tbuckley/cabot-search huggingface dataset:
Endothelial dendritic cell vaccines inhibit tumor growth and metastasis of colon cancer through anti-angiogenesis
Authors: Satomi Yoneyama, Nelson Tsuno, Yurai Okaji, Kazushige Kawai, Takeshi Tsuchiya, Jun Yamada, Yasutaka Syuuno, Takeshi Nishikawa, Eiji Sunami, Takuya Osada, Joji Kitayama, Koki Takahashi, Hirokazu Nagawa
Journal: Cancer Research (2007)

2737   Background: One novel approach to the treatment of solid cancers involves therapeutic agents that inhibit vascularization of growing tumors. Recent studies have shown that vaccination with the autologous antigens of activated endothelium can inhibit tumor growth and metastasis through induction of anti-angiogenesis. Dendritic cells (DCs) are highly effective antigen-presenting cells and play a pivotal role in T cell-mediated immunity. DCs have been shown to induce strong antitumor immune responses in vitro and in vivo. Moreover, compared with vaccination strategies directed against a single antigen, cell lysate as the source of antigen offers the potential advantage of inducing a broad T-cell response against multiple known, as well as unknown antigens. We hypothesized that an active immunotherapeutic approach targeting endothelial cells might inhibit tumor angiogenesis and metastasis.  Objective: In an attempt to increase the potential clinical applicability of endothelial vaccines, we investigated the ability of dendritic cells pulsed with activated endothelium (EC-DC) to induce specific immunity against tumor angiogenesis, and inhibit tumor growth.  Method: We immunized mice with dendritic cells pulsed with either murine hepatic sinusoidal endothelial cells (HSE-DC) or human umbilical vein endothelial cells (HUVEC-DC) in two syngeneic models of the mouse colon cancer cell line, Colon-26, to examine their effects. Mice were carefully monitored with respect to tumor growth, and the development of side-effects. We also examined whether HUVEC-DC could induce human cytotoxic T lymphocytes (CTLs) specific to the target cells  in vitro . Monocyte-derived DCs of healthy donors were pulsed with lysate generated from HUVEC. Specific cytotoxic T lymphocyte (CTL) activity against cultured endothelial cells was tested using  in vitro  assays.  Result: Vaccination with the respective EC-DC significantly inhibited tumor growth and metastasis, the effect of autologous HSE-DC being more pronounced than that of xenogeneic HUVEC-DC. In addition, the anti-tumor effect of the respective EC-DC was stronger than that of unpulsed DC, and  in vitro  analysis showed that it could be attributed to the induction of CTLs, specifically recognizing and lyzing activated endothelium but not tumor cells. High levels on IFN-γ could be detected in the supernatants of CTL-HUVEC co-cultures, indicating T-cell immune response.Conclusion: Our present results suggest that endothelial dendritic cell vaccines can overcome peripheral tolerance of self-angiogenic antigens, and support important clinical implications of vaccines targeting tumor angiogenesis.
Genetic Mapping Reveals an Anthocyanin Biosynthesis Pathway Gene Potentially Influencing Evolutionary Divergence between Two Subspecies of Scarlet Gilia (Ipomopsis aggregata)
Authors: Brandon E Campitelli, Amanda M Kenney, Robin Hopkins, Jacob Soule, John T Lovell, Thomas E Juenger
Journal: Molecular Biology and Evolution (2017)

Immense floral trait variation has likely arisen as an adaptation to attract pollinators. Different pollinator syndromes-suites of floral traits that attract specific pollinator functional groups-are repeatedly observed across closely related taxa or divergent populations. The observation of these trait syndromes suggests that pollinators use floral cues to signal the underlying nectar reward, and that complex trait combinations may persist and evolve through genetic correlations. Here, we explore pollinator preferences and the genetic architecture of floral divergence using an extensive genetic mapping study in the hybrid zone of two Ipomopsis aggregata subspecies that exhibit a hummingbird and a hawkmoth pollinator syndrome. We found that natural selection acts on several floral traits, and that hummingbirds and hawkmoths exhibited flower color preferences as predicted by their respective pollinator syndromes. Our quantitative trait loci (QTL) analyses revealed 46 loci affecting floral features, many of which colocalize across the genome. Two of these QTL have large effects explaining >15% of the phenotypic variance. The strongest QTL was associated with flower color and localized to a SNP in the anthocyanin biosynthesis pathway gene, dihydroflavonol-4-reductase (DFR). Further analysis revealed strong associations between DFR SNP variants, gene expression, and flower color across populations from the hybrid zone. Hence, DFR may be a target of pollinator-mediated selection in the hybrid zone of these two subspecies. Together, our findings suggest that hummingbirds and hawkmoths exhibit contrasting flower color preferences, which may drive the divergence of several floral traits through correlated trait evolution.
Mucosectomía multibandas para el tratamiento de lesiones colónicas planas y difíciles
Authors: J Rodríguez Sánchez, E De La Santa Belda, P Olivencia Palomar, M Úbeda Muñoz, J Olmedo Camacho
Journal: Endoscopy (2017)

La resección endoscópica mucosa es el gold estándar en el tratamiento de lesiones colorrectales no pediculadas. Sin embargo, en múltiples situaciones como detrás de pliegues, pólipos fibrosados o con morfología extremadamente plana, la técnica resulta difícil de realizar debido a la imposibilidad de capturar el tejido con el asa de diatermia.
Characterization of CD45RO+ memory T lymphocytes in keloid disease
Authors: Z. Chen, L. Zhou, T. Won, Z. Gao, X. Wu, L. Lu
Journal: British Journal of Dermatology (2017)

Summary Background Memory T cells, a highly effective subset of T lymphocytes, have been reported to be involved in many inflammatory skin disorders. However, the potential role of memory T cells in keloid disease (KD) remains unclear. Objectives Due to their important role in regulating inflammation, we investigated the characteristics of CD45RO+ memory T cells in KD. Methods Primary cutaneous cells were isolated from keloid scars and normal skin by enzymic digestion. Peripheral blood mononuclear cells were isolated from a related blood sample, and flow cytometry was applied to identify the phenotypic and functional abnormalities of memory T cells in KD. Results We observed that the majority of T lymphocytes in keloid scars had the memory phenotype, and a greater number of the CD8+ memory T cells in keloid scars produced lower levels of tumour necrosis factor (TNF)-α. This abnormal cytokine production was even more distinct in Forkhead box (FOX)P3− CD8− memory T cells, with lower TNF-α production and enhanced interferon-γ production. Furthermore, FOXP3+ CD8− memory T cells in keloid scars were abnormal, including showing reduced CD25 and cytotoxic T-lymphocyte-associated antigen 4 expression and interleukin-10 production. In addition, a significant decrease in the number of CD4+ CD25high FOXP3+ regulatory T cells was identified in patients with multiple keloid scars. We also found that there was significantly increased infiltration of CD103+ CD8+ memory T cells in keloid scars. Conclusions Our findings preliminarily elucidate the abnormalities of CD45RO+ memory T cells in keloid scars and provide early evidence that a disrupted T-cell response contributes to the progression of KD.
Abstract B42: An investigation into the synergistic action of chemotherapy and photodynamic therapy (PDT) in resistant human melanoma
Authors: Fleury Augustin Nsole-Biteghe, Olawale Ajuwon, Lester M. Davids
Journal: Cancer Research (2017)

Abstract Cutaneous melanoma represents the most lethal form of skin cancer and remains refractory to current therapies. Failure of treatment has been attributed to the over-expression of ABC transporters. Alternative combinatorial approaches comprising chemotherapeutics and photodynamic therapy have been proposed to overcome resistance. The aim of this study was therefore to use the chemotherapeutic drug dacarbazine (DTIC), together with PDT on pigmented and unpigmented metastatic melanoma cell lines in vitro to assess efficacy and potentially identify mechanisms of resistance. We show a possible synergism of PDT+DTIC in reducing melanoma cell viability in vitro. At 24h post-treatment, only the unpigmented melanomas were sensitive to DTIC treatment (20-25% death at 1250µM). At 48h, a lethal dose of 50% was reached in these cells in contrast to the pigmented melanoma (20% at 48h). The same trend was observed with the combination therapy (PDT+DTIC) at both timepoints. Furthermore, PDT+DTIC suppressed the self-renewal capacity of both melanoma cell lines. No significant differences in ABCG2 protein expression was found at 24h post-treatment. Overall, these results suggest that ABCG2 transporters may not play a role in melanoma resistance to therapies and thus further work is required to elucidate the clinical efficacy of combination treatments in the fight against skin cancer. Citation Format: Fleury Augustin Nsole-Biteghe, Olawale Ajuwon, Lester M. Davids. An investigation into the synergistic action of chemotherapy and photodynamic therapy (PDT) in resistant human melanoma [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B42.
Reply
Authors: S. F. J. van de Graaf, Davor Slijepcevic
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. We read Dr. Levy's letter with interest. We reported that conjugated bile salts (BSs) are transported only by NTCP and OATP1A/1B in mice,1 and not by microsomal epoxide hydrolase (mEH/EPHX1). Dr. Levy states that mEH is an alternative basolateral uptake transporter of BSs. In our opinion, the stated arguments do not support this hypothesis. First, our data and previously published mathematical models of BS kinetics2 show that BS levels do not rise in plasma unless hepatic BS uptake is strongly reduced. Therefore, the two patients that display hypercholanemia despite an apparently intact/functional NTCP described by Shneider et al.3 are unlikely to represent an isolated hepatic BS uptake defect. This is supported by their phenotype including pruritus and jaundice, two symptoms that are absent in individuals with isolated hypercholanemia. Second, Dr. Levy suggests that mEH could contribute to hepatic BS uptake in fch/fch mice. However, these mice display highly elevated BS levels (>4 mM), which was attributed to the extremely reduced NTCP and OATP1A1 protein levels by the authors.4 Injection of radiolabeled taurocholate supported the conclusion of reduced hepatic BS clearance, because a large fraction of the label remained in plasma even 30 minutes after injection. Dr. Levy states in his letter that mEH expression is normal in these mice, indicating that the contribution of this enzyme to hepatic BS uptake is minimal. Third, in vitro evidence for mEH‐mediated BS transport has yet to be independently verified, and mEH knockout mice do not show a BS‐related phenotype.5
Shifts in podocyte histone H3K27me3 regulate mouse and human glomerular disease
Authors: Syamantak Majumder, Karina Thieme, Sri N. Batchu, Tamadher A. Alghamdi, Bridgit B. Bowskill, M. Golam Kabir, Youan Liu, Suzanne L. Advani, Kathryn E. White, Laurette Geldenhuys, Karthik K. Tennankore, Penelope Poyah, Ferhan S. Siddiqi, Andrew Advani
Journal: Journal of Clinical Investigation (2017)

Histone protein modifications control fate determination during normal development and dedifferentiation during disease. Here, we set out to determine the extent to which dynamic changes to histones affect the differentiated phenotype of ordinarily quiescent adult glomerular podocytes. To do this, we examined the consequences of shifting the balance of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark in podocytes. Adriamycin nephrotoxicity and subtotal nephrectomy (SNx) studies indicated that deletion of the histone methylating enzyme EZH2 from podocytes decreased H3K27me3 levels and sensitized mice to glomerular disease. H3K27me3 was enriched at the promoter region of the Notch ligand Jag1 in podocytes, and derepression of Jag1 by EZH2 inhibition or knockdown facilitated podocyte dedifferentiation. Conversely, inhibition of the Jumonji C domain-containing demethylases Jmjd3 and UTX increased the H3K27me3 content of podocytes and attenuated glomerular disease in adriamycin nephrotoxicity, SNx, and diabetes. Podocytes in glomeruli from humans with focal segmental glomerulosclerosis or diabetic nephropathy exhibited diminished H3K27me3 and heightened UTX content. Analogous to human disease, inhibition of Jmjd3 and UTX abated nephropathy progression in mice with established glomerular injury and reduced H3K27me3 levels. Together, these findings indicate that ostensibly stable chromatin modifications can be dynamically regulated in quiescent cells and that epigenetic reprogramming can improve outcomes in glomerular disease by repressing the reactivation of developmental pathways.
Appropriateness of clinical severity classification of new WHO childhood pneumonia guidance: a multi-hospital, retrospective, cohort study
Authors: Ambrose Agweyu, Richard J Lilford, Mike English, Grace Irimu, Philip Ayieko, Sam Akech, David Githanga, Fred Were, Barnabas Kigen, Samuel Ng'arng'ar, Nick Aduro, Rachel Inginia, Beatrice Mutai, Grace Ochieng, Lydia Thuranira, Francis Kanyingi, Magdalene Kuria, Sam Otido, Kigondu Rutha, Peris Njiiri, Martin Chabi, Charles Nzioki, Joan Ondere, Caren Emadau, Cecelia Mutiso, Loice Mutai, Christine Manyasi, David Kimutai, Celia Muturi, Agnes Mithamo, Anne Kamunya, Alice Kariuki, Grace Wachira, Melab Musabi, Sande Charo, Naomi Muinga, Mercy Chepkirui, Timothy Tuti, Boniface Makone, Wycliffe Nyachiro, George Mbevi, Thomas Julius, Susan Gachau, Morris Ogero, Michael Bitok, James Wafula
Journal: The Lancet Global Health (2017)

Management of pneumonia in many low-income and middle-income countries is based on WHO guidelines that classify children according to clinical signs that define thresholds of risk. We aimed to establish whether some children categorised as eligible for outpatient treatment might have a risk of death warranting their treatment in hospital.
Strontium and bisphosphonate coated iron foam scaffolds for osteoporotic fracture defect healing
Authors: Seemun Ray, Ulrich Thormann, Marlen Eichelroth, Matthäus Budak, Christoph Biehl, Markus Rupp, Ursula Sommer, Thaqif El Khassawna, Francisca I. Alagboso, Marian Kampschulte, Marcus Rohnke, Anja Henß, Klaus Peppler, Vanessa Linke, Peter Quadbeck, Axel Voigt, Florian Stenger, Daniel Karl, Reinhard Schnettler, Christian Heiss, Katrin S. Lips, Volker Alt
Journal: Biomaterials (2017)
Haploinsufficiency of A20 causes autoinflammatory and autoimmune disorders
Authors: Tomonori Kadowaki, Hidenori Ohnishi, Norio Kawamoto, Tomohiro Hori, Kenichi Nishimura, Chie Kobayashi, Tomonari Shigemura, Shohei Ogata, Yuzaburo Inoue, Tomoki Kawai, Eitaro Hiejima, Masatoshi Takagi, Kohsuke Imai, Ryuta Nishikomori, Shuichi Ito, Toshio Heike, Osamu Ohara, Tomohiro Morio, Toshiyuki Fukao, Hirokazu Kanegane
Journal: Journal of Allergy and Clinical Immunology (2017)
Bringing Surgical Care to the Home Through Video Visits
Authors: Chad Ellimoottil, Richard J. Boxer
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
Homologous Recombination Deficiency and Platinum-Based Therapy Outcomes in Advanced Breast Cancer
Authors: Eric Y. Zhao, Yaoqing Shen, Erin Pleasance, Katayoon Kasaian, Sreeja Leelakumari, Martin Jones, Pinaki Bose, Carolyn Ch'ng, Caralyn Reisle, Peter Eirew, Richard Corbett, Karen L. Mungall, Nina Thiessen, Yussanne Ma, Jacqueline E. Schein, Andrew J. Mungall, Yongjun Zhao, Richard A. Moore, Wendie Den Brok, Sheridan Wilson, Diego Villa, Tamara Shenkier, Caroline Lohrisch, Stephen Chia, Stephen Yip, Karen Gelmon, Howard Lim, Daniel Renouf, Sophie Sun, Kasmintan A. Schrader, Sean Young, Ian Bosdet, Aly Karsan, Janessa Laskin, Marco A. Marra, Steven J.M. Jones
Journal: Clinical Cancer Research (2017)

Purpose: Recent studies have identified mutation signatures of homologous recombination deficiency (HRD) in over 20% of breast cancers, as well as pancreatic, ovarian, and gastric cancers. There is an urgent need to understand the clinical implications of HRD signatures. Whereas BRCA1/2 mutations confer sensitivity to platinum-based chemotherapies, it is not yet clear whether mutation signatures can independently predict platinum response.Experimental Design: In this observational study, we sequenced tumor whole genomes (100× depth) and matched normals (60×) of 93 advanced-stage breast cancers (33 platinum-treated). We computed a published metric called HRDetect, independently trained to predict BRCA1/2 status, and assessed its capacity to predict outcomes on platinum-based chemotherapies. Clinical endpoints were overall survival (OS), total duration on platinum-based therapy (TDT), and radiographic evidence of clinical improvement (CI).Results: HRDetect predicted BRCA1/2 status with an area under the curve (AUC) of 0.94 and optimal threshold of 0.7. Elevated HRDetect was also significantly associated with CI on platinum-based therapy (AUC = 0.89; P = 0.006) with the same optimal threshold, even after adjusting for BRCA1/2 mutation status and treatment timing. HRDetect scores over 0.7 were associated with a 3-month extended median TDT (P = 0.0003) and 1.3-year extended median OS (P = 0.04).Conclusions: Our findings not only independently validate HRDetect, but also provide the first evidence of its association with platinum response in advanced breast cancer. We demonstrate that HRD mutation signatures may offer clinically relevant information independently of BRCA1/2 mutation status and hope this work will guide the development of clinical trials. Clin Cancer Res; 23(24); 7521-30. ©2017 AACR.
Social recovery therapy in combination with early intervention services for enhancement of social recovery in patients with first-episode psychosis (SUPEREDEN3): a single-blind, randomised controlled trial
Authors: David Fowler, Jo Hodgekins, Paul French, Max Marshall, Nick Freemantle, Paul McCrone, Linda Everard, Anna Lavis, Peter B Jones, Tim Amos, Swaran Singh, Vimal Sharma, Max Birchwood
Journal: The Lancet Psychiatry (2017)

Provision of early intervention services has increased the rate of social recovery in patients with first-episode psychosis; however, many individuals have continuing severe and persistent problems with social functioning. We aimed to assess the efficacy of early intervention services augmented with social recovery therapy in patients with first-episode psychosis. The primary hypothesis was that social recovery therapy plus early intervention services would lead to improvements in social recovery.We did this single-blind, phase 2, randomised controlled trial (SUPEREDEN3) at four specialist early intervention services in the UK. We included participants who were aged 16-35 years, had non-affective psychosis, had been clients of early intervention services for 12-30 months, and had persistent and severe social disability, defined as engagement in less than 30 h per week of structured activity. Participants were randomly assigned (1:1), via computer-generated randomisation with permuted blocks (sizes of four to six), to receive social recovery therapy plus early intervention services or early intervention services alone. Randomisation was stratified by sex and recruitment centre (Norfolk, Birmingham, Lancashire, and Sussex). By necessity, participants were not masked to group allocation, but allocation was concealed from outcome assessors. The primary outcome was time spent in structured activity at 9 months, as measured by the Time Use Survey. Analysis was by intention to treat. This trial is registered with ISRCTN, number ISRCTN61621571.Between Oct 1, 2012, and June 20, 2014, we randomly assigned 155 participants to receive social recovery therapy plus early intervention services (n=76) or early intervention services alone (n=79); the intention-to-treat population comprised 154 patients. At 9 months, 143 (93%) participants had data for the primary outcome. Social recovery therapy plus early intervention services was associated with an increase in structured activity of 8·1 h (95% CI 2·5-13·6; p=0·0050) compared with early intervention services alone. No adverse events were deemed attributable to study therapy.Our findings show a clinically important benefit of enhanced social recovery on structured activity in patients with first-episode psychosis who received social recovery therapy plus early intervention services. Social recovery therapy might be useful in improving functional outcomes in people with first-episode psychosis, particularly in individuals not motivated to engage in existing psychosocial interventions targeting functioning, or who have comorbid difficulties preventing them from doing so.National Institute for Health Research.
Monomorphic Post Transplant Lymphoproliferative Disorder (Diffuse Large B Cell Lymphoma subtype) Successfully Treated without Chemotherapy after Solid Organ Transplant in Children
Authors: Marta Rojas Vasquez, Sunil J. Desai, Anthea Peters, Simon Urschel, Jason Yap, Raymond Lai, Catherine Morgan, Jutta Preiksaitis
Journal: Blood (2017)
Abstract A33: Population and evolutionary genomics of prostate cancer-associated variants: implications for health disparities in men of African descent
Authors: Joseph Lachance, Ali Berens, Matthew Hansen, Andrew Teng, Sarah Tishkoff, Timothy Rebbeck
Journal: Cancer Research (2017)

Abstract To determine why African men are more likely to suffer from prostate cancer (CaP), we integrated GWAS results and scans of selection with allele frequency data from 64 global populations. Despite substantial overlap in genetic risk scores across populations, we find that predicted CaP risk is highest in West Africans and that a small number of loci drive these differences in risk. There is a strong concordance between genetic risk scores and clinical estimates of CaP mortality. Although most CaP-associated loci are evolving neutrally, we find multiple instances where alleles have hitchhiked to high frequencies with linked locally adaptive alleles. Citation Format: Joseph Lachance, Ali Berens, Matthew Hansen, Andrew Teng, Sarah Tishkoff, Timothy Rebbeck. Population and evolutionary genomics of prostate cancer-associated variants: implications for health disparities in men of African descent [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A33.