bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-HER3 Monoclonal Antibody Inhibits Acquired Trastuzumab-Resistant Gynecologic Cancers
Authors: Li Xinying , Duan Yanting , Qiao Chunxia , Zhou Tingting , Yu Ming , Geng Jing , Feng Jiannan , Shen Beifen , Lv Ming , Li Yan 
Published: June 2015

Background: Antibody resistance, both de novo and acquired, is usually related to high risk of recurrence and lower survival rate in gynecologic cancers. Prevention or reversal of the resistance often yields beneficial clinical results. It was reported that anti-human epidermal growth factor receptor 3 monoclonal antibody was effective against trastuzumab-resistant breast cancer cells. Here in our laboratory, an acquired trastuzumab-resistant ovarian cancer cell line, SKOV3-T, was established previously. Further, human epidermal growth factor receptor 3 was observed to be upregulated in this cell line by microarray detection, suggesting that the antagonist against human epidermal growth factor receptor 3 might be effective to inhibit the resistant cells. Methods: We developed an anti-human epidermal growth factor receptor 3 monoclonal antibody, LMAb3, and its affinity to bind human epidermal growth factor receptor 3 was calculated by the Biacore method. Preliminarily, LMAb3’s antitumor activity was evaluated in vitro using cell growth/proliferation and clone formation assays in the breast cancer cell line MCF-7. Furthermore, LMAb3 was also evaluated for its inhibitory effect on the carcinogenicity of the SKOV3-T cells, which were induced to overexpress human epidermal growth factor receptor 3, both in vitro and in vivo. The possible underlying signal transduction mechanisms were also identified by Western blot in the MCF-7 and SKOV3-T cells. Results: LMAb3 was able to inhibit the cell growth/proliferation, clone, and tumor formation both in vitro (in the MCF-7 and SKOV3-T cells) and in vivo. The underlying mechanism of LMAb3 possibly involves inactivation of the HER family proteins (human epidermal growth factor receptor 1, human epidermal growth factor receptor 2, and especially human epidermal growth factor receptor 3) as well as the downstream mitogen-activated protein kinase and protein kinase B pathways. Conclusion: Our work suggests that satisfactory curative effects might be achieved with LMAb3 to treat the trastuzumab-resistant, human epidermal growth factor receptor 3-positive cases of gynecologic cancers.
Radix Astragali and Tanshinone Help Carboplatin Inhibit B16 Tumor Cell Growth
Authors: Wu Jinyi , Xu Haiming , Zhang Lei , Zhang Xiuying 
Published: June 2015

Background: Excessive UV radiation causes increased melanoma incidence. Postoperation chemotherapy will destroy lymphocytes and compromise immune response. Immunodepression is also detected in patients with cancers. Previous studies suggested that polysaccharide–protein complexes manifested immunomodulatory and antitumor activities. Radix Astragali (RA) extract is a product of polysaccharide–protein complexes, which has been used in the treatment of a variety of diseases because of its low toxicity to the host. Tanshinone (TA) is a derivative of phenanthrenequinone isolated from Danshen, which is suggested to inhibit tumor growth by inducing apoptosis in tumor cells. Carboplatin (CA) is a commonly used chemotherapeutic drug in melanoma treatment. Therefore, we hypothesized that the combination of RA and TA will help CA better inhibit the B16 cell growth. Purpose: The study will test that the efficacy of growth inhibition of tumor cell produced by CA + RA + TA is better than CA + RA or CA + TA. Methods: The B16 tumor cells were injected to Swiss-Hauschka (ICR) mice subcutaneously. Twenty-four hours later, mice received CA intraperitoneally, CA + RA (RA were administered gastrically at the dosage of 10 g/kg body weight), CA + TA (TA were administered gastrically at the dosage of 0.5 g/kg body weight), or no treatment (model group). Tumor weight, volume, latency, incidence, the percentage of CD4+ and CD8+ in spleen, and natural killer (NK), and cytotoxic lymphocyte (CTL) activities were measured and compared among different groups. Results: Compared with mice treated with CA + RA, CA + TA, or CA alone, the mice treated with CA + RA + TA showed (1) significantly smaller tumor weight and tumor volume; (2) significantly longer tumor latency; (3) significantly lower tumor incidence; and (4) significantly increased percentage of CD4+ and CD8+ in spleen and increased activities of NK and CTL. Conclusion: Combination of RA and TA can help CA produce more effective inhibition on B16 cell growth.
Inhibition of Mcl-1 with the pan–Bcl-2 family inhibitor (–)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia
Authors: Pan Rongqing , Ruvolo Vivian R. , Wei Jun , Konopleva Marina , Reed John C. , Pellecchia Maurizio , Andreeff Michael , Ruvolo Peter P. 
Published: June 2015

Key Points
Mcl-1 inhibition by pan-active Bcl-2 inhibitor (–)BI97D6 kills AML cells via induction of mitochondrial apoptosis. Mcl-1 inhibition by (–)BI97D6 overcomes intrinsic and extrinsic drug resistance to ABT-737.
Eradication of B-ALL using chimeric antigen receptor–expressing T cells targeting the TSLPR oncoprotein
Authors: Qin Haiying , Cho Monica , Haso Waleed , Zhang Ling , Tasian Sarah K. , Oo Htoo Zarni , Negri Gian Luca , Lin Yongshun , Zou Jizhong , Mallon Barbara S. , Maude Shannon , Teachey David T. , Barrett David M. , Orentas Rimas J. , Daugaard Mads , Sorensen Poul H. B. , Grupp Stephan A. , Fry Terry J. 
Published: June 2015

Key Points
Adoptive transfer of T cells genetically modified to express anti-TSLPR chimeric antigen receptors can cure B-ALL in xenograft models. Anti-TSLPR CAR constructs containing a CH2CH3 spacer domain were inactive against TSLPR-overexpressing B-ALL.
Microenvironmental interleukin-6 suppresses toll-like receptor signaling in human leukemia cells through miR-17/19A
Authors: Li Yanmei , Shi Yonghong , McCaw Lindsay , Li You-Jun , Zhu Fang , Gorczynski Reg , Duncan Gordon S. , Yang Burton , Ben-David Yaacov , Spaner David E. 
Published: June 2015

Key PointsIL-6 from splenic stromal cells prevents CLL cells from responding strongly to TLR ligands. IL-6–signaling inhibitors enhance TLR-mediated responses of CLL cells in vitro and in vivo.
Near-infrared emitting AgInTe2 and Zn-Ag-In-Te colloidal nanocrystals
Authors: Langevin Marc-Antoine , Pons Thomas , Ritcey Anna M. , Nì. Allen Claudine 
Published: June 2015

Abstract
The synthesis of AgInTe2 nanocrystals emitting between 1095 nm and 1160 nm is presented. Evolution of the Ag:In:Te ratio shows progressive incorporation of In3+ in Ag2Te, leading to the formation of orthorhombic AgInTe2. When zinc is added to the synthesis, the photoluminescence quantum yield reaches 3.4 %.
Appraisal of the technologies and review of the genomic landscape of ductal carcinoma in situ of the breast
Authors: Pang Jia-Min B. , Gorringe Kylie L. , Wong Stephen Q. , Dobrovic Alexander , Campbell Ian G. , Fox Stephen B. 
Published: June 2015

AbstractDuctal carcinoma in situ is a biologically diverse entity. Whereas some lesions are cured by local surgical excision, others recur as in situ disease or progress to invasive carcinoma with subsequent potential for metastatic spread. Reliable prognostic biomarkers are therefore desirable for appropriate clinical management but remain elusive. In common with invasive breast cancer, ductal carcinoma in situ exhibits many genomic changes, predominantly copy number alterations. Although studies have revealed the genomic heterogeneity within individual ductal carcinoma in situ lesions and the association of certain copy number alterations with nuclear grade, none of the genomic changes defined so far is consistently associated with invasive transformation or recurrence risk in pure ductal carcinoma in situ. This article will review the current landscape of genomic alterations in ductal carcinoma in situ and their potential as prognostic biomarkers together with the technologies used to define these.
CD24+ cells fuel rapid tumor growth and display high metastatic capacity
Authors: Rostoker Ran , Abelson Sagi , Genkin Inna , Ben-Shmuel Sarit , Sachidanandam Ravi , Scheinman Eyal J. , Bitton-Worms Keren , Orr Zila Shen , Caspi Avishay , Tzukerman Maty , LeRoith Derek 
Published: June 2015

Abstract
Introduction
Breast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epithelial cells isolation, recently it was suggested as a potential prognostic marker in a wide variety of malignancies. Here, we demonstrate that CD24+ cells create intra-tumor heterogeneity, and display highly metastatic properties.

Methods
The mammary carcinoma Mvt1 cells were sorted into CD24− and CD24+ cells. Both subsets were morphologically and phenotypically characterized, and tumorigenic capacity was assessed via orthotopic inoculation of each subset into the mammary fat pad of wild-type and MKR mice. The metastatic capacity of each subset was determined with the tail vein metastasis assay. The role of CD24 in tumorigenesis was further examined with shRNA technology. GFP-labeled cells were monitored in vivo for differentiation. The genetic profile of each subset was analyzed using RNA sequencing.

Results
CD24+ cells displayed a more spindle-like cytoplasm. The cells formed mammospheres in high efficiency and CD24+ tumors displayed rapid growth in both WT and MKR mice, and were more metastatic than CD24- cells. Interestingly, CD24-KD in CD24+ cells had no effect both in vitro and in vivo on the various parameters studied. Moreover, CD24+ cells gave rise in vivo to the CD24− that comprised the bulk of the tumor. RNA-seq analysis revealed enrichment of genes and pathways of the extracellular matrix in the CD24+ cells.

Conclusion
CD24+ cells account for heterogeneity in mammary tumors. CD24 expression at early stages of the cancer process is an indication of a highly invasive tumor. However, CD24 is not a suitable therapeutic target; instead we suggest here new potential targets accounting for early differentiated cancer cells tumorigenic capacity.
Common fixed point theorems for generalized k-ordered contractions and B-contractions on noncommutative Banach spaces
Authors: Xin Qiaoling , Jiang Lining 
Published: June 2015

AbstractThe paper introduces the concepts of the generalized k-ordered contraction and the k-ordered B-contraction in noncommutative Banach spaces. Then some common fixed point theorems are given. As an application, the existence and uniqueness theorem for a common solution of integral equations is presented.
Maximum flow approach to prioritize potential drug targets of Mycobacterium tuberculosis H37Rv from protein‐protein interaction network
Authors: Melak Tilahun , Gakkhar Sunita 
Published: June 2015

AbstractBackgroundIn spite of the implementations of several strategies, tuberculosis (TB) is overwhelmingly a serious global public health problem causing millions of infections and deaths every year. This is mainly due to the emergence of drug‐resistance varieties of TB. The current treatment strategies for the drug‐resistance TB are of longer duration, more expensive and have side effects. This highlights the importance of identification and prioritization of targets for new drugs. This study has been carried out to prioritize potential drug targets of Mycobacteriumtuberculosis H37Rv based on their flow to resistance genes.MethodsThe weighted proteome interaction network of the pathogen was constructed using a dataset from STRING database. Only a subset of the dataset with interactions that have a combined score value ≥770 was considered. Maximum flow approach has been used to prioritize potential drug targets. The potential drug targets were obtained through comparative genome and network centrality analysis. The curated set of resistance genes was retrieved from literatures. Detail literature review and additional assessment of the method were also carried out for validation.ResultsA list of 537 proteins which are essential to the pathogen and non‐homologous with human was obtained from the comparative genome analysis. Through network centrality measures, 131 of them were found within the close neighborhood of the centre of gravity of the proteome network. These proteins were further prioritized based on their maximum flow value to resistance genes and they are proposed as reliable drug targets of the pathogen. Proteins which interact with the host were also identified in order to understand the infection mechanism.ConclusionPotential drug targets of Mycobacteriumtuberculosis H37Rv were successfully prioritized based on their flow to resistance genes of existing drugs which is believed to increase the druggability of the targets since inhibition of a protein that has a maximum flow to resistance genes is more likely to disrupt the communication to these genes. Purposely selected literature review of the top 14 proteins showed that many of them in this list were proposed as drug targets of the pathogen.
Ultrafiltration of natural organic matter from water by vertically aligned carbon nanotube membrane
Authors: Jafari Ali , Mahvi Amir Hossein , Nasseri Simin , Rashidi Alimorad , Nabizadeh Ramin , Rezaee Reza 
Published: June 2015

Abstract
In this study vertically aligned carbon nanotubes (VA-CNT) was grown on anodized aluminum oxide (AAO) substrate. The synthesized AAO-CNT membrane was characterized using Raman spectroscopy, field emission scanning electron microscopy (FESEM), contact angle and BET. The pure water flux, humic acid (HA) (as representative of natural organic matters) rejection and fouling mechanism were also evaluated. The fabricated membrane has pore density of 1.3 × 1010 pores per cm2, average pore size of 20 ± 3 nm and contact angle of 85 ± 8o. A significant pure water flux of 3600 ± 100 L/m2.h was obtained at 1 bar of pressure by this membrane due to the frictionless structure of CNTs. High contact angle exhibited the hydrophobic property of the membrane. It was revealed that HA is primarily rejected by adsorption in the membrane pores due to hydrophobic interactions with HA. Flux decline occurred rapidly through both cross flow and dead end filtration of the HA. Based on the blocking laws, internal pore constriction is dominant fouling mechanism in which HA adsorbs in membrane pores results in pores blockage and flux decline.
Use of in-silico assays to characterize the ADMET profile and identify potential therapeutic targets of fusarochromanone, a novel anti-cancer agent
Authors: El-Saadi Madison Wynne , Williams-Hart Tara , Salvatore Brian A , Mahdavian Elahe 
Published: June 2015

Abstract
Purpose
For 30 years nature has provided a plethora of natural products with potential meaningful anti-cancer activity. Fusarochromanone (FC101a) is a small molecule fungal metabolite exhibiting potent in-vitro growth inhibitory effects and is capable of inducing apoptosis, suppressing angiogenesis and tumorigenesis, and inhibiting endothelial cell growth in multiple cancer cell lines. Despite all we know regarding FC101a, the mechanism of action and molecular target(s) of this compound have remained an enigma. Furthermore, modest in-vivo activity has been documented and requires addressing.

Method
Early stage pharmacokinetics (PK) assessment is vital to successful drug development. Herein, we aimed to use in-silico assays to i) characterize an in-depth ADMET profile of FC101a and ii) to probe for possible therapeutic targets. Two-dimensional SDF files of FC101a and 13 analogs were introduced into ADMET Predictor Version 7.1 that parses the structures in order to calculate molecular descriptors, which are used to estimate ADMET properties. Calculated ADMET values were analyzed and subjected to multiple drug-like indices, delivering a PK profile of each analog. To probe for possible targets, a total of 49 proteins were introduced into SYBYL-X Version 2.0 platform and the deepest binding pocket of each protein was virtually docked with parent compound, FC101a; with the negative control, FC101b; and with the model compound, kynurenine.

Results
Each analog showed promising ADMET qualities, although FC101 Oxazole was identified as the most optimized analog. Despite FC101a having a desirable ADME and toxicity profile, areas of concern were identified and must be addressed in-vitro. These include potential mutagenic properties and estrogen receptor toxicity. We provide potential avenues medicinal chemists could use to achieve higher effective permeation, higher blood brain barrier (BBB) penetration, and higher aqueous solubility in FC101a. Molecular docking assays revealed procaspase-8 - cFLIP(L) complex as a potential biological target and led to proposed mechanisms of action by which FC101a facilitates procaspase-8 heterodimerization, thereby increasing proteolytic activity and up regulating extrinsic apoptosis.

Conclusion
Our data revealed both potential mechanisms of action and a promising ADMET profile of FC101a. These attributes render FC101a a promising lead candidate for development into a low toxic anti-cancer agent effective against a broad range of cancers.
Lithium nephrotoxicity
Authors: Azab Abed N. , Shnaider Alla , Osher Yamima , Wang Dana , Bersudsky Yuly , Belmaker R. H. 
Published: June 2015

AbstractReports of toxic effects on the kidney of lithium treatment emerged very soon after lithium therapy was introduced. Lithium-induced nephrogenic diabetes insipidus is usually self-limiting or not clinically dangerous. Some reports of irreversible chronic kidney disease and renal failure were difficult to attribute to lithium treatment since chronic kidney disease and renal failure exist in the population at large. In recent years, large-scale epidemiological studies have convincingly shown that lithium treatment elevates the risk of chronic kidney disease and renal failure. Most patients do not experience renal side effects. The most common side effect of polyuria only weakly predicts increasing creatinine or reduced kidney function. Among those patients who do experience decrease in creatinine clearance, some may require continuation of lithium treatment even as their creatinine increases. Other patients may be able to switch to a different mood stabilizer medication, but kidney function may continue to deteriorate even after lithium cessation. Most, but not all, evidence today recommends using a lower lithium plasma level target for long-term maintenance and thereby reducing risks of severe nephrotoxicity.
Maternal depression during pregnancy and offspring depression in adulthood: Role of child maltreatment
Authors: Plant Dominic T. , Pariante Carmine M. , Sharp Deborah , Pawlby Susan 
Published: June 2015

BackgroundStudies have shown that maternal depression during pregnancy predicts offspring depression in adolescence. Child maltreatment is also a risk factor for depression.AimsTo investigate (a) whether there is an association between offspring exposure to maternal depression in pregnancy and depression in early adulthood, and (b) whether offspring child maltreatment mediates this association.MethodProspectively collected data on maternal clinical depression in pregnancy, offspring child maltreatment and offspring adulthood (18–25 years) DSM-IV depression were analysed in 103 mother–offspring dyads of the South London Child Development Study.ResultsAdult offspring exposed to maternal depression in pregnancy were 3.4 times more likely to have a DSM-IV depressive disorder, and 2.4 times more likely to have experienced child maltreatment, compared with non-exposed offspring. Path analysis revealed that offspring experience of child maltreatment mediated the association between exposure to maternal depression in pregnancy and depression in adulthood.ConclusionsMaternal depression in pregnancy is a key vulnerability factor for offspring depression in early adulthood.
An N2-compatible Ni0 Metal–Organic Chemical Vapor Deposition (MOCVD) Precursor
Authors: Tran Viet-Ha , Yatabe Takeshi , Matsumoto Takahiro , Nakai Hidetaka , Suzuki Kazuharu , Enomoto Takao , Ogo Seiji 
Published: June 2015

Abstract
We report the first example of a Ni0 precursor that provides a contamination-free (&lt;1%) nickel film by metal–organic chemical vapor deposition (MOCVD) using N2 as the carrier gas. The structure and physical properties of the Ni0 precursor and subsequent film are described.
Classification of Project Management Mathematical Models
Authors: �������  , Tsarkov Igor 
Published: June 2015

Mathematical models in Project Management became one of the key elements
that in the 50th of the past century had formed a new branch of science
� Project management. Since then there have been developed a large
number of mathematical models adapted for solving partial problems. Unfortunately
no universal practical models, which allow managing projects in
conditions of resource or budget restriction, have been invented. Therefore
the classification of different mathematical models is the pressing problem
which could bring to order all these models from the one hand and reveal
the most perspective directions of further research. In this paper existing
classifications are analyzed and a new classification is proposed.
Complex Reference Values for Endocrine and Special Chemistry Biomarkers across Pediatric, Adult, and Geriatric Ages: Establishment of Robust Pediatric and Adult Reference Intervals on the Basis of the Canadian Health Measures Survey
Authors: Adeli Khosrow , Higgins Victoria , Nieuwesteeg Michelle , Raizman Joshua E , Chen Yunqi , Wong Suzy L , Blais David 
Published: June 2015

Abstract

BACKGROUND
Defining laboratory biomarker reference values in a healthy population and understanding the fluctuations in biomarker concentrations throughout life and between sexes are critical to clinical interpretation of laboratory test results in different disease states. The Canadian Health Measures Survey (CHMS) has collected blood samples and health information from the Canadian household population. In collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), the data have been analyzed to determine reference value distributions and reference intervals for several endocrine and special chemistry biomarkers in pediatric, adult, and geriatric age groups.

METHODS
CHMS collected data and blood samples from thousands of community participants aged 3 to 79 years. We used serum samples to measure 13 immunoassay-based special chemistry and endocrine markers. We assessed reference value distributions and, after excluding outliers, calculated age- and sex-specific reference intervals, along with corresponding 90% CIs, according to CLSI C28-A3 guidelines.

RESULTS
We observed fluctuations in biomarker reference values across the pediatric, adult, and geriatric age range, with stratification required on the basis of age for all analytes. Additional sex partitions were required for apolipoprotein AI, homocysteine, ferritin, and high sensitivity C-reactive protein.

CONCLUSIONS
The unique collaboration between CALIPER and CHMS has enabled, for the first time, a detailed examination of the changes in various immunochemical markers that occur in healthy individuals of different ages. The robust age- and sex-specific reference intervals established in this study provide insight into the complex biological changes that take place throughout development and aging and will contribute to improved clinical test interpretation.