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Articles 361 - 390 of 891

Full-Text Articles in Medical Specialties

Normal Saline Remodels The Omentum And Stimulates Its Receptivity For Transcoelomic Metastasis, Hironari Akasaka, Wonjae Lee, Song Yi Ko, Ernst Lengyel, Honami Naora Jun 2023

Normal Saline Remodels The Omentum And Stimulates Its Receptivity For Transcoelomic Metastasis, Hironari Akasaka, Wonjae Lee, Song Yi Ko, Ernst Lengyel, Honami Naora

Faculty, Staff and Student Publications

The omentum contains immune cell structures called milky spots that are niches for transcoelomic metastasis. It is difficult to remove the omentum completely, and there are no effective strategies to minimize the risk of colonization of preserved omental tissues by cancer cells that circulate in the peritoneal fluid. Normal saline is commonly administered into the peritoneal cavity for diagnostic and intraoperative lavage. Here we show that normal saline, when administered into the peritoneal cavity of mice, is prominently absorbed by the omentum, exfoliates its mesothelium, and induces expression of CX3CL1, the ligand for CX3CR1, within and surrounding the omental vasculature. …


Proteogenomic Landscape Of Gastric Adenocarcinoma Peritoneal Metastases, Shuangtao Zhao, Ruiping Wang, Shumei Song, Dapeng Hao, Guangchun Han, Xingzhi Song, Jianhua Zhang, Melissa Pool Pizzi, Namita Shanbhag, Andrew Futreal, Brian Badgwell, Kazuto Harada, George Calin, Jody Vykoukal, Chuan-Yih Yu, Hiroyuki Katayama, Samir M Hanash, Linghua Wang, Jaffer A Ajani Jun 2023

Proteogenomic Landscape Of Gastric Adenocarcinoma Peritoneal Metastases, Shuangtao Zhao, Ruiping Wang, Shumei Song, Dapeng Hao, Guangchun Han, Xingzhi Song, Jianhua Zhang, Melissa Pool Pizzi, Namita Shanbhag, Andrew Futreal, Brian Badgwell, Kazuto Harada, George Calin, Jody Vykoukal, Chuan-Yih Yu, Hiroyuki Katayama, Samir M Hanash, Linghua Wang, Jaffer A Ajani

Faculty, Staff and Student Publications

Advanced gastric adenocarcinoma (GAC) often leads to peritoneal carcinomatosis (PC) and is associated with very poor outcome. Here we report the comprehensive proteogenomic study of ascites derived cells from a prospective GAC cohort (n = 26 patients with peritoneal carcinomatosis, PC). A total of 16,449 proteins were detected from whole cell extracts (TCEs). Unsupervised hierarchical clustering resulted in three distinct groups that reflected extent of enrichment in tumor cells. Integrated analysis revealed enriched biological pathways and notably, some druggable targets (cancer-testis antigens, kinases, and receptors) that could be exploited to develop effective therapies and/or tumor stratifications. Systematic comparison of expression …


Loss Of Ampkα2 Promotes Melanoma Tumor Growth And Brain Metastasis, Ping Yuan, Da Teng, Evelyn De Groot, Man Li, Sebastian Trousil, Che-Hung Shen, Jason Roszik, Michael A Davies, Y N Vashisht Gopal, Bin Zheng Jun 2023

Loss Of Ampkα2 Promotes Melanoma Tumor Growth And Brain Metastasis, Ping Yuan, Da Teng, Evelyn De Groot, Man Li, Sebastian Trousil, Che-Hung Shen, Jason Roszik, Michael A Davies, Y N Vashisht Gopal, Bin Zheng

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is a critical cellular energy sensor at the interface of metabolism and cancer. However, the role of AMPK in carcinogenesis remains unclear. Here, through analysis of the TCGA melanoma dataset, we found that PRKAA2 gene that encodes the α2 subunit of AMPK is mutated in ∼9% of cutaneous melanomas, and these mutations tend to co-occur with NF1 mutations. Knockout of AMPKα2 promoted anchorage-independent growth of NF1-mutant melanoma cells, whereas ectopic expression of AMPKα2 inhibited their growth in soft agar assays. Moreover, loss of AMPKα2 accelerated tumor growth of NF1-mutant melanoma and enhanced their brain …


A Novel Bioactive Peptide, T14, Selectively Activates Mtorc1 Signalling: Therapeutic Implications For Neurodegeneration And Other Rapamycin-Sensitive Applications, Sanskar Ranglani, Anna Ashton, Kashif Mahfooz, Joanna Komorowska, Alexandru Graur, Nadine Kabbani, Sara Garcia-Rates, Susan Greenfield Jun 2023

A Novel Bioactive Peptide, T14, Selectively Activates Mtorc1 Signalling: Therapeutic Implications For Neurodegeneration And Other Rapamycin-Sensitive Applications, Sanskar Ranglani, Anna Ashton, Kashif Mahfooz, Joanna Komorowska, Alexandru Graur, Nadine Kabbani, Sara Garcia-Rates, Susan Greenfield

Faculty, Staff and Student Publications

T14 modulates calcium influx via the α-7 nicotinic acetylcholine receptor to regulate cell growth. Inappropriate triggering of this process has been implicated in Alzheimer's disease (AD) and cancer, whereas T14 blockade has proven therapeutic potential in in vitro, ex vivo and in vivo models of these pathologies. Mammalian target of rapamycin complex 1 (mTORC1) is critical for growth, however its hyperactivation is implicated in AD and cancer. T14 is a product of the longer 30mer-T30. Recent work shows that T30 drives neurite growth in the human SH-SY5Y cell line via the mTOR pathway. Here, we demonstrate that T30 induces an …


Covid-19 Severity And Cardiovascular Outcomes In Sars-Cov-2-Infected Patients With Cancer And Cardiovascular Disease, Melissa Y.Y. Moey, Cassandra Hennessy, Benjamin French, Jeremy L. Warner, Matthew D. Tucker, Daniel J. Hausrath, Dimpy P. Shah, Jeanne M. Decara, Ziad Bakouny, Chris Labaki, Toni K. Choueiri, Susan Dent, Nausheen Akhter, Roohi Ismail-Khan, Lisa Tachiki, David Slosky, Tamar S. Polonsky, Joy A. Awosika, Audrey Crago, Trisha Wise-Draper, Nino Balanchivadze, Clara Hwang, Leslie A. Fecher, Cyndi Gonzalez Gomez, Brandon Hayes-Lattin, Michael J. Glover, Sumit A. Shah, Dharmesh Gopalakrishnan, Elizabeth A. Griffiths, Daniel H. Kwon, Vadim S. Koshkin, Sana Mahmood, Babar Bashir, Taylor Nonato, Pedram Razavi, Rana R. Mckay, Gayathri Nagaraj, Eric Oligino, Matthew Puc, Polina Tregubenko, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Thorvardur R. Halfdanarson, Dimitrios Farmakiotis, Elizabeth J. Klein, Elizabeth V. Robilotti, Gregory J. Riely, Jean-Bernard Durand, Salim S. Hayek, Lavanya Kondapalli, Stephanie Berg, Timothy E. O'Connor, Mehmet A. Bilen, Cecilia Castellano, Melissa K. Accordino, Blau Sibel, Lisa B. Weissmann, Chinmay Jani, Daniel B. Flora, Lawrence Rudski, Miriam Santos Dutra, Bouganim Nathaniel, Erika Ruíz-García, Diana Vilar-Compte, Shilpa Gupta, Alicia Morgans, Anju Nohria Jun 2023

Covid-19 Severity And Cardiovascular Outcomes In Sars-Cov-2-Infected Patients With Cancer And Cardiovascular Disease, Melissa Y.Y. Moey, Cassandra Hennessy, Benjamin French, Jeremy L. Warner, Matthew D. Tucker, Daniel J. Hausrath, Dimpy P. Shah, Jeanne M. Decara, Ziad Bakouny, Chris Labaki, Toni K. Choueiri, Susan Dent, Nausheen Akhter, Roohi Ismail-Khan, Lisa Tachiki, David Slosky, Tamar S. Polonsky, Joy A. Awosika, Audrey Crago, Trisha Wise-Draper, Nino Balanchivadze, Clara Hwang, Leslie A. Fecher, Cyndi Gonzalez Gomez, Brandon Hayes-Lattin, Michael J. Glover, Sumit A. Shah, Dharmesh Gopalakrishnan, Elizabeth A. Griffiths, Daniel H. Kwon, Vadim S. Koshkin, Sana Mahmood, Babar Bashir, Taylor Nonato, Pedram Razavi, Rana R. Mckay, Gayathri Nagaraj, Eric Oligino, Matthew Puc, Polina Tregubenko, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Thorvardur R. Halfdanarson, Dimitrios Farmakiotis, Elizabeth J. Klein, Elizabeth V. Robilotti, Gregory J. Riely, Jean-Bernard Durand, Salim S. Hayek, Lavanya Kondapalli, Stephanie Berg, Timothy E. O'Connor, Mehmet A. Bilen, Cecilia Castellano, Melissa K. Accordino, Blau Sibel, Lisa B. Weissmann, Chinmay Jani, Daniel B. Flora, Lawrence Rudski, Miriam Santos Dutra, Bouganim Nathaniel, Erika Ruíz-García, Diana Vilar-Compte, Shilpa Gupta, Alicia Morgans, Anju Nohria

Kimmel Cancer Center Faculty Papers

BACKGROUND: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited.

OBJECTIVES: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF.

METHODS: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD

RESULTS: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity …


The Integrative Studies On The Functional A-To-I Rna Editing Events In Human Cancers, Sijia Wu, Zhiwei Fan, Pora Kim, Liyu Huang, Xiaobo Zhou Jun 2023

The Integrative Studies On The Functional A-To-I Rna Editing Events In Human Cancers, Sijia Wu, Zhiwei Fan, Pora Kim, Liyu Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases …


Immunometabolic Reprogramming, Another Cancer Hallmark, Vijay Kumar, John H. Stewart May 2023

Immunometabolic Reprogramming, Another Cancer Hallmark, Vijay Kumar, John H. Stewart

School of Medicine Faculty Publications

Molecular carcinogenesis is a multistep process that involves acquired abnormalities in key biological processes. The complexity of cancer pathogenesis is best illustrated in the six hallmarks of the cancer: (1) the development of self-sufficient growth signals, (2) the emergence of clones that are resistant to apoptosis, (3) resistance to the antigrowth signals, (4) neo-angiogenesis, (5) the invasion of normal tissue or spread to the distant organs, and (6) limitless replicative potential. It also appears that non-resolving inflammation leads to the dysregulation of immune cell metabolism and subsequent cancer progression. The present article delineates immunometabolic reprogramming as a critical hallmark of …


Guaranteed Income And Financial Treatment Trial (Gift Trial Or Giftt): A 12-Month, Randomized Controlled Trial To Compare The Effectiveness Of Monthly Unconditional Cash Transfers To Treatment As Usual In Reducing Financial Toxicity In People With Cancer Who Have Low Incomes, Meredith Doherty, Jonathan Heintz, Amy Leader, David Wittenburg, Yonatan Ben-Shalom, Jessica Jacoby, Amy Castro, Stacia West May 2023

Guaranteed Income And Financial Treatment Trial (Gift Trial Or Giftt): A 12-Month, Randomized Controlled Trial To Compare The Effectiveness Of Monthly Unconditional Cash Transfers To Treatment As Usual In Reducing Financial Toxicity In People With Cancer Who Have Low Incomes, Meredith Doherty, Jonathan Heintz, Amy Leader, David Wittenburg, Yonatan Ben-Shalom, Jessica Jacoby, Amy Castro, Stacia West

Department of Medical Oncology Faculty Papers

Cancer-related financial hardship (i.e., financial toxicity) has been associated with anxiety and depression, greater pain and symptom burden, treatment nonadherence, and mortality. Out-of-pocket healthcare costs and lost income are primary drivers of financial toxicity, however, income loss is a pronounced risk factor for cancer patients with low incomes. There has been little progress in developing an income intervention to alleviate financial toxicity cancer patients with low incomes. Unconditional cash transfers (UCT), or guaranteed income, have produced positive health effects in experiments with general low-income populations, but have not yet been evaluated in people with cancer. The Guaranteed Income and Financial …


Rare Presentation Of Metastatic Hepatocellular Carcinoma In The Finger: Case Report And Review Of Literature, F. Rhana Mousavi, Bassem Bekheit, Emon Alavi, Nick A. Hirad, Abanoub Gabra May 2023

Rare Presentation Of Metastatic Hepatocellular Carcinoma In The Finger: Case Report And Review Of Literature, F. Rhana Mousavi, Bassem Bekheit, Emon Alavi, Nick A. Hirad, Abanoub Gabra

Research Day

Hepatocellular carcinoma (HCC) is a primary tumor of the liver that primarily develops in the setting of chronic liver disease. HCC is difficult to diagnose due to it requiring the use of multiple imaging modalities with the goal to detect tumors when they are less than or equal to 2 cm in size to allow all possible treatment options to be used. Herein, we discuss a 69-year-old male with stage IV liver cancer residing in hospice presenting with left middle finger osteomyelitis and extreme pain. Radiology revealed a destructive lesion but pathology provided the diagnosis of metastatic hepatocellular carcinoma in …


Development Of Combination Therapy Strategies To Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors, Nicholas Mullen May 2023

Development Of Combination Therapy Strategies To Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors, Nicholas Mullen

Theses & Dissertations

Cancer cells require supraphysiologic levels of nucleotide triphosphates to fuel their malignant behaviors, including uncontrolled proliferation, immune evasion, metastasis, and therapy resistance. This requirement is met by hyperactive flux through the de novo pyrimidine and de novo purine pathways. Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo pyrimidine pathway that can be targeted by FDA approved and experimental drug compounds. A robust body of preclinical evidence, encompassing hundreds of independent studies over several decades, demonstrates impressive activity of DHODH inhibitors in animal models of cancer. Paradoxically, however, all clinical trials to date have failed to demonstrate efficacy …


Using Cancer Proteomics Data To Identify Gene Candidates For Therapeutic Targeting, Diana Monsivais, Sydney E Parks, Darshan S Chandrashekar, Sooryanarayana Varambally, Chad J Creighton May 2023

Using Cancer Proteomics Data To Identify Gene Candidates For Therapeutic Targeting, Diana Monsivais, Sydney E Parks, Darshan S Chandrashekar, Sooryanarayana Varambally, Chad J Creighton

Faculty, Staff and Students Publications

Gene-level associations obtained from mass-spectrometry-based cancer proteomics datasets represent a resource for identifying gene candidates for functional studies. When recently surveying proteomic correlates of tumor grade across multiple cancer types, we identified specific protein kinases having a functional impact on uterine endometrial cancer cells. This previously published study provides just one template for utilizing public molecular datasets to discover potential novel therapeutic targets and approaches for cancer patients. Proteomic profiling data combined with corresponding multi-omics data on human tumors and cell lines can be analyzed in various ways to prioritize genes of interest for interrogating biology. Across hundreds of cancer …


Meditation-Type Exercise For The Management Of Chemotherapy Related Cognitive Impairment In Breast Cancer Patients, Christine Cain May 2023

Meditation-Type Exercise For The Management Of Chemotherapy Related Cognitive Impairment In Breast Cancer Patients, Christine Cain

Evidence-Based Practice Project Reports

Chemotherapy-related cognitive impairment (CRCI), or “chemobrain”, is one of the most troublesome side effects of chemotherapy (Dijkshoorn et al., 2020). Ongoing CRCI may negatively affect relationships, confidence, sleep, fatigue, anxiety, and the ability to return to work activities leading to a decreased quality of life (Johns et al., 2016; Gokal et al., 2018). The purpose of this evidence-based practice (EBP) project was to assess the efficiency of a meditation-type exercise intervention, chair yoga, on decreasing perceived cognitive impairment (PCI) in breast cancer patients. The PICOT question for this project was: In breast cancer patients with chemotherapy related cognitive impairment (P), …


An In Vivo Biocompatibility Analysis Of A Novel Tissue Regeneration Matrix Using A Pig Model, Shamar Thomas May 2023

An In Vivo Biocompatibility Analysis Of A Novel Tissue Regeneration Matrix Using A Pig Model, Shamar Thomas

All Theses

The goal of this project is to develop an injectable bead scaffold to promote tissue regeneration in the void created by lumpectomy and to alleviate post lumpectomy problems by preventing local recurrence and minimizing surgical-related infections. Microbeads were synthesized from collagen type I and crosslinked with tannic acid to form the basis for this injectable therapeutic. Tannic acid acts as a therapeutic anticancer agent. The action mechanisms of tannins in breast cancer cells have been studied with studies showing tannins to be cytotoxic to cancer cells in a dose-dependent manner. Tannic acid induces apoptosis in breast cancer cells via caspase …


Highlights From The Second Choosing Wisely Africa Conference: A Roadmap To Value-Based Cancer Care In East Africa (9–10 February 2023, Dar Es Salaam, Tanzania), Rugengamanzi Eulade, Godwin Abdiel Nnko, Jerry Ndumbalo, Nazima Dharsee, Larry O. Akoko, Christian Ntizimira, Beda Likonda, Harrison Chuwa, Salum Lidenge, Verna Vanderpuye, Nazik Hammad, Sikudhani Muya, Rubagumya Rubagumya May 2023

Highlights From The Second Choosing Wisely Africa Conference: A Roadmap To Value-Based Cancer Care In East Africa (9–10 February 2023, Dar Es Salaam, Tanzania), Rugengamanzi Eulade, Godwin Abdiel Nnko, Jerry Ndumbalo, Nazima Dharsee, Larry O. Akoko, Christian Ntizimira, Beda Likonda, Harrison Chuwa, Salum Lidenge, Verna Vanderpuye, Nazik Hammad, Sikudhani Muya, Rubagumya Rubagumya

Internal Medicine, East Africa

The ecancer Choosing Wisely conference was held for the second time in Africa in Dar es Salaam, Tanzania, from the 9th to 10th of February 2023. ecancer in collaboration with the Tanzania Oncology Society organised this conference which was attended by more than 150 local and international delegates. During the 2 days of the conference, more than ten speakers from different specialties in the field of oncology gave insights into Choosing Wisely in oncology. Topics from all fields linked to cancer care such as radiation oncology, medical oncology, prevention, oncological surgery, palliative care, patient advocacy, pathology, radiology, clinical trials, research …


Optimized 18f-Fdg Pet-Ct Method To Improve Accuracy Of Diagnosis Of Metastatic Cancer., Richard Black, Jelle Barentsz, David Howell, David G Bostwick, Stephen B Strum Apr 2023

Optimized 18f-Fdg Pet-Ct Method To Improve Accuracy Of Diagnosis Of Metastatic Cancer., Richard Black, Jelle Barentsz, David Howell, David G Bostwick, Stephen B Strum

Oncology Articles

The diagnosis of cancer by FDG PET-CT is often inaccurate owing to subjectivity of interpretation. We compared the accuracy of a novel normalized (standardized) method of interpretation with conventional non-normalized SUV. Patients (


Resolution Of Cisplatin-Induced Fatigue Does Not Require Endogenous Interleukin-10 In Male Miceb, Kiersten Scott, Nabila Boukelmoune, Cullen Taniguchi, A Phillip West, Cobi J Heijnen, Robert Dantzer Apr 2023

Resolution Of Cisplatin-Induced Fatigue Does Not Require Endogenous Interleukin-10 In Male Miceb, Kiersten Scott, Nabila Boukelmoune, Cullen Taniguchi, A Phillip West, Cobi J Heijnen, Robert Dantzer

Faculty, Staff and Student Publications

Based on previous results showing a pivotal role of endogenous interleukin-10 (IL-10) in the recovery from cisplatin-induced peripheral neuropathy, the present experiments were carried out to determine whether this cytokine plays any role in the recovery from cisplatin-induced fatigue in male mice. Fatigue was measured by decreased voluntary wheel running in mice trained to run in a wheel in response to cisplatin. Mice were treated with a monoclonal neutralizing antibody (IL-10na) administered intranasally during the recovery period to neutralize endogenous IL-10. In the first experiment, mice were treated with cisplatin (2.83 mg/kg/day) for five days and IL-10na (12 μg/day for …


Resolution Of Cisplatin-Induced Fatigue Does Not Require Endogenous Interleukin-10 In Male Mice, Kiersten Scott, Nabila Boukelmoune, Cullen Taniguchi, A Phillip West, Cobi J Heijnen, Robert Dantzer Apr 2023

Resolution Of Cisplatin-Induced Fatigue Does Not Require Endogenous Interleukin-10 In Male Mice, Kiersten Scott, Nabila Boukelmoune, Cullen Taniguchi, A Phillip West, Cobi J Heijnen, Robert Dantzer

Faculty, Staff and Student Publications

Based on previous results showing a pivotal role of endogenous interleukin-10 (IL-10) in the recovery from cisplatin-induced peripheral neuropathy, the present experiments were carried out to determine whether this cytokine plays any role in the recovery from cisplatin-induced fatigue in male mice. Fatigue was measured by decreased voluntary wheel running in mice trained to run in a wheel in response to cisplatin. Mice were treated with a monoclonal neutralizing antibody (IL-10na) administered intranasally during the recovery period to neutralize endogenous IL-10. In the first experiment, mice were treated with cisplatin (2.83 mg/kg/day) for five days and IL-10na (12 μg/day for …


Diagnosis And Management Of Colon Cancer Patients Presenting In Advanced Stages Of Complications, Vlad Denis Constantin, Adrian Silaghi, Dragos Epistatu, Anca Silvia Dumitriu, Stana Paunica, Daniela Gabriela Bălan, Bogdan Socea Apr 2023

Diagnosis And Management Of Colon Cancer Patients Presenting In Advanced Stages Of Complications, Vlad Denis Constantin, Adrian Silaghi, Dragos Epistatu, Anca Silvia Dumitriu, Stana Paunica, Daniela Gabriela Bălan, Bogdan Socea

Journal of Mind and Medical Sciences

Colorectal cancer is an important health problem with a significant impact on the individual and society. Malignancy (including colorectal cancer) is usually slightly symptomatic in its initial stages. This causes cancer to be discovered in some patients accidentally (either through screening tests in predisposed individuals or during routine investigations for other diseases), while in other patients the colorectal cancer is discovered in late stages, when the symptoms are much more intense due to complications. Unfortunately, such advanced cases of the disease have high rates of morbidity and mortality even with treatment. Current treatment methods are usually complex, interdisciplinary, causing significant …


Tumor Suppressor Candidate 2 (Tusc2): Discovery, Functions, And Cancer Therapy, Austin Arrigo, Angelina T Regua, Mariana K Najjar, Hui-Wen Lo Apr 2023

Tumor Suppressor Candidate 2 (Tusc2): Discovery, Functions, And Cancer Therapy, Austin Arrigo, Angelina T Regua, Mariana K Najjar, Hui-Wen Lo

Faculty, Staff and Student Publications

Tumor Suppressor Candidate 2 (TUSC2) was first discovered as a potential tumor suppressor gene residing in the frequently deleted 3p21.3 chromosomal region. Since its discovery, TUSC2 has been found to play vital roles in normal immune function, and TUSC2 loss is associated with the development of autoimmune diseases as well as impaired responses within the innate immune system. TUSC2 also plays a vital role in regulating normal cellular mitochondrial calcium movement and homeostasis. Moreover, TUSC2 serves as an important factor in premature aging. In addition to TUSC2's normal cellular functions, TUSC2 has been studied as a tumor suppressor gene that …


Increased Breast And Colorectal Cancer Risk In Type 2 Diabetes: Awareness Among Adults With And Without Diabetes And Information Provision On Diabetes Websites, Laura Ashley, Kathryn A Robb, Daryl B O'Connor, Rebecca Platt, Mollie Price, Olivia Robinson, Elizabeth Travis, Lorraine Lipscombe, Ramzi Ajjan, Rebecca Birch Apr 2023

Increased Breast And Colorectal Cancer Risk In Type 2 Diabetes: Awareness Among Adults With And Without Diabetes And Information Provision On Diabetes Websites, Laura Ashley, Kathryn A Robb, Daryl B O'Connor, Rebecca Platt, Mollie Price, Olivia Robinson, Elizabeth Travis, Lorraine Lipscombe, Ramzi Ajjan, Rebecca Birch

Faculty, Staff and Student Publications

BACKGROUND: People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening.

PURPOSE: Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites.

METHODS: Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites …


Identifying Signatures Of Ev Secretion In Metastatic Breast Cancer Through Functional Single-Cell Profiling, Mohsen Fathi, Melisa Martinez-Paniagua, Ali Rezvan, Melisa J Montalvo, Vakul Mohanty, Ken Chen, Sendurai A Mani, Navin Varadarajan Apr 2023

Identifying Signatures Of Ev Secretion In Metastatic Breast Cancer Through Functional Single-Cell Profiling, Mohsen Fathi, Melisa Martinez-Paniagua, Ali Rezvan, Melisa J Montalvo, Vakul Mohanty, Ken Chen, Sendurai A Mani, Navin Varadarajan

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) regulate the tumor microenvironment by facilitating transport of biomolecules. Despite extensive investigation, heterogeneity in EV secretion among cancer cells and the mechanisms that support EV secretion are not well characterized. We developed an integrated method to identify individual cells with differences in EV secretion and performed linked single-cell RNA-sequencing on cloned single cells from the metastatic breast cancer cells. Differential gene expression analyses identified a four-gene signature of breast cancer EV secretion: HSP90AA1HSPH1EIF5, and DIAPH3. We functionally validated this gene signature by testing it across cell lines with different metastatic potential …


Deletion Of The Mrna Stability Factor Elavl1 (Hur) In Pancreatic Cancer Cells Disrupts The Tumor Microenvironment Integrity, Grace A Mccarthy, Roberto Di Niro, Jennifer M Finan, Aditi Jain, Yifei Guo, Cory R Wyatt, Alexander R Guimaraes, Trent A Waugh, Dove Keith, Terry K Morgan, Rosalie C Sears, Jonathan R Brody Apr 2023

Deletion Of The Mrna Stability Factor Elavl1 (Hur) In Pancreatic Cancer Cells Disrupts The Tumor Microenvironment Integrity, Grace A Mccarthy, Roberto Di Niro, Jennifer M Finan, Aditi Jain, Yifei Guo, Cory R Wyatt, Alexander R Guimaraes, Trent A Waugh, Dove Keith, Terry K Morgan, Rosalie C Sears, Jonathan R Brody

Department of Surgery Faculty Papers

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, αsmooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell–cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of …


The Abscopal Effect In Patients With Cancer Receiving Immunotherapy, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah Apr 2023

The Abscopal Effect In Patients With Cancer Receiving Immunotherapy, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah

Faculty, Staff and Student Publications

Interest in the abscopal effect has been rekindled over the past decade with the advent of immunotherapy. Although purportedly elusive, this phenomenon is being increasingly reported. Venturing further using a multimodality approach with an array of systemic agents and unconventional modalities is direly needed. In this perspective, we describe the fundamentals of abscopal responses (ARs), explore combinations with systemic therapies that hold promise in eliciting ARs, and reconnoiter unconventional modalities that may induce ARs. Finally, we scrutinize prospective agents and modalities that exhibit preclinical ability to elicit ARs and discuss prognostic biomarkers, their limitations, and pathways of abscopal resistance for …


Targeting Mirnas And Other Non-Coding Rnas As A Therapeutic Approach: An Update, Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo Apr 2023

Targeting Mirnas And Other Non-Coding Rnas As A Therapeutic Approach: An Update, Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo

Faculty, Staff and Student Publications

Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such …


Dna Damage Repair Kinase Dna-Pk And Cgas Synergize To Induce Cancer-Related Inflammation In Glioblastoma, Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana-Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille-Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean-Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette Apr 2023

Dna Damage Repair Kinase Dna-Pk And Cgas Synergize To Induce Cancer-Related Inflammation In Glioblastoma, Clara Taffoni, Johanna Marines, Hanane Chamma, Soumyabrata Guha, Mathilde Saccas, Amel Bouzid, Ana-Luiza Chaves Valadao, Clément Maghe, Jane Jardine, Mi Kyung Park, Katarzyna Polak, Mara De Martino, Claire Vanpouille-Box, Maguy Del Rio, Celine Gongora, Julie Gavard, Nicolas Bidère, Min Sup Song, Donovan Pineau, Jean-Philippe Hugnot, Karima Kissa, Laura Fontenille, Fabien P Blanchet, Isabelle K Vila, Nadine Laguette

Faculty, Staff and Student Publications

Cytosolic DNA promotes inflammatory responses upon detection by the cyclic GMP-AMP (cGAMP) synthase (cGAS). It has been suggested that cGAS downregulation is an immune escape strategy harnessed by tumor cells. Here, we used glioblastoma cells that show undetectable cGAS levels to address if alternative DNA detection pathways can promote pro-inflammatory signaling. We show that the DNA-PK DNA repair complex (i) drives cGAS-independent IRF3-mediated type I Interferon responses and (ii) that its catalytic activity is required for cGAS-dependent cGAMP production and optimal downstream signaling. We further show that the cooperation between DNA-PK and cGAS favors the expression of chemokines that promote …


The Glycoprotein Cd147 Defines Mirna-Enriched Extracellular Vesicles That Derive From Cancer Cells, Song Yi Ko, Wonjae Lee, Melanie Weigert, Eric Jonasch, Ernst Lengyel, Honami Naora Apr 2023

The Glycoprotein Cd147 Defines Mirna-Enriched Extracellular Vesicles That Derive From Cancer Cells, Song Yi Ko, Wonjae Lee, Melanie Weigert, Eric Jonasch, Ernst Lengyel, Honami Naora

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) are ideal for liquid biopsy, but distinguishing cancer cell‐derived EVs and subpopulations of biomarker‐containing EVs in body fluids has been challenging. Here, we identified that the glycoproteins CD147 and CD98 define subpopulations of EVs that are distinct from classical tetraspanin+ EVs in their biogenesis. Notably, we identified that CD147+ EVs have substantially higher microRNA (miRNA) content than tetraspanin+ EVs and are selectively enriched in miRNA through the interaction of CD147 with heterogeneous nuclear ribonucleoprotein A2/B1. Studies using mouse xenograft models showed that CD147+ EVs predominantly derive from cancer cells, whereas the majority of tetraspanin+ EVs are not …


Health-Related Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy: A Scoping Review, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Lauren M Andring, Yimin Geng, Ramez Kouzy, J Andrew Livingston, Susan K Peterson, Andrew J Bishop, Grace L Smith, Jillian R Gunther, Susan K Parsons, Michael Roth Mar 2023

Health-Related Quality Of Life In Adolescents And Young Adults With Cancer Who Received Radiation Therapy: A Scoping Review, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Lauren M Andring, Yimin Geng, Ramez Kouzy, J Andrew Livingston, Susan K Peterson, Andrew J Bishop, Grace L Smith, Jillian R Gunther, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) is a critical component of treatment for adolescents and young adults (AYAs, age 15-39 years old) diagnosed with cancer. Limited prior studies have focused on AYAs receiving RT despite the potentially burdensome effects of RT. We reviewed the literature to assess health-related quality of life (HRQOL) in AYAs with cancer who received RT.

Methods: The MEDLINE, EMBASE, and Web of Science databases were searched in January 2022 to identify studies that analyzed HRQOL measured by patient-reported outcomes in AYAs who received RT. After title (n = 286) and abstract (n = 58) screening and full-text review …


Risk And Resilient Functioning Of Families Of Children With Cancer During The Covid-19 Pandemic., Renee Gilbert, Carolyn R Bates, Devanshi Khetawat, Meredith Dreyer Gillette, Rachel Moore Mar 2023

Risk And Resilient Functioning Of Families Of Children With Cancer During The Covid-19 Pandemic., Renee Gilbert, Carolyn R Bates, Devanshi Khetawat, Meredith Dreyer Gillette, Rachel Moore

Manuscripts, Articles, Book Chapters and Other Papers

Previous literature highlights the impact of COVID-19 on family functioning. Less is known about the impact of the pandemic on families of pediatric cancer patients. In order to determine universal and unique risk and resilience factors of these families during the pandemic, a qualitative analysis was conducted on families currently receiving cancer treatment at a Midwestern hospital. Results of the data analysis depict ways in which these families have been impacted by and have adapted to COVID-19. These findings suggest that families of pediatric cancer patients have unique experiences in the context of COVID-19, in addition to universal experiences outlined …


Hypermitotic Meningiomas Harbor Dna Methylation Subgroups With Distinct Biological And Clinical Features, Abrar Choudhury, William C Chen, Calixto-Hope G Lucas, James C Bayley, Akdes S Harmanci, Sybren L N Maas, Sandro Santagata, Tiemo Klisch, Arie Perry, Wenya Linda Bi, Felix Sahm, Akash J Patel, Stephen T Magill, David R Raleigh Mar 2023

Hypermitotic Meningiomas Harbor Dna Methylation Subgroups With Distinct Biological And Clinical Features, Abrar Choudhury, William C Chen, Calixto-Hope G Lucas, James C Bayley, Akdes S Harmanci, Sybren L N Maas, Sandro Santagata, Tiemo Klisch, Arie Perry, Wenya Linda Bi, Felix Sahm, Akash J Patel, Stephen T Magill, David R Raleigh

Faculty, Staff and Students Publications

BACKGROUND: Meningiomas, the most common primary intracranial tumors, can be separated into 3 DNA methylation groups with distinct biological drivers, clinical outcomes, and therapeutic vulnerabilities. Alternative meningioma grouping schemes using copy number variants, gene expression profiles, somatic short variants, or integrated molecular models have been proposed. These data suggest meningioma DNA methylation groups may harbor subgroups unifying contrasting theories of meningioma biology.

METHODS: A total of 565 meningioma DNA methylation profiles from patients with comprehensive clinical follow-up at independent discovery (n = 200) or validation (n = 365) institutions were reanalyzed and classified into Merlin-intact, Immune-enriched, or Hypermitotic DNA methylation …


Development Of An Equitable, Interprofessional Medical Cannabis Education, Certification And Research Program In An Nci-Designated Cancer Center, Gregory Garber, Msw, Jillian Van Sciver, Mba, Denise Young, Msw, Latrisha Bentch, Ba, Bracken Babula, Md, Brooke Worster, Md Mar 2023

Development Of An Equitable, Interprofessional Medical Cannabis Education, Certification And Research Program In An Nci-Designated Cancer Center, Gregory Garber, Msw, Jillian Van Sciver, Mba, Denise Young, Msw, Latrisha Bentch, Ba, Bracken Babula, Md, Brooke Worster, Md

Department of Medical Oncology Posters

Background: Medical cannabis (MC), state-regulated cannabis programs accessible with a physician certification for a qualifying diagnosis, now exist in 47 states. Little attention has been paid to ensuring equitable access to such programs for the most vulnerable cancer patients.1 Estimates of cannabis use in cancer patients range from 30-40%2 yet access to MC is highly dependent on a number of variables including: geography, cost, availability of certifying providers, lack of provider education and a confusing array of state programs coupled with ongoing federal illegality. The historic criminalization of cannabis and the disproportionate impact on People of Color creates another …