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Articles 21151 - 21180 of 76850

Full-Text Articles in Medical Specialties

Enhancing Efficacy Of The Mek Inhibitor Trametinib With Paclitaxel In Kras-Mutated Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid Powell, Yong Sung Park, Clifford Stephan, E Scott Kopetz, Lee M Ellis, Rajat Bhattacharya Jan 2024

Enhancing Efficacy Of The Mek Inhibitor Trametinib With Paclitaxel In Kras-Mutated Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid Powell, Yong Sung Park, Clifford Stephan, E Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Background: KRAS is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Objective: Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with KRAS-mutated mCRC.

Design: In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that …


Enhanced Tumor Control And Survival In Preclinical Models With Adoptive Cell Therapy Preceded By Low-Dose Radiotherapy, Nahum Puebla-Osorio, Natalie Wall Fowlkes, Hampartsoum B Barsoumian, Kristina Xega, Gitika Srivastava, Claudia Kettlun-Leyton, Sara Nizzero, Tiffany Voss, Thomas S Riad, Christina Wong, Ailing Huang, Yun Hu, Joylise Mitchell, Mingee Kim, Zahid Rafiq, Kewen He, Duygu Sezen, Ethan Hsu, Fatemeh Masrorpour, Aurian Maleki, Carola Leuschner, Maria Angelica Cortez, Philipp Oertle, Marko Loparic, Marija Plodinec, Janet L Markman, James W Welsh Jan 2024

Enhanced Tumor Control And Survival In Preclinical Models With Adoptive Cell Therapy Preceded By Low-Dose Radiotherapy, Nahum Puebla-Osorio, Natalie Wall Fowlkes, Hampartsoum B Barsoumian, Kristina Xega, Gitika Srivastava, Claudia Kettlun-Leyton, Sara Nizzero, Tiffany Voss, Thomas S Riad, Christina Wong, Ailing Huang, Yun Hu, Joylise Mitchell, Mingee Kim, Zahid Rafiq, Kewen He, Duygu Sezen, Ethan Hsu, Fatemeh Masrorpour, Aurian Maleki, Carola Leuschner, Maria Angelica Cortez, Philipp Oertle, Marko Loparic, Marija Plodinec, Janet L Markman, James W Welsh

Faculty, Staff and Student Publications

Introduction: Effective infiltration of chimeric antigen receptor T (CAR-T) cells into solid tumors is critical for achieving a robust antitumor response and improving therapeutic outcomes. While CAR-T cell therapies have succeeded in hematologic malignancies, their efficacy in solid tumors remains limited due to poor tumor penetration and an immunosuppressive tumor microenvironment. This study aimed to evaluate the potential of low-dose radiotherapy (LDRT) administered before T-cell therapy to enhance the antitumor effect by promoting CAR-T cell infiltration. We hypothesized that combining LDRT with T-cell therapy would improve tumor control and survival compared to either treatment alone.

Methods: We investigated this hypothesis …


Postprogression Therapy And Confounding For The Estimated Treatment Effect On Overall Survival In Phase Iii Oncology Trials, Alexander D Sherry, Pavlos Msaouel, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Esther J Beck, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Eugene J Koay, Clifton David Fuller, Charles R Thomas, Zachary R Mccaw, Ethan B Ludmir Jan 2024

Postprogression Therapy And Confounding For The Estimated Treatment Effect On Overall Survival In Phase Iii Oncology Trials, Alexander D Sherry, Pavlos Msaouel, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Esther J Beck, Avital M Miller, Adina H Passy, Gabrielle S Kupferman, Eugene J Koay, Clifton David Fuller, Charles R Thomas, Zachary R Mccaw, Ethan B Ludmir

Faculty, Staff and Student Publications

Objective: Estimations of the treatment effect on overall survival (OS) may be influenced by post-progression therapies (PPTs). It is unclear how often OS analyses account for PPT effects. The purpose of this cross-sectional analysis was to determine the prevalence of OS analyses accounting for PPT effects in phase III oncology trials.

Methods and analysis: We screened two-arm, superiority design, phase III, randomised, oncology trials reporting OS from ClinicalTrials.gov. The primary outcome was the frequency of OS analyses adjusting for PPT confounding. Logistic regressions computed ORs for the association between trial-level covariates and the outcome.

Results: A total of 334 phase …


Combination Chemotherapy Optimization With Discrete Dosing, Temitayo Ajayi, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Clifton D Fuller Jan 2024

Combination Chemotherapy Optimization With Discrete Dosing, Temitayo Ajayi, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Clifton D Fuller

Faculty, Staff and Student Publications

Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens; one way to alleviate this burden and better inform future trials is to build reliable models for drug administration. This paper presents a mixed-integer program for combination chemotherapy (utilization of multiple drugs) optimization that incorporates various important operational constraints and, besides dose and concentration limits, controls treatment toxicity based on its effect on the count of white blood cells. To address the uncertainty of tumor heterogeneity, we also propose chance constraints that guarantee reaching an operable tumor size with a high probability in …


The Use Of Mr-Guided Radiation Therapy For Head And Neck Cancer And Recommended Reporting Guidance, Brigid A Mcdonald, Riccardo Dal Bello, Clifton D Fuller, Panagiotis Balermpas Jan 2024

The Use Of Mr-Guided Radiation Therapy For Head And Neck Cancer And Recommended Reporting Guidance, Brigid A Mcdonald, Riccardo Dal Bello, Clifton D Fuller, Panagiotis Balermpas

Faculty, Staff and Student Publications

Although magnetic resonance imaging (MRI) has become standard diagnostic workup for head and neck malignancies and is currently recommended by most radiological societies for pharyngeal and oral carcinomas, its utilization in radiotherapy has been heterogeneous during the last decades. However, few would argue that implementing MRI for annotation of target volumes and organs at risk provides several advantages, so that implementation of the modality for this purpose is widely accepted. Today, the term MR-guidance has received a much broader meaning, including MRI for adaptive treatments, MR-gating and tracking during radiotherapy application, MR-features as biomarkers and finally MR-only workflows. First studies …


Camrelizumab Combined With Apatinib And Nanoparticle Albumin-Bound Paclitaxel In Lung Adenocarcinoma (Capap-Lung): A Single-Arm Phase Ii Study, Xingxiang Pu, Gen Lin, Maoliang Xiao, Jie Lin, Qianzhi Wang, Yi Kong, Xuejun Yan, Fang Xu, Yan Xu, Jia Li, Kang Li, Bolin Chen, Xiaoping Wen, Yali Tan, Fengzhuo Cheng, Kangle Zhu, Na Li, Lin Wu Jan 2024

Camrelizumab Combined With Apatinib And Nanoparticle Albumin-Bound Paclitaxel In Lung Adenocarcinoma (Capap-Lung): A Single-Arm Phase Ii Study, Xingxiang Pu, Gen Lin, Maoliang Xiao, Jie Lin, Qianzhi Wang, Yi Kong, Xuejun Yan, Fang Xu, Yan Xu, Jia Li, Kang Li, Bolin Chen, Xiaoping Wen, Yali Tan, Fengzhuo Cheng, Kangle Zhu, Na Li, Lin Wu

Faculty, Staff and Student Publications

Background: Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma.

Methods: In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma …


Knowledge Mapping Of Anaplastic Thyroid Cancer Treatments: A Bibliometric Analysis (2000–2023), Shiqiang Liu, Xingmin Yan, Yalong Yang, Yun Xia, Panshi Zhang Jan 2024

Knowledge Mapping Of Anaplastic Thyroid Cancer Treatments: A Bibliometric Analysis (2000–2023), Shiqiang Liu, Xingmin Yan, Yalong Yang, Yun Xia, Panshi Zhang

Faculty, Staff and Student Publications

Context: Anaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature.

Methodology: A systematic search was …


Considerations On Design And Analysis Of External Control In Pediatric Oncology, Jingjing Ye, Haitao Pan, Gregory Reaman, Satrajit Roychoudhury, Chengxing Lu, Lindsay A Renfro, Yuan Ji, Rong Liu, Ying Yuan, Weidong Zhang Jan 2024

Considerations On Design And Analysis Of External Control In Pediatric Oncology, Jingjing Ye, Haitao Pan, Gregory Reaman, Satrajit Roychoudhury, Chengxing Lu, Lindsay A Renfro, Yuan Ji, Rong Liu, Ying Yuan, Weidong Zhang

Faculty, Staff and Student Publications

Pediatric cancer consists of a diverse group of rare diseases. Due to limited patient populations, standard randomized and controlled trials are often infeasible. As a result, single-arm trials are common in pediatric oncology and the use of external controls is often desirable or necessary to help generate actionable evidence and contextualize trial results. In this paper, we illustrate unique features in pediatric oncology clinical trials and describe their impact on the use of external controls. Various types of relevant external control data sources are described in terms of their utility and drawbacks. Statistical methodologies and design implications with external control …


Development Of The “Laser Surgical Skills Evaluation For Residents” (Laser) Scale Through A Modified Delphi Method, E Sédillot-Daniel, A Melkane, C Chiesa, N Fakhry, V N Young, L J Smith, J R Lechien, L Guertin, M J Olivier, A Maniakas, R Jun Lin, E Bissada, A Christopoulos, T Ayad, Andrée-Anne Leclerc Jan 2024

Development Of The “Laser Surgical Skills Evaluation For Residents” (Laser) Scale Through A Modified Delphi Method, E Sédillot-Daniel, A Melkane, C Chiesa, N Fakhry, V N Young, L J Smith, J R Lechien, L Guertin, M J Olivier, A Maniakas, R Jun Lin, E Bissada, A Christopoulos, T Ayad, Andrée-Anne Leclerc

Faculty, Staff and Student Publications

Background: The CO2 laser is frequently used during microlaryngeal surgery (MLS) for a variety of pathology including laryngeal malignancy and stenosis. Learning how to use the laser safely is part of the curriculum for every otolaryngology resident. However, assessment of laryngoscopy technical skills can be challenging for supervisors, making it difficult to adequately provide feedback to trainees.

Objectives: "LAser Surgical skills Evaluation for Residents" (LASER) Scale aims to facilitate the evaluation of residents' performance and promote constructive feedback.

Methods: The initial evaluation grid was based on a literature review of CO2 laser laryngoscopy (with an emphasis on indications, technique, safety, …


A Review Of The Clinical Introduction Of 4d Particle Therapy Research Concepts, Barbara Knäusl, Gabriele Belotti, Jenny Bertholet, Juliane Daartz, Stella Flampouri, Mischa Hoogeman, Antje C Knopf, Haibo Lin, Astrid Moerman, Chiara Paganelli, Antoni Rucinski, Reinhard Schulte, Shing Shimizu, Kristin Stützer, Xiaodong Zhang, Ye Zhang, Katarzyna Czerska Jan 2024

A Review Of The Clinical Introduction Of 4d Particle Therapy Research Concepts, Barbara Knäusl, Gabriele Belotti, Jenny Bertholet, Juliane Daartz, Stella Flampouri, Mischa Hoogeman, Antje C Knopf, Haibo Lin, Astrid Moerman, Chiara Paganelli, Antoni Rucinski, Reinhard Schulte, Shing Shimizu, Kristin Stützer, Xiaodong Zhang, Ye Zhang, Katarzyna Czerska

Faculty, Staff and Student Publications

Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments.

Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic.

Results: Available technological capabilities …


Simultaneous Submission Of Seven Ctsa Proposals: Um1, K12, R25, T32-Predoctoral, T32-Postdoctoral, And Rc2: Strategies, Evaluation, And Lessons Learned, Carolina Lema, Kwai Wa Cheng, Delanderia M Anderson, Charles C Miller, Daniel D Karp, David D Mcpherson, Satya Sree N Kolar Jan 2024

Simultaneous Submission Of Seven Ctsa Proposals: Um1, K12, R25, T32-Predoctoral, T32-Postdoctoral, And Rc2: Strategies, Evaluation, And Lessons Learned, Carolina Lema, Kwai Wa Cheng, Delanderia M Anderson, Charles C Miller, Daniel D Karp, David D Mcpherson, Satya Sree N Kolar

Faculty, Staff and Student Publications

Translation is the process of turning observations in the research laboratory, clinic, and community into interventions that improve people's health. The Clinical and Translational Science Awards (CTSA) program is a National Center for Advancing Translational Sciences (NCATS) initiative to advance translational science and research. Currently, 64 "CTSA hubs" exist across the nation. Since 2006, the Houston-based Center for Clinical Translational Sciences (CCTS) has assembled a well-integrated, high-impact hub in Texas that includes six partner institutions within the state, encompassing ∼23,000 sq. miles and over 16 million residents. To achieve the NCATS goal of "more treatments for all people more quickly," …


Sample Multiplexing In Cytof: Path To Optimize Single-Cell Proteomic Profiling, Muharrem Muftuoglu, Michael Andreeff Jan 2024

Sample Multiplexing In Cytof: Path To Optimize Single-Cell Proteomic Profiling, Muharrem Muftuoglu, Michael Andreeff

Faculty, Staff and Student Publications

Sample multiplexing significantly enhanced the depth of single-cell proteomic analysis in CyTOF (Cytometry by Time-Of-Flight). New polymer-based chelators have broadened the utility of metal isotopes, enabling improved tagging and simultaneous analysis of multiple samples. These approaches minimize batch effects, streamline experiments, conserve valuable samples, reduce costs, enhance throughput, and increase the accuracy of biological data, thereby facilitating novel discoveries.


Demographic Disparities In Incidence And Mortality Rates Of Current Dengue Outbreak In Bangladesh, Sadia Ashraf, Muhammad Mainuddin Patwary, Alfonso J Rodriguez-Morales Jan 2024

Demographic Disparities In Incidence And Mortality Rates Of Current Dengue Outbreak In Bangladesh, Sadia Ashraf, Muhammad Mainuddin Patwary, Alfonso J Rodriguez-Morales

Faculty, Staff and Student Publications

No abstract provided.


Exposure To Urban Green Spaces And Mental Health During The Covid-19 Pandemic: Evidence From Two Low And Lower-Middle-Income Countries, Muhammad Mainuddin Patwary, Mondira Bardhan, Hüseyin Ertan İnan, Matthew H E M Browning, Asma Safia Disha, Md Zahidul Haque, Mai Helmy, Sadia Ashraf, Angel M Dzhambov, Faysal Kabir Shuvo, Md Ashraful Alam, Sharif Mutasim Billah, Md Pervez Kabir, Md Riad Hossain, Md Golam Azam, Md Mijanur Rahman, Sarya Swed, Ranjit Sah, Juan J Montenegro-Idrogo, D Katterine Bonilla-Aldana, Alfonso J Rodriguez-Morales Jan 2024

Exposure To Urban Green Spaces And Mental Health During The Covid-19 Pandemic: Evidence From Two Low And Lower-Middle-Income Countries, Muhammad Mainuddin Patwary, Mondira Bardhan, Hüseyin Ertan İnan, Matthew H E M Browning, Asma Safia Disha, Md Zahidul Haque, Mai Helmy, Sadia Ashraf, Angel M Dzhambov, Faysal Kabir Shuvo, Md Ashraful Alam, Sharif Mutasim Billah, Md Pervez Kabir, Md Riad Hossain, Md Golam Azam, Md Mijanur Rahman, Sarya Swed, Ranjit Sah, Juan J Montenegro-Idrogo, D Katterine Bonilla-Aldana, Alfonso J Rodriguez-Morales

Faculty, Staff and Student Publications

INTRODUCTION: The COVID-19 pandemic has had a significant impact on mental health globally, with limited access to mental health care affecting low- and middle-income countries (LMICs) the most. In response, alternative strategies to support mental health have been necessary, with access to green spaces being a potential solution. While studies have highlighted the role of green spaces in promoting mental health during pandemic lockdowns, few studies have focused on the role of green spaces in mental health recovery after lockdowns. This study investigated changes in green space access and associations with mental health recovery in Bangladesh and Egypt across the …


Generation Of A Wt1 Conditional Deletion, Nuclear Red Fluorescent Protein Reporter Allele In The Mouse, Jace A Aloway, E Cristy Ruteshouser, Vicki Huff, Richard R Behringer Jan 2024

Generation Of A Wt1 Conditional Deletion, Nuclear Red Fluorescent Protein Reporter Allele In The Mouse, Jace A Aloway, E Cristy Ruteshouser, Vicki Huff, Richard R Behringer

Faculty, Staff and Student Publications

A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of …


Author Correction: Neoadjuvant Atezolizumab For Resectable Non-Small Cell Lung Cancer: An Open-Label, Single-Arm Phase Ii Trial, Jamie E Chaft, Filiz Oezkan, Mark G Kris, Paul A Bunn, Ignacio I Wistuba, David J Kwiatkowski, Dwight H Owen, Yan Tang, Bruce E Johnson, Jay M Lee, Gerard Lozanski, Maciej Pietrzak, Michal Seweryn, Woo Yul Byun, Katja Schulze, Alan Nicholas, Ann Johnson, Jessica Grindheim, Stephanie Hilz, David S Shames, Chris Rivard, Eric Toloza, Eric B Haura, Ciaran J Mcnamee, G Alexander Patterson, Saiama N Waqar, Valerie W Rusch, David P Carbone Jan 2024

Author Correction: Neoadjuvant Atezolizumab For Resectable Non-Small Cell Lung Cancer: An Open-Label, Single-Arm Phase Ii Trial, Jamie E Chaft, Filiz Oezkan, Mark G Kris, Paul A Bunn, Ignacio I Wistuba, David J Kwiatkowski, Dwight H Owen, Yan Tang, Bruce E Johnson, Jay M Lee, Gerard Lozanski, Maciej Pietrzak, Michal Seweryn, Woo Yul Byun, Katja Schulze, Alan Nicholas, Ann Johnson, Jessica Grindheim, Stephanie Hilz, David S Shames, Chris Rivard, Eric Toloza, Eric B Haura, Ciaran J Mcnamee, G Alexander Patterson, Saiama N Waqar, Valerie W Rusch, David P Carbone

Faculty, Staff and Student Publications

No abstract provided.


Pregnancy-Related Factors Responsible For Delivering Low Birth Weight Babies: An Institutional-Based Cross-Sectional Study, Jamnagar, Gujarat, Harsh K Patel, Jitesh P Mehta, Bela A Patel, Rohitkumar Ram, Dipesh V Parmar Jan 2024

Pregnancy-Related Factors Responsible For Delivering Low Birth Weight Babies: An Institutional-Based Cross-Sectional Study, Jamnagar, Gujarat, Harsh K Patel, Jitesh P Mehta, Bela A Patel, Rohitkumar Ram, Dipesh V Parmar

Faculty, Staff and Student Publications

BACKGROUND: The WHO defines LBW as "Birth weight less than 2500 grams" regardless of gestational age. Being born with a low birth weight also incurs enormous economic costs, including higher medical expenditures and social service expenses, and decreased productivity in adulthood.

OBJECTIVE: To study distribution of newborns' according to pregnancy related factors and its association with newborns' birth weight.

METHODS: An institutional based cross-sectional study. New-borns delivered at study institute were considered as study participants. Estimated final sample size was 500. Guardians (mothers) were face-to-face interviewed and also recorded data were collected from the case file and Mother and Child …


Dietary Practices Among Type 2 Diabetes Patients Visiting A Non-Communicable Disease (Ncd) Clinic In A District Of Western India: A Cross-Sectional Study, Bela Patel, Sumit Unadkat, Harsh Patel, Mittal Rathod Jan 2024

Dietary Practices Among Type 2 Diabetes Patients Visiting A Non-Communicable Disease (Ncd) Clinic In A District Of Western India: A Cross-Sectional Study, Bela Patel, Sumit Unadkat, Harsh Patel, Mittal Rathod

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Diabetes is becoming a major public health problem in the country. One of the most important lifestyle modifications necessary for diabetic patients is maintaining healthy dietary choices. These modifications in dietary practices are supposed to be followed lifelong, along with medication, for better glycemic control. Despite understanding the importance of dietary control and physical activity in the management of diabetes, adherence to these practices is poor. This study aimed to assess the dietary practices of type 2 diabetes mellitus (T2DM) patients and various factors that determine adherence to these healthy dietary practices. The secondary objective was to …


Endovascular Interventions In Cancer Patients With Compromise Of The Mediastinal Vasculature: A Review, Steven Yevich, Nicolas Cardenas, Rahul Sheth, Joshua Kuban, Milan Patel, Ketan Shah, Koustav Pal, Stephen R Chen, Alda Tam Jan 2024

Endovascular Interventions In Cancer Patients With Compromise Of The Mediastinal Vasculature: A Review, Steven Yevich, Nicolas Cardenas, Rahul Sheth, Joshua Kuban, Milan Patel, Ketan Shah, Koustav Pal, Stephen R Chen, Alda Tam

Faculty, Staff and Student Publications

The mediastinal vasculature can be affected by various etiologies in cancer patients. Both direct and indirect sequela of cancer may result in life-threatening clinical presentations. Tumor growth may cause vessel narrowing and decreased blood flow from either extrinsic mass effect, invasion into the vascular wall, or tumor thrombus within the lumen. In addition, cancer patients are predisposed to indirect sequela to the mediastinal vasculature from an increased risk of benign thromboembolic events, tumor thrombus, or iatrogenic complications during cancer treatments. Benign thrombus may result in partial or complete occlusion of the superior vena cava (SVC) or pulmonary artery. Vascular damage …


A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer Jan 2024

A Goldilocks Computational Protocol For Inhibitor Discovery Targeting Dna Damage Responses Including Replication-Repair Functions, Davide Moiani, John A Tainer

Faculty, Staff and Student Publications

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing …


Incidence And Impact Of Fungal Infections In Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis And Haploidentical Hematopoietic Cell Transplantation: A Center For International Blood And Marrow Transplant Research Analysis, Genovefa A Papanicolaou, Min Chen, Naya He, Michael J Martens, Soyoung Kim, Marjorie V Batista, Neel S Bhatt, Peiman Hematti, Joshua A Hill, Hongtao Liu, Sunita Nathan, Matthew D Seftel, Akshay Sharma, Edmund K Waller, John R Wingard, Jo-Anne H Young, Christopher E Dandoy, Miguel-Angel Perales, Roy F Chemaly, Marcie Riches, Celalettin Ustun Jan 2024

Incidence And Impact Of Fungal Infections In Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis And Haploidentical Hematopoietic Cell Transplantation: A Center For International Blood And Marrow Transplant Research Analysis, Genovefa A Papanicolaou, Min Chen, Naya He, Michael J Martens, Soyoung Kim, Marjorie V Batista, Neel S Bhatt, Peiman Hematti, Joshua A Hill, Hongtao Liu, Sunita Nathan, Matthew D Seftel, Akshay Sharma, Edmund K Waller, John R Wingard, Jo-Anne H Young, Christopher E Dandoy, Miguel-Angel Perales, Roy F Chemaly, Marcie Riches, Celalettin Ustun

Faculty, Staff and Student Publications

Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.

Methods: Patients who underwent their first …


Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang Jan 2024

Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang

Faculty, Staff and Student Publications

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune …


Distinct Reproductive Phenotypes Segregate With Differences In Body Weight In Adolescent Polycystic Ovary Syndrome., Angie Chen-Patterson, Angelina Bernier, Tania S. Burgert, Vanessa Davis, Tazeena Khan, David Geller, Emily Paprocki, Rachana Shah, Selma F. Witchel, Camila Pereira-Eshraghi, Aviva B. Sopher, Melanie G. Cree, Laura C. Torchen Jan 2024

Distinct Reproductive Phenotypes Segregate With Differences In Body Weight In Adolescent Polycystic Ovary Syndrome., Angie Chen-Patterson, Angelina Bernier, Tania S. Burgert, Vanessa Davis, Tazeena Khan, David Geller, Emily Paprocki, Rachana Shah, Selma F. Witchel, Camila Pereira-Eshraghi, Aviva B. Sopher, Melanie G. Cree, Laura C. Torchen

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a heterogenous clinical syndrome defined by hyperandrogenism and irregular menses. In adult women with PCOS, discrete metabolic and reproductive subgroups have been identified. We hypothesize that distinct phenotypes can be distinguished between adolescent girls who are lean (LN-G) and girls with obesity (OB-G) at the time of PCOS diagnosis.

METHODS: Data were extracted from the CALICO multisite PCOS database. Clinical data collected at the time of diagnosis were available in 354 patients (81% with obesity) from 7 academic centers. Patients with body mass index (BMI) < 85th percentile for age and sex were characterized as lean (LN-G) and those with BMI percentile ≥ 95th percentile as obese (OB-G). We compared metabolic and reproductive phenotypes in LN-G and OB-G.

RESULTS: Reproductive phenotypes differed between the groups, with LN-G …


Orthodontically Induced Changes To The Genetic Profile In Periodontal Ligament Tissue And Cytokine Release In Gingival Crevicular Fluid – A Pilot Investigation, Nutthakarn Ratanasereeprasert, Li-Fang Hsu, Shih-Kai Wang, Chung-Chen Jane Yao Jan 2024

Orthodontically Induced Changes To The Genetic Profile In Periodontal Ligament Tissue And Cytokine Release In Gingival Crevicular Fluid – A Pilot Investigation, Nutthakarn Ratanasereeprasert, Li-Fang Hsu, Shih-Kai Wang, Chung-Chen Jane Yao

Faculty, Staff and Student Publications

BACKGROUND/PURPOSE: It has been known that genetic factors influence orthodontic tooth movement, however, scientific research on humans is lacking. Therefore, this study aimed to investigate dynamic changes to the genetic profile in human periodontal ligament (PDL) tissue and cytokine release in gingival crevicular fluid (GCF) during the first 28 days of orthodontic treatment.

MATERIALS AND METHODS: Fifteen teeth from three patients were recruited. Full-mouth fixed appliances with extraction of four premolars and one maxillary third molar was planned for orthodontic treatment. GCF collection and tooth extraction were performed following force application for 0, 1, 3, 7, and 28 days. GCF …


A Novel Odaph Mutation Causing Amelogenesis Imperfecta And Its Expression In Human Dental Tissues, Shih-Kai Wang, Zhe-Hao Lee, Parissa Aref, Kuan-Yu Chu Jan 2024

A Novel Odaph Mutation Causing Amelogenesis Imperfecta And Its Expression In Human Dental Tissues, Shih-Kai Wang, Zhe-Hao Lee, Parissa Aref, Kuan-Yu Chu

Faculty, Staff and Student Publications

BACKGROUND/PURPOSE: Amelogenesis imperfecta (AI), an assemblage of genetic diseases with dental enamel malformations, is generally grouped into hypoplastic, hypomaturation, and hypocalcified types. This study aimed to identify the genetic etiology for a consanguineous Iranian family with autosomal recessive hypocalcified AI.

MATERIALS AND METHODS: Dental defects were characterized, and whole exome analysis conducted to search for disease-causing mutations. Minigene assay and RT-PCR were performed to evaluate molecular consequences of the identified mutation and expression of the causative gene in human dental tissues.

RESULTS: The defective enamel of erupted teeth showed extensive post-eruptive failure and discoloration. Partial enamel hypoplasia and indistinct dentino-enamel …


A Frequent Diagnostic Pitfall: Dermatological Clinical Features And Pathological Results In Diagnosing Pagetoid Squamous Cell Carcinoma In Situ (Case Series), Sheng-Kai Wang, Jia-Wei Cai, Yu Zhang, Ya-Jing Lin, Yi-Hui Yang Jan 2024

A Frequent Diagnostic Pitfall: Dermatological Clinical Features And Pathological Results In Diagnosing Pagetoid Squamous Cell Carcinoma In Situ (Case Series), Sheng-Kai Wang, Jia-Wei Cai, Yu Zhang, Ya-Jing Lin, Yi-Hui Yang

Faculty, Staff and Student Publications

Squamous cell carcinoma (SCC) in situ can occur on any skin or mucus surface and is more commonly found in elderly patients on areas of skin that have been sunburnt. Most previous case reports are from dermatologists, with few published reports from pathologists. In this study, three patients underwent pathological routine and auxiliary immunohistochemical (IHC) examination and were ultimately diagnosed with pagetoid SCC in situ - a different diagnosis from the initial clinical assessment. All three patients received a complete resection of the skin mass. After follow-up, as of June 2023, the patients had no tumour recurrence or metastasis. Pagetoid …


Activation Of Piezo1 Increases The Sensitivity Of Breast Cancer To Hyperthermia Therapy, Shao-Kang Wang, Xiao-Ting Zhang, Xuan-Yao Jiang, Bi-Jiang Geng, Tao-Lin Qing, Lei Li, Yun Chen, Jin-Feng Li, Xiao-Fang Zhang, Shuo-Gui Xu, Jiang-Bo Zhu, Yu-Ping Zhu, Mei-Tang Wang, Ji-Kuai Chen Jan 2024

Activation Of Piezo1 Increases The Sensitivity Of Breast Cancer To Hyperthermia Therapy, Shao-Kang Wang, Xiao-Ting Zhang, Xuan-Yao Jiang, Bi-Jiang Geng, Tao-Lin Qing, Lei Li, Yun Chen, Jin-Feng Li, Xiao-Fang Zhang, Shuo-Gui Xu, Jiang-Bo Zhu, Yu-Ping Zhu, Mei-Tang Wang, Ji-Kuai Chen

Faculty, Staff and Student Publications

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress


Faslpr Gene Dosage Tunes The Extent Of Lymphoproliferation And T Cell Differentiation In Lupus, Ritu Bohat, Xiaofang Liang, Yanping Chen, Chunyu Xu, Ningbo Zheng, Ashley Guerrero, Jiakai Hou, Roshni Jaffery, Nicholas A Egan, Yaxi Li, Yitao Tang, Esra Unsal, Adolfo Robles, Si Chen, Angela M Major, Hadil Elldakli, Sang-Hyuk Chung, Han Liang, M John Hicks, Yong Du, Jamie S Lin, Xiqun Chen, Chandra Mohan, Weiyi Peng Jan 2024

Faslpr Gene Dosage Tunes The Extent Of Lymphoproliferation And T Cell Differentiation In Lupus, Ritu Bohat, Xiaofang Liang, Yanping Chen, Chunyu Xu, Ningbo Zheng, Ashley Guerrero, Jiakai Hou, Roshni Jaffery, Nicholas A Egan, Yaxi Li, Yitao Tang, Esra Unsal, Adolfo Robles, Si Chen, Angela M Major, Hadil Elldakli, Sang-Hyuk Chung, Han Liang, M John Hicks, Yong Du, Jamie S Lin, Xiqun Chen, Chandra Mohan, Weiyi Peng

Faculty, Staff and Student Publications

Sle1 and Faslpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Faslpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Faslpr/+ (Sle1homo.lprhet) and compared it with B6.Faslpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Faslpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly …


Editorial: Updates On Radiation-Induced Lymphopenia, Pim J J Damen, Steven H Lin, Peter S N Van Rossum Jan 2024

Editorial: Updates On Radiation-Induced Lymphopenia, Pim J J Damen, Steven H Lin, Peter S N Van Rossum

Faculty, Staff and Student Publications

Radiotherapy is a commonly employed and effective treatment for cancer, seeking to achieve an optimal balance between tumor cell death and minimizing damage to healthy tissues. Radiation-induced lymphopenia (RIL) is a common side effect due to the high radiosensitivity of lymphocytes even at low doses (< 1Gy), leading to their direct depletion (1). While the detrimental effects of radiotherapy on lymphocytes have been recognized since 1905, its influence on tumor control and survival has remained largely unclear until recently (2). Moreover, awareness and understanding of the prognostic effects of RIL remain limited in daily clinical practice.


Mri-Guided High-Dose-Rate Gynecologic Brachytherapy Using An Mr-Linac As An Mr Simulator: A Single Institutional Experience, Whitney Massock, Yusung Kim, M Alex Dresner, Wenqing Sun, Joseph Caster, Quentin Adams, Jill Jespersen, Joel St-Aubin Jan 2024

Mri-Guided High-Dose-Rate Gynecologic Brachytherapy Using An Mr-Linac As An Mr Simulator: A Single Institutional Experience, Whitney Massock, Yusung Kim, M Alex Dresner, Wenqing Sun, Joseph Caster, Quentin Adams, Jill Jespersen, Joel St-Aubin

Faculty, Staff and Student Publications

Purpose: The goal of this study was to commission the use of a magnetic resonance linear accelerator (MR-linac; Unity) for imaging of gynecologic high-dose-rate (HDR) brachytherapy. This included optimizing imaging protocols and workflow development.

Methods and materials: T1-weighted and T2-weighted HDR imaging protocols were optimized on the Unity for HDR gynecologic imaging and treatment planning. Phantom measurements using these protocols were performed to determine geometric distortion and to assess reconstruction accuracy of the applicator compared with the ground truth computed tomography image. A treatment plan was created within the treatment planning system that was then delivered to a phantom. New …