Medical Specialties Commons^™

Selinexor In Combination With Weekly Paclitaxel In Patients With Metastatic Solid Tumors: Results Of An Open Label, Single-Center, Multi-Arm Phase 1b Study With Expansion Phase In Ovarian Cancer, Shannon N Westin, Siqing Fu, Apostolia Tsimberidou, Sarina Piha-Paul, Fechukwu Akhmedzhanov, Bulent Yilmaz, Lacey Mcquinn, Amanda L Brink, Jing Gong, Cheuk Hong Leung, Heather Lin, David S Hong, Shubham Pant, Brett Carter, Amir Jazaeri, David Gershenson, Anil K Sood, Robert L Coleman, Jatin Shah, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

OBJECTIVE: Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound which blocks Exportin-1 (XPO1). Our objective was to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel.

METHODS: This was an open label, single-center, multi-arm phase 1b study utilizing a "3 + 3" design and a "basket-type" expansion in recurrent solid tumors. Selinexor (60 mg or 80 mg twice weekly orally) and weekly paclitaxel (80 mg IV 2 week on, 1 week off) were one of 13 parallel arms. Efficacy was evaluated using RECIST version 1.1.

RESULTS: All 35 patients …

View-Sharing For 4d Magnetic Resonance Imaging With Randomized Projection-Encoding Enables Improvements Of Respiratory Motion Imaging For Treatment Planning In Abdominothoracic Radiotherapy, Ergys Subashi, Li Feng, Yilin Liu, Scott Robertson, Paul Segars, Bastiaan Driehuys, Christopher R Kelsey, Fang-Fang Yin, Ricardo Otazo, Jing Cai

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BACKGROUND AND PURPOSE: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

MATERIALS AND METHODS: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize …

Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata

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Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. …

Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian

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INTRODUCTION: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

AIM: We aimed to determine expression levels of …

Disruption Of Fos Causes Craniofacial Anomalies In Developing Zebrafish, Lorena Maili, Bhavna Tandon, Qiuping Yuan, Simone Menezes, Frankie Chiu, S Shahrukh Hashmi, Ariadne Letra, George T Eisenhoffer, Jacqueline T Hecht

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Craniofacial development is a complex and tightly regulated process and disruptions can lead to structural birth defects, the most common being nonsyndromic cleft lip and palate (NSCLP). Previously, we identified FOS as a candidate regulator of NSCLP through family-based association studies, yet its specific contributions to oral and palatal formation are poorly understood. This study investigated the role of fos during zebrafish craniofacial development through genetic disruption and knockdown approaches. Fos was expressed in the periderm, olfactory epithelium and other cell populations in the head. Genetic perturbation of fos produced an abnormal craniofacial phenotype with a hypoplastic oral cavity that …

Spatial Modelling Of The Tumor Microenvironment From Multiplex Immunofluorescence Images: Methods And Applications, Gayatri Kumar, Renganayaki Krishna Pandurengan, Edwin Roger Parra, Kasthuri Kannan, Cara Haymaker

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Spatial modelling methods have gained prominence with developments in high throughput imaging platforms. Multiplex immunofluorescence (mIF) provides the scope to examine interactions between tumor and immune compartment at single cell resolution using a panel of antibodies that can be chosen based on the cancer type or the clinical interest of the study. The markers can be used to identify the phenotypes and to examine cellular interactions at global and local scales. Several translational studies rely on key understanding of the tumor microenvironment (TME) to identify drivers of immune response in immunotherapy based clinical trials. To improve the success of ongoing …

Effect Of Nodule Size And Stiffness On Phonation Threshold And Collision Pressures In A Synthetic Hemilaryngeal Vocal Fold Model, Mohsen Motie-Shirazi, Matías Zañartu, Sean D Peterson, Daryush D Mehta, Robert E Hillman, Byron D Erath

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Synthetic vocal fold (VF) replicas were used to explore the role of nodule size and stiffness on kinematic, aerodynamic, and acoustic measures of voiced speech production. Emphasis was placed on determining how changes in collision pressure may contribute to the development of phonotrauma. This was performed by adding spherical beads with different sizes and moduli of elasticity at the middle of the medial surface of synthetic silicone VF models, representing nodules of varying size and stiffness. The VF models were incorporated into a hemilaryngeal flow facility. For each case, self-sustained oscillations were investigated at the phonation threshold pressure. It was …

Review Article: New Treatments For Advanced Differentiated Thyroid Cancers And Potential Mechanisms Of Drug Resistance, Sarah Hamidi, Marie-Claude Hofmann, Priyanka C Iyer, Maria E Cabanillas, Mimi I Hu, Naifa L Busaidy, Ramona Dadu

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The treatment of advanced, radioiodine refractory, differentiated thyroid cancers (RR-DTCs) has undergone major advancements in the last decade, causing a paradigm shift in the management and prognosis of these patients. Better understanding of the molecular drivers of tumorigenesis and access to next generation sequencing of tumors have led to the development and Food and Drug Administration (FDA)-approval of numerous targeted therapies for RR-DTCs, including antiangiogenic multikinase inhibitors, and more recently, fusion-specific kinase inhibitors such as RET inhibitors and NTRK inhibitors. BRAF + MEK inhibitors have also been approved for BRAF-mutated solid tumors and are routinely used in RR-DTCs in …

Understanding Fertility Behavior Of The Forcibly Displaced Myanmar Nationals In Bangladesh: A Qualitative Study, Md Anwer Hossain, Mohammad Bellal Hossain

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INTRODUCTION: Rohingya- the Forcibly Displaced Myanmar Nationals (FDMN)- are largely characterized by a high total fertility rate (TFR) and a low contraceptive prevalence rate. This study aimed to explore the reasons behind their high fertility behavior by utilizing the Theory of Planned Behavior.

DATA AND METHOD: We adopted a cross-sectional qualitative research approach. Fifteen semi-structured, face-to-face in-depth interviews were conducted with the Rohingya husbands, wives, and community leaders (Majhi and Imam/Khatib) living in Camps 1 and 2 of Ukhiya Refugee Camp, Cox's Bazar, Bangladesh. We analyzed the qualitative data using the thematic analysis approach.

RESULTS: The Muslim-majority FDMN predominantly constructed …

Trends And Correlates Of Low Hiv Knowledge Among Ever-Married Women Of Reproductive Age: Evidence From Cross-Sectional Bangladesh Demographic And Health Survey 1996–2014, Md Tariqujjaman, Md Mehedi Hasan, Mohammad Abdullah Heel Kafi, Md Alamgir Hossain, Saad A Khan, Nadia Sultana, Rashidul Azad, Md Arif Hossain, Mahfuzur Rahman, Mohammad Bellal Hossain

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BACKGROUND: The human immunodeficiency virus (HIV) burden has frequently been changing over time due to epidemiological and demographic transitions. To safeguard people, particularly women of reproductive age, who can be exposed to transmitting this burden to the next generation, knowledge regarding this life-threatening virus needs to be increased. This research intends to identify the trends and associated correlates of "low" HIV knowledge among ever-married women of reproductive age in Bangladesh from 1996 to 2014.

METHODS: We analyzed data derived from six surveys of Bangladesh Demographic and Health Surveys conducted in 1996, 1999, 2004, 2007, 2011, and 2014. Analyses were primarily …

Trem-1, Trem-2 And Their Association With Disease Severity In Patients With Covid-19, Ruyue Fan, Zuowang Cheng, Zhisheng Huang, Ying Yang, Na Sun, Bin Hu, Peibin Hou, Bo Liu, Chuanjun Huang, Shuai Liu

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BACKGROUND: Delayed diagnosis and inadequate treatment caused by limited biomarkers are associated with the outcomes of COVID-19 patients. It is necessary to identify other promising biomarkers and candidate targets for defining dysregulated inflammatory states.

METHODS: The triggering receptors expressed on myeloid cell (TREM)-1 and TREM-2 expression from hospitalized COVID-19 patients were characterized using ELISA and flow cytometry, respectively. Their correlation with disease severity and contrast with the main clinical indicators were evaluated.

RESULTS: Increased expression of soluble TREM-1 and TREM-2 in the plasma of COVID-19 patients was found compared to the control group. Moreover, membrane-bound TREM-1 and TREM-2 expression was …

Using Rna-Based Therapies To Target The Kidney In Cardiovascular Disease, Trecia C Palmer, Robert W Hunter

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RNA-based therapies are currently used for immunisation against infections and to treat metabolic diseases. They can modulate gene expression in immune cells and hepatocytes, but their use in other cell types has been limited by an inability to selectively target specific tissues. Potential solutions to this targeting problem involve packaging therapeutic RNA molecules into delivery vehicles that are preferentially delivered to cells of interest. In this review, we consider why the kidney is a desirable target for RNA-based therapies in cardiovascular disease and discuss how such therapy could be delivered. Because the kidney plays a central role in maintaining cardiovascular …

Gibbs Process Distinguishes Survival And Reveals Contact-Inhibition Genes In Glioblastoma Multiforme, Afrooz Jahedi, Gayatri Kumar, Lavanya Kannan, Tarjani Agarwal, Jason Huse, Krishna Bhat, Kasthuri Kannan

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Tumor growth is a spatiotemporal birth-and-death process with loss of heterotypic contact-inhibition of locomotion (CIL) of tumor cells promoting invasion and metastasis. Therefore, representing tumor cells as two-dimensional points, we can expect the tumor tissues in histology slides to reflect realizations of spatial birth-and-death process which can be mathematically modeled to reveal molecular mechanisms of CIL, provided the mathematics models the inhibitory interactions. Gibbs process as an inhibitory point process is a natural choice since it is an equilibrium process of the spatial birth-and-death process. That is if the tumor cells maintain homotypic contact inhibition, the spatial distributions of tumor …

Longitudinal Dynamic Contrast-Enhanced Mri Radiomic Models For Early Prediction Of Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Bikash Panthi, Rania M Mohamed, Beatriz E Adrada, Medine Boge, Rosalind P Candelaria, Huiqin Chen, Kelly K Hunt, Lei Huo, Ken-Pin Hwang, Anil Korkut, Deanna L Lane, Huong C Le-Petross, Jessica W T Leung, Jennifer K Litton, Sanaz Pashapoor, Frances Perez, Jong Bum Son, Jia Sun, Alastair Thompson, Debu Tripathy, Vicente Valero, Peng Wei, Jason White, Zhan Xu, Wei Yang, Zijian Zhou, Clinton Yam, Gaiane M Rauch, Jingfei Ma

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Early prediction of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) patients could help oncologists select individualized treatment and avoid toxic effects associated with ineffective therapy in patients unlikely to achieve pathologic complete response (pCR). The objective of this study is to evaluate the performance of radiomic features of the peritumoral and tumoral regions from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquired at different time points of NAST for early treatment response prediction in TNBC. This study included 163 Stage I-III patients with TNBC undergoing NAST as part of a prospective clinical trial (NCT02276443). Peritumoral and tumoral regions …

Regional Disparities In Major Cancer Incidence In Korea, 1999–2018, Eun Hye Park, Mee Joo Kang, Kyu-Won Jung, Eun Hye Park, E Hwa Yun, Hye-Jin Kim, Hyun-Joo Kong, Chang Kyun Choi, Jeong-Soo Im, Hong Gwan Seo

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OBJECTIVES: This study investigated regional disparities in the incidence of 8 major cancers at the municipal level in Korea during 1999-2018 and evaluated the presence or absence of hot spots of cancer clusters during 2014-2018.

METHODS: The Korea National Cancer Incidence Database was used. Age-standardized incidence rates were calculated by gender and region at the municipal level for 4 periods of 5 years and 8 cancer types. Regional disparities were calculated as both absolute and relative measures. The possibility of clusters was examined using global Moran's I with a spatial weight matrix based on adjacency or distance.

RESULTS: Regional disparities …

Heterogeneity Of Memory T Cells In Aging, Abhinav Jain, Ines Sturmlechner, Cornelia M Weyand, Jörg J Goronzy

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Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population. Here we review how T cell memory is influenced by age. T cell memory is maintained by a dynamic population of T cells that are heterogeneous in …

C4b-Binding Protein Inhibits Particulate- And Crystalline-Induced Nlrp3 Inflammasome Activation, Damien Bierschenk, Nikolina Papac-Milicevic, Ian P Bresch, Valentina Kovacic, Serena Bettoni, Mateusz Dziedzic, Rick A Wetsel, Susanne Eschenburg, Christoph J Binder, Anna M Blom, Ben C King

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Dysregulated NLRP3 inflammasome activation drives a wide variety of diseases, while endogenous inhibition of this pathway is poorly characterised. The serum protein C4b-binding protein (C4BP) is a well-established inhibitor of complement with emerging functions as an endogenously expressed inhibitor of the NLRP3 inflammasome signalling pathway. Here, we identified that C4BP purified from human plasma is an inhibitor of crystalline- (monosodium urate, MSU) and particulate-induced (silica) NLRP3 inflammasome activation. Using a C4BP mutant panel, we identified that C4BP bound these particles

Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Antônio L Teixeira, Fabiola M Ribeiro

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TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 …

Children Then, Adults Now: Long-Term Outcomes-Performance At 15, 20, And 25 Years Of Cochlear Implant Use, João Elói Moura, Jorge Humberto Martins, Marisa Alves, Graça Oliveira, Daniela Ramos, Helena Alves, Ricardo Caiado, António Teixeira, Luís Filipe Silva, Jorge Migueis

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MOTIVATION: Severe to profound sensorineural hearing loss interferes with a child's development at the cognitive, linguistic, academic, and social levels. Since the beginning of the pediatric auditory rehabilitation program through cochlear implantation in the Ear, Nose, and Throat (ENT) Service of the Coimbra Hospital and University Center (CHUC), Portugal, its mentors defended the early diagnosis of hearing loss followed by timely intervention, and this was considered the starting point to optimize (re)habilitation through this method. Three decades or so later, recently we conducted this study to evaluate the performance of patients implanted in the initial phase of the cochlear implantation …

High Resting Energy Expenditure In Women With Episodic Migraine: Exploring The Use Of Predictive Formulas, Laís Bhering Martins, Jéssica Sales Ribeiro, Ana Maria Dos Santos Rodrigues, Luana Caroline Dos Santos, Antonio Lúcio Teixeira, Adaliene Versiani Matos Ferreira

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INTRODUCTION: Migraine is a common and disabling primary headache, and its pathophysiology is not fully understood. Previous studies have suggested that pain can increase humans' Resting Energy Expenditure (REE). However, no previous study has investigated whether the REE of individuals with migraine differs from the general population. Therefore, this study aims to assess whether the REE of women with migraine differs from that of women without headaches. We also tested the accuracy of REE predictive formulas in the migraine patients.

METHODS: This cross-sectional study involves 131 adult women aged between 18 and 65 years, 83 with migraine and 48 without …

Circulating Long Non-Coding Rnas As Novel Diagnostic Biomarkers For Alzheimer’S Disease (Ad): A Systematic Review And Meta-Analysis, Parnian Shobeiri, Sanam Alilou, Mehran Jaberinezhad, Farshad Zare, Nastaran Karimi, Saba Maleki, Antonio L Teixeira, George Perry, Nima Rezaei

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BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to be involved in the pathogenesis of neurodegenerative diseases. It has also been hypothesized that plasma exosomal lncRNAs may be used as Alzheimer's disease (AD) biomarkers. In this systematic review, we compiled all studies on the subject to evaluate the accuracy of lncRNAs in identifying AD cases through meta-analysis.

METHODS: A PRISMA-compliant systematic search was conducted in PubMed/MEDLINE, EMBASE, and Web of Science databases for English publications till September 2022. We included all observational studies published which investigated the sensitivity and specificity of various lncRNAs in plasma samples of AD diagnosis. Our …

Brain-Derived Neurotrophic Factor In Fibromyalgia: A Systematic Review And Meta-Analysis Of Its Role As A Potential Biomarker, Amir Hossein Behnoush, Amirmohammad Khalaji, Shaghayegh Khanmohammadi, Parsa Alehossein, Behrad Saeedian, Parnian Shobeiri, Antonio L Teixeira, Nima Rezaei

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BACKGROUND: Fibromyalgia (FM) is a form of chronic pain disorder accompanied by several tender points, fatigue, sleeping and mood disturbances, cognitive dysfunction, and memory problems. Brain-derived neurotrophic factor (BDNF) is also a mediator of neurotrophin for many activity-dependent processes in the brain. Despite numerous research studies investigating BDNF in FM, contradictory results have been reported. Thus, we investigated the overall effect shown by studies to find the association between peripheral BDNF concentrations and its gene polymorphisms with FM.

METHODS: A systematic search in online international databases, including PubMed, Cochrane Library, Embase, the Web of Science, and Scopus was performed. Relevant …

Non-Invasive Brain Stimulation For Fatigue In Post-Acute Sequelae Of Sars-Cov-2 (Pasc), Kelly Santana, Eduardo França, João Sato, Ana Silva, Maria Queiroz, Julia De Farias, Danniely Rodrigues, Iara Souza, Vanessa Ribeiro, Egas Caparelli-Dáquer, Antonio L Teixeira, Leigh Charvet, Abhishek Datta, Marom Bikson, Suellen Andrade

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BACKGROUND: and purpose: Fatigue is among the most common persistent symptoms following post-acute sequelae of Sars-COV-2 infection (PASC). The current study investigated the potential therapeutic effects of High-Definition transcranial Direct Current Stimulation (HD-tDCS) associated with rehabilitation program for the management of PASC-related fatigue.

METHODS: Seventy patients with PASC-related fatigue were randomized to receive 3 mA or sham HD-tDCS targeting the left primary motor cortex (M1) for 30 min paired with a rehabilitation program. Each patient underwent 10 sessions (2 sessions/week) over five weeks. Fatigue was measured as the primary outcome before and after the intervention using the Modified Fatigue Impact …

“It’S Hard To Feel A Part Of Something When You’Ve Never Met People”: Defining “Learning Community” In An Online Era, Lucy Prodgers, Elizabeth Travis, Madeleine Pownall

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Feeling part of a community of learners has been shown to foster students' engagement and sense of belonging, leading to higher retention and achievement of learning outcomes. The pivot to online teaching caused by the COVID-19 pandemic has prompted a reappraisal of all aspects of the student experience, including students' capacity and opportunity to engage in meaningful learning communities online. There has been some emergent literature which considers how to facilitate online learning communities in the emergency remote teaching context prompted by COVID-19. However, there is a notable lack of literature which considers how learning communities are defined, understood, and …

Transcriptome-Wide Profiling Of Acute Stress Induced Changes In Ribosome Occupancy Level Using External Standards, Annie W Shieh, Sandeep K Bansal, Zhen Zuo, Sidney H Wang

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Acute cellular stress is known to induce a global reduction in mRNA translation through suppression of cap dependent translation. Selective translation in response to acute stress has been shown to play important roles in regulating the stress response. However, accurately profiling translational changes transcriptome-wide in response to acute cellular stress has been challenging. Commonly used data normalization methods operate on the assumption that any systematic shifts are experimental artifacts. Consequently, if applied to profiling acute cellular stress-induced mRNA translation changes, these methods are expected to produce biased estimates. To address this issue, we designed, produced, and evaluated a panel of …

Fgf Signaling In Cranial Suture Development And Related Diseases, Xiaolei Zhao, Shannon Erhardt, Kihan Sung, Jun Wang

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Suture mesenchymal stem cells (SMSCs) are a heterogeneous stem cell population with the ability to self-renew and differentiate into multiple cell lineages. The cranial suture provides a niche for SMSCs to maintain suture patency, allowing for cranial bone repair and regeneration. In addition, the cranial suture functions as an intramembranous bone growth site during craniofacial bone development. Defects in suture development have been implicated in various congenital diseases, such as sutural agenesis and craniosynostosis. However, it remains largely unknown how intricate signaling pathways orchestrate suture and SMSC function in craniofacial bone development, homeostasis, repair and diseases. Studies in patients with …

Association Of Immune-Related Adverse Events With The Outcomes Of Immune Checkpoint Inhibitors In Patients With Dmmr/Msi-H Metastatic Colorectal Cancer, Vincenzo Nasca, Francesco Barretta, Francesca Corti, Sara Lonardi, Monica Niger, Maria Elena Elez, Marwan Fakih, Priya Jayachandran, Aakash Tushar Shah, Massimiliano Salati, Elisabetta Fenocchio, Lisa Salvatore, Chiara Cremolini, Javier Ros, Margherita Ambrosini, Giacomo Mazzoli, Rossana Intini, Michael J Overman, Rosalba Miceli, Filippo Pietrantonio

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BACKGROUND: Immune checkpoint inhibitors (ICIs) show a tremendous activity in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC), but a consistent fraction of patients does not respond. Prognostic/predictive markers are needed. Despite previous investigations in other tumor types, immune-related adverse events (irAEs) have not been well evaluated in patients with MSI-H cancers treated with ICIs.

METHODS: We conducted an international cohort study at tertiary cancer centers collecting clinic-pathological features from 331 patients with MSI-H mCRC treated with ICIs. Of note, the irAEs were summarized using a 'burden score' constructed in a way that the same score value could be obtained by …

Wnt Signaling In Liver Regeneration, Disease, And Cancer, Gengyi Zou, Jae-Il Park

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The liver exhibits the highest recovery rate from acute injuries. However, in chronic liver disease, the long-term loss of hepatocytes often leads to adverse consequences such as fibrosis, cirrhosis, and liver cancer. The Wnt signaling plays a pivotal role in both liver regeneration and tumorigenesis. Therefore, manipulating the Wnt signaling has become an attractive approach to treating liver disease, including cancer. Nonetheless, given the crucial roles of Wnt signaling in physiological processes, blocking Wnt signaling can also cause several adverse effects. Recent studies have identified cancer-specific regulators of Wnt signaling, which would overcome the limitation of Wnt signaling target approaches. …

Gankyrin-Mediated Interaction Between Cancer Cells And Tumor-Associated Macrophages Facilitates Prostate Cancer Progression And Androgen Deprivation Therapy Resistance, Guang Peng, Chao Wang, Hongru Wang, Min Qu, Keqin Dong, Yongwei Yu, Yuquan Jiang, Sishun Gan, Xu Gao

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Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions.

Bayesian Feature Selection For Radiomics Using Reliability Metrics, Katherine Shoemaker, Rachel Ger, Laurence E Court, Hugo Aerts, Marina Vannucci, Christine B Peterson

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Introduction: Imaging of tumors is a standard step in diagnosing cancer and making subsequent treatment decisions. The field of radiomics aims to develop imaging based biomarkers using methods rooted in artificial intelligence applied to medical imaging. However, a challenging aspect of developing predictive models for clinical use is that many quantitative features derived from image data exhibit instability or lack of reproducibility across different imaging systems or image-processing pipelines. Methods: To address this challenge, we propose a Bayesian sparse modeling approach for image classification based on radiomic features, where the inclusion of more reliable features is favored via a probit …