Sources of the Increased Longitudinal Relaxation Rates Observed in Melanotic Melanoma An In Vitro Study of Synthetic Melanins

Enochs, W S; Hyslop, W. Brian; Bennett, Harold F.; Brown, Russell D.; Koenig, Seymour H.; Swartz, Harold M.

doi:10.1097/00004424-198910000-00014

Cited by 62 publications

(38 citation statements)

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“…The signal intensity of melanin is related to the binding of melanin to paramagnetic metals such as Cu 2+ , Fe 3+ , Zn 2+ , and Mn 2+ ; however, it shows a particularly strong affinity for Fe 3+ which affects the signal intensity of melanin on T1WI [84,85]. Melanin appears in the brain as neuromelanin [86] and in the presence of metastatic melanoma, primary diffuse meningeal melanomatosis, neurocutaneous melanosis, and Aspergillus infection [8].…”

Section: Ironmentioning

confidence: 99%

Contribution of metals to brain MR signal intensity: review articles

et al. 2016

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Section: Ironmentioning

confidence: 99%

Contribution of metals to brain MR signal intensity: review articles

et al. 2016

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“…Undoubtedly calcium binding and exchange represents an important function for the melanins in the inner ear (8,24). This property of the melanins to act as a buffer for binding calcium has not been fully explored in the skin where these ions play a key role in both cell differentiation and pigmentation (16,19).…”

Section: Eumelaninmentioning

confidence: 99%

“…It is known that melanins can form supermolecular aggregates that vary in size as a function of pH and ionic strength (16,17). Changes in aggregation state are often monitored through light scattering.…”

Section: Kowichi Jimbow Dept Of Dermatologymentioning

confidence: 99%

What's the use of generating melanin?

Wood¹,

Jimbow²,

Boissy³

et al. 1999

Experimental Dermatology

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The CONTROVERSIES featured in the August 1998 issue of Exp Dermatol have discussed the controls of melanogenesis (Schallreuter et al., Exp Dermatol 7: 143-150, 1998). Now, we explore the biological functions of the endproduct of melanogenesis, the various melanin biopolymers. As delineated in the subsequent contributions, melanins are func- Viewpoint 1Melanins are found in highly oxidizing situations where significant concentrations of oxygen radicals are generated. Such reactive oxygen species (ROS) are produced by UV-light in the skin and eye, by sound and ultrasound in the inner ear, and in the highly oxidizing conditions of catecholaminergic neurons in the brain. The role of the melanins as oxygen radical trapping polymers, UV-light filters, polymeric buffers for transition metals, calcium and catecholamines will be considered in this viewpoint. For the Dermatologist it is of special interest to understand those factors that control melanogenesis in the skin and hair (3). In this context the pterins, alpha melanocyte stimulating hormone (a-MSH) and calcium appear to be central in the regulation of both melanin content and composition in melanocytes. There is accumulating evidence that the evolution of melanogenesis in human melanocytes is primarily antioxidant in character and is designed to protect these pigment cells from the cytotoxicity of ROS. However, the subtle link between calcium homeostasis and melanogenesis suggests that natural skin colours in the human population may have evolved secondarily as a consequence of salt balance/dehydration fac-153 tionally much more complex and fascinating than their evident colour-awarding and UV-light-filtering properties suggest, and dermatologists and pigment biologists alike have yet to discover and define the full range of biologically relevant melanin functions in health and disease.tors as primates adapted to extreme differences in local climates. It is tempting to speculate that skin colour emerged as a side effect through Darwinian natural selection principles in tropical versus temperate climates.There is increasing evidence that melanogenesis represents a major antioxidant defence mechanism in melanocytes. Melanocytes in the human epidermis (in vivo) or in cell cultures (in vitro) have been shown to be much more sensitive to the cytotoxicity of ROS than keratinocytes (17, 27). This concept is especially well-documented by the cytotoxicity of hydrogen peroxide (H 2 O 2 ) to melanocytes both (in vivo) and (in vitro) (6,14,15,17). Consequently, melanocytes have evolved an effective strategy to deal with the removal of superoxide anion radicals (O 2 ª ) before these radical anions disproportionate to H 2 O 2 .The preferential utilization of O 2 ª compared to dioxygen (O 2 ) is quite a common event in the skin. The enzymes tyrosinase, proline hydroxylase and indoleamine 2,3 dioxygenase selectively utilize O 2 ª as the preferred substrate over O 2 for the formation of dopaquinone, hydroxyproline residues in collagen, and kynurenic acid respectively (2, 20, 21,...

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“…1984), leading to a lower ratio of free-to-bound water in necrotic regions than in the tumour interstitium . Moreover, necrotic regions in tumours can contain extravasated erythrocytes, releasing paramagnetic ferric iron during haemoglobin denaturation (Woodruff et al 1987, Enochs et al 1989) . Finally, the concentration of freely dissolved paramagnetic ions may be increased in necrotic tumour tissue due to the denaturation of enzymes and other proteins with which the ions are complexed in the intact cell (Negendank et al .…”

Section: Increased T and T 2 Have Been Reported Particu-mentioning

confidence: 99%

“…Melanin is paramagnetic due to chelated metallic cations (Okazaki et al 1985, Enochs et al . 1989) and/or stable free radicals (Jimbow et al 1984, Sealy 1984) .…”

Section: Paramagnetic Relaxation Enhancement By Melaninmentioning

confidence: 99%

Magnetic Resonance Imaging of Human Melanoma Xenograftsin Vivo: Proton Spin—lattice and Spin—spin Relaxation Times Versus Fractional Tumour Water Content and Fraction of Necrotic Tumour Tissue

Rofstad

Steinsland

Kaalhus

et al. 1994

International Journal of Radiation Biology

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Proton nuclear magnetic resonance (1H-nmr) imaging is used routinely in clinical oncology to provide macroscopic anatomical information, whereas its potential to provide physiological information about tumours is not well explored. To evaluate the potential usefulness of 1H-nmr imaging in the prediction of tumour treatment resistance caused by unfavourable microenvironmental conditions, possible correlations between proton spin-lattice and spin-spin relaxation times (T1 and T2) and physiological parameters of the tumour microenvironment were investigated. Tumours from six human melanoma xenograft lines were included in the study. 1H-nmr imaging was performed at 1.5 T using spin-echo pulse sequences. T1- and T2-distributions were generated from the images. Fractional tumour water content and the fraction of necrotic tumour tissue were measured immediately after 1H-nmr imaging. Significant correlations across tumour lines were found for T1 and T2 versus fractional tumour water content (p < 0.001) as well as for T1 and T2 versus fraction of necrotic tumour tissue (p < 0.05). Tumours with high fractional water contents had high values of T1 and T2, probably caused by free water in the tumour interstitium. Fractional water content is correlated to interstitial fluid pressure in tumours, high interstitial fluid pressure being indicative of high vascular resistance. Tumours with high fractional water contents are thus expected to show regions with radiobiologically hypoxic cells as well as poor intravascular and interstitial transport of many therapeutic agents. T1 and T2 decreased with increasing fraction of necrotic tumour tissue, perhaps because complexed paramagnetic ions were released during development of necrosis. Viable tumour cells adjacent to necrotic regions are usually chronically hypoxic. Tumours with high fractions of necrotic tissue are thus expected to contain significant proportions of radiobiologically hypoxic cells. Consequently, quantitative 1H-nmr imaging has the potential to be developed as an efficient clinical tool in prediction of tumour treatment resistance caused by hypoxia and/or transport barriers for therapeutic agents. However, much work remains to be done before this potential can be adequately evaluated. One problem is that high fractional tumour water contents result in longer T1 and T2 whereas high fractions of necrotic tumour tissue result in shorter T1 and T2; i.e. the two parameters which are indicative of treatment resistance contribute in opposite directions. Another problem is that the correlations for T1 and T2 versus fraction of necrotic tumour tissue are not particularly strong.

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Sources of the Increased Longitudinal Relaxation Rates Observed in Melanotic Melanoma An In Vitro Study of Synthetic Melanins

Cited by 62 publications

References 0 publications

Contribution of metals to brain MR signal intensity: review articles

Contribution of metals to brain MR signal intensity: review articles

What's the use of generating melanin?

Magnetic Resonance Imaging of Human Melanoma Xenograftsin Vivo: Proton Spin—lattice and Spin—spin Relaxation Times Versus Fractional Tumour Water Content and Fraction of Necrotic Tumour Tissue

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