Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many attempts have been made to develop a suitable animal model to study more effectively the aetiology, pathogenesis, diagnosis and therapy of intraocular (uveal) melanoma. Uveal melanoma may spontaneously occur in some animals, including dogs, cats, horses, rats, mice, birds and fish. The histological features, metastatic behaviour and unpredictable nature of occurrence of these uncommon spontaneous tumours detract from their suitability as a model. Several methods have been developed to induce intraocular melanoma chemically or by radiation in laboratory animals. Some of these induced tumours resemble human uveal melanoma, although the majority originate from the retinal pigment epithelium. Uveal proliferations have been biologically induced by feline leukaemia/sarcoma virus and simian virus 40, although the presence of virus in tumour cells and extraocular tumours resulting from shed virus detract from the utility of this model. Inoculation of tissue culture hamster, murine or human melanoma cells into animal eyes has the advantage that the inoculation site and size of inoculum can be controlled. Disadvantages include the immune suppression necessary for tumour growth in some models as well as the fact that many of the melanoma cell lines are of cutaneous origin. Transgenic murine models have been developed using the promoter region of the tyrosinase gene to target expression of oncogenes in melanin-producing cells. Spontaneous intraocular pigmented tumours and distant metastases may occur, although many, if not all, of the intraocular tumours arise in the retinal pigment epithelium.
Melanoma Res 2000 Jun
PMID:Animal models of uveal melanoma. 1089 Mar 73

Targeted alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 were chelated to cancer specific monoclonal antibodies to form alpha-immunoconjugates (AIC) against melanoma, leukaemia, prostate and colorectal cancer, and to the plasminogen activator inhibitor type-2 (PAI2) to form alpha-PAI2 (API) against breast and prostate cancer. These conjugates were found to be highly stable, specific and cytotoxic in vitro. Melanoma and breast cancer tumour growth was observed in nude mouse models for untreated controls and non-specific AIC/API at 2 days post-subcutaneous inoculation of cancer cells. Complete inhibition of melanoma and breast cancer growth was found for local injections of AIC and API, respectively. Intra-lesional TAT of established melanoma showed that all melanomas regressed with 100 microCi injections of AIC. These results point to the potential application of local and systemic TAT in the management of metastatic cancer.
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PMID:In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers. 1141 11

Hyperthermia produces regression of human cancer. Because hyperthermia has produced only limited results, attention has focused on searching for substances able to sensitize tumour cells to the effects of hyperthermia. The flavonoid quercetin has been reported to be a hyperthermic sensitizer in ovarian and uterine cervical tumours and in leukaemia. Quercetin and tamoxifen inhibit melanoma cell growth. We therefore investigated whether quercetin and tamoxifen can sensitize M10, M14 and MNT1 human melanoma cells to hyperthermia. We observed that both quercetin and tamoxifen synergize with hyperthermia (42.5 degrees C) in reducing the clonogenic activity of M14 and MNT1 and in inducing apoptotic cell death in all three cell lines. As revealed by flow cytometric and Northern blot analyses, quercetin and tamoxifen reduced heat shock protein-70 expression at both protein and mRNA levels. Our results suggest that quercetin and tamoxifen can be usefully combined with hyperthermia in the therapy of recurrent and/or metastatic melanoma.
Melanoma Res 2001 Oct
PMID:Quercetin and tamoxifen sensitize human melanoma cells to hyperthermia. 1159 83

Cell membrane localization of the 72 kDa heat shock protein 70 (Hsp70) has been found on different tumour cell lines, on biopsy material from solid tumours and metastases and on leukaemic blasts from acute myelogenous leukaemia patients, but not on the corresponding normal tissues, as determined by flow cytometry using the Hsp70-specific monoclonal antibody C92F3B1. In the present study Hsp70 membrane expression was studied on primary malignant melanomas, melanoma metastases, melanocytes, human skin fibroblasts and peripheral blood lymphocytes, together with expression of the melanoma-associated markers Mel-1, Mel-2 and Mel-5, major histocompatibility complex class I and the fibroblast-specific marker ASO2. As previously shown, fibroblasts and peripheral blood lymphocytes from healthy human volunteers were found to be negative for Hsp70 and for the melanoma-associated markers Mel-1, Mel-2 and Mel-5. Human melanocytes from healthy human donors were also negative for Hsp70, but were positive for Mel-1 and Mel-5. Independent of the Clark's level, all the malignant melanomas (n = 9) and metastases (n = 11) exhibited were positive for both Mel-1 and Mel-2. The primary melanomas could be divided into two groups according to their Hsp70 and Mel-5 expression pattern: those with an Hsp70-negative and a Mel-5-positive phenotype (-/+) (five out of nine), and those with an Hsp70-positive and a Mel-5-negative phenotype (+/-) (four out of nine). All the melanoma metastases (n = 11) had an Hsp70-positive, Mel-5-negative phenotype (+/-). These data provide the first hint that the marker combination Hsp70 positive/Mel-5 negative might be useful in estimating the metastatic potential of a melanoma. Investigations on changes in the marker combination Hsp70/Mel-5 during onset of melanoma disease and progression will clarify its potential as a prognostic risk factor.
Melanoma Res 2003 Apr
PMID:Heat shock protein 70 membrane expression and melanoma-associated marker phenotype in primary and metastatic melanoma. 1269 Feb 97

The title compound has been designed for antitumor activity based on structural features of related known antitumor gold agents, that is, gold-monophosphine and gold-diphosphine derivatives. It is a gold complex that contains both types of phosphine ligands, thus suggesting a possible synergistic action. The results of a single crystal X-ray structure determination of this molecule show the metal surrounded by 3 P atoms and one Cl anion in a distorted tetrahedral arrangement. The chloro anion, however, is weakly bound to the metal and so the species shows ionic character. The P NMR study, performed in solution, confirms the structural features observed in the solid and, in addition, indicates partial formation of other known gold(I)-diphosphine antitumor agents. The ionic character and strong Au-P bonds of this novel gold(I) species are similar to those of the most active antitumor gold compounds so far studied. The former feature contributes to solubility in biological fluids, and the latter prevents fast biomolecular attack. In addition, the title compound is less lipophilic, a feature recently correlated to lower liver toxicity. The title compound shows in vitro antitumor activity in the two initial National Cancer Institute protocols against human tumors. In the first screening, a unique dose (0.10 mM) of the title compound reduced cell growth of MCF7 (breast cancer), NCI-H460 (lung cancer), and SF-268 (Central Nervous System cancer-CNS) to 5, 8, and 11%, respectively. In the second protocol a 60-cell line panel was analyzed with the title compound concentration in the 0.1 mM-0.01 microM range. The highest activity was for the breast tumor cell line MCF7 with a LC(50) less than 0.01 microM. LC(50) values in the micromolar range were obtained for 29 cell lines. With the exception of leukemia, these micromolar activities were observed in at least one cell line for each subgroup tumor (non small lung, colon, CNS, melanoma, renal, prostate, breast, and ovarian). The leukemia inactivity was unexpected, as all antitumor gold(I) phosphine compounds in the literature described thus far are active. Melanoma was the most sensitive subgroup screened (five out of seven cell lines).
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PMID:Antitumor activity of the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I). 1269 91

Previous reports of cancer after kidney transplantation have been limited by small numbers of patients in single-center studies and incomplete ascertainment of cases in large registries. We examined rates of malignancies among first-time recipients of deceased or living donor kidney transplantations in 1995-2001 (n = 35 765) using Medicare billing claims. For most common tumors, e.g. colon, lung, prostate, stomach, esophagus, pancreas, ovary and breast, cancer rates were roughly twofold higher after kidney transplantation compared with the general population. Melanoma, leukemia, hepatobiliary tumors, cervical and vulvovaginal tumors were each approximately fivefold more common. Testicular and bladder cancers were increased approximately threefold, while kidney cancer was approximately 15-fold more common. Kaposi's sarcoma, non-Hodgkin's lymphomas, and nonmelanoma skin cancers were more than 20-fold increased than in the general population. Compared with patients on the waiting list, several tumors were more common after transplantation (p < 0.01): nonmelanoma skin cancers (2.6-fold), melanoma (2.2-fold), Kaposi's sarcoma (9.0-fold), non-Hodgkin's lymphoma (3.3-fold), cancer of the mouth (2.2-fold), and cancer of the kidney (39% higher). The rates for most malignancies are higher after kidney transplantation compared with the general population. Cancer should continue to be a major focus of prevention in kidney transplantation.
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PMID:Cancer after kidney transplantation in the United States. 1514 14

Violacein is the main pigment produced by Chromobacterium violaceum, a saprophytic gram-negative bacillus. Violacein is formed by the condensation of two modified tryptophan molecules and has potential anti-neoplastic effects. The purpose of this pilot study was to investigate the in vitro activity of violacein in human uveal melanoma cell lines. Human uveal melanoma cell lines 92.1 and OCM-1 were incubated with five different concentrations of violacein (10(-5)-10(-9) M), and the total cellular protein content was measured by means of the sulphorhodamine B assay. Dose-response curves were obtained and the concentration inhibiting cell growth by 50% (IC50) together with the concentration inhibiting the net cell growth by 50% (GI50) were calculated for both cell lines. Violacein IC50 and GI50 concentrations to cell line 92.1 were 2.78 x 10(-6) M and 1.69 x 10(-6) M, respectively. The IC50 and GI50 concentrations to cell line OCM-1 were 3.69 x 10(-6) M and 2.12 x 10(-6) M, respectively. Previous studies using the same methodology have revealed violacein to have a GI50 in the range (3-6) x 10(-8) M for MOLT-4 leukaemia, NCI-H460 large cell lung cancer and KM12 colon cancer cell lines. Violacein displayed borderline cytotoxic activity in human uveal melanoma cell lines 92.1 and OCM-1, as measured by the sulphorhodamine B assay, and further studies are necessary to define its suitability as a potential therapeutic agent for metastatic uveal melanoma.
Melanoma Res 2004 Oct
PMID:Cytotoxic effects of violacein in human uveal melanoma cell lines. 1545

A few twin studies on cancer have addressed questions on the possible carcinogenic or protective effects of twining by comparing the occurrence of cancer in twins and singletons. The nationwide Swedish Family-Cancer Database of 10.2 million individuals and 69,654 0- to 70-year-old twin pairs were used to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancers compared to singletons. The overall risk of cancer in same- or different-sex twins was at the same level as the risk for singletons. Testicular cancer, particularly seminoma, was increased among same-sex twins (1.54) and all twins to an SIR of 1.38. Among other tumors, neurinomas and non-thyroid endocrine gland tumors were increased. Colorectal cancers and leukemia were decreased among all twins. Melanoma and squamous cell skin cancer were decreased in male same-sex twins. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. In utero hormonal exposures or postnatal growth stimulation may be related to the risk of testicular cancer and pituitary tumors. Protective effects against colorectal cancer may be related to a beneficial diet, and in melanoma and skin cancer, to socioeconomic factors. The study involved multiple comparisons, and internal consistency between the results was one of the main factors considered for their plausibility. The results should encourage others working on twin and singleton populations to examine the specific associations and emerging hypotheses.
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PMID:Are twins at risk of cancer: results from the Swedish family-cancer database. 1621 40

Arylamine carcinogens and drugs are N-acetylated by cytosolic N-acetyltransferase (NAT), which uses acetyl-coenzyme A as a cofactor. NAT plays an initial role in the metabolism of these arylamine compounds. 2-Aminofluorene is one of the arylamine carcinogens which have been demonstrated to undergo N-acetylation in laboratory animals and humans. Our previous study showed that human cancer cell lines (colon cancer, colo 205; liver cancer, Hep G2; bladder cancer, T24; leukemia, HL-60; prostate cancer, LNCaP; osteogenic sarcoma, U-2 OS; malignant melanoma, A375.S2) displayed NAT activity, which was affected by aloe-emodin in human leukemia cells. The purpose of this study was to determine whether aloe-emodin could affect the enzyme activity and gene expression of NAT at the mRNA and protein levels in malignant human melanoma A375.S2 cells. The results showed that aloe-emodin inhibited NAT1 activity (decreased N-acetylation of 2-aminofluorene) in intact cells in a dose-dependent manner. The effect of aloe-emodin on NAT1 at the protein level was determined by Western blotting and the mRNA levels were examined by polymerase chain reaction (PCR) and cDNA microarray. These results clearly indicate that aloe-emodin inhibits the mRNA expression and enzyme activity of NAT1 in A375.S2 cells.
Melanoma Res 2005 Dec
PMID:Effect of inhibition of aloe-emodin on N-acetyltransferase activity and gene expression in human malignant melanoma cells (A375.S2). 1631 33

No systematic population-based studies have been conducted on familial eye cancers. Reliable data on familial risks are important for clinical counselling and cancer genetics. The current analysis was based on the nation-wide Swedish Family-Cancer Database on 10.5 million individuals, containing families with parents and offspring. Cancer data were retrieved from the Swedish Cancer Registry from the years 1958 to 2002, including 3636 patients with any type of eye cancer. Familial risk for offspring was defined using the standardized incidence ratio (SIR), adjusted for many variables. Ocular melanoma was detected in two parent-offspring pairs, but the SIR of 3.90 was not significant. Parental upper aerodigestive tract (2.05), left-sided colon (1.83) and male non-medullary thyroid (6.98) cancers showed an association with ocular melanoma, albeit some with a borderline significance. The SIR for leukaemia was increased when parents were diagnosed with eye melanoma. There was no evidence for the association of ocular melanoma with cutaneous melanoma. The SIR for ocular melanoma was 1.76 when a sister was diagnosed with breast cancer, but there was no increase when a mother was diagnosed with breast cancer. When both a child and the parent presented with retinoblastoma, the SIR was 900. The parents of children with retinoblastoma had an excess of small intestinal and rectal cancers and Hodgkin's disease. The present findings were based on a limited number of cases, but they display a complex and heterogeneous pattern of familial associations in ocular melanoma, including an association with breast cancer through a putative recessive mechanism.
Melanoma Res 2006 Apr
PMID:Familial risks for eye melanoma and retinoblastoma: results from the Swedish Family-Cancer Database. 1656 75


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