Life Sciences Commons^™

The Pharmaceutical Applications Of Poisonous Compounds Found In Datura Stramonium, Ruby M. Raffaldt

Senior Theses

Datura stramonium is a plant that is known for its toxicity. However, a facet of this plant’s noxious chemicals, namely its tropane alkaloids, can be used medicinally. The aim of this paper was to compile knowledge on the botanical, chemical, and medicinal properties of Datura stramonium L with a focus on atropine, scopolamine, and anisodamine; three tropane alkaloid compounds with the ability to be both a poison and a medicine. Information was compiled using pre-existing studies, articles, and literature reviews on D. stramonium. For each of the three alkaloids, their biosynthetic pathways, targets, administration, distribution, metabolism, and excretion were discussed. …

Silver Nanoparticles And Vanillin Can Inhibit Collagenase Activities Of Serratia Marcescens, Elaine Vanterpool, Mya St. Louis, Josel Bryant, Kennedi Ewan, Taylor Hall, Leah Marcelle, Mayah Seal

Student Posters

Serratia marcescens is a gram-negative, disease-causing agent that belongs to the Enterobacteriaceae family. This rod-shaped microbe causes many infectious diseases such as urinary and respiratory infections, wound infections, and peritonitis, which can result in fatal bacteremia. Collagenase is an enzyme that breaks down collagen, while also playing a key role in the extracellular matrix. Collagenase uses zinc to operate that helps it break down the peptide bonds in collagen. Testing Agents ❖ Metronidazole is an antimicrobial drug used to treat infections caused by different anaerobic bacteria, such as infections in the blood, liver, bones, joints, and meninges. ❖ Vanillin is …

Silver Nanoparticles And Natural Compounds Can Modulate Proteolytic Activities Of Escherichia Coli, Elaine Vanterpool, Simone Chotan, Wendolyn Johnson, Emilee Duany, Antonio Ward

Student Posters

Investigating the impact of antibacterial agents on Escherichia coli (E. coli) protease activity is vital for advancing new approaches to combat bacterial infections. Proteases are crucial enzymes in bacterial physiology that contribute to immune system evasion, biofilm development, and host tissue degradation. Due to these enzymes being directly involved in E. coli virulence, understanding how antibacterial compounds affect protease function may lead to innovative treatment strategies. E. coli is a gram-negative, facultatively anaerobic bacterium that exists both as a harmless intestinal commensal and a significant human pathogen. Many lives have been negatively affected by severe E. coli infections in the …

Analyzing The Inhibition Of Chemical Compounds On Protease In P. Aeruginosa, Elaine Vanterpool, Micah Andrews, Marielle Cooper, Mitspah Eshette, Anaya Moodie-Lee, Jayda Russell, Jordon Vanterpool

Student Posters

Pseudomonas aeruginosa is a gram-negative, bacillus-shaped opportunistic pathogen, notorious for invading immunocompromised individual leading to secondary infections. These opportunistic microbes typically are implicated mild to more severe infections including burn or wound infections to more serious systemic infections. The bacterium Ps. aeruginosa utilizes a variety of virulence factors to enhance the pathogenicity of the organism. Virulence factors secreted by Ps. aeruginosa include its pili, adhesins, capsule, exotoxin A, and lipopolysaccharide (LPS). The proteases produced by Ps. aeruginosa are powerful virulence factors that can lead to tissue destruction and immune invasion. It is imperative that we find ways of regulating the …

Improving Biocompatibility And Structural Integrity Of Decellularized Biomaterials, Elaine Vanterpool, Jayden Vanterpool, Ayanna Liburd, Andrew Mcintosh, Cayden Pyform, Cameron Scott, Jea Joseph Msie

Student Posters

Venous grafting using synthetic and biomaterials has been one of the forefront issues of the scientific community. For years, in vitro experimentation of both bio and synthetic materials has been carried out with the hope of treating issues like chronic venous insufficiency, heart attacks, artery blockage, etc. Within these issues, there has been much success. Numerous cases have made it to clinical trials with grafts lasting as long as two years within the patient. Nonetheless, some common and persistent issues occur within all the cases observed. Despite extensive experimentation and development of the most prestigious technology, thrombosis, negative immune response, …

Using Secreted Biomarkers In The Development Of The Detection Of Advanced Cancer Screening System, Elaine Vanterpool, Jaydan Vanterpool, Jordon Vanterpool, Robert Lister, Shania Swain, Enock Ngoga, Jovaughn Redley, Imani Shields, Dalen Jones, Santiago Moreno, Ronnie Nichalson, Jea Joseph Msie

Student Posters

As of 2020, there were an estimated 19.3 million new cancer cases and almost 10 million cancer deaths. Among the different types of cancers in the world, the most prevalent cancer, lung cancer, accounted for 23% of all cancer deaths (CDC) and has been relatively steady since 1999. However, by using Detection of Advanced Cancer Screening (D.A.C.S), many patients with cancer cases would receive efficient, reliable treatment in a timely manner. According to Cancer.gov, multiple participants reported being screened for cancer, “After they had ‘aged out of the recommended range for routine cancer screening”. (Dr. Moss) “We found that over …

Mutations In The Pms1 Gene Associating With Ovarian Cancer, Elaine Vanterpool, Erin Hough

Student Posters

Ovarian cancer occurs when abnormal cells in the ovaries grow and divide uncontrollably, destroying healthy body tissue. Common symptoms of ovarian cancer include weight loss, fatigue, discomfort in the pelvic area, or changes in bowel habits. This study focuses on how ovarian cancer is related to the PMS1 gene. The PMS1 gene encodes MLH1, a protein involved in DNA mismatch repair (MMR) system. MMR helps connect errors that occur during DNA replication, preventing mutations and potential cancer development. When this gene is mutated, there is an increased risk of developing ovarian and other endometrial cancer. Bioinformaic softwares allow us to …

An Evaluation Of Exercise-Related Self-Efficacy Metrics Following A Resistance Training Program In Individuals Treated For Cancer, Kayla S. Adler

Senior Theses

As the number of cancer survivors grows, managing treatment side effects and promoting healthy behaviors like physical activity is crucial. Low exercise self-efficacy, an individual's belief in their capability to perform exercise, is a significant barrier to physical activity adherence. This study assessed if an 8-week supervised resistance training program could improve self-efficacy for exercise (SEE) and outcome expectations of exercise (OEE) in individuals treated for cancer. Participants (n=25) attended twice-weekly, one-hour sessions. SEE and OEE scales were administered pre- and post-intervention. Results indicated a significant increase in SEE scores (mean difference = 8.96 ± 19.87, p = 0.041), demonstrating …

Emergence Of Transferable Daptomycin Resistance In Gram-Positive Bacteria, Tessa Marciniak, Lukas Kirchner, Silver A. Wolf, Birgit Walther, Thorsten Bischler, Justin Nyasinga, R Gunturu, Torsten Semmler, Tom Gräfenhan, Andrew Whitelaw

Pathology, East Africa

Daptomycin (DAP) is a last-resort antibiotic to treat infections by multiresistant Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. DAP resistance and clinical treatment failure has been associated with adaptive chromosomal mutations, but so far not with transmissible resistance traits. Here we report for the first time an acquired DAP-R determinant (named drc) that we detected in a livestock-associated Mammaliicoccus sciuri isolate. drc consists of a two-gene operon (drcAB) that is controlled by an adjacent two-component system (drcRS). The DrcAB proteins, which mediate DAP inactivation, are similar to BceAB-like antimicrobial peptide transporters of Gram-positives, but are distinct from …

Impact Of Msx1 And Irf6 Gene Variants On Orofacial Cleft And Facial Development, Elaine Vanterpool, Lisa Banks

Student Posters

A cleft lip or palate is a congenital anomaly that occurs when a baby's mouth doesn’t form properly during pregnancy. It happens when the tissues that shape the upper lip or roof of the mouth fail to join during development. It is among the most common birth defects associated with genetic conditions or syndromes. Orofacial cleft can be caused by a combination of genes and other factors like the mother's exposure to environmental things, diet, and medications during pregnancy. Examining the genes involved and making connections that provide insight into the improper formations of the maxillary tissues during fetal stages …

Effects Of Cell-Free Supernatants Of Commercial Yogurt Products On Salmonella Survival, Juliet Durant, Akayla King

Student Posters

Salmonellosis remains a global public health challenge and Salmonella enterica serovar Enteritidis and Typhimurium are the primary causes. Salmonella virulence mechanisms involve attachment and invasion of intestinal epithelial cells. Gut microbiota and probiotics that contain Lactobacillus species have been shown to prevent Salmonella infection. Yogurt is a commonly consumed probiotic product containing Lactobacillus species. Yogurts made under laboratory conditions and the cell-free supernatants have been shown to inhibit Salmonella growth. The many commercial yogurt products on the market may vary in antimicrobial components based on production methods. Therefore, the present study aimed to evaluate the survival of 5 log CFU/mL …

Title: An Analysis Of Hmbs Variants Associated With Acute Intermittent Porphyria, Elaine Vanterpool, Jason Kahari

Student Posters

HMBS, also known as hydroxymethylbilane synthase, is a gene that is responsible for providing instructions for making the enzyme named hydroxymethylbilane synthase. This enzyme is involved in the creation of a molecule called heme. Heme plays an important part in all of the body’s vital organs. It is important to all organs however, it is most prevalent in the blood, bone marrow, and liver. Heme is essential in making iron-containing proteins called hemeproteins. To produce heme, an eight-step process must occur that requires 8 different enzymes. “Hydroxymethylbilane synthase is responsible for the third step in this process, which combines four …

The Association Of Abca3 Variants In Hypertension Pathogenesis, Elaine Vanterpool, Jea Joseph

Student Posters

Hypertension affects around 48.1% of people living in the United States. This number of adults with hypertension between the ages of 30-70 has increased from 650 million to 1.28 billion in the last 30 years. Hypertension is characterized as a condition that affects the arteries of the blood. High blood pressure and high cholesterol have a huge correlation to each other. When the body cannot rid cholesterol from the blood stream, it can deposit along artery walls and clog them, making blood flow harder and increases blood pressure. ABCA3 is a member of the ATP binding cassette family of proteins …

An Analysis Of Oas1 Variants Associated In Diabetes Mellitus, Elaine Vanterpool, Ashley Tannis

Student Posters

Type 1 diabetes is caused by a combination of multiple genetic and environmental factors that precipitate autoimmune destruction of the insulin-producing β-cells of the pancreas. Individuals with type 1 diabetes have higher frequencies of OAS1 GG and GA genotypes than nondiabetic's.OAS1, an interferon-induced gene, also known by its official name, 2'-5'-oligoadenylate synthetase 1, encodes proteins that play a crucial role in innate cellular antiviral response which prevents viral replication by activating the adaptive immune system to erase the virus trying to spread. OAS1 is also involved in additional cellular processes such as cell growth and cell death. This gene is …

External Validation Of An Algorithm To Detect Vertebral Level Mislabeling And Autocontouring Errors, Tucker J Netherton, Didier Duprez, Tina Patel, Gizem Cifter, Laurence E Court, Christoph Trauernicht, Ajay Aggarwal

Faculty, Staff and Student Publications

Background and purpose: This work performs external validation of a previously developed vertebral body autocontouring tool and investigates a post-processing method to increase performance to clinically acceptable levels.

Materials and methods: Vertebral bodies within CT scans from two separate institutions (40 from institution A and 41 from institution B) were automatically 1) localized and enumerated, 2) contoured, and 3) screened as a means of quality assurance (QA) for errors. Identification rate, contour acceptability rate, and QA accuracy were calculated to assess the tool's performance. These metrics were compared to those calculated on CTs from the model's original training dataset, and …

Long Term Results Of Venetoclax Combined With Flag-Ida Induction And Consolidation For Newly Diagnosed And Relapsed Or Refractory Acute Myeloid Leukemia, Courtney D Dinardo, Wei-Ying Jen, Koichi Takahashi, Tapan M Kadia, Sanam Loghavi, Naval G Daver, Lianchun Xiao, Patrick K Reville, Ghayas C Issa, Nicholas J Short, Koji Sasaki, Sa A Wang, Jillian K Mullin, Sherry Pierce, Corey Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Alessandra Ferrajoli, Mahesh Swaminathan, Maro Ohanian, Hussein A Abbas, Danielle Hammond, Jan Burger, Fadi Haddad, Guillermo Montalban-Bravo, Kelly Chien, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Intensive chemotherapy remains the standard for newly diagnosed (ND) acute myeloid leukemia (AML); however, relapse risk remains high. Additionally, most patients with relapsed/refractory (RR) AML have poor outcomes. We report the long-term experience of 138 patients, 77 ND and 61 RR, treated with FLAG-IDA in combination with venetoclax. In the ND cohort, the overall response rate (ORR) was 97%, with a composite complete remission (CRc) rate of 95% and undetectable measurable residual disease (MRD) status by flow cytometry in 90%. The 3-year OS and EFS rates were 66 and 64%, respectively. Outcomes were similar across European LeukemiaNet (ELN) 2022 risk …

Efficacy And Safety Of Denileukin Diftitox-Cxdl, An Improved Purity Formulation Of Denileukin Diftitox, In Patients With Relapsed Or Refractory Cutaneous T-Cell Lymphoma, Francine M Foss, Youn H Kim, H Miles Prince, Oleg E Akilov, Christiane Querfeld, Lucia Seminario-Vidal, David C Fisher, Timothy M Kuzel, Costas K Yannakou, Larisa J Geskin, Tatyana Feldman, Lubomir Sokol, Pamela Blair Allen, Nam Hoang Dang, Fernando Cabanillas, Henry K Wong, Chean Eng Ooi, Dongyuan Xing, Nicholas Sauter, Preeti Singh, Myron Czuczman, Madeleine Duvic

Faculty, Staff and Student Publications

Purpose: Denileukin diftitox (DD)-cxdl is a fusion protein comprising diphtheria toxin fragments A and B and human interleukin-2. This phase III, multicenter, open-label, single-arm registrational trial evaluated the efficacy and safety of DD-cxdl in patients with relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL).

Patients and methods: In the main study, which followed a dose-finding lead-in, DD-cxdl was administered intravenously daily (5 days; 9 µg/kg/d once daily) every 21 days for up to eight cycles. Patients in the primary efficacy analysis set (PEAS) were required to have stage IA-IIIB CTCL (mycosis fungoides and/or Sézary syndrome) and at least ≥one previous systemic therapy. …

Evaluation Of A Comprehensive Set Of Normal Tissue Complication Probability Models For Patients With Head And Neck Cancer In An International Cohort, Suzanne P M De Vette, Maria I Van Rijn-Dekker, Lisa Van Den Bosch, Kylie Keijzer, Hendrike Neh, Hung Chu, Yan Li, Mark L Frederiks, Hans Paul Van Der Laan, Jolien Heukelom, Peter Van Luijk, Arjen Van Der Schaaf, Roel J H M Steenbakkers, Nanna M Sijtsema, Katherine A Hutcheson, Clifton D Fuller, Johannes A Langendijk, Amy C Moreno, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Background/purpose: Normal tissue complication probability (NTCP) models can be used to guide radiation therapy (RT) decisions by estimating side-effect risks pretreatment to minimize (late) side-effects. Recently, a comprehensive individual toxicity risk (CITOR) profile of NTCP models addressing common side-effects in head and neck cancer (HNC) patients was developed. This study investigates the generalizability of these models in an international setting, with different treatment approaches and side-effect assessments, promoting their integration into more widespread clinical practice.

Materials/methods: From a prospective registry study, 407 HNC patients were included who were treated with definitive RT with or without systemic therapy between 2015 and …

Cytokine Storms In Covid-19, Hemophagocytic Lymphohistiocytosis, And Car-T Therapy, James P Long, Rishab Prakash, Paul Edelkamp, Mark Knafl, Anath C Lionel, Ranjit Nair, Sairah Ahmed, Paolo Strati, Luis E Malpica Castillo, Ajlan Al-Zaki, Kelly Chien, Dai Chihara, Jason Westin, Fareed Khawaja, Loretta J Nastoupil, Victor Mulanovich, Andrew Futreal, Scott E Woodman, Naval G Daver, Christopher R Flowers, Sattva Neelapu, Joanna-Grace Manzano, Swaminathan P Iyer

Faculty, Staff and Student Publications

Importance: Cytokine storm (CS) is a hyperinflammatory syndrome causing multiorgan dysfunction and high mortality, especially in patients with malignant hematologic neoplasms. Triggers include malignant neoplasm-associated hemophagocytic lymphohistiocytosis (MN-HLH), cytokine release syndrome from chimeric antigen receptor T-cell therapy (CAR-T CRS), and COVID-19, but the underlying mechanisms of inflammation and their impact on outcomes are poorly understood.

Objective: To delineate the inflammatory patterns characterizing different CS etiologies and their association with clinical outcomes.

Design, setting, and participants: This retrospective cohort study was conducted at the MD Anderson Cancer Center in Houston, Texas, between March 1, 2020, and November 20, 2022, using the …

Self-Reported Cognitive Function In Older Breast Cancer Survivors After Chemotherapy Treatment, Rachel Kim, Julia Peña, Kai-Ping Liao, Susan K Peterson, Liang Li, Daria Zorzi, Holly M Holmes, Mariana Chavez-Macgregor, Sharon H Giordano

Faculty, Staff and Student Publications

Purpose: This study evaluated self-reported cognitive function in older breast cancer survivors and its association with prior chemotherapy.

Materials and methods: Breast cancer survivors aged 65-years and older, diagnosed 2012-2013, with local and regional stage disease, were identified through the linked Texas Cancer Registry-Medicare dataset. Survivors completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-CogV3) instrument and provided demographic and clinical data. A PCI--sub-score of less than 54 was used to identify cognitive impairment. Linear regression models were used to examine the FACT-CogV3 primary score, and logistic regression models evaluated the PCI--sub-score.

Results: Of 4448 eligible survivors, 1594 (35.8 %) …

Lysyl Hydroxylase 2 Glucosylates Collagen Vi To Drive Lung Cancer Progression, Shike Wang, Houfu Guo, Reo Fukushima, Masahiko Terajima, Min Liu, Guan-Yu Xiao, Lenka Koudelková, Chao Wu, Xin Liu, Jiang Yu, Emma Burris, Jun Xu, Alvise Schiavinato, William K Russell, Mitsuo Yamauchi, Xiaochao Tan, Jonathan M Kurie

Faculty, Staff and Student Publications

Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable collagen cross links in tumor stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain on LH2-modified type-VI collagen (Col6) to promote lung adenocarcinoma (LUAD) growth and metastasis. In tumors generated by LUAD cells lacking LH2 GGT domain activity, stroma was less stiff, and stable types of collagen cross links were reduced. Mass spectrometric analysis of total and glycosylated peptides in parental and GGT-inactive tumor samples identified Col6 chain α3 (Col6a3), a component of …

Immunotherapy Targeting A Leader Sequence Cathepsin G-Derived Peptide, Chunhua Shi, Ze Tian, Jun Yan, Mao Zhang, Pariya Sukhumalchandra, Edward Chang, Guojun Yang, Junping You, Meng Cui, Qing Shi, Celine Kerros, Anne Philips, Na Qiao, Hiroki Torikai, Sathvik Patchametla, Anna Sergeeva, Lisa St John, Helen He, Dmitri Wiederschain, Benjamin H Lee, Geraldine L C Paulus, Dongxing Zha, Jeffrey Molldrem, Gheath Alatrash

Faculty, Staff and Student Publications

Myeloid azurophil granules provide a rich source of intracellular leukemia antigens. Cathepsin G (CG) is a serine protease that has higher expression in acute myeloid leukemia (AML) blasts in comparison to normal myeloid progenitors. Based on the unique biology of HLA-A*0201 (HLA-A2), in which presentation of leader sequence (LS)-derived peptides is favored, we focused on the LS-CG-derived peptide CG1 (FLLPTGAEA). We previously detected CG1/HLA-A2 complexes on the surface of primary HLA-A2+ AML blasts and cell lines, and immunity targeting CG1/HLA-A2 in leukemia patients. T cell receptor (TCR)-mimic (m) antibodies are immunotherapeutic antibodies that target peptide-HLA (pHLA) complexes. Here we report …

Insulin-Like Growth Factor 2 As A Driving Force For Exponential Expansion And Differentiation Of The Neonatal Thymus, Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

Faculty, Staff and Student Publications

Like all organs, the thymus grows in size and function rapidly during development, but this growth comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated that IGF2 activity promotes a cortical thymic epithelial cell-specific proliferation …

A New Cure Model Accounting For Longitudinal Data And Flexible Patterns Of Hazard Ratios Over Time, Can Xie, Xuelin Huang, Ruosha Li, Yu Shen, Nicholas J Short, Kapil N Bhalla

Faculty, Staff and Student Publications

With the advancement of medical treatments, many historically incurable diseases have become curable. An accurate estimation of the cure rates is of great interest. When there are no clear biomarker indicators for cure, the estimation of cure rate is intertwined with and influenced by the specification of hazard functions for uncured patients. Consequently, the commonly used proportional hazards (PH) assumption, when violated, may lead to biased cure rate estimation. Meanwhile, longitudinal biomarker measurements for individual patients are usually available. To accommodate non-PH functions and incorporate individual longitudinal biomarker trajectories, we propose a new joint model for cure, survival, and longitudinal …

Diet And Survival After A Diagnosis Of Ovarian Cancer: A Pooled Analysis From The Ovarian Cancer Association Consortium, Christina M Nagle, Torukiri I Ibiebele, Renhua Na, Elisa V Bandera, Daniel Cramer, Jennifer A Doherty, Graham G Giles, Marc T Goodman, Gillian E Hanley, Holly R Harris, Allan Jensen, Susanne K Kjaer, Alice Lee, Valerie Mcguire, Roger L Milne, Bo Qin, Jean Richardson, Naoko Sasamoto, Joellen M Schildkraut, Weiva Sieh, Kathryn L Terry, Linda Titus, Britton Trabert, Nicolas Wentzensen, Anna H Wu, Andrew Berchuck, Malcolm C Pike, Celeste Leigh Pearce, Penelope M Webb, Multidisciplinary Ovarian Cancer Outcomes Group And Ovarian Cancer Association Consortium

Faculty, Staff and Student Publications

Background: Prognosis after a diagnosis of invasive epithelial ovarian cancer is poor. Some studies have suggested modifiable behaviors, like diet, are associated with survival but the evidence is inconsistent.

Objectives: This study aims to pool data from studies conducted around the world to evaluate the relationships among dietary indices, foods, and nutrients from food sources and survival after a diagnosis of ovarian cancer.

Methods: This analysis from the Multidisciplinary Ovarian Cancer Outcomes Group within the Ovarian Cancer Association Consortium included 13 studies with 7700 individuals with ovarian cancer, who completed food-frequency questionnaires regarding their prediagnosis diet. Adjusted hazard ratios (aHRs) …

Crowd-Sourced Benchmarking Of Single-Sample Tumor Subclonal Reconstruction, Adriana Salcedo, Maxime Tarabichi, Alex Buchanan, Shadrielle M G Espiritu, Hongjiu Zhang, Kaiyi Zhu, Tai-Hsien Ou Yang, Ignaty Leshchiner, Dimitris Anastassiou, Yuanfang Guan, Gun Ho Jang, Mohammed F E Mootor, Kerstin Haase, Amit G Deshwar, William Zou, Imaad Umar, Stefan Dentro, Jeff A Wintersinger, Kami Chiotti, Jonas Demeulemeester, Clemency Jolly, Lesia Sycza, Minjeong Ko, Pcawg Evolution And Heterogeneity Working Group, Smc-Het Participants, David C Wedge, Quaid D Morris, Kyle Ellrott, Peter Van Loo, Paul C Boutros

Faculty, Staff and Student Publications

Subclonal reconstruction algorithms use bulk DNA sequencing data to quantify parameters of tumor evolution, allowing an assessment of how cancers initiate, progress and respond to selective pressures. We launched the ICGC-TCGA (International Cancer Genome Consortium-The Cancer Genome Atlas) DREAM Somatic Mutation Calling Tumor Heterogeneity and Evolution Challenge to benchmark existing subclonal reconstruction algorithms. This 7-year community effort used cloud computing to benchmark 31 subclonal reconstruction algorithms on 51 simulated tumors. Algorithms were scored on seven independent tasks, leading to 12,061 total runs. Algorithm choice influenced performance substantially more than tumor features but purity-adjusted read depth, copy-number state and read mappability …

Concurrent Bone Marrow Acute Undifferentiated Leukemia And Mediastinal T‐Lymphoblastic Lymphoma With Identical Set::Nup214 Fusion And Phf6 And Ezh2 Mutations, Qing Wei, Fatima Z Jelloul, Sa A Wang, Guilin Tang, Shaoying Li, Pei Lin, Sanam Loghavi, Huan-You Wang, L Jeffrey Medeiros, Jie Xu

Faculty, Staff and Student Publications

Acute undifferentiated leukemia (AUL) is a rare hematologic malignancy lacking lineage‐specific markers. Concurrent, clonally related AUL and T‐lymphoblastic lymphoma (T‐LBL) has not been reported previously. Here we describe a patient who was diagnosed with AUL in the bone marrow and T‐LBL in the mediastinum after a thorough immunophenotyping by flow cytometry and immunohistochemistry. Despite their immunophenotypic differences, the AUL and T‐LBL showed identical genetic alterations: SET::NUP214 fusion, PHF6, and EZH2 mutations. The patient achieved and remained in complete remission after chemotherapy and stem cell transplantation. This case underscores the value of comprehensive immunophenotyping and genetic analysis in rare hematologic …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Nicotinic Acetylcholine Receptor Expression In Merkel Cell Carcinoma Is Associated With Clinical And Histopathologic Parameters, Christopher R Cunningham, Yiannis P Dimopoulos, Ian M García-Quiñones, Denái R Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G Prieto, José A Lasalde-Dominicci, Leomar Y Ballester, Phyu P Aung

Faculty, Staff and Student Publications

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.

Methods: The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7-234.1). We performed immunohistochemistry using antibodies against the …

Characterization Of A Time-Resolved, Real-Time Scintillation Dosimetry System For Ultra-High Dose-Rate Radiation Therapy Applications, Alexander Baikalov, Daline Tho, Kevin Liu, Stefan Bartzsch, Sam Beddar, Emil Schüler

Faculty, Staff and Student Publications

Purpose: Scintillation dosimetry has promising qualities for ultra-high-dose-rate (UHDR) radiation therapy (RT), but no system has shown compatibility with mean dose rates (DR¯) above 100 Gy/s and doses per pulse (Dp) exceeding 1.5 Gy typical of UHDR (FLASH)-RT. The aim of this study was to characterize a novel scintillation dosimetry system with the potential of accommodating UHDRs.

Methods and materials: We undertook a thorough dosimetric characterization of the system on an UHDR electron beamline. The system's response as a function of dose, DR¯, Dp, and the pulse dose-rate (DRp) was investigated, as was the system's dose sensitivity (signal per unit …