Essels after repeated HBO treatment. However, Fukumura et al. [48] stated that
Essels after repeated HBO treatment. However, Fukumura et al. [48] stated that even though the structures with lymphatic endothelial marker are present in tumors, they probably do not transport fluid or macromolecules. This, together with the observed lowering of tumor Pif after repeated HBO treatment, should lead to an XAV-939 web increase in ECV. Nevertheless, ECV, PV and TTW did not change in tumors after repeated HBO treatment compared to control, indicating that neither the lowered Pif nor the disintegrated lymphatics after HBO contribute to the unchanged ECV found inPage 7 of(page number not for citation PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29069523 purposes)BMC Cancer 2009, 9:http://www.biomedcentral.com/1471-2407/9/the present study. As already mentioned, the possible “normalization” of the tumor vasculature, after repeated HBO treatment, is expected to normalize capillary permeability, and thereby prevent any increase in ECV, even though Pif is decreased. Reactive oxygen species and oxidative stress are considered to be important in several aspects of malignancies, both in tumor development as well as therapeutic strategies such as radiotherapy [49]. Since changes in oxygen concentration may affect the production of its reactive derivatives in the tumor, it is relevant to suggest that antitumor effects of HBO may be due to oxidative stress. Furthermore, as stated in the introduction, some chemotherapeutic drugs require oxygen to generate free radicals that induce cytotoxicity. However, our measurements of lipid peroixidation (MDA) did not indicate any significant effect on the oxidative status of the tumor tissue. Oxidative stress is therefore not likely to be involved in the potentiated effect of 5FU after HBO. Most solid tumors depend on increased rates of glycolysis to satisfy their energy demand [50]. This leads to decreased pH in the tumor microenvironment due to excessive lactate secretion. Hyperoxic treatment enhances oxygenation of the tumor tissue, and may therefore promote a reversion from the anaerobic metabolism back to non-tumorigentic, oxidative metabolism and thereby increased pH [21]. A less acidic microenvironment may therefore have a positive effect on the cytotoxicity of chemotherapy. However, although increased cytotoxicity has previously been postulated to be the main determinant of the enhanced effect of chemotherapy after HBO treatment in addition to enhanced neovascularisation, the present study has shown that it is also due to an active uptake of the drug into the tumor tissue. In conclusion, we showed that hyperoxia increases the uptake of [3H]-5FU in DMBA-induced mammary tumors, independently of changes in Pif, collagen fibril density, or transendothelial transport alone, as one could expect from the literature. The mechanism by which such an uptake occurs is PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27484364 clearly stimulated by elevated pO2, but still not elucidated.ume experiments. RKR and LS participated in the study design, interpretation of data and manuscript drafting. All authors read and approved the final manuscript.AcknowledgementsThis study was supported by grants from Helse Vest (Grants 911370), Edel and Ole Stakvold’s foundation and The Norwegian cancer society. Ingrid Strand and e Rye Eriksen are gratefully acknowledged for technical assistance.
Varona et al. BMC Cancer 2010, 10:193 http://www.biomedcentral.com/1471-2407/10/RESEARCH ARTICLEResearch articleOpen AccessExpression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependentAdo.
