Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen previously untreated patients with extensive small-cell lung cancer (SCLC) were treated with the investigational agent amonafide in a dose of 300 mg/m2 intravenously (IV) over 1 hour daily for 5 consecutive days. No responses were seen in 12 eligible patients. Myelosuppression was only occasionally seen. Other toxicities included diaphoresis, chest pain, local irritation at the injection site, arthralgias, nausea and vomiting, and neuromuscular problems. There were two early deaths, both attributable to tumor progression with resultant obstruction of a vital structure. Ten patients crossed over to alternate active therapy (etoposide [VP-16]-cisplatin) and five responded. The median survival time (MST) of the whole group of treated patients was 31 weeks. In future trials of investigational new drugs in previously untreated SCLC, we recommend that patients with the following characteristics be excluded: Eastern Cooperative Oncology Group (ECOG) performance status 2, 3, and 4; superior vena cava (SVC) obstruction; any major paraneoplastic syndrome; serious comorbid illness; and extensive hepatic involvement by tumor. The trial design should include prompt crossover to active alternative therapy, such as VP-16 and cisplatin, for disease progression or for failure to respond after two treatment cycles. Also, the trial design should use an early stopping rule based on interest in identifying only very active agents with a minimum response rate of 30%.
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PMID:Phase II study of amonafide: results of treatment and lessons learned from the study of an investigational agent in previously untreated patients with extensive small-cell lung cancer. 215 6

We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38-68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer. Patients received i.v. cisplatin 200 mg/m2 over 5 days and i.v. etoposide 600 mg/m2/day for 3 days (total of 1,800 mg/m2) that was escalated to 800, 1,000, 1,200, 1,400, and 1,600 mg/m2/day for 3 days (total of 2,400-4,800 mg/m2). Cryopreserved autologous bone marrow was thawed and reinfused through a central venous catheter the second day after the completion of chemotherapy. Toxicities included nausea, vomiting, alopecia, high-tone hearing loss, mucositis, diarrhea, renal insufficiency, metabolic acidosis, and severe myelosuppression. The duration of neutropenia (less than 500 neutrophils/microliter) ranged from 5 to 22 days (median of 11 days) and the duration of severe thrombocytopenia (platelets of less than 20,000/microliters untransfused) ranged from 2 to 19 days (median of 9 days). Reversible renal insufficiency (peak serum creatinines of 6.7, 6.6, 4.3, and 3.5 mg/dl) occurred in four patients who completed the therapy. In three patients, death occurred within 4 weeks of chemotherapy and marrow reinfusion. Three complete and 12 partial remissions (range of 1+(-)22+ months, median of 3 months) were observed. No response was noted in eight patients and tumor progression within 1 month of transplant occurred in two patients. The maximally tolerated dose of etoposide was 1,400 mg/m2/day (total of 4,200 mg/m2), since two of three patients developed life-threatening diarrhea at the 1,600 mg/m2/day (total of 4,800 mg/m2) dose. The encouraging antitumor effects of this regimen suggest that this approach may be useful therapy for lung cancer and other tumors sensitive to VP-16 and cisplatin.
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PMID:Phase I trial of high-dose etoposide, high-dose cisplatin, and reinfusion of autologous bone marrow for lung cancer. 215 15

In order to evaluate the determinants of cell type in patients with primary lung cancer, we compared smoking characteristics in 1,939 patients (1,474 men and 465 women). Patients with squamous cell carcinomas, adenocarcinomas, or small-cell carcinomas were eligible. This study did not consider smoking as a risk factor for lung cancer, as all subjects had a confirmed diagnosis. We were interested in smoking history and the pattern of smoking among those whose risk was 100 percent. Among these patients, we confirmed that a larger subset of nonsmoking individuals developed adenocarcinomas than squamous cell or small-cell carcinomas; however, the duration and intensity of cigarette smoking, as measured by pack-years, were not determinants of tumor cell type in male patients. Small-cell carcinomas in women were more strongly associated with cigarette smoking than either squamous cell carcinomas or adenocarcinomas. More than 3,500 different substances have been measured in tobacco smoke, including tumor initiators, promoters, and those involved in tumor progression. These data confirm the hypothesis that factors other than cigarette smoking are more likely to be involved in the initiation of adenocarcinomas than other cell types. Endogenous and exogenous factors related to gender may be more important than the duration or intensity of cigarette smoking.
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PMID:Determinants of cell type in patients with cancer of the lungs. 217 83

The development of human lung cancer may require multiple genetic deletions affecting a number of chromosomes, e.g., 1, 3, 11, 13, and 17. These genetic aberrations may induce the activation of proto-oncogenes (c-jun, ras, c-raf1) and the loss of tumor suppressor genes (p53). Some of the activated proto-oncogenes and tumor suppressor genes are more selectively expressed or absent in small-cell lung cancer (L-myc, c-myb, c-scr, Rb gene) or non-small-cell lung cancer (c-erbB-2, c-sis, c-fes). These genes may thus be of importance for selection of differentiation pathway. The c-myc oncogene is frequently amplified in small-cell lung cancer cell lines in a much higher frequency than in vivo. This indicates that c-myc seems to be related to tumor progression and a relatively late event in the lung cancer development. The uncontrolled production of multiple growth factors has been identified in human lung cancer cell lines. These factors can promote and inhibit the proliferation via paracrine and autocrine loops via specific receptors. The products from some of the activated proto-oncogenes (c-sis, c-erbB-2) are sequences homologous to a certain growth factor (PDGF) and a receptor (EGF) identified in lung cancer. The production and action of these growth factors may be of major importance for further activation of proto-oncogenes via intracellular signal transduction and specific oncogenic activation leading to further tumor progression.
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PMID:Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes. 217 59

During the years 1975-1988, twenty lung cancer patients with symptomatic pericardial effusion were treated conservatively at our center. Echocardiography demonstrated small pericardial effusion in 2 patients, medium size effusion in 3 patients and large amount of fluid in 15 patients. Fifteen patients developed cardiac tamponade; in three of these patients, this was the presenting manifestation of lung cancer. Pericardiocentesis resulted in prompt, though temporary, symptomatic relief in all patients. Fluid cytology demonstrated suspected malignant cells in 2 patients and malignant cells in 13 patients. Based on cytology, the diagnosis of adenocarcinoma was established in six patients, small cell carcinoma in three patients, and epidermoid carcinoma in one patient. All patients were dead within 9 months from the time of diagnosis of pericardial effusion; 17 died within less than 3 months. It is concluded that pericardial effusion in lung cancer is indicative of rapid tumor progression and short survival. Fluid cytology provides an immediate and accurate means of diagnosis.
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PMID:Symptomatic pericardial effusion in lung cancer patients: the role of fluid cytology. 221 90

Method of immunodiffusion titration of rabbit monospecific antiserum (The I. M. Mechnikov Central Research Institute of Vaccines and Sera of the USSR Ministry of Health) in agar was used to measure blood C-reactive protein (C-RP) level in patients with acute pneumonia (32), protracted pneumonia or activation of chronic non-specific lung pathology (101) and lung cancer (153) after a 3-4-week course of complex antiinflammatory treatment and a 10-14-day course of immunostimulation with pyrogenal (The N. F. Gamaleya Research Institute of Epidemiology and Microbiology). A decrease in the incidence (from 81.2% to 14.2%) and level (from 1.4 +/- 0.3 to 0.3 +/- 0.03 mg%) of C-RP was observed in cases of non-tumor pathology whereas in patients with lung cancer those values rose in step with tumor progression (from 72.2% and 0.4 +/- 0.07 mg% at stage I to 96.3% and 1.2 +/- 0.12 mg% at stage IV). Treatment with pyrogenal allowed to identify C-RP in patients with false-negative reaction in all subgroups. Two-week dynamic C-RP curves characterizing non-tumor and tumor pathology of the lung were plotted.
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PMID:[Stimulation of the synthesis of C-reactive protein using pyrogenal in non-neoplastic diseases and cancer of the lungs]. 221 34

In order to analyse the possible mode and pathways of adrenal metastases from lung cancer, the frequency of adrenal metastases ipsilateral and contralateral to the site of the primary cancer was investigated based on autopsied lung cancer cases. In 405 of 1,607 such cases, adrenal metastases could be found: on both sides, 234; ipsilateral only, 105; contralateral only, 66 cases. In the early stages of tumor progression, a striking difference can be seen between the two sides. Ipsilateral metastases were of significantly higher incidence in early metastatic tumor stages, but later, in cases having six or more involved organs, the ipsilateral/contralateral quotient reaches 1. It is postulated that in the early stages adrenal metastases from lung cancer probably develop mainly by lymphogenous, but later mainly by hematogenous routes.
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PMID:Do adrenal metastases from lung cancer develop by lymphogenous or hematogenous route? 231 2

Quantitative determination of human glioma-associated antigen in cerebrospinal fluids (CSFs) obtained from 66 patients with a variety of neurological diseases was performed by solid-phase radioimmunoassay with a monoclonal antibody (G-22). In this system, the minimum detectable amount of the antigen in the CSF was 8 ng/ml. It was demonstrated that CSF diagnosis of glioblastoma might be possible in the case of small tumors with a diameter of less than 2 cm. CSFs obtained from all 18 patients with glioma were positive and the level varied from 11.2 to 186.1 ng/ml. The antigen level in the cystic fluid of the tumor was higher than that in CSF. There was a tendency for the antigen level in CSF to be correlated with the tumor size and the type of histology. The malignant types of glioblastoma or medulloblastoma showed higher levels than the benign type of ependymoma and astrocytoma. Most types of non-gliomatous brain tumor were negative except immature teratoma, meningioma with central neurofibromatosis, and metastatic brain tumor from lung cancer. We also noted that tumor progression or regression of malignant glioma could be predicted by the monitoring of the antigen in the CSF.
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PMID:Radioimmunoassay of glioma-associated antigen in cerebrospinal fluid and its usefulness for the diagnosis and monitoring of human glioma. 191 50

To facilitate understanding of the mechanisms underlying pulmonary diseases, including lung cancer and cystic fibrosis, we have transformed and characterized cultures of human tracheal epithelial cells. Cells were transfected by calcium phosphate precipitation with a plasmid containing a replication-defective simian virus 40 (SV40) genome. Colonies of cells with enhanced growth potential were isolated and analyzed for transformation- and epithelial-specific characteristics. Precrisis cells were observed to express the SV40 large tumor antigen, produce cytokeratins, have microvilli, and form tight junctions. After crisis, cells continued to express the SV40 large tumor antigen as well as epithelial-specific cytokeratins and to display the apical membrane microvilli. Apical membrane Cl channels were opened in postcrisis cells exposed to 50 microM forskolin. These channels showed electrical properties similar to those observed in primary cultures. The postcrisis cells have been in culture for greater than 250 generations and are potentially "immortal." In addition to providing a useful in vitro model for the study of ion transport by human airway epithelial cells, the cells can be used to examine stages of neoplastic progression.
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PMID:Characterization of human tracheal epithelial cells transformed by an origin-defective simian virus 40. 245 4

Tumour progression is dependent on many factors including antiproteases and proteases released by tumour cells or host cells infiltrating the tumour. In the present study, we evaluated the antiprotease content, namely alpha 2-macroglobulin (A2M) and alpha 1-proteinase inhibitor (A1PI) and neutrophil (PMN) elastase complexed with A1PI, in limited and extended lung cancer patients compared to a nonsmoker and smoker control population. Data showed that A2M and A1PI were increased in the involved lung from limited cancer when compared to normals. In extended lung cancer, A2M content was also increased in the uninvolved side. The concentration of PMN elastase-A1PI complex was increased on both sides in lung cancer patients (10.2 ng.ml-1 in the uninvolved side, 8.2 ng.ml-1 in the involved side) when compared to nonsmokers (1.9 ng.ml-1, p less than 0.001) and smokers (3.8 ng.ml-1, p less than 0.005). This increase was not solely due to the smoking habit. We conclude that antiproteases and PMN elastase complexed with antiprotease are increased in lung cancer area. This increase could result in extracellular changes in lung cancer.
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PMID:Local increase of antiprotease and neutrophil elastase-alpha 1-proteinase inhibitor complexes in lung cancer. 247 29


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