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  1. Abstract

    Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. We found that applied mechanical tension can dramatically alter gene expression in breast cancer cells, leading to decreased proliferation, increased resistance to chemotherapeutic treatment and enhanced adhesion to inflamed endothelial cells and collagen I under fluidic shear stress. A mechanistic analysismore »of the pathways involved in these effects supported a complex signaling network that included Abl1, Lck, Jak2 and PI3K to regulate pro-survival signaling and enhancement of adhesion under flow. Studies using mouse xenograft models demonstrated reduced proliferation of breast cancer cells with orthotopic implantation and increased metastasis to the skull when the cancer cells were treated with mechanical load. Using high throughput mechanobiological screens we identified pathways that could be targeted to reduce the effects of load on metastasis and found that the effects of mechanical load on bone colonization could be reduced through treatment with a PI3Kγ inhibitor.

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  2. Abstract Photocoagulation of blood vessels offers unambiguous advantages to current radiofrequency approaches considering the high specificity of blood absorption at available laser wavelengths (e.g., 532 nm and 1.064 µm). Successful treatment of pediatric vascular lesions, such as port-wine stains requiring microvascular hemostasis, has been documented. Although laser treatments have been successful in smaller diameter blood vessels, photocoagulation of larger sized vessels is less effective. The hypothesis for this study is that a primary limitation in laser coagulation of large diameter blood vessels (500–1000 µm) originates from shear stress gradients associated with higher flow velocities along with temperature-dependent viscosity changes. Laser (1.07 µm) coagulation ofmore »blood vessels was tested in the chicken chorio-allantoic membrane (CAM). A finite element model is developed that includes hypothetical limitations in laser coagulation during irradiation. A protocol to specify laser dosimetry is derived from OCT imaging and angiography observations as well as finite element model results. Laser dosimetry is applied in the CAM model to test the experimental hypothesis that blood shear stress and flow velocity are important parameters for laser coagulation and hemostasis of large diameter blood vessels (500–1000 µm). Our experimental results suggest that shear stress and flow velocity are fundamental in the coagulation of large diameter blood vessels (500–1000 µm). Laser dosimetry is proposed and demonstrated for successful coagulation and hemostasis of large diameter CAM blood vessels.« less
    Free, publicly-accessible full text available December 1, 2023
  3. Our experience managing conflicting needs for a summer Research Experience for Undergraduate program.
  4. This paper describes a preliminary analysis of a summer Research Experience for Undergraduates (REU) Site sponsored by the biomedical engineering department at a large public institution in the southwest United States. Data were compiled from the 2018 and 2019 cohorts of the program.Twenty-four participants from different undergraduate majors and universities were selected from competitive applicant pools, paired with a research mentor in the department, and tracked over each program’s duration. The participants were given a 37-question survey upon arrival and after the completion of the 10-week summer program (i.e., pre-test and post-test). These questions were broadly split among four categoriesmore »to evaluate the participants’ comfort with (1) scientific writing, (2) scientific presentation, and students’ strength of association with the identities and careers of (3) researchers and (4) engineers. Students reported significant increases in their scientific writing skills and tended to identify more as researchers after the program. Conversely, students noted little change in their ability to present in a scientific setting and reported that their identity as engineers was not stronger. Separate focus groups with the visiting scholars and their graduate student mentors were conducted after the program to identify the strengths and weaknesses of the current iteration of the REU program. Possible improvements to the REU are proposed at the end of the paper.« less
  5. Introduction: Head and neck cancer (HNC) and its treatment can result in facial disfigurement and functional defects in speech, swallowing, and vision that persist after reconstructive surgery. Body image concerns are pervasive among HNC patients, and a large portion of these concerns stem from worries about social interaction. Our overarching goal is to develop normative interventions to inform HNC patients about how others will respond to the changes in their facial appearance. In this study, we investigated saliency map algorithms for highlighting regions of interest on a clinically disfigured face that are expected to draw an observer’s eye based onmore »color, intensity, etc.« less
  6. Introduction: Skin Cancer is the most common cancer by which people are afflicted. While most forms of skin cancer have high survival rates if they are caught early, both Squamous Cell Carcinoma and Melanoma can metastasize and are very difficult to treat once this happens. Matrix Metallopeptidases (MMPs), Normally involved in cell growth, movement, and death, can become overactive in patients with cancer. While research suggested that MMP inhibitors could be used to treat many forms of cancer, clinical trials in late stage cancer patients showed that this was not the case. While they were not useful in shrinking latemore »stage tumors, they were effective in preventing growth and metastasis of existing tumors. For this reason, they may be especially useful in the treatment of skin cancers as they may prevent metastasis. While MMP inhibitors can be delivered systemically, whether orally, or intravenously, systemic delivery can give rise to severe unwanted off-target side effects. As such, localized delivery is preferable. By incorporating MMP inhibitors into polymer gels, the drug can be administered topically and its distribution within the skin and into the systemic circulation may be controlled. Formulations may therefore be customized to alter the depth which the drug is delivered.« less
  7. Introduction: RE1-silencing transcription factor (REST) silences neuronal differentiation genes. Its overexpression in an aggressive subset of gliomas is believed to support the enhanced tumor-initiating and self-renewal capacities of glioblastoma cancer stem cells (GSCs). Therefore, REST knockdown is hypothesized to inhibit tumor growth and recurrence. Because REST, as a large protein, is difficult to target directly with small molecules, our study focuses on knocking down REST by inhibiting one of its regulatory enzymes, small C-terminal domain phosphatase 1 (SCP1). Dephosphorylation of REST by SCP1 protects the former from degradation; consequently, SCP1 inhibition with an experimental drug, T62, is expected to reducemore »REST protein levels. This REST knockdown is hypothesized to induce the expression of neuronal differentiation genes, thereby forcing differentiation of GSCs and making them more vulnerable to standard treatments. We begin our study by validating patient-derived GSC lines and subsequently testing the efficacy of T62 drug in these cells. Our work supports an effort to understand various molecular pathologies of GBM and its intrinsic GSCs in order to develop novel therapeutic strategies.« less
  8. Introduction: Members of the Ras protein family are involved in sending signals through the human body to regulate processes including cell growth. Acting as a molecular switch, Ras alternates between its active and inactive states (“on” and “off”) depending on its binding to either GTP or GDP. Upon the introduction of a mutation, Ras becomes incapable of performing the GTP hydrolysis reaction at a controlled rate. This results in the protein remaining in the “on” state for prolonged periods of time, disturbing its role in the regulation of cell growth and causing tumors to form. In the genome of cancerousmore »tumors, mutations that permanently activate Ras have been observed and analyzed at three distinct locations, one being Q61. Previous research1 shows how the Q61 residue contributes to the protein’s function by stabilizing the water molecule in the active site, but little research has been done studying the Y32 residue, which has also been implicated in the mechanism. This research investigates the role Y32 plays in activating Ras via introduction of a different amino acid and measurement of the mutated protein’s activity in the hydrolysis of GTP.« less
  9. Introduction: The American Cancer Society predicted that approximately 96,480 people will be diagnosed with melanoma skin cancer this year, and 7,230 of them will die [1]. Minimally-invasive alternatives for melanoma treatment are a clinical need, and a continued unmet need exists for combinatorial therapies with limited toxicity and/or resistance profiles. Photothermal therapy (PTT) can be used as a non-invasive treatment by delivering targeted nanoparticles and a laser source (typically in the near-infrared range) to the tumor site. We propose to use a biodegradable nanoparticle platform based in polymers to reduce the toxic risks. Our goal is to evaluate the cellularmore »lethality of nanoparticles on melanoma cells as a response to dosimetry using an in vitro model.« less