Radiofrequency Coil for the Creation of Large Ablations: Ex Vivo and In Vivo Testing

2012 ◽  
Vol 23 (11) ◽  
pp. 1522-1528 ◽  
Author(s):  
Alex Furse ◽  
Brock J. Miller ◽  
Claire McCann ◽  
John R. Kachura ◽  
Michael A. Jewett ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Radiofrequency Coil ◽  
In Vivo Testing ◽  
The Creation

Cadaveric Evaluation of Load to Failure in Canine Gingiva Apposed With Varied Suture Patterns Using Poliglecaprone 25

2021 ◽  
pp. 089875642110109
Author(s):  
Jane E. Pegg ◽  
Jennifer E. Rawlinson ◽  
Jennifer L Kelley ◽  
Eric Monnet
Keyword(s):  
Ex Vivo ◽  
Barbed Suture ◽  
Usp 4 ◽  
Extraction Site ◽  
Significant Difference ◽  
Load To Failure ◽  
In Vivo Testing ◽  
Suture Patterns ◽  
Poliglecaprone 25

The purpose of the study was to determine the effect of suture pattern and repair length on the load to failure in an ex vivo canine gingival model. Healthy mandibular gingiva and mucosa were harvested from fresh cadavers euthanized for purposes unrelated to the study. Samples were randomly assigned by length and pattern. Lingual and buccal free gingival margins were apposed using a simple interrupted (SI), cruciate (XT), simple continuous (SC), or unidirectional knotless continuous barbed suture (SF) closure technique with USP 4-0 poliglecaprone 25i, ii applied over 2 lengths (3 cm and 6 cm). A custom template was used to ensure uniform suture bite application. Surgical time was recorded. Using a soft tissue mechanical testing frame, samples were tensioned to failure. Testing was video recorded and reviewed in conjunction with the tension trace data for tension at initial failure (Tfail) and maximum tension sustained (Tmax). Two factor ANOVA by length and pattern was performed followed by individual one way T-tests. Statistically significant findings were XT-SC-SF patterns were quicker to perform than SI. SF was more likely to fail by suture breakage than tissue tearing, and SF withstood less tension at the 3 cm length than SI-XT-SC. No significant difference was detected in Tmax or Tfail between SI and SC or XT. The study demonstrates that SC and XT are comparable to SI in tension resistance and faster to perform suggesting that SC and XT could replace SI for extraction site closure although further in vivo testing is required.

scholarly journals CMET-26. IN-VITRO & IN-VIVO CULTURE OF PATIENT (PT) DERIVED CSF-CTCS IN LEPTOMENINGEAL DISEASE (LMDZ) FROM MELANOMA TO IDENTIFY NOVEL TREATMENT STRATEGIES

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi57-vi57
Author(s):  
Vincent Law ◽  
Brittany Evernden ◽  
John Puskas ◽  
Gisela Caceres ◽  
Elena Ryzhova ◽  
...  
Keyword(s):  
Single Cell Analysis ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Braf V600e ◽  
Leptomeningeal Disease ◽  
Immunodeficient Mice ◽  
In Vivo Culture ◽  
In Vivo Testing

Abstract BACKGROUND Approx. 5% of melanoma pts develop LMDz. There are essentially no models of LMDz available for therapeutic development. Here we report, the in-vitro & in-vivo culturing of CSF-CTCs. METHODS CSF-CTCs were detected by the Veridex CellSearch® System. Cell-free DNA and cell-associated DNA were extracted, sequenced and profiled. Expanded ex-vivo CSF-CTCs were grown in-vitro and tested for drug sensitivity. CSF-CTCs were grown successfully in-vivo from 1 pt; labeled human Braf V600E WM164 cells were injected IT in as a control. RESULTS CSF-CTCs: 12 LMDz pts and 8 melanoma pts without LMDz were studied. All but 1 LMDz pts (92%) had CSF-CTCs (avg: 2148.6; range 23 - 3055 CTCs/ml). In contrast, 3/8 (37%) melanoma Brain Mets pts without LMDz had CSF-CTCs but fewer of them (avg: 0.31; range 0.13 - 0.6 CTCs/ml CSF). CSF-CTCs Profile: These had BrafV600E (83%), and GNAQ Q209P & NRAS Q61R in 1 pt each. Ex-vivoculture of CSF-CTCs and PDX model: After lengthy optimization of conditions we successfully expanded CSF-CTCs in vitro(~25% of pts), and in-vivo in immunodeficient mice from 1 pt (~10% of samples). Ceritinib, used as a FAK inhibitor, with MEKi was effective in-vitro (p=3.17e-6) and prolonged survival in-vivo in LMDz (median survival: >32 days vs control: 18 days; p=7.81e-5). CONCLUSIONS Though the sample size is small, this is the first report of the successful in-vitro & in-vivo culture of CSF-CTCs from pts with LMDz. Single cell analysis to determine how representative these models are and further in-vivo testing are in progress.

scholarly journals Design, Synthesis, In Vitro and In Vivo Evaluation of Heterobivalent SiFAlin-Modified Peptidic Radioligands Targeting Both Integrin αvβ3 and the MC1 Receptor—Suitable for the Specific Visualization of Melanomas?

2021 ◽  
Vol 14 (6) ◽  
pp. 547
Author(s):  
Xia Cheng ◽  
Ralph Hübner ◽  
Valeska von von Kiedrowski ◽  
Gert Fricker ◽  
Ralf Schirrmacher ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Ex Vivo ◽  
Integrin Αvβ3 ◽  
In Vivo Evaluation ◽  
Design Synthesis ◽  
Pet Ct ◽  
In Vivo Testing ◽  
Radiochemical Yields

Combining two peptides addressing two different receptors to a heterobivalent peptidic ligand (HBPL) is thought to enable an improved tumor-targeting sensitivity and thus tumor visualization, compared to monovalent peptide ligands. In the case of melanoma, the Melanocortin-1 receptor (MC1R), which is stably overexpressed in the majority of primary malignant melanomas, and integrin αvβ3, which is involved in lymph node metastasis and therefore has an important role in the transition from local to metastatic disease, are important target receptors. Thus, if a radiolabeled HBPL could be developed that was able to bind to both receptor types, the early diagnosis and correct staging of the disease would be significantly increased. Here, we report on the design, synthesis, radiolabeling and in vitro and in vivo testing of different SiFAlin-modified HBPLs (SiFA = silicon fluoride acceptor), consisting of an MC1R-targeting (GG-Nle-c(DHfRWK)) and an integrin αvβ3-affine peptide (c(RGDfK)), being connected by a symmetrically branching framework including linkers of differing length and composition. Kit-like 18F-radiolabeling of the HBPLs 1–6 provided the labeled products [18F]1–[18F]6 in radiochemical yields of 27–50%, radiochemical purities of ≥95% and non-optimized molar activities of 17–51 GBq/µmol within short preparation times of 25 min. Besides the evaluation of radiotracers regarding logD(7.4) and stability in human serum, the receptor affinities of the HBPLs were investigated in vitro on cell lines overexpressing integrin αvβ3 (U87MG cells) or the MC1R (B16F10). Based on these results, the most promising compounds [18F]2, showing the highest affinity to both target receptors (IC50 (B16F10) = 0.99 ± 0.11 nM, IC50 (U87MG) = 1300 ± 288 nM), and [18F]4, exhibiting the highest hydrophilicity (logD(7.4) = −1.39 ± 0.03), were further investigated in vivo and ex vivo in a xenograft mouse model bearing both tumors. For both HBPLs, clear visualization of B16F10, as well as U87MG tumors, was feasible. Blocking studies using the respective monospecific peptides demonstrated both peptide binders of the HBPLs contributing to tumor uptake. Despite the somewhat lower target receptor affinities (IC50 (B16F10) = 6.00 ± 0.47 nM and IC50 (U87MG) = 2034 ± 323 nM) of [18F]4, the tracer showed higher absolute tumor uptakes ([18F]4: 2.58 ± 0.86% ID/g in B16F10 tumors and 3.92 ± 1.31% ID/g in U87MG tumors; [18F]2: 2.32 ± 0.49% ID/g in B16F10 tumors and 2.33 ± 0.46% ID/g in U87MG tumors) as well as higher tumor-to-background ratios than [18F]2. Thus, [18F]4 demonstrates to be a highly potent radiotracer for the sensitive and bispecific imaging of malignant melanoma by PET/CT imaging and impressively illustrates the suitability of the underlying concept to develop heterobivalent integrin αvβ3- and MC1R-bispecific radioligands for the sensitive and specific imaging of malignant melanoma by PET/CT.

scholarly journals LPTO-03. IN-VITRO & IN-VIVO CULTURE OF PATIENT (PT) DERIVED CSF-CTCs IN LEPTOMENINGEAL DISEASE (LMDz) FROM MELANOMA TO IDENTIFY NOVEL TREATMENT STRATEGIES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i6-i7
Author(s):  
Vincent Law ◽  
Brittany Evernden ◽  
Rajappa Kenchappa ◽  
John Puskas ◽  
Gisela Caceres ◽  
...  
Keyword(s):  
Single Cell Analysis ◽  
Ex Vivo ◽  
Treatment Strategies ◽  
Braf V600e ◽  
Leptomeningeal Disease ◽  
Immunodeficient Mice ◽  
In Vivo Culture ◽  
In Vivo Testing

Abstract BACKGROUND: Approximately 5% of melanoma pts develop LMDz. There are essentially no models of LMDz available for therapeutic development. Here we report, the in-vitro & in-vivo culturing of CSF-CTCs. METHODS: CSF-CTCs were detected by the Veridex CellSearch® System. Cell-free DNA and cell-associated DNA were extracted, sequenced and profiled. Expanded ex-vivo CSF-CTCs were grown in-vitro and tested for drug sensitivity. CSF-CTCs were grown successfully in-vivo from 1 pt; labeled human Braf V600E WM164 cells were injected IT in as a control. RESULTS: CSF-CTCs: 12 LMDz pts and 8 melanoma pts without LMDz were studied. All but 1 LMDz pts (92%) had CSF-CTCs (avg: 2148.60; range 23 - 3055 CTCs/ml). In contrast, 3/8 (37%) melanoma Brain Mets pts without LMDz had CSF-CTCs but fewer of them (avg: 0.31; range 0.13 - 0.6 CTCs/ml CSF). CSF-CTCs Profile: These had BrafV600E (83%), and GNAQ Q209P & NRAS Q61R in 1 pt each. Ex-vivo culture of CSF-CTCs and PDX model: After lengthy optimization of conditions we successfully expanded CSF-CTCs in-vitro (~25% of pts), and in-vivo in immunodeficient mice from 1 pt (~10% of samples). Ceritinib, used as a FAK inhibitor, with MEKi was effective in-vitro (p=3.17e-6) and prolonged survival in-vivo in LMDz (median survival: >32 days vs control: 18 days; p=7.81e-5). CONCLUSIONS: Though the sample size is small, this is the first report of the successful in-vitro & in-vivo culture of CSF-CTCs from pts with LMDz. Single cell analysis to determine how representative these models are and further in-vivo testing are in progress.

scholarly journals Development of a drug-eluting microstent for micro-invasive glaucoma surgery

2018 ◽  
Vol 4 (1) ◽  
pp. 603-606
Author(s):  
Stefan Siewert ◽  
Sylvia Pfensig ◽  
Swen Großmann ◽  
Michael Stiehm ◽  
Klaus-Peter Schmitz ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Glaucoma Surgery ◽  
Surgical Approaches ◽  
Outer Diameter ◽  
Complication Rates ◽  
In Vivo Testing ◽  
Drug Eluting ◽  
Model Drug

AbstractGlaucoma represents the leading cause of irreversible blindness worldwide. Therapeutic approaches are based on the lowering of intraocular pressure (IOP). Micro-invasive glaucoma surgery (MIGS) offers perspectives for implant based IOP-reduction with reduced complication rates compared to conventional surgical approaches. Nevertheless, available devices suffer from complications like hypotony and fibrotic encapsulation. The current work focuses on the development of a minimally invasive implantable drugeluting microstent for the drainage of aqueous humour into suprachoroidal or subconjunctival space. Technical feasibility of a micro-scale resorbable nonwoven for the prevention of hypotony and of a drug-eluting coating for the prevention of fibrosis is assessed. Microstent base bodies with a length of 10 mm and an inner/outer diameter of 0.20 mm / 0.35 mm were manufactured. For the prevention of hypotony, resorbable nonwovens with an adequate flow resistance of 1.543 mmHg/μl min-1 were manufactured in the inflow area of microstents. A drug-eluting coating in the outflow area of microstents was developed based on the model drug fluorescein diacetate. Micro-invasive ab interno implantation of a microstent prototype into suprachoroidal space of a porcine eye post mortem was successfully performed, using an injector device. Future studies will focus on the development of an antifibrotic drug-eluting coating and further in vitro, ex vivo and in vivo testing of the devices.

Immunologic efficacy of E39 & E39' vaccination in a phase I/IIa trial in ovarian and endometrial cancer patients.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 75-75
Author(s):  
Tommy A Brown ◽  
Kaitlin M. Peace ◽  
John W Myers ◽  
Timothy J Vreeland ◽  
Diane F Hale ◽  
...  
Keyword(s):  
Phase I ◽  
Ex Vivo ◽  
Treatment Options ◽  
Booster Vaccination ◽  
Standard Of Care ◽  
Expression Level ◽  
Delayed Type Hypersensitivity ◽  
Folate Binding Protein ◽  
In Vivo Testing

75 Background: The treatment options for cancer are ever-evolving & now include vaccines targeting tumor-specific immunogenic peptides to induce tumor cytolysis. Folate binding protein (FBP) is a tumor-associated antigen (TAA) highly expressed in most endometrial & ovarian cancers (Ca), shielded from the normal immune system. The most promising FBP peptides are E39 & an attenuated form, E39' (aka J65). In our most recent phase I/IIa trial we evaluated an E39+GM-CSF inoculation series at 3 doses (VG) vs controls (CG) as well as booster vaccination with E39 or E39' after the initial inoculation series. Here we present the immunologic data from this phase I/IIa trial. Methods: Patients (pts) with ovarian or endometrial Ca who were disease-free after standard of care therapy but at risk for recurrence were enrolled. HLA-A2+ pts were vaccinated in a 3+3 dose escalation of 100mcg, 500mcg, & 1000mcg. The remaining pts received 1000mcg inoculations. Vaccine was given every 3-4 weeks for a total of 6 inoculums. Pts were then offered to participate in booster vaccination with 9 pts randomized to receive E39 & 9 pts E39'. FBP expression level was measured on the resected disease. Overall immunologic response & by subgroups was measured by delayed type hypersensitivity (DTH) & ELISPOT in the VG. Results: A total of 29 pts were vaccinated. Mean DTH prior to the initial dose of E39 was 5.74mm & after final dose was 10.33mm (p = 0.018). Mean overall ELISPOT change over time through 18 months was +69.1 when compared to baseline (p = 0.675). At 18 months, mean ELISPOT increased by 97.1 in 1000mcg vs -57.0 in < 1000mcg dosed pts (p = 0.047) & by +255.33 in pts with > average initial DTH vs -0.75 in < average initial DTH (p = 0.004) when compared to baseline. Immunological analyses were not significantly different between FBP hi/lo expression or E39 vs E39’ booster (p > 0.05). Conclusions: E39 demonstrated significant overall immunogenicity on in vivo testing as measured by DTH. Ex vivo analysis (ELISPOT) suggests that E39 is more immunogenically efficacious in pts with > average initial DTH & those who are optimally dosed (1000mcg). FBP expression level & E39 vs E39’ use in booster inoculations did not significantly impact in vivo or ex vivo immunogenicity. Clinical trial information: NCT01580696.

scholarly journals Gdnf, a germ cell-derived factor, regulates zebrafish germ cell stemness through the creation of new spermatogonial niches (germ and Sertoli cells) and inhibition of spermatogonial differentiation in an autocrine and paracrine manners

2021 ◽  
Author(s):  
Lucas Doretto ◽  
Arno J. Butzge ◽  
Rafael T. Nakajima ◽  
Emanuel R.M. Martinez ◽  
Beatriz Marques ◽  
...  
Keyword(s):  
Germ Cell ◽  
Sertoli Cells ◽  
Genome Duplication ◽  
Ex Vivo ◽  
Spermatogonial Stem Cell ◽  
Mrna Levels ◽  
Type B ◽  
The Creation ◽  
First Time

Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GDNF Family Receptor α1 - GFRα1) are well known to mediate spermatogonial stem cell (SSC) proliferation and survival in the mammalian testes. In nonmammalian species, Gdnf and Gfrα1 orthologs have been found but their functions remain poorly investigated in the testis. Considering this background, this study aimed to understand the roles of Gdnf-Gfrα1 signaling pathway in the zebrafish testis by combining in vivo, in silico and ex vivo approaches. Our analysis showed that zebrafish exhibited two paralogs of Gndf (gdnfa and gdnfb) and its receptor, Gfrα1 (gfrα1a and gfrα1b), in agreement with the teleost-specific third round (3R) of whole genome duplication. Expression analysis further revealed that gdnfa and gfrα1a were the most expressed copies in the zebrafish adult testes. Subsequently, we demonstrated that gdnfa is expressed in the germ cells, while Gfrα1a was detected in early spermatogonia (mainly in types Aund and Adiff) and Sertoli cells. Functional ex vivo analysis showed that Gdnf promoted the creation of new available niches by stimulating proliferation of both type Aund spermatogonia and their surrounding Sertoli cells, but without changing pou5f3 mRNA levels. Strikingly, Gdnf also inhibited late spermatogonial differentiation as shown by the decrease of type B spermatogonia and down-regulation of dazl in the co-treatment with Fsh. Altogether, our data revealed for the first time that a germ cell-derived factor is associated with maintaining germ cell stemness through the creation of new available niches, supporting development of differentiating spermatogonial cysts and inhibiting late spermatogonial differentiation in autocrine and paracrine manners.

Instrumentation for Testing Soft Tissue Undergoing Large Deformation: Ex Vivo and In Vivo Studies

2008 ◽  
Vol 2 (4) ◽  
Author(s):  
Tie Hu ◽  
Alan C. W. Lau ◽  
Jaydev P. Desai
Keyword(s):  
Soft Tissue ◽  
Surface Area ◽  
Ex Vivo ◽  
Tissue Sample ◽  
Biomechanical Property ◽  
Probe Surface ◽  
In Vivo Experiments ◽  
In Vivo Testing ◽  
Force Resolution

Biomechanical property of soft tissue derived from experimental measurements is critical to develop a reality-based soft-tissue model for minimally invasive surgical training and simulation. In our research, we have focused on developing a biomechanical model of the liver with the ultimate goal of using this model for local tool-tissue interaction tasks and providing feedback to the surgeon through a haptic (sense of touch) display. In this paper, we present two devices that we have designed and built, namely, ex vivo and in vivo testing devices. We used them to measure the experimental force and displacement data of pig liver tissue. The device for ex vivo experiments uses a PC-based control system to control the motion of the probe and acquire the experimental force and displacement data. The force resolution for ex vivo testing was 0.002N (as per the resolution information provided by the manufacturer) and the probe velocity ranged from 0.1mm∕s to 25.4mm∕s. The device was designed so that it could be easily used for both small probe (tissue sample larger than the indenting probe surface area) testing as well as large probe (tissue sample smaller than the indenting probe surface area) testing. The device for in vivo experiments used a microcontroller-based instrumentation to control the motion and acquire and store the data on a multimedia memory disk. This device is designed for the purpose of acquiring experimental force and displacement data in vivo. The primary challenge in the design of the device for in vivo experiments was the limited workspace for device operation. The force resolution for in vivo testing was 0.015N and the displacement resolution was 0.02mm. The sampling frequency for data acquisition for in vivo testing was 50Hz.

scholarly journals Dynamic Physiological Culture of Ex Vivo Human Tissue: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2870
Author(s):  
Daniel Ll Hughes ◽  
Aron Hughes ◽  
Zahir Soonawalla ◽  
Somnath Mukherjee ◽  
Eric O’Neill
Keyword(s):  
Systematic Review ◽  
Tissue Culture ◽  
Human Tissue ◽  
Ex Vivo ◽  
Self Regulation ◽  
Success Rates ◽  
Diverse Range ◽  
Wide Range ◽  
The Creation

Conventional static culture fails to replicate the physiological conditions that exist in vivo. Recent advances in biomedical engineering have resulted in the creation of novel dynamic culturing systems that permit the recapitulation of normal physiological processes ex vivo. Whilst the physiological benefit for its use in the culture of two-dimensional cellular monolayer has been validated, its role in the context of primary human tissue culture has yet to be determined. This systematic review identified 22 articles that combined dynamic physiological culture techniques with primary human tissue culture. The most frequent method described (55%) utilised dynamic perfusion culture. A diverse range of primary human tissue was successfully cultured. The median duration of successful ex vivo culture of primary human tissue for all articles was eight days; however, a wide range was noted (5 h–60 days). Six articles (27%) reported successful culture of primary human tissue for greater than 20 days. This review illustrates the physiological benefit of combining dynamic culture with primary human tissue culture in both long-term culture success rates and preservation of native functionality of the tissue ex vivo. Further research efforts should focus on developing precise biochemical sensors that would allow for real-time monitoring and automated self-regulation of the culture system in order to maintain homeostasis. Combining these techniques allows the creation of an accurate system that can be used to gain a greater understanding of human physiology.

Sign in / Sign up

Export Citation Format

Share Document