Facts and fiction: premalignant lesions of lung tissues.

Pathology. 2013 Feb 27;

Authors: Klebe S, Henderson DW

Abstract
SUMMARY: Lung cancer is now the leading cause of death from cancer in Australia. Most patients are diagnosed with late-stage disease. Although diagnosis at pre-invasive stages could theoretically improve outcomes, mooted precursor lesions are often asymptomatic and often undetectable by non-invasive investigations. Nonetheless, they merit study to identify early and essential molecular steps involved in lung carcinoma pathogenesis, with the aim of developing therapies targeted against one or more such steps. Some lung cancers appear to develop via a series of progressive morphological changes with correlating molecular alterations, but others seem to arise in histologically normal epithelium, and these differences may reflect anatomically and functionally distinct epithelial compartments of the respiratory tract. Pre-invasive precursor lesions recognised by the World Health Organization (WHO) include squamous metaplasia with dysplasia and carcinoma in situ, atypical adenomatous hyperplasia, and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Other lesions that likely represent pre-invasive lesions, but which are not currently WHO-listed, include human papillomavirus (HPV)-related respiratory papillomatosis and mesothelioma in situ.No single cancer stem cell marker has been identified. Field cancerisation plays an important role in lung cancer development, and includes the spread of pre-invasive clones along the respiratory epithelium or the occurrence of multiple separate foci of pre-invasive abnormalities such as squamous dysplasia and carcinoma in situ.In addition to well-characterised step-wise progression in squamous cell carcinomas and some adenocarcinomas, alternative pathways exist, and are currently being investigated. In addition, molecular techniques, including miRNA screening on blood samples or cytology samples-such as sputum samples-may become clinically relevant and more accurate in predicting lung cancer progression.

PMID: 23448809 [PubMed - as supplied by publisher]

Oral treatment with etoposide in small cell lung cancer - dilemmas and solutions.

Radiol Oncol. 2013 Mar;47(1):1-13

Authors: Rezonja R, Knez L, Cufer T, Mrhar A

Abstract
BACKGROUND: Etoposide is a chemotherapeutic agent, widely used for the treatment of various malignancies, including small cell lung cancer (SCLC), an aggressive disease with poor prognosis. Oral etoposide administration exhibits advantages for the quality of life of the patient as well as economic benefits. However, widespread use of oral etoposide is limited by incomplete and variable bioavailability. Variability in bioavailability was observed both within and between patients. This suggests that some patients may experience suboptimal tumor cytotoxicity, whereas other patients may be at risk for excess toxicity. CONCLUSIONS: The article highlights dilemmas as well as solutions regarding oral treatment with etoposide by presenting and analyzing relevant literature data. Numerous studies have shown that bioavailability of etoposide is influenced by genetic, physiological and environmental factors. Several strategies were explored to improve bioavailability and to reduce pharmacokinetic variability of oral etoposide, including desired and undesired drug interactions ( with ketoconazole), development of suitable drug delivery systems, use of more water-soluble prodrug of etoposide, and influence on gastric emptying. In addition to genotype-based dose administration, etoposide is suitable for pharmacokinetically guided dosing, which enables dose adjustments in individual patient. Further, it is established that oral and intravenous schedules of etoposide in SCLC patients do not result in significant differences in treatment outcome, while results of toxicity are inconclusive. To conclude, the main message of the article is that better prediction of the pharmacokinetics of oral etoposide may encourage its wider use in routine clinical practice.

PMID: 23450046 [PubMed - in process]

Peripheral immune cell gene expression changes in advanced non-small cell lung cancer patients treated with first line combination chemotherapy.

PLoS One. 2013;8(2):e57053

Authors: Chen YC, Hsiao CC, Chen KD, Hung YC, Wu CY, Lie CH, Liu SF, Sung MT, Chen CJ, Wang TY, Chang JC, Tang P, Fang WF, Wang YH, Chung YH, Chao TY, Leung SY, Su MC, Wang CC, Lin MC

Abstract
INTRODUCTION: Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate chemotherapy.
METHODS: To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment.
RESULTS: Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The pathway was significantly enriched in both tumor progression and chemotherapy signatures. and were down-regulated, while and were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated () and down-regulated () genes in the patients, and the six up-regulated () and down-regulated () genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality.
CONCLUSIONS: Our results suggest a potential role of the pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.

PMID: 23451142 [PubMed - in process]

New research examines the role of PKC in airway smooth muscle contraction and raises the possibility that this enzyme could be a therapeutic target for treating asthma, COPD, and other lung diseases. In the lungs, pathological increases in the contraction of the smooth muscle cells (SMCs) lining airway walls - a process that decreases airflow - contribute to the chain of events leading to asthma and COPD, two common lung diseases... (Source: Health News from Medical News Today)