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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An improved method for the detection of deoxythymidine kinase (TK) in human sera is reported. The method which utilizes 125I-iododeoxyuridine (IdUrd) as a substrate was used to measure TK in sera from patients with different diseases. Sera collected during the acute stage of infectious mononucleosis were found to contain elevated levels of TK, in most cases 10-40 times the normal value. The serum TK activity disappeared gradually and reached a normal level within 4 weeks. Sera from patients with other viral infections contained in most cases normal serum TK levels except in connection with measles, rubella, varicella, herpes simplex virus and cytomegalovirus infections. Additional studies revealed that sera from patients with different types of advanced lymphomas, acute leukemias, chronic granulocytic leukemia and lung cancer of the small-cell type with metastases, contained high TK levels which fluctuated in parallel with alterations in activity of the disease. The TK activity in sera from patients with both mononucleosis and tumor disease was characterized by electrophoresis and by its ability to utilize cytidine triphosphate as the phosphate donor. The results showed that the serum TK has the same properties as the human cytosolar TKI, except in connection with varicella.
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PMID:Application of an in vitro assay for serum thymidine kinase: results on viral disease and malignancies in humans. 669 95

The appearance of soft tissue concentrations of technitium labeled phosphate compounds has been observed in a variety of pathological conditions. The mechanism and pathophysiology of this phenomenon remain unclear.Seven new patients diagnosed with lung cancer received (99m)Tc diphosphonate bone scans during the period of January 1975 to November 1975. Three of the seven subjects showed a significant accumulation of isotope in the region of the chest infiltrate at the time of diagnosis. Upon repeat technitium bone scans six months post radiation, two patients showed a sharp reduction in the soft tissue activity previously observed.The material is presented and a possible explanation of this phenomenon is offered.
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PMID:Disappearance of soft tissue 99mTc diphosphonate activity following radiation therapy. 732 86

Etoposide phosphate, a water soluble prodrug of etoposide, has several potential advantages including easier and more rapid administration, avoidance of large fluid loads, and elimination of hypersensitivity reactions and other problems related to the solubilizer. This randomized Phase II study was done to evaluate the efficacy and toxicity of etoposide phosphate and etoposide, when used in combination with cisplatin in the treatment of patients with small cell lung cancer. Previously untreated small cell lung cancer patients were randomized to receive cisplatin in combination with molar equivalent does of either etoposide or etoposide phosphate. The patients were evaluated with respect to response rate, time to progression, survival, and toxicity. Response rates with etoposide phosphate and etoposide were 61% (95% confidence interval 55-67%) and 58% (95% confidence interval 52-64%), respectively (P = 0.85). Median time to progression was 6.9 months for patients who received etoposide phosphate and 7.0 months for those with etoposide (P = 0.50). For extensive stage disease patients, median survival with etoposide phosphate was 9.5 months versus 10 months for etoposide (P = 0.93). The corresponding median survivals for patients with limited stage disease were > 16 months and 17 months, respectively (P = 0.62). Myelosuppression was the most common toxicity; Grade 3 and 4 leukopenia occurred in 63% of patients receiving etoposide phosphate compared with 77% receiving etoposide (P = 0.16). The combination of etoposide phosphate and cisplatin is effective in the treatment of small cell lung cancer, and can be administered with acceptable toxicity. This study was not designed to be a formal Phase III comparative trial, but the efficacy and toxicity observed with this regimen were found to be similar to a standard etoposide/cisplatin regimen, using molar equivalent etoposide doses. Etoposide phosphate is preferable to etoposide because it is easier to use.
Lung Cancer 1995 Jun
PMID:Etoposide phosphate or etoposide with cisplatin in the treatment of small cell lung cancer: randomized phase II trial. 755 61

We have recently isolated and characterized a novel gene that is expressed in a neuroendocrine-specific fashion and was therefore designated neuroendocrine-specific protein (NSP)-gene. The NSP-gene encodes three transcripts of different size, with unique 5'-sequences and completely overlapping 3'-sequences. The resulting proteins have an apparent molecular mass of 135 kDa as determined for NSP-A and 23 kDa as found for NSP-C. In the present study we focused on the biochemical characterization and subcellular localization of NSP-B, so far only found to be expressed in the neuroendocrine lung cancer cell line NCI-H82, and its relation to NSP-A. Transfection studies with the NSP-B transcript in COS-1 cells, followed by immunoprecipitation, resulted in a set of proteins ranging in molecular mass from 35 to 45 kDa, identical to NSP-Bs detected by immunoblotting in NCI-H82. In this cell line a major NSP-B triplet in the 43 to 45 kDa range and a 35 kDa NSP-B were consistently detected. Only the 45 kDa NSP-B was found to be phosphorylated. The observed pI values of the 43 to 45 kDa triplet ranged from 4.8 to 5.0, while the 35 kDa NSP-B has a more basic pI value of 5.7. Gel filtration studies show that NSP-A and NSP-B form supramolecular aggregates with a molecular mass of over 500 kDa, present to a minor extent in the phosphate buffered saline soluble cell fraction, but mainly occurring in the membranous pellet fraction from which they can be solubilized by Triton X-100.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Subcellular localization and supramolecular organization of neuroendocrine-specific protein B (NSP-B) in small cell lung cancer. 772 Jul 28

In preparation for a clinical trial of the recombinant p53 adenovirus Ad5CMV-p53 for the treatment of lung cancer, the potential adverse effects of Ad5CMV-p53 were assessed in vitro and in vivo. No infectious replication of Ad5CMV-p53 was detectable in HeLa cells infected with extracts from HeLa cells previously infected with Ad5CMV-p53. No Ad5CMV-p53 DNA replication was detected by 32Pi labeling in lung cancer cells infected with Ad5CMV-p53 at multiplicities of infection (moi) up to 1,000 pfu/cell (total of 5 x 10(9) pfu viruses). The infectivity and cytotoxicity of Ad5CMV-p53 were examined in vitro in normal human bronchial epithelial (NHBE) cells. At a moi of 50 pfu/cell, Ad5CMV-p53 infection and expression were detectable in 80% of the treated cells. The exogenous p53 protein was first detected by western blotting at 8 hr and peaked at 48 hr after infection. Growth of NHBE cells was not affected by Ad5CMV-p53 infection at a moi of 100 pfu/cell. The pathogenicity of Ad5CMV-p53 was assessed in BALB/c mice. The virus was given to four groups of mice by intratracheal injection at dosages from 10(7) to 10(10) pfu; a fifth group received phosphate-buffered saline alone. None of the viral injections proved to be lethal. Mild to moderate peribronchiolar and perivascular infiltration by mononuclear cells and lymphocytes, with patches of pneumonitis, was the most acute toxic effect detected by histologic analysis in the two high-dose groups. Immunohistochemical analysis of the same paraffin-embedded sections showed that infectivity and level of expression of p53 in lung tissue were dose-dependent. Our results demonstrate that Ad5CMV-p53 is a replication-defective virus that yields a relatively low degree of acute toxicity in mice; these data document a safety profile encouraging for clinical trials of Ad5CMV-p53 in the therapy of lung cancer.
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PMID:Safety evaluation of Ad5CMV-p53 in vitro and in vivo. 773 16

Human monoclonal antibody (MAb) AE6F4, which had been shown potentially useful for the immunocytological detection of lung cancer cells in sputum, was characterized for its antigen(s). Of the three MAb-reacting materials found in A549 cells by the immunoblotting analysis, the cytoplasmic 31-kDa protein extractable with phosphate-buffered saline was evidenced as the most plausible antigen by its highest content and outstanding affinity to the MAb AE6F4-derivatized Sepharose 4B column. This 31-kDa protein was identified by the amino acid sequence analysis of the CNBr-cleaved fragment as the 14-3-3 family of proteins, the members of which are known to play important physiological roles such as in the regulation of neurotransmitter levels and intracellular signal transduction. The purified 14-3-3 protein from bovine brain showed a comparable MAb-reacting activity to that of the 31-kDa protein from A549 cells in the enzyme-linked immunosorbent assay (ELISA). The significant reactivity of bovine 14-3-3 protein by MAb AE6F4, shown by the cross inhibition of antibody binding to the coated 31-kDa antigen in ELISA as well as by the inhibition of immunostaining with lung cancer tissues, consistently demonstrated that the antigen(s) recognized by the MAb was involved in the 14-3-3 protein family. It was found that the expression of the 14-3-3 protein was significantly enhanced in lung cancer tissues compared with the neighboring normal part of the lung as examined by the immunoblotting method. These results implicated that some member(s) of the 14-3-3 protein family can be the tumor marker(s), providing a rational basis for the immunocytological diagnosis of lung cancer with this human MAb.
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PMID:The 14-3-3 protein as the antigen for lung cancer-associated human monoclonal antibody AE6F4. 775 77

Cyclocreatine, an analog of creatine, is an efficient substrate for creatine kinase, but its phosphorylated form is a poor phosphate donor in comparison with creatine phosphate. Cyclocreatine was not very cytotoxic upon 24 h of exposure of human SW2 small-cell lung cancer cells to concentrations of up to 5 mM. However, combinations of cyclocreatine (0.5 mM, 24 h) with each of four antitumor alkylating agents, cis-diamminedichloroplatinum(II), melphalan, 4-hydroperoxycyclophosphamide, and carmustine, resulted in additive to greater-than-additive cytotoxicity toward exponentially growing SW2 cells. The greatest levels of synergy were seen at higher concentrations of 4-hydroperoxycyclophosphamide and carmustine as determined by isobologram analysis. In vivo cyclocreatine (0.5 or 1 g/kg) was more effective if given i.v. rather than i.p. The longest tumor-growth delays, up to 10 days, were produced by extended regimens of cyclocreatine. Cyclocreatine was an effective addition to therapy with standard anticancer agents including cis-diamminedichloroplatinum(II), cyclophosphamide, Adriamycin, or 5-fluorouracil. No additional toxicity was observed when 10 days of cyclocreatine treatment was given with full standard-dose regimens of each drug. The resultant increases in tumor-growth delay were 1.7- to 2.4-fold as compared with those obtained for each of the drugs alone. These results indicate that cyclocreatine may be an effective single agent and an effective addition to combination chemotherapy regimens.
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PMID:Cyclocreatine in cancer chemotherapy. 785 Sep 23

We focused here on steady-state mRNA levels of genes involved in antioxidant defense, i.e., manganese superoxide dismutase and copper-zinc superoxide dismutase, and in cell proliferation, i.e., ornithine decarboxylase, c-jun, and glyceraldehyde-3-phosphate-dehydrogenase in whole-lung homogenates from Fischer 344 rats at 3 h to 20 d after exposure to crocridolite asbestos. Changes in gene expression were correlated with histopathologic findings, total and differential cell counts in bronchoalveolar lavage, and levels of hydroxyproline in lung. Dosage-dependent increases in mRNA levels of antioxidant enzymes and proliferation-related genes were observed. Differential cell counts revealed a dose-related infiltration of neutrophils that preceded elevations in gene expression. Neutrophil infiltration into lung and focal lesions of fibrosis as well as increased levels of hydroxyproline were observed only at high concentrations of asbestos. These results indicate that high airborne concentrations of asbestos cause molecular changes in lung that may be related to antioxidant defense and the triggering of cell proliferation, a feature of asbestosis and lung cancer.
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PMID:Dose-responsive increases in pulmonary fibrosis after inhalation of asbestos. 802 51

A Phase I trial was conducted to investigate the clinical toxicity, pharmacokinetics, and chemiluminescence (CL) responses of alveolar macrophages (AMs), peripheral blood neutrophils, and monocytes after subcutaneous injection of recombinant interferon-gamma (rIFN-gamma). Six patients with lung cancer received rIFN-gamma subcutaneously as single doses of 0.2, 0.6, and 1.8 mg. Bronchoalveolar lavage was performed three times: 21 h before as well as 6-7 and 27 h after injection. Serum samples were taken five times during the 27-h follow-up. IFN concentrations were measured from alveolar epithelial lining fluid (ELF) and serum by using an antiviral bioassay. IFN-gamma was not detectable in ELF after subcutaneous injection. AMs did not effect an increase in CL responses to N-formyl-methionyl-leucyl-phenylalanine or to phosphate-buffered saline. Circulating IFN-gamma was detectable at 3-12 h after an injection of 1.8 mg of rIFN-gamma, the highest dose given. CL responses of peripheral blood monocytes increased in all patients after injection, whereas the responses of neutrophils were less clear-cut. All patients developed systemic side effects such as transient fever, nausea, headaches, and flu-like symptoms. The findings suggest that rIFN-gamma passes poorly from the blood to the pulmonary alveoli. On the basis of this and our previous findings of increased CL responses in AMs and measurable IFN concentrations in ELF after inhalation of rIFN-gamma, we recommend inhalation rather than the parenteral route of IFN-gamma for the treatment of respiratory diseases.
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PMID:Subcutaneously administered recombinant interferon-gamma in humans: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages, blood neutrophils, and monocytes. 806 1

We have developed an intraoperative intrapleural treatment with the use of distilled water combined with cisplatin for carcinomatous pleuritis found at thoracotomy in patients with non-small-cell lung cancer. In the in vitro experiment, three different cell lines were used as a model of malignant pleural effusion. Cell growth was examined after a 3-day culture, which was preceded by exposure of the cells to cisplatin in either phosphate-buffered saline solution or distilled water for 1/2 to 5 minutes. The growth inhibition of tumor cells after hypotonic cisplatin treatment was significantly greater than after treatment with saline solution and cisplatin. Tumor that was obtained by resection of non-small-cell lung cancer was used as a model to demonstrate decreased viability of the tumor after exposure to hypotonic cisplatin. The viability of the tumor in a 6-day culture, preceded by exposure to hypotonic cisplatin (50 micrograms/ml) for 10 minutes, was markedly decreased. Intraoperative intrapleural hypotonic cisplatin was instilled in seven patients with pleural carcinomatosis without side effects and with control of pleural dissemination and pleural effusion for 6 to 29 months.
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PMID:Hypotonic cisplatin treatment for carcinomatous pleuritis found at thoracotomy in patients with lung cancer. In vitro experiments and preliminary clinical results. 838 66


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