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Richard P. Hill - One of the best experts on this subject based on the ideXlab platform.

  • interstitial Fluid Pressure in tumors therapeutic barrier and biomarker of angiogenesis
    Future Oncology, 2008
    Co-Authors: Sarah Jane Lunt, Anthony Fyles, Richard P. Hill, Michael Milosevic
    Abstract:

    Interstitial Fluid Pressure is elevated in virtually all solid malignant tumors as a result of abnormalities of the vasculature and interstitium. High interstitial Fluid Pressure is an independent predictor of disease recurrence in cervical cancer patients treated with radiotherapy, has been implicated as an important factor that impairs the delivery of chemotherapy to tumors and may influence the regulation and distribution of cytokines and growth factors. Targeted molecular treatments that inhibit angiogenesis or alter interstitial Fluid dynamics also produce early reductions in interstitial Fluid Pressure. Reductions in interstitial Fluid Pressure due to anti-angiogenic treatment have been associated with improved therapeutic outcome in preclinical studies when these agents are combined with radiotherapy or conventional cytotoxic chemotherapy. Pretreatment interstitial Fluid Pressure and the change in Pressure during treatment may provide important predictive information that in the future will be used...

  • interstitial Fluid Pressure vascularity and metastasis in ectopic orthotopic and spontaneous tumours
    BMC Cancer, 2008
    Co-Authors: Sarah Jane Lunt, Richard P. Hill, Michael Milosevic, Tuula Kalliomaki, Allison L Brown, Victor X D Yang
    Abstract:

    Background High tumour interstitial Fluid Pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread.

  • Interstitial Fluid Pressure in tumors: Therapeutic barrier and biomarker of angiogenesis
    Future Oncology, 2008
    Co-Authors: Milos Milosevic, Sarah Jane Lunt, Anthony Fyles, Richard P. Hill
    Abstract:

    Interstitial Fluid Pressure is elevated in virtually all solid malignant tumors as a result of abnormalities of the vasculature and interstitium. High interstitial Fluid Pressure is an independent predictor of disease recurrence in cervical cancer patients treated with radiotherapy, has been implicated as an important factor that impairs the delivery of chemotherapy to tumors and may influence the regulation and distribution of cytokines and growth factors. Targeted molecular treatments that inhibit angiogenesis or alter interstitial Fluid dynamics also produce early reductions in interstitial Fluid Pressure. Reductions in interstitial Fluid Pressure due to anti-angiogenic treatment have been associated with improved therapeutic outcome in preclinical studies when these agents are combined with radiotherapy or conventional cytotoxic chemotherapy. Pretreatment interstitial Fluid Pressure and the change in Pressure during treatment may provide important predictive information that in the future will be used to optimize therapy in individual patients.

  • the human tumor microenvironment invasive needle measurement of oxygen and interstitial Fluid Pressure
    Seminars in Radiation Oncology, 2004
    Co-Authors: Richard P. Hill, Michael Milosevic, A Fyles, David W Hedley
    Abstract:

    Abstract Invasive needle-based assessments of the extracellular environment in human tumors have yielded important prognostic information that has shaped the direction of future translational research and begun to influence clinical practice. This review focuses on electrode measurements of oxygenation in human tumors, particularly in relation to the practicalities of applying these techniques in the clinic and the relationship to patient outcome. Elevated tumor interstitial Fluid Pressure (IFP) has been shown to be an important independent prognostic factor in cervix cancer. The pathophysiology of elevated IFP is discussed, along with possible explanations for the strong influence on patient outcome and directions for future research.

Rakesh K Jain - One of the best experts on this subject based on the ideXlab platform.

  • coevolution of solid stress and interstitial Fluid Pressure in tumors during progression implications for vascular collapse
    Cancer Research, 2013
    Co-Authors: Triantafyllos Stylianopoulos, John D Martin, Matija Snuderl, Fotios Mpekris, Saloni R Jain, Rakesh K Jain
    Abstract:

    The stress harbored by the solid phase of tumors is known as solid stress. Solid stress can be either applied externally by the surrounding normal tissue or induced by the tumor itself due to its growth. Fluid Pressure is the isotropic stress exerted by the Fluid phase. We recently showed that growth-induced solid stress is on the order of 1.3 to 13.0 kPa (10-100 mmHg)--high enough to cause compression of fragile blood vessels, resulting in poor perfusion and hypoxia. However, the evolution of growth-induced stress with tumor progression and its effect on cancer cell proliferation in vivo is not understood. To this end, we developed a mathematical model for tumor growth that takes into account all three types of stresses: growth-induced stress, externally applied stress, and Fluid Pressure. First, we conducted in vivo experiments and found that growth-induced stress is related to tumor volume through a biexponential relationship. Then, we incorporated this information into our mathematical model and showed that due to the evolution of growth-induced stress, total solid stress levels are higher in the tumor interior and lower in the periphery. Elevated compressive solid stress in the interior of the tumor is sufficient to cause the collapse of blood vessels and results in a lower growth rate of cancer cells compared with the periphery, independently from that caused by the lack of nutrients due to vessel collapse. Furthermore, solid stress in the periphery of the tumor causes blood vessels in the surrounding normal tissue to deform to elliptical shapes. We present histologic sections of human cancers that show such vessel deformations. Finally, we found that Fluid Pressure increases with tumor growth due to increased vascular permeability and lymphatic impairment, and is governed by the microvascular Pressure. Crucially, Fluid Pressure does not cause vessel compression of tumor vessels.

  • interstitial Fluid Pressure in intracranial tumours in patients and in rodents
    British Journal of Cancer, 1997
    Co-Authors: Yves Boucher, Hassan A Salehi, Brian Witwer, G R Harsh, Rakesh K Jain
    Abstract:

    Fluid transport parameters in intracranial tumours influence the delivery of therapeutic agents and the resolution of peritumoral oedema. The tumour and cortex interstitial Fluid Pressure (IFP) and the cerebrospinal Fluid Pressure (CSFP) were measured during the growth of brain and pial surface tumours [R3230AC mammary adenocarcinoma (R3230AC) and F98 glioma (F98)] in rats. Intratumoral and intracranial Pressures were also measured in rodents and patients treated with dexamethasone, mannitol and furosemide (DMF), and hypocapnia. The results show that (1) for the R3230AC on the pial surface, IFP increased with tumour volume and CSFP increased exponentially for tumours occupying a brain volume of 5% or greater; (2) in F98 with volumes of approximately 10 mm3, IFP decreased from the tumour to the cortex, whereas for tumour volumes > 16 mm3 IFP equilibrates between F98 and the cortex; (3) DMF treatment reduced the IFP of intraparenchymal tumours significantly and induced a Pressure gradient from the tumour to the cortex; and (4) in 11 patients with intracranial tumours, the mean IFP was 2.0 +/- 2.5 mmHg. In conclusion, the IFP gradient between intraparenchymal tumours and the cortex decreases with tumour growth, and treatment with DMF can increase the Pressure difference between the tumour and surrounding brain. The results also suggest that antioedema therapy in patients with brain tumours is responsible in part for the low tumour IFP.

  • reduction of interstitial Fluid Pressure after tnf alpha treatment of three human melanoma xenografts
    British Journal of Cancer, 1996
    Co-Authors: C A Kristensen, Mutsumi Nozue, Yves Boucher, Rakesh K Jain
    Abstract:

    Tumour necrosis factor-alpha (TNF-alpha) reduced the interstitial Fluid Pressure (IFP) to 54-64% (P < 0.05) and the mean arterial blood Pressure (MABP) to 70% (P < 0.01) of control values after 5 h in three human melanoma tumour lines transplanted to nude mice.

  • changes in tumour blood flow oxygenation and interstitial Fluid Pressure induced by pentoxifylline
    British Journal of Cancer, 1994
    Co-Authors: Yves Boucher, Thomas J Demhartner, Rakesh K Jain
    Abstract:

    Pentoxifylline (PTX) has been shown to increase radiation damage to tumours and to decrease late radiation-induced injury to normal tissues. This tumour radiation sensitisation results from increased oxygen supply via improved tumour perfusion. We propose that the improved perfusion results from decreased viscous resistance and/or geometric resistance. The decreased flow resistance may be accompanied by a reduction in microvascular Pressure (MVP). Since MVP is approximately equal to the interstitial Fluid Pressure (IFP), PTX should lead to a decrease in IFP. To test this hypothesis, we measured PO2, laser Doppler flow (RBC flux) and IFP in FSaII murine tumours at two doses (PTX at 25 and 100 mg per kg body weight) which sensitise this tumour to X-irradiation. We found that 25 mg kg-1 PTX was ineffective, but 100 mg kg-1 PTX was effective in increasing the PO2 of this tumour. PTX at 100 mg kg-1 (i.p.) increased median PO2 from 5 to 7 mmHg (P < 0.05) within 2 h, and decreased the fraction of PO2 values < 5 mmHg from 65% to 45% (P < 0.05). In support of our hypothesis, we found that with this dose of PTX, RBC flux in the tumour centre increased significantly (n = 6, P < 0.05) prior to an approximately 40% decrease (n = 13, P < 0.05) in tumour interstitial Fluid Pressure (TIFP), without changes in mean arterial blood Pressure (MABP). In conclusion, a single i.p. administration of PTX at 100 mg kg-1 can increase oxygen availability in the tumour due to ameliorate hypoxia in tumour microregions. Second, PTX can lower the elevated TIFP without lowering the MABP.

  • photodynamic therapy induced alterations in interstitial Fluid Pressure volume and water content of an amelanotic melanoma in the hamster
    British Journal of Cancer, 1994
    Co-Authors: M Leunig, Gerd Zetterer, Fernando Gamarra, K Messmer, Alwin E Goetz, Rakesh K Jain
    Abstract:

    The effect of photodynamic therapy (PDT) on interstitial Fluid Pressure (IFP), tumour volume and water content was measured in melanomas grown in hamsters. Unlike control tumours, treated tumours exhibited a 40-60% increase in volume at 1, 3 and 6 h post PDT. IFP also increased at 1 and 3 h after PDT, but decreased to 50% of control value after 24 h, presumably as a result of PDT-induced microcirculatory impairment.

Kristofer Rubin - One of the best experts on this subject based on the ideXlab platform.

Rolf K Reed - One of the best experts on this subject based on the ideXlab platform.

  • effects of the taxanes paclitaxel and docetaxel on edema formation and interstitial Fluid Pressure
    American Journal of Physiology-heart and Circulatory Physiology, 2004
    Co-Authors: Aurora Bronstad, Ansgar Berg, Rolf K Reed
    Abstract:

    Interstitial Fluid Pressure (Pif) is important for maintaining constant interstitial Fluid volume. In several acute inflammatory reactions, a dramatic lowering of Pif has been observed, increasing ...

  • Fluid Pressure in human dermal fibroblast aggregates measured with micropipettes
    American Journal of Physiology-cell Physiology, 2003
    Co-Authors: L E B Stuhr, A Reith, S Lepsoe, Reidar Myklebust, Helge Wiig, Rolf K Reed
    Abstract:

    Previous studies indicated that connective tissue cells in dermis are involved in control of interstitial Fluid Pressure (Pif). We wanted to develop and characterize an in vitro model representativ...

  • lowering of tumor interstitial Fluid Pressure specifically augments efficacy of chemotherapy
    The FASEB Journal, 2003
    Co-Authors: Alexei V Salnikov, Rolf K Reed, Christian Sundberg, Vegard Vereide Iversen, Markus Koisti, Lars Johansson, Linda Stuhr, Mats Sjoquist, Hakan Ahlstrom, Kristofer Rubin
    Abstract:

    Chemotherapy of solid tumors is presently largely ineffective at dosage levels that are compatible with survival of the patient. Here, it is argued that a condition of raised interstitial Fluid Pressure (IFP) that can be observed in many tumors is a major factor in preventing optimal access of systemically administered chemotherapeutic agents. Using prostaglandin E1-methyl ester (PGE1), which is known transiently to reduce IFP, it was shown that 5-fluorouracil (5-FU) caused significant growth inhibition on two experimental tumors in rats but only after administration of PGE1. Furthermore, timing experiments showed that only in the period in which IFP is reduced did 5-FU have an antitumor effect. These experiments uniquely demonstrate a clear and, according to the starting hypothesis, logical, synergistic effect of PGE1 and 5-FU that offers hope for better treatment of many tumors in which raised IFP is likely to be inhibiting optimal results with water-soluble cancer chemotherapeutic agents.

  • new and active role of the interstitium in control of interstitial Fluid Pressure potential therapeutic consequences
    Acta Anaesthesiologica Scandinavica, 2003
    Co-Authors: Helge Wiig, Kristofer Rubin, Rolf K Reed
    Abstract:

    Abstract Here we present recent data indicating that the present view of the interstitium as a passive Fluid reservoir has to be revised. The connective tissue cells and extracellular matrix have a role in the control of P(if) and a fundamental role in the rapid development of edema in burns and in the initial swelling in inflammation by generating a lowering of interstitial Fluid Pressure. In this process, the beta1-integrin system seems to provide a common pathway by which the cells can lower as well as raise P(if). Inflammatory swelling can be reversed by endo- and exogenous substances, thereby suggesting that the connective tissue can serve as a novel target for pharmacological intervention. Furthermore, the new knowledge in interstitial physiology on means to reduce interstitial Fluid Pressure may be of importance for drug delivery into solid tumors, where a high P(if) limits the uptake of therapeutic agents.

  • cytochalasin d induces edema formation and lowering of interstitial Fluid Pressure in rat dermis
    American Journal of Physiology-heart and Circulatory Physiology, 2001
    Co-Authors: Ansgar Berg, Kristofer Rubin, Rolf K Reed
    Abstract:

    The increased capillary Fluid filtration required to create a rapid edema formation in acute inflammation can be generated by lowering the interstitial Fluid Pressure (PIF). The lowering of PIF app...

Michael Milosevic - One of the best experts on this subject based on the ideXlab platform.

  • interstitial Fluid Pressure in tumors therapeutic barrier and biomarker of angiogenesis
    Future Oncology, 2008
    Co-Authors: Sarah Jane Lunt, Anthony Fyles, Richard P. Hill, Michael Milosevic
    Abstract:

    Interstitial Fluid Pressure is elevated in virtually all solid malignant tumors as a result of abnormalities of the vasculature and interstitium. High interstitial Fluid Pressure is an independent predictor of disease recurrence in cervical cancer patients treated with radiotherapy, has been implicated as an important factor that impairs the delivery of chemotherapy to tumors and may influence the regulation and distribution of cytokines and growth factors. Targeted molecular treatments that inhibit angiogenesis or alter interstitial Fluid dynamics also produce early reductions in interstitial Fluid Pressure. Reductions in interstitial Fluid Pressure due to anti-angiogenic treatment have been associated with improved therapeutic outcome in preclinical studies when these agents are combined with radiotherapy or conventional cytotoxic chemotherapy. Pretreatment interstitial Fluid Pressure and the change in Pressure during treatment may provide important predictive information that in the future will be used...

  • interstitial Fluid Pressure vascularity and metastasis in ectopic orthotopic and spontaneous tumours
    BMC Cancer, 2008
    Co-Authors: Sarah Jane Lunt, Richard P. Hill, Michael Milosevic, Tuula Kalliomaki, Allison L Brown, Victor X D Yang
    Abstract:

    Background High tumour interstitial Fluid Pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread.

  • the human tumor microenvironment invasive needle measurement of oxygen and interstitial Fluid Pressure
    Seminars in Radiation Oncology, 2004
    Co-Authors: Richard P. Hill, Michael Milosevic, A Fyles, David W Hedley
    Abstract:

    Abstract Invasive needle-based assessments of the extracellular environment in human tumors have yielded important prognostic information that has shaped the direction of future translational research and begun to influence clinical practice. This review focuses on electrode measurements of oxygenation in human tumors, particularly in relation to the practicalities of applying these techniques in the clinic and the relationship to patient outcome. Elevated tumor interstitial Fluid Pressure (IFP) has been shown to be an important independent prognostic factor in cervix cancer. The pathophysiology of elevated IFP is discussed, along with possible explanations for the strong influence on patient outcome and directions for future research.