scholarly journals Radiologic-Pathologic Analysis of Increased Ethanol Localization and Ablative Extent Achieved by Ethyl Cellulose

2020 ◽  
Author(s):  
Erika Chelales ◽  
Robert Morhard ◽  
Corrine Nief ◽  
Brian Crouch ◽  
Alan Sag ◽  
...  
Keyword(s):  
Ethyl Cellulose ◽  
Ethanol Concentration ◽  
Liver Tumors ◽  
Ex Vivo ◽  
Low Cost ◽  
Distribution Volume ◽  
Target Tissue ◽  
Pure Ethanol ◽  
Middle Income

Abstract PurposeEthanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. The authors demonstrate that incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. This therapy may have a low barrier of entry for cancer care in low- and middle- income countries.Materials and MethodsThe relationship of radiodensity to ethanol concentration was characterized with water-ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n=6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n=6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were explanted, sectioned and stained with NADH-diaphorase to determine the ablative extent.ResultsCT imaging of ethanol-water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than 8-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume 3 times greater and an ablation zone 6 times greater than pure ethanol.Conclusions EC-ethanol, a novel gel formulation injectable ablative injectate, safely increases distribution and necrosis compared to pure ethanol.

scholarly journals Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Erika Chelales ◽  
Robert Morhard ◽  
Corrine Nief ◽  
Brian Crouch ◽  
Jeffrey I. Everitt ◽  
...  
Keyword(s):  
Ethyl Cellulose ◽  
Time Course ◽  
Ethanol Concentration ◽  
Ex Vivo ◽  
Ct Imaging ◽  
Distribution Volume ◽  
Ablation Zone ◽  
Pure Ethanol ◽  
The Relationship

AbstractEthanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water–ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol–water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1–4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

Emergency surgical obstetrics simulation training: an ex vivo low-cost model using bovine uterus and porcine bladder for haemostatic uterine brace suture techniques

2020 ◽  
Vol 7 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Amy Sinclair ◽  
Mohamed Sayed Allam ◽  
Evelyn Jean Ferguson ◽  
Mohamed Khairy Mehasseb
Keyword(s):  
Postpartum Haemorrhage ◽  
Ex Vivo ◽  
Cost Model ◽  
Low Cost ◽  
Broad Ligament ◽  
Training Model ◽  
Mortality And Morbidity ◽  
Emergency Situations ◽  
Healthcare Settings

Postpartum haemorrhage remains a leading cause of maternal mortality and morbidity. While conventional obstetrics training curricula describe at length the management of postpartum haemorrhage, obstetrics trainees rarely have exposure to surgical management of postpartum haemorrhage in emergency situations due to reduced hours of training. Procedures such as the transverse or longitudinal haemostatic uterine brace sutures are recognised to be safe, simple and allow for the preservation of the uterus. Training during emergency situations is rarely practical or ideal. We describe a simple model that simulates the atonic postnatal uterus and allows trainees to practise the safe placement of the brace sutures. We use a bovine uterus model with attached broad ligament, bladder and ureters for the transverse haemostatic suture. For the longitudinal brace suture, we use a porcine bladder to simulate the uterus, with the ureters and bladder mesentery simulating the tubes and broad ligaments. The placement of the sutures can be practised with the uterus/bladder closed, or open akin to a caesarean section. Tissue dissection and feedback is almost similar to in vivo conditions. The sutures are inserted and driven using the material and correct placement used during real surgery. Our wet lab training model allows the acquisition, maintenance and enhancement of the required technical skills in a controlled environment, using inexpensive, reproducible and widely available specimens. The model has proved successful in both high and low-resource healthcare settings.

scholarly journals Real-Time Wireless Platform for In Vivo Monitoring of Bone Regeneration

Sensors ◽  
2020 ◽  
Vol 20 (16) ◽  
pp. 4591 ◽  
Author(s):  
Pablo Blázquez-Carmona ◽  
Manuel Sanchez-Raya ◽  
Juan Mora-Macías ◽  
Juan Antonio Gómez-Galán ◽  
Jaime Domínguez ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Real Time ◽  
Ex Vivo ◽  
Low Cost ◽  
Bone Lengthening ◽  
Bone Callus ◽  
Reliable Solution ◽  
Regeneration Processes

For the monitoring of bone regeneration processes, the instrumentation of the fixation is an increasingly common technique to indirectly measure the evolution of bone formation instead of ex vivo measurements or traditional in vivo techniques, such as X-ray or visual review. A versatile instrumented external fixator capable of adapting to multiple bone regeneration processes was designed, as well as a wireless acquisition system for the data collection. The design and implementation of the overall architecture of such a system is described in this work, including the hardware, firmware, and mechanical components. The measurements are conditioned and subsequently sent to a PC via wireless communication to be in vivo displayed and analyzed using a developed real-time monitoring application. Moreover, a model for the in vivo estimation of the bone callus stiffness from collected data was defined. This model was validated in vitro using elastic springs, reporting promising results with respect to previous equipment, with average errors and uncertainties below 6.7% and 14.04%. The devices were also validated in vivo performing a bone lengthening treatment on a sheep metatarsus. The resulting system allowed the in vivo mechanical characterization of the bone callus during experimentation, providing a low-cost, simple, and highly reliable solution.

scholarly journals Smartphone microendoscopy for high resolution fluorescence imaging

2016 ◽  
Vol 09 (05) ◽  
pp. 1650046 ◽  
Author(s):  
Xiangqian Hong ◽  
Vivek K. Nagarajan ◽  
Dale H. Mugler ◽  
Bing Yu
Keyword(s):  
High Resolution ◽  
Rural Areas ◽  
Ex Vivo ◽  
Cost Effective ◽  
Internal Organs ◽  
Middle Income ◽  
Middle Income Countries ◽  
The Past

High resolution optical endoscopes are increasingly used in diagnosis of various medical conditions of internal organs, such as the cervix and gastrointestinal (GI) tracts, but they are too expensive for use in resource-poor settings. On the other hand, smartphones with high resolution cameras and Internet access have become more affordable, enabling them to diffuse into most rural areas and developing countries in the past decade. In this paper, we describe a smartphone microendoscope that can take fluorescence images with a spatial resolution of 3.1 [Formula: see text]m. Images collected from ex vivo, in vitro and in vivo samples using the device are also presented. The compact and cost-effective smartphone microendoscope may be envisaged as a powerful tool for detecting pre-cancerous lesions of internal organs in low and middle-income countries (LMICs).

scholarly journals Raman Needle Arthroscopy for In Vivo Molecular Assessment of Cartilage

2021 ◽  
Author(s):  
Kimberly Kroupa ◽  
Man I Wu ◽  
Juncheng Zhang ◽  
Magnus Jensen ◽  
Wei Wong ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Low Cost ◽  
Femoral Condyle ◽  
Cartilage Explants ◽  
Anatomical Site ◽  
Superficial Zone ◽  
Human Cartilage ◽  
Polarized Raman ◽  
Bovine Cartilage

The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present a novel arthroscopic Raman probe that can optically biopsy cartilage and quantify key ECM biomarkers for determining cartilage composition, structure, and material properties in health and disease. Technological and analytical innovations to optimize Raman analysis include: 1) multivariate decomposition of cartilage Raman spectra into ECM-constituent-specific biomarkers (glycosaminoglycan [GAG], collagen [COL], water [H2O] scores), and 2) multiplexed polarized Raman spectroscopy to quantify superficial zone collagen anisotropy via a PLS-DA-derived Raman collagen alignment factor (RCAF). Raman measurements were performed on a series of ex vivo cartilage models: 1) chemically GAG-depleted bovine cartilage explants (n=40), 2) mechanically abraded bovine cartilage explants (n=30), 3) aging human cartilage explants (n=14), and 4) anatomical-site-varied ovine osteochondral explants (n=6). Derived Raman GAG score biomarkers predicted 95%, 66%, and 96% of the variation in GAG content of GAG-depleted bovine explants, human explants, and ovine explants, respectively (p<0.001). RCAF values were significantly different for explants with abrasion-induced superficial zone collagen loss (p<0.001). The multivariate linear regression of Raman-derived ECM biomarkers (GAG and H2O scores) predicted 94% of the variation in elastic modulus of ovine explants (p<0.001). Finally, we demonstrated the first in vivo Raman arthroscopy assessment of an ovine femoral condyle through intraarticular entry into the synovial capsule. This work advances Raman arthroscopy towards a transformative low cost, minimally invasive diagnostic platform for objective monitoring of treatment outcomes from emerging OA therapies.

scholarly journals Gene Therapy Approaches

2021 ◽  
Vol 1 (1) ◽  
pp. 52-56
Author(s):  
Hogir Saadi
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Nuclear Translocation ◽  
Viral Vector ◽  
Ex Vivo ◽  
Genetic Material ◽  
Target Tissue ◽  
Human Beings ◽  
Vector Systems

Gene therapy can be described broadly as the transfer of genetic material to control a disease or at least to enhance a patient's clinical status. The transformation of viruses into genetic shuttles is one of the core principles of gene therapy, which will introduce the gene of interest into the target tissue and cells. To do this, safe strategies have been invented, using many viral and non-viral vector delivery. Two major methods have emerged: modification in vivo and modification ex vivo. For gene therapeutic approaches which are focused on lifelong expression of the therapeutic gene, retrovirus, adenovirus, adeno-associated viruses are acceptable. Non-viral vectors are much less successful than viral vectors, but because of their low immune responses and their broad therapeutic DNA ability, they have advantages. The addition of viral functions such as receptor-mediated uptake and nuclear translocation of DNA may eventually lead to the development of an artificial virus in order to improve the role of non-viral vectors. For human use in genetic conditions, cancers and acquired illnesses, gene transfer techniques have been allowed. The ideal delivery vehicle has not been identified, although the accessible vector systems are capable of transporting genes in vivo into cells. Therefore, only with great caution can the present viral vectors be used in human beings and further progress in the production of vectors is required. Current progresses in our understanding of gene therapy approaches and their delivery technology, as well as the victors used to deliver therapeutic genes, are the primary goals of this review. For that reason, a literature search on PubMed and Google Scholar was carried out using different keywords.

scholarly journals Pilot in vivo studies on transcutaneous boiling histotripsy in porcine liver and kidney

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tatiana D. Khokhlova ◽  
George R. Schade ◽  
Yak-Nam Wang ◽  
Sergey V. Buravkov ◽  
Valeriy P. Chernikov ◽  
...  
Keyword(s):  
Peak Power ◽  
Ex Vivo ◽  
Respiratory Gating ◽  
Subcutaneous Fat ◽  
High Intensity Focused Ultrasound ◽  
In Vivo Studies ◽  
Swine Model ◽  
Target Tissue ◽  
Porcine Liver

AbstractBoiling histotripsy (BH) is a High Intensity Focused Ultrasound (HIFU) method for precise mechanical disintegration of target tissue using millisecond-long pulses containing shocks. BH treatments with real-time ultrasound (US) guidance allowed by BH-generated bubbles were previously demonstrated ex vivo and in vivo in exposed porcine liver and small animals. Here, the feasibility of US-guided transabdominal and partially transcostal BH ablation of kidney and liver in an acute in vivo swine model was evaluated for 6 animals. BH parameters were: 1.5 MHz frequency, 5–30 pulses of 1–10 ms duration per focus, 1% duty cycle, peak acoustic powers 0.9–3.8 kW, sonication foci spaced 1–1.5 mm apart in a rectangular grid with 5–15 mm linear dimensions. In kidneys, well-demarcated volumetric BH lesions were generated without respiratory gating and renal medulla and collecting system were more resistant to BH than cortex. The treatment was accelerated 10-fold by using shorter BH pulses of larger peak power without affecting the quality of tissue fractionation. In liver, respiratory motion and aberrations from subcutaneous fat affected the treatment but increasing the peak power provided successful lesion generation. These data indicate BH is a promising technology for transabdominal and transcostal mechanical ablation of tumors in kidney and liver.

Predicting and monitoring tumor response to epidermal growth factor receptor inhibitor gefitinib in patients with locally advanced esophageal adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14112-14112
Author(s):  
M. K. Gibson ◽  
H. Mezzadra ◽  
L. Kleinberg ◽  
S. Jagannath ◽  
M. Brock ◽  
...  
Keyword(s):  
Western Blot ◽  
Esophageal Adenocarcinoma ◽  
Ex Vivo ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Target Tissue ◽  
Chemosensitivity Assay ◽  
Pre Treatment ◽  
Pathway Inhibition

14112 Background: This study aimed to validate an ex vivo chemosensitivity assay to measure the pharmacodynamic effect of gefitinib on esophageal adenocarcinoma (EAC) prior to treatment with pre-operative concomitant chemoradiotherapy (CRT). Methods: A 14 day run-in period with 250 mg/day of gefitinib preceded CRT. Endoscopic biopsies (D 0 and 14) in 4 patients with T2–3N0/1M0/1a EAC were analyzed by ex vivo chemosensitivity assay. Day 0 tissue was exposed to gefitinib ex vivo, then tumor was exposed to gefitinib for 14 days in vivo (ie in the patient). Phosphorylation of the EGFR, raf/MEK/ERK and PI3/AKT pathways was measured by Western blot. Profiles were compared for correlation between ex vivo and in vivo exposure, and patterns were correlated with response to CRT. The effects were also characterized by immunohistochemistry (IHC). EGFR, K-Ras, and PI3K mutations, serum concentrations of gefitinib and PTEN status were measured as potential confounders. Results: One patient with stage T3N1 died of unexplained hemorrhage during surgery. Three had clinical and path stages of: T3N1/T0N0, T3N0/T3N0, T3N1/T2N1. Gefitinib levels were constant, confirming exposure of target tissue to the drug. Ex vivo exposure yielded four distinct pathway patterns. The exact same patterns were seen after in vivo exposure. No mutations were identified in exons 18–21 of the EGFR, exons 2/3 of K-ras or exons 9/22 of PI3K. PTEN levels were similar in all tumors. PCNA expression correlated with raf/MEK/ERK pathway inhibition, but not with inhibition of EGFR activity. IHC correlated with Western blot for expression of EGFR, and phospho- and total ERK levels. No correlation was observed between gefitinib effect and pathologic response to CRT. Conclusions: This study used a novel ex vivo chemosensitivity assay to demonstrate the activity of gefitinib to inhibit target in tumor tissue obtained from patients with EAC. The exact correlation of pre- and post-treatment profiles suggests potential use in the pre-treatment setting to predict in vivo effects of targeted therapies. This approach may facilitate the further refinement of patient selection to maximize potential benefit while sparing patients unlikely to respond to a given agent. No significant financial relationships to disclose.

FTY720 Abrogates the Therapeutic Potential of Adoptively Transferred Treg Via Inhibition of IL-2 Induced in Vivo Expansion

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2584-2584
Author(s):  
Anna Maria Wolf ◽  
Kathrin Hochegger ◽  
Robert Zeiser ◽  
Christoph Duerr ◽  
Michael Sixt ◽  
...  
Keyword(s):  
T Cells ◽  
Adoptive Transfer ◽  
Chemokine Receptors ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Effective Means ◽  
Effector T Cells ◽  
Target Tissue

Abstract CD4+CD25+ T cells (Treg) entry into secondary lymphoid organs (SLO) and local expansion after activation is at least in part responsible for their immunosuppressive action. Thus we hypothesized that trapping of adoptively transferred Treg in SLO would be an effective means to tip the balance towards a more immunosuppressive milieu within the LN microenvironment. Systemic application of the sphingosine-phosphate receptor agonist FTY720 has been proven to trap harmful effector T cells in SLO, thereby inhibiting their migration and destruction of target tissue. Here we provide first evidence that selective entrapment of adoptively transferred Treg in inflammatory LN can be achieved by blockade of SP-receptors upon ex vivo exposure of Treg to FTY720 before adoptive transfer. FTY720 exposure did not interfere with proper Treg localization within the T-cell areas of SLO as determined by immunofluorescent microscopy after co-transfer of either FTY720- or solvent exposed and subsequently differentially labelled Treg. However, despite the fact that the in vitro phenotype (including expression of adhesion and chemokine receptors), function (including anergy and suppressive activity) and survival (determined by Annexin/PI staining) of Treg remained unaltered by FTY720, it abrogated their protective effect after adoptive transfer in a murine model of acute experimental glomerulonephritis (determined by quantification of proteinuria and histological analysis) as well as in an acute GvHD model (determined by survival analysis and quantification of the in vivo expansion of luciferase-transgenic effector T cells by bioluminiscence technology). Notably, adoptive transfer of CFSE-labelled Treg revealed a markedly impaired proliferation of Treg in inflammatory SLO when pre-exposed to FTY720 ex vivo. Accordingly, FTY720 blocked Treg-proliferation induced by TCR-stimulation in combination with IL-2 in vitro. In line with this observation, FTY720 completely abolishes IL-2 induced phosphorylation of STAT-5. Thus, SP-1P receptors induce Treg trapping in inflammatory SLO but abrogate their in vivo immunosuppressive potential by inhibition of local Treg expansion.

scholarly journals Targeting the COX2/MET/TOPK signaling axis induces apoptosis in gefitinib-resistant NSCLC cells

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Juanjuan Xiao ◽  
Fei Wang ◽  
Hui Lu ◽  
Sanpeng Xu ◽  
Ling Zou ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Low Cost ◽  
Progression Free Survival ◽  
Signaling Axis ◽  
Approved Drugs ◽  
Gefitinib Resistance ◽  
Resistant Cells

Abstract MET overactivation is one of the crucial reasons for tyrosine kinase inhibitor (TKI) resistance, but the mechanisms are not wholly clear. Here, COX2, TOPK, and MET expression were examined in EGFR-activating mutated NSCLC by immunohistochemical (IHC) analysis. The relationship between COX2, TOPK, and MET was explored in vitro and ex vivo. In addition, the inhibition of HCC827GR cell growth by combining COX2 inhibitor (celecoxib), TOPK inhibitor (pantoprazole), and gefitinib was verified ex vivo and in vivo. We found that COX2 and TOPK were highly expressed in EGFR-activating mutated NSCLC and the progression-free survival (PFS) of triple-positive (COX2, MET, and TOPK) patients was shorter than that of triple-negative patients. Then, we observed that the COX2-TXA2 signaling pathway modulated MET through AP-1, resulting in an inhibition of apoptosis in gefitinib-resistant cells. Moreover, we demonstrated that MET could phosphorylate TOPK at Tyr74 and then prevent apoptosis in gefitinib-resistant cells. In line with these findings, the combination of celecoxib, pantoprazole, and gefitinib could induce apoptosis in gefitinib-resistant cells and inhibit tumor growth ex vivo and in vivo. Our work reveals a novel COX2/MET/TOPK signaling axis that can prevent apoptosis in gefitinib-resistant cells and suggests that a triple combination of FDA-approved drugs would provide a low-cost and practical strategy to overcome gefitinib resistance.

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