Tumor Cell Content and RNA Integrity of Surgical Tissues from Different Types of Tumors and Its Correlation with Ex Vivo and In Vivo Ischemia

2018 ◽  
Vol 25 (12) ◽  
pp. 3764-3770
Author(s):  
Xiao-Hui Zheng ◽  
Shao-Dan Zhang ◽  
Pei-Fen Zhang ◽  
Xi-Zhao Li ◽  
Ye-Zhu Hu ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Ex Vivo ◽  
Cell Content ◽  
Rna Integrity ◽  
Different Types

scholarly journals MINDIN secretion by prostate tumors induces premetastatic changes in bone via β-catenin

2020 ◽  
Vol 27 (7) ◽  
pp. 441-456
Author(s):  
Juan A Ardura ◽  
Luis Álvarez-Carrión ◽  
Irene Gutiérrez-Rojas ◽  
Peter A Friedman ◽  
Arancha R Gortázar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Tumor Cell ◽  
Ex Vivo ◽  
Prostate Tumor ◽  
Tumor Cell Adhesion ◽  
Prostate Tumors ◽  
Cell Homing

Bone metastases are common in advanced prostate cancer patients, but mechanisms by which specific pro-metastatic skeletal niches are formed before tumor cell homing are unclear. We aimed to analyze the effects of proteins secreted by primary prostate tumors on the bone microenvironment before the settlement and propagation of metastases. Here, using an in vivo pre-metastatic prostate cancer model based on the implantation of prostate adenocarcinoma TRAMP-C1 cells in immunocompetent C57BL/6 mice, we identify MINDIN as a prostate tumor secreted protein that induces bone microstructural and bone remodeling gene expression changes before tumor cell homing. Associated with these changes, increased tumor cell adhesion to the endosteum ex vivo and to osteoblasts in vitro was observed. Furthermore, MINDIN promoted osteoblast proliferation and mineralization and monocyte expression of osteoclast markers. β-catenin signaling pathway revealed to mediate MINDIN actions on osteoblast gene expression but failed to affect MINDIN-induced adhesion to prostate tumor cells or monocyte differentiation to osteoclasts. Our study evidences that MINDIN secretion by primary prostate tumors creates a favorable bone environment for tumor cell homing before metastatic spread.

scholarly journals PKHB1 Tumor Cell Lysate Induces Antitumor Immune System Stimulation and Tumor Regression in Syngeneic Mice with Tumoral T Lymphoblasts

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Ana Carolina Martínez-Torres ◽  
Kenny Misael Calvillo-Rodríguez ◽  
Ashanti Concepción Uscanga-Palomeque ◽  
Luis Gómez-Morales ◽  
Rodolfo Mendoza-Reveles ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Tumor Cell ◽  
Immune Tolerance ◽  
Tumor Regression ◽  
Ex Vivo ◽  
Cell Lysate ◽  
Hematological Cancers ◽  
Tumor Cell Lysate

Acute lymphocytic leukemia (ALL) is the most common pediatric cancer. Currently, treatment options for patients with relapsed and refractory ALL mostly rely on immunotherapies. However, hematological cancers are commonly associated with a low immunogenicity and immune tolerance, which may contribute to leukemia relapse and the difficulties associated with the development of effective immunotherapies against this disease. We recently demonstrated that PKHB1, a TSP1-derived CD47 agonist peptide, induces immunogenic cell death (ICD) in T cell ALL (T-ALL). Cell death induced by PKHB1 on T-ALL cell lines and their homologous murine, L5178Y-R (T-murine tumor lymphoblast cell line), induced damage-associated molecular patterns (DAMPs) exposure and release. Additionally, a prophylactic vaccination with PKHB1-treated L5178Y-R cells prevented tumor establishment in vivo in all the cases. Due to the immunogenic potential of PKHB1-treated cells, in this study we assessed their ability to induce antitumor immune responses ex vivo and in vivo in an established tumor. We first confirmed the selectivity of cell death induced by PKBH1 in tumor L5178Y-R cells and observed that calreticulin exposure increased when cell death increased. Then, we found that the tumor cell lysate (TCL) obtained from PKHB1-treated L5178YR tumor cells (PKHB1-TCL) was able to induce, ex vivo, dendritic cells maturation, cytokine production, and T cell antitumor responses. Finally, our results show that in vivo, PKHB1-TCL treatment induces tumor regression in syngeneic mice transplanted with L5178Y-R cells, increasing their overall survival and protecting them from further tumor establishment after tumor rechallenge. Altogether our results highlight the immunogenicity of the cell death induced by PKHB1 activation of CD47 as a potential therapeutic tool to overcome the low immunogenicity and immune tolerance in T-ALL.

scholarly journals [68Ga]Ga-DFO-c(RGDyK): Synthesis and Evaluation of Its Potential for Tumor Imaging in Mice

2021 ◽  
Vol 22 (14) ◽  
pp. 7391
Author(s):  
Sona Krajcovicova ◽  
Andrea Daniskova ◽  
Katerina Bendova ◽  
Zbynek Novy ◽  
Miroslav Soural ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Imaging ◽  
Ex Vivo ◽  
Cell Uptake ◽  
Αvβ3 Integrin ◽  
In Vitro Characterization ◽  
Positron Emission ◽  
Gallium 68

Angiogenesis has a pivotal role in tumor growth and the metastatic process. Molecular imaging was shown to be useful for imaging of tumor-induced angiogenesis. A great variety of radiolabeled peptides have been developed to target αvβ3 integrin, a target structure involved in the tumor-induced angiogenic process. The presented study aimed to synthesize deferoxamine (DFO)-based c(RGD) peptide conjugate for radiolabeling with gallium-68 and perform its basic preclinical characterization including testing of its tumor-imaging potential. DFO-c(RGDyK) was labeled with gallium-68 with high radiochemical purity. In vitro characterization including stability, partition coefficient, protein binding determination, tumor cell uptake assays, and ex vivo biodistribution as well as PET/CT imaging was performed. [68Ga]Ga-DFO-c(RGDyK) showed hydrophilic properties, high stability in PBS and human serum, and specific uptake in U-87 MG and M21 tumor cell lines in vitro and in vivo. We have shown here that [68Ga]Ga-DFO-c(RGDyK) can be used for αvβ3 integrin targeting, allowing imaging of tumor-induced angiogenesis by positron emission tomography.

scholarly journals An efficient routing protocol for internet of medical things focusing hot spot node problem

2021 ◽  
Vol 17 (2) ◽  
pp. 155014772199170
Author(s):  
Ghufran Ahmed ◽  
Danish Mehmood ◽  
Khurram Shahzad ◽  
Rauf Ahmed Shams Malick
Keyword(s):  
Internet Of Things ◽  
Ex Vivo ◽  
Hot Spot ◽  
Healthcare Budget ◽  
Care Workers ◽  
Different Types ◽  
Monitoring Performance ◽  
Node Problem ◽  
Day By Day

The healthcare budget is increasing day-by-day as the population of the world increases. The same is the case regarding the workload of health care workers, that is, doctors and other practitioners. Under such a scenario where workload and cost are increasing drastically, there is a dire need of integrating recent technological enhancements with the said domain. Since the last decade, a lot of work is in the process considering the said integration bringing revolutionary changes. For remote monitoring, existing systems use different types of Internet of things devices that measure different health parameters. One of the major problems in such a system is to find an optimum routing approach that can resolve energy and thermal issues that are taking the limelight in the research arena. In this article, a dynamic routing technique is proposed which is keen to connect multiple in vivo/ex vivo Internet of things devices and a sink (focusing thermal and energy problem) and then forwarding data from sink to remote location for monitoring. Performance parameters are kept energy efficiency and thermal awareness and analytical results show that the proposed protocol supersedes existing approaches in said metrics.

In Vivo Bioluminescence Imaging to Study the Contribution of TNF-TNFR Interactions on Immune and Parenchymal Cells to Tumor Cell Progression in a Syngenic Mouse Model

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1110-1110
Author(s):  
Martin Chopra ◽  
Simone S Riedel ◽  
Viktoria von Krosigk ◽  
Carina A Bäuerlein ◽  
Christian Brede ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Tumor Cell ◽  
Knockout Mice ◽  
Bioluminescence Imaging ◽  
Ex Vivo ◽  
Tumor Burden ◽  
Cell Progression ◽  
In Vivo Bioluminescence Imaging

Abstract Abstract 1110 The cytokine tumor necrosis factor-α (TNF) has pleiotropic functions both in normal physiology and disease. TNF and its relative lymphotoxin-α (LT) signal by activating two cell surface receptors TNFR1 and TNFR2. TNFR1 is expressed on most cells whereas TNFR2 is mainly expressed in cells of the hematopoietic system. TNF-TNFR interactions were shown to play a major role in graft-versus-leukemia effect and in the immunosurveillance of solid tumors. To study the contribution of TNF-TNFR interactions on tumor cell progression we employed a syngenic B16 melanoma mouse model combined with in vivo bioluminescence imaging. Firefly luciferase-transgenic B16 melanoma cells were injected intravenously into syngenic albino C57BL/6 hosts. The host mice were either of wildtype, TNF, LT, TNFR1, TNFR2 knockout or TNFR1R2 double knockout genotype. The localization and expansion of the B16 cells was monitored by in vivo bioluminescence imaging for up to 14 days. On days 15, mice were sacrificed and internal organs were imaged ex vivo to further elucidate the organ-specific tumor burden. B16 tumors were primarily found in the lungs of all genotypes. All female knockout genotypes displayed a higher lung tumor burden than wildtype mice. In male mice, only TNF knockout presented enhanced tumor cell signals. Following ex vivo imaging we evaluated the pulmonary infiltration of NK1.1 or NKp46, CD8, CD4 and CD4/CD25/Foxp3 regulatory T cells by flow cytometry and immunofluorescence microscopy. Compared to wildtype mice, more regulatory T cells infiltrated the lungs of female TNFR1 knockout mice (200%). In LT knockout mice, very few NK cells (<20%) but more CD4+ cells (160%) infiltrated the lungs. Only subtle changes occurred in the other deficient mouse strains. However, these changes were independent of the presence of tumor cells and could also be found in normal knockout mice without B16 tumors. Within sections of tumor-bearing lungs, we found that TNF and all three TNFR knockouts exhibited less CD8+ cells within tumors than did wildtype or LT knockout mice. The number of CD8+ cells in normal lung tissue was not altered across the different genotypes. The deficit in NK cells of LT knockout mice was confirmed by histology. The enhanced tumor progression in all knockout mice could be a secondary effect due to their altered immune phenotype rather than to the loss of TNF-TNFR interactions. To circumvent this potential experimental bias and to further assess the influence of the loss of expression of parts of the TNF/TNFR-system in immune cells only, we generated bone marrow chimeras by reconstituting lethally irradiated female wildtype mice with bone marrow derived from TNF, LT, TNFR1 or TNFR2 knockout mice. Tumor cell signals in these chimeric mice progressed more than in normal wildtype mice. In contrast to the first set of experiments with knockout mice, we found that mice reconstituted with either TNF or TNFR2 knockout bone marrow presented less tumor cell signal than did mice reconstituted with wildtype bone marrow. TNF-TNFR interactions between immune cells appear to exhibit pro-tumorigenic functions in our mouse model. These results show that TNF-TNFR interactions are an important step in tumor cell progression and that the outcome of these interactions differs, depending on whether immune or parenchymal cells are deficient in TNF-TNFR signalling components. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A syntenin-deficient microenvironment educates AML for aggressiveness

2021 ◽  
Author(s):  
Raphael Leblanc ◽  
Joanna Fares ◽  
Armelle Goubard ◽  
Remy Castellano ◽  
Luc Camoin ◽  
...  
Keyword(s):  
Cell Survival ◽  
Stromal Cells ◽  
Myeloid Leukemia ◽  
Ex Vivo ◽  
Related Factors ◽  
Stromal Microenvironment ◽  
Different Types ◽  
Pdz Protein

In acute myeloid leukemia (AML), the stromal microenvironment plays a prominent role in promoting tumor cell survival and progression. Although widely explored, the crosstalk between leukemic and stromal cells remains poorly understood. Syntenin, a multi-domain PDZ protein, controls both the trafficking and signaling of key molecules involved in intercellular communication. Therefore, we aimed to clarify the role of environmental syntenin in the progression of AML. By in vivo approaches in syngeneic mice, we demonstrate that a syntenin-deficient environment reprograms AML blasts to survive independently of the stroma. Up-regulation of EEF1A2 in the blasts controls this gain of cell survival. Furthermore, using ex vivo co-culture systems, we show that syntenin-deficient bone marrow stromal cells (BMSC) enhance the survival of different types of AML cells, including patient samples, and suffice to educate syngeneic AML, recapitulating micro-environmental effects observed in vivo. We establish that syntenin-deficiency causes an increase of eIF5A and autophagy-related factors in BMSC, and provide evidence that the inhibition of autophagy prevents syntenin-deficient BMSC to stimulate AML survival. Altogether, these findings indicate that host-syntenin in the BM microenvironment acts as a repressor of AML aggressiveness.

scholarly journals Particulate Debris Released From Breast Implant Surfaces Are Highly Dependent on Implant Type

2021 ◽  
Author(s):  
Nadim James Hallab ◽  
Lauryn Samelko ◽  
Dennis Hammond
Keyword(s):  
Total Mass ◽  
Ex Vivo ◽  
Breast Implant ◽  
Breast Implants ◽  
Particulate Material ◽  
Tissue Analysis ◽  
Implant Surface ◽  
Different Types ◽  
Particulate Debris

Abstract Background While Breast Implants (BIs) have never been safer, factors such as implant debris may influence complications such as chronic inflammation and illness such as ALCL. Do different types of BIs produce differential particulate debris? Objectives Our objective was to quantify, investigate and characterize the size, amount, and material-type of both loosely bound and adherent surface particles, using five different surface types of commercial BIs. Methods Surface particles from 5 surface types of BIs (n=5/group); Biocell, Microcell, Siltex, Smooth, SmoothSilk, and Traditional-Smooth were: 1) removed by a rinsing procedure and 2) removed using ultrapure-adhesive carbon-tabs. Particles were characterized (ASTM 1877-16) using Scanning-Electron-Microscopy and EDX-chemical analysis. Results Particles rinsed from Biocell, Microcell and Siltex were &lt;1 micron in diameter while SmoothSilk and Traditional-Smooth surfaces had median sizes &gt;1micron (range: 0.4-2.7microns). The total mass of particles rinsed from the surfaces indicated Biocell had &gt;5 fold-more particulate compared to all other implants, and &gt;30 fold-more than SmoothSilk or Traditional-Smooth implants (&gt;100x more for post rinse adhesion analysis). EDX analysis indicated particulate material for Biocell, Microcell and Siltex was silicone (&gt;50%), while particulate from SmoothSilk and Traditional-Smooth implants were predominantly carbon-based polymers, eg, polycarbonate-urethane, consistent with packaging (and were detected on all implant types). Generally, SmoothSilk and Traditional-Smooth implant groups had &gt;10x fewer particles released than Biocell, Microcell and Siltex surfaces. Pilot ex-vivo tissue analysis supported these findings. Conclusions Particulate debris released from BIs are highly dependent on the type of implant surface and is a likely key determinant of in vivo performance.

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