tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemoradiotherapy combined with sequential perioperative toripalimab in locally advanced esophageal squamous cell cancer
Authors: Xin Xu, Zhiyong Sun, Qiang Liu, Yao Zhang, Lei Shen, Chenpeng Zhang, Haiping Lin, Bin Hu, Ling Rong, Haiyan Chen, Xiaohang Wang, Xiaojing Zhao, Yong-Rui Bai, Qing Ye, Xiumei Ma
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Programmed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC. Methods From July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m 2 and cisplatin 25 mg/m 2 ) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes. Results A total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients. Conclusions nCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined. Trial registration number NCT04437212 .
Changes in right ventricular function and clinical outcomes following tricuspid transcatheter edge‐to‐edge repair
Authors: Tetsu Tanaka, Atsushi Sugiura, Refik Kavsur, Can Öztürk, Nihal Wilde, Sebastian Zimmer, Georg Nickenig, Marcel Weber, Johanna Vogelhuber
Journal: European Journal of Heart Failure (2024)

Abstract Aims Prognostic impact of post‐procedural changes in right ventricular (RV) function after tricuspid transcatheter edge‐to‐edge repair (T‐TEER) is still unclear. We investigated association of RV function and its post‐procedural changes with clinical outcomes in patients undergoing T‐TEER. Methods and results We retrospectively analysed 204 patients who underwent T‐TEER and echocardiographic follow‐up at 3 months after T‐TEER. RV function was assessed by RV fractional area change (RVFAC), and RV dysfunction was defined as RVFAC &lt;35%. Patients with an increase in RVFAC from baseline to the follow‐up were considered as RV responders. Patients were divided into four groups according to baseline RVFAC and the RV responder. The primary outcome was a composite of mortality and hospitalization due to heart failure within 1 year. Forty‐five of 204 patients (22.1%) had RVFAC &lt;35% at baseline, and 71 (34.8%) were RV responders. The association between the RV responder and the composite outcome had a significant interaction with RVFAC at baseline. Among patients with baseline RVFAC &lt;35%, RV responders had a lower risk of the composite outcome than RV non‐responders, while this association was not significant in those with baseline RVFAC ≥35%. Among patients with baseline RVFAC &lt;35%, a smaller RV diameter and a greater reduction of tricuspid regurgitation were predictors for the RV responder. Conclusion Post‐procedural increase in RVFAC after T‐TEER is associated with improved outcomes in patients with RV dysfunction. The factors related to the increase in RVFAC may support patient selection for T‐TEER in patients with RV dysfunction.
Recombination in bdelloid rotifer genomes: asexuality, transfer and stress
Authors: Christopher G. Wilson, Tymoteusz Pieszko, Reuben W. Nowell, Timothy G. Barraclough
Journal: Trends in Genetics (2024)

Bdelloid rotifers constitute a class of microscopic animals living in freshwater habitats worldwide. Several strange features of bdelloids have drawn attention: their ability to tolerate desiccation and other stresses, a lack of reported males across the clade despite centuries of study, and unusually high numbers of horizontally acquired, non-metazoan genes. Genome sequencing is transforming our understanding of their lifestyle and its consequences, while in turn providing wider insights about recombination and genome organisation in animals. Many questions remain, not least how to reconcile apparent genomic signatures of sex with the continued absence of reported males, why bdelloids have so many horizontally acquired genes, and how their remarkable ability to survive stress interacts with recombination and other genomic processes.
Diagnostic limitations and challenges in current clinical guidelines and potential application of metagenomic sequencing to manage pulmonary invasive fungal infections in patients with haematological malignancies
Authors: Sarah Y. Park, Monica I. Ardura, Sean X. Zhang
Journal: Clinical Microbiology and Infection (2024)

Background Pulmonary invasive fungal infections (pIFI) disproportionately affect patients with haematological malignancies (HM). Establishing a rapid and accurate diagnosis of pIFI is challenging. Multiple guidelines recommend diagnostic testing of invasive fungal infections but lack consensus and may contribute to inconsistent diagnostic approaches. Objective To identify key diagnostic challenges and review metagenomic sequencing data. Sources PubMed, professional consortium, and scientific society websites search to identify relevant, published, evidence-based clinical guidelines within the past five years. PubMed search for papers describing clinically relevant novel diagnostic technologies. Content Current guidelines of patients with HM and suspected pIFI recommend chest CT imaging and specimen testing with microscopic examination (including calcofluor white stain, histopathology, cytopathology etc), Aspergillus galactomannan, beta-D-glucan, PCR, and culture, each with certain limitations. Emerging real-world data support the adjunctive use of metagenomic sequencing-based tests for the timely diagnosis of pIFI. Implications High quality evidence from robust clinical trials is needed to determine whether guidelines should be updated to include novel diagnostic technologies. Trials should ask whether the combination of powerful novel diagnostics such as pathogen-agnostic metagenomic sequencing technologies in conjunction with conventional testing can optimize the diagnostic yield for all potential pIFI pathogens that impact the health of patients with HM.
Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis
Authors: Onorina L. Manzo, Jasmine Nour, Linda Sasset, Alice Marino, Luisa Rubinelli, Sailesh Palikhe, Martina Smimmo, Yang Hu, Maria Rosaria Bucci, Alain Borczuk, Olivier Elemento, Julie K. Freed, Giuseppe Danilo Norata, Annarita Di Lorenzo
Journal: Circulation Research (2024)

Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis. Yet, how sphingolipid metabolism and signaling change and contribute to endothelial dysfunction and atherosclerosis remain poorly understood.
A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization
Authors: Ping Yu, Tanwei Gu, Yueyang Rao, Weimin Liang, Xi Zhang, Huanguo Jiang, Jindi Lu, Jianglian She, Jianmin Guo, Wei Yang, Yonghong Liu, Yingfeng Tu, Lan Tang, Xuefeng Zhou
Journal: Acta Pharmaceutica Sinica B (2024)

Insufficient therapeutic strategies for acute kidney injury (AKI) necessitate precision therapy targeting its pathogenesis. This study reveals the new mechanism of the marine-derived anti-AKI agent, piericidin glycoside S14, targeting peroxiredoxin 1 (PRDX1). By binding to Cys83 of PRDX1 and augmenting its peroxidase activity, S14 alleviates kidney injury efficiently in
Context-dependent bird body mass responses to climate change
Authors: Natalia Ocampo-Peñuela
Journal: Trends in Ecology & Evolution (2024)

<h2>Abstract</h2> Previous studies demonstrated decreasing body size of birds in response to rising temperatures. Recently, Neate-Clegg et al. documented that birds have been becoming larger in an Afromontane forest over four decades. This highlights the complexity of morphological responses to climate, the importance of context, and the need to study phenomena in a diversity of regions.
Pioneering new frontiers in circadian medicine chronotherapies for cardiovascular health
Authors: Ifene David Festus, Jeri Spilberg, Martin E. Young, Sean Cain, Sepideh Khoshnevis, Michael H. Smolensky, Fariya Zaheer, Giannina Descalzi, Tami A. Martino
Journal: Trends in Endocrinology and Metabolism (2024)

Cardiovascular disease (CVD) is a global health concern. Circadian medicine improves cardiovascular care by aligning treatments with our body's daily rhythms and their underlying cellular circadian mechanisms. Time-based therapies, or chronotherapies, show special promise in clinical cardiology. They optimize treatment schedules for better outcomes with fewer side effects by recognizing the profound influence of rhythmic body cycles. In this review, we focus on three chronotherapy areas (medication, light, and meal timing) with potential to enhance cardiovascular care. We also highlight pioneering research in the new field of rest, the gut microbiome, novel chronotherapies for hypertension, pain management, and small molecules that targeting the circadian mechanism.
Hybrid epithelial-mesenchymal status of lung cancer dictates metastatic success through differential interaction with NK cells
Authors: Monica Parodi, Giovanni Centonze, Fabio Murianni, Paola Orecchia, Francesca Andriani, Ilaria Roato, Cecilia Gardelli, Melissa Balsamo, Massimo Moro, Giulia Taiè, Ugo Pastorino, Andrea Petretto, Chiara Lavarello ‎, Massimo Milione, Gabriella Sozzi, Luca Roz, Massimo Vitale, Giulia Bertolini
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Epithelial to mesenchymal transition (EMT) endows cancer cells with pro-metastatic properties, which appear most effective when cells enter an intermediate hybrid (H) state, characterized by integrated mesenchymal (M) and epithelial (E) traits. The reasons for this advantage are poorly known and, especially, it is totally unexplored whether the interplay between H-cells and NK cells could have a role. Here we characterize the pro-metastatic mechanics of non-small cell lung cancer (NSCLC) H-cells and their subset of cancer-initiating cells (CICs), dissecting crucial interactions with NK cells. Methods Human lung cancer cell lines and sublines representative of E, M, or H states, assessed by proteomics, were analyzed in vivo for their tumor-forming and disseminating capabilities. Interactions with NK cells were investigated in vitro using migration assays, cytotoxic degranulation assays, and evaluation of CD133+ CICs modulation after coculture, and validated in vivo through NK cell neutralization assays. Correlation between EMT status, NK cell infiltration, and survival data, was evaluated in a cohort of surgically resected NSCLC cases (n=79). Results We demonstrated that H-cells, have limited dissemination capability but show the highest potential to initiate metastases in vivo. This property was related to their ability to escape NK cell surveillance. Mechanistically, H-cells expressed low levels of NK-attracting chemokines (CXCL1 and CXCL8), generating poorly infiltrated metastases. Accordingly, proteomics and GO enrichment analysis of E, H, M cell lines showed that the related secretory processes could change during EMT. Furthermore, H-CICs uniquely expressed high levels of the inhibitory ligand B7-H3, which protected H-CIC from NK cell-mediated clearance. In vivo neutralization assays confirmed that, indeed, the pro-metastatic properties of H-cells are poorly controlled by NK cells. Finally, the analysis of patients revealed that detection of hybrid phenotypes associated with low NK infiltration in NSCLC clinical specimens could identify a subset of patients with poor prognosis. Conclusions Our study demonstrates that H-cells play a central role in the metastatic spread in NSCLC. Such pro-metastatic advantage of H-cells is supported by their altered interaction with NK cells and by the critical role of B7-H3 in preserving their H-CIC component, indicating B7-H3 as a potential target in combined NK-based therapies.
Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases
Authors: Friederike Oltmanns, Ana Vieira Antão, Pascal Irrgang, Vera Viherlehto, Leticia Jörg, Anna Schmidt, Jannik T Wagner, Michael Rückert, Ann-Sophie Flohr, Carol Imanuel Geppert, Benjamin Frey, Wibke Bayer, Claudia Gravekamp, Matthias Tenbusch, Udo Gaipl, Dennis Lapuente
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Generally, early-stage breast cancer has a good prognosis. However, if it spreads systemically, especially with pulmonary involvement, prospects worsen dramatically. Importantly, tumor-infiltrating T cells contribute to tumor control, particularly intratumoral T cells with a tissue-resident memory phenotype are associated with an improved clinical outcome. Methods Here, we use an adenoviral vector vaccine encoding endogenous tumor-associated antigens adjuvanted with interleukin-1β to induce tumor-specific tissue-resident memory T cells (TRM) in the lung for the prevention and treatment of pulmonary metastases in the murine 4T1 breast cancer model. Results The mucosal delivery of the vaccine was highly efficient in establishing tumor-specific TRM in the lung. Concomitantly, a single mucosal vaccination reduced the growth of pulmonary metastases and improved the survival in a prophylactic treatment. Vaccine-induced TRM contributed to these protective effects. In a therapeutic setting, the vaccination induced a pronounced T cell infiltration into metastases but resulted in only a minor restriction of the disease progression. However, in combination with stereotactic radiotherapy, the vaccine increased the survival time and rate of tumor-bearing mice. Conclusion In summary, our study demonstrates that mucosal vaccination is a promising strategy to harness the power of antitumor TRM and its potential combination with state-of-the-art treatments.
Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response
Authors: Hailong Qi, Zhongjie Sun, Tianle Gao, Yanling Yao, Yu Wang, Weiwei Li, Xudong Wang, Xiaofang Wang, Defang Liu, Jian-Dong Jiang
Journal: Molecular Cancer (2024)

Abstract Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines in vivo. We found that fusion with different chemokines shifted the nature of the immune response against the antigens. Although a number of chemokines were able to amplify specific CD8 + T-cell or humoral response alone or simultaneously. CCL11 was identified as the most potent chemokine in improving immunogenicity, promoting specific CD8 + T-cell stemness and generating tumor rejection. Fusing CCL11 with E6/E7 antigen as a therapeutic DNA vaccine significantly improved treatment effectiveness and caused eradication of established large tumors in 92% tumor-bearing mice ( n = 25). Fusion antigens with CCL11 expanded the TCR diversity of specific T cells and induced the infiltration of activated specific T cells, neutrophils, macrophages and dendritic cells (DCs) into the tumor, which created a comprehensive immune microenvironment lethal to tumor. Combination of the DNA vaccine with anti-CTLA4 treatment further enhanced the therapeutic effect. In addition, CCL11 could also be used for mRNA vaccine design. To summarize, CCL11 might be a potent T cell enhancer against cancer.
Network-based screening identifies sitagliptin as an antitumor drug targeting dendritic cells
Authors: Ian-Ian Ng, Jiaqi Zhang, Tingzhong Tian, Qi Peng, Zheng Huang, Kaimin Xiao, Xiyue Yao, Lui Ng, Jianyang Zeng, Haidong Tang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Dendritic cell (DC)-mediated antigen presentation is essential for the priming and activation of tumor-specific T cells. However, few drugs that specifically manipulate DC functions are available. The identification of drugs targeting DC holds great promise for cancer immunotherapy. Methods We observed that type 1 conventional DCs (cDC1s) initiated a distinct transcriptional program during antigen presentation. We used a network-based approach to screen for cDC1-targeting therapeutics. The antitumor potency and underlying mechanisms of the candidate drug were investigated in vitro and in vivo. Results Sitagliptin, an oral gliptin widely used for type 2 diabetes, was identified as a drug that targets DCs. In mouse models, sitagliptin inhibited tumor growth by enhancing cDC1-mediated antigen presentation, leading to better T-cell activation. Mechanistically, inhibition of dipeptidyl peptidase 4 (DPP4) by sitagliptin prevented the truncation and degradation of chemokines/cytokines that are important for DC activation. Sitagliptin enhanced cancer immunotherapy by facilitating the priming of antigen-specific T cells by DCs. In humans, the use of sitagliptin correlated with a lower risk of tumor recurrence in patients with colorectal cancer undergoing curative surgery. Conclusions Our findings indicate that sitagliptin-mediated DPP4 inhibition promotes antitumor immune response by augmenting cDC1 functions. These data suggest that sitagliptin can be repurposed as an antitumor drug targeting DC, which provides a potential strategy for cancer immunotherapy.
How gut microbiota may impact ocular surface homeostasis and related disorders
Authors: Marc Labetoulle, Christophe Baudouin, Jose M. Benitez del Castillo, Maurizio Rolando, Maria Rescigno, Elisabeth M. Messmer, Pasquale Aragona
Journal: Progress in Retinal and Eye Research (2024)

Changes in the bacterial flora in the gut, also described as gut microbiota, are readily acknowledged to be associated with several systemic diseases, especially those with an inflammatory, neuronal, psychological or hormonal factor involved in the pathogenesis and/or the perception of the disease. Maintaining ocular surface homeostasis is also based on all these four factors, and there is accumulating evidence in the literature on the relationship between gut microbiota and ocular surface diseases. The mechanisms involved are mostly interconnected due to the interaction of central and peripheral neuronal networks, inflammatory effectors and the hormonal system. A better understanding of the influence of the gut microbiota on the maintenance of ocular surface homeostasis, and on the onset or persistence of ocular surface disorders could bring new insights and help elucidate the epidemiology and pathology of ocular surface dynamics in health and disease. Revealing the exact nature of these associations could be of paramount importance for developing a holistic approach using highly promising new therapeutic strategies targeting ocular surface diseases.
An oncolytic vaccinia virus encoding hyaluronidase reshapes the extracellular matrix to enhance cancer chemotherapy and immunotherapy
Authors: Shibing Wang, Yuxin Li, Chuning Xu, Jie Dong, Jiwu Wei
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The redundant extracellular matrix (ECM) within tumor microenvironment (TME) such as hyaluronic acid (HA) often impairs intratumoral dissemination of antitumor drugs. Oncolytic viruses (OVs) are being studied extensively for cancer therapy either alone or in conjunction with chemotherapy and immunotherapy. Here, we designed a novel recombinant vaccinia virus encoding a soluble version of hyaluronidase Hyal1 (OVV-Hyal1) to degrade the HA and investigated its antitumor effects in combination with chemo drugs, polypeptide, immune cells, and antibodies. Methods We constructed a recombinant oncolytic vaccinia virus encoding the hyaluronidase, and investigated its function in remodeling the ECM of the TME, the antitumor efficacy both in vitro and in several murine solid tumors either alone, or in combination with chemo drugs including doxorubicin and gemcitabine, with polypeptide liraglutide, with immune therapeutics such as PD-L1/PD-1 blockade, CD47 antibody, and with CAR-T cells. Results Compared with control OVV, intratumoral injection of OVV-Hyal1 showed superior antitumor efficacies in a series of mouse subcutaneous tumor models. Moreover, HA degradation by OVV-Hyal1 resulted in increased intratumoral dissemination of chemo drugs, infiltration of T cells, NK cells, macrophages, and activation of CD8 + T cells. When OVV-Hyal1 was combined with some antitumor therapeutics, for example, doxorubicin, gemcitabine, liraglutide, anti-PD-1, anti-CD47 blockade, or CAR-T cells, more profound therapeutic outcomes were obtained. Conclusions OVV-Hyal1 effectively degrades HA to reshape the TME, therefore overcoming some major hurdles in current cancer therapy, such as limited OVs spread, unfavored dissemination of chemo drugs, polypeptides, antibodies, and insufficient infiltration of effector immune cells. OVV-Hyal1 holds the promise to improve the antitumor outcomes of current cancer therapeutics.