bluuebunny/crossref_metadata_2025_split huggingface dataset:
17β‐hydroxysteroid dehydrogenase Type 1, and not Type 12, is a target for endocrine therapy of hormone‐dependent breast cancer
Authors: Day Joanna M. , Foster Paul A. , Tutill Helena J. , Parsons Michael F.C. , Newman Simon P. , Chander Surinder K. , Allan Gillian M. , Lawrence Harshani R. , Vicker Nigel , Potter Barry V.L. , Reed Michael J. , Purohit Atul 
Published: January 2008

AbstractOestradiol (E2) stimulates the growth of hormone‐dependent breast cancer. 17β‐hydroxysteroid dehydrogenases (17β‐HSDs) catalyse the pre‐receptor activation/inactivation of hormones and other substrates. 17β‐HSD1 converts oestrone (E1) to active E2, but it has recently been suggested that another 17β‐HSD, 17β‐HSD12, may be the major enzyme that catalyses this reaction in women. Here we demonstrate that it is 17β‐HSD1 which is important for E2 production and report the inhibition of E1‐stimulated breast tumor growth by STX1040, a non‐oestrogenic selective inhibitor of 17β‐HSD1, using a novel murine model. 17β‐HSD1 and 17β‐HSD12 mRNA and protein expression, and E2 production, were assayed in wild type breast cancer cell lines and in cells after siRNA and cDNA transfection. Although 17β‐HSD12 was highly expressed in breast cancer cell lines, only 17β‐HSD1 efficiently catalysed E2 formation. The effect of STX1040 on the proliferation of E1‐stimulated T47D breast cancer cells was determined in vitro and in vivo. Cells inoculated into ovariectomised nude mice were stimulated using 0.05 or 0.1 μg E1 (s.c.) daily, and on day 35 the mice were dosed additionally with 20 mg/kg STX1040 s.c. daily for 28 days. STX1040 inhibited E1‐stimulated proliferation of T47D cells in vitro and significantly decreased tumor volumes and plasma E2 levels in vivo. In conclusion, a model was developed to study the inhibition of the major oestrogenic 17β‐HSD, 17β‐HSD1, in breast cancer. Both E2 production and tumor growth were inhibited by STX1040, suggesting that 17β‐HSD1 inhibitors such as STX1040 may provide a novel treatment for hormone‐dependent breast cancer. © 2008 Wiley‐Liss, Inc.
Diagnostic targeting of colon cancer using a novel fluorescent somatostatin conjugate in a mouse xenograft model
Authors: Kostenich Genady , Oron‐Herman Mor , Kimel Sol , Livnah Nurit , Tsarfaty Ilan , Orenstein Arie 
Published: January 2008

AbstractColorectal carcinoma is one of the more prevalent, highly malignant human tumors, occurring in about 7% of the population. However, if diagnosed and treated in its early stages, colon cancer is curable. In our study, we used a mouse xenograft model to investigate the capability of a fluorescent conjugate of a novel synthetic somatostatin (SST) analog to improve detection of human colorectal tumors that are characterized by over‐expressed SST receptors. Human HT‐29 colon carcinomas were induced in nude mice. After administration of the fluorescent SST conjugate, in vivo low‐ and high‐magnification fluorescence microscopy, as well as high‐resolution spectrally resolved imaging were performed, and the time‐dependent biodistribution was determined quantitatively (using fiber‐optic spectroscopy). Administration of the conjugate (at concentrations of 6 mg/kg body weight) enabled targeting small (1–5 mm diameter) tumors with high sensitivity and selectivity. Toxicity studies at dosages up to 1,000 mg/kg body weight did not reveal any drug related abnormalities. In conclusion, the SST conjugate significantly enhanced the detection of HT‐29 colon tumors by fluorescence imaging because of a 5‐ to 8‐fold increase in the contrast between malignant and normal tissues. © 2008 Wiley‐Liss, Inc.
Evidence of a novel docetaxel sensitizer, garlic‐derived S‐allylmercaptocysteine, as a treatment option for hormone refractory prostate cancer
Authors: Howard Edward W. , Lee Davy T. , Chiu Yung Tuen , Chua Chee Wai , Wang Xianghong , Wong Yong Chuan 
Published: January 2008

AbstractThe recent introduction of docetaxel in the treatment of hormone refractory prostate cancer (HRPC) has made a small but significant impact on patient survival. However, its effect is limited by intolerance and resistance. The aim of our study was to investigate if the garlic‐derived compound, S‐allylmercaptocysteine (SAMC), was able to act as a docetaxel sensitizing agent. First, the effect of SAMC on docetaxel sensitivity was examined on 3 HRPC cell lines by colony forming assay. We found that SAMC increased the efficacy of docetaxel on colony forming inhibition by 9–50% compared to single agent treatment. Second, using the HRPC CWR22R nude mice model, we found that the combination of SAMC and docetaxel was 53% more potent than docetaxel alone (p = 0.037). In addition, there was no additive toxicity in the mice treated with the combination therapy evidenced by histological and functional analysis of liver, kidney and bone marrow. These results suggest that SAMC is able to increase the anticancer effect of docetaxel without causing additional toxic effect in vivo. Third, flow cytometry and Western blotting analysis on HRPC cell lines demonstrated that SAMC promoted docetaxel‐induced G2/M phase cell cycle arrest and apoptotic induction. In addition, immunohistochemistry on CWR22R xenograft revealed a suppression of Bcl‐2 expression and upregulation of E‐cadherin in the SAMC and docetaxel treated animals. These results suggest that SAMC may promote docetaxel‐induced cell death through promoting G2/M cell cycle arrest and apoptosis. Our study implies a potential role for SAMC in improving docetaxel based chemotherapy for the treatment of HRPC. © 2008 Wiley‐Liss, Inc.
Time‐space trends in cancer incidence in The Netherlands in 1989–2003
Authors: Siesling Sabine , van der Aa Maaike A. , Coebergh Jan W.W. , Pukkala Eero ,   on behalf of the Working Group of The Netherlands Cancer Registry
Published: January 2008

AbstractIncidence of cancer may vary within a country and over time because of previous differences in exposure to risk factors or interventions for early detection (screening). This study describes time‐space trends of incidence of common cancer sites across the Netherlands during the period 1989–2003 and speculates on the reasons for the observations. From the Netherlands Cancer Registry, World standardized incidence rates per municipality were smoothed calculating weighted averages for each 2 km by 2 km grid of the population mid‐points of neighbouring municipalities and presented as map animations. Spatial relative changes in incidence were estimated by comparing the periods 1989–1994 and 1998–2003. Complete time‐space trends can be found as map animations on http://maps.ikcnet.nl. The incidence of cervical and stomach cancer (for both sexes) decreased, being higher in the cities than in the rural areas during all periods and contrasting the trends in colorectal and breast cancer. The relative increase in incidence of lung cancer among females was highest in the rural north, but the incidence remained higher in the cities of the mid‐west Netherlands. For males, there was a marked decrease in lung cancer incidence across the country since 1991. Incidence of melanoma increased, rates being twice as high in the coastal area than in the cities. Prostate cancer maps largely replicated the known history of PSA‐testing in the Netherlands. Time‐space cancer incidence patterns gave insight into effects of changes in exposure to risk determinants and early detection. The maps illustrate marked potential for cancer prevention at the national and regional level. © 2008 Wiley‐Liss, Inc.
Acrylamide exposure and incidence of breast cancer among postmenopausal women in the Danish Diet, Cancer and Health Study
Authors: Thonning Olesen Pelle , Olsen Anja , Frandsen Henrik , Frederiksen Kirsten , Overvad Kim , Tjønneland Anne 
Published: January 2008

AbstractAcrylamide, a probable human carcinogen, is formed in several foods during high‐temperature processing. So far, epidemiological studies have not shown any association between human cancer risk and dietary exposure to acrylamide. The purpose of this study was to conduct a nested case control study within a prospective cohort study on the association between breast cancer and exposure to acrylamide using biomarkers. N‐terminal hemoglobin adduct levels of acrylamide and its genotoxic metabolite, glycidamide in red blood cells were analyzed (by LC/MS/MS) as biomarkers of exposure on 374 breast cancer cases and 374 controls from a cohort of postmenopausal women. The adduct levels of acrylamide and glycidamide were similar in cases and controls, with smokers having much higher levels (∼3 times) than nonsmokers. No association was seen between acrylamide‐hemoglobin levels and breast cancer risk neither unadjusted nor adjusted for the potential confounders HRT duration, parity, BMI, alcohol intake and education. After adjustment for smoking behavior, however, a positive association was seen between acrylamide‐hemoglobin levels and estrogen receptor positive breast cancer with an estimated incidence rate ratio (95% CI) of 2.7 (1.1–6.6) per 10‐fold increase in acrylamide‐hemoglobin level. A weak association between glycidamide hemoglobin levels and incidence of estrogen receptor positive breast cancer was also found, this association, however, entirely disappeared when acrylamide and glycidamide hemoglobin levels were mutually adjusted. © 2008 Wiley‐Liss, Inc.
Increased antitumor potential of the raloxifene prodrug, raloxifene diphosphate
Authors: Okamoto Yoshinori , Liu Xiaoping , Suzuki Naomi , Okamoto Kanako , Sekimoto Masashi , Laxmi Y.R. Santosh , Shibutani Shinya 
Published: January 2008

AbstractRaloxifene (RAL) significantly reduced the incidence of breast cancer in women at high risk of developing the disease. Unlike tamoxifen (TAM), an increased incidence of endometrial cancer was not observed in women treated with RAL. However, RAL, having two hydroxyl moieties, can be conjugated rapidly through phase II metabolism and excreted, making it difficult to achieve adequate bioavailability by oral administration in humans. As a result, higher doses must be administered to obtain an efficacy equivalent to that achieved with TAM. To improve oral bioavailability and antitumor potential, RAL diphosphate was prepared as a prodrug. RAL diphosphate showed several orders of magnitude lower binding potential to both ERα and ERβ and weak antiproliferative potency on cultured human MCF‐7 and ZR‐75‐1 breast cancer cells, as compared to RAL. However, RAL diphosphate has a much higher bioavailability than RAL, endowing it with higher antitumor potential than RAL against both 7,12‐dimethylbenz(a)anthracene‐induced mammary carcinoma in rats and human MCF‐7 breast cancer implanted in athymic nude mice. The RAL prodrug may provide greater clinical benefit for breast cancer therapy and prevention. © 2008 Wiley‐Liss, Inc.
Sustainability of rice‐dominated cropping system in the Hirakud canal command, Orissa, India
Authors: Raul S. K. , Panda S. N. , Hollaender H. , Billib M. 
Published: January 2008

AbstractThe present rice‐based cropping system in the canal command of the Hirakud irrigation project, Orissa (India), is under severe threat due to waterlogging in the monsoon season and acute irrigation water deficit in the non‐monsoon season. Estimation of irrigation water supply and demand reveals that at the present level of cropping, canal water availability during the monsoon is just sufficient to meet the irrigation requirements of crops at only 10% probability of exceedance. During the non‐monsoon season, irrigation water requirement at 10% probability of exceedance exceeds canal water availability by more than 1050 million m3. Groundwater table fluctuation study reveals that during the monsoon more than 90% of the command area remains and during the non‐monsoon, in more than 40% of the area the groundwater table remains within 2–4 m of the surface. Hence there is ample scope for groundwater development. However, even at the permissible limit of groundwater development, the annual water deficit is more than 1000 million m3 at 50% probability of exceedance of irrigation water demand, which can only be mitigated by replacing the existing non‐monsoon rice by other crops with low water requirements as cultivated in the command. Copyright © 2008 John Wiley & Sons, Ltd.
Doxycycline treatment prevents alveolar destruction in VEGF‐deficient mouse lung
Authors: Rossiter Harry B. , Scadeng Miriam , Tang Kechun , Wagner Peter D. , Breen Ellen C. 
Published: January 2008

AbstractIn vivo lung‐targeted VEGF gene inactivation results in pulmonary cell apoptosis, airspace enlargement, and increased lung compliance consistent with an emphysema‐like phenotype. The predominant hypothesis for the cause of lung destruction in emphysema is an imbalance between active lung protease and anti‐protease molecules. Therefore, we investigated the role of protease (e.g., matrix metalloproteinases—MMPs) and anti‐protease (e.g., tissue inhibitors of metalloproteinases—TIMPs) expression in contributing to the lung structural remodeling observed in pulmonary‐VEGF‐deficient mice. VEGFLoxP mice instilled through the trachea with an adeno‐associated virus expressing Cre recombinase (AAV/Cre) manifest airspace enlargement and a greater (P < 0.05) mean linear intercept (MLI: 44.2 ± 4.2 µm) compared to mice instilled with a control virus expressing LacZ (31.3 ± 2.5 µm). Airspace enlargement was prevented by the continuous administration of the general MMP inhibitor, doxycycline (Dox) (Cre + Dox: 32.6 ± 2.5 µm), and MLI values were not different from either control (LacZ + Dox: 30.5 ± 1.2 µm). In situ magnetic resonance imaging of VEGF gene inactivated mouse lungs revealed uneven inflation, residual trapped gas volumes upon oxygen absorption deflation/re‐inflation, and loss of parenchymal structure; effects that were largely prevented by Dox. Five weeks after AAV/Cre infection Western blot revealed a 9.9‐fold increase in pulmonary MMP‐3, and 2‐fold increases in MMP‐9 and TIMP‐2. However, the increase in MMP‐3 was prevented by Dox administration and was associated with a 2‐fold increase in serpin b5 (Maspin) expression. These results suggest that doxycycline treatment largely prevents the aberrant lung remodeling response observed in VEGF‐deficient mouse lungs and is associated with changes in protease and anti‐protease expression. J. Cell. Biochem. 104: 525–535, 2008. © 2008 Wiley‐Liss, Inc.
Synthesis of 14C‐labeled and 13C‐,15N‐labeled dasatinib and its piperazine N‐dealkyl metabolite
Authors: Allentoff Alban J. , Lago Michael W. , Ogan Marc , Chen Bang‐Chi , Zhao Rulin , Iyer Ramaswarmy A. , Christopher Lisa J. , Rinehart J. Kent , Balasubramanian Balu , Bonacorsi Samuel J. 
Published: January 2008

AbstractDasatinib (SPRYCEL®) is a multiple kinase inhibitor approved for the treatment of chronic myelogenous leukemia and Philadelphia chromosome‐positive acute lymphoblastic leukemia in patients with resistance to prior therapy, including imatinib mesylate (Gleevec®). Radiolabeled dasatinib and its piperazine N‐dealkyl metabolite were synthesized to investigate absorption, distribution, metabolism, and elimination of the compounds in humans and animals. These compounds were prepared following a three‐step sequence, which included thiazole carboxamide formation via cyclization of labeled thiourea with a brominated oxyacrylamide precursor. In the final step a common intermediate was converted to either [14C]dasatinib or the radiolabeled piperazine N‐dealkyl metabolite with labeling in the aminothiazole ring. Syntheses of both compounds were achieved with radiochemical purities in excess of 98%. Stable‐labeled dasatinib and the piperazine N‐dealkyl metabolite were also needed for use as mass spectral internal standards in support of bioanalytical assays. By following the same route used for the carbon‐14 synthesis, [13C4, 15N2]dasatinib and the [13C4, 15N2]metabolite were prepared with labeling in both the dichloropyrimidine and thiazole ring systems. This convergent process introduced stable isotope labeling through (1, 2, 3‐13C3) diethyl malonate and [13C,15N2]thiourea. Copyright © 2008 John Wiley & Sons, Ltd.
Hepatocellular carcinoma treated with radio frequency ablation: An early evaluation with magnetic resonance imaging
Authors: Khankan Azzam A. , Murakami Takamichi , Onishi Hiromitsu , Matsushita Masaki , Iannaccone Riccardo , Aoki Yoshiko , Tono Takeshi , Kim Tonsok , Hori Masatoshi , Osuga Keigo , Passariello Roberto , Nakamura Hironobu 
Published: January 2008

AbstractPurposeTo determine the usefulness of nonenhanced T1‐weighted spoiled gradient‐recalled acquisition in the steady‐state (SPGR) MRI in the early assessment of the efficacy of radio frequency (RF) therapy for hepatocellular carcinoma (HCC).Materials and MethodsA total of 23 patients with 28 HCC nodules treated with percutaneous RF ablation underwent nonenhanced MRI within two days after the RF procedure and contrast‐enhanced computed tomography (CT) one week after. MR assessment of ablation efficacy according to the concentric zonal pattern on T1‐weighted SPGR imaging was compared with the one‐week CT and presence of local recurrence by means of follow‐up study for 12 months or more.ResultsIn 18 of 28 ablated nodules, SPGR images revealed a central hyperintense zone covering the entire tumor, CT showed a nonenhanced area covering the entire tumor, and no local recurrence was demonstrated in the follow‐up studies. In nine of 28 nodules, the central hyperintense zone did not cover the entire tumor; and local recurrence was demonstrated in three nodules. In the remaining one nodule, no signal change was seen in the treated area on SPGR images and CT showed the presence of residual viable tumor.ConclusionNonenhanced T1‐weighted MRI was considered useful for early assessment of the efficacy of RF therapy for HCC. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
A modified fourier‐based phase unwrapping algorithm with an application to MRI venography
Authors: Bagher‐Ebadian Hassan , Jiang Quan , Ewing James R. 
Published: January 2008

AbstractPurposeTo present a single‐step deterministic procedure for unwrapping MRI phase maps.Materials and MethodsUsing an algorithm previously developed for optical applications, Laplacian operators were applied in the Fourier space of the MRI phase map. The original Fourier‐based phase unwrapping algorithm was modified so that demodulation accomplished the required signal symmetrization in Fourier space. To evaluate the method's performance in the presence of thermal noise, a set of wrapped phase maps were simulated at different levels of noise in k‐space, and the response of the algorithm at different levels of signal‐to‐noise ratio (SNR) was evaluated for stability. To demonstrate its utility in MRI, the algorithm was applied to the wrapped phase maps of susceptibility‐weighted imaging (SWI) studies, which were then used to generate venograms.ResultsIn simulated phase wrapping, the algorithm correctly reproduced the original phase for a wide range of phase gradients and noise. The procedure was fast and produced useful maps of venous structures in SWI images.ConclusionA fast and stable single‐step deterministic method for unwrapping MRI phase maps is available for such applications as SWI and mapping of static magnetic field inhomogeneity. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
First‐pass myocardial perfusion image registration by maximization of normalized mutual information
Authors: Wong Kelvin K. , Yang Edward S. , Wu Ed X. , Tse Hung‐Fat , Wong Stephen T. 
Published: January 2008

AbstractPurposeTo evaluate a left ventricular image registration algorithm for first‐pass MR myocardial perfusion.Materials and MethodsA normalized mutual information based motion correction algorithm was proposed and tested on 27 adenosine stressed myocardial perfusion cases consisting of pretreatment and posttreatment of 15 patients undergone autologous bone marrow mononuclear cell transplant therapy. An image mask approximately covering the left and right ventricles was manually defined to include a region of interest for registration. A two‐dimensional multiresolution registration approach was used to register consecutively acquired multislice images with in‐plane translations. The method was validated by manual registration and singular value deconvolution based perfusion analysis.ResultsThe proposed image registration algorithm was found to be robust in minimizing the in‐plane motion of the left ventricle in first‐pass myocardial perfusion. The image mask including the left and right ventricle was found to be more robust than including the left ventricle alone. A smooth estimate of normalized mutual information coefficients were achieved for images with large contrast changes.ConclusionThe proposed semiautomatic multiresolution registration algorithm was able to register first‐pass MR myocardial perfusion images and may be useful in quantitative perfusion analysis. J. Magn. Reson. Imaging 2008. © 2008 Wiley‐Liss, Inc.
YFa, a chimeric opioid peptide, induces kappa‐specific antinociception with no tolerance development during 6 days of chronic treatment
Authors: Vats Ishwar Dutt , Dolt Karamjit Singh , Kumar Krishan , Karar Jayashree , Nath Mahendra , Mohan Anita , Pasha M. A. Qadar , Pasha Santosh 
Published: January 2008

AbstractOur previous study showed that YGGFMKKKFMRFamide (YFa), a chimeric peptide of Met‐enkephalin, and Phe‐Met‐Arg‐Phe‐NH2induced naloxone‐reversible antinociception and attenuated the development of tolerance to morphine analgesia. In continuation, the present study investigated which specific opioid receptors—μ, δ or κ—mediate the observed YFa antinociception pharmacologically using specific antagonists and whether chronic administration of YFa at 26.01 μmol/kg per day induces tolerance and its effect on the expression of μ and κ opioid receptors from day 4 to day 6, with endomorphine‐1 (EM‐1) and saline taken as positive and negative controls, respectively. Quantitative differential expression analysis was carried out by real‐time reverse‐transcriptase polymerase chain reaction, and the corresponding changes in protein levels were assessed by Western blot. A pharmacological investigation revealed that nor‐binaltorphimine, a specific κ opioid receptor–1 (KOR1) antagonist, completely antagonized the antinociception induced by 39.01 μmol/kg of YFa. Importantly, its chronic intraperitoneal administration did not result in significant tolerance over 6 days, whereas EM‐1 induced significant tolerance after day 4. Differential expression analysis revealed that EM‐1 caused up‐regulation of μ opioid receptor–1 on day 4, followed by down‐regulation on later days. Interestingly, YFa treatment caused a decrease on day 4, followed by an increase in the expression of KOR1 from day 5 onward. In conclusion, YFa induces kappa‐specific antinociception, with no development of tolerance during 6 days of chronic treatment, which further articulates new directions for improved designing of peptide‐based analgesics that may be devoid of adverse effects like tolerance. © 2008 Wiley‐Liss, Inc.