tbuckley/cabot-search huggingface dataset:
Sarcoma Cells Secrete Hypoxia-Modified Collagen VI to Weaken the Lung Endothelial Barrier and Promote Metastasis
Authors: Ying Liu, Ileana Murazzi, Ashley M. Fuller, Hehai Pan, Valerie M. Irizarry-Negron, Ann Devine, Rohan Katti, Nicolas Skuli, Gabrielle E. Ciotti, Koreana Pak, Michael A. Pack, M. Celeste Simon, Kristy Weber, Kumarasen Cooper, T.S. Karin Eisinger-Mathason
Journal: Cancer Research (2024)

Intratumoral hypoxia correlates with metastasis and poor survival in patients with sarcoma. Using an impedance sensing assay and a zebrafish intravital microinjection model, we demonstrated here that the hypoxia-inducible collagen-modifying enzyme lysyl hydroxylase PLOD2 and its substrate collagen type VI (COLVI) weaken the lung endothelial barrier and promote transendothelial migration. Mechanistically, hypoxia-induced PLOD2 in sarcoma cells modified COLVI, which was then secreted into the vasculature. Upon reaching the apical surface of lung endothelial cells, modified COLVI from tumor cells activated integrin β1 (ITGβ1). Furthermore, activated ITGβ1 colocalized with Kindlin2, initiating their interaction with F-actin and prompting its polymerization. Polymerized F-actin disrupted endothelial adherens junctions and induced barrier dysfunction. Consistently, modified and secreted COLVI was required for the late stages of lung metastasis in vivo. Analysis of patient gene expression and survival data from The Cancer Genome Atlas (TCGA) revealed an association between the expression of both PLOD2 and COLVI and patient survival. Furthermore, high levels of COLVI were detected in surgically resected sarcoma metastases from patient lungs and in the blood of tumor-bearing mice. Together, these data identify a mechanism of sarcoma lung metastasis, revealing opportunities for therapeutic intervention.
Breast Cancer Stem Cells Secrete MIF to Mediate Tumor Metabolic Reprogramming That Drives Immune Evasion
Authors: Linlin Yan, Mingming Wu, Tianyu Wang, Hui Yuan, Xiao Zhang, Huafeng Zhang, Tao Li, Vijay Pandey, Xinghua Han, Peter E. Lobie, Tao Zhu
Journal: Cancer Research (2024)

Abstract Reprogramming of energy metabolism exerts pivotal functions in cancer progression and immune surveillance. Identification of the mechanisms mediating metabolic changes in cancer may lead to improved strategies to suppress tumor growth and stimulate antitumor immunity. Here, it was observed that the secretomes of hypoxic breast cancer cells and breast cancer stem cells (BCSC) induced reprogramming of metabolic pathways, particularly glycolysis, in normoxic breast cancer cells. Screening of the BCSC secretome identified MIF as a pivotal factor potentiating glycolysis. Mechanistically, MIF increased c-MYC–mediated transcriptional upregulation of the glycolytic enzyme aldolase C by activating WNT/β-catenin signaling. Targeting MIF attenuated glycolysis and impaired xenograft growth and metastasis. MIF depletion in breast cancer cells also augmented intratumoral cytolytic CD8+ T cells and proinflammatory macrophages while decreasing regulatory T cells and tumor-associated neutrophils in the tumor microenvironment. Consequently, targeting MIF improved the therapeutic efficacy of immune checkpoint blockade in triple-negative breast cancer. Collectively, this study proposes MIF as an attractive therapeutic target to circumvent metabolic reprogramming and immunosuppression in breast cancer. Significance: MIF secreted by breast cancer stem cells induces metabolic reprogramming in bulk tumor cells and engenders an immunosuppressive microenvironment, identifying MIF targeting as a strategy to improve immunotherapy efficacy in breast cancer.
Stromal interaction molecule 1/microtubule‐associated protein 1A/1B‐light chain 3B complex induces metastasis of hepatocellular carcinoma by promoting autophagy
Authors: Jingchun Wang, Qichao Xie, Lei Wu, Yu Zhou, Yanquan Xu, Yu Chen, Jiangang Zhang, Ran Ren, Shiming Yang, Yongsheng Li, Huakan Zhao
Journal: MedComm (2024)

Metastasis is the leading cause of death in hepatocellular carcinoma (HCC) patients, and autophagy plays a crucial role in this process by orchestrating epithelial-mesenchymal transition (EMT). Stromal interaction molecule 1 (STIM1), a central regulator of store-operated calcium entry (SOCE) in nonexcitable cells, is involved in the development and spread of HCC. However, the impact of STIM1 on autophagy regulation during HCC metastasis remains unclear. Here, we demonstrate that STIM1 is temporally regulated during autophagy-induced EMT in HCC cells, and knocking out (KO) STIM1 significantly reduces both autophagy and EMT. Interestingly, STIM1 enhances autophagy through both SOCE-dependent and independent pathways. Mechanistically, STIM1 directly interacts with microtubule-associated protein 1A/1B-light chain 3B (LC3B) to form a complex via the sterile-α motif (SAM) domain, which promotes autophagosome formation. Furthermore, deletion of the SAM domain of STIM1 abolishes its binding with LC3B, leading to a decrease in autophagy and EMT in HCC cells. These findings unveil a novel mechanism by which the STIM1/LC3B complex mediates autophagy and EMT in HCC cells, highlighting a potential target for preventing HCC metastasis.
Author Correction: Characterization of the genetic architecture of infant and early childhood body mass index
Authors: Øyvind Helgeland, Marc Vaudel, Pol Sole-Navais, Christopher Flatley, Julius Juodakis, Jonas Bacelis, Ingvild L. Koløen, Gun Peggy Knudsen, Bente B. Johansson, Per Magnus, Ted Reichborn Kjennerud, Petur B. Juliusson, Camilla Stoltenberg, Oddgeir L. Holmen, Ole A. Andreassen, Bo Jacobsson, Pål R. Njølstad, Stefan Johansson
Journal: Nature Metabolism (2024)
Glycerol‐3‐phosphate acyltransferase 3‐mediated lipid droplets accumulation confers chemoresistance of colorectal cancer
Authors: Ying Wang, Caihua Xu, Xianfeng Yang, Xiaofei Liu, Zijian Guo, Xinyu Lin, Lihua Li, Zhaohui Huang
Journal: MedComm (2024)

Colorectal cancer (CRC) is the third most common malignancy worldwide. It is well known that lipid metabolism reprogramming contributes to the tumor progression. However, the lipid metabolic alterations and potential remodeling mechanism underlying the chemoresistance of CRC remain largely unclear. In this study, we compared the gene expression profiles of chemoresistant versus control CRC cells from the GEO database and identified a key factor, Glycerol-3-phosphate acyltransferase 3 (GPAT3), that promotes lipid droplet (LD) production and confers chemoresistance of CRC. With applying of HPLC-MS and molecular dynamics simulation, we also demonstrated that the activity of lysophosphatidic acid synthesis by GPAT3 was dependent on its acetylation at K316 site. In particular, GPAT3-mediated LD accumulation inhibited immunogenic cell death of tumor, and thus facilitated CD8+ T-cell exhaustion and malignant progression in mouse xenografts and hepatic-metastasis tumors in CRC patients. High GPAT3 expression turned CRC cells into nonimmunogenic cells after (Oxaliplatin) Oxa treatment, which was supported by a decrease in cytotoxic IFN-γ release and CD8+ T-cell exhaustion. In conclusion, these findings revealed the role of GPAT3-associated LD accumulation, which conferred a malignant phenotype (chemoresistance) and regulated the tumor microenvironment of CRC. These results suggest that GPAT3 is a potential target to enhance CRC chemosensitivity and develop novel therapeutic interventions.
Synthetic self‐adjuvanted multivalent Mucin 1 (MUC1) glycopeptide vaccines with improved in vivo antitumor efficacy
Authors: Yang Zhou, Xinru Li, Yajing Guo, Ye Wu, Lixin Yin, Luyun Tu, Sheng Hong, Hui Cai, Feiqing Ding
Journal: MedComm (2024)

The tumor-associated glycoprotein Mucin 1 (MUC1) is aberrantly glycosylated on cancer cells and is considered a promising target for antitumor vaccines. The weak immunogenicity and low sequence homology of mouse mucins and human MUC1 are the main obstacles for the development of vaccines. Herein, a self-adjuvanted strategy combining toll-like receptor 2 lipopeptide ligands and T-cell epitopes and the multivalent effect were used to amplify the immune response and evade the unpredictable immunogenicity, generating two self-adjuvanted three-component MUC1 vaccines (mono- and trivalent MUC1 vaccines). To simulate the aberrantly glycosylated MUC1 glycoprotein, the MUC1 tandem repeat peptide was bounded with Tn antigens at T9, S15, and T16, and served as B-cell epitopes. Results showed that both vaccines elicited a robust antibody response in wild-type mice compared with a weaker response in MUC1 transgenic mice. The trivalent vaccine did not elevate the antibody response level compared with the monovalent vaccine; however, a more delayed tumor growth and prolonged survival time was realized in wild-type and transgenic mouse models treated with the trivalent vaccine. These results indicate that the self-adjuvanted three-component MUC1 vaccines, especially the trivalent vaccine, can trigger robust antitumor effects regardless of sequence homology, and, therefore, show promise for clinical translation.
Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases
Authors: Márta Korbonits, Joanne C. Blair, Anna Boguslawska, John Ayuk, Justin H. Davies, Maralyn R. Druce, Jane Evanson, Daniel Flanagan, Nigel Glynn, Claire E. Higham, Thomas S. Jacques, Saurabh Sinha, Ian Simmons, Nicky Thorp, Francesca M. Swords, Helen L. Storr, Helen A. Spoudeas
Journal: Nature Reviews Endocrinology (2024)

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing. This article is the second part of the first-ever comprehensive, two-part, consensus guideline to cover the care of children and young people under 19 years of age with pituitary adenoma. Part 2 details 57 recommendations for CYP with prolactinomas, Cushing disease, growth hormone excess, clinically non-functioning adenomas and TSHomas.
miRNome targeting NF-κB signaling orchestrates macrophage-triggered cancer metastasis and recurrence
Authors: Dong-Ping Chen, Jun-Cheng Wang, Zheng-Yu Liu, Pei-Lin Li, Ka-Wo Chan, Xiang-Ning Wu, Wu-De-Xin Yao, Tingting Yao, Dong-Ming Kuang, Yuan Wei
Journal: Molecular Therapy (2024)
Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice
Authors: Savannah M. Lawton, Megan A. Manson, Meng-Ni Fan, Ting-Yen Chao, Chun-Yu Chen, Peter Kim, Carley Campbell, Xiaohe Cai, Amber Vander Kooi, Carol H. Miao
Journal: Molecular Therapy (2024)
A potential bivalent mRNA vaccine candidate protects against both RSV and SARS-CoV-2 infections
Authors: Namei Wu, Jiachen Zhang, Yanqiong Shen, Xinghai Zhang, Jinge Zhou, Yan Wu, Entao Li, Xiaoming Meng, Xia Chuai, Sandra Chiu, Yucai Wang
Journal: Molecular Therapy (2024)
Beyond the adverse effects of the systemic route: Exploiting nanocarriers for the topical treatment of skin cancers
Authors: Beatriz da Silva Gomes, Ana Cláudia Paiva-Santos, Francisco Veiga, Filipa Mascarenhas-Melo
Journal: Advanced Drug Delivery Reviews (2024)

Skin cancer is a heterogeneous disease that can be divided into two main groups, melanoma and nonmelanoma skin cancers. Conventional therapies for skin cancer have numerous systemic side effects and a high recurrence rate. Topical treatment is an alternative approach, but drug permeability remains a challenge. Therefore, nanocarriers appear as important nanotechnology tools that reduces both the side effects and improves clinical outcomes. This is why they are attracting growing interest. In this review, scientific articles on the use of nanocarriers for the topical treatment of skin cancer were collected. Despite the promising results of the presented nanocarriers and considering that some of them are already on the market, there is an urgent need for investment in the development of manufacturing methods, as well as of suitable toxicological and regulatory evaluations, since the conventional methods currently used to develop these nanocarriers-based products are more time-consuming and expensive than conventional products.
Executive summary: Consensus treatment guidelines for the use of methotrexate for inflammatory skin disease in pediatric patients
Authors: Heather A. Brandling-Bennett, Lisa M. Arkin, Yvonne E. Chiu, Adelaide A. Hebert, Jeffrey P. Callen, Leslie Castelo-Soccio, Dominic O. Co, Kelly M. Cordoro, Megan L. Curran, Austin M. Dalrymple, Carsten Flohr, Ken B. Gordon, Diane Hanna, Alan D. Irvine, Susan Kim, A. Yasmine Kirkorian, Irene Lara-Corrales, Jill Lindstrom, Amy S. Paller, Melissa Reyes, Wendy Smith Begolka, Wynnis L. Tom, Abby S. Van Voorhees, Ruth Ann Vleugels, Lara Wine Lee, Olivia Davies, Elaine C. Siegfried
Journal: Journal of the American Academy of Dermatology (2024)
“Sex is not just an act but also a place to be human, to be authentic.” A qualitative interview study on practices of healthcare professionals in sexological care for transgender and non-binary people
Authors: Noor C. Gieles, Karl Gerritse, Eva Zandbergen, Stephanie Both, Baudewijntje P. C. Kreukels
Journal: International Journal of Transgender Health (2024)

Background Transgender or non-binary (TNB) individuals face specific challenges regarding their sexual well-being. Transition is associated with changes in sexual self-concept, sexual development and sexual experiences. Scientific literature and clinical guidance on sexological care provision tailored to TNB clients who experience sexual problems is limited. However, healthcare professionals (HCPs) with experience in sexological care for TNB clients may hold valuable practice-based knowledge that could inform HCPs' training in sexology.
PROTAC-mediated NR4A1 degradation as a novel strategy for cancer immunotherapy
Authors: Lei Wang, Yufeng Xiao, Yuewan Luo, Rohan P. Master, Jiao Mo, Myung-Chul Kim, Yi Liu, Chandra K. Maharjan, Urvi M. Patel, Umasankar De, Madison E. Carelock, Tanzia Islam Tithi, Xiangming Li, Donald R. Shaffer, Kevin R. Guertin, Haoyang Zhuang, Emily Moser, Keiran S.M. Smalley, Dongwen Lv, Daohong Zhou, Guangrong Zheng, Weizhou Zhang
Journal: The Journal of Experimental Medicine (2024)

An effective cancer therapy requires killing cancer cells and targeting the tumor microenvironment (TME). Searching for molecules critical for multiple cell types in the TME, we identified NR4A1 as one such molecule that can maintain the immune suppressive TME. Here, we establish NR4A1 as a valid target for cancer immunotherapy and describe a first-of-its-kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 degrades NR4A1 within hours in vitro and exhibits long-lasting NR4A1 degradation in tumors with an excellent safety profile. NR-V04 inhibits and frequently eradicates established tumors. At the mechanistic level, NR-V04 induces the tumor-infiltrating (TI) B cells and effector memory CD8+ T (Tem) cells and reduces monocytic myeloid-derived suppressor cells (m-MDSC), all of which are known to be clinically relevant immune cell populations in human melanomas. Overall, NR-V04–mediated NR4A1 degradation holds promise for enhancing anticancer immune responses and offers a new avenue for treating various types of cancers such as melanoma.
An anti-CD19/CTLA-4 switch improves efficacy and selectivity of CAR T cells targeting CD80/86-upregulated DLBCL
Authors: Lars Fabian Prinz, Tobias Riet, Daniel Felix Neureuther, Simon Lennartz, Danuta Chrobok, Hanna Hübbe, Gregor Uhl, Nicole Riet, Petra Hofmann, Marianna Hösel, Adrian Georg Simon, Luis Tetenborg, Paul Segbers, Joji Shimono, Philipp Gödel, Hyatt Balke-Want, Ruth Flümann, Gero Knittel, Hans Christian Reinhardt, Christoph Scheid, Reinhard Büttner, Björn Chapuy, Roland Tillmann Ullrich, Michael Hallek, Markus Martin Chmielewski
Journal: Cell Reports Medicine (2024)

Chimeric antigen receptor T cell (CAR T) therapy is a potent treatment for relapsed/refractory (r/r) B cell lymphomas but provides lasting remissions in only ∼40% of patients and is associated with serious adverse events. We identify an upregulation of CD80 and/or CD86 in tumor tissue of (r/r) diffuse large B cell lymphoma (DLBCL) patients treated with tisagenlecleucel. This finding leads to the development of the CAR/CCR (chimeric checkpoint receptor) design, which consists of a CD19-specific first-generation CAR co-expressed with a recombinant CTLA-4-linked receptor with a 4-1BB co-stimulatory domain. CAR/CCR T cells demonstrate superior efficacy in xenograft mouse models compared with CAR T cells, superior long-term activity, and superior selectivity in in vitro assays with non-malignant CD19+ cells. In addition, immunocompetent mice show an intact CD80−CD19+ B cell population after CAR/CCR T cell treatment. The results reveal the CAR/CCR design as a promising strategy for further translational study.
Questioning the cycad theory of Kii ALS–PDC causation
Authors: Yasumasa Kokubo, Satoru Morimoto, Mari Yoshida
Journal: Nature Reviews Neurology (2024)

Questioning the cycad theory of Kii ALS-PDC causation I n a recent Review by Menšíková and colleagues (Menšíková, K. et al.Endemic parkinsonism: clusters, biology and clinical features.Nat.Rev. Neurol.19, 599-616 ( 2023) 1 ), we have identified several statements in relation to the Kii amyotrophic lateral sclerosisparkinsonism-dementia complex (ALS-PDC) that conflict with our own observations.There are several misconceptions and errors that should not be overlooked regarding epidemiology, clinical features, neuropathology and genetics, especially in the section on causative factors, in which the authors assert that extracts from highly toxic cycad seeds were used in traditional medicine to treat diseases such as diarrhoea, dysmenorrhoea, gonorrhoea and haemorrhoids and were given to children in the belief that they would strengthen their bodies and support their development.However, Y.K. has worked directly with many patients with ALS-PDC and their families on the Kii Peninsula for over 30 years and also resided in a multi-occurrence area for 3 years, and he has noted that no residents in areas of high ALS-PDC occurrence eat or drink cycad.The use of cycad in herbal and folk medicine is very rare and seems to be unrelated to the development of ALS-PDC.Furthermore, it is uncommon to use cycad as a tonic in children.Additional findings cast doubt on the proposed link between cycad ingestion and ALS-PDC.First, S. Yokoi was a Japanese soldier who survived for 28 years in the jungles of Guam and developed symptoms of parkinsonism in his later years.He was suspected to have PDC
Reply to: Questioning the cycad theory of Kii ALS–PDC causation
Authors: Katerina Menšíková, Raymond Rosales, Carlo Colosimo, Peter Spencer, Annie Lannuzel, Yoshikazu Ugawa, Ryogen Sasaki, Santiago Giménez-Roldán, Radoslav Matej, Lucie Tuckova, Dominik Hrabos, Kristyna Kolarikova, Radek Vodicka, Radek Vrtel, Miroslav Strnad, Petr Hlustik, Pavel Otruba, Martin Prochazka, Martin Bares, Susana Boluda, Luc Buee, Gerhard Ransmayr, Petr Kaňovský
Journal: Nature Reviews Neurology (2024)
Unraveling the complexity of the senescence-associated secretory phenotype in adamantinomatous craniopharyngioma using multimodal machine learning analysis
Authors: Eric W Prince, John R Apps, John Jeang, Keanu Chee, Stephen Medlin, Eric M Jackson, Roy Dudley, David Limbrick, Robert Naftel, James Johnston, Neil Feldstein, Laura M Prolo, Kevin Ginn, Toba Niazi, Amy Smith, Lindsay Kilburn, Joshua Chern, Jeffrey Leonard, Sandi Lam, David S Hersh, Jose Mario Gonzalez-Meljem, Vladimir Amani, Andrew M Donson, Siddhartha S Mitra, Pratiti Bandopadhayay, Juan Pedro Martinez-Barbera, Todd C Hankinson
Journal: Neuro-Oncology (2024)

Abstract Background Cellular senescence can have positive and negative effects on the body, including aiding in damage repair and facilitating tumor growth. Adamantinomatous craniopharyngioma (ACP), the most common pediatric sellar/suprasellar brain tumor, poses significant treatment challenges. Recent studies suggest that senescent cells in ACP tumors may contribute to tumor growth and invasion by releasing a senesecence-associated secretory phenotype. However, a detailed analysis of these characteristics has yet to be completed. Methods We analyzed primary tissue samples from ACP patients using single-cell, single-nuclei, and spatial RNA sequencing. We performed various analyses, including gene expression clustering, inferred senescence cells from gene expression, and conducted cytokine signaling inference. We utilized LASSO to select essential gene expression pathways associated with senescence. Finally, we validated our findings through immunostaining. Results We observed significant diversity in gene expression and tissue structure. Key factors such as NFKB, RELA, and SP1 are essential in regulating gene expression, while senescence markers are present throughout the tissue. SPP1 is the most significant cytokine signaling network among ACP cells, while the Wnt signaling pathway predominantly occurs between epithelial and glial cells. Our research has identified links between senescence-associated features and pathways, such as PI3K/Akt/mTOR, MYC, FZD, and Hedgehog, with increased P53 expression associated with senescence in these cells. Conclusions A complex interplay between cellular senescence, cytokine signaling, and gene expression pathways underlies ACP development. Further research is crucial to understand how these elements interact to create novel therapeutic approaches for patients with ACP.
Transcriptional programming of translation by BCL6 controls skeletal muscle proteostasis
Authors: Krithika Ramachandran, Christopher R. Futtner, Meredith A. Sommars, Mattia Quattrocelli, Yasuhiro Omura, Ellen Fruzyna, Janice C. Wang, Nathan J. Waldeck, Madhavi D. Senagolage, Carmen G. Telles, Alexis R. Demonbreun, Erin Prendergast, Nicola Lai, Daniel Arango, Ilya R. Bederman, Elizabeth M. McNally, Grant D. Barish
Journal: Nature Metabolism (2024)
<i>Weizmannia coagulans</i> BCF-01: a novel gastrogenic probiotic for <i>Helicobacter pylori</i> infection control
Authors: Zhenhui Chen, Ziyu Tang, Wendan Li, Xiaoshi Deng, Lu Yu, Jixiang Yang, Jiaxin Liu, Yunshui Cheng, Wanwen Huang, Xiaotong Guo, Jiamin Shan, Daixuan Zhou, Weisen Zeng, Yang Bai, Hongying Fan
Journal: Gut Microbes (2024)

The widespread prevalence of