Disparate responses of tumour vessels to angiotensin II: tumour volume-dependent effects on perfusion and oxygenation

Perfusion and oxygenation of experimental tumours were studied during angiotensin II (AT II) administration whereby the rate of the continuous AT II infusion was chosen to increase the mean arterial blood pressure (MABP) by 50–70 mmHg. In subcutaneous DS- sarcomas the red blood cell (RBC) flux was assessed using the laser Doppler technique and the mean tumour oxygen partial pressure (p O 2) was measured polarographically using O 2-sensitive catheter and needle electrodes. Changes in RBC flux with increasing MABP depended mainly on tumour size. In small tumours, RBC flux decreased with rising MABP whereas in larger tumours RBC flux increased parallel to the MABP. As a result of these volume-dependent effects on tumour blood flow, the impact of AT II on tumour p O 2 was also mainly tumour volume-related. In small tumours oxygenation decreased with increasing MABP during AT II infusion, whereas in large tumours a positive relationship between blood pressure and O 2 status was found. This disparate behaviour might be the result of the co-existence of two functionally distinct populations of tumour vessels. In small tumours, perfusion decreases presumably due to vasoconstriction of pre-existing host vessels feeding the tumour. In larger malignancies, newly formed tumour vessels predominate and seem not to have this vasoresponsive capability (lack of smooth muscle cells and/or AT receptors), resulting in an improvement of perfusion which is not tumour-related per se, but is due to the increased perfusion pressure. © 2000 Cancer Research Campaig

Dynamic interplay between tumour, stroma and immune system can drive or prevent tumour progression

In the tumour microenvironment, cancer cells directly interact with both the immune system and the stroma. It is firmly established that the immune system, historically believed to be a major part of the body's defence against tumour progression, can be reprogrammed by tumour cells to be ineffective, inactivated, or even acquire tumour promoting phenotypes. Likewise, stromal cells and extracellular matrix can also have pro-and anti-tumour properties. However, there is strong evidence that the stroma and immune system also directly interact, therefore creating a tripartite interaction that exists between cancer cells, immune cells and tumour stroma. This interaction contributes to the maintenance of a chronically inflamed tumour microenvironment with pro-tumorigenic immune phenotypes and facilitated metastatic dissemination. A comprehensive understanding of cancer in the context of dynamical interactions of the immune system and the tumour stroma is therefore required to truly understand the progression toward and past malignancy.Comment: 36 pages, 4 figures, 1 tabl

Temperature-induced smearing of the coulomb gap: experiment and computer simulation

We present the first verification of the theoretically predicted effect of temperature-induced smearing of the Coulomb gap. Measurements of the variable-range-hopping conductivity (VRH) in samples of ion-implanted Si:As and computer simulation are used to study the density of states (DOS) near the Fermi level (FL) in the impurity band. The VRH is determined by the DOS integrated over some energy range that depends on temperature T and on the magnetic field B. Using the interplay between T and B we find that the DOS in the vicinity of the FL increases with increasing T

Expression pattern of the urokinase-plasminogen activator system in rat DS-sarcoma: Role of oxygenation status and tumour size

The urokinase plasminogen activator system plays a central role in malignant tumour progression. Both tumour hypoxia and enhancement of urokinase plasminogen activator, urokinase plasminogen activator-receptor and plasminogen activator inhibitor type 1 have been identified as adverse prognostic factors. Upregulation of urokinase plasminogen activator or plasminogen activator inhibitor type 1 could present means by which hypoxia influences malignant progression. Therefore, the impact of hypoxia on the expression pattern of the urokinase plasminogen activator system in rat DS-sarcoma in vivo and in vitro was examined. In the in vivo setting, tumour cells were implanted subcutaneously into rats, which were housed under either hypoxia, atmospheric air or hyperoxia. For in vitro studies, DS-sarcoma cells were incubated for 24 h under hypoxia. Urokinase plasminogen activator and urokinase plasminogen activator-receptor expression were analysed by flow cytometry. Urokinase plasminogen activator activity was measured using zymography. Plasminogen activator inhibitor type 1 protein levels in vitro and in vivo were examined with ELISA. PAI-1 mRNA levels were determined by RT–PCR. DS-sarcoma cells express urokinase plasminogen activator, urokinase plasminogen activator-receptor, and plasminogen activator inhibitor type 1 in vitro and in vivo. The urokinase plasminogen activator activity is enhanced in DS-sarcomas compared to normal tissues and rises with increasing tumour volume. The oxygenation level has no impact on the urokinase plasminogen activator activity in cultured DS-sarcoma cells or in solid tumours, although in vitro an increase in plasminogen activator inhibitor type 1 protein and mRNA expression after hypoxic challenge is detectable. The latter plasminogen activator inhibitor type 1 changes were not detectable in vivo. Hypoxia has been demonstrated to contribute to the upregulation of some components of the system in vitro, although this effect was not reproducible in vivo. This may indicate that the serum level of plasminogen activator inhibitor type 1 is not a reliable surrogate marker of tumour hypoxia

Nonclassical statistics of intracavity coupled χ(2)\chi^{(2)} waveguides: the quantum optical dimer

A model is proposed where two $\chi^{(2)}$ nonlinear waveguides are contained in a cavity suited for second-harmonic generation. The evanescent wave coupling between the waveguides is considered as weak, and the interplay between this coupling and the nonlinear interaction within the waveguides gives rise to quantum violations of the classical limit. These violations are particularly strong when two instabilities are competing, where twin-beam behavior is found as almost complete noise suppression in the difference of the fundamental intensities. Moreover, close to bistable transitions perfect twin-beam correlations are seen in the sum of the fundamental intensities, and also the self-pulsing instability as well as the transition from symmetric to asymmetric states display nonclassical twin-beam correlations of both fundamental and second-harmonic intensities. The results are based on the full quantum Langevin equations derived from the Hamiltonian and including cavity damping effects. The intensity correlations of the output fields are calculated semi-analytically using a linearized version of the Langevin equations derived through the positive-P representation. Confirmation of the analytical results are obtained by numerical simulations of the nonlinear Langevin equations derived using the truncated Wigner representation.Comment: 15 pages, 8 figures, submitted to Phys. Rev.

Imaging oxygenation of human tumours

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. (18)F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy