Citations

Purpose: We conducted this study because the duration of excess lung cancer risk among former smokers has been inconsistently reported, doubt has been raised regarding the population impact of smoking cessation, and differential risk reduction by histologic cell type after smoking cessation needs to be confirmed. Methods: The Iowa Women’s Health Study is a prospective cohort study of 41,836 Iowa women aged 55 to 69 years. In 1986, mailed questionnaires were used to collect detailed smoking history. Age-adjusted lung cancer incidence through 1999 was analyzed according to years of smoking abstinence. Relative risks were estimated using Cox regression analysis. Results: There were 37,078 women in the analytic cohort. Compared with the never smokers, former smokers had an elevated lung cancer risk (relative risk, 6.6; 95% confidence interval, 5.0 to 8.7) up to 30 years after smoking cessation for all former smokers. However, a beneficial effect of smoking cessation was observed among recent and distant former smokers. The risk of adenocarcinoma remained elevated up to 30 years for both former heavier and former lighter smokers. Conclusion: The risk for lung cancer is increased for both current and former smokers compared with never smokers and declines for former smokers with increasing duration of abstinence. The decline in excess lung cancer risk among former smokers is prolonged compared with other studies, especially for adenocarcinoma and for heavy smokers, suggesting that more emphasis should be placed on smoking prevention and lung cancer chemoprevention.

The allergic reaction begins with the antigen-induced aggregation of occupied high-affinity IgE receptors expressed on mast cell surface, their activation, and the release of proinflammatory mediators that cause the “early phase” of this process. In addition, mast cell activation induces the onset of a “late phase” reaction characterized by the tissue infiltration of inflammatory cells, mainly eosinophils. We have hypothesized that during the late phase mast cells interact with and are activated by eosinophils. Here we report that highly purified human lung mast cells became responsive to eosinophil major basic protein (MBP) when in coculture with human lung fibroblasts. In addition, cord blood–derived mast cells maintained in coculture with 3T3 fibroblasts released more histamine and prostaglandin D2 (PGD2) compared with cells maintained in suspension. The fibroblast-derived membrane form of stem cell factor (SCF) was found to be involved in the mast cell increased responsiveness to MBP. In fact, cord blood–derived mast cells cocultured with 3T3 in the presence of antisense for SCF or cocultured with fibroblasts that do not express the membrane form of SCF were inhibited in their histamine-releasing activity toward MBP. In addition, this form of SCF induced the expression of a pertussis toxin–sensitive Gi protein, Gi3 that interacts with MBP to trigger mast cell non-IgE–dependent activation in a manner similar to other cationic compounds such as compound 48/80. Mast cell responsiveness to eosinophil mediators is a potentially novel evidence for an alternative pathway of allergen-independent activation able to contribute to the perpetuation of allergy.

ABSTRACT: Lung cancer is the second most common form of cancer in the United States, and although it accounts for 15% of all cancers, it is the most lethal, accounting for approximately 28% of cancer deaths. In 2002, it is estimated that 177,000 new cases of lung cancer will be diagnosed in the United States, and an estimated 160,000 men and women will die from the disease. This mortality rate is greater than that attributable to colorectal, breast, and prostate cancer combined. Systemic treatments for lung cancer with standard chemotherapy agents are still relatively ineffective. Agents targeting novel proliferative and survival pathways in lung cancer are needed to improve treatment outcomes. In recent years, numerous agents inhibiting aberrant processes in tumor cells have undergone clinical evaluation. This review is the first of a two-part series that summarizes pertinent preclinical and clinical information on novel drugs that target critical abnormalities in lung cancer. In this article, agents inhibiting growth factor receptors and various molecules downstream of activated signaling cascades, such as cytoplasmic second messengers, are described.

ABSTRACT: Lung cancer is the second most common form of cancer in the United States, and although it accounts for 15% of all cancers, it is the most lethal, accounting for approximately 28% of cancer deaths. In 2002, it is estimated that 177,000 new cases of lung cancer will be diagnosed in the United States, and an estimated 160,000 men and women will die from the disease. This mortality rate is greater than that attributable to colorectal, breast, and prostate cancer combined. Systemic treatments for lung cancer with standard chemotherapy agents are still relatively ineffective. Agents targeting novel proliferative and survival pathways in lung cancer are needed to improve treatment outcomes. In recent years, numerous agents inhibiting aberrant processes in tumor cells have undergone clinical evaluation. This review is the second of a two-part series that summarizes pertinent preclinical and clinical information on novel drugs that target critical abnormalities in lung cancer. In this article, agents that were developed to inhibit various aspects of tumor protein trafficking and protein degradation, cell cycle regulation, angiogenesis, and antigenicity are described. Future approaches to treatment are suggested.

PURPOSE: There is a current lack of consensus about the effectiveness of nicotine dependence treatment for cancer patients. This retrospective study examined the 6-month tobacco abstinence rate among lung cancer patients treated clinically for nicotine dependence. PATIENTS AND METHODS: A date-of-treatment matched case control design was used to compare lung cancer patients (201 lung cancer patients, 41% female) and nonlung cancer patients (201 controls, 45% female) treated in the Mayo Clinic Nicotine Dependence Center between 1988 and 2000. The intervention involves a brief consultation with a nicotine dependence counselor. A treatment plan individualized to the patient’s needs is then developed. The primary end point was the self-reported, 7-day point prevalence abstinence from tobacco at 6-month follow-up. RESULTS: At baseline, compared with the controls, the lung cancer patients were significantly older (P < .001), reported higher motivation to stop smoking (P = .003), and were at a higher stage of change (P = .002). The 6-month tobacco abstinence rate was 22% for the lung cancer patients compared with 14% of the control patients (P = .024). After adjusting for age, sex, baseline cigarettes smoked per day, and stage of change, no significant difference was detected between lung cancer patients and controls on the tobacco abstinence rate. CONCLUSION: The results suggest that nicotine dependence treatment is effective for patients with a diagnosis of lung cancer. The majority of lung cancer patients were motivated to stop smoking.

Background— Although aortic valve replacement can be performed at an acceptable risk level in selected patients with left ventricular systolic dysfunction and low-output, low-gradient aortic stenosis, not all patients presenting with these hemodynamics will benefit from the operation. Some patients may have only mild aortic stenosis, despite a small calculated valve area. We report on the clinical utility of diagnostic dobutamine stimulation during cardiac catheterization in these diagnostically challenging patients. Methods and Results— Thirty-two patients with low-output, low-gradient aortic stenosis and an ejection fraction <40% had dobutamine infusion in the catheterization laboratory. On the basis of the results of the dobutamine test, 21 patients underwent aortic valve replacement. All patients with a final aortic valve area ≤1.2 cm 2 at peak dobutamine infusion and a mean gradient of >30 mm Hg were found to have severe calcific aortic stenosis at operation. In the 15 patients in whom contractile reserve was identified during dobutamine challenge (increase in stroke volume >20%), 1 patient died perioperatively (7% mortality) and 12 patients were alive in New York Heart Association class I or II status at follow-up. Conclusions— In patients with left ventricular systolic dysfunction and aortic stenosis with a low output and a low mean gradient, dobutamine challenge may aid in selecting those who would benefit from an aortic valve operation.

The National Heart, Lung, and Blood Institute (NHLBI) recently convened the Heart and Lung Xenotransplantation Working Group to identify hurdles to the clinical application of xenotransplantation, defined as the use of animal organs or tissue for transplantation, and to recommend possible solutions to these problems. The group consisted of experts in xenotransplantation from academia, industry, and federal agencies, and the discussions focused on those areas within the mission of the NHLBI. The areas covered included immunologic and physiological barriers to xenotransplantation, the limitations of the current animal models, the need for collaboration among groups, the high costs of studies using nonhuman primates and genetic engineering of pigs, and the unique problems of lung xenotransplantation. This report is a summary of those discussions.

ABSTRACT We developed a rapid thermocycling, real-time detection (also known as real-time PCR) method for the detection of Legionella species directly from clinical specimens. This method uses the LightCycler (Roche Molecular Biochemicals, Indianapolis, Ind.) and requires approximately 1 to 2 h to perform. Both a Legionella genus PCR assay and Legionella pneumophila species-specific PCR assay were designed. A total of 43 archived specimens from 35 patients were evaluated, including 19 bronchoalveolar lavage (BAL) specimens and 24 formalin-fixed, paraffin-embedded open lung biopsy specimens. Twenty-five of the specimens were culture-positive for Legionella (9 BAL specimens and 16 tissue specimens). BAL specimens were tested by LightCycler PCR (LC-PCR) methods and by a direct fluorescent antibody (DFA) assay, which detects L. pneumophila serogroups 1 to 6 and several other Legionella species. Tissue sections were tested by the two LC-PCR methods, by DFA, by an in situ hybridization (ISH) assay, specifically designed to detect L. pneumophila , and by Warthin-Starry (WS) staining. The results were compared to the “gold standard” method of bacterial culture. With BAL specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by Legionella genus LC-PCR, 100 and 100%; Legionella genus detection by DFA assay, 33 and 100%; and L. pneumophila detection by L. pneumophila species-specific LC-PCR, 100 and 100%. With open lung biopsy specimens the following assays yielded the indicated sensitivities and specificities, respectively: Legionella genus detection by LC-PCR 68.8 and 100%; Legionella genus detection by DFA assay, 44 and 100%; Legionella genus detection by WS staining, 63 and 100%; L. pneumophila species-specific detection by LC-PCR, 17 and 100%; and L. pneumophila species-specific detection by ISH, 100 and 100%. The analytical sensitivity of both LC-PCR assays was <10 CFU/reaction. LC-PCR is a reliable method for the direct detection of Legionella species from BAL specimens. The Legionella genus LC-PCR assay could be performed initially; if positive, L. pneumophila species-specific LC-PCR could then be performed (if species differentiation is desired). The speed with which the LC-PCR procedure can be performed offers significant advantages over both culture-based methods and conventional PCR techniques. In contrast, for the methods evaluated, culture was the best for detecting multiple Legionella species in lung tissue. WS staining, Legionella genus LC-PCR, and L. pneumophila species-specific ISH were useful as rapid tests with lung tissue.