ABO blood group and other genetic variants associated with pancreatic cancer

Pancreatic adenocarcinoma is the fourth leading cause of cancer death in the United States. Recent reports, including genome-wide association studies and self-reported blood serotype studies, have shown that individuals of European ancestry who carry non-O blood group are at an increased risk of developing pancreatic cancer. Two recent genome-wide association studies of pancreatic cancer have identified associations between pancreatic cancer risk and genetic variants in the ABO blood group gene, the locus containing the telomerase reverse transcriptase (hTERT) gene, the nuclear receptor family gene NR5A2 and a non-genic region on chromosome 13q22.1

Practice Variation in the Immediate Postoperative Care of Pediatric Kidney Transplantation: A National Survey

Introduction Advances in organ allocation, surgical technique, immunosuppression, and long-term follow-up have led to a significant improvement in kidney transplant outcomes. Although there are clear recommendations for several aspects of kidney transplant management, there are no pediatric-specific guidelines for immediate postoperative care. The aim of this survey is to examine practice variations in the immediate postoperative care of pediatric kidney transplant patients. Methods We surveyed medical directors of Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)-affiliated pediatric intensive care units regarding center-specific immediate postoperative management of pediatric kidney transplantation. Results The majority of PALISI centers admit patients to the pediatric intensive care unit postoperatively, and 97% of the centers involve a pediatric nephrologist in immediate postoperative care. Most patients undergo invasive hemodynamic monitoring; 97% of centers monitor invasive arterial blood pressure and 88% monitor central venous pressure. Most centers monitor serum electrolytes every 4 to 6 hours. Wide variation exists regarding blood pressure goal, fluid replacement type, frequency of obtaining kidney ultrasound, and use of prophylactic anticoagulation. Conclusion There is consistent practice across PALISI centers in regards to many aspects of immediate postoperative management of pediatric kidney transplantation. However, variation still exists in some management aspects that warrant further discussions to reach a national consensus

Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors

Background: One of the most provocative recent observations in cancer epigenetics is the discovery of large hypomethylated blocks, including single copy genes, in colorectal cancer, that correspond in location to heterochromatic LOCKs (large organized chromatin lysine-modifications) and LADs (lamin-associated domains). Methods: Here we performed a comprehensive genome-scale analysis of 10 breast, 28 colon, nine lung, 38 thyroid, 18 pancreas cancers, and five pancreas neuroendocrine tumors as well as matched normal tissue from most of these cases, as well as 51 premalignant lesions. We used a new statistical approach that allows the identification of large hypomethylated blocks on the Illumina HumanMethylation450 BeadChip platform. Results: We find that hypomethylated blocks are a universal feature of common solid human cancer, and that they occur at the earliest stage of premalignant tumors and progress through clinical stages of thyroid and colon cancer development. We also find that the disrupted CpG islands widely reported previously, including hypermethylated island bodies and hypomethylated shores, are enriched in hypomethylated blocks, with flattening of the methylation signal within and flanking the islands. Finally, we found that genes showing higher between individual gene expression variability are enriched within these hypomethylated blocks. Conclusion: Thus hypomethylated blocks appear to be a universal defining epigenetic alteration in human cancer, at least for common solid tumors. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0061-y) contains supplementary material, which is available to authorized users

Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop

A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI) on "Pancreatitis-Diabetes-Pancreatic Cancer" focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on (a) an overview of the problem of PDAC; (b) CP as a risk factor of PDAC; (c) DM as a risk factor of PDAC; (d) pancreatogenic, or type 3c, DM; (e) genomic associations of CP, DM, and PDAC; (f) surveillance of high-risk populations and early detection of PDAC; and (g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and the discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article

Contemporary Issues of Open Data in Information Systems Research: Considerations and Recommendations

Researchers, governments, and funding agencies are calling on research disciplines to embrace open data—data that anyone can access and use. They have done so based on the premise that research efforts can draw and generate several benefits from open data because it might provide further insight and enable individuals to replicate and extend current knowledge in different contexts. These potential benefits, coupled with a global push towards open data policies, bring open data into the agenda of research disciplines, which includes information systems (IS). In this paper, we respond to these developments as follows. We outline themes in the ongoing discussion around open data in the IS discipline. The themes fall into two clusters: 1) the motivation for open data includes themes of mandated sharing, benefits to the research process, extending the life of research data, and career impact; and 2) the implementation of open data includes themes of governance, socio-technical system, standards, data quality, and ethical considerations. In this paper, we outline the findings from a pre-ICIS 2016 workshop on the topic of open data. The workshop discussion confirmed themes and identified issues that require attention in terms of the approaches that IS researchers currently use. The IS discipline offers a unique knowledge base, tools, and methods that can advance open data across disciplines. Based on our findings, we provide suggestions on how IS researchers can drive the open data conversation. Further, we provide advice for adopting and establishing procedures and guidelines for archiving, evaluating, and using open data

Performance of lateral flow device and galactomannan for the detection of Aspergillus species in bronchoalveolar fluid of patients at risk for invasive pulmonary aspergillosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111755/1/myc12327.pd

Aldehyde dehydrogenase 1A1 and gelsolin identified as novel invasion-modulating factors in conditioned medium of pancreatic cancer cells

Conditioned medium (CM) from clonal sub-populations of the pancreatic cancer cell line, MiaPaCa-2 with differing invasive abilities, were examined for their effect on in vitro invasion. Conditioned medium from Clone #3 (CM#3) strongly promoted invasion, while CM from Clone #8 (CM#8) inhibited invasion in vitro. 2D DIGE followed by MALDI-TOF MS analysis of CM#3 and CM#8 identified 41 proteins which were differentially regulated; 27 proteins were down-regulated and 14 proteins up-regulated in the invasion-promoting CM#3 when compared to CM#8. Western blotting analysis confirmed the down-regulated expression of gelsolin and the up-regulation of aldehyde dehydrogenase 1A1 in CM#3. Down-regulation of aldehyde dehydrogenase 1A1 in Clone #3 CM and gelsolin levels in Clone #8 CM by siRNA transfection revealed an important involvement of these proteins in promoting and inhibiting invasion in these pancreatic cancer cell lines

Mesothelin-specific CD8+ T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients

Tumor-specific CD8+ T cells can potentially be activated by two distinct mechanisms of major histocompatibility complex class I–restricted antigen presentation as follows: direct presentation by tumor cells themselves or indirect presentation by professional antigen-presenting cells (APCs). However, controversy still exists as to whether indirect presentation (the cross-priming mechanism) can contribute to effective in vivo priming of tumor-specific CD8+ T cells that are capable of eradicating cancer in patients. A clinical trial of vaccination with granulocyte macrophage–colony stimulating factor–transduced pancreatic cancer lines was designed to test whether cross-presentation by locally recruited APCs can activate pancreatic tumor-specific CD8+ T cells. Previously, we reported postvaccination delayed-type hypersensitivity (DTH) responses to autologous tumor in 3 out of 14 treated patients. Mesothelin is an antigen demonstrated previously by gene expression profiling to be up-regulated in most pancreatic cancers. We report here the consistent induction of CD8+ T cell responses to multiple HLA-A2, A3, and A24-restricted mesothelin epitopes exclusively in the three patients with vaccine-induced DTH responses. Importantly, neither of the vaccinating pancreatic cancer cell lines expressed HLA-A2, A3, or A24. These results provide the first direct evidence that CD8 T cell responses can be generated via cross-presentation by an immunotherapy approach designed to recruit APCs to the vaccination site

Somatic mutations in the chromatin remodeling gene ARID1A occur in several tumor types

Mutations in the chromatin remodeling gene ARID1A have recently been identified in the majority of ovarian clear cell carcinomas (OCCCs). To determine the prevalence of mutations in other tumor types, we evaluated 759 malignant neoplasms including those of the pancreas, breast, colon, stomach, lung, prostate, brain, and blood (leukemias). We identified truncating mutations in 6% of the neoplasms studied; nontruncating somatic mutations were identified in an additional 0.4% of neoplasms. Mutations were most commonly found in gastrointestinal samples with 12 of 119 (10%) colorectal and 10 of 100 (10%) gastric neoplasms, respectively, harboring changes. More than half of the mutated colorectal and gastric cancers displayed microsatellite instability (MSI) and the mutations in these tumors were out‐of‐frame insertions or deletions at mononucleotide repeats. Mutations were also identified in 2–8% of tumors of the pancreas, breast, brain (medulloblastomas), prostate, and lung, and none of these tumors displayed MSI. These findings suggest that the aberrant chromatin remodeling consequent to ARID1A inactivation contributes to a variety of different types of neoplasms. Hum Mutat 33:100–103, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89516/1/humu_21633_sm_Mat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/89516/2/21633_ftp.pd

Prevention and early detection of prostate cancer

This Review was sponsored and funded by the International Society of Cancer Prevention (ISCaP), the European Association of Urology (EAU), the National Cancer Institute, USA (NCI) (grant number 1R13CA171707-01), Prostate Cancer UK, Cancer Research UK (CRUK) (grant number C569/A16477), and the Association for International Cancer Research (AICR