Long-term performance of interstial fluid pressure and hypoxia as prognostic factors in cervix cancer

Fyles, Anthony; Milosevic, Michael; Pintilie, Melania; Syed, A.M. Nisar; Levin, W.; Manchul, L.; Hill, Richard P.

doi:10.1016/j.radonc.2006.07.014

Cited by 122 publications

(76 citation statements)

References 13 publications

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“…On the other hand, neither K trans nor v e correlated with IFP in this study, an observation that is consistent with studies having revealed that the IFP of tumors does not correlate with tumor oxygen tension [40,41] and the suggestion that tumor IFP is independent of the extent of tumor hypoxia [38]. Although weak correlations between K trans -and v erelated MR parameters and IFP have been reported for some melanoma xenograft models [31], other MR parameters may be more appropriate for non-invasive assessment of the IFP of PDACs.…”

Section: Discussionsupporting

confidence: 91%

Dynamic contrast-enhanced MRI of the microenvironment of pancreatic adenocarcinoma xenografts

et al. 2017

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Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor outcome. Resistance to treatment is associated with impaired vascularity, extensive hypoxia, and interstitial hypertension. In this study, the potential of dynamic contrast-enhanced (DCE)-MRI as a method for assessing the microvascular density (MVD), the fraction of hypoxic tissue, and the interstitial fluid pressure (IFP) of PDACs was investigated. Material and methods: Intramuscular BxPC-3, Capan-2, MIAPaCa-2, and Panc-1 PDAC xenografts were used as preclinical models of human PDACs. DCE-MRI with Gd-DOTA as contrast agent was conducted with a 7.05-T scanner, and the DCE-MRI series were analyzed voxelwise by using the Tofts pharmacokinetic model. Tumor MVD and hypoxia were measured in histological preparations by using pimonidazole as a hypoxia marker and CD31 as a marker of endothelial cells. IFP was measured with a Millar catheter. Results: K trans (the volume transfer constant of Gd-DOTA) increased with increasing MVD and decreased with increasing hypoxic fraction, but was not associated with IFP. Any association between v e (the fractional distribution volume of Gd-DOTA) and MVD, hypoxic fraction, or IFP could not be detected. Conclusions: This study shows that DCE-MRI is a useful modality for assessing important features of the microenvironment of PDAC xenografts and thus provides the basis for future preclinical and clinical DCE-MRI investigations of PDAC.

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Section: Discussionsupporting

confidence: 91%

Dynamic contrast-enhanced MRI of the microenvironment of pancreatic adenocarcinoma xenografts

et al. 2017

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“…Hypoxic tumor cells exist in colorectal cancer, and the level of hypoxia is prognostic for clinical outcome (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Hypoxia may give rise to genetic instability by downregulating multiple DNA repair pathways, including the DNA mismatch repair (MMR) and homologous recombination (HR) pathways (20)(21)(22)(23)(24)(25)(26)(27). For example, Chan and colleagues demonstrated an alternate mechanism of translational inhibition of the HR proteins RAD51 and BRCA2 (23).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Provokes Base Excision Repair Changes and a Repair-Deficient, Mutator Phenotype in Colorectal Cancer Cells

Chan

Ali

McCallum

et al. 2014

Molecular Cancer Research

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Regions of acute and chronic hypoxia exist within solid tumors and can lead to increased rates of mutagenesis and/ or altered DNA damage and repair protein expression. Base excision repair (BER) is responsible for resolving small, non-helix-distorting lesions from the genome that potentially cause mutations by mispairing or promoting DNA breaks during replication. Germline and somatic mutations in BER genes, such as MutY Homolog (MUTYH/ MYH) and DNA-directed polymerase (POLB), are associated with increased risk of colorectal cancer. However, very little is known about the expression and function of BER proteins under hypoxic stress. Using conditions of chronic hypoxia, decreased expression of BER proteins was observed because of a mechanism involving suppressed BER protein synthesis in multiple colorectal cancer cell lines. Functional BER was impaired as determined by MYH-and 8-oxoguanine (OGG1)-specific glycosylase assays. A formamidopyrimidine-DNA glycosylase (Fpg) Comet assay revealed elevated residual DNA base damage in hypoxic cells 24 hours after H 2 O 2 treatment as compared with normoxic controls. Similarly, high-performance liquid chromatography analysis demonstrated that 8-oxo-2 0 -deoxyguanosine lesions were elevated in hypoxic cells 3 and 24 hours after potassium bromate (KBrO 3 ) treatment when compared with aerobic cells. Correspondingly, decreased clonogenic survival was observed following exposure to the DNA base damaging agents H 2 O 2 and MMS, but not to the microtubule interfering agent paclitaxel. Thus, a persistent downregulation of BER components by the microenvironment modifies and facilitates a mutator phenotype, driving genetic instability and cancer progression.

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“…Such convective forces inhibit the transfer of drugs to the tumor interstitium and facilitate tumor cell intravasation into the vascular or lymphatic circulation, and hence promote metastasis (7). Furthermore, there are clinical data showing that tumor IFP correlates with response to treatment, with strong evidence for high IFP as a poor prognostic indicator in patients with cervical cancer treated with radiotherapy (6,8). Patients are significantly more likely to develop distant recurrence if they present with a tumor IFP value above the group median (19 mmHg), which suggests a role for IFP in metastatic spread (9).…”

Section: Introductionmentioning

confidence: 99%

High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma

et al. 2013

International Journal of Molecular Medicine

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Abstract.It has been shown that interstitial fluid pressure (IFP) is elevated in many solid tumors. The elevated IFP in tumors is responsible, at least in part, for the poor blood supply, inadequate delivery of therapeutic agents to solid tumors and poor treatment response in patients. The present study was carried out to examine alterations in malignant phenotypes in oral squamous cell carcinoma cells subjected to conditions mimicking IFP and to identify the relevant molecular mechanisms. We investigated tumor cell proliferation and invasion using SCC-4 and SCC-9 cells subjected to an increased extracellular pressure of 0, 15 and 30 mmHg in vitro. The results revealed that the increased IFP resulted in a marked increase in cancer cell proliferation, survival and invasion in vitro and altered the expression of >1,800 genes involved in invasion and metastasis, the heat shock pathway, the p38 and JNK signaling pathway, apoptosis and the cell growth and differentiation signaling pathway. These results suggest the important potential clinical application of measuring IFP, which can be used as a generic marker of prognosis and response to therapy.

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Long-term performance of interstial fluid pressure and hypoxia as prognostic factors in cervix cancer

Cited by 122 publications

References 13 publications

Dynamic contrast-enhanced MRI of the microenvironment of pancreatic adenocarcinoma xenografts

Dynamic contrast-enhanced MRI of the microenvironment of pancreatic adenocarcinoma xenografts

Hypoxia Provokes Base Excision Repair Changes and a Repair-Deficient, Mutator Phenotype in Colorectal Cancer Cells

High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma

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