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Biomedical subjects

James L Mulshine

Publications and source records attributed to James L Mulshine.

26 records · Page 2Linked to original sources
PubMed2003

Lung cancer chemoprevention: moving from concept to a reality.

Vast numbers of individuals who have stopped smoking have already been exposed to critical amounts of tobacco combustion products and are at significant risk of developing lung cancer. If these individuals are diagnosed with regional or distant metastatic disease this condition is not typically curable with existing systemic therapy. The need for more effective tools to detect and intervene with early lung cancer detection is a pressing public health priority. A major challenge in this regard is the development of safe and effective lung cancer chemoprevention. The factors influencing the development of this new clinical tool are reviewed in the context of existing trends for lung cancer care. Existing pharmaceutical efforts have involved evaluation of existing treatments for advanced cancer or other disorders in early lung cancer. The paper describes approaches to tailor chemoprevention development specifically to the biological, pharmacological and anatomical realities of this most lethal cancer.

Antineoplastic Agents↗
PubMed2003

Screening for lung cancer: in pursuit of pre-metastatic disease.

One reason for the high death rate of lung cancer is that tumours are not usually detected until the disease is at a late stage, at which point the cancer is non-curable. Spiral computerized tomography is a highly sensitive imaging method that could be used to screen high-risk populations, such as current or former smokers, for early-stage tumours. Trials to validate this tool are just underway, but beyond the imaging tools, population-based care of pre-metastatic lung cancer requires considerable evolution in clinical management approaches. More sensitive imaging tools might also provide a window into earlier biology, enabling the molecular dynamics of lung cancer progression to be elucidated.

Carcinoma, Non-Small-Cell Lung↗
PubMed2003

Downregulation of hnRNP A2/B1 expression in tumor cells under prolonged hypoxia.

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has been previously shown to be overexpressed in breast and lung tumors. Because hypoxia is a feature inherent in solid tumors, the regulation of hnRNP A2/B1 expression and subcellular localization under hypoxic conditions was studied on human lung and breast carcinoma cell lines. We found that sustained hypoxic treatment downregulated hnRNP A2/B1 expression in MCF7 and H157 cell lines. Northern blot analysis showed that this decay: (i) was observed as a marked diminution of transcript levels after 24-48 h of exposure to low oxygen tension; (ii) is not mediated by the transcription factor, hypoxia inducible factor-1; and (iii) is partially dependent on a higher hnRNP A2/B1 messenger RNA turnover under hypoxic than normoxic conditions. Immunocytochemical staining also showed a significant diminution of hnRNP A2/B1 staining in these cell lines after 24-48 h of hypoxia, together with a predominant loss of cytoplasmic staining. Further investigations are warranted to evaluate the relevance of modulation of hnRNP A2/B1 in hypoxic environments relative to its previously reported utility as a marker of early lung carcinogenesis.

Base Sequence↗
PubMed2003

The potential contributions of chronic inflammation to lung carcinogenesis.

A number of lines of evidence suggests that chronic inflammation contributes to the process of carcinogenesis. In this article, this theme is explored with particular emphasis on the involvement of inflammation in the development of lung cancer. A number of molecular pathways activated in chronic inflammation may contribute to lung carcinogenesis. The challenge is to conceptualize a cohesive picture of this complex biology that allows for effective pharmaceutical intervention. Initial therapeutic efforts involve strategies to block single pathways, such as with cyclooxygenase (COX) activity. However, the more that is learned about the consequences of COX activity, the more evident are the relationships of this enzyme to other classes of regulatory molecules such as the potent nuclear factor-kB. In light of this emerging picture, more global intervention strategies, such as with drug combinations, may be essential for success. Further basic study is essential to sort out possible molecular relationships and to permit elucidation of the most critical regulatory circuits. Given the complexity of these molecular interactions, well-designed clinical trials that specifically evaluate the precise effects of particular antiinflammatory drugs on lung carcinogenesis will also be critical to sort out the complexity and to validate successful approaches to arresting lung carcinogenesis.

Anti-Inflammatory Agents↗
PubMed2002

Lung cancer evolution to preinvasive management.

Cancer screening measures generally are accepted for cervical, breast, and colon cancer. With prostate cancer screening, the practice is used broadly, but the evidence for this approach is not established clearly. The aggregate clinical experience with these screening procedures provides a useful precedent to consider in designing a new approach to lung cancer screening. For instance, formidable logistic issues exist in responsibly evaluating the vast at-risk population for lung cancer. Obvious issues include the needs for cost-economy and precise classification procedures. In the field of cervical cancer screening, recent developments in automated image analysis highlight the potential for improving the precision of diagnosis by moving beyond traditional manual cytomorphologic evaluation. The authors have outlined how the overexpression of hnRNP A2/B1 was associated significantly with the eventual development of lung cancer, as corroborated by several independent studies. In discussing this marker, they reviewed several issues with relevance to the general challenge in using biomarkers as screening tools for lung cancer. The experience with cervical cancer screening informs the development of a cellular diagnostic screening platform for lung cancer. Issues such as optimized cell preparation, reproducibility, and assay precision are fundamental to the success of the platform for lung cancer detection. The recent Institute of Medicine study of health care delivery provides an excellent point of departure in outlining the global infrastructure that will be necessary in the evolution of a prevention-oriented lung cancer care system. The power of early detection in saving lives from cancer is reflected in the fact that more people die from a single cancer without any validated screening tool (i.e., lung cancer) than die from the aggregate of the four other major cancers, including breast cancer, colon cancer, prostate cancer, and cervical cancer cases--which all have more established early detection approaches. New technologies may provide an opportunity to engage lung cancer routinely at a fundamentally early stage in its natural history, which may provide an opportunity for clinicians to reconsider what may be the best way to manage lung cancer. Further sustained efforts will be required to define the true value of these new approaches through clinical trials as the specialty moves responsibly to routine preventative care of individuals at risk for lung cancer.

Aerosols↗
PubMed2002

Radiologic screening for lung cancer.

Lung cancer is the leading cause of cancer death. A number of screening trials have been carried out over the past two decades and have failed to demonstrate a reduction of lung cancer-related mortality. Recent advances in new forms of technology--spiral low-dose CT--have resuscitated interest in screening programs. Preliminary results are promising but the outstanding question is whether the magnitude of improvement is sufficient to affect a measurable reduction in lung cancer mortality?

Disease Progression↗