gebhart/patrepeval huggingface dataset:
Combination efficacy of mTOR and MEK inhibitor in malignant pleural mesothelioma (MPM). (2013)

e18557 Background: Malignant pleural mesothelioma (MPM) is an aggressive tumor and poor prognosis. Active new agents is an urgent priority for patients with MPM. PI3K/AKT/mTOR pathway inhibitors in MPM have reported, but, the results has limited. Because PI3K/AKT/mTOR pathway inhibitors will make signaling feedback loops and cross-talk between signaling pathways. Combining PI3K/AKT/mTOR pathway inhibitors with other inhibitors might improve efficacy. Activation of RTKs stimulates both the PI3K/AKT/mTOR and RAS/RAF/MEK signaling pathways, and some study shows that inhibition of both pathways may be more effective than targeting either alone. We speculated that simultaneous inhibition both of mTOR and MEK by everolimus and selumetinib might improve the treatment of MPM. Methods: At first, we examined the growth inhibitory effects of everolimus or selumetinib alone on MPM cell lines. Next we examined combination efficacyofeverolimus with selumetinib on MPM cell lines, H226 was examined by computer-assisted analysis using the CalcuSyn software. We next confirmed the in vivo efficacy of everolimus or selumetinib alone, and the combination of both compounds in H226 MPM xenograft model. Results: Everolimus inhibited the growth of MPM cell lines with IC 50 values 1.19-21.5 μM. Selumetinib also inhibited the growth of MPM cell lines with IC 50 values 4.68-88.2μM. Next we examined combination efficacyofeverolimus with selumetinib on MPM cell lines, H226 was examined by computer-assisted analysis using the CalcuSyn software. With H226, the combination index (CI) at fraction (Fa) 0.5 and 0.8 were (0.56 ± 0.30) and (0.76 ± 0.48), respectively, indicating everolimus and selumetinib act synergistic, respectively. Everolimus or selumetinib alone showed significant antitumor activity, and the combination of everolimus and selumetinib enhanced the individual antitumor activity in H226 MPM xenograft model. (p&lt;0.05). Conclusions: These findings indicate that the combination of everolimus and selumetinib is effective in MPM growth inhibition not only in vitro but in vivo and chemotherapy regimens involving the combination of everolimus and selumetinib may be new molecular target therapy for MPM patients
HOMOTRANSPLANTATION OF THE LIVER (1967)

The feasibility of hepatic homotransplantation has been clearly established in principle inasmuch as several animals are still alive almost 3 years after complete hepatectomy and liver replacement. Both orthotopic and auxiliary operations are complicated surgical techniques. Nevertheless, the results in dogs are comparable to those which can be obtained with homotransplantation of the kidney. In man the problem is more difficult. In patients who have a need for such operations, there is invariably a metabolic disorder more complex than that caused by renal failure. In addition, the new organ must function efficiently from the beginning since its complete functional failure leads to death within a few hours. There is no recourse to an artificial liver to maintain life until the reversal of an injury which is caused by either ischemia or rejection. Nevertheless, research of several kinds may soon make possible the successful use of hepatic transplantation procedures for the definitive treatment of human liver disease as exemplified by the reports in this symposium concerning new techniques of organ preservation, histocompatibility analysis, and immunosuppression.
The Incorporation of NMDA Receptors with a Distinct Subunit Composition at Nascent Hippocampal SynapsesIn Vitro (1999)

Activity-dependent synaptic rearrangements during CNS development require NMDA receptor activation. The control of NMDA receptor function by developmentally regulated subunit expression has been proposed as one mechanism for this receptor dependence. We examined the phenotype of synaptic and extrasynaptic NMDA receptors during the development of synaptic load using the NMDA receptor 2B (NR2B)-selective antagonist ifenprodil. In cultured rat hippocampal neurons when relatively few synapses had formed, the ifenprodil block of EPSCs was less than whole-cell currents, the latter of which included both synaptic and extrasynaptic receptors. At the same developmental stage, we found that extrasynaptic receptors outnumbered synaptic receptors by 3:1; thus whole-cell currents were dominated by the extrasynaptic population. We used the macroscopic kinetics of ifenprodil block to distinguish between the receptor populations. The ifenprodil kinetics of whole-cell currents from neurons before and during the development of synaptic load was comparable with that of whole-cell currents in HEK293 cells transfected with NR1 and NR2B cDNA, indicating that extrasynaptic receptors are largely NR1/NR2B heteromers. In contrast, synaptic receptors included both a highly ifenprodil-sensitive (NR1/NR2B) component as well as a second population with lower ifenprodil sensitivity; the reduced ifenprodil block of EPSCs was attributable to synaptic receptors with lower ifenprodil sensitivity rather than to the appearance of ifenprodil-insensitive (NR1/NR2A) receptors. Our data indicate that the synaptic NMDA receptor complement changes quickly after synapse formation. We suggest that synapses containing predominately NR1/NR2B heteromers represent "immature" sites, whereas mature sites express NMDA receptors with a distinct, presumably triheteromeric, subunit composition.
Predicting breast cancer behavior by microarray analysis (2003)

The remarkable generation of scores of increasingly sophisticated mouse models of mammary cancer over the past two decades has provided tremendous insights into molecular derangements that can lead to cancer. The relationships of these models to human breast cancer, however, remain problematic. Recent advances in genomic technologies offer significant opportunities to identify critical changes that occur during cancer evolution and to distinguish in a complex and comprehensive manner the key similarities and differences between mouse models and human cancer. Comparisons between mouse and human tumors are being performed using comparative genomic hybridization, gene expression profiling, and proteomic analyses. The appropriate use of genetically engineered mouse models of mammary cancer in preclinical studies remains an important challenge which may also be aided by genomic technologies. Genomic approaches to cancer are generating huge datasets that represent a complex system of underlying networks of genetic interactions. Mouse models offer a tremendous opportunity to identify such networks and how they relate to human cancer. The challenge of the future remains to decipher these networks in order to identify the genetic nodes of oncogenesis that may be important targets for chemoprevention and therapy.
High-Brightness Wavelength Beam Combined Semiconductor Laser Diode Arrays (2007)

We report the wavelength beam combining of an array of high-power high-brightness 970-nm slab-coupled optical waveguide lasers. A 50-W peak power under quasi-continuous-wave (CW) operation was measured in an output beam with a beam quality of M <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x,y</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> =1.2, and 30 W under CW operation was measured with a beam quality of M <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x,y </sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> =2
Fluorinated carbohydrates. Use of DAST in the synthesis of fluorinated sugars (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorinated carbohydrates. Use of DAST in the synthesis of fluorinated sugarsPeter J. CardCite this: J. Org. Chem. 1983, 48, 3, 393–395Publication Date (Print):February 1, 1983Publication History Published online1 May 2002Published inissue 1 February 1983https://pubs.acs.org/doi/10.1021/jo00151a027https://doi.org/10.1021/jo00151a027research-articleACS PublicationsRequest reuse permissionsArticle Views1090Altmetric-Citations77LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Detection of Pulsus Paradoxus Associated With Large Pericardial Effusions in Pediatric Patients by Analysis of the Pulse-Oximetry Waveform (2002)

Analysis of pulse-oximetry waveforms may be a widely available, easily interpretable, and reliable method of detecting the pulsus paradoxus associated with large pericardial effusions in pediatric patients.
Serum IL-33 levels are increased in patients with psoriasis (2015)

These results suggest that serum IL-33 levels generally reflect increased inflammation in patients with psoriasis.
Variable antigens of Ureaplasma urealyticum containing both serovar-specific and serovar-cross-reactive epitopes (1990)

Currently there are 14 recognized serovars of Ureaplasma urealyticum, and it has been postulated that only certain ones may be associated with disease and that lack of serovar-specific antibody may be an important risk factor. Unfortunately, ureaplasma antigens important in the human immune response and disease pathogenesis are poorly defined. By using sera from ureaplasma-infected patients and antiureaplasma monoclonal antibodies, the present study has demonstrated, for serovars 3, 8, and 10, antigens which (i) are species specific, (ii) contain both serovar-specific and cross-reactive epitope(s), (iii) are produced not only in vitro but also in vivo, (iv) undergo a high rate of structural variation in vitro, (v) are present and structurally variable on invasive ureaplasma isolates (i.e., those from placenta, lung, and cerebrospinal fluid), and (vi) are among the predominant antigens recognized during infections in humans. Furthermore, we have shown that monoclonal antibodies to these antigens can inhibit the growth of the organisms in vitro, indicating the potential for these antigens to be important for host defense.
Chemokine Receptors of T Cells and of B Cells in Lymphatic Filarial Infection: A Role for CCR9 in Pathogenesis (2005)

We examined the expression of chemokine receptors on the surfaces of T cells and B cells from 27 individuals either with lymphatic filarial disease (lymphedema), with the asymptomatic or subclinical form of filarial infection, or without filarial infection. Individuals with lymphedema exhibited increased percentages of CCR9-expressing T cells and CCR9-expressing B cells and decreased percentages of both CXCR1-and-CXCR3-expressing T cells and CXCR1-and-CXCR3-expressing B cells, compared with asymptomatic or uninfected individuals. A significant correlation was found between the grade of lymphedema and the percentage of CCR9-expressing T cells and CCR9-expressing B cells. The percentages of CCR9-expressing T cells and CCR9-expressing B cells from patients with lymphedema was significantly up-regulated in response to live, infective-stage larvae of Brugia malayi but not to microfilariae of this parasite. Finally, individuals with lymphedema had significantly higher concentrations of interleukin-8, macrophage inflammatory protein (MIP)-1alpha , MIP-1beta , monocyte chemotactic protein 1, thymus-and-activation-regulated chemokine, and interferon-inducible protein 10 in their serum than did uninfected individuals. These results suggest that chemokine receptors (particularly CCR9) are involved in the pathogenesis of lymphatic filarial disease and that trafficking of particular cellular subsets may influence clinical outcome.
HIGH-THROUGHPUT, MASSIVELY PARALLEL DNA SEQUENCING TECHNOLOGY FOR THE ERA OF PERSONALIZED MEDICINE (2006)

A challenge to the realization of the vision of personalized medicine is our lack of understanding of the amount of genetic variation contained in the human species, which has been prohibitively expensive to acquire to date. In this review, we discuss a new system based on massively parallel picotiter plate based sequencing. This approach, now commercially available, delivers in excess of 200,000 individual clonal reads in a single five hour run and hence provides orders of magnitude improvement in speed and cost over conventional Sanger-based sequencing. The system is scalable well beyond its current performance and its emergence makes plausible the routine sequencing of individual human genomes in the near future. In this review, our system is presented in light of recent NHGRI sequencing technology grants, and a number of new applications enabled by ready access to hundreds of thousands of individual clonal reads are discussed with a particular focus on their potential impact on human health.
EGFRvIII mCAR-Modified T-Cell Therapy Cures Mice with Established Intracerebral Glioma and Generates Host Immunity against Tumor-Antigen Loss (2013)

All together, these data support that third-generation, EGFRvIII-specific mCARs are effective against gliomas in the brain and highlight the importance of syngeneic, immunocompetent models in the preclinical evaluation of tumor immunotherapies.
Improved sacral neuromodulation in the treatment of the hyperactive detrusor: signal modification in an animal model (2003)

These results show that QT-stimulation suppresses uncontrollable detrusor contractions in the minipig more effectively than the conventional rectangular stimulation presently applied in sacral neuromodulation.
Recent advances in all-epitaxial growth and properties of orientation-patterned gallium arsenide (OP-GaAs) (2009)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text P. G. Schunemann, L. A. Pomeranz, Y. E. Young, L. Mohnkern, and A. Vera, "Recent advances in all-epitaxial growth and properties of orientation-patterned gallium arsenide (OP-GaAs)," in Conference on Lasers and Electro-Optics/International Quantum Electronics Conference, OSA Technical Digest (CD) (Optica Publishing Group, 2009), paper CWJ5. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Danazol treatment of severely symptomatic fibrocystic breast disease and long‐term follow‐up—the Hjørring project (1984)

The purpose of the investigation was to study various aspects of danazol treatment in patients with fibrocystic breast disease and pronounced mastodynia. To qualify for inclusion, the patients in this study had to have a mammographically confirmed prominent glandular structure and/or severe cystic breast disease, associated with pronounced cyclical mastodynia lasting at least one week per menstrual cycle for more than 6 months. They also had to be premenopausal and not undergoing hormonal therapy. Of 109 patients with a mean age of 40 +/- 6.2 (SD) years, who completed 6 months' treatment with danazol, 65% had a pre-treatment history of more than 5 years. According to detailed mammographic characterization, only 18% of the patients had no visible cysts. Of the 82% with visible cysts, half presented with both small (less than 1 cm) and large cysts. The patients were treated in two consecutive groups, 55 patients receiving 400 mg a day and 54 patients 200 mg a day. The therapeutic response was similar following both dosages. Mastodynia responded rapidly and total elimination was noted in about 90% of cases. A marked decrease in prominence of palpable structure was observed in virtually all patients. Mammographically, a decrease in the amount of glandular tissue was observed. These changes during treatment were statistically highly significant (p less than 0.001), irrespective of dose or category of patient. Non-cystic nodularities gradually decreased in 85% and resolved completely in 58% of the cases, but the degree of resolution in the groups of patients with no or only small (less than 1 cm) visible cysts was significantly greater (p less than 0.02 or less) than in the group which also had large cysts and which included the most severe and intractable cases. The mammographical visualization of cysts, ductal system, and fibrous tissue increased initially due to the marked regression of obscuring glandular tissue. Thereafter, a decrease in the number and spread of small cysts was observed in a significant proportion of patients and in some cases a reduction in duct diameter could be demonstrated by means of galactography. Nipple discharge also decreased. The extent of fibrosis appeared to be unaffected by therapy. In the 46 patients with large cysts and, in most cases, a documented history of repeated cyst formation, danazol treatment was found to arrest the development of new cysts and to prevent recurrence for a considerable time thereafter.(ABSTRACT TRUNCATED AT 400 WORDS)
The latent transforming growth factor β binding protein (LTBP) family (2000)

The transforming growth factor β (TGFβ) cytokines are a multi-functional family that exert a wide variety of effects on both normal and transformed mammalian cells. The secretion and activation of TGFβs is regulated by their association with latency-associated proteins and latent TGFβ binding proteins (LTBPs). Over the past few years, three members of the LTBP family have been identified, in addition to the protoype LTBP1 first sequenced in 1990. Three of the LTBP family are expressed in a variety of isoforms as a consequence of alternative splicing. This review summarizes the differences between the isoforms in terms of the effects on domain structure and hence possible function. The close identity between LTBPs and members of the fibrillin family, mutations in which have been linked directly to Marfan's syndrome, suggests that anomalous expression of LTBPs may be associated with disease. Recent data indicating that differential expression of LTBP1 isoforms occurs during the development of coronary heart disease is considered, together with evidence that modulation of LTBP function, and hence of TGFβ activity, is associated with a variety of cancers.
HER2 therapy. Small molecule HER-2 tyrosine kinase inhibitors (2007)

Overexpression of the human epidermal growth factor receptor (HER)-2 oncogenic receptor tyrosine kinase, which occurs in 25% of breast cancers, portends poor clinical outcome and consequently represents an attractive target for therapeutic intervention. Small molecule tyrosine kinase inhibitors that compete with ATP binding at the cytoplasmic catalytic kinase domain of HER-2 block autophosphorylation and activation of HER-2, resulting in inhibition of downstream proliferation and survival signals. These agents have exhibited clinical activity in patients with HER-2 overexpressing breast cancers. Here we review the development of HER-2 tyrosine kinase inhibitors, their mechanisms of action, their biological and clinical activities, their safety profile, and combination strategies including conventional cytotoxics and other targeted agents.
Lanthanide-Loaded Erythrocytes As Highly Sensitive Chemical Exchange Saturation Transfer MRI Contrast Agents (2013)

Chemical exchange saturation transfer (CEST) agents are a new class of frequency-encoding MRI contrast agents with a great potential for molecular and cellular imaging. As for other established MRI contrast agents, the main drawback deals with their low sensitivity. The sensitivity issue may be tackled by increasing the number of exchanging protons involved in the transfer of saturated magnetization to the "bulk" water signal. Herein we show that the water molecules in the cytoplasm of red blood cells can be exploited as source of exchangeable protons provided that their chemical shift is properly shifted by the intracellular entrapment of a paramagnetic shift reagent. The sensitivity of this system is the highest displayed so far among CEST agents (less than 1 pM of cells), and the natural origin of this system makes it suitable for in vivo applications. The proposed Ln-loaded RBCs may be proposed as reporters of the blood volume in the tumor region.
Standards and standardization in mastocytosis: Consensus Statements on Diagnostics, Treatment Recommendations and Response Criteria (2007)

Although a classification for mastocytosis and diagnostic criteria are available, there remains a need to define standards for the application of diagnostic tests, clinical evaluations, and treatment responses. To address these demands, leading experts discussed current issues and standards in mastocytosis in a Working Conference. The present article provides the resulting outcome with consensus statements, which focus on the appropriate application of clinical and laboratory tests, patient selection for interventional therapy, and the selection of appropriate drugs. In addition, treatment response criteria for the various clinical conditions, disease-specific symptoms, and specific pathologies are provided. Resulting recommendations and algorithms should greatly facilitate the management of patients with mastocytosis in clinical practice, selection of patients for therapies, and the conduct of clinical trials.
Different Effects of Insulin and Platelet‐Derived Growth Factor on Phosphatidylinositol 3‐Kinase at the Subcellular Level in 3T3‐L1 Adipocytes (1996)

Insulin stimulates glucose uptake by induction of the translocation of vesicles that contain the glucose transporter Glut 4 to the plasma membrane. Phosphatidylinositol 3‐kinase (PtdIns 3‐kinase), which is thought to be involved in intracellular trafficking, could play a critical role in insulin‐induced glucose transport. In 3T3‐L1 adipocytes, insulin and platelet‐derived‐growth‐factor (PDGF) stimulated glucose uptake by 5.8‐fold and 2.4‐fold, respectively, but PDGF had no significant effect on Glut 4 translocation. Nevertheless, both hormones activated PtdIns 3‐kinase activity in total cell extracts. However, insulin and PDGF had different effects on the stimulation of PtdIns 3‐kinase activity in several subcellular fractions, and the movements of insulin‐receptor substrate (IRS) 1 and the p85 subunit of PtdIns 3‐kinase between subcellular compartments. PDGF stimulated PtdIns 3‐kinase activity almost exclusively in the plasma membrane, and induced translocation of the p85 subunit from the cytosol to the plasma membrane, where the PDGF receptor was phosphorylated on tyrosine residues. In contrast, insulin stimulated PtdIns 3‐kinase activity in the plasma membrane, in low‐density microsomes (LDM) and in cytosol. Furthermore, insulin induced the translocation of p85 from the cytosol to LDM and the translocation of IRS 1 from LDM to the cytosol. These data indicate that insulin and PDGF have different effects on the activation of PtdIns 3‐kinase and on the movement of IRS 1 and PtdIns 3‐kinase between subcellular compartments. We would like to suggest that a crucial event in the stimulation of glucose uptake by insulin could be that insulin, but not PDGF, induces activation of PtdIns 3‐kinase in the cytosol and in LDM, the compartment enriched in Glut‐4‐containing vesicles.