Helen Swede

Age related differences in learning to use a text-editing system

Abstract The increased use of computer technology in most occupations means that many middle-aged and older workers who lack computer experience will need to acquire skills to interact with this technology. This study examined age-group differences in learning to use a text-editing system. One hundred and thirty-five females ranging in age from 25 to 70 participated in the study. They received training under one of three training conditions: instructor-based, online or manual-based. Age differences were assessed by comparing performance on criterion tasks. Results indicated significant differences among the groups in learning success, younger learners being the most successful. There were no significant age by training interactions. The findings indicate a need to develop more effective training strategies to teach older learners to use computer technologies. They also indicate the need for changes in system design because computer applications are difficult for novice users to learn.

Regular aspirin use and lung cancer risk.

BackgroundAlthough a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk.MethodsWe conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year.ResultsResults indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41–0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day × years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer.ConclusionsOverall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

National population-based biobanks for genetic research.

Clinical practice guidelines derived from genetic research using population-based biobanks could dramatically change the nature of personal and public health medicine. Centralized population-based biobanks have been established or proposed in at least nine countries to date, and many lessons have been learned from these landmark developments. Scientific and governmental leaders in the United States are currently contemplating pending federal legislation regarding the establishment of centralized and networked biobanks. Public health practitioners and clinical care providers may be called on to serve pronounced planning roles at the state level. Possible responsibilities include: formulating legislation, gathering public comment, reviewing research proposals, and developing procedures for informed consent, participant withdrawal, and confidentiality protection. State health agencies may also need to create and/or administer banking facilities. Proper planning may ensure that individual rights are protected while research benefits are maximized.

Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer.

BackgroundUncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC).Methods128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis.ResultsOf the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample.ConclusionThe results suggest that higher tumor proliferation and motility may be important in the prognosis of NSCLC, and composite application of biomarkers might be of greater value than single marker application in assessing tumor prognosis.

Association of Regular Aspirin Use and Breast Cancer Risk

Of the limited number of epidemiological investigations on aspirin (and other nonsteroidal anti-inflammatory drugs) and breast cancer, the majority observe a protective role, yet only a few report dose-response effects for frequency or duration of use. We studied aspirin use among 1,478 breast cancer patients diagnosed from 1982 to 1998, and 3,383 cancer-free hospital controls at the Roswell Park Cancer Institute. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Compared to never use,both regular (≧1 tablet per week for ≧1 year) and occasional use were inversely associated with breast cancer (adjusted OR = 0.84, 95% CI 0.64–0.97; adjusted OR = 0.80, 95% CI 0.67–0.96, respectively). Among regular users, an inverse trend was found for number of tablets consumed per week (1, 2–6, or ≧7) with corresponding ORs of 0.95, 0.80, and 0.74 (Ptrend = 0.01). Daily use spanning 10 or more years was associated with a more pronounced reduction in risk (Ptrend = 0.005). Our findings corroborate the growing body of observational evidence that regular aspirin use may be associated with reduced risk of breast cancer.

Ovarian cancer immunotherapy: opportunities, progresses and challenges.

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

Up-Regulated Dicer Expression in Patients with Cutaneous Melanoma

Background MicroRNAs (miRNAs) are small non-coding RNAs (18–24 nucleotides) that have recently been shown to regulate gene expression during cancer progression. Dicer, a central enzyme in the multi-component miRNA biogenesis pathway, is involved in cutting precursor miRNAs to functionally mature forms. Emerging evidence shows that Dicer expression is deregulated in some human malignancies and it correlates with tumor progression, yet this role has not yet been investigated in skin cancers. Methods and Findings Using an anti-human monoclonal antibody against Dicer and immunohistochemistry, we compared the expression of Dicer protein among 404 clinically annotated controls and skin tumors consisting of melanocytic nevi (n = 71), a variety of melanomas (n = 223), carcinomas (n = 73) and sarcomas (n = 12). Results showed a cell-specific up-regulated Dicer in 81% of cutaneous, 80% of acrolentiginous and 96% of metastatic melanoma specimens compared to carcinoma or sarcoma specimens (P<0.0001). The expression of Dicer was significantly higher in melanomas compared to benign melanocytic nevi (P<0.0001). In patients with cutaneous melanomas, Dicer up-regulation was found to be significantly associated with an increased tumor mitotic index (P = 0.04), Breslows depth of invasion (P = 0.03), nodal metastasis (P = 0.04) and a higher American Joint Committee on Caner (AJCC) clinical stage (P = 0.009). Using western blot analysis, we confirmed the cell-specific up-regulation of Dicer protein in vitro. A pooled-analysis on mRNA profiling in cutaneous tumors showed up-regulation of Dicer at the RNA level in cutaneous melanoma, also showing deregulation of other enzymes that participate in the biogenesis and maturation of canonical miRNAs. Conclusions Increased Dicer expression may be a clinically useful biomarker for patients with cutaneous melanoma. Understanding deregulation of Dicer and its influence on miRNA maturation is needed to predict the susceptibility of melanoma patients to miRNA-based therapy in the future.

Squamous Cell Carcinoma of the Head and Neck in Nonsmokers and Nondrinkers: An Analysis of Clinicopathologic Characteristics and Treatment Outcomes

Background: The objective of this study was to describe the clinicopathologic manifestations of disease and outcomes of treatment among individuals without a history of smoking tobacco or consuming alcohol who develop head and neck cancer.Methods: Of 1648 invasive head and neck cancer cases treated between 1970 and 2001 at Roswell Park Cancer Institute, 40 patients were identified as never having smoked tobacco or consumed alcohol during their lifetime. These cases were reviewed to gather data on multiple clinicopathologic variables.Results: Mean age at presentation of nonsmoker/nondrinker head and neck cancer patients was 60 years (range, 27 to 90 years), and 78% (n = 31) of the patients were women. The distributions of tumor sites were 75.0% oral cavity (n = 30), 20.0% oropharynx (n = 8), and 5.0% larynx (n = 2). Sixteen patients (40%) experienced a recurrence of disease during the follow-up period, and 10 patients (25.0%) developed a second primary tumor a median of 6 years after their initial diagnosis.Conclusions: The nonsmoker/nondrinker head and neck cancer patient tends to be elderly and female, have oral cavity primary tumors, and be predisposed to second primary tumor development.

p53 Mutation Analysis in Breast Tumors by a DNA Microarray Method

The p53 gene acts as a regulator of cell growth and DNA repair in normal cells; inactivation of the gene seems to lead to cancer. It is the most commonly mutated gene in human cancers, and a high-throughput sequencing method is needed for cancer etiology studies using large sample sets. In our population-based case-control study of breast cancer, the p53 gene was amplified by PCR for 392 subjects from seven hospitals in Western New York using the Affymetrix GeneChip technology. One hundred thirty-eight (35%) of the breast tumors had p53 mutations, of which 88% were located in exons 5 to 8. New hotspots were identified at codons 179, 195, 196, 213, 217, 249, 254, 278, 281, and 298, and previously reported hotspots were found at codons 175, 248, and 273. Manual sequencing for exons 5 to 9 of the p53 gene was done for 139 tumors to validate the Affymetrix assay. The two methods had 100% concordance for mutations detectable by the Affymetrix assay. We also successfully assayed paraffin-embedded breast and lung tumors from as early as 1958 and employed a nested PCR strategy to improve weak PCR amplification. To have statistical power, the investigation of gene environment interactions and cancer requires a large number of tumor analyses, which are frequently only available from archived tissue from multiple sources. We have shown the utility of the Affymetrix GeneChip method under these challenging conditions and provided new data for the mutational spectra of breast cancer in a population-based study. (Cancer Epidemiol Biomarkers Prev 2006;15(1):80–5)

Disparities in Periodontitis Prevalence among Chronic Kidney Disease Patients

Because of adverse effects of uremia in the innate and adaptive immune systems, we hypothesized that chronic kidney disease (CKD) patients would have higher prevalence of moderate periodontitis compared with individuals without CKD. We examined this hypothesis using the NHANES III dataset, including 12,081 adults stratified by Race-Ethnicity. We followed the American Academy of Periodontology/Centers for Disease Control and Prevention definition for moderate periodontitis. Estimated glomerular filtration rate (GFR) was calculated based on calibrated serum creatinine levels according to the Modification of Diet in Renal Disease Study formula. Analyses incorporated NHANES sampling weights. Overall, 14.6% of individuals with CKD were classified as having moderate periodontitis, compared with 8.7% in the non-CKD group (p = 0.001). A significant dose-response association (p = 0.001) was observed between prevalence of moderate periodontitis and CKD stages among non-Hispanic Blacks and Mexican-Americans, but not so for non-Hispanic Whites. Prevalence of periodontitis among participants with CKD was substantially higher among non-Hispanic Blacks (38.9%) and Mexican-Americans (37.3%) compared with non-Hispanic Whites (12.9%). Multivariate logistic regression models showed that Mexican-Americans and non-Hispanic Blacks with CKD were approximately 30% to 60% more likely to have moderate periodontitis compared with those without CKD, after adjustment for diabetes status and other potential confounders.