tbuckley/cabot-search huggingface dataset:
Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression via AKT/GSK3β/IL-8 signaling pathway
Authors: Yumiao Zhao, Jiaxin Sun, Yin Li, Xiuman Zhou, Wenjie Zhai, Yahong Wu, Guanyu Chen, Shanshan Gou, Xinghua Sui, Wenshan Zhao, Lu Qiu, Yongjie Yao, Yixuan Sun, Chunxia Chen, Yuanming Qi, Yanfeng Gao
Journal: Acta Pharmaceutica Sinica B (2021)

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3β, and polarization of M2 macrophages by upregulating interleukin-8 (IL-8) to accelerate tumor progression in the tumor microenvironment (TME). Collectively, our results discovered that TDO2 could upregulate IL-8 through AKT/GSK3β to direct the polarization of M2 macrophages in ESCC, and suggested that TDO2 could represent as an attractive therapeutic target and prognostic marker to ESCC.
Abstract 11080: Differences in Post-Test Invasive Angiography Referral Patterns Between PET and SPECT
Authors: Firas Al Badarin, John A Spertus, Paul C Chan, krishna K patel, Kevin F Kennedy, Timothy M Bateman
Journal: Circulation (2018)

Background: The paradigm of ischemia-driven post-MPI referral to angiography is predicated upon data from an era dominated by single photon emission computed tomography (SPECT) utilization. Positro...
IgM Autoantibodies to Complement Factor H in Atypical Hemolytic Uremic Syndrome
Authors: Massimo Cugno, Silvia Berra, Federica Depetri, Silvana Tedeschi, Samantha Griffini, Elena Grovetti, Sonia Caccia, Donata Cresseri, Piergiorgio Messa, Sara Testa, Fabio Giglio, Flora Peyvandi, Gianluigi Ardissino
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Atypical hemolytic uremic syndrome (aHUS) is often related to complement dysregulation, but its pathophysiology remains unknown in at list 30% of patients. Anti-factor H autoantibodies of the IgG class are responsible for 10% of patients with aHUS; autoantibodies of IgM class have not been reported. The authors found anti-factor H IgM autoantibodies in seven of 186 patients with aHUS, with a frequency six-fold higher in patients with a history of hematopoietic stem cell transplantation. The purified IgM autoantibodies recognize the active site of the factor H molecule and inhibit its binding to C3b. These findings indicate that some forms of aHUS of unknown origin could be placed within the setting of autoimmune diseases, stemming from the presence of IgM autoantibodies specific for factor H’s active site. Background Atypical hemolytic uremic syndrome (aHUS), a severe thrombotic microangiopathy, is often related to complement dysregulation, but the pathomechanisms remain unknown in at least 30% of patients. Researchers have described autoantibodies to complement factor H of the IgG class in 10% of patients with aHUS but have not reported anti-factor H autoantibodies of the IgM class. Methods In 186 patients with thrombotic microangiopathy clinically presented as aHUS, we searched for anti-factor H autoantibodies of the IgM class and those of the IgG and IgA classes. We used immunochromatography to purify anti-factor H IgM autoantibodies and immunoenzymatic methods and a competition assay with mapping mAbs to characterize interaction with the target protein. Results We detected anti-factor H autoantibodies of the IgM class in seven of 186 (3.8%) patients with thrombotic microangiopathy presented as aHUS. No association was observed between anti-factor H IgM and homozygous deletions involving CFHR3-CFHR1 . A significantly higher proportion of patients with bone marrow transplant–related thrombotic microangiopathy had anti-factor H IgM autoantibodies versus other patients with aHUS: three of 20 (15%) versus four of 166 (2.4%), respectively. The identified IgM autoantibodies recognize the SCR domain 19 of factor H molecule in all patients and interact with the factor H molecule, inhibiting its binding to C3b. Conclusions Detectable autoantibodies to factor H of the IgM class may be present in patients with aHUS, and their frequency is six-fold higher in thrombotic microangiopathy forms associated with bone marrow transplant. The autoantibody interaction with factor H’s active site may support an autoimmune mechanism in some cases previously considered to be of unknown origin.
Stigmatizing Alopecia—Perspectives of a Bald Dermatologist
Authors: Carolyn Goh
Journal: JAMA Dermatology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Living to Dream
Authors: Donald L. Bliwise, Lynn Marie Trotti
Journal: JAMA Neurology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Abstract 429: Thoracic Aortic Smooth Muscle Cell Phenotype and Contractility are Altered With Aging
Authors: Jason B Wheeler, Robert E Stroud, Elizabeth K Nadeau, Rupak Mukherjee, John S Ikonomidis, Jeffrey A Jones
Journal: Circulation Research (2016)

Background: Age-related changes in the thoracic aorta, including alterations in medial extracellular matrix (ECM) in terms of increased collagen and reduced medial cellularity, are associated with a loss of contractility in isolated smooth muscle cells (SMCs). SMCs can regulate both the passive ECM content and mechanical properties of the aorta. However, the age-dependent effects on cellular proliferation, migration, adhesion, and gene expression (phenotype) of aortic SMCs remains unknown. Accordingly, the goal of this study was to determine the age-dependent changes in these characteristics of aortic SMCs. Methods/Results: Primary cultures of SMCs were established from thoracic aortic explants harvested from 6 month (n=6) and 21 month old (n=6) C57BL/6 mice. Cellular proliferation (by Cyquant assay), migration (Boyden chamber), and adhesion (on a cell culture treated surface) were reduced in the SMCs from old mice compared to those from young mice. Expression of ECM remodeling genes, including ECM proteins, matrix metalloproteinases, and tissue inhibitors of MMPs, produced a distinct genotypic profile between old and young SMCs (Figure). Conclusions: Findings from this study demonstrated that thoracic aortic SMCs from old mice are phenotypically distinct compared to those from young mice. Further, the changes in gene expression with age are consistent with the ECM changes observed in the aorta. Future studies will be required to define the role of these age-related changes in aortic SMC phenotype in aortopathies.
血管内超音波画像においてgiant lipid poolを有した冠動脈狭窄病変に対してPTCAを施行した一例
Authors: 栗山根広, 横山正樹, 吉田俊彦, 浪川進, 行木瑞雄, 小泉智三, 小室一成, 小宮山伸之, 山本豊
Journal: Circulation (2002)
Magnetically Navigated Protein Transduction In Vivo using Iron Oxide‐Nanogel Chaperone Hybrid
Authors: Riku Kawasaki, Yoshihiro Sasaki, Tomoki Nishimura, Kiyofumi Katagiri, Kei‐ichi Morita, Yurina Sekine, Shin‐ichi Sawada, Sada‐atsu Mukai, Kazunari Akiyoshi
Journal: Advanced Healthcare Materials (2021)

Abstract Systems for “protein transduction,” intracellular delivery of functional proteins, are needed to address deliverability challenges of protein therapeutics. However, in vivo protein transduction remains challenging because of instability in serum, extracellular protease digestion and rapid excretion from the bloodstream. Here, a magnetically guided in vivo protein transduction using magnetic nanogel chaperone (MC) composed of iron oxide nanoparticles and a polysaccharide nanogel, a protein carrier inspired by “catch and release” mechanisms of molecular chaperones is demonstrated. The MC system enables efficient delivery of anti‐cancer proteins, saporin and RNaseA, into cultured tumor lines and inhibits cell proliferation, mainly via apoptosis. Magnetic in vivo protein transduction via intravenous whole body administration is demonstrated in a fibrosarcoma model. By in vivo optical imaging, MC accumulated in tumor tissues under magnetic field three times more than without irradiation. With subcutaneous injection, saporin is delivered by MC to the cytoplasm in magnetically targeted tissues. In an oral cancer model, MC‐delivered magnetically targeted saporin decreased tumor volume without significant body weight changes and no regrowth of tumor at 3 months after complete regression. Protein transduction with MC shows promise for cancer therapeutics and, potentially, for regenerative medicine and other biomedical applications.
Neddylation stabilizes Nav1.1 to maintain interneuron excitability and prevent seizures in murine epilepsy models
Authors: Wenbing Chen, Bin Luo, Nannan Gao, Haiwen Li, Hongsheng Wang, Lei Li, Wanpeng Cui, Lei Zhang, Dong Sun, Fang Liu, Zhaoqi Dong, Xiao Ren, Hongsheng Zhang, Huabo Su, Wen-Cheng Xiong, Lin Mei
Journal: Journal of Clinical Investigation (2021)

The excitability of interneurons requires Nav1.1, the α subunit of the voltage-gated sodium channel. Nav1.1 deficiency and mutations reduce interneuron excitability, a major pathological mechanism for epilepsy syndromes. However, the regulatory mechanisms of Nav1.1 expression remain unclear. Here, we provide evidence that neddylation is critical to Nav1.1 stability. Mutant mice lacking Nae1, an obligatory component of the E1 ligase for neddylation, in parvalbumin-positive interneurons (PVINs) exhibited spontaneous epileptic seizures and premature death. Electrophysiological studies indicate that Nae1 deletion reduced PVIN excitability and GABA release and consequently increased the network excitability of pyramidal neurons (PyNs). Further analysis revealed a reduction in sodium-current density, not a change in channel property, in mutant PVINs and decreased Nav1.1 protein levels. These results suggest that insufficient neddylation in PVINs reduces Nav1.1 stability and thus the excitability of PVINs; the ensuing increased PyN activity causes seizures in mice. Consistently, Nav1.1 was found reduced by proteomic analysis that revealed abnormality in synapses and metabolic pathways. Our findings describe a role of neddylation in maintaining Nav1.1 stability for PVIN excitability and reveal what we believe is a new mechanism in the pathogenesis of epilepsy.
Abstract 248: Stabilization of cIAP2 during Postconditioning protects Endothelial Cells from Reperfusion Injury
Authors: Krishnaveni Gadiraju, Frauke V Haertel, Hans M Piper, Thomas Noll
Journal: Circulation (2007)

Hypoxia-reperfusion causes a perturbance in the complex equilibrium of pro and anti apoptotic mechanisms which ultimately leads to apoptosis in the reperfused myocardium. Postconditioning (intermittent hypoxia at the onset of reperfusion) is a proven strategy to reduce reperfusion injury, however, the mechanisms are largely unknown in endothelial cells. Here we analyze the effect of postconditioning in endothelial cells and hypothesize that the ‘inhibitors of apoptosis proteins’ (IAPs), known as antiapoptotic mediators, are key elements of this protective mechanism. Methods and Results: Exposure of human umbilical vein endothelial cells to severe hypoxia (Po 2 &lt; 2 mmHg) for 2 hrs causes a 2.1±0.5-fold increase in caspase 3 activation (western blot analysis; P&lt;0.05, n=3, for all further parameters) and a 2.3±04-fold increase in apoptosis (annexin V staining) after 24 hrs of reoxygenation. cIAP2 but not cIAP1 is rapidly increased during hypoxia in a biphasic manner. Transcription inhibitor, Actinomycin D (20μg/ml) reveals that the 2.5-fold increase within 5 min of hypoxia (first phase) was independent of transcription, but the 3.1-fold increase after 60 min (second phase) was induced by gene transcription. cIAP2 levels dropped down to basal value with the onset of reperfusion. Importantly, cIAP2 levels could be maintained by postconditioning (3 short periods of intermittent hypoxia, 5 minutes each separated by a 5 minute reoxygenation) which abolished hypoxia-reoxygenation-induced apoptosis. Down regulation of IAP2 by siRNA strategy enhanced hypoxia-reoxygenation-induced apoptosis and diminished the protective effect of postconditioning. Conclusions: The present study shows for the first time that postconditioning can protect endothelial cells against hypoxia-reoxygenation induced apoptosis. This protective effect is conferred by the cIAP2, which is stabilized during hypoxia and could be maintained at an elevated level by postconditioning.
Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer
Authors: Ravi A Madan, Fatima Karzai, Renee N Donahue, Munjid Al-Harthy, Marijo Bilusic, Inger I Rosner, Harpreet Singh, Philip M Arlen, Marc R Theoret, Jennifer L Marté, Lisa Cordes, Anna Couvillon, Amy Hankin, Moniquea Williams, Helen Owens, Sarah E Lochrin, Cindy H Chau, Seth Steinberg, William Douglas Figg, William Dahut, Jeffrey Schlom, James L Gulley
Journal: Journal for ImmunoTherapy of Cancer (2021)

The standard treatment for non-metastatic castration sensitive prostate cancer (nmCSPC) is androgen deprivation therapy (ADT) or surveillance. This study evaluated the potential synergy of immunotherapy and enzalutamide (without ADT) in nmCSPC. In addition, the immunologic impact of enzalutamide was also evaluated in men with normal testosterone.
Detection of Cauda Equine Syndrome With 18F-FDG PET/CT and Leptomeningeal Metastasis by 68Ga-DOTATATE in the Same Patient With Large Cell Neuroendocrine Carcinoma of Lung
Authors: Esra Arslan, Özge Erol, Ediz Beyhan, Rahime Şahin, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2021)

Leptomeningeal metastasis is the metastatic spread of the disease to leptomeninges from solid tumors such as breast, lung cancer, and melanoma. Cauda equine syndrome is a neurological condition caused by compression of the cauda equine. The incidence of large cell neuroendocrine carcinoma in resected lung cancers appears to be 2.1% and 3.5%. The incidence of clinically diagnosed leptomeningeal metastasis in patients with solid tumors is approximately 5%. Here, we present cauda equine syndrome caused by the metastasis of large cell neuroendocrine carcinoma detected by 18F-FDG PET/CT and also 68Ga-DOTATATE PET/CT.
Myocardial perfusion PET imaging to evaluate coronary microvascular dysfunction in men with prostate cancer receiving androgen deprivation therapy.
Authors: Vivek Narayan, Marie Guerraty, Biniyam G Demissei, Naomi B. Haas, Samuel U Takvorian, Ravi Bharat Parikh, David J. Vaughn, Daniel A. Pryma, David A. Mankoff, Bonnie Ky
Journal: Journal of Clinical Oncology (2021)

211 Background: Strategies to inform cardiovascular (CV) risk are needed for prostate cancer patients initiating androgen deprivation therapy (ADT). Reduced myocardial blood flow reserve (MBFR) and coronary microvascular dysfunction (CMD) represent functional counterparts of traditional CV risk factors, including hyperlipidemia, insulin-resistance, and the metabolic syndrome. Myocardial perfusion PET stress imaging quantifies MBFR and detects CMD. However, the potential utility of these measures to indicate adverse CV changes in prostate cancer patients receiving ADT is poorly understood. Methods: In this prospective study (NCT03535987), eligible prostate cancer patients were planned for at least 6 months of ADT and curative-intent radiation therapy. All patients had a Framingham 10-year general CV risk score of at least 10% and no prior ADT exposure. Myocardial perfusion PET stress imaging was performed within 3 weeks of ADT initiation and again following 6 months of ADT exposure. MBFR was calculated as the ratio of MBF during stress / MBF during rest, and CMD was defined per established criteria as reduced MBFR (ratio &lt; 2.0) in patients without coronary artery disease. Study outcomes included the change in MBFR following 6 months of ADT exposure and the incidence of reduced MBFR and CMD. McNemar’s test and Wilcoxon signed rank test were used for comparison of paired data. Results: Fifteen patients completed baseline myocardial perfusion PET imaging, of whom 13 completed follow-up imaging at 6 months. At baseline, the median (IQR) Framingham CV risk score was 30.4% (19.6, 35.5). One patient (7.7%) had reduced MBFR at baseline, and 5 additional patients (46.2%) developed newly reduced MBFR (ratio &lt; 2.0) within 6 months of ADT initiation (p = 0.025). While no patients had CMD at baseline, 3 patients (30%) developed incident CMD (p = 0.083). MBFR declined in 69% of patients [median decline -0.32 (IQR -0.51, -0.22)] over 6 months ADT exposure. Conclusions: Myocardial perfusion PET imaging demonstrated a high incidence of reduced MBFR and CMD within 6 months of ADT initiation. These findings support further investigation of myocardial PET imaging, a widely-available clinical tool, as a potential research and clinical strategy to inform CV risk assessment in prostate cancer patients receiving ADT. Clinical trial information: NCT03535987.
Vascular Normalization to Improve Treatment of COVID-19: Lessons from Treatment of Cancer
Authors: Lance L. Munn, Triantafyllos Stylianopoulos, Natalie K. Jain, C. Corey Hardin, Melin J. Khandekar, Rakesh K. Jain
Journal: Clinical Cancer Research (2021)

Abstract The dramatic impact of the COVID-19 pandemic has resulted in an “all hands on deck” approach to find new therapies to improve outcomes in this disease. In addition to causing significant respiratory pathology, infection with SARS-CoV-2 (like infection with other respiratory viruses) directly or indirectly results in abnormal vasculature, which may contribute to hypoxemia. These vascular effects cause significant morbidity and may contribute to mortality from the disease. Given that abnormal vasculature and poor oxygenation are also hallmarks of solid tumors, lessons from the treatment of cancer may help identify drugs that can be repurposed to treat COVID-19. Although the mechanisms that result in vascular abnormalities in COVID-19 are not fully understood, it is possible that there is dysregulation of many of the same angiogenic and thrombotic pathways as seen in patients with cancer. Many anticancer therapeutics, including androgen deprivation therapy (ADT) and immune checkpoint blockers (ICB), result in vascular normalization in addition to their direct effects on tumor cells. Therefore, these therapies, which have been extensively explored in clinical trials of patients with cancer, may have beneficial effects on the vasculature of patients with COVID-19. Furthermore, these drugs may have additional effects on the disease course, as some ADTs may impact viral entry, and ICBs may accelerate T-cell–mediated viral clearance. These insights from the treatment of cancer may be leveraged to abrogate the vascular pathologies found in COVID-19 and other forms of hypoxemic respiratory failure.
Malonate Promotes Adult Cardiomyocyte Proliferation and Heart Regeneration
Authors: Jiyoung Bae, Rebecca J. Salamon, Emma B. Brandt, Wyatt G. Paltzer, Ziheng Zhang, Emily C. Britt, Timothy A. Hacker, Jing Fan, Ahmed I. Mahmoud
Journal: Circulation (2021)

Neonatal mouse cardiomyocytes undergo a metabolic switch from glycolysis to oxidative phosphorylation, which results in a significant increase in reactive oxygen species production that induces DNA damage. These cellular changes contribute to cardiomyocyte cell cycle exit and loss of the capacity for cardiac regeneration. The mechanisms that regulate this metabolic switch and the increase in reactive oxygen species production have been relatively unexplored. Current evidence suggests that elevated reactive oxygen species production in ischemic tissues occurs as a result of accumulation of the mitochondrial metabolite succinate during ischemia via succinate dehydrogenase (SDH), and this succinate is rapidly oxidized at reperfusion. Mutations in SDH in familial cancer syndromes have been demonstrated to promote a metabolic shift into glycolytic metabolism, suggesting a potential role for SDH in regulating cellular metabolism. Whether succinate and SDH regulate cardiomyocyte cell cycle activity and the cardiac metabolic state remains unclear.Here, we investigated the role of succinate and SDH inhibition in regulation of postnatal cardiomyocyte cell cycle activity and heart regeneration.Our results demonstrate that injection of succinate into neonatal mice results in inhibition of cardiomyocyte proliferation and regeneration. Our evidence also shows that inhibition of SDH by malonate treatment after birth extends the window of cardiomyocyte proliferation and regeneration in juvenile mice. Remarkably, extending malonate treatment to the adult mouse heart after myocardial infarction injury results in a robust regenerative response within 4 weeks after injury via promoting adult cardiomyocyte proliferation and revascularization. Our metabolite analysis after SDH inhibition by malonate induces dynamic changes in adult cardiac metabolism.Inhibition of SDH by malonate promotes adult cardiomyocyte proliferation, revascularization, and heart regeneration via metabolic reprogramming. These findings support a potentially important new therapeutic approach for human heart failure.