Objective Pancreatic cancer (PC) is a lethal disease with disappointing results from current treatment modalities, suggesting that novel therapeutic strategies are urgently needed. Since microRNAs (miRNAs) are important player in biology, the clinical utility of miRNAs for designing novel therapeutics is an active area of research. The objective of the present study was to examine differentially expressed miRNAs between normal and tumor tissues, and in plasma samples obtained from PC patients, chronic pancreatitis (CP) patients and healthy subjects (HC). Material and methods The miRNA expression profiling using formalin-fixed paraffin embedded (FFPE) tissues from normal and tumor specimens was accomplished using miRBase version 19 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was subsequently performed in individual samples for 7 selected miRNAs. In addition, qRT-PCR was also performed for assessing the expression of 8 selected miRNAs in plasma samples. Results A significant difference in the expressions of miR-21, miR-205, miR-155, miR-31, miR-203, miR-214 and miR-129-2 were found in tumor tissue samples. Lower expression of miR-214 was found to be associated with better overall survival. We also observed differential expression of 8 miRNAs in plasma samples of CP and PC patients compared to HC. Interestingly, over expression of miR-21, and miR-31 was noted in both tumor tissues and in the plasma. Conclusion We found deregulated expression of miRNAs that could distinguish normal from PC in two different types of samples (tissues and plasma). Interestingly, lower expression of miR-214 was found to be associated with better overall survival. Although not statistically significant, we also observed higher expression of let-7a and lower expression of miR-508 to be associated with overall better survival. We conclude that our study nicely lays the foundation for detailed future investigations for assessing the role of these miRNAs in the pathology of pancreatic cancer.
BackgroundThe Center for Disease Control and Prevention recommends strict contact isolation precautions (CP) that include hand hygiene (HH) and barrier (gloves and gown) precautions upon entering and leaving the rooms of patients diagnosed with multidrug-resistant organism or Clostridium difficile infections. Although this policy has been in place for several years, compliance rate among HCW is rarely studied. The aim of our study was to covertly monitor, analyze, and compare the overall bundle compliance (OBC) and individual (HH, glove and gown) component compliance (ICC) among HCWs during routine patient care.MethodsA prospective observational study was done in six Detroit Medical Centers (July 2017 to February 2018). Trained observers audited both inpatient and intensive care units on random days and time. Components audited (1) HH before donning and after doffing (2) gowning and gloving techniques before entering and after existing the patient room. A mobile application (speedy audit) was used to record all data. A pilot targeted education program (TEP) was also conducted in one of the hospitals where education was focused only on strict HH practice before donning.ResultsA total of 6,274 observations were collected. The OBC was 38%. Common HCWs observed included nurses (registered nurse and nursing student) 47%; physicians (attending’s, residents, fellows) 28%; service workers including Environmental Service, Food service, Patient transporter, Social worker, Pastoral care- 14%; Allied Health Professions including Dietician, Blood Collection, Physiotherapist, Radiology Tech, Respiratory Therapist 4%; The OBC among all HCW were below 50%. For the ICC, HH (49%) was way below the gloving (80%,) and gowning (62%) compliance. HH compliance before donning was strikingly lower (40%) than the compliance after doffing (62%). This trend was similar in all HCW. Within a month of TEP, a drastic increase in both HH [↑ to 75% from 26% (P < 0.001)] and OBC [↑ to 68% from 16% (P < 0.001)] was seen.ConclusionCommon misconception that gloves are substitute to HH could explain the low HH rates before donning. Recognition of this gap and focused education on HH before donning has led to improved compliance in all HCW.Disclosures All authors: No reported disclosures.
We describe an unusual case of severe pulmonary bullous disease developing during treatment of marginal zone B-Cell lymphoma (MALT) involving the pulmonary parenchyma. The patient originally presented with pneumonia-like symptoms along with hemoptysis and was diagnosed with MALT lymphoma after a video-assisted thoracic surgical (VATS) lung biopsy. Computed tomography (CT) of the chest at diagnosis revealed multiple opacities, but no bullous disease. During the ensuing 4 years, and while on chemotherapy for the MALT lymphoma, sequential CT and pulmonary function tests revealed the development of progressive bullous disease resulting in the replacement of large portions of the lung parenchyma with bilateral bullae. This complication is rare, has been reported only once before in a patient with concomitant amyloidosis, and may be related to activation of proteolytic enzymes by lymphoma cells or chemotherapeutic agents.
Background: Comprehensive molecular profiling of microRNAs (miRNAs) and subsequent target gene analysis of pancreatic cancer (PaCa) can provide tumor specific miRNAs signatures to improve diagnostic accuracy, refine prognostic and predictive capabilities, and may also serve as therapeutic targets. In PaCa such a comprehensive analysis has not been reported.Design: RNA extracted from scant amounts of formalin fixed paraffin embedded PaCa tumor and normal pancreatic tissues were profiled for miRNA expression using microfluidic biochip microarrays (which interrogate 2019 unique mature miRNAs,LC Sciences). The expression of abnormal miRNAs was then validated and quantified using real time RT-PCR. Data was statistically analyzed using the Student's t-test. Survival data obtained in each case was correlated with the miRNA data using Kaplan-Meier analysis. Oncogenic potential, therapeutic modulation and downstream target genes of altered miRNA were evaluated by real time RT-PCR using PaCa cells for mRNA expression.Results: miRNA profiling showed high expression of miR-221 in PaCa tissues compared to normal pancreas (p=0.001). These findings were validated and quantified using qRT- PCR (p=0.0029) . Survival analysis using Kaplan-Meier, demonstrated shorter survival of patients with higher expression of miR-221 compared to those with relatively lower levels of miR-221 . The cell proliferation index of PaCa cells was increased by miR-221 mimics transfection and decreased by miR-221 inhibitors. The predicted target genes of miR-221 identified by RT-PCR were PTEN, p27kip1, p57kip2 and PUMA.Conclusions: High throughput miRNA expression profiling showed high expression of miR-221 in PaCa tissues. Higher levels of miR-221 demonstrated poorer prognosis, suggesting the oncogenic potential of miR-221 in PaCa. Its target genes are PTEN, p27kip1, p57kip2 and PUMA which are tumor suppressors, and found to be deregulated by over-expression or under-expression of miR-221 transfection studies in PaCa cells. These results provide molecular evidence of oncogenic potential of miR-221 in PaCa which may have a significant clinical impact on prognosis & risk stratification and in designing novel targeted molecular therapeutics in the future to achieve the goal of personalized and precision medicine. Citation Format: Seema Sethi, Shaan Sarkar, Hala Dubaybo, Shadan Ali, Priscila Goncalves, Spilakshmi Kollepara, Philip Philip, Yiwei Li. Molecular diagnostic, prognostic and therapeutic role of mir-221 in pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5589. doi:10.1158/1538-7445.AM2014-5589
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