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)

An antigen, protein X (Px), was purified from immune complexes isolated from malignant pleural effusions from patients with adenocarcinoma of the lung by EDTA treatment, PEG 8000 precipitation, protein A affinity chromatography, and Sephadex G-200 separation in the presence of 3 M NaCl. The purified antigen had a M(r) 17,000 by SDS-PAGE, and consisted of isoelectric species of pI 6.3 and 6.6. Purified Px recombined with Ig isolated from pleural fluids from patients with lung adenocarcinoma, but not with Ig from patients with breast carcinoma. Using an autologous human and heterologous chicken antibody, Px was found, by immunohistology, in the cytoplasm of some of the well-differentiated lung adenocarcinoma cells, but was not seen in normal lung or a variety of other malignant tissues. A liquid-phase competitive-inhibition RIA was developed. Over 30 ng/ml of Px were found in 9 of 15 pleural fluids from patients with lung carcinoma, none of 20 from patients with breast, ovary, stomach or colon cancer, and in 3 of 15 patients with unknown primary tumor. Our data suggest that Px may be a lung-cancer-associated autoantigen which can elicit a host humoral response in vivo.
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PMID:Characterization of a lung-cancer-associated auto-antigen. 139 30

3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine (FUdR-dipalmitate), a lipophilic prodrug of 5-fluoro-2'-deoxyuridine (FUdR), was incorporated in different types of liposomes. The in vivo distribution and intrahepatic deacylation of liposomal FUdR-dipalmitate was found to be strongly dependent on liposome composition and on drug to lipid ratio. The use of fluid-type liposomes (egg PC/PS/CHOL) rendered FUdR-dipalmitate more susceptible to enzymatic breakdown than solid-type liposomes (DSPC/DPPG/CHOL). A decrease of the retention of the drug in the body was also obtained when FUdR-dipalmitate was incorporated in solid-type liposomes with high drug to lipid ratio (1:10) than with low ratio (1:50). In spite of these substantial differences in the rates at which FUdR was liberated from liposomes with different fluidity, size, or drug to lipid ratio, only minor differences in therapeutic effect were observed in a number of murine tumour models (P388 leukaemia, Lewis Lung carcinoma, B16 melanoma and a C26 adenocarcinoma liver metastasis model). The lipophilic prodrug of FUdR exhibited antitumour activity at 100-600 times lower doses than the free drug. However, at these therapeutic doses FUdR-dipalmitate was also far more toxic. This prohibited the use of higher doses to increase antitumour activity.
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PMID:In vivo distribution and antitumour activity of liposomal 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine. 140 84

To identify DNA sequences that are deleted in human lung cancer, genomic subtraction hybridization was used to construct plasmid libraries that are enriched for DNA sequences deleted in the small cell lung carcinoma cell line SK-LC-17. The clones of the libraries contained predominantly single copy sequences, allowing direct screening of normal and tumor DNA by genomic Southern blotting. Of 150 clones tested, three independent clones (del-27, del-118, and del-109) were identified that specifically hybridized with normal human DNA but not with tumor DNA from the cell line SK-LC-17. The corresponding DNA sequences are localized on human chromosomes 5, 8, and X/Y. The DNA regions identified by del-109 and del-118 were also found to be deleted in several other lung carcinoma cell lines. Moreover, del-118 was deleted in a freshly isolated lymph node metastasis of a human lung adenocarcinoma. It is therefore reasonable to speculate that the identified clones are derived from independent genetic loci encoding potential tumor suppressor genes.
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PMID:Isolation of DNA sequences deleted in lung cancer by genomic difference cloning. 140 87

Sixteen cases of lung carcinoma with spindle cell components were studied by conventional histochemistry and immunohistochemistry. The epithelial components were squamous cell carcinoma in six cases, adenocarcinoma in four, adenosquamous carcinoma in five, and large cell carcinoma in one. In every case sarcomatous areas were distinctly observed and, in general, neoplastic spindle cells proliferated in close proximity to the epithelial elements. Some of the histochemical procedures suggested mesenchymal features in the stroma of the exophytic portions of three cases, but heterogeneous elements, such as bone or striated muscle, were not observed. By immunohistochemical examination the epithelial elements showed positive reactions for keratin, epithelial membrane antigen, and/or carcinoembryonic antigen to a varying degree according to the histologic types. The spindle cell elements revealed a positive immunoreaction for keratin in all but one case. Epithelial membrane antigen was demonstrated in sarcomatous areas of only five cases and carcinoembryonic antigen was not expressed at all. In contrast, vimentin was distinctly demonstrated in sarcomatous areas of five cases, although other mesenchymal markers, such as desmin, actin, and myosin, were negative. These findings indicate that the spindle cell components in these 16 cases may represent mesenchymal features with partial or complete loss of epithelial features.
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PMID:Lung carcinoma with spindle cell components: sixteen cases examined by immunohistochemistry. 142 56

S 9788 is a novel triazinoaminopiperidine derivative which does not belong to any of the classes of compounds known to reverse multidrug resistance (MDR). S 9788 was far more potent than verapamil (VRP) in reversing resistance to adriamycin (ADR) in the ADR-selected murine leukaemia cell lines P388/ADR-1 and P388/ADR-10, and the human chronic myelogenous leukaemia K562/R. Fold reversion with S 9788 (5 microM) was, respectively, 3.5, 5.4 and 11.3 times greater than that with VRP (5 microM). S 9788 was also a more potent reversant of ADR resistance in the intrinsically resistant human colon adenocarcinoma COLO 320DM (2.3 fold), and of vincristine (VCR) resistance in the human MDR1 gene-transfected squamous lung carcinoma line S1/tMDR1 (5.6 fold). The activity of S 9788 depended on both the MDR cell line and the cytotoxic agent. S 9788 (50-100 mg/kg/d) administered IP once a day on days 1-4 resulted in a dose-dependent increase in the chemotherapeutic effect of VCR (0.25 mg/kg/d) in P388/VCR - bearing mice and ADR (4 mg/kg/d) in P388/ADR - bearing mice. Increases in antitumor activity were (% T/C) of +20-34% in the P388/ADR model and + 50-78% in the P388/VCR model with respect to cytotoxic agent treatment alone. S 9788 appeared to be devoid of toxicity at its effective doses. The mechanism of action of S 9788 is unknown but S 9788 (0.5-10 microM) induced a dose-dependent increase in ADR accumulation in KB-Al cells and compared to verapamil its effect was twice as active and approximately seven times more potent. We conclude that S 9788 is a novel agent capable of reversing MDR in vitro and in vivo, and whose pharmacological profile warrants its selection as a candidate drug for eventual assessment in the clinic.
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PMID:In vitro and in vivo circumvention of multidrug resistance by Servier 9788, a novel triazinoaminopiperidine derivative. 142 23

Fifty-seven tannins and related compounds, including gallotannins, ellagitannins, and condensed and complex tannins, were evaluated for their cytotoxicities against human tumor cell lines, including malignant melanoma, lung carcinoma, ileocecal adenocarcinoma, epidermoid carcinoma, malignant melanoma, and medulloblastoma cell lines. Among them, chebulagic acid [1], geraniin [2], sanguiin H-11 [3], 4,5-di-O-galloylquinic acid [12], 1,3,4,5-tetra-O-galloylquinic acid [15], 1(beta)-O-galloylpedunculagin [24], furosin [29], castalagin [38], sanguiin H-2 [34], vescalagin [39], grandinin [40], phyllyraeoidin A [42], (-)-epicatechin 3-O-gallate [50], cinnamtannin B2 [55], and acutissimin A [56] exhibited moderate selective cytotoxicity against PRMI-7951 melanoma cells with ED50 values in the range of 0.1-0.8 microgram/ml. Selective cytotoxicities against the melanoma cells were also observed for strictinin [22], pedunculagin [23], eugeniin [25], elaeocarpusin [28], punicacortein C [37], casuarinin [41], sanguiin H-6 [43], procyanidin B-2 3,3'-di-O-gallate [51], procyanidin C-1 3,3',3"-tri-O-gallate [52], and cinnamtannin B1 [54] with ED50 values of 1-4 micrograms/ml. All of the tannins were found to be inactive (greater than 10 micrograms/ml) against lung carcinoma (A-549), ileocecal adenocarcinoma (HCT-8), epidermoid carcinoma of nasopharnyx (KB), and medulloblastoma (TE-671) tumor cells.
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PMID:Antitumor agents, 129. Tannins and related compounds as selective cytotoxic agents. 143 32

The cyclopropylpyrroloindole analogues are DNA minor-groove binders containing a cyclopropyl group, which mediates N3-adenine covalent adduct formation in a sequence-selective fashion. Carzelesin (U-80244) is a cyclopropylpyrroloindole prodrug containing a relatively nonreactive chloromethyl precursor to the cyclopropyl function. Activation of carzelesin requires two steps, (a) hydrolysis of a phenylurethane substituent to form U-76073, followed by (b) ring closure to form the cyclopropyl-containing DNA-reactive U-76074. The formation of the DNA-reactive U-76074, via U-76073, from carzelesin was shown to proceed very slowly in phosphate-buffered saline (t1/2 greater than 24 h) but to occur rapidly in plasma from mouse, rat, dog, and human (initial t1/2 values ranging from 18 min for mouse to 52 min for rat) and in cell culture medium (t1/2 approximately 40 min). Although carzelesin was less potent in terms of in vitro cytotoxicity and in vivo optimal dosage and showed low affinity for binding to DNA, it was therapeutically more efficacious against mouse L1210 leukemia than was U-76074 or adozelesin (U-73975), another cyclopropylpyrroloindole analogue which is currently in phase I clinical trials. Carzelesin also proved to be more efficacious than U-76074 or adozelesin against mouse pancreatic ductal 02 adenocarcinoma, a system reported to be resistant to every agent tested. Carzelesin was highly effective against this tumor and produced 97% tumor growth inhibition. In addition, i.v. administered carzelesin showed significant activity (National Cancer Institute criteria) against i.v. or s.c. implanted Lewis lung carcinoma, i.p. or s.c. implanted B16 melanoma, s.c. implanted colon 38 carcinoma, and five s.c. implanted human tumor xenografts, including clear cell Caki-1 carcinoma, colon CX-1 adenocarcinoma, lung LX-1 tumor, ovarian 2780 carcinoma, and prostatic DU-145 carcinoma. Carzelesin treatment produced 100% complete remissions (no palpable tumor mass at the termination of the experiment) in mice bearing early-stage human ovarian 2780. Pharmacologically, carzelesin proved to be relatively schedule and route independent and was highly active against i.p. implanted L1210 leukemia, regardless of whether the analogue was given i.v., i.p., s.c., or p.o. These results, collectively, suggest that carzelesin is absorbed and distributed well. Both carzelesin and adozelesin caused marked tumor shrinkage in mice bearing human lung LX-1 or advanced-stage human ovarian 2780 carcinoma; however, tumor regrowth occurred shortly after the treatment with adozelesin was stopped. Little or no apparent tumor regrowth occurred after treatment with carzelesin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytotoxicity and antitumor activity of carzelesin, a prodrug cyclopropylpyrroloindole analogue. 151 47

We report the fine needle aspiration cytology findings in six cases of neuroendocrine tumor of the pancreas. Three cases were from the pancreas, two from hepatic metastases and one from a peripancreatic lymph node metastasis. The cytologic features that permitted a preoperative diagnosis of pancreatic neuroendocrine tumor were: a cellular aspirate; numerous isolated cells and irregular, loose, dyshesive cellular aggregates; minimal nuclear pleomorphism; infrequent mitoses; fine, evenly dispersed nuclear chromatin with occasional inconspicuous nucleoli; a scant-moderate amount of granular, amphophilic, well-defined cytoplasm; clustering of tumor cells around segments of capillaries; and rosette formation. The differential diagnosis includes cells derived from normal pancreatic acini, islet cell hyperplasia, acinic cell carcinoma, well-differentiated pancreatic adenocarcinoma, metastatic small cell undifferentiated carcinoma of the lung, pancreatic small cell anaplastic carcinoma and malignant lymphoma. The application of immunocytochemistry to cytologic smears can be easily and reliably performed to confirm the neuroendocrine nature of the tumor and identify the specific type of polypeptide hormone or hormones produced by these tumors. Four aspirates showed immunoreactivity for chromogranin, and one was positive for gastrin. Cells of a lipid-rich neuroendocrine tumor were negative for chromogranin; however, the tissue section contained neuron specific enolase, and neurosecretory granules were demonstrated by electron microscopy.
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PMID:Fine needle aspiration cytology of neuroendocrine tumors of the pancreas. A cytologic, immunocytochemical and electron microscopic study. 152 21

Carcinoembryonic antigen (CEA) was measured in 21 consecutive fine needle aspirates (FNA) of solid pancreatic lesions from 20 patients to determine whether elevated levels would predict the presence of pancreatic carcinoma in cytologically negative aspirates. Final diagnoses were correlated with clinical, radiologic, and pathologic (four patients) findings and follow-up. Twenty aspirates had malignancy, and one was benign. FNAs were performed under radiologic guidance with a 22-gauge Chiba needle and a 20-ml syringe. Cytologic examination was rendered on Papanicolaou-stained slides and, when available, hematoxylin and eosin-stained cell blocks. CEA was measured by enzyme immunoassay (Abbott Laboratories). Sensitivity of cytologic diagnosis was 80%; specificity was 100%. With 5 ng/ml as cutoff, the sensitivity of CEA for malignancy was 70% and for adenocarcinoma of pancreas, 78%; the specificity was 100%. The mean CEA in pancreatic carcinoma was 152.1 ng/ml (range 1.4 to greater than 880 ng/ml). The mean CEA for lymphoma, metastatic lung carcinoma, and benign aspirate was 1.0 ng/ml. Elevated CEA was diagnostic of pancreatic carcinoma in three cytologically negative aspirates. Combined sensitivity of CEA and cytology was 95%. Elevated CEA in FNA of pancreas increases the sensitivity of cytologic diagnosis and may suggest carcinoma in cytologically negative aspirates.
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PMID:Carcinoembryonic antigen assay in fine needle aspirate of pancreas: a diagnostic adjunct to cytology. 155 44

This prospective study was designed to determine the efficacy of iodized talc pleurodesis in patients with pleural effusions. Thirty-four patients underwent this treatment (three bilaterally) between October 1, 1989, and March 31, 1991. All patients had to have complete or nearly complete lung reexpansion after tube thoracostomy with fluid drainage less than 100 ml in 24 hours. A slurry containing 5 gm of talc and 3 gm of thymol iodide was instilled into the pleural space through the chest tube. Chest tubes were removed after complete reexpansion and clearing of the effusions, usually in 3 to 5 days. The patients' ages ranged from 26 to 88 years (average 50 years). Eighteen patients had lung carcinoma, two had mesothelioma, and one each had carcinoma of the ovary, breast, or anorectum, multiple myeloma, schwannoma, or Hodgkin's lymphoma. Two patients had an unknown adenocarcinoma primary and five other patients had acquired immunodeficiency syndrome. One patient had congestive heart failure. Nineteen patients had left, 12 had right, and three had bilateral pleural effusions. The effusion was serosanguineous in 26 and serofibrinous in eight patients. Serial chest radiography showed complete response in all patients. The period of follow-up ranged from 1 to 21 (average 4.9) months, with no recurrences. Twenty-three patients have died during the follow-up period, and there was no sign that reaccumulated pleural effusion existed in any, despite clinical evidence of systemic tumor progression. These observations indicate that intrapleural instillation of a slurry of iodized talc is a safe, adequate, and effective treatment for control of neoplastic or benign pleural effusions.
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PMID:Iodized talc pleurodesis for the treatment of pleural effusions. 156 70


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