tbuckley/cabot-search huggingface dataset:
<i>Escherichia coli</i>adhesin protein-conjugated thermal responsive hybrid nanoparticles for photothermal and immunotherapy against cancer and its metastasis
Authors: Juyoung Hwang, Wei Zhang, Hae-Bin Park, Dhananjay Yadav, Yong Hyun Jeon, Jun-O Jin
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Advanced cancer therapy is targeted at primary tumors and also recurrent or metastatic cancers. Combinational cancer treatment has recently shown high efficiency against recurrent and metastatic cancers. In this study, we synthesized a thermal responsive hybrid nanoparticle (TRH) containing FimH, an immune stimulatory recombinant protein, for the induction of a combination of photothermal therapy (PTT) and immunotherapy against cancer and its metastasis. Methods The hybrid nanoparticle was incorporated with a near-infrared (NIR) absorbent, indocyanine green, and decorated with FimH on its surface to form F-TRH. F-TRH was evaluated for its anticancer and antimetastatic effects against CT-26 carcinoma in mice by combining PTT and immunotherapy. Results NIR laser irradiation elicited an elevation of temperature in F-TRH, which induced apoptosis in CT-26 carcinoma cells in vitro. In addition, F-TRH and NIR laser irradiation promoted photothermal-mediated therapeutic effects against CT-26 and 4T1 tumors in mice. The release of FimH from F-TRH in response to elevated temperature and apoptotic bodies of cancer cells via PTT elicited dendritic cell-mediated cancer antigen-specific T-cell responses, which subsequently inhibited the second challenge of CT-26 and 4T1 cell growth in the lung. Conclusions These data demonstrate the potential use of F-TRH for immuno-photothermal therapy against cancer and its recurrence and metastasis.
Greater Numbers of People in the US Are Living With Vision Loss
Authors: Anita Slomski
Journal: JAMA (2021)

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Enhanced Assessment of Perioperative Mortality Risk in Adults With Congenital Heart Disease
Authors: Andrew Constantine, Giulia Costola, Paolo Bianchi, Massimo Chessa, Alessandro Giamberti, Aleksander Kempny, Isma Rafiq, Sonya V. Babu-Narayan, Michael A. Gatzoulis, Andreas Hoschtitzky, Darryl Shore, Tuan-Chen Aw, Marco Ranucci, Konstantinos Dimopoulos
Journal: Journal of the American College of Cardiology (2021)
Abstract 17390: Pre-Operative Right Ventricular Outflow Tract and Pulmonary Artery Geometry Predicts Pulmonary Valve Replacement Outcomes in Patients With Tetralogy of Fallot
Authors: Veronica Toro Arana, Frandics Chan, Nicole Shiavone, Doff McElhinney, Sushma Reddy, Alison Marsden
Journal: Circulation (2018)

Introduction: Patients with Tetralogy of Fallot who had pulmonary valve replacement (PVR) are at risk for prosthetic valve failure that requires repeated valve replacement. Hypothesis: We hypothesize that the pre-operative geometry of the right ventricular outflow tract (RVOT) and the central pulmonary arteries is a predictor of future prosthetic valve dysfunction. Methods: In a retrospective study, using pre-operative cardiac MRI, we measured morphologic parameters including bifurcation angles, length, major and minor diameters, area, and circumference in various locations along the RVOT, pulmonary trunk (PT) and branch pulmonary arteries (BPAs) in 48 patients with Tetralogy of Fallot before they underwent PVR. Physiologic data was collected from their imaging reports (age, weight, height, body surface area (BSA), ventricular volumes and ejection fractions, valvular regurgitant fractions). All measurements were normalized by the patients’ BSA. Post-operative pulmonary valve function was assessed using Echocardiograms performed at an average of 5.5 years after the surgery. Valve dysfunction was defined as pulmonary regurgitation and/or pulmonary stenosis of at least moderate intensity. All geometric and physiologic parameters were compared between the group of patients who developed pulmonary valve dysfunction and those who did not, using a two-tailed Student t-test. Results: Patients who developed valve dysfunction had (1) greater RVOT circumference (p=0.038), (2) a more acute bifurcation angle between the PT and the Left Pulmonary Artery (p=0.016), and (3) smaller cross-sectional area at the distal BPAs (p=0.031, p=0.026). Conclusions: A dilated RVOT leading to flow vortices may increase the shear stress experienced by the valve, a sharp bifurcation angle disrupts flow patterns, adding dynamic load to the valve, and stenosis in the distal BPAs lead to increased resistance and an increased volume load to the valve - all promoting valve degeneration. Our findings are consistent with physiologic expectations and will be further explored using computational fluid dynamic simulations to elucidate how the parameters identified impact the hemodynamics around the pulmonary valve. A deeper understanding of the hemodynamic implications may ultimately reduce the incidence of valve degeneration by helping surgeons identify patients who are at high risk for valve dysfunction and guiding them to reconstruct the RVOT in specific configurations.
肥満細胞(MC)から派生した胸腺間質性リンパ球新生因子(TSLP)による喘息気道でIL-5を生成するためのNKT細胞の活性化
Authors: Okayama Y, Sagara H, Okumura S, Watanabe N, Fueki M, Sugiyama K, Fukuda T, Takeda K, Ra C, Saito H
Journal: Journal of Allergy and Clinical Immunology (2008)
Abstract 241: Organ Procurement Rates in a Statewide System of Cardiac Arrest Centers
Authors: Shadi Rafael, Madalyn Karamooz, Kyle Mccarty, Tyler Vadeboncoeur, Margaret Mullins, Alyson Welch, Bentley Bobrow
Journal: Circulation (2010)

Objectives: Prognostication after out-of-hospital cardiac arrest (OHCA) is difficult and many who regain a pulse but remain comatose on hospital arrival have care terminated in the emergency depart...
Abstract 2229: Landscape of RB1 alterations in 22,432 Chinese solid tumor patients
Authors: Nan Wang, Xueke She, Depei Huang, Xudong Shen, Hushan Zhang, Gang Ji
Journal: Cancer Research (2021)

Abstract Background: The retinoblastoma susceptibility gene (RB1) is one of tumor suppressor genes. This gene is mutated at variable frequencies in a variety of other human cancers. Cancer genome sequencing revealed that most types of cancer with RB1 mutation were retinoblastomas, osteosarcomas, and small-cell lung cancers, and its mutation was also found in other cancer types with a lower frequency, for instance, prostate cancer, breast cancer and etc. RB1 protein plays a prominent role in a variety of molecular processes related to DNA including gene transcription, DNA replication, DNA repair, and mitosis. However, no comprehensive status of RB1 alterations in Chinese populations with solid tumor has been reported yet. Methods: The Formalin-Fixed Paraffin-Embedded (FFPE) tissues from solid tumor patients who have underwent next-generation sequencing (NGS) from January 01, 2017 to April 15, 2020 in 3DMed Clinical Laboratory Inc. (a College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory) were analyzed. The diagnosis of the tissues was confirmed by hematoxylin and eosin (H&amp;E) staining. The single nucleotide variants (SNVs), copy number variants (CNVs) and gene rearrangements data of these patients were analyzed. Results: Of 22,432 Chinese solid tumor patients with more than 20 tumor types (58% males and 42% females, with median age was 60 years), genomic alterations in RB1 were observed in 1712 (7.6%) patients. RB1 mutations occurred most frequently in small cell lung cancer (138/165, 83.6%), followed by neuroendocrine neoplasms (42/170, 24.7%), sarcoma (127/554, 22.9%), biliary tract cancer (40/209, 19.1%), head and neck cancer (4/22, 18.2%), and liver cancer (232/1649, 14.1%). And (185/1712, 10.8%) patients were detected with germline RB1 mutation. When stratified by the mutational types, 1,443 (6.4%) patients were with SNVs, 59 (0.3%) with fusions, and 210 (0.9%) with loss in RB1 gene. Conclusion: Our results suggested RB1 alteration was widely occurred in solid tumor patients in China, and specific alteration rates differed largely between tumor types. Our study also suggested usage of NGS in the need for individualized characterization of cancers and further investigations are warranted for the cancer treatment upon molecular profiling in the clinical therapeutic setting. Citation Format: Nan Wang, Xueke She, Depei Huang, Xudong Shen, Hushan Zhang, Gang Ji. Landscape of RB1 alterations in 22,432 Chinese solid tumor patients [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 2229.
Abstract 2892: Silencing cancer-neuronal crosstalk suppresses perineural invasion in colorectal cancer
Authors: Colewyn Knoblich, Khosrow Rezvani
Journal: Cancer Research (2021)

Abstract Colorectal cancer (CRC) is one of the most diagnosed cancers and is a leading cause of cancer related mortality. Metastasis away from the primary site of CRC creates further complications, resulting in poor prognosis and decreased overall survival of patients. Perineural invasion (PNI) is an emerging field in cancer research that involves interactions between cancer and the nervous system as an alternative route for metastasis. Various studies have been conducted to understand the underlying mechanisms for metastasis, but PNI has been relatively understudied. Accumulating evidence indicate several signaling pathways are key players in the dynamic crosstalk between cancer cells and the nervous system portending the poor prognosis of patients facilitated by PNI. We hypothesize that colon and rectum cancer cells bi-directionally communicate with their adjacent nervous system influencing cancer progression and metastasis. We are using a combination of in vitro and animal models to define mechanisms underlying PNI in CRC. There are two set of experiments in this study as follow: Aim 1 determines whether neuron- cell lines co-cultured with diverse human colon and rectum cancer cells employed both selective soluble and exosome-based communications to have a stimulatory effect on the migration of colon and rectal cancer cells. We use a set of immunocytometry, western blot, flow-cytometry and proteomic approaches to determine key factors selectively used by colon/rectal cancer cells and neuronal cells to promote downstream metastatic pathways. Aim 2 uses a colon or rectal sciatic NIH-III immunodeficient mouse model to study the influence of the nervous system on cancer cells progression and involved signaling pathways in animal model. Completion of this study will uncover the soluble and vesicle factors released by cancer cells and nerve endings during cancer progression and their potential relevance in the treatment of CRC cancer. Citation Format: Colewyn Knoblich, Khosrow Rezvani. Silencing cancer-neuronal crosstalk suppresses perineural invasion in colorectal cancer [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 2892.
Abstract 1760: Role of Batf-dependant Th17 immune response in PTEN-null mouse model
Authors: Qiuyang Zhang, Sen Liu, Bing Zhang
Journal: Cancer Research (2021)

Abstract Basic leucine zipper transcription factor ATF-like (BATF) belongs to the activator protein 1 (AP-1) family of transcription factors and has been shown to be predominantly expressed in cells of hematopoietic origin, especially in T cells. Mice deficient for BATF were first described to lack T helper cell type 17 (Th17). Th17 cells are a distinct lineage of CD4+ T helper cells that provide protective immunity to infections but are also involved in chronic inflammation and autoimmunity. However, the role of Th17 response in prostate cancer remains controversial. In this study, we took a genetic approach to explore the role of BATF-dependent Th17 cells in prostate cancers by interbreeding BATF-deficient (Batf-/-) mice with mice that are conditionally mutant for PTEN, an established preclinical model for prostate cancer. Batf+/+;Pten-/- and Batf+/-;Pten-/- mice presented similar prostate phenotypes thus were put into one group (named Batf+), which were compared to the Batf-/-;Pten-/- group (named Batf-). We found that Batf- prostates were clearly smaller than Batf+ prostates at 30 weeks. The genitourinary bloc weight was significantly heavier in Batf+ mice than in Batf- mice at 12 and 30 weeks. Batf+ mice developed significantly higher percent of invasive adenocarcinomas in different prostate lobes at 9, 12, and 30 weeks, respectively compared to Batf- mice. Tumors in Batf- mice exhibited lower rates of cellular proliferation and higher apoptosis, as well as reduced inflammatory cell infiltration and angiogenesis in the prostatic stroma. Moreover, Batf- mice exhibited significantly reduced mRNA and protein levels of Th17 cytokines, AP-1 family members and IL-23R, and reduced NF-kB pathway activity in both spleen and prostate tissues. CD4+ T cells from Batf- mice cultured under Th17 conditions for 4 days, expressed reduced AP-1 family-regulated genes compared to Batf+ mice. Prostate cancer cells (LNCaP) with overexpression of BATF in vitro exhibited increased IL-23R expression. Prostate tissues from Batf- mice cultured under IL-6 or Th17 conditions for 4 days had reduced IL-23R expression compared to that from Batf+ mice. Taken together, our results suggest that Batf promotes the initiation and progression of prostate adenocarcinoma via Th17-mediated inflammatory immune responses and that the Batf-IL-23-IL-17 axis is a critical pathway that is needed for prostate adenocarcinoma development and progression. This work was supported by the NIH-National Institute of General Medical Sciences COBRE on Aging and Regenerative Medicine (P20GM103629, PD: S. Michal Jazwinski; PI: Q.Z.) and the Carol Lavin Bernick Faculty Grant from Tulane University (PI: Q.Z.). Citation Format: Qiuyang Zhang, Sen Liu, Bing Zhang. Role of Batf-dependant Th17 immune response in PTEN-null mouse model [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 1760.
Abstract 1442: Targeting ATM kinase and mTOR signaling reverses bone marrow stromal cell-mediated protection of FLT3-ITD AML from FLT3-targeted therapy
Authors: Hae J. Park, Mark A. Gregory, Vadym Zaberezhnyy, James DeGregori
Journal: Cancer Research (2021)

Abstract Internal tandem duplication (ITD) mutations in FMS-like tyrosine kinase 3 (FLT3) are among the most common mutations in acute myeloid leukemia (AML) and are associated with poor prognosis. FLT3-ITD causes constitutive activation of FLT3, and the strong evidence that activated FLT3 drives leukemogenesis has led to the development of several FLT3-targeted inhibitors. However, clinical studies of FLT3-targeted inhibitors have demonstrated much more effective clearing of leukemic burden in the periphery than in the bone marrow, implicating the bone marrow microenvironment as a potential contributor to drug resistance. As previously reported, the conditioned media of human bone marrow stromal cells (CM-BMSC) protects human FLT3-ITD AML cells from the killing effect of FLT3-targeted therapy despite complete inhibition of FLT3. We further show that genetic knockdown of Ataxia Telangiectasia Mutated (ATM) in combination with FLT3 inhibition substantially reverses the protection from cell death mediated by CM-BMSC. While autophosphorylation activity of ATM is downregulated upon FLT3 inhibition in regular media, CM-BMSC prevented the loss of ATM activity. Interestingly, genetic knockdown of ATM in human FLT3-ITD AML cells impaired the activity of mTOR Complex 1, and unbiased analyses of gene expression and signaling pathways by RNA-seq analysis and Reverse Phase Protein Arrays (RPPA) showed that mTOR signaling is downregulated with FLT3 inhibition in regular media, coinciding with marked inhibition of the protein translation machinery. Both mTOR signaling and protein translation were maintained during FLT3 inhibition in the presence of CM-BMSC. Furthermore, human FLT3-ITD AML cells treated with mTOR inhibitor everolimus in combination with the FLT3 inhibitor quizartinib reversed the protection mediated by CM-BMSC, and combination therapies are currently being tested in mouse models. These data suggest that ATM kinase and mTOR signaling play a key role in bone marrow stoma-mediated protection against FLT3 targeted therapy. Findings from this research provide new insights into the mechanism of bone marrow stroma-mediated protection of FLT3-ITD AML from FLT3-targeted therapy, identifying additional candidates for combinatorial therapies designed to overcome the protective effects of bone marrow stromal cells and improve patient outcomes. Citation Format: Hae J. Park, Mark A. Gregory, Vadym Zaberezhnyy, James DeGregori. Targeting ATM kinase and mTOR signaling reverses bone marrow stromal cell-mediated protection of FLT3-ITD AML from FLT3-targeted therapy [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 1442.
Abstract 1319: Rapid accumulation of cytotoxic payload in tumor tissue drives BT5528 activity in tumor models
Authors: Johanna Lahdenranta, Gavin Bennett, Philip Huxley, Gemma Mudd, Punit Upadhyaya, Phil Jeffrey, Nicholas Keen
Journal: Cancer Research (2021)

Abstract BT5528 was developed as a Bicycle® toxin conjugate to deliver monomethyl auristatin E (MMAE) -payload to EphA2 overexpressing tumors. It consists of a bicyclic peptide targeting the tumor antigen EphA2, linked to the cytotoxin MMAE via a molecular spacer and cleavable linker. Administration of BT5528 results in rapid uptake of payload into EphA2 overexpressing xenograft tumors associated with persistent toxin levels in tumor tissue and limited systemic exposure of both parent drug and payload (1). BT5528 showed a favorable preclinical profile supporting the initiation of a first-in-human Phase I/II study (NCT04180371) to investigate safety and efficacy of BT5528 in indications with evidence of EphA2 expression including non-small-cell lung cancer (NSCLC), ovarian cancer, triple-negative breast cancer (TNBC), gastric/upper gastrointestinal (GI), pancreatic and urothelial cancers (2). We have used EphA2 overexpressing tumor xenograft models in both mice and rats to elucidate the relative differences between toxin payload delivery and systemic exposure of BT5528. Comparison of payload-delivery and systemic exposure from EphA2 -targeted Bicycle toxin conjugate and antibody-drug conjugate (ADC) demonstrate the differentiation of these toxin-payload delivery platforms. ADC payload delivery depends upon a sustained plateau-like pharmacokinetic (PK) profile that exposes target and potentially nontarget organs to intact ADC for several days. In contrast, BT5528 achieves prolonged toxin delivery to tumors, following transient exposure in plasma of less than one hour. A Phase I/II study of BT5528 in patients with solid tumors is ongoing, which will investigate if this PK novel, differentiated pharmacokinetic profile, unique to Bicycle toxin conjugates, gives rise to a favorable balance of efficacy and safety. References: 1. Bennett et al. Mol. Cancer Ther. 2020;19:1385-942. 2. Bendell et al. TPS3655 Journal of Clinical Oncology 38, no. 15_suppl Citation Format: Johanna Lahdenranta, Gavin Bennett, Philip Huxley, Gemma Mudd, Punit Upadhyaya, Phil Jeffrey, Nicholas Keen. Rapid accumulation of cytotoxic payload in tumor tissue drives BT5528 activity in tumor models [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 1319.
99mTc-Pyrophosphate Retention in Atelectatic Pulmonary Tissues of a Patient With Transthyretin Cardiac Amyloidosis
Authors: Yu Pan, Yue Wang, Yilei Zhou, Yun Xi, Yifan Zhang
Journal: Clinical Nuclear Medicine (2021)

A 61-year-old man was hospitalized for suspected cardiac amyloidosis. 99mTc-Pyrophosphate scintigraphy showed intense radiotracer uptake in the heart compared with the ribs, suggestive of transthyretin cardiac amyloidosis. Subsequent genetic test showed missense mutations in the transthyretin gene, which confirmed the diagnosis. Incidentally, a regional radiotracer uptake was seen in the bilateral lungs, respectively, corresponding to areas of atelectasis on the localizing CT of the SPECT/CT. Attention should be paid to radiotracer retention in lung atelectasis as it influences the H/CL (heart-to-contralateral lung) ratio calculation and may hinder the diagnosis of cardiac amyloidosis based on the quantitative H/CL ratio.
MicroRNA-26a-3p rescues depression-like behaviors in male rats via preventing hippocampal neuronal anomalies
Authors: Ye Li, Cuiqin Fan, Liyan Wang, Tian Lan, Rui Gao, Wenjing Wang, Shu Yan Yu
Journal: Journal of Clinical Investigation (2021)

Depression is a neuropsychiatric disease associated with neuronal anomalies within specific brain regions. In the present study, we screened microRNA (miRNA) expression profiles in the dentate gyrus (DG) of the hippocampus and found that miR-26a-3p was markedly downregulated in a rat model of depression, whereas upregulation of miR-26a-3p within DG regions rescued the neuronal deterioration and depression-like phenotypes resulting from stress exposure, effects that appear to be mediated by the PTEN pathway. The knockdown of miR-26a-3p in DG regions of normal control rats induced depression-like behaviors, effects that were accompanied by activation of the PTEN/PI3K/Akt signaling pathway and neuronal deterioration via suppression of autophagy, impairments in synaptic plasticity, and promotion of neuronal apoptosis. In conclusion, these results suggest that miR-26a-3p deficits within the hippocampal DG mediated the neuronal anomalies contributing to the display of depression-like behaviors. This miRNA may serve as a potential therapeutic target for the treatment of depression.