bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRAS40 Deregulates Apoptosis in Malignant Melanoma
Authors: Madhunapantula SubbaRao V. , Sharma Arati , Robertson Gavin P. 
Published: April 2007

Abstract
Malignant melanoma is the most invasive and deadly form of skin cancer with no effective therapy to treat advanced disease, leading to poor survival rates. Akt3 signaling plays an important role in deregulating apoptosis in ∼70% of melanomas. Thus, targeting Akt3 signaling in melanoma patients has significant therapeutic potential for inhibiting melanomas, but no Akt3-specific chemotherapeutic agent exists. Unfortunately, nonspecific Akt inhibitors can cause systemic toxicity or increase metastasis. Identifying and targeting the Akt3 substrate that deregulates apoptosis might circumvent these complications but would require demonstration of its functional importance in disrupting normal apoptosis. In this study, PRAS40 was identified as an Akt3 substrate that deregulated apoptosis to promote melanoma tumorigenesis. Levels of phosphorylated PRAS40 (pPRAS40) increased during melanoma tumor progression paralleling increasing Akt3 activity. Majority of melanomas from patients with elevated Akt activity also had correspondingly higher levels of pPRAS40. Targeting PRAS40 or upstream Akt3 similarly reduced anchorage-independent growth in culture and inhibited tumor development in mice. Mechanistically, decreased pPRAS40 increased tumor cell apoptosis as well as sensitivity of melanoma cells to apoptosis-inducing agents, thereby decreasing chemoresistance. Collectively, these studies provide a solid mechanistic basis for targeting PRAS40 to inhibit the Akt3 signaling cascade and thereby retard melanoma development. [Cancer Res 2007;67(8):3626–36]
Gene Expression Profiling of Breast, Prostate, and Glioma Cells following Single versus Fractionated Doses of Radiation
Authors: Tsai Mong-Hsun , Cook John A. , Chandramouli Gadisetti V.R. , DeGraff William , Yan Hailing , Zhao Shuping , Coleman C. Norman , Mitchell James B. , Chuang Eric Y. 
Published: April 2007

Abstract
Studies were conducted to determine whether gene expression profiles following a single dose of radiation would yield equivalent profiles following fractionated radiation in different tumor cell lines. MCF7 (breast), DU145 (prostate), and SF539 (gliosarcoma) cells were exposed to a total radiation dose of 10 Gy administered as a single dose (SD) or by daily multifractions (MF) of 5 × 2 Gy. Following radiation treatment, mRNA was isolated at 1, 4, 10, and 24 h and processed for cDNA microarray analysis. To determine the influence of the tumor microenvironment on gene expression, one cell type (DU145) was evaluated growing as a solid tumor in athymic nude mice for both radiation protocols. Unsupervised hierarchical cluster map analysis showed significant differences in gene expression profiles between SD and MF treatments for cells treated in vitro, with MF yielding a more robust induction compared with SD. Several genes were uniquely up-regulated by MF treatment, including multiple IFN-related genes (STAT1, G1P2, OAS1, OAS3, G1P3, IFITM1) and TGF-β–associated genes (EGR1, VEGF, THBS1, and TGFB2). DU145 cells grown in vivo exhibited a completely different set of genes induced by both SD and MF compared with the same cells exposed in vitro. The results of the study clearly show distinct differences in the molecular response of cells between SD and MF radiation exposures and show that the tumor microenvironment can significantly influence the pattern of gene expression after radiation exposures. [Cancer Res 2007;67(8):3845–52]
p53 and p21 Determine the Sensitivity of Noscapine-Induced Apoptosis in Colon Cancer Cells
Authors: Aneja Ritu , Ghaleb Amr M. , Zhou Jun , Yang Vincent W. , Joshi Harish C. 
Published: April 2007

Abstract
We have previously discovered the naturally occurring antitussive alkaloid noscapine as a tubulin-binding agent that attenuates microtubule dynamics and arrests mammalian cells at mitosis via activation of the c-Jun NH2-terminal kinase pathway. It is well established that the p53 protein plays a crucial role in the control of tumor cell response to chemotherapeutic agents and DNA-damaging agents; however, the relationship between p53-driven genes and drug sensitivity remains controversial. In this study, we compared chemosensitivity, cell cycle distribution, and apoptosis on noscapine treatment in four cell lines derived from the colorectal carcinoma HCT116 cells: p53+/+ (p53-wt), p53−/− (p53-null), p21−/− (p21-null), and BAX−/− (BAX-null). Using these isogenic variants, we investigated the roles of p53, BAX, and p21 in the cellular response to treatment with noscapine. Our results show that noscapine treatment increases the expression of p53 over time in cells with wild-type p53 status. This increase in p53 is associated with an increased apoptotic BAX/Bcl-2 ratio consistent with increased sensitivity of these cells to apoptotic stimuli. Conversely, loss of p53 and p21 alleles had a counter effect on both BAX and Bcl-2 expression and the p53-null and p21-null cells were significantly resistant to the antiproliferative and apoptotic effects of noscapine. All but the p53-null cells displayed p53 protein accumulation in a time-dependent manner on noscapine treatment. Interestingly, despite increased levels of p53, p21-null cells were resistant to apoptosis, suggesting a proapoptotic role of p21 and implying that p53 is a necessary but not sufficient condition for noscapine-mediated apoptosis. [Cancer Res 2007;67(8):3862–70]
Resilience to Transformation and Inherent Genetic and Functional Stability of Adult Neural Stem Cells Ex vivo
Authors: Foroni Chiara , Galli Rossella , Cipelletti Barbara , Caumo Andrea , Alberti Sara , Fiocco Roberta , Vescovi Angelo 
Published: April 2007

Abstract
Recent observations have suggested that extensive culturing of adult neural stem cells (ANSCs) by exploiting the NeuroSphere assay might select for aggressive cell clones, endowed with neoplastic potential, that overgrow the rest of the native stem cells. However, a detailed study of the propensity of ANSCs to transform has never been thoroughly undertaken. Here, we report the first demonstration that ANSCs can be propagated in vitro for over a year, maintaining a strikingly stable profile with regard to self-renewal, differentiation, growth factor dependence, karyotype, and molecular profiling. Most importantly, the long-term culturing of ANSCs did not result in the formation of tumors in vivo, even when ANSCs were transduced with Myc and Ras oncogenes. The cancer resistance could depend on specific mechanisms aimed at protecting ANSCs and preserved by optimal nonstressful culture conditions. In conclusion, besides a plentiful and safe source of cells for therapeutic applications, ANSCs provide an ideal model to study aging and cancer in the context of stemness. [Cancer Res 2007;67(8):3725–33]
Acidic Triterpenes Compromise Growth and Survival of Astrocytoma Cell Lines by Regulating Reactive Oxygen Species Accumulation
Authors: Martín Rubén , Carvalho Juliana , Ibeas Elvira , Hernández Marita , Ruiz-Gutierrez Valentina , Nieto María Luisa 
Published: April 2007

Abstract
Several studies have shown how pentacyclic triterpenes can inhibit proliferation and induce apoptosis of some tumor cell lines; however, its effect on astrocytic tumors, one of the most malignant forms of cancer, has rarely been reported. The aim of this study was to examine how the pentacyclic triterpenes, oleanolic acid and maslinic acid, isolated from olive juice, affected astrocytoma cell morphology and survival. Cell proliferation was inhibited in 1321N1 astrocytoma cells by using 1 to 50 μmol/L of either oleanolic acid or maslinic acid, with an average IC50 of 25 μmol/L. Growth inhibition led to morphologic and cytoskeletal alterations associated with the loss of stellate morphology and characterized by a retraction of the cytoplasm and collapse of actin stress fibers. Using 4′,6-diamidino-2-phenylindole and Annexin V, we showed that astrocytoma cell death induced by oleanolic acid or maslinic acid were mainly due to apoptotic events. Furthermore, we showed that caspase-3 is activated as a consequence of triterpene treatment. Finally, we found that exposure of the cells to oleanolic acid or maslinic acid resulted in a significant increase of intracellular reactive oxygen species, followed by loss of mitochondrial membrane integrity. Importantly, enzymatic scavengers, such as catalase, or phenolic antioxidants, such as butylated hydroxytoluene, rescued cells from the triterpene-mediated apoptosis, suggesting that the potential therapeutic effect of these acidic triterpenes is dependent on oxidative stress. Our data show that acidic triterpenes play a major role in 1321N1 astrocytoma morphology and viability and support the conclusion that oleanolic acid and maslinic acid may thus be promising new agents in the management of astrocytomas. [Cancer Res 2007;67(8):3741–51]
Huntingtin Interacting Protein 1 Is a Novel Brain Tumor Marker that Associates with Epidermal Growth Factor Receptor
Authors: Bradley Sarah V. , Holland Eric C. , Liu Grace Y. , Thomas Dafydd , Hyun Teresa S. , Ross Theodora S. 
Published: April 2007

Abstract
Huntingtin interacting protein 1 (HIP1) is a multidomain oncoprotein whose expression correlates with increased epidermal growth factor receptor (EGFR) levels in certain tumors. For example, HIP1-transformed fibroblasts and HIP1-positive breast cancers have elevated EGFR protein levels. The combined association of HIP1 with huntingtin, the protein that is mutated in Huntington's disease, and the known overexpression of EGFR in glial brain tumors prompted us to explore HIP1 expression in a group of patients with different types of brain cancer. We report here that HIP1 is overexpressed with high frequency in brain cancers and that this overexpression correlates with EGFR and platelet-derived growth factor β receptor expression. Furthermore, serum samples from patients with brain cancer contained anti-HIP1 antibodies more frequently than age-matched brain cancer–free controls. Finally, we report that HIP1 physically associates with EGFR and that this association is independent of the lipid, clathrin, and actin interacting domains of HIP1. These findings suggest that HIP1 may up-regulate or maintain EGFR overexpression in primary brain tumors by directly interacting with the receptor. This novel HIP1-EGFR interaction may work with or independent of HIP1 modulation of EGFR degradation via clathrin-mediated membrane trafficking pathways. Further investigation of HIP1 function in brain cancer biology and validation of its use as a prognostic or predictive brain tumor marker are now warranted. [Cancer Res 2007;67(8):3609–15]
Mutations in BRAF and KRAS Differentially Distinguish Serrated versus Non-Serrated Hyperplastic Aberrant Crypt Foci in Humans
Authors: Rosenberg Daniel W. , Yang Shi , Pleau Devon C. , Greenspan Emily J. , Stevens Richard G. , Rajan Thiruchandurai V. , Heinen Christopher D. , Levine Joel , Zhou Yijian , O'Brien Michael J. 
Published: April 2007

Abstract
We previously reported that colon carcinomas, adenomas, and hyperplastic polyps exhibiting a serrated histology were very likely to possess BRAF mutations, whereas when these same advanced colonic lesions exhibited non-serrated histology, they were wild type for BRAF; among hyperplastic polyps, KRAS mutations were found mainly in a non-serrated variant. On this basis, we predicted that hyperplastic aberrant crypt foci (ACF), a putative precancerous lesion found in the colon, exhibiting a serrated phenotype would also harbor BRAF mutations and that non-serrated ACF would not. In contrast, KRAS mutations would be found more often in the non-serrated ACF. We examined 55 ACF collected during screening colonoscopy from a total of 28 patients. Following laser capture microdissection, DNA was isolated, and mutations in BRAF and KRAS were determined by direct PCR sequencing. When hyperplastic lesions were further classified into serrated and non-serrated histologies, there was a strong inverse relationship between BRAF and KRAS mutations: a BRAFV600E mutation was identified in 10 of 16 serrated compared with 1 of 33 non-serrated lesions (P = 0.001); conversely, KRAS mutations were present in 3 of 16 serrated compared with 14 of 33 non-serrated lesions. Our finding of a strong association between BRAF mutations and serrated histology in hyperplastic ACF supports the idea that these lesions are an early, sentinel, or a potentially initiating step on the serrated pathway to colorectal carcinoma. [Cancer Res 2007;67(8):3551–4]
Production and Transportation Integration for a Make-to-Order Manufacturing Company with a Commit-to-Delivery Business Mode
Authors: Stecke Kathryn E. , Zhao Xuying 
Published: April 2007

When a make-to-order manufacturing company adopts a commit-to-delivery business mode, it commits a delivery due date for an order and is responsible for the shipping cost. Without loss of generality, we consider that transportation is done by a third-party logistics company, such as FedEx or UPS, which provides multiple shipping modes such as overnight, one-day, two-day delivery, and more. When the transportation time has to be short, clearly, shipping cost is more expensive than it could have been. How should a company schedule production for accepted orders so that the company can leave enough transportation time for orders to take slow shipping modes to reduce the shipping cost? We study this problem of integrating the production and transportation functions for a manufacturing company producing a variety of customized products in a make-to-order environment with a commit-to-delivery mode of business. Various realistic scenarios are investigated in increasing order of complexity. When partial delivery is allowed by customers, we provide both a mixed-integer programming (MIP) model and a minimum cost flow model. We show that nonpreemptive earliest due date (NEDD) production schedules are optimal when partial delivery is allowed and shipping cost is a decreasing convex function with transportation time. When partial delivery is not allowed, we develop an MIP model and prove that the problem is NP-hard. An efficient heuristic algorithm with polynomial computation time is provided for the NP-hard problem. It gives near-optimal production schedules, as shown via thousands of numerical experiments. We also provide models and analysis for other scenarios where shipping cost accounts for customer locations and quantity discounts.
Endogenous factors involved in the regulation of movement and "memory" in plants
Authors: Ueda Minoru , Nakamura Yoko , Okada Masahiro 
Published: April 2007

Abstract
The bioorganic basis of plant movement in two plant systems is described in this article: the circadian rhythmic leaf movement known as nyctinasty and trap movement in the Venus flytrap. The bioactive substances responsible for plant movement, the chemical mechanism of the rhythm, and studies on the key protein controlling nyctinasty are presented.
The nyctinastic leaf movement is induced by a pair of leaf-movement factors, and one of each pair is a glucoside. There are two key proteins that are involved in the control of nyctinasty. One is β-glucosidase: a biological clock regulates the activity of β-glucosidase, which deactivates the glucoside-type leaf-movement factor, controlling the balance in the concentrations of the leaf-closing and -opening factors. The other is the specific receptor for each leaf-movement factor: the genuine target cell for each leaf-movement factor is confirmed to be a motor cell from leaflet pulvini, and the specific receptors that regulate the turgor of motor cells are localized in the membrane fraction.
The article also discusses the isolation of the "memory" substance from the Venus flytrap and presents a mechanism for this action.
Chemistry and evolution of the Piperaceae
Authors: Kato Massuo J. , Furlan Maysa 
Published: April 2007

Abstract
The chemistry of members of the family Piperaceae is of great interest owing to the variety of biological properties displayed. A survey of structural diversity and bioactivity reveals that groups of species specialize in the production of amides, phenylpropanoids, lignans and neolignans, benzoic acids and chromenes, alkaloids, polyketides, and a plethora of compounds of mixed biosynthetic origin. Bioassays against Cladosporium cladosporioides and C. sphaerospermun have resulted in the characterization of various amides, prenylated phenolic compounds, and polyketides as potential classes of antifungal agents. Studies on the developmental process in seedlings of Piper solmsianum have shown that phenylpropanoid are produced instead of the tetrahydrofuran lignans found in adult plants. In suspension cultures of P. cernuum and P. crassinervium, phenylethylamines and alkamides predominate, whereas in the adult plants prenylpropanoids and prenylated benzoic acids are the respective major compound classes. Knowledge of the chemistry, bioactivity, and ecology of Piperaceae species provides preliminary clues for an overall interpretation of the possible role and occurrence of major classes of compounds.
Recent advances in the chemistry and biological activities of the Pimpinella species of Turkey
Authors: Baser K. Hüsnü Can , Tabanca Nurhayat , Kirimer Nese , Bedir Erdal , Khan Ikhlas A. , Wedge David E. 
Published: April 2007

Abstract
Two new natural products incorporating a phenylpropyl subunit ("phenylpropanoids"), [4-(prop-2-enyl)phenyl angelate and 4-(3-methyloxiranyl)phenyl 2-methylbutyrate], one new bisabolene-type sesquiterpenoid [1-methyl-4-(6-methylhepta-1,5-dien-2-yl)-7-oxabicyclo[4.1.0]heptane ("aureane")], and one new trinorsesquiterpene [4-(6-methylbicyclo[4.1.0]hept-2-en-7yl)butan-2-one ("traginone")] have been isolated from the essential oils of Pimpinella species occurring in Turkey, together with nine known phenylpropanoids and other natural products. Six of the known compounds are newly reported for Umbelliferae, whilst one is newly reported for Pimpinella species. Compound structures were determined by 1D and 2D NMR analysis. Isolated compounds were evaluated for antimalarial, antimicrobial, estrogenic, and aphidicidal activities. Pure compounds were also tested for antifungal activity against strawberry anthracnose-causing fungal plant pathogens Colletotrichum acutatum, C. fragariae, and C. gloeosporioides using direct bioautography and microdilution broth assays.
Discovery, chemistry, and chemical biology of microbial products
Authors: Ōmura Satoshi , Shiomi Kazuro 
Published: April 2007

Abstract
Our long-standing and continual screening of microorganisms, especially for antiparasitic agents, has produced a wide variety of compounds of global importance, such as the avermectins. Recent discoveries include nafuredin, atpenins, argifin, and argadin. Nafuredin is a helminth-specific inhibitor of electron-transport enzyme, complex I, which exhibits anthelmintic activity against Haemonchus contortus in sheep. The atpenins are the most potent complex II inhibitors ever reported. Co-crystallization study of atpenin A5 and E. coli complex II indicated the binding mechanism of ubiquinone to complex II. Argifin and argadin are the first cyclic peptides to inhibit chitinase at low concentration. Though structurally similar, their chitinase inhibition mechanisms are quite different.
Synthesis of an analog of mycothiazole and total synthesis of pseudotrienic acid B
Authors: Amans Dominique , Le Flohic Alexandre , Bellosta Véronique , Meyer Christophe , Cossy Janine 
Published: April 2007

Abstract
An analog of mycothiazole and pseudotrienic acid B were synthesized efficiently by using ring-closing metathesis or cross-metathesis as key reactions.
Total synthesis of the marine natural product (+)-discodermolide in multigram quantities
Authors: Mickel Stuart J. 
Published: April 2007

Abstract
The novel polyketide (+)-discodermolide was isolated in very small quantities from sponge extracts. This compound is one of several microtubule stabilizers showing promise as novel chemotherapeutic agents for the treatment of cancer. The clinical evaluation of this and similar compounds is hampered by lack of material, and at present, the only way to obtain the necessary quantities is total chemical synthesis.
Diversity in isoprene unit biosynthesis: The methylerythritol phosphate pathway in bacteria and plastids
Authors: Rohmer Michel 
Published: April 2007

Abstract
The long-overlooked methylerythritol phosphate (MEP) pathway represents an alternative to the mevalonate route for the formation of isoprene units. It is found in most bacteria as well as in the plastids of all phototrophic organisms. A selection of significant steps of its discovery and elucidation are presented in this contribution, as well as a complete hypothetical biogenetic scheme for the last reduction step.
Reference intervals for follicle-stimulating hormone, luteinizing hormone and prolactin in children and young adults on the bioMérieux Mini-Vidas system
Authors: Koskas Thu , Souaré Karamo , Ouahabi Tarik , Porquet Dominique , Chevenne Didier 
Published: April 2007

AbstractWe measured serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin concentrations on a bioMérieux Mini Vidas system in a pediatric population ranging in age from 1 to 19 years. Reference intervals were established separately for females and males, with stratification by age group and by Tanner's pubertal stage. FSH values were higher in females than in males, and were lowest in both sexes of age class 2 (4–8 years), increasing thereafter to the upper limit for stage PIV (females) and stage PV (males). LH values showed a similar pattern of change: concentrations were lowest for class 1 (1–3 years) and class 2 (4–8 years), and highest for stage PII (females) and stage PV (males). No significant difference was observed according to gender. Prolactin values did not differ markedly according to gender or pubertal status.Clin Chem Lab Med 2007;45:541–5.
Percutaneous coronary intervention-induced variations in systemic parameters of inflammation: relationship with the mode of stenting
Authors: Brasselet Camille , Garnotel Roselyne , Pérotin Sophie , Vitry Fabien , Elaerts Jacques , Lafont Antoine , Metz Damien , Gillery Philippe 
Published: April 2007

AbstractClin Chem Lab Med 2007;45:526–30.
The genetic polymorphisms of β3-adrenergic receptor (AR) Trp64Arg and β2-AR Gln27Glu are associated with obesity in Chinese male hypertensive patients
Authors: Mo Wei , Zhang Guang-Gan , Yang Tian-Lun , Dai Xing-Ping , Li Hui-Hua , Zeng Hui , Liu Jie , Tan Yuan-Ming , Zhou Hong-Hao , Liu Zhao-Qian 
Published: April 2007

AbstractClin Chem Lab Med 2007;45:493–8.
Associations of common polymorphisms in the thymidylate synthase, reduced folate carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase genes with folate and homocysteine levels and venous thrombosis risk
Authors: Gellekink Henkjan , Blom Henk J. , den Heijer Martin 
Published: April 2007

AbstractClin Chem Lab Med 2007;45:471–6.
A724A polymorphism of sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) in hypertensive patients
Authors: Kiec-Wilk Beata , Dembinska-Kiec Aldona , Olszanecka Agnieszka , Bodzioch Marek , Schmitz Gerd , Kawecka-Jaszcz Kalina 
Published: April 2007

AbstractClin Chem Lab Med 2007;45:467–70.
Diagnostic accuracy of the FIDIS multiplex fluorescent microsphere immunodetection system for anti-extractable nuclear antigen (ENA) antibodies in connective tissue diseases
Authors: Vercammen Martine , Meirlaen Patricia , Sennesael Jacques , Velkeniers Brigitte , T'Kint Sara , Verbruggen Leon , Haentjens Patrick , Broodtaerts Linda , Demanet Christian , De Waele Marc 
Published: April 2007

AbstractClin Chem Lab Med 2007;45:505–12.