tbuckley/cabot-search huggingface dataset:
Cuproptosis: Mechanism, role, and advances in urological malignancies
Authors: Jialong Wu, Jide He, Zenan Liu, Xuehua Zhu, Ziang Li, Anjing Chen, Jian Lu
Journal: Medicinal Research Reviews (2024)

Prostate, bladder, and kidney cancers are the most common malignancies of the urinary system. Chemotherapeutic drugs are generally used as adjuvant treatment in the middle, late, or recurrence stages after surgery for urologic cancers. However, traditional chemotherapy is plagued by problems such as poor efficacy, severe side effects, and complications. Copper-containing nanomedicines are promising novel cancer treatment modalities that can potentially overcome these disadvantages. Copper homeostasis and cuproptosis play crucial roles in the development, adaptability, and therapeutic sensitivity of urological malignancies. Cuproptosis refers to the direct binding of copper ions to lipoylated components of the tricarboxylic acid cycle, leading to protein oligomerization, loss of iron-sulfur proteins, proteotoxic stress, and cell death. This review focuses on copper homeostasis and cuproptosis as well as recent findings on copper and cuproptosis in urological malignancies. Furthermore, we highlight the potential therapeutic applications of copper- and cuproptosis-targeted therapies to better understand cuproptosis-based drugs for the treatment of urological tumors in the future.
Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off‐the‐shelf versatile tumor delivery vehicle
Authors: Mojtaba Taheri, Hossein Abdul Tehrani, Sadegh Dehghani, Mona Alibolandi, Ehsan Arefian, Mohammad Ramezani
Journal: Medicinal Research Reviews (2024)

Abstract Targeting actionable mutations in oncogene‐driven cancers and the evolution of immuno‐oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor‐tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC‐mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.
Association of N-terminal pro–brain natriuretic peptide with survival among US cancer survivors
Authors: Chao Cao, Lin Yang, Anju Nohria, Erica L Mayer, Ann H Partridge, Jennifer A Ligibel
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background N-terminal pro–brain natriuretic peptide (NT-proBNP) is a cardiac biomarker associated with the risk of heart failure and death in the general population, but it has not been explored in cancer survivors. Methods Using a US nationally representative sample of adults 20 years of age and older from the National Health and Nutrition Examination Survey from 1999 to 2004, this study compared NT-proBNP levels between adults without cancer (n = 12 574) and adult cancer survivors (n = 787). It examined the association of NT-proBNP with all-cause and cause-specific mortality among cancer survivors. Results Cancer survivors had higher NT-proBNP levels than adults without cancer (median [interquartile range] = 125.4 pg/mL [52.4-286.0] vs 43.2 pg/mL [20.3-95.0]). In particular, survivors of breast, prostate, and colorectal cancers had higher NT-proBNP levels than adults without cancer (multivariable-adjusted P &amp;lt; .05). In total, 471 survivors died (141 from cancer; 95 from cardiac disease) during a median follow-up period of 13.4 years (9393 person-years). Among cancer survivors, higher NT-proBNP levels were statistically associated with increased risks of all-cause death (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.18 to 1.46) and cardiac death (HR = 1.55, 95% CI = 1.21 to 2.00) but not with death from cancer (HR = 1.10, 95% CI = 0.92 to 1.32]). Higher NT-proBNP levels were associated with elevated overall mortality in survivors of prostate cancer (HR = 1.49, 95% CI = 1.22 to 1.81) and colorectal cancer (HR = 1.78, 95% CI = 1.00 to 3.16) (P = .169 for interaction). Nonlinear dose-response relationships were observed between NT-proBNP and mortality, with statistically significant relationships emerging above 125 pg/mL. Conclusions Cancer survivors had higher NT-proBNP levels than adults without cancer, and elevated NT-proBNP levels were associated with higher risks of all-cause and cardiac mortality in cancer survivors.
Author Correction: BCG immunization induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-γ-mediated trained immunity
Authors: Kim A. Tran, Erwan Pernet, Mina Sadeghi, Jeffrey Downey, Julia Chronopoulos, Elizabeth Lapshina, Oscar Tsai, Eva Kaufmann, Jun Ding, Maziar Divangahi
Journal: Nature Immunology (2024)
Structural stigma, gender-affirming interventions, and identity concealment as determinants of depression and life satisfaction among trans adults in 28 European countries
Authors: Berk C. Ünsal, Yagmur Ar-Karci, Zsolt Demetrovics, Melinda Reinhardt
Journal: International Journal of Transgender Health (2024)

Although medical gender-affirming interventions (GAIs) are vital for most transgender individuals, previous evidence regarding their impacts on psychological well-being is mixed. While some studies reported improvements, others failed to find such effects. Using a large-scale dataset of trans adults from 28 European countries, we aimed to understand how structural stigma and identity concealment might explain this inconsistency. 15,845 trans adults who participated in the EU-LGBTI-II survey, including measures of gender-affirming interventions, identity concealment, and life satisfaction and depression, were included in the analyses. Structural stigma was measured as the discriminatory laws, social policies, and public attitudes. The data was analyzed with multilevel moderated mediation analyses. Results demonstrated that structural stigma was associated with lower levels of undergoing GAIs. Also, GAIs were indirectly associated with higher levels of life satisfaction and lower levels of depression through increased identity concealment. Structural stigma moderated this association such that these indirect effects were amplified for trans adults living in countries with lower structural stigma. Results suggest that identity concealment might protect the mental health of trans adults undergoing GAIs, especially in low-stigma contexts, via increased identity concealment. Thus, policies and interventions targeting discriminatory legislation and negative societal attitudes should be implemented to promote access to GAIs and to improve the well-being of transgender individuals, and trans individuals should be supported in their identity management processes.
LncRNA CHKB-DT Downregulation Enhances Dilated Cardiomyopathy Through ALDH2
Authors: Xiang Nie, Jiahui Fan, Beibei Dai, Zheng Wen, Huaping Li, Chen Chen, Dao Wen Wang
Journal: Circulation Research (2024)

Human cardiac long noncoding RNA (lncRNA) profiles in patients with dilated cardiomyopathy (DCM) were previously analyzed, and the long noncoding RNA CHKB (choline kinase beta) divergent transcript (CHKB-DT) levels were found to be mostly downregulated in the heart. In this study, the function of CHKB-DT in DCM was determined.
Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds
Authors: Pejman Ghelich, Mohamadmahdi Samandari, Alireza Hassani Najafabadi, Adam Tanguay, Jacob Quint, Nikhil Menon, Delaram Ghanbariamin, Farnoosh Saeedinejad, Fatemeh Alipanah, Ramaswamy Chidambaram, Roman Krawetz, Kristo Nuutila, Steven Toro, Lindsay Barnum, Gregory D. Jay, Tannin A. Schmidt, Ali Tamayol
Journal: Advanced Healthcare Materials (2024)

Abstract Sustained inflammation can halt or delay wound healing, and macrophages play a central role in wound healing. Inflammatory macrophages are responsible for the removal of pathogens, debris, and neutrophils, while anti‐inflammatory macrophages stimulate various regenerative processes. Recombinant human Proteoglycan 4 (rhPRG4) is shown to modulate macrophage polarization and to prevent fibrosis and scarring in ear wound healing. Here, dissolvable microneedle arrays (MNAs) carrying rhPRG4 are engineered for the treatment of skin wounds. The in vitro experiments suggest that rhPRG4 modulates the inflammatory function of bone marrow‐derived macrophages. Degradable and detachable microneedles are developed from gelatin methacryloyl (GelMA) attach to a dissolvable gelatin backing. The developed MNAs are able to deliver a high dose of rhPRG4 through the dissolution of the gelatin backing post‐injury, while the GelMA microneedles sustain rhPRG4 bioavailability over the course of treatment. In vivo results in a murine model of full‐thickness wounds with impaired healing confirm a decrease in inflammatory biomarkers such as TNF‐ α and IL‐6, and an increase in angiogenesis and collagen deposition. Collectively, these results demonstrate rhPRG4‐incorporating MNA is a promising platform in skin wound healing applications.
Atrial fibrillation: pathophysiology, genetic and epigenetic mechanisms
Authors: Manlio Vinciguerra, Dobromir Dobrev, Stanley Nattel
Journal: The Lancet Regional Health - Europe (2024)

Atrial fibrillation (AF) is the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence dramatically increases with age and could reach up to ∼10% in the elderly. The management of AF is a complex issue that is object of extensive ongoing basic and clinical research, it depends on its genetic and epigenetic causes, and it varies considerably geographically and also according to the ethnicity. Mechanistically, over the last decade, Genome Wide Association Studies have uncovered over 100 genetic loci associated with AF, and have shown that European ancestry is associated with elevated risk of AF. These AF-associated loci revolve around different types of disturbances, including inflammation, electrical abnormalities, and structural remodeling. Moreover, the discovery of epigenetic regulatory mechanisms, involving non-coding RNAs, DNA methylation and histone modification, has allowed unravelling what modifications reshape the processes leading to arrhythmias. Our review provides a current state of the field regarding the identification and functional characterization of AF-related genetic and epigenetic regulatory networks, including ethnic differences. We discuss clear and emerging connections between genetic regulation and pathophysiological mechanisms of AF.
Reversal of Pulmonary Hypertension in a Human-Like Model: Therapeutic Targeting of Endothelial DHFR
Authors: Priya Murugesan, Yixuan Zhang, Yuanli Huang, Nobel Chenggong Zong, Ji Youn Youn, Wenhui Chen, Chen Wang, Joseph Loscalzo, Hua Cai
Journal: Circulation Research (2024)

Pulmonary hypertension (PH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and elevated mean pulmonary arterial pressure, resulting in right heart failure.
Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment
Authors: Jiang Lin, Chengshuo Wang, Xiangdong Wang, Faming Chen, Wei Zhang, Hongchen Sun, Fuhua Yan, Yaping Pan, Dongdong Zhu, Qintai Yang, Shaohua Ge, Yao Sun, Kuiji Wang, Yuan Zhang, Mu Xian, Ming Zheng, Anchun Mo, Xin Xu, Hanguo Wang, Xuedong Zhou, Luo Zhang
Journal: International Journal of Oral Science (2024)

Abstarct Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.
Reply to: ERS/ATS spirometry interpretation standards: a gap in grading severity of airflow obstruction
Authors: Sanja Stanojevic, David A. Kaminsky, Martin R. Miller, Bruce Thompson
Journal: European Respiratory Journal (2024)

<h3>Tweetable abstract</h3> <b>A clinical interpretation or decision based on severity of physiological obstruction must always be specific to the individual and be informed by the presence of symptoms or risk factors</b>https://bit.ly/3tLRFYO
Genetic and Epigenetic Landscape for Drug Development in Polycystic Ovary Syndrome
Authors: Yi Chen, Guiquan Wang, Jingqiao Chen, Congying Wang, Xi Dong, Hsun-Ming Chang, Shuai Yuan, Yue Zhao, Liangshan Mu
Journal: Endocrine Reviews (2024)

Abstract The treatment of polycystic ovary syndrome (PCOS) faces challenges as all known treatments are merely symptomatic. The US Food and Drug Administration has not approved any drug specifically for treating PCOS. As the significance of genetics and epigenetics rises in drug development, their pivotal insights have greatly enhanced the efficacy and success of drug target discovery and validation, offering promise for guiding the advancement of PCOS treatments. In this context, we outline the genetic and epigenetic advancement in PCOS, which provide novel insights into the pathogenesis of this complex disease. We also delve into the prospective method for harnessing genetic and epigenetic strategies to identify potential drug targets and ensure target safety. Additionally, we shed light on the preliminary evidence and distinctive challenges associated with gene and epigenetic therapies in the context of PCOS.
Long-term benefits of dapagliflozin on renal outcomes of type 2 diabetes under routine care: a comparative effectiveness study on propensity score matched cohorts at low renal risk
Authors: Gian Paolo Fadini, Enrico Longato, Mario Luca Morieri, Stefano Del Prato, Angelo Avogaro, Anna Solini, Mariella Baldassarre, Agostino Consoli, Sara Morganet, Antonella Zugaro, Marco Giorgio Baroni, Francesco Andreozzi, Adriano Gatti, Adriano Gatti, Stefano De Riu, Andrea Del Buono, Raffaella Aldigeri, Riccardo Bonadonna, Alessandra Dei Cas, Angela Vazzana, Monica Antonini, Valentina Moretti, Patrizia Li Volsi, Miranda Cesare, Giorgio Zanette, Silvia Carletti, Paola D'Angelo, Gaetano Leto, Frida Leonetti, Luca D'Onofrio, Ernesto Maddaloni, Raffaella Buzzetti, Simona Frontoni, Giselle Cavallo, Susanna Morano, Tiziana Filardi, Umberto Capece, Andrea Giaccari, Antonio C. Bossi, Giancarla Meregalli, Fabrizio Querci, Alessia Gaglio, Veronica Resi, Emanuela Orsi, Stefano Fazion, Ivano G. Franzetti, Cesare Berra, Silvia Manfrini, Gabriella Garrapa, Giulio Lucarelli, Lara Riccialdelli, Elena Tortato, Marco Zavattaro, Gianluca Aimaretti, Franco Cavalot, Guglielmo Beccuti, Fabio Broglio, Bruno Fattor, Giuliana Cazzetta, Olga Lamacchia, Anna Rauseo, Salvatore De Cosmo, Rosella Cau, Mariangela Ghiani, Antonino Di Benedetto, Antonino Di Pino, Salvatore Piro, Francesco Purrello, Lucia Frittitta, Agostino Milluzzo, Giuseppina Russo
Journal: The Lancet Regional Health - Europe (2024)

Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D.
Tumor Volume Growth as Surrogate Endpoint in IDH-mt Glioma—Letter
Authors: Emmanuel Mandonnet
Journal: Clinical Cancer Research (2024)

Given the very long survivals of patients treated for an IDH-mutated glioma, monitoring treatment efficacy is challenging. While overall survival remains the major endpoint, there is a need of surrogate endpoint as a guide for decision-making in daily practice. Bhatia and colleagues recently investigated the tumor volume postoperative growth rates as a biomarker of prognosis (1). Assessing tumor kinetics on longitudinal MRI follow-up was already known to be a very helpful information in the preoperative period (2), and it is all the merit of the authors to have replicated these results in the postoperative period. However, the choice of modeling the tumor volume as following an exponential law is highly disputable. Biomathematical modeling of glioma growth predicts that the edge of the tumor should increase linearly with time, i.e., D ∝ t, D being the tumor diameter (3). Consequently, we would expect V ∝ t3. So it would have been more appropriate to fit the tumor volume growth curve neither with an exponential, nor a linear, but a 3rd order polynomial law. Of note, it is much easier to convert the exact volume V in an equivalent diameter, through the formula D = (2V)1/3. Tumor growth is then expressed in mm/year, which makes it much more intuitive for both clinicians and patients. It would be highly interesting if authors could reanalyze their data by assessing kinetics with a linear fit of the equivalent diameter and to see if some of their conclusions would still hold true. In particular, we wonder whether the absence of difference in tumor volume growth rates according to 1p19q status would be confirmed, as previous studies relying on equivalent diameter reported that 1p19q non-codeleted tumors exhibited preoperatively a faster growth than 1p19q codeleted tumors (4). Finally, monitoring the growth curve of the diameter is a very sensitive tool for assessing drug effects, as any deviation from the linear extrapolation of the pretreatment curve indicates response or failure to treatment (diameter respectively below or above its predicted value from the linear fit). The change of the slope (in mm/year) can even quantify the intensity of the response. In summary, while the work of Bhatia and colleagues is an important step towards integrating tumor kinetics in the management of patients with IDH-mutated glioma, as previously suggested by others (5), using linear fit of equivalent diameter would have rendered its implementation much more attractive.See the Response, p. 639No disclosures were reported.
Abstract A017: Computational and mouse models of adaptive therapy with multiple drugs in breast cancer
Authors: Carlo C. Maley, Sareh Seyedi, Daniel Saha, Alexander Anderson
Journal: Cancer Research (2024)

Abstract Adaptive therapy is an evolutionary approach to cancer therapy designed to maintain control of therapeutically resistant cells and thereby extend both time to progression and patient survival. Most of the previous work in adaptive therapy has used a single cytotoxic drug, and yet there are still many variations of adaptive therapy protocols. Although multidrug therapy is standard for most cancers, there is a combinatorial explosion of possible protocols with an increase in the number of drugs used. We set out to explore which protocols are likely to work best, under which conditions, using computational models. We explored 2 drug therapies but allowed the drugs to be cytotoxic or cytostatic. We tested the effects of varying the fitness cost of resistance, the amount of turnover in the tumors, and the ability of cells to replace their neighbors under crowded conditions. Adaptive therapy tends to work best when there is more competition between cells in the cancers. We also explored different dosing schedules with both fixed doses and with varying the doses as a function of tumor burden dynamics. We also selected ER+ breast cancer (MCF7) cells to be resistant to both fulvestrant (an anti-estrogen therapy) and palbociclib (a CDK4/6 targeted therapy). These endocrine-resistant ER+ breast cancer cells represent the target population for a clinical trial in endocrine-resistant ER+ metastatic breast cancer that we are seeking to open at the Mayo Clinic. We tested a few of the adaptive therapy protocols with those cells in immune-compromised mice, using either gemcitabine, capecitabine or both drugs. In general, our computational models suggest that the less drug that a protocol uses, the longer we are able to keep control over the cancers. This was corroborated in our mouse experiments. However, if too little drug is used it can’t even control the sensitive cells in the tumors, leading to a sort of Goldilocks effect for the dosing. Capping the maximum dose at a relatively low level, and modulating the dose below that level, led to long-term control for many of the protocols. Many of the tumors in the mice remained dormant for many weeks after we stopped adaptive therapy, for unknown reasons. Our results support adaptive therapy as a promising approach for both extending time to progression and improving quality of life by reducing toxicity. We are using these results to design our clinical trial. Citation Format: Carlo C. Maley, Sareh Seyedi, Daniel Saha, Alexander Anderson. Computational and mouse models of adaptive therapy with multiple drugs in breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A017.