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)

To assess the effect and toxicity of hypotonic cisplatin treatment (HPT) consisting of the intrapleural administration of cisplatin in distilled water for malignant pleural effusion in patients with non-small-cell lung cancer (NSCLC). Non-small-cell lung cancer patients with cytologically proven and previously untreated malignant pleural effusion were enrolled into this study. Firstly, the lung was fully re-expanded by a tube thoracostomy, and then 25 mg cisplatin in 500 ml of distilled water was instilled through a chest tube and then the tube was clamped. After 1 h, the tube was declamped and allowed to drain. The chest tube was removed when the pleural effusion volume decreased to 200 ml or less per day. A complete response (CR) was considered to occur when the pleural effusion disappeared. A partial response (PR) was determined to occur when the volume of pleural effusion remained under (1/4) of hemithorax. The response at 4 weeks was evaluated by an extramural review. Out of 84 patients enrolled from February 1998 to August 2002, 80 patients were eligible and analysed in the present study. The toxicity of HPT was acceptable. Neither a haematological toxicity of any grade nor grade 4 nonhaematological toxicity was observed. Grade 3 nonhaematological toxicities were observed, including nausea (4%), vomiting (3%), pyothorax (1%) and dyspnoea (1%). The median time of drainage from HTP was 4 days. Twenty-seven (34%) and 39 (49%) patients achieved CR and PR, respectively, for an overall response rate of 83% (95% confidence interval, 74-91%). The median duration of the response was 206 days. The median survival time of all patients was 239 days. Hypotonic cisplatin treatment for malignant pleural effusion of NSCLC is therefore considered to be feasible and effective. A phase III study of HPT is thus warranted.
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PMID:Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-small-cell lung cancer: a multi-institutional phase II trial. 1694 Sep 82

A case of tension pneumothorax developed after placement of a tunneled pleural catheter for treatment of malignant pleural effusion in a patient with advanced lung cancer. The catheter placement was carried out by an experienced operator under direct ultrasound guidance, and the patient showed immediate symptomatic improvement with acute decompensation occurring several hours later. Possible mechanisms for this serious complication of tunneled pleural catheter placement are described, and potential strategies to avoid or prevent it in future are discussed.
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PMID:Tension pneumothorax after placement of a tunneled pleural drainage catheter in a patient with recurrent malignant pleural effusions. 1696 12

Accumulating evidence implicates epigenetic changes such as hypermethylation in carcinogenesis. We investigated whether DNA methylation of 5 tumor suppressor genes in pleural fluid samples could aid in diagnosis of malignant effusion. In samples from 47 patients with malignant pleural effusions and 34 with nonmalignant effusions, we used a methylation-specific polymerase chain reaction to detect aberrant hypermethylation of the promoters of the DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT), p16(INK4a), ras association domain family 1A (RASSF1A), apoptosis-related genes, death-associated protein kinase (DAPK), and retinoic acid receptor beta (RARbeta). Promoter hypermethylation was associated with malignant effusion for MGMT (Odds ratio (OR) = infinity), p16(INK4a) (OR = infinity), RASSF1A (OR = 13.8; CI, 1.71-112), and RARbeta (OR = 3.17; CI, 1.10-9.11), but not for DAPK. Instead, DAPK methylation was associated with the length of smoking (p < 0.05). Patients with hypermethylation of MGMT, p16(INK4a), RASSF1A or RARbeta were 5.68 times more likely to have malignant effusions than patients without methylation (p = 0.008). Methylations per patient were more numerous for lung cancer than nonmalignant pulmonary disease (0.915 vs. 0.206, p < 0.001). Sensitivity, specificity, and positive predictive value of methylation in one or more genes for diagnosis of malignant effusion were 59.6%, 79.4%, and 80.0% respectively. In conclusion, aberrant promoter methylation of tumor suppressor genes in pleural fluid DNA could be a valuable diagnostic marker for malignant pleural effusion.
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PMID:Aberrant promoter methylation in pleural fluid DNA for diagnosis of malignant pleural effusion. 1728 79

We previously demonstrated a dominant IgG response against XAGE-1b antigen in a lung cancer patient by serological analysis of antigens by recombinant expression cloning (SEREX) analysis using a cDNA library from the autologous OU-LU-6 tumor cell line. In this study, we investigated recognition of XAGE-1b on OU-LU-6 tumor by the patient CD4-expressing tumor-infiltrating lymphocytes (CD4 TIL). The response of CD4 TIL obtained from malignant pleural effusion was determined against autologous OU-LU-6 tumor cells and XAGE-1b mRNA-transfected PHA-stimulated CD4 T-cells (T-APC) from healthy individuals sharing HLA-DR with the patient by performing IFNgamma secretion and ELISPOT assays. The patient CD4 TIL recognized OU-LU-6 in an HLA-DR-restricted manner and XAGE-1b mRNA-transfected T-APC derived from DRB1 *0901-sharing healthy donor (HD)1 and HD2, but not DRB1 *1101-sharing HD3 or HD4. Epitope analysis using 17 18-mer peptides with 12 overlapping amino acids revealed that the CD4 TIL recognized XAGE-1b 33-49. The findings suggest that the patient CD4 T-cells recognized the XAGE-1b 33-49-related epitope on autologous OU-LU-6 tumor cells in a manner restricted by DR *0901.
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PMID:Identification of DR9-restricted XAGE antigen on lung adenocarcinoma recognized by autologous CD4 T-cells. 1733 21

For the treatment of lung cancer with advanced pleural spread, aggressive local treatment could offer a chance of cure. This study evaluates the early and midterm results of our Phase I trial for the new modality of two-stage approach combining thoracoscopic intrapleural perfusion hyperthermic chemotherapy (TIPHC) and panpleuropneumonectomy for the disease. Five patients were enrolled in this study. All had proven lung cancer with major malignant pleural effusion or numerous pleural dissemination. The combined regimen was planned first with TIPHC using high doses of cisplatin, followed by a second stage with panpleuropneumonectomy with full-thoracotomy approach as radical surgery. All patients successfully completed this treatment, and there were no serious complications. Panpleuropneumonectomy was performed 14+/-1.2 days after TIPHC, and the mean operation time was 280+/-35 min, the blood loss was 620+/-89 ml. One patient with pathological N2 developed liver metastases 8 months after surgery and died. The other four patients are living and have not experienced any recurrence to date. The mean survival time is 19 months, and the longest is 32 months. Our new treatment modality is feasible and seems to provide a possibility for safe and effective radical local tumor control for patients of lung cancer with advanced carcinomatous pleuritis.
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PMID:Combined surgery of intrapleural perfusion hyperthermic chemotherapy and panpleuropneumonectomy for lung cancer with advanced pleural spread: a pilot study. 1767 Jan 54

To evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin (BLM), OK-432 (a pulverized product of heat-killed Streptococcus pyogenes) or cisplatin plus etoposide (PE) for the management of malignant pleural effusion (MPE) in previously untreated non-small cell lung cancer. Eligible patients were randomized to the BLM arm: BLM 1mg/kg (maximum 60mg/body), the OK-432 arm: OK-432 0.2 Klinische Einheit units (KE)/kg (maximum 10KE/body), or the PE arm: cisplatin (80mg/m(2)) and etoposide (80mg/m(2)). Pleural response was evaluated every 4 weeks according to the study-specific criteria. All responders received systemic chemotherapy consisting of PE every 3-4 weeks for two or more courses. Pleural progression-free survival (PPFS) was defined as the time from randomization to the first observation of pleural progression or death due to any cause. The primary endpoint was the 4-week PPFS rate. Of 105 patients enrolled, 102 were assessed for response. The 4-week PPFS rate for the BLM arm was 68.6%, 75.8% for the OK-432 arm, and 70.6% for PE arm. Median survival time (MST) for the BLM arm was 32.1 weeks, 48.1 weeks for the OK-432 arm, and 45.7 weeks for the PE arm. However, the outcomes did not differ significantly between groups. Toxicity was tolerable in all arms except for one treatment-related death due to interstitial pneumonia induced by BLM. We will select intrapleural treatment using OK-432 in the management of MPE in NSCLC for further investigation because it had the highest 4-week PPFS rate.
Lung Cancer 2007 Dec
PMID:Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer: JCOG 9515. 1771 79

Distinguishing malignant from benign pleural effusions using routine cytology is a common diagnostic problem. Recently, genetic alterations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), have been described in malignant pleural effusions and proposed as methods improving diagnostics. The purpose of this study was to evaluate a panel of molecular markers for the detection of genetic alterations of cells in pleural effusions and to determine their diagnostic value as an additional test to cytologic examination. Pleural fluid and peripheral blood from 48 patients (36 male and 12 female, median age 71 years) were analyzed. Twenty-six patients had malignant pleural effusion, including 23 lung cancer and three metastatic non-pulmonary carcinoma. The control group consisted of 22 patients with benign pleural effusions. Only 14 malignancy-associated pleural effusions were cytology-positive for malignant cells (54%), whereas all benign pleural effusions were negative. DNA was extracted from all the samples and analysed for MSI and/or LOH using the following microsatellite markers: D3S1234, D9S171, D12S363, D17S250, D5S346 and TP53Alu, located at five chromosomal regions: 3p, 9p, 12q, 17q, 5q. Microsatellite analysis of the pleural fluid pellet exhibited genetic alterations in two neoplastic pleural fluid cases and in one inflammatory case. Two out of 26 (7.6%) patients with malignant pleural effusion showed genetic alterations. One exhibited MSI in three different microsatellite markers (D17S250, D9S171, D3S134) and the other showed LOH in marker D3S134. One out of 22 (4.5%) patients with benign pleural effusion showed LOH in marker D3S134. In conclusion, genetic alterations at the level of microsatellite DNA, were detected only in very few cases of malignant pleural effusions, and in one case of benign pleural effusion. Thus, our data suggest that microsatellite DNA analysis does not facilitate the diagnosis of malignant pleural effusion.
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PMID:Microsatellite DNA analysis does not distinguish malignant from benign pleural effusions. 1798 37

Cells or cell-free fluid of malignant pleural effusion could be important clinical specimen for epidermal growth factor receptor (EGFR) mutation screening in advanced non-small cell lung cancer (NSCLC) patients. However, their usefulness in mutation detection has not been well compared. In this study we recruited 26 East Asian NSCLC patients with malignant pleural effusion, determined the mutation status of EGFR in both cells and matched cell-free fluid with the use of sequencing and mutant-enriched PCR. After comparing the mutation spectrums, we found both the cells and cell-free pleural fluid may be feasible clinical specimen for EGFR mutation detection in unresectable NSCLC given sensitive genotyping assays employed. Direct sequencing could miss a significant portion of mutations in these heterogeneous specimens. More sensitive methods, such as mutant-enriched PCR and gene scan, could provide more reliable mutational information.
Lung Cancer 2008 May
PMID:Detection and comparison of epidermal growth factor receptor mutations in cells and fluid of malignant pleural effusion in non-small cell lung cancer. 1806 5

In the present study, the expressions of B cell activating factor belonging to the tumor necrosis factor family (BAFF) and its receptors (BAFF-R and TACI) on T lymphocytes from malignant pleural effusion (MPE) were examined by fluorescence-activated cell sorting (FACS) analysis, and compared with those on the T lymphocytes from non-malignant pleural effusion (NMPE) and healthy controls. It was found that CD3 positive T lymphocytes (including CD4, CD8, and part of CD25 and CD69 positive cells) of MPE in lung cancer highly and consistently expressed the BAFF molecule, while high expressions of BAFF could only be found in phytohemagglutinin (PHA) or interleukin 2 (IL-2) induced T lymphocytes from NMPE or healthy controls. These results were consistent with the results from BAFF mRNA detection by real-time PCR. In addition, T lymphocytes from MPE expressed significantly more BAFF-R than those from NMPE or healthy controls, while the expression of TACI was increased on CD4+ T cells but decreased on CD8+ T cells when compared with controls. The Annexin/PI assay suggested that recombinant human BAFF (rhBAFF) could promote the survival rate of T lymphocytes from MPE, while the decoy receptor TACI-Fc fusion protein could promote the apoptosis rate of T lymphocytes. Cytokines in the supernatant detected by ELISA assay showed that rhBAFF could significantly upregulate the secretion of IFN-gamma in vitro, and the IFN-gamma level in the TACI-Fc-treated group resembled that of the control groups. All of these results indicated that the abnormally high expression of BAFF on T lymphocytes from MPE may play a role of anti-tumor effect.
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PMID:Abnormally high expression of BAFF on T lymphocytes from lung cancer-associated pleural effusions and its potent anti-tumor effect. 1806 89

The diagnosis and management of a malignant pleural effusion can be one of the most vexing problems faced by physicians and their patients. Lung cancer is the most common primary tumor of origin with a prognosis that is limited, but variable and correlated with performance status (PS). Therefore, with a poor PS and known advanced lung cancer, establishing whether or not an effusion is malignant might not be necessary. Conversely, identifiable subsets of patients will have a much better survival, and establishing a definitive diagnosis could be of critical importance. In the great majority of cases, a diagnosis can be determined by serial thoracenteses with or without closed pleural biopsy. However, thoracoscopy is increasingly being utilized and can expedite the workup by obviating the need for repeated thoracenteses and/or closed pleural biopsy, while in the same setting providing definitive palliative treatment. Although studies comparing diagnostic and treatment strategies are limited, we will present the available data with the intention of providing the practicing oncologist with a practical strategy for the diagnosis and management of malignant pleural effusions due to lung cancer. The interventional pulmonologist can play an important role from diagnosis to palliation, greatly facilitating the care of patients with malignant pleural effusions.
Clin Lung Cancer 2007 Nov
PMID:The evolving role of interventional pulmonary in the interdisciplinary approach to the staging and management of lung cancer. Part III: diagnosis and management of malignant pleural effusions. 1818 58


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