bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autocrine Signaling by Wnt-5a Deregulates Chemotaxis of Leukemic Cells and Predicts Clinical Outcome in Chronic Lymphocytic Leukemia
Authors: Janovska Pavlina , Poppova Lucie , Plevova Karla , Plesingerova Hana , Behal Martin , Kaucka Marketa , Ovesna Petra , Hlozkova Michaela , Borsky Marek , Stehlikova Olga , Brychtova Yvona , Doubek Michael , Machalova Michaela , Baskar Sivasubramanian , Kozubik Alois , Pospisilova Sarka , Pavlova Sarka , Bryja Vitezslav 
Published: August 2015

Abstract
Purpose: ROR1, a receptor in the noncanonical Wnt/planar cell polarity (PCP) pathway, is upregulated in malignant B cells of chronic lymphocytic leukemia (CLL) patients. It has been shown that the Wnt/PCP pathway drives pathogenesis of CLL, but which factors activate the ROR1 and PCP pathway in CLL cells remains unclear.
Experimental Design: B lymphocytes from the peripheral blood of CLL patients were negatively separated using RosetteSep (StemCell) and gradient density centrifugation. Relative expression of WNT5A, WNT5B, and ROR1 was assessed by quantitative real-time PCR. Protein levels, protein interaction, and downstream signaling were analyzed by immunoprecipitation and Western blotting. Migration capacity of primary CLL cells was analyzed by the Transwell migration assay.
Results: By analyzing the expression in 137 previously untreated CLL patients, we demonstrate that WNT5A and WNT5B genes show dramatically (five orders of magnitude) varying expression in CLL cells. High WNT5A and WNT5B expression strongly associates with unmutated IGHV and shortened time to first treatment. In addition, WNT5A levels associate, independent of IGHV status, with the clinically worst CLL subgroups characterized by dysfunctional p53 and mutated SF3B1. We provide functional evidence that WNT5A-positive primary CLL cells have increased motility and attenuated chemotaxis toward CXCL12 and CCL19 that can be overcome by inhibitors of Wnt/PCP signaling.
Conclusions: These observations identify Wnt-5a as the crucial regulator of ROR1 activity in CLL and suggest that the autocrine Wnt-5a signaling pathway allows CLL cells to overcome natural microenvironmental regulation. Clin Cancer Res; 22(2); 459–69. ©2015 AACR.
HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis
Authors: Abdel-Fatah Tarek M.A. , McArdle Stephanie E.B. , Agarwal Devika , Moseley Paul M. , Green Andrew R. , Ball Graham R. , Pockley A. Graham , Ellis Ian O. , Rees Robert C. , Chan Stephen Y.T. 
Published: August 2015

Abstract
Purpose: The expression of HAGE as a novel prognostic and predictive tool was assessed in 1,079 triple-negative breast cancers (TNBC).
Experimental Design: HAGE protein expression was investigated in an early primary TNBC (EP-TNBC; n = 520) cohort who received adjuvant chemotherapy (ACT) and in a locally advanced primary TNBC cohort who received anthracycline combination Neo-ACT (n = 110; AC-Neo-ACT). HAGE-mRNA expression was evaluated in the METABRIC-TNBC cohort (n = 311) who received ACT and in a cohort of patients with TNBC who received doxorubicin/cyclophosphamide Neo-ACT, followed by 1:1 randomization to ixabepilone (n = 68) or paclitaxel (n = 64) as part of a phase II clinical trial. Furthermore, a cohort of 128 tumors with integrated HAGE gene copy number changes, mRNA, and protein levels were analyzed.
Results: In patients with EP-TNBC, who were chemotherapy-naïve, high HAGE protein expression (HAGE+) was associated with a higher risk of death [HR, 1.3; 95% confidence interval (CI), 1.2–1.5; P = 0.000005] when compared with HAGE− cases. Patients who received ACT and expressed mRNA-HAGE+ were at a lower risk of death than those who were mRNA–HAGE− (P = 0.004). The expression of HAGE was linked to the presence of tumor-infiltrating lymphocytes (TIL), and both features were found to be independent predictors for pathologic complete response (pCR, P &lt; 0.001) and associated with prolonged survival (P &lt; 0.01), following AC-Neo-ACT. In patients with residual disease, HAGE+ had a 2-fold death risk increase (P = 0.018) compared with HAGE−.
Conclusions: HAGE expression is a potential prognostic marker and a predictor of response to anthracycline treatment in TNBC. A prospective clinical trial to examine the therapeutic value of HAGE for TNBC cases is warranted. Clin Cancer Res; 22(4); 905–14. ©2015 AACR.
Glycogen Synthase Kinase 3 Beta Predicts Survival in Resected Adenocarcinoma of the Pancreas
Authors: Ben-Josef Edgar , George Asha , Regine William F. , Abrams Ross , Morgan Meredith , Thomas Dafydd , Schaefer Paul L. , DiPetrillo Thomas A. , Fromm Mitchel , Small William , Narayan Samir , Winter Kathryn , Griffith Kent A. , Guha Chandan , Williams Terence M. 
Published: August 2015

AbstractPurpose: GSK3β is a protein kinase that can suppress a number of key oncoproteins. We have previously shown in preclinical models of pancreatic ductal adenocarcinoma (PDAC) that inhibition of GSK3β causes stabilization and nuclear translocation of β-catenin, poor differentiation, proliferation, and resistance to radiation. The objective of this study was to determine its utility as a biomarker of clinical outcomes.Experimental Design: Automated Quantitative Immunofluorescence Analysis (AQUA) of GSK3β was performed on a tissue microarray with samples from 163 patients treated on RTOG 9704. On the basis of findings in an exploratory cohort, GSK3β was analyzed as a categorical variable using its upper quartile (&gt;Q3) as a cut point. Overall survival (OS) and disease-free survival (DFS) were estimated with the Kaplan–Meier method, and GSK3β groupings were compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to determine associations between GSK3β and OS/DFS.Results: The 3-year OS rates for GSK3β≤Q3 versus GSK3β &gt;Q3 were 16% (95% confidence intervals; CI, 10%–23%) and 30% (95% CI, 17%–44%), respectively, P = 0.0082. The 3-year DFS rates were 9% (95% CI, 5%–15%) and 20% (95% CI, 9%–33%) respectively, P value = 0.0081. On multivariable analysis, GSK3β was a significant predictor of OS. Patients with GSK3β &gt;Q3 had a 46% reduced risk of dying of pancreatic cancer (HR, 0.54; 95% CI, 0.31–0.96, P value = 0.034). The HR for DFS was 0.65 (95% CI, 0.39–1.07; P value = 0.092).Conclusions: GSK3β expression is a strong prognosticator in PDAC, independent of other known factors such as tumor (T) stage, nodal status, surgical margins and CA19-9. Clin Cancer Res; 21(24); 5612–8. ©2015 AACR.
Abstract 3914: IGF-II causes translocation of estrogen receptor beta to the mitochondria in triple negative breast cancer cell lines
Authors: O'Bannon-Joseph Chane' , DeLeon Daisy D. ,   Center for Health Disparities and Molecular Medicine
Published: August 2015

Abstract
Breast cancer is the most frequently diagnosed cancer and is the leading cause of death among women worldwide. Breast cancer is classified by the presence or absence of the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2). Triple negative breast cancers (TNBCs) lack all 3 receptors and account for approximately 15-20% of all breast cancers. Due to lack of targeted treatments TNBCs become aggressive and can metastasize to other parts of the body. The insulin-like growth factor-II (IGF-II) has an important role in fetal and cancer development. IGF-II signals through the IGF-I receptor (IGF-IR), insulin receptor (Ins-R), and has been associated in cross-talk with the estrogen receptors alpha and beta (ERα, ERß). Our lab has demonstrated that IGF-II activates the translocation of estrogen receptor alpha (ER-α) and estrogen receptor beta (ER-β) in the absence of the estrogen ligand. When co-expressed, ER-β counteracts the proliferative function of ER-α, however the role of ER-β in ER-α negative breast cancers is unclear. Although TNBC accounts for 20% of all BC, 50-90% of all TNBC express high levels of ER-β. Triple negative breast cancer can be more aggressive and difficult to treat. Also, the cancer is more likely to spread and recur. With the elevated levels of expression of the ER-β found in TNBC our lab demonstrated through western blotting and confocal microscopy that not only did treatment with IGF-II increase the expression of ER-β in both ER positive (MCF-7) and TNBC cell lines (CRL-231, 2335, and HS578-T) but it also stimulated translocation predominantly to the mitochondria in the TNBC cell lines. The presence of ER-β in the mitochondria suggests a need for further study on the action of ER-β in the mitochondria of all BC cell lines, especially TNBC cell lines.
Citation Format: Chane' O'Bannon-Joseph, Daisy D. DeLeon, Center for Health Disparities and Molecular Medicine. IGF-II causes translocation of estrogen receptor beta to the mitochondria in triple negative breast cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3914. doi:10.1158/1538-7445.AM2015-3914
Abstract 4606: Fine mapping of 64 prostate cancer GWAS regions identifies multiple novel association signals
Authors: Kote-Jarai Zsofia , Al Olama Ali Amin , Dadaev Tokhir , Hazelett Dennis , Li Qiuyan , Leongamornlert Daniel , Saunders Ed , Feedman Matthew , Conti David , Easton Douglas , Coetzee Gerhard , Eeles Rosalind ,   The PRACTICAL Consortium
Published: August 2015

Abstract
Genome-wide association studies (GWAS) have identified 100 common prostate cancer (PrCa) susceptibility loci to date. We performed comprehensive fine-mapping of 64 GWAS regions using genotyping and imputation to a 1000 Genomes reference panel for 25,779 PrCa cases and 26,218 controls of European ancestry from the PRACTICAL Consortium and two UK GWAS studies. In order to identify independent variants associated to PrCa, SNPs significant at P ≤10-4 were included in a stepwise logistic regression (SLR). Where the initial SLR identified multiple independent SNPs in a region, we re-analysed the region conditioning on the top hit. The adjusted results were subsequently trimmed using a P-value cut-off of ≤10-5 and a second SLR performed to identify independently significant index SNPs. We observed a single independent signal at 39 regions, with a novel, more significantly associated index SNP at 35 of these. Amongst these, we confirmed association in the European population for 2 loci previously reported in Asian GWAS. At 16 regions there was evidence for multiple independent signals, 14 of these contain newly identified additional significant associations. Functional annotation using data from ENCODE filtered for PrCa cell lines showed enrichment for overlap with bio-features within the fine-mapped SNP set and eQTL analysis identified novel candidate genes regulated by SNPs discovered in this study. Furthermore, we observed a 7% (from 32%-to 39%) improvement in the estimated proportion of familial relative risk explained through these refined and newly identified genetic variants. This study demonstrates the utility of fine-mapping, in silico functional annotation and eQTL approaches to narrow down the number of candidate functional variants. In addition, since a greater proportion of GWAS loci contained multiple independent risk variants than previously appreciated; this may explain a proportion of the missing heritability of complex diseases.
Citation Format: Zsofia Kote-Jarai, Ali Amin Al Olama, Tokhir Dadaev, Dennis Hazelett, Qiuyan Li, Daniel Leongamornlert, Ed Saunders, Matthew Feedman, David Conti, Douglas Easton, Gerhard Coetzee, Rosalind Eeles, The PRACTICAL Consortium. Fine mapping of 64 prostate cancer GWAS regions identifies multiple novel association signals. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4606. doi:10.1158/1538-7445.AM2015-4606
ERBB2 Emerges as a New Target for Colorectal Cancer
Authors: Pectasides Eirini , Bass Adam J. 
Published: August 2015

Abstract
Summary: ERBB2 mutations and amplifications are present in 7% of colorectal cancers. The presence of these alterations may be a marker of resistance to anti-EGFR therapy and, more importantly, could help identify patients who would benefit from ERBB2-directed therapy. Cancer Discov; 5(8); 799–801. ©2015 AACR.
See related article by Kavuri et al., p. 832.
Clonal Evolution: Multiregion Sequencing of Esophageal Adenocarcinoma Before and After Chemotherapy
Authors: Devarakonda Siddhartha , Govindan Ramaswamy 
Published: August 2015

Abstract
Summary: It is possible to decipher the clonal architecture of a tumor and the sequence in which cancer clones acquire genomic alterations through multiregion sequencing (M-seq). Serial evaluation of tumor specimens through M-seq can provide valuable information on the molecular basis of resistance to therapy. Cancer Discov; 5(8); 796–8. ©2015 AACR.
See related article by Murugaesu et al., p. 821.
MET Receptor Juxtamembrane Exon 14 Alternative Spliced Variant: Novel Cancer Genomic Predictive Biomarker
Authors: Ma Patrick C. 
Published: August 2015

Abstract
Clinical studies on MET-targeting cancer therapeutics have yielded mixed results in recent years, and MET-relevant predictive biomarkers remain elusive. New studies now reveal METex14 alternative splicing aberrations to represent potential predictive cancer genomic biomarker, hence renewing optimism and directions in the quest for optimized MET-targeting personalized cancer therapy. Cancer Discov; 5(8); 802–5. ©2015 AACR.
See related article by Paik et al., p. 842.
See related article by Frampton et al., p. 850.
Two new species of Euphorbia subg. Chamaesyce (Euphorbiaceae) from Baja California Sur, Mexico and their phylogenetic relationships
Authors: Maya-Lastra Carlos Alonso , Steinmann Victor W. 
Published: August 2015

Two new species of Euphorbia subg. Chamaesyce sect. Anisophyllum are described and illustrated. Both are endemic to the Sonoran Desert of Baja California Sur, Mexico, and were previously determined as Euphorbia polycarpa. Their recognition is highly supported by both molecular and morphological data. Euphorbia vizcainensis occurs in the Vizcaíno and Magdalena subdivisions at elevations from 20 to 250 m. It differs from E. polycarpa in having rugose seeds with transverse ridges (vs. smooth seeds). It is most similar to E. pondii from which it is separated by features of the stipules, involucral appendages, and seeds. Euphorbia cerralvensis is restricted to the Cerralvo Island in the municipality of La Paz of the Central Gulf Coast subdivision, and occurs at elevations from 10 to 300 m. It also differs from E. polycarpa by having seeds with transverse ridges. Morphologically it is very distinct from other Euphorbia species in the region. Phylogenetic evidence suggests that it belongs to a clade with E. dentosa, E. leucophylla, E. petrina, and E. brandegeei, species from which it is distinguished by its suffrutescent ascending habit (vs. herbaceous prostrate habit).
Zmiany sytuacji językowej w Wierszynie koło Irkucka w warunkach dwujęzyczności polsko-rosyjskiej
Authors: Głuszkowski Michał 
Published: August 2015

Changes in the language situation of Vershina near Irkutsk in the conditions of Polish-Russian bilingualismVershina was founded in 1910 by Polish voluntary settlers from Lesser Poland. There are three main periods in Vershina’s history, with different social conditions affecting the language choice. During its first three decades the settlers preserved Polish language (a mixture of dialects from their regions of origin), traditions and the Roman Catholic religion. The effects of the Revolution of 1917 and political changes came to a village in taiga only in the late 1930’s. Vershina lost its former ethnocultural homogeneity because of Russian and Buryat workers in the local kolkhoz. It was the beginning of the increasing role of Russian language in the village’s life. The process of intensive sovietization as well as heterogeneous marriages affected language choice in many domains. In the late 1980’s the inhabitants of Vershina regained their minority rights: they can pray in their own church, learn Polish in a local school and found cultural organisations. However, during the years of communism, the language situation changed irreversibly. There are some factors which may hinder the increasing domination of Russian language, such as activity of local Polish organisation, Roman Catholic parish and folk group “Jazhumbek” but their influence is limited. Изменения языковой ситуации в Вершине Иркутской области в условиях польско-русского билингвизма Вершина была основана в 1910 г. польскими добровольными переселенцами из Малой Польши. В истории деревни мы можем выделить три основных периода, характеризирующиеся разными социальными условиями, влияющими на выбор языка. За первые три десятилетия жители Вершины сохраняли польский язык (смесь диалектов из их родных регионов), традиции и римско-католическое вероисповедание. Вершининцы (как они сами называют себя) почувствовали последствия Октябрьской революции и политические изменения только в конце 30-х гг. ХХ века. Вершина потеряла прежнюю этнокультурную гомогенность из-за присоединения к местному колхозу бурятских и русских хуторов. Роль русского языка в жизни деревни стала постепенно увеличиваться. Процесс интенсивной советизации, а также смешанные браки повлияли на выбор языка во многих сферах жизни. В конце 80-х гг. ХХ века жителям Вершины вернули их права меньшинства: они могут молиться в своем костеле, учиться польскому языку в местной школе и создавать организации, но время коммунизма неотвратимо изменило языковую ситуацию общины. Увеличивающееся преобладание русского языка может остановить лишь активная деятельность местной польской организации, римско-католического прихода и фольклорного ансамбля «Яжумбек» („Рябчик”), но их влияние ограничено.
Język polski w Rosji Radzieckiej w okresie międzywojennym a polszczyzna na Białorusi radzieckiej (na materiale wybranych zagadnień fleksji rzeczowej)
Authors: Graczykowska Tamara 
Published: August 2015

The Polish language in Soviet Russia in the interwar period and the Polish language in Soviet Belarus (based on selected features of noun inflexion)In this present paper the author makes an attempt to compare several specific features of noun inflexion excerpted from “Trybuna Radziecka” with the adequate material from the Belarussian press published in the interwar period too. “Trybuna Radziecka” was the Polish newspaper published in Moscow from 1927 to 1938 and edited by Polish Communists, living as political émigrés in the post-revolution Soviet Russia. The Polish language (including the language of the Polish press) in Soviet Russia was subject to two powerful mechanisms: communist propaganda and totalitarianism. The language of the Polish press is characteristic of numerous divergences in relation to general Polish especially in vocabulary (the lexical level is dominated by the Russicisms and Sovietic elements). Comaparative analysis shows that the deviations from the general Polish occurred in both sources, but the specific inflexion features are not numerous. The flexion level is arisen under the influence of foreign language system (Belarussian and Russian). All the regional features still function in the postwar Northern Borderland Polish. Польский язык в советской России в период между первой и второй мировой войнами и польский язык в советской Белоруссии (на избранных примерах флексии имени существительного)В статье сопоставлен язык газеты „Trybuna Radziecka”, издаваемой польскими коммунистами в Москве в межвоенный период, с языком польской прессы, публикуемой в советской Белоруссии в то же веремя. Анализ ведётся на избранных примерах флексии имени существительного. Большинство явлений отмечено в обоих источниках. Следует подчеркнуть, что почти все представленные особенности флексии существительного появились вследствие восточнославянского воздействия, прежде всего русского. Некоторые отклонения представляют собой общепольские тенденции того времени (напр. колебания -i (-y) // -owie в именительном падеже существительных м.р. типа liberali или колебания ø // -i в родительном падеже мн.ч. существительных ж.р. типа czytelń). Как показало исследование, все указанные явления в области флексии зафиксированы также в послевоенной вильнюсской прессе. Автор подчёркивает, что ком мунистическая пропаганда и тоталитаризм оставили на польском языке (включая язык польской прессы) в советской России в межвоенный период сильный отпечаток (особенно в лексике).
Zapożyczenia litewskie oznaczające skłonności i stany człowieka oraz sposoby wyrażania czułości lub niechęci (na materiale gwar polskich na Litwie)
Authors: Rutkowska Krystyna 
Published: August 2015

Lithuanian borrowings denoting human states, dispositions and the ways of expressing frankness and unwillingness (based on the material of Polish dialects in Lithuania)The present article is a continuation of the previous studies (Rutkowska, 2009, 2010) dedicated to Lithuanian borrowings. Two previous articles have been related to human appearance and mental characteristics. The subject of the present article is Lithuanian borrowings which describe specific human dispositions and mental states, as well as the usage of epithets and the ways of addressing other people (terms of endearment). The lexical material of the article and vocabulary analyzed previously allows to state that the words referring to man make up a group of fairly large vocabulary of Lithuanian origin. It has been observed that words of such semantic categories as agriculture, weaving, fishery, construction are characterized nowadays as archaic because of the disappearance of a particular type of folk culture and changes in the field of rural activities. However, different ways of describing a person are still present in various dialect areas. A varying degree of adaptation of borrowed lexemes suggests that the penetration of such lexemes was a continuous process, which lasted throughout the period of the contact of Polish and Lithuanian dialects, and this process is continuing at the present day. The reason for the linguistic behavior of this type of Lithuanian words in Polish dialects is semantic capacity and expressiveness of these lexemes. Литуанизмы, обозначающие состояния и склонности человека, а также способы выражения им нежности или пренебрежения (на материале польских говоров в Литве)Данная статья является продолжением предыдущих исследований, посвященных заимствованиям из литовского языка, характеризующим человека (Rutkowska, 2009, 2010). Две предыдущих статьи были посвящены анализу лексики, определяющей внешний облик и черты характера человека. Предметом исследования в данной статье являются слова, связанные с типичными склонностями человека, а также афектонимы и прозвища. Лексика, представленная в трех очередных статьях, свидетельствует о многочисленности заимствований данной лексико-семантической группы и ее продуктивности. Если слова, принадлежащие к таким семантическим категориям, как земледелие, ткачество, строительство, характеризуются архаичностью в силу перемен, происходящих в сельскохозяйственной сфере жизни, то названия, определяющие человека, и в дальнейшем употребляются на разных диалектных ареалах Литвы. Различная степень адаптации данных лексем свидетельствует о том, что процесс проникновения заимствованной лексики был длительным и существовал на протяжениии всего периода контактирования польских и литовских говоров, активно подолжается и в настоящее время. Причиной сохранения в польских говорах данной лексики является ее антропоцентризм, семантическая наполненность и экспрессивность.