bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remarks on Separation of Convex Sets, Fixed-Point Theorem, and Applications in Theory of Linear Operators
Authors: Soltanov Kamal N 
Published: July 2007

AbstractSome properties of the linear continuous operator and separation of convex subsets are investigated in this paper and a dual space for a subspace of a reflexive Banach space with a strictly convex norm is constructed. Here also an existence theorem and fixed-point theorem for general mappings are obtained. Moreover, certain remarks on the problem of existence of invariant subspaces of a linear continuous operator are given.
Trastuzumab causes antibody-dependent cellular cytotoxicity–mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance
Authors: Barok Márk , Isola Jorma , Pályi-Krekk Zsuzsanna , Nagy Péter , Juhász István , Vereb György , Kauraniemi Päivikki , Kapanen Anita , Tanner Minna , Vereb György , Szöllösi János 
Published: July 2007

AbstractTrastuzumab is a recombinant antibody drug that is widely used for the treatment of breast cancer. Despite encouraging clinical results, some cancers are primarily resistant to trastuzumab, and a majority of those initially responding become resistant during prolonged treatment. The mechanisms of trastuzumab resistance have not been fully understood. We examined the role of antibody-dependent cellular cytotoxicity (ADCC) using JIMT-1 cells that are ErbB2 positive but intrinsically resistant to trastuzumab in vitro. Unexpectedly, in experiments mimicking adjuvant therapy of submacroscopic disease in vivo (JIMT-1 cells inoculated s.c. in severe combined immunodeficiency mice), trastuzumab was able to inhibit the outgrowth of macroscopically detectable xenograft tumors for up to 5–7 weeks. The effect is likely to be mediated via ADCC because trastuzumab-F(ab′)2 was ineffective in this model. Moreover, in vitro ADCC reaction of human leukocytes was equally strong against breast cancer cells intrinsically sensitive (SKBR-3) or resistant (JIMT-1) to trastuzumab or even against a subline of JIMT-1 that was established from xenograft tumors growing despite trastuzumab treatment. These results suggest that ADCC may be the predominant mechanism of trastuzumab action on submacroscopic tumor spread. Thus, measuring the ADCC activity of patient's leukocytes against the tumor cells may be a relevant predictor of clinical trastuzumab responsiveness in vivo. [Mol Cancer Ther 2007;6(7):2065–72]
Intratumoral expression of respiratory syncytial virus fusion protein in combination with cytokines encoded by adenoviral vectors asin situtumor vaccine for colorectal cancer
Authors: Hoffmann Dennis , Bayer Wibke , Grunwald Thomas , Wildner Oliver 
Published: July 2007

AbstractAlthough cancers can naturally elicit immune responses, immune ignorance is a common observation preventing immune-mediated elimination of tumor cells. We assessed whether intratumoral expression of respiratory syncytial virus fusion (RSV-F) protein, encoded by a replication-defective adenovirus vector (Ad.RSV-F), alone or in combination with local coexpression of cytokines can induce tumor-specific immune responses in a syngeneic murine colon cancer model. We confirmed in vitro by dye colocalization that transduction of murine cells with Ad.RSV-F induces cell-cell fusion. In vivo, we showed in a bilateral syngeneic s.c. colon cancer model in C57BL/6 and BALB/c mice that intratumoral injection of Ad.RSV-F leads to a significant volume reduction not only of the directly vector-treated tumor but also of the contralateral not directly vector-treated tumor. The intratumoral administration of Ad.RSV-F in combination with adenovirus vectors encoding interleukin (IL)-2, IL-12, IL-18, IL-21, or granulocyte macrophage colony-stimulating factor significantly enhanced the antitumor effect on the directly vector-treated tumor and also on the contralateral tumor. The antineoplastic efficacy of this combined treatment was significantly higher than that of the individual treatment components and was associated with the induction of a tumor-specific CTL response and increased infiltration of the tumors by natural killer cells and macrophages. Intratumoral coexpression of RSV-F and IL-21 resulted in the highest tumor growth inhibition and improved survival. Our experimental data indicate that intratumoral expression of RSV-F in combination with cytokines is a promising novel tool for the development of in situ tumor vaccination approaches. [Mol Cancer Ther 2007;6(7):1942–50]
Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells
Authors: Weisberg Ellen , Kung Andrew L. , Wright Renee D. , Moreno Daisy , Catley Laurie , Ray Arghya , Zawel Leigh , Tran Mary , Cools Jan , Gilliland Gary , Mitsiades Constantine , McMillin Douglas W. , Jiang Jingrui , Hall-Meyers Elizabeth , Griffin James D. 
Published: July 2007

Abstract
Members of the inhibitor of apoptosis protein (IAP) family play a role in mediating apoptosis. Studies suggest that these proteins may be a viable target in leukemia because they have been found to be variably expressed in acute leukemias and are associated with chemosensitivity, chemoresistance, disease progression, remission, and patient survival. Another promising therapeutic target, FLT3, is mutated in about one third of acute myelogenous leukemia (AML) patients; promising results have recently been achieved in clinical trials investigating the effects of the protein tyrosine kinase inhibitor PKC412 on AML patients harboring mutations in the FLT3 protein. Of growing concern, however, is the development of drug resistance resulting from the emergence of point mutations in targeted tyrosine kinases used for treatment of acute leukemia patients. One approach to overriding resistance is to combine structurally unrelated inhibitors and/or inhibitors of different signaling pathways. The proapoptotic IAP inhibitor, LBW242, was shown in proliferation studies done in vitro to enhance the killing of PKC412-sensitive and PKC412-resistant cell lines expressing mutant FLT3 when combined with either PKC412 or standard cytotoxic agents (doxorubicin and Ara-c). In addition, in an in vivo imaging assay using bioluminescence as a measure of tumor burden, a total of 12 male NCr-nude mice were treated for 10 days with p.o. administration of vehicle, LBW242 (50 mg/kg/day), PKC412 (40 mg/kg/day), or a combination of LBW242 and PKC412; the lowest tumor burden was observed in the drug combination group. Finally, the combination of LBW242 and PKC412 was sufficient to override stromal-mediated viability signaling conferring resistance to PKC412. [Mol Cancer Ther 2007;6(7):1951–61]
Lessons learned in the development of targeted therapy for malignant gliomas
Authors: Omuro Antonio M.P. , Faivre Sandrine , Raymond Eric 
Published: July 2007

Abstract
The prognosis of patients with glioblastoma, anaplastic astrocytoma, and anaplastic oligodendroglioma remains poor despite standard treatment with radiotherapy and temozolomide. Molecular targeted therapy holds the promise of providing new, more effective treatment options with minimal toxicity. However, the development of targeted therapy for gliomas has been particularly challenging. The oncogenetic process in such tumors is driven by several signaling pathways that are differentially activated or silenced with both parallel and converging complex interactions. Therefore, it has been difficult to identify prevalent targets that act as key promoters of oncogenesis and that can be successfully addressed by novel agents. Several drugs have been tested, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib and erlotinib), mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus), and vascular endothelial growth factor receptor (VEGFR), protein kinase C-β, and other angiogenesis pathways inhibitors (vatalanib, bevacizumab, and enzastaurin). Although preliminary efficacy results of most trials in recurrent disease have fallen short on expectations, substantial advances have been achieved by associated translational research. In this article, we seek to recapitulate the lessons learned in the development of targeted therapy for gliomas, including challenges and pitfalls in the interpretation of preclinical data, specific issues in glioma trial design, insights provided by translational research, changes in paradigms, and future perspectives. [Mol Cancer Ther 2007;6(7):1909–19]
Sensitizing HER2-overexpressing cancer cells to luteolin-induced apoptosis through suppressing p21WAF1/CIP1 expression with rapamycin
Authors: Chiang Chun-Te , Way Tzong-Der , Lin Jen-Kun 
Published: July 2007

Abstract
HER2 overexpression, which confers resistance to various therapeutic regimens, correlates with a poor clinical prognosis. In this study, we showed that luteolin, a naturally occurring flavonoid, is a potent stimulator of HER2 degradation. Luteolin effectively inhibited cell proliferation and induced apoptosis in HER2-overexpressing cancer cells. Furthermore, we found that low doses of luteolin up-regulated p21 expression and high doses of luteolin down-regulated its expression. Examination of the Akt/mammalian target of rapamycin (mTOR) signaling revealed that this signaling was only transiently inhibited by low doses of luteolin, which suggested that the inability to cause sustained Akt/mTOR inhibition may contribute to p21 induction and provide a survival advantage to HER2-overexpressing cancer cells. To test this hypothesis, we showed that the combined use of luteolin and mTOR inhibitor rapamycin prevented low doses of luteolin from inducing p21 expression, and HER2-overexpressing cancer cells would be sensitized toward luteolin-induced apoptosis. In addition, p21 small interfering RNA also increased the luteolin-induced cell death. In nude mice with xenografted SKOV3.ip1-induced tumors, luteolin significantly inhibited HER2 expression and tumor growth in a dose-dependent manner, and rapamycin further enhanced the effect of luteolin with a concomitant p21 inhibition. These results reveal an intriguing finding that suppressing p21 expression might have therapeutic implications and further suggest that combination of mTOR inhibitors may be a promising strategy to help increase the efficacy of preventive or therapeutic compounds against HER2-overexpressing tumors. [Mol Cancer Ther 2007;6(7):2127–38]
Ovarian cancer cell–derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis
Authors: Hagemann Thorsten , Robinson Stephen C. , Thompson Richard G. , Charles Kellie , Kulbe Hagen , Balkwill Frances R. 
Published: July 2007

AbstractIn view of our previous findings that tumor cell–derived macrophage migration inhibitory factor (MIF) increased macrophage-mediated ovarian cancer cell invasiveness in vitro, we investigated the wider significance of ovarian cancer cell–derived MIF for tumor growth, metastasis, and angiogenesis. We found that MIF is expressed in borderline and malignant ovarian tumors, and active MIF is found in malignant ascitic fluid. We next investigated the expression and function of MIF in a syngeneic ovarian cancer model. Stable knockdown of MIF in the murine ovarian cancer cell line ID8 decreased in vivo tumor burden and overall survival. Tumors arising from MIF knockdown cells had decreased proliferation and significantly increased apoptosis. This was associated with an increased phosphorylation of p53 and reduced Akt phosphorylation. MIF knockdown led to a changed cytokine profile in the ascitic microenvironment; tumor necrosis factor-α, interleukin-6 (IL-6), and IL-10 expression were all significantly decreased. Accompanying this decrease in cytokine expression was a significant decrease in macrophage infiltration into ascites. Additionally, MIF knockdown reduced the expression of proangiogenic cytokines vascular endothelial growth factor and keratinocyte chemoattractant (KC) and reduced the amount of endothelial cells in the malignant ascites. We conclude that autocrine production of MIF by ovarian cancer cells stimulates other cytokines, chemokines, and angiogenic factors that may promote colonization of the peritoneum and neovascularization of tumor deposits. [Mol Cancer Ther 2007;6(7):1993–2002]
Inhibition of the mitogen-activated protein kinase pathway results in the down-regulation of P-glycoprotein
Authors: Katayama Kazuhiro , Yoshioka Sho , Tsukahara Satomi , Mitsuhashi Junko , Sugimoto Yoshikazu 
Published: July 2007

AbstractThe multidrug resistance gene 1 (MDR1) product, P-glycoprotein (P-gp), pumps out a variety of anticancer agents from the cell, including anthracyclines, Vinca alkaloids, and taxanes. The expression of P-gp therefore confers resistance to these anticancer agents. In our present study, we found that FTI-277 (a farnesyltransferase inhibitor), U0126 [an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)], and 17-allylamino-17-demethoxygeldanamycin (an inhibitor of heat shock protein 90) reduced the endogenous expression levels of P-gp in the human colorectal cancer cells, HCT-15 and SW620-14. In contrast, inhibitors of phosphatidylinositol 3-OH kinase, mammalian target of rapamycin, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase did not affect P-gp expression in these cells. We further found that U0126 down-regulated exogenous P-gp expression in the MDR1-transduced human breast cancer cells, MCF-7/MDR and MDA-MB-231/MDR. However, the MDR1 mRNA levels in these cells were unaffected by this treatment. PD98059 (a MEK inhibitor), ERK small interfering RNA, and p90 ribosomal S6 kinase (RSK) small interfering RNA also suppressed P-gp expression. Conversely, epidermal growth factor and basic fibroblast growth factor enhanced P-gp expression, but the MDR1 mRNA levels were unchanged in epidermal growth factor–stimulated cells. Pulse-chase analysis revealed that U0126 promoted P-gp degradation but did not affect the biosynthesis of this gene product. The pretreatment of cells with U0126 enhanced the paclitaxel-induced cleavage of poly(ADP-ribose) polymerase and paclitaxel sensitivity. Furthermore, U0126-treated cells showed high levels of rhodamine123 uptake. Hence, our present data show that inhibition of the MEK-ERK-RSK pathway down-regulates P-gp expression levels and diminishes the cellular multidrug resistance. [Mol Cancer Ther 2007;6(7):2092–2102]
ZD4054, a specific antagonist of the endothelin A receptor, inhibits tumor growth and enhances paclitaxel activity in human ovarian carcinoma in vitro and in vivo
Authors: Rosanò Laura , Di Castro Valeriana , Spinella Francesca , Nicotra Maria Rita , Natali Pier Giorgio , Bagnato Anna 
Published: July 2007

Abstract
The autocrine endothelin (ET)-1/endothelin A receptor (ETAR) pathway is an important regulator of several processes involved in ovarian cancer progression, and its overexpression is associated with aggressive disease. These features have led to the proposal of the ETAR receptor as a potential target for improving ovarian cancer treatment. In this study, we evaluated in vitro and in vivo the effects of ZD4054, an orally active antagonist that specifically binds ETAR, as monotherapy, and in combination with paclitaxel. In the human ovarian cancer ETAR-positive cell lines HEY, OVCA 433, SKOV-3, and A-2780, ZD4054 effectively inhibited the basal and ET-1–induced cell proliferation, associated with the inhibition of AKT and p42/44MAPK phosphorylation, and with increased apoptosis, through the inhibition of bcl-2 and activation of caspase-3 and poly(ADP-ribose) polymerase proteins. ZD4054 treatment also resulted in a reduction of ETAR-driven angiogenesis and invasive mediators, such as vascular endothelial growth factor, cyclooxygenase-1/2, and matrix metalloproteinase (MMP). The combination of ZD4054 and paclitaxel led to the potentiation of all these effects, indicating that ZD4054, by blocking the ETAR-dependent proliferative, invasive, and antiapoptotic signals, can enhance sensitivity to paclitaxel. In HEY ovarian cancer xenografts, ZD4054 significantly inhibited tumor growth to the same degree as paclitaxel. Furthermore, ZD4054-dependent tumor growth inhibition was associated with a reduction in proliferation index, microvessel density, and MMP-2 expression. Interestingly, the combination of ZD4054 and paclitaxel produced additive antitumor effects, with 40% of mice remaining tumor-free, supporting a rationale for the clinical use of ZD4054 as monotherapy or in combination with cytotoxic drugs. [Mol Cancer Ther 2007;6(7):2003–11]
Cross-Cultural Negotiating: A Japanese-American Case Study from Higher Education
Authors: Prestwich Roger 
Published: July 2007

AbstractThis article discusses a cross-cultural negotiation process between a new Japanese university and an established American university to create a joint business venture – a dual-degree program. The parties failed to sign a contract, and there were indicators during negotiations pointing to the likelihood of a failed outcome. Negotiation style convergence was evident, with the Japanese adopting an erabi ('either-or') style and the Americans an awase ('more-or-less') style. The 7-Step framework used to structure the negotiation discussion may be better suited to analyzing Japanese negotiation processes than American. The implications will be of value to Japanese and American/Western businesspeople or educational administrators involved in joint venture-type negotiations.
The Road To Helsinki: The Aceh Agreement and Indonesia's Democratic Development
Authors: Morfit Michael 
Published: July 2007

AbstractDespite considerable skepticism, the August 2005 Helsinki agreement between the Government of Indonesia and Free Aceh Movement were largely successful in resolving nearly 30 years of armed conflict. The December 2006 local elections are now widely recognized as marking the consolidation of that peace agreement. Conventional accounts of the Helsinki negotiations do not capture the complexity and richness of the various political, military, institutional and personal forces at play. A closer examination reveals the extent to which the Helsinki Memorandum of Understanding was a key milestone in Indonesia's continuing democratic development.
Transfer function characterization of pressure signal tubes for the measurement of large amplitude pressure fluctuations
Authors: Sims-Williams D B , Luck D A 
Published: July 2007

The measurement of fluctuating pressures in gasses is relevant to a wide range of fluid flow applications. The frequency response of pressure measurement systems using remote transducers is usually limited by the response of the connecting tubing. For small fluctuation levels it is well established that the signal distortion can be corrected using a transfer function technique. This work extends the approach to include the more challenging issue of large amplitude fluctuations where the transfer function is strongly dependent on the fluctuation amplitude as well as frequency. The tubing transfer function was found to closely depend on the ratio of the standard deviation of the pressure fluctuation and the absolute pressure ( PSTD/ PABS). An algorithm for correction is described and demonstrated. Levels of PSTD/ PABS of up to 0.6 have been tested and distortions of up to 250 per cent have been corrected to within 5 per cent.
Resistance Measurements of Microcrystals of Single-component Molecular Metals Using Finely Patterned Interdigitated Electrodes
Authors: Tanaka Hisashi , Hara Shigeo , Tokumoto Madoka , Kobayashi Akiko , Kobayashi Hayao 
Published: July 2007

Abstract
Two-probe resistance measurements on the micro-crystalline samples using finely patterned interdigitated electrodes revealed single-component molecular conductors, [Au(tmdt)2] and [Ni(dmdt)2], to be metallic down to liquid helium temperature.
Chemical States of Ag in Ag(DMe-DCNQI)2 Photoproducts and a Proposal for Its Photoinduced Conductivity Change Mechanism
Authors: Miyamoto Takeshi , Niimi Hironobu , Chun Wang-Jae , Kitajima Yoshinori , Sugawara Hideyuki , Inabe Tamotsu , Naito Toshio , Asakura Kiyotaka 
Published: July 2007

Abstract
UV–vis light converts Ag(DM)2 (DM = 2,5-dimethyl-N,N′-dicyanoquionediimine; DMe-DCNQI) to several solids with metallic, semiconducting, or insulating conductivities depending on the irradiation conditions. Ag valence state in each photochemical product was determined by Ag L3-edge XANES. The XANES result requires the correction of the redox mechanism to explain the photoinduced conductivity change of Ag(DM)2 photoproducts.
Application of Squaric Acid Esters in Aminodeoxy Sugar Chemistry
Authors: Sztaricskai Ferenc , Roth Erzsébet , Andrei Mária , Pelyvás István F , Herczegh Pál 
Published: July 2007

Abstract
The reaction of dimethyl squarate with aminodeoxy sugars, aminodeoxy alditols, amino aldonic acids, and glycosyl amines under neutral conditions furnished the squaric amide esters, which were converted in more alkaline media (pH ≈8) into the asymmetric squaric diamides. The unprotected squaric acid amide esters are suitable for constructing a specific anchor (spacer, linker) function that favorably influences the water-solubility of the resulting drugs and glycoconjugates.
Synthesis and Spectroscopic Properties of New Fluorescent 3,6-Diaryl-4-phenyl-2-pyridone Derivatives
Authors: Minakata Satoshi , Moriwaki Shouta , Inada Hiroshi , Komatsu Mitsuo , Kajii Hirotake , Ohmori Yutaka , Tsumura Manabu , Namura Kiyoyuki 
Published: July 2007

Abstract
Novel fluorescent 3,6-diaryl-4-phenyl-2-pyridone derivatives were synthesized and their fluorescent properties were investigated. These compounds emit intense brilliant blue fluorescence only in the solid state, not in solution. An electron-donating substituent on the 6-phenyl group caused a red-shift in fluorescence maxima.
Spectral Properties and Charge-transfer Complexes of the Cyclophanes Having the Pyrene Moiety
Authors: Tsuge Akihiko , Ikeura Yukihiro , Moriguchi Tetsuji , Yamaji Minoru 
Published: July 2007

Abstract
Novel cyclophanes having the pyrene moiety have been synthesized. The fluorescence and phosphorescence properties have been examined in terms of their structure. It has been found out that their charge-transfer complexes reflect the transannular π–π interaction based on the structure.