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Full-Text Articles in Medicine and Health Sciences

What Matters To You? Engaging With Children In The James Lind Alliance Children’S Cancer Priority Setting Partnership, Susie Aldiss, Penelope Hart-Spencer, Loveday Langton, Sonia Malik, Keeley Mcevoy, Jessica E Morgan, Rosa Reed-Berendt, Rachel Hollis, Bob Phillips, Faith Gibson, James Lind Alliance Children’S Cancer Priority Setting Partnership Steering Group Nov 2023

What Matters To You? Engaging With Children In The James Lind Alliance Children’S Cancer Priority Setting Partnership, Susie Aldiss, Penelope Hart-Spencer, Loveday Langton, Sonia Malik, Keeley Mcevoy, Jessica E Morgan, Rosa Reed-Berendt, Rachel Hollis, Bob Phillips, Faith Gibson, James Lind Alliance Children’S Cancer Priority Setting Partnership Steering Group

Faculty, Staff and Student Publications

BACKGROUND: Previous priority setting exercises have sought to involve children, but in the final reporting, it is evident that few children had been engaged through the process. A primary aim in the Children's Cancer Priority Setting Partnership was to find out from children what they want research to focus on. We report on our experience to inform methods of engagement with children in future James Lind Alliance Priority Setting Partnerships and similar exercises.

METHODS: We followed the James Lind Alliance process, collecting and shortlisting questions via online surveys with adult survivors of childhood cancer, carers, and professionals, and holding a …


Pediatric Hiv+ Kaposi Sarcoma Exhibits Clinical, Virological, And Molecular Features Different From The Adult Disease, Carolina Caro-Vegas, Alice Peng, Angelica Juarez, Allison Silverstein, William Kamiyango, Jimmy Villiera, Casey L Mcatee, Rizine Mzikamanda, Tamiwe Tomoka, Erin C Peckham-Gregory, Razia Moorad, Carrie L Kovarik, Liane R Campbell, Parth S Mehta, Peter N Kazembe, Carl E Allen, Michael E Scheurer, Nmazuo W Ozuah, Dirk P Dittmer, Nader Kim El-Mallawany Nov 2023

Pediatric Hiv+ Kaposi Sarcoma Exhibits Clinical, Virological, And Molecular Features Different From The Adult Disease, Carolina Caro-Vegas, Alice Peng, Angelica Juarez, Allison Silverstein, William Kamiyango, Jimmy Villiera, Casey L Mcatee, Rizine Mzikamanda, Tamiwe Tomoka, Erin C Peckham-Gregory, Razia Moorad, Carrie L Kovarik, Liane R Campbell, Parth S Mehta, Peter N Kazembe, Carl E Allen, Michael E Scheurer, Nmazuo W Ozuah, Dirk P Dittmer, Nader Kim El-Mallawany

Center for Medical Ethics and Health Policy Staff Publications

BACKGROUND

Kaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.

METHODS

This was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were …


The Transcription Factor Irf4 Determines The Anti-Tumor Immunity Of Cd8+ T Cells, Hui Yan, Yulin Dai, Xiaolong Zhang, Hedong Zhang, Xiang Xiao, Jinfei Fu, Dawei Zou, Anze Yu, Tao Jiang, Xian C Li, Zhongming Zhao, Wenhao Chen Nov 2023

The Transcription Factor Irf4 Determines The Anti-Tumor Immunity Of Cd8+ T Cells, Hui Yan, Yulin Dai, Xiaolong Zhang, Hedong Zhang, Xiang Xiao, Jinfei Fu, Dawei Zou, Anze Yu, Tao Jiang, Xian C Li, Zhongming Zhao, Wenhao Chen

Faculty, Staff and Student Publications

Understanding the factors that regulate T cell infiltration and functional states in solid tumors is crucial for advancing cancer immunotherapies. Here, we discovered that the expression of interferon regulatory factor 4 (IRF4) was a critical T cell intrinsic requirement for effective anti-tumor immunity. Mice with T-cell-specific ablation of IRF4 showed significantly reduced T cell tumor infiltration and function, resulting in accelerated growth of subcutaneous syngeneic tumors and allowing the growth of allogeneic tumors. Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into …


Membrane Anchoring Of The Diras3 N-Terminal Extension Permits Tumor Suppressor Function, Xiaowen Liang, Sung Yun Jung, Lon Wolf Fong, Gamze Bildik, Joshua P Gray, Weiqun Mao, Shuxing Zhang, Steven W Millward, Alemayehu A Gorfe, Yong Zhou, Zhen Lu, Robert C Bast Nov 2023

Membrane Anchoring Of The Diras3 N-Terminal Extension Permits Tumor Suppressor Function, Xiaowen Liang, Sung Yun Jung, Lon Wolf Fong, Gamze Bildik, Joshua P Gray, Weiqun Mao, Shuxing Zhang, Steven W Millward, Alemayehu A Gorfe, Yong Zhou, Zhen Lu, Robert C Bast

Faculty, Staff and Student Publications

DIRAS3 is an imprinted tumor suppressor gene encoding a GTPase that has a distinctive N-terminal extension (NTE) not found in other RAS proteins. This NTE and the prenylated C-terminus are required for DIRAS3-mediated inhibition of RAS/MAP signaling and PI3K activity at the plasma membrane. In this study, we applied biochemical, biophysical, and computational methods to characterize the structure and function of the NTE. The NTE peptide recognizes phosphoinositides PI(3,4,5)P3 and PI(4,5)P2 with rapid kinetics and strong affinity. Lipid binding induces NTE structural change from disorder to amphipathic helix. Mass spectrometry identified N-myristoylation of DIRAS3. All-atom molecular dynamic simulations predict DIRAS3 …


Dlx2 Promotes Osteosarcoma Epithelial-Mesenchymal Transition And Doxorubicin Resistance By Enhancing Hoxc8-Cdh2 Axis, Boya Zhang, Xinhui Du, Yichao Fan, Guoxin Qu, Lon Kai Pang, Ruiying Zhao, Weitao Yao Nov 2023

Dlx2 Promotes Osteosarcoma Epithelial-Mesenchymal Transition And Doxorubicin Resistance By Enhancing Hoxc8-Cdh2 Axis, Boya Zhang, Xinhui Du, Yichao Fan, Guoxin Qu, Lon Kai Pang, Ruiying Zhao, Weitao Yao

Faculty, Staff and Student Publications

Metastasis and doxorubicin resistance are challenges in the clinical diagnosis and treatment of osteosarcoma, the mechanisms underlying these phenomena remain unclear. In this study, we found that DLX2 is highly expressed in metastatic osteosarcoma and is closely related to clinical prognosis. Knockdown of DLX2 inhibited tumor proliferation and migration in vitro and inhibited tumor growth in vivo. Mechanistically, we found that DLX2 enhanced the repression of CDH2 transcription by binding to HOXC8, thereby promoting the epithelial-mesenchymal transition in osteosarcoma cells. Through subsequent exploration, we found that targeting DLX2/HOXC8 signaling significantly restores the sensitivity of osteosarcoma cells to doxorubicin. In …


Research Data Management Readiness At Uganda Cancer Institute, Edward Mukiibi, Joyce Bukirwa Nov 2023

Research Data Management Readiness At Uganda Cancer Institute, Edward Mukiibi, Joyce Bukirwa

Library Philosophy and Practice (e-journal)

The study explored research data management readiness at the Uganda Cancer Institute. Its objectives were to; establish the state of research data and the institutional readiness for research data management practices. The case study applied a survey method using a questionnaire modified from the Data Asset Framework and the Community Capability Model Framework. The respondents were 60 staff members at different professional levels purposively selected. The findings show massive data generated from clinical trials, and routine cancer clinics at the institute. The business processes are mainly manual except for the funded research projects which are hybrid. The existing data sets …


Editorial: Resilience, Quality Of Life And Psychosocial Outcomes Of Cancer Patients And Their Caregivers, Nida Zahid, Nargis Asad, Ashraf El-Metwally Nov 2023

Editorial: Resilience, Quality Of Life And Psychosocial Outcomes Of Cancer Patients And Their Caregivers, Nida Zahid, Nargis Asad, Ashraf El-Metwally

Department of Surgery Docs

No abstract provided.


An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo Nov 2023

An Overview Of The Immune Modulatory Properties Of Long Non-Coding Rnas And Their Potential Use As Therapeutic Targets In Cancer, Moises Martinez-Castillo, Abdelrahman M Elsayed, Gabriel López-Berestein, Paola Amero, Cristian Rodríguez-Aguayo

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field …


Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn Nov 2023

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …


In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood Nov 2023

In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood

Faculty, Staff and Student Publications

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …


Recent Strategies For Cancer Therapy: Polymer Nanoparticles Carrying Medicinally Important Phytochemicals And Their Cellular Targets, Metin Yıldırım, Melike Sessevmez, Samet Poyraz, Nejat Düzgüneş Nov 2023

Recent Strategies For Cancer Therapy: Polymer Nanoparticles Carrying Medicinally Important Phytochemicals And Their Cellular Targets, Metin Yıldırım, Melike Sessevmez, Samet Poyraz, Nejat Düzgüneş

Pacific Faculty Work

Cancer is a leading cause of death in the world today. In addition to the side effects of the chemotherapeutic drugs used to treat cancer, the development of resistance to the drugs renders the existing drugs ineffective. Therefore, there is an urgent need to develop novel anticancer agents. Medicinally important phytochemicals such as curcumin, naringenin, quercetin, epigallocatechin gallate, thymoquinone, kaempferol, resveratrol, genistein, and apigenin have some drawbacks, including low solubility in water, stability and bioavailability issues, despite having significant anticancer effects. Encapsulation of these natural compounds into polymer nanoparticles (NPs) is a novel technology that could overcome these constraints. In …


Structural Surfaceomics Reveals An Aml-Specific Conformation Of Integrin Β2 As A Car T Cellular Therapy Target, Kamal Mandal, Gianina Wicaksono, Clinton Yu, Jarrett J Adams, Michael R Hoopmann, William C Temple, Adila Izgutdina, Bonell Patiño Escobar, Maryna Gorelik, Christian H Ihling, Matthew A Nix, Akul Naik, William H Xie, Juwita Hübner, Lisa A Rollins, Sandy M Reid, Emilio Ramos, Corynn Kasap, Veronica Steri, Juan Antonio Camara Serrano, Fernando Salangsang, Paul Phojanakong, Melanie Mcmillan, Victor Gavallos, Andrew D Leavitt, Aaron C Logan, Cliona M Rooney, Justin Eyquem, Andrea Sinz, Benjamin J Huang, Elliot Stieglitz, Catherine C Smith, Robert L Moritz, Sachdev S Sidhu, Lan Huang, Arun P Wiita Nov 2023

Structural Surfaceomics Reveals An Aml-Specific Conformation Of Integrin Β2 As A Car T Cellular Therapy Target, Kamal Mandal, Gianina Wicaksono, Clinton Yu, Jarrett J Adams, Michael R Hoopmann, William C Temple, Adila Izgutdina, Bonell Patiño Escobar, Maryna Gorelik, Christian H Ihling, Matthew A Nix, Akul Naik, William H Xie, Juwita Hübner, Lisa A Rollins, Sandy M Reid, Emilio Ramos, Corynn Kasap, Veronica Steri, Juan Antonio Camara Serrano, Fernando Salangsang, Paul Phojanakong, Melanie Mcmillan, Victor Gavallos, Andrew D Leavitt, Aaron C Logan, Cliona M Rooney, Justin Eyquem, Andrea Sinz, Benjamin J Huang, Elliot Stieglitz, Catherine C Smith, Robert L Moritz, Sachdev S Sidhu, Lan Huang, Arun P Wiita

Faculty, Staff and Students Publications

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture ‘structural surfaceomics’. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β2 …


Social Determinants Of Health And Lung Cancer Surgery: A Qualitative Study, Dede K. Teteh, Betty Ferrell, Oluwatimilehin Okunowo, Aidea Downie, Loretta Erhunmwunsee, Susanne B. Montgomery, Dan J. Raz, Rick Kittles, Jae Y. Kim, Virginia Sun Oct 2023

Social Determinants Of Health And Lung Cancer Surgery: A Qualitative Study, Dede K. Teteh, Betty Ferrell, Oluwatimilehin Okunowo, Aidea Downie, Loretta Erhunmwunsee, Susanne B. Montgomery, Dan J. Raz, Rick Kittles, Jae Y. Kim, Virginia Sun

Health Sciences and Kinesiology Faculty Articles

Introduction: Social determinants of health (SDOH) are non-clinical factors that may affect the outcomes of cancer patients. The purpose of this study was to describe the influence of SDOH factors on quality of life (QOL)-related outcomes for lung cancer surgery patients.

Methods: Thirteen patients enrolled in a randomized trial of a dyadic self-management intervention were invited and agreed to participate in semi-structured key informant interviews at study completion (3 months post-discharge). A conventional content analysis approach was used to identify codes and themes that were derived from the interviews. Independent investigators coded the qualitative data, which were subsequently …


Ethnobotanical Survey Of Medicinal Plants Used In The Management Of Cancer In Uganda, John Baptist Asiimwe, Prakash B. Nagendrappa, Esther C. Atukunda, Ivan Kahwa, Lina S. Mathew Alonga, Clement O. Ajayi, Casim U. Tolo, Patrick E. Ogwang, Maud M. Kamatenesi Oct 2023

Ethnobotanical Survey Of Medicinal Plants Used In The Management Of Cancer In Uganda, John Baptist Asiimwe, Prakash B. Nagendrappa, Esther C. Atukunda, Ivan Kahwa, Lina S. Mathew Alonga, Clement O. Ajayi, Casim U. Tolo, Patrick E. Ogwang, Maud M. Kamatenesi

School of Nursing & Midwifery, East Africa

Introduction: Patients with cancer in Africa embrace the use of herbal medicine more than anywhere else in the world. This study identified and documented medicinal plant species used to manage cancer in ten (10) districts of Uganda.

Methods: An ethnobotanical survey was conducted between October 2021 and January 2022. In total, 18 (out of 55) traditional medicine practitioners (TMPs) having more than 10 years of experience in managing patients with cancer were interviewed using a semi-structured questionnaire.

Data were analysed using descriptive statistics. The Relative frequency of citation (RFC) and Family importance value (FIV) indices were also computed. …


Tigit Contributes To The Regulation Of 4-1bb And Does Not Define Nk Cell Dysfunction In Glioblastoma, Kyle B. Lupo, Sandra Torregrosa-Allen, Bennett D. Elzey, Sagar Utturkar, Nadia A. Lanman, Aaron A. Cohen-Gadol, Veronika Silvova, Mackenzie Mcintosh, Karen E. Pollok, Sandro Matosevic Oct 2023

Tigit Contributes To The Regulation Of 4-1bb And Does Not Define Nk Cell Dysfunction In Glioblastoma, Kyle B. Lupo, Sandra Torregrosa-Allen, Bennett D. Elzey, Sagar Utturkar, Nadia A. Lanman, Aaron A. Cohen-Gadol, Veronika Silvova, Mackenzie Mcintosh, Karen E. Pollok, Sandro Matosevic

Purdue University Libraries Open Access Publishing Fund

TIGIT is a receptor on human natural killer (NK) cells. Here, we report that TIGIT does not spontaneously induce inhibition of NK cells in glioblastoma (GBM), but rather acts as a decoy-like receptor, by usurping binding partners and regulating expression of NK activating ligands and receptors. Our data show that in GBM patients, one of the underpinnings of unresponsiveness to TIGIT blockade is that by targeting TIGIT, NK cells do not lose an inhibitory signal, but gains the potential for new interactions with other, shared, TIGIT ligands. Therefore, TIGIT does not define NK cell dysfunction in GBM. Further, in GBM, …


Significance Of Targeting Rna Polymerase I In Intrahepatic Cholangiocarcinoma, Muhammad A. Bangash, Aun A. Bangash, Haider Ahsan, Sahir Alvi, Mudassier Ahmad, Alejandro Rincon, Samuel Owusu-Mireku, Bilal Hafeez Oct 2023

Significance Of Targeting Rna Polymerase I In Intrahepatic Cholangiocarcinoma, Muhammad A. Bangash, Aun A. Bangash, Haider Ahsan, Sahir Alvi, Mudassier Ahmad, Alejandro Rincon, Samuel Owusu-Mireku, Bilal Hafeez

MEDI 9331 Scholarly Activities Clinical Years

Intrahepatic cholangiocarcinoma (IHCC) is a much-overlooked cancer with a mortality rate that has increased throughout recent years, as stated by the American Cancer Society [1]. In the United States alone, there are an estimated 8,000 adults being diagnosed with IHCC every year, with a five-year survival rate of 9% [2]. Chemotherapy options for the treatment of IHCC include systemic chemotherapy such as gemcitabine, capecitabine, and oxaliplatin. These medications carry a wide array of adverse factors that may warrant discontinuation due to the detriment to the well-being of the patient. Additionally, a broad field of therapy that may also be used, …


Focalizing Regions Of Biomarker Relevance Facilitates Biomarker Prediction On Histopathological Images, Jiefeng Gan, Hanchen Wang, Hui Yu, Zitong He, Wenjuan Zhang, Ke Ma, Lianghui Zhu, Yutong Bai, Zongwei Zhou, Alan Yullie, Xiang Bai, Mingwei Wang, Dehua Yang, Yanyan Chen, Guoan Chen, Joan Lasenby, Chao Cheng, Jia Wu, Jianjun Zhang, Xinggang Wang, Yaobing Chen, Guoping Wang, Tian Xia Oct 2023

Focalizing Regions Of Biomarker Relevance Facilitates Biomarker Prediction On Histopathological Images, Jiefeng Gan, Hanchen Wang, Hui Yu, Zitong He, Wenjuan Zhang, Ke Ma, Lianghui Zhu, Yutong Bai, Zongwei Zhou, Alan Yullie, Xiang Bai, Mingwei Wang, Dehua Yang, Yanyan Chen, Guoan Chen, Joan Lasenby, Chao Cheng, Jia Wu, Jianjun Zhang, Xinggang Wang, Yaobing Chen, Guoping Wang, Tian Xia

Faculty, Staff and Student Publications

Image-based AI has thrived as a potentially revolutionary tool for predicting molecular biomarker statuses, which aids in categorizing patients for appropriate medical treatments. However, many methods using hematoxylin and eosin-stained (H&E) whole-slide images (WSIs) have been found to be inefficient because of the presence of numerous uninformative or irrelevant image patches. In this study, we introduced the region of biomarker relevance (ROB) concept to identify the morphological areas most closely associated with biomarkers for accurate status prediction. We actualized this concept within a framework called saliency ROB search (SRS) to enable efficient and effective predictions. By evaluating various lung adenocarcinoma …


Got Pidd1? Natural Killer Cells Clear Polyploid Cells To Ensure A Balanced Genome, Alexandra N Brown-Suedel, Lisa Bouchier-Hayes Oct 2023

Got Pidd1? Natural Killer Cells Clear Polyploid Cells To Ensure A Balanced Genome, Alexandra N Brown-Suedel, Lisa Bouchier-Hayes

Faculty, Staff and Students Publications

Removal of polyploid cells is essential to preventing cancer and restricting tumor growth. A new study published in The EMBO Journal shows assembly of the NEMO-PIDDosome on extra centrioles. Activation of this protein complex leads to NF-κB activation that, in turn, induces NK cell-mediated cell clearance.


Sptan1/Numb Axis Senses Cell Density To Restrain Cell Growth And Oncogenesis Through Hippo Signaling, Dongxue Su, Yuxi Li, Weiji Zhang, Huan Gao, Yao Cheng, Yongqiang Hou, Junhong Li, Yi Ye, Zhangjian Lai, Zhe Li, Haitao Huang, Jiaxin Li, Jinhuan Li, Mengyu Cheng, Cheng Nian, Na Wu, Zhien Zhou, Yunzhi Xing, Yu Zhao, He Liu, Jiayu Tang, Qinghua Chen, Lixin Hong, Wengang Li, Zhihai Peng, Bin Zhao, Randy L Johnson, Pingguo Liu, Wanjin Hong, Lanfen Chen, Dawang Zhou Oct 2023

Sptan1/Numb Axis Senses Cell Density To Restrain Cell Growth And Oncogenesis Through Hippo Signaling, Dongxue Su, Yuxi Li, Weiji Zhang, Huan Gao, Yao Cheng, Yongqiang Hou, Junhong Li, Yi Ye, Zhangjian Lai, Zhe Li, Haitao Huang, Jiaxin Li, Jinhuan Li, Mengyu Cheng, Cheng Nian, Na Wu, Zhien Zhou, Yunzhi Xing, Yu Zhao, He Liu, Jiayu Tang, Qinghua Chen, Lixin Hong, Wengang Li, Zhihai Peng, Bin Zhao, Randy L Johnson, Pingguo Liu, Wanjin Hong, Lanfen Chen, Dawang Zhou

Faculty, Staff and Student Publications

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin α chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and …


Synthesis And Antitumor Activity Of Brominated-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Hassan Mandil, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chuahan Oct 2023

Synthesis And Antitumor Activity Of Brominated-Ormeloxifene (Br-Orm) Against Cervical Cancer, Mohammed Sikander, Shabnam Malik, John Apraku, Sonam Kumari, Parvez Khan, Hassan Mandil, Sheema Khan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chuahan

School of Medicine Publications

Aberrant regulation of β-catenin signaling is strongly linked with cancer proliferation, invasion, migration, and metastasis, thus, small molecules that can inhibit this pathway might have great clinical significance. Our molecular modeling studies suggest that ormeloxifene (ORM), a triphenylethylene molecule that docks with β-catenin, and its brominated analogue (Br-ORM) bind more effectively with relatively less energy (−7.6 kcal/mol) to the active site of β-catenin as compared to parent ORM. Herein, we report the synthesis and characterization of a Br-ORM by NMR and FTIR, as well as its anticancer activity in cervical cancer models. Br-ORM treatment effectively inhibited tumorigenic features (cell proliferation …


Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi Oct 2023

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …


Anticancer Drug Screening Using Invitro Cell Proliferation Assay, Kristopher L. Ezell, Kyle Doxtater, Samantha Lopez, Sophia M. Leslie, Justin Wendel, Kamaldeep Paul, Vijay Lauxmi, Manish Tripathi Oct 2023

Anticancer Drug Screening Using Invitro Cell Proliferation Assay, Kristopher L. Ezell, Kyle Doxtater, Samantha Lopez, Sophia M. Leslie, Justin Wendel, Kamaldeep Paul, Vijay Lauxmi, Manish Tripathi

Research Colloquium

Introduction: In this presentation cell proliferation methods and how they are related to screening for effective chemotherapy drugs will be reviewed. Cancer in its most basic form is the unchecked mass dividing of cells while normal apoptosis is not undertaken for various reasons, some of which that have yet to be discovered. By these means’ tumors form that inhibit the functions of the organs it is residing in and the effected cells may metastasize and spread throughout the body. For this reason, chemotherapy drugs must be assessed through introduction into working strains of cultured cancer cells that are then screened …


Functional Analysis Reveals Driver Cooperativity And Novel Mechanisms In Endometrial Carcinogenesis, Matthew Brown, Alicia Leon, Katarzyna Kedzierska, Charlotte Moore, Hayley L Belnoue-Davis, Susanne Flach, John P Lydon, Francesco J Demayo, Annabelle Lewis, Tjalling Bosse, Ian Tomlinson, David N Church Oct 2023

Functional Analysis Reveals Driver Cooperativity And Novel Mechanisms In Endometrial Carcinogenesis, Matthew Brown, Alicia Leon, Katarzyna Kedzierska, Charlotte Moore, Hayley L Belnoue-Davis, Susanne Flach, John P Lydon, Francesco J Demayo, Annabelle Lewis, Tjalling Bosse, Ian Tomlinson, David N Church

Faculty, Staff and Students Publications

High-risk endometrial cancer has poor prognosis and is increasing in incidence. However, understanding of the molecular mechanisms which drive this disease is limited. We used genetically engineered mouse models (GEMM) to determine the functional consequences of missense and loss of function mutations in Fbxw7, Pten and Tp53, which collectively occur in nearly 90% of high-risk endometrial cancers. We show that Trp53 deletion and missense mutation cause different phenotypes, with the latter a substantially stronger driver of endometrial carcinogenesis. We also show that Fbxw7 missense mutation does not cause endometrial neoplasia on its own, but potently accelerates carcinogenesis caused by Pten …


Survival Disparities Between Border And Non-Border Counties In Colorectal Cancer Patients Using The Tcr, Michael Machiorlatti, Michael Brian Lapelusa Oct 2023

Survival Disparities Between Border And Non-Border Counties In Colorectal Cancer Patients Using The Tcr, Michael Machiorlatti, Michael Brian Lapelusa

Research Colloquium

Along the US Texas Mexico border constant migration, developing medical infrastructure and income disparity leads to poorer access to healthcare and poorer health outcomes. Given 32 of the 254 counties in TX are on the border with roughly 9.8% of the Texas residing in these counties (2.8 million people), this represents a significant population susceptible to adverse health outcomes. We investigate comparisons between border and non-border counties as well as how sociodemographic and diagnostic criterion influence survival of colorectal cancer. Data was obtained from the Texas Department of State Health Service’s TCR. Patients were 18 or older and excluded for …


Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou Oct 2023

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Faculty, Staff and Student Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …


The Impact Of Modern Dietary Practices On Cancer Risk And Progression: A Systematic Review, Stephanie Nagy, Stephanie N. Petrosky, Michelle Demory Beckler, Marc M. Kesselman Oct 2023

The Impact Of Modern Dietary Practices On Cancer Risk And Progression: A Systematic Review, Stephanie Nagy, Stephanie N. Petrosky, Michelle Demory Beckler, Marc M. Kesselman

HPD Articles

Cancer is a leading cause of mortality around the world, despite continued advancements in the management of cancer. Recent research efforts have shifted to evaluating the role that modifiable risk factors play in cancer risk and development, as diet and nutrition have been found to play a significant role in the onset and progression of cancer. As a result, there has been an increasing focus on the impact of dietary modifications on preventing the onset, progression, and reoccurrence of cancer. In this systematic review, data were collected on three common diets, the Mediterranean diet (MD), ketogenic diet (KD), and plant-based …


Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo Oct 2023

Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In this comprehensive review, we will dissect the impact of research on proteoglycans focusing on recent developments involved in their synthesis, degradation, and interactions, while critically assessing their usefulness in various biological processes. The emerging roles of proteoglycans in global infections, specifically the SARS-CoV-2 pandemic, and their rising functions in regenerative medicine and biomaterial science have significantly affected our current view of proteoglycans and related compounds. The roles of proteoglycans in cancer biology and their potential use as a next-generation protein-based adjuvant therapy to combat cancer is also emerging as a constructive and potentially beneficial therapeutic strategy. We will discuss …


Raman Spectral Cytopathology For Cancer Diagnostic Applications, Fiona Lyng, Damian Traynor, Isha Behl, Declan O'Dea, Hugh Byrne Oct 2023

Raman Spectral Cytopathology For Cancer Diagnostic Applications, Fiona Lyng, Damian Traynor, Isha Behl, Declan O'Dea, Hugh Byrne

Books/Book Chapters

Histopathology is currently regarded as the “gold standard” patient sampling technique for cancer diagnostics. It involves extraction of a tissue sample, or biopsy, which is then sectioned and stained for evaluation by a pathologist [1]. Cytopathology, on the other hand, is the field of disease diagnosis at the cellular level [2], necessitating only the microscopic evaluation of samples of cells which can be harvested by less invasive methods such as exfoliative brushing, needle probes or from biofluids. Based on the identification of abnormalities in cellular appearance, cytopathology is currently widely used to aid in the screening of cancer, as well …


Early Palliative Care Screening Among Solid Tumor Oncology Patients, Kaitlin Lothe Oct 2023

Early Palliative Care Screening Among Solid Tumor Oncology Patients, Kaitlin Lothe

Doctor of Nursing Practice Scholarly Projects

While there are extensive benefits of integration of early palliative care, referral to this specialty tends to occur late in the disease course after some form of suffering has already occurred (Hausner et al., 2021). The purpose of this DNP student’s quality improvement project was to improve care coordination and increase rate of palliative care referrals of solid tumor oncology patients through implementation of an evidence-based trigger tool for palliative care screening. Participants were recruited from a 36-bed inpatient adult medical oncology unit where identified patients meeting criteria were included in the study. Data for this study included participant demographics, …


Increasing Hpv Vaccination Uptake In Female College Students Aged 18-26, Gabrielle B. Scott Oct 2023

Increasing Hpv Vaccination Uptake In Female College Students Aged 18-26, Gabrielle B. Scott

Doctor of Nursing Practice Scholarly Projects

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world. Most people infected with HPV remain asymptomatic, but infections may result in several types of cancer. Three HPV vaccines are available with the recommended initiation of vaccination between 11–12 years, but the vaccine may be administered to females through 45 years old. Despite HPV vaccine efficacy, vaccination rates among college-age students remain low, particularly in certain geographical areas such as the Southeastern United States. This project aimed to increase HPV vaccination uptake among females between the ages of 18-26 in the Women’s Health Clinic through patient education …