Experimental studies on intra-luminal implantation of tumor cells in stomach and colon

1971 ◽  
Vol 6 (2) ◽  
pp. 91-92
Author(s):  
Y. Yokoyama ◽  
H. Matsushige ◽  
T. Takahashi ◽  
S. Majima
Keyword(s):  
Tumor Cells ◽  
Experimental Studies

scholarly journals Local Anesthetics and Recurrence after Cancer Surgery-What’s New? A Narrative Review

2021 ◽  
Vol 10 (4) ◽  
pp. 719
Author(s):  
Sarah D. Müller ◽  
Jonathan S. H. Ziegler ◽  
Tobias Piegeler
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Local Anesthetics ◽  
Experimental Studies ◽  
Perioperative Period ◽  
Cancer Surgery ◽  
Narrative Review ◽  
Future Research ◽  
Inflammatory Stress ◽  
Research Activities

The perioperative use of regional anesthesia and local anesthetics is part of almost every anesthesiologist’s daily clinical practice. Retrospective analyses and results from experimental studies pointed towards a potential beneficial effect of the local anesthetics regarding outcome—i.e., overall and/or recurrence-free survival—in patients undergoing cancer surgery. The perioperative period, where the anesthesiologist is responsible for the patients, might be crucial for the further course of the disease, as circulating tumor cells (shed from the primary tumor into the patient’s bloodstream) might form new micro-metastases independent of complete tumor removal. Due to their strong anti-inflammatory properties, local anesthetics might have a certain impact on these circulating tumor cells, either via direct or indirect measures, for example via blunting the inflammatory stress response as induced by the surgical stimulus. This narrative review highlights the foundation of these principles, features recent experimental and clinical data and provides an outlook regarding current and potential future research activities.

scholarly journals Metabolism in experimental malignant tumors. (Problems of Oncology, 1928, No. 1)

1929 ◽  
Vol 25 (1) ◽  
pp. 104-104
Keyword(s):  
Tumor Cells ◽  
Malignant Tumor ◽  
Water Exchange ◽  
Malignant Tumors ◽  
Experimental Studies ◽  
The Body ◽  
Dramatic Effect ◽  
Enzymatic Nature ◽  
Nitrogenous Metabolism

Experimental studies have convinced Professor A.V. Repreva (Vopr. Oncology, 1928, No. 1) that inoculation of the smallest pieces of a malignant tumor to an animal has a dramatic effect on the metabolism in the body of the latter and, above all, on water exchange, then on salt metabolism, nitrogenous metabolism, etc. Obviously, tumor cells contain substances close to bodies of an enzymatic nature.

scholarly journals A Novel Oral Arginase 1/2 Inhibitor Enhances the Antitumor Effect of PD-1 Inhibition in Murine Experimental Gliomas by Altering the Immunosuppressive Environment

2021 ◽  
Vol 11 ◽  
Author(s):  
Paulina Pilanc ◽  
Kamil Wojnicki ◽  
Adria-Jaume Roura ◽  
Salwador Cyranowski ◽  
Aleksandra Ellert-Miklaszewska ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Rna Sequencing ◽  
Checkpoint Inhibitors ◽  
Oral Treatment ◽  
Experimental Studies ◽  
Myeloid Cells ◽  
Antitumor Effects ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Arginase 1

Glioblastomas (GBM) are the common and aggressive primary brain tumors that are incurable by conventional therapies. Immunotherapy with immune checkpoint inhibitors is not effective in GBM patients due to the highly immunosuppressive tumor microenvironment (TME) restraining the infiltration and activation of cytotoxic T cells. Clinical and experimental studies showed the upregulation of expression of the arginase 1 and 2 (ARG1 and ARG2, respectively) in murine and human GBMs. The elevated arginase activity leads to the depletion of L-arginine, an amino-acid required for the proliferation of T lymphocytes and natural killer cells. Inhibition of ARG1/2 in the TME may unblock T cell proliferation and activate effective antitumor responses. To explore the antitumor potential of ARG1/2 inhibition, we analyzed bulk and single-cell RNA sequencing (scRNA-seq) data from human and murine gliomas. We found the upregulation of ARG1/2 expression in GBMs, both in tumor cells and in tumor infiltrating microglia and monocytes/macrophages. We employed selective arginase inhibitors to evaluate if ARG1/2 inhibition in vitro and in vivo exerts the antitumor effects. A novel, selective ARG1/2 inhibitor - OAT-1746 blocked microglia-dependent invasion of U87-MG and LN18 glioma cells in a Matrigel invasion assay better than reference compounds, without affecting the cell viability. OAT-1746 effectively crossed the blood brain barrier in mice and increased arginine levels in the brains of GL261 glioma bearing mice. We evaluated its antitumor efficacy against GL261 intracranial gliomas as a monotherapy and in combination with the PD-1 inhibition. The oral treatment with OAT-1746 did not affect the immune composition of TME, it induced profound transcriptomic changes in CD11b+ cells immunosorted from tumor-bearing brains as demonstrated by RNA sequencing analyses. Treatment with OAT-1746 modified the TME resulting in reduced glioma growth and increased antitumor effects of the anti-PD-1 antibody. Our findings provide the evidence that inhibition of ARG1/2 activity in tumor cells and myeloid cells in the TME unblocks antitumor responses in myeloid cells and NK cells, and improves the efficacy of the PD-1 inhibition.

scholarly journals Improving the Antitumor Effect of Doxorubicin in the Treatment of Eyeball and Orbital Tumors

2021 ◽  
Author(s):  
Maletskyy Anatoliy Parfentievich ◽  
Samchenko Yuriy Markovich ◽  
Bigun Natalia Mikhailivna
Keyword(s):  
Tumor Cells ◽  
Soft Tissues ◽  
Malignant Tumors ◽  
Release Kinetics ◽  
Experimental Studies ◽  
Diffusion Kinetics ◽  
Therapeutic Level ◽  
Polyvinyl Formal ◽  
Orbital Tissue ◽  
Kinetics Of

Malignant tumors of the orbit are the main cause for 41–45.9% of orbital tumor, and they will threaten both the organ of vision and the life of the patient. In our opinion, improving the effectiveness of treatment of malignant tumors can be implemented in the following areas: a) immobilization of doxorubicin in synthetic polymeric materials, which will fill the tissue structures that were resected and reduce the percentage of tumor recurrence. b) the use of nanomaterials for the delivery of doxorubicin to tumor cells. To develop a hydrogel implant and nanoparticles, to study the diffusion kinetics of doxorubicin in a hydrogel implant and the ability of nanoparticles to transport doxorubicin. The developed gels based on acrylic acid (AAc) were obtained by radical polymerization of an aqueous solution of monomers (AAc and N, N-methylenebisacrylamide (MBA)) at a temperature of 70°C. Matrices based on polyvinyl formal (PVF) were obtained by treatment of polyvinyl alcohol (PVA) with formaldehyde in the presence of a strong acid. Experimental studies were performed on rabbits of the Chinchilla breed, weighing 2–3 kg, aged 5–6 months, which during the study were in the same conditions. We implanted the hybrid gel in the scleral sac; orbital tissue and in the ear tissue of rabbits: Evaluation of the response of soft tissues and bone structures to implant materials was carried out on the basis of analysis of changes in clinical and pathomorphological parameters was performed after 10, 30 and 60 days. Diffusion of doxorubicin was examined by using UV spectroscopy [spectrophotometer-fluorimeter DS-11 FX + (DeNovix, USA)], analyzing samples at regular intervals during the day at a temperature of 25° C. The concentration of active substances was determined by the normalized peak absorption of doxorubicin at 480 nm. The release kinetics of the antitumor drug doxorubicin were investigated by using a UV spectrometer “Specord M 40” (maximum absorption 480 nm). The developed hydrogel implant has good biocompatibility and germination of surrounding tissues in the structure of the implant, as well as the formation of a massive fibrous capsule around it. An important advantage of the implant is also the lack of its tendency to resorption. Moreover, the results showed that the diffusion kinetics of doxorubicin from a liquid-crosslinked hydrogel reaches a minimum therapeutic level within a few minutes, while in the case of a tightly crosslinked - after a few hours. It was also found that the liquid-crosslinked hydrogel adsorbs twice as much as the cytostatic - doxorubicin. The analysis of the research results approved that the size of the nanoparticles is the main factor for improving drug delevary and penetration. Thus, nanoparticles with a diameter of less than 200 nm can penetrate into cells and are not removed from the circulatory system by macrophages, thereby prolonging their circulation in the body. About 10 nm. The developed hybrid hydrogel compositions have high mechanical strength, porosity, which provides 100% penetration of doxorubicin into experimental animal tissues. It was found that the kinetics of diffusion of drugs from liquid-crosslinked hydrogel reaches a minimum therapeutic level within a few minutes, whereas in the case of densely crosslinked hydrogel diffusion begins with a delay of several hours and the amount of drug released at equilibrium reaches much lower values (20–25%). The obtained preliminary experimental results allow us to conclude that our developed pathways for the delivery of drugs, in particular, doxorubicin to tumor cells will increase the effectiveness of antitumor therapy.

scholarly journals Modelling of macrophage interactions by partial differential equations

2017 ◽  
Vol 13 (2) ◽  
Author(s):  
Mohd Rashid Admon ◽  
Normah Maan
Keyword(s):  
Partial Differential Equations ◽  
Differential Equations ◽  
Tumor Cells ◽  
Cell Density ◽  
Experimental Studies ◽  
Decay Rates ◽  
Production Rates ◽  
Partial Differential ◽  
Paracrine Signalling ◽  
Autocrine Signalling

The recruitment of macrophages at the tumor sites is the earliest immune response takes place during tumor progression. In breast cancer, experimental studies reveals that the tumor cells are capable of taking advantage on the plasticity of macrophages. Tumor cells respond to epidermal growth factor, EGF that released by macrophages while macrophages respond to colony stimulating factor 1, CSF-1 that released by tumor cells. This chains continues and results a paracrine signalling loop. Consequently, tumor cells and macrophages will aggregate and invade to other tissues or organ. Tumor cells also receive their own signals, adding a new feature of interaction called autocrine signalling loop. By considering in vitro interactions, a system of partial differential equations that incorporate the saturating functions for secretion terms was developed. This functions describes the production of chemical signals saturates with increasing cell density. Stability analysis are then performed to investigate the conditions for aggregation. For a given average of cells density, the homogeneous steady state is non-trivial and the concentration of CSF-1 and EGF are produced in the saturated production. Stability results show that regions for instability are reduced, compared to previous model which assumes the production rates are linear with increasing cell density. Besides, the inclusion of autocrine signalling loop increase the occurrence of aggregation. Decreasing the production rates and chemotaxis sensitivity, together with increasing the decay rates are required to impede the aggregation from initiated. This results should provide valuable clinical suggestions in guiding medical experts during drug designs.

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