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

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.
 ...
PMID:[Porfimer sodium (Photofrin-II)]. 766 80

Sodium channels of human small-cell lung cancer (SCLC) cells were examined with whole-cell and single-channel patch clamp methods. In the tumor cells from SCLC cell line NCI-H146, the majority of the voltage-gated Na+ channels are only weakly tetrodotoxin (TTX)-sensitive (Kd = 215 nM). With the membrane potential maintained at -60 to -80 mV, these cells produced all-or-nothing action potentials in response to depolarizing current injection (> 20 pA). Similar all-or-nothing spikes were also observed with anodal break excitation. Removal of external Ca2+ did not affect the action potential production, whereas 5 microM TTX or substitution of Na+ with choline abolished it. Action potentials elicited in the Ca(2+)-free condition were reversibly blocked by 4 mM MnCl2 due to the Mn(2+)-induced inhibition of voltage-dependent sodium currents (INa). Therefore, Na+ channels, not Ca2+ channels, underlie the excitability of SCLC cells. Whole-cell INa was maximal with step-depolarizing stimulations to 0 mV, and reversed at +45.2 mV, in accord with the predicted Nernst equilibrium potential for a Na(+)-selective channel. INa evoked by depolarizing test potentials (-60 to +40 mV) exhibited a transient time course and activation/inactivation kinetics typical of neuronal excitable membranes; the plot of the Hodgkin-Huxley parameters, m infinity and h infinity, also revealed biophysical similarity between SCLC and neuronal Na+ channels. The single channel current amplitude, as measured with the inside-out patch configuration, was 1.0 pA at -20 mV with a slope conductance of 12.1 pS. The autoantibodies implicated in the Lambert-Eaton myasthenic syndrome (LES), which are known to inhibit ICa and INa in bovine adrenal chromaffin cells, also significantly inhibited INa in SCLC cells. These results indicate that (i) action potentials in human SCLC cells result from the regenerative increase in voltage-gated Na+ channel conductance; (ii) fundamental characteristics of SCLC Na+ channels are the same as the classical sodium channels found in a variety of excitable cells; and (iii) in some LES patients, SCLC Na+ channels are an additional target of the pathological IgG present in the patients' sera.
 ...
PMID:Voltage-dependent sodium channels in human small-cell lung cancer cells: role in action potentials and inhibition by Lambert-Eaton syndrome IgG. 773 Oct 34

Photodynamic therapy (PDT) has been used investigationally for the treatment of lung cancer since 1980. Following systemic administration of a photosensitizing agent such as porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), specialized optical delivery systems are engaged to deliver light of a specific wavelength (630 nm for porfimer sodium) to neoplastic tissue. A promising use of PDT appears to be treatment of early stage lung carcinoma. Phase I-II clinical trials by Hayata's group in Japan showed that for superficial early lung cancer less than 1 cm in surface diameter, complete eradication can be achieved in approximately 90% of cases. Additional phase II-III clinical trials have demonstrated an average of 90% complete response rates for superficial tumors less than 1 cm in diameter. Preoperative PDT may be useful for larger neoplasms to reduce tumor burden and potentially lessen the degree of surgery required. At the British Columbia Cancer Agency, 22 patients with 30 radiologically occult cancers were treated with PDT. In contrast to Hayata's studies, most of these patients had rather extensive tumor burden. Thirty percent of the tumors involved two or more bronchi, and more than half of them were greater than 1 cm in surface diameter. Twenty-three percent of the cases were bronchial stump recurrences. In the group of patients with bronchial stump recurrence, although a complete response was obtained with PDT initially, local recurrences occurred in 75% of cases. These results suggest that recurrent tumor in the bronchial stump should not be treated with PDT because of difficulty in delivering light endobronchially to distal tissues. Photodynamic therapy may have a role in the palliation of advanced, inoperable, obstructive bronchial tumors. Phytodynamic therapy in combination with external radiotherapy may produce better local control than external radiotherapy alone in patients with obstructive bronchial cancers. Photodynamic therapy and conventional Nd:YAG laser therapy appear to be equally effective in relieving intraluminal obstruction by tumor. An advantage of PDT for this purpose is longer time to treatment failure; a disadvantage is photosensitization that usually occurs for up to 4 weeks after treatment. In summary, PDT is a promising curative treatment for patients with small early bronchial cancers.
 ...
PMID:Photodynamic therapy of lung cancer. 799 2

Acute adrenal insufficiency is an uncommon complication of lung cancer and adrenal metastasis resection. Diagnosis is difficult to establish but an early recognition and treatment may be life-saving. A 55-year-old man underwent right upper lobectomy and adrenalectomy for lung carcinoma with right adrenal metastasis. Anaesthesia was obtained with propofol, alfentanil, atracurium and isoflurane. Blood pressure remained stable throughout surgical procedure and blood loss was about 3,000 ml. Several hours after the end of the procedure which was uneventful the circulator status worsened. The blood pressure was initially controlled with 500 ml of gelatin. External blood loss was about 200 ml. Clinical examination, chest X-ray and ECG were normal. Postoperative laboratory data showed a serum sodium at 134 mmol-1.l-1 and a serum potassium 5.1 mmol.l-1; haemoglobin concentration was 93 g.l-1. Arterial blood gas analysis, with a 5.1.min-1 nasal O2 flow showed a PaO2 at 108 mmHg, a PaCO2 at 30 mmHg and a pH at 7.44. Twelve hours later, a transient cardiac arrest occurred which responded to fluid load, dopamine and dobutamine. Six hours later, the patient went in ventricular fibrillation responding to an external electric countershock. No change in clinical status was noticed, except hyperthermia at 39.5% degrees C. Serum potassium concentration before cardiac arrest was 4.7 mmol-l-1. Main considered diagnoses were septic shock and acute adrenal insufficiency. Antibiotics (imipenem, amikacin and vancomycin) and hormonal treatment (hydrocortisone 200 mg.day-1), after blood samples had been obtained for bacteriological and hormonal examinations. The patient's condition improved dramatically within 48 hours. Shock was under control, dopamine and dobutamine were rapidly discontinued.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Postoperative acute adrenal insufficiency]. 801 76

Although the mechanisms responsible for alveolar liquid clearance have been studied in several species, there has not been any information regarding the effect of ion transport agonists or antagonists on alveolar liquid clearance in the human lung. Therefore, we studied alveolar liquid clearance in the recently resected human lung from patients who underwent surgery for lung cancer. A test solution of 40 ml of isosmolar albumin solution was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air spaces very slowly, the concentration of alveolar protein over 4 h was used to quantify alveolar liquid clearance. Basal alveolar liquid clearance was 12 +/- 2% over 4 h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, and ouabain (10(-3) M), an inhibitor of Na,K-ATPase activity, reduced alveolar liquid clearance by 40 and 49%, respectively (p < 0.005). Terbutaline (10(-3) or 10(-4) M) doubled alveolar liquid clearance to 28 +/- 9% over 4 h (p < 0.05). Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in alveolar liquid clearance. In conclusion, (1) alveolar liquid clearance in the human lung can be markedly reduced by inhibition of apical sodium channel uptake or Na,K-ATPase activity, and (2) beta-adrenergic stimulation markedly increases the rate of alveolar liquid clearance in the resected human lung without pulmonary perfusion.
 ...
PMID:Alveolar fluid clearance in the resected human lung. 804 6

We retrospectively reviewed the charts of 151 consecutive patients diagnosed as small cell lung cancer in our department and who had at least one course of chemotherapy. Nineteen patients died during the first 2 months, of the probability were reported to construct a receiver operating characteristic curve i.e. 13% of the population. The probability of dying within 2 months was investigated through a stepwise logistic regression. A performance status < or = 70 (Karnofsky index), an age > 60, a platelet count < or = 150,000/mm3, elevated alkaline phosphatase and a sodium < or = 135 mmol/l were independent predictors of a very short term survival and contributed to the equation for the probability of dying within a 2-month period. Sensitivity and specificity for various cutoff points characteristic curve allowing one to determine for a given patient his risk of being a very short term survivor. Such an approach could prevent inclusion of patients with high risk of early death in clinical trials and help to choose appropriate treatments for such poor risk patients.
Lung Cancer 1993 Dec
PMID:Can we predict very short term survival in small cell lung cancer? 807 68

Patients with lung cancer (n = 263) were studied to determine the relationship among ectopic production of atrial natriuretic factors (ANF) and arginine vasopressin (AVP), serum sodium, and patient outcome. Of 133, 21 (16%) patients with small cell lung cancer (SCLC) had hyponatremia (serum sodium, < 130 mmol/liter), compared to none of 130 (0%) patients with non-small cell lung cancer (P < 0.0001). Patients with extensive-stage SCLC and hyponatremia had shorter survival than patients with extensive stage SCLC and normal serum sodium values (P = 0.012). Of the 11 hyponatremic patients with SCLC and tumor cell lines available for study, 9 produced ANF mRNA, 7 of 11 produced AVP mRNA, and 5 of 11 produced both ANF mRNA and AVP mRNA. All 11 cell lines produced either ANF mRNA and ANF peptide or AVP mRNA and AVP peptide, or both. The quantity of AVP peptide in the tumor cell lines was more closely associated with hyponatremia in the patients (P = 0.0026, r2 = 0.28) than was the production of ANF peptide (P = 0.066, r2 = 0.12), although neither association was strong. All tumor cell lines studied from SCLC patients with hyponatremia produce ANF and/or AVP mRNA and peptides.
 ...
PMID:Atrial natriuretic factor and arginine vasopressin production in tumor cell lines from patients with lung cancer and their relationship to serum sodium. 838 Jan 26

A total of 53 patients with advanced lung cancer [non-small-cell (NSC), 21; small-cell (SC), 32] were treated with brequinar sodium. All of the NSC patients were chemotherapy-naive, but 31/32 (97%) SC patients had failed a multiagent chemotherapy program prior to study entry. Brequinar was given intravenously at a median weekly dose of 1200 mg/m2. The toxicity was moderate, with 19 patients (36%) experiencing grade 3 or 4 toxicity. Objective responses were observed in one NSC and two SC patients. We conclude that at this dose and on this schedule, brequinar does not have sufficient activity in patients with NSC or in patients with previously treated SC to warrant further evaluation. However, since responses were observed in previously treated SC lung-cancer patients, further evaluation in chemotherapy-naive patients may be warranted.
 ...
PMID:Multicenter phase II study of brequinar sodium in patients with advanced lung cancer. 838 37

The follow-up of a cohort of workers employed in an electrochemical plant producing cobalt and sodium, previously studied from 1950-1980, has been extended from 1981-1988. The standardized mortality ratio (SMR) for all causes of death was 0.85 (95% confidence interval [CI] = 0.76-0.95, 309 observed) for the whole cohort, and 0.95 (95% CI = 0.83-1.08, 247 observed) for the subcohort of workers born in France. With regard to lung cancer mortality among cobalt production workers, which is the main objective of the study, the SMRs were, respectively, 0.85 (95% CI = 0.18-2.50, 3 observed) and 1.16 (95% CI = 0.24-3.40, 3 observed). Neither did any excess of mortality from diseases of the circulatory and of the respiratory systems appear among cobalt production workers. Maintenance workers, however, exhibited high SMRs for lung cancer, reaching statistical significance for duration of exposure and time since first exposure > or 30 years. This study does not support the hypothesis of a relationship between lung cancer and cobalt exposure.
 ...
PMID:A mortality study of cobalt production workers: an extension of the follow-up. 842 56

Little information is available regarding the effect of ion transport agonists and antagonists on ion transport in the human lung. Therefore, we studied ion transport in lungs resected from patients with lung cancer. A test solution of 45 ml of isosmotic albumin was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air space very slowly, the concentration of alveolar protein over 4 h was used to quantify the volume of alveolar fluid. Ion transport was measured from the changes in ion concentrations and the volume of alveolar fluid. In the basal condition, the net efflux of Na+ and Cl- were 4.66 +/- 0.83 mEq/l/h and 3.52 +/- 0.84 mEq/l/h, respectively. In contrast, the net influx of K+ was 0.44 +/- 0.07 mEq/l/h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, ouabain (10(-3) M), an inhibitor of Na(+)-K+ ATPase, and hypothermia (8 degrees C) reduced the efflux of Na+ and Cl-. Ouabain and hypothermia increased the net influx of K+. Terbutaline (10(-3) or 10(-4) M) increased the efflux of Na+ and Cl-, but did not affect the influx of K+. Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in the transport of Na+ and Cl-. Alveolar fluid clearance was closely correlated with Na+ transport and with Cl- transport. However, the values of Na+ transport were greater than those of Cl- transport. These data suggest that Na+ transport is accompanied by Cl- transport and fluid movement out of the alveolar space in resected human lungs.
 ...
PMID:[Transport of ions across alveolar epithelial cells in resected human lungs]. 853 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>