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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The design, synthesis and biological evaluation of novel seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and the seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) analogues of the duocarmycins are described. These novel analogues (4-7) were designed on the premise that the lone pair of electrons on the furano-oxygen atom could enter into conjugation with the isocyclopropylfurano[e]indolone (iso-CFI) alkylating moiety, formed from the loss of HCl in compounds 4-7. The seco-iso-CFI DNA alkylating pharmacophore was synthesized through a well precedented approach of 5-exo-trig aryl radical cyclization with a vinyl chloride. In our studies, in addition to the formation of the seco-iso-CFI product, an equal amount of an unexpected seco-CFQ product was also generated during the radical cyclization reaction. Like CC-1065 and adozelesin, using Taq DNA polymerase stop and thermal cleavage assays, the seco-iso-CFI compounds (4 and 6) and the seco-CFQ compounds (5 and 7) were shown to preferentially alkylate the adenine-N3 position within the minor groove of long stretches of A residues. A MM2 energy optimized molecular model of a 1:1 complex of compound 6 with DNA reveals that the iso-CFI compound fits snugly within the minor groove. Using a MTT based experiment, the cytotoxicity of compounds 4-7 were determined against the growth of murine leukemia (L1210), mastocytoma (P815) and melanoma (B16) cell lines. The concentrations of compounds required to inhibit the growth of these tumor cells by 50% is in the range of 10(-8)M. These compounds were also tested against a panel of human cancer cells by the National Cancer Institute, demonstrating that the compounds exhibited a high level of activity against selected solid tumors. At a concentration of 0.0084 microM (based on the IC(50) of compound 17 (seco-CBI-TMI) against the growth L1210 cells), while compounds 4 and 17 were toxic against murine bone marrow cells as judged by a colony forming study of freshly isolated murine progenitor hematopoeitic cells, compound 5, a seco-CFQ compound, was significantly less toxic. Flow cytometric analysis of P815 cells that had been incubated for 24h with compounds 4 and 5 at their cytotoxic IC(50) concentrations indicated the induction of apoptosis in a large percentage of cells, thereby suggesting that this might be the mechanism by which the iso-CFI compounds kill cells.
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PMID:Novel furano analogues of duocarmycin C1 and C2: design, synthesis, and biological evaluation of seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) analogues. 1211 Mar 16

We investigated the antitumor activity of oregonin, a diarylheptanoid derivative purified from Alnus hirsuta Turcz, Betulaceae. Oregonin is a potential novel immunomodulator, which augments the activation of natural killer (NK) cells, and thereby leads to a powerful antitumor activity. To evaluate the cytotoxicity of oregonin against tumor cells, we examined the effectiveness of NK cells and determined that oregonin could increase NK cell cytotoxicity. This was confirmed by MTT assay. In addition, the survival time of C57BL/6 mice were measured by inoculating B16-F10 melanoma cells to mice via intra muscular (i.m.) injection. Oregonin treatment after 10 hours of inoculation at 10 mg/kg dosage showed a significant extension of survival time by up to 51.32%, when compared to the control group. Moreover, oregonin significantly reduced the incidence of pulmonary metastasis, which may be developed from B16-F10 melanoma cells. These findings suggest that oregonin may be classified as a new and novel immunomodulator due to its potential antitumor activity.
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PMID:Enhancement of NK cytotoxicity, antimetastasis and elongation effect of survival time in B16-F10 melanoma cells by oregonin. 1221 62

Ceramide is implicated in the regulation of various signaling pathways leading to proliferation, differentiation or apoptotic cell death, but there have been few investigations about the effects of ceramide on the cell growth and the melanogenesis of melanocytes. In the present study, we investigated the effects of cell-permeable ceramide on Malme-3M human melanoma cell line. MTT proliferation assay showed that C2-ceramide inhibited the growth of Malme-3M cells in a dose-dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase and an increase in the G0/G1 phase. Flow cytometric analysis for apoptotic cells and morphological observations indicated that the antiproliferative effect of C2-ceramide was not due to apoptosis. We next investigated the effects of C2-ceramide on the pigmentation of Malme-3M melanoma cells. The results showed that C2-ceramide induced only a slight decrease of tyrosinase activity and melanin synthesis. To investigate the ceramide signaling pathway, we studied the influence of C2-ceramide on extracellular signal-regulated kinase (ERK) and Akt activation by Western blot. We demonstrated that the amount of phosphorylated Akt was decreased by C2-ceramide, whereas ERK was activated transiently. Because of a well-known involvement of ceramide in apoptosis, we further investigated the level of caspase-3 and HSP70 after treatment of C2-ceramide. We found that the caspase-3 was not activated and the expression of HSP70 increased moderately. In conclusion, C2-ceramide inhibited the cell growth of Malme-3M cells without the induction of apoptosis. We suggest that increased HSP70 may be related to the resistance against apoptosis.
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PMID:Effects of C2-ceramide on the Malme-3M melanoma cell line. 1235 15

The aim of the study was to investigate the antitumor and/or preventive effect of BC-4, an isomeric compound isolated from the plant Boswellia carteri Birdw. containing alpha- and beta-boswellic acid acetate in 1:1, MW 498.3. We used the MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide) assay to study the growth inhibition activity of BC-4. Tumor cells migration within a three-dimensional collagen matrix was recorded by time-lapse videomicroscopy and computer-assisted cell tracking. Topoisomerase II was isolated from mouse melanoma B16F10 cells and its activity was determined by its ability to cut plasmid pBR322 DNA. The secretion and activity of matrix metalloproteinases (MMPs) from human fibrosarcoma HT-1080 cells were determined by gelatin zymography. BC-4 was a cytostatic compound and could induce the differentiation of B16F10 mouse melanoma cells, blocked the cell population in G1 phase and inhibited topoisomerase II activity. The G1 phase population of B16F10 cells was increased from 57.4 to 87.7%, while S phase population was reduced from 33.3 to 5.9% after treatment with BC-4 at 25 microM concentration for 48 h. BC-4 also inhibited the migration activity of B16F10. BC-4 could induce apoptosis of HT-1080 cells, as proved by acridine orange fluorescence staining, Wright-Giemsa staining, electromicroscopy, DNA fragmentation and flow cytometry. BC-4 inhibited the secretion of MMPs from HT-1080 cells, too. In conclusion, if it turns out that BC-4 is a well tolerated substance, exhibiting no significant toxicity or side effects, being evaluated currently in China, BC-4 is a good candidate for the prevention of primary tumor, invasion and metastasis.
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PMID:Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells. 1260 Apr 19

There is still no therapy method in the colorectal cancers that is good enough for such a complex disease. Combined surgery, chemotherapy, and radiotherapy improved survival, but the side effects and the poor performance status of the patients seriously affect the use of these methods. We used a therapeutical approach of surgery and chemotherapy combined with biotherapy by Viscum album extract Isorel, aiming to improve the patients' resistance to the disease and to render the treatment's side effects more tolerable. Isorel is aqueous extract well known for its anticancer effects obtained by various in vitro and in vivo experimental models and which was validated by an in vitro bioassay on murine melanoma B16F10 and human cervical carcinoma HeLa cells. Isorel strongly reduced human colon cancer HT 29 cell line growth in vitro in the MTT bioassay. Hence, it was further used in a prospective, randomized, and controlled study which compared the postoperative results for patients with colorectal cancer stages Dukes C (40 patients) and D (24 patients) who, beside surgery, received either only chemotherapy (5-FU), 6 cycles (either the Mayo or the De Gramont protocol) or chemotherapy combined with Isorel biotherapy. These 64 patients were randomly allocated into three groups "only chemotherapy" for 21 cases, chemo + biotherapy for 29 cases and 14 patients underwent only surgery as the control group. We noted no toxic deaths due to either chemo or biotherapy. The patients operated on and treated with chemo and biotherapy had median survival significantly better and a cumulative proportion survival (Kaplan-Maier) superior to those of the patients receiving only postoperative chemotherapy. Thus, colorectal cancer patients seem to benefit in terms of survival from combined postoperative chemotherapy and Isorel biotherapy, either adjuvant or palliative.
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PMID:The influence of isorel on the advanced colorectal cancer. 1266 6

Interferon-gamma (IFNgamma) has been shown to induce apoptosis through the induction of the Fas antigen in certain cell lines. In this study, we used four melanoma cell lines (MMN9, PMP, MAA and HMG) to study the antiproliferative effect of exogenous IFNgamma treatment, the expression of IFNgamma-induced Fas antigen, and the combined effect of IFNgamma and anti-Fas antibody (CH-11). We also investigated the relationship between Fas-mediated apoptosis and the expression of the bcl-2 family, measured using Western blotting. IFNgamma increased the mean fluorescence intensity of Fas in MMN9 and PMP cells as measured by flow cytometry. Combined therapy had a significant antiproliferative effect on MMN9 and PMP cells, as measured by the MTT assay. After exposure to IFNgamma and anti-Fas antibody, cleavage of bcl-2 occurred in apoptotic cells, and the signal intensity of both bcl-2 and bak decreased in surviving MMN9 cells, as shown by Western blotting analysis. Our results indicate that IFNgamma induces overexpression of Fas and consequently enhances the sensitivity of melanoma cells to Fas-mediated apoptosis. Furthermore, it is possible that cleavage of bcl-2 correlates with the induction of apoptosis induced by IFNgamma and anti-Fas antibody in melanoma cells. We conclude that combined therapy with IFNgamma and anti-Fas antibody may provide an alternative and more efficient chemotherapeutic approach against melanoma cells by inducing the overexpression of Fas after exposure to IFNgamma.
Melanoma Res 2003 Apr
PMID:Interferon-gamma and anti-Fas antibody-induced apoptosis in human melanoma cell lines and its relationship to bcl-2 cleavage and bak expression. 1269 Feb 98

Cutaneous melanoma and vitiligo are diseases etiology of which evolves around melanocytes. The nature of immunological disturbances associated with these diseases is not elucidated. The experiments performed in this work were aimed to determine antimelanoma immunotoxicity in patients with melanoma and patients with vitiligo. Twelve patients with melanoma, ten patients with vitiligo and seventeen healthy volunteers were studied. The cytotoxicity of PBMC was evaluated indirectly through determination of target melanoma (Fem-x) or control tumor (HeLa) cell survival, in the presence of 15% of AB or autologous sera, by MTT test. The mean values of antimelanoma cytotoxicity in AB serum were similar in both patients groups and in controls. However, the frequency of patients with the enhanced cytotoxicity against melanoma cells, in relation to control tumor cells, was lower in both patients groups than in controls. The intensity of antimelanoma cell-mediated cytotoxicity in melanoma patients, in the presence of autologous serum, was significantly lower in comparison to that found in control subjects and vitiligo patients (p<0.014, in both cases). This indicates that some factors from melanoma patient's sera contribute to impairment of the cytotoxicity of autologous PBMC, while other factors from the serum of vitiligo patients and control subjects enhanced their PBMC antimelanoma cytotoxicity.
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PMID:Antimelanoma immunity in vitiligo and melanoma patients. 1293 46

Copaiba oil resin (COR) obtained from Copaifera multijuga Hayne has been used in popular medicine as an antinflammatory and for the treatment of bronchitis, ulcers and cancer. The aim of this study was to evaluate the action of COR and its fractions on the inhibition of lung metastasis and tumour growth induced by B16F10 melanoma cells in mice and cytotoxicity in vitro using Trypan Blue exclusion method and MTT conversion. Mice which have received subcutaneously B16F10 cells developed a solid tumour that reached a peak at 17 days. Together with the increase in tumour growth we also observed an increase in the number of lung nodules. There was a positive correlation between the in vitro cytotoxic assay and in vivo antitumour activity. The oral administration of COR (at 2 g/Kg in the days 3, 5, 7, 10, 12 and 14 after inoculation of tumoral cells) reduced tumour growth by 58% and tumour weight by 76%. At the same dose COR reduced the number of lung nodules by 47.1%. In vitro experiments showed that COR incubated with the melanoma cell line reduced cell viability in a concentration and time-dependent manner. Diterpenic and sesquiterpenic fractions or reconstituted oil induced cytotoxicity. Our results shows that COR and its fractions have tumouricidal activity in the melanoma cell line in both models in vivo and in vitro.
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PMID:In vivo and in vitro studies on the anticancer activity of Copaifera multijuga hayne and its fractions. 1459 85

Eighteen main compounds, including four norsesquiterpenoids (1-4) and 14 phenolic compounds (5-18) isolated previously from Phyllanthus emblica, together with a main constituent, proanthocyanidin polymers (19) identified at this time from the roots, were estimated for their antiproliferative activities against MK-1 (human gastric adenocarcinoma), HeLa (human uterine carcinoma), and B16F10 (murine melanoma) cells using an MTT method. All of the phenolic compounds including the major components 5-8 from the fruit juice, 8, 9, and 12 from the branches and leaves, and 19 from the roots showed stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth. Norsesquiterpenoid glycosides 3 and 4 from the roots exhibited significant antiproliferative activities, although their aglycon 1 and monoglucoside 2 showed no inhibitory activity against these tumor cells.
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PMID:Antiproliferative activity of the main constituents from Phyllanthus emblica. 1475 47

The effects of the immunomodulation and antitumor metastasis of the Chinese medicinal fungus water extract (FWE) were investigated. After B16 melanoma cells were implanted in C57BL/6 mice through their tail veins, the mice were orally administered by FWE at low dose (160 mg/kg/day) and high dose (400 mg/kg/day) for 14 days. The tumor metastatic foci on the lung surface were observed under dissecting microscope. Phagocytosis of peritoneal macrophages was detected through ingesting chicken red blood cells (CRBC) test. Lymphocyte proliferation and the natural killer (NK) cell activity were determined by MTT method and lactate-dehydrogenase (LDH)-release assay, respectively. The expressions of bcl-2 and p53 of livers and lungs were assayed by immunohistochemical method. The results showed that FWE could increase body weights of mice dose dependently. The lung metastasis inhibition rates (MIR) of B16 melanoma cells by low dose and high dose of FWE were 15.5% and 72.7%, respectively. FWE at the two doses enhanced significantly (p<0.05) the phagocytosis, which was evaluated using the phagocytic rate (PR) and phagocytic index (PI). FWE had significantly promoted mice' NK activity at high dose (p<0.001). Lymphocyte proliferation was not significantly elevated in both of low- and high-dose groups. FWE depressed the levels of bcl-2 and p53 protein in the liver and lung cells at both of the two doses. These results indicate that FWE not only promoted the mouse's immunity, but also inhibited tumor metastasis.
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PMID:Effects of Chinese medicinal fungus water extract on tumor metastasis and some parameters of immune function. 1503 23


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