Pancreatic cancer is the fourth leading cause of cancer-related death in the world. The etiology of pancreatic cancer is heterogeneous with a wide range of alterations that have already been reported at the level of the genome, transcriptome, and proteome. The past decade has witnessed a large number of experimental studies using high-throughput technology platforms to identify genes whose expression at the transcript or protein levels is altered in pancreatic cancer. Based on expression studies, a number of molecules have also been proposed as potential biomarkers for diagnosis and prognosis of this deadly cancer. Currently, there are no repositories which provide an integrative view of multiple Omics data sets from published research on pancreatic cancer. Here, we describe the development of a web-based resource, Pancreatic Cancer Database (http://www.pancreaticcancerdatabase.org), as a unified platform for pancreatic cancer research. PCD contains manually curated information pertaining to quantitative alterations in miRNA, mRNA, and proteins obtained from small-scale as well as high-throughput studies of pancreatic cancer tissues and cell lines. We believe that PCD will serve as an integrative platform for scientific community involved in pancreatic cancer research.

Tissue microarrays have become a valuable tool for high-throughput analysis using immunohistochemical labeling. However, the large majority of biochemical studies are carried out in cell lines to further characterize candidate biomarkers or therapeutic targets with subsequent studies in animals or using primary tissues. Thus, cell line-based microarrays could be a useful screening tool in some situations. Here, we constructed a cell microarray (CMA) containing a panel of 40 pancreatic cancer cell lines available from American Type Culture Collection in addition to those locally available at Johns Hopkins. As proof of principle, we performed immunocytochemical labeling of an epithelial cell adhesion molecule (Ep-CAM), a molecule generally expressed in the epithelium, on this pancreatic cancer CMA. In addition, selected molecules that have been previously shown to be differentially expressed in pancreatic cancer in the literature were validated. For example, we observed strong labeling of CA19-9 antigen, a prognostic and predictive marker for pancreatic cancer. We also carried out a bioinformatics analysis of a literature curated catalog of pancreatic cancer biomarkers developed previously by our group and identified two candidate biomarkers, HLA class I and transmembrane protease, serine 4 (TMPRSS4), and examined their expression in the cell lines represented on the pancreatic cancer CMAs. Our results demonstrate the utility of CMAs as a useful resource for rapid screening of molecules of interest and suggest that CMAs can become a universal standard platform in cancer research.

Tissue microarrays (TMAs) have become an invaluable tool in cancer research to evaluate expression and subcellular localization of proteins in cells and tissues. As the catalogs of candidate biomarkers and therapeutic targets become more extensive, there is a need to characterize and validate these targets and biomarkers in cell lines as a primary biological system in research laboratories. Thus, cell microarrays (CMAs) are useful as a high-throughput screening tool. Here, we constructed a CMA containing 32 publicly available immortalized breast cell lines with the goal of creating a method to rapidly screen for antigens of interest in breast cancer research in a relatively easy, rapid and cost-effective manner. As proof of concept, we performed immunocytochemical staining of the HER2 receptor, as the status of this protein is relevant to breast cancer and has previously been reported for these cell lines. We observed a complete concordance of our staining with the published status of HER2 in these cell lines. In addition, we examined the expression of CD44, epithelial markers EpCAM and E-cadherin and tyrosine phosphoproteins. The labeling of these proteins correlates with the known biology of the cell lines. Our results demonstrate the utility of our method to screen for potential biomarkers and therapeutic targets in breast cancer and we suggest that CMAs be used as a general approach in breast cancer research.

Background: Resident physicians are known to be infrequent reporters of patient safety events (PSE). Previous studies assessing barriers to resident PSE reporting have not considered possible cultural barriers faced by international medical graduates (IMG). This study aimed to assess the knowledge and attitudes of residents regarding PSE and possible barriers contributing to poor resident reporting.Methods: A cross sectional survey of all house staff undergoing post-graduate residency training at two independent community hospital based academic medical centers was conducted through an online questionnaire. Sample case vignettes were created to assess the residents’ ability to identify safety events and classify them as near miss, adverse events or sentinel events and decide whether they were reportable.Results: The Reporting of PSE increased significantly by year of residency training (p < 0.005), with time taken to file a PSE being the strongest perceived barrier. There was no difference in PSE reporting between IMG’s and non- IMG’s. We identified major knowledge gaps with only 73.9%, 79.6% and 94.3% of respondents correctly identifying sentinel events, adverse events, and near misses, respectively. 58.1% of respondents did not think near misses were reportable.Conclusions: A lack of knowledge is the most important barrier towards PSE reporting. A different cultural background and lack of previous exposure to patient safety report by IMGs is not a significant barrier towards safety event reporting. In the short-term, it appears that focusing limited institutional resources on education rather than acculturation issues would have the greatest benefit.

The development of esophageal squamous cell carcinoma (ESCC) is poorly understood and the major regulatory molecules involved in the process of tumorigenesis have not yet been identified. We had previously employed a quantitative proteomic approach to identify differentially expressed proteins in ESCC tumors. A total of 238 differentially expressed proteins were identified in that study including S100 calcium binding protein A9 (S100A9) as one of the major downregulated proteins. In the present study, we carried out immunohistochemical validation of S100A9 in a large cohort of ESCC patients to determine the expression and subcellular localization of S100A9 in tumors and adjacent normal esophageal epithelia. Downregulation of S100A9 was observed in 67% (n = 192) of 288 different ESCC tumors, with the most dramatic downregulation observed in the poorly differentiated tumors (99/111). Expression of S100A9 was restricted to the prickle and functional layers of normal esophageal mucosa and localized predominantly in the cytoplasm and nucleus whereas virtually no expression was observed in the tumor and stromal cells. This suggests the important role that S100A9 plays in maintaining the differentiated state of epithelium and suggests that its downregulation may be associated with increased susceptibility to tumor formation.

Background: Patient safety events (PSE) are opportunities to improve patient care but physicians rarely report them. In a previous study, residents identified knowledge regarding what constitutes a PSE, perceived lack of time, complexity of the reporting process, lack of feedback, and perceived failure to resolve the issue despite reporting to be barriers limiting their PSE reporting. The residency programs and system patient safety and quality improvement departments created targeted interventions to address identified barriers. Objective: Assess effectiveness of targeted interventions on improving PSE reporting rates amongst residents. Methods: As part of a multi-residency patient safety project, interventions were created to focus on the removal of barriers to reporting PSE identified previously. Post-interventions, an identical cross-sectional survey of the residents at the same two community teaching hospitals was conducted from Sept to Dec 2018 through an online questionnaire tool. Results: 78 out of 149 residents (52.3%) completed the survey. We found a significant improvement in the number of residents who endorsed reporting a PSE in the past 1 year (51.2% vs 23.5%, p = 0.001), as well as during the course of their training (52.6% vs 26.5%, P = 0.001). There was also a significant decrease in the number of residents who were unsure of how to report a PSE (p = 0.031) as well as those who viewed medical error as a sign of incompetence (p = 0.036). Conclusion: Our study demonstrates that simplifying the PSE reporting process, improving knowledge and acceptance of patient safety/quality improvement principles and promotion of a just culture improves resident PSE reporting.

Background: Breast cancer is the most common cancer in women worldwide. With early detection and advancement in treatment, majority of women diagnosed with breast cancer will be cured. Some of these breast cancer survivors report Cognitive Impairment (CI) also known as “chemo-brain” or “mental fog”, especially those who have received chemotherapy. Few studies using functional neuroimaging have been conducted to foresee possible neurological alterations that could be linked to CI but research in this area remains in its early stages. Cognivue ® is an FDA cleared medical device that helps in assessment of cognitive dysfunction using novel computerized technology and is reported to be useful in detecting early stages of CI. Methods: We conducted a pilot study at the Lipson Cancer Institute/Rochester General Hospital for evaluation of CI in patients with breast cancer who received curative chemotherapy within the last 12 months of enrollment and self-reported CI. We enrolled 23 female patients between ages 19 and 90 years. Patients were subjected to Mini Mental Status Examination (MMSE) and St. Louis University Mental Status examination (SLUMS) as well as Cognivue ® testing. MMSE and SLUMS were scored according to scoring range guidance and digital data was obtained from the Cognivue® software. Analysis was performed using correlations of numeric data, ANOVA with Tukey’s post-hoc tests for categorical data, and Positive/Negative Percent Agreement (PPA/NPA) analysis for comparison of all cognitive testing methods. Results: Cognivue ® provides higher sensitivity to evaluate CI than MMSE and SLUMS, mainly in detecting earlier stages of CI. The cognitive domains most affected were executive function, abstraction and memory. There was a statistically significant correlation between Cognivue/CI score and duration of chemotherapy (p = 0.02). Age, type of chemotherapy or hormonal status of breast cancer were not significantly related with CI. Conclusions: Cognivue appears to be beneficial in its ability to detect CI in breast cancer patients. Specifically, detection of impairment in executive function domain could be predictive of daily life activity issues in such patients post-chemotherapy. This study also provides a possibility of detecting early cognitive dysfunction as well as the potential to develop a predictive algorithm of early intervention strategies for better patient outcomes. Citation Format: Manasi M Godbole, Mukul Singal, Reina Benabou, Iqra Choudary, Mehul P Patel. Objective measurement of cognitive impairment in breast cancer survivors who received chemotherapy with the use of novel computerized testing [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-07.

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