Centrally located adenocarcinoma with endobronchial polypoid growth: clinicopathological analysis of five cases.

Lung adenocarcinomas that exhibit endobronchial polypoid growth and arise from the central portion of the respiratory tree are extremely rare and their clinicopathological features are not well understood. We report the clinicopathological characteristics of five cases of centrally located adenocarcinomas. Histologically, in three cases (cases 1, 2, and 3) the tumor had a papillary, acinar, and solid structure.

Reduced transcription of the Smad4 gene during pulmonary carcinogenesis in idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk of developing lung cancer. To identify key molecules involved in malignant transformation in IPF, we analyzed the expression profiles of lung and lung tumor tissue from patients with lung cancer and IPF (lung cancer/IPF) using cDNA arrays and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Reduced expression of the Smad4 gene was identified in all eight tumor samples from the lung cancer/IPF patients using real-time RT-PCR.

Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model.

To ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the antitumor effects of trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSA and vorinostat both displayed strong antitumor activities in 50% of NSCLC cell lines, suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.

E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib.

It is known that an epidermal growth factor receptor (EGFR) gene mutation(s) is present in a percentage of non-small cell lung cancers (NSCLCs). Gefitinib, an inhibitor of the tyrosine kinase activity of EGFR, is effective on most of them. The EGFR mutation status alone cannot fully predict the response to gefitinib and the prognosis for the patients.

Gemcitabine resistance in a highly metastatic subpopulation of a pulmonary adenocarcinoma cell line resistant to gefitinib.

The response rates to combination chemotherapy in metastatic non-small cell lung cancer (NSCLC) cases have been reported to be lower than those to induction chemotherapy in locally advanced cases. To understand the relationship between highly metastatic potential and chemosensitivity, we examined the drug sensitivity of a highly metastatic human lung adenocarcinoma cell subpopulation, PC9/f14, which had been previously established in an experimental metastasis model, to commonly used anti-cancer agents (paclitaxel, SN38, gemcitabine, vindesine, etoposide, cisplatin, and carboplatin) via the 3-(4, 5-dimethylthiazol-2-yl)2, 5-diphenyltetrazolium bromide assay. We found that the PC9/f14 subpopulation, which we previously reported to be resistant to gefitinib, was also resistant to gemcitabine (2',2'-difluoro-2'-deoxy-cytidine), a nucleoside analogue.

PTEN inactivation in lung cancer cells and the effect of its recovery on treatment with epidermal growth factor receptor tyrosine kinase inhibitors.

To understand the mechanisms of PTEN inactivation, which is reported to be involved in tumor progression and drug resistance in lung cancer, we analyzed the expression levels of PTEN at mRNA and protein levels, along with the genetic and epigenetic status of the PTEN gene, in a panel of lung cancer cell lines. Western blot analysis showed that six out of 25 (24%) cell lines displayed low expression of PTEN protein. The level of PTEN mRNA correlated well with corresponding protein expression in each of these six cell lines.

Carbonic anhydrase IX expression is associated with tumor progression and a poor prognosis of lung adenocarcinoma.

Carbonic anhydrase (CA) IX catalyzes the hydration of carbon dioxide into carbonic acid and participates in a variety of physiological and biological processes. The aim of this study was to evaluate the prognostic significance of CA IX expression in patients with lung adenocarcinoma. Standard immunohistochemical techniques were used to study CA IX expression in 134 patients who underwent curative resection for adenocarcinoma of the lung at our hospital between January 1995 and December 1996.

Phase I/II study of paclitaxel + carboplatin for refractory or recurrent non-small cell lung cancer.

A gene-drug correlation analysis was previously performed in lung cancer cell lines using the NC160 program. On the basis of this work, a phase I/II pilot study of weekly paclitaxel and carboplatin (CBDCA) was subsequently planned for refractory or recurrent non-small cell lung cancer (NSCLC). Safety and antitumor effects were evaluable in all 30 patients registered for this study.

Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database.

Background: The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer.

Differences in clinicopathological and biological features between central-type and peripheral-type squamous cell carcinoma of the lung.

The central type and peripheral type squamous cell carcinoma (SCC) of the lung have different clinicopathological characteristics, but, little is known about their biological characteristics. We investigated differences between the properties and phenotypes of peripheral-type (P-type) and central-type (C-type) SCC by performing an immunohistochemical analysis of each type by tissue microarray analysis with a large panel of antibodies. To examine strictly, we selected 20 P-type SCCs that were pathological stage T1 and limited to more peripherally than the fifth bronchial bifurcation, and 21 C-type SCCs that were pathological stage T1 and limited to a lobar bronchus.

Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human lung cancer.

The ING1 gene is involved in the regulation of the cell cycle, senescence, and apoptosis and is a novel candidate tumor suppressor gene. ING2, another gene in the ING family, was identified and cloned. The functions of ING1 and ING2 largely depend on the activity of p53.

Weekly administration of irinotecan (CPT-11) plus cisplatin for refractory or relapsed small cell lung cancer.

Purpose: Weekly administrations of CPT-11 plus cisplatin together with an anti-diarrheal program, the Oral Alkalization and Control of Defecation [Int J Cancer 1999;83:491; Int J Cancer 2001;92:269; Cancer Res 2002;62:179], were evaluated in this phase II study for patients with refractory or relapsed small cell lung cancer.

Methods: Patients were treated by weekly administrations of 60 mg/m(2) CPT-11 plus 30 mg/m(2) cisplatin on Days 1, 8 and 15 over 4 weeks. Coinciding with the infusions and for 4 days thereafter, the anti-diarrheal program was practiced using orally administered sodium bicarbonate, magnesium oxide and basic water.

Reduced transcription of the RB2/p130 gene in human lung cancer.

Reduced expression of the retinoblastoma gene (RB)2/p130 protein, as well as mutation of exons 19, 20, 21, and 22 of the same gene, has been reported in primary lung cancer. However, it has been suggested by other investigators that mutational inactivation and loss of the RB2/p130 gene and protein, respectively, are rare events in lung cancer. In order to determine the contribution and mechanisms of RB2/p130 gene inactivation to lung cancer development and progression, we quantified RB2/p130 mRNA expression levels in a range of human lung cancer cell lines (n = 13) by real-time reverse transcription (RT)-polymerase chain reaction (PCR) analysis.

[A case of secondary pulmonary cryptococcosis showing various radiographic changes during its natural course without antifungal treatment].

A 58-year-old man who had been prescribed corticosteroids for rheumatoid arthritis in another hospital was admitted to our hospital for examination of an abnormal chest shadow. We obtained a positive result for cryptococcal antigen in the serum, in a measurement done as a screening test for abnormal chest shadows. We diagnosed secondary pulmonary cryptococcosis through a transbronchial biopsy.