the combined treatment in vitro and compared their differential genetic fingerprints related to EMT/PMT transition to the GSCs PMT transition, when embedded in their natural microenvironment in the GBM organoid model. The differential gene expression upon GSCs therapeutic perturbation (when alone and vs in the tumoroid microenvironment) will reveal the effects of the major candidate genes, associated with micronevironmendt stromal cells and matrix are contributing their observed EMT/PMT transition of GSCs in vivo. •1. Majc, B., Sever, T., Zarić, M, Breznik, B., Turk, B, Lah Turnšek, T. Epithelial- to-mesenchymal transition as the driver of changing carcinoma and glioblastoma microenvironment. DOI: 10.1016/j.bbamcr.2020.118782

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Targeting Cancer Cell Tight Junctions Enhances PLGA-Based Photothermal Sensitizers’ Performance In Vitro and In Vivo

Pharmaceutics ◽

10.3390/pharmaceutics14010043 ◽

2021 ◽

Vol 14 (1) ◽

pp. 43

Author(s):

Victoria O. Shipunova ◽

Vera L. Kovalenko ◽

Polina A. Kotelnikova ◽

Anna S. Sogomonyan ◽

Olga N. Shilova ◽

...

Keyword(s):

Epithelial Mesenchymal Transition ◽

3D Culture ◽

Intercellular Junctions ◽

Cell Junctions ◽

Multicellular Spheroids ◽

Mesenchymal Transition ◽

Non Invasive ◽

Order Of Magnitude

The development of non-invasive photothermal therapy (PTT) methods utilizing nanoparticles as sensitizers is one of the most promising directions in modern oncology. Nanoparticles loaded with photothermal dyes are capable of delivering a sufficient amount of a therapeutic substance and releasing it with the desired kinetics in vivo. However, the effectiveness of oncotherapy methods, including PTT, is often limited due to poor penetration of sensitizers into the tumor, especially into solid tumors of epithelial origin characterized by tight cellular junctions. In this work, we synthesized 200 nm nanoparticles from the biocompatible copolymer of lactic and glycolic acid, PLGA, loaded with magnesium phthalocyanine, PLGA/Pht-Mg. The PLGA/Pht-Mg particles under the irradiation with NIR light (808 nm), heat the surrounding solution by 40 °C. The effectiveness of using such particles for cancer cells elimination was demonstrated in 2D culture in vitro and in our original 3D model with multicellular spheroids possessing tight cell contacts. It was shown that the mean inhibitory concentration of such nanoparticles upon light irradiation for 15 min worsens by more than an order of magnitude: IC50 increases from 3 µg/mL for 2D culture vs. 117 µg/mL for 3D culture. However, when using the JO-4 intercellular junction opener protein, which causes a short epithelial–mesenchymal transition and transiently opens intercellular junctions in epithelial cells, the efficiency of nanoparticles in 3D culture was comparable or even outperforming that for 2D (IC50 = 1.9 µg/mL with JO-4). Synergy in the co-administration of PTT nanosensitizers and JO-4 protein was found to retain in vivo using orthotopic tumors of BALB/c mice: we demonstrated that the efficiency in the delivery of such nanoparticles to the tumor is 2.5 times increased when PLGA/Pht-Mg nanoparticles are administered together with JO-4. Thus the targeting the tumor cell junctions can significantly increase the performance of PTT nanosensitizers.

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