Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers

Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted.

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Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker

Scientific Reports ◽

10.1038/s41598-020-79903-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Skaidre Jankovskaja ◽

Johan Engblom ◽

Melinda Rezeli ◽

György Marko-Varga ◽

Tautgirdas Ruzgas ◽

...

Keyword(s):

Skin Cancer ◽

Relative Increase ◽

Cancer Biomarker ◽

Cancer Diagnostics ◽

Sampling Time ◽

Skin Permeability ◽

Experimental Conditions ◽

Non Invasive

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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Demonstration of Z-RNA in the Dog Eye Lens Epithelium (Germinative Zone)

Microscopy and Microanalysis ◽

10.1017/s1431927600025666 ◽

1998 ◽

Vol 4 (S2) ◽

pp. 1108-1109

Author(s):

C.E. Gagna ◽

J.H. Chen ◽

H.R. Kuo ◽

W.C. Lambert

Keyword(s):

Cellular Localization ◽

Cultured Cells ◽

Polyclonal Antibodies ◽

Phosphate Buffer Solution ◽

Buffer Solution ◽

Solution Ph ◽

Immunogold Staining ◽

Z Dna

The purpose of this scientific investigation was to determine the presence and specific cellular localization of left-handed Z-RNA, within germinative zone (GZ) epithelium of the lens (Fig. 1), using anti-Z-RNA IgG polyclonal antibodies. Right-handed B-DNA has the ability to adopt the Z-DNA conformation in vitro (Sinden, 1994). Right-handed A-RNA can be transformed into Z-RNA under specific conditions (Hall et al., 1984), and Z-RNA has been identified in cultured cells (Zarling et al., 1990). Strong evidence supports the idea of Z-DNA in vivo (Sinden, 1994). Removal of proteins by fixatives can induce supercoiling which stabilizes Z-DNA (Sinden, 1994).Anti-Z-RNA antibodies were produced in rabbits immunized with injections of Z-RNA: brominated-poly[ribosomal(G-C)]. For light microscopy, immunohistochemical studies (ABC method), normal dog lens tissues (1 yr old) were fixed in Carnoy's, embedded in paraffin and sectioned 2 μm thick. For electron microscopy (immunogold staining), pieces of epithelium from the GZ of normal dog lens (1 yr old) were fixed with 5% glutaraldehyde in 0.05 M phosphate buffer solution, pH 7.3.

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Photosensitizing Medications and Skin Cancer: A Comprehensive Review

Cancers ◽

10.3390/cancers13102344 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2344

Author(s):

Elisabeth A. George ◽

Navya Baranwal ◽

Jae H. Kang ◽

Abrar A. Qureshi ◽

Aaron M. Drucker ◽

...

Keyword(s):

Skin Cancer ◽

Cancer Risk ◽

Cell Carcinoma ◽

The United States ◽

In Vivo Studies ◽

Cancer Risk Factors ◽

Skin Cancer Risk ◽

Number Of Patients

(1) The incidence of skin cancer is increasing in the United States (US) despite scientific advances in our understanding of skin cancer risk factors and treatments. In vitro and in vivo studies have provided evidence that suggests that certain photosensitizing medications (PSMs) increase skin cancer risk. This review summarizes current epidemiological evidence on the association between common PSMs and skin cancer. (2) A comprehensive literature search was conducted to identify meta-analyses, observational studies and clinical trials that report on skin cancer events in PSM users. The associated risks of keratinocyte carcinoma (squamous cell carcinoma and basal cell carcinoma) and melanoma are summarized, for each PSM. (3) There are extensive reports on antihypertensives and statins relative to other PSMs, with positive and null findings, respectively. Fewer studies have explored amiodarone, metformin, antimicrobials and vemurafenib. No studies report on the individual skin cancer risks in glyburide, naproxen, piroxicam, chlorpromazine, thioridazine and nalidixic acid users. (4) The research gaps in understanding the relationship between PSMs and skin cancer outlined in this review should be prioritized because the US population is aging. Thus the number of patients prescribed PSMs is likely to continue to rise.

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Plumbagin-Loaded Glycerosome Gel as Topical Delivery System for Skin Cancer Therapy

Polymers ◽

10.3390/polym13060923 ◽

2021 ◽

Vol 13 (6) ◽

pp. 923

Author(s):

Shadab Md ◽

Nabil A. Alhakamy ◽

Hibah M. Aldawsari ◽

Mohammad Husain ◽

Nazia Khan ◽

...

Keyword(s):

Skin Cancer ◽

Zeta Potential ◽

Skin Permeation ◽

Entrapment Efficiency ◽

Aqueous Solubility ◽

Skin Layer ◽

Vesicle Size ◽

Cytotoxicity Activities

Plumbagin (PLM) is a phytochemical which has shown cytotoxicity against of cancer cells both in vitro and in vivo. However, the clinical application of PLM has been hindered due to poor aqueous solubility and low bioavailability. The aim of the present study was to develop, optimize and evaluate PLM-loaded glycerosome (GM) gel and compare with conventional liposome (CL) for therapeutic efficacy against skin cancer. The GM formulations were optimized by employing design expert software by 3-level 3-factor design. The prepared GMs were characterized in vitro for vesicle size, size distribution, zeta potential, vesicle deformability, drug release, skin permeation, retention, texture, antioxidant and cytotoxicity activities. The optimized formulation showed a vesicle size of 119.20 ± 15.67 nm with a polydispersity index (PDI) of 0.145 ± 0.02, the zeta potential of −27 ± 5.12 mV and entrapment efficiency of 76.42 ± 9.98%. The optimized PLM-loaded GM formulation was transformed into a pre-formed gel which was prepared using Carbopol 934 polymer. The drug diffusion fluxes of CL gel and GM-loaded gel were 23.31 ±6.0 and 79.43 ± 12.43 µg/ cm2/h, respectively. The result of texture analysis revealed the adequate hardness, cohesiveness, consistency, and viscosity of the developed GM-loaded gel compared to CL gel. The confocal images showed that glycerosomal gel has deeper skin layer penetration as compared to the control solution. GM-loaded gel treated rat skin showed significantly (p < 0.05) higher drug accumulation in the dermis, higher cytotoxicity and higher antioxidant activity as compared to CL gel and PLM suspension. Thus, findings revealed that novel GM-loaded gel could be potential carriers for therapeutic intervention in skin cancer.

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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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The Study of Albumin Release from Silica/Albumin as a Potential Drug Delivery Carrier

Jurnal Teknologi ◽

10.11113/jt.v69.3216 ◽

2014 ◽

Vol 69 (5) ◽

Author(s):

Shafiyah Pondi ◽

Jon Efendi ◽

Ho Chin Siong ◽

Lai Sin Yuan ◽

Sheela Chandren ◽

...

Keyword(s):

Drug Delivery ◽

Fumed Silica ◽

In Vitro Release ◽

Phosphate Buffer Solution ◽

Buffer Solution ◽

Solution Ph ◽

Drug Delivery Carrier ◽

High Interaction ◽

Uv Visible

The drug-delivery field has been an attractive as well as challenging area for research. With the emerging of new formulated drugs and pharmaceutical compounds, development of good drug-delivery system (DDS) is crucially required. This study aims to utilize albumin as the drug template in silica/albumin/drug (S/A/D) system. Prior to designing this system, the interaction between silica and albumin was investigated. It is hypothesized that high interaction between silica and albumin may result in slower drug release over time, which is preferred for a good DDS. Silica and albumin (S/A) materials were prepared by using fumed silica and tetraethyl orthosilicate (TEOS) as the silica precursors. Three different S/A samples were prepared; fumed silica with albumin (FS/A), fumed silica with pre-treated albumin by sodium borohydrate (FS/A-N), and silica sol (TEOS) with albumin (SS/A). In-vitro release of albumin in phosphate buffer solution (pH 7) was carried out to examine the interaction between albumin and silica. The concentration of albumin was detected at 280 nm by UV-visible spectrophotometer. All samples were characterized by diffuse reflectance-UV-visible spectrophotometer (DR-UV), Fourier transform infrared spectrophotometer (FTIR) dan thermogravimetric-differential thermal analysis (TG-DTA). DR-UV results show that SS/A exhibited the lowest absorption intensity at 280 nm, which indicates better interaction between silica and albumin. This result was supported by the presence of Si-O stretching band of silanol at 952 cm-1 from the FTIR spectrum. Release study of albumin demonstrated that the release of albumin from SS/A was slowest compared to those of FS/A and FS/A-N.

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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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