bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoids interfere with therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors
Authors: Sui Meihua , Chen Feng , Chen Zhi , Fan Weimin 
Published: February 2006

AbstractPaclitaxel is a widely used naturally occurring antineoplastic agent that has shown great promise in the treatment of a variety of human solid tumors, particularly for advanced breast and ovarian cancers. Recent studies in our laboratory discovered that glucocorticoids could selectively inhibit paclitaxel‐induced apoptosis in a number of human solid tumor cell lines in vitro. Since glucocorticoids (such as dexamethasone) are routinely used as a premedication in the clinical application of paclitaxel to prevent hypersensitivity reactions and other adverse effects, the inhibitory effect of glucocorticoids on paclitaxel‐induced apoptosis has raised a clinically relevant question as to whether the pretreatment with glucocorticoids might interfere with the therapeutic efficacy of paclitaxel. In the present study, through development of animal models bearing human breast and ovarian xenograft tumors, we evaluated the potential influence of dexamethasone on antitumor activity of paclitaxel in vivo. The results demonstrated that pretreatment of dexamethasone significantly attenuated therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors. The inhibition rate of 20 mg paclitaxel/kg on the growth of breast and ovarian xenograft tumors was around 20–25% less when the animals were pretreated with 1 mg dexamethasone/kg. Further analyses with histological examination and TdT‐mediated dUTP nick end labeling assay indicate that pretreatment with dexamethasone clearly interferes with the cytotoxic effects of paclitaxel on both morphological alterations and induction of cell death. Additionally, immunohistochemical staining of proliferation marker Ki‐67 indicates that the percentage of proliferating cells in xenograft tumors with pretreatment of dexamethasone is much higher than that in the tumors treated with paclitaxel alone. Put together, the results obtained from the animal experiments show that pretreatment of xenograft tumors with dexamethasone results in significant inhibition of the therapeutic efficacy of paclitaxel in vivo. This finding may have a potential implication on the clinical practice of paclitaxel‐based chemotherapy. © 2006 Wiley‐Liss, Inc.
Novel role of TGF‐β in differential astrocyte‐TIMP‐1 regulation: Implications for HIV‐1‐dementia and neuroinflammation
Authors: Dhar Alok , Gardner Jessica , Borgmann Kathleen , Wu Li , Ghorpade Anuja 
Published: February 2006

AbstractAstrocyte production of tissue inhibitor of metalloproteinase (TIMP)‐1 is important in central nervous system (CNS) homeostasis and inflammatory diseases such as HIV‐1‐associated dementia (HAD). TIMPs and matrix metalloproteinases (MMPs) regulate the remodeling of the extracellular matrix. An imbalance between TIMPs and MMPs is associated with many pathologic conditions. Our recently published studies uniquely demonstrate that HAD patients have reduced levels of TIMP‐1 in the brain. Astrocyte‐TIMP‐1 expression is differentially regulated in acute and chronic inflammatory conditions. In this and the adjoining report (Gardner et al., 2006), we investigate the mechanisms that may be involved in differential TIMP‐1 regulation. One mechanism for TIMP‐1 downregulation is the production of anti‐inflammatory molecules, which can activate signaling pathways during chronic inflammation. We investigated the contribution of transforming growth factor (TGF)‐signaling in astrocyte‐MMP/TIMP‐1‐astrocyte regulation. TGF‐β1 and β2 levels were upregulated in HAD brain tissues. Co‐stimulation of astrocytes with IL‐1β and TGF‐β mimicked the TIMP‐1 downregulation observed with IL‐1β chronic activation. Measurement of astrocyte‐MMP protein levels showed that TGF‐β combined with IL‐1β increased MMP‐2 and decreased proMMP‐1 expression compared to IL‐1β alone. We propose that one of the mechanisms involved in TIMP‐1 downregulation may be through TGF‐signaling in chronic immune activation. These studies show a novel extracellular regulatory loop in astrocyte‐TIMP‐1 regulation. © 2006 Wiley‐Liss, Inc.
Generation of graftable dopaminergic neuron progenitors from mouse ES cells by a combination of coculture and neurosphere methods
Authors: Morizane Asuka , Takahashi Jun , Shinoyama Mizuya , Ideguchi Makoto , Takagi Yasushi , Fukuda Hitoshi , Koyanagi Masaomi , Sasai Yoshiki , Hashimoto Nobuo 
Published: February 2006

AbstractParkinson's disease is characterized by a loss of midbrain dopamine (DA) neurons and is generally viewed as a potential target for stem cell therapy. Although several studies have reported the generation of postmitotic DA neurons from embryonic stem (ES) cells, it is unknown whether the proliferative progenitors of DA neurons can be isolated in vitro. To investigate this possibility, we have developed a combined approach in which ES cells are cocultured with PA6 stromal cells to expose them to stromal cell‐derived inducing activity (SDIA) and are then cultured as neurospheres. Mouse ES cell colonies were detached from PA6 feeder cells after 8 days of SDIA treatment and then expanded as spheres for another 4 days in serum‐free medium supplemented with fibroblast growth factor‐2. The spheres exhibited neural stem cell characteristics and contained few DA neurons at this stage of culture. After being induced to differentiate on polyornithine/laminin‐coated dishes for 7 days, these spheres generated DA neurons in vitro at a relatively low frequency. Intriguingly, addition of PA6 cell conditioned medium to the sphere culture medium significantly increased the percentage of DA neurons to 25–30% of the total number of neurons. Transplantation of conditioned medium‐treated day 4 spheres, which contained DA neuron progenitors, into the mouse striatum resulted in the generation of a significant number of graft‐derived DA neurons. These findings suggest that progenitors of DA neurons are generated and can proliferate in ES cell‐derived neurospheres induced by serial SDIA and PA6 conditioned medium treatment. © 2006 Wiley‐Liss, Inc.
Hippocampal neurodegeneration, spontaneous seizures, and mossy fiber sprouting in the F344 rat model of temporal lobe epilepsy
Authors: Rao Muddanna S. , Hattiangady Bharathi , Reddy Doodipala S. , Shetty Ashok K. 
Published: February 2006

AbstractThe links among the extent of hippocampal neurodegeneration, the frequency of spontaneous recurrent motor seizures (SRMS), and the degree of aberrant mossy fiber sprouting (MFS) in temporal lobe epilepsy (TLE) are a subject of contention because of variable findings in different animal models and human studies. To understand these issues further, we quantified these parameters at 3–5 months after graded injections of low doses of kainic acid (KA) in adult F344 rats. KA was administered every 1 hr for 4 hr, for a cumulative dose of 10.5 mg/kg bw, to induce continuous stages III–V motor seizures for >3 hr. At 4 days post‐KA, the majority of rats (77%) exhibited moderate bilateral neurodegeneration in different regions of the hippocampus; however, 23% of rats exhibited massive neurodegeneration in all hippocampal regions. All KA‐treated rats displayed robust SRMS at 3 months post‐KA, and the severity of SRMS increased over time. Analyses of surviving neurons at 5 months post‐KA revealed two subgroups of rats, one with moderate hippocampal injury (HI; 55% of rats) and another with widespread HI (45%). Rats with widespread HI exhibited greater loss of CA3 pyramidal neurons and robust aberrant MFS than rats with moderate HI. However, the frequency of SRMS (∼3/hr) was comparable between rats with moderate and widespread HI. Thus, in comparison with TLE model using Sprague‐Dawley rats (Hellier et al. [1998] Epilepsy Res. 31:73–84), a much lower cumulative dose of KA leads to robust chronic epilepsy in F344 rats. Furthermore, the occurrence of SRMS in this model is always associated with considerable bilateral hippocampal neurodegeneration and aberrant MFS. However, more extensive hippocampal CA3 cell loss and aberrant MFS do not appear to increase the frequency of SRMS. Because most of the features are consistent with mesial TLE in humans, the F344 model appears ideal for testing the efficacy of potential treatment strategies for mesial TLE. © 2006 Wiley‐Liss, Inc.
Adipocyte‐derived angiopoietin‐1 supports neurite outgrowth and synaptogenesis of sensory neurons
Authors: Kosacka Joanna , Nowicki Marcin , Kacza Johannes , Borlak Jürgen , Engele Jürgen , Spanel‐Borowski Katharina 
Published: February 2006

AbstractSensory and sympathetic innervation of the white fat tissue (WAT) contributes to lipolysis. In addition, both fiber types adapt in density to weight gain and loss. Because these findings are indicative for a tight control of nerve fiber plasticity by adipokines, we tested whether adipocytes control neurite growth of sensory neurons through angiopoietin‐1 (Ang‐1). We further considered initial hints that Ang‐1‐induced neuritogenesis involves transactivation of the high‐affinity nerve growth factor (NGF) receptor trkA. Coculturing dorsal root ganglion (DRG) cells with 3T3‐L1 adipocytes supported neurite outgrowth. These neurotrophic effects were associated with the increased expression of Ang‐1 (presumably in adipocytes) as well as of trkA. The effects were abolished upon inactivating Ang‐1 in culture with selective antibodies. Likewise, neurite outgrowth was impaired in the presence of inactivating NGF antibodies as well as upon inhibition of the NGF high‐affinity trkA receptor with the antagonist K252a, indicating a tight cooperation of Ang‐1 and NGF in the control of neuritogenesis. DRG‐adipipocyte cocultures were further used to establish whether sensory neurons would form synaptic contacts with adipocytes. Electron microscopy demonstrated that cultured sensory neurons develop predominantly neuroneuronal synapses but seem to affect adipocytes by synapses en passant. Comparably to the case for neuritogenesis, expression of the presynaptic protein synaptophysin as well of the postsynaptic protein PSD‐95 correlated with Ang‐1 levels in culture. It is concluded that adipocyte‐secreted Ang‐1 supports neurite outgrowth, which is involved in synaptogenesis. The novel function of Ang‐1 appears to play a physiological role in WAT plasticity. © 2006 Wiley‐Liss, Inc.
Modulation of apoptosis in the mouse brain after morphine treatments and morphine withdrawal
Authors: Emeterio Estela Pérez‐San , Tramullas Mónica , Hurlé María A. 
Published: February 2006

AbstractWe have examined the effects of acute or chronic morphine and naltrexone‐precipitated withdrawal on mouse brain apoptotic cell death. The associated changes in the expression of apoptosis regulatory proteins were also analyzed. After a single dose of morphine, no apoptotic cells were detected by TUNEL or active caspase‐3 immunocytochemistry. Concurrently, a down‐regulation of the proapoptotic proteins FasL and Bad was detected in cortical lysates. On the other hand, the brains of chronic‐morphine‐treated mice and abstinent mice exhibited scattered apoptotic neurons and astrocytes throughout the brain. This neurotoxic effect was accompanied by up‐regulation of the proapoptotic proteins FasL, Fas, and Bad and the active fragments of caspases‐8 and ‐3 in cortical and hippocampal lysates. Abstinent mice also displayed a reduced expression of the antiapoptotic protein Bcl‐2. No changes on t‐Bid expression were detected under any experimental condition. These results suggest a neurotoxic effect exerted by chronic, but not acute, morphine and its withdrawal by activating both the intrinsic and the extrinsic apoptotic pathways. The possible clinical implications of our findings are discussed. © 2006 Wiley‐Liss, Inc.
Prolonged dark adaptation changes connexin expression in the mouse retina
Authors: Kihara Alexandre Hiroaki , Mantovani de Castro Leandro , Moriscot Anselmo Sigari , Hamassaki Dânia Emi 
Published: February 2006

AbstractIn the retina, ambient light levels influence the cell coupling provided by gap junction (GJ) channels, to compensate the visual function for various lighting conditions. However, the effects of ambient light levels on expression of connexins (Cx), the proteins that form the GJ channels, are poorly understood. In the present study, we first determined whether gene expression of specific Cx (Cx26, Cx31.1, Cx36, Cx37, Cx40, Cx43, Cx45, Cx50, and Cx57) was affected by prolonged dark adaptation. Cx mRNA relative levels were determined in mouse retinas dark adapted for 3 hr, 1 day, and 7 days by using quantitative real‐time PCR. Transcript levels of some Cx were repressed after 3 hr (Cx57), 1 day (Cx45), or 7 days (Cx36 and Cx43) of dark adaptation; others were increased after 1 day (Cx50) or 7 days (Cx31.1 and Cx37); and two of them (Cx26 and Cx40) were not significantly altered. The second aim was to determine whether prolonged dark adaptation affects protein expression of two important Cx in retina: neuronal Cx36 and glial Cx43. We were able to demonstrate that important changes in protein distribution and expression also took place in retina during long‐term dark adaptation. Given their localization, the specific alterations in Cx expression may reflect their distinct response to ambient light levels. © 2006 Wiley‐Liss, Inc.
Radical excision of malignant sacral tumors using a modified threadwire saw
Authors: Osaka Shunzo , Kondoh Osamu , Yoshida Yukihiro , Ryu Junnosuke 
Published: February 2006

AbstractBackgroundSurgical treatment of malignant sacral tumors is difficult, and has a high rate of recurrence.ObjectivesThe aim of this study was to examine the wide margin of large and small malignant sacral tumors using a threadwire saw (T‐saw).Materials and MethodsWe devised a flexible silver guide probe connected to a modified threadwire saw by a suture thread to perform osteotomies. We operated on 10 patients with sacral tumors using this device. The sacral excisions were performed via a posterior approach by four surgeons (two on each side) working simultaneously.ResultsWe obtained a wide margin in all cases and no recurrence, after a mean follow‐up of 4 years 2 months (range, 1 year 8 months–7 years 8 months). In one case, one nerve root on the right side was injured.ConclusionsOur new method is easier and faster than the conventional method in cases in which bilateral sacral nerve root canals require sectioning, and it produces a wide tumor margin. J. Surg. Oncol. 2006;93:312–317. © 2006 Wiley‐Liss, Inc.
Liver resection for hepatocellular carcinoma in patients who have undergone prior renal transplantation
Authors: Cheng Shao‐Bin , Yeh Dah‐Cherng , Shu Kuo‐Hsiung , Wu Cheng‐Chung , Wen Mei‐Chin , Liu Tse‐Jia , P'eng Fang‐Ku 
Published: February 2006

AbstractBackground and ObjectivesBecause renal transplantation recipients require immunosuppressive drugs, they have a higher incidence of subsequent malignancies. Among them, hepatocellular carcinoma (HCC) is common. Although liver resection remains an option for curing HCC, the role of liver resection in renal transplantation recipients remains unclear.MethodsA retrospective review of liver resection for newly diagnosed HCC in 680 patients was conducted. Among them, 18 patients had undergone prior renal transplantation (RT group). The patient background, tumor characteristics, early and long‐term results after liver resection were compared with the other 662 patients who had not previously undergone renal transplantation (non‐RT group).ResultsThe patient's background characteristics were comparable between RT and non‐RT group. The tumor characteristics, postoperative morbidity, and mortality were not significantly different between the two groups. The 5‐year disease‐free survival rates in RT and non‐RT groups were 18.8% and 41.2%, respectively (P = 0.242), whereas 5‐year actuarial survival rates in RT and non‐RT groups were 59.1% and 58.3%, respectively (P = 0.738). Two patients lost their graft kidney 3 and 8 years after liver resection.ConclusionWith careful protection of the graft kidney, liver resection is still a justified treatment option for HCC in patients who have undergone renal transplantation. J. Surg. Oncol. 2006;93: 273–278. © 2006 Wiley‐Liss, Inc.
Dephosphorylation of p‐ERK1/2 in relation to tumor remission after HER‐2 and Raf1 blocking therapy in a conditional mouse tumor model
Authors: Hausherr Carolin K. , Schiffer Ilka B. , Gebhard Susanne , Banić Andreas , Tanner Berno , Kolbl Heinz , Thoenes Eric , Beckers Thomas , Spangenberg Christian , Prawitt Dirk , Trost Tatjana , Zabel Bernhard , Oesch Franz , Hermes Matthias , Hengstler Jan G. 
Published: February 2006

AbstractSeveral studies have shown that HER‐2/neu (erbB‐2) blocking therapy strategies can cause tumor remission. However, the responsible molecular mechanisms are not yet known. Both ERK1/2 and Akt/PKB are critical for HER‐2‐mediated signal transduction. Therefore, we used a mouse tumor model that allows downregulation of HER‐2 in tumor tissue by administration of anhydrotetracycline (ATc). Switching‐off HER‐2 caused a rapid tumor remission by more than 95% within 7 d of ATc administration compared to the volume before switching‐off HER‐2. Interestingly, HER‐2 downregulation caused a dephosphorylation of p‐ERK1/2 by more than 80% already before tumor remission occurred. Levels of total ERK protein were not influenced. In contrast, dephosphorylation of p‐Akt occurred later, when the tumor was already in remission. These data suggest that in our HER‐2 tumor model dephosphorylation of p‐ERK1/2 may be more critical for tumor remission than dephosphorylation of p‐Akt. To test this hypothesis we used a second mouse tumor model that allows ATc controlled expression of BXB‐Raf1 because the latter constitutively signals to ERK1/2, but cannot activate Akt/PKB. As expected, downregulation of BXB‐Raf1 in tumor tissue caused a strong dephosphorylation of p‐ERK1/2, but did not decrease levels of p‐Akt. Interestingly, tumor remission after switching‐off BXB‐Raf1 was similarly efficient as the effect of HER‐2 downregulation, despite the lack of p‐Akt dephosphorylation. In conclusion, two lines of evidence strongly suggest that dephosphorylation of p‐ERK1/2 and not that of p‐Akt is critical for the rapid tumor remission after downregulation of HER‐2 or BXB‐Raf1 in our tumor model: (i) dephosphorylation of p‐ERK1/2 but not that of p‐Akt precedes tumor remission after switching‐off HER‐2 and (ii) downregulation of BXB‐Raf1 leads to a similarly efficient tumor remission as downregulation of HER‐2, although no p‐Akt dephosphorylation was observed after switching‐off BXB‐Raf1. © 2006 Wiley‐Liss, Inc.
US‐style contingent fees and UK‐style conditional fees: agency problems and the supply of legal services
Authors: Emons Winand , Garoupa Nuno 
Published: February 2006

AbstractUnder contingent fees, the attorney gets a share of the judgment; under conditional fees, the lawyer gets an upscale premium if the case is won which is, however, unrelated to the adjudicated amount. We compare conditional and contingent fees in a principal–agent framework where the lawyer chooses unobservable effort after she has observed the amount at stake. Contingent fees provide better incentives than conditional fees independently of whether upfront payments are restricted to be non‐negative or not. Under contingent fees, the attorney uses her information about what is at stake more efficiently. Copyright © 2006 John Wiley & Sons, Ltd.
Glutathione content and glutathione peroxidase expression in in vivo and in vitro matured equine oocytes
Authors: Luciano Alberto M. , Goudet Ghylène , Perazzoli Federica , Lahuec Cecile , Gérard Nadine 
Published: February 2006

AbstractThe in vitro developmental competence of equine oocytes is still low in comparison with other domestic mammals. A major factor affecting the viability of cells during in vitro culture is the increased oxidative stress. Oxidative modifications could be responsible for oocyte incompetence for in vitro maturation (IVM). Cysteamine, a glutathione (GSH) synthesis enhancer, has been shown to increase intracellular GSH content and to improve embryo development when added during IVM of bovine, porcine, and ovine oocytes. The aim of the present study was (1) to determine whether equine cumulus–oocyte complexes (COCs) benefit from the addition of cysteamine during IVM, (2) to compare the GSH content of oocytes after in vivo maturation and IVM, (3) to assess whether cysteamine administration during IVM of equine oocyte enhances early embryonic developmental capability following ICSI, (4) to study the glutathione peroxidase (GPX) mRNA level in COCs. In vivo matured COCs were collected by aspiration from preovulatory follicles, and analyzed at collection. Immature COCs were collected in vivo or from slaughterhouse ovaries and matured in culture media supplemented or not with 100 µM cysteamine. After nuclear stage assessment, oocytes were analyzed for GSH concentration and both oocytes and cumulus cells were analyzed for GPX and GAPDH mRNA. Our data showed that the maturation capability was similar in both in vivo aspirated oocytes and in those isolated from slaughterhouse ovaries. Moreover, the addition of cysteamine during IVM affected neither GSH content nor maturation rate. At the time of collection, intra‐oocyte GSH content was not influenced by the chromatin status. GSH concentration was similar in in vivo and in vitro matured metaphase II (MII) stage oocytes, and was significantly higher in MII than immature germinal vesicle stage oocytes. Moreover, the presence of serum inhibited whereas its absence stimulated the accumulation of GSH within oocytes during IVM. After ICSI, a similar proportion of zygotes in each group developed beyond the two‐cell stage after 72 hr of culture. Cumulus cells expressed GPX mRNA, while GPX transcript was absent in both immature and mature oocytes. Cumulus expression of GPX mRNA was significantly higher when analyzed at collection than after IVM. Taken together, our results demonstrate that in equine oocytes, GSH increases during IVM but the relative intra‐oocyte content of this thiol does not affect maturation and early development efficiency after fertilization. We hypothesize that factor(s) other than GSH/GPX are responsible for the limited in vitro early developmental capability of equine oocytes. Mol. Reprod. Dev. 73: 658–666, 2006 © 2006 Wiley‐Liss, Inc.