The microcirculation of choroidal and ciliary body melanomas

Folberg, Robert; Mehaffey, Mary G.; Gardner, Lynn M.G.; Meyer, M.; Rummelt, Volker; Pe’er, Jacob

doi:10.1038/eye.1997.57

Cited by 74 publications

(63 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Second, PAS-positive networks were traced in serial sections to connect with the vortex vein, which drains the choroid. 6 Third, the patterns splay open and contain red blood cells ( Figure 1E). Fourth, comparisons of adjacent tissue sections stained alternately with PAS and with Ulex europaeus agglutinin I showed histological correspondence between PAS-positive patterns with Ulex staining.…”

Section: Histology Of the Melanoma Microcirculation Its Prognostic Smentioning

confidence: 99%

“…7 Finally, three-dimensional reconstructions by laser scanning confocal microscopy of thick melanoma tissue sections stained with Ulex revealed anastomosing tubular and sinusoidal structures, consistent with vascular channels. 6,35 The ability to directly visualize the circulation of blood in a tumor in the absence of lymphatics makes the angiographic study of intraocular melanoma an ideal venue for investigating the functional perfusion of the patterned matrix-associated vascular channels in patients. Two patients from a series of 18 patients whose uveal melanomas were imaged clinically with this technique had their eyes removed after confocal angiography.…”

Section: Histology Of the Melanoma Microcirculation Its Prognostic Smentioning

confidence: 99%

“…In contrast, the interior of the eye lacks lymphatics, and uveal melanoma, which develops in one of the most capillary-rich tissues of the body, is a paradigm for pure hematogeneous dissemination of cancer. 6 Therefore, the development of a tumor microcirculation in uveal melanoma is a rate-limiting step for hematological metastasis and serves as an important model for study of the cellular and molecular infrastruc-ture of the melanoma microvasculature, isolated from the influence of a concomitant lymphatic circulation.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Maniotis

Folberg

Hess

et al. 1999

The American Journal of Pathology

Self Cite

1,754

1,636

View full text Add to dashboard Cite

Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy , by transmission electron microscopy , or by using an immunohistochemical panel of endothelial cell markers (Factor VIIIrelated antigen , Ulex , CD31 , CD34 , and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in threedimensional cultures containing Matrigel or dilute Type I collagen , without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye , highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions , even after the addition of conditioned medium from metastatic pattern- It is generally assumed that tumors require a blood supply for growth and metastasis. 1 The development of the tumor microcirculation compartment includes both the production of new blood vessels (angiogenesis) and their remodeling. 2 In fact, the number of vessels 3 and the patterning of the microcirculation 4 by remodeling events are used as histological markers of tumor progression. Although attention has been focused on factors that stimulate and suppress tumor angiogenesis, the molecular mechanisms underlying tumor remodeling remain enigmatic. It is therefore critical to investigate remodeling of the intratumoral microvasculature in various tumor models.Melanoma is among the better characterized tumor models with respect to prognostic staging of disease progression. The rising incidence of cutaneous melanoma makes this tumor an important public health problem. Melanoma of the interior of the eye, uveal melanoma, although much less common than cutaneous melanoma, poses a threat to vision and significant morbidity; nearly 50% of patients with uveal melanoma die from metastatic melanoma. 5 Cutaneous melanoma may disseminate through lymphatics or blood vessels. In contrast, the interior of the eye lacks lymphatics, and uveal melanoma, which develops in one of the most capillary-rich tissues of the body, is a paradigm for pure hematogeneous dissemination of cancer. 6 Therefore, the development of a tumor microcirculation in uveal melanoma is a rate-limiting step for hematological metastasis and serves as an important model for study of the cellular and molecular infrastruc-

show abstract

Section: Histology Of the Melanoma Microcirculation Its Prognostic Smentioning

confidence: 99%

Section: Histology Of the Melanoma Microcirculation Its Prognostic Smentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Maniotis

Folberg

Hess

et al. 1999

The American Journal of Pathology

Self Cite

1,754

1,636

View full text Add to dashboard Cite

show abstract

“…20,21 The histologic detection of loops, networks and crosslinking parallel matrix was strongly associated with death from metastatic melanoma. 22 Our findings indicate that antiangiogenic therapy represents a promising approach to uveal melanoma treatment and prevention of metastases.…”

Section: Discussionmentioning

confidence: 71%

“…Angiogenesis seems to be an important prognostic factor in uveal melanomas. [20][21][22][23][24][25][26] The above-mentioned studies provide important information on the relative potency of a number of antiangiogenic gene products previously shown to possess antitumor activity. 10,11,13,14,[27][28][29][30][31] However, there is a dearth of information on the antitumor activity of Can.…”

Section: Discussionmentioning

confidence: 99%

A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer

et al. 2006

View full text Add to dashboard Cite

Different antiangiogenic and antimetastatic recombinant adenoviruses were tested in a transgenic mouse model of metastatic ocular cancer (TRP1/SV40 Tag transgenic mice), which is a highly aggressive tumor, developed from the pigmented epithelium of the retina. These vectors, encoding amino-terminal fragments of urokinase plasminogen activator (ATF), angiostatin Kringles (K1-3), endostatin (ES) and canstatin (Can) coupled to human serum albumin (HSA) were injected to assess their metastatic and antiangiogenic activities in our model. Compared to AdCO1 control group, AdATF-HSA did not significantly reduce metastatic growth. In contrast, mice treated with AdK1-3-HSA, AdES-HSA and AdCan-HSA displayed significantly smaller metastases (1.1971.19, 0.8771.5, 0.4370.56 vs controls 4.0475.12 mm 3 ). Moreover, a stronger inhibition of metastatic growth was obtained with AdCan-HSA than with AdK1-3-HSA (P ¼ 0.04). Median survival was improved by 4 weeks. A close correlation was observed between the effects of these viruses on metastatic growth and their capacity to inhibit tumor angiogenesis. Our study indicates that systemic antiangiogenic factors production by recombinant adenoviruses, particularly Can, might represent an effective way of delaying metastatic growth via inhibition of angiogenesis.

show abstract

Imaging the Microvasculature of Choroidal Melanomas With Confocal Indocyanine Green Scanning Laser Ophthalmoscopy

Mueller¹

1998

Arch Ophthalmol

View full text Add to dashboard Cite

The microcirculation of choroidal and ciliary body melanomas

Cited by 74 publications

References 85 publications

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic Mimicry

A gene transfer comparative study of HSA-conjugated antiangiogenic factors in a transgenic mouse model of metastatic ocular cancer

Imaging the Microvasculature of Choroidal Melanomas With Confocal Indocyanine Green Scanning Laser Ophthalmoscopy

Contact Info

Product

Resources

About