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)

The isolated laminin receptor (LN-R) labeled by 125I was reconstituted into liposomes. 125I-LN-R-liposomes and free 125I-LN-R were separated by Sepharose 4B column chromatography. The LN-R-liposomes showed affinity for laminin (LN) and were capable of binding to immobilized LN substrate. In order to make transplantation of LN-R, LN-R-liposomes were fused with cultured murine Lewis lung carcinoma cells with the help of polyethylene glycol (PEG) induction. The radiation with the fused cells was not removed by salt solution. The binding of the fused cells enriched in foreign LN-R to LN substrate increased by 87.5%. Furthermore, the murine Lewis lung carcinoma cells with and without transplanted LN-R were injected into C57BL/6J mice through tail veins (5 x 10(5) cells/each mouse) respectively. The mice in the test group died earlier than those in the control group. The total weight of lung tumor in the test group remarkably increased in comparison with those in the control group. The results taken together directly demonstrated that LN-R on carcinoma cell surface were involved in the recognition and binding of the cancer cells to LN in basement membranes, and also LN-R was of a crucial biological molecule in cancer metastasis.
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PMID:Studies on transplantation of the laminin receptor and its roles in experimental metastasis of murine Lewis lung carcinoma cells. 130 46

The recovery of the enzyme poly(ADP-ribose) polymerase (pADPRp) in the nuclease- and 1.6 M NaCl-resistant nuclear subfraction prepared from a number of different sources was assessed by Western blotting. When rat liver nuclei were treated with DNase I and RNase A followed by 1.6 M NaCl, approximately 10% of the nuclear pADPRp was recovered in the sedimentable fraction. The proportion of pADPRp recovered with the residual fraction decreased to less than 5% of the total nuclear polymerase when nuclei were prepared in the presence of the sulfhydryl blocking reagent iodoacetamide and increased to approximately 50% of the total nuclear pADPRp when nuclei were treated with the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) prior to fractionation. To determine whether this effect of disulfide bond formation was unique to rat liver nuclei, nuclear matrix/cytoskeleton structures were prepared in situ by sequentially treating monolayers of tissue culture cells with Nonidet-P40, DNase I and RNase A, and 1.6 M NaCl (S.H. Kaufmann and J.H. Shaper (1991) Exp. Cell Res. 192, 511-523). When nuclear monolayers were prepared from HTC rat hepatoma cells, CaLu-1 human lung carcinoma cells, and CHO hamster ovary cells in the absence of NaTT, pADPRp was undetectable in the nuclease- and 1.6 M NaCl-resistant fraction. In contrast, when nuclear monolayers were isolated in the presence of NaTT, from 5% (CaLu-1) to 26% (HTC cells) of the total nuclear pADPRp was recovered with the nuclease- and salt-resistant fraction. Examination of these residual structures by SDS-polyacrylamide gel electrophoresis under nonreducing conditions suggested that pADPRp was present as a component of disulfide cross-linked complexes. Further analysis by immunofluorescence revealed that the pADPRp was diffusely distributed throughout the CaLu-1 or CHO nuclear matrix. In addition, when matrices were prepared in the absence of RNase A, pADPRp was also observed in the residual nucleoli. These observations reveal that the recovery of pADPRp with a nuclease- and salt-resistant nuclear subfraction is dependent on the source of the nuclei and on the conditions used to fractionate those nuclei. In addition, these observations raise the possibility that there might be different functional classes of pADPRp molecules within the nucleus.
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PMID:Association of poly(ADP-ribose) polymerase with the nuclear matrix: the role of intermolecular disulfide bond formation, RNA retention, and cell type. 170 86

The hydrosoluble triazene derivatives of phenylacetic, phenylbutyric and cinnamic acid have been synthesized and their logP and pKa values were simultaneously determined according to a multiparametric fitting of potentiometric data. The antitumor activity caused by the synthesized compounds in mice bearing either Lewis lung carcinoma or TLX5 lymphoma was evaluated and discussed in comparison with the parent compound (p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK, CAS 70055-49-1). The tested compounds were at least as active as DM-COOK, the cinnamic and the phenylacetic derivatives being the more active compounds in mice bearing TLX5 lymphoma and Lewis lung carcinoma, respectively.
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PMID:Synthesis and antitumor activity of hydrosoluble analogs of p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt. 181 Feb 63

Purification of the gastrin-releasing peptide (GRP) or bombesin receptor has proved elusive in part due to technical difficulties. In the present studies, the problem of oxidized radioligand was avoided by the use of 125I-GRP, which was verified to be not oxidized by high performance liquid chromatography. Specific 125I-GRP binding (at 0 degrees C) to intact human small cell lung carcinoma NCI-H345 cells which had been subjected to a dilute acid wash was 6 fmol/10(6) cells. Inhibition of GRP degradation by human H345 cell membranes through the use of phenanthroline or phosphoramidon permitted the development of binding assays for the GRP receptor in detergent-solubilized crude membrane preparations. The solubilized GRP receptor exhibited saturable, high affinity (KD = 1.3 nM), temperature-dependent specific binding averaging 402 +/- 65 fmol/mg protein (mean +/- S.E. for eight separate membrane preparations with 125I-GRP concentration = 3 nM), with a Bmax = 434 fmol/mg protein using a gel filtration binding assay. That the GRP receptor had been solubilized was demonstrated by its failure to pellet when centrifuged at 100,000 x g for 60 min, its passage through a 0.22-micron filter without loss of binding activity, and its elution in the void volume of a Sephadex G-50 gel filtration column, but within the inclusion volume of a Sephacryl S-200 column (Ve/V0 = 1.1). Isolation of the GRP receptor from human H345 cell-solubilized membranes was achieved by ligand affinity chromatography. A unique 70-kDa band on silver-stained reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis was reproducibly eluted from GRP14-27 affinity columns by an acidic high salt buffer, but binding activity was denatured by these conditions. The protein nature of the GRP receptor was demonstrated by its sensitivity to proteases after isolation. In addition, two unique bands of 65 and 70 kDa were eluted from the GRP14-27 affinity column with GRP14-27 in neutral buffer, and this eluate possessed specific 125I-GRP binding with a stoichiometry of approximately 1:1. Thus, reported here is the isolation of a functional membrane-associated, saturable, high affinity GRP receptor with temperature-dependent binding from the solubilized membranes of human H345 cells.
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PMID:Isolation of the bombesin/gastrin-releasing peptide receptor from human small cell lung carcinoma NCI-H345 cells. 185 48

The antitumor and antimetastatic effects of p-(3-methyl-1-triazeno)benzoic acid potassium salt (MM-COOK) as compared with those of the parent 3,3-dimethyl derivative (DM-COOK) were examined using Lewis lung carcinoma, MCa mammary carcinoma of the CBA mouse and TLX5 lymphoma. Similarly to DM-COOK, MM-COOK reduces metastasis formation and significantly prolongs the survival of mice bearing the Lewis lung carcinoma when given at a daily dose corresponding to one-half that of DM-COOK. Unlike DM-COOK, MM-COOK exhibits significant cytotoxicity to metastatic foci and pronounced inhibition of primary tumor development. MM-COOK also causes cytotoxic effects on TLX5 lymphoma cell growing in the peritoneal cavity, even when used at low doses. The antimetastatic effects observed in mice bearing MCa mammary carcinoma are unrelated to the inhibition of primary tumor growth and are more likely due to the selection of clones endowed with lower metastatic ability. It appears that MM-COOK exhibits the same antineoplastic activity as DM-COOK, but the former does so at a lower daily dose and produces interesting cytotoxic effects other than those reflecting its antimetastatic properties. It thus seems to be a valid alternative to DM-COOK, in view of the possible introduction of newer aryltriazenes into clinical use.
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PMID:Antineoplastic action of p-(3-methyl-1-triazeno)benzoic acid potassium salt, a monomethyl derivative of the antimetastatic compound DM-COOK. 201 12

The aim of this study is to investigate the hydrolysis of 1,3-di(p-carboxyphenyl)triazene dipotassium salt, AVIS (1), over a pH range of 2.60-8.50. This compound decomposes into p-aminobenzoic acid and the corresponding diazonium cation with no formation of alkylcarbo cations; the same compounds are formed from hydrolyses of DM-COOK (2), an antimetastatic agent, and of its possible demethylated metabolite, MM-COOK (3), a chemical xenogenization inducer. In these latter cases, however, a methylcarbo cation is formed. The pH dependence of the pseudo-first-order rate constants is intermediate between 2 and 3. Preliminary data on its toxicity and antitumor activity on both Lewis lung carcinoma and TLX5 lymphoma seem to indicate the essential role of alkylcarbo cation in mediating the antitumor action of aryldimethyltriazenes.
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PMID:Kinetic investigation of the aqueous stability and antitumor activity of a hydrosoluble diaryltriazene, AVIS, related to the antimetastatic agent DM-COOK. 208 82

Therapeutic effects were obtained after systemic treatment of athymic mice bearing an epidermoid non-small cell human lung carcinoma (NSCLC) xenograft with tricyclodecan-9-yl xanthogenate (D609) and the potassium salt of a fatty (dodecanoic) acid. Extensive intratumoral necrosis was observed 3 days after the treatment.
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PMID:Systemic treatment of a human epidermoid non-small cell lung carcinoma xenograft with a xanthate compound causes extensive intratumoral necrosis. 217 4

A novel antitumor compound, N-beta-dimethyl-aminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of greater than 200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1-5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a greater than 280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1-5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1-5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a greater than 300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3-10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1-5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3-10), and a greater than 161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3-10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1-5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.
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PMID:In vivo activity on murine tumors of a novel antitumor compound, N-beta-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190). 292 70

Endogenous carbohydrate-binding proteins (lectins) were detected in specimens of tumor tissue (undifferentiated carcinoma and xenografted small-cell carcinoma) from human lung. Fractionation of salt and detergent extracts on different sets of Sepharose columns covalently derivatized with lactose, asialofetuin, melibiose, mannan, and fucose, successive elution with a chelating agent and a specific sugar, and analysis of the eluates by gel electrophoresis, resulted in the characterization of the profiles of endogenous carbohydrate-binding proteins. All preparations were devoid of enzymatic activity. Comparison between the patterns of the two types of lung carcinoma showed significant qualitative differences, e.g. the presence of fucose-binding proteins of apparent molecular weights 60,000 and 80,000 in the undifferentiated carcinoma, and the presence of beta-galactoside-binding proteins of apparent molecular weights 18,000 and 22,000 in the small-cell lung carcinoma. These proteins were not detectable in normal lung tissue. Such differences, documented for the first time for human lung tumors, are of potential importance as a step towards a lectin-based refinement of lung-cancer diagnosis and therapy.
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PMID:Expression of endogenous lectins in human small-cell carcinoma and undifferentiated carcinoma of the lung. 304 Feb 51

Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. It has demonstrated antitumor activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia K-1964, adenocarcinoma 755, mammary carcinoma YMC, reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma 124F. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved. The major route of elimination is the kidneys, with 35%-71% of the infused dose excreted within 24 hours. Three phase I studies suggested the following phase II doses: 700-750 mg/m2 by short infusion, once every 2-3 weeks; 300 mg/m2/day by short infusion for 3 consecutive days, to be repeated every 2 weeks; and 300 mg/m2/day by continuous infusion for 7 consecutive days, to be repeated every 3-5 weeks. The major organ toxicity reported was renal; however, this can be adequately controlled either by hydration and osmotic diuresis or by use of continuous schedule. (Either maneuver appears to allow delivery of the recommended phase II dose with a less than 30% risk of change in serum creatinine.) In limited phase II evaluation, the drug has shown antitumor activity in patients with either refractory lymphomas or small cell lung carcinoma, with total objective response rates of 28% and 11%, respectively. In addition, it has been effective in the treatment of patients with cancer-related hypercalcemia by having an inhibitory effect on calcium reabsorption from bone. Single-agent phase II studies are planned in all major tumor types. Some are already ongoing in patients with genitourinary malignancies (renal, bladder, prostate, testicular), small cell lung carcinoma, and multiple myeloma. Metabolic studies are in progress at Memorial Sloan-Kettering Cancer Center to further elucidate the mechanism or mechanisms of the hypocalcemic effects.
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PMID:Gallium nitrate: the second metal with clinical activity. 353 51


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