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)

We have studied the effects of low-dose recombinant interleukin-2 preceded by low-dose cyclophosphamide on malignant melanoma. Thirty eight outpatients aged from 25 to 75 years were treated with interleukin-2, 3.6 million Cetus units/m2 i.v. daily for five days on two successive weeks beginning three days after 350 mg/m2 of intravenous cyclophosphamide. This schedule was repeated at least twice more with a one-week interval between cycles, usually at the same dosage level. Ten of the 38 patients (26.3%) had clinically significant remissions: two complete (5.3%), seven partial (18.4%), and one ongoing, long-term (greater than 18 mo) "minor" response (2.6%). Four others (10.5%) had shorter minor responses and four (10.5%) a mixed response. One patient with disease restricted to the skin had a complete remission, while the other patient with a complete remission had had three lung nodules and an enlarged hilar lymph node. It was gratifying that one of the major sites of disease responding to treatment was the liver. Two complete and two partial remissions (i.e., greater than 50% regressions for greater than four weeks at this site) were obtained in 10 patients with liver involvement. Lung metastases also responded in four of 16 patients (one complete and three partial remissions). Subcutaneous nodules responded in seven of 21 patients (two complete, five partial remissions), while lymph node metastases diminished significantly in four of 14 patients (one complete, three partial remissions). The median duration of response was nine months (range, 1.5-20 months), with four patients treated for more than one year. Toxicity was moderate and controllable, and only two patients required hospitalization, both overnight. Lymphokine activated killer cell activation was induced in 24 of 38 patients, including all nine of the major responders. Conversely, none of 14 patients without lymphokine activated killer cell activation had a significant clinical remission. This regimen appeared to be as effective in melanoma as those involving ex vivo activation of lymphokine activated killer cells, and was more tolerable than therapy with high doses of interleukin-2.
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PMID:Low-dose cyclophosphamide and low-dose interleukin-2 for malignant melanoma. 253 54

The oral administration of hen egg-white lysozyme to mice bearing B16 melanoma significantly reduces the formation of spontaneous lung metastases and, when combined with surgical removal of the primary tumor, prolongs the survival of the treated hosts. The antimetastatic effect, comparable with that found in the Lewis lung carcinoma and MCa mammary carcinoma systems, is independent of the direct interaction of lysozyme with tumor cells and tends to indicate the suggested intervention of an indirect action mediated by the induction of host responses.
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PMID:Reduction of B16 melanoma metastases by oral administration of egg-white lysozyme. 259 13

CGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i.m. or s.c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.
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PMID:CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties. 271 56

Forty-seven patients with metastatic malignant melanoma took part in a phase II trial of tauromustine (TCNU), a new chlorethylnitrosourea based on the endogenous amino acid taurine. TCNU was given orally at a dosage of 130 mg/m2 every fifth week. No patient had previously received cytotoxic therapy. Among 37 evaluable patients, 26 patients experienced progressive disease including seven patients with early death, five showed no change, and six partial responses, yielding an objective response rate of 16%. Responses were limited to subcutaneous, lymph node, bone and lung metastases. Median time to progression was 26 weeks for responders. The treatment schedule was well tolerated with a median dose of 88% of the predicted dose given during all cycles. Dose-limiting toxicity was thrombocytopenia. It appears that TCNU is active in disseminated malignant melanoma with a response rate similar to other nitrosoureas.
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PMID:Phase II study of tauromustine in disseminated malignant melanoma. 271 42

Melanomas growing in the feet of syngeneic C57BL/6 mice were treated with a single dose of X-irradiation. After doses of 0, 3.75, 7.5, 10, 20, or 30 Gy the tumor-bearing limb was amputated at tumor sizes 1, 2, 3, 4, or 5 mm. After doses of 40, 50, 62.5, or 72.5 Gy, progressive tumor growth did not occur, and amputation of tumor-bearing limbs was done when controls were 1, 2, 3, 4, or 5 mm in size. Eighteen days after amputation the mice were killed, and pulmonary metastases were documented at autopsy. None of the mice developed pulmonary metastases after curative irradiation of the primary foot tumor. After subcurative irradiation there was a significant increase (P less than .003) in pulmonary metastases. The size of the primary melanoma is important in the prediction of these metastases. In this model melanomas can be cured by an adequate dose of irradiation, but in those not cured the incidence of lung metastases is increased. The impact of this biologic phenomenon on survival is unclear.
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PMID:Lung metastases after curative or noncurative irradiation of microscopic primary melanomas. 271 31

B16 melanoma-derived cell lines and clones that initiate rapid-growing and nonmetastatic tumors in normal young (2-month-old) mice were previously shown to form slower-growing and highly metastatic tumors in normal mature or aged (greater than 10-month-old) mice. Similarly, slower tumor growth and enhanced metastasis occurred in young mice hyperimmunized against tumor-associated antigens. The metastatic characteristics of subcutaneous tumors initiated by one B16 melanoma clone, G3.26, were examined in normal young mice, normal mature mice, young mice immunized against G3.26 cells, and young mice maintained on a diet of 50% less food than usual. In normal young mice, tumors rarely disseminated viable lung metastases, even at very large sizes, and viable tumor cells were not detected in blood obtained by whole-body vascular perfusion. In contrast, tumors in mature, in immunized, and in calorie-restricted mice gave rise to visible lung metastases in 60-90% of mice, with dissemination beginning at relatively small tumor sizes. These tumors grew 27-78% slower than tumors in normal young mice, but in no case was expression of metastatic activity dependent on longer host survival. In all three experimental hosts, metastatic activity was transient and not expressed during subsequent growth of metastases in young mice. Different host mechanisms operating in mature, immune, and calorie-restricted mice were probably responsible for suppressing tumor growth. However, the consistent generation of metastatic activity under such diverse conditions suggests a common basis for promotion of metastasis, possibly related to intratumor environment alterations resulting from slower tumor growth.
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PMID:The role of intratumor environment in determining spontaneous metastatic activity of a B16 melanoma clone. 273 43

Experimental lung metastases regularly developed in athymic Han:rnu/rnu Rowett rats after i.v. injection of LOX human malignant melanoma cells. When 5 x 10(5) tumor cells were injected into 4-week-old rats, 89% of the animals died of lung tumors, with a mean survival time of 18 days. With 5- and 6-week-old rats, however, the fraction of animals that died decreased to 80 and 46%, with mean survival times of 35 and 38 days, respectively. The number of detectable lung colonies in each animal was about 35 in 5- and 6-week-old animals, compared to nearly 300 in 4-week-old rats. In the latter, a correlation was found between the number of tumor cells injected and the number of detectable lung colonies. The capacity of the LOX tumor to grow s.c. and to form experimental lung metastases was, by and large, similar in young nude rats and in nude mice, and no significant difference in morphology between the different tumors in the two species was seen. A high-resolution radiographic method was used to visualize lung colonies in the nude rats, and single tumors with diameters as small as 2-4 mm could be detected. By this method, for the first time, the effect of chemotherapy on a human tumor growing in a visceral organ of a rodent host could be followed by repeat X-ray examinations, mimicking a situation commonly faced in the clinic. This procedure may prove particularly useful for experimental chemotherapy studies, and may be extended to other human tumors that frequently metastasize to the lungs. Indications were obtained that some host-specific differences in tissue-preferenced growth might exist, a possibility that will be further explored.
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PMID:A human tumor lung metastasis model in athymic nude rats. 276 84

Trehalose-6,6'-dimycolate (TDM) and its monosaccharide-type analogues were synthesized, and their lethal and adjuvant activities were examined in mice. All the monosaccharide-type analogues with a glucose or N-acetylglucosamine moiety were devoid of lethal toxicity to mice; in particular, D-GlcNAcM(1-deoxy) and D-GlcNM did not cause any loss of body weight at an early stage after intravenous administration as a 9% oil-in-water emulsion. Intraperitoneal administration of D-GlcNAcM(1-deoxy) in aqueous suspension, as well as TDM, could activate macrophages to become tumoricidal against tumour cells, whereas D-GlcNAcM(1-deoxy) in oil emulsion, unlike TDM, caused no granulomatous formation in the lung after intravenous injection. Squalane-treated D-GlcNAcM(1-deoxy) showed significant inhibition of spontaneous lung metastases by B16-BL6 melanoma cells when it was administered twice intratumorally. The non-toxic monosaccharide-type analogue of TDM [D-GlcNAcM(1-deoxy)] was a beneficial adjuvant for the activation of macrophages and the prevention of cancer metastasis.
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PMID:Lethal toxicity and adjuvant activities of synthetic TDM and its related compounds in mice. 278 60

Adoptive immunotherapy with lymphokine-activated killer (LAK) cells and systemic administration of recombinant Interleukin-2 (RIL-2) was carried out in a case of malignant melanoma with lung metastases. Histological specimens from the lung showed a metastatic melanoma heavily invaded by atypical lymphoid cells with convoluted nuclei of varying size. Immunohistochemistry revealed that these cells had the characteristic exclusively of natural killer cell (Leu-7+). Nodules of these cells mimicked the appearance of non-Hodgkin's lymphoma of pleomorphic type. Molecular cytogenetic analysis, however, showed the absence of rearranged bands for the T-cell receptor beta-chain gene, indicating the absence of T-cell clones. At autopsy, 1 month after the LAK therapy, the heavy invasion of convoluted cells had disappeared. These findings clearly indicate that the LAK cell plus RIL-2 therapy induced Leu-7+ lymphoid cells, phenotypically suggestive of natural killer cell aggregation in the tumours.
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PMID:Histological evidence of natural killer cell aggregation against malignant melanoma induced by adoptive immunotherapy with lymphokine-activated killer cells. 278 98

The production of colony-stimulating factor (CSF) by murine transformed cells was investigated in 10 cell lines derived from spontaneous or chemically induced tumours and from cells transformed by SV40 or Moloney-MSV; histologic types included carcinomas, sarcomas and melanoma. Nine of 10 supernatants contained CSF activity as judged by in vitro proliferation and differentiation of normal murine monocytic and granulocytic progenitors in agar cultures. Tumours induced with CSF-producing cells caused alterations of haemopoiesis which can include leukocytosis, granulocytosis and splenomegaly. Haemopoietic alterations were also evident in the absence of a local tumour in mice bearing large experimental lung metastases. Production of CSF seems to be a frequent finding among murine cell lines, and its biological and immunological consequences on host-tumour relationships should be taken into account.
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PMID:In vivo and in vitro production of haemopoietic colony-stimulating activity by murine cell lines of different origin: a frequent finding. 280 50


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