EGFR mutated lung cancer: current therapies and potential future treatments

Lung cancer is the leading cause of cancer related deaths in the United States, with an estimated 158, 040 deaths in 2015, accounting for 27% of all cancer deaths. Recent research has identified several important molecular driver oncogenes, including epidermal growth factor receptor (EGFR). EGFR is encoded by exons 18-21, each of which harbor specific mutations within the tyrosine kinase domain. These mutations can drive cell growth, proliferation, and survival, resulting in the formation of non-small cell lung cancer. The development of EGFR tyrosine kinase inhibitors, allows the targeting of these specific mutations without the toxicity normally associated with standard chemotherapy. Unfortunately, inevitably resistance to therapy manifests, requiring a change in therapy and adding complexity to treatment decision making for clinicians and patients alike. Through a comprehensive examination of current literature, this review will establish a standard for first line, targeted treatment for specific genetic mutations within the EGFR gene, as well as address treatment options once resistance to first-line therapy inevitably develops

Spectrophotometric study of the Boron-Curcumin system

With mechanism and structure in mind, the aim of this research project was to investigate the role played by the various reagents used in the curcumin spectrophotometric method. The reagents were used in varied concentrations and at times some eliminated entirely, in the hope that a greater understanding be gained in the overall mechanism followed by the reaction. One of the major objectives was to try to determine the structure of the colored substance formed in the reaction. A step towards this goal was gained by obtaining molar ratios of the entities suspected to be an intricate part of the colored substance. Most of the studies made were studies of absorption using the visible range of the spectrum (550 millimicrons) where the colored substance was found to absorb at its maximum. A photoelectric colorimeter could have been used instead or a spectrophotometer, however the resolution and precision would not have been as great. A potentiometric titration study was also carried out so as to gain greater insight into the preliminary reaction occurring between boric acid and oxalic acid prior to the addition of curcumin in the final color forming step of the method

Micropattern traction microscopy: a technique for the simplification of cellular traction force measurements

Thesis (Ph.D.)--Boston UniversityCells respond to a number of cues that affect how they interact with their surrounding environment, such as topology, the presentation of adhesive ligands, and stiffness. Recent advancements in the field ofmechanobiology have revealed that one of the main ways in which cells sense these cues is through contractile forces. Mechanobiology research seeks to understand how environmental cues affect the forces that cells exert on their surronnding environment and how these mechanical forces are communicated to the cell and transformed into biochemical signals. Therefore, quantitative methods have been developed to determine cell contractility on soft, optically transparent, deformable surfaces by quantifying substrate deformation in terms of cellular traction forces. However, the currently available tools that are used to study cell interactions are limited in their applicability due to the need for specialized technical expertise that is not amenable to the widespread adaptation of these techniques. Therefore, we have sought to develop a novel traction force microscopy technique known as micropattem traction microscopy. With this technique, we hope to greatly simplify the current traction force microscopy techniques and provide a method which will be able to be adopted by a wide range of laboratories. This dissertation describes the process ofthe development and application of this novel traction force technique to probe questions in mechanobiology that have not been previously broached due to the lack of appropriate tools. The technique itself uses indirect microcontact printing to create a regularized array of fluorescent protein onto a glass substrate, which is then transferred to an optically transparent, soft, elastic polyacrylamide hydrogel. Cells, limited by their ability to adhere only to patterned regions, will deform the pattern at these defined points. Thus, with knowledge of the bulk elastic properties ofthe substrate and a priori knowledge of the pattern, we are able to quantify the force a cell is exerting without its removal. We also developed and released a robust, automated MATLAB program that will aid users in the calculation of traction forces so that people with limited experience with programming can utilize the program without significant investments into training. This indirect approach allows for not only individual proteins, but also for multiple, spatially distinct, fluorescent proteins such as fibronectin and gelatin to be simultaneously patterned onto this surface as well. The ability to pattern multiple proteins in a spatially defmed region significantly aids in giving users control over as many parameters as possible. Finally, we will explore the current and future potential that this technique has to offer to researchers in the field of mechanobiology

The accuracy of computer-assisted feedback and students’ responses to it

Various researchers in second language acquisition have argued for the effectiveness of immediate rather than delayed feedback. In writing, truly immediate feedback is impractical, but computer-assisted feedback provides a quick way of providing feedback that also reduces the teacher’s workload. We explored the accuracy of feedback from Criterion®, a program developed by Educational Testing Service, and students’ responses to it. Thirty-two students received feedback from Criterion on four essays throughout a semester, with 16 receiving the feedback immediately and 16 receiving it several days after writing their essays. Results indicated that 75% of the error codes were correct, but that Criterion missed many language errors. Students responded to the correct error codes 73% of the time and responded to more of the codes over the course of the semester, while the condition—delayed versus immediate—did not affect their response rates nor their accuracy on the first drafts. Although we cannot support claims that immediate feedback may be more helpful, we believe that, with proper training, Criterion can help students correct certain aspects of language

Strong Neighborhoods: A Quality of Life Survey in New Auburn, Auburn, Maine

This project was completed in collaboration with the City of Auburn’s Department of Community Development and the Citizens Advisory Committee in order to help determine the allocation of funds from a potential Housing and Urban Development (HUD) Community Block grant for the city of Auburn, Maine. This project involved conducting a quality-of-life survey of local residents in order to evaluate the current situation in the three blighted neighborhoods. The overall goal was to gather public opinion so that the Citizen’s Advisory Committee and the Director of Community Development could make informed decisions about future neighborhood projects and improvements. Urban blight is often defined as simply the decay and deterioration of an urban area due to neglect or age. However, “… an ambiguous conceptualization of blight can lead to mismatches between actual urban conditions and codified public policy targets” (Weaver and Bagchi-Sen, 2013, 61). Weaver and Bagchi-Sen make it clear in this quote that because it is difficult to define or conceptualize blight, it is often poorly addressed with public policies. Therefore, it is crucial to understand that urban blight is a complex and dynamic term. Furthermore, it is important to remember that it is often faulty city planning, and not the people themselves, that result in the dilapidation of urban areas. People do not embody blight. It is important to distinguish people living in blighted areas and blight itself (Weaver, 2013, 62). Although it is often traditionally those in power who are given the opportunity to determine the content of a landscape, it is those directly experiencing blight who can provide the best advice on how to address issues in their neighborhoods. Therefore, for this project we will be conducting quality of life surveys in three Auburn neighborhoods affected by blight: New Auburn, Union Street, and Downtown. The implementation of a survey seems to be the most effective first step towards improving the quality of life in an urban neighborhood because it is taking into account the needs of the actual residents, rather than the ideals of the policy-makers. Residents were asked to judge their respective neighborhoods based on several characteristics ranging from attractiveness to infrastructure. The primary results from this project suggest that residents in the New Auburn neighborhood specifically would like to see the expansion of green spaces such as community gardens, bike and jogging trails, and easy access to river areas. A large percentage of residents also want to see “better” housing, although they were not asked to specify in what way. In general, residents throughout Auburn do not take full advantage of the bus system. Residents among all three neighborhood would also like to see improvements to sidewalks and unsafe street intersections

The Predictive Link between Matrix and Metastasis

Cancer spread (metastasis) is responsible for 90% of cancer-related fatalities. Informing patient treatment to prevent metastasis, or kill all cancer cells in a patient\u27s body before it becomes metastatic is extremely powerful. However, aggressive treatment for all non-metastatic patients is detrimental, both for quality of life concerns, and the risk of kidney or liver-related toxicity. Knowing when and where a patient has metastatic risk could revolutionize patient treatment and care. In this review, we attempt to summarize the key work of engineers and quantitative biologists in developing strategies and model systems to predict metastasis, with a particular focus on cell interactions with the extracellular matrix (ECM), as a tool to predict metastatic risk and tropism