Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunomodulatory substances have been used as antineoplastic agents in experimental and human systems. Many of these agents were derived from microorganisms. Several biologically active fractions have been isolated from Nocardia. These derivatives were shown to induce interferon production, to activate natural killer cells and macrophages and to exert an antitumoral effect. We attempted to examine the mechanism of the antitumoral activity of the Nocardia water-soluble mitogen (NWSM). The tumor tested was the Lewis lung carcinoma (3LL). Regular histological examination and identification of the cellular immune reaction by monoclonal antibodies against macrophages (Mac 1 antigen), B- (IgG expressing) and T-lymphocytes (anti-Lyt-1), analysed by flow cytometry, were performed on samples of the tumor site and of the spleen. Intratumoral administration of the immunomodulators resulted in a massive accumulation of inflammatory cells around the tumor in mice treated with NWSM. The thick rim of infiltrating cells consisted of macrophages and lymphocytes, while the nontreated tumor was found to provoke only a scanty lymphocyte infiltration. Macrophages were, therefore, present at the tumor site and were directly implicated in the antitumoral effect of the Nocardia immunomodulator. T-lymphocytes were also observed at the site of the tumor. The spleen reaction consisted of marked extramedullary hematopoiesis and enlarged follicles containing prominent germinal centres (assessed also by a FACS-demonstrated increase in B-lymphocytes). In view of the inefficiency of chemotherapy in the treatment of advanced cancer, it is of major importance to explore alternative cancer treatment modalities. Immunotherapy is a particularly interesting alternative since it can potentially affect metastatic disease.
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PMID:Antitumoral activity of an immunomodulatory fraction of Nocardia opaca: mechanism of action. 792 96

2'-Deoxy-2'-isocyano-1-beta-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2'-azido-2'-deoxy-1-beta-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2'-deoxy-2'-isocyanocytidine (14b) failed due to the insertion of the 2'-alpha isocyano group into the 3'-OH group, affording the 2',3'-oxazoline derivative 15b. Stability of the isocyano derivative 6a and 2',3'-oxazoline derivative 15a under basic and acidic conditions were examined. The isocyano group in 6a was stable in basic conditions but unstable even in weakly acidic conditions to furnish the corresponding 2'-beta formamide derivative 17. Compound 15a was easily hydrolyzed the corresponding 2'-alpha formamide derivative 16 on treatment with H2O at room temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor volume inhibition.
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PMID:Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-beta-D-arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents. 827

Paclitaxel-2-ethylcarbonate (PC) is a prototype for a family of paclitaxel prodrugs that have significant levels of antitumor activities in rodent models for human cancer. In this study, an enzyme responsible for the conversion of PC to paclitaxel was purified from rat serum. N-terminal amino acid sequence analysis indicated that the isolated enzyme was rat serum carboxylesterase. This enzyme was shown to significantly enhance the cytotoxic activities of both PC and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), a water-soluble analogue of camptothecin, on lung carcinoma and melanoma cell lines. Rat serum carboxylesterase may have applications for the site-specific delivery of anticancer drugs to tumor masses.
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PMID:The role of rat serum carboxylesterase in the activation of paclitaxel and camptothecin prodrugs. 860 86

Six patients are with inappropriate secretion of antidiuretic hormone syndrome are reported (two with bacterial acute meningitis, two with bacterial pneumonia, one with oat cell lung carcinoma, other with mediterranean fever boutonneuse) and the clinical manifestations were: mind changes (four cases) nausea-vomiting (two cases) and inappetence (six cases). All patients presented hyponatremia criteria, serum decreased osmolarity, urinary sodium and osmolarity increased, without edemas, renal disease endocrine (hypophysis, thyroids, adrenal) without diuretic treatment. Treatment was, effective water restriction in three patients and hydrochloride of demeclocycline in other three patients.
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PMID:[Inappropriate ADH secretion syndrome]. 867 42

Natural killer (NK) cells have been described as being very sensitive to oxidative stress. Thus it has been previously shown that chronic administration of oestrone in drinking water of athymic mice xenografted with a wide variety of human tumours, increases their growth and development. In this study an investigation was made to see whether oestrone supplementation could influence the NK cell activity by changes in the antioxidant defences which result in an oxidative stress and influence the proliferation of tumours. Supplementary oestrone was administered in drinking water of athymic mice xenografted with two different human tumours which lack oestrogen receptors: a bladder carcinoma and a small-cell lung carcinoma. The growth of the urothelial carcinoma was poorly affected by oestrone, but oestrone significantly (p<0.01) increased the proliferation of the small-cell lung carcinoma. The average uterus weight was increased by 62% in oestrone treated mice with no modifications in plasma zinc and selenium status, nor in erythrocyte copper zinc superoxide dismutase level. Nevertheless a slight decrease in erythrocyte glutathione peroxidase activity was noted. Trace elements and antioxidant enzymes in liver homogenates remained unchanged. Oestrone treatment also had no effect on plasma and liver lipid peroxides. The immune response was evaluated by measuring NK activity of splenocytes against 51Cr labelled YAC-I target cells. A 35.5% decrease in the NK activity (p<0.001) was observed after oestrone treatment and may be responsible for graft tolerance. However, the results of these experiments seem to exclude the role of oxidative stress in the modulation of NK activity.
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PMID:Effect of oestrone on the natural killer (NK) cell activity, antioxidant status and tumour growth in athymic mice xenografted with human tumours. 868 41

In vitro studies have suggested that vitamin A lowers invasive potential of squamous cell carcinoma. Epidemiological data have also indicated that high dose vitamin A may improve survival in patients with previously resected lung carcinoma. To our knowledge, no studies have attempted to test the in vivo effect of vitamin A on the morphology and growth rate of lung and head and neck cancer. Freshly resected tumor cell suspensions were obtained by ex vivo fine needle aspiration and injected subcutaneously in duplicate in athymic male nude mice. Two to six weeks post-engraftment tests and controls were separated for each xenograft. Mice with test xenografts were given water soluble vitamin A (Aquasol ATM, Astra pharmaceutical, Westborough, MA, U.S.A) at a dose of 10,000 U/Kg/day intraperitoneally for 6 to 10 weeks (median 8 weeks). One to two hours prior to sacrifice bromodexouridine (BrdU) was injected intraperitoneally to assess the S-phase fraction in both test and control xenografts. Blood vitamin A levels in test and control animals were measured after sacrifice using high performance liquid chromatography (HPLC). Sections of test and control xenografts were routinely stained to assess morphologic differentiation and mitotic counts. Unstained sections of xenografts were immunostained by the antibody to BrdU to test for BrdU labeling index (BLI) reflecting S-phase fraction (SPF) and also by the MIB-1 antibody to assess proliferative activity. Eighteen tumors were studied. These included 9 squamous cell carcinomas of the lung, 5 squamous cell carcinomas of the head and neck, and 4 adenocarcinomas of the lung. Blood levels of vitamin A in test animals were 7 to 23 times those of the control animals (median 13 times). Neovascularization of the xenografts was seen in all cases. The morphology and mitotic activity of the test and control xenografts showed no significant difference. SPF and proliferative activity measured by BrdU and MIB-1 immunolabelling respectively showed no significant difference between test and control xenografts. Our study suggests that there is no significant in vivo effect of high dose vitamin A on the morphology and growth rate of xenografted non small cell carcinoma of the lung or squamous cell carcinoma of the head and neck.
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PMID:The effect of high dose vitamin A on the morphology and proliferative activity of xenograft lung and head and neck cancer. 879 35

Cachexia frequently occurs in the late stages of cancer, and is difficult to manage. We previously reported that interleukin-6 (IL-6) cDNA transfection into Lewis lung carcinoma (LLC-IL6) induced cachexia-like symptoms in C57BL/6 mice. This was thought to be a useful experimental model of cancer cachexia. We have examined the effects of two eicosanoids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in order to evaluate whether they could relieve cachexia. LLC-IL6-bearing animals were divided into three treatment groups receiving DHA, EPA or water as the control; 80-microliter samples of these compounds (purity > 95%) were administered orally by catheter daily starting 7 days after tumor transplantation. Tumor growth curves were similar in the three groups. There were no differences in water or food intake in the three groups. However, body weight, a marker of cachexia, was significantly higher in treated mice than in the control group. Sixteen days after tumor transplantation, the mean body weight was 17.45 g (P < 0.05), 17.2 g and 16.41 g in the groups receiving DHA, EPA and water respectively. The eicosanoids did not affect serum levels of IL-6. Ubiquitination of muscle protein, a marker of proteolysis coupled to cachexia, was compared in LLC-IL6- and LLC-transplanted mice. The eicosanoids prevented the ubiquitination of approximately 180 kDa protein. These results suggest that eicosanoids may prevent the cachexia mediated by IL-6.
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PMID:Improvement by eicosanoids in cancer cachexia induced by LLC-IL6 transplantation. 895 67

Various kinds of water-soluble quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines were synthesized in a search for compounds with potent antitumor activity and low toxicity. Some compounds exhibited more potent antitumor activities than elliptinium (1) and SUN 4599 (3). In particular, 2-(3'-methoxy-2'-oxopropanoxy)-9- hydroxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazolium bromide (4d) showed potent antitumor activities against P388 leukemia, colon 26, and Lewis lung carcinoma.
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PMID:Synthesis and antitumor activity of quaternary salts of 2-(2'-oxoalkoxy)-9-hydroxyellipticines. 902 75

Various kinds of water-soluble 9-acyloxyellipticine derivatives were synthesized in a search for compounds with potent antitumor activity. Antitumor activities against several tumors in mice (P388 leukemia, colon 26, Lewis lung carcinoma and B16 melanoma) were evaluated by using intravenous administration. Many compounds exhibited good antitumor activities; in particular, the glutarate derivative (5o) showed potent antitumor activity. This compound (5o) may be converted to 9-hydroxyellipticine (2) by enzyme-catalyzed hydrolysis in the body.
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PMID:Synthesis and antitumor activity of 9-acyloxyellipticines. 924 49

Although hyperthermia potentiates the effect of radiation, the combined effect decreases as the time between irradiation and hyperthermia increases. The purpose of this study was to prevent the rapid loss of efficacy by the local injection of epinephrine or peplomycin(PEP), two agents known as hyperthermic potentiators. In this study, Lewis lung carcinoma implanted in the foot of BDF1 mice was used for the assessment of tumor growth, skin reactions, and lung metastasis. The tumors were irradiated, then warmed in a water bath for 45 min. The retarding effects of hyperthermia on tumor growth and skin reactions were lost 2 days after irradiation. However, when PEP or epinephrine was injected before hyperthermia, tumor growth was distinctly delayed. The effect of epinephrine was greater than PEP and still showed enhancement 8 days after irradiation. For skin reactions, no significant enhancing effect was observed. Lung metastasis was significantly inhibited by the addition of epinephrine either 0 or 2 days after irradiation. In conclusion, the local administration of epinephrine combined with hyperthermia significantly retarded tumor growth without an increase in skin reactions or lung metastases. Possible mechanism underlying this phenomenon was discussed.
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PMID:Epinephrine or peplomycin combined with hyperthermia in irradiated Lewis lung carcinoma: effects on tumor growth, skin reaction, and lung metastasis. 930 Sep 77


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