bluuebunny/crossref_metadata_2025_split huggingface dataset:
M30 Neoepitope Expression in Epithelial Cancer: Quantification of Apoptosis in Circulating Tumor Cells by CellSearch Analysis
Authors: Rossi Elisabetta , Basso Umberto , Celadin Romina , Zilio Francesca , Pucciarelli Salvatore , Aieta Michele , Barile Carmen , Sava Teodoro , Bonciarelli Giorgio , Tumolo Salvatore , Ghiotto Cristina , Magro Cristina , Jirillo Antonio , Indraccolo Stefano , Amadori Alberto , Zamarchi Rita 
Published: October 2010

Abstract
Purpose: This study aimed to detect the M30 neoepitope on circulating tumor cells (CTC) as a tool for quantifying apoptotic CTC throughout disease course and treatment.
Experimental Design: An automated sample preparation and analysis platform for computing CTC (CellSearch) was integrated with a monoclonal antibody (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 (CK18) in early apoptosis. The assay was validated using cell lines and blood samples from healthy volunteers and patients with epithelial cancer.
Results: M30-positive CTC could be detected in &gt;70% of CTC-positive carcinoma patients, which were free for both chemotherapy and radiologic treatments. The fraction of M30-positive CTC varied from 50% to 80%, depending on the histotype. To investigate the potential application of the M30 CTC assay for the evaluation of response in early phase trials, CTC and M30-positive CTC were enumerated in a small case series of breast cancer patients during treatment. Results indicate that changes in the balance of M30-negative/positive CTC may be used as a dynamic parameter indicating an active disease, as documented by consistent radiologic findings.
Conclusions: M30 expression on CTC is detectable by immunofluorescence. The M30-integrated test has potential for monitoring dynamic changes in the quote of apoptotic CTC (in addition to CTC count) to evaluate response in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research, in which there is a pressing need for informative circulating biomarkers. Clin Cancer Res; 16(21); 5233–43. ©2010 AACR.
SCH 2047069, a Novel Oral Kinesin Spindle Protein Inhibitor, Shows Single-Agent Antitumor Activity and Enhances the Efficacy of Chemotherapeutics
Authors: Basso Andrea D. , Liu Ming , Dai Chaoyang , Gray Kimberly , Nale Lissette , Tevar Seema , Lee Suining , Liang Lianzhu , Ponery Abdul , Yaremko Bohdan , Smith Elizabeth , Tang Huadong , Sheth Payal R. , Siddiqui M. Arshad , Hicklin Daniel J. , Kirschmeier Paul 
Published: October 2010

Abstract
Kinesin spindle protein (KSP) is a mitotic kinesin required for the formation of the bipolar mitotic spindle, and inhibition of this motor protein results in mitotic arrest and cell death. KSP inhibitors show preclinical antitumor activity and are currently undergoing testing in clinical trials. These agents have been dosed intravenously using various dosing schedules. We sought to identify a KSP inhibitor that could be delivered orally and thus provide convenience of dosing as well as the ability to achieve more continuous exposure via the use of dose-dense administration. We discovered SCH 2047069, a potent KSP inhibitor with oral bioavailability across species and the ability to cross the blood-brain barrier. The compound induces mitotic arrest characterized by a monaster spindle and is associated with an increase in histone H3 and mitotic protein monoclonal 2 phosphorylation both in vitro and in vivo. SCH 2047069 showed antitumor activity in a variety of preclinical models as a single agent and in combination with paclitaxel, gemcitabine, or vincristine. Mol Cancer Ther; 9(11); 2993–3002. ©2010 AACR.
Paclitaxel-Dependent Cell Lines Reveal a Novel Drug Activity
Authors: Ganguly Anutosh , Yang Hailing , Cabral Fernando 
Published: October 2010

Abstract
We previously described the isolation of Tax 18 and Tax 11-6, two paclitaxel-dependent cell lines that assemble low amounts of microtubule polymer and require the drug for cell division. In the present studies, fluorescence time-lapse microscopy was used to measure microtubule dynamic instability behavior in these cells. The mutations were found to cause small decreases in microtubule growth and shortening, but the changes seemed unable to explain the defects in microtubule polymer levels or cell division. Moreover, paclitaxel further suppressed microtubule dynamics at low drug concentrations that were insufficient to rescue the mutant phenotype. Wild-type (WT) cells treated with similar low drug concentrations also had highly suppressed microtubules, yet experienced no problems with cell division. Thus, the effects of paclitaxel on microtubule dynamics seemed to be unrelated to cell division in both WT and mutant cell lines. The higher drug concentrations needed to rescue the mutant phenotype instead inhibited the formation of unstable microtubule fragments that appeared at high frequency in the drug-dependent, but not WT, cell lines. Live cell imaging revealed that the fragments were generated by microtubule detachment from centrosomes, a process that was reversed by paclitaxel. We conclude that paclitaxel rescues mutant cell division by inhibiting the detachment of microtubule minus ends from centrosomes rather than by altering plus-end microtubule dynamics. Mol Cancer Ther; 9(11); 2914–23. ©2010 AACR.
A Novel Human Dynactin-Associated Protein, dynAP, Promotes Activation of Akt, and Ergosterol-Related Compounds Induce dynAP-Dependent Apoptosis of Human Cancer Cells
Authors: Kunoh Tatsuki , Noda Takanori , Koseki Koichi , Sekigawa Masayuki , Takagi Motoki , Shin-ya Kazuo , Goshima Naoki , Iemura Shun-ichiro , Natsume Tohru , Wada Shu-ichi , Mukai Yukio , Ohta Shinji , Sasaki Ryuzo , Mizukami Tamio 
Published: October 2010

Abstract
There are several human genes that may encode proteins whose functions remain unknown. To find clues to their functions, we used the mutant yeast defective in Mad2, a component of the spindle checkpoint complex. Phenotypes that were provoked by the expression of a human C18orf26 protein in the mutant yeast encouraged further characterization of this protein in human cells. This protein was designated dynAP (dynactin-associated protein) because of its interaction with dynactin subunits that comprised a microtubule-based motor protein complex. The dynAP is a transmembrane protein localizing to Golgi apparatus and plasma membrane in a microtubule-dependent manner. This protein was expressed in half of human cancer cell lines but barely in normal human fibroblasts tested. The SV40-transformed fibroblasts expressed dynAP. Importantly, the expression of dynAP activated Akt (also known as protein kinase B) by promoting Ser473 phosphorylation required for the full activation, whereas knockdown of dynAP abolished this activation. The ergosterol-related compounds identified by the yeast cell–based high-throughput screen abrogated activation of Akt and induced apoptosis in a dynAP-dependent manner. We propose a possible advantage of dynAP expression in cancer cells; the survival of cancer cells that express dynAP is supported by dynAP-induced activation of Akt, sustaining high rates of proliferation. The inactivation of dynAP by the selected compounds nullifies this advantage, and thereby, the apoptotic machinery is allowed to operate. Taken together, dynAP can be a new target for cancer therapy, and the selected chemicals are useful for developing a new class of anticancer drugs. Mol Cancer Ther; 9(11); 2934–42. ©2010 AACR.
Constitutional Methylation of the BRCA1 Promoter Is Specifically Associated with BRCA1 Mutation-Associated Pathology in Early-Onset Breast Cancer
Authors: Wong Ee Ming , Southey Melissa C. , Fox Stephen B. , Brown Melissa A. , Dowty James G. , Jenkins Mark A. , Giles Graham G. , Hopper John L. , Dobrovic Alexander 
Published: October 2010

Abstract
Women carrying germline mutations in BRCA1 are at a substantially elevated risk of breast cancer and their tumors typically have distinctive morphologic features. We hypothesized that constitutional methylation of the BRCA1 promoter region could give rise to such breast cancers in women. We selected 255 women diagnosed with breast cancer before the age of 40 years for whom BRCA1 germline mutations had not been identified. Of them, 52 had five or more of nine BRCA1 mutation-associated morphologic features (group 1), 39 had four (group 2), and 164 had three or less (group 3). The prevalence of detectable BRCA1 promoter methylation in peripheral blood DNA decreased from 31% to 10% to 5% across groups 1–3, respectively (P = 0.000002), and was significantly greater than the 4% frequency in unaffected controls (P = 0.004). Peripheral blood methylation was associated with a 3.5-fold (95% CI, 1.4–10.5) increased risk of having early onset breast cancer. Methylation was consistently mosaic in the peripheral blood where the estimated allelic frequency of BRCA1 promoter methylation ranged from 0.1% to 17%. Group 1 women, but not group 3 women, with detectable methylation of peripheral blood DNA had high levels of BRCA1 promoter methylation of their tumor DNA, indicating that constitutional BRCA1 methylation strongly predisposes toward the development of BRCA1 methylated tumors that then have features resembling BRCA1 mutated tumors. Screening peripheral blood for BRCA1 promoter methylation might thus predict early-onset breast cancers. This raises the possibility of chemoprevention or other intervention to diminish the risk of developing breast cancer in these women. Cancer Prev Res; 4(1); 23–33. ©2010 AACR. Cancer Prev Res; 4(1); 23–33. ©2010 AACR.
Strenuous physical exercise adversely affects monocyte chemotaxis
Authors: Caidahl Kenneth , Olieslagers Servé , Krook Anna , Rickenlund Anette , Rickenlund Anette , Zierath Juleen , Czepluch Frauke , Barrès Romain , Waltenberger Johannes 
Published: October 2010

SummaryPhysical exercise is important for proper cardiovascular function and disease prevention, but it may influence the immune system. We evaluated the effect of strenuous exercise on monocyte chemotaxis. Monocytes were isolated from blood of 13 young, healthy, sedentary individuals participating in a three-week training program which consisted of repeated exercise bouts. Monocyte chemotaxis and serological biomarkers were investigated at baseline, after three weeks training and after four weeks recovery. Chemotaxis towards vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β1 (TGF-β1) was completely inhibited immediately after training (p<0.01), and remained so after four weeks recovery. Likewise, monocyte chemoattractant protein-1 (MCP-1)-induced migration declined after training (p<0.01) and improved only partially during the recovery period. MCP-1 serum levels were significantly reduced after four weeks recovery compared to baseline (p<0.01). Total blood antioxidant capacity was enhanced at this time point (p<0.01). Monocyte chemokinesis, TGF-β1 and nitric oxide serum levels remained unchanged during the study. Strenuous three-week training consisting of repeated exercise bouts in healthy, sedentary individuals reduces monocyte chemotaxis. It remains to be established, whether this is a sound adaptation to increased stimuli or an untoward reaction to overtraining. Nevertheless, the effect remains for several weeks with no exercise.
Increased risk of gestational vascular complications in women with low free tissue factor pathway inhibitor plasma levels out of pregnancy
Authors: Ittel Antoine , Bretelle Florence , Gris Jean-Christophe , Chau Cécile , Sébahoun Gérard , Boubli Léon , Arnoux Dominique 
Published: October 2010

SummaryTissue factor pathway inhibitor (TFPI) plays a crucial role in haemostasis by regulating TF-induced initiation of coagulation. Since it is expressed by endothelial and trophoblastic cells, TFPI is of particular importance at the placental level and might be involved in the occurrence of gestational vascular complications (GVC). In the present study, we investigated plasma free TFPI antigen in four groups of women: healthy non-pregnant women without history of pregnancy complications; women at the beginning (<12 weeks) and women during the third trimester of a normal pregnancy; women with late pregnancy complications (pre-eclampsia / HELLP syndrome, intra-uterine fetal death, fetal growth retardation) at the time of obstetrical event and/or at distance from pregnancy. In normal pregnancy, TFPI increased between first trimester and delivery (median 5.0 ng/ml vs. 7.1 ng/ml; p<0.0001) but remained lower than in non-pregnant controls (median 8.2 ng/ml; p<0.0001). In patients, when measured concomitantly to the obstetrical event, TFPI showed no difference with normal late pregnancy levels. In contrast, at distance from pregnancy, in the absence of any hormonal influence, TFPI was significantly lower than in non-pregnant controls (median 5.9 vs. 8.2ng/ml, p < 0.0001). After categorisation into quartiles, an inverse dose-effect relationship was demonstrated between TFPI categories recorded apart from pregnancy and GVC risk, with a crude odds ratio of 43.5 (95% confidence interval 8.2–230) for patients with TFPI values in the lowest quartile (< 5.7 ng/ml). In conclusion, low free TFPI at distance from pregnancy appears to be a strong indicator of GVC risk.
Stability of the high on-treatment platelet reactivity phenotype over time in clopidogrel-treated patients
Authors: Jaitner Juliane , Stegherr Julia , Morath Tanja , Braun Siegmund , Bernlochner Isabell , Schömig Albert , Kastrati Adnan , Dirk Sibbing 
Published: October 2010

SummaryInterindividual response variability to clopidogrel treatment is a well established phenomenon. In recent studies and ongoing large-scale trials where patients with high on-treatment platelet reactivity (HPR) to clopidogrel are being randomised to an intensified antiplatelet treatment, confirmation of the HPR phenotype is based on one single platelet function assessment. The stability of the HPR phenotype over time has never been investigated but should be considered crucial for justification of intensified antiplatelet treatment regimens beyond clinical trials. The goal of this study was to test for the stability of the HPR phenotype over time in clopidogrel-treated patients. Patients (n=31) under chronic clopidogrel treatment (75 mg/day) were investigated by serial adenosine diphosphate (ADP)-induced platelet aggregation assessment with multiple electrode aggregometry (MEA) on a Multiplate analyser and light transmission aggregometry (LTA) at three different time points (once per week) during monitored antiplatelet treatment. On the basis of a cut-off level approach (468 AU*min for MEA, 53% for LTA) patients were classified into patients with (n=27) or without (n=4) HPR. For MEA, the phenotype was stable in 93.5% (n=29) of patients whereas 6.5% (n=2) crossed the cut-off level. For LTA, the phenotype was stable in 68% (n=21) of patients whereas 32% (n=10) patients crossed the cut-off level (chi-square P=0.01 for comparison of pheno-type stability between both assays). In conclusion, the HPR phenotype is stable over time in the majority of clopidogrel-treated patients. Comparative assessment of phenotype stability across available platelet function assays warrants further investigation.
Phylogeography of Psammodromus algirus (Lacertidae) revisited: systematic implications
Authors: Carranza Salvador , Salvador Alfredo , Verdú-Ricoy Joaquín , Díaz José , Busack Stephen 
Published: November 2010

AbstractRelationships among Psammodromus algirus populations from the Iberian Peninsula and North Africa, including recently described P. jeanneae and P. manuelae, were estimated from mitochondrial DNA gene sequences. This enlarged data set confirmed the presence of two divergent eastern and western mitochondrial DNA lineages on the Iberian Peninsula, the distributions for which are separated by a narrow zone of contact across the centre of the Peninsula. Paratypes of P. jeanneae and topotypes of P. manuelae represent southern and northern clades of the western lineage, respectively, making P. algirus paraphyletic. This, together with the low level of allozymic and mitochondrial DNA substructuring within western populations, is not sufficient to retain P. jeanneae and P. manuelae as valid species, and we relegate them to the status of junior synonyms of P. algirus.
The mitochondrial genome complete sequence and organization of the Pig-nosed Turtle Carettochelys insculpta (Testudines, Carettochelyidae) and its phylogeny position in Testudines
Authors: Xiong Lei , Li Xiao-san , Wang Ling , Zhou Ke , Nie Liu-wang 
Published: November 2010

AbstractThe Pig-nosed Turtle Carettochelys insculpta (Testudines; Cryptodira; Carettochelyidae) is the sole living representative of the Carettochelyidae. The phylogenetic position of C. insculpta within Testudines has not yet been determined unequivocally. To address this issue, we sequenced the whole mitochondrial DNA (mtDNA) of C. insculpta using the long-and-accurate PCR (LA-PCR) method. The results show that the length of C. insculpta mtDNA is 16 439 bp and its structure is conserved compared to those of other turtles and other vertebrates except the NADH4 gene beginning with an ATC start codon. The 3′-side of the control region in mtDNA has two tandem repeat motifs, each consisting of nine 5′-CA-3′ units and sixteen 5′-AT-3′ units. To assess the phylogenetic position of C. insculpta, Maximum parsimony (MP), Maximum likelihood (ML) and Bayesian (BI) analyses were conducted based on complete mtDNA from 22 taxa. MP analyses robustly supported that the earliest phylogenetic tree splits separated into three basal branches: the Pelomedusidae (Pelomedusa subrufa), the Carettochelyidae (C. insculpta) and an assemblage of 18 cryptodiran turtle species; while ML and BI analyses suggested that Carettochelyidae and Trionychidae formed a clade, and that this clade was the sister taxon to all other cryptodiran turtles.
Novel therapeutic agents for B-cell lymphoma: developing rational combinations
Authors: Reeder Craig B. , Ansell Stephen M. 
Published: October 2010

AbstractSeveral novel targeted therapies have recently emerged as active in the treatment of non-Hodgkin lymphoma, including small molecules that inhibit critical signaling pathways, promote apoptotic mechanisms, or modulate the tumor microenvironment. Other new agents target novel cell surface receptors or promote DNA damage. Although most of these drugs have single-agent activity, none have sufficient activity to be used alone. This article reviews the utility and potential role of these new agents in the treatment of non-Hodgkin lymphoma with a specific focus on data that highlight how these agents may be incorporated into current standard treatment approaches.
Quality of life of homosexual males with genital warts: a qualitative study
Authors: Lee Mortensen Gitte , Larsen Helle K 
Published: November 2010

AbstractBackgroundA recent qualitative study in Denmark showed that genital warts (GWs) can considerably lower the quality of life of heterosexual patients. In this follow-up study, we interviewed men having sex with men (MSM) suffering from GWs to obtain an in-depth understanding of their perception of GWs and determine the extent to which minority (homosexual) cultural issues affect these patients' experiences. Qualitative interviews with six MSM were performed using a semi-structured interview guide. Questions were formulated on the basis of the earlier qualitative study in heterosexual patients with GWs along with a literature review. Data were analysed using a medical anthropological approach.FindingsMany MSM worried about being stigmatised and excluded from the small homosexual'scene', their key social group, thereby lowering their chances of finding sex and love. Most participants had suffered from GWs for several years which added to the negative psycho-sexual and social effects of the disease. Participants' fears of developing anal cancer were similar to those expressed about cervical cancer by females with GWs.ConclusionsAno-genital human papillomavirus (HPV) infection is common and has a serious psychological and sexual impact among MSM. However, they do not benefit to the same extent as heterosexual men from the herd immunity effect of HPV vaccination of girls. The pathological profile and concerns specific to MSM should be addressed when communicating with these patients, and should be taken into account when considering HPV vaccination of boys.
Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus
Authors: Daridon Capucine , Blassfeld Daniela , Reiter Karin , Mei Henrik E , Giesecke Claudia , Goldenberg David M , Hansen Arne , Hostmann Arwed , Frölich Daniela , Dörner Thomas 
Published: November 2010

Abstract
Introduction
Epratuzumab, a humanized anti-CD22 monoclonal antibody, is under investigation as a therapeutic antibody in non-Hodgkin's lymphoma and systemic lupus erythematosus (SLE), but its mechanism of action on B-cells remains elusive. Treatment of SLE patients with epratuzumab leads to a reduction of circulating CD27negative B-cells, although epratuzumab is weakly cytotoxic to B-cells in vitro. Therefore, potential effects of epratuzumab on adhesion molecule expression and the migration of B-cells have been evaluated.

Methods
Epratuzumab binding specificity and the surface expression of adhesion molecules (CD62L, β7 integrin and β1 integrin) after culture with epratuzumab was studied on B-cell subsets of SLE patients by flow cytometry. In addition, in vitro transwell migration assays were performed to analyze the effects of epratuzumab on migration towards different chemokines such as CXCL12, CXCL13 or to CXCR3 ligands, and to assess the functional consequences of altered adhesion molecule expression.

Results
Epratuzumab binding was considerably higher on B-cells relative to other cell types assessed. No binding of epratuzumab was observed on T-cells, while weak non-specific binding of epratuzumab on monocytes was noted. On B-cells, binding of epratuzumab was particularly enhanced on CD27negative B-cells compared to CD27positive B-cells, primarily related to a higher expression of CD22 on CD27negative B-cells. Moreover, epratuzumab binding led to a decrease in the cell surface expression of CD62L and β7 integrin, while the expression of β1 integrin was enhanced. The effects on the pattern of adhesion molecule expression observed with epratuzumab were principally confined to a fraction of the CD27negative B-cell subpopulation and were associated with enhanced spontaneous migration of B-cells. Furthermore, epratuzumab also enhanced the migration of CD27negative B-cells towards the chemokine CXCL12.

Conclusions
The current data suggest that epratuzumab has effects on the expression of the adhesion molecules CD62L, β7 integrin and β1 integrin as well as on migration towards CXCL12, primarily of CD27negative B-cells. Therefore, induced changes in migration appear to be part of the mechanism of action of epratuzumab and are consistent with the observation that CD27negative B-cells were found to be preferentially reduced in the peripheral blood under treatment.