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

Two Japanese females complained of cough and bronchorrhea for which chest radiographs showed infiltrate in the lungs. The patients were subsequently diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy. After receiving systemic chemotherapy, their symptoms were slightly improved. A few months later, their bronchorrhea and dyspnea worsened, and they were then treated with gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor. Bronchorrhea and dyspnea were improved within 24 h after treatment with gefitinib where the improvement was evident after 6 h for one patient and 24 h for the other patient. Thereafter, their radiological findings showed gradual improvement. Rapid relief of bronchorrhea preceded the improvement seen by the radiological findings. These observations suggest that gefitinib may inhibit mucin production as well as exert anti-proliferative activity against bronchioloalveolar carcinoma.
Lung Cancer 2005 Jul
PMID:Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma; two case reports. 1594 98

A hypothesis of multistep carcinogenesis of lung adenocarcinoma from atypical adenomatous hyperplasia (AAH) to invasive adenocarcinoma through bronchioloalveolar carcinoma (BAC) has been proposed. However, the genetic alterations that play a role during these processes are not yet clear. Recently, somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in lung adenocarcinoma. We examined the status of EGFR mutations in AAH and BAC to elucidate the role they play during multistage of lung adenocarcinoma. We found somatic EGFR mutations in 3% (1/35) of AAH, 10.8% (4/37) of BAC and 41.9% (13/31) of invasive adenocarcinoma. Sixteen of 18 EGFR mutations were found in exon 19 and two were in exon 21. Among the 16 EGFR mutations in exon 19, 13 were deletions of 15bp and one was an insertion/duplication of 18bp. Mutations of the K-ras gene were detected in 26.7% (8/30) of AAH, 16.7% (5/30) of BAC and 10% (3/30) of invasive adenocarcinoma. None of the tumors with EGFR mutations had K-ras mutation simultaneously. Patients who had invasive adenocarcinoma with EGFR mutations were younger than those without mutations (60.6 versus 67.4 years, p=0.03). These results suggest that tumors with EGFR mutations may progress more rapidly and develop into invasive cancer faster than those without mutations. Alternatively it is also possible that some invasive adenocarcinomas with EGFR mutations may not follow the AAH-adenocarcinoma sequence. We analyzed 24 patients with multiple lung lesions and 13 patients had at least one lesion that had either an EGFR or K-ras mutation. In all cases each lesion had a different mutation status. This finding suggests that the genetic alterations responsible for the development of lung adenocarcinoma occur randomly even under exposure to the same carcinogen.
Lung Cancer 2005 Oct
PMID:Mutations of the epidermal growth factor receptor gene in atypical adenomatous hyperplasia and bronchioloalveolar carcinoma of the lung. 1595 Mar 15

Limited resection for early lung cancer has been associated with significantly higher local recurrence rates based on previous reports such as those from lung cancer study groups. On the other hand, a few groups demonstrated that patients with small peripheral cancer who undergo limited resection have comparable survival rates with those who undergo lobectomy. Recent advances in radiologic investigation and pathologic analysis have broadened the indications for limited resection. Since the introduction of the adenocarcinoma classification by Noguchi surgery for localized bronchioloalveolar carcinoma has focused on limited resection. Caution is necessary when performing wedge resection even if 10 mm or less in diameter and in compromised segmentectomy for early lung cancer. Although limited resection is still controversial intentional segmentectomy for localized bronchioloalveolar carcinoma or less than 20 mm or less in diameter may be recommended without evidence-based medicine. It is important to accumulate further evidence clarifying the survival and function benefits of limited resection. New therapeutic modalities for limited surgery for small-sized lung cancer may increase patient life expectancy.
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PMID:[Review and evaluation of limited resection for early lung cancer]. 1597 81

Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is an active agent in non-small cell lung cancer, and rapidly relieves bronchorrhea in patients with bronchioloalveolar carcinoma before the improvement of radiological findings. In addition, epidermal growth factor regulates mucin secretion in normal airway goblet cells. The present study was designed to clarify whether gefitinib modifies mucin production in lung cancer cell lines apart from its anti-proliferative effects, using A549 adenocarcinoma and NCI-H292 mucoepidermoid carcinoma cells expressing EGFR and MUC5AC mRNA. Mucin synthesis was measured by RT-PCR and ELISA, and MAPK and Akt, the downstream targets of EGFR, were examined by Western blotting assay. The clinically-achievable concentration of 1muM gefitinib inhibited the growth of both cells by only 10%, but gefitinib suppressed MUC5AC mRNA levels subsequent to a decrease in intracellular and secreted MUC5AC protein. Gefitinib also inhibited the phosphorylation of MAPK and Akt, and the selective inhibitors PD98059 and LY294002 also suppressed MUC5AC protein synthesis. These findings suggest that gefitinib may inhibits MUC5AC synthesis, at least in part, through MAPK and Akt signaling pathways. Thus, gefitinib inhibits mucin production, which is encouraging for trials involving its use against bronchorrhea in patients with lung cancer.
Lung Cancer 2005 Oct
PMID:Gefitinib inhibits MUC5AC synthesis in mucin-secreting non-small cell lung cancer cells. 1600 52

We report a case of a 52-year-old female with spontaneous disappearance of focal ground-glass opacity (GGO) detected on high-resolution computed tomography (HRCT). She initially was found to have a focal GGO lesion on follow-up computed tomography five years after left lower lobectomy for primary lung adenocarcinoma. Two months later, this lesion spontaneously disappeared in spite of the suspicion of subsequent lung cancer. A GGO appearance on HRCT can be found in a variety of diseases with partial air-space filling or interstitial thickening. Lung cancer, especially bronchioloalveolar carcinoma, is also included in the differential diagnosis for GGO lesions. However, there is little definite evidence about the management of lesions showing a GGO appearance. When we detect a GGO lesion, initial monitoring for several months may be useful for excluding the presence of lung neoplasms.
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PMID:Spontaneous disappearance of focal ground-glass opacity in the lung detected on the high-resolution computed tomography. 1609 44

Angiogenesis is required for lung cancer growth, which is mediated by various growth factors such as vascular endothelial growth factor (VEGF). Increases in VEGF and angiogenesis have been correlated with poor prognosis and survival in patients with lung cancer. In addition, recent reports show that estradiol and nicotine play important roles in lung tumor initiation and progression. In this report, we demonstrate that estradiol and nicotine exposure enhances the growth of A549 bronchioloalveolar carcinoma xenografts in mice through the stimulation of cell proliferation, VEGF secretion and angiogenesis. We detect a four-fold increase in microvascular density in tumors from mice exposed to estradiol and nicotine compared to control tumors resulting in an increase in tumor growth. Intriguingly, the effects on angiogenesis and tumor growth by the combination of agents were additive when compared to either agent alone. Furthermore, estradiol promotes VEGF secretion from various non-small cell lung carcinoma (NSCLC) cells and this effect is augmented by nicotine in a tumor xenograft model. These results indicate that aside from their roles in promoting cell proliferation, estradiol and nicotine appear to have additive effects on the induction of angiogenesis through the stimulation of VEGF secretion during NSCLC progression.
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PMID:Estradiol and nicotine exposure enhances A549 bronchioloalveolar carcinoma xenograft growth in mice through the stimulation of angiogenesis. 1639 87

Previous lung cancer screening trials in the United States (US) employing chest X ray and sputum cytology did not demonstrate reductions in lung cancer mortality. However, recent case control studies in Japan demonstrated a decrease in lung cancer mortality in the computed tomography (CT) screened group. Lung cancer screening using chest CT detected more cancers at an earlier stage than chest X ray. Before CT screening is widely performed, lung cancer mortality reduction should be proved in a scientific manner. The problem of a much higher false positive rate of this method should be solved. The subtypes of adenocarcinoma; bronchioloalveolar carcinoma (BAC) tends to show specific CT findings called ground glass opacity (GGO) and a favorable prognosis can be expected. BAC is usually invisible by chest X ray and detected only by CT. Recent studies have shown the proportion of GGO is strongly related to biological malignancy of small adenocarcinoma. Based on this fact, thoracic surgeons wish to identify the possibility of limited resection for minimally invasive cancers. Lung cancer researchers are interested in evaluating the nature of small adenocarcinoma as well as the carcinogenic process. A comprehensive understanding of screening-detected cancers including the CT images, pathology and genetic analysis is necessary for optimum management of such nodules.
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PMID:Present strategy of lung cancer screening and surgical management. 1640 83

Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.
Lung Cancer 2006 Apr
PMID:Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung. 1715 91

The aquaporins represent a family of transmembrane water channel proteins that play a major role in trans-cellular and transepithelial water movement. Most tumors have been shown to exhibit high vascular permeability and interstitial fluid pressure, but the transport pathways for water within tumors remain unknown. Here, we tested 10 non-small cell lung cancer cell lines of various origins by reverse transcriptase-polymerase chain reaction and Western blot analysis and identified clear expression of aquaporin 1 (AQP1) in seven cell lines. We next examined the distribution of the AQP1 protein in several types of primary lung tumors (16 squamous cell carcinomas, 21 adenocarcinomas, and 7 bronchoalveolar carcinomas) by immunohistochemical staining. AQP1 was overexpressed in 62% (13 of 21) and 75% (6 of 8) of adenocarcinoma and bronchoalveolar carcinoma, respectively, whereas all cases of squamous cell carcinoma and normal lung tissue were negative. Forced expression of full-length AQP1 cDNA in NIH-3T3 cells induced many phenotypic changes characteristic of transformation, including cell proliferation-enhancing activity by the MTT assay and anchorage-independent growth in soft agar. Although further details on the molecular function of AQP1 related to tumorigenesis remain to be elucidated, our results suggest a potential role of AQP1 as a novel therapeutic target for the management of lung cancer.
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PMID:Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth. 2290 56

Bronchioloalveolar carcinoma (BAC) is classified as a subset of lung adenocarcinoma but has a distinct clinical presentation, tumor biology, response to therapy, and prognosis compared with other subtypes of non-small-cell lung carcinoma (NSCLC). Bronchioloalveolar carcinoma disproportionately affects women, never-smokers, and Asians and is characterized by growth along alveolar septae without evidence of stromal, vascular, or pleural invasion. Although pure BAC accounts for approximately 4% of lung cancers, tumors with histologically mixed BAC and adenocarcinoma account for > 20% of all NSCLCs, and the incidence of BAC might be increasing. Bronchioloalveolar carcinoma histology is most commonly found in small lesions identified incidentally on chest radiographs or computed tomography scans and might represent a precursor lesion to invasive adenocarcinoma. As with other subsets of NSCLC, surgical resection is the only potentially curative treatment. Patients with unresectable BAC are more likely to respond to the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib than patients with other subtypes of NSCLC. Stage for stage, patients with BAC have a higher rate of long-term survival but might have an increased rate of intrathoracic recurrence than patients with other subtypes of NSCLC.
Clin Lung Cancer 2006 Mar
PMID:Bronchioloalveolar carcinoma: a review. 1664 Jul 99


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