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

In this study, we investigated the generation of dendritic cells (DCs) from blood monocytes and mature macrophages from untreated primary lung cancer patients. Blood monocytes were separated by adherence from blood mononuclear cells (MNC) from ten lung cancer patients and ten control subjects, and cultured for 7 days in medium with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL-) 4. In all cases examined, DCs with typical characteristics were obtained even in lung cancer patients after 7 days culture with these cytokines, and there was no significant difference in phenotype and stimulatory activity in allogeneic lymphocyte proliferation between DCs derived from monocytes from lung cancer patients and those from control subjects. Next, we examined whether alveolar and pleural macrophages in malignant pleural effusion separated by magnetic beads could differentiate to immunostimulatory DCs. Conventional culture conditions with GM-CSF and IL-4 did not induce efficient numbers of DCs from mature macrophages, whereas the addition of tumor necrosis factor-alpha (TNF-alpha) to GM-CSF and IL-4 effectively contributed to generate DCs. These findings suggest that both mature macrophages and blood monocytes from lung cancer patients could differentiate to DCs, and might be a useful source of DCs for immunotherapy.
Lung Cancer 2001 Nov
PMID:Efficient generation of dendritic cells from alveolar and pleural macrophages as well as blood monocytes in patients with lung cancer. 1167 78

Talc pleurodesis is an effective technique for the management of symptomatic malignant pleural effusions. It is assumed that a good dispersion of talc suspension contributes to the final success of this treatment. For this purpose, guidelines often advise to rotate the patient after intra-pleural instillation of the sclerosant. This prospective, randomized study analyses the dispersion of talc suspension and the overall success rate in patients with malignant effusions. After instillation of 99mTc-sestamibi-labeled talc suspension ten subjects were rotated for 1 h, while the ten other patients remained in a stable supine body position. Scintigraphic imaging was done in two directions immediately after instillation and after 1 h with a clamped drain. The overall success of the treatment was assessed 1 month after the pleurodesis. The dispersion of talc was limited and unequal in 75% of the subjects. In two patients with apparently good distribution on anterior views, the lateral views of the scintigraphy showed only limited distribution. Rotation of the patients did not influence the dispersion of sludge after 1 min or 1 h. Pleurodesis was successful in 85% of the patients after 1-month follow-up. Standard rotation protocols for patients with malignant pleural effusion do not affect the overall dispersion of talc suspension and should be abolished because of the discomfort caused to the patients.
Lung Cancer 2002 Apr
PMID:Distribution of talc suspension during treatment of malignant pleural effusion with talc pleurodesis. 1189 Oct 37

The aim of this pilot study was to evaluate the activity and toxicity of docetaxel plus carboplatin as second-line treatment in patients with metastatic non-small cell lung cancer (NSCLC). Patients received docetaxel 75 mg/m(2) followed by carboplatin AUC 5 on day 1 every 3 weeks in an out-patient setting. Twenty-six patients were enrolled; 23 patients were diagnosed stage IV disease and three patients had a IIIB disease with malignant pleural effusion. The median interval from first to second-line treatment was 3.5 months (range 1-13). Patients received a total of 101 cycles with a median number of four cycles per patient (range 1-6). Five patients achieved a partial remission (19.23%; 95% confidence interval (CI) 6.55-39.35%), 11 had stable disease (42.31%) and ten progressed (38.46%) after initiation of second-line therapy. Median survival was 243 days (95% CI 182-336 days), the median progression-free survival was 118 days (95% CI 89-170 days), and the 1-year survival rate was 25.98% (95% CI 6.33-45.63%). Moderate haematological and mild nonhaematological toxicities were observed. No treatment-related death occurred. In conclusion, docetaxel plus carboplatin as second-line regimen has a reasonable activity with good tolerance and encouraging survival data.
Lung Cancer 2002 Jun
PMID:Docetaxel and carboplatin as second-line chemotherapy for metastatic non-small cell lung cancer. 1200 43

In pursuing a tissue diagnosis of a suspected lung cancer, there is a range of procedures to choose from. The principal goals are ideally to diagnose and pathologically stage the patient's lung cancer at the same time, preferably by using the safest, least invasive, and least costly tests. If there is clinical or radiographic evidence of extrapulmonary spread of disease, including supraclavicular N3 nodal involvement or a malignant pleural effusion, then radiology-guided or open biopsy will confirm tumor cell type and stage the patient as unresectable. For patients with symptoms, such as increasing cough or hemoptysis, that are suggestive of airways involvement. with or without radiographic finding of central lesions, sputum cytology is the least invasive study with a high specificity. A positive finding of cancer is especially helpful if the patient is not a surgical candidate because of anatomic location of the lesion or severe physiologic limitations. The limited sensitivity of sputum cytology and poor NPV may improve with improved sputum induction and collection and processing techniques. Bronchoscopy with direct examination of the visible airways is most often the preferred invasive diagnostic procedure. Although the procedure should be geared toward sampling the highest staged lesion to provide an accurate tissue staging at the time of diagnosis, additional procedures can be performed in sequence to sample different nodal stations, is well as the primary lung mass. The incidental finding of an unexpected central airways lesions or a synchronous second endobronchial lung primary will also affect plans for treatment. Autofluorescence bronchoscopy can improve the sensitivity for detecting early intraepithelial neoplasia. Bronchoscopy for central and peripheral lung masses that are suspected to be lung cancer should be performed with ROSE whenever available. For visible endobronchial lesions, given the similar yield of EBBX and EBNA, EBNA may provide an immediate diagnosis, thus obviating additional, possibly morbid, procedures such as BB or EBBX. For submucosal lesions, EBNA is superior. For central cancers that are peribronchial, TBNA performed as for regional nodal sampling should have a yield that is comparable to TBNA for staging. TBBX and TBNA of peripheral nodules that are smaller than 3 cm have a lower diagnostic yield. Coming generations of thin bronchoscopes and improved radiographic guidance systems may improve our ability to biopsy these lesions with greater accuracy and safety. Under all circumstances, immediate cytology feedback with ROSE will confirm the adequacy of the retrieved specimen for a definitive tissue diagnosis, thus avoiding the need for extra biopsies, or worse yet, the need for a second invasive procedure because of insufficient diagnostic material. ROSE is educational to the clinician and fellow-in-training in getting immediate feedback on the procedural techniques and in learning pulmonary pathology, as well. The diagnostic sensitivity of TTNA is high, especially for the larger peripheral-based lung lesion, and TTNA is a relatively rapid procedure. TTNA's sensitivity falls for smaller or more central lesions, where the false negative rate can approach 25% to 30%; the risk of pneumothoraces and bleeding increases with central biopsies. Furthermore, TTNA usually does not provide information about nodal staging, unless the TTNA is initially directed toward central lymph nodes. The central airways are not examined in the same appointment to address issues of resection margins when there may be central spread of disease. TTNA should, therefore, be held in reserve for cases in which the sputum cytology and subsequent bronchoscopy are negative, and the patient is not a surgical candidate or refuses surgery, even if the cancer is potentially resectable. TTNA may then provide the tissue diagnosis to permit initiation of cytotoxic chemotherapy and radiotherapy. TTNA may also be helpful in cases where the likelihood of cancer is only intermediate, such that a specific benign diagnosis or an adequate sample without cancer will greatly reduce the likelihood ratio of missing a cancer, and justify to the patient and physician an approach of careful observation. To maximize the yield of these diagnostic procedures, there must be continued improvement in the hands-on teaching of clinical fellows and pulmonary practitioners in the use of the various techniques of TBNA and TBBX, as well as the applications of new endoscopic technology, such as EBUS. Definitive curative surgery remains the goal for patients with lung cancer, with accurate pathological staging performed intraoperatively. Complete lobectomy or pneumonectomy remains the standard resectional approach. Therefore, for patients with sufficient cardiopulmonary reserve who can be clinically staged as IA or IB, either by good quality CT with contrast or increasingly with 18-FDG PET, the initial tissue diagnosis may be at the time of surgery, when a frozen section preceding a complete lobectomy with lymph node sampling will combine diagnosis and therapy.
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PMID:Tissue diagnosis of suspected lung cancer: selecting between bronchoscopy, transthoracic needle aspiration, and resectional biopsy. 1282 Jul 12

Soluble Fas (sFas) has the ability to block Fas-mediated apoptosis, suggesting that sFas at tumor sites might inhibit tumor cell-killing by immune effector cells. We examined the sFas level in pleural effusion associated with lung cancer. The level of sFas in malignant pleural effusion was significantly higher than those in transudate and tuberculous pleural effusion. There was no significant difference in the sFas concentration among various histological types of lung cancer. The cytotoxicity mediated by anti-Fas agonistic antibody against Jurkat cells was inhibited by the addition of malignant pleural effusion, being inversely correlated with the sFas concentration. When Fas expression was examined using flow cytometry, eight of ten (80%) lung cancer cell lines expressed cell surface Fas. On the other hand, sFas protein and mRNA were detected in six of ten (60%) lung cancer cell lines, but there was no correlation between Fas and sFas expression. Furthermore, although the expressions of Fas and sFas were clearly detected in tumor cells derived from malignant effusion, the sFas expression was down-regulated in an in vitro culture. These results suggest that sFas in malignant pleural effusion is at least in part produced by lung cancer cells, and might play a role in local immunosuppression by tumor cells.
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PMID:Soluble Fas in malignant pleural effusion and its expression in lung cancer cells. 1282 26

The use of dendritic cells (DCs) for cancer vaccination is effective in suppressing cancer progression. This is because the DCs play a crucial role in priming tumor-specific immunity efficiently as antigen-presenting cells. In this study, we analyzed the ability of DCs to elicit tumor-specific immunity and clinical effects of DC vaccine immunotherapy targeting MUC1 tumor antigens. DCs from 14 patients with advanced or metastatic breast or lung cancer (9 positive for MUC1 and 5 negative for MUC1) were loaded with MUC1 antigens or tumor lysate and used for therapeutic vaccination. After vaccination, all the MUC1-positive patients acquired antigen-specific immunity whereas only 1 case with MUC1-negative cancer showed the specific immunity. Clinically, marked effects such as reduction in tumor sizes or tumor marker levels or disappearance of malignant pleural effusion were observed in 7 of the 9 MUC1-positive cases. However, MUC1-negative patients did not respond to DC vaccines, with the exception of 1 case with MAGE3-positive lung cancer. Survival of MUC1-positive patients was significantly prolonged in comparison with MUC1-negative patients (mean survival: 16.75 versus 3.80 months, p=0.0101). These data suggest that MUC1 is sufficiently immunogenic to elicit strong anti-tumor immunity as a tumor antigen and that DC vaccines targeting MUC1 are useful for immunotherapy of cancer.
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PMID:Dendritic cell vaccine immunotherapy of cancer targeting MUC1 mucin. 1296 25

Endostatin is an angiogenesis inhibitor that is an endogenously produced proteolytic fragment of type XVIII collagen. Although serum levels of endostatin have extensively been studied in patients with malignant diseases, endostatin in pleural effusion has not been fully evaluated. In order to determine whether endostatin is present in pleural effusion, and to determine whether endostatin levels vary in pleural effusion of different etiology, we measured levels of endostatin in 38 malignant pleural effusion due to lung cancer patients and 29 patients with non-malignant disease using an ELISA kit. Free form of endostatin was measurable (> 11.2 pg/ml) in 26 of 38 malignant and 13 of 29 non-malignant pleural effusion. Endostatin levels in the 38 malignant pleural effusion were significantly higher than those in patients with the 29 patients with non-malignant diseases ( p = 0.0131). However, there was not statistically significant difference between the patients with pleuropneumonia and those with tuberculous pleurisy ( p = 0.2194). In malignant pleural effusion due to lung cancer, the pleural effusion endostatin levels did not differ when the histological types of lung cancer were considered ( p = 0.0674). Endostatin was present in both malignant and non-malignant pleural effusion, and elevated levels of endostatin were observed in malignant pleural effusion. Although the mechanisms are unclear, elevated levels of endostatin in pleural effusion may represent the local productions of endostatin in pleural space.
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PMID:Endostatin levels in exudative pleural effusions. 1474 37

The role of non-platinum combination chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has not yet been clarified. In this phase I study, the dose-limiting toxicity (DLT), the maximum tolerable dose (MTD) and the antitumor activity of a two-drug combination of docetaxel (DCT) and irinotecan (CPT) in patients with advanced NSCLC were evaluated. Previously untreated patients with NSCLC in stage IIIB with malignant pleural effusion or stage IV were eligible. Both drugs were administered by 1-h intravenous infusion on day 1, and repeated every 3 weeks. DCT was given before CPT administration. Five escalating dose levels of DCT/CPT (40/135, 50/135, 50/150, 60/150, and 60/165 mg/m2) were studied. Eighteen patients received 44 courses. The DLT was considered to be neutropenia, because grade 4 neutropenia lasting for 3 days or more was observed in three patients, which was accompanied with three episodes of febrile neutropenia. As a non-hematological toxicity, grade 3 diarrhea occurred in three patients. Since all the three patients treated at the fifth dose level (DCT at 60 mg/m2 and CPT at 165 mg/m2) experienced DLT (grade 4 neutropenia in two patients and grade 3 hepatic toxicity in one), this dose level was determined to be the MTD. The objective response rate was 33.3%, and the median survival time was 13.6 months. To confirm the effectiveness of this combination for advanced NSCLC which was suggested in the present study, a phase II study with the recommended doses (150 mg/m2 for CPT and 50-60 mg/m2 for DCT) is warranted.
Lung Cancer 2004 Jul
PMID:Phase I study of docetaxel and irinotecan in patients with advanced non-small-cell lung cancer. 1519 38

The objective of the study was to evaluate the number of myeloid (DC1) and lymphoid (DC2) dendritic cells in malignant pleural effusion and peripheral blood of patients with lung cancer as well as to estimate changes in their presence during intrapleural interferon alpha treatment. The study comprised eight subjects including two patients treated with Roferon A. Isolated mononuclear cells were phenotyped with the following monoclonal antibodies: anti-BDCA-1 FITC and anti-BDCA-2 FITC, and analyzed using FACSCalibur flow cytometry. Very low percentage of DC2 and high BDCA-1/BDCA-2 ratio in malignant pleural effusion of patients not treated with IFN-alpha suggest intensive Th1 response probably responsible for inflammatory state maintenance and effusion constant development. The results of our study indicate that apart from the suggested antitumour activity, IFN-alpha therapy may result in unfavourable immunotolerance caused by increased DC2 activity.
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PMID:Presence of dendritic cells in malignant pleural effusion: pilot study. 1531 85

Malignant pleural effusion develops frequently in patients with advanced lung cancer. Chemical pleurodesis is the most effective palliative treatment for these patients. The efficacy of pleurodesis using both OK-432, a preparation of Streptococcus pyogenes, and doxorubicin for 20 patients with cytology-proven malignant pleural effusion associated with lung cancer was evaluated. After complete removal of pleural effusion, OK-432 and 30 mg of doxorubicin were injected via an inserted chest tube. Treatment was terminated when the volume of daily drainage reached <200 mL. If the daily volume remained >200 mL, an additional OK-432 was administered every 3 days. In total, 16 patients (80%) revealed a complete response, two patients (10%) revealed a partial response, and no response was seen in two patients. Eighteen patients with complete or partial responses did not show subsequent reaccumulation of pleural effusion after pleurodesis. The chest tube remained in place for an average of 6.4 days, draining a mean of 2,854 mL. The main side-effects were fever and pain that were easily treated with nonsteroidal anti-inflammatory drugs. Pleurodesis using both OK-432 and doxorubicin showed high efficacy for controlling malignant pleural effusions caused by lung cancer.
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PMID:Efficacious pleurodesis with OK-432 and doxorubicin against malignant pleural effusions. 1533 95


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