Different Pathways of Macromolecule Extravasation from Hyperpermeable Tumor Vessels

Feng, Dian; Nagy, Janice A.; Dvorak, Ann M.; Dvorak, Harold F.

doi:10.1006/mvre.1999.2207

Cited by 87 publications

(83 citation statements)

References 20 publications

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“…Extravasation of plasma constituents by means of convective currents across the microvascular wall originates from the incomplete or totally missing endothelial lining of the rapidly formed vessels in tumours growing beyond a mass of 10 6 cells (Feng et al, 2000;Hashizume et al, 2000;Kuszyk et al, 2001). Since Evans blue accumulated more in RIF-1 than in R1 tumours over a large tumour weight range, it could be concluded that the larger amount of marker extravasated in RIF-1 tumours was due to an increased permeability of the tumour vessels.…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the tumoritropic principle of hypericin

Putte¹,

Roskams

Vandenheede

et al. 2005

Br J Cancer

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Hypericin is a potent agent in the photodynamic therapy of cancers. To better understand its tumoritropic behaviour, we evaluated the major determinants of the accumulation and dispersion of hypericin in subcutaneously growing mouse tumours. A rapid exponential decay in tumour accumulation of hypericin as a function of tumour weight was observed for each of the six tumour models investigated, and a similar relationship was found between tumour blood flow and tumour weight. Moreover, there was a close correlation between the higher hypericin uptake in RIF-1 tumours compared to R1 tumours and tumour vessel permeability. To define the role of lipoproteins in the transport of hypericin through the interstitial space, we performed a visual and quantitative analysis of the colocalisation of hypericin and DiOC 18 -labelled lipoproteins in microscopic fluorescent overlay images. A coupled dynamic behaviour was found early after injection (normalised fluorescence intensity differences were on the whole less than 10%), while a shifted pattern in localisation of hypericin and DiOC 18 was seen after 24 h, suggesting that during its migration through the tumour mass, hypericin is released from the lipoprotein complex. In conclusion, we were able to show that the tumour accumulation of hypericin is critically determined by a combination of biological (blood flow, vessel permeability) and physicochemical elements (affinity for interstitial constituents).

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Section: Discussionmentioning

confidence: 99%

Elucidation of the tumoritropic principle of hypericin

Putte¹,

Roskams

Vandenheede

et al. 2005

Br J Cancer

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“…This is particularly true for sites of tumor growth where there is induction of neovasculature and the release of factors, such as VEGF, which cause increases in blood vessel permeability to circulating macromolecules. [31][32][33] Studies demonstrating the therapeutic activity of ASOs in vivo have had to rely on prolonged drug administration, therefore it is anticipated that liposomal formulations of ASO should improve therapy by increasing delivery of the intact sequence to sites of disease and, perhaps, by reducing the frequency of drug administration.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that VEGF can increase vascular permeability in these blood vessels, a process that is associated with increased influx of macromolecules in the plasma compartment into the peritoneal cavity. 32,33 Expression of VEGF in tumors derived from s.c. injection of MDA-MB-435 and MDA4345/LCC6 cells are shown in Figure 2. Sections derived from A431 tumors were used as a positive control for VEGF expression ( Fig.…”

Section: Assessment Of Vegf and Her-2/neu Status In The Mda435/lcc6mentioning

confidence: 99%

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

Waterhouse¹,

Dragowska²,

Gelmon³

et al. 2004

Cancer Biology & Therapy

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The nature of anti-cancer therapeutics is currently undergoing a paradigm change, with biologic agents slowly being introduced into the therapeutic armory, displacing or complimenting the traditionally used cytotoxic agents. These new agents include monoclonal antibodies, recombinant DNA, antisense oligonucleotides (ASO) and others. To assess the new therapeutics, new predictive models are required. Utilizing the MDA435/LCC6 human breast cancer xenograft model, the pharmacokinetic behavior of antisense oligonucleotides targeted against vascular endothelial growth factor and HER-2/neu was assessed. For pharmacodynamic analysis, ASO in buffer or encapsulated in a liposomal formulation were injected intravenously or intraperitoneally into MDA435/LCC6 ascites tumor-bearing mice. Plasma antisense elimination, tissue distribution, total peritoneal antisense and peritoneal cell associated antisense levels were determined. Liposomal encapsulation led to significant decreases in the plasma elimination rate, as evidenced by an approximate 10-fold increase in mean AUC over 24 hours, as well as enhanced peritoneal cell delivery in mice bearing ascites tumors. Tissue distribution studies of both free and liposome encapsulated ASO indicated that ASO distribution was dictated primarily by the liposomal carrier when administered in liposomal form.

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“…[20][21] Mais recentemente, a descoberta de uma estrutura no endotélio venoso, a organela vesiculovacuolar, ofereceu via transendotelial alternativa para o extravasamento de proteínas plasmáticas em resposta a fatores de permeabilidade. [21][22][23] …”

Section: 1-permeabilidade Vascularunclassified

Aspectos celulares da cicatrização

Mendonça

Coutinho‐Netto

2009

An. Bras. Dermatol.

133

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Resumo: O processo cicatricial compreende uma sequência de eventos moleculares e celulares que interagem para que ocorra a restauração do tecido lesado. Desde o extravasamento de plasma, com a coagulação e agregação plaquetária até a reepitelização e remodelagem do tecido lesado o organismo age tentando restaurar a funcionalidade tecidual. Assim, este trabalho abrange os diversos aspectos celulares envolvidos no processo cicatricial, bem como os principais medicamentos utilizados no tratamento de patologias relacionadas às deficiências na cicatrização. São abordados também, os aspectos econômicos referentes, sobretudo, às feridas crônicas de pés diabéticos. Palavras-chave: Agentes indutores da angiogênese; Cicatrização de feridas; Permeabilidade capilar Abstract: Wound healing is a dynamic interactive process that involves a sequence of molecular and cellular events. Recent advances in cellular and molecular biology have greatly expanded our understanding of the biological process involved in wound repair and tissue regeneration. From plasma extravasation, with coagulation and platelet aggregation, to reepithelialization and remodeling of injured tissue, the organism acts by trying to restore functionality tissue. Thus, the present study encompasses several cellular aspects involved in the wound healing process, as well as the main drugs used in treating the pathology related to wound healing complications. Economic aspects are also addressed, mainly related to chronic wounds of diabetic feet. Keywords: Angiogenesis inducing agents; Capillary permeability; Wound healing REVISÃO INTRODUÇÃOOs custos dos tratamentos de patologias relacionadas à deficiência cicatricial aumentam a importância dos estudos em busca de medicamentos e curativos capazes de interagir com o tecido lesado, tendo por objetivo acelerar o processo. Por exemplo, o retardo de cicatrização, como ocorre no caso de úlceras de pés diabéticos, constitui grave problema mundial, tanto financeiro quanto social. Dados dos Estados Unidos informam que 15,5% da população mundial com idade superior a 30 anos é composta de diabéti-cos, dos quais cerca de 15% desenvolvem úlceras de difícil cicatrização ao longo da vida, principalmente, nos membros inferiores. Assim, 6% das internações hospitalares relacionadas aos diabéticos são consequência dessas úlceras e, em caso de amputação, o tempo médio de internação é de cerca de três semanas. Esses casos geram para os sistemas de saúde custo extra que varia de U$ 8.000 a U$ 12.000/paciente. Dos amputados vão a óbito em cinco anos cerca de 39 a 68%. 1 No Brasil estima-se a existência de dois milhões de casos, entre os aposentados e os que recebem auxílios-doença em função da diabetes. 2 A cicatrização de feridas é processo complexo que envolve a organização de células, sinais químicos e matriz extracelular com o objetivo de reparar o tecido. Por sua vez, o tratamento de feridas busca o fechamento rápido da lesão de forma a se obter cicatriz funcional e esteticamente satisfatória. Para tanto, é indis-

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Different Pathways of Macromolecule Extravasation from Hyperpermeable Tumor Vessels

Cited by 87 publications

References 20 publications

Elucidation of the tumoritropic principle of hypericin

Elucidation of the tumoritropic principle of hypericin

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

Aspectos celulares da cicatrização

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