Photodynamic therapy-induced alterations in interstitial fluid pressure, volume and water content of an amelanotic melanoma in the hamster

Leunig, Michael; Goetz, AE; Gamarra, Fernando; Zetterer, Gerd; Meßmer, K.; Jain, Rakesh K.

doi:10.1038/bjc.1994.15

Cited by 48 publications

(20 citation statements)

References 13 publications

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“…This study also demonstrates that IFP is elevated in skin melanoma, corroborating previous studies showing elevated IFP in human melanoma (Boucher et al, 1991), human melanoma xenografts in mice (Kristensen et al, 1996;Tufto et al, 1996), and hamster melanomas (Leunig et al, 1992(Leunig et al, , 1994.…”

Section: Discussionsupporting

confidence: 91%

“…Our recent findings revealed decreased neovascularization following intrinsic (NG2 knockout mice) or extrinsic (hydron polymer pellets containing NG2 neutralizing antibody) targeting of NG2 proteoglycan . Lowering tumor IFP by targeting NG2 proteoglycan on pericytes may be a useful approach in improving anticancer drug (conventional chemotherapy) efficacy.This study also demonstrates that IFP is elevated in skin melanoma, corroborating previous studies showing elevated IFP in human melanoma (Boucher et al, 1991), human melanoma xenografts in mice (Kristensen et al, 1996;Tufto et al, 1996), and hamster melanomas (Leunig et al, 1992(Leunig et al, , 1994. …”

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confidence: 91%

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Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

Özerdem¹

2006

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 5e. TASK NUMBER 5f. WORK UNIT NUMBER REPORT DATE 01-04-2006 REPORT TYPE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERLa Jolla Institute for Molecular Medicine San Diego, CA 92121 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white. ABSTRACTThe walls of neovascular capillaries in prostate cancer are composed of endothelial cells and pericytes. Pericytes of postnatal pathological neovascularization have dual origin: They derive from bone marrow progenitors (vasculogenesis),or by sprouting from pre-existing vessels (angiogenesis). NG2+ nascent pericytes promote neovascularization and increase interstitial fluid pressure in tumors. The aims of this investigation are to determine whether therapeutic interference with pericyte-NG2 proteoglycan decreases prostate cancer neovascularization, and controls tumor growth. The anti-angiogenic effect of hydron pellets containing NG2 neutralizing antibody was quantified in intracorneal PC-3 and LNCaP xenografts. TRAMP and TRAMP-C1 tumors grafted in NG2 knockout mice represented intrinsic pericyte targeting. TRAMP and TRAMP-C1 grafts were analyzed with confocal microscope for microvascular density (MVD) and lymphatic vascular density (LVD). NG2 neutralizing antibody decreased corneal neovascularization in PC3 (p<0.0001), and LNCaP (p=0.0079) xenografts. Mean MVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 71% (p=0.0006) and 63% (p=0.0011) lower than wild type controls, respectively. Mean LVD in TRAMP and TRAMP-C1 tumors in NG2 knockout mice were 73% (p=0.0003) and 84% (p<0.0001) lower than wild type controls, respectively. Targeting of pericyte-NG2 decreases neovascularization , lymphangiogenesis and tumor progression in prostate cancer significantly. SUBJECT TERMSangiogenesis, lymphatics, ...

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Section: Discussionsupporting

confidence: 91%

supporting

confidence: 91%

Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

Özerdem¹

2006

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“…The wickin-needle technique is invasive and can be used to measure IFP only in superficial tumours. A non-invasive method for measurement of IFP would therefore be useful for predicting the uptake of macromolecules in tumours and hence therapeutic response.Studies of experimental tumours have suggested that the IFP is related to tumour water content in some tumour lines (Lee et al, 1992;Leunig et al, 1994). The proton spin-lattice and spin-spin relaxation times (T1 and T2) of tumour tissue are, to a large extent, (Braunschweiger et al, 1986;Belfi et al, 1991).…”

mentioning

confidence: 99%

“…Studies of experimental tumours have suggested that the IFP is related to tumour water content in some tumour lines (Lee et al, 1992;Leunig et al, 1994). The proton spin-lattice and spin-spin relaxation times (T1 and T2) of tumour tissue are, to a large extent, (Braunschweiger et al, 1986;Belfi et al, 1991).…”

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confidence: 99%

Proton relaxation times and interstitial fluid pressure in human melanoma xenografts

Lyng

Tufto²,

Skretting³

et al. 1997

Br J Cancer

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Summary The interstitial fluid pressure (IFP) and the proton spin-lattice and spin-spin relaxation times (T, and T2) of some experimental tumours have been shown to be related to tumour water content. These observations have led to the hypothesis that magnetic resonance imaging (MRI) might be a clinically useful non-invasive method for assessment of tumour IFP. The purpose of the work reported here was to examine the general validity of this hypothesis. R-1 8 human melanoma xenografts grown intradermally in Balb/c nu/nu mice were used as the tumour model system. Median T, and T2 were determined by spin-echo MRI using a 1 .5-T clinical whole-body tomograph. IFP was measured using the wick-in-needle technique. No correlation was found between tumour IFP and fractional tumour water content. Moreover, there was no correlation between median T, or T2 and IFP, suggesting that proton T, and T2 values determined by MRI cannot be used clinically to assess tumour IFP and thereby to predict the uptake of macromolecular therapeutic agents.Keywords: melanoma xenografts; interstitial fluid pressure; magnetic resonance imaging; relaxation times; tumour water content Most tumours show an elevated interstitial fluid pressure (IFP) compared with normal tissues (Jain, 1987). Highly elevated IFP might lead to a pressure difference between the microvascular and interstitial space that is close to 0 mmHg and hence to inadequate uptake and heterogeneous distribution of monoclonal antibodies and other macromolecular therapeutic agents (Jain and Baxter, 1988;Cobb, 1989). Many human tumours show a maximum antibody uptake per gram of tissue of only around 0.005% of the injected dose per gram of body weight (Bradwell et al, 1985). Antibodies are preferentially distributed in regions close to blood vessels, and there are many regions without or with negligible antibody uptake (Jones et al 1986;Sands et al, 1988).Measurements of IFP in human tumours using the wickin-needle technique have shown that the IFP can differ substantially among individual tumours of the same histological type (Boucher et al, 1991;Less et al, 1992). Patients with tumours showing an IFP close to normal tissue values, i.e. tumours with a significant pressure difference between the microvascular and interstitial space are more likely to benefit from treatment modalities involving macromolecular therapeutic agents than patients with highly elevated tumour IFP (Jain and Baxter, 1988). The wickin-needle technique is invasive and can be used to measure IFP only in superficial tumours. A non-invasive method for measurement of IFP would therefore be useful for predicting the uptake of macromolecules in tumours and hence therapeutic response.Studies of experimental tumours have suggested that the IFP is related to tumour water content in some tumour lines (Lee et al, 1992;Leunig et al, 1994). The proton spin-lattice and spin-spin relaxation times (T1 and T2) of tumour tissue are, to a large extent, (Braunschweiger et al, 1986;Belfi et al, 1991). These observations have le...

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“…7-11], evaluation of photodynamic therapy [e.g. [12][13][14][15], microcirculation and shock research [16][17][18][19][20][21], studies on mediators of brain edema and damage [e.g. [22][23][24], xenotransplantation and monitoring of transplant patients [e.g.…”

Section: Which Size Should Research Institutes Have?mentioning

confidence: 99%

Surgical Research and Clinical Routine in the New Century

Kempski

2002

Eur Surg Res

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Photodynamic therapy-induced alterations in interstitial fluid pressure, volume and water content of an amelanotic melanoma in the hamster

Cited by 48 publications

References 13 publications

Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

Targeting Microvascular Pericytes in Angiogenic Vessels of Prostate Cancer

Proton relaxation times and interstitial fluid pressure in human melanoma xenografts

Surgical Research and Clinical Routine in the New Century

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