Life Sciences Commons^™

Consequences Of Host Life Cycles For Symbiont Genome Evolution, Ashley Elizabeth Dederich

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Aphids are small insects that feed exclusively on plant sap, a notoriously low source of nutrients due to the high sugar content and low amino acid content. To make up for these deficiencies in nutrition, aphids harbor Buchnera aphidicola, a bacterial endosymbiont that resides in a specialized organ called the bacteriome. B. aphidicola provides essential amino acids and vitamins for the aphid in exchange for a safe place to live. Over the course of the symbiosis (established 160 million years ago), B. aphidicola has lost much of its genome, including essential genes for cell envelope synthesis, DNA replication and …

Social Factors Driving Grouping Dynamics In Bighorn Sheep Ewe, Toni Proescholdt

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Understanding and predicting movement is critical for conservation planning and disease risk mitigation, and important environmental drivers of animal movement have received extensive attention in the ecological literature. Social factors surrounding group fission and fusion events also directly affect movement. However, these events are infrequently measured in the wild and rarely linked to underlying mechanisms such as relatedness, agreement in reproductive status, or shared life stage. While some social factors cannot be directly observed in the field, individual animals congregating in groups and moving about a landscape can. In animal societies, groups may merge together in a fusion event, and …

Use Of Protective Lactic Acid Bacteria Adjunct Cultures To Decrease The Incidence Of Gas Defects In Cheddar Cheese, Rhees T. Crompton

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Gas production in cheese making is becoming increasingly prevalent in the dairy industry. This gas is produced by microbes that are naturally found in the cheese, and when they metabolize sugar or other sources of energy, they can produce gas. This gas causes slits and cracks in the cheese, which causes the cheese to be worth less and causes issues during slicing and shredding. There are many microbes that cause unwanted gas in cheese, this research focuses on four know gas producers and five other protective microbes that use the same energy sources or have the ability to inhibit the …

The Management Of Non-Ige-Mediated Allergies In Human Milk-Fed Infants, Sarah Kelly Rowe

Graduate Theses

Background: Non-IgE (immunoglobulin E)-mediated food allergies (FA) present diagnostic and management challenges despite guidelines due to knowledge gaps amongst clinicians. Given that 60% of food protein-induced allergic proctocolitis (FPIAP) cases occur in breast-fed infants, maternal elimination diets are routinely prescribed to manage allergy symptoms. The implications of maternal dietary eliminations extend beyond maternal nutrition to consideration of infant nutrition and feeding skill acquisition.

Methods: A survey-based retrospective, cross-sectional study sought to identify dietary triggers and symptom management techniques practiced by (n=59) lactating mothers of infants with confirmed and suspected cases of non-IgE FA in the United States. Statistical significance was …

Quantitative Dual-Energy Ct Image Guidance For Thermochemical Ablation: In Vivo Results In The Rabbit Vx2 Model, Emily A Thompson, Natalie W Fowlkes, Megan C Jacobsen, Rick R Layman, Erik N K Cressman

Faculty, Staff and Student Publications

PURPOSE: To evaluate the feasibility of using dual-energy computed tomography (CT) and theranostic cesium hydroxide (CsOH) for image guidance of thermochemical ablation (TCA) in a rabbit VX2 tumor model.

MATERIALS AND METHODS: In vivo experiments were performed on New Zealand white rabbits, where VX2 tumor fragments (0.3 mL) were inoculated into the right and left flanks (n = 16 rabbits, 32 tumors). Catheters were placed in the approximate center of 1- to 2-cm diameter tumors under ultrasound guidance. TCA was delivered in 1 of 3 treatment groups: untreated control, 5-M TCA, or 10-M TCA. The TCA base reagent was doped …

Impact Of Biomarker-Matched Therapies On Outcomes In Patients With Sarcoma Enrolled In Early-Phase Clinical Trials (Samba 101), Roberto Carmagnani Pestana, Justin T Moyers, Jason Roszik, Shiraj Sen, David S Hong, Aung Naing, Cynthia E Herzog, Siqing Fu, Sarina A Piha-Paul, Jordi Rodon, Timothy A Yap, Daniel D Karp, Apostolia M Tsimberidou, Shubham Pant, Maria A Zarzour, Ravin Ratan, Vinod Ravi, Robert S Benjamin, Alexander J Lazar, Wei-Lien Wang, Najat Daw, Jonathan B Gill, Douglas J Harrison, Valerae O Lewis, Christina L Roland, Shreyaskumar R Patel, J Andrew Livingston, Neeta Somaiah, Joseph A Ludwig, Anthony P Conley, Nelson Hamerschlak, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah

Faculty, Staff and Student Publications

Purpose: Developing new therapeutics for any of the more than 100 sarcoma subtypes presents a challenge. After progression from standard therapies, patients with sarcoma may be referred for enrollment in early-phase trials. This study aimed to investigate whether enrollment in biomarker-matched early-phase clinical trials leads to better outcomes for patients with advanced sarcoma.

Experimental design: In this retrospective analysis, investigational treatment characteristics and longitudinal survival outcomes were analyzed in patients with biopsy-confirmed sarcoma enrolled in early-phase trials at MD Anderson Cancer Center from May 2006 to July 2021.

Results: Five hundred eighty-seven patients were included [405 soft tissue, 122 bone, …

Oxygen Consumption In Highly Skilled Baseball Pitchers, Jesse Clingman

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study was to describe the physiological demands of highly skilled baseball pitchers during pitching, along with pitch metrics. Three junior college and three professional (n = 6) baseball pitchers participated in this study. Participants completed a graded exercise test (GXT) to volitional exhaustion to determine maximal oxygen consumption (VO2 max) and estimated body fat percentage, height, and body mass were measured on day one of testing. Next, participants faced live batters on a baseball field while wearing a portable metabolic analyzer (Cosmed K5) to measure respiratory gases including oxygen consumption (VO2) and carbon dioxide produced (VCO2) …

Biochemical Characterization Of Fsa1572 From Fervidibacter Sacchari, The First Hyperthermophilic Gh50 With Β-1, 4-Glucanase Activity, Jonathan Covington

UNLV Theses, Dissertations, Professional Papers, and Capstones

The bacterium Fervidibacter sacchari is an aerobic hyperthermophile that catabolizes various polysaccharides and is the only cultivated member of the class Fervidibacteria within the phylum Armatimonadota. Among its glycoside hydrolase (GH) cache is an enzyme from GH family 50 (GH50), an understudied family with only 25 characterized representatives and two known activities from 1,518 predicted members in the Carbohydrate-Active EnZyme (CAZy) Database. Here, we expressed, purified, and functionally characterized an extracellular GH50 from F. sacchari called Fsa1572. Using colorimetric assays, we show it has novel β-1,4-glucanase activity and only weak agarose activity that is typical for GH50 enzymes. The purified …

Long-Range Regulation By The Shigella Virulence Gene Regulator, Virb, Cody Cris

UNLV Theses, Dissertations, Professional Papers, and Capstones

Nucleoid-structuring proteins (NSPs) in bacterial cells can exert gene regulatory effects over great distances on DNA. This contrasts with the traditional view of bacterial transcriptional regulation, where transcription factors bind cis-acting regulatory sites proximal (<250 bp) to promoters to influence gene expression. In Shigella species, the histone-like nucleoid-structuring protein (H-NS) transcriptionally silences many genes on the large (~220 kb) virulence plasmid. During host colonization, however, silencing by H-NS is alleviated by the anti-silencer protein, VirB, which remodels the H-NS:DNA complex. This transcriptional anti-silencing is mediated by VirB:DNA interactions and the modulation of DNA supercoiling, which lead to the up-regulation of virulence genes. VirB is a central regulator of Shigella virulence, but the mechanistic basis for transcriptional regulation is incompletely characterized. Here, I focus on the potential for VirB to regulate transcription from remotely located DNA binding sites. Employing complementary in vivo approaches, I assessed the spatial stringency of the VirB binding site and elucidated how varying cellular VirB levels impacts regulation over different distances. I also evaluated how a molecular roadblock on DNA influences remote regulation by VirB. Additionally, I developed control tools to validate the ability of VirB to spread along DNA, an activity of VirB that putatively drives transcriptional regulation. These data are consistent with transcriptional anti-silencing being driven by VirB spreading along DNA. Overall, these findings highlight how VirB is not a conventional transcriptional regulator and broaden our perspective on transcriptional control in bacteria. Furthermore, this work contributes to our understanding of long-range gene regulatory effects, which are frequently overlooked and poorly characterized in bacteria.

The Influence Of Transcranial Alternating Current Stimulation On Fatigue Resistance, Kayla De Guzman

UNLV Theses, Dissertations, Professional Papers, and Capstones

Fatigue is an exercise-induced reduction in muscle force generating capacity. Several studies have shown that some forms of non-invasive brain stimulation can increase the resistance to fatigue during sustained isometric contractions. The purpose was to determine the influence of transcranial alternating current stimulation (tACS) on the time to task failure (TTF) of a precision grip task in young adults. Twenty-two healthy young men and women participated in the study. The study utilized a randomized, double-blind, SHAM-controlled, within-subjects, crossover design. Each participant completed two experimental sessions (tACS, SHAM) with a 7-day washout period between sessions. Each session involved performance of a …

Desert Spring Prokaryotes And Benthic Macroinvertebrates: Geological And Ecological Controls, Ariel D. Friel

UNLV Theses, Dissertations, Professional Papers, and Capstones

Desert springs are aquatic oases, being considered among the most diverse and imperiled ecosystems on Earth. Despite the ecological significance and threatened status of desert springs, few studies have surveyed the microorganisms in these systems or their interactions with other community members. The primary goal of this dissertation was to describe the major controls influencing the community ecology of prokaryotic and BMI communities in cold- and moderate-temperature desert springs of the southern hydrographic Great Basin. Chapter 1 provides a broad overview of spring ecosystems and of each chapter included in this dissertation. Chapter 2 documents the first-ever, regional-scale survey of …

Effects Of Cations And Dipicolinic Acid On B. Anthracis Spore Physiology And Cytotoxicity, Chandler P. Hassan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Inhalation of Bacillus anthracis spores leads to the most severe form of anthrax. Following phagocytosis by alveolar macrophages, spores germinate inside the phagolysosome. The mechanism used by the newly germinated B. anthracis cells to survive within macrophages is not completely understood.B. anthracis spores contain large concentrations of calcium in complex with dipicolinic acid (Ca-DPA). Upon germination, the cell excretes the large depot of Ca-DPA. DPA is an amphipathic molecule that could act as a buffer and modulate phagolysosome acidification. Intracellular calcium overload can disrupt signaling pathways required for normal macrophage function and trigger cell death. We hypothesized the release of …

Assistance Dog Considerations: A Lecture For Occupational Therapy Students, Kayla Kinney

UNLV Theses, Dissertations, Professional Papers, and Capstones

Assistance dogs can mitigate the effects of an individual’s disability. Occupational therapists consider the whole being when providing interventions through the individual’s meaningful occupations to improve health, well-being, and quality of life. Occupational therapists can make referrals or become a valuable team member for clients who wish to explore assistance dogs as an assistive technology option to improve physical, mental, and psychosocial considerations for increased independence in their clients. Few occupational therapy practitioners are educated about the benefits and disadvantages of the partnership between assistance dog and handler. Therefore, they are unable to adequately recommend assistance dogs for their clients, …

Physiological Effects Of A Traditional Active Warm-Up Versus A Passive Warm-Up During Submaximal Endurance Exercise, Vernice Ollano

UNLV Theses, Dissertations, Professional Papers, and Capstones

The purpose of this study is to investigate physiological responses during a traditional active warm-up and a passive warm-up consisting of wearing heated trousers during a submaximal endurance cycling workout. Participants included 10 cyclists/triathletes (3 females, 7 males; age: 48 ± 13 years old; mass: 157.9 ± 33.8 kg; height: 169.3 ± 8.65 cm; percent body fat: 25.3 ± 8.53 %) of at least 18 years of age who could continuously cycle for at least 120 minutes and had knowledge of their individual FTP. Experimental 1-day testing included a randomized crossover design where participants proceeded with two different protocols: an …

Poop! There It Is! Anti-Germinants And Biological Variables As Modulators Of Clostridioides Difficile Infection (Cdi), Jacqueline Renee Phan

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea. Due to its insidious nature, the Centers for Disease Control and Prevention (CDC) has declared CDI an urgent threat. A key characteristic of C. difficile is its ability to form dormant spores that act as the infectious vehicles for disease. In the gut, spores recognize bile salts to germinate into toxin-producing cells.Dysbiosis of the gut microbiome is a key factor in allowing the C. difficile spores to germinate. Normal gut microbiota naturally protects from CDI. However, biological variables such as diet and sex have been found to modulate to …

Morphologic Comparisons Of Recrystallized And Neocrystallized Fibrous Amphibole Asbestos: Implications For Corresponding Health Risk Potential, Natalie G. Renkes

UNLV Theses, Dissertations, Professional Papers, and Capstones

The presence of naturally-occurring asbestos (NOA) is increasingly concerning for scientists, health and regulatory agencies, and citizens living in impacted areas. It is commonly believed that fibrous amphibole asbestos can only form through neocrystallization. In southern Nevada, NOA occurs as a result of hydrothermal alteration of granitic rock producing fibrous amphibole both as cross-cutting neocrystallized veins and via recrystallization of original magmatic hornblende crystals. Fibers with a greater aspect ratio are known to have increased toxicity. This study measured the maximum length and average width of both neocrystallized and recrystallized fibers to see if the morphologies were similar. Neocrystallized and …

Oral Prevalence Of Akkermancia Muciniphila Among Pediatric And Adult Orthodontic And Non-Orthodontic Patients, Ching Shen

UNLV Theses, Dissertations, Professional Papers, and Capstones

Akkermansia muciniphila (AM) is one of many highly abundant intestinal microbes that influences homeostasis and metabolic disorders and may also play a role in oral disorders. However, there is little evidence regarding the oral prevalence of this organism. Based upon this lack of evidence, the primary goal of this project is to survey an existing saliva repository to determine the overall prevalence of this organism and any associations with demographic or patient characteristics (age, sex, body mass index, race/ethnicity, orthodontic therapy). Using an approved protocol, a total n = 141 pediatric samples from an existing saliva repository were screened using …

Applying Unsupervised Multi-Omic Learning To Identify Patterns Of Human Genomic Regulatory Regions With An Emphasis In Characterizing Hervh Loci., Corinne Sexton

UNLV Theses, Dissertations, Professional Papers, and Capstones

With the increase of diverse genomic data types, machine learning provides an opportunity to integrate several omics datasets into one cohesive annotation. In this dissertation, I apply an unsupervised clustering approach to a novel representation of 3D chromosome conformation data and chromatin mark data. Specifically I use this new method to annotate the regulatory function of human endogenous retrovirus H (HERVH). In chapter 1, I propose a synthesized model of HERVH function as an activating lncRNA based on previously published work. As HERVH and transposable elements in general are repetitive due to their methods of retrotransposition, in chapter 2 I …

The Effects Of Habitat Isolation On Fine-Scale Genetic And Geographic Structure Of Populations Of Two Threatened Endemic Insects In Southern Nevada, Pseudocotalpa Giulianii And Icaricia Shasta Charlestonensis, Kristen Tovar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Assessing the role geographic isolation and ecological specialization have on phylogeographic patterns contributes to our understanding of the evolutionary history of a species and the processes that erode genetic diversity. I used mitochondrial and nuclear genomic sequences to assess whether habitat isolation has shaped the fine-scale patterns of present-day genetic structure and diversity in two threatened insect species endemic to southern Nevada. Pseudocotalpa giulianii (Coleoptera; Scarabaeidae) is a dune obligate scarab beetle endemic to only two small, isolated sand dunes in Nye County, Nevada, with a usable habitat of less than 4.2 km sq that is impacted by on-going degradation. …

Musculoskeletal Injury Concealment In The Reserve Officers’ Training Corps, Joshua D. Wooldridge

UNLV Theses, Dissertations, Professional Papers, and Capstones

INTRODUCTION: Among service members, musculoskeletal injuries threaten military readiness and place a substantial burden on medical and financial resources. While musculoskeletal injuries (MSKIs) are a leading threat to military readiness, service members’ unwillingness to seek care constrains current prevention and surveillance efforts. A growing body of evidence shows US service members conceal a large proportion of injuries, especially in training environments. The Reserve Officers’ Training Corps is a critical training environment for future US military commissioned officers. Reserve Officers’ Training Corps (ROTC) is the largest commissioning source of new officers for the US military. ROTC cadets are college students concurrently …

Emp1+ Tumor Cells Drive Metastatic Relapse, Oscar E Villarreal, Scott Kopetz

Faculty, Staff and Student Publications

No abstract provided.

Molecular Identity Changes Of Tumor-Associated Macrophages And Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening In A Mouse Glioblastoma Model, Yanrong Zhang, Jing Wang, Sara Natasha Ghobadi, Haiyan Zhou, Ai Huang, Marco Gerosa, Qingyi Hou, Olivier Keunen, Anna Golebiewska, Frezghi G Habte, Gerald A Grant, Ramasamy Paulmurugan, Kevin S Lee, Max Wintermark

Faculty, Staff and Student Publications

An orthotopically allografted mouse GL26 glioma model (Ccr2^RFP/wt-Cx3cr1^GFP/wt) was used to evaluate the effect of transient, focal opening of the Blood Brain Barrier (BBB) on the composition of tumor-associated macrophages and microglia (TAMs). BBB Opening was induced by Magnetic Resonance Imaging (MRI)-guided focused ultrasound (MRgFUS) combined with microbubbles. CX3CR1-GFP cells and CCR2-RFP cells in brain tumors were quantified in microscopic images. Tumors in animals treated with a single session of MRgFUS did not show significant changes in cell numbers when compared to tumors in animals not receiving FUS. However, tumors that received two or three sessions …

Prioritizing Clinical Trial Quality Assurance For Photons And Protons: A Failure Modes And Effects Analysis (Fmea) Comparison, Paige A Taylor, Elizabeth Miles, Lone Hoffmann, Sarah M Kelly, Stephen F Kry, Ditte Sloth Møller, Hugo Palmans, Kamal Akbarov, Marianne C Aznar, Enrico Clementel, Coreen Corning, Rachel Effeney, Brendan Healy, Alisha Moore, Mitsuhiro Nakamura, Samir Patel, Maddison Shaw, Markus Stock, Joerg Lehmann, Catharine H Clark

Faculty, Staff and Student Publications

Background and purpose: The Global Clinical Trials RTQA Harmonization Group (GHG) set out to evaluate and prioritize clinical trial quality assurance.

Methods: The GHG compiled a list of radiotherapy quality assurance (QA) tests performed for proton and photon therapy clinical trials. These tests were compared between modalities to assess whether there was a need for different types of assessments per modality. A failure modes and effects analysis (FMEA) was performed to assess the risk of each QA failure.

Results: The risk analysis showed that proton and photon therapy shared four out of five of their highest-risk failures (end-to-end anthropomorphic phantom …

A Protocol For A Cluster Randomized Trial Of Care Delivery Models To Improve The Quality Of Smoking Cessation And Shared Decision Making For Lung Cancer Screening, Lisa M Lowenstein, Ya-Chen Tina Shih, Jennifer Minnix, Maria A Lopez-Olivo, Kristin G Maki, George Kypriotakis, Viola B Leal, Sanjay S Shete, James Fox, Shawn P Nishi, Paul M Cinciripini, Robert J Volk

Faculty, Staff and Student Publications

BACKGROUND: Patients eligible for lung cancer screening (LCS) are those at high risk of lung cancer due to their smoking histories and age. While screening for LCS is effective in lowering lung cancer mortality, primary care providers are challenged to meet beneficiary eligibility for LCS from the Centers for Medicare & Medicaid Services, including a patient counseling and shared decision-making (SDM) visit with the use of patient decision aid(s) prior to screening.

METHODS: We will use an effectiveness-implementation type I hybrid design to: 1) identify effective, scalable smoking cessation counseling and SDM interventions that are consistent with recommendations, can be …

Combining Physics-Based Models With Deep Learning Image Synthesis And Uncertainty In Intraoperative Cone-Beam Ct Of The Brain, Xiaoxuan Zhang, Alejandro Sisniega, Wojciech B Zbijewski, Junghoon Lee, Craig K Jones, Pengwei Wu, Runze Han, Ali Uneri, Prasad Vagdargi, Patrick A Helm, Mark Luciano, William S Anderson, Jeffrey H Siewerdsen

Faculty, Staff and Student Publications

BACKGROUND: Image-guided neurosurgery requires high localization and registration accuracy to enable effective treatment and avoid complications. However, accurate neuronavigation based on preoperative magnetic resonance (MR) or computed tomography (CT) images is challenged by brain deformation occurring during the surgical intervention.

PURPOSE: To facilitate intraoperative visualization of brain tissues and deformable registration with preoperative images, a 3D deep learning (DL) reconstruction framework (termed DL-Recon) was proposed for improved intraoperative cone-beam CT (CBCT) image quality.

METHODS: The DL-Recon framework combines physics-based models with deep learning CT synthesis and leverages uncertainty information to promote robustness to unseen features. A 3D generative adversarial network …

Alendronate Conjugate For Targeted Delivery To Bone-Forming Prostate Cancer, Jossana A Damasco, Guoyu Yu, Ajay Kumar, Joy Perez, Rio Carlo M Lirag, Elizabeth M Whitley, Sue-Hwa Lin, Marites P Melancon

Faculty, Staff and Student Publications

Bone is the primary metastasis site for lethal prostate cancer, often resulting in poor prognosis, crippling pain, and diminished functioning that drastically reduce both quality of life and survivability Uniquely, prostate cancer bone metastasis induces aberrant bone overgrowth, due to an increase of osteoblasts induced by tumor-secreted bone morphogenetic protein 4 (BMP4). Conjugating drugs to substances that target the tumor-induced bone area within the metastatic tumor foci would be a promising strategy for drug delivery. To develop such a strategy, we conjugated a near infrared (NIR) fluorescent probe, the dye Cy5.5, to serve as a surrogate for drugs, with alendronate, …

Phase I Trial Of Autologous Rna-Electroporated Cmet-Directed Car T Cells Administered Intravenously In Patients With Melanoma And Breast Carcinoma, Payal D Shah, Alexander C Huang, Xiaowei Xu, Robert Orlowski, Ravi K Amaravadi, Lynn M Schuchter, Paul Zhang, Julia Tchou, Tina Matlawski, Amanda Cervini, Joanne Shea, Joan Gilmore, Lester Lledo, Karen Dengel, Amy Marshall, E John Wherry, Gerald P Linette, Andrea Brennan, Vanessa Gonzalez, Irina Kulikovskaya, Simon F Lacey, Gabriela Plesa, Carl H June, Robert H Vonderheide, Tara C Mitchell

Faculty, Staff and Student Publications

PURPOSE: Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET.

EXPERIMENTAL DESIGN: Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated.

RESULTS: Mean age was …

Sting Agonist-Loaded Mesoporous Manganese-Silica Nanoparticles For Vaccine Applications, Cheng Xu, Hannah E Dobson, Mengjie Yu, Wang Gong, Xiaoqi Sun, Kyung Soo Park, Andrew Kennedy, Xingwu Zhou, Jin Xu, Yao Xu, Andrew W Tai, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2. MnOx@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnOx@HMSN(CDA) amplified the activation of the STING pathway and enhanced the …

High-Dose Once-Daily Thoracic Radiotherapy In Limited-Stage Small-Cell Lung Cancer: Calgb 30610 (Alliance)/Rtog 0538, Jeffrey Bogart, Xiaofei Wang, Gregory Masters, Junheng Gao, Ritsuko Komaki, Laurie E Gaspar, John Heymach, James Bonner, Charles Kuzma, Saiama Waqar, William Petty, Thomas E Stinchcombe, Jeffrey D Bradley, Everett Vokes

Faculty, Staff and Student Publications

PURPOSE: Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated.

METHODS: This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity …

Long Noncoding Rna 01534 Maintains Cancer Stemness By Downregulating Endoplasmic Reticulum Stress Response In Colorectal Cancer, Momoko Ichihara, Hidekazu Takahashi, Naohiro Nishida, Cristina Ivan, Daisuke Okuzaki, Yuhki Yokoyama, Masahisa Ohtsuka, Norikatsu Miyoshi, Mamoru Uemura, Shinji Tanaka, George Adrian Calin, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi, Hirofumi Yamamoto

Faculty, Staff and Student Publications

Background: Studies have shown that cancer stemness and the endoplasmic reticulum (ER) stress response are inversely regulated in colorectal cancer (CRC), but the mechanism has not been fully clarified. Long noncoding RNAs (lncRNAs) play key roles in cancer progression and metastasis. In this study we investigated lncRNA 01534 (LINC01534) as a possible modulator between cancer stemness and ER stress response.

Methods: In vitro experiments using CRC cell lines were performed to explore a possible role of LINC01534. The expression of LINC01534 in clinical CRC samples was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and in situ hybridization.

Results: Silencing …