Citations

Abstract Much of the ability of the MUC1 oncoprotein to foster tumorigenesis and tumor progression likely originates from the interaction of its cytoplasmic tail with proteins involved in oncogenic signaling. Many of these interactions are regulated by phosphorylation, as the cytoplasmic tail contains seven highly conserved tyrosines and several serine/threonine phosphorylation sites. We have developed a cell line–based model system to study the effects of tyrosine phosphorylation on MUC1 signaling, with particular emphasis on its effects on gene transcription. COS-7 cells, which lack endogenous MUC1, were stably infected with wild-type MUC1 or a MUC1 construct lacking all seven tyrosines (MUC1 Y0) and analyzed for effects on transcription mediated by the extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) pathways. COS.MUC1 Y0 cells showed heightened active ERK1/2 with increased activator protein-1 (AP-1) and signal transducer and activator of transcription 3 (STAT3) transcriptional activity; there was also a simultaneous decrease in NF-κB transcriptional activity and nuclear localization. These changes altered the phenotype of COS.MUC1 Y0 cells, as this line displayed increased invasion and enhanced [3H]thymidine incorporation. Analysis of the three lines also showed significant differences in their cell cycle profile and bromodeoxyuridine incorporation when the cells were serum starved. These data support the growing evidence that MUC1 is involved in transcriptional regulation and link MUC1 for the first time to the NF-κB pathway. (Mol Cancer Res 2006;4(7):489–97)

The purpose of this paper is to describe the intraoperative management of a type IIIb endoleak after deployment of a bifurcated endograft in a patient with narrow iliac access vessels. A 62-year-old man underwent elective endovascular repair (EVAR) of a 53 mm abdominal aortic aneurysm. After device deployment, a large IIIb endoleak, arising from the main body of the device, was visualized. Narrow iliac vessels precluded deployment of a second bifurcated graft, and the endoleak was successfully excluded with an aortomonoiliac device, followed by contralateral iliac occlusion and subsequent creation of a femorofemoral bypass. At 1-year follow-up, the aneurysm remains excluded and is decreasing in size. Type III endoleaks are a known complication of EVAR, requiring immediate treatment through their association with aneurysm enlargement and rupture. If an additional bifurcated graft cannot be used, aortomonoiliac conversion represents a feasible endovascular alternative treatment for type III endoleaks, other than conversion to open surgical repair. Therefore, aortomonoiliac converters with appropriate occluder devices should be readily available during deployment of bifurcated devices.

Stent-grafts are ideally terminated within the common iliac artery (CIA). However, CIA ectasia may require hypogastric artery occlusion, with stent-graft extension to the external iliac artery. Alternatively, the diameter of the distal stent-graft may be increased, or flared, to allow exclusion of the abdominal aortic aneurysm. This report details the authors’ experience with this technique. Forty-one patients received bifurcated stent-grafts (BSG): 20 received an AneuRx device, and 21 received a Zenith device. CIA ectasia (diameter 15–25 mm) was treated with a distal flare of 2–4 mm greater than the CIA diameter. Patients were followed up with computed tomography scan at 1, 6, and 12 months. Statistical analysis was performed using ANOVA within groups and unpaired two-tailed t test between groups. A p value of <0.05 was considered significant. Eight of 20 patients (40%) (11 CIA) received an AneuRx device and 13/21 (62%) (17 CIA) received a Zenith device, with a distal flare. Values are (n) mean (mm) ± SE. There were no deaths, endoleaks, migrations, or conversions to open repair. Follow-up mean was 24.7 and 20.6 (range 15–28) months for AneuRx and Zenith groups, respectively. In comparing initial and 12-month CIA diameters, AneuRx grafts 20 ±0.8 vs 21.5 ±1.0 were not significantly different, p= 0.2, nor was the same comparison for Zenith, 17 ±0.5 vs 19.1 ±0.4, significant, p= 0.57. At a mean follow-up of 12 months, distal flare of iliac limbs with either AneuRx or Zenith devices affords a seal for CIA ectasia and/or aneurysms complicating EVAR.

Abstract Intervention trials with supplemental β-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7–16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. β-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87–1.11; highest versus lowest quintile). The RRs for α-carotene, lutein/zeaxanthin, and lycopene were also close to unity. β-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67–0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in β-cryptoxanthin, such as citrus fruit, may modestly lower the risk.

PurposeFulvestrant is an antiestrogen that leads to estrogen receptor degradation and has demonstrated efficacy in breast cancer patients who have had disease recurrence or progression after tamoxifen. This study was designed to examine the efficacy and toxicity of fulvestrant in patients with disease progression on a third-generation aromatase inhibitor (AI).Patients and MethodsA one-stage phase II trial was conducted in postmenopausal women with measurable disease by Response Evaluation Criteria in Solid Tumors criteria who experienced disease progression after treatment with a third-generation AI and, at most, one additional hormonal agent. Tumors must have been estrogen receptor and/or progesterone receptor positive. The primary end point was objective response rate, and secondary end points were time to disease progression, survival, duration of response, and toxicity.ResultsEighty patients were enrolled, and three were ineligible. Characteristics of the 77 eligible patients included median age of 68 years, performance score of 0 or 1 in 91% of patients, visceral dominant disease in 88% of patients, two prior hormonal treatments in 73% of patients, and prior chemotherapy for metastatic disease in 32% of patients. Eleven patients (14.3%) achieved a partial response, and 16 patients (20.8%) had stable disease for at least 6 months, for a clinical benefit rate of 35%. Antitumor activity seemed to be higher in women with prior treatment with AI alone compared with women whose prior treatment also included tamoxifen. Median time to progression was 3 months, and median survival time was 20.2 months. Fulvestrant was well tolerated.ConclusionFulvestrant is a well-tolerated treatment and has efficacy against breast cancers that have progressed after therapy with a third-generation AI.

AbstractBackgroundThe Cognitive and Emotional Health Project (CEHP) seeks to identify the demographic, social, and biological determinants of cognitive and emotional health in the older adult. As part of the CEHP, a critical evaluation study committee was formed to assess the state of epidemiological research on demographic, social, and biological determinants of cognitive and emotional health.MethodsCriteria for inclusion in the survey were large cohort studies, longitudinal in design, participants predominantly 65 years or older, with measurements of both cognition and emotion, and information on a wide variety of demographic, psychosocial, and biological factors. North American and European studies, which met these criteria, were selected for the review. Outcome measures included cognition, cognitive decline, and cognitive function. For emotion, symptoms included depression and anxiety, positive and negative affect, subjective well being, mastery, and resilience.ResultsNinety‐six papers were identified that addressed cognitive and emotional outcomes. A large variety of risk factors were consistently identified with cognitive outcomes, particularly those previously associated with increased risk of cardiovascular disease. There was considerable overlap between risk factors for cognitive and emotional outcomes.ConclusionThis review identifies a large number of lifestyle and health behaviors that alter the risk for maintenance of cognitive and emotional health. Large longitudinal cohort studies are a unique source to explore factors associated with cognitive and emotional health. Secondary analyses of these studies should be encouraged as should the development of standardized questionnaires to measure cognitive and emotional health. Future research in this field should study cognitive and emotional health simultaneously.

Pulse pressure, the difference between systolic and diastolic blood pressure, is an independent risk factor for cardiovascular disease. Increased pulse pressure reflects reduced compliance of arteries and is a marker of atherosclerosis. To locate genes that affect pulse pressure, a genome-wide linkage scan for quantitative trait loci influencing pulse pressure was performed using variance components methods as implemented in sequential oligogenic linkage analysis routines. The analysis sample included 10 798 participants in 3320 families who were recruited as part of the Family Blood Pressure Program and were phenotyped with an oscillometric blood pressure measurement device using a consistent protocol across centers. Pulse pressure was adjusted for the effects of sex, age, age 2 , age-by-sex interaction, age 2 -by-sex interaction, body mass index, and field center to remove sources of variation other than the genetic effects related to pulse pressure. Significant linkage was observed on chromosome 18 (logarithm of odds [LOD]=3.2) in a combined racial sample, chromosome 20 (LOD=4.4), and 17 (LOD=3.6) in Hispanics, chromosome 21 (LOD=4.3) in whites, chromosome 19 (LOD=3.1) in a combined sample of blacks and whites, and chromosome 7 (logarithm of odds [LOD]=3.1) in blacks from the GenNet Network. Our genome scan shows significant evidence for linkage for pulse pressure in multiple areas of the genome, supporting previous published linkage studies. The identification of these loci for pulse pressure and the apparent congruence with other blood pressure phenotypes provide increased support that these regions contain genes influencing blood pressure phenotypes.