Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activity

<p>Abstract</p> <p>Background</p> <p>Integrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking.</p> <p>Methods</p> <p>In this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line.</p> <p>Results</p> <p>Using variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A/α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A/α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc.</p> <p>Conclusion</p> <p>The findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin variant expression in colon cancer cell biology.</p

Effectiveness of a structured motivational intervention including smoking cessation advice and spirometry information in the primary care setting: the ESPITAP study

<p>Abstract</p> <p>Background</p> <p>There is current controversy about the efficacy of smoking cessation interventions that are based on information obtained by spirometry. The objective of this study is to evaluate the effectiveness in the primary care setting of structured motivational intervention to achieve smoking cessation, compared with usual clinical practice.</p> <p>Methods</p> <p>Design</p> <p>Multicentre randomized clinical trial with an intervention and a control group.</p> <p>Setting</p> <p>12 primary care centres in the province of Tarragona (Spain).</p> <p>Subjects of study</p> <p>600 current smokers aged between 35 and 70 years with a cumulative habit of more than 10 packs of cigarettes per year, attended in primary care for any reason and who did not meet any of the exclusion criteria for the study, randomly assigned to structured intervention or standard clinical attention.</p> <p>Intervention</p> <p>Usual advice to quit smoking by a general practitioner as well as a 20-minute personalized visit to provide detailed information about spirometry results, during which FEV1, FVC, FEF 25-75% and PEF measurements were discussed and interpreted in terms of theoretical values. Additional information included the lung age index (defined as the average age of a non-smoker with the same FEV1 as the study participant), comparing this with the chronological age to illustrate the pulmonary deterioration that results from smoking.</p> <p>Measurements</p> <p>Spirometry during the initial visit. Structured interview questionnaire administered at the primary care centre at the initial visit and at 12-month follow-up. Telephone follow-up interview at 6 months. At 12-month follow-up, expired CO was measured in patients who claimed to have quit smoking.</p> <p>Main variables</p> <p>Smoking cessation at 12 months.</p> <p>Analysis</p> <p>Data will be analyzed on the basis of "intention to treat" and the unit of analysis will be the individual smoker.</p> <p>Expected results</p> <p>Among active smokers treated in primary care we anticipate significantly higher smoking cessation in the intervention group than in the control group.</p> <p>Discussion</p> <p>Application of a motivational intervention based on structured information about spirometry results, improved abstinence rates among smokers seen in actual clinical practice conditions in primary care.</p> <p>Trial registration</p> <p>ClinicalTrial.gov, number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01194596">NCT01194596</a>.</p

TRP channels in airway smooth muscle as therapeutic targets

Cation channels are of fundamental importance in regulating the function of airway smooth cells especially bronchoconstriction in response to spasmogens, and are therefore key players in the pathogenesis of asthma. To date, the identity of these cation channels remains a mystery. However, the recently emerged transient receptor potential (TRP) cation channel family has provided several promising channel candidates. The identification of the key TRP channels involved in regulating airway smooth muscle contractility, and therefore airway tone, could provide new and exciting prospects for the development of novel therapies for the treatment of airway diseases such as asthma. © Springer-Verlag 2005