bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of 1,2,4‐Triazolo[4,3‐a]pyrimidine Derivatives by Cyclocondensation of a 2‐Thioxopyrimidin‐4(3H)‐one with Hydrazonoyl Halides
Authors: Elwan Nehal M. , Awad Enas M. , Hassaneen Hamdi M. , Linden Anthony , Heimgartner Heinz 
Published: March 2003

AbstractThe reaction of 1,2‐dihydro‐6‐(phenylamino)‐2‐thioxopyrimidin‐4(3H)one (16) with N‐arylhydrazonoyl halides 15 in CHCl3 in the presence of Et3N under reflux afforded the corresponding 1,2,4‐triazolo[4,3‐a]pyrimidin‐5‐ones of type 20 in good yields (Scheme 3). The structure of one of the derivatives, 20d, has been established by X‐ray crystallography. Conceivable reaction mechanisms are discussed in Schemes 3 and 4. The products of type 20 easily undergo reactions with electrophiles such as benzenediazonium chloride, chloroacetyl chloride, and NaNO2 in AcOH to give 6‐phenylazo, 6‐chloroacetyl, and 6‐nitroso derivatives 21, 23, and 25, respectively (Scheme 5).
Enamides via Long‐Distance Migration of Double Bonds
Authors: Sergeyev Sergey A. , Hesse Manfred 
Published: March 2003

AbstractA new method for preparation of enamides (N‐(alken‐1‐yl) amides) by means of the ‘long‐distance' migration of the double bond in unsaturated amides in the presence of [Fe(CO)5] is described. The method is shown to be particularly useful for the isomerization of N‐(but‐3‐enyl)amides, while, in the case of N‐(pent‐4‐enyl) and N‐(hex‐5‐enyl) amides the mixture of products was formed and the yield of the enamide was relatively low.
Synthesis and Cytotoxicity Evaluation of Metal‐Chelator‐Bearing Flavone, Carbazole, Dibenzofuran, Xanthone, and Anthraquinone
Authors: Chen Yeh‐Long , Chen Po‐Hsu , Chung Chao‐Ho , Li Kuang‐Chieh , Jeng Haw‐Yaun , Tzeng Cherng‐Chyi 
Published: March 2003

Abstract2‐(Aryloxymethyl)‐5‐benzyloxy‐1‐methyl‐1H‐pyridin‐4‐ones 8a–8g, 2‐(aryloxymethyl)‐5‐hydroxy‐4H‐pyran‐4‐ones 9a–9g, and 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a–10g were prepared from the known 5‐benzyloxy‐2‐(hydroxymethyl)pyran‐4‐one (3) in a good overall yield. These compounds were evaluated in vitro against a three‐cell lines panel consisting of MCF7 (breast), NCI‐H460 (lung), and SF‐268 (CNS), and the active compounds passed on for evaluation in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results indicated that 5‐hydroxy derivatives are more favorable than their corresponding 5‐benzyloxy precursors (10a–10g vs. 8a–8g), and 1‐methyl‐1H‐pyridin‐4‐ones are more favorable than their corresponding pyran‐4(1H)‐ones (10a–10g vs. 9a–9g). Among these three types of compounds, 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a–10g were the most cytotoxic; they inhibited the growth of almost all the cancer cells tested. On the contrary, compound 8a (a mean GI50=27.8 μM), 8b (38.5), 8d (11.0), and 8e (30.5) are especially active against the growth of SK‐MEL‐5 (a melanoma cancer cell) with a GI50 of <0.01, 5.65, 0.55, and 0.03 μM, respectively (cf. Table 2).
Effect of Through‐Bond Interaction on Conformation and Structure in Rod‐Shaped Donor–Acceptor Systems. Part 2.
Authors: De Ridder Dirk J. A. , Goubitz Kees , Schenk Henk , Krijnen Bert , Verhoeven Jan W. 
Published: March 2003

AbstractThe crystal structures of seven N‐aryltropan‐3‐one (=8‐aryl‐8‐azabicyclo[3.2.1]octan‐3‐one) derivatives 1T1, 2T1, 2T2, 3T2, 5T2, 2T3, and 3T3 are presented (Fig. 2 and Tables 1–5) and discussed together with the derivatives 1T2 and 4T2 published previously. The piperidine ring adopts a chair conformation. In all structures, the aryl group is in the axial position, with the plane through the aryl C‐atoms nearly perpendicular to the mirror plane of the piperidine ring. The through‐bond interaction between the piperidine ring N‐atom (one‐electron donor) and the substituted exocyclic CC bond (acceptor) not only elongates the central CC bonds of the piperidine ring but also increases the pyrimidalization at C(4) of the piperidine ring. Flattening of the C(2)–C(6) part of the piperidine ring decreases the through‐bond interaction.
Simplified Sialyl Lewisx Analogues with Improved E‐Selectin Inhibition
Authors: Thoma Gebhard , Schwarzenbach Franz 
Published: March 2003

AbstractThe simplified sialyl Lewisx mimic 5 containing a D‐arabinose, a 3‐cyclohexyl‐2‐hydroxypropanoate, and a tetrahydropyran building block instead of L‐fucose, sialic acid, and N‐acetylglucosamine, respectively was synthesized. Compound 5 was 10‐fold more potent than sLex in a static E‐selectin binding assay and showed at 50 μM 75% inhibition in a dynamic‐flow assay in which sLex did not inhibit neutrophil rolling at up to 1000 μM. Compound 7 with a lactic acid instead of sialic acid building block showed threefold improved potency compared to sLex.
Possible predictors of response to fluvoxamine for depression
Authors: Morishita Shigeru , Arita Seizaburo 
Published: March 2003

AbstractIntroductionAn investigation of the characteristics of patients being treated with antidepressants would seem to be useful in determining which patients would be most likely benefit from antidepressant medication.AimsThe purpose of this preliminary study was to examine the possible predictors of response to fluvoxamine for depression.MethodA retrospective cohort analysis was carried out among depression patients treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000. Seventy two patients were identified who were receiving fluvoxamine to treat depression.ResultsA variety of clinical factors including age, gender, type of depression, frequency of episodes, family history and daily dose of fluvoxamine were examined as possible predictors of the response to fluvoxamine. A Weibull regression analysis showed age, frequency of episodes and daily dose to be the independent predictive factors of improvement in fluvoxamine treatment. The most influential factor was age (ecoef = 2.109), followed by daily dose (ecoef = 0.648) and frequency of episode (ecoef = 0.512). An age of 49 years or younger (χ2 = 6.767, df = 1, p = 0.0093), a first episode (χ2 = 9.079, df = 1, p = 0.0026) and a daily dose of 100–150 mg (χ2 = 5.353, df = 1, p = 0.02) were significantly better predictors of improvement.ConclusionsAge, the frequency of episodes and the daily dose of fluvoxamine may be considered as predictors of the response to fluvoxamine treatment for depression. This result should be examined in future prospective study. Copyright © 2002 John Wiley & Sons, Ltd.
Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder
Authors: Atmaca Murad , Kumru Selahattin , Tezcan Ertan 
Published: March 2003

AbstractClinical trials have demonstrated that serotonin reuptake inhibitors (SRIs) and the extract of Vitex agnus castus are effective for the treatment of premenstrual dysphoric disorder (PMDD). However, to the best of our knowledge, there has been no study comparing the efficacy of the SRIs with Vitex agnus castus (AC) extract. Therefore, the aim of the present study was to compare the efficacy of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), with that of the AC extract, a natural choice. After a period of 2 screening months to screen the patients for suitability, 41 patients with PMDD according to DSM‐IV were recruited into the study. The patients were randomized to fluoxetine or AC for 2 months of single‐blind, rater‐ blinded and prospective treatment period. The outcome measures included the Penn daily symptom report (DSR), the Hamilton depression rating scale (HAM‐D), and the clinical global impression‐severity of illness (CGI‐SI) and ‐improvement (CGI‐I) scales. At endpoint, using the clinical criterion for improvement, a similar percentage of patients responded to fluoxetine (68.4%, n = 13) and AC (57.9%, n = 11). There was no statistically significant difference between the groups with respect to the rate of responders. This preliminary study suggests that patients with PMDD respond well to treatment with both fluoxetine and AC. However, fluoxetine was more effective for psychological symptoms while the extract diminished the physical symptoms. Copyright © 2002 John Wiley & Sons, Ltd.
Differential effects of alcohol and alcohol expectancy on risk‐taking during simulated driving
Authors: Burian Scott E. , Hensberry Rebecca , Liguori Anthony 
Published: March 2003

AbstractThis study examined the separate and combined effects of alcohol (0.0 or 0.5 g/kg) and alcohol expectancies (none or 2–3 standard drinks) on risk‐taking using a simulated‐driving lane choice task. In this task, risk‐taking was operationalized as choosing a cone‐defined lane with a higher relative probability of hitting a cone. When alcohol was received but not expected, the probability of a risky lane choice increased compared with when alcohol was neither expected nor received. However, when subjects both expected and received alcohol, the probability of a risky lane choice was significantly decreased compared with when alcohol was neither expected nor received. These findings suggest that the knowledge of dose received can differentially influence the pharmacological effect of alcohol on decision‐making. Copyright © 2003 John Wiley & Sons, Ltd.
Childhood cancer registries in Ontario, Canada: Lessons learned from a comparison of two registries
Authors: Greenberg Mark L. , Barr Ronald D. , DiMonte Bruna , McLaughlin Eva , Greenberg Corin 
Published: March 2003

AbstractTwo childhood cancer registries exist in Ontario. One (POGO) accrues by active registration by pediatric cancer centers, utilizing a histologically based classification system. The other accrues by passive linkage within a larger adult oriented cancer registry (OCR) using a topographically based classification. A reportedly high incidence of childhood cancer based on the latter registry prompted a comparison of the content of the two registries over a 2‐year period with the hypothesis that there would be systematic accrual errors. All registrations in both registries for the specified period were reviewed systematically and validated by pathology reports. A small number (2.6%) of registrations in the passive registry were not incident cases, while 2 particular pathologic diagnoses were included in the histologically based registry and not the topographically based registry. These were low grade gliomas and Langerhans cell histiocytosis (LCH). The validated annual incident rate (15.6 per 100,000 children 0–14 years of age, excluding LCH) is slightly higher than that reported in other industrialized countries. Ninety‐six percent of children aged 0–14 were treated in pediatric oncology centers, while only 46% of adolescents aged 15–17 were treated in such centers. Of the remaining adolescents, more than one‐third had lymphomas. This maldistribution of care provided for the young adolescent population may compromise their survival prospects. The results of this study should prompt revision of health care policy and patterns of service delivery. © 2003 Wiley‐Liss, Inc.
Vascular targeting effect of combretastatin A‐4 phosphate dominates the inherent angiogenesis inhibitory activity
Authors: Ahmed Bisan , van Eijk Loes I. , Bouma‐ter Steege Jessica C.A. , van der Schaft Daisy W.J. , van Esch Anita M. , Joosten‐Achjanie Susan R. , Lambin Philippe , Landuyt Willy , Griffioen Arjan W. 
Published: March 2003

AbstractThe current research aimed to define hypothesis‐based anti‐angiogenic properties of the vascular targeting agent combretastatin A‐4 phosphate (combreAp). The in vitro wound assay indicated that combreAp potently inhibited migration of endothelial cells (EC). A significant inhibition of migration could already be measured after 2 hr of treatment. In a three‐dimensional (3D) tube formation assay, combreAp inhibited sprout formation at concentrations that did not inhibit the proliferation of EC. At sub‐ng concentrations the half‐maximal response was reached. Interestingly, although combreAp is considered a vascular targeting agent, the human tumor cell lines tested were found to be 20–30 times more sensitive for combreAp than the human umbilical vein endothelial cells (HUVEC). A similar response difference between rat EC and R1 rat rhabdomyosarcoma tumor cells was observed. The growth inhibition in EC was only in part mediated by induction of apoptosis. The growth delay results obtained with the in vivo rodent tumor models involving repeat dosing of combreAp can partly be explained by anti‐angiogenic activity of the compound. The results obtained with the various in vitro and in vivo assays substantiate an anti‐angiogenic profile of combreAp, largely at the level of EC migration. This mechanism may operate to a different extent in different tumor types. © 2003 Wiley‐Liss, Inc.
Restricted expression of membrane type 1‐matrix metalloproteinase by myofibroblasts adjacent to human breast cancer cells
Authors: Bisson Christèle , Blacher Silvia , Polette Myriam , Blanc Jean‐Frédéric , Kebers Florence , Desreux Joëlle , Tetu Bernard , Rosenbaum Jean , Foidart Jean‐Michel , Birembaut Philippe , Noel Agnès 
Published: March 2003

AbstractThe membrane type‐1 matrix metalloproteinase (MT1‐MMP), a protease originally identified in breast carcinoma, is characterized by its capacity to activate other MMPs (MMP‐2 and MMP‐13) and to degrade extracellular matrix. Our study was undertaken to localize and identify the MT1‐MMP expressing cells in human breast adenocarcinomas. A textural analysis of images obtained by immunohistochemistry and in situ hybridization showed precisely the co‐expression of alpha smooth muscle actin (αSM actin) and MT1‐MMP in myofibroblasts. MT1‐MMP expression is confined to myofibroblasts in close contact with tumor cells. In sharp contrast, the expression of MMP‐2 was more widely distributed in both αSM actin positive and negative cells close to and at distance from cancer cell clusters. Our in vitro observations are consistent with the higher level of MT1‐MMP expression and of MMP‐2 activation observed in αSM actin positive fibroblasts derived from breast tumors, as compared to normal breast fibroblasts. Collectively, these results implicate myofibroblasts as major producer of MT1‐MMP in breast cancer and emphasize the importance of stromal‐epithelial cell interactions in their progression. © 2003 Wiley‐Liss, Inc.
Mutation analysis of DMBT1 in glioblastoma, medulloblastoma and oligodendroglial tumors
Authors: Pang Jesse Chung‐sean , Dong Zhiqian , Zhang Rong , Liu Yanhui , Zhou Liang‐fu , Chan Bik Wan , Poon Wai Sang , Ng Ho‐keung 
Published: March 2003

AbstractDMBT1 has been implicated as a candidate tumor suppressor gene on chromosome 10q for brain, gastrointestinal and lung cancer. Homozygous deletion and lack of expression are 2 known mechanisms for inactivating DMBT1. We evaluated whether somatic mutation, which represents a major inactivation mechanism for most tumor suppressor genes, occurs in the DMBT1 gene. A total of 102 primary brain tumors, consisting of 25 glioblastoma multiforme, 24 medulloblastoma and 53 oligodendroglial tumors, were analyzed by conformation‐sensitive gel electrophoresis in all 54 coding exons of DMBT1. Twelve different base substitutions were detected in 26 (25%) tumors. Eight base substitutions resulted in amino acid changes and 4 were silent. These base changes were also detected in tumor‐matched blood samples, however, indicating that the base variations represent genetic polymorphisms. We also assessed homozygous deletions of the DMBT1 gene in the series and found that 16 of 95 (5 glioblastomas, 5 medulloblastomas, 6 oligodendroglial tumors; total 17%) tumors harbor such alteration. High‐quality blood DNA samples were available in 5 tumors carrying homozygous deletion and, using long‐range PCR, 3 of these blood samples showed germline hemizygous deletions in a region between introns 10 and 26 of DMBT1. Our results showed that mutation does not play a role in inactivation of DMBT1 in brain tumors. Intragenic homozygous deletion of DMBT1 is common in brain tumors and is likely a result of a germline deletion of 1 allele followed by loss of the second allele during tumor development. © 2003 Wiley‐Liss, Inc.
Imatinib inhibits various types of activating mutant kit found in gastrointestinal stromal tumors
Authors: Chen Hui , Isozaki Koji , Kinoshita Kazuo , Ohashi Akiko , Shinomura Yasuhisa , Matsuzawa Yuji , Kitamura Yukihiko , Hirota Seiichi 
Published: March 2003

AbstractMutations of proto‐oncogene c‐KIT in gastrointestinal stromal tumors (GISTs) are considered to cause a constitutive activation of KIT responsible for their oncogenesis. Imatinib has therapeutic potential for GISTs because of its inhibitory effect on KIT kinase activity. To investigate the effect of Imatinib on various c‐KIT mutations found in GISTs, we examined kinase activity of KIT, cell proliferation and tumorigenicity of transfectants with various c‐KIT mutations. Murine lymphoid Ba/F3 cells transfected with one of the three types of mutants (KITdel559–560, KIT642Glu, and KIT820Tyr) or wild‐type KIT were used for the experiments. Phosphorylation of KIT, mitogen‐activated protein (MAP) and Akt was studied by immunoblotting with or without immunoprecipitation. In vitro studies on cell proliferation using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenylcetrazolium bromide colorimetric assay and in vivo tumorigenicity assay using nude mice were also carried out. Imatinib could inhibit the KIT, MAP and Akt phosphorylation of all the transfectants but had a weaker effect on KIT820Tyr. Imatinib potently inhibited the proliferation of cells transfected with KIT820Tyr at the concentration of 10 μM whereas it inhibited the other 3 types at 1 μM. Moreover, Imatinib could inhibit the tumor formation in nude mice transplanted with transfectants. In various types of activating mutant KIT, Imatinib could inhibit the constitutive activation of KIT signal transduction and cell proliferation both in vitro and in vivo although the effect of Imatinib on KIT820Tyr was weaker than that on KITdel559–560 or KIT642Glu. © 2003 Wiley‐Liss, Inc.
Promoter hypermethylation profile of tumor‐associated genes p16, p15, hMLH1, MGMT and E‐cadherin in oral squamous cell carcinoma
Authors: Viswanathan Muthusamy , Tsuchida Nobuo , Shanmugam Govindaswamy 
Published: March 2003

AbstractAberrant promoter hypermethylation of tumor‐associated genes leading to their inactivation is a common event in many cancer types. Using a sensitive restriction‐multiplex PCR method, we studied the promoter hypermethylation profile of the p16, p15, hMLH1, MGMT and E‐cad genes in oral squamous cell carcinoma (OSCC) of Indians. We analyzed a total of 51 samples for the p15 tumor‐suppressor gene and 99 samples for each of the remaining genes. Our studies indicate an incidence of promoter hypermethylation of 23% each for p16 and p15, 8% for hMLH1, 41% for MGMT and 35% for E‐cad. We observed aberrant hypermethylation of the promoter region of at least 1 of these genes in 74.5% of cases (n = 51) for which all the 5 genes were studied. Abnormal methylation was detected in tumors irrespective of stage and location in the oral cavity, whereas no abnormal methylation was detectable in normal oral squamous tissues obtained from 25 OSCC patients. Detection of aberrant hypermethylation patterns of cancer‐associated genes listed above is therefore suitable for diagnosis of OSCC in individuals at high risk for this disease. © 2003 Wiley‐Liss, Inc.
Expression of the human cachexia‐associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia
Authors: Wang Zejing , Corey Eva , Hass G. Michael , Higano Celestia S. , True Lawrence D. , Wallace David , Tisdale Michael J. , Vessella Robert L. 
Published: March 2003

AbstractProstate cancer (CaP) patients with disseminated disease often suffer from severe cachexia, which contributes to mortality in advanced cancer. Human cachexia‐associated protein (HCAP) was recently identified from a breast cancer library based on the available 20‐amino acid sequence of proteolysis‐inducing factor (PIF), which is a highly active cachectic factor isolated from mouse colon adenocarcinoma MAC16. Herein, we investigated the expression of HCAP in CaP and its potential involvement in CaP‐associated cachexia. HCAP mRNA was detected in CaP cell lines, in primary CaP tissues and in its osseous metastases. In situ hybridization showed HCAP mRNA to be localized only in the epithelial cells in CaP tissues, in the metastatic foci in bone, liver and lymph node, but not in the stromal cells or in normal prostate tissues. HCAP protein was detected in 9 of 14 CaP metastases but not in normal prostate tissues from cadaveric donors or patients with organ‐confined tumors. Our Western blot analysis revealed that HCAP was present in 9 of 19 urine specimens from cachectic CaP patients but not in 19 urine samples of noncachectic patients. HCAP mRNA and protein were also detected in LuCaP 35 and PC‐3M xenografts from our cachectic animal models. Our results demonstrated that human CaP cells express HCAP and the expression of HCAP is associated with the progression of CaP and the development of CaP cachexia. © 2003 Wiley‐Liss, Inc.
Tenascin‐C upregulates matrix metalloproteinase‐9 in breast cancer cells: Direct and synergistic effects with transforming growth factor β1
Authors: Kalembeyi Ilunga , Inada Hiroyasu , Nishiura Rika , Imanaka‐Yoshida Kyoko , Sakakura Teruyo , Yoshida Toshimichi 
Published: March 2003

AbstractTenascin‐C (TN‐C) and matrix metalloproteinases (MMPs) are highly expressed in cancer tissues and probably promote cell migration during cancer progression. TN‐C and MMPs are often co‐localized in areas of active tissue remodeling in pathologic conditions, suggesting reciprocal regulation. To investigate whether TN‐C regulates MMPs expression in cancer cells, we first exposed mammary cancer cells derived from TN‐C‐deficient mice to TN‐C and examined MMPs expression. TN‐C was then compared with fibronectin (FN), laminin (LN), basic fibroblast growth factor (b‐FGF) and transforming growth factor‐beta1 (TGF‐β1). Results of endpoint RT‐PCR, quantitative real‐time RT‐PCR and gelatin zymography demonstrated that TN‐C, strongly and dose dependently, upregulates MMP‐9 expression in murine mammary cancer cells. TN‐C weakly induced MMP‐2, MMP‐3 and MMP‐13. FN and LN induced MMP‐9 to lesser extents compared with TN‐C. b‐FGF had no effect on MMP‐9 expression. TGF‐β1 induced MMP‐9 expression in a dose‐dependent manner, and this induction was significantly enhanced by addition of TN‐C. TN‐C and TGF‐β1 also upregulated MMP‐9 expression in the human breast cancer cell line MDA‐MB‐231. Neutralization with specific anti‐TGF‐β1 antibody showed decreased expression of MMP‐9, indicating that TGF‐β controls the baseline MMP‐9 expression by a direct autocrine mechanism. Under neutralization of TGF‐β, addition of TN‐C still upregulated MMP‐9. Conversely, neutralization of endogenous TN‐C (in a TN‐C‐positive mammary cancer cell line) downregulated TGF‐β‐induced MMP‐9 expression. Thus, TN‐C induces MMP‐9 expression directly and by collaboration with TGF‐β. These findings reveal a novel role of TN‐C in breast cancer progression. © 2003 Wiley‐Liss, Inc.