Neoplasms Commons^™

Neutrophil Elastase Remodels Mammary Tumors To Facilitate Lung Metastasis, Amriti R Lulla, Said Akli, Cansu Karakas, Joseph A Caruso, Lucas D Warma, Natalie W Fowlkes, Xiayu Rao, Jing Wang, Kelly K Hunt, Stephanie S Watowich, Khandan Keyomarsi

Faculty, Staff and Student Publications

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways …

Early Screening Of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis Of Nanoscale Chromatin Modifications, Andrew Chang, Sravya Prabhala, Ali Daneshkhah, Jianan Lin, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity …

Prediction Of Cancer Incidence And Mortality In Korea, 2024, Kyu-Won Jung, Mee Joo Kang, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Jeong-Eun Kim, Hyun-Joo Kong, Jeong-Soo Im, Hong Gwan Seo

Faculty, Staff and Student Publications

PURPOSE: This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea's current cancer burden.

MATERIALS AND METHODS: Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which …

Randomized Phase 2 Trial Of Tremelimumab And Durvalumab In Combination Versus Sequentially In Recurrent Platinum-Resistant Ovarian Cancer, Emily M Hinchcliff, Anne Knisely, Naomi Adjei, Bryan Fellman, Ying Yuan, Ami Patel, Cai Xu, Shannon N Westin, Anil K Sood, Pamela T Soliman, Aaron Shafer, Nicole D Fleming, David M Gershenson, Raghunandan Vikram, Tharakeswara Bathala, David Vining, Dhakshina M Ganeshan, Karen H Lu, Charlotte C Sun, Larissa A Meyer, Amir A Jazaeri

Faculty, Staff and Student Publications

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end …

The Remission Status Of Aml Patients After Allo-Hct Is Associated With A Distinct Single-Cell Bone Marrow T-Cell Signature, Anna Mathioudaki, Xizhe Wang, David Sedloev, Richard Huth, Aryan Kamal, Michael Hundemer, Yi Liu, Spyridoula Vasileiou, Premal Lulla, Carsten Müller-Tidow, Peter Dreger, Thomas Luft, Tim Sauer, Michael Schmitt, Judith B Zaugg, Caroline Pabst

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in …

Development Of Solitary Keratoacanthoma From A Cutaneous Wart, Joshua M. Ninan, Veronica Salazar

Research Symposium

Background: Common cutaneous warts, referred to in medicine as verrucae vulgaris, are proliferative lesions caused by human papillomavirus. These lesions are mostly benign and usually resolve without incident, except in the case of the patient mentioned in this report. Our patient developed a solitary keratoacanthoma, currently accepted as a clinical variant of squamous cell carcinoma, as a result of several risk factors and traumatic exposure. The current literature does not have an established association of HPV with solitary keratoacanthomas. This case report explores the presentation and pathogenesis of solitary keratoacanthomas within the setting of HPV.

Case Presentation: 48-year-old Caucasian female …

Deep Learning Approaches For Cancer Prognosis Prediction Using Histopathological, Omics, And Clinical Data, Shuai Jiang

Dartmouth College Ph.D Dissertations

Accurate prediction of patient outcomes is crucial for shared clinical decision-making, treatment planning, and patients' psychological adjustment. Histopathological features of cancer, including tumor size, lymph node involvement, and metastasis, are commonly incorporated into survival prediction models, underscoring the prognostic value of whole slide images (WSIs). Concurrently, studies have highlighted the significance of omics data, such as transcriptomics, in providing valuable insights into cancer prognosis.

The emerging deep learning methods have brought new opportunities in biomedical informatics. Despite a growing body of studies on the application of deep learning methods for predicting prognosis using WSIs, the results are varied, primarily due …

Apparent Diffusion Coefficient Values Predict Response To Brachytherapy In Bulky Cervical Cancer, Elizabeth E Dong, Junqian Xu, Joo-Won Kim, Jason Bryan, Jewel Appleton, Daniel A Hamstra, Michelle S Ludwig, Alexander N Hanania

Faculty, Staff and Students Publications

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer.

METHODS: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of …

Hippo Cooperates With P53 To Maintain Foregut Homeostasis And Suppress The Malignant Transformation Of Foregut Basal Progenitor Cells, Yu Jiang, Haidi Huang, Jiangying Liu, Dan Luo, Rongzi Mu, Jianghong Yuan, Jihong Lin, Qiyue Chen, Wufan Tao, Ling Yang, Man Zhang, Pingping Zhang, Fengqin Fang, Jianming Xu, Qingqiu Gong, Zhiping Xie, Yongchun Zhang

Faculty, Staff and Students Publications

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of

The Effects Of Curcumin On Erα, P53, And P21 In The Mcf-7 Breast Cancer Cell Line, Samantha E. Pfiffner, Mia Morse, Erin Hallman, Kaylin Whittaker, Aisha Zanib, Sumi Dinda Ph.D.

Medical Student Research Symposium

Curcumin is a golden-yellow flavonoid compound derived from the turmeric plant root that has been used in Chinese and Indian medicine for centuries. Curcumin has been shown to have antioxidant and anti-inflammatory properties, and because of this, has been gaining traction in the field of cancer research. Breast cancer is the most commonly diagnosed cancer in women, and is the second leading cause of cancer death in women, next to lung cancer. Because of the prevalence and mortality of breast cancer, possible therapeutics must be investigated. Due to the beneficial properties of curcumin and pervasiveness of breast cancer, we have …

Wnt5b As A Therapeutic Target For Osteosarcoma Stemness, Metastasis, And Chemoresistance, Rachel S. Perkins

Alternative Theses and Dissertations (AETDs)

Osteosarcoma is a pediatric bone cancer that has no targeted therapy and has had no treatment advances for the last three decades. Osteosarcoma frequently metastasizes to the lungs and is highly chemotherapy resistant, reducing patient survival with metastatic disease to 20% after 5 years. New therapies targeted to metastasis and drug resistance in osteosarcoma are essential to improving patient outcomes.

Osteosarcoma is a pediatric bone cancer that has no targeted therapy and has had no treatment advances for the last three decades. Osteosarcoma frequently metastasizes to the lungs and is highly chemotherapy resistant, reducing patient survival with metastatic disease to …

Incidental Ring-Hyperenhancing Liver Micronodules At Ct Hepatic Arteriography-Guided Percutaneous Thermal Ablation Of Colorectal Liver Metastases, Jessica Albuquerque, Yuan-Mao Lin, Iwan Paolucci, Caleb S O'Connor, Ching-Wei Tzeng, Jean-Nicolas Vauthey, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

CT during hepatic arteriography (CTHA) is a highly sensitive imaging method for detecting colorectal liver metastases (CLMs), which supports its use during percutaneous thermal liver ablation. In contrast to its high sensitivity, its specificity for incidental small CLMs not detected at preablation cross-sectional imaging is believed to be low given the absence of specific imaging signatures and the common presence of pseudolesions. In this retrospective study of 22 patients (mean age, 55 years ± 10.6 [SD]; 63.6% male, 36.4% female) with CLMs undergoing CTHA-guided microwave percutaneous thermal ablation between November 2017 and October 2022, the authors provided a definition of …

Trps1 Expression In Non-Melanocytic Cutaneous Neoplasms: An Immunohistochemical Analysis Of 200 Cases, Yi A Liu, Phyu P Aung, Yunyi Wang, Jing Ning, Priyadharsini Nagarajan, Jonathan L Curry, Carlos A Torres-Cabala, Doina Ivan, Victor G Prieto, Qingqing Ding, Woo Cheal Cho

Faculty, Staff and Student Publications

BACKGROUND: Although trichorhinophalangeal syndrome type 1 (TRPS1) was initially thought to be highly sensitive and specific for carcinomas and mesenchymal tumors of mammary origin, more recent data suggest its expression is not limited to breast neoplasms but also can be seen in other cutaneous neoplasms, such as extramammary Paget disease and squamous cell carcinoma (SCC) in situ.

METHODS: Two-hundred cases of non-melanocytic cutaneous neoplasm, including basal cell carcinomas (BCCs) (n = 41), SCCs (n = 35), Merkel cell carcinomas (MCCs) (n = 25), and adnexal neoplasms (n = 99), were tested for TRPS1 expression using a monoclonal anti- TRPS1 rabbit …

Safety, Efficacy And Determinants Of Response Of Allogeneic Cd19-Specific Car-Nk Cells In Cd19+ B Cell Tumors: A Phase 1/2 Trial, David Marin, Ye Li, Rafet Basar, Hind Rafei, May Daher, Jinzhuang Dou, Vakul Mohanty, Merve Dede, Yago Nieto, Nadima Uprety, Sunil Acharya, Enli Liu, Jeffrey Wilson, Pinaki Banerjee, Homer A Macapinlac, Christina Ganesh, Peter F Thall, Roland Bassett, Mariam Ammari, Sheetal Rao, Kai Cao, Mayra Shanley, Mecit Kaplan, Chitra Hosing, Partow Kebriaei, Loretta J Nastoupil, Christopher R Flowers, Sadie Mae Moseley, Paul Lin, Sonny Ang, Uday R Popat, Muzaffar H Qazilbash, Richard E Champlin, Ken Chen, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were …

Case Report: Contralateral Progression Of A Vestibular Schwannoma After Resection In A Patient With Neurofibromatosis Type 2, Ihika Rampalli, Collin William English, Tyler Lazaro, Benjamin Daniel Lovin, Sungho Lee, Andrew Tsao Huang, Ali Jalali, Kathleen Kelly Gallagher, Jacob J Mandel, Alex Daniel Sweeney, Akash J Patel

Faculty, Staff and Students Publications

BACKGROUND AND IMPORTANCE: Bilateral vestibular schwannomas (VS) are a distinctive feature of neurofibromatosis type 2 (NF2) that result in a serious reduction in the quality of life for patients. The growth rates of these schwannomas are variable, and the early detection of increased growth is fundamental for improving outcomes.

CLINICAL PRESENTATION: A 17-year-old man with NF2 and bilateral VS presented with complete right facial paralysis and sudden right hearing loss less than 1 month after resection of a left VS. Imaging revealed rapid growth of the right VS with intratumoral hemorrhage, and the patient underwent urgent surgical resection with some …

Endocrine-Sensitive Disease Rate In Postmenopausal Patients With Estrogen Receptor-Rich/Erbb2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, Or Their Combination: A Phase 3 Randomized Clinical Trial, Cynthia X Ma, Vera J Suman, Souzan Sanati, Kiran Vij, Meenakshi Anurag, A Marilyn Leitch, Gary W Unzeitig, Jeremy Hoog, Aranzazu Fernandez-Martinez, Cheng Fan, Richard A Gibbs, Mark A Watson, Travis J Dockter, Olwen Hahn, Joseph M Guenther, Abigail Caudle, Erika Crouch, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Mothaffar F Rimawi, Anna Weiss, Eric P Winer, Kelly K Hunt, Charles M Perou, Matthew J Ellis, Ann H Partridge, Lisa A Carey

Faculty, Staff and Students Publications

IMPORTANCE: Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested in early-stage disease.

OBJECTIVE: To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone.

DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or …

Gamma Delta T Cells In Acute Myeloid Leukemia: Biology And Emerging Therapeutic Strategies, Adishwar Rao, Akriti Agrawal, Gautam Borthakur, Venkata Lokesh Battula, Abhishek Maiti

Faculty, Staff and Student Publications

γδ T cells play an important role in disease control in acute myeloid leukemia (AML) and have become an emerging area of therapeutic interest. These cells represent a minor population of T lymphocytes with intrinsic abilities to recognize antigens in a major histocompatibility complex-independent manner and functionally straddle the innate and adaptive immunity interface. AML shows high expression of phosphoantigens and UL-16 binding proteins that activate the Vδ2 and Vδ1 subtypes of γδ T cells, respectively, leading to γδ T cell-mediated cytotoxicity. Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of …

Mortality After Major Cardiovascular Events In Survivors Of Childhood Cancer, Wendy Bottinor, Cindy Im, David R Doody, Saro H Armenian, Alexander Arynchyn, Borah Hong, Rebecca M Howell, David R Jacobs, Kirsten K Ness, Kevin C Oeffinger, Alexander P Reiner, Gregory T Armstrong, Yutaka Yasui, Eric J Chow

Faculty, Staff and Student Publications

Background: Adult survivors of childhood cancer are at risk for cardiovascular events.

Objectives: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations.

Methods: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical …

Radio-Histopathological Presentation And Multidisciplinary Treatment Of Adolescent Paratesticular Rhabdomyosarcoma: A Case Report, Troy Nguyen, Joseph Hatem, Abhijit Datir, Joel Thompson

Advances in Clinical Medical Research and Healthcare Delivery

Paratesticular rhabdomyosarcoma (PRMS) is a rare condition predominantly affecting the pediatric and adolescent population. In this case report, we discuss a 17-year-old male with a slow-growing, painless scrotal mass, ultimately diagnosed as embryonal PRMS — the most common and favorable rhabdomyosarcoma subtype. The report underscores the typical clinico-radiological presentation of PRMS and the pivotal part of histopathological evaluation in establishing a definitive diagnosis. Multidisciplinary intervention including surgery and chemoradiotherapy resulted in total remission. Therefore, this report underlines the significance of prompt diagnosis and comprehensive management in ensuring a favorable prognosis of PRMS.

Rapid Anti-Myeloma Activity By T Cells Expressing An Anti-Bcma Car With A Human Heavy-Chain-Only Antigen-Binding Domain, Lekha Mikkilineni, Danielle A Natrakul, Norris Lam, Elisabet E Manasanch, Jennifer Mann, Katherine A Weissler, Nathan Wong, Jennifer N Brudno, Stephanie L Goff, James C Yang, Micaela Ganaden, Rashmika Patel, Zhili Zheng, Jared J Gartner, Kathryn R Martin, Hao-Wei Wang, Constance M Yuan, Tyler Lowe, Irina Maric, Lipei Shao, Ping Jin, David F Stroncek, Steven L Highfill, Steven A Rosenberg, James N Kochenderfer

Faculty, Staff and Student Publications

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater …

Cocaine Use And Head And Neck Cancer Risk: A Pooled Analysis In The International Head And Neck Cancer Epidemiology Consortium, Mingyan Zhang, Chu Chen, Guojun Li, Alzina Koric, Yuan-Chin Amy Lee, Hal Morgenstern, Stephen M Schwartz, Erich M Sturgis, Paolo Boffetta, Mia Hashibe, Zuo-Feng Zhang

Faculty, Staff and Students Publications

BACKGROUND: Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC).

METHODS: The analyses were conducted by pooling data from three case-control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face-to-face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models.

RESULTS: Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC …

Timely Delivery Of Port For Head And Neck Squamous Cell Carcinoma In A County Hospital, Ana Maria Rosas Herrera, Angela D Haskins, Alexander N Hanania, Pavan M Jhaveri, Christina H Chapman, Quillan Huang, David J Hernandez

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway.

METHODS: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days …

Delays Starting Postoperative Radiotherapy Among Head And Neck Cancer Patients: A Systematic Review And Meta-Analysis, Kelsey A Duckett, Mohamed Faisal Kassir, Shaun A Nguyen, Emily A Brennan, Bhishamjit S Chera, Katherine R Sterba, Chanita Hughes Halbert, Elizabeth G Hill, Jessica Mccay, Sidharth V Puram, Vlad C Sandulache, Russel Kahmke, Salma Ramadan, Brian Nussenbaum, Anthony J Alberg, Evan M Graboyes

Faculty, Staff and Students Publications

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks (42 days) of surgery is the first and only Commission on Cancer (CoC) approved quality metric for head and neck squamous cell carcinoma (HNSCC). No study has systematically reviewed nor synthesized the literature to establish national benchmarks for delays in starting PORT.

DATA SOURCES: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed a systematic review of PubMed, Scopus, and CINAHL.

REVIEW METHODS: Studies that described time-to-PORT or PORT delays in patients with HNSCC treated in the United States after 2003 were included. Meta-analysis of proportions and continuous measures …

Quality Assurance For Stereotactic Body Radiation Therapy For Gynecologic Malignancies, Samuel N Andersen, Mark D Bonnen, Michelle S Ludwig, Shraddha M Dalwadi

Faculty, Staff and Students Publications

The use of stereotactic body radiation therapy (SBRT) is not well studied or reported in the treatment of gynecologic malignancies, despite its success in the definitive management of other cancer sites. This report describes a rigorous quality assurance process for patients to undergo dose escalation to the pelvis via stereotactic photon beam irradiation. Patients who receive SBRT must be ineligible for conventional brachytherapy boost and undergo comprehensive informed consent. Fiducial placement, bowel prep, Foley catheter placement with standardized bladder filling, computerized tomography (CT) simulation with whole-body immobilization, magnetic resonance imaging (MRI)-assisted target delineation, planning aims based on the established brachytherapy …

Reconstitution Of Human Pdac Using Primary Cells Reveals Oncogenic Transcriptomic Features At Tumor Onset, Yi Xu, Michael H Nipper, Angel A Dominguez, Zhenqing Ye, Naoki Akanuma, Kevin Lopez, Janice J Deng, Destiny Arenas, Ava Sanchez, Francis E Sharkey, Colin M Court, Aatur D Singhi, Huamin Wang, Martin E Fernandez-Zapico, Lu-Zhe Sun, Siyuan Zheng, Yidong Chen, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations. The acinar organoids undergo dramatic transcriptional alterations but maintain a recognizable DNA methylation signature. The transcriptomes of acinar organoids are similar to those of disease-specific cell populations. Oncogenic KRAS alone do not transform acinar organoids. However, acinar organoids can form PDAC in vivo after acquiring the …

Simultaneous Detection Of Helicobacter Pylori Infection Comparing Between White Light And Image-Enhanced Endoscopy, Boonyaorn Chatrangsun, Natsuda Aumpan, Bubpha Pornthisarn, Soonthorn Chonprasertsuk, Sith Siramolpiwat, Patommatat Bhanthumkomol, Pongjarat Nunanan, Navapan Issariyakulkarn, Varocha Mahachai, Yoshio Yamaoka, Ratha-Korn Vilaichone

Faculty, Staff and Students Publications

BACKGROUND: Helicobacter pylori (H. pylori) is associated with gastric cancer. Early and accurate diagnosis of H. pylori infection can reduce risk of gastric cancer. Conventional white light imaging (WLI) and image-enhanced endoscopic (IEE) techniques such as narrow-band imaging (NBI), linked color imaging (LCI) and blue laser imaging (BLI) plays pivotal role in H. pylori diagnosis. This study aimed to determine diagnostic performance of real-time endoscopy between WLI and other IEE techniques for diagnosis of H. pylori infection.

METHODS: This prospective study compared endoscopic images by gastroscopy using WLI and IEE techniques (LCI, Magnifying-BLI, and Magnifying-NBI) at Thammasat University Hospital, Thailand …

Non-Canonical Hedgehog Signaling Mediates Profibrotic Hematopoiesis-Stroma Crosstalk In Myeloproliferative Neoplasms, Jessica E Pritchard, Juliette E Pearce, Inge A M Snoeren, Stijn N R Fuchs, Katrin Götz, Fabian Peisker, Silke Wagner, Adam Benabid, Niklas Lutterbach, Vanessa Klöker, James S Nagai, Monica T Hannani, Anna K Galyga, Ellen Sistemich, Bella Banjanin, Niclas Flosdorf, Eric Bindels, Kathrin Olschok, Katharina Biaesch, Nicolas Chatain, Neha Bhagwat, Andrew Dunbar, Rita Sarkis, Olaia Naveiras, Marie-Luise Berres, Steffen Koschmieder, Ross L Levine, Ivan G Costa, Hélène F E Gleitz, Rafael Kramann, Rebekka K Schneider

Faculty, Staff and Student Publications

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs. We show that Gli1 protein levels in patient peripheral blood mononuclear cells (PBMCs) mark fibrotic progression and that, in murine MPN models, absence of hematopoietic Gli1, but not Gli2 or Smo, significantly reduces MPN phenotype and fibrosis, indicating that GLI1 in the MPN clone can be activated in a non-canonical fashion. Additionally, we establish that hematopoietic Gli1 has a …

Lung Cancer In Ever- And Never-Smokers: Findings From Multi-Population Gwas Studies, Yafang Li, Xiangjun Xiao, Jianrong Li, Younghun Han, Chao Cheng, Gail F. Fernandes, Shannon E. Slewitzke, Susan M. Rosenberg, Meng Zhu, Jinyoung Byun, Yohan Bossé, James D. Mckay, Demetrios Albanes, Stephan Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, Maria T. Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C. Christiani, Gad Rennert, Susanne M. Arnold, Gary E. Goodman, John K. Field, Diptasri Mandal, Et Al

School of Graduate Studies Faculty Publications

BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including eQTL colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. RESULTS: Five novel independent loci, GABRA4, inter-genic region 12q24.33, LRRC4C, LINC01088, …

The Complex Protein Analysis Of Purified Extracellular Vesicles In The Study Of Colorectal Cancer, Renee Boone, Cecilia Osthoff

Science University Research Symposium (SURS)

Proteomics, the study of complex protein mixtures in which liquid chromatography-mass spectrometry (LC-MS) is used to analyze peptide sequences, is commonly utilized to study the double membrane, cell-derived vesicles known as exosomes. Exosomes are double membrane, cell-derived vesicles that contain cell components such as DNA, lipids, and proteins. They function to transport proteins and cellular materials between cells and are involved in the progression and metastasis of cancer. The impact of these extracellular vesicles on cancer spread can be analyzed using proteomics, through the purification of the proteins isolated from the vesicles. The purpose of our research is to analyze …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …