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

Oxygen radical generation by blood cells before and after chemotherapy was investigated in 16 elderly (72.8 +/- 1.0 years) and 14 adult (45.0 +/- 2.4 years) patients with lung cancer, using a lucigenin-dependent chemiluminescence method. The oxygen radical generation by 100 microliters of blood before chemotherapy in the elderly and the adults was 3,784 +/- 123 and 3,969 +/- 125 chemiluminescence (CL), respectively. The value decreased gradually and reached a nadir at 2 weeks after therapy (elderly: 1,090 +/- 37; adult: 1,114 +/- 38 CL). Peripheral leukocyte counts also reached a nadir then: 1,308 +/- 140 and 1,288 +/- 44/mm3, respectively. However, the oxygen-radical-generating activity per leukocyte was not different before and after the therapy (elderly: 0.94 +/- 0.14 CL before to 0.83 +/- 0.09 CL after; adult: 0.97 +/- 0.13 CL before to 0.87 +/- 0.10 CL after). These results indicate that a decrease in oxygen radical generation by blood following chemotherapy is mainly due to a decrease in the number of polymorphonuclear neutrophils both in elderly and adult patients.
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PMID:Influences of cisplatin combination chemotherapy on oxygen radical generation by blood in elderly and adult patients with lung cancer. 765 70

Porfimer sodium (Photofrin II) is a photosensitizer which distributes selectively to tumor tissues, and causes tumor cell death by combination with light irradiation. Photodynamic therapy (PDT) by combination of porfimer sodium and laser was developed as a new cancer therapy. Tumor selectivity of porfimer sodium are based on the following reasons; 1) high affinity for lipoprotein, especially, low density lipoprotein (LDL), 2) elevation of LDL receptor activity in cancer tissue, and 3) lack or imcompleteness of lymphatic system in cancer tissue. Porfimer sodium is activated by laser irradiation at 630 nm, which can reacts with tissue oxygen to produce highly reactive excited siglet oxygen (1O2). This highly reactive molecule is subsequently capable of killing tumor cells through oxidation of cellular component like mitochondrial enzymes. In addition, this highly reactive intermediate causes destruction of the tumor capillaries, which accelerates tumor cell death. The growth suppression or lethal damage to tumor cells by PDT of porfimer sodium and excimer dye laser were observed in experimental tumor models. In human clinical trials, the rates of complete response (CR) for roentgenographically occult lung cancer, stage I lung cancer, superficial esophageal cancer, superficial gastric cancer and carcinoma in situ or dysplasia of the cervix were 84.8%, 50.0%, 90.0%, 87.5% and 94.4%, respectively. The major side effects were cutaneous symptoms e.g. photosensitivity, pigmentation, increasing GOT, GPT but these symptoms were not severe. PDT using porfimer sodium and excimer dye laser must be clinically useful for the treatment of inoperable early cancer or conservation of organ functions.
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PMID:[Porfimer sodium (Photofrin-II)]. 766 80

It has been shown that chronic lung diseases which increase the concentration of pulmonary carbon dioxide (CO2) at the expense of oxygen stimulate the secretion of biogenic amines and neuropeptides by pulmonary neuroendocrine cells (PNE cells) in man and laboratory animals. This increase in secretory activity is always accompanied by hyperplasia of PNE cells, and smokers with chronic obstructive lung disease are at high risk for the development of neuroendocrine lung cancer. We have previously shown that nicotine and the structurally related nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), stimulate the proliferation of neuroendocrine cell lines derived from lung carcinoid tumors via interaction with nicotinic acetylcholine receptors (nAChR). In our current experiment, we have addressed the mechanisms of cell proliferation in response to nicotine and NNK in normal PNE cells derived from fetal hamster lungs, and two cell lines derived from human neuroendocrine lung cancers. Our data show that in these systems the mitogenic effects of nicotine and NNK are potentiated in a concentration-dependent manner by elevated levels of CO2, an effect blocked by inhibitors of protein kinase C(PKC) and reduced by antagonists of receptors for 5-hydroxytryptamine (5-HT, serotonin) and mammalian bombesin. The observed effects of CO2 were saturable and independent of changes in the acidity of the tissue culture media. Our data suggest that increases in CO2 concentration at the expense of oxygen may stimulate signal transduction pathways in normal and neoplastic neuroendocrine lung cells thus enhancing their susceptibility to the mitogenic effects of tobacco-specific toxicants.
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PMID:Carbon dioxide potentiates the mitogenic effects of nicotine and its carcinogenic derivative, NNK, in normal and neoplastic neuroendocrine lung cells via stimulation of autocrine and protein kinase C-dependent mitogenic pathways. 771 58

The analysis of expired gas with exercise testing was conducted preoperatively with lung cancer patients in order to examine the relationship between maximum oxygen consumption (VO2 max) and postoperative complications, determining the cut-off of VO2 max/m2. The usefulness of the test as a preoperative screening test for both pulmonary ventilation and circulation was evaluated in comparison to pulmonary ventilation tests with spirometry and pulmonary circulation tests with Swan-Ganz catheter. Preoperative VO2 max/m2 was calculated from VO2 max in 111 patients with lung cancer who underwent lobectomy of more than one lobe. Also preoperatively conducted were pulmonary ventilation tests by spirometry and pulmonary circulation tests using the Swan-Ganz catheter to measure VC, %VC, FEV1.0, FEV1.0%, mean pulmonary arterial pressure (PPA) and cardiac output coefficient (C.I.). Form theses measurements, VC/m2, FEV1.0/m2 and total pulmonary vascular resistance (TPVR) were calculated. After the cut-off values of VO2 max/m2 were set tentatively at three stages, 600, 650 and 700 ml/min/m2 based on the incidence of postoperative complications, the 111 patients were divided into two groups in each cut-off value; one with VO2 max/m2 greater than the cut-off value and the other less than the cut-off value. Comparison of measurements obtained by spirometry between the two groups disclosed significant differences (p < 0.001) in VC/m2, %VC and FEV1.0/m2 in all cut-off values. Similarly, comparison of measurements obtained using the Swan-Ganz catheter between the two groups yielded significant differences (p < 0.05 to p < 0.01) in PPA and TPVR in all cut-off values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pre-operative screening tests for lung cancer using the analysis of expired gas with exercise testing--principally VO2 max/m2]. 779 8

The occurrence of inflammatory processes and of cancer in the human respiratory tract is intimately associated. One of the major factors in this is probably the recruitment of and stimulated activity of polymorphonuclear leukocytes (PML) in conjunction with the ability of these cells to convert various carcinogens to their ultimate active metabolites. In this study, we demonstrate that nitrite and sulfite, the major dissolution products of the environmental pollutants nitrogen dioxide and sulfur dioxide in water enhance the metabolic activation of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-dihydrodiol), the proximal carcinogen of benzo[a]pyrene, to trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and tetraols, the corresponding hydrolysis products, in human PML prestimulated with 12-O-tetradecanoylphorbol-13-acetate. Nitrite was more efficient than sulfite in stimulating the formation of reactive intermediates of BP-7,8-dihydrodiol in PML that covalently bind to extracellular DNA and, in particular, to intracellular proteins. The mechanism by which sulfite stimulates the metabolism of BP-7,8-dihydrodiol most probably involves the intermediate formation of a sulfur trioxide radical anion (SO3.-) the subsequent formation of the corresponding sulfur peroxyl radical anion (.OOSO3-) in the presence of oxygen. The mechanism underlying the stimulatory action of nitrite is less clear but the major pathway seems to involve myeloperoxidase. These results offer an explanation for the increased incidence of lung cancer in cigarette smokers living in urban areas. The major glutathione transferase (GST) isoenzyme in human PML is GST P1-1, a Pi-class form. The GST activity of PML was found to be inversely correlated with the extent of binding of BP-7,8-dihydrodiol products to exogenous DNA. These results suggest that individuals exhibiting high GST-activity in the PML may be better protected against the type of carcinogenic dealt with in this study.
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PMID:Stimulatory effects of sulfur and nitrogen oxides on carcinogen activation in human polymorphonuclear leukocytes. 782 Dec 91

Surgical resection for lung cancer provides the only real chance for cure. However, there is a high risk of postoperative complications including death for patients with pulmonary dysfunction. Therefore preoperative identification of patients at risk is necessary. Apart from history and physical examination three tests are currently used: 1. resting lung function (RFL), 2. invasive measurement of pulmonary vascular resistance (PVR) and 3. exercise testing with measurement of oxygen consumption (VO2). Main studies in the literature report the probability of abnormal tests for prediction of pulmonary complications (positive predictive value) and the probability of normal tests for prediction of uneventful outcome (negative predictive value) as follows: [table: see text] In conclusion, the "ideal" test predictive for morbidity and mortality after lung resection has not been found. The positive predictive values of RLF and PVR are disappointing, while the negative predictive values are acceptable. Measurement of VO2 is simple, noninvasive and might predict survivable morbidity, as suggested in the literature. Obviously, additional studies are necessary.
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PMID:[Predictive value of ergospirometry in preoperative assessment of risk factors before lung resections]. 794 67

The medical criteria for inoperability have been difficult to define in patients with lung cancer. Sixty-six patients with non-small cell lung cancer and radiographically resectable lesions were evaluated prospectively in a clinical trial. The patients were considered by cardiac or pulmonary criteria to be high risk for pulmonary resection. If exercise testing revealed a peak oxygen uptake of 15 mL.kg-1.min-1 or greater, the patient was offered surgical treatment. Of the 20 procedures performed, nine were lobectomies, two were bilobectomies, and nine were wedge or segmental resections. All patients were extubated within 24 hours and discharged within 22 days after operation (median time to discharge, 8 days). There were no deaths, and complications occurred in 8 (40%) of the 20 patients. Five patients whose peak oxygen uptake was lower than 15 mL.kg-1.min-1 also underwent surgical intervention; there was one death. Thirty-four patients whose peak oxygen uptake was less than 15 mL.kg-1.min-1 and 7 who declined operation underwent radiation therapy alone (35 patients) or radiation therapy and chemotherapy (6 patients). There were no treatment-related deaths, and the morbidity rate was 12% (5/41). The median duration of survival was 48 +/- 4.3 months for the patients treated surgically and 17 +/- 2.7 months for those treated medically (p = 0.0014). We conclude that a subgroup of patients who would be considered to have inoperable disease by traditional medical criteria can be selected for operation on the basis of oxygen consumption exercise testing. There is a striking survival benefit to an aggressive surgical approach in these patients.
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PMID:Resection of lung cancer is justified in high-risk patients selected by exercise oxygen consumption. 794 92

The progression of intraepithelial and postinvasive neoplasia depends on the occurrence of clonal evolution, defined as the continuous development of mutations and selective clonal expansions in the neoplastic cell population. The two continuously repeating events of clonal evolution, mutation and clonal expansion, occur at unpredictable times and locations. Therefore the neoplastic process is best characterized as a stochastic, i.e., probabilistic, continuum. The rate of intraepithelial neoplastic progression is continuously driven by the dosage level of exposure to mutagens and mitogens. For example, in chronic smokers the length of time before development of lung cancer depends on the number of cigarettes smoked per day. A commonly held misconception is that human carcinogenesis develops after an initial short period of mutation followed by a long period of stimulated proliferation (the multistage model). This incorrect idea derives from the sequential nature of the consecutive two- or three-step operational protocols imposed on experimental animal models by the experimenter. In reality, human carcinogenesis develops as the result of simultaneous and continuous exposure to mutagens and mitogens over the entire period of tumor development. A recent example is the finding that the intraepithelial neoplasia of colorectal adenomas continuously progresses through serial waves of mutation and clonal expansion. The rational design of chemopreventive agents should be based on blocking the two parameters which continuously drive neoplasia: mutagenesis and mitogenesis. In addition to blocking exposure, chemopreventive agents may act at many points during activation and DNA adduction of mutagens, or during stimulation of the proliferation signal pathway by mitogens. Based on the chemopreventive strategy of blocking mutagenesis and mitogenesis, chemopreventive agents are classed as either antimutagenic or antimitogenic. A third class, the antioxidants, are both antimutagenic and antimitogenic, and operate by the common mechanism of breaking free radical chain reactions initiated by reactive oxygen species. In the program of the Chemoprevention Investigational Studies Branch, Division of Cancer Prevention and Control, National Cancer Institute, preclinical development of antimutagens, antimitogens, and antioxidants is well under way, and some of these agents are highlighted here.
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PMID:Intraepithelial and postinvasive neoplasia as a stochastic continuum of clonal evolution, and its relationship to mechanisms of chemopreventive drug action. 800 92

Patients with diagnosed or suspected lung cancer first require appropriate staging and proven anatomic resectability. Excellent pre-operative spirometric data (FEV1 > 2.0 L, > 60% predicted) should recommend the patient for surgery immediately without further testing. Those whose preoperative FEV1 is less than 60% predicted or whose DLCO is less than 60% predicted should be sent for quantitative lung scanning to estimate postoperative spirometry and diffusing capacity. Results showing FEV1-PPO and DLCO-PPO greater than 40% of normal suggest an acceptable surgical risk, and the patient should be referred accordingly. Those whose results are less than 40% of predicted should be exercised in some capacity to assess oxygen transport. We believe that cycle ergometry with incremental workloads and the standard monitoring is the best technique available for this (Table 1). Patients with a predicted postoperative FEV1 (or DLCO) greater than 35% of normal values and whose peak exercise VO2 is greater than 15 mL/kg/min should be offered surgery with the goal of removing the smallest volume of tissue that would be compatible with a cure. Those who do not meet these criteria, however, should not be summarily refused surgery if they are willing to accept the possibility of an earlier death or prolonged disability over the certainty of a cancer-related death in the foreseeable months ahead. Because the lung scan prediction of postoperative regional physiology and the exercise test of global oxygen transport examine different aspects of physiologic operability, we would not disagree with anyone who would advocate doing both tests in those at high risk by virtue of spirometric criteria. The logic of this combined approach is illustrated by Figure 1.
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PMID:Role of exercise stress testing in preoperative evaluation of patients for lung resection. 808

Coronary artery bypass grafting (CABG) in a patient who had undergone left pneumonectomy for lung cancer 13 years earlier is described. Preoperative pulmonary function was reduced; percent vital capacity was 55% and percent forced expiratory volume in 1 second was 77%. Triple CABG was performed with saphenous vein grafts. A retractor designed for use in harvesting of the internal thoracic artery was useful to obtain a good operative view because the heart had shifted to the left. Oxygen tension of the arterial blood decreased transiently after extracorporeal circulation. The early postoperative course was uneventful and the patient was discharged on day 57 after the operation. This is the first report, to the best our knowledge, of CABG after pneumonectomy for lung cancer in Japan. We think it possible, with careful management, to perform open heart surgery on a patient after pneumonectomy if pulmonary function is adequate.
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PMID:[Coronary artery bypass grating 13 years after pneumonectomy]. 808 84


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