bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proapoptotic ability of oncogenic H-Ras to facilitate apoptosis induced by histone deacetylase inhibitors in human cancer cells
Authors: Choudhary Shambhunath , Wang Hwa-Chain Robert 
Published: March 2007

Abstract
More than 35% of human urinary bladder cancers involve oncogenic H-Ras activation. In addition to tumorigenic ability, oncogenic H-Ras possesses a novel proapoptotic ability to facilitate the induction of apoptosis by histone deacetylase inhibitors (HDACI). HDACIs are a new class of anticancer agents and are highly cytotoxic to transformed cells. To understand the connection between the selectivity of HDACIs on transformed cells and the proapoptotic ability of oncogenic H-Ras to facilitate HDACI-induced apoptosis, we introduced oncogenic H-Ras into urinary bladder J82 cancer cells to mimic an acquisition of the H-ras gene activation in tumor development. Expression of oncogenic H-Ras promoted J82 cells to acquire tumorigenic ability. Meanwhile, oncogenic H-Ras increased susceptibility of J82 cells to HDACIs, including FR901228 and trichostatin A, for inducing apoptosis. The caspase pathways, the B-Raf and extracellular signal-regulated kinase pathway, p21Cip1 and p27Kip1, and core histone contents are regulated differently by FR901228 in oncogenic H-Ras–expressed J82 cells than their counterparts in parental J82 cells, contributing to the increased susceptibility to the induction of selective apoptosis. Our results lead us to a suggestion that HDACIs activate the proapoptotic ability of oncogenic H-Ras, indicating a potential therapeutic value of this new class of anticancer agents in the control of human urinary bladder cancer that has progressed to acquire oncogenic H-Ras. [Mol Cancer Ther 2007;6(3):1099–111]
In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00
Authors: Joshi Kalpana S. , Rathos Maggie J. , Joshi Rajendra D. , Sivakumar Meenakshi , Mascarenhas Malcolm , Kamble Shrikant , Lal Bansi , Sharma Somesh 
Published: March 2007

Abstract
Cyclin-dependent kinases (Cdk) and their associated pathways represent some of the most attractive targets for the development of anticancer therapeutics. Based on antitumor activity in animal models, a variety of Cdk inhibitors are undergoing clinical evaluation either as a single agent or in combination with other approved drugs. In our anticancer drug discovery program, a novel series of flavones have been synthesized for evaluation against the activity of Cdk4-D1. This enzyme catalyzes the phosphorylation of retinoblastoma protein, thus inhibiting its function. We have identified a series of potent Cdk4-D1 inhibitors with IC50 below 250 nmol/L. In this report, we have described the properties of one of the best compound, P276-00 of the flavone's series. P276-00 shows 40-fold selectivity toward Cdk4-D1, compared with Cdk2-E. The specificity toward 14 other related and unrelated kinases was also determined. P276-00 was found to be more selective with IC50s &lt;100 nmol/L for Cdk4-D1, Cdk1-B, and Cdk9-T1, as compared with other Cdks, and less selective for non-Cdk kinases. It showed potent antiproliferative effects against various human cancer cell lines, with an IC50 ranging from 300 to 800 nmol/L and was further compared for its antiproliferative activity against cancer and normal fibroblast cell lines. P276-00 was found to be highly selective for cancer cells as compared with normal fibroblast cells. To delineate its mechanism of action, the effect of P276-00 on cell cycle proteins was studied in human breast cancer cell line (MCF-7) and human non–small cell lung carcinoma (H-460). A significant down-regulation of cyclin D1 and Cdk4 and a decrease in Cdk4-specific pRb Ser780 phosphorylation was observed. P276-00 produced potent inhibition of Cdk4-D1 activity that was found to be competitive with ATP and not with retinoblastoma protein. The compound also induced apoptosis in human promyelocytic leukemia (HL-60) cells, as evidenced by the induction of caspase-3 and DNA ladder studies. These data suggest that P276-00 has the potential to be developed as an anti-Cdk chemotherapeutic agent. [Mol Cancer Ther 2007;6(3):918–25]
Blockade of the phosphatidylinositol-3-kinase–Akt signaling pathway enhances the induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the pathway is constitutively activated
Authors: Fujiwara Yusuke , Hosokawa Yoshihisa , Watanabe Kazushi , Tanimura Susumu , Ozaki Kei-ichi , Kohno Michiaki 
Published: March 2007

AbstractConstitutive activation of the phosphatidylinositol-3-kinase (PI3K)–Akt signaling pathway is associated with the neoplastic phenotype in many human tumor cell types. Given the antiapoptotic role of this pathway, we examined whether its specific blockade might sensitize human tumor cells to the induction of apoptosis by various anticancer drugs. Although specific blockade of the PI3K-Akt pathway alone with inhibitors such as LY294002 did not induce cell death, it resulted in marked and selective enhancement of the induction of apoptosis by microtubule-destabilizing agents such as vincristine. This effect was apparent only in tumor cells in which the PI3K-Akt pathway is constitutively activated. Blockade of the PI3K-Akt pathway induced the activation of glycogen synthase kinase-3β, which phosphorylates microtubule-associated proteins such as tau and thereby reduces their ability to bind and stabilize microtubules. The consequent destabilization of microtubules induced by the inhibition of PI3K-Akt signaling appeared to increase their sensitivity to low concentrations of microtubule-destabilizing agents that alone do not lead to the disruption of cytoplasmic microtubules in tumor cells. Such a synergistic effect on microtubule integrity was not apparent for stable microtubules in the neurites of neuronal cells. These results suggest that the administration of a combination of a PI3K-Akt pathway inhibitor and a microtubule-destabilizing agent is a potential chemotherapeutic strategy for the treatment of tumor cells in which this signaling pathway is constitutively activated. [Mol Cancer Ther 2007;6(3):1133–42]
Resistance to c-KIT kinase inhibitors conferred by V654A mutation
Authors: Roberts Kathryn G. , Odell Adam F. , Byrnes Ellen M. , Baleato Rosa M. , Griffith Renate , Lyons Alan Bruce , Ashman Leonie K. 
Published: March 2007

Abstract
Certain mutations within c-KIT cause constitutive activation of the receptor and have been associated with several human malignancies. These include gastrointestinal stromal tumors (GIST), mastocytosis, acute myelogenous leukemia, and germ cell tumors. The kinase inhibitor imatinib potently inhibits c-KIT and is approved for treatment of GIST. However, secondary point mutations can develop within the kinase domain to confer resistance to imatinib and cause drug-resistant relapse. A common mutation, which results in a V654A substitution, has been documented in imatinib-resistant GIST patients. We expressed c-KIT cDNA constructs encoding the V654A substitution alone and in combination with a typical activating exon 11 mutation characteristic of GIST, V560G, in factor-dependent FDC-P1 cells. The V654A substitution alone resulted in enhanced proliferation in c-KIT ligand (stem cell factor) but not factor independence. Cells expressing the double mutant were, like those expressing single V560G mutant c-KIT, factor independent. Analysis of cellular proliferation in the presence of imatinib showed that the V654A substitution alone conferred resistance. The difference in sensitivity was especially pronounced for cells expressing single mutant V560G c-KIT compared with double mutant V560G/V654A c-KIT. The findings were supported by studies of c-KIT phosphorylation. Analysis of the crystal structure of imatinib in complex with the kinase domain of c-KIT predicts that the V654A substitution directly affects the binding of imatinib to the receptor. Alternative c-KIT inhibitors, nilotinib (AMN107) and PKC412, were also less active on V560G/V654A c-KIT than on the V560G single mutant; however, nilotinib, like imatinib, potently inhibited the V560G mutant. PKC412 strongly inhibited imatinib-resistant D816V c-KIT. [Mol Cancer Ther 2007;6(3):1159–66]
Dietary grape seed proanthocyanidins inhibit UVB-induced oxidative stress and activation of mitogen-activated protein kinases and nuclear factor-κB signaling in in vivo SKH-1 hairless mice
Authors: Sharma Som D. , Meeran Syed M. , Katiyar Santosh K. 
Published: March 2007

Abstract
We have shown previously that dietary grape seed proanthocyanidins (GSP) inhibit UVB-induced photocarcinogenesis in mice. As UVB-induced oxidative stress and oxidative stress–mediated signaling has been implicated in photocarcinogenesis, this study was designed to investigate the effect of dietary GSPs on UVB-induced oxidative stress in in vivo SKH-1 hairless mice. Here, we report that provision of dietary GSPs (0.2 and 0.5%, w/w) to mice exposed to either acute UVB irradiation (120 mJ/cm2) or chronic irradiation of UVB inhibited depletion of glutathione peroxidase, catalase, and glutathione, and inhibited UVB-induced H2O2, lipid peroxidation, protein oxidation, and nitric oxide in mouse skin. As UV-induced oxidative stress mediates activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways, we determined the effect of dietary GSPs on these pathways. We observed that dietary GSPs inhibited UVB-induced phosphorylation of extracellular signal-regulated kinase 1/2, c-Jun-NH2-kinase, and p38 proteins of MAPK family, which seems to be mediated through reactivation of MAPK phosphatases. GSPs inhibited UVB-induced activation of NF-κB/p65 through inhibition of degradation of IκBα and activation of IκB kinase α (IKKα). As NF-κB–targeted genes play critical roles in inflammation and cellular proliferation, we assessed the effect of GSPs on proteins encoded by these genes. Dietary GSPs resulted in inhibition of the expression of proliferating cell nuclear antigen, cyclin D1, inducible nitric oxide synthase, and cyclooxygenase-2 in the skin. Collectively, our data show that GSPs have the ability to protect the skin from the adverse effects of UVB radiation via modulation of the MAPK and NF-κB signaling pathways and provide a molecular basis for the photoprotective effects of GSPs in an in vivo animal model. [Mol Cancer Ther 2007;6(3):995–1005]
Inactivation of glycogen synthase kinase-3β, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells
Authors: Kunnimalaiyaan Muthusamy , Vaccaro Abram M. , Ndiaye Mary A. , Chen Herbert 
Published: March 2007

Abstract
Glycogen synthase kinase-3β (GSK-3β) is an important regulator of cell proliferation and survival. Conflicting observations have been reported regarding the regulation of GSK-3β and extracellular signal–regulated kinase (ERK1/2) in cancer cells. In this study, we found that raf-1 activation in human medullary thyroid cancer cells, TT cells, resulted in phosphorylation of GSK-3β. Inactivation of GSK-3β in TT cells with well-known GSK-3β inhibitors such as lithium chloride (LiCl) and SB216763 is associated with both growth suppression and a significant decrease in neuroendocrine markers such as human achaete-scute complex-like 1 and chromogranin A. Growth inhibition by GSK-3β inactivation was found to be associated with cell cycle arrest due to an increase in the levels of cyclin-dependent kinase inhibitors such as p21, p27, and p15. Additionally, LiCl-treated TT xenograft mice had a significant reduction in tumor volume compared with those treated with control. For the first time, we show that GSK-3β is a key downstream target of the raf-1 pathway in TT cells. Also, our results show that inactivation of GSK-3β alone is sufficient to inhibit the growth of TT cells both in vitro and in vivo. [Mol Cancer Ther 2007;6(3):1151–8]
Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel
Authors: Sarkaria Jann N. , Yang Lin , Grogan Patrick T. , Kitange Gaspar J. , Carlson Brett L. , Schroeder Mark A. , Galanis Evanthia , Giannini Caterina , Wu Wenting , Dinca Eduard B. , James C. David 
Published: March 2007

Abstract
In the current study, we examined a panel of serially passaged glioblastoma xenografts, in the context of an intracranial tumor therapy response model, to identify associations between glioblastoma molecular characteristics and tumor sensitivity to the epidermal growth factor receptor (EGFR) kinase inhibitor erlotinib. From an initial evaluation of 11 distinct glioblastoma xenografts, two erlotinib-sensitive tumors were identified, each having amplified EGFR and expressing wild-type PTEN. One of these tumors expressed truncated EGFRvIII, whereas the other expressed full-length EGFR. Subsequent cDNA sequence analysis revealed the latter tumor as expressing an EGFR sequence variant with arginine, rather than leucine, at amino acid position 62; this was the only EGFR sequence variant identified among the 11 xenografts, other than the aforementioned vIII sequence variant. EGFR cDNAs were then examined from 12 more xenografts to determine whether additional missense sequence alterations were evident, and this analysis revealed one such case, expressing threonine, rather than alanine, at amino acid position 289 of the extracellular domain. This glioblastoma was also amplified for EGFR, but did not display significant erlotinib sensitivity, presumably due to its lacking PTEN expression. In total, our study identified two erlotinib-sensitive glioblastoma xenografts, with the common molecular characteristics shared by each being the expression of wild-type PTEN in combination with the expression of amplified and aberrant EGFR. [Mol Cancer Ther 2007;6(3):1167–74]
Making a Doughnut-shaped Egg Mass: Oviposition Behaviour of Vibrissaphora boringiae (Anura: Megophryidae)
Authors: Zheng Yuchi , Fu Jinzhong 
Published: March 2007

AbstractVibrissaphora boringiae produces doughnut-shaped egg masses (i.e., circular mass with central depression) that are attached to the underside of submerged rocks in running water. The oviposition behaviour of this species was observed for the first time, and explains how egg masses were shaped. The male used the right hindlimb to push the eggs up to the bottom surface of the rock, while the pair rotated horizontally and counter clockwise. Three limbs of the female provided the support and power for the rotation. The male was positioned on the dorsal-left side of the female, and formed a rare asymmetric inguinal amplexus. This type of oviposition behaviour may be common in megophryid frogs that produce doughnut-shaped and circular egg masses.
Courtship and mating behaviours of two syntopic species of skink (Plestiodon anthracinus and Plestiodon fasciatus)
Authors: Pyron Robert Alexander , Camp Carlos Duane 
Published: March 2007

AbstractCourtship and mating behaviours are widely conserved throughout the scincid lizard genus Plestiodon, and ethological isolation between closely related species depends heavily on differentiating chemical cues. The purpose of this study was to determine whether or not subtle, as yet undetected differences are present in the mating behaviours of two syntopic, distantly related skinks, P. anthracinus and P. fasciatus. Observed courtship and mating behaviours were similar between the two species and to those reported for other species within this genus. However, survival analysis determined significant interspecific differences in the duration of pre-coital behaviours. Investigation of such subtle differences between species more closely related than these two may generate further insights into the evolution of ethological isolating mechanisms in lizards.
The influence of internote-interval variation of the advertisement call on the phonotactic behaviour in male Allobates femoralis (Dendrobatidae)
Authors: Hödl Walter , Franz Alexander , Göd Mario 
Published: March 2007

AbstractAcoustic conspecific recognition depends on spectral and temporal call properties, but not all of these are necessary for species identification. To test the importance of the advertisement call's internote interval of the dendrobatid frog Allobates (=Epipedobates) femoralis, we conducted field playback experiments with modified conspecific calls and investigated phonotactic responses. Allobates femoralis males showed positive phonotaxis when calls with internote intervals varying up to ±60% of the population's mean were presented. No phonotactic approach was observed in response to modified advertisement calls containing internote intervals of the syntopic heterospecific leptodactylid frog Adenomera hylaedactyla. However, 26.7% of the A. femoralis males tested showed positive phototoxic when altered advertisement calls with internote intervals of the syntopic heterospecific dendrobatid frog Epipedobates cf. hahneli were presented. Our results show that only a combination of different acoustic call parameters provides correct species-specific recognition.
Promiscuity and high level of multiple paternity in common wall lizards (Podarcis muralis): data from microsatellite markers
Authors: Oppliger Anne , Degen Loic , John-Alder Henry-B. , Bouteiller-Reuter Caroline 
Published: March 2007

AbstractLittle is known about the mating system of the common wall lizard Podarcis muralis. Behavioural and observational data have demonstrated that females frequently mate with multiple males. However, the possible occurrence of multiple paternity has never been investigated. By using microsatellite paternity analysis in a wild population, we document this species indeed mate promiscuously and these matings resulted in multiple paternity in at least 87% of the clutches examined.
The effects of temperature and pH on the embryonic development of two species of Triturus (Caudata: Salamandridae)
Authors: Vignoli Leonardo , Bologna Marco , D'Amen Manuela 
Published: March 2007

AbstractAmphibian populations are especially sensitive to aquatic parameters, in particular during embryonic and larval life. Our aim was to test for an effect of temperature (T = 13°C, 20°C and 25°C at constant pH = 7) and pH (pH = 5.5, 7 and 8.5 at constant T= 20°C) on embryos of two species of Triturus, T. carnifex carnifex and T. italicus (Amphibia, Salamandridae) using GLM procedure. Trend of embryogenesis processes, time to hatching and rate of development have a similar effect in both species in the used range of temperature and pH. Time to hatching decreased significantly with the increasing temperature. The pH experimental conditions had no effect on T. carnifex embryos survival, while the acidic pH condition raised the mortality rate in T. italicus, whose embryos should be more vulnerable than those of T. carnifex to acidification in nature.
Estimating population size in the European tree frog (Hyla arborea) using individual recognition and chorus counts
Authors: Helfer Véronique , Pellet Jérôme , Yannic Glenn 
Published: March 2007

AbstractChorus counts are widely used to assess population abundance in breeding anurans. It is however unclear how such counts translate into true population sizes. We monitored chorus activity in two populations of the European tree frog (Hyla arborea) over three years, while simultaneously conducting a capture-mark-recapture (CMR) study on breeding males. Three to four capture sessions were made each year, spread across the acme of the breeding season. Individual recognition was ensured by photographs of the linea marginalis. We used Pollock's robust design to test several biological hypotheses and estimate demographic parameters. Male survival was estimated as mean ±SE = 0.297 ± 0.154. Population trends deduced from chorus counts (maximum or mean) and modelled male population sizes were not concordant. We showed that there is no simple relationship between maximum or mean chorus size and modelled male population sizes estimated from CMR study and that population trends inferred from chorus counts are likely to be biased to an unknown extent. Even though CMR methods need significant time and personnel investments in order to produce reliable results, we advocate their use in the study of pond breeding amphibians' demography, as it provides unbiased and more precise estimates.
Hierarchical competition in pond-breeding anuran larvae in a Mediterranean area
Authors: Richter-Boix Alex , Llorente Gustavo , Montori Albert 
Published: March 2007

AbstractThe anuran larval guild is frequently characterised by the co-occurrence, with high niche overlap, of distinct species in the same pond at variables densities during development. Anuran larvae have therefore been widely studied as a model system for competition. Body size and activity level are considered the most important factors that influence the outcome of competition between tadpoles. As species from temporary ponds normally show higher activity levels in order to achieve rapid growth and thus reduce the risk of desiccation, these species are often considered superior competitors. We designed several laboratory experiments to examine the intra- and interspecific effects on growth rate, mass at metamorphosis and survival to metamorphosis of six species in a Mediterranean area. Body size and activity level were used as explanatory covariables to determine competitive ability among species. An asymmetric and hierarchical relationship was found among the six species. Larger tadpole species were more successful in competitive interactions than smaller ones, but no relationship was found between activity level and competition effects. Species typically found in temporary ponds (Pelodytes punctatus and Bufo calamita) were considered poor competitors in contrast with other communities studied. Species with low competitive ability can persist by using refuges in which competition is reduced (e.g. ephemeral ponds).
Sleep apnoea in heart failure
Authors: Schulz R. , Blau A. , Börgel J. , Duchna H. W. , Fietze I. , Koper I. , Prenzel R. , Schädlich S. , Schmitt J. , Tasci S. , Andreas S. 
Published: March 2007

Studies from the USA have reported that sleep apnoea is common in congestive heart failure (CHF), with Cheyne–Stokes respiration (CSR) being the most frequent type of sleep-disordered breathing (SDB) in these patients. Within the present study, the authors sought to assess the prevalence and type of SDB among CHF patients in Germany.A total of 203 CHF patients participated in this prospective multicentre study. All patients were stable in New York Heart Association classes II and III and had a left ventricular ejection fraction (LVEF) <40%. The patients were investigated by polygraphy and all data were centrally analysed. Patient enrolment was irrespective of sleep-related symptoms.The majority of patients were male with a mean age of 65 yrs and hospitalised. Of the 203 patients, 145 (71%) had an apnoea/hypopnoea index >10·h−1, obstructive sleep apnoea (OSA) occurred in 43% (n = 88) and CSR in 28% (n = 57) of patients.The prevalence of sleep-disordered breathing is high in patients with stable severe congestive heart failure from a European population. As sleep-disordered breathing may have a negative impact on the prognosis of congestive heart failure, a sleep study should be performed in every patient with congestive heart failure and a left ventricular ejection fraction of <40%. This diagnostic approach should probably be adopted for all of these patients irrespective of the presence of sleep-related symptoms.