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Articles 3631 - 3660 of 14295

Full-Text Articles in Medicine and Health Sciences

"I Just Assumed This Was Already Being Done": Canadian Patient Preferences For Enhanced Data Sharing For Precision Oncology, Samantha Pollard Pollard, Morgan Ehman, Anna Hermansen, Deirdre Weymann, Emanuel Krebs, Cheryl Ho, Howard J. Lim, Steven Jones, Yvonne Bombard, Tania M. Bubela Aug 2024

"I Just Assumed This Was Already Being Done": Canadian Patient Preferences For Enhanced Data Sharing For Precision Oncology, Samantha Pollard Pollard, Morgan Ehman, Anna Hermansen, Deirdre Weymann, Emanuel Krebs, Cheryl Ho, Howard J. Lim, Steven Jones, Yvonne Bombard, Tania M. Bubela

Office of the Provost

Purpose: In Canada, health data are siloed, slowing bioinnovation and evidence generation for personalized cancer care. Secured data-sharing platforms (SDSPs) can enable data analysis across silos through rapid concatenation across trial and real-world settings and timely researcher access. To motivate patient participation and trust in research, it is critical to ensure that SDSP design and oversight align with patients' values and address their concerns. We sought to qualitatively characterize patient preferences for the design of a pan-Canadian SDSP.
Methods: Between January 2022 and July 2023, we conducted pan-Canadian virtual focus groups with individuals who had a personal history of cancer. …


The Use Of Near-Infrared Angiography In Evaluating Bowel Anastomosis During A Gynecologic Oncology Surgery, Lea A. Moukarzel, Sarah Andres, Oliver Zivanovic Aug 2024

The Use Of Near-Infrared Angiography In Evaluating Bowel Anastomosis During A Gynecologic Oncology Surgery, Lea A. Moukarzel, Sarah Andres, Oliver Zivanovic

Abington Jefferson Health Papers

Reducing anastomotic leak rates after bowel resection is a priority among patients undergoing gynecologic oncology surgery. While near-infrared (NIR) angiography has been investigated in the colorectal literature, more recent work has demonstrated promising results when used in gynecologic cancer surgery. It has been repeatedly shown to be a safe intervention that can offer real time assessment of bowel perfusion, offering the surgeon the opportunity to act on the results in the hopes of decreasing the risk of complications.


Emerging Role Of Mucins In Antibody Drug Conjugates For Ovarian Cancer Therapy, Shabnam Malik, Mohammed Sikander, Natasha Bell, Daniel Zubieta, Maria C. Bell, Murali Yallapu, Subhash Chauhan Aug 2024

Emerging Role Of Mucins In Antibody Drug Conjugates For Ovarian Cancer Therapy, Shabnam Malik, Mohammed Sikander, Natasha Bell, Daniel Zubieta, Maria C. Bell, Murali Yallapu, Subhash Chauhan

School of Medicine Publications

Ovarian cancer stands as the deadliest gynecologic malignancy, responsible for nearly 65% of all gynecologic cancer-related deaths. The challenges in early detection and diagnosis, coupled with the widespread intraperitoneal spread of cancer cells and resistance to chemotherapy, contribute significantly to the high mortality rate of this disease. Due to the absence of specific symptoms and the lack of effective screening methods, most ovarian cancer cases are diagnosed at advanced stages. While chemotherapy is a common treatment, it often leads to tumor recurrence, necessitating further interventions. In recent years, antibody-drug conjugates (ADCs) have emerged as a valuable tool in targeted cancer …


The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton Aug 2024

The Dna Methylome Of Pediatric Brain Tumors Appears Shaped By Structural Variation And Predicts Survival, Fengju Chen, Yiqun Zhang, Lanlan Shen, Chad J Creighton

Faculty, Staff and Students Publications

Structural variation heavily influences the molecular landscape of cancer, in part by impacting DNA methylation-mediated transcriptional regulation. Here, using multi-omic datasets involving >2400 pediatric brain and central nervous system tumors of diverse histologies from the Children's Brain Tumor Network, we report hundreds of genes and associated CpG islands (CGIs) for which the nearby presence of somatic structural variant (SV) breakpoints is recurrently associated with altered expression or DNA methylation, respectively, including tumor suppressor genes ATRX and CDKN2A. Altered DNA methylation near enhancers associates with nearby somatic SV breakpoints, including MYC and MYCN. A subset of genes with SV-CGI methylation associations …


Cefiderocol Heteroresistance Associated With Mutations In Tonb-Dependent Receptor Genes In Pseudomonas Aeruginosa Of Clinical Origin, Stephanie L Egge, Samie A Rizvi, Shelby R Simar, Manuel Alcalde, Jose R W Martinez, Blake M Hanson, An Q Dinh, Rodrigo P Baptista, Truc T Tran, Samuel A Shelburne, Jose M Munita, Cesar A Arias, Morgan Hakki, William R Miller Aug 2024

Cefiderocol Heteroresistance Associated With Mutations In Tonb-Dependent Receptor Genes In Pseudomonas Aeruginosa Of Clinical Origin, Stephanie L Egge, Samie A Rizvi, Shelby R Simar, Manuel Alcalde, Jose R W Martinez, Blake M Hanson, An Q Dinh, Rodrigo P Baptista, Truc T Tran, Samuel A Shelburne, Jose M Munita, Cesar A Arias, Morgan Hakki, William R Miller

Faculty, Staff and Student Publications

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa …


Video And Phone Visit Use Differed By Language Preference Among Us Latino And Chinese Adults During The First 9 Months Of The Covid-19 Pandemic: A Cross-Sectional Electronic Health Record Study, Nancy P Gordon, Teresa Y Lin, Antonia Torreblanca, Mary E Reed Aug 2024

Video And Phone Visit Use Differed By Language Preference Among Us Latino And Chinese Adults During The First 9 Months Of The Covid-19 Pandemic: A Cross-Sectional Electronic Health Record Study, Nancy P Gordon, Teresa Y Lin, Antonia Torreblanca, Mary E Reed

Faculty, Staff and Student Publications

BACKGROUND: During the first nine months of the COVID-19 emergency, patients were encouraged to use virtual versus clinic visits if in-person care was not deemed necessary by clinical staff. This study examined the association of spoken language preference and ethnicity with use of video versus phone virtual visits by US Latino and Chinese adult patients who got care in the same healthcare system.

METHODS: We analyzed electronic health record data for four groups of adults aged 26-85y who had ≥ 1 primary or specialty care outpatient clinician visits during April-December 2020: 80,869 Latino adults preferring Spanish (LEP Latino); 214,765 Latino …


Bispecific Antibodies And Autologous Chimeric Antigen Receptor T Cell Therapies For Treatment Of Hematological Malignancies, Samer Al Hadidi, Helen E Heslop, Malcolm K Brenner, Masataka Suzuki Aug 2024

Bispecific Antibodies And Autologous Chimeric Antigen Receptor T Cell Therapies For Treatment Of Hematological Malignancies, Samer Al Hadidi, Helen E Heslop, Malcolm K Brenner, Masataka Suzuki

Faculty, Staff and Students Publications

In recent years, the therapeutic landscape for hematological malignancies has markedly advanced, particularly since the inaugural approval of autologous chimeric antigen receptor T cell (CAR-T) therapy in 2017 for relapsed/refractory acute lymphoblastic leukemia (ALL). Autologous CAR-T therapy involves the genetic modification of a patient's T cells to specifically identify and attack cancer cells, while bispecific antibodies (BsAbs) function by binding to both cancer cells and immune cells simultaneously, thereby triggering an immune response against the tumor. The subsequent approval of various CAR-T therapies and BsAbs have revolutionized the treatment of multiple hematological malignancies, highlighting high response rates and a subset …


Pkd1 Mutant Clones Within Cirrhotic Livers Inhibit Steatohepatitis Without Promoting Cancer, Min Zhu, Yunguan Wang, Tianshi Lu, Jason Guo, Lin Li, Meng-Hsiung Hsieh, Purva Gopal, Yi Han, Naoto Fujiwara, Darren P Wallace, Alan S L Yu, Xiangyi Fang, Crystal Ransom, Sara Verschleisser, David Hsiehchen, Yujin Hoshida, Amit G Singal, Adam Yopp, Tao Wang, Hao Zhu Aug 2024

Pkd1 Mutant Clones Within Cirrhotic Livers Inhibit Steatohepatitis Without Promoting Cancer, Min Zhu, Yunguan Wang, Tianshi Lu, Jason Guo, Lin Li, Meng-Hsiung Hsieh, Purva Gopal, Yi Han, Naoto Fujiwara, Darren P Wallace, Alan S L Yu, Xiangyi Fang, Crystal Ransom, Sara Verschleisser, David Hsiehchen, Yujin Hoshida, Amit G Singal, Adam Yopp, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

Somatic mutations in non-malignant tissues are selected for because they confer increased clonal fitness. However, it is uncertain whether these clones can benefit organ health. Here, ultra-deep targeted sequencing of 150 liver samples from 30 chronic liver disease patients revealed recurrent somatic mutations. PKD1 mutations were observed in 30% of patients, whereas they were only detected in 1.3% of hepatocellular carcinomas (HCCs). To interrogate tumor suppressor functionality, we perturbed PKD1 in two HCC cell lines and six in vivo models, in some cases showing that PKD1 loss protected against HCC, but in most cases showing no impact. However, Pkd1 haploinsufficiency …


Disability In Cluster Headache Is More Than Attack Frequency – Results From And Validation Of The English Version Of The Cluster Headache Impact Questionnaire (Chiq), Katharina Kamm, Andreas Straube, Mark Burish, Ruth Ruscheweyh Aug 2024

Disability In Cluster Headache Is More Than Attack Frequency – Results From And Validation Of The English Version Of The Cluster Headache Impact Questionnaire (Chiq), Katharina Kamm, Andreas Straube, Mark Burish, Ruth Ruscheweyh

Faculty, Staff and Student Publications

BACKGROUND: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire.

METHODS: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group.

RESULTS: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by …


Adjuvant External Beam Radiotherapy Combined With Brachytherapy For Intermediate-Risk Cervical Cancer, Nuria Agusti, David Viveros-Carreño, Alexander Melamed, Rene Pareja, Alexa Kanbergs, Chi-Fang Wu, Roni Nitecki, Lauren Colbert, Jose Alejandro Rauh-Hain Aug 2024

Adjuvant External Beam Radiotherapy Combined With Brachytherapy For Intermediate-Risk Cervical Cancer, Nuria Agusti, David Viveros-Carreño, Alexander Melamed, Rene Pareja, Alexa Kanbergs, Chi-Fang Wu, Roni Nitecki, Lauren Colbert, Jose Alejandro Rauh-Hain

Faculty, Staff and Student Publications

Objective: Patients with intermediate-risk cervical cancer receive external beam radiotherapy (EBRT) as adjuvant treatment. It is commonly administered with brachytherapy without proven benefits. Therefore, we evaluated the frequency of brachytherapy use, the doses for EBRT administered alone or with brachytherapy, and the overall survival impact of brachytherapy in patients with intermediate-risk, early-stage cervical cancer.

Methods: This retrospective cohort study was performed using data collected from the National Cancer Database. Patients diagnosed with cervical cancer from 2004 to 2019 who underwent a radical hysterectomy and lymph node staging and had disease limited to the cervix but with tumors larger than 4 …


The Oncolytic Adenovirus Delta-24-Rgd In Combination With Onc201 Induces A Potent Antitumor Response In Pediatric High-Grade And Diffuse Midline Glioma Models, Daniel De La Nava, Iker Ausejo-Mauleon, Virginia Laspidea, Marisol Gonzalez-Huarriz, Andrea Lacalle, Noelia Casares, Marta Zalacain, Lucía Marrodan, Marc García-Moure, Maria C Ochoa, Antonio Carlos Tallon-Cobos, Reyes Hernandez-Osuna, Javier Marco-Sanz, Laasya Dhandapani, Irati Hervás-Corpión, Oren J Becher, Javad Nazarian, Sabine Mueller, Timothy N Phoenix, Jasper Van Der Lugt, Mikel Hernaez, Elizabeth Guruceaga, Carl Koschmann, Sriram Venneti, Joshua E Allen, Matthew D Dun, Juan Fueyo, Candelaria Gomez-Manzano, Jaime Gallego Perez-Larraya, Ana Patiño-García, Sara Labiano, Marta M Alonso Aug 2024

The Oncolytic Adenovirus Delta-24-Rgd In Combination With Onc201 Induces A Potent Antitumor Response In Pediatric High-Grade And Diffuse Midline Glioma Models, Daniel De La Nava, Iker Ausejo-Mauleon, Virginia Laspidea, Marisol Gonzalez-Huarriz, Andrea Lacalle, Noelia Casares, Marta Zalacain, Lucía Marrodan, Marc García-Moure, Maria C Ochoa, Antonio Carlos Tallon-Cobos, Reyes Hernandez-Osuna, Javier Marco-Sanz, Laasya Dhandapani, Irati Hervás-Corpión, Oren J Becher, Javad Nazarian, Sabine Mueller, Timothy N Phoenix, Jasper Van Der Lugt, Mikel Hernaez, Elizabeth Guruceaga, Carl Koschmann, Sriram Venneti, Joshua E Allen, Matthew D Dun, Juan Fueyo, Candelaria Gomez-Manzano, Jaime Gallego Perez-Larraya, Ana Patiño-García, Sara Labiano, Marta M Alonso

Faculty, Staff and Student Publications

BACKGROUND: Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated.

METHODS: The production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the …


The Bench To Community Initiative: Community-Based Participatory Research Model For Translating Research Discoveries Into Community Solutions, Jazma L. Tapia, Abigail Lopez, D. Bing Turner, Tonya Fairley, Tiah Tomlin-Harris, Maggie Hawkins, Pastor Rhonda Holbert, Lindsey S. Treviño, Dede K. Teteh-Brooks Aug 2024

The Bench To Community Initiative: Community-Based Participatory Research Model For Translating Research Discoveries Into Community Solutions, Jazma L. Tapia, Abigail Lopez, D. Bing Turner, Tonya Fairley, Tiah Tomlin-Harris, Maggie Hawkins, Pastor Rhonda Holbert, Lindsey S. Treviño, Dede K. Teteh-Brooks

Health Sciences and Kinesiology Faculty Articles

Methods: Community-based participatory research (CBPR) is an effective methodology for translating research findings from academia to community interventions. The Bench to Community Initiative (BCI), a CBPR program, builds on prior research to engage stakeholders across multiple disciplines with the goal of disseminating interventions to reduce breast cancer disparities and improve quality of life of Black communities.

The BCI program was established to understand sociocultural determinants of personal care product use, evaluate the biological impact of endocrine disrupting chemicals, and develop community interventions. The three pillars of the program include research, outreach and engagement as well as advocacy activities. The research …


A Comparative Analysis Of Helical Tomotherapy Planning With Active Versus Total Bone Marrow Sparing Using Dual-Energy Computed Tomography, April E. Premo Aug 2024

A Comparative Analysis Of Helical Tomotherapy Planning With Active Versus Total Bone Marrow Sparing Using Dual-Energy Computed Tomography, April E. Premo

Masters Projects

Purpose: This study aims to compare helical tomotherapy (HT) plans using active bone marrow (ABM) sparing contouring versus traditional bone marrow (BM) sparing contouring using dual-energy computed tomography (DECT) in the treatment of gynecologic (GYN) cancers. The goal is to evaluate the effects of using ABM contours in optimization on organs at risk (OAR) and planning target volumes (PTVs).

Methods: The study involved creating HT plans for GYN cancer patients, utilizing both ABM and BM contouring techniques. DECT was used to distinguish between active and inactive bone marrow. Dosimetric comparisons were made between BM and ABM sparing plans. Statistical analyses …


Tumour-Intrinsic Endomembrane Trafficking By Arf6 Shapes An Immunosuppressive Microenvironment That Drives Melanomagenesis And Response To Checkpoint Blockade Therapy, Yinshen Wee, Junhua Wang, Emily C Wilson, Coulson P Rich, Aaron Rogers, Zongzhong Tong, Evelyn Degroot, Y N Vashisht Gopal, Michael A Davies, H Atakan Ekiz, Joshua K H Tay, Chris Stubben, Kenneth M Boucher, Juan M Oviedo, Keke C Fairfax, Matthew A Williams, Sheri L Holmen, Roger K Wolff, Allie H Grossmann Aug 2024

Tumour-Intrinsic Endomembrane Trafficking By Arf6 Shapes An Immunosuppressive Microenvironment That Drives Melanomagenesis And Response To Checkpoint Blockade Therapy, Yinshen Wee, Junhua Wang, Emily C Wilson, Coulson P Rich, Aaron Rogers, Zongzhong Tong, Evelyn Degroot, Y N Vashisht Gopal, Michael A Davies, H Atakan Ekiz, Joshua K H Tay, Chris Stubben, Kenneth M Boucher, Juan M Oviedo, Keke C Fairfax, Matthew A Williams, Sheri L Holmen, Roger K Wolff, Allie H Grossmann

Faculty, Staff and Student Publications

Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with …


Non-Receptor Tyrosine Kinases: Their Structure And Mechanistic Role In Tumor Progression And Resistance, Abdulaziz M. Eshaq, Thomas W. Flanagan, Sofie Yasmin Hassan, Sara A. Al Asheikh, Waleed A. Al-Amoudi, Simeon Santourlidis, Sarah Lilly Hassan, Maryam O. Alamodi, Marcelo L. Bendhack, Mohammed O. Alamodi, Youssef Haikel, Mossad Megahed, Mohamed Hassan Aug 2024

Non-Receptor Tyrosine Kinases: Their Structure And Mechanistic Role In Tumor Progression And Resistance, Abdulaziz M. Eshaq, Thomas W. Flanagan, Sofie Yasmin Hassan, Sara A. Al Asheikh, Waleed A. Al-Amoudi, Simeon Santourlidis, Sarah Lilly Hassan, Maryam O. Alamodi, Marcelo L. Bendhack, Mohammed O. Alamodi, Youssef Haikel, Mossad Megahed, Mohamed Hassan

School of Graduate Studies Faculty Publications

Protein tyrosine kinases (PTKs) function as key molecules in the signaling pathways in addition to their impact as a therapeutic target for the treatment of many human diseases, including cancer. PTKs are characterized by their ability to phosphorylate serine, threonine, or tyrosine residues and can thereby rapidly and reversibly alter the function of their protein substrates in the form of significant changes in protein confirmation and affinity for their interaction with protein partners to drive cellular functions under normal and pathological conditions. PTKs are classified into two groups: one of which represents tyrosine kinases, while the other one includes the …


Translational Modeling-Based Evidence For Enhanced Efficacy Of Standard-Of-Care Drugs In Combination With Anti-Microrna-155 In Non-Small-Cell Lung Cancer, Prashant Dogra, Vrushaly Shinglot, Javier Ruiz-Ramírez, Joseph Cave, Joseph D Butner, Carmine Schiavone, Dan G Duda, Ahmed O Kaseb, Caroline Chung, Eugene J Koay, Vittorio Cristini, Bulent Ozpolat, George A Calin, Zhihui Wang Aug 2024

Translational Modeling-Based Evidence For Enhanced Efficacy Of Standard-Of-Care Drugs In Combination With Anti-Microrna-155 In Non-Small-Cell Lung Cancer, Prashant Dogra, Vrushaly Shinglot, Javier Ruiz-Ramírez, Joseph Cave, Joseph D Butner, Carmine Schiavone, Dan G Duda, Ahmed O Kaseb, Caroline Chung, Eugene J Koay, Vittorio Cristini, Bulent Ozpolat, George A Calin, Zhihui Wang

Faculty, Staff and Student Publications

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.

METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.

RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg …


Kinesin Facilitates Phenotypic Targeting Of Therapeutic Resistance In Advanced Prostate Cancer, Maddison Archer, Diane Begemann, Edgar Gonzalez-Kozlova, Prerna R Nepali, Estefania Labanca, Peter Shepherd, Navneet Dogra, Nora Navone, Natasha Kyprianou Aug 2024

Kinesin Facilitates Phenotypic Targeting Of Therapeutic Resistance In Advanced Prostate Cancer, Maddison Archer, Diane Begemann, Edgar Gonzalez-Kozlova, Prerna R Nepali, Estefania Labanca, Peter Shepherd, Navneet Dogra, Nora Navone, Natasha Kyprianou

Faculty, Staff and Student Publications

Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer. Previous work showed that dynamic interconversions between epithelial-mesenchymal transition to mesenchymal-epithelial transition defines the phenotypic landscape of prostate tumors, as a potential driver of the emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa patient-derived xenograft models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between antiandrogen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype. Transcriptomic profiling revealed that resistant and sensitive prostate cancer C4-2B cells have a unique differential …


Brca1-Mediated Dual Regulation Of Ferroptosis Exposes A Vulnerability To Gpx4 And Parp Co-Inhibition In Brca1-Deficient Cancers, Guang Lei, Chao Mao, Amber D Horbath, Yuelong Yan, Shirong Cai, Jun Yao, Yan Jiang, Mingchuang Sun, Xiaoguang Liu, Jun Cheng, Zhihao Xu, Hyemin Lee, Qidong Li, Zhengze Lu, Li Zhuang, Mei-Kuang Chen, Anagha Alapati, Timothy A Yap, Mien-Chie Hung, Mingjian James You, Helen Piwnica-Worms, Boyi Gan Aug 2024

Brca1-Mediated Dual Regulation Of Ferroptosis Exposes A Vulnerability To Gpx4 And Parp Co-Inhibition In Brca1-Deficient Cancers, Guang Lei, Chao Mao, Amber D Horbath, Yuelong Yan, Shirong Cai, Jun Yao, Yan Jiang, Mingchuang Sun, Xiaoguang Liu, Jun Cheng, Zhihao Xu, Hyemin Lee, Qidong Li, Zhengze Lu, Li Zhuang, Mei-Kuang Chen, Anagha Alapati, Timothy A Yap, Mien-Chie Hung, Mingjian James You, Helen Piwnica-Worms, Boyi Gan

Faculty, Staff and Student Publications

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i …


Rosiglitazone And Trametinib Exhibit Potent Anti-Tumor Activity In A Mouse Model Of Muscle Invasive Bladder Cancer, Sakina A Plumber, Tiffany Tate, Hikmat Al-Ahmadie, Xiao Chen, Woonyoung Choi, Merve Basar, Chao Lu, Aaron Viny, Ekatherina Batourina, Jiaqi Li, Kristjan Gretarsson, Besmira Alija, Andrei Molotkov, Gregory Wiessner, Byron Hing Lung Lee, James Mckiernan, David J Mcconkey, Colin Dinney, Bogdan Czerniak, Cathy Lee Mendelsohn Aug 2024

Rosiglitazone And Trametinib Exhibit Potent Anti-Tumor Activity In A Mouse Model Of Muscle Invasive Bladder Cancer, Sakina A Plumber, Tiffany Tate, Hikmat Al-Ahmadie, Xiao Chen, Woonyoung Choi, Merve Basar, Chao Lu, Aaron Viny, Ekatherina Batourina, Jiaqi Li, Kristjan Gretarsson, Besmira Alija, Andrei Molotkov, Gregory Wiessner, Byron Hing Lung Lee, James Mckiernan, David J Mcconkey, Colin Dinney, Bogdan Czerniak, Cathy Lee Mendelsohn

Faculty, Staff and Student Publications

Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. …


Znf397 Deficiency Triggers Tet2-Driven Lineage Plasticity And Ar-Targeted Therapy Resistance In Prostate Cancer, Yaru Xu, Yuqiu Yang, Zhaoning Wang, Martin Sjöström, Yuyin Jiang, Yitao Tang, Siyuan Cheng, Su Deng, Choushi Wang, Julisa Gonzalez, Nickolas A Johnson, Xiang Li, Xiaoling Li, Lauren A Metang, Atreyi Mukherji, Quanhui Xu, Carla R Tirado, Garrett Wainwright, Xinzhe Yu, Spencer Barnes, Mia Hofstad, Yu Chen, Hong Zhu, Ariella B Hanker, Ganesh V Raj, Guanghui Zhu, Housheng H He, Zhao Wang, Carlos L Arteaga, Han Liang, Felix Y Feng, Yunguan Wang, Tao Wang, Ping Mu Aug 2024

Znf397 Deficiency Triggers Tet2-Driven Lineage Plasticity And Ar-Targeted Therapy Resistance In Prostate Cancer, Yaru Xu, Yuqiu Yang, Zhaoning Wang, Martin Sjöström, Yuyin Jiang, Yitao Tang, Siyuan Cheng, Su Deng, Choushi Wang, Julisa Gonzalez, Nickolas A Johnson, Xiang Li, Xiaoling Li, Lauren A Metang, Atreyi Mukherji, Quanhui Xu, Carla R Tirado, Garrett Wainwright, Xinzhe Yu, Spencer Barnes, Mia Hofstad, Yu Chen, Hong Zhu, Ariella B Hanker, Ganesh V Raj, Guanghui Zhu, Housheng H He, Zhao Wang, Carlos L Arteaga, Han Liang, Felix Y Feng, Yunguan Wang, Tao Wang, Ping Mu

Faculty, Staff and Students Publications

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming that allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified zinc finger protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a ten-eleven translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our …


Adult-Onset T-Cell Acute Lymphoblastic Lymphoma-Leukemia Presenting With Petechial Rash: A Case Report., Kelly Kimball, Vissy Elad, Edward J Hamad, Christopher Wasco Aug 2024

Adult-Onset T-Cell Acute Lymphoblastic Lymphoma-Leukemia Presenting With Petechial Rash: A Case Report., Kelly Kimball, Vissy Elad, Edward J Hamad, Christopher Wasco

Oncology Articles

T-cell acute lymphoblastic lymphoma-leukemia (T-ALL) is a rare neoplastic disease with presenting symptoms that are often non-specific. As such, accurate diagnosis requires high clinical suspicion and assessment of bone marrow aspirate with flow cytometry and morphology. While remission is achievable in most patients, the five-year survival rate is only 48% despite treatment. The standard chemotherapy regimen is referred to as hyper-CVAD, where CVAD stands for cyclophosphamide, vincristine sulfate, Adriamycin (doxorubicin), methotrexate, and dexamethasone. In this study, we describe a 38-year-old female who presented with atraumatic abdominal bruising and a petechial rash on the upper and lower extremities. Imaging revealed a …


A Retrospective Comparison Between Analytical Anisotropic Algorithm (Aaa) And Acuros Xb (Axb) Calculation Algorithms Concerning The Left Anterior Descending Coronary Artery Radiation Dose In Left Breast Cancer Patients Utilizing Deep Inspiration Breath Hold, Melissa Wilkinson Aug 2024

A Retrospective Comparison Between Analytical Anisotropic Algorithm (Aaa) And Acuros Xb (Axb) Calculation Algorithms Concerning The Left Anterior Descending Coronary Artery Radiation Dose In Left Breast Cancer Patients Utilizing Deep Inspiration Breath Hold, Melissa Wilkinson

Masters Projects

Abstract

Background: Minimizing radiation exposure to the left anterior descending coronary artery (LAD) is crucial during left-sided breast cancer radiation therapy to prevent cardiac complications. Dose calculation algorithms can significantly impact the estimated LAD dose. This study investigates the differences between the Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB) algorithms in LAD dose calculations.

Methods: Thirty patients treated with radiation therapy after breast-conserving surgery were included. Dosimetric data for LAD, including mean and maximum dose, was calculated using AAA and AXB algorithms. The results were compared using statistical analysis.

Results: Statistically significant reductions in mean LAD dose were observed …


The Invisible Co-Afflicted: Caregivers Of Rectal Cancer Survivors, Qi Chen Aug 2024

The Invisible Co-Afflicted: Caregivers Of Rectal Cancer Survivors, Qi Chen

Publications and Research

Formal survivorship care after successful rectal cancer treatment is lacking, and this burden falls to caregivers. Caregivers, many of whom have no healthcare training, are asked to take on management of bowel function difficulties, ostomy care, while providing tangible, emotional, and financial support for rectal cancer survivors. The rise of young-onset rectal cancer also adds new survivorship care needs, such as family planning and returning to workplace, which compounds existing caregiver responsibilities and burdens.


Growing The Global Cancer Care System: Success Stories From Around The World And Lessons For The Future, Edward Christopher Dee, C. S. Pramesh, Christopher M. Booth, Fidel Rubagumya, Miriam Mutebi, Erin Jay G. Feliciano, Michelle Ann B. Eala, Giovanni G. Cerri, Ophira Ginsburg, Bishal Gyawali, Fabio Ynoe Moraes Aug 2024

Growing The Global Cancer Care System: Success Stories From Around The World And Lessons For The Future, Edward Christopher Dee, C. S. Pramesh, Christopher M. Booth, Fidel Rubagumya, Miriam Mutebi, Erin Jay G. Feliciano, Michelle Ann B. Eala, Giovanni G. Cerri, Ophira Ginsburg, Bishal Gyawali, Fabio Ynoe Moraes

Ateneo School of Medicine and Public Health Publications

Despite major biomedical advancements in various realms of oncology, the benefits of these developments are not equitably distributed, particularly in underresourced settings. Although much work has described the challenges and systemic barriers in global cancer control, in this article we focus on success stories. This article describes clinical care delivered at Rwanda’s Butaro Cancer Center of Excellence, the cancer research collaborations under India’s National Cancer Grid, and the efforts of Latin America’s Institute of Cancer of São Paulo in advancing cancer care and training. These examples highlight the potential of strategic collaborations and resource allocation strategies in improving cancer care …


High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine Aug 2024

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …


Women's Experience Of Cancer Treatment During Covid-19 On The Texas-Mexico Border, Kayla E. Castañeda Aug 2024

Women's Experience Of Cancer Treatment During Covid-19 On The Texas-Mexico Border, Kayla E. Castañeda

Nursing Theses and Dissertations

The COVID-19 pandemic exposed existing racial, ethnic, socioeconomic, geographic, and gender disparities in cancer care and highlighted the need for more research in understudied populations. No studies have elucidated the experience of women living on the Texas-Mexico border receiving cancer treatment during the pandemic. This study explored the lived experience of receiving cancer treatment during the COVID-19 pandemic in 2020 for women living on the Texas-Mexico border and identified participants' self-identified unmet needs while receiving cancer treatment during the COVID-19 pandemic on the Texas-Mexico border. Following IRB approval and informed consent, ten women living on the Texas-Mexico border who received …


Association Between Time From Surgery To Radiation Therapy And Multimodality Treatment Outcomes In Hpv+ Head And Neck Cancer: A Multi-Institutional Cohort Experience, Muneeb Niazi, Ryan Miller, Ryann Kolb, Wenyan Ji, Alicia Lozano, Monica Ahrens, Alexandra Hanlon, Max Pickles, Andrew Song, Voichita Bar-Ad, Neil Hockstein, Sujung Park, Adam Raben, Gaurav Shukla Aug 2024

Association Between Time From Surgery To Radiation Therapy And Multimodality Treatment Outcomes In Hpv+ Head And Neck Cancer: A Multi-Institutional Cohort Experience, Muneeb Niazi, Ryan Miller, Ryann Kolb, Wenyan Ji, Alicia Lozano, Monica Ahrens, Alexandra Hanlon, Max Pickles, Andrew Song, Voichita Bar-Ad, Neil Hockstein, Sujung Park, Adam Raben, Gaurav Shukla

Department of Radiation Oncology Faculty Papers

Purpose: Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs. We hypothesized that TSRT beyond 6 weeks may not portend poorer outcomes for the former. Methods: We identified nonmetastatic, high-risk HPV+ OPSCCs treated with multimodal therapy at 2 institutions. Prolonged TSRT was defined as >6 weeks and was evaluated for association with recurrence-free survival (RFS). Radiation treatment time …


Adopting A Systems-Thinking Approach To Optimise Dietary And Exercise Referral Practices For Cancer Survivors, Ria Joseph, Nicolas H. Hart, Natalie Bradford, Fiona Crawford-Williams, Matthew P. Wallen, Reegan Knowles, Chad Y. Han, Vivienne Milch, Justin J. Holland, Raymond J. Chan Aug 2024

Adopting A Systems-Thinking Approach To Optimise Dietary And Exercise Referral Practices For Cancer Survivors, Ria Joseph, Nicolas H. Hart, Natalie Bradford, Fiona Crawford-Williams, Matthew P. Wallen, Reegan Knowles, Chad Y. Han, Vivienne Milch, Justin J. Holland, Raymond J. Chan

Research outputs 2022 to 2026

Purpose: Service referrals are required for cancer survivors to access specialist dietary and exercise support. Many system-level factors influence referral practices within the healthcare system. Hence, the aim of this study was to identify system-level factors and their interconnectedness, as well as strategies for optimising dietary and exercise referral practices in Australia. Methods: A full-day workshop involving national multidisciplinary key stakeholders explored system-level factors impacting dietary and exercise referral practices. Facilitated group discussions using the nominal group technique identified barriers and facilitators to referral practices based on the six World Health Organisation (WHO) building blocks. The systems-thinking approach generated six …


Utilising Discriminant Function Analysis (Dfa) For Classifying Osteoarthritis (Oa) Patients And Volunteers Based On Biomarker Concentration, Laura Jane Coleman, John L Byrne, Stuart Edwards, Rosemary O'Hara Aug 2024

Utilising Discriminant Function Analysis (Dfa) For Classifying Osteoarthritis (Oa) Patients And Volunteers Based On Biomarker Concentration, Laura Jane Coleman, John L Byrne, Stuart Edwards, Rosemary O'Hara

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of cartilage, causing pain, stiffness, and limited movement. Early diagnosis is crucial for effective management but remains challenging due to non-specific early symptoms. This study explores the application of Discriminant Function Analysis (DFA) to classify OA patients and healthy volunteers based on biomarker concentrations of Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α), and Myeloperoxidase (MPO). DFA was employed to analyse biomarker data from 86 participants (58 patients, 28 volunteers) to evaluate the discriminatory power of these biomarkers in predicting OA. Significant differences were observed in MPO and TNF-α levels between …


Institution-Wide Retreats Foster Organizational Learning And Action At A Comprehensive Cancer Center, Benjamin R Schrank, John A Fuller, Colleen M Gallagher, Van K Morris, Emma B Holliday, Kelly Merriman, Lynne Nguyen, Lou Weaver, Kelly Nelson, Elizabeth Chiao, Albert C Koong, Ernest Hawk, Shine Chang Aug 2024

Institution-Wide Retreats Foster Organizational Learning And Action At A Comprehensive Cancer Center, Benjamin R Schrank, John A Fuller, Colleen M Gallagher, Van K Morris, Emma B Holliday, Kelly Merriman, Lynne Nguyen, Lou Weaver, Kelly Nelson, Elizabeth Chiao, Albert C Koong, Ernest Hawk, Shine Chang

Faculty, Staff and Student Publications

Providing safe and informed healthcare for sexual and gender minority (SGM) individuals with cancer is stymied by the lack of sexual orientation and gender identity (SOGI) data reliably available in health records and by insufficient training for staff. Approaches that support institutional learning, especially around sensitive topics, are essential for hospitals seeking to improve practices impacting patient safety and research. We engineered annual institutional retreats to identify and unify stakeholders, promote awareness of gaps and needs, identify initiatives, minimize redundant projects, and coordinate efforts that promote improvements in SGM cancer care, education, and research. The 2022 and 2023 retreats employed …