bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression analysis in Interleukin‐12‐induced suppression of mouse mammary carcinoma
Authors: Shi Xiaoyan , Liu Jianguo , Xiang Zhaoying , Mitsuhashi Maki , Wu Rita S. , Ma Xiaojing 
Published: April 2004

AbstractInterleukin‐12 (IL‐12) has potent antitumor activities via natural killer cells and cytotoxic T lymphocytes. However, the molecular mechanisms whereby IL‐12 induces tumoricidal activities are poorly understood. Here, we report the genome‐wide analysis of gene expression in a primary murine mammary carcinoma model that resembles human breast cancer, following the therapeutic application of recombinant IL‐12, which restricted tumor growth and metastasis. IL‐12 was able to curtail neovascularization in the tumor as well as enhance the number of tumor‐infiltrating lymphocytes. Comprehensive examination of global gene expression revealed IL‐12‐induced molecular changes associated with tumor regression and reduced lung metastasis, thus providing a high‐resolution snapshot of a host response against a developing malignancy and a rich source of potential targets for therapeutic intervention of breast cancer. © 2004 Wiley‐Liss, Inc.
Breast carcinoma cells promote the differentiation of CD34+ progenitors towards 2 different subpopulations of dendritic cells with CD1ahighCD86−Langerin‐ and CD1a+CD86+Langerin+ phenotypes
Authors: Thomachot Marie Cécile , Bendriss‐Vermare Nathalie , Massacrier Catherine , Biota Cathy , Treilleux Isabelle , Goddard Sophie , Caux Christophe , Bachelot Thomas , Blay Jean Yves , Menetrier‐Caux Christine 
Published: April 2004

AbstractPrimary breast carcinoma are frequently infiltrated by dendritic cells (DC). The mechanisms involved in the localization and status of activation of DC within primary breast carcinoma were investigated. CCL20/MIP3α, a chemokine involved in immature DC and their precursors attraction, was detected by immunohistochemistry on cryopreserved tissue sections of primary breast tumors and by ELISA and biological assay in metastatic effusion fluids from breast cancer patients but not from other tumors. In vitro, irradiated breast carcinoma cell lines (BCC) as well as their conditioned media promoted CD34+ cell differentiation into CD1a+ Langerhans cells (LC) precursors as early as day 6, while at day 12, 2 different CCR6+ subpopulations of DC with a Langerhans cell (CD1a+Langerin+CD86+) and an immature DC (CD1ahighLangerin‐CD86−HLA‐DRlowCD40low) phenotype were observed. This phenomenon was partly driven by a TGFβ‐dependent mechanism since a pan TGFβ polyclonal antibody completely blocks BCC‐induced LC differentiation and partly reduces immature DC development. These DC failed to maturate in response to sCD40L or LPS stimuli and CD1ahighLangerin−CD86− cells have a reduced T‐cell stimulatory capacity in MLR experiments. The absolute number of T cells was reduced by 50% in both the CD4+ or CD8+ compartments, these T cells expressing lower levels of the CD25 Ag and producing less IFNγ. These results show that breast carcinoma cells produce soluble factors, which may attract DC and their precursors in vivo, and promote the differentiation of the latter into LC and immature DC with altered functional capacities. The infiltration of BCC by these altered DC may contribute to the impaired immune response against the tumor. © 2004 Wiley‐Liss, Inc.
Polymorphisms in the one‐carbon metabolic pathway, plasma folate levels and colorectal cancer in a prospective study
Authors: Chen Jia , Kyte Charles , Valcin Martin , Chan Wendy , Wetmur James G. , Selhub Jacob , Hunter David J. , Ma Jing 
Published: April 2004

AbstractOne‐carbon (e.g., folate) metabolism plays a pivotal role in the etiology of colorectal cancer (CRC). Cytosolic serine hydroxymethyltransferase (cSHMT), methylenetetrahydrofolate dehydrogenase (MTHFD1) and glutamate carboxypeptidase II (GCPII) are key genes involved in this pathway. Several new polymorphisms have been identified and there is evidence implicating their functionality. We examined whether polymorphisms in these genes, i.e., cSHMT L474F, MTHFD1 R653Q and GCPII H475Y, modify the risk of CRC in the prospective Physicians' Health Study. Among the 270 incident CRC cases and 453 controls, none of the one‐carbon polymorphisms were associated with risk of CRC. Compared to the wild‐type genotype, the multivariate‐adjusted relative risks and 95% confidence intervals were 1.14 [0.68, 1.93] for cSHMT 474FF, 1.04 [0.67, 1.62] for MTHFD1 653QQ and 1.00 [0.55, 1.82] for GCPII 474HY. Furthermore, we examined the associations between one‐carbon polymorphisms and folate status in terms of plasma folate and homocysteine levels in this population. No independent gene effect was observed. Although compound homozygous variants at cSHMT and MTHFD1 loci had the lowest plasma folate levels compared to other compound genotypes, no significant gene‐gene interactions were observed. Findings from our prospective investigation indicate that these newly identified polymorphisms in one‐carbon metabolizing genes have limited functionality in modifying folate status and related CRC risk. © 2004 Wiley‐Liss, Inc.
Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice
Authors: Murakami Akira , Tanaka Takuji , Lee Ji‐Yoon , Surh Young‐Joon , Kim Ha Won , Kawabata Kyuichi , Nakamura Yoshimasa , Jiwajinda Suratwadee , Ohigashi Hajime 
Published: April 2004

AbstractWe recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines. In our present study, the anti‐tumor initiating and promoting activities of zerumbone in mouse skin were evaluated using a conventional 2‐stage carcinogenesis model. A single topical pretreatment to mouse skin (2 μmol) 24 hr before application of dimethylbenz[a]anthracene (0.2 μmol) markedly suppressed tumor incidence by 60% and the number of tumors by 80% per mouse. Repeated pretreatment (16 nmol) twice weekly during the post‐initiation phase reduced the number of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA, 1.6 nmol)‐induced tumors by 83% as well as their diameter by 57%. Multiple reverse transcriptase (RT) PCR experiments revealed that zerumbone (2 μmol) enhanced the mRNA expression level of manganese superoxide dismutase, glutathione peroxidase‐1, glutathione S‐transferase‐P1 and NAD(P)H quinone oxidoreductase in the epidermis, but not that of cytochrome P450 1A1 or 1B1. Further, it diminished TPA‐induced cyclooxygenase‐2 protein expression and phosphorylation of extracellular signal‐regulated kinase 1/2, while pretreatment(s), in either the priming or activation stage or both, reduced double TPA application‐induced hydrogen peroxide formation and edema induction by 29% to 86%, respectively. Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen‐labeling indices. Together, our results indicate that zerumbone is a promising agent for the prevention of both tumor initiating and promoting processes, through induction of anti‐oxidative and phase II drug metabolizing enzymes as well as attenuation of proinflammatory signaling pathways. © 2004 Wiley‐Liss, Inc.
Maternal breast cancer risk after the death of a child
Authors: Lambe Mats , Cerrato Ruha , Askling Johan , Hsieh Chung‐cheng 
Published: April 2004

AbstractThe possible association between a severe traumatic life event (death of a child) and breast cancer risk was examined in a case‐control study nested within a nation‐wide cohort in Sweden. Our study population included 27,571 women with breast cancer and 141,798 control women born between 1925–1976. After adjustment for age, parity, age at first birth and education, the overall risk estimate for breast cancer among all women that had experienced the death of a child was 1.05 (95% confidence interval [CI] = 0.96–1.15). Among uniparous women the corresponding odds ratio (OR) was 1.27 (95% CI = 0.98–1.64). When stratifying for child's age at death a significant risk increase was detected among women that had lost their only child when the child was between 1–4 years of age (OR = 2.65; 95% CI = 1.06–6.60). These findings do not support an overall increase in breast cancer risk after the death of a child, a severe traumatic life event. Based on a small number of subjects, our finding of an increased risk in a subgroup of uniparous women losing their only child could be due to chance. © 2004 Wiley‐Liss, Inc.
Promoter polymorphisms of tumor necrosis factor‐α are associated with risk of gastric mucosa–associated lymphoid tissue lymphoma
Authors: Wu Ming‐Shiang , Chen Li‐Tzong , Shun Chia‐Tung , Huang Shih‐Pei , Chiu Han‐Mo , Wang Hsiu‐Po , Lin Ming‐Tsang , Cheng Ann‐Lii , Lin Jaw‐Town 
Published: April 2004

AbstractGenes involved in regulating antimicrobial immunity and inflammation may modulate the risk of Helicobacter pylori–associated diseases. IL‐1 and TNF‐α are major cytokines detected in H. pylori–infected tissues. We aimed to determine the role of gene polymorphisms for these cytokines and their receptors in 2 distinct H. pylori–related gastric malignancies, adenocarcinoma (GAC) and maltoma. Genotyping for IL‐1β (–31 C/T, –511 C/T), TNF‐α (–238 G/A, –308 G/A, –857 C/T, –863 C/A, –1031 T/C), TNFR1 (–383 A/C) and TNFR2 (196 G/T) was undertaken for 70 patients with maltoma and 204 patients with noncardia GAC and compared to 210 unrelated healthy controls. Genotype frequencies showed no differences among patients with GAC or maltoma and controls for IL‐1β, TNFR1 or TNFR2. The TNF‐α –857 T variant was significantly underrepresented in maltoma compared to controls (6.4% vs. 14.3%, p = 0.018), conferring a 3‐fold decrease in risk (OR = 0.33, 95% CI 0.15–0.75). Comparison of allele frequencies between GAC and controls failed to show any statistical significance for TNF‐α polymorphisms. We concluded that TNF‐α –857 T itself or a neighboring gene may modify the risk of maltoma. The differences in genetic background as well as divergent clinicopathologic features between GAC and maltoma support the notion that fundamental mechanistic differences exist in these 2 well‐defined H. pylori–related malignancies. © 2004 Wiley‐Liss, Inc.
Poly(phosphoester) ionomers as tissue‐engineering scaffolds
Authors: Wan Andrew C. A. , Mao Hai‐Quan , Wang Shu , Phua Su Hui , Lee Gin Ping , Pan Jisheng , Lu Shen , Wang Jun , Leong Kam W. 
Published: April 2004

AbstractRegenerative medicine requires scaffolds of divergent physicochemical properties for different tissue‐engineering applications. To this end, a series of biodegradable poly(phosphoester) ionomers of the general composition [p(BHET‐EOP‐HOP/TC)] was synthesized, with BHET(bis‐hydroxyl ethylene phosphate):EOP(ethylene phosphate):HOP(free phosphate) ratios of 60:20:20, 70:10:20, and 75:5:20, respectively. The 60/20/20 ionomer possessed the best tensile properties, exhibiting an average tensile modulus of 68 MPa and strain at break of 31%. Calcium treatment of the ionomer films led to significantly higher hardness and elastic moduli as measured by indentation. Calcium binding was evident from the increase in glass transition and melting temperatures, and a shift in the P→O absorption in the FTIR spectrum. Stable N‐hydroxysuccinimide ester (NHS) of the ionomers could be synthesized to facilitate derivatization, as demonstrated by conjugation of GRGDS in this study. The polymers conjugated with NHS were hydrolyzed in a biphasic mode, with a fast initial phase occurring in the first few hours, followed by a slower phase in the next few days. These ionomers represent a novel class of biomaterials with readily controllable physical and chemical attributes for tissue engineering. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 91–102, 2004
Flexural fatigue behavior of machinable and light‐activated hybrid composites for esthetic restorations
Authors: Yoshida Keiichi , Morimoto Nobuko , Tsuo Yukiko , Atsuta Mitsuru 
Published: April 2004

AbstractThe purpose of this study was to determine the flexural strength and flexural fatigue strength of a machinable composite (GN‐I) and three hybrid composites (Artglass, Estenia, and Gradia). Specimens (2 × 2 × 25 mm) were polymerized in a laboratory photo‐curing unit and then immersed in water at 37°C for 24 h, 6 months, and 1 year. After each immersion period, flexural strengths (4‐PFS) were measured at a cross‐head speed of 1 mm/min in 4‐point bending (span = 20 mm; distance between inside loading points = 10 mm). The cyclic fatigue test was performed at 2.0 Hz on a fatigue tester. The staircase method was employed for flexural fatigue strength (FFS) using a 5000 cyclic load limitation, 5‐MPa stress increment, and 20 specimens for each material. Both 4‐PFS and FFS of the machinable composite after all immersion periods were significantly greater than those of the three hybrid composites. The FFS results followed the same pattern as those of the 4‐PFS. The Estenia material exhibited the highest 4‐PFS and FFS after 24 h of immersion among three hybrid composites, whereas after 1 year of immersion, all three composites showed almost identical 4‐PFS and FFS statistically. A strong correlation was observed between 4‐PFS and FFS of the machinable composite and three hybrid resin composites. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 70B: 218–222, 2004
Improvement of endothelium‐dependent coronary vasodilation after a single LDL apheresis in patients with hypercholesterolemia
Authors: Igarashi Keiichi , Tsuji Masahiro , Nishimura Masaharu , Horimoto Masashi 
Published: April 2004

AbstractThe purpose of this study was to determine whether a single LDL apheresis would improve impaired endothelium‐dependent dilation of the coronary artery in patients with hypercholesterolemia. Hypercholesterolemia is associated with impaired endothelial function, and human studies using cholesterol‐lowering drugs indicate that endothelial function in the coronary arteries improves with reduction of serum LDL cholesterol over 6 to 12 months. The internal diameter of the left coronary artery and the coronary blood flow were measured by intracoronary Doppler‐wire measurement and quantitative angiography before and immediately after a single LDL apheresis in a population of 15 patients with familial hypercholesterolemia. Endothelium‐dependent vasodilation was assessed by intracoronary infusion of acetylcholine (1, 10, and 50 μg/min), and endothelium‐independent vasodilation was assessed by intracoronary bolus infusion of isosorbide dinitrate (2.5 mg) or papaverine (10 mg). A single 3‐hour LDL apheresis reduced serum LDL cholesterol by an average of 86.6 ± 1.7%. After the LDL apheresis, the changes in the coronary artery diameter and coronary blood flow in response to an infusion of 50 μg/min of acetylcholine increased significantly compared to the pre‐apheresis values (from −19.7 ± 4.8 to −2.9 ± 3.0% [P < 0.01] and from 80.7 ± 27.6 to 155.3 ± 23.5% [P < 0.01], respectively). The LDL apheresis did not significantly change the response of either parameter to infusion with isosorbide dinitrate or papaverine. The endothelial function of the epicardial coronary artery and the coronary microvasculature improved in hypercholesterolemic patients after only a single LDL apheresis, a procedure that markedly reduces the serum level of LDL cholesterol. J. Clin. Apheresis 19:11–16, 2004. © 2004 Wiley‐Liss, Inc.
Seasonal environmental changes modulate the prolactin receptor expression in an eurythermal fish
Authors: San Martín Rody , Cáceres Pilar , Azócar Rodrigo , Alvarez Marco , Molina Alfredo , Vera María I. , Krauskopf Manuel 
Published: April 2004

AbstractEurythermal fish have evolved compensatory responses to the cyclical seasonal changes of the environment. The complex adaptive mechanisms include the transduction of the physical parameters variations into molecular signals. Studies in carp have indicated that prolactin and growth hormone expression is associated with acclimatization, suggesting that the pituitary gland is a relevant physiological node in the generation of the homeostatic rearrangement that occurs in this adaptive process. Here, we report the cloning and characterization of a full‐length carp prolactin receptor cDNA, which codes for the long form of the protein resembling that found in mammalian prolactin receptors. We identified up to three receptor transcript isoforms in different tissues of the teleost and assessed cell‐ and temporal‐specific transcription and protein expression in carp undergoing seasonal acclimatization. The distinctive pattern of expression that carp prolactin receptor (cPRLr) depicts upon seasonal acclimatization supports the hypothesis that prolactin and its receptor are clearly involved in the new homeostatic stage that the eurythermal fish needs to survive during the cyclical changes of its habitat. © 2004 Wiley‐Liss, Inc.
How do glucocorticoids compare to oligo decoys as inhibitors of collagen synthesis and potential toxicity of these therapeutics?
Authors: Cutroneo Kenneth R. , Sterling Kenneth M. 
Published: April 2004

AbstractThis article demonstrates how glucocorticoids decrease collagen synthesis. The parameters used to assess procollagen synthesis in our laboratory will be compared to those used by others. This article will note all the pertinent literature on the molecular mechanisms of this down regulation of procollagen synthesis. For example, what are the effects of glucocorticoids at the levels of transcription and translation of collagen mRNAs? Finally, we will define a molecular mechanism to inhibit Type I collagen synthesis by decreasing the binding of the TGF‐β activator protein complex to the TGF‐β element in the distal promoter of the proα1 Type I collagen gene, preventing the 2:1 ratio of α1 to α2 chains in the processed Type I collagen molecule. We will next ask “How do sense oligo decoys decrease Type I collagen synthesis at the in vivo and at the cell levels?” In primary fibrotic cell culture, the double‐stranded phosphorothioate oligodeoxynucleotide decoys were more effective than their sense single‐stranded counterparts. The molecular mechanism for the decrease in Type I collagen synthesis is the same as glucocorticoids, that is by decreasing the binding of the TGF‐β activator protein complex to the TGF‐β element in the distal promoter of the proα1 Type I collagen gene for the transcription of the proα1 mRNAs. The reason for using sense oligo decoys as anti‐fibrotic agents as compared to the anti‐fibrotic glucocorticoids, is that presently marketed and FDA approved glucocorticoids have many untoward side effects which the sense oligo decoys do not have. © 2004 Wiley‐Liss, Inc.
Vascular endothelial growth factor expression in heart of rats exposed to hypobaric hypoxia: Differential response between mRNA and protein
Authors: Birot Olivier J.G. , Peinnequin André , Simler Nadine , Cuyck‐Gandré Hélène van , Hamel Rodolphe , Bigard Xavier A. 
Published: April 2004

AbstractThis study investigated the role of vascular endothelial growth factor (VEGF) in the neoangiogenesis induced in heart in response to hypoxia. The time‐course of adaptive changes in capillary supply, expression of VEGF mRNA and protein was studied in right (RV) and left ventricles (LV) of rats exposed to hypobaric hypoxia during 1–25 days (barometric pressure = 505 hPa). VEGF mRNA levels encoding for VEGF 188 and 164 isoforms were measured by reverse transcription‐polymerase chain reaction (RT‐PCR) and VEGF protein was determined by Western blotting. Relative RV weight (i.e., weight of RV related to body weight) increased with hypoxia and was 102% higher than in controls after 15 days of exposure (P < 0.01), while relative LV weight remained unaltered. A rapid and transient increase in VEGF 188 mRNA occurred after 1 day of hypoxia in LV (P < 0.05). Thereafter, a delayed increase in VEGF 188 mRNA expression occurred in RV (ANOVA, P < 0.001). By day 18, VEGF 188 mRNA level was higher in hypoxic than in control rats (P < 0.005) and then decreased to base line levels. Hypoxia did not affect the expression of VEGF 164 mRNA neither in LV nor in RV. One of the main results was that these hypoxia‐induced alterations in VEGF transcripts were not followed by associated increase in VEGF protein. These results suggest that capillary growth observed in RV after prolonged exposure to ambient hypoxia likely results from other molecular mechanisms than VEGF. © 2004 Wiley‐Liss, Inc.
Activity and expression of Xenopus laevis matrix metalloproteinases: Identification of a novel role for the hormone prolactin in regulating collagenolysis in both amphibians and mammals
Authors: Jung Jae‐Chang , West‐Mays Judith A. , Stramer Brian M. , Byrne Michael H. , Scott Sumi , Mody Mehernosh K. , Sadow Peter M. , Krane Stephen M. , Fini M. Elizabeth 
Published: April 2004

AbstractProlactin (PRL) has long been implicated in Xenopus metamorphosis as an anti‐metamorphic and/or juvenilizing hormone. Numerous studies showed that PRL could prevent effects of either endogenous or exogenous thyroid hormone (TH; T3). It has been shown that expression of matrix metalloproteinases (MMPs) is induced by TH during Xenopus metamorphosis. Direct in vivo evidence, however, for such anti‐TH effects by PRL with respect to MMPs has not been available for the early phase of Xenopus development or metamorphosis. To understand the functional role of PRL, we investigated effects of PRL on Xenopus collagenase‐3 (XCL3) and collagenase‐4 (XCL4) expression in a cultured Xenopus laevis cell line, XL‐177. Northern blot analysis demonstrated that XCL3 and XCL4 expression were not detected in control or T3‐treated cells, but were differentially induced by PRL in a dose‐ and time‐dependent fashion. Moreover, treatment with IL‐1α as well as phorbol myristate acetate (PMA), a protein kinase C (PKC) activator, or H8, a protein kinase A (PKA) inhibitor, augmented PRL‐induced collagenase expression, suggesting that multiple protein kinase pathways and cytokines may participate in PRL‐induced collagenase expression. Interestingly, XCL3 expression could be induced in XL‐177 cells by T3, but only when co‐cultured with prometamorphic Xenopus tadpole tails (stage 54/55), suggesting that the tails secrete a required intermediate signaling molecule(s) for T3‐induced XCL3 expression. Taken together, these data demonstrate that XCL3 and XCL4 can be differentially induced by PRL and T3 and further suggest that PRL is a candidate regulator of TH‐independent collagenase expression during the organ/tissue remodeling which occurs in Xenopus development. J. Cell. Physiol. 201: 155–164, 2004. © 2004 Wiley‐Liss, Inc.