Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome in advanced non-small cell lung cancer.

Introduction: Epidermal growth factor receptor (EGFR) gene intron 1 contains a polymorphic single sequence dinucleotide repeat (CA)n whose length has been found to inversely correlate with transcriptional activity. This study was designed to assess the role of (CA)n polymorphism in predicting the outcome of gefitinib treatment in advanced non-small cell lung cancer (NSCLC).

Methods: Blood and tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were collected.

Predictive and prognostic significance of neuron-specific enolase (NSE) in non-small cell lung cancer.

Background: The predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate.

Patients And Methods: To study these aspects, serum NSE was prospectively measured at baseline of first-line chemotherapy treatment and tested for correlation with clinical outcome in 129 advanced NSCLC patients.

Results: An objective response was achieved in 27 out of 65 (41.

Buccal mucosa cells as in vivo model to evaluate gefitinib activity in patients with advanced non small cell lung cancer.

Purpose: To evaluate the role of pretreatment and posttreatment expression in buccal mucosa cells of signal transduction proteins activated by epidermal growth factor receptor, including phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated mitogen-activated protein kinase (p-MAPK), and phosphorylated AKT (p-AKT), in predicting gefitinib activity in advanced non-small cell lung cancer patients. Expression of the same proteins was also assessed on corresponding tissue samples for comparison. Moreover, EGFR gene mutations and copy number were analyzed.

In vitro study of CI-994, a histone deacetylase inhibitor, in non-small cell lung cancer cell lines.

CI-994 (N-acetyldinaline) is a novel oral compound with a wide spectrum of antitumor activity in preclinical models, in vitro and in vivo. The mechanism of action may involve inhibition of histone deacetylation and cell cycle arrest. We studied the action of CI-994 on two non-small cell lung cancer (NSCLC) cell lines: A-549 (adenocarcinoma) and LX-1 (squamous cell carcinoma).

Epidermal growth factor receptor inhibitors: a new prospective in the treatment of lung cancer.

Lung cancer is the leading cause of death worldwide. Current treatment modalities, including chemotherapy, radiotherapy and surgery, provide only limited improvement in the natural course of this disease. Therefore, the development of new therapeutic strategies is highly awaited.

Farnesylated proteins as anticancer drug targets: from laboratory to the clinic.

The knowledge that Ras was readily prenylated by protein FTase and that the inhibition of this reaction has the ability to revert the transformed phenotype, provided the rationale for the development of FTIs as anticancer drugs. Studies have shown that farnesylation of Ras is the first, obligatory first step in a series of post-translational modifications leading to membrane association, which, in turn, determines the switch from an inactive to an active Ras-GTP bound form. Based on the theorical assumption that preventing Ras farnesylation might result in the inhibition of Ras functions, a range of FTIs have been synthesized.

In vitro study of farnesyltransferase inhibitor SCH 66336, in combination with chemotherapy and radiation, in non-small cell lung cancer cell lines.

K-ras alterations have been reported in 20-30% of non-small cell lung cancer (NSCLC) and represent a suitable target for the development of novel anticancer agents, such as Farnesyl transferase inhibitors (FTi), a new class of agents inhibiting the post-translational modification of the K-ras proteins. The effectiveness of FTi SCH66336 in inhibiting cell proliferation and deranging cell cycle of NSCLC cell lines as well as its interaction with chemotherapy or radiation have been evaluated. The activity of FTi SCH66336, alone or in combination with paclitaxel, gemcitabine, and radiotherapy, was examined in 3 cell lines, A-549, LX-1 and CaLu-6, by colorimetric MTT assay.

Enhanced effectiveness of last generation antiblastic compounds vs. cisplatin on malignant pleural mesothelioma cell lines.

The purpose of this study was to examine the antiproliferative potentialities of a pool of new generation compounds (Paclitaxel, Docetaxel, Gemcitabine, Topotecan, SN-38) together with fenretinide, a synthetic derivative of retinoic acid, in comparison with the current first choice treatment cisplatin molecule, on a pool of human malignant pleural mesothelioma cell lines derived from either bioptic and pleural effusions samples. To evaluate the chemosensitivity features of malignant mesothelioma cells in vitro, we resorted to a rapid and reproducible colorimetric assay, a useful widely recognized tool for preclinical drug screening. In addition, by DNA content analysis and cellular morphologic assessment, we focused on the apoptosis as a potential mechanism of drug activity.

Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers.

The aim of this study was to investigate the prognostic significance of a panel of biological parameters in patients with radically resected non-small cell lung cancers (NSCLC). 269 cases with pathological stage I-IIIA NSCLC were retrospectively analysed. Immunohistochemistry was performed to detect protein expression of p53, bcl-2, proliferating cell nuclear antigen (PCNA) and CD34.

Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines.

Integration of chemotherapy and radiation is the standard practice in the management of locally advanced inoperable NSCLC. To assess the biological interaction between third generation chemotherapeutic agents and radiation in non-small cell lung cancer (NSCLC) in vitro, we tested a number of different drugs (paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cisplatin) combined with radiation, in lung cancer cell lines. Cellular chemosensitivity was determined, using the semi-automated colorimetric MTT assay, after 48, 72 and 96 h of exposure to increasing drug concentrations, (0.

The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer.

Brain is the most common site of metastatic spread in small-cell lung cancer (SCLC). Approximately 10% of SCLC patients have brain metastases (BM) already at diagnosis and an additional 40% will develop central nervous system (CNS) involvement during their disease course. Although whole brain radiotherapy and corticosteroids is considered the treatment of choice, accumulating evidence suggests that systemic chemotherapy may also play an important role.

Pre-clinical evaluation of new antineoplastic agents in NSCLC cell lines: evidence of histological subtype-dependent cytotoxicity.

The antiproliferative effect of paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cis-platin was studied on 5 non-small cell lung cancer (NSCLC) cell lines, 3 of which were adenocarcinoma (ADK) and 2 squamous cell carcinoma (SCC). Cellular chemosensitivity was determined using the MTT in vitro assay after 48, 72 and 96 h of exposure to drug in concentration ranging from 0.001 to 100 microM.

Analysis of K-ras, p53, bcl-2 and Rb expression in non-small cell lung cancer cell lines.

Six non-small cell lung cancer (NSCLC) cell lines (A-549, Ca-Lu-6, SK-Lu-1, Ca-Lu-1, SK-Mes-1 and LX-1) were studied to assess the presence of multiple concomitant alterations of different oncogenes (K-ras, bcl-2) and tumor suppressor genes (p53, Rb) in NSCLC. K-ras (exon 1) and p53 (exons 5-8) gene mutations were determined via a PCR-based-DGGE (Denaturing Gradient Gel Electro-phoresis) and by sequencing approach. Different mutations were found in the Ist exon of K-ras gene in 5 of 6 cell lines examined.