tbuckley/cabot-search huggingface dataset:
Guidelines for reporting on animal fecal transplantation (GRAFT) studies: recommendations from a systematic review of murine transplantation protocols
Authors: Kate R. Secombe, Ghanyah H. Al-Qadami, Courtney B. Subramaniam, Joanne M. Bowen, Jacqui Scott, Ysabella Z.A. Van Sebille, Matthew Snelson, Caitlin Cowan, Gerard Clarke, Cassandra E. Gheorghe, John F. Cryan, Hannah R. Wardill
Journal: Gut Microbes (2021)

Fecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation reflects a current lack of authoritative guidance on reporting standards that would facilitate replication efforts and ultimately reproducible science. We therefore systematically reviewed all FMT protocols used in mouse models with the goal of formulating recommendations on the reporting of preclinical FMT protocols. Search strategies were applied across three databases (PubMed, EMBASE, and Ovid Medline) until June 30, 2020. Data related to donor attributes, stool collection, processing/storage, recipient preparation, administration, and quality control were extracted. A total of 1753 papers were identified, with 241 identified for data extraction and analysis. Of the papers included, 92.5% reported a positive outcome with FMT intervention. However, the vast majority of studies failed to address core methodological aspects including the use of anaerobic conditions (91.7% of papers lacked information), storage (49.4%), homogenization (33.6%), concentration (31.5%), volume (19.9%) and administration route (5.3%). To address these reporting limitations, we developed theGuidelines for Reporting Animal Fecal Transplant (GRAFT) that guide reporting standards for preclinical FMT. The GRAFT recommendations will enable robust reporting of preclinical FMT design, and facilitate high-quality peer review, improving the rigor and translation of knowledge gained through preclinical FMT studies.
Dichotomous impact of affinity on the function of T cell engaging bispecific antibodies
Authors: Mathilde Poussin, Arlene Sereno, Xiufeng Wu, Flora Huang, Jason Manro, Shanshan Cao, Carmine Carpenito, Andrew Glasebrook, Daniel J Powell Jr, Stephen J Demarest
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Bispecific T cell engagers represent the majority of bispecific antibodies (BsAbs) entering the clinic to treat metastatic cancer. The ability to apply these agents safely and efficaciously in the clinic, particularly for solid tumors, has been challenging. Many preclinical studies have evaluated parameters related to the activity of T cell engaging BsAbs, but many questions remain. Main body This study investigates the impact of affinity of T cell engaging BsAbs with regards to potency, efficacy, and induction of immunomodulatory receptors/ligands using HER-2/CD3 BsAbs as a model system. We show that an IgG BsAb can be as efficacious as a smaller BsAb format both in vitro and in vivo. We uncover a dichotomous relationship between tumor-associated antigen (TAA) affinity and CD3 affinity requirements for cells that express high versus low levels of TAA. HER-2 affinity directly correlated with the CD3 engager lysis potency of HER-2/CD3 BsAbs when HER-2 receptor numbers are high (~200 K/cell), while the CD3 affinity did not impact potency until its binding affinity was extremely low (&lt;600 nM). When HER-2 receptor numbers were lower (~20 K/cell), both HER-2 and CD3 affinity impacted potency. The high affinity anti-HER-2/low CD3 affinity BsAb also demonstrated lower cytokine induction levels in vivo and a dosing paradigm atypical of extremely high potency T cell engaging BsAbs reaching peak efficacy at doses &gt;3 mg/kg. This data confirms that low CD3 affinity provides an opportunity for improved safety and dosing for T cell engaging BsAbs. T cell redirection also led to upregulation of Programmed cell death 1 (PD-1) and 4-1BB, but not CTLA-4 on T cells, and to Programmed death-ligand 1 (PD-L1) upregulation on HER-2 HI SKOV3 tumor cells, but not on HER-2 LO OVCAR3 tumor cells. Using this information, we combined anti-PD-1 or anti-4-1BB monoclonal antibodies with the HER-2/CD3 BsAb in vivo and demonstrated significantly increased efficacy against HER-2 HI SKOV3 tumors via both combinations. Conclusions Overall, these studies provide an informational dive into the optimization process of CD3 engaging BsAbs for solid tumors indicating that a reduced affinity for CD3 may enable a better therapeutic index with a greater selectivity for the target tumor and a reduced cytokine release syndrome. These studies also provide an additional argument for combining T cell checkpoint inhibition and co-stimulation to achieve optimal efficacy.
Abstract 1852: A novel PD1-CD40 bispecific antibody YH008 induces potent anti-tumor activity <i>in vivo</i> by PD1 dependent activation of CD40 signaling
Authors: Baihong Liu, Li Hui, Chonghui Liu, Zhihong Li, Fangxia Pan, Benny Yang, Qingcong Lin
Journal: Cancer Research (2021)

Abstract Immunotherapies that target PD1/PDL1 pathway have marked a new era of cancer therapy. Combinatorial treatment of inhibiting PD1/PDL1 signaling and other immunomodulating agents has been widely tested and validated as a better strategy compared to single agent treatment. CD40 (TNFRSF5) is a member of the TNFR super family, a key T cell co-stimulatory signal critical for B-cell maturation and immunoglobulin class switching. Biocytogen developed a novel first in class PD1-CD40 bispecific antibody (YH008) that agonizes CD40 conditionally upon PD1 binding. In vitro study data shows YH008 can block the interaction of PD1 to PDL1 and induced dose dependent NFAT activation. YH008 was able to activate human CD40 on reporter cells in the presence of PD1-expressing jurkat cells in a dose dependent manner without relying on FcγR expressing cells. This feature is beneficial for conditionally activation of CD40+ cells in tumor microenvironment and tumor-draining lymph nodes, where tumor specific PD1+ T cells are enriched. In vivo study result shows that YH008 demonstrated robust anti-tumor efficacy against MC38 and B16F10 tumors in PD1/CD40 double humanized mice (B-hPD1/hCD40). In hCD40 mice which has no human PD1 engagement, YH008 did not show anti-tumor activity against MC38 tumor. Furthermore, YH008 did not elevate liver enzymes of MC38 bearingB-hPD1/hCD40 mice at dose as high as 26 mg/kg, demonstrating improved liver safety profile than selicrelumab. Taken together, these data demonstrated that YH008 is a promising new immunotherapeutic candidate in cancer treatment. Citation Format: Baihong Liu, Li Hui, Chonghui Liu, Zhihong Li, Fangxia Pan, Benny Yang, Qingcong Lin. A novel PD1-CD40 bispecific antibody YH008 induces potent anti-tumor activity in vivo by PD1 dependent activation of CD40 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1852.
Triboelectric Nanogenerators for Self‐Powered Wound Healing
Authors: Xiao Xiao, Xiao Xiao, Ardo Nashalian, Alberto Libanori, Yunsheng Fang, Xiyao Li, Jun Chen
Journal: Advanced Healthcare Materials (2021)

Abstract Wound healing, one of the most complex processes in the human body, involves the spatial and temporal synchronization of a variety of cell types with distinct roles. Slow or nonhealing skin wounds have potentially life‐threatening consequences, ranging from infection to scar, clot, and hemorrhage. Recently, the advent of triboelectric nanogenerators (TENGs) has brought about a plethora of self‐powered wound healing opportunities, owing to their pertinent features, including wide range choices of constitutive biocompatible materials, simple fabrication, portable size, high output power, and low cost. Herein, a comprehensive review of TENGs as an emerging biotechnology for wound healing applications is presented and covered from three unique aspects: electrical stimulation, antibacterial activity, and drug delivery. To provide a broader context of TENGs applicable to wound healing applications, state‐of‐the‐art designs are presented and discussed in each section. Although some challenges remain, TENGs are proving to be a promising platform for human‐centric therapeutics in the era of Internet of Things. Consequently, TENGs for wound healing are expected to provide a new solution in wound management and play an essential role in the future of point‐of‐care interventions.
Outcomes of artificial urinary sphincter implantation in irradiated patients: A multicenter study
Authors: J. Mamane, S. Sanchez, A.G. Lellouch, M. El-Akrhi, T. Cousin, G. Capon, I. Bentellis, D. Chevallier, M. Durand, D. Robin, J-N. Cornu, H. Dupuis, V. Gaillard, B. Poussot, T. Tricard, C. Saussine, A. Ruffion, A. Pitout, P. Lecoanet, N. Hermieu, J-F. Hermieu, B. Peyronnet, P. Bertrand-Leon
Journal: European Urology (2021)
Neurovascular Structure-Adjacent Frozen-section Examination (NeuroSAFE) Robotic Radical Prostatectomy: Functional outcomes from the first 500 consecutive cases
Authors: J.P. Noël, N. Spencer, S. Lodia, S. Karim, S. Taneja, D. Moghanchizadeh, A. Nayak, A. Tamhankar, R. Swamy, S. Agarwal, A. Narula, T. Lane, J. Adshead, N. Vasdev
Journal: European Urology (2021)
Nanocapsule-mediated sustained H2 release in the gut ameliorates metabolic dysfunction-associated fatty liver disease
Authors: Zhaokui Jin, Yuan Sun, Tian Yang, Lunbo Tan, Peixun Lv, Qingqing Xu, Geru Tao, Shucun Qin, Xifeng Lu, Qianjun He
Journal: Biomaterials (2021)
Abstract 1403: Efficacy of microtubule targeting agents on triple negative breast cancer cells influenced by adenomatous polyposis coli loss
Authors: Pamela D. Arenas, Sara M. Maloney, Jenifer R. Prosperi
Journal: Cancer Research (2021)

Abstract Triple negative breast cancer (TNBC) accounts for about 20% of all breast cancers. TNBC is an aggressive subtype of breast cancer that lacks the expression of estrogen and progesterone receptors and HER2 protein. This lack of functioning receptors results in limited treatment options, usually resulting in the use of taxanes, platinums, and anthracyclines. Although TNBC often starts as being sensitive to traditional chemotherapies, tumor relapse and/or resistance often develops. Paclitaxel (PTX) is a commonly used taxane for TNBC, well known to induce mitotic arrest through stabilization of microtubules (MT) leading to an interference with the treadmilling function of MT through the activation of the spindle assembly checkpoint. We have previously shown that loss of the Adenomatous Polyposis Coli (APC) tumor suppressor significantly increases resistance to PTX in APC knockdown (APCKD) cells generated in two human TNBC cell lines, MDA-MB-157 and MDA-MB-231. Given this striking PTX resistance, we were interested in seeing if resistance in APCKD can be seen using other non-taxane MT targeting agents. To accomplish this, we have used an epothilone (Epothilone B) and a vinca alkaloid (Vinblastine), that function by stabilizing and destabilizing the MTs, respectively. Our previous investigations demonstrated that APC loss results in increased CDK1 and CDK6, so these have been used as markers of cell cycle progression after drug treatment. In addition, changes in apoptosis were measured through the use of Annexin V and PI staining, and cleaved caspase 3 expression. Examined together, a better understanding of how APC loss influences chemoresistance in TNBC can lead to more efficient treatments for TNBC patients resistant to taxanes. Given the critical interaction between APC and MTs, this may be an avenue for targeted therapies to overcome taxane resistance. Citation Format: Pamela D. Arenas, Sara M. Maloney, Jenifer R. Prosperi. Efficacy of microtubule targeting agents on triple negative breast cancer cells influenced by adenomatous polyposis coli loss [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1403.
Abstract 3185: Integrin signaling is critical for myeloid-mediated support of T-ALL
Authors: Aram Lyu, Seo Hee Nam, Zicheng Hu, Dhivya Arasappan, Terzah M. Horton, Lauren I. Ehrlich
Journal: Cancer Research (2021)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a malignant transformation of immature T cells. Although T-ALL harbors multiple pro-leukemic genetic alterations, T-ALL blasts require exogenous signals to survive. We recently reported that tumor-associated myeloid cells provide critical support for T-ALL in mouse models and in pediatric patient samples, at least partially through activation of IGF1R signaling. However, IGF1 alone is not sufficient to support T-ALL survival, implicating additional mechanisms in myeloid-mediated T-ALL support. We previously found that T-ALL cells make prolonged and frequent contacts with tumor-associated myeloid cells in live tissue sections; thus, we hypothesized that cell-cell interactions are essential for myeloid-mediated support of T-ALL. Here, we confirm that cell contact is required for myeloid cells to support T-ALL cell survival in vitro. Analysis of transcriptional profiling data revealed enrichment of gene signatures associated with integrin pathways in T-ALL cells relative to healthy T cells, implicating integrin-mediated cell adhesion as a potential mechanism underlying contact-dependent T-ALL support. Blockade of integrin αL ± integrin β1 or their ligands ICAM-1 ± VCAM-1 via antibodies or pharmacologic inhibitors significantly decreased T-ALL survival and reduced activation of IGF1R in T-ALL cells co-cultured with tumor-associated myeloid cells. Consistent with these findings, inhibition of integrins or their ligands in vivo via antibody blockade or genetic manipulation resulted in a significant reduction of T-ALL burden at multiple leukemic sites and prolonged survival. Consistent with mouse models, blockade of integrin-mediated cell adhesion significantly reduced survival of primary pediatric T-ALL cells co-cultured with myeloid cells. Furthermore, analyses of published transcriptomic datasets from pediatric T-ALL patients showed that enrichment of integrin pathways correlates with elevated myeloid gene signatures and poor patient prognosis. Together, our studies demonstrate that tumor-associated myeloid cells promote survival of T-ALL cells by activating integrin signaling, implicating the associated integrins and downstream signals as targets for therapeutic intervention. Citation Format: Aram Lyu, Seo Hee Nam, Zicheng Hu, Dhivya Arasappan, Terzah M. Horton, Lauren I. Ehrlich. Integrin signaling is critical for myeloid-mediated support of T-ALL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3185.
Abstract 2345: Development of a novel diagnostic system for bile duct cancer using urinary metabolites
Authors: Hizuru Amano, Akinari Hinoki, Hiroo Uchida, Kazuki Yokota, Takashi Ishigaki, Minoru Sakairi, Mayumi Abe, Yasushi Terui, Hirohisa Oda, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, satoshi Makita, Aitaro Takimoto, Masamune Okamoto, Akihiro Yasui, Yoichi Nakagawa
Journal: Cancer Research (2021)

Abstract Background and Aim: Urine contains numerous small molecular metabolites that can be used as reliable, non-invasive cancer biomarkers. The aim of this study was to identify biomarkers for bile duct cancer by comprehensively analyzing urinary metabolites from patients with bile duct cancer. Materials and Methods: This study was carried out on urine samples collected before and after tumor resection in 13 patients with bile duct cancer. Urine metabolites were extracted using liquid chromatography/mass spectrometry. Biomarker candidates were identified using the Wilcoxon rank-sum test, random forest method, and orthogonal partial least squares discriminant analysis. Results: We developed an AI technology that efficiently searched for urine tumor markers based on the detailed medical information of each urine sample and used them to construct cancer test models. About 1500 metabolites, such as amino acids, nucleic acids, and lipids, were detected in one urine sample. Ten urine tumor marker candidates for bile duct cancer were identified. Conclusions: We identified novel urine tumor marker candidates for bile duct cancer. We are currently investigating additional urine samples from 23 patients with bile duct cancer. The possibility of detecting and monitoring bile duct cancer using urine tumor markers has been examined. Citation Format: Hizuru Amano, Akinari Hinoki, Hiroo Uchida, Kazuki Yokota, Takashi Ishigaki, Minoru Sakairi, Mayumi Abe, Yasushi Terui, Hirohisa Oda, Takahisa Tainaka, Chiyoe Shirota, Wataru Sumida, satoshi Makita, Aitaro Takimoto, Masamune Okamoto, Akihiro Yasui, Yoichi Nakagawa. Development of a novel diagnostic system for bile duct cancer using urinary metabolites [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2345.
Abstract 1910: Augmented secretion of IL-1α from mouse oral squamous cell carcinoma (OSCC) cells caused by the serum deprivation and hypoxia promotes immune-suppressive activity of mesenchymal stromal cells
Authors: Nobuo Kondoh, Akihiro Matsunami, Masako Mizuno-Kamiya, Naoki Umemura, Eiji Takayama, Harumi Kawaki, Kyouhei Ueno, Hiroe Morimoto-Ito, Yasunori Muramatsu, Shinichiro Sumitomo
Journal: Cancer Research (2021)

Abstract Objectives; We have already reported that mouse oral squamous carcinoma (OSCC), Sq-1979-1, cells produce IL-1α which specifically enhances the immunosuppressive activity of co-cultured mesenchymal stromal, 10T1/2, cells (Morimoto-Ito, Open Dent J. 2019). In this report, we evaluated conditions promoting the expression of IL-1α of Sq-1979-1 cells to further enhance immunosuppressive function of the 10T1/2 cells, and also examined the expression in OSCC tissues. Methods; Expression of IL-1α in Sq-1979-1 cells was evaluated by RT-PCR, western blots and enzyme-linked immune sorbent assay (ELISA). Conditioned mediums (CMs) from Sq-1979-1 cells were co-cultured with 10T1/2 cells and anti-CD3 antibody-stimulated mouse spleen cells. The production of interferon (IFN)- γ and IL-1α was evaluated using ELISA. The function of IL-1α in CM was examined by anti- IL-1α antibody. Immunohistochemical analysis of OSCC tissues was performed. Results; The production of IL-1α from Sq-1979-1 cells was specifically enhanced in lower serum (0.5% or 1.0%FBS), or under hypoxia (1.0% oxygen) compared to that in the standard growth condition supplemented with 10% FBS under normoxia. Compared to standard CM, the CMs prepared in 0.5% and 1.0% FBS, or under hypoxia significantly reduced IFN-γ production from stimulated spleen cells co-cultured with 10T1/2 cells. These functions of the CMs completely abolished by anti- IL-1α antibody. Expression of IL-1α in OSCC tissues was prominent in the midst of carcinomatous cellular lesion, or nearby necrotic lesion, where the supply deficiency could be occurred. Conclusions; The promotion of immunosuppressive activity of mesenchymal cells by Sq-1979-1 cells was specifically augmented in lower serum and hypoxic conditions, mediated by increased IL-1α production. Citation Format: Nobuo Kondoh, Akihiro Matsunami, Masako Mizuno-Kamiya, Naoki Umemura, Eiji Takayama, Harumi Kawaki, Kyouhei Ueno, Hiroe Morimoto-Ito, Yasunori Muramatsu, Shinichiro Sumitomo. Augmented secretion of IL-1α from mouse oral squamous cell carcinoma (OSCC) cells caused by the serum deprivation and hypoxia promotes immune-suppressive activity of mesenchymal stromal cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1910.
Abstract 17337: Postconditioning with Netrin-1 Protects Against Myocardial Ischemia-Reperfusion Injury Via a DCC/ERK1/2/eNOS Mechanism
Authors: Jalaleddinne O Bouhidel, Hua L Cai
Journal: Circulation (2011)

Given as a pre-conditioning mimetic, we have previously shown that netrin-1 markedly reduces myocardial ischemia-reperfusion (I/R) injury by increasing nitric oxyde (NO) bioavailability. However, its potential beneficial effect remains unknown if given as a post-conditioning agent. Langendorff perfused hearts isolated from C57BL/6 wild-type (WT) mice or DCC+/- mice underwent 20-min of global ischemia followed by 60-min of reperfusion (n=6). DCC (deleted in colorectal cancer) is one of the netrin-1 receptors we found to be however specifically involved in netrin-1 pre-conditioning induced cardioprotection. Netrin-1 was infused post-conditionally at the onset of reperfusion at 100 ng/mL concentration with and without UO126, a specific MEK1/2 inhibitor or 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a NO-scavenger. In WT mice, netrin-1 postconditioning significantly reduced infarct size to 17±2.5% from 43.3±4.6% in the untreated control I/R group. This phenomenon is now further confirmed using an in vivo model of myocardial ischemic injury, 30-min coronary occlusion followed by 24-hr reperfusion. UO126 or PTIO administration alone had no effect on infarct size (respectively 44.8±3% and 39.8±1.7% vs 43.3±4.6% in the untreated control I/R group) but abolished the effects of netrin-1, implicating intermediate roles of MEK/ERK1/2 and NO (respectively 44.8±2% and 43.5±2.9% vs 17±2.5% in the netrin-1 treated I/R group). Indeed, ERK1/2 and eNOS phosphorylation was significantly upregulated by netrin-1 treatment. Interestingly, the protective effect of netrin-1 was markedly diminished in the DCC+/- mice (infarct size increased to 44.5±2% from 15±2.6 % in the DCC+/+ group), indicating a dependency on DCC of netrin-1 post-conditoning induced cardioprotection. Netrin-1 also feed-forwardly upregulated DCC protein expression. Taken together, these results strongly suggest that netrin-1 protects against I/R injury in the murine heart as a post-conditioning mimetic by increasing NO production via activation of a ERK1/2/eNOS pathway, which also involves DCC activation and upregulation. These findings demonstrate that netrin-1 can serve as an innovative and powerful agent for acute treatment of myocardial infarction.