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)

Adult fish of an interstrain hybrid (F1) of inbred medaka, obtained from crosses between HO4C and HB32C, were exposed for 2 hr to an aqueous solution of the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine at concentrations of 15, 20, 25, 30, and 35 ppm. Survival and neoplastic changes were examined over a 6-month period. A large variety of neoplasms were induced, including melanoma, papilloma, ovarian tumors, olfactory epithelioma, branchioblastoma and fibroma. More than 60% of the tumors were classified as melanoma on the basis of histological examinations. A markedly higher cumulative incidence of the melanoma with a dose-related response was demonstrated in the F1 hybrid fish compared to the parental strains. The latent period for melanoma development, however, remained unchanged in F1 compared to the parents. The variety of tumors induced in the F1 fish was greater than in the parental strains. The results indicate the usefulness of F1 hybrid fish in testing the carcinogenicity of certain water-soluble chemicals, due to their high sensitivity.
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PMID:Higher susceptibility to N-methyl-N'-nitro-N-nitrosoguanidine-induced tumorigenesis in an interstrain hybrid of the fish, Oryzias latipes (medaka). 311 60

The anti-metastatic effect of two chemotherapeutic agents was analyzed in a murine melanoma model. Difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, was administered as a 2% aqueous solution in the drinking water. A second drug, dacarbazine (DTIC) was administered intravenously in single bolus injections. Each drug produced significant anti-metastatic effects that were manifested by a reduction in the number of pulmonary metastases and in the prolongation of host survival times. Maximal chemotherapy was achieved when both drugs were combined. The specificity, low toxicity, ease of administration, infrequent side effects, and therapeutic effectiveness of DFMO make it an attractive candidate for clinical use in human subjects being treated for uveal melanoma. The effectiveness of DTIC against blood-borne melanoma cells suggests that this drug may prove useful as a prophylactic adjunct in patients undergoing enucleation of a melanoma-containing eye.
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PMID:Suicide enzyme inhibition as a chemotherapeutic strategy for controlling metastases derived from intraocular melanomas. 311 18

We had earlier shown that a single round of interleukin 2 (IL-2) in chronically indomethacin treated mice can totally or nearly totally ameliorate established, experimental lung metastases and reactivate natural killer (NK) and lymphokine activated killer-like cells in the spleen. The present study examined whether a lasting cure of metastasis is obtainable by chronic indomethacin therapy (CIT) combined with single or multiple rounds of IL-2, and if so, what are the morphological, phenotypic, and functional properties of tumoricidal cells generated in situ. Experimental lung metastasis was produced in B6 mice by an i.v. injection of 10(6) B16F10 melanoma cells to compare therapeutic effects of six protocols: (a) CIT (14 micrograms/ml via drinking water) starting on day 5 when pulmonary micrometastases are well established; (b) CIT combined with a single round of IL-2 (25,000 units, i.p., every 8 h for 5 days on days 10 through 14); (c) CIT combined with two rounds of IL-2 (days 10-14 and 20-24); (d) two rounds of IL-2 alone; (e) two rounds of IL-2 plus indomethacin given only during the IL-2 therapy; and (f) which was similar to (c), but in addition, followed by repeated injections of IL-2 (25,000 units twice a day on Mondays and Fridays for 8 consecutive weeks). Results revealed that chronic indomethacin therapy alone or two rounds of IL-2 alone, or two rounds of IL-2 plus discontinuous indomethacin therapy reduced the lung metastases (examined at 21-25 days) by about two-thirds. In contrast, both single and multiple rounds of IL-2 in chronically indomethacin treated mice totally or nearly totally eradicated the lung metastases. However, long-term disease-free survival (greater than 13-16 months) resulted only with multiple rounds of IL-2. With chronic indomethacin therapy alone, NK-like (AGM-1+, Thy-1-,Lyt-2-) killer lymphocytes (capable of killing NK sensitive YAC-1 lymphoma and B16F10 melanoma targets) appeared in the spleen, but not lungs; no killer activity was generated in macrophages at either site. Addition of a single round of IL-2 generated lymphokine activated killer-like killer lymphocytes (also capable of killing an NK resistant target) of the same phenotype, but of higher activity in the spleen; some lymphokine activated killer-like killer function was generated among pulmonary lymphocytes which were AGM-1+, Thy-1+,Lyt-2-, as well as among splenic but not pulmonary macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cure of B16F10 melanoma lung metastasis in mice by chronic indomethacin therapy combined with repeated rounds of interleukin 2: characteristics of killer cells generated in situ. 312 54

Swainsonine, an indolizidine alkaloid, has been found to inhibit the experimental metastasis of B16-F10 melanoma cells when administered systemically to syngeneic C57BL/6 mice. The inhibition was both potent and dose dependent with greater than or equal to 80% reduction in pulmonary colonization being observed after only 24-h exposure to 3 micrograms/ml of swainsonine in drinking water. In contrast, the inhibitory activity of swainsonine was completely abrogated when assays were performed in mice depleted of their natural killer (NK) cell activity either experimentally (anti-asialo-GM1 antibody- or cyclophosphamide-treated C57BL/6 mice) or as a result of genetic mutation (homozygous C57BL/6bg/bg beige mice). Swainsonine elicited a 32.0% increase in spleen cell number 2 days after administration and induced a concomitant 2- to 3-fold increase in splenic NK cell activity. These results indicate (a) an absolute requirement for a functional NK cell population in order for swainsonine to exert its inhibitory effects on experimental metastasis, and (b) that the antimetastatic activity of swainsonine is mediated primarily through the ability of the drug to augment NK cell reactivity. On the basis of these findings, swainsonine can be classified as a new immunomodulator that has the ability, at least in a prophylactic setting, to block tumor metastasis.
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PMID:Augmentation of murine natural killer cell activity by swainsonine, a new antimetastatic immunomodulator. 312 63

At the Finsen Institute, Copenhagen, from 1971 to 1981, 134 patients were treated for lymph node metastases from primary cutaneous malignant melanoma of axial localization (e.g., in the head and neck and trunk), where metastases to regional lymph node groups were the first sign of dissemination. Due to the lack of sufficient clinical data, 27 patients were excluded from the study. Median time from excision of primary tumor to diagnosis of node metastases was 11 months. In 42 of 85 (49%) patients with truncal melanoma, the primary tumor was placed in the lymphatic water-shed areas. Two patients among this group showed bilateral simultaneous metastases to two different node groups. In the remaining 43 patients with truncal tumors located outside water-shed areas, node metastases developed in unexpected groups in seven (16%) patients. Of 22 patients with head and neck tumors, two (9%) patients demonstrated metastases to distant lymph node groups without metastases to the regional node basins.
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PMID:Patterns of the first lymph node metastases in patients with cutaneous malignant melanoma of axial localization. 316 20

In experiments using cultured cells, LS2616 has been shown to decrease growth of primary tumors and pulmonary metastasis of murine melanoma. In the current study, we examine the efficacy of LS2616 for the prophylactic and therapeutic treatment of metastases from ocular and flank inoculations of the highly aggressive in vivo derived B16F10 melanoma in C57BL/6J mice. Experimental animals were treated with 160 mg/kg/day of this drug in drinking water, until they became moribund or died. When mice were pretreated for 7 days and inoculated subcutaneously (sc) or intracamerally (ic) with 10(5) in vivo derived B16F10 tumor cells, the mean number of pulmonary metastases was significantly reduced, and the incidence of pulmonary metastases decreased. In ocular experiments, when pretreatment with drug was combined with enucleation at day 7, the mean number of lung nodules was significantly reduced, the incidence of metastasis to the lung and lymph nodes decreased and survival increased. An apparent cure rate of 31% was observed. Treatment beginning on the day of enucleation (day 7) resulted in a reduction of pulmonary metastases, a decrease in metastasis to the lungs and lymph nodes and no change in survival. LS2616 did not alter tumorigenicity of either sc or ic inoculations. In an in vivo neutralization assay, spleen cells of mice treated for 7 days with LS2616 demonstrated an increase in cytostatic or cytotoxic activity when incubated with B16F10 melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A treatment for metastasis of murine ocular melanoma. 317 Jan 23

Iproplatin [cis-dichlor-trans-dihydroxy-bis-isopropylamine platinum (CHIP, JM9)] is a new antineoplastic platinum analogue with an octahedral conformation. It has more water solubility than does cisplatin and was found to have less neurotoxicity and nephrotoxicity in experimental animals than cisplatin. Like cisplatin, it has been demonstrated to have a broad spectrum of activity in experimental tumor systems. A phase I study of iproplatin was conducted in 28 patients (12 with melanoma, 8 with sarcoma, 6 with breast cancer, and 2 with colon cancer). All patients had failed prior chemotherapy. Four consecutive doses of iproplatin were administered at weekly intervals followed by a rest period of two weeks for hematologic recovery (one course). One hundred forty-two weekly doses were administered with all patients except three receiving at least one full course. The weekly starting dose of 40 mg/m2 was increased to 120 mg/m2 given over 30 minutes without hydration. Myelosuppression predominantly thrombocytopenia, was the dose-limiting toxicity at weekly doses of greater than or equal to 95 mg/m2 per course. With iproplatin doses 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median granulocyte counts were 2.6 x 10(3)/mm3, 2.2 x 10(3)/mm3, and 1.8 x 10(3)/mm3, respectively. Similarly, at iproplatin doses of 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median platelet counts were 144 x 10(3)/mm3, 99 x 10(3)/mm3, and 31 x 10(3)/mm3, respectively. Mild to moderate nausea and vomiting were observed in the majority of patients. No significant neurotoxicity, nephrotoxicity, or ototoxicity was observed. Objective tumor regression was not observed in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of weekly-administered iproplatin [cis-dichloro-trans-dihydroxy-bis-isopropylamine platin (chip, JM9)]. 322 43

Cultured human melanoma and gastrointestinal carcinoma cells were detached from substrate and further dissociated by placing the culture vessel into a water-filled ultrasonic cleaner (43 kHz) and sonicating it for 10-50 s. Plating efficiency and long-term growth of three melanoma cell lines were similar after ultrasound or trypsin detachment. Binding of monoclonal antibodies that define normal and tumor-associated antigens on melanoma and colorectal carcinoma cells was not affected by ultrasound in 21 out of 23 cases. The 40 kDa colorectal carcinoma-associated antigen defined by monoclonal antibody CO 17-1A was more highly expressed after ultrasonication than trypsinization. The antigen defined by antibody CO 44.1 on these cells was more sensitive to sonication. This method represents a rapid, effective and gentle alternative to trypsin detachment of cultured cells, especially when repeated cell washing or centrifugation steps are required.
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PMID:Rapid dissociation of adherent human tumor cells by ultrasound. 331 90

Generalized malnutrition results in inhibition of tumorigenesis and tumor growth in experimental animal models. Neither the specific nutrient deficiency nor the mechanism has been definitely elucidated. We have shown previously that dietary sodium deprivation in rapidly growing rats retards protoplasmic growth. This effect was correlated to the extracellular fluid (ECF) volume expansion which is dependent on sodium accumulation. Since solid tumors are composed of a large quantity of ECF (which includes plasma volume) it was postulated that preventing the accumulation of new ECF by means of sodium restriction would influence tumor growth. The present study was designed to determine the effects of salt restriction on tumor growth and to relate these effects to ECF volume. Approximately 10(6) viable B16 melanoma cells were injected into C57BL/6 x DBA/2 F1 and C57 mice. A salt restricted diet (sodium less than 3 microeq/g) was provided ad libitum. The drinking solution was distilled water for the experimental group and 0.45% saline solution for the controls. There was a significant decrease in tumor growth rates during sodium restriction. The total body ECF volume increased when dietary sodium was supplied but did not change during salt restriction. Therefore, the only source for the ECF in the tumor mass was from nontumorous tissue. We conclude that during dietary sodium restriction solid tumor growth is retarded and can proceed only to the extent that ECF is released from cachectic body tissues.
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PMID:Restriction of tumor growth in mice by sodium-deficient diet. 337 Jun 41

The antimetastatic effect of a new water-soluble derivative of camptothecin, 7-ethyl-10-(4-(1-piperidino)-1-piperidino) carbonyloxy-camptothecin (CPT-11), were examined in several metastatic murine tumor systems. Intravenous (i.v.) injection of CPT-11 into BALB/c mice inhibited lung metastasis by i.v. inoculated, metastatic colonic adenocarcinoma 26 (C26) cells, C26NL-17, in BALB/c mice. This treatment was also effective in C57BL/6 mice against lung metastasis by i.v. inoculated B16-F10 and B16-BL6 cells, highly metastatic variants of the B16 melanoma. Furthermore, intraperitoneal (i.p.) injection of CPT-11 significantly inhibited the growth of C26NL-22 cells, a highly metastatic variant of C26, inoculated subcutaneously (s.c.) into the left front footpads of BALB/c mice. Also, i.p. or i.v. injection of CPT-11 effectively inhibited the growth of 3LL tumors inoculated s.c. into the hind footpads of C57BL/6 mice. Moreover, following s.c. inoculation of either C26NL-22 or 3LL cells, combined surgical excision of the primary tumor and either i.p. or i.v. CPT-11 injections given before or after surgery markedly inhibited the formation of pulmonary metastases. These results show that a new derivative of camptothecin, CPT-11, has a potent inhibitory effect against both spontaneous and experimental lung metastasis.
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PMID:Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. 337 Jul 38


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