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Biomedical subjects

Erik O Pettersen

Publications and source records attributed to Erik O Pettersen.

6 recordsLinked to original sources
PubMed2005

Pericellular oxygen depletion during ordinary tissue culturing, measured with oxygen microsensors.

Recent research has found important differences in oxygen tension in proximity to certain mammalian cells when grown in culture. Oxygen has a low diffusion rate through cell culture media, thus, as a result of normal respiration, a decrease in oxygen tension develops close to the cells. Therefore, for the purpose of standardization and optimization, it is important to monitor pericellular oxygen tension and cell oxygen consumption. Here, we describe an integrated oxygen microsensor and recording system that allows measurement of oxygen concentration profiles in vertical transects through a 1.6-mm deep, stagnant, medium layer covering a cell culture. The measurement set-up reveals that, when confluent, a conventional culture of adherent cells, although exposed to the constant oxygen tension of ambient air, may experience pericellular oxygen tensions below the level required to sustain full oxidative metabolism. Depletions reported are even more prominent and potentially aggravating when the cell culture is incubated at reduced oxygen tensions (down to around 4% oxygen). Our results demonstrate that, if the pericellular oxygen tension is not measured, it is impossible to relate in vitro culture results (for example, gene expression to the oxygen tension experienced by the cell), as this concentration may deviate very substantially from the oxygen concentration recorded in the gas phase.

Calibration↗
PubMed2003

pH effects on the cellular uptake of four photosensitizing drugs evaluated for use in photodynamic therapy of cancer.

The difference in extracellular pH in malignant as compared to normal healthy tissues has been proposed to contribute to selective uptake of photosensitizers in tumors. Hematoporphyrin IX (HpIX), disulfonated meso-tetraphenylporphine (TPPS(2a)), meso-tetra(3-hydroxyphenyl)porphine (mTHPP) and meso-tetra(3-hydroxyphenyl)chlorin (mTHPC) were chosen to examine the pH dependence of their cellular drug uptake. The study was performed in the pH range 6.5-8.0 and showed that significantly higher amounts of the drug are taken up by T-47D cells at low pH values only in the case of HpIX. The pH value of the incubation medium did not influence the cellular uptake of mTHPP, mTHPC and TPPS(2a) significantly. The present work indicates that tumor selectivity of dyes, which get more lipophilic with decreasing pH value, may be related to the low extracellular pH value.

Breast Neoplasms↗
PubMed2002

Cell cycle inhibitors and outcome after radiotherapy in bladder cancer patients.

The aim of this study was to correlate the expression of cell cycle inhibitors with outcome of patients with muscle-invasive bladder cancer treated with preoperative radiotherapy (46 Gy/4-5 weeks or 20 Gy/1 week) and cystectomy. Patients with pT3b (n = 42) or pT0 (n = 17) were included in the study. Expression of p16INK4a and p27KIP1 was assessed immunohistochemically in pre-radiotherapy biopsies and cystectomy specimens. Previously reported results of p21CP1 expression were also included. No difference in pretreatment protein expression was found between patients with pT0 and pT3b. Expression of p21CIP1 and p27KIP1 was lower in cystectomy specimens than in pretreatment biopsies. None of the proteins showed significant impact on survival when analysed separately. However, patients with tumours showing > 50% expression of p16INK4a, p21CIP1, or p27KIP1 displayed poorer cancer-specific survival rates compared with the remaining patients (p = 0.025). This effect was more pronounced in patients receiving 46 Gy than in those receiving 20 Gy. In conclusion, low expression of cell cycle inhibitors is related to favourable survival after pre-cystectomy radiotherapy.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

Role of ribonucleotide reductase in regulation of cell cycle progression during and after exposure to moderate hypoxia.

Earlier studies have shown that the retinoblastoma protein (pRb) is involved in cell-cycle regulation under conditions of moderate hypoxia, which is the term we use to denote oxygen concentrations just above the lower level giving full respiration, ie. 1300 ppm O2. We have studied the cell cycle regulatory influence of varying levels of ribonucleotide reductase under moderate hypoxia in human cancer cells with either functional (T47D and T47DHU-res) or non-functional pRb due to expression of HPV18 E7 (HeLa S3). In this study we adapted a cell-line to hydroxyurea (T47DHU-res) resulting in an increased level of ribonucleotide reductase tyrosyl-radical that is not cell-cycle dependent. Under moderate hypoxic stress, pRb becomes dephosphorylated and rebound in the cell nucleus in all phases of the cell cycle, in contrast to its function under aerobic conditions where it binds only during early G1. We have shown in this paper that, upon reoxygenation, dephosphorylation and binding to the nucleus of pRb is reversible in T47D cells, although phosphorylation is delayed by more than 12 hours. As a result of the dephosphorylation of pRb, T47D cells are between 12 and 24 hours slower in reinitiating their S-phase progression than HeLa S3 cells (not containing functional pRb) following reoxygenation. However, with an increased level of ribonucleotide reductase tyrosyl-radical in the T47DHU-res cells, the S-phase progression after reoxygenation is reinitiated earlier, although the pRb status of these cells is the same as in T47D cells.

Animals↗
PubMedDate not supplied

The role of p27 in controlling the oxygen-dependent checkpoint of mammalian cells in late G1.

We have studied hypoxia-induced cell cycle arrest in human cells where the retinoblastoma tumour suppressor protein (pRb) is either functional (T-47D cells) or abrogated by expression of the HPV18 E7 oncoprotein (NHIK 3025 cells). Cells of both types are arrested in a restriction point in late G1, here denoted as the oxygen-dependent restriction point in late G1. This arrest seems to occur under extreme hypoxia in all types of mammalian cells so far tested. During an 18-h exposure to extreme hypoxia, the p27 protein level increased in G1-phase in both cells lines investigated and was followed by a binding between p27 and CDK2. This was observed both in the pRb-positive T-47D cells and in the pRb-negative NHIK 3025 cells. We, therefore, believe that p27 and not pRb is the mediator of this oxygen-dependent checkpoint in late G1. Our results also suggest that p27 regulates the restart of cell cycle progression of these arrested cells after reoxygenation.

Breast Neoplasms↗