Life Sciences Commons^™

Research Career Intentions Among Non-Native English-Speaking Graduate And Postdoctoral Trainees In Stem-Results From Cross-Sectional And Longitudinal Studies, Hwa Young Lee, Shine Chang, Cheryl B Anderson, Erin K Dahlstrom, Carrie Cameron

Faculty, Staff and Student Publications

International graduate trainees, many of whom are non-native English-speaking (L2) trainees, comprise more than half of graduate-level trainees in STEM, but little is known regarding factors that influence their career intentions, especially those that foster their growth as scientists to achieve their full potential in research. Thus, the purpose of our studies was to examine the relationship between L2 status and contextual factors that help shape the learning experiences and plans for research-focused careers. Study 1 collected cross-sectional survey data from doctoral and postdoctoral trainees (N=510) from research institutes in the Texas Medical Center in Houston. We examined which factors …

The Impact Of Merkel Cell Polyomavirus Positivity On Prognosis Of Merkel Cell Carcinoma: A Systematic Review And Meta-Analysis, Aimin Yang, Wilson Adrian Wijaya, Lei Yang, Yinhai He, Ying Cen

Faculty, Staff and Student Publications

INTRODUCTION: There are numerous findings over the past decade have indicated that Merkel cell carcinoma (MCC) may have two pathways of pathogenesis: one related to ultraviolet irradiation and the other to the Merkel cell polyomavirus (MCPyV). However, the predictive and clinicopathological value of MCPyV positivity in MCC patients is still debatable. This article aims to examine the most recent data regarding this issue.

METHODS: The thorough literature searches were conducted in the Medline Ovid, PubMed, Web of Science, the Cochrane CENTRAL Databases, and Embase Databases until December 31, 2021. The associations between overall survival (OS), Merkel cell carcinoma-specific survival (MSS), …

High-Resolution Metabolomics Of Exposure To Tobacco Smoke During Pregnancy And Adverse Birth Outcomes In The Atlanta African American Maternal-Child Cohort, Youran Tan, Dana Boyd Barr, P Barry Ryan, Veronika Fedirko, Jeremy A Sarnat, Che-Jung Chang, Carmen J Marsit, Elizabeth J Corwin, Dean P Jones, Anne L Dunlop, Donghai Liang

Faculty, Staff and Student Publications

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014-2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed …

Clinical Implementation And Initial Experience With A 15 Tesla Mr-Linac For Mr-Guided Radiation Therapy For Gynecologic Cancer: An R-Ideal Stage 1 And 2a First In Humans Feasibility Study Of New Technology Implementation, David S Lakomy, Jinzhong Yang, Sastry Vedam, Jihong Wang, Belinda Lee, Pamela Castillo, Mustefa Mohammedsaid, Anuja Jhingran, Ann H Klopp, Seungtaek Choi, C David Fuller, Lilie L Lin

Faculty, Staff and Student Publications

PURPOSE: Magnetic resonance imaging-guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiation therapy plans. Here, we report our early clinical experience using a MR-linac for adaptive radiation therapy of gynecologic malignancies.

METHODS AND MATERIALS: Treatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here, …

A Transgenic Bacterial Artificial Chromosome Approach To Identify Regulatory Regions That Direct Amhr2 And Osterix Expression In Müllerian Duct Mesenchyme, Malcolm M Moses, Rachel D Mullen, Daniel I Idowu, Peter Maye, Soazik P Jamin

Faculty, Staff and Student Publications

A transgenic mouse approach using bacterial artificial chromosomes (BAC) was used to identify regulatory regions that direct Müllerian duct expression for Amhr2 and Osterix (Osx, also known as Sp7). Amhr2 encodes the receptor that mediates anti-Müllerian hormone (AMH) signaling for Müllerian duct regression in male embryos. Amhr2 is expressed in the Müllerian duct mesenchyme of both male and female embryos. A ∼147-kb BAC clone containing the Amhr2 locus was used to generate transgenic mice. The transgene was able to rescue the block in Müllerian duct regression of Amhr2-null males, suggesting that the BAC clone contains regulatory …

Combining Tumor Segmentation Masks With Pet/Ct Images And Clinical Data In A Deep Learning Framework For Improved Prognostic Prediction In Head And Neck Squamous Cell Carcinoma, Kareem A Wahid, Renjie He, Cem Dede, Abdallah S R Mohamed, Moamen Abobakr Abdelaal, Clifton D Fuller

Faculty, Staff and Student Publications

PET/CT images provide a rich data source for clinical prediction models in head and neck squamous cell carcinoma (HNSCC). Deep learning models often use images in an end-to-end fashion with clinical data or no additional input for predictions. However, in the context of HNSCC, the tumor region of interest may be an informative prior in the generation of improved prediction performance. In this study, we utilize a deep learning framework based on a DenseNet architecture to combine PET images, CT images, primary tumor segmentation masks, and clinical data as separate channels to predict progression-free survival (PFS) in days for HNSCC …

Use Of Specific Duodenal Dose Constraints During Treatment Planning Reduces Toxicity After Definitive Paraaortic Radiation Therapy For Cervical Cancer, David S Lakomy, Juliana Wu, Bhavana V Chapman, Zhiqian Henry Yu, Belinda Lee, Anuja Jhingran, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: This study aimed to validate the safety of paraaortic nodal (PAN) radiation therapy (RT) for patients with cervical cancer when the duodenal dose is limited to V55 < 15 cm3 and V60 < 2 cm3.

Methods and materials: A total of 97 patients who were treated with RT for cervical cancer between 2010 and 2018 received at least 56 Gy to grossly involved PANs. Patients were treated with concurrent chemoradiation (n = 88; 91%), with 93% of patients (n = 90) receiving intensity modulated RT to the initial PAN field and 98% (n = 95) receiving intensity modulated RT to a sequential PAN boost. The V55 < 15 cm3 and V60 < 2 cm3 criteria were implemented in 2014. Normal tissues were contoured on computed tomography (CT) simulation data sets, and the duodenum was contoured from the gastric outlet to the duodenojejunal flexure. Sixty-six patients (68%) had a resimulation scan after approximately 20 fractions. Composite duodenal doses were calculated using the initial CT scan for 50 patients (52%) and the resimulation CT scan for 47 patients (48%) depending on the anatomic changes throughout treatment.

Results: …

Landmark Mediation Survival Analysis Using Longitudinal Surrogate, Jie Zhou, Xun Jiang, H Amy Xia, Brian P Hobbs, Peng Wei

Faculty, Staff and Student Publications

Clinical cancer trials are designed to collect radiographic measurements of each patient's baseline and residual tumor burden at regular intervals over the course of study. For solid tumors, the extent of reduction in tumor size following treatment is used as a measure of a drug's antitumor activity. Statistical estimation of treatment efficacy routinely reduce the longitudinal assessment of tumor burden to a binary outcome describing the presence versus absence of an objective tumor response as defined by RECIST criteria. The objective response rate (ORR) is the predominate method for evaluating an experimental therapy in a single-arm trial. Additionally, ORR is …

Clinical Characteristics And Outcomes Of Castleman Disease: A Multicenter Consortium Study Of 428 Patients With 15-Year Follow-Up, Wanying Liu, Qingqing Cai, Tiantian Yu, Paolo Strati, Frederick B Hagemeister, Mingzhi Zhang, Xiaosheng Fang, Jianyong Li, Ruifang Sun, Shanxiang Zhang, Hanjin Yang, Zhaoming Wang, Wenbian Qian, Noriko Iwaki, Yasuharu Sato, Eric Oksenhendler, Zijun Y Xu-Monette, Ken H Young, Li Yu

Faculty, Staff and Student Publications

Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology …

Urinary T Cells Are Detected In Patients With Immune Checkpoint Inhibitor-Associated Immune Nephritis That Are Clonotypically Identical To Kidney T Cell Infiltrates, Shailbala Singh, Leticia C Clemente, Edwin R Parra, Amanda Tchakarov, Chao Yang, James P Long, Jamie S Lin

Faculty, Staff and Student Publications

Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune …

Complexities And Complications Of Extreme Obesity, Haval Ali, Udit Naik, Michelle Mcdonald, Mohammad Almosa, Karen Horn, Louis Maximilian Buja

Faculty, Staff and Student Publications

Obesity is a common chronic disorder and has detrimental long-term consequences if left untreated. Herein, we report a case of a young lady who suffered from morbid obesity and many of its consequences, and we present a literature review of these complications. While the cause of obesity is multifactorial, the genetic component is particularly important in the pathophysiology of marked obesity. Resistance to Leptin is considered one of the main causes of obesity. There is a unique relationship between polycystic ovary syndrome and obesity, as observed in our case. Obesity is associated with cardiovascular and lung diseases such as heart …

Impact Of Psychosocial, Behavioral And Lifestyle Factors On Subjective Cognitive Complaints And Perceived Quality Of Life In A Large Cohort Of Italian Breast Cancer Patients, Thomas West, Corrado Cavallero, Rita Ceccherini, Silva Foladore, Daniele Generali, Bruna Scaggiante

Faculty, Staff and Student Publications

The impact of psychosocial and behavioral factors on Cancer Related Cognitive Impairment manifestations is still under debate. Study's purpose is to determine the prevalence rate of cancer related cognitive impairment in a cohort of Italian breast cancer patients and to evaluate the implication of specific behavioral factors. For these purposes, a total of 233 women (106 breast cancer patients and 127 age-matched controls without oncological diagnosis) completed a questionnaire investigating cognitive functionality (FACT-Cog v3.0), sociodemographic characteristics, clinical information, psychosocial and behavioral factors (cognitive reserve, sleep quality, dietary habits, physical activity). The results indicated a higher prevalence rate of subjective cognitive …

Recent Advances On Dna Base Flipping: A General Mechanism For Writing, Reading, And Erasing Dna Modifications, Ren Ren, John R Horton, Samuel Hong, Xiaodong Cheng

Faculty, Staff and Student Publications

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine-5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine-have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine-N4-methylcytosine and N6-methyladenine-are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, several crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified …

Checkpoint Inhibitors As Immunotherapy For Fungal Infections: Promises, Challenges, And Unanswered Questions, Sebastian Wurster, Stephanie S Watowich, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic …

A Haplotype Resolved Chromosomal Level Avocado Genome Allows Analysis Of Novel Avocado Genes, Ardashir Kharabian Masouleh

Faculty, Staff and Student Publications

Avocado (Persea americana) is a member of the magnoliids, an early branching lineage of angiosperms that has high value globally with the fruit being highly nutritious. Here, we report a chromosome-level genome assembly for the commercial avocado cultivar Hass, which represents 80% of the world’s avocado consumption. The DNA contigs produced from Pacific Biosciences HiFi reads were further assembled using a previously published version of the genome supported by a genetic map. The total assembly was 913 Mb with a contig N50 of 84 Mb. Contigs assigned to the 12 chromosomes represented 874 Mb and covered 98.8% of …

Association Of Proton Pump Inhibitor Use With Survival Outcomes In Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review And Meta-Analysis, Baoqing Chen, Chen Yang, Mihnea P Dragomir, Dongmei Chi, Wenyan Chen, David Horst, George A Calin, Qiaoqiao Li

Faculty, Staff and Student Publications

Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients.

Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI …

Toward A Topology-Based Therapeutic Design Of Membrane Proteins: Validation Of Napi2b Topology In Live Ovarian Cancer Cells, Arina Timonina

Faculty, Staff and Student Publications

NaPi2b is a sodium-dependent phosphate transporter that belongs to the SLC34 family of transporters which is mainly responsible for phosphate homeostasis in humans. Although NaPi2b is widely expressed in normal tissues, its overexpression has been demonstrated in ovarian, lung, and other cancers. A valuable set of antibodies, including L2 (20/3) and MX35, and its humanized versions react strongly with an antigen on the surface of ovarian and other carcinoma cells. Although the topology of NaPi2b was predicted

Update On Mri In Evaluation And Treatment Of Endometrial Cancer, Ekta Maheshwari, Stephanie Nougaret, Erica B Stein, Gaiane M Rauch, Ken-Pin Hwang, Ann H Klopp, Katherine E Maturen, Andrea G Rockall, Susanna I Lee, Elizabeth A Sadowski, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Endometrial cancer is the second most common gynecologic cancer worldwide and the most common gynecologic cancer in the United States, with an increasing incidence in high-income countries. Although the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer is a surgical staging system, contemporary published evidence-based data and expert opinions recommend MRI for treatment planning as it provides critical diagnostic information on tumor size and depth, extent of myometrial and cervical invasion, extrauterine extent, and lymph node status, all of which are essential in choosing the most appropriate therapy. Multiparametric MRI using a combination of T2-weighted sequences, …

Screening Of Hydrocarbon-Stapled Peptides For Inhibition Of Calcium-Triggered Exocytosis, Ying Lai, Michael J Tuvim, Jeremy Leitz, John Peters, Richard A Pfuetzner, Qiangjun Zhou, Jason B Cross, Philip Jones, Burton F Dickey, Axel T Brunger

Faculty, Staff and Student Publications

The so-called primary interface between the SNARE complex and synaptotagmin-1 (Syt1) is essential for Ca2+-triggered neurotransmitter release in neuronal synapses. The interacting residues of the primary interface are conserved across different species for synaptotagmins (Syt1, Syt2, Syt9), SNAP-25, and syntaxin-1A homologs involved in fast synchronous release. This Ca2+-independent interface forms prior to Ca2+-triggering and plays a role in synaptic vesicle priming. This primary interface is also conserved in the fusion machinery that is responsible for mucin granule membrane fusion. Ca2+-stimulated mucin secretion is mediated by the SNAREs syntaxin-3, SNAP-23, VAMP8, Syt2, and other proteins. Here, we designed and screened a …

Morphological Description Of Laevicaulisstuhlmanni (Simroth, 1895) (Pulmonata, Veronicellidae) From Egypt, Reham Fathey Ali, David G Robinson, Fabio Liberto

Faculty, Staff and Student Publications

BACKGROUND: Terrestrial slugs and snails are increasingly becoming serious pests of agricultural, horticultural and ornamental plants in Egypt, resulting in major economic losses.

NEW INFORMATION: This paper provides a detailed morphological and anatomical description of the veronicellid slug Laevicaulisstuhlmanni (Simroth, 1895) that has been recently recorded from Egypt. This population from Egypt is compared with Laevicaulis populations recently reported and described from Libya as L.striatus (Simroth, 1896) and with available data in literature. Some notes and a distribution map of the veronicellids introduced in north-eastern Africa are provided.

Engineered Cord Blood Megakaryocytes Evade Killing By Allogeneic T-Cells For Refractory Thrombocytopenia, Bijender Kumar, Vahid Afshar-Kharghan, Mayela Mendt, Robert Sackstein, Mark R Tanner, Jeremy Ramdial, Juan Jimenez, Rafet Basar, Luciana Melo Garcia, Mayra Shanley, Mecit Kaplan, Xinhai Wan, Vandana Nandivada, Francia Reyes Silva, Vernikka Woods, April Gilbert, Ricardo Gonzalez-Delgado, Sunil Acharya, Paul Lin, Hind Rafei, Pinaki Prosad Banerjee, Elizabeth J Shpall

Faculty, Staff and Student Publications

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, …

Blockade Of Growth Hormone Receptor Signaling By Using Pegvisomant: A Functional Therapeutic Strategy In Hepatocellular Carcinoma, Ahmed O Kaseb, Abedul Haque, Deeksha Vishwamitra, Manal M Hassan, Lianchun Xiao, Vishal Sahu, Roberto Carmagnani Pestana, Jamie Lynne Lombardo, Rony Avritscher, James C Yao, Robert A Wolff, Asif Rashid, Jeffrey S Morris, Hesham M Amin

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is an aggressive neoplasm with poor clinical outcome because most patients present at an advanced stage, at which point curative surgical options, such as tumor excision or liver transplantation, are not feasible. Therefore, the majority of HCC patients require systemic therapy. Nonetheless, the currently approved systemic therapies have limited effects, particularly in patients with advanced and resistant disease. Hence, there is a critical need to identify new molecular targets and effective systemic therapies to improve HCC outcome. The liver is a major target of the growth hormone receptor (GHR) signaling, and accumulating evidence suggests that GHR signaling …

The Current Status And Shortcomings Of Stereotactic Radiosurgery, Hunter Mehrens, Trang Nguyen, Sharbacha Edward, Shannon Hartzell, Mallory Glenn, Nadia Hernandez, Andrea Molineu, Paige Taylor, Stephen Kry

Faculty, Staff and Student Publications

Background: Stereotactic radiosurgery (SRS) is a common treatment for intracranial lesions. This work explores the state of SRS treatment delivery to characterize current treatment accuracy based on treatment parameters.

Methods: NCI clinical trials involving SRS rely on an end-to-end treatment delivery on a patient surrogate (credentialing phantom) from the Imaging and Radiation Oncology Core (IROC) to test their treatment accuracy. The results of 1072 SRS phantom irradiations between 2012 and 2020 were retrospectively analyzed. Univariate analysis and random forest models were used to associate irradiation conditions with phantom performance. The following categories were evaluated in terms of how they predicted …

Single-Incision Laparoscopic Splenectomy In Children With Massive Splenomegaly: A Prospective, Monocentric Pilot Study, Congjun Wang, Cheng Su, Chao Chen, Xianming Tang, Hong Wang, Yanqiang Li, Peng Chen, Yong Li, Yige Luo

Faculty, Staff and Student Publications

BACKGROUND: Single-incision laparoscopic splenectomy (SILS) remains a challenging procedure because of the technical difficulty. In this prospective study, we aimed to evaluate the efficacy and safety of SILS in children with massive splenomegaly.

METHODS: Pediatric patients with massive splenomegaly were recruited for SILS in a university-affiliated hospital. The data on patient demographics, clinical features, operative variables, and perioperative outcomes were collected prospectively and analyzed. According to the different surgical instruments, the patients were randomly assigned into two groups: the SILS with straight surgical instrument (SILS-S) group and the SILS with curved surgical instrument (SILS-C) group. A two-group comparative analysis was …

The Seen And The Unseen: Molecular Classification And Image Based-Analysis Of Gastrointestinal Cancers, Corina-Elena Minciuna, Mihai Tanase, Teodora Ecaterina Manuc, Stefan Tudor, Vlad Herlea, George A Calin

Faculty, Staff and Student Publications

Gastrointestinal cancers account for 22.5% of cancer related deaths worldwide and represent circa 20% of all cancers. In the last decades, we have witnessed a shift from histology-based to molecular-based classifications using genomic, epigenomic, and transcriptomic data. The molecular based classification revealed new prognostic markers and may aid the therapy selection. Because of the high-costs to perform a molecular classification, in recent years immunohistochemistry-based surrogate classification were developed which permit the stratification of patients, and in parallel multiple groups developed hematoxylin and eosin whole slide image analysis for sub-classifying these entities. Hence, we are witnessing a return to an image-based …

Re-Thinking Therapeutic Development For Cns Metastatic Disease, Chantal Saberian, Michael A Davies

Faculty, Staff and Student Publications

There has been unprecedented progress in the development of systemic therapies for patients with metastatic melanoma over the last decade. There is now tremendous potential and momentum to further and markedly reduce the impact of this disease. However, developing more effective treatments for metastases to the CNS remains a critical challenge for patients with melanoma. Melanoma patients with active CNS metastases have largely been excluded from both early-phase and registration trials for all currently approved targeted and immune therapies for this disease. While this exclusion has generally been justified in clinical research due to concerns about poor prognosis, lack of …

Leveraging Deep Learning-Based Segmentation And Contours-Driven Deformable Registration For Dose Accumulation In Abdominal Structures, Molly M Mcculloch, Guillaume Cazoulat, Stina Svensson, Sergii Gryshkevych, Bastien Rigaud, Ezgi Kirimli, Ryan T Mathew, Mohamed Zaid, Dalia Elganainy, Christine B Peterson, Peter Balter, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

PURPOSE: Discrepancies between planned and delivered dose to GI structures during radiation therapy (RT) of liver cancer may hamper the prediction of treatment outcomes. The purpose of this study is to develop a streamlined workflow for dose accumulation in a treatment planning system (TPS) during liver image-guided RT and to assess its accuracy when using different deformable image registration (DIR) algorithms.

MATERIALS AND METHODS: Fifty-six patients with primary and metastatic liver cancer treated with external beam radiotherapy guided by daily CT-on-rails (CTOR) were retrospectively analyzed. The liver, stomach and duodenum contours were auto-segmented on all planning CTs and daily CTORs …

Predicting Clinical Response To Everolimus In Er+ Breast Cancers Using Machine-Learning, Aritro Nath, Patrick A Cosgrove, Jeffrey T Chang, Andrea H Bild

Faculty, Staff and Student Publications

Endocrine therapy remains the primary treatment choice for ER+ breast cancers. However, most advanced ER+ breast cancers ultimately develop resistance to endocrine. This acquired resistance to endocrine therapy is often driven by the activation of the PI3K/AKT/mTOR signaling pathway. Everolimus, a drug that targets and inhibits the mTOR complex has been shown to improve clinical outcomes in metastatic ER+ breast cancers. However, there are no biomarkers currently available to guide the use of everolimus in the clinic for progressive patients, where multiple therapeutic options are available. Here, we utilized gene expression signatures from 9 ER+ breast cancer cell lines and …

Exploiting Induced Vulnerability To Overcome Parpi Resistance And Clonal Heterogeneity In Brca Mutant Triple-Negative Inflammatory Breast Cancer, David J H Shih, Mei-Kuang Chen, Jun Yin, Daniel J Mcgrail, Hui Dai, Jing Zhang, Kim-Anh Do, Liuqing Yang, Mien-Chie Hung, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Acquired resistance and clonal heterogeneity are critical challenges in cancer treatment, and the lack of effective computational tools hampers the discovery of new treatments to overcome resistance. Using high-throughput transcriptomic databases of compound perturbation profiles, we have developed a bioinformatic strategy for identifying candidate drugs to overcome resistance with combinatorial therapy. We devised this strategy during an investigation into the acquired resistance against PARP inhibitors (PARPi) in a triple-negative inflammatory breast cancer cell line. In this study, we derived multiple PARPi-resistant clones and characterized their transcriptomic adaptations compared to the parental clone. The transcriptomes of the resistant clones showed substantial …

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Ken Chen, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …