bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer
Authors: Li Lan , Ahmed Bilal , Mehta Kapil , Kurzrock Razelle 
Published: April 2007

Abstract
The role of curcumin (diferuloylmethane), a proapoptotic compound, for the treatment of cancer has been an area of growing interest. Curcumin in its free form is poorly absorbed in the gastrointestinal tract and therefore may be limited in its clinical efficacy. Liposome encapsulation of this compound would allow systemic administration. The current study evaluated the preclinical antitumor activity of liposomal curcumin in colorectal cancer. We also compared the efficacy of liposomal curcumin with oxaliplatin, a standard chemotherapy for this malignancy. In vitro treatment with liposomal curcumin induced a dose-dependent growth inhibition [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt] and apoptosis [poly(ADP-ribose) polymerase] in the two human colorectal cancer cell lines tested (LoVo and Colo205 cells). There was also synergism between liposomal curcumin and oxaliplatin at a ratio of 4:1 in LoVo cells in vitro. In vivo, significant tumor growth inhibition was observed in Colo205 and LoVo xenografts, and the growth inhibition by liposomal curcumin was greater than that for oxaliplatin (P &lt; 0.05) in Colo205 cells. Tumors from animals treated with liposomal curcumin showed an antiangiogenic effect, including attenuation of CD31 (an endothelial marker), vascular endothelial growth factor, and interleukin-8 expression by immunohistochemistry. This study establishes the comparable or greater growth-inhibitory and apoptotic effects of liposomal curcumin with oxaliplatin both in vitro and in vivo in colorectal cancer. We are currently developing liposomal curcumin for introduction into the clinical setting. [Mol Cancer Ther 2007;6(4):1276–82]
Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal kinase–mediated p53 phosphorylation and stabilization
Authors: Shi Ranxin , Huang Qing , Zhu Xinqiang , Ong Yeong-Bing , Zhao Bin , Lu Jia , Ong Choon-Nam , Shen Han-Ming 
Published: April 2007

Abstract
Luteolin is an important flavonoid with a potential anticancer effect. In this study, we examined the molecular mechanisms involved in the sensitization effect of luteolin on cancer cell killing induced by cisplatin, an important cancer chemotherapeutic agent. First, we provided evidence that the sensitization effect of luteolin on cisplatin-induced apoptosis is p53 dependent, as such effect is only found in p53 wild-type cancer cells but not in p53 mutant cancer cells. Moreover, knockdown of p53 by small interfering RNA made p53 wild-type cancer cells resistant to luteolin and cisplatin. Second, we observed a significant increase of p53 protein level in luteolin-treated cancer cells without increase of p53 mRNA level, indicating the possible effect of luteolin on p53 posttranscriptional regulation. Third, we identified the critical role of c-Jun NH2-terminal kinase (JNK) in regulation of p53 protein stability: luteolin activates JNK, and JNK then stabilizes p53 via phosphorylation, leading to reduced ubiquitination and proteasomal degradation. Finally, by using an in vivo nude mice xenograft model, we confirmed that luteolin enhanced the cancer therapeutic activity of cisplatin via p53 stabilization and accumulation. In summary, data from this study reveal a novel molecular mechanism involved in the anticancer effect of luteolin and support its potential clinical application as a chemosensitizer in cancer therapy. [Mol Cancer Ther 2007;6(4):1338–47]
Uncommon tumors and exceptional therapies: paradox or paradigm?
Authors: Braiteh Fadi , Kurzrock Razelle 
Published: April 2007

Abstract
Why does it seem that, repeatedly, when a new treatment with a striking effect is discovered in the cancer field, it is effective for a very rare cancer type? For example, groundbreaking therapeutic discoveries have been made for extremely uncommon malignancies such as hairy cell leukemia, chronic myelogenous leukemia, seminoma, gastrointestinal stromal tumor, (del)5q myelodysplastic syndrome, and acute promyelocytic leukemia. In contrast, progress in the most common and most intensively studied tumors—lung, breast, prostate, and colon cancer—has been slow and incremental. We hypothesize that the reason for this phenomenon is that the pathophysiologic basis for a tumor being rare is one and the same as the reason that it may ultimately be so treatable. That is, if a cancer can be derived only via a single aberrant molecular genetic aberration, then it should be both rare and easily targeted by a molecular cancer therapeutic approach. If, on the other hand, many distinct pathways can lead to the development of a specific tumor type, it should occur much more commonly and be significantly more difficult to treat. The corollary to our hypothesis is the prediction that new therapies will continue to show their most salutary effects in rare cancers. Furthermore, only by stratifying the common tumors, especially when using targeted agents, into the molecular subsets of diseases that compose them are we likely to achieve a substantial effect in these disorders. [Mol Cancer Ther 2007;6(4):1175–9]
Loss of ataxia telangiectasia mutated– and Rad3-related function potentiates the effects of chemotherapeutic drugs on cancer cell survival
Authors: Wilsker Deborah , Bunz Fred 
Published: April 2007

Abstract
The diverse responses of human cells to various forms of DNA damage are controlled by a complex network of signaling proteins. There has been considerable interest in the components of this signaling apparatus as potential targets for new forms of anticancer therapy. In this report, we examine the contributions of an upstream signaling molecule, the ataxia telangiectasia mutated– and Rad3-related (ATR) protein kinase, to the resistance of cancer cells to DNA-damaging agents that are commonly used as anticancer therapeutics. Loss of ATR function in knock-in cancer cells strikingly enhanced the effects of several of the most commonly used therapeutic compounds, impeding the progression of the cell cycle and reducing long-term cancer cell survival. Loss of ATR function potentiated the toxicity of alkylating agents most strikingly, antimetabolites moderately, and double-strand break–inducing agents to a lesser extent. These results suggest that specific inhibition of ATR activity will be a valid strategy to increase the effectiveness of currently used modes of therapy. [Mol Cancer Ther 2007;6(4):1406–13]
Loss of mitochondrial membrane potential is inhibited by bombesin in etoposide-induced apoptosis in PC-3 prostate carcinoma cells
Authors: Salido Mercedes , Gonzalez Juan L. , Vilches Jose 
Published: April 2007

Abstract
Neuroendocrine secretory products and their interactions with epithelial prostate cells are currently under investigation in order to understand their significance in the pathogenesis, prognosis, and therapy of prostate carcinoma. These neuropeptides have the potential to disrupt the balance between cell death and cell growth in the tumor. Our research was based on the role of bombesin in modulating the mitochondrial membrane potential (Δψm) in cell death induced by etoposide on PC-3 cells. Cells were cultured and stained with 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). At low membrane potentials, JC-1 produces a green fluorescence, and at high membrane potentials, it forms “J aggregates” with red fluorescence. Cells were examined in a confocal microscope. For quantitative analyses, regions of interest were selected. The size, number of pixels, and ratios between fluorescence intensity in the red and green channels in each region of interest were calculated. The loss of Δψm in etoposide-treated PC-3 cells was prevented by bombesin. The quantitative analysis of JC-1–stained cells revealed a significant decrease in the red (high Δψm) to green (low Δψm) ratio in etoposide-treated cells when compared with control cells, which was restored in the presence of bombesin (P &lt; 0.00001). The interaction between treatments and area (P = 0.0002) was highly significant, and confirms that PC-3 cells keep their apoptosis machinery, showing an apoptotic volume decrease in response to etoposide. The protection by bombesin occurs by inhibition of apoptosis and maintenance of mitochondrial integrity. New therapeutic protocols and trials need to be developed to test drugs acting through the neutralization of antiapoptotic intracellular pathways mediated by neuroendocrine hormones. [Mol Cancer Ther 2007;6(4):1292–9]
Clofibric acid, a peroxisome proliferator–activated receptor α ligand, inhibits growth of human ovarian cancer
Authors: Yokoyama Yoshihito , Xin Bing , Shigeto Tatsuhiko , Umemoto Mika , Kasai-Sakamoto Akiko , Futagami Masayuki , Tsuchida Shigeki , Al-Mulla Fahd , Mizunuma Hideki 
Published: April 2007

AbstractRecent reports have shown that peroxisome proliferator–activated receptor (PPAR)α ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARα on growth of ovarian malignancy, in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted s.c. and significantly prolonged the survival of mice with malignant ascites derived from DISS cells as compared with control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased the expression of carbonyl reductase (CR), which promotes the conversion of prostaglandin E2 (PGE2) to PGF2α, in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE2 level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3–tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE2 level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with a reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs. [Mol Cancer Ther 2007;6(4):1379–86]
Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues
Authors: Sharp Swee Y. , Prodromou Chrisostomos , Boxall Kathy , Powers Marissa V. , Holmes Joanna L. , Box Gary , Matthews Thomas P. , Cheung Kwai-Ming J. , Kalusa Andrew , James Karen , Hayes Angela , Hardcastle Anthea , Dymock Brian , Brough Paul A. , Barril Xavier , Cansfield Julie E. , Wright Lisa , Surgenor Allan , Foloppe Nicolas , Hubbard Roderick E. , Aherne Wynne , Pearl Laurence , Jones Keith , McDonald Edward , Raynaud Florence , Eccles Sue , Drysdale Martin , Workman Paul 
Published: April 2007

Abstract
Although the heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) shows clinical promise, potential limitations encourage development of alternative chemotypes. We discovered the 3,4-diarylpyrazole resorcinol CCT018159 by high-throughput screening and used structure-based design to generate more potent pyrazole amide analogues, exemplified by VER-49009. Here, we describe the detailed biological properties of VER-49009 and the corresponding isoxazole VER-50589. X-ray crystallography showed a virtually identical HSP90 binding mode. However, the dissociation constant (Kd) of VER-50589 was 4.5 ± 2.2 nmol/L compared with 78.0 ± 10.4 nmol/L for VER-49009, attributable to higher enthalpy for VER-50589 binding. A competitive binding assay gave a lower IC50 of 21 ± 4 nmol/L for VER-50589 compared with 47 ± 9 nmol/L for VER-49009. Cellular uptake of VER-50589 was 4-fold greater than for VER-49009. Mean cellular antiproliferative GI50 values for VER-50589 and VER-49009 for a human cancer cell line panel were 78 ± 15 and 685 ± 119 nmol/L, respectively, showing a 9-fold potency gain for the isoxazole. Unlike 17-AAG, but as with CCT018159, cellular potency of these analogues was independent of NAD(P)H:quinone oxidoreductase 1/DT-diaphorase and P-glycoprotein expression. Consistent with HSP90 inhibition, VER-50589 and VER-49009 caused induction of HSP72 and HSP27 alongside depletion of client proteins, including C-RAF, B-RAF, and survivin, and the protein arginine methyltransferase PRMT5. Both caused cell cycle arrest and apoptosis. Extent and duration of pharmacodynamic changes in an orthotopic human ovarian carcinoma model confirmed the superiority of VER-50589 over VER-49009. VER-50589 accumulated in HCT116 human colon cancer xenografts at levels above the cellular GI50 for 24 h, resulting in 30% growth inhibition. The results indicate the therapeutic potential of the resorcinylic pyrazole/isoxazole amide analogues as HSP90 inhibitors. [Mol Cancer Ther 2007;6(4):1198–211]
A new paradigm of mechanical energy dissipation. Part 2: Experimental investigation and effectiveness of a novel car damper
Authors: Eroshenko V A , Piatiletov I , Coiffard L , Stoudenets V 
Published: April 2007

Solid-liquid interfaces can be used as a damper to dissipate mechanical energy. Owing to its original properties, a heterogeneous lyophobic system consisting of a nanoporous solid and a non-wetting liquid can dissipate energy under specific pressures. The dissipation process is fast enough to consider its use in damping high-frequency disturbances and for other applications. In this paper, a prototype automobile damper is described. One of the objectives of the device is to exert a clipping effect on major forces induced by the fast and large mechanical disturbance applied to the rod. The prototype is a hybrid of a viscous damper that contains a small volume of oil and throttle valves for conventional viscous dissipation, and a heterogeneous lyophobic system that can significantly enhance mechanical dissipation for velocities greater than adjustable threshold piston rod speeds. The mechanical properties of the device and its energy performance are evaluated and comprehensively discussed.
Investigating Consumers’ Purchase Incidence and Brand Choice Decisions Across Multiple Product Categories: A Theoretical and Empirical Analysis
Authors: Mehta Nitin 
Published: April 2007

We propose a framework to investigate consumers’ brand choice and purchase incidence decisions across multiple categories, where both decisions are modeled as an outcome of a consumer’s basket utility maximization. We build the model from first principles by theoretically explicating a general model of basket utility maximization and then examining the reasonable restrictions that can be placed to make the solution tractable without sacrificing its flexibility. Comparing with prior models, we show why prior multicategory purchase incidence models overemphasize the role of the cross effects of a market mix of brands in other categories on the purchase incidence decision of a given category. Additionally, we show that prior single-category models are a special case of the proposed model when further restrictions are placed on the basket utility structure.We estimate the model on household basket data for the laundry family of categories. We show (i) why prior single-category and multicategory models would systematically bias the estimates of the own- and cross-price/promotional purchase incidence elasticities; and (ii) how the market mix of each brand in each category affects the purchases across all categories, which can help retailers make promotional decisions across a portfolio of products.
Chemistry of oxylipin pathways in marine diatoms
Authors: Fontana Angelo , d'Ippolito Giuliana , Cutignano Adele , Miralto Antonio , Ianora Adrianna , Romano Giovanna , Cimino Guido 
Published: April 2007

Abstract
Oxylipins are important signal transduction molecules widely distributed in animals and plants where they regulate a variety of events associated with physiological and pathological processes. The family embraces several different metabolites that share a common origin from the oxygenase-catalyzed oxidation of polyunsaturated fatty acids. The biological role of these compounds has been especially studied in mammalians and higher plants, although a varied and very high concentration of these products has also been reported from marine macroalgae. This article gives a summary of our results concerning the oxylipin chemistry of marine diatoms, a major class of planktonic microalgae that discourage predation from their natural grazers, zooplanktonic copepods, using chemical warfare. These apparently harmless microscopic cells produce a plethora of oxylipins, including short-chain unsaturated aldehydes, hydroxyl-, keto-, and epoxyhydroxy fatty acid derivatives, that induce reproductive failure in copepods through abortions, congenital malformations, and reduced larval growth. The biochemical process involved in the production of these compounds shows a simple regulation based on decompartmentation and mixing of preexisting enzymes and requires hydrolysis of chloroplast-derived glycolipids to feed the downstream activities of C16 and C20 lipoxygenases.
Mitsoamide: A cytotoxic linear lipopeptide from the Madagascar marine cyanobacterium Geitlerinema sp.
Authors: Andrianasolo Eric H. , Goeger Douglas , Gerwick William H. 
Published: April 2007

Abstract
A new cytotoxic and linear peptide (IC50 460 nM to NCI-H460 human lung tumor cells) was isolated from the marine cyanobacterium Geitlerinema sp. The planar structure of mitsoamide was deduced by 1D and 2D NMR experiments in combination with MS analyses. The structure of mitsoamide contains an unusual polyketide unit (3,7-dimethoxy-5-methyl-nonanedioic acid, DMNA), incorporates a homolysine (HomoLys) residue and possesses a highly unusual piperidine aminal moiety. The configurations of the relatively common amino acids present in mitsoamide (Ala, Ile, N-Me-Ile, Phe, Val) were determined by chiral HPLC analysis of the acid hydrolysate.
Recent progress in the synthesis of bioactive polycyclic natural products
Authors: Miyashita Masaaki 
Published: April 2007

Abstract
The zoanthamine alkaloids, a type of heptacyclic marine alkaloid isolated from colonial zoanthids of the genus Zoanthus sp., have distinctive biological and pharmacological properties as well as their unique chemical structures with stereochemical complexity. Namely, norzoanthamine can suppress the loss of bone weight and strength in ovariectomized mice and has been considered a promising candidate for an antiosteoporotic drug, whereas zoanthamine has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects. Recently, norzoanthamine derivatives were demonstrated to inhibit strongly the growth of P-388 murine leukemia cell lines, in addition to their potent antiplatelet activities on human platelet aggregation. These distinctive biological properties, combined with novel chemical structures, make this family of alkaloids extremely attractive targets for chemical synthesis. However, the chemical synthesis of the zoanthamine alkaloids has been impeded owing to their densely fuctionalized complex stereostructures. We report here the first and highly stereoselective total syntheses of norzoanthamine and zoanthamine, which involves stereoselective synthesis of the requisite triene for intramolecular Diels-Alder reaction via three-component coupling reactions, a key intramolecular Diels-Alder reaction, and subsequent crucial bis-aminoacetalization as the key steps.
Influence of C-terminal amidation on the antimicrobial and hemolytic activities of cationic α-helical peptides
Authors: Strandberg Erik , Tiltak Deniz , Ieronimo Marco , Kanithasen Nathalie , Wadhwani Parvesh , Ulrich Anne S. 
Published: April 2007

Abstract
The effect of C-terminal amidation on the antimicrobial and hemolytic activities of antimicrobial peptides was studied using three cationic peptides which form amphiphilic α-helices when bound to membranes. The natural antimicrobial peptide PGLa, the designer-made antibiotic MSI-103, and the cell-penetrating "model amphipathic peptide" (MAP) are all amidated in their original forms, and their biological activities were compared with the same sequences carrying a free C-terminus. It was found that, in general, a free COOH-terminus reduces both the antimicrobial activity and the hemolytic side effects of the peptides. The only exception was observed for MSI-103, whose antimicrobial activity was not decreased in the acid form. Having shown that the therapeutic index (TI) of this novel peptide is significantly higher than for the other tested peptides, with high antibiotic activity and little undesired effects, we suggest that it could be a useful starting point for further development of new peptide antibiotics.
Porphyrins as spectroscopic sensors for conformational studies of DNA
Authors: Balaz Milan , Bitsch-Jensen Klaus , Mammana Angela , Ellestad George A. , Nakanishi Koji , Berova Nina 
Published: April 2007

Abstract
Molecular systems containing two or more interacting porphyrins show remarkable spectroscopic features that allow for a very sensitive detection of conformational changes on the microscale level by different methods, such as fluorescence and electronic circular dichroism (ECD). Covalent porphyrin-DNA assemblies can provide a CD profile (exciton couplet) within the porphyrin Soret band region which is very diagnostic for DNA conformational changes. Additionally, covalently linked porphyrins have been shown to function as DNA molecular caps and to stabilize the non-self-complementary non-Watson-Crick guanine-adenine DNA sequence via their strong π-π stacking.
Phytochemical genomics in Arabidopsis thaliana: A case study for functional identification of flavonoid biosynthesis genes
Authors: Tohge Takayuki , Yonekura-Sakakibara Keiko , Niida Rie , Watanabe-Takahashi Akiko , Saito Kazuki 
Published: April 2007

Abstract
The completion of the whole genome sequence of Arabidopsis thaliana has made it possible to explore the phytochemical genomics in this species by determining gene-to-metabolite correlation through the comprehensive analysis of metabolite accumulation and gene expression. In this study, flavonoid profiling of wild-type plants and T-DNA insertion mutants was analyzed using ultra-performance liquid chromatography (UPLC)/photodiode array detection (PDA)/electrospray ionization (ESI)/multiple-stage mass spectrometry (MSn). Detailed analysis of the metabolite changes in the mutants suggested the functions of genes that have been mutated. In silico coexpression analysis of genes involved in flavonoid metabolism in Arabidopsis was performed using a publicly available transcriptome database of DNA microarrays. We inferred a coexpression framework model of the genes involved in the pathways of flavonol, anthocyanin, and proanthocyanidin synthesis, suggesting specific functions and coregulation of the genes of pathway enzymes and transcription factors. The metabolic profiling of the omt1 mutant lacking a methyltransferase gene narrowed down by the coexpression analysis showed that AtOMT1 (At5g54160) is involved not only in the production of lignins and sinapoyl esters but also in the methylation of flavonols forming isorhamnetin. These results suggest that the functional genomics approach by detailed target-metabolite profiling with transcriptome coexpression analysis provides an efficient way of identifying novel gene functions involved in plant metabolism.