Pancreatic cancer-induced neutrophil extracellular traps: A potential contributor to cancer-associated thrombosis

Pancreatic cancer (PaCa) is a highly metastatic cancer, and patients are at high risk of developing venous thromboembolism (VTE). Neutrophil extracellular traps (NETs) have been associated with cancer metastasis and cancer-associated thrombosis, but the ability of cancer to stimulate NET release is not known. The release of NETs has been shown to be a slow process and requires reactive oxygen species (ROS) production. Studies suggest that activated platelets are important mediators in the release. Here, we show that PaCa cells can stimulate the rapid release of NETs, independently of ROS production. We further assessed the role of platelets in PaCa-induced NETs and observed a trend of increased the NET release by PaCa-primed platelets. Additionally, NETs promoted thrombus formation under venous shear stress ex vivo. Taken together, our results suggest that PaCa-induced NETs can contribute to the high risk of venous thromboembolism development in PaCa patients, and reveal NETs as a potential therapeutic target

Information Technology Adoption by Small Businesses Owners

Small business owners need effective strategies to increase profitability. One such strategy is the adoption of information technology (IT). The purpose of this multiple case study was to explore the strategies used by small business enterprise (SBE) owners to implement IT solutions for increased profitability within 3 years of opening their business. The population consisted of 3 small business owners in Orange County Southern California who were profitable by their third year of business. The conceptual framework for this study was based upon general systems theory. Data for this study were collected through semistructured interviews and a review of company documents. Transcript review and member checking were included for validity and reliability purposes. Methodological triangulation, achieved through analysis of business plans, financial documents, and probability trends documents allowed identification of 4 emergent themes: Essential strategies small business owners use to implement IT solutions for increased profitability, the essential relationship between network orientation and successful IT implementation, the relationship between IT consultants and successful implementation, and the relationship between internal IT resources and successful implementation. The findings from this study could impact social change because when SBEs are profitable, SBE owners will contribute to the affluence of their workers, communities, local economies, and society

Antiplatelet drug ticagrelor enhances chemotherapeutic efficacy by targeting the novel P2Y12-AKT Pathway in pancreatic cancer cells

Background: Extensive research has reported that extracellular ADP in the tumour microenvironment can stimulate platelets through interaction with the platelet receptor P2Y12. In turn, activated platelets release biological factors supporting cancer progression. Experimental data suggest that the tumour microenvironment components, of which platelets are integral, can promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Thus, overcoming chemoresistance requires combining multiple inhibitors that simultaneously target intrinsic pathways in cancer cells and extrinsic factors related to the tumour microenvironment. We aimed to determine whether ticagrelor, an inhibitor of the ADP–P2Y12 axis and a well-known antiplatelet drug, could be a therapeutic option for PDAC. Methods: We investigated a functional P2Y12 receptor and its downstream signalling in a panel of PDAC cell lines and non-cancer pancreatic cells termed hTERT-HPNE. We tested the synergistic effect of ticagrelor, a P2Y12 inhibitor, in combination with chemotherapeutic drugs (gemcitabine, paclitaxel and cisplatin), in vitro and in vivo. Results: Knockdown studies revealed that P2Y12 contributed to epidermal growth factor receptor (EGFR) activation and the expression of SLUG and ZEB1, which are transcriptional factors implicated in metastasis and chemoresistance. Studies using genetic and pharmacological inhibitors showed that the P2Y12–EGFR crosstalk enhanced cancer cell proliferation. Inhibition of P2Y12 signalling significantly reduced EGF-dependent AKT activation and promoted the anticancer activity of anti-EGFR treatment. Importantly, ticagrelor significantly decreased the proliferative capacity of cancer but not normal pancreatic cells. In vitro, synergism was observed when ticagrelor was combined with several chemodrugs. In vivo, a combination of ticagrelor with gemcitabine significantly reduced tumour growth, whereas gemcitabine or ticagrelor alone had a minimal effect. Conclusions: These findings uncover a novel effect and mechanism of action of the antiplatelet drug ticagrelor in PDAC cells and suggest a multi-functional role for ADP-P2Y12 signalling in the tumour microenvironment

Platelet-cancer Crosstalk: Mechanisms and Therapeutic Implications

Platelets are small anucleate blood cells that are central to primary haemostasis. However, platelets are also implicated in cancer pathogenesis. This thesis showed that cancer cells promote thrombosis by activating platelets, and in turn, platelets provide cancer cells with growth factors to render cancer more aggressive and chemoresistant. The thesis demonstrated a therapeutic benefit of combined antiplatelet, ticagrelor, and chemo drugs, on cancer treatment

Teaching Middle School Science Through Project Based Learning

The focus on technology is becoming increasingly critical to our society today. In 2013, the Next Generation Science Standards (NGSS) were released. These standards list focused on the importance of how the subjects of science, technology, engineering, and mathematics (STEM) should be taught in a “hands on way” versus with facts and memorization. With this, the goal of the NGSS is to prioritize restructuring pK-12th grade STEM courses, in that it focuses more on career readiness while also tailoring to all different types of students and learning styles. This Interactive Qualifying Project (IQP), “Teaching Middle School Science Through Project Based Learning (PBL)” hopes to adapt the Project Based Learning principals WPI has undertaken, to a middle school setting, while also determining the effectiveness of PBL and the students’ attitudes in relation to STEM. This IQP’s goal is to formulate lessons in regard to the principals of PBL and determine how effective the correlating project is with incorporating these principals. A major note was during the employment of this IQP, the COVID-19 pandemic was at large and as a result, the PBL unit was deployed in a hybrid classroom environment. To evaluate the PBL unit, an anonymous Pre- and Post-Assessment were administered to the students on the topics of physical forces, such as electric force, gravity, and magnetism. These lessons were implemented in one class, which was further split into two cohorts. It was found that there was a substantial improvement to the students’ scores in the two cohorts, with the lesson plans given utilizing group work and activities to demonstrate the topics given, which finally led to the final project of observing a car race. The final race car project designed encouraged students and engaged them to learn and improved their attitudes towards STEM. To learn and obtain a better understanding of how the students felt towards STEM, an anonymous Pre- and Post-Assessment was given at the beginning of the lessons implementations and at the end once all the lessons were completed. It was concluded that the project, which utilized PBL, was valuable for the students and benefited them. The hope for this project is to be utilized and implemented in the future, in classrooms everywhere. With hopes to help the future generations of scientists and engineers become more readily prepared to enter the workforce

Epithelial-mesenchymal transition as a therapeutic target for overcoming chemoresistance in pancreatic cancer

Pancreatic cancer has one of the worst prognoses among all cancers due to the late manifestation of identifiable symptoms and high resistance to chemo- and radiation therapies. In recent years, a cancer development phase termed epithelial-mesenchymal transition (EMT) has gained increasing research focus. The process is implicated in tumour metastasis, and emerging evidence suggests EMT also contributes or induces chemoresistance in several cancers. Nevertheless, the applicability of therapeutic targeting of EMT faces many challenges. In this mini-review, we summarise the evidence supporting the role of EMT in pancreatic cancer progression, focusing particularly on its association with chemoresistance

Options for Water Reuse in Optical Fiber Production

The goal of this MQP report was to investigate the manufacturing process of optical fibers at the OFS plant in Sturbridge, MA. Our goal was to reduce water usage to encourage environmental benefits and cost-saving initiatives through our project work. First, we focused on constructing a lab-scale process to deionize the wastewater effluent stream so it could be repurposed. We then redesigned a seal water recirculation system that would eliminate a major source of single-pass water within the plant. The series of recommendations presented in this report and to the OFS team foresee large cost and water savings