3,896 research outputs found
A naturally occurring soluble form of vascular endothelial growth factor receptor 2 detected in mouse and human plasma
No full textAngiogenesis and vasculogenesis are regulated in large
part by several different growth factors and their
associated receptor tyrosine kinases (RTKs). Foremost
among these is the vascular endothelial growth factor
(VEGF) family including VEGF receptor (VEGFR)-2
and -1. VEGFR ligand binding and biological activity are
regulated at many levels, one of which is by a soluble,
circulating form of VEGFR-1 (sVEGFR-1). This sVEGFR-1
can act as a competitive inhibitor of its ligand, serve
as a possible biomarker, and play important roles in
cancer and other diseases such as preeclampsia.
Recombinant forms of sVEGFR-2 have been shown to
have antiangiogenic activity, but a naturally occurring
sVEGFR-2 has not been described previously. Here,
we report such an entity. Having a molecular weight
of f160 kDa, sVEGFR-2 can be detected in mouse and
human plasma with several different monoclonal and
polyclonal anti-VEGFR-2 antibodies using both ELISA
and immunoprecipitation techniques. In vitro studies
have determined that the sVEGFR-2 fragment can
be found in the conditioned media of mouse and
human endothelial cells, thus suggesting that it may
be secreted, similar to sVEGFR-1, or proteolytically
cleaved from the cell. Potential biological activity of this
protein was inferred from experiments in which mouse
sVEGFR-2 could bind to VEGF-coated plates. Similar
to sVEGFR-1 and other soluble circulating RTKs,
sVEGFR-2 may have regulatory consequences with
respect to VEGF-mediated angiogenesis as well
as potential to serve as a quantitative biomarker of
angiogenesis and antiangiogenic drug activity,
particularly for drugs that target VEGF or VEGFR-2
Tumor growth kinetics of human LM2-4LUC+ triple negative breast carcinoma cells
No full textCell culture and data set
Tumor growth data used in this study were obtained from experiments involving the use of a LM2-4LUC+ cells (or LM2-4), a metastatic variant of the human triple-negative breast carcinoma MDA-MB-231 cells. Animal studies were performed as described previously under Roswell Park Comprehensive Cancer Center (RPCCC) Institutional Animal Care and Use Committee (IACUC) protocol number 1227M [1-6]. Tumor growth data were pooled from eight separate experiments conducted with a total of 581 observations, and represent control (vehicle-treated) animals from published studies [1-6]. Vehicle formulation was carboxymethylcellulose sodium (USP, 0.5% w/v), NaCl (USP, 1.8% w/v), Tween-80 (NF, 0.4% w/v), benzyl alcohol (NF, 0.9% w/v), and reverse osmosis deionized water (added to final volume) and adjusted to pH 6 (see [3]) and was given at 10ml/kg/day for 7-14 days prior after tumor implantation and before tumor resection [1-6].
Tumor injections
LM2-4LUC+ cells were orthotopically implanted (106 cells per injection) into the right inguinal mammary fat pads of 6- to 8-week-old female severe combined immunodeficient (SCID) mice.
Tumor measurements
Tumor size was measured regularly with calipers to a maximum volume of 2 cm3, calculated by the formula
(ellipsoid) where L is the largest and w is the smallest tumor diameter.
References
[1] Benzekry, S., Lamont, C., Beheshti, A., Tracz, A., Ebos, J. M. L., Hlatky, L., & Hahnfeldt, P. (2014). Classical mathematical models for description and prediction of experimental tumor growth. PLoS Comput Biol, 10(8), e1003800. http://doi.org/10.1371/journal.pcbi.1003800
[2] Benzekry S, Tracz A, Mastri M, Corbelli R, Barbolosi D, Ebos JML. (2016) Modeling Spontaneous Metastasis Following Surgery: An In Vivo-In Silico Approach. Cancer Res.;76(3):535–547. doi:10.1158/0008-5472.CAN-15-1389.
[3] Ebos JML, Lee CR, Bogdanovic E, Alami J, Van Slyke P, Francia G, et al. (2008) Vascular Endothelial Growth Factor-Mediated Decrease in Plasma Soluble Vascular Endothelial Growth Factor Receptor-2 Levels as a Surrogate Biomarker for Tumor Growth. Cancer Res.;68(2):521–529. doi:10.1158/0008-5472.CAN-07-3217.
[4] Ebos JML, Mastri M, Lee CR, Tracz A, Hudson JM, Attwood K, et al. (2014) Neoadjuvant antiangiogenic therapy reveals contrasts in primary and metastatic tumor efficacy. EMBO Mol Med;6:1561–76. https://doi.org/10.15252/emmm.201403989
[5] Ebos JML, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. (2009) Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell;15:232–9. https://doi.org/10.1016/j.ccr.2009.01.021
[6] Mastri M, Tracz A, Lee CR, Dolan M, Attwood K, Christensen JG, et al. (2018) A Transient Pseudosenescent Secretome Promotes Tumor Growth after Antiangiogenic Therapy Withdrawal. Cell Rep.; 25 (13):3706–20 e8. Epub 2018/12/28. https://doi.org/10.1016/j.celrep.2018.12.017</p
Down-regulation of DNA mismatch repair proteins in human and murine tumor spheroids: implications for multicellular resistance to alkylating agents
No full textSimilar to other anticancer agents, intrinsic or acquired resistance to DNA-damaging chemotherapeutics is a major obstacle for cancer therapy. Current strategies aimed at overcoming this problem are mostly based on the premise that tumor cells acquire heritable genetic mutations that contribute to drug resistance. Here, we present evidence for an epigenetic, tumor cell adhesion-mediated, and reversible form of drug resistance that is associated with a reduction of DNA mismatch repair proteins PMS2 and/or MLH1 as well as other members of this DNA repair process. Growth of human breast cancer, human melanoma, and murine EMT-6 breast cancer cell lines as multicellular spheroids in vitro, which is associated with increased resistance to many chemotherapeutic drugs, including alkylating agents, is shown to lead to a reproducible down-regulation of PMS2, MLH1, or, in some cases, both as well as MHS6, MSH3, and MSH2. The observed down-regulation is in part reversible by treatment of tumor spheroids with the DNA-demethylating agent, 5-azacytidine. Thus, treatment of EMT-6 mouse mammary carcinoma spheroids with 5-azacytidine resulted in reduced and/or disrupted cell-cell adhesion, which in turn sensitized tumor spheroids to cisplatin-mediated killing in vitro. Our results suggest that antiadhesive agents might sensitize tumor spheroids to alkylating agents in part by reversing or preventing reduced DNA mismatch repair activity and that the chemosensitization properties of 5-azacytidine may conceivably reflect its role as a potential antiadhesive agent as well as reversal agent for MLH1 gene silencing in human tumors
The SSC of the Generalised Jahangir’s Graph Jm,k and its Algebraic Characterizations
No full textIn this article, we present important combinatorial and algebraicproperties of spanning simplicial complex (SSC) of the generalised Jahangir’sgraph Jm,k. We describe the relation to find f−vectors associatedto Δs(Jm,k) and determine the Hilbert series for the SR-ring KΔs(Jm,k).In the end, we present the associated primes of the facet ideal IF(Δs(Jm,k))and the Cohen-Macaulay characterization of the SR-ring of Δs(Jm,k).AMS (MOS) Subject Classification Codes: Primary 13-P10, Secondary 13-F20, 13-C14, 13-H10.Corresponding Author: Agha KashifKey Words: Simplicial Complexes, f-vectors, Spanning Trees, Face Ring, Hilbert Series, CohenMacaulay
To <i>JM</i> on Its 75th Anniversary
No full text This article discusses how Journal of Marketing ( JM) has influenced marketing science and practice by publishing articles on substantive topics relevant to customers, managers, organizations, markets, and society. The journal's 75th anniversary coincides with the 50th anniversary of the Marketing Science Institute (MSI). Frequently, JM and MSI have collaborated to address important substantive marketing issues identified in MSI's Research Priorities. The author highlights seminal articles on brand equity; business-to-business marketing (including sales force management); connecting marketing information, metrics, and strategy; consumer behavior; innovation, new product development. and product management; marketing orientation and capabilities; and market research, methodology and services. She also draws attention to articles that have won the Sheth Foundation/ JM Award and the H. Paul Root Award. The article describes how JM‘s knowledge dissemination is amplified by powerful social network effects. Ideas in JM articles diffuse through the business community, influencing the mind-set of managers worldwide. </jats:p
JM-20, a Benzodiazepine-Dihydropyridine Hybrid Molecule, Inhibits the Formation of Alpha-Synuclein-Aggregated Species
No full text\ua9 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Studies showed that JM-20, a benzodiazepine-dihydropyridine hybrid molecule, protects against rotenone and 6-hydroxydopamine neurotoxicity. However, its protective effects against cytotoxicity induced by endogenous neurotoxins involved in Parkinson’s disease (PD) pathogenesis have never been investigated. In this study, we evaluated the ability of JM-20 to inhibit alpha-synuclein (aSyn) aggregation. We also evaluated the interactions of JM-20 with aSyn by molecular docking and molecular dynamics and assessed the protective effect of JM-20 against aminochrome cytotoxicity. We demonstrated that JM-20 induced the formation of heterogeneous amyloid fibrils, which were innocuous to primary cultures of mesencephalic cells. Moreover, JM-20 reduced the average size of aSyn positive inclusions in H4 cells transfected with SynT wild-type and synphilin-1-V5, but not in HEK cells transfected with synphilin-1-GFP. In silico studies showed the interaction between JM-20 and the aSyn-binding site. Additionally, we showed that JM-20 protects SH-SY5Y cells against aminochrome cytotoxicity. These results reinforce the potential of JM-20 as a neuroprotective compound for PD and suggest aSyn as a molecular target for JM-20
Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies
No full textA major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non-tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, with the maximum values peaking when doses previously determined to be optimally therapeutic were used. Plasma VEGF should be considered as a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs that block VEGFR-2 (KDR) activity in a clinical setting
Uterine transplantation: a promising surrogate to surrogacy?
No full textUterine transplantation: a promising surrogate to surrogacy?
Grynberg M1, Ayoubi JM, Bulletti C, Frydman R, Fanchin R.
Author information
Abstract
Infertility due to the inability of the uterus to carry a pregnancy ranks among the most unresolved issues in reproductive medicine. It affects millions of women worldwide who have congenital or acquired uterine affections, often requiring hysterectomy, and potentially represents a considerable fraction of the general infertile population. Patients suffering from severe uterine infertility are currently compelled to go through gestational surrogacy or adoption; both approaches, unfortunately, deprive them of the maternal experience of pregnancy and birth. Uterine transplantation represents an outstanding, yet complex, perspective to alleviating definitive uterine infertility. In the past decades, a number of scientific experiments conducted both in animals and women, focusing on uterine transplantation, have led to promising results. Collectively, these findings undoubtedly constitute a sound basis to clinically apply uterine transplantation in the near future. This paper is, however, an overview not only of the extent and limitations of accumulated scientific knowledge on uterine transplantation, but also its ethical implications, in an effort to define the actual place of such an approach among the therapeutic arsenal for alleviating infertility.
© 2011 New York Academy of Sciences
Translation and interpretation: Translation redundancy reconsidered
No full textInterpretation is an integral part of the process of translating. This article raises the question of whether interpretation fo a literary work by a translator should be guided by extratextual factors or not. The discussion is illustrated with examples taken from David Hawkes' translation of a Chinese classic, A Dream of Red Mansions. As the work of a scholar-translator, Hawkes' version is richly supplemented with disclosures concerning the characters and explanations of the cultural environment embodied in the novel. In many cases, however, this translation procedure is redundant and explanatory, enlightening the readers but at the same time robbing them of the pleasure of literary interpretation and cultural exploration. By means of this illustration of translation redundancy, the author points out that there is difference between a scholar who helps the interpretation fo a work and a translator who presents a work close to its original version. It is particularly important to pay attention tot his difference in literary translations in a cross-cultural situation involving two enormously different cultures.Language & LinguisticsA&HCI0ARTICLE1,SI115-12
INTERNATIONAL FINANCIAL REPORTING STANDARDS (IFRS), BAIK BAGI USAHA MIKRO KECIL MENENGAH? (Studi Kasus: UMKM JM KERIPIK)
No full textABSTRAKUndang-undang nomor 20 tahun 2008 tentang Usaha Makro Kecil Menengah (UMKM), usaha kecil adalah usaha ekonomi produktif yang berdiri sendiri, yang dilakukan oleh orang perseorangan atau badan usaha yang bukan merupakan anak perusahaan atau bukan cabang perusahaan yang memiliki, dikuasai atau menjadi bagian baik langsung maupun tidak langsung dari usaha menengah atau usaha besar yang memenuhi kriteria. JM Keripik merupakan salah salah UMKM yang bergelut dibidang produksi dan penjualan. IFRS merupakan seperangkat standard yang dikeluarkan oleh Dewan Standard Akuntansi Internasional (IASB). IFRS berguna untuk menyusun laporan keuangan yang dapat diterima di dunia Global.Penulistertarik untukmengetahuipencatatankeuanganJM Keripik dan apakah perlu merekomendasikan IFRS pada UMKM JM Keripik. Metode penelitian yang digunakaan penulis adalah kualitatif yaitu observasi dan wawancara. Dari hasil penelitian banyak terdapat pencatatan-pencatatan yang kurang terperinci, UMKM JM Keripik hanya memilki empat macam pencatatan yaitu pencatatan mengenai: 1.Stock barang, 2.Supliyer, 3.Costumer dan 4.Stock toko, pencatatan ini hanya dapat dimengerti oleh pemilik JM Keripik. Sebaiknya pemilik UMKM JM Keripik mengganti laporan keuangan yang sederhana ke laporan keuangan yang semestinya dan yang berbasis IFRS karena IFRS membawa dampak positif bagi UMKM dan merupakan standar akuntansi keuangan yang digunakan dunia global. Kata Kunci : UMKM, IFRS, JM Keripik ABSTRACT Act number 20 of 2008 concerning the Macro Small and Medium Enterprises, small businesses are productive economic activities that stand alone, carried out by an individual or business entity that is not a subsidiary or not a branch of the company that owns, controlled or become part either directly or indirectly from medium or large businesses that meet the criteria. JM Keripik which deals in the field of production and sales. IFRS is a set of standards issued by the International Accounting Standards Board (IASB). IFRS is useful for preparing financial statements that is acceptable in the global world. Authors interested in knowing the financial records of JM Keripik and whether to recommend IFRS on JM Keripik. The research method is qualitative author of observation and interviews. From the research there are many registries are less detailed, JM Keripik has only four kinds of recording is recording about: 1.Stock goods, 2.Supliyer, 3.Costumer and 4.Stock shop, registration can only be understood by the owner of JM Keripik. JM Keripik owners should replace the simple financial reports to the appropriate financial statements and IFRS-based IFRS for Macro Small and Medium Enterprises had a positive impact and a financial accounting standards global world. Keywords : UMKM, IFRS, JM Keripi
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