Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conversion of dopachrome (DC) in the eumelanin pathway has been analyzed to determine the specific product and the role of enzyme control. 5,6-Dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) were quantitated by HPLC with fluorescent detection, after DC incubation with heated and unheated preparations of B-16 melanoma derived dopachrome oxidoreductase (DCOR). The enzyme-catalyzed reaction produced DHICA as the major product, while DHI formed with the spontaneous reaction. It had originally been suggested that the major product of DC conversion was DHI, with DHICA being formed as a minor product of this conversion [Raper, H.S. (1927) Biochem. J. 21, 89-96]. Copper, nickel, and cobalt ions promoted conversion of DC, with nickel simulating DCOR activity. Removal of free ions from unheated DCOR did not alter DC conversion. We conclude that the major product of DC conversion is DHICA and that DCOR is responsible for this conversion.
 ...
PMID:Function of dopachrome oxidoreductase and metal ions in dopachrome conversion in the eumelanin pathway. 314 18

Combined oral contraceptives (COCs) affect the skin 3 different ways. They decrease the amount of androgenic hormones produced in the ovaries and adrenal gland. They also limit the quantity of biologically active circulating testosterone. Finally, estrogen markedly decreases oil production in the sebaceous glands. Physicians should prescribe to women with acne a COC that is low in progestogen and high in estrogen. A biphasic pill with no more than 500 mcg norethisterone/day meets these requirements. If a woman is taking systemic antibiotics to treat acne, however, the physician should prescribe a biphasic pill containing 50 mcg ethinyl estradiol. Even though many believe that using COCs causes hair loss, there is little evidence to support it. Nevertheless, if a woman has indeed experienced hair loss, she should take a COC with a high estrogen to progestogen ratio. As in some pregnant women, cholasma may occur in women taking COCs when not protected from sunlight. Physicians need to prescribe the lowest possible dose of hormones in these women and counsel them to shield their face from sunlight. To err on the side of safety, women who have had a malignant melanoma should not use a hormonal contraceptive. In addition, women who have experienced many bouts of skin candidiasis should use an alternative contraceptive. Other skin disorders that they have been found to be more prevalent in women taking COCs include erythema nodosum, accelerated systemic lupus erythematosus, porphyria cutanea tarda, herpes gestationis, spider naevus, and telangiectasia. There also exists an association between dermatitis and barrier methods and spermicides. Some articles have suggested that copper containing IUDs have also cause a variety of skin disorders.
 ...
PMID:Effect of contraceptives on the skin. 324 Jan 55

Challenge of human A375 melanoma cells with sodium arsenite induced the synthesis of stress proteins and stimulated [3H]mannose incorporation into a novel component migrating on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular mass of 14 kDa (designated M14). Enhanced M14 expression was elicited by heavy metals (zinc, copper, cadmium, and nickel), thiol-reactive agents (iodoacetamide and auranofin), and hyperthermia. The kinetics of M14 induction and recovery from stress were similar to those of the stress proteins, but M14 half-life was only 15 min. Incorporation of [3H]mannose into M14 was inhibited by tunicamycin but not by cycloheximide or actinomycin D. M14 was metabolically labeled with [32P]orthophosphate but not by [35S] methionine or [3H]asparagine. Further studies revealed that M14 was selectively soluble in chloroform/methanol/water (10:10:3) and sensitive to both endo-beta-N-acetylglucosaminidase H digestion and mild acid hydrolysis. The latter released a water-soluble mannose-labeled moiety which eluted from Bio-Gel P-6 in a manner similar to Glc3Man9GlcNAc2. Together, these data suggest that M14 is a lipid-oligosaccharide intermediate of N-linked protein glycosylation and that enhanced expression of this class of molecule in response to chemical insults and hyperthermia is a newly described cellular reaction to stress.
 ...
PMID:Alterations in lipid-linked oligosaccharide metabolism in human melanoma cells concomitant with induction of stress proteins. 366 5

In about 350 patients with malignant melanoma of the choroid 32 serological tumor tests, specific as well as nonspecific, were carried out. Significant differences were found in: leukocyte adherence inhibition test (LAI), electrophoresis mobility test (EMT), carcinoembryonic antigen (CEA), acid alpha-1-glycoprotein (AGP), immunoglobin G, vitamin A, copper, and magnesium. For early diagnosis of malignant melanoma of the choroid the LAI test, together with the examination of immunoreactive lymphocyte subpopulations (helper and suppressor cells) proved to be the most valuable.
 ...
PMID:[Value of serologic tumor tests in malignant melanoma of the choroid]. 371 79

We have previously reported the cytotoxicity and antitumor activity of bis(diphenylphosphino)ethane (DPPE) and a variety of its transition metal complexes. During studies of the chemistry of a gold complex of this group [(AuCl)2(DPPE)], it was observed that this complex readily underwent ring closure on reaction with DPPE to form the tetrahedral complex [Au(DPPE)2]+. Various counterion forms (e.g., Cl-) of this cation were isolated and were found to exhibit a remarkably high stability in solution. Evaluation of [Au(DPPE)2]Cl in mice bearing i.p. P388 leukemia demonstrated that the compound produced an average of 87% increase in life span at its maximally tolerated dose (2-3 mumol/kg/day for 5 days). Activity was also seen in i.p. M5076 reticulum cell sarcoma (60% increase in life span) and s.c. mammary adenocarcinoma 16/c. Modest activity was evident in i.p. B16 melanoma and L1210 leukemia. A subline of P388 leukemia resistant to cisplatin was not cross-resistant to [Au(DPPE)2]Cl. In addition, combination therapy of [Au(DPPE)2]Cl and cisplatin against i.p. P388 demonstrated an advantage over single-agent therapy. In vitro studies of [Au(DPPE)2]Cl showed that the compound: is cytotoxic to tumor cell lines; is only minimally inhibited in its cytotoxic activity by the presence of serum; produces DNA protein cross-links and DNA strand breaks in cells; and inhibits macromolecular synthesis with a preferential inhibitory effect on protein synthesis relative to DNA and RNA synthesis. 31P nuclear magnetic resonance spectroscopy indicated that the compound is stable in the presence of serum proteins, thiols, or disulfides and that it reacts with Cu(II) resulting in the formation of a Cu(I)DPPE complex. The results of these in vivo and in vitro experiments suggest that the contrasting pharmacological profile of [Au(DPPE)2]Cl with respect to other gold(I) phosphine complexes may be related to both the kinetic stability of the complex and its stability in the presence of thiols.
 ...
PMID:In vivo antitumor activity and in vitro cytotoxic properties of bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride. 375 97

Histochemical tests for copper, iron, and zinc revealed their presence in the stratum germinativum of normal skin and skin from which an early melanoma and basal cell and squamous cell carcinomas originated. However, only copper was seen in invasive cells of basal and squamous cell carcinomas originating from skin. The normal oral mucous membrane was free of copper, iron, and zinc, but cells of invasive squamous carcinoma originating from the oral mucous membrane contained copper. The fluorescent brightening agent, applied as a counterstain, aided in the location of the specimen.
 ...
PMID:Histochemical determination of copper, zinc, and iron in some benign and malignant tissues. 377 15

The nature of the essential residues at the active site of Harding-Passey mouse melanoma tyrosinase has been explored by kinetic and photochemical modification studies. Km for L-dopa depends strongly on pH, so that acidic pH prevents the formation of the enzyme-substrate complex because the protonation of an enzyme group with a pKa of 6.6. Halide ions inhibit competitively the enzyme activity, being F the more potent one. This inhibition is also pH-dependent, showing the involvement of a protonatable group of the enzyme with apparent pKa ranging from 5.9 to 7.0. Tyrosinase has also been modified with visible light using Rose Bengal as photosensitizer, yielding a pH-dependent photoinactivation, characteristic of histidyl residues. All these results strongly support that histidine plays an important role in the dopa-oxidase activity of the enzyme, very probably acting as the ligand of copper at the active site of the enzyme.
 ...
PMID:The involvement of histidine at the active site of Harding-Passey mouse melanoma tyrosinase. 393 27

Groups of BDF1 and DBA mice were treated with either the cupric chelate of nitrilotriacetic acid (NTA-Cu+2) or the cuprous chelate of neocuproine (NC-Cu+1) every other day for 7 days prior to either i.p. or s.c. inoculation with 10(6) viable B16 melanoma cells, and then every other day for 15 days post-tumor inoculation. This treatment schedule was non-toxic to host mice. NC-Cu+1 acted as a tumor growth promoting factor in mice by enhancing tumorigenicity, stimulating body weight gain, inhibiting encapsulation of i.p. tumors that permitted growth as unrestrained ascites, and increasing final tumor weight over a shortened host survival period regardless of the site of tumor inoculation. Treatment with NTA-Cu+2 inhibited pigmentation in DBA mice bearing s.c. tumors, while treatment with NC-Cu+1 enhanced tumor pigmentation regardless of the site of tumor inoculation and murine strain. These results suggest that exogenous copper in the form of chelates alters the growth characteristics of a copper-requiring tumor system in both a copper-chelate- and murine-specific manner, and further suggests that the growth promoting activity of exogenous copper in the B16 melanoma system involves both enhanced copper nutrition and concomitant alteration of host reactions to tumors.
 ...
PMID:Pharmacological perturbation of murine melanoma growth by copper chelates. 397 9

Exogenous copper was found to enhance tumorigenicity of B16 melanoma in heterogenetic mice that were treated with either the cupric chelate of nitrilotriacetic acid (NTA-Cu+2) or the cuprous chelate of neocuproine (NC-Cu+1). Both copper chelates were nontoxic to host mice given in the treatment schedule used here. Transplanted B16 melanoma cells were rejected after ip inoculation into CDF1 mice unless they were pretreated with copper chelates, which permitted 100% tumor takes. A limited number of tumor takes were observed in untreated NIH Swiss mice, and treatment with copper chelates doubled the number of ip tumor takes. Treatment with NC-Cu+1 enhanced tumor pigmentation and inhibited tumor encapsulation, a characteristic not shared with NTA-Cu+2. Tumors without capsules grew as unrestrained ascites and this was associated with an earlier onset of morbidity and decreased survival. Only mice treated with copper chelates permitted sc tumor takes. Treatment with NC-Cu+1 caused a reversible suppression of body weight, indicating that tumors grew slowly and independently of host body weight accretion until treatment was stopped. Treatment with NC-Cu+1 enhanced tumorigenicity of sc tumors as evidenced by an earlier onset of palpability, enhanced tumor takes in NIH Swiss mice, decreased final tumor weight and tumor burden, and shortened host survival. These results suggest that copper chelates alter the biological growth characteristics of B16 melanoma in both a murine and copper chelate-specific manner, and that the growth-promoting activity of NC-Cu+1 on tumors is related to the oxidation state of copper in chelates and enhanced copper nutriture of tumors. The potentially adverse interaction of elevated plasma copper levels in cancer patients with chemotherapeutic agents is discussed.
 ...
PMID:Enhancement of tumorigenicity of B16 melanoma in heterogenetic mice by administration of copper chelates. 409 91

Previous results had shown that the human leprosy bacilli possess a phenoloxidase, which, when compared with the enzyme from mammalian and plant sources, seemed unique in the range of substrates utilized and in the nature of the products formed. The effect of several inhibitors on the enzyme in Mycobacterium leprae was tested. Compounds which bind copper were found to be more effective than substrate analogues. Diethyldithiocarbamate penetrated the bacillus and completely suppressed its phenolase activity. Diasone (a derivative of diaminodiphenylsulfone used in the treatment of leprosy) proved to be a potent inhibitor of phenoloxidase of mammalian and plant origin. However, it was less efficient in the case of M. leprae. A biochemical peculiarity of M. leprae was observed in its ability to metabolize mimosine and penicillamine. These compounds produced total inhibition of tyrosinase in melanoma extract and of mushroom tyrosinase. Nontoxic inhibitors of phenoloxidase in the leprosy bacilli may be of value in developing a rational approach to chemotherapy of the disease.
 ...
PMID:Effect of inhibitors on phenoloxidase of Mycobacterium leprae. 498 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>