bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Strategies in Prostate Cancer: Targeting Lipogenic Pathways and the Energy Sensor AMPK
Authors: Zadra Giorgia , Priolo Carmen , Patnaik Akash , Loda Massimo 
Published: April 2010

Abstract
Although the role of metabolic syndrome (MS) and a high fat diet in prostate cancer (PCa) risk is still a matter of intense debate, it is becoming increasingly clear that obesity can cause perturbations in metabolic pathways that contribute to the pathogenesis and progression of PCa. Moreover, prostate epithelial cells per se undergo a series of metabolic changes, including an increase in de novo lipogenesis, during the process of tumor formation. These metabolic alterations, at both the cellular and organismal levels, are intertwined with genetic aberrations necessary for neoplastic transformation. Thus, altered metabolism is currently subject to intense research efforts and might provide preventative and therapeutic opportunities, as well as a platform for biomarker development. In this article, we review evidence that the metabolic sensor 5′-AMP-activated protein kinase (AMPK), which physiologically integrates nutritional and hormonal signals and regulates cell survival and growth-related metabolic pathways to preserve intracellular ATP levels, represents a link between energy homeostasis and cancer. Thus, when AMPK is not activated, as in the setting of MS and obesity, systemic metabolic alterations permissive to the development of PCa are allowed to proceed unchecked. Hence, the use of AMPK activators and inhibitors of key lipogenic enzymes may represent a promising therapeutic strategy for PCa. Clin Cancer Res; 16(13); 3322–8. ©2010 AACR.
Inhibition of Fatty Acid Synthase Suppresses c-Met Receptor Kinase and Induces Apoptosis in Diffuse Large B-Cell Lymphoma
Authors: Uddin Shahab , Hussain Azhar R. , Ahmed Maqbool , Bu Rong , Ahmed Saeeda O. , Ajarim Dahish , Al-Dayel Fouad , Bavi Prashant , Al-Kuraya Khawla S. 
Published: April 2010

Abstract
Fatty acid synthase (FASN), the enzyme responsible for de novo synthesis of fatty acids, has emerged as a potential therapeutic target for several cancers; however, its role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. In this study, we investigated the role of FASN in a large series of DLBCL tissues in a tissue microarray (TMA) format followed by in vitro studies using DLBCL cell lines. FASN was found to be expressed in 62.6% DLBCL samples and was seen in highly proliferative tumors, manifested by high Ki67 (P &lt; 0.0001). Significant association was found between tumors expressing high FASN and c-Met tyrosine kinase (P &lt; 0.0002), as well as p-AKT (P = 0.0309). In vitro, pharmacological FASN inhibition and small interference RNA (siRNA) targeted against FASN triggered caspase-dependent apoptosis and suppressed expression of c-Met kinase in DLBCL cell lines, which further highlighted the molecular link between FASN and c-Met kinase. Finally, simultaneous targeting of FASN and c-Met with specific chemical inhibitors induced a synergistically stimulated apoptotic response in DLBCL cell lines. These findings provide evidence that FASN, via c-Met tyrosine kinase, plays a critical role in the carcinogenesis of DLBCL and strongly suggest that targeting FASN may have therapeutic value in treatment of DLBCL. Mol Cancer Ther; 9(5); 1244–55. ©2010 AACR.
Epigallocatechin Gallate Suppresses Lung Cancer Cell Growth through Ras–GTPase-Activating Protein SH3 Domain-Binding Protein 1
Authors: Shim Jung-Hyun , Su Zheng-Yuan , Chae Jung-Il , Kim Dong Joon , Zhu Feng , Ma Wei-Ya , Bode Ann M. , Yang Chung S. , Dong Zigang 
Published: April 2010

Abstract
Green tea is a highly popular beverage globally. Green tea contains a number of polyphenol compounds referred to as catechins, and (−)-epigallocatechin gallate (EGCG) is believed to be the major biologically active compound found in green tea. EGCG has been reported to suppress lung cancer, but the molecular mechanisms of the inhibitory effects of EGCG are not clear. We found that EGCG interacted with the Ras–GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) with high binding affinity (Kd = 0.4 μmol/L). We also showed that EGCG suppressed anchorage-independent growth of H1299 and CL13 lung cancer cells, which contain an abundance of the G3BP1 protein. EGCG was much less effective in suppressing anchorage-independent growth of H460 lung cancer cells, which express much lower levels of G3BP1. Knockdown shG3BP1-transfected H1299 cells exhibited substantially decreased proliferation and anchorage-independent growth. shG3BP1 H1299 cells were resistant to the inhibitory effects of EGCG on growth and colony formation compared with shMock-transfected H1299 cells. EGCG interfered with the interaction of G3BP1 and the Ras–GTPase-activating protein and further suppressed the activation of Ras. Additional results revealed that EGCG effectively attenuated G3BP1 downstream signaling, including extracellular signal-regulated kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, in wild-type H1299 and shMock H1299 cells but had little effect on H460 or shG3BP1 H1299 cells. Overall, these results strongly indicate that EGCG suppresses lung tumorigenesis through its binding with G3BP1. Cancer Prev Res; 3(5); 670–9. ©2010 AACR.
Is Prostate Cancer Prevention with Selenium All in the Genes?
Authors: Platz Elizabeth A. 
Published: April 2010

Abstract
This perspective discusses how well-conducted research by Penney et al. (beginning on page 604 in this issue of the journal) contributes to the incremental uncovering of the complex association between selenium and prostate cancer. These investigators' earlier findings and current questions, approaches, and findings regarding selenium for prostate cancer prevention are discussed. This group's work raises the following important inferences: Selenium may prevent poorer-prognosis prostate cancer and its progression to bony metastases and death, but only in men with genetic backgrounds that influence the requirement for selenium. These inferences point toward how to reconcile inconsistent prostate cancer risk results from the two randomized trials of selenium conducted to date. Cancer Prev Res; 3(5); 576–8. ©2010 AACR.
Privileges and Immunities of Global Public-Private Partnerships: A Case study of the Global Fund to Fight AIDs, Tuberculosis and Malaria
Authors: Aziz Davinia Abdul 
Published: April 2010

AbstractThe question of whether it is at all appropriate to extend privileges and immunities regimes beyond international organizations to the increasingly ubiquitous global public-private partnership structure has received little attention to date in the scholarly literature. This article examines this question through a study of the Global Fund to Fight AIDS, Tuberculosis and Malaria, a permanent global public-private partnership that formally incorporates non-state actors as equal players in its core governance structures. The article concludes that considerations of genesis and administrative law-type analyses of institutional design may, to some extent, substitute for the constituent treaty of classical international law in order to identify which global public-private partnerships should benefit from privileges and immunities, as well as the specific privileges and immunities to be granted in each case to facilitate the effective fulfilment of these partnerships' mandates.
Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells
Authors: Schreibelt Gerty , Benitez-Ribas Daniel , Schuurhuis Danita , Lambeck Annechien J. A. , van Hout-Kuijer Maaike , Schaft Niels , Punt Cornelis J. A. , Figdor Carl G. , Adema Gosse J. , de Vries I. Jolanda M. 
Published: April 2010

AbstractCurrently dendritic cell (DC)–based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limited availability of clinical-grade TLR ligands significantly hampers the translation of these findings into DC-based vaccines. Therefore, we explored 15 commonly used preventive vaccines as a possible source of TLR ligands. We have identified a cocktail of the vaccines BCG-SSI, Influvac, and Typhim that contains TLR ligands and is capable of optimally maturing DCs. These DCs (vaccine DCs) showed high expression of CD80, CD86, and CD83 and secreted interleukin-12. Although vaccine DCs exhibited an impaired migratory capacity, this could be restored by addition of prostaglandin E2 (PGE2; vaccine PGE2 DCs). Vaccine PGE2 DCs are potent inducers of T-cell proliferation and induce Th1 polarization. In addition, vaccine PGE2 DCs are potent inducers of tumor antigen-specific CD8+ effector T cells. Finally, vaccine PGE2–induced DC maturation is compatible with different antigen-loading strategies, including RNA electroporation. These data thus identify a new clinical application for a mixture of commonly used preventive vaccines in the generation of Th1-inducing clinical-grade mature DCs.
Telomere dysfunction-induced foci arise with the onset of telomeric deletions and complex chromosomal aberrations in resistant chronic lymphocytic leukemia cells
Authors: Brugat Thibaut , Nguyen-Khac Florence , Grelier Aurore , Merle-Béral Hélène , Delic Jozo 
Published: April 2010

AbstractIn somatic cells, eroded telomeres can induce DNA double-strand break signaling, leading to a form of replicative senescence or apoptosis, both of which are barriers to tumorigenesis. However, cancer cells might display telomere dysfunctions which in conjunction with defects in DNA repair and apoptosis, enables them to circumvent these pathways. Chronic lymphocytic leukemia (CLL) cells exhibit telomere dysfunction, and a subset of these cells are resistant to DNA damage-induced apoptosis and display short telomeres. We show here that these cells exhibit significant resection of their protective telomeric 3′ single-stranded overhangs and an increased number of telomere-induced foci containing γH2AX and 53BP1. Chromatin immunoprecipitation and immunofluorescence experiments demonstrated increased levels of telomeric Ku70 and phospho-S2056-DNA-PKcs, 2 essential components of the mammalian nonhomologous end-joining DNA repair system. Notably, these CLL cells display deletions of telomeric signals on one or 2 chromatids in parallel with 11q22 deletions, or with 13q14 deletions associated with another chromosomal aberration or with a complex karyotype. Taken together, our results indicate that a subset of CLL cells from patients with an unfavorable clinical outcome harbor a novel type of chromosomal aberration resulting from telomere dysfunction.
Variations in morphology and PSII photosynthetic capabilities during the early development of tetraspores of Gracilaria vermiculophylla (Ohmi) Papenfuss (Gracilariales, Rhodophyta)
Authors: Xie Xiujun , Wang Guangce , Pan Guanghua , Gao Shan , Xu Pu , Zhu Jianyi 
Published: April 2010

AbstractBackgroundRed algae are primitive photosynthetic eukaryotes, whose spores are ideal subjects for studies of photosynthesis and development. Although the development of red alga spores has received considerable research attention, few studies have focused on the detailed morphological and photosynthetic changes that occur during the early development of tetraspores ofGracilaria vermiculophylla(Ohmi) Papenfuss (Gracilariales, Rhodophyta). Herein, we documented these changes in this species of red algae.ResultsIn the tetraspores, we observed two types of division, cruciate and zonate, and both could develop into multicellular bodies (disks). During the first 84 hours, tetraspores divided several times, but the diameter of the disks changed very little; thereafter, the diameter increased significantly. Scanning electron microscopy observations and analysis of histological sections revealed that the natural shape of the disk remains tapered over time, and the erect frond grows from the central protrusion of the disk. Cultivation of tissue from excised disks demonstrated that the central protrusion of the disk is essential for initiation of the erect frond. Photosynthetic (i.e., PSII) activities were measured using chlorophyll fluorescence analysis. The results indicated that freshly released tetraspores retained limited PSII photosynthetic capabilities; when the tetraspores attached to a substrate, those capabilities increased significantly. In the disk, the PSII activity of both marginal and central cells was similar, although some degree of morphological polarity was present; the PSII photosynthetic capabilities in young germling exhibited an apico-basal gradient.ConclusionsAttachment of tetraspores to a substrate significantly enhanced their PSII photosynthetic capabilities, and triggered further development. The central protrusion of the disk is the growth point, may have transfer of nutritive material with the marginal cells. Within the young germling, the hetero-distribution of PSII photosynthetic capabilities might be due to the differences in cell functions.
Large impact of the apoplast on somatic embryogenesis in Cyclamen persicum offers possibilities for improved developmental control in vitro
Authors: Hoenemann Claudia , Richardt Sandra , Krüger Katja , Zimmer Andreas D , Hohe Annette , Rensing Stefan A 
Published: April 2010

Abstract

Background
Clonal propagation is highly desired especially for valuable horticultural crops. The method with the potentially highest multiplication rate is regeneration via somatic embryogenesis. However, this mode of propagation is often hampered by the occurrence of developmental aberrations and non-embryogenic callus. Therefore, the developmental process of somatic embryogenesis was analysed in the ornamental crop Cyclamen persicum by expression profiling, comparing different developmental stages of embryogenic cell cultures, zygotic vs. somatic embryos and embryogenic vs. non-embryogenic cell cultures.

Results
The analysis was based on a cDNA microarray representing 1,216 transcripts and was exemplarily validated by realtime PCR. For this purpose relative transcript abundances of homologues of a putative receptor kinase, two different glutathione S-transferases (GST), a xyloglucan endotransglycosylase (XET) and a peroxidase (POX) were quantitatively measured by realtime PCR for three different comparisons. In total, 417 genes were found to be differentially expressed. Gene Ontology annotation revealed that transcripts coding for enzymes that are active in the extracellular compartment (apoplast) were significantly overrepresented in several comparisons. The expression profiling results are underpinned by thorough histological analyses of somatic and zygotic embryos.

Conclusions
The putative underlying physiological processes are discussed and hypotheses on improvement of the protocol for in vitro somatic embryogenesis in Cyclamen persicum are deduced. A set of physiological markers is proposed for efficient molecular control of the process of somatic embryogenesis in C. persicum. The general suitability of expression profiling for the development and improvement of micropropagation methods is discussed.
Association and interaction of PPAR-complex gene variants with latent traits of left ventricular diastolic function
Authors: Juang Jyh-Ming Jimmy , de las Fuentes Lisa , Waggoner Alan D , Gu C Charles , Dávila-Román Víctor G 
Published: April 2010

Abstract

Background
Abnormalities in myocardial metabolism and/or regulatory genes have been implicated in left ventricular systolic dysfunction. However, the extent to which these modulate left ventricular diastolic function (LVDF) is uncertain.

Methods
Independent component analysis was applied to extract latent LVDF traits from 14 measured echocardiography-derived endophenotypes of LVDF in 403 Caucasians. Genetic association was assessed between measured and latent LVDF traits and 64 single nucleotide polymorphisms (SNPs) in three peroxisome proliferator-activated receptor (PPAR)-complex genes involved in the transcriptional regulation of fatty acid metabolism.

Results
By linear regression analysis, 7 SNPs (4 in PPARA, 2 in PPARGC1A, 1 in PPARG) were significantly associated with the latent LVDF trait, whereas a range of 0-4 SNPs were associated with each of the 14 measured echocardiography-derived endophenotypes. Frequency distribution of P values showed a greater proportion of significant associations with the latent LVDF trait than for the measured endophenotypes, suggesting that analyses of the latent trait improved detection of the genetic underpinnings of LVDF. Ridge regression was applied to investigate within-gene and gene-gene interactions. In the within-gene analysis, there were five significant pair-wise interactions in PPARGC1A and none in PPARA or PPARG. In the gene-gene analysis, significant interactions were found between rs4253655 in PPARA and rs1873532 (p = 0.02) and rs7672915 (p = 0.02), both in PPARGC1A, and between rs1151996 in PPARG and rs4697046 in PPARGC1A (p = 0.01).

Conclusions
Myocardial metabolism PPAR-complex genes, including within and between genes interactions, may play an important role modulating left ventricular diastolic function.
Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection
Authors: Gregg Jennifer L , Brown Kathleen E , Mintz Eric M , Piontkivska Helen , Fraizer Gail C 
Published: April 2010

Abstract

Background
The prostate gland represents a multifaceted system in which prostate epithelia and stroma have distinct physiological roles. To understand the interaction between stroma and glandular epithelia, it is essential to delineate the gene expression profiles of these two tissue types in prostate cancer. Most studies have compared tumor and normal samples by performing global expression analysis using a mixture of cell populations. This report presents the first study of prostate tumor tissue that examines patterns of differential expression between specific cell types using laser capture microdissection (LCM).

Methods
LCM was used to isolate distinct cell-type populations and identify their gene expression differences using oligonucleotide microarrays. Ten differentially expressed genes were then analyzed in paired tumor and non-neoplastic prostate tissues by quantitative real-time PCR. Expression patterns of the transcription factors, WT1 and EGR1, were further compared in established prostate cell lines. WT1 protein expression was also examined in prostate tissue microarrays using immunohistochemistry.

Results
The two-step method of laser capture and microarray analysis identified nearly 500 genes whose expression levels were significantly different in prostate epithelial versus stromal tissues. Several genes expressed in epithelial cells (WT1, GATA2, and FGFR-3) were more highly expressed in neoplastic than in non-neoplastic tissues; conversely several genes expressed in stromal cells (CCL5, CXCL13, IGF-1, FGF-2, and IGFBP3) were more highly expressed in non-neoplastic than in neoplastic tissues. Notably, EGR1 was also differentially expressed between epithelial and stromal tissues. Expression of WT1 and EGR1 in cell lines was consistent with these patterns of differential expression. Importantly, WT1 protein expression was demonstrated in tumor tissues and was absent in normal and benign tissues.

Conclusions
The prostate represents a complex mix of cell types and there is a need to analyze distinct cell populations to better understand their potential interactions. In the present study, LCM and microarray analysis were used to identify novel gene expression patterns in prostate cell populations, including identification of WT1 expression in epithelial cells. The relevance of WT1 expression in prostate cancer was confirmed by analysis of tumor tissue and cell lines, suggesting a potential role for WT1 in prostate tumorigenesis.
Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study
Authors: Kim Hyo Song , Kim Eun Kyoung , Jun Hyun Jung , Oh Sung Yong , Park Keon Woo , Lim Do Hyoung , Lee Soon Il , Kim Jung Han , Kim Kyoung Mee , Lee Dae Ho , Lee Jeeyun 
Published: April 2010

Abstract

Background
We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection.

Methods
Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria.

Results
Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04).

Conclusion
Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.
Bone mineral density acquisition in peripubertal female rhythmic gymnasts is directly associated with plasma IGF1/IGF-binding protein 3 ratio
Authors: Maïmoun Laurent , Coste Olivier , Galtier Florence , Mura Thibault , Mariano-Goulart Denis , Paris Françoise , Sultan Charles 
Published: April 2010

ObjectivesIntense physical activity in peripubertal girls may delay menarche and cause menstrual disorders and estrogen deficiency, particularly in sport disciplines that require strict weight control. It may also have a deleterious effect on bone mass acquisition. The aim of this study was to determine the time-course of bone mass accretion in peripubertal elite female rhythmic gymnasts (FRGs) over a 1-year period, as well as the anthropometric and hormone parameters that could be helpful for predicting bone mineral density (BMD) gain.Methods and designWe conducted a 1-year follow-up study in 29 FRGs (10.7–16.1 years old). Whole body composition and BMD of the whole body, proximal femur, lumbar spine, mid-radius, and skull were measured by dual energy X-ray absorptiometry (DXA). Moreover, baseline growth- and bone metabolism-related hormones such as IGF1, IGF-binding protein 3 (IGFBP3), leptin, and bone markers were measured.ResultsBMD increased significantly at all bone sites throughout puberty, particularly between Tanner stages II and IV–V (P=0.025 toP<0.001). The IGF1 level, IGF1/IGFBP3 ratio, and leptin level were higher in late pubertal stages (i.e. IV–V) compared with early stage (i.e. I). In simple and multivariate analyses, only the IGF1/IGFBP3 ratio was strongly correlated with the BMD change at all bone sites (r=0.49,P=0.02 tor=0.77,P<0.0001).ConclusionThis 1-year follow-up study of peripubertal FRGs showed that BMD gain was maximal around Tanner stage III. The plasma IGF1/IGFBP3 ratio was associated with bone mass acquisition in this period, and it may thus serve as a surrogate marker of bone mass gain in this population.