Digital Commons Network^™

Repurposing Niclosamide For Targeting Pancreatic Cancer By Inhibiting Hh/Gli Non-Canonical Axis Of Gsk3Β, Jyoti B. Kaushal, Rakesh Bhatia, Ranjana K. Kanchan, Pratima Raut, Surya Mallapragada, Quan P. Ly, Surinder K. Batra, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive …

Emerging Role Of Mir-345 And Its Effective Delivery As A Potential Therapeutic Candidate In Pancreatic Cancer And Other Cancers, Nagabhishek Sirpu Natesh, Brianna M. White, Maia M. C. White, Metin Uz, Rakhee Rathnam Kalari Kandy, Surinder K. Batra, Surya K. Mallapragada, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, poor prognosis, and palliative treatments, due to the rapid upregulation of alternative compensatory pathways and desmoplastic reaction. miRNAs, small non-coding RNAs, have been recently identified as key players regulating cancer pathogenesis. Dysregulated miRNAs are associated with molecular pathways involved in tumor development, metastasis, and chemoresistance in PDAC, as well as other cancers. Targeted treatment strategies that alter miRNA levels in cancers have promising potential as therapeutic interventions. miRNA-345 (miR-345) plays a critical role in tumor suppression and is differentially expressed in various cancers, including pancreatic cancer (PC). The underlying …

Disruption Of Fdps/Rac1 Axis Radiosensitizes Pancreatic Ductal Adenocarcinoma By Attenuating Dna Damage Response And Immunosuppressive Signalling, Parthasarathy Seshacharyulu, Sushanta Halder, Rama Krishna Nimmakayala, Satyanarayana Rachagani, Sanjib Chaudhary, Pranita Atri, Ramakanth C. Venkata, Michel M. Ouellette, Joseph Carmicheal, Shailendra K. Gautam, Raghupathy Vengoji, Shuo Wang, Sicong Li, Lynette M. Smith, Geoffrey A. Talmon, Kelsey Klute, Quan P. Ly, Bradley N. Reames, Jean L. Grem, Lyudmyla Berim, James C. Padussis, Sukhwinder Kaur, Sushil Kumar, Moorthy P. Ponnusamy, Maneesh Jain, Chi Lin, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Radiation therapy (RT) has a suboptimal effect in patients with pancreatic ductal adenocarcinoma (PDAC) due to intrinsic and acquired radioresistance (RR). Comprehensive bioinformatics and microarray analysis revealed that cholesterol biosynthesis (CBS) is involved in the RR of PDAC. We now tested the inhibition of the CBS pathway enzyme, farnesyl diphosphate synthase (FDPS), by zoledronic acid (Zol) to enhance radiation and activate immune cells.

METHODS: We investigated the role of FDPS in PDAC RR using the following methods: in vitro cell-based assay, immunohistochemistry, immunofluorescence, immunoblot, cell-based cholesterol assay, RNA sequencing, tumouroids (KPC-murine and PDAC patient-derived), orthotopic models, and PDAC patient's …

Differential Gene Expression-Based Connectivity Mapping Identified Novel Drug Candidate And Improved Temozolomide Efficacy For Glioblastoma, Raghupathy Vengoji, Pranita Atri, Muzafar A. Macha, Parthasarathy Seshacharyulu, Naveenkumar Perumal, Kavita Mallya, Yutong Liu, Lynette M. Smith, Satyanarayana Rachagani, Sidharth Mahapatra, Moorthy P. Ponnusamy, Maneesh Jain, Surinder K. Batra, Nicole Shonka

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Glioblastoma (GBM) has a devastating median survival of only one year. Treatment includes resection, radiation therapy, and temozolomide (TMZ); however, the latter increased median survival by only 2.5 months in the pivotal study. A desperate need remains to find an effective treatment.

METHODS: We used the Connectivity Map (CMap) bioinformatic tool to identify candidates for repurposing based on GBM's specific genetic profile. CMap identified histone deacetylase (HDAC) inhibitors as top candidates. In addition, Gene Expression Profiling Interactive Analysis (GEPIA) identified HDAC1 and HDAC2 as the most upregulated and HDAC11 as the most downregulated HDACs. We selected PCI-24781/abexinostat due to …

Fgdb: Database Of Follicle Stimulating Hormone Glycans, Sushil Kumar Shakyawar, Sanjit Pandey, David J. Harvey, George Bousfield, Chittibabu Guda

Journal Articles: Genetics, Cell Biology & Anatomy

Glycomics, the study of the entire complement of sugars of an organism has received significant attention in the recent past due to the advances made in high throughput mass spectrometry technologies. These analytical advancements have facilitated the characterization of glycans associated with the follicle-stimulating hormones (FSH), which play a central role in the human reproductive system both in males and females utilizing regulating gonadal (testicular and ovarian) functions. The irregularities in FSH activity are also directly linked with osteoporosis. The glycoanalytical studies have been tremendously helpful in understanding the biological roles of FSH. Subsequently, the increasing number of characterized FSH …

The Healers Issue (2021), University Of Montana--Missoula. School Of Journalism

Byline

Taking the Reins: Providing therapeutic horseback riding to Montanans in need -- More than Superstition: A haunted prison fosters connection during COVID-19 -- Public Health: Local healers leave after divisive legislative session -- Misrepresented and Misunderstood: Why media needs to listen to autistics -- Confronting the Past: Recovering from Native American boarding school trauma -- Welcoming Them Home: The return of native species is healing the land of the Aaniiih and Nakoda -- No Place to Stay: The pandemic is pushing people into Montana - and others out -- They didn't bring any houses with them -- As Missoula affordable …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

Transgender Rights & The Eighth Amendment, Jennifer Levi, Kevin M. Barry

Faculty Scholarship

The past decades have witnessed a dramatic shift in the visibility, acceptance, and integration of transgender people across all aspects of culture and the law. The treatment of incarcerated transgender people is no exception. Historically, transgender people have been routinely denied access to medically necessary hormone therapy, surgery, and other gender-affirming procedures; subjected to cross-gender strip searches; and housed according to their birth sex. But these policies and practices have begun to change. State departments of corrections are now providing some, though by no means all, appropriate care to transgender people, culminating in the Ninth Circuit’s historic decision in Edmo …

Erasing Evidence Of Historic Injustice: The Cannabis Criminal Records Expungement Paradox, Julie E. Steiner

Faculty Scholarship

Cannabis prohibition and its subsequent enforcement have yielded an epic societal tragedy. The decision to criminalize cannabis was a paradigm-shifting moment in legal history because it converted lawful medicinal or intoxicant seeking conduct into criminal activity, inviting government intrusion into matters previously self-controlled.

Scholars increasingly recognize that prohibition was built upon a decades-long, false, media-driven narrative that “marijuana” was one of society’s worst menacing enemies. Using overtly racist propaganda, the narrative successfully captured the audience, fomenting public anxiety and unfairly demonizing cannabis and its users. This misinformation campaign ultimately led to its current status as prohibited under the federal Controlled …

Family Law—The Revictimization Of Survivors Of Domestic Violence And Their Children: The Heartbreaking Unintended Consequence Of Separating Children From Their Abused Parent, Jeanne Kaiser, Caroline M. Foley

Faculty Scholarship

Massachusetts law governing child custody recognizes the damaging effect that witnessing domestic violence can have on a child. Accordingly, the law requires courts to give special attention to the effects of domestic violence on a child when determining custody. An unintended consequence of this scrutiny is that parents who have been the victims of domestic violence can lose custody, or even their parental rights, for failing to protect children from witnessing their abuse. This result can be prevented by requiring courts to apply the same level of attention to the effects of domestic violence when removing a child from an …

Gene Selection For Cancer Classification: A New Hybrid Filter-C5.0 Approach For Breast Cancer Risk Prediction, Mohammed Hamim, Ismail El Moudden, Hicham Moutachaouik, Mustapha Hain

Department of Medicine Faculty Publications

Despite the significant progress made in data mining technologies in recent years, breast cancer risk prediction and diagnosis at an early stage using DNA microarray technology still a real challenging task. This challenge comes especially from the high-dimensionality in gene expression data, i.e., an enormous number of genes versus a few tens of subjects (samples). To overcome this problem of data imbalance, a gene selection phase becomes a crucial step for gene expression data analysis. This study proposes a new Decision Tree model-based attributes (genes) selection strategy, which incorporates two stages: fisher-score-based filter technique and the gene selection ability of …

Yimby And Covid-19, Michael Lewyn

Scholarly Works

Discusses whether the COVID-19 pandemic strengthens the case for the pro-housing YIMBY (Yes In My Back Yard) movement.

Racial Disparity In The Timely Treatment Of Non-Small Cell Lung Cancer, P Neroda, Mei-Chin Hsieh, Xiao-Cheng Wu, K Cartmell, R Mayo, Jiande Wu, Chindo Hicks, L Zhang

School of Public Health Faculty Publications

No abstract provided.

Reimagining Schools’ Role Outside The Family Regulation System, Brianna Harvey, Joshua Gupta-Kagan, Christopher Church

Faculty Scholarship

The United States’ family regulation system often begins with well-intentioned professionals making child protection hotline calls, jeopardizing their own ability to work with families and subjecting the families to surveillance. By the system’s own standards, most of this surveillance leads to no meaningful action. Nowhere is this reality more present than in schools. Educational personnel serve as the leading driver of child maltreatment allegations, yet decades worth of data reveal educator reports of maltreatment are the least likely to be screened-in and the least likely to be substantiated or confirmed. In other words, education personnel — whether motivated by genuine …

Times They Are A-Changin': When Tech Employees Revolt!, Anat Alon-Beck

Maryland Law Review

No abstract provided.

A Conceptual Framework For Digital-Asset Securities: Tokens And Coins As Debt And Equity, Yuliya Guseva

Maryland Law Review

No abstract provided.

The Trap Chronicles, Vol. 1, How U.S. Housing Policy Impairs Criminal Justice Reform, Lahny Silva

Maryland Law Review

No abstract provided.

The Natural Gas Paradox: Shutting Down A System Designed To Operate Forever, Heather Payne

Maryland Law Review

No abstract provided.

Force Majeure And The Coronavirus: Exposing The “Foreseeable” Clash Between Force Majeure’S Common Law And Contractual Significance, Robyn S. Lessans

Maryland Law Review

No abstract provided.

Republican National Committee V. Democratic National Committee: Reinterpreting The Court’S Role In Election Law Challenges, Carly L. Brody

Maryland Law Review

No abstract provided.

Allen V. Cooper: Raising The Flag Of Sovereign Immunity In The Shifting Seas Of Copyright, Will R. Gallagher

Maryland Law Review

No abstract provided.

Upgrading Unconscionability: A Common Law Ally For A Digital World, Babette E. Boliek

Maryland Law Review

No abstract provided.

Political Executive Control Of The Administrative State: How Much Is Too Much?, Conor Casey

Maryland Law Review

No abstract provided.

"Revolution" At The Capitol: How Law Hindered The Response To The Events Of January 6, 2021, Jill I. Goldenziel

Maryland Law Review

No abstract provided.

A Third Reconstruction, Rebecca Zietlow

Maryland Law Review

No abstract provided.

The Promise Of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are The Data?, Kimberly Scarsi, Susan Swindells

Journal Articles: Infectious Diseases

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community …

A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells

Journal Articles: Infectious Diseases

During the COVID-19 pandemic, HIV clinics had to transform care delivery for people with HIV (PWH). We developed a multifaceted telehealth implementation strategy and monitored number of out of care patients (OOC), medical visit frequency (MVF), gap in care (GiC) and viral suppression (VS), and compared measures to baseline data. Between April and October 2020, 1559 visits were scheduled; 328 (21%) were missed, and 63 (4%) were new to care. Of the remaining 1168 follow-up visits, 412 (35%) were telehealth visits. As of October 2020, there were 53 patients OOC, MVF was 55% and GiC was 24% compared to 34, …

Gendered Differences In Consent And Brochures For Permanent Birth Control, Caleb Ayers, Arika L. Hoffman, Jenenne A. Geske

EMET Projects

Background

Gendered differences have been documented for many healthcare outcomes. One cause of such differences is gendered differences in language, which has been documented in many fields. The difference in language used to describe permanent birth control to women (tubal ligation) versus men (vasectomy) has not been studied.

Objectives

To analyze consent forms and brochures for female and male permanent sterilization for gendered differences in language.

Methods

A convenience sample of consent forms and brochures was obtained and analyzed for differences in the emphasis on various subject matter.

Results

Physiologic explanations and insurance and/or cost was discussed more in documents …

Effects Of Neuraxial Anesthesia On Post Operative Pain Scores In Children With Osteogenesis Imperfecta, Lauren Greufe, Nick Bohannon, Amy Beethe, Maegen Wallace, Paul Esposito, Jenenne A. Geske, Susan Evans, Jessica Goeller

EMET Projects

No abstract provided.

Frequency Of Aortic Miscannulation During Fluoroscopy-Free Endovascular Navigation, Sruti Prathivadhi-Bhay

EMET Projects

No abstract provided.