bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic cancer: current management and treatment strategies
Authors: Gall Tamara M H , Tsakok Maria , Wasan Harpreet , Jiao Long R 
Published: August 2015

ABSTRACT
The 5-year survival of patients with pancreatic cancer is poor and, despite oncological advances over the past two decades, has not significantly improved. However, there have been several surgical and oncological advances which have improved morbidity and mortality in surgery and more efficacious chemotherapy regimens, resulting in a better patient experience and an increase in survival by a number of months. Most patients have a tumour at the head of the pancreas and those with resectable disease undergo a pancreaticoduodenectomy, which can be performed laparoscopically. Those who have a pancreatic resection have an increased survival in comparison with those receiving oncological treatment only; however, only a quarter of patients have resectable disease at diagnosis. Some centres are now performing venous resections and/or arterial resections in order to increase the number of patients eligible for curative surgery. Innovative techniques using ablation technologies to downstage tumours for resection are also being investigated. After surgery, all patients should be offered adjuvant gemcitabine-based chemotherapy. Those with locally advanced tumours not suitable for surgery should be offered FOLFIRINOX chemotherapy, after which the tumour may be suitable for surgical resection. The use of radiotherapy in this group of patients is controversial but offered by a few centres. Patients with metastatic disease at diagnosis should also be offered FOLFIRINOX chemotherapy, which can improve survival by a few months. As our knowledge of the tumour biology of pancreatic cancer progresses, a number of new agents targeting specific genes and proteins are under investigation and there is hope that median survival will continue to improve over the next decade.
Shortest, Fastest, and Foremost Broadcast in Dynamic Networks
Authors: Casteigts Arnaud , Flocchini Paola , Mans Bernard , Santoro Nicola 
Published: August 2015

Highly dynamic networks rarely offer end-to-end connectivity at a given time. Yet, connectivity in these networks can be established over time and space, based on temporal analogues of multi-hop paths (also called journeys). Attempting to optimize the selection of the journeys in these networks naturally leads to the study of three cases: shortest (minimum hop), fastest (minimum duration), and foremost (earliest arrival) journeys. Efficient centralized algorithms exists to compute all cases, when the full knowledge of the network evolution is given. In this paper, we study the distributed counterparts of these problems, i.e. shortest, fastest, and foremost broadcast with termination detection (TDB), with minimal knowledge on the topology. We show that the feasibility of each of these problems requires distinct features on the evolution, through identifying three classes of dynamic graphs wherein the problems become gradually feasible: graphs in which the re-appearance of edges is recurrent (class [Formula: see text]), bounded-recurrent ([Formula: see text]), or periodic ([Formula: see text]), together with specific knowledge that are respectively n (the number of nodes), Δ (a bound on the recurrence time), and p (the period). In these classes it is not required that all pairs of nodes get in contact — only that the overall footprint of the graph is connected over time. Our results, together with the strict inclusion between [Formula: see text], [Formula: see text], and [Formula: see text], implies a feasibility order among the three variants of the problem, i.e. TDB[foremost] requires weaker assumptions on the topology dynamics than TDB[shortest], which itself requires less than TDB[fastest]. Reversely, these differences in feasibility imply that the computational powers of [Formula: see text], [Formula: see text], and [Formula: see text] also form a strict hierarchy.
Symmetries of the Feinberg–Zee random hopping matrix
Authors: Hagger Raffael 
Published: August 2015

We study the symmetries of the spectrum of the Feinberg–Zee Random Hopping Matrix introduced in [J. Feinberg and A. Zee, Spectral curves of non-Hermitian Hamiltonians, Nucl. Phys. B 552 (1999) 599–623] and studied in various papers thereafter (e.g. [S. N. Chandler-Wilde, R. Chonchaiya and M. Lindner, eigenvalue Problem meets Sierpinski triangle: Computing the spectrum of a non-self-adjoint random operator, Oper. Matrices 5 (2011) 633–648; S. N. Chandler-Wilde, R. Chonchaiya and M. Lindner, On the spectra and pseudospectra of a class of non-self-adjoint random matrices and operators, Oper. Matrices 7 (2013) 739–775; S. N. Chandler-Wilde and E. B. Davies, Spectrum of a Feinberg–Zee sandom hopping matrix, J. Spectral Theory 2 (2012) 147–179; R. Hagger, On the spectrum and numerical range of tridiagonal random operators, preprint (2014), arXiv: 1407.5486; D. E. Holz, H. Orland and A. Zee, On the remarkable spectrum of a non-Hermitian random matrix model, J. Phys. A: Math. Gen. 36 (2003) 3385–3400]). In [J. Spectral Theory 2 (2012) 147–179], Chandler-Wilde and Davies proved that the spectrum of the Feinberg–Zee Random Hopping Matrix is invariant under taking square roots, which implied that the unit disk is contained in the spectrum (a result already obtained slightly earlier in [Oper. Matrices 5 (2011) 633–648]. In a similar approach we show that there is an infinite sequence of symmetries at least in the periodic part of the spectrum (which is conjectured to be dense). Using these symmetries and the result of [J. Spectral Theory 2 (2012) 147–179], we can exploit a considerably larger part of the spectrum than the unit disk. As a further consequence we find an infinite sequence of Julia sets contained in the spectrum. These facts may serve as a part of an explanation of the seemingly fractal-like behavior of the boundary.
Whole-Body Vibration Exercise for Knee Osteoarthritis: A Systematic Review and Meta-Analysis
Authors: Li Xin , Wang Xue-Qiang , Chen Bing-Lin , Huang Ling-Yan , Liu Yu 
Published: August 2015

Objectives. To assess the effects of WBV exercise on patients with KOA.Methods. Eight databases including Pubmed, EMBASE, Cochrane Library, CINAHL, Web of Science, the Physiotherapy Evidence Database, CNKI, and Wanfang were searched up to November 2014. Randomized controlled trials (RCTs) of WBV for KOA were eligible. The outcomes were pain intensity, functional performances, self-reported status, adverse events, and muscle strength. A meta-analysis was conducted.Results. Five trials with 168 participants provided data for the meta-analysis. No significant difference was shown in pain intensity and self-reported status between WBV and other forms of exercise. Improvement in functional performance (evaluated by BBS; WMD, 2.96; 95% CI, 1.29 to 4.62;P=0.0005) was greater in WBV group, but the other parameters of functional performance (including 6MWT and TGUG) revealed no statistically significant difference. Adverse events were only reported in one trial and no significant difference was discovered in muscle strength. The overall quality of evidence was very low.Conclusion.Currently there is only limited evidence that suggested that WBV is effective in the treatment of KOA. Large, well-designed RCTs with better designs are needed.Erratum to “Whole-Body Vibration Exercise for Knee Osteoarthritis: A Systematic Review and Meta-Analysis”
Abstract 1: Noxa and ceramide: Crosstalk between Bcl-2 family members and ceramide in mediating intrinsic apoptosis in Molt-4 human T-cell leukemia
Authors: Kobeissy Hadile , Hage-Sleiman Rouba , Dbaibo Ghassan 
Published: August 2015

Abstract
The sphingolipid breakdown product, ceramide, has been proposed as a coordinator of many cellular processes, one of which is apoptosis. We have previously shown that γ-irradiation induces p53-dependent apoptosis through ceramide accumulation in Molt-4 human T-cell leukemia cell line. Noxa, a BH3-only pro-apoptotic protein and a member in the Bcl-2 family, is activated by p53 and regulates downstream proteins that initiate mitochondrial outer membrane permeabilization (MOMP) and subsequently apoptosis. Here we identify a novel link between Noxa and ceramide in the apoptotic pathway that were previously thought to work independently. Specifically, we knocked down either p53 or Noxa protein expression in γ-irradiated Molt-4 cells and measured ceramide level in response to γ-irradiation. Our results demonstrate that ceramide accumulation requires the expression of both p53 and Noxa whereas inhibition of either p53 or Noxa totally inhibits ceramide accumulation. Furthermore, lipid and protein analysis of mitochondria isolated from Molt-4 cells showed a simultaneous ceramide accumulation and cytochrome c release, suggesting that ceramide's role is intricately related to the execution phase of apoptosis. These findings establish a role for Noxa in regulating ceramide at the mitochondrial level and provide a better understanding of the mechanisms of apoptosis initiated by p53.
Citation Format: Hadile Kobeissy, Rouba Hage-Sleiman, Ghassan Dbaibo. Noxa and ceramide: Crosstalk between Bcl-2 family members and ceramide in mediating intrinsic apoptosis in Molt-4 human T-cell leukemia. [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 1. doi:10.1158/1538-7445.AM2015-1
Abstract 1015: Misaponin B induces G2-M arrest and autophagy via upregulation of miR1290 in non-small cell lung cancer (NSCLC) A549 cells
Authors: Won Gunho , Sohn Eun Jung , Jeong Myoung Seok , Yoon Sang Wook , Lee Jihyun , Kim Bonglee , Kim Sung Hoon 
Published: August 2015

Abstract
Though Mi-saponin B is found to be the potent component among a mixture of saponins, its function still remains unlcear. Thus, in the present study, we investigated the anti-tumor mechanism of Mi-saponin B in non-small cell lung cancer (NSCLC) A549 cells. Mi-saponin B treatment caused cell growth inhibition via G2/M arrest in A549 cells. Moreover, Western blotting and qRT-PCR assays showed that Mi-saponin B induced conversion of LC3I to LC3II, a maker of autophagy. Immunofluorescence assay revealed that Mi-saponin B treatment formed the puncta of GFP-fused LC3II. Conversely, 3MA, an inhibitor of autophagy, attenuated the LC3II expression induced by Mi-saponin B in A549 cells. Also, transmission electron microscopy (TEM) showed that Mi-saponin B induces the autophagic vacuoles. Interestingly, miR1290 was upregulated in a dose dependent manner in Mi-saponin B treated A549 cells by qRT-PCR. Also, combined treatment of miR1290 and Mi-saponin B increased the expression of LC3II at protein and mRNA levels and also enhanced the formation of puncta of LC3II in A549 cells. Overall, our findings for the first time demonstrate that Mi-saponin B induces G2/M arrest and autophagy via upregulation of miR1290 in A549 cells as a potent anti-cancer agent.
Citation Format: Gunho Won, Eun Jung Sohn, Myoung Seok Jeong, Sang Wook Yoon, Jihyun Lee, Bonglee Kim, Sung Hoon Kim. Misaponin B induces G2-M arrest and autophagy via upregulation of miR1290 in non-small cell lung cancer (NSCLC) A549 cells. [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 1015. doi:10.1158/1538-7445.AM2015-1015
Abstract 1022: DYRK1A kinase regulates mTOR signaling via modulating the TSC complex
Authors: Menon Vijay R. , Litovchick Larisa 
Published: August 2015

Abstract
The Dual specificity Tyrosine-phosphorylation-Regulated Kinase 1A (DYRK1A) kinase is encoded on chromosome 21 and is involved in the pathogenesis of Down syndrome. Earlier studies have shown that DYRK1A is essential for cells to undergo growth arrest following serum starvation, at least in part by promoting the assembly of the DREAM repressor complex. However, the function of this important kinase is not fully understood. Using MudPIT MS/MS proteomic analysis of DYRK1A-interacting proteins followed by immunoprecipitation-Western blotting, we characterized the binding between DYRK1A and the subunits of the TSC tumor suppressor protein complex, a major regulator of the mTORC1 pathway. This interaction was mapped to the kinase domain of DYRK1A, suggesting that the TSC could serve as a substrate for DYRK1A phosphorylation. Indeed, overexpression of DYRK1A increased phosphorylation of both TSC1 and TSC2; this effect was fully reversed by the DYRK1A inhibitor, harmine. Functional studies revealed that loss of DYRK1A in two different cancer cell lines resulted in increased phosphorylation of mTORC1 substrates S6K1 and 4E-BP1. This effect of DYRK1A knockdown was inhibited by rapamycin, confirming the involvement of mTORC1 signaling. Thus, our work revealed novel function of DYRK1A in the regulation of mTOR signaling that controls cell growth, proliferation, and survival.
Citation Format: Vijay R. Menon, Larisa Litovchick. DYRK1A kinase regulates mTOR signaling via modulating the TSC complex. [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 1022. doi:10.1158/1538-7445.AM2015-1022
Abstract 1025: Protein kinase D2 promotes the proliferation of glioma cells by regulating golgi phosphoprotein 3
Authors: Zhou Xiuping , Xue Pengfei , Yang Minglin , Shi Hengliang , Lu Dong , Shi Qiong , Hu Jinxia , Yu Rutong 
Published: August 2015

Abstract
Protein kinase D2 (PKD2) has been demonstrated to promote tumorigenesis in many types of cancers. However, how PKD2 regulates cancer cell growth is largely unknown. In this study, we found that over-expression of PKD2 promoted glioma cell growth but down-regulation of PKD2 inhibited it. Further investigation indicated that PKD2 down-regulation decreased the protein level of Golgi phosphoprotein 3(GOLPH3) as well as p-AKT level. On the contrary, over-expression of PKD2 increased the protein level of GOLPH3 and p-AKT. In addition, GOLPH3 exhibited similar effect on glioma cell growth to that of PKD2. Interestingly, GOLPH3 down-regulation partially abolished glioma cell proliferation induced by PKD2 over-expression, while over-expression of GOLPH3 also partially rescued the inhibition effect of PKD2 down-regulation on glioma cell growth. Importantly, the level of PKD2 and GOLPH3 significantly increased and was positively correlated in a cohort of glioma patients, as well as in patients from TCGA database. Taken together, these results reveal that PKD2 promotes glioma cell proliferation by regulating GOLPH3 and then AKT activation. Our findings indicate that both PKD2 and GOLPH3 play important roles in the progression of human gliomas and PKD2-GOLPH3-AKT signaling pathway might be a potential glioma therapeutic target.
Citation Format: Xiuping Zhou, Pengfei Xue, Minglin Yang, Hengliang Shi, Dong Lu, Qiong Shi, Jinxia Hu, Rutong Yu. Protein kinase D2 promotes the proliferation of glioma cells by regulating golgi phosphoprotein 3. [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 1025. doi:10.1158/1538-7445.AM2015-1025
Abstract 1033: Alternative tumor suppressor mechanisms in lung carcinomas - modulation of senescence by growth factor-induced signaling
Authors: Markova Boyka , Breitenbuecher Frank , Schuler Martin 
Published: August 2015

Abstract
Cellular signaling pathways integrate multiple intra- and extracellular signals and thereby influence cell fate. Outcome of oncogene-targeted pharmacotherapies (cell cycle inhibition, apoptosis, senescence, autophagy) depends on variable factors (e.g. compound, dose, duration, cellular genetic background etc.). Oncogene-induced senescence is recognized as an important tumor-suppressive mechanism, bypassing of which may contribute to malignant transformation of the cells. On the other hand, senescence induction, in addition to apoptosis stimulation and proliferation suppression, is responsible for the cytostatic activity of many commonly used anticancer drugs. Therefore, senescence escape must be considered as an important drug-resistance factor.
In our work we characterize,,DNA Damage-independent” senescence induced by tyrosine kinase inhibitors (TKI) and growth factor deprivation of non-small cell lung cancer (NSCLC) cell lines and other EGFR-dependent cells.
Treatment of different cell lines with various concentrations of EGFR-TKIs was followed by the assessment of cell fate (i.e. apoptosis, cell cycle distribution, senescence and clonogenic survival) as well as intracellular signaling. We could show that treatment of EGFR-dependent cells with specific EGF receptor tyrosine kinase inhibitors (EGFR-TKI) can lead to generation of reactive oxygen species (ROS), activation of a DNA damage response (DDR) program and cellular senescence. Surprisingly, under certain experimental conditions DDR activation was found to be independent from detectable DNA damage. Key players of DDR signaling were shown to be essential for senescence induction.
Molecular dissection of crucial signaling nodes and molecular switches involved in modulation of cell fate in oncogene dependent cells treated with specific EGFR-inhibitors is currently being performed. Furthermore, our work is focussed on the identification and characterization of cellular factors activating DNA damage response (DDR) pathways in the absence of DNA damage under certain experimental conditions.
Understanding the interplay between theses decision making pathways either leading to proliferative arrest, cellular senescence or apoptosis will help improve current pharmacotherapies and develop new therapeutic approaches.
Note: This abstract was not presented at the meeting.
Citation Format: Boyka Markova, Frank Breitenbuecher, Martin Schuler. Alternative tumor suppressor mechanisms in lung carcinomas - modulation of senescence by growth factor-induced signaling. [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 1033. doi:10.1158/1538-7445.AM2015-1033
Abstract 104: ATF7IP does not alter the substrate specificity of the lysine methyltransferase SETDB1
Authors: Basavapathruni Aravind , Gureasko Jodi , Porter Scott Margaret , Boriack-Sjodin P. Ann , Wigle Timothy J. , Riera Thomas V. , Copeland Robert A. 
Published: August 2015

Abstract
The histone methyltransferase (HMT) SETDB1 is a strong candidate oncogene in melanoma and lung carcinomas. SETDB1 methylates lysine 9 of histone 3 (H3K9), utilizing S-adenosylmethionine (SAM) as the methyl donor. Its activity has been shown to be regulated by its partner protein ATF7IP, and here we examine the contribution of ATF7IP to the in vitro activity and substrate specificity of SETDB1. SETDB1 and ATF7IP were co-expressed in Sf21 insect cells and 1:1 stoichiometric complexes were purified for comparison against apo-SETDB1 enzyme. We employed both radiometric flashplate-based and MALDI mass spectrometry assays to follow methylation on histone 3 15-mer peptides where lysine 9 was either unmodified, mono-, or di-methylated. These two methods provide orthogonal readouts on H3K9 methylation: the radiometric flashplate-based assay employs 3H-labeled SAM and provides quantitation of labeled, methylated peptide. The MALDI mass spectrometry assay offers quantitation of consumption and accumulation of each individual H3K9 methylation state (H3K9me0, me1, me2, and me3). Results show that both apo-SETDB1 and SETDB1:ATF7IP complex catalyzed both monomethylation and dimethylation of H3K9 peptide substrates, but were unable to perform H3K9 trimethylation. While ATF7IP did not impact the substrate methylation profile, the activity of the complex was lower than apo-SETDB1 by a factor of 4. This difference was due to a decrease in the value of kcat as the substrate KM values were comparable between apo-SETDB1 and the SETDB1:ATF7IP complex. ATF7IP therefore does not alter SETDB1's substrate specificity. H3K9 monomethylation and dimethylation by SETDB1 occurred in a distributive manner and was unaffected by the presence of ATF7IP. This finding is important as H3K9 can be methylated by HMTs other than SETDB1 and a distributive mechanism would allow for interplay between multiple HMTs on H3K9me1 and H3K9me2. The results presented here indicate that ATF7IP does not alter substrate specificity of SETDB1 in vitro, and though it decreases SETDB1's catalytic activity, our data points to a nonenzymatic function of ATF7IP in regulating SETDB1 function.
Citation Format: Aravind Basavapathruni, Jodi Gureasko, Margaret Porter Scott, P. Ann Boriack-Sjodin, Timothy J. Wigle, Thomas V. Riera, Robert A. Copeland. ATF7IP does not alter the substrate specificity of the lysine methyltransferase SETDB1. [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 104. doi:10.1158/1538-7445.AM2015-104
Abstract 1057: Characterization of methylation patterns in cancer tissue shown by targeted Next-Gen bisulfite sequencing
Authors: Alexander Jessica , Drennan Ryan , Meyer Ann , Xu Jessica , Poulin Matthew L. , Timp Winston 
Published: August 2015

Abstract
Continuing research demonstrates an ever increasing number of genes with measurable dysregulation in their DNA methylation state.We have developed a panel of targeted NextGen bisulfite sequencing amplicon assays (TGBS) centered on cancer genes with altered DNA methylation. This cancer panel includes tumor suppressor genes (BRCA1, RASSF1, RUNX3), DNA methyltransferases (DNMTs and MGMT), DNA repeats (LINE1 and Sat2), oncogenes (MYC,ERBB2), receptor genes (EGFR, ESRRA, NR2E1), Homeobox genes (HOXA10, HOXA11, EN1) and detoxification genes (GSTM1, GSTM2) among others. A total of 80 genes covering over 1500 CpG sites were selected and assays for these regions were developed and validated using PCR/Pyrosequencing. 10 pairs of DNA samples (tumor vs adjacent normal) for four cancer types (ovarian cancer, breast cancer, cervical cancer, and colorectal cancer) were sequenced using this panel on an Ion Torrent PGM™ system. We have used this data to characterize the general behavior of these cancer samples as compared to normal in three specific ways. First, we have assayed the change in overall methylation level between normal and cancer samples using these multiplexed amplicons, using these values for both an unsupervised hierarchical clustering and principal component analyses. We have then attempted to establish a per tissue normal methylation profile, and measured the distance to this normal profile for each of the cancer samples. As has been discussed in previous work, cancer has more of an anti-normal profile than a characteristic pattern per se. Finally, we have examined the methylation patterns within individual reads, and assessed the measured methylation entropy or randomness of these patterns in normal versus cancer samples
Citation Format: Jessica Alexander, Ryan Drennan, Ann Meyer, Jessica Xu, Matthew L. Poulin, Winston Timp. Characterization of methylation patterns in cancer tissue shown by targeted Next-Gen bisulfite sequencing. [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 1057. doi:10.1158/1538-7445.AM2015-1057