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)

Picibanil (OK432), a pharmaceutical preparation of a low virulent Su strain of Streptococcus pyogenes, possesses cell regulatory activity particularly in its ability to augment natural killer (NK) cell activity and to activate macrophages to exert a tumoricidal effect both in vitro and in vivo. It is effective in retarding and/or inhibiting the growth of three different tumors: MBL-2 lymphoma, M109 alveolar adenocarcinoma, and B16 melanoma. The antitumor effect is mediated through regulation of NK cells and macrophages, possibly by its ability to stimulate the production and secretion of interferon and interleukin 1 and 2. It is a very effective adjuvant for tumor cell vaccines that elicit cytotoxic T-cell responses. Following cytoreductive chemotherapy (Cytoxan) Picibanil treatment leads to an earlier reconstitution of both bone marrow cellularity and differentiation to granulocyte-macrophage colonies.
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PMID:Cell regulatory and immunorestorative activity of picibanil (OK432). 348 58

The encapsulation of Cyclophosphamide in MLV (PC:CH 1:1) revealed a total loss of antineoplastic activity in the P 388 tumour model compared to an equal dose of the free drug, though a moderate toxicity, registered as decrease of leukocyte and platelet counts, was still present. CCNU in liposomes of different size and composition showed in lower doses a diminished therapeutic effectiveness in the P388 or L 1210 leukaemia and the B 16 melanoma, while in higher doses toxic deaths occurring with the free drug could be prevented totally by using liposomes. Liposomal encapsulation also influenced body weight change and leukocyte counts, causing them to be less drastically reduced than with use of the free drug. The entrapment of Cytostasan, an N-lost derivative, had the same effect on the increase of lifespan of tumour-bearing animals (mammary carcinoma 1142 A) as equal doses of the free drug and caused only a slight improvement of toxicity. In general, liposomal encapsulation of alkylating cytostatics seems advantageous only for certain lipophilic drugs.
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PMID:Antineoplastic activity and toxicity of some alkylating cytostatics (cyclophosphamide, CCNU, cytostasan) encapsulated in liposomes in different murine tumour models. 350 81

Both B16 melanoma and Lewis lung carcinoma growing in C57/Bl mice spontaneously metastasize to the lungs and other organs. When the tumors are grown in the mouse tail to a specific volume and amputated, the spontaneously disseminated tumor cells can then be independently treated. The effects of a single dose of cyclophosphamide (200 mg/kg), cis-platinum (6 mg/kg) and melphalan (10 mg/kg) on the appearance of pulmonary and other metastases were measured. The cis-platinum treatment was shown to reduce the number and incidence of metastases of both tumors at various times after treatment. The antimetastatic effectiveness of cis-platinum against these two tumors was increased when 2.4 mg/kg was administered each day for five consecutive days after amputation of the primary. Cyclophosphamide, when administered at two-thirds maximum tolerated dose, had a small promoting effect on the number and incidence of pulmonary metastases of Lewis lung carcinoma, whereas, applied in the same dose, it had efficacy in the treatment of disseminated B16 melanoma and inhibited appearance of both pulmonary and lymph-node metastases. When melphalan was administered in single- and multiple-dose regimens, the number and incidence of metastases of both tumors increased at various times after primary tumor amputation. These data suggest that melphalan can promote the growth of disseminated tumor cells in both the lungs and other sites and that some systemic chemotherapies may result in promotion instead of suppression of metastatic disease.
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PMID:The effectiveness of cis-platinum, cyclophosphamide and melphalan in treating disseminated tumor cells in mice. 365 51

Immunotherapeutic agents are often reported to induce opposite effects -- inhibitory and stimulatory -- on tumor growth, depending on the dose, timing or route of administration of the drug. The reason underlying these opposite effects is not yet known. The immunomodulatory polysaccharide levan (polyfructose) has been found to exert such opposite effects on the growth of the F10 variant of B16 melanoma. Low doses inhibit and high doses enhance tumor growth. Cyclophosphamide (CY) augment the inhibitory effect of levan. In order to clarify the mechanism of this switch, we tried in the present study to determine the changes induced by levan at inhibitory and stimulatory treatments, alone or with CY, on the morphology of spleens and lymph nodes of the melanoma-bearing mice. The growth of the tumor in non-treated mice was found to induce a moderate splenomegaly. Microscopically, two main changes were observed: a mild extramedullary hematopoiesis and a sharp increase in the number of germinal centers. A parallel increase in germinal center number was found in the lymph nodes. The data presented suggest that the immune system plays a role in both the inhibition and stimulation of tumor growth by levan. Levan induced a dose dependent splenomegaly, even more pronounced in combination with CY, due to an extramedullary hematopoiesis. Levan reduced the B cell activity caused by the tumor, proportionally to its dose. In combination with CY, levan accelerated the recovery of the B cell activity at the low dose, while the high dose prevented it. A similar trend was found in the lymph nodes. The changes involved in the switch inhibition-stimulation could be either the degree of reduction in B cell activity or the degree of extramedullary hematopoiesis or some interplay between the myelocytic and lymphocytic series, which was found to change in an opposite fashion under the influence of various treatments. Since the immune system is a finely equilibrated system, it is possible that immunomodulation rather than immunostimulation should be aimed at in cancer immunotherapy. However, the conditions required for achieving this equilibrium have to be defined.
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PMID:Effect of tumor inhibitory and stimulatory doses of levan, alone and in combination with cyclophosphamide, on spleen and lymph nodes. 374 40

A total of 14 patients, 7 male and 7 female, received in all 21 evaluable courses of cyclophosphamide administered by 5-day continuous infusion. Cyclophosphamide doses were escalated from 300 to 400 mg/m2 per day for 5 days and repeated every 21-28 days. The patient population had a median age of 55 years (range 38-76) and a median Karnofsky performance status of 80 (range 60-100). Only 1 patient had not received prior therapy; 5 patients had received only prior chemotherapy, 1 had received only prior radiotherapy, and 7 had received both. Tumor types were gastric (1), lung (2), colon (4), urethral adenocarcinoma (1), cervical (2), chondrosarcoma (1), melanoma (1), uterine leiomyosarcoma (1), and pancreatic (1). The dose-limiting toxicity was granulocytopenia, with median WBC nadir of 1700/microliter (range 100-4800) in 8 heavily pretreated patients treated at 350 mg/m2 per day for 5 days. One patient without heavy prior treatment received two courses at 400 mg/m2 and had WBC nadirs of 800/microliter and 600/microliter. WBC nadirs occurred between days 9 and 21 (median 14). Drug-induced thrombocytopenia occurred in only one patient (350 mg/m2 per day, nadir 85,000/microliter). Neither hyponatremia nor symptomatic hypo-osmolality was observed. Radiation-induced hemorrhagic cystitis may have been worsened in one patient. Nausea and vomiting were mild. Objective remissions were not observed. The maximum tolerated dose for previously treated patients is 350 mg/m2 per day for 5 days. This dose approximates the doses of cyclophosphamide commonly used with bolus administration. Plasma steady-state concentrations (Css) of cyclophosphamide, measured by gas liquid chromatography, were 2.09-6.79 micrograms/ml. Steady state was achieved in 14.5 +/- 5.9 h (mean +/- SD). After the infusion, cyclophosphamide disappeared from plasma monoexponentially, with a t 1/2 of 5.3 +/- 3.6 h. The area under the curve of plasma cyclophosphamide concentrations versus time (AUC) was 543 +/- 150 micrograms/ml h and reflected a cyclophosphamide total-body clearance (CLTB) of 103 +/- 31.6 ml/min. Plasma alkylating activity, assessed by p-nitrobenzyl-pyridine, remained steady at 1.6-4.3 micrograms/ml nor-nitrogen mustard equivalents. Urinary excretion of cyclophosphamide and alkylating activity accounted for 9.3% +/- 7.6% and 15.1% +/- 2.0% of the administered daily dose, respectively. The t1/2 and AUC of cyclophosphamide associated with the 5-day continuous infusion schedule are similar to those reported after administration of cyclophosphamide 1500 mg/m2 as an i.v. bolus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase I clinical and pharmacokinetic study of cyclophosphamide administered by five-day continuous intravenous infusion. 375 57

Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean +/- SD) were as follows: cyclophosphamide, 30 +/- 24 mg/day; azathioprine, 74 +/- 44 mg/day; and hydroxychloroquine sulfate, 210 +/- 92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; cyclophosphamide should be replaced with a nonalkylating agent; and the place of combined drug therapy remains uncertain in the absence of controlled trials.
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PMID:Treatment of intractable rheumatoid arthritis with combined cyclophosphamide, azathioprine, and hydroxychloroquine. A follow-up study. 395 21

Twenty-eight patients with advanced life-threatening metastatic malignant melanoma were treated with high dose (140-260 mgm-2) intravenous melphalan and autologous bone marrow. Cyclophosphamide "priming" 300 mgm-2 i.v. was given to 19 patients one week previously and this resulted in clinical but not histological evidence of amelioration of gastrointestinal toxicity. In 11 patients (43%) there was evidence of tumour response to treatment and in 2 patients complete remissions were observed. However in most patients, responses were short-lived and no patient lived longer than 17 months from start of treatment or 24 months from first recorded evidence of distant metastatic disease.
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PMID:Treatment of advanced malignant melanoma with high-dose melphalan and autologous bone marrow transplantation. 635 83

C57/BL mice bearing either Lewis lung tumor or B16 melanoma tumor were treated with radiation and concurrent chemotherapy. The treatment results were determined in vivo by tumor regrowth delay assay. When continuous infusion of either Cyclophosphamide (CYCLO) or 5-Fluorouracil (5-FU) or Adriamycin (ADRIA) or Mitomycin-C (MITO-C) was used in combination with continuous radiation at 1 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. When multiple drug chemotherapy, FAM (5-FU, ADRIA, MITO-C) was administered in combination with radiation at 80 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. In these two murine tumor models, when clinically relevant concentrations of commonly used chemotherapy agents were combined with radiation, no therapeutic advantage was observed.
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PMID:Radiation and concurrent chemotherapy for the treatment of Lewis lung tumor and B16 melanoma tumor in C57/BL mice. 643 48

The antitumor activity of ASTA Z 7557, a stabilized primary metabolite of cyclophosphamide, was evaluated in comparison with cyclophosphamide (CP) against different rodent tumor systems. At equimolar doses, which corresponded in mg/kg to the optimal doses of each compound, Z 7557 showed a higher therapeutic activity than CP when both drugs were administered intraperitoneally (ip) during 5 consecutive days. The drug remained active against a P388 subline totally resistant to CP, but to a much lesser extent. The ip-implanted B16 melanoma was highly sensitive to 100 and 50 mg/kg administered during 9 consecutive days: an increase in lifespan (ILS) of 244% was produced and 5 mice out of 10 were cured. This treatment administered against Lewis lung carcinoma (LL) transplanted intravenously (iv) induced an ILS of 179% and 3 mice out of 10 survived on day 60. This effect was slightly inferior to that produced by 50 mg/kg of CP, but is balanced by the number of long-term survivors recorded after administration of low doses of Z 7557. When mice bearing the subcutaneously (sc) implanted colon 38 (C38) tumor were treated with 200 mg/kg on days 2 and 9, the tumor growth was inhibited by 83% in comparison to the control mice. The wide range of activity of Z 7557, its stability and its different chemical reactivity as compared to CP appear to justify interest in this activated oxazaphosphorine.
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PMID:Antineoplastic activity of ASTA Z 7557 (NSC-345842, INN mafosfamide) on transplantable murine tumors. 646 11

Insulin and glucagon injected separately or simultaneously into CBA, C57BL, A, or C3Hf/Bu mice with aplastic carcinoma, fibrosarcoma, melanoma B16, Ehrlich tumor, lymphatic leukemia, or thymoma suppressed tumor growth and prolonged the mouse's mean survival time. Basic mechanistic features of growth retardation by insulin and glucagon were delineated for aplastic carcinoma and fibrosarcoma. In mice bearing these 2 tumors, stimulated plaque-forming capacity and phagocytosis were shown for these hormones. Cyclophosphamide abolished the growth retardation. Insulin- and glucagon-induced tumor suppression appeared mainly mediated by maintenance of high immune reactivity and phagocytosis.
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PMID:Retarded growth of murine tumors in vivo by insulin- and glucagon-stimulated immunity and phagocytosis. 701 67


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