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

We have investigated the effect of high dose iv bolus interleukin-2 (IL-2) therapy on sex hormone and adrenal steroid concentrations in six men treated for metastatic renal cell carcinoma or malignant melanoma. Blood concentrations of testosterone, 17 beta-estradiol, LH, FSH, cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) were measured before and after a 5-day course of IL-2 therapy. Cortisol levels rose and DHEA-S decreased insignificantly. DHEA declined, reaching a nadir (P less than 0.001) on day 6, and testosterone decreased significantly on day 2 and reached a nadir on day 6 (P less than 0.0001). Concentrations of both steroids then gradually rose. Estradiol rose on day 4 (P less than 0.001) and then declined. Neither LH nor FSH was affected significantly, although there was a rise in the mean level of LH after IL-2 therapy. Our results suggest that high dose IL-2 therapy in men affects both adrenal and testicular androgen production without inhibiting pituitary trophic hormone secretion. These effects of IL-2 on plasma sex steroids may be the result of cytokines stimulated by IL-2 therapy, rather than direct responses to IL-2.
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PMID:Reduction of testosterone synthesis after high dose interleukin-2 therapy of metastatic cancer. 183 90

The nutritional and immunological status have been evaluated in 28 consecutive patients with esophageal cancer. Patients (21 male and 7 female), had a mean age of 61 years, ranging from 34 to 84 years. The tumor histological type was squamous in 25 patients. A melanoma, an oat cell carcinoma and a adenocarcinoma were observed in the remaining cases. The nutritional status was assessed by means of weight loss, triceps skinfold, midarm muscle circumference and serum levels of albumin and transferrin. On the basis of this data the patients were divided into two groups: A, 19 patients (68%), normal nourished group (or with a mild malnutrition) and B, 9 patients (32%) with a severe malnutrition. The immunological status was assessed by determining the lymphocyte absolute number (H-6000-Technicon), the T-Lymphocyte sub-populations (flow-cytometry with monoclonal antibodies--Ortho Diagnostic System) and the patient's response to intradermally placed recall antigens (Multitest Merieux). Significative immunological abnormalities were found only in malnourished patients, group B (p less than 0.05). Moreover a reduction of OKT4 helper (less than 30%) and the inversion of OKT4/OKT8 ratio (less than 0.9%) were also observed only in the malnourished group (p less than 0.01). Therefore, we conclude that acquired immunodeficiency, when present in patients with esophageal cancer, is due to the severe malnutrition rather than to the cancer itself.
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PMID:[Relationship between nutritional and immunologic status in patients with esophageal cancer]. 194

The MEL-85 human melanoma cell line was used to investigate the effects of both estradiol and dexamethasone on expression of laminin (LM) receptors and cell adhesion capacity. Immunoblotting of eluates from whole-cell extracts applied to LM Sepharose indicates the presence of an LM-binding protein of 116-130 kDa that reacted with an anti-beta 1 integrin antibody, suggesting that the putative LM receptor of MEL-85 cells is a member of the integrin family. Analysis of 125I-LM binding to whole cells indicates the existence of low-affinity components which display positive co-operativity. LM-fragment-8 competes for this binding to the same extent as unlabelled LM (75%), while fragment PI is inactive and fibronectin (FN) competes by about 30% only. Binding of labelled fragment-8 exhibits a pattern similar to that of intact LM. Cell adhesion to substrates coated with LM and LM fragments closely parallels binding to cells in suspension. MEL-85 cells were estradiol-receptor-negative. Estradiol treatment did not stimulate LM receptor levels or attachment to LM. Growth rate also remained unaltered. To characterize the glucocorticoid dependence of MEL-85 cells, we first established the presence of glucocorticoid receptors and an inhibitory effect on growth rate. Dexamethasone treatment resulted in marked enhancement of adhesion to LM, without altering LM receptor number or affinity. In addition, dexamethasone changed the morphology of MEL-85 cells in conjunction with higher LM expression as evaluated by immunofluorescence.
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PMID:Effects of steroids on laminin-binding integrins in a human melanoma cell line. 201 59

The tolerance of a recombinant human interleukin-2 (rIL-2, r-met Hu IL-2 [ala-125], Ortho Pharmaceutical) and its antitumor effectiveness in combination with lymphokineactivated killer (LAK) cells was examined in 26 patients with metastatic solid tumors, including 14 renal cell carcinomas, seven melanomas, three extragonadal germ cell tumors refractory to chemotherapy and two colon carcinomas. rIL-2 was administered as a bolus at 30,000 U/kg every 8 h on days 1-5 and days 12-19. Leukapheresis was done on days 8-12, lymphocytes were incubated with rIL-2 for 3 or 4 days in vitro and reinfused on days 12, 13 and 15. The mean number of reinfused cells was 5.1 x 10(10) per patient. IL-2 dose and schedule were adjusted according to toxicity. Patients received a median of 100% (range 87-100%) of planned rIL-2 on days 1-5 and a median of 71% (range 13-100%) on days 12-19. Capillary leak syndrome with hypotension and impaired renal function and CNS toxicity were the major reasons for dose modification. Patients with renal cell carcinoma, most of whom underwent a prior nephrectomy, had a reduced tolerance to rIL-2. Partial responses were documented in three renal cell carcinomas and one melanoma. The median response duration was 5.5 (range 1-6) months.
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PMID:Tolerance and effectiveness of recombinant interleukin-2 (r-met Hu IL-2 [ala-125]) and lymphokine-activated killer cells in patients with metastatic solid tumors. 268 3

A malignant hamster melanoma cell line HM-1 derived from the heterogenous malignant hamster melanoma MM1 contains a specific, high affinity binding protein for estrogens. Partial purification of the binding protein with ammonium sulfate (40% saturation) increased mean binding content (3.1 +/- 1.2 (SD) fmol/mg protein) 15-fold without any change in affinity (10(10) M-1). The binding protein sedimented at 8-9S on 10-30% low salt sucrose gradients and 9-10S in the presence of 20 mM molybdate ion. Addition of 0.4 M KCl shifted the 8S peak to 4S. Binding was specific, saturable, and indicative of a single class of high affinity sites over a concentration range of 0.01-10.0 nM [3H]estradiol. Estradiol produced a dose related inhibition of HM-1 growth in vitro without altering the growth of an additional line (HM-2) which did not bind estrogen. The antiestrogen tamoxifen (10(-7) M) also significantly inhibited HM-1 melanoma growth in vitro, which was reversed by the addition of estradiol (10(-9) M). HM-1 xenografts grew faster in female BALB/c-nu/nu mice than male mice while there was no sex difference in HM-2 growth. Pharmacological doses of estradiol and the antiestrogen nafoxidine significantly inhibited HM-1 growth without altering tumor incidence or latency. Our observations suggest that HM-1 cell lines bind estrogens specifically and with high affinity and that hamster melanoma cells positive for this binding protein respond to estrogen.
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PMID:Inhibition of hamster melanoma growth by estrogen. 309 10

The effect of estrogens on tyrosinase (EC 1.14.18.1) activity was studied in B16/C3 melanoma cultures. Estradiol, estriol, and other related steroids failed to influence tyrosinase activity when added to the medium of proliferating cultures. Imidazole (10 mM), on the other hand, induced the activity of that enzyme 3-fold, as reported previously. Estradiol and estriol blocked imidazole induction, however, unlike the other estrogenic compounds. The blockade occurred within 15 min of hormone addition and was reversible. Dose-response studies revealed that the maximal estradiol effect occurred at 0.75 nM and the half-maximal effect occurred at 0.5 nM. Estriol was more potent, with the maximal blockade occurring at approximately 0.5 nM and half-maximal effect at 0.25 nM. The induction of tyrosinase by imidazole and the blockade of this induction by estradiol and estriol could not be demonstrated in broken cell preparations, suggesting that direct enzyme activation-inactivation was not involved. Studies utilizing inhibitors of protein and RNA synthesis suggest that this effect is mediated at a pre-translational level and is independent of mRNA destabilization.
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PMID:Inhibition of imidazole-induced tyrosinase activity by estradiol and estriol in cultured B16/C3 melanoma cells. 312 3

Physiochemical properties of an estrogen binding protein were characterized in three human melanoma cell lines, UISO-MEL-1, UISO-MEL-2, and UISO-MEL-4. Estrogen binding to melanoma cytosol was saturable, specific for estrogens, and represented by a single class of high-affinity, limited-capacity binding sites (Kd 5.5 x 10(-10) M, 2.7 +/- 0.5 fmol/mg of cytosol protein, UISO-MEL-2; 2.2 x 10(-10) M, 7.8 +/- 3.3, UISO-MEL-4) (SEM). UISO-MEL-1 cytosols did not bind estradiol. The binding protein in UISO-MEL-2 and -4 sedimented at 8.5S and 9.2S, respectively, in the presence of 10 mM sodium molybdate. Solid-phase radioimmunoassay with a monoclonal antibody specific for human estrogen receptor (H222 sp lambda) showed good correlation (r = 0.84) with a hydroxyapatite biochemical assay of identical melanoma cytosols. Exposure of UISO-MEL-2 to estradiol produced a time- and temperature-dependent increase in total nuclear receptor for estrogen in vitro. Estradiol treatment of athymic mice also significantly increased cytosol progesterone receptor content in UISO-MEL-2 and UISO-MEL-4 xenografts. Estradiol had no effect on the plating efficiency or growth of any melanoma cell line or normal melanocytes in vitro. Tamoxifen also had no effect on melanoma growth in vitro. In contrast, chronic exposure of athymic mice carrying estrogen receptor-positive UISO-MEL-2 to estradiol resulted in a sex-dependent increase in tumor latency and overall inhibition of tumor growth. Taken together, these observations suggest that a subset of human melanomas contains limited amounts of an estrogen binding protein similar to that observed in other estrogen-responsive tissues. The lack of effect of estradiol on melanocyte and melanoma growth in vitro, coupled with a decrease in tumor growth in athymic mice, suggests that, while inhibition may be receptor mediated, possible indirect actions of estradiol must also be considered.
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PMID:Effect of 17 beta-estradiol on the growth of estrogen receptor-positive human melanoma in vitro and in athymic mice. 319 86

This article presents the case of a 30-year-old woman who developed halo cutaneous melanoma. She had been taking oral contraceptives (Norinyl) for about 5 years before diagnosis. Following wide excision of the melanoma, the patient remained clinically free of tumor for 5 years. However, in a subsequent pregnancy, she developed metastases to the liver that became evident in the immediate postpartum period. Long-term survival associated with cutaneous hypopigmentation has been reported and occurred in this patient. There is considerable debate as to whether oral contraceptives or pregnancy can influence the occurrence and course of melanoma. Also unclear is whether oral contraceptive use or a subsequent pregnancy in women with a history of melanoma will accelerate the growth of latent metastases, stimulate a benign pigmented lesion to become malignant, or cause a previously removed melanoma to recur and metastasize. Given the lack of uncertainty in this area, it is recommended that women with a history of melanoma use a nonhormonal method of contraception. Frequent follow up and thorough physical examinations during pregnancy are essential, and any suspicious skin lesions should be biopsied early. To better answer the questions raised by cases such as this, establishment of an organized mechanism for the registry of patients with melanoma who subsequently become pregnant is suggested. A cooperative prospective melanoma study could accumulate the necessary data on tumor site and thickness, staging, parity, and the use of hormonal contraception.
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PMID:Pregnancy and hormonal influences on malignant melanoma. 381 62

Estradiol (E2) receptor-binding protein was measured in 42 neoplasms and normal tissues from the head and neck region. Tissues with high E2 receptor protein content included normal skin and normal mucosa of the nose and the floor of the mouth and of the parotid and submandibular salivary glands. Two of four papillary carcinomas of the thyroid, three of five pleomorphic adenomas of the parotid, four of six squamous cell carcinomas of the oral cavity, one of angiofibroma of the nose, and an eye (sclera) melanoma also had a high content of E2-binding protein. The demonstration of estrogen receptors in these neoplasms may indicate that these tumors also, as many breast lesions, may be hormone-dependent. If this is correct, an appropriate hormonal treatment may influence their biological evolution.
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PMID:Estradiol receptor-binding protein in head and neck neoplastic and normal tissue. 625 38

MCF-7 human breast cancer cells secrete two immunologic types of plasminogen activator, one related to urokinase, the other unrelated. We have now examined whether estrogen stimulation of secreted plasminogen activator activity reflects an increase in one or both types. Examined semiquantitatively by sodium dodecyl sulfate-polyacrylamide gel electrophoretic zymography, the conditioned media of control cells were seen to contain a major activator band (Mr approximately 54,000) immunologically related to urokinase and a barely discernible doublet (Mr approximately 64,000 and Mr approximately 68,000). Addition of estradiol or, at much higher concentrations, testosterone led to marked enhancement of doublet activity, while the 54-kDa band was invariant. The 64-68-kDa doublet was immunoreactive with antiserum directed against Bowes melanoma tissue plasminogen activator but not with antiurokinase antibodies. Enhancement of doublet activity was correlated with hormone-induced increases in total secreted plasminogen activator activity. Neither progesterone nor dexamethasone increased total activity or the 64-68-kDa zones of lysis. Estradiol and testosterone alterations were blocked by appropriate concentrations of an estrogen antagonist (LY156758), actinomycin D, or cycloheximide. Regulation of MCF-7 cell-secreted tissue plasminogen activators thus appears to be mediated by an estrogen receptor process and to require sustained RNA and protein synthesis.
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PMID:Estradiol preferentially enhances extracellular tissue plasminogen activators of MCF-7 breast cancer cells. 654 3


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