tbuckley/cabot-search huggingface dataset:
Is tryptase a novel serum bio-marker predictive of radical surgery in colo-rectal cancer patients?
Authors: Michele Ammendola, Rosario Sacco, Giuseppe Donato, Valeria ZuccalÃ, Veronica Goffredo, Rosa Patruno, Mario Brandi, Giuseppe Sammarco, Eustachio Ruggieri, Severino Montemurro, Cosmo Damiano Gadaleta, Girolamo Ranieri
Journal: Journal of Clinical Oncology (2013)

e22104 Background: Data from experimental tumour models suggest that mast cells (MCs) accumulate near tumour cells before the onset of angiogenesis. Tryptase is a serin protease stored in mast cell granules that plays a role in tumour angiogenesis. Mast cells (MCs) can release tryptase following c-Kit receptor activation. Here we aims to assess tryptase serum levels in CRC patients before and after radical surgery resection and c-Kit expressing cells in primary tumour tissue. Methods: In this study patients with stage B and C CRC (according to Astler e Coller staging system) were selected. Samples of blood were taken from CRC patients between 7 and 9 a.m. 1 day before and 1 day after tumour surgical resection. Venous blood was dispensed into a tube for serum (Becton Dickinson Hemogard Vacutainer Systems, Plymouth, UK). Serum blood samples were centrifuged at 1,500g for 10 minutes and then aliquoted and frozen at -80 °C. Tryptase levels were measured using the UniCAP Tryptase Fluoroenzymeimmunoassay (Pharmacia,Uppsala, Sweden). In addition primary tissue section were immunostained with a primary anti c-Kit antibody (A4502; Dako, Glostrup, Denmark) by mean of immunohistochemistry. Results: Mean ± s.d. tryptase level pre-tumour surgical resection was 6.38 ± 4.49 μg/L, and mean ± s.d. tryptase level post tumour surgical resection was 5.11 ± 3.81 μg/L. A statistically significant difference between pre-tumour surgical resection and post-tumour surgical resection tryptase level concentrations was found: p=0.000 by t-test. A strong correlation between pre-tumour surgical tryptase level and c-Kit expressing cells was also found (r=0.81, p=0.000). Conclusions: This is the first report that analyzes the possible significance of serum tryptase levels changes in CRC patients who underwent radical surgical resection. Our results demonstrated higher serum tryptase levels CRC patients suggesting the release of tryptase from c-Kit expressing cells CRC tissue. We suggest that tryptase may play a role as a novel serum tumour bio-marker predictive of radical surgery in CRC patients. In this context tryptase inhibitors might be evaluated in adjuvant clinical trials as a new antiangiogenetic approach.
Ethics and the Importance of Good Clinical Practices
Authors: Katherine E. Nelson, Annie Janvier, Pamela G. Nathanson, Chris Feudtner
Journal: The American Journal of Bioethics (2020)

Katherine E. Nelsona , Annie Janvierb , Pamela G. Nathansonc & Chris Feudtnerc* a Hospital for Sick Children; b University of Montreal; c Children's Hospital of Philadelphia
Targeting 7-Dehydrocholesterol Reductase Integrates Cholesterol Metabolism and IRF3 Activation to Eliminate Infection
Authors: Jun Xiao, Weiyun Li, Xin Zheng, Linlin Qi, Hui Wang, Chi Zhang, Xiaopeng Wan, Yuxiao Zheng, Ruiyue Zhong, Xin Zhou, Yao Lu, Zhiqi Li, Ying Qiu, Chang Liu, Fang Zhang, Yanbo Zhang, Xiaoyan Xu, Zhongzhou Yang, Hualan Chen, Qiwei Zhai, Bin Wei, Hongyan Wang
Journal: Immunity (2019)
Genotype-free demultiplexing of pooled single-cell RNA-seq
Authors: Jun Xu, Caitlin Falconer, Quan Nguyen, Joanna Crawford, Brett D. McKinnon, Sally Mortlock, Anne Senabouth, Stacey Andersen, Han Sheng Chiu, Longda Jiang, Nathan J. Palpant, Jian Yang, Michael D. Mueller, Alex W. Hewitt, Alice Pébay, Grant W. Montgomery, Joseph E. Powell, Lachlan J.M Coin
Journal: Genome biology (2019)

Abstract A variety of methods have been developed to demultiplex pooled samples in a single cell RNA sequencing (scRNA-seq) experiment which either require hashtag barcodes or sample genotypes prior to pooling. We introduce scSplit which utilizes genetic differences inferred from scRNA-seq data alone to demultiplex pooled samples. scSplit also enables mapping clusters to original samples. Using simulated, merged, and pooled multi-individual datasets, we show that scSplit prediction is highly concordant with demuxlet predictions and is highly consistent with the known truth in cell-hashing dataset. scSplit is ideally suited to samples without external genotype information and is available at: https://github.com/jon-xu/scSplit
A review of use of the word ‘flare’ in hidradenitis suppurativa studies
Authors: J.S. Kirby, B. Moore, P. Leiphart, K. Shumaker, A. Mammis-Gierbolini, F. Benhadou, V. del Marmol
Journal: British Journal of Dermatology (2020)

Hidradenitis suppurativa (HS) causes red, painful, draining bumps and tunnels in the skin. About 0.1 to 1% of people have HS in the U.S.A. and Europe. HS is more common in females. HS lesions (affected areas) happen mostly in folds of the body, such as the armpits, under the breast, groin, or buttocks.
Comparison of traditional Chinese medicine (TCM) herbal mixture LQ and paclitaxel on the phase of cancer cell cycle blockage and cancer cell invasion.
Authors: Robert M. Hoffman, Chengyu Wu, Shuya Yano, Lei Zhang
Journal: Journal of Clinical Oncology (2013)

e22014 Background: Although Traditional Chinese Medicine (TCM) has been used to treat cancer for thousands of years, the mechanisms of action are either poorly understood or unknown. In the present report, we use state-of-the-art technology to investigate the anti-cancer mechanism of the TCM herbal mixture LQ. Methods: Fluorescence ubiquitination-based cell cycle indicator (FUCCI) was used to monitor cell cycle arrest HeLa cells after LQ treatment. FUCCI-HeLa cells were cultured in two dimensional (2D) monolayer, Matrigel and 3D Gelfoam. Changes of cell cycle status were observed using the Olympus FV1000 confocal imaging system whereby cycling cells fluoresce green and quiescent cells red. Paclitaxel (Taxol) was used as the positive control. Results: Paclitaxel induced a G 2 /M cell cycle block. In contrast, LQ blocked FUCCI-HeLa cells in the G 0 /G 1 phase of the cell cycle in all 3 culture models. In monolayer culture, the paclitaxel positive control had approximately 45% of the cells in G 2 /M phase. In contrast, the LQ-treated cells were mostly in the G 0 /G 1 phase (&gt;90%). In Matrigel culture, HeLa cells formed spheres. The spheres in the paclitaxel control group had 40% of the cells in G 2 /M phase, but only 15% in LQ-treated cultures. In 3D Gelfoam culture, cells grew along the structures of the Gelform. The paclitaxel positive control culture had approximately 45% of cells in G 2 /M phase. In contrast, the cells in LQ-treated culture were mostly in G 0 /G 1 phase (&gt;80%). The cells in pacilitaxel control group invaded to 250~300 µm deep in the Gelfoam, but only 150~200 µm deep in LQ-treated culture. Conclusions: The anti-cancer mechanism of TCM herbal mixture LQ involves cancer cell cycle arrest at G 0 /G 1 and inhibition of cancer cell invasion.
Dynamics of T-cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T cells.
Authors: Simona Partlova, Anna Fialova, Ludek Sojka, Lukas Rob, Jirina Bartunkova, Radek Spisek
Journal: Journal of Clinical Oncology (2013)

e22129 Background: Ovarian cancer is diagnosed in more than 190,000 new patients every year and is known to have the highest mortality rate among gynaecologic cancers. The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. Methods: We studied the immune cells infiltrating the tumor tissue of ovarian cancer patients at different stages of disease. We analysed the patterns of T lymphocytes in fresh tumor tissue as well as blood samples of 44 newly diagnosed ovarian cancer patients by flow cytometry. To evaluate whether regulatory T cells (Tregs) develop in situ or migrate to tumor tissue, we measured a concentration of chemokine CCL22 in tumor cell culture supernatants. We also determined the expression of CCR4 on circulating as well as tumor-infiltrating Tregs by flow cytometry. Results: The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (stage III-IV), we detected a dominant population of Helios+ activated regulatory T cells along with high numbers of macrophages and immature myeloid dendritic cells. Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNgamma. Conclusions: Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.
THP-1 macrophages stimulate proliferation, protect against tamoxifen killing, and modulate angiogenesis-related gene expression in MCF-7 breast cancer cells
Authors: Georgia A. Henry, Theodore A. Bremner
Journal: Cancer Research (2004)

5201  Stromal cells influence tumor cell proliferation and tumor progression. The emergence of aggressive phenotypes may involve signals extrinsic to cancer cells that are generated in the interaction between cancer cells and stromal cells. We examined breast cancer cell-macrophage interactions in a simulated tumor environment, using co-cultures of THP-1 macrophages (Mφ) and MCF-7 breast cancer cells. We hypothesized that (1) Mφ, in the tumor context, may secrete factors that promote tumor cell growth and drug resistance, and (2) tamoxifen (TMX) may stimulate Mφ production of pro-angiogenic or pro-metastatic factors despite its ability to inhibit tumor cell proliferation. MCF-7 cells and THP-1 Mφ were co-cultured in varying concentrations of tamoxifen (0 –15 μM) for 3 d under normoxia or hypoxia (94% N2, 1% O2, 5% CO2). MCF-7 cell proliferation and survival were measured by the MTT assay. For gene expression analysis, total RNA was extracted from Mφ and MCF-7 cells, labeled, and hybridized to gene arrays. Up-regulation of candidate genes was confirmed by RT-PCR. Apoptotic killing of MCF-7 by TMX was assessed by DNA laddering. Under normoxia, MCF-7 cells proliferated more rapidly when co-cultured with THP-1 Mφ. In the absence of Mφ, only 17% of MCF-7 cells survived 15 μM TMX, whereas in the presence of Mφ, survival was 72%. Under hypoxia, survival in the absence of Mφ was 9%, and 55% in the presence of Mφ. These data suggest that Mφ reduced the susceptibility of MCF-7 cells to TMX killing. The most dramatic differences in growth factor- and angiogenesis-related gene expression were observed between MCF-7 cells alone and MCF-7 in co-culture, under hypoxia. Therefore, the presence of Mφ modulated gene expression in MCF-7 cells. Specifically, in TMX-treated (10 μM) co-cultures, VEGF, VEGF-D, osteopontin, thrombospondin, and HIF-1α were all up-regulated in MCF-7 cells under hypoxia. Additionally, Mφ induced the expression of IL-8, MDK, TβRs, 1, 2, 3, and ID3. Our findings suggest that the killing efficiency of TMX may be increased by its combination with drugs that suppress Mφ control of angiogenesis-related gene expression. A more extensive study of the effects of TMX on the interaction between Mφ and tumor cells may provide valuable information for the development of combination therapies directed at both tumor cells and tumor-associated Mφ. Sponsored by the U.S Army Medical Research and Acquisition Activity, Award NO: DAMD17-02-1-0408 to Theodore Bremner (PI). The content of this report does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred.
Disclose and Manage Conflicts of Interest at Cancer Centers—Reply
Authors: David Carr, H. Gilbert Welch
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
Unnecessary Bimanual Pelvic Examinations and Papanicolaou Testing in Adolescents and Young Women—Learning How to Unlearn
Authors: Melissa A. Simon
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine 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 Internal Medicine journal
Abstract 16665: Caveolin-1 and α7nachr Interaction is Essential in Preventing Nicotine Induced Vascular Inflammatory Response in Mice
Authors: Rui Guo, Zheyi Yan, Qin Ma, Yanwei Zhang, Xin Ma, Yajing Wang
Journal: Circulation (2015)

Nicotine is an independent risk factor of and associated with the development of atherosclerosis. Dysfunction of endothelial Cavolin-1 (Cav-1) can accelerate atherosclerosis progression via boosting inflammation response. However, the causative link between nicotine and atherosclerosis remains unknown. Here, we utilized molecular and cellular experiments revealed that in human endothelial cells (HUVECs), 10-6 M nicotine increased intracellular oxygen free radical generation, inhibited eNOS activity, augmented pathological NO production from iNOS, promoted nitrative stress (Nitrotyrosine), and increased adhesion molecule expression when compared with vehicle. In vivo administration of nicotine upregulated plasma adhesion molecule levels and significantly increased nitrotyrosine levels in vascular tissue (2±0.4 fold compared with untreated group, p&lt;0.05). Bioinformatics analysis predicted that α7nAChR motif (151YIDVRWFPF159 and 168FGSWSYGGW176) may interact with Cav-1 via Cav-1 scaffolding domain (82DGIWKASFTTFTVTKYWFYR101). The bioinformatic analysis was confirmed by immunocytochemistry and immunoprecipitation showing that α7nAChR co-localizes with caveolin-1 (Cav-1) and these two molecules interact reciprocally. Although 10-6M nicotine did not alter expression levels of Cav-1, it significantly decreased the interaction between Cav-1 and nicotine receptor (α7nAchR). After siRNA Cav-1 gene silence, nicotine treatment further significantly increased ROS generation (1.37 + 0.33 times vs. scrambled siRNA, p&lt;0.05), enhanced pathological NO production (1.35 ± 0.4 fold, p&lt;0.05), and increased adhesion molecule expression (1.4 ±0.4 fold, p&lt;0.05). AMPKα1, a sensor of oxidative stress, was phosphorylated after nicotine treatment. However, siRNA AMPK gene silence failed to block nicotine induced adhesion molecule expression. Taken together, these results demonstrated that reduced α7nAchR/Cav-1interaction plays an important role in nicotine induced endothelial inflammatory response; this inflammation signal pathway is AMPK independent. Preserving and strengthening stability of Cav- 1/α7nAchR interaction is a potential target in treatment of vascular dysfunction caused by smoking.
Transgenic zebrafish modeling low-molecular-weight proteinuria and lysosomal storage diseases
Authors: Zhiyong Chen, Alessandro Luciani, José María Mateos, Gery Barmettler, Rachel H. Giles, Stephan C.F. Neuhauss, Olivier Devuyst
Journal: Kidney International (2019)

Epithelial cells lining the proximal tubule of the kidney reabsorb and metabolize most of the filtered low-molecular-weight proteins through receptor-mediated endocytosis and lysosomal processing. Congenital and acquired dysfunctions of the proximal tubule are consistently reflected by the inappropriate loss of solutes including low-molecular-weight proteins in the urine. The zebrafish pronephros shares individual functional segments with the human nephron, including lrp2a/megalin-dependent endocytic transport processes of the proximal tubule. Although the zebrafish has been used as a model organism for toxicological studies and drug discovery, there is no available assay that allows large-scale assessment of proximal tubule function in larval or adult stages. Here we establish a transgenic Tg(lfabp::½vdbp-mCherry) zebrafish line expressing in the liver the N-terminal region of vitamin D-binding protein coupled to the acid-insensitive, red monomeric fluorescent protein mCherry (½vdbp-mCherry). This low-molecular-weight protein construct is secreted into the bloodstream, filtered through the glomerulus, reabsorbed by receptor-mediated endocytosis and processed in the lysosomes of proximal tubule cells of the fish. Thus, our proof-of-concept studies using zebrafish larvae knockout for lrp2a and clcn7 or exposed to known nephrotoxins (gentamicin and cisplatin) demonstrate that this transgenic line is useful to monitor low-molecular-weight proteinuria and lysosomal processing. This represents a powerful new model organism for drug screening and studies of nephrotoxicity.
Considerations in Weaning or Withdrawing Dupilumab Therapy—Nothing Is Forever
Authors: Peter A. Lio
Journal: JAMA Dermatology (2019)

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
Syk degradation restrains plasma cell formation and promotes zonal transitions in germinal centers
Authors: Natalia Davidzohn, Adi Biram, Liat Stoler-Barak, Amalie Grenov, Bareket Dassa, Ziv Shulman
Journal: The Journal of Experimental Medicine (2019)

Germinal centers (GCs) are sites at which B cells proliferate and mutate their antibody-encoding genes in the dark zone (DZ), followed by affinity-based selection in the light zone (LZ). B cell antigen receptor (BCR) signals induce Syk activation followed by rapid phosphatase-mediated desensitization; however, how degradation events regulate BCR functions in GCs is unclear. Here, we found that Syk degradation restrains plasma cell (PC) formation in GCs and promotes B cell LZ to DZ transition. Using a mouse model defective in Cbl-mediated Syk degradation, we demonstrate that this machinery attenuates BCR signaling intensity by mitigating the Kras/Erk and PI3K/Foxo1 pathways, and restricting the expression of PC transcription factors in GC B cells. Inhibition of Syk degradation perturbed gene expression, specifically in the LZ, and enhanced the generation of PCs without affecting B cell proliferation. These findings reveal how long-lasting attenuation of signal transduction by degradation events regulates cell fate within specialized microanatomical sites.
Rationale and design of the Transformative Research in Diabetic Nephropathy (TRIDENT) Study
Authors: Raymond R. Townsend, Paolo Guarnieri, Christos Argyropoulos, Shira Blady, Carine M. Boustany-Kari, Kishor Devalaraja-Narashimha, Lori Morton, Amy K. Mottl, Uptal Patel, Matthew Palmer, Michael J. Ross, Lea Sarov-Blat, Kathryn Steinbugler, Katalin Susztak, Randy Luciano, Michael Ross, Pietro Canetta, Krik Campbell, Jonathan Hogan, Amy Mottl, Oliver Lenz, Harold Szerlip, Shweta Bansal, Chip Brosius, Jeffery Schelling, Salem Almaani, Matthias Kretzler, Tamara Isakova, Rupali Avasare, Richard Lafayette, Christos Argyropoulos
Journal: Kidney International (2019)
Housing and Healthy Child Development: Known and Potential Impacts of Interventions
Authors: James R. Dunn
Journal: Annual Review of Public Health (2019)

Housing is often described as an important determinant of health, but less commonly of child health. Despite acknowledgment of the importance of housing to health, however, there are relatively few studies of the effects of housing interventions on health, and again even fewer on child health. This article argues that a broad focus on healthy child development—as opposed to just physical health—coupled with a conceptual framework outlining specific attributes of housing with the potential to influence child health, should be adopted to guide a comprehensive approach to public health policy for healthy child development. Most housing interventions address direct pathways linking in-home hazard exposures to child health outcomes, with promising but mixed results. But few housing interventions address the broader aspects of healthy child development. This review addresses potential housing interventions that could impact the broader determinants of healthy child development and accompanying methodological challenges.