tbuckley/cabot-search huggingface dataset:
Abstract 14735: Epicardial Placement of Instantly Produced Fibrin Glue-Incorporating Mesenchymal Stromal Cells for the Treatment of Heart Failure
Authors: Yuki Ichihara, Nobuko Tano, Laura Fields, Nilaani Murugesu, Yusuke Shintani, Masaru Ishida, Nobuhiko Sato, Ken Suzuki
Journal: Circulation (2016)

Introduction:  Transplantation of mesenchymal stromal cells (MSC) is an emerging treatment for heart failure, but the cell-delivery route needs to be optimized. Recent reports suggest that placement onto the heart surface (epicardial placement) may be more effective and safer than the current injection methods. This study aimed to explore the efficacy of epicardial placement of fibrin glue (FG)-incorporating MSC, which is produced instantly on the site of treatment. Mechanisms by which FG improves the effects of MSC-therapy were also examined in vivo and in vitro.   Methods & Results:  Four weeks after induction of myocardial infarction, female rats were transplanted with 4x10 6  syngeneic male bone marrow MSC by means of FG-aided epicardial placement or intramyocardial injection. Sham treatment was also examined as control. Upon mixing fibrinogen, thrombin, and MSC suspensions on the exposed heart, this promptly formed adhesive fibrin-containing MSC and strongly adhered to the heart surface. This resulted in greater initial retention and subsequent presence of donor MSC compared to intramyocardial injection (93.0±7.2% vs 48.1±9.2% at 1 hour post-transplantation; 32.5±1.4% vs 10.3±1.2% at Day 7; 11.1±0.8% vs 0.7±0.2% at Day 28; % to the total transplanted cell number assessed by qPCR for Sry gene). This led to amplified recovery of cardiac function and structure as measured by echocardiography and catheterization. This effect was underpinned by enhanced repair of the failing myocardium (i.e. increased neovascular formation, attenuated pathological fibrosis, and reduced cardiomyocyte hypertrophy) in association with upregulation of repair-related genes (including Il10, Cxcl12, Igf1, Hif1a, Tgfb1, Vcam1, Timp1). In addition, in-vitro studies showed that culture in FG improved survival as well as secretional ability of MSC, which would contribute to the FG-amplified effect of MSC-therapy.   Conclusions:  These data suggest a great potential of epicardial placement of instantly produced MSC-FG complex for the treatment of ischemic heart failure. Not only FG supports physical retention of donor MSC in the heart, but also enhances their cellular competence. Further development of this user-friendly therapy is warranted toward clinical application.
Model evaluation for the prediction of solubility of active pharmaceutical ingredients (APIs) to guide solid–liquid separator design
Authors: Kuveneshan Moodley, Jürgen Rarey, Deresh Ramjugernath
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The assumptions and models for solubility modelling or prediction in systems using non-polar solvents, or water and complex triterpene and other active pharmaceutical ingredients as solutes aren't well studied. Furthermore, the assumptions concerning heat capacity effects (negligibility, experimental values or approximations) are explored, using non-polar solvents (benzene), or water as reference solvents, for systems with solute melting points in the range of 306-528 K and molecular weights in the range of 90-442 g/mol. New empirical estimation methods for the ΔfusCpi of APIs are presented which correlate the solute molecular masses and van der Waals surface areas with ΔfusCpi . Separate empirical parameters were required for oxygenated and non-oxygenated solutes. Subsequently, the predictive capabilities of the various approaches to solubility modelling for complex pharmaceuticals, for which data is limited, are analysed. The solute selection is based on a principal component analysis, considering molecular weights, fusion temperatures, and solubilities in a non-polar solvent, alcohol, and water, where data was available. New NRTL-SAC parameters were determined for selected steroids, by regression. The original UNIFAC, modified UNIFAC (Dortmund), COSMO-RS (OL), and COSMO-SAC activity coefficient predictions are then conducted, based on the availability of group constants and sigma profiles. These are undertaken to assess the predictive capabilities of these models when each assumption concerning heat capacity is employed. The predictive qualities of the models are assessed, based on the mean square deviation and provide guidelines for model selection, and assumptions concerning phase equilibrium, when designing solid-liquid separators for the pharmaceutical industry on process simulation software. The most suitable assumption regarding ΔfusCpi was found to be system specific, with modified UNIFAC (Dortmund) performing well in benzene as a solvent system, while original UNIFAC performs better in aqueous systems. Original UNIFAC outperforms other predictive models tested in the triterpene/steroidal systems, with no significant influence from the assumptions regarding ΔfusCpi .
Malignant Lymphoma of Uveal Tract
Authors: E L COPPER, J L RIKER
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Antibody persistence and booster responses 24–36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial
Authors: Federico Martinón-Torres, Alfonso Carmona Martinez, Róbert Simkó, Pilar Infante Marquez, Josep-Lluis Arimany, Francisco Gimenez-Sanchez, José Antonio Couceiro Gianzo, Éva Kovács, Pablo Rojo, Huajun Wang, Chiranjiwi Bhusal, Daniela Toneatto
Journal: Journal of Infection (2017)

ObjectivesThis phase IIIb, open-label, multicentre, extension study (NCT01894919) evaluated long-term antibody persistence and booster responses in participants who received a reduced 2 + 1 or licensed 3 + 1 meningococcal serogroup B vaccine (4CMenB)-schedule (infants), or 2-dose catch-up schedule (2–10-year-olds) in parent study NCT01339923.Materials and methodsChildren aged 35 months to 12 years (N = 851) were enrolled. Follow-on participants (N = 646) were randomised 2:1 to vaccination and non-vaccination subsets; vaccination subsets received an additional 4CMenB dose. Newly enrolled vaccine-naïve participants (N = 205) received 2 catch-up doses, 1 month apart (accelerated schedule). Antibody levels were determined using human serum bactericidal assay (hSBA) against MenB indicator strains for fHbp, NadA, PorA and NHBA. Safety was also evaluated.ResultsAntibody levels declined across follow-on groups at 24–36 months versus 1 month post-vaccination. Antibody persistence and booster responses were similar between infants receiving the reduced or licensed 4CMenB-schedule. An additional dose in follow-on participants induced higher hSBA titres than a first dose in vaccine-naïve children. Two catch-up doses in vaccine-naïve participants induced robust antibody responses. No safety concerns were identified.ConclusionAntibody persistence, booster responses, and safety profiles were similar with either 2 + 1 or 3 + 1 vaccination schedules. The accelerated schedule in vaccine-naïve children induced robust antibody responses.
Interventions to Address Sexual Problems in People With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Adaptation of Cancer Care Ontario Guideline
Authors: Jeanne Carter, Christina Lacchetti, Barbara L. Andersen, Debra L. Barton, Sage Bolte, Shari Damast, Michael A. Diefenbach, Katherine DuHamel, Judith Florendo, Patricia A. Ganz, Shari Goldfarb, Sigrun Hallmeyer, David M. Kushner, Julia H. Rowland
Journal: Journal of Clinical Oncology (2017)

Purpose The adaptation of the Cancer Care Ontario (CCO) guideline Interventions to Address Sexual Problems in People With Cancer provides recommendations to manage sexual function adverse effects that occur as a result of cancer diagnosis and/or treatment. Methods ASCO staff reviewed the guideline for developmental rigor and updated the literature search. An ASCO Expert Panel ( Table A1 ) was assembled to review the guideline content and recommendations. Results The ASCO Expert Panel determined that the recommendations from the 2016 CCO guideline are clear, thorough, and based upon the most relevant scientific evidence. ASCO statements and modifications were added to adapt the CCO guideline for a broader audience. Recommendations It is recommended that there be a discussion with the patient, initiated by a member of the health care team, regarding sexual health and dysfunction resulting from cancer or its treatment. Psychosocial and/or psychosexual counseling should be offered to all patients with cancer, aiming to improve sexual response, body image, intimacy and relationship issues, and overall sexual functioning and satisfaction. Medical and treatable contributing factors should be identified and addressed first. In women with symptoms of vaginal and/or vulvar atrophy, lubricants in addition to vaginal moisturizers may be tried as a first option. Low-dose vaginal estrogen, lidocaine, and dehydroepiandrosterone may also be considered in some cases. In men, medication such as phosphodiesterase type 5 inhibitors may be beneficial, and surgery remains an option for those with symptoms or treatment complications refractory to medical management. Both women and men experiencing vasomotor symptoms should be offered interventions for symptomatic improvement, including behavioral options such as cognitive behavioral therapy, slow breathing and hypnosis, and medications such as venlafaxine and gabapentin.Additional information is available at: www.asco.org/survivorship-guidelines and www.asco.org/guidelineswiki .
Abstract 13013: Bleeding Risk and Major adverse Events in Patients With Cancer on Oral Anticoagulation Therapy
Authors: Yong-Joon Lee, Jin-kyu Park, Jae-Sun Uhm, Jong-Yun Kim, Hui-Nam Pak, Moon-Hyoung Lee, Jung-Hoon Sung, Boyoung Joung
Journal: Circulation (2015)

Introduction: Bleeding and thromboembolism are the major concerns for oral anticoagulation therapy (OAT), especially in atrial fibrillation (AF) patients with history of cancer. The aim of this study was to evaluate the usefulness of OAT in AF patients with cancer for protecting major stroke and brain hemorrhage. Methods: The study included 2,168 AF patients with cancer at a tertiary hospital. We compared composite end points including major adverse cardiac events (MACE) and major bleeding between patients with OAT (OAT+, n=1,182) and without OAT (OAT-, n=936). Results: CHA 2 DS 2 -VASc and HAS-BELD score were higher in OAC+ than OAT- group. During the follow up period of 3.9 ± 2.8 years, 142 (12%) and 88 (9%) patients had MACE in OAT+ and OAT-, respectively (p = 0.055). Major bleeding (11% vs. 8%, p=0.023) and composite endpoints (21% vs. 16%, p = 0.002) were significantly higher in OAT+ than OAT- group. OAT+ patients had lower cumulative survival free of composite endpoints than OAT- patients (p=0.024). Among 230 MACE and 207 major bleeding events, 117 (47%) and 86 (42%) events occurred within first year after the diagnosis of cancer. During this period, optimal INR level was achieved in only 288 (24%) patients because of cancer treatment. OAT failed to prevent MACE in stomach and renal cancer patients with statistical significance (Figure 1A*). Furthermore, OAT+ patients with prostate, thyroid, pancreato-biliary, head-neck and breast cancers tended to have more MACE than OAT- group. Conclusion: In AF patients with cancer, composite end point including MACE and bleeding was not improved by OAT at the first year because of poor control of INR. Therefore, meticulous control of INR is needed in these patients. Moreover, OAT might fail to prevent MACE in specific cancers.
Targeting Transmembrane BAX Inhibitor Motif Containing 1 Alleviates Pathological Cardiac Hypertrophy
Authors: Ke-Qiong Deng, Guang-Nian Zhao, Zhihua Wang, Jing Fang, Zhou Jiang, Jun Gong, Feng-Juan Yan, Xue-Yong Zhu, Peng Zhang, Zhi-Gang She, Hongliang Li
Journal: Circulation (2017)

Cardiac hypertrophy and its resultant heart failure are among the most common causes of mortality worldwide. Abnormal protein degradation, especially the impaired lysosomal degradation of large organelles and membrane proteins, is involved in the progression of cardiac hypertrophy. However, the underlying mechanisms have not been fully elucidated.We investigated cardiac transmembrane BAX inhibitor motif containing 1 (TMBIM1) mRNA and protein expression levels in samples from patients with heart failure and mice with aortic banding (AB)-induced cardiac hypertrophy. We generated cardiac-specific Tmbim1 knockout mice and cardiac-specific Tmbim1-overexpressing transgenic mice and then challenged them with AB surgery. We used microarray, confocal image, and coimmunoprecipitation analyses to identify the downstream targets of TMBIM1 in cardiac hypertrophy. Tmbim1/Tlr4 double-knockout mice were generated to investigate whether the effects of TMBIM1 on cardiac hypertrophy were Toll-like receptor 4 (TLR4) dependent. Finally, lentivirus-mediated TMBIM1 overexpression in a monkey AB model was performed to evaluate the therapeutic potential of TMBIM1.TMBIM1 expression was significantly downregulated on hypertrophic stimuli in both human and mice heart samples. Silencing cardiac Tmbim1 aggravated AB-induced cardiac hypertrophy. This effect was blunted by Tmbim1 overexpression. Transcriptome profiling revealed that the TLR4 signaling pathway was disrupted dramatically by manipulation of Tmbim1. The effects of TMBIM1 on cardiac hypertrophy were shown to be dependent on TLR4 in double-knockout mice. Fluorescent staining indicated that TMBIM1 promoted the lysosome-mediated degradation of activated TLR4. Coimmunoprecipitation assays confirmed that TMBIM1 directly interacted with tumor susceptibility gene 101 via a PTAP motif and accelerated the formation of multivesicular bodies that delivered TLR4 to the lysosomes. Finally, lentivirus-mediated TMBIM1 overexpression reversed AB-induced cardiac hypertrophy in monkeys.TMBIM1 protects against pathological cardiac hypertrophy through promoting the lysosomal degradation of activated TLR4. Our findings reveal the central role of TMBIM1 as a multivesicular body regulator in the progression of pathological cardiac hypertrophy, as well as the role of vesicle trafficking in signaling regulation during cardiac hypertrophy. Moreover, targeting TMBIM1 could be a novel therapeutic strategy for treating cardiac hypertrophy and heart failure.
Establishment of collagen gel based co-culture models and protein analysis for a study of carcinoma-mesenchymal interaction
Authors: Zhong Min Che, Tae Whub Jung, Hyun Jung Jung, Jung Hee Choi, Eun Ju Lee, Do Jun Yoon, Jin Kim
Journal: Cancer Research (2005)

5493   Epithelial mesenchymal interaction(EMI) is well known to be essential in embryonic development and wound healing. Recent cancer studies have begun to know that tumor stroma can play active roles in cancer initiation and progression as well as invasive potential. However,  in vitro  model for recapitulating  in vivo  environment should be established to understand the reciprocal communication between cancer cells and stromal cells. This study is aimed to design  in vitro  model for EMI and to screen the difference of protein expression pattern by this model system. This study used oral squamous cell carcinoma cell line(YD-10B). To investigate the difference of protein expression of cancer cells influenced by variable  in vitro  conditions, three different models were designed; cancer cell culture model(C) with only collagen gel base, cancer cell co-culture model(M2) with collagen gel embedded with Swiss 3T3 fibroblasts, and sandwich co-culture model(M1) composed of three layers which have pure collagen layer between cancer cells and collagen gel with fibroblasts. Two Dimensional electrophoresis was performed to compare the difference of protein expression pattern of cancer cells among three model systems. Protein analysis was done by MALDI-TOF. As results, protein expression pattern was quite different between monolayer culture and collagen gel based culture. Additionally, protein expression was different between the collagen gel based co-culture models with fibroblasts and without fibroblasts. Among differential protein spots, cathepsin D was identified by MALDI-TOF, which is known to be associated with cancer invasion and metastasis. Cathepsin D expression was increased from only collagen gel base model to Ml to M2 model by Western blotting, suggesting that cathepsin D expression may be activated by direct and indirect control of stromal fibroblasts. From these results, these models are thought to be appropriate for EMI study and Cathepsin D might be induced by epithelial mesenchymal communication. This study was supported by the Korea Science and Engineering Foundation (R01-2002-000-00454-0).
Safety and Efficacy of Adoptively Transferred Donor-Derived Tumor-Directed T Cells with Relapsed AML Post-Allogeneic HSCT
Authors: Premal Lulla, Swati Naik, Ifigeneia Tzannou, Carlos A. Ramos, Rammurti Kamble, Catherine Robertson, Ayumi Watanabe, Manik Kuvalekar, Bambi J. Grilley, George Carrum, Helen E. Heslop, Juan F. Vera, Ann M. Leen
Journal: Blood (2017)
Influence of pluripotent stem cell gene polymorphisms on breast cancer susceptibility and response to chemotherapy in a north Indian cohort.
Authors: Gaurav Agarwal, Sonam Tulsyan, Punita Lal, Balraj Mittal
Journal: Journal of Clinical Oncology (2014)

1050 Background: OCT4, NANOG, LIN28 and SOX2 are the key transcription factors critical for the pluripotency and self-renewal of embryonic stem cells. Their dys-regulation leads to breast cancer cell growth, differentiation and tumor metastasis. We aimed to explore the role of pluripotent stem cell gene polymorphisms in breast cancer susceptibility and response to chemotherapy (CTx). Methods: This case-control study included 297 histologically proven female breast cancer patients and 273 healthy controls. Response to CTx was studied in 128 patients receiving neo-adjuvant CTx and evaluated for response as per RECIST criteria. The association of tagger SNPs in OCT4 (rs3130932), NANOG (rs11055786), LIN28 (rs4274112) and SOX2 (rs11915160) gene with breast cancer susceptibility and response to CTx were examined using Taqman allelic discrimination assays. Statistical analysis was done using SPSS ver 17. Results: Heterozygous genotype (P=0.019) and variant allele (P=0.003) of rs11915160 were found to be significantly associated with breast cancer susceptibility in premenopausal women. Similar association was found in dominant model (P=0.014). On univariate analysis of correlation of genotype with clinico-pathological characters, genotype (AG+GG) of rs4274112 polymorphism was found significantly associated with larger tumor size (P=0.040) and positive lymph node (P=0.002). However in multivariate analysis, larger tumor size was not significantly associated, but lymph node metastases was significantly associated with genotype (AG+GG) of rs4274112 polymorphism (P=0.007). Significant association was seen between hormone receptor positive tumors and rs3130932 polymorphism in multivariate analysis, both at the genotypic (AC+AA) (P=0.033) as well as the allelic (C) (P=0.023) levels. Conclusions: The SOX2 rs11915160 variants may confer breast cancer risk in premenopausal women. OCT4 rs3130932 and LIN28 rs4274112 genetic variants may have significant effect in clinico-pathological characteristics of breast cancer patients. However, no association was found between any of the studied polymorphisms with response to CTx.
Abstract #2218: Leptin induces migration of breast cancer cells via upregulation of anti-apoptotic protein, survivin
Authors: Brandi Brandon Knight, Elaine Oberlick, Arumugam Nagalingam, LaTonia Taliaferro-Smith, Prashanti Karna, Lily Yang, Neeraj Saxena, Dipali Sharma
Journal: Cancer Research (2009)

Obesity is an independent risk factor for breast cancer and obese breast cancer patients exhibit a higher risk for larger tumor burden and increased metastasis. Obesity affects carcinogenesis by autocrine and paracrine effects of the adipocytokine leptin. Leptin, a product of the obese (ob) gene, has been found to play a role in tumor progression and metastasis in addition to its functions in maintaining energy balance and satiety. Previously we found that leptin induces breast cancer growth by overexpressing cyclin D1 via Stat3 activation. More recently we showed that leptin crosstalks with IGF1 signaling and increases metastatic properties of breast cancer cells by transactivating epidermal growth factor receptor (EGFR). In the present study, we investigated the molecular mechanisms underlying leptin-induced migration of breast cancer cells. We found that leptin increases expression of anti-apoptotic protein, survivin in both estrogen receptor positive and negative breast cancer cells whereas no change was observed in the expression of X-linked inhibitor of apoptosis (XIAP). Our results show that leptin treatment increases migration of breast cancer cells. Further molecular analysis showed that leptin induced migration of breast cancer cells involves upregulation of survivin as overexpression of survivin further increases leptin-induced breast cancer cell migration. Intriguingly, silencing of survivin abrogates the effect of leptin on breast cancer cell migration. Taken together, these data suggest a novel mechanism involving survivin by which leptin increases migration of breast cancer cells. Our findings indicate a novel role of anti-apoptotic protein, survivin and putforth survivin as a potential therapeutic target to inhibit breast cancer cell migration.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2218.
Dual responses of CD14 methylation to distinct environments: a role in asthma and allergy
Authors: Yong Song, Siew-Kim Khoo, Khui Hung Lee, Mika Mäkelä, Tari Haahtela, Peter LeSouëf, Guicheng (Brad) Zhang
Journal: European Respiratory Journal (2017)

Gene–environment interactions are believed to cause an increased prevalence of asthma and allergic diseases in Western Countries, in comparison to Eastern Countries. To date, research has been inconclusive about which specific genetic and environmental risk factors are important, how the epigenetics/genetics interact with the environment, and which pathogenic mechanisms underlie the development of asthma and allergy. Inconsistencies in research outcomes are mainly attributed to substantial variations in genetic backgrounds and environmental conditions between different populations. Furthermore, a poor understanding of epigenetics might partially account for the observed disparities. This study shows that CD14 DNA methylation is differentially regulated by environmental factors <http://ow.ly/zlla30gxNWW>