Genetic Phenomena Commons^™

Going Circular: History, Present, And Future Of Circrnas In Cancer, Giuseppina Pisignano, David C Michael, Tanvi H Visal, Radu Pirlog, Michael Ladomery, George A Calin

Faculty, Staff and Student Publications

To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their …

Time For Bugs: The Immune Microenvironment And Microbes In Precancer, Mikayla Borthwick Bowen, Beth A Helmink, Jennifer A Wargo, Melinda S Yates

Faculty, Staff and Student Publications

Major advances in our understanding of the tumor immune microenvironment (TIME) in established cancer have been made, including the influence of host-intrinsic (host genomics) and -extrinsic factors (such as diet and the microbiome) on treatment response. Nonetheless, the immune and microbiome milieu across the spectrum of precancerous tissue and early neoplasia is a growing area of interest. There are emerging data describing the contribution of the immune microenvironment and microbiota on benign and premalignant tissues, with opportunities to target these factors in cancer prevention and interception. Throughout this review, we provide rationale for not only the critical need to further …

Exceptional Responses To Selpercatinib In Ret-Fusion Driven Metastatic Pancreatic Cancer, Deepak Bhamidipati, Sireesha Yedururi, Jason Huse, Sri Veda Chinapuvvula, Jie Wu, Vivek Subbiah

Faculty, Staff and Student Publications

No abstract provided.

Ras Gtpases And Interleaflet Coupling In The Plasma Membrane, Junchen Liu, Neha Arora, Yong Zhou

Faculty, Staff and Student Publications

RAS genes are frequently mutated in cancer. The primary signaling compartment of wild-type and constitutively active oncogenic mutant RAS proteins is the inner leaflet of the plasma membrane (PM). Thus, a better understanding of the unique environment of the PM inner leaflet is important to shed further light on RAS function. Over the past few decades, an integrated approach of superresolution imaging, molecular dynamic simulations, and biophysical assays has yielded new insights into the capacity of RAS proteins to sort lipids with specific headgroups and acyl chains, to assemble signaling nanoclusters on the inner PM. RAS proteins also sense and …

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

The Y Of Cancer Sex Differences, Jiexi Li, Ronald A Depinho

Faculty, Staff and Student Publications

No abstract provided.

Cancer Informatics For Cancer Centers: Sharing Ideas On How To Build An Artificial Intelligence-Ready Informatics Ecosystem For Radiation Oncology, Danielle S Bitterman, Michael F Gensheimer, David Jaffray, Daniel A Pryma, Steve B Jiang, Olivier Morin, Jorge Barrios Ginart, Taman Upadhaya, Katherine A Vallis, John M Buatti, Joseph Deasy, H Timothy Hsiao, Caroline Chung, Clifton D Fuller, Emily Greenspan, Kristy Cloyd-Warwick, Samir Courdy, Allen Mao, Jill Barnholtz-Sloan, Umit Topaloglu, Isaac Hands, Ian Maurer, May Terry, Walter J Curran, Quynh-Thu Le, Sorena Nadaf, Warren Kibbe

Faculty, Staff and Student Publications

In August 2022, the Cancer Informatics for Cancer Centers brought together cancer informatics leaders for its biannual symposium, Precision Medicine Applications in Radiation Oncology, co-chaired by Quynh-Thu Le, MD (Stanford University), and Walter J. Curran, MD (GenesisCare). Over the course of 3 days, presenters discussed a range of topics relevant to radiation oncology and the cancer informatics community more broadly, including biomarker development, decision support algorithms, novel imaging tools, theranostics, and artificial intelligence (AI) for the radiotherapy workflow. Since the symposium, there has been an impressive shift in the promise and potential for integration of AI in clinical care, accelerated …

Uncovering The Il-1Β-Pcaf-Nnt Axis: A New Player In Ferroptosis And Tumor Immune Evasion, Qidong Li, Boyi Gan

Faculty, Staff and Student Publications

No abstract provided.

Prognostic Significance Of Trophoblastic Cell Surface Antigen 2 Expression And Pathologic Parameters In Patients With Ampullary Adenocarcinoma, Yujie Zhang, Hua Wang, Michael Overman, Matthew Hg Katz, Huamin Wang

Faculty, Staff and Student Publications

Trophoblastic cell surface antigen 2 (TROP2) has been reported to be up-regulated in several types of carcinomas and is associated with aggressive behavior and poor survival. However, TROP2 expression and its clinical significance in ampullary adenocarcinoma (AA) have not been investigated. We examined TROP2 expression by immunohistochemistry in 112 patients with AAs. The associations of TROP2 expression with clinicopathologic characteristics were evaluated by χ2 analyses or Fisher's exact tests. The associations of TROP2 expression and pathologic parameters with survival were evaluated by the Kaplan-Meier method and univariate and multivariate Cox regression analyses. Eighty-six AAs (76.8%) were positive for TROP2, which …

Phase 2 Trial Of Stereotactic Ablative Radiotherapy For Patients With Primary Renal Cancer, Raquibul Hannan, Mark F Mclaughlin, Laurentiu M Pop, Ivan Pedrosa, Payal Kapur, Aurelie Garant, Chul Ahn, Alana Christie, James Zhu, Tao Wang, Liliana Robles, Deniz Durakoglugil, Solomon Woldu, Vitaly Margulis, Jeffrey Gahan, James Brugarolas, Robert Timmerman, Jeffrey Cadeddu

Faculty, Staff and Student Publications

Background: Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.

Objective: To investigate whether SAbR is effective in the management of primary RCCs.

Design, setting, and participants: Patients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.

Outcome measurements and statistical analysis: The primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 …

Making Waves: Integrating Wastewater Surveillance With Dynamic Modeling To Track And Predict Viral Outbreaks, Tin Phan, Samantha Brozak, Bruce Pell, Jeremiah Oghuan, Anna Gitter, Tao Hu, Ruy M Ribeiro, Ruian Ke, Kristina D Mena, Alan S Perelson, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Wastewater surveillance has proved to be a valuable tool to track the COVID-19 pandemic. However, most studies using wastewater surveillance data revolve around establishing correlations and lead time relative to reported case data. In this perspective, we advocate for the integration of wastewater surveillance data with dynamic within-host and between-host models to better understand, monitor, and predict viral disease outbreaks. Dynamic models overcome emblematic difficulties of using wastewater surveillance data such as establishing the temporal viral shedding profile. Complementarily, wastewater surveillance data bypasses the issues of time lag and underreporting in clinical case report data, thus enhancing the utility and …

Exploring Stakeholders' Perspectives On Implementing Universal Germline Testing For Colorectal Cancer: Findings From A Clinical Practice Survey, Linda Rodgers-Fouche, Sanjeevani Arora, Charité Ricker, Dan Li, Maheen Farooqi, Francesc Balaguer, Mev Dominguez-Valentin, Jose G Guillem, Priyanka Kanth, David Liska, Joshua Melson, Kathryn A Mraz, Brian H Shirts, Eduardo Vilar, Bryson W Katona, Rachel Hodan

Faculty, Staff and Student Publications

Purpose: New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers.

Methods: A cross-sectional survey was sent to 317 active members of CGA-IGC. The survey included sections on demographics, clinical practice specialty, established institutional practices for testing, and questions pertaining to support …

Trans-Pacific Multicenter Collaborative Study Of Minimally Invasive Proximal Versus Total Gastrectomy For Proximal Gastric And Gastroesophageal Junction Cancers, Naruhiko Ikoma, Travis Grotz, Hirofumi Kawakubo, Hyoung-Il Kim, Satoru Matsuda, Yuki Hirata, Atsushi Nakao, Loretta A Williams, Xin Shelley Wang, Tito Mendoza, Xuemei Wang, Brian D Badgwell, Paul F Mansfield, Woo-Jin Hyung, Vivian E Strong, Yuko Kitagawa

Faculty, Staff and Student Publications

Background: The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts …

Outcomes Of Treatment With Neoadjuvant Cemiplimab For Patients With Advanced, Resectable Cutaneous Squamous Cell Carcinoma Of The Head And Neck: Secondary Analysis Of A Phase 2 Clinical Trial, Renata Ferrarotto, Priyadharsini Nagarajan, Jacob M Maronge, Jason M Johnson, David I Rosenthal, Jeffrey N Myers, Neil D Gross

Faculty, Staff and Student Publications

This secondary analysis of a phase 2 clinical trial examines long-term survival for resectable cutaneous squamous cell carcinoma of the head and neck according to pathologic response.

A Review Of Pulmonary Neutrophilia And Insights Into The Key Role Of Neutrophils In Particle-Induced Pathogenesis In The Lung From Animal Studies Of Lunar Dusts And Other Poorly Soluble Dust Particles, Chiu-Wing Lam, Vincent Castranova, Kevin Driscoll, David Warheit, Valerie Ryder, Ye Zhang, Patti Zeidler-Erdely, Robert Hunter, Robert Scully, William Wallace, John James, Brian Crucian, Mayra Nelman, Richard Mccluskey, Donald Gardner, Roger Renne, Roger Mcclellan

Faculty, Staff and Student Publications

The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), …

Inhibition Of Menin, Bcl-2, And Flt3 Combined With A Hypomethylating Agent Cures Npm1/Flt3-Itd/-Tkd Mutant Acute Myeloid Leukemia In A Patient-Derived Xenograft Model, Bing Z Carter, Po Yee Mak, Wenjing Tao, Lauren B Ostermann, Duncan H Mak, Baozhen Ke, Peter Ordentlich, Gerard M Mcgeehan, Michael Andreeff

Faculty, Staff and Student Publications

No abstract provided.

Cobimetinib Plus Vemurafenib In Patients With Solid Tumors With Braf Mutations: Results From The Targeted Agent And Profiling Utilization Registry Study, Funda Meric-Bernstam, Michael Rothe, Pam K Mangat, Elizabeth Garrett-Mayer, Rodolfo Gutierrez, Eugene R Ahn, Timothy L Cannon, Steven Powell, John C Krauss, Christopher M Reynolds, Margaret Von Mehren, Deepti Behl, Carmen J Calfa, Herbert L Duvivier, Henry G Kaplan, Michael B Livingston, Manish R Sharma, Walter J Urba, Gina N Grantham, Dominique C Hinshaw, Abigail Gregory, Susan Halabi, Richard L Schilsky

Faculty, Staff and Student Publications

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported.

Methods: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of …

Important Considerations For Real-World Analysis Of Neurotrophic Tyrosine Receptor Kinase Fusion Cancer And Tropomyosin Receptor Kinase Inhibitors, Marcia S Brose, David S Hong, Alexander Drilon

Faculty, Staff and Student Publications

No abstract provided.

Adagrasib In Advanced Solid Tumors Harboring A Krasg12c Mutation, Tanios S Bekaii-Saab, Rona Yaeger, Alexander I Spira, Meredith S Pelster, Joshua K Sabari, Navid Hafez, Minal Barve, Karen Velastegui, Xiaohong Yan, Aditya Shetty, Hirak Der-Torossian, Shubham Pant

Faculty, Staff and Student Publications

Purpose: Adagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). KRASG12C mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRASG12C mutation.

Methods: In this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C-mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response …

Diversity, Equity, And Inclusion In The Melanoma Research Community, Marie E Portuallo, David Y Lu, Gretchen M Alicea, Joel Bolling, Rebecca Lee, Jennifer Mcquade, Allison Betof Warner, Michael Davies, Ashani Weeraratna, Jessie Villanueva, Vito W Rebecca

Faculty, Staff and Student Publications

The inaugural Diversity and Inclusion in Science Session was held during the 2021 Society for Melanoma Research (SMR) congress. The goal of the session was to discuss diversity, equity, and inclusion in the melanoma research community and strategies to promote the advancement of underrepresented melanoma researchers. An international survey was conducted to assess the diversity, equity, and inclusion (DEI) climate among researchers and clinicians within the Society for Melanoma Research (SMR). The findings suggest there are feelings and experiences of inequity, bias, and harassment within the melanoma community that correlate with one's gender, ethnic/racial group, and/or geographic location. Notably, significant …

Safety, Efficacy, And Pk/Pd Of Vorasidenib In Previously Treated Patients With Midh1/2 Hematologic Malignancies: A Phase 1 Study, Courtney D Dinardo, Stéphane De Botton, Daniel A Pollyea, Richard M Stone, Jessica K Altman, Amir T Fathi, Tharin Limsakun, Min Liang, Sung Choe, Mohammad Hossain, Adriana E Tron, Qian Meng, Stephanie M Kapsalis, Shuchi S Pandya, Eytan M Stein

Faculty, Staff and Student Publications

No abstract provided.

Safety, Tolerability, And Clinical Activity Of Selinexor In Combination With Pembrolizumab In Treatment Of Metastatic Non-Small Cell Lung Cancer, Mehmet Altan, Janet Tu, Denái R Milton, Bulent Yilmaz, Yanyan Tian, Frank V Fossella, Frank E Mott, George R Blumenschein, Bettzy Stephen, Daniel D Karp, Funda Meric-Bernstam, John V Heymach, Aung Naing

Faculty, Staff and Student Publications

Background: In lung cancer, overexpression of nuclear export proteins can result in inactivation of critical tumor suppressor proteins and cell-cycle regulators. Selective suppression of nuclear export proteins has immunomodulatory activities. Here, clinical safety and early efficacy data are presented on the combination of pembrolizumab and an oral selective nuclear export inhibitor, selinexor, for the treatment of metastatic non-small cell lung cancer (mNSCLC).

Methods: The primary objective of this prospective investigator-initiated study was to determine the safety and tolerability of selinexor in combination with pembrolizumab in patients with mNSCLC. Secondary objectives included determination of objective tumor response rate, disease control rate, …

Evolving Trends And Outcomes In Older Patients With Acute Myeloid Leukemia Including Allogeneic Stem Cell Transplantation, Alexandre Bazinet, Hagop Kantarjian, Naszrin Arani, Uday Popat, Alex Bataller, Koji Sasaki, Courtney D Dinardo, Naval Daver, Musa Yilmaz, Hussein A Abbas, Nicholas J Short, Ghayas Issa, Elias Jabbour, Sherry A Pierce, Julianne Chen, Ricky Garcia, Marina Konopleva, Guillermo Garcia-Manero, Amin Alousi, Elizabeth J Shpall, Richard E Champlin, Gautam Borthakur, Farhad Ravandi, Tapan Kadia

Faculty, Staff and Student Publications

Outcomes in older patients with acute myeloid leukemia (AML) have historically been poor. Given advances in low-intensity therapy (LIT) and stem cell transplantation (SCT), we performed a retrospective single-center study to evaluate the contemporary outcomes of this population. We reviewed all patients ≥60 years with newly diagnosed AML between 2012 and 2021 and analyzed treatment and SCT-related trends and outcomes. We identified 1073 patients with a median age of 71 years. Adverse clinical and cytomolecular findings were frequent within this cohort. In total, 16% of patients were treated with intensive chemotherapy, 51% with LIT alone, and 32% with LIT plus …

Worth A Pound Of Cure? Emerging Strategies And Challenges In Cancer Immunoprevention, Saurav D Haldar, Eduardo Vilar, Anirban Maitra, Neeha Zaidi

Faculty, Staff and Student Publications

Cancer immunoprevention applies immunologic approaches such as vaccines to prevent, rather than to treat or cure, cancer. Despite limited success in the treatment of advanced disease, the development of cancer vaccines to intercept premalignant states is a promising area of current research. These efforts are supported by the rationale that vaccination in the premalignant setting is less susceptible to mechanisms of immune evasion compared with established cancer. Prophylactic vaccines have already been developed for a minority of cancers mediated by oncogenic viruses (e.g., hepatitis B and human papillomavirus). Extending the use of preventive vaccines to non-virally driven malignancies remains an …

Feasibility And Clinical Acceptability Of Automation-Assisted 3d Conformal Radiotherapy Planning For Patients With Cervical Cancer In A Resource-Constrained Setting, Sikudhani Muya, Jerry Ndumbalo, Sarah Kutika Nyagabona, Shaid Yusuf, Dong Joo Rhee, Beatrice Paul Mushi, Benjamin Li, Li Zhang, Surbhi Grover, Mary Feng, I-Chow Hsu, Elia Mmbaga, Katherine Van Loon, Laurence Court, Melody Xu

Faculty, Staff and Student Publications

Purpose: The Ocean Road Cancer Institute (ORCI) in Tanzania began offering 3D conformal radiation therapy (3DCRT) in 2018. Steep learning curves, high patient volume, and a limited workforce resulted in long radiation therapy (RT) planning workflows. We aimed to establish the feasibility of implementing an automation-assisted cervical cancer 3DCRT planning system.

Materials and methods: We performed chart abstractions on 30 patients with cervical cancer treated with 3DCRT at ORCI. The Radiation Planning Assistant (RPA) generated a new automated set of contours and plans on the basis of anonymized computed tomography images. Each were assessed for edit time requirements, dose-volume safety …

Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication In Infected Patients With Solid Tumors, Marcel Yibirin, Khalis Mustafayev, Jeff Hosry, Pooja Pundhir, Joseph Klingen, Eduardo Yepez Guevara, Bruno P Granwehr, Ahmed Kaseb, Aung Naing, Sapna Patel, Amishi Y Shah, Ferdinandos Skoulidis, Hussein A Tawbi, Lan Wang, Ethan Miller, Hao Chi Zhang, Amado Zurita-Saavedra, Harrys A Torres

Faculty, Staff and Student Publications

Introduction: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety.

Methods: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI.

Results: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men …

Autotaxin Suppresses Cytotoxic T Cells Via Lpar5 To Promote Anti-Pd-1 Resistance In Non-Small Cell Lung Cancer, Jessica M Konen, B Leticia Rodriguez, Haoyi Wu, Jared J Fradette, Laura Gibson, Lixia Diao, Jing Wang, Stephanie Schmidt, Ignacio I Wistuba, Jianjun Zhang, Don L Gibbons

Faculty, Staff and Student Publications

Non-small cell lung cancers that harbor concurrent KRAS and TP53 (KP) mutations are immunologically warm tumors with partial responsiveness to anti-PD-(L)1 blockade; however, most patients observe little or no durable clinical benefit. To identify novel tumor-driven resistance mechanisms, we developed a panel of KP murine lung cancer models with intrinsic resistance to anti-PD-1 and queried differential gene expression between these tumors and anti-PD-1-sensitive tumors. We found that the enzyme autotaxin (ATX), and the metabolite it produces, lysophosphatidic acid (LPA), were significantly upregulated in resistant tumors and that ATX directly modulated antitumor immunity, with its expression negatively correlating with total and …

Information-Seeking Preferences In Diverse Patients Receiving A Genetic Testing Result In The Clinical Sequencing Evidence-Generating Research (Cser) Study, Anne Slavotinek, Hannah Prasad, Simon Outram, Sarah Scollon, Shannon Rego, Tiffany Yip, Hannah Hoban, Kate M Foreman, Whitley Kelley, Candice Finnila, Jonathan Berg, Priyanka Murali, Katherine E Bonini, Lisa J Martin, Adam Hott

Faculty, Staff and Students Publications

Purpose: Accurate and understandable information after genetic testing is critical for patients, family members, and professionals alike.

Methods: As part of a cross-site study from the Clinical Sequencing Evidence-Generating Research consortium, we investigated the information-seeking practices among patients and family members at 5 to 7 months after genetic testing results disclosure, assessing the perceived utility of a variety of information sources, such as family and friends, health care providers, support groups, and the internet.

Results: We found that individuals placed a high value on information obtained from genetics professionals and health care workers, independent of genetic testing result case classifications …

Epigenome-Wide Association Study Using Peripheral Blood Leukocytes Identifies Genomic Regions Associated With Periodontal Disease And Edentulism In The Atherosclerosis Risk In Communities Study, Naisi Zhao, Flavia Teles, Jiayun Lu, Devin C Koestler, James Beck, Eric Boerwinkle, Jan Bressler, Karl T Kelsey, Elizabeth A Platz, Dominique S Michaud

Faculty, Staff and Student Publications

AIM: To investigate individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood.

MATERIALS AND METHODS: We included 1077 African American and 457 European American participants of the Atherosclerosis Risk in Communities (ARIC) study who had completed a dental examination or reported being edentulous at Visit 4 and had available data on DNA methylation from Visit 2 or 3. DNA methylation levels were compared by periodontal disease severity and edentulism through discovery analyses and subsequent testing of individual CpGs.

RESULTS: Our discovery analysis replicated findings from a previous study reporting a region in gene ZFP57 (6p22.1) that …

Oral Delivery Of Rnai For Cancer Therapy, Humayra Afrin, Renu Geetha Bai, Raj Kumar, Sheikh Shafin Ahmad, Sandeep K Agarwal, Md Nurunnabi

Faculty, Staff and Students Publications

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very …