The effect of oxygenation on the biological behaviour of tumours

2007 ◽  
Vol 148 (30) ◽  
pp. 1415-1420 ◽  
Author(s):  
József Tóth
Keyword(s):  

A rosszindulatú daganatokban gyakran ún. hypoxiás, csökkent oxigéntartalmú területek vannak (az oxigéntenzió < 7 Hgmm). A preklinikai, valamint klinikai vizsgálatok igazolták, hogy a hypoxia fokozza a tumorok progresszióját, agresszivitását. Szövettenyészeteken tanulmányozva az oxigén hatását, bebizonyosodott, hogy az oxigenizáció in vitro önmagában is gátolja az ép szövetek, a benignus és malignus tumorok sejtjeinek növekedését. Az onkoterápia szempontjából rendkívül fontos megállapítás, hogy ha egy daganatban az oxigén parciális nyomása kevesebb, mint 2,5 Hgmm, a sugárérzékenység lecsökken (intrinszik radiorezisztencia). Hypoxiás tumorokban számos kemoterápiás gyógyszer is hatástalan (kemorezisztencia). Oxigén hiányában vagy hypoxiás szövetekben a fotodinámiás kezelés is eredménytelennek bizonyult. Mindezen kísérleti és klinikai tapasztalatok alapján már évtizedek óta egyes intézetekben kiegészítő kezelésként, de egymagában is próbálkoznak a daganatos betegek oxigenizációjával. A leggyakoribb kezelési forma az oxigéngáz belélegeztetése (hiperbarikus oxigénterápia), vagy az oxigénnel telített víz alkalmazása fürdő vagy ivókúra formájában. A ma már nemzetközi kooperációban is végzett vizsgálatok egyértelműen igazolják az oxigénbevitel jótékony terápiás, radio- és kemoszenzitizáló hatását. Az általánosan alkalmazott eritropoietin-kezelés is bizonyítja az oxigenizáció jelentőségét a tumorterápiában. Időszerűnek látszik Magyarországon szakintézetekben nagy beteganyagon kivizsgálni az oxigenizáció tumorgátló, radio- és kemoszenzitizáló hatását.

2017 ◽  
Vol 14 (9/10/11) ◽  
pp. 816 ◽  
Author(s):  
K.J. Sourabh Monnappa ◽  
Nikhath Firdose ◽  
G. Madhu Shree ◽  
Kaustav Nath ◽  
P.N. Navya ◽  
...  

2020 ◽  
Vol 8 (17) ◽  
pp. 3896-3907 ◽  
Author(s):  
Francesca Ercole ◽  
Yuhuan Li ◽  
Michael R. Whittaker ◽  
Thomas P. Davis ◽  
John F. Quinn

A comprehensive in vitro study into trisulfide-bearing PEG-conjugates was conducted. For these materials the combination of a cholesteryl group and an H2S donating moiety is required to confer cytoprotective and ROS-mitigating effects.


2020 ◽  
Vol 92 (11) ◽  
pp. 1303-1321 ◽  
Author(s):  
Johannes Partzsch ◽  
Christian Mayr ◽  
Massimiliano Giulioni ◽  
Marko Noack ◽  
Stefan Hänzsche ◽  
...  

Abstract Real-time coupling of cell cultures to neuromorphic circuits necessitates a neuromorphic network that replicates biological behaviour both on a per-neuron and on a population basis, with a network size comparable to the culture. We present a large neuromorphic system composed of 9 chips, with overall 2880 neurons and 144M conductance-based synapses. As they are realized in a robust switched-capacitor fashion, individual neurons and synapses can be configured to replicate with high fidelity a wide range of biologically realistic behaviour. In contrast to other exploration/heuristics-based approaches, we employ a theory-guided mesoscopic approach to configure the overall network to a range of bursting behaviours, thus replicating the statistics of our targeted in-vitro network. The mesoscopic approach has implications beyond our proposed biohybrid, as it allows a targeted exploration of the behavioural space, which is a non-trivial task especially in large, recurrent networks.


2020 ◽  
Vol 14 (1) ◽  
pp. 63-70
Author(s):  
Cecilia Guedes-Silva ◽  
Andrea Rodas ◽  
Flávio Carvalho ◽  
Olga Higa ◽  
Thiago Ferreira

Titanium, silicon and calcium ions have demonstrated positive effects in bone healing. Therefore, this paper investigates the densification, mechanical properties and in vitro biological behaviour of TiO2, together with SiO2 and CaO, on silicon nitride ceramics to be used in clinical applications. The results revealed that the sintered samples reached high values of relative density and fracture toughness, non-cytotoxicity as well as good ability to promote cell proliferation and form a layer of carbonated hydroxyapatite on their surfaces, after immersion in simulated body fluid. The sample with the highest amount of TiO2 reached the highest value of relative density and the best results of cell proliferation and fracture toughness, indicating the great potential to be explored by in vivo experiments for later application as intervertebral devices.


2020 ◽  
Author(s):  
Taiana Ferreira-Paes ◽  
Karen S. Charret ◽  
Merienny R.S. Ribeiro ◽  
Raquel F. Rodrigues ◽  
Leon L. Leon

AbstractLeishmania infantum infantum (LII) is one of the species that causes visceral leishmaniasis (VL) in the Old World, while L. infantum chagasi (LIC), and is present in the New World. Few studies address the biological differences, as well as the behaviour of these strains during infection. These parasites live inside the cells of their hosts, continuously evading the microbicidal mechanisms and modulating the immune response of these cells. One of the mechanisms used by these protozoa involves the L-arginine metabolism. Given the importance of the understanding of differences between Leishmania species, as well as establishing a better murine model to study leishmaniases, the objectives of this work were to analyse the biological and molecular differences between two Leishmania infantum strains (LII and LIC) and the degree of susceptibility of mice with different genetic backgrounds to infection, as well as to understand the role of arginase (ARG)/nitric oxide synthase (NOS) in the parasite-host relationship. The infectivity in vivo and in vitro of LII and LIC was performed in BALB/c and Swiss Webster mice, as well the NOS and ARG activities. The LII strain showed more infective than the LIC strain both in vivo and in vitro. In animals infected by both strains, a difference in NOS and ARG activities occurred. In vitro, promastigotes of LII isolated from BALB/c and Swiss Webster mice showed higher ARG activity than the LIC during the growth curve, however, no difference was observed in intracellular NO production by promastigotes between these strains. A comparison of the sequences of the ARG gene was made and both strains were identical. However, despite the similarity, the strains showed different expression of this gene. It can be concluded that although L. chagasi strains are considered identical to L. infantum strains, both have different biological behaviour.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yin-Zhe An ◽  
Eunae Cho ◽  
Junqi Ling ◽  
Xianglan Zhang

Abstract Background In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behaviour of CAFs and bone invasion in OSCC. Methods The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples from patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behaviour of OSCC cells and CAFs was further investigated both in vitro and in vivo. Results Axin2 expression was significantly associated with Snail expression, the desmoplasia status, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2 expression, and Snail expression were independent poor prognostic factors in our cohort. Consistent with these findings, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 (CCL5) and interleukin 8 (IL8) demonstrated a strong influence on the biological behaviour of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using a BALB/c athymic nude mouse xenograft model. Conclusions Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves but rather extend to CAFs via regulation of the cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as a poor prognosis in OSCC.


2000 ◽  
Vol 350 (1) ◽  
pp. 245-251 ◽  
Author(s):  
József DUDÁS ◽  
Giuliano RAMADORI ◽  
Thomas KNITTEL ◽  
Katrin NEUBAUER ◽  
Dirk RADDATZ ◽  
...  

Proteoglycan assembly in malignant tumours is subject to profound changes. The significance of these alterations is not well understood; especially, their role in nuclear regulation is a topic for debate. The capacity of heparin and liver carcinoma heparan sulphate (HS) to alter DNA–transcription factor interactions has been studied to provide further evidence concerning the regulatory potential of glycosaminoglycan (GAG) in the nucleus. Experiments both in vitro and in vivo indicated that heparin and HS are capable of inhibiting the interaction of transcription factors with their consensus oligonucleotide elements. Among five transcription factors studied, AP-1, SP-1, ETS-1 and nuclear factor κB proved to be sensitive to heparin and heparan sulphate, whereas TFIID was hardly inhibited in either in vitro or in vivo systems. Interestingly, HS from peritumoral liver was five times more effective than heparin. Liver carcinoma HS was less effective than liver HS, but its activity was comparable with that of heparin. These results indicate that the structural differences of GAG chains strongly influence their biological behaviour. The loss of their recognized functional activity in malignant tumours might promote the development of uncontrolled growth and gene expression favouring the neoplastic process.


2018 ◽  
Vol 46 (4) ◽  
pp. 1606-1616 ◽  
Author(s):  
Peng Li ◽  
Xiao Yang ◽  
Wenbo Yuan ◽  
Chengdi Yang ◽  
Xiaolei Zhang ◽  
...  

Background/Aims: CircRNAs regulate gene expression in different malignancies. However, the role of Cdr1as in the tumourigenesis of bladder cancer and its potential mechanisms remain unknown. Methods: qRT-PCR was used to detect Cdr1as and target miRNA expression in bladder cancer tissues and cell lines. Biological functional experiments were performed to detect the effects of Cdr1as on the biological behaviour of bladder cancer cells in vivo and in vitro. Bioinformatic analysis was utilised to predict potential miRNA target sites on Cdr1as. Ago2 RNA binding protein immunoprecipitation assay, RNA antisense purification assay, biotin pull down assay and RNA FISH were performed to detect the interaction between Cdr1as and target miRNAs. Western blot was used to determine the expression level of p21 in bladder cancer cells. Results: Cdr1as was significantly down-regulated in bladder cancer tissues compared with adjacent normal tissues. Overexpression of Cdr1as inhibited the proliferation, invasion and migration of bladder cancer cells in vitro and slowed down tumour growth in vivo. Cdr1as sponged multiple miRNAs in bladder cancer. Moreover, Cdr1as directly bound to miR-135a and inhibited its activity in bladder cancer. Conclusion: Cdr1as is down-regulated and sponges multiple miRNAs in bladder cancer. It exerts anti-oncogenic functions by sponging microRNA-135a.


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