Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic investigation into the nature of melanin monomer and polymer synthesis in pigment cells has revealed many of the new underlying factors involved in its regulation and control by three melanogenesis-related genes, tyrosinase, TRP-1 and TRP-2, and other non-tyrosinase glycoproteins. Pigment cells can undergo clinically and biologically recognizable progressive multi-step carcinogenesis. Generally parallel to this progressive cancerization is accentuated melanogenesis. Using this accentuated melanogenesis to develop a specific diagnosis and cure for melanoma (Mm) has long been a challenge. However, until recently, no success was achieved. As an example, attempting to utilize the fact that dopa accumulates as a melanin substrate within Mm cells, hybrid compounds of dopa and cytotoxic drugs were developed. However, these compounds were found to have severe systemic side effects and were therefore unusable. Another newer Mm treatment involves high energy radiation such as fast neutrons. But this is quite non-selective, killing both the target cancer and the normal surrounding tissue. Since 1972, I have developed the idea of coupling the high energy releasing system of thermal neutron irradiation with the non-toxic 10B-dopa analogue, 10B1-L-p-boronophenylalanine (10B1-L-BPA). Thermal neutrons are essentially harmless, but, after specific absorption by 10B, release high LET alpha-particles and 7Li-atoms with an energy of 2.33 MeV up to a distance of 14 mu, the diameter of Mm cells, thus selectively killing them without damaging surrounding normal tissue. After the synthesis of 10B1-L-BPA, exhaustive in vitro and in vivo radiological studies on its enhanced killing effect were done to develop optimal Mm Boron Neutron Capture Therapy (NCT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Melanogenesis investigation leading to selective melanoma neutron capture therapy and diagnosis. 785 54

To investigate the mechanism of uptake of para-boronophenylalanine (p-BPA), a capture agent for boron neutron capture therapy (BNCT) of melanoma and brain tumour, into melanoma cells, we studied the relationship between melanin synthesis and the concentration of boron using tyrosinase-deficient mouse amelanotic melanoma cells (A1059) and melanotic melanoma cells (TA1059). A1059 was established from mouse B16F10 cells, and TA1059 was constructed by transfecting human tyrosinase cDNA into A1059. The melanin content of TA1059 was 1.5-fold higher than that of B16F10, and was undetectable in A1059. The order of p-BPA uptake was TA1059 > B16F10 > A1059 at the time points examined, and the boron content of TA1059 was approximately 1.5-fold higher than that of B16F10. Our experimental findings indicated that melanin synthesis is a very important factor for characterizing the increase in accumulation of p-BPA in melanoma cells. A significant difference in boron uptake into TA1059 was observed between p-BPA and meta-BPA (m-BPA), but there were no apparent differences in the case of A1059. The difference in accumulation of p-BPA and m-BPA could be due to differences in the properties of p-BPA as a tyrosine analogue needed for melanin synthesis.
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PMID:Selective uptake of para-boronophenylalanine increases in amelanotic melanoma cells transfected by the tyrosinase gene. 1089 Mar 85

Utilizing increased melanin pigmentation and accentuated melanogenesis seen in malignant melanoma, we newly developed melanoma-selective boron neutron capture therapy (BNCT) after designing and synthesizing the 10B-DOPA analogue, 10B-p-boronophenylalanine (10B-BPA). After multi-disciplined and extensive basic and pre-clinical investigations, we successfully treated 18 cases of human melanoma. Recently, we found that accentuated synthesis of melanin monomers, richest within coated vesicles (CV) in melanoma cells, plays a critical role in attracting 10B-BPA through chemical complex formation of monomers and 10B-BPA. CV are indeed BPA-localizing organelles. This led us to the new clinical endeavor that BPA may possess the potential ability to suppress melanin polymer formation through 'melanin monomer trapping' out of the melanogenic pathway which is highly regulated by the function of CV in pigment cells. It was soon found that melanin polymer formation can be suppressed by BPA at the chemical and cellular levels, then at the clinical level. Our discovery, that single molecule 10B-BPA possesses the dual nature of eradication of melanoma with BNCT and suppression of melanin hyperpigmentation, resulted from pursuing bilateral feedback at each stage from pure science to clinical application and vice versa. A further example of bilateral feedback is the development of gene-transfer applied BNCT (gBNCT). This also has its roots in clinical hurdles faced in treating amelanotic melanomas by 10B-BPA BNCT. The transfer of tyrosinase and melanin monomer synthesis-related genes into target cancer cells has produced more effective BNCT and may lead to gBNCT for non-melanoma cancers.
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PMID:Dual control of melanogenesis and melanoma growth: overview molecular to clinical level and the reverse. 1104 53