julilili42/papers huggingface dataset:
Abstract 3416: Cetuximab promotes immunotoxicity against rhabdomyosarcoma in vitro
2010-04-01

Abstract Novel treatment strategies have to be evaluated to improve the prognosis of advanced stage rhabdomyosarcoma (RMS) and to deal with clinical problems such as metastatic invasion, local tumor recurrence or multidrug resistance. Immunotherapy may represent an alternative specific, effective, less toxic and more promising therapeutic approach. Potential targets for antibody therapy of RMS are currently unknown. Differential gene expression analysis between the two main histopathological subtypes - embryonal and alveolar RMS - on 12 primary RMS samples was performed with Affymetrix array technology. Statistical analysis revealed 211 up-regulated and 323 down-regulated transcripts. Ingenuity Pathways analysis based on these results indicated the epidermal growth factor receptor (EGFR) as a central molecule with a 3.9-fold higher expression in embryonal compared to alveolar RMS. Subsequently, the expression of EGFR as well as the binding of the corresponding humanized antibody Cetuximab on embryonal (RD, A-204) and alveolar (Rh30) RMS cell lines was evaluated by flow cytometry. High expression of EGFR was detected in Rh30 and RD cells, whereas Cetuximab did not bind to A-204 at a concentration of 10 μg/ml. Next, the activity of Cetuximab was quantified using proliferation assays, in which viability of the above RMS cell lines ranged between 68% and 107% and was influenced neither by Cetuximab (concentrations ranging from 1 - 100 μg/ml) nor by 10 ng/ml EGF. However, antibody-dependent cellular cytotoxicity assays with PBMCs revealed potent activity of Cetuximab even at a low concentration of 0.05 μg/ml and a 3- to 4-fold enhanced specific lysis of RMS cells expressing EGFR. These promising effects of Cetuximab must now be tested in a suitable animal model. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3416.
Abstract 1180: MicroRNAs and their target messenger RNAs associated with progression of breast cancer
2010-04-01

Abstract Background Based on own results using laser micro dissected cells of invasive ductal (IDC) and ductal in situ (DCIS) breast cancer of the same tumor combined with Affymetrix microarray technology 445 differentially transcribed candidate genes have been identified (Schütz et al., Cancer Research 2006, 66:5278-5286). In this project differential expression of miRNAs and mRNAs was investigated in the same DCIS/IDC breast cancers and pure DCIS fixed in formalin and embedded in paraffin (FFPE). Aims The aim was (1) to identify miRNAs and their target mRNAs to serve as progression markers between DCIS and IDC and (2) to find an miRNA/mRNA set to characterize aggressive DCIS with a high invasive potential. Material and Methods Bioinformatic analysis using support vector machine and principle component analyses was applied to extract a prognostic gene set from the set of differentially expressed genes and qRT-PCR validation was carried out on micro dissected FFPE epithelial cells. Additionally, Illumina microarray technology was applied for mRNA and miRNA expression analysis. For functional analysis transmigration assays were performed in combination with siRNA mediated knock down of target genes. Results We obtained a 9-gene progression set which is able to correctly classify DCIS and IDC in 23 out of 24 cases (95.8%). Eight of the 9 possible marker genes were correctly validated in FFPE tissues. Further, expression of these genes also varied between pure DCIS and DCIS areas of DCIS/IDC mixed tumors - expression validation is currently done with qRT-PCR. Nineteen miRNAs were differentially expressed between DCIS and IDC, of which 4 had already been described in tumors. These 4 miRNAs have binding sites on 5 of the 9 candidate genes. Microarray analysis of mRNA from FFPE tissues confirmed differential expression of LRRC15 which has been found to be functionally relevant for breast cancer cell invasion and of LRRC32. An siRNA mediated knock down of LRRC32 reduced invasive potential of MDA-MB-231 breast cancer cells in transmigration assays. Conclusions A small gene set of potential progression markers obtained by microarray analysis of native breast carcinomas was successfully validated on FFPE tissues. In addition, a set of targeting miRNAs was identified that might thus serve as prognostic markers. Further analyses are still ongoing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1180.
Abstract 3551: Role of proteasome in the development of multidrug resistance in childhood rhabdomyosarcoma
2010-04-01

Abstract Multidrug resistance (MDR) is a common problem in the treatment of childhood rhabdomyosarcoma (RMS). The aim of this study was to investigate different mechanism of MDR in childhood RMS and to analyze possible reversal strategies. Female athymic mice underwent xenotransplantation with embryonal (A204) or alveolar (Rh30) RMS cells and were treated with vincristine (0.75 mg/kg/d i.p.). Gene expression analysis with Affymetrix oligonucleotide microarrays HU-Gene 1.0 revealed 2314 differentially expressed genes between the groups in alveolar RMS and 1387 in embryonal RMS. Ingenuity Pathways Analysis of biological pathways and functions of these genes revealed a cluster 21 genes related to the ubiquitin pathway. Among them 4 genes shown an up-regulation and 17 a 0.5 lower expression in vincristine treated samples. Furthermore, among of 45 genes of the proteasome cluster with 35 being down-regulated in RMS from animals treated with vincristine, putative mediating the development of MDR. Changes of gene expression were confirmed by qRT-PCR for selected proteasome components, such as PSMB1, PSMB6 and PSMD14. Specific inhibition of proteasome activity with bortezomib and MG132 inhibits proliferation of RMS cells, but reduces the cytotoxic activity of vincristine in a cell vitality assay. Our results emphasize the role of proteasome in the development of MDR in rhabdomyosarcoma treated with vincristine. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3551.
Interscapular fat is strongly associated with insulin resistance
2010-04-01

Context: Subcutaneous abdominal adipose tissue (SCAAT), visceral adipose tissue (VAT), fat in the neck area [interscapular fat (IF)], and liver fat (LF) are associated with metabolic traits related to insulin resistance. Whole body magnetic resonance imaging (MRI) and spectroscopy (MRS) offer a unique approach to quantify fat depots in larger cohorts.
Abstract 5582: NY-ESO-1-specific T-cells in melanoma patients with good clinical outcome after vaccination using mRNA as the immunogen
2010-04-01

Abstract Although success in active cancer immunotherapy is often disappointing, vaccination against cancer- associated antigens has become an important tool in cancer management, resulting in an increasing list of possible antigen targets. However, previous studies have shown that vaccination against certain antigens results in a better clinical outcome than others. This indicates the importance of immune monitoring by helping to choose the antigens with the highest potential for success. In order to address this issue, we have analysed CD4+ and CD8+ T-cell responses against four common melanoma-associated antigens, namely NY-ESO-1, Melan-A, MAGE-A3 and Survivin, in melanoma patients undergoing immunotherapy. Blood samples from 5 long-term survivors after treatment with anti-CTLA-4 antibody as well as 12 patients vaccinated with mRNA encoding these four antigens were tested in this study. Antigen-specific T-cell responses were detected using peptide mixtures spanning the whole sequence of the antigen after one round of in vitro sensitization. Intracellular production of six different cytokines (IFN-γ, TNF, IL-2, IL-4, IL-10 and IL-17) was measured in CD4+ and CD8+ T-cells by 14 colour multiparameter flow cytometry, allowing simultaneous analysis of the phenotype and effector functions (TH1, TH2, TH17) on a single-cell basis. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were detected in 4/5 long-term (up to 3 years and continuing) survivors receiving anti-CTLA-4 treatment, whereas responses against the remaining three antigens were either absent or present at lower frequencies. In the mRNA vaccination trial, NY-ESO-1-specific responses were detected in the only stage IV patient with &amp;gt;25% shrinkage in the size of the metastasis and two stage IV patients, who have remained tumor-free for 21 and 12 months since start of the vaccination. NY-ESO-1-specific immune responses were present in only 1/9 patients who progressed or died during this period. In all 6 patients with clinical benefit, the NY-ESO-1-specific T-cells produced high levels of IFNγ and TNF. Our data suggest that NY-ESO-1 might be a promising target antigen in melanoma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5582.
Abstract 4522: Oncogenic stress-induced cell death following Imatinib deprivation in Bcr-Abl overexpressing Imatinib-resistant ALL cells
2010-04-01

Abstract Imatinib resistance is a major problem in treatment of Bcr-Abl positive leukemias, particularly in patients with ALL and advanced CML. One of the major mechanisms of this resistance is overexpression of Bcr-Abl. We investigated the effects of Imatinib deprivation in Bcr-Abl overexpressing Imatinib-resistant ALL cell lines. Removal of Imatinib from culture medium led to a huge induction of Bcr-Abl autophosphorylation and concomitant overstimulation of PI3K-, MAPK-, and JAK/STAT signalling leading to an elevated cell size and cellular protein content. Massive induction of cell death was then observed at later time points (48 hours after Imatinib deprivation) accompanied by loss of outer and inner mitochondrial membrane integrity. Using a protein kinase inhibitor library, we identified inhibitors of glycogen synthase kinase-3 (GSK3) and p38-MAPK as the most potent compounds which completely prevented induction of cell death upon removal of Imatinib whereas the same inhibitors had synergistic effects with Imatinib in Imatinib-sensitive ALL cells. In contrast to GSK3- and p38, inhibition of PI3K had no effect on oncogenic stress upon Imatinib withdrawal in the resistant clones. Importantly, oncogenic stress-induced cell death could not be blocked by the pan-caspase inhibitor z-VAD-fmk whereas the RIP1 inhibitor Necrostatin partially rescued the cells upon Imatinib deprivation. We also detected a posttranslational modification of RIP1 upon Imatinib withdrawal that was completely absent in cells pre-treated with GSK3- or p38 inhibitors indicating a central role of RIP1 for oncogenic stress-induced cell death. In conclusion, we found a massive induction of a necroptosis-like cell death in Bcr-Abl overexpressing ALL cells as a consequence of oncogenic stress upon Imatinib deprivation. GSK3 and p38 turned out to play the most prominent role for oncogenic stress induced cell death. These data implicate that a discontinuous treatment with Imatinib (periods of Imatinib treatment followed by short periods without Imatinib) may prevent the appearance of cell clones with Bcr-Abl overexpression. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4522.
When Did Adam Wear the Garments of Light?
2010-04-01

Jewish and Christian authors in Late Antiquity share a common tradition in regard of Adam being vested in ‘garments of light/glory/honour’. While according to Christian texts Adam wears this vestment before the fall, Jewish writers have him receive it after the fall, the kothnoth ̔or of Gen. 3:21 being interpreted in midrash Genesis Rabbah as kothnoth ̓or , ‘garments of light’. Since garments of light in early Jewish literature are mostly known from eschatological contexts, there seems to be a discrepancy between the motif’s use by midrash and pre-rabbinic literature. An explanation for this can be found if one supposes a polemic in the midrash to Christian baptismal practice, which focuses upon the loss and regain of Adam’s primordial clothing. The midrash subverts this altogether by stating that Adam received his eschatological garment long before and thus there is no need for another.
Abstract 1425: Dasatinib reverses the phenotype of cancer associated fibroblasts (CAFs) to a normal fibroblast (NAF) like phenotype
2010-04-01

Abstract Cancer associated fibroblasts (CAFs) show a molecular and functional phenotype that is different from their normal counterparts (normal fibroblasts, NAFs). It is a well established phenomenon that these modified and activated fibroblasts possess permissive and promoting properties for epithelial tumor cells and therefore play a central role in tumor progression, metastasis, and probably also in sensitivity to antitumor agents. We asked whether CAFs could be reverted back pharmacologically to normal homeostasis by inhibiting PDGFR signalling. We therefore evaluated the efficacy of the FDA approved PDGFR inhibitor Dasatinib on proliferation and gene expression profile of CAF strains isolated from different lung carcinoma specimens. Dasatinib significantly reduced proliferation without inducing cell death in all 40 CAF strains investigated. Genome-wide microarray analysis of 9 CAF strains cultivated in presence or absence of Dasatinib identified 491 genes whose expression was significantly changed at least twofold. 104 of these encoded cell cycle related proteins with a great majority of 97 being down-regulated by Dasatinib. To determine the relevance of the differentially regulated genes in Dasatinib treated cells, we compared the Dasatinib expression signature to the previously described signatures of NAFs and CAFs derived from breast cancer patients (Sadlanova et al., 2008). Importantly, 102 of the 491 genes regulated by Dasatinib were also shown to be differentially expressed in CAFs versus NAFs. The expression of 72 of the genes we identified as down-regulated by Dasatinib was also reduced in NAFs compared to CAFs (p&amp;lt;0.0001 in Fisher's exact analysis). In addition, 30 genes identified as up-regulated by Dasatinib were also found to be elevated in NAFs compared to CAFs (p&amp;lt;0.0001 in Fisher's exact analysis). In summary, our data suggest that Dasatinib may reverse the cancer-activated phenotype of CAFs to a normal fibroblast like phenotype. Dasatinib treatment may therefore also reverse the tumor-promoting properties of CAFs. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1425.
ChemInform Abstract: From Cluster to Cluster: Structural Transformation Reactions Among Tungsten Chloride Clusters
2010-04-01

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Akt/PKB‐sensitive proximal tubular glucose and phosphate transport
2010-04-01

Akt/PKB stimulates the glucose carrier GLUT4. Here we explored whether Akt directly regulates Na + ‐coupled transport of glucose (by SGLT1) or phosphate (by NaPiIIa). Immunohistochemistry showed that Akt2 is expressed in proximal renal tubules. According to dual electrode voltage clamp experiments the coexpression of Akt increased the glucose‐induced current in SGLT1‐expressing and the phosphate‐induced current in NapiIIa‐expressing Xenopus oocytes. Renal transport was further studied using Akt2 deficient ( akt2 −/− ) and wild type mice ( akt2 +/+ ). akt2 −/− mice suffered from glucosuria which was partially due to increased plasma glucose levels but was not observed in akt2 +/+ mice made similarly hyperglycemic as akt2 −/− mice by fructose feeding pointing to defective renal tubular glucose reabsorption. Glucose‐induced depolarization was significantly smaller in isolated perfused renal tubules from akt2 −/− than from akt2 +/+ mice. In addition, the phosphate clearance was higher in akt2 −/− than in akt2 +/+ mice despite a significantly decreased plasma PTH and enhanced 1,25‐dihydroxyvitamin D 3 concentration and a tendency of lower plasma phosphate. Bone density was significantly reduced in akt2 −/− mice. In conclusion, Akt plays a role in the regulation of renal glucose and phosphate transport contributing to the maintenance of phosphate balance and adequate mineralization of bone.
Onset of Convective Rainfall During Gradual Late Miocene Rise of the Central Andes
2010-04-02

Separated About Lift The uplift history of the Andes of South America is a contentious issue, with the two main hypotheses polarizing from rapid growth between roughly 10 and 7 million years ago to more gradual elevation over most of the past 40 million years. The oxygen isotopic composition of soil carbonates has been used as a proxy for altitude and to measure the timing of uplift. Poulsen et al. (p. 490 , published online 1 April) applied a global atmospheric general circulation model to show that the oxygen isotopic composition changes seen in carbonates formed in the late Miocene were driven more by changes in the amount of precipitation than by the altitude at which the precipitation forms. Consequently, it seems that oxygen isotopes are not a reliable paleoaltimeter, and Andean uplift may not have been as precipitate as thought.
Is there a role for benzodiazepines in the management of lumbar disc prolapse with acute sciatica?
2010-04-02

Patients with acute lumbar disc prolapse with sciatica who are not considered candidates for surgery are usually treated with physiotherapy and non-steroidal anti-inflammatory agents. Moreover, the treatment with benzodiazepines is common practice in the absence of class I or II level of evidence. Here we assessed the role of benzodiazepines in the conservative management of acute lumbar disc prolapse. Using a placebo-controlled, double-blinded design, 60 patients were randomized to receive placebo or diazepam in addition to mechanical physiotherapy and analgesics for the first 7 days of conservative treatment of clinically and radiologically confirmed lumbar disc prolapse. The primary objective was to evaluate if physiotherapy plus analgesics, but without benzodiazepines, is equivalent to the same therapy plus benzodiazepines. The primary endpoint was centralization of referred pain at day 7. Twenty-six female and 34 male patients were enrolled. The median age was 42 years (range 22-68 years). Analysis of the primary endpoint demonstrated equivalence between placebo and diazepam (median 60% vs. 50% reduction of distance of referred pain at day 7) within the predefined equivalence tolerance of 20% at a significance level of p<0.05. Regarding the secondary endpoints, the median duration of the stay in hospital was shorter in the placebo arm (8 vs. 10 days, p=0.008), and the probability of pain reduction on a visual analog scale by more than 50% was twice as high in placebo patients (p<0.0015). Benzodiazepines should not be used routinely in patients treated with mechanical physiotherapy for lumbar disc prolapse.
Slowly rotating relativistic stars in tensor-vector-scalar theory
2010-04-02

In order to examine the rotational effect around neutron star in\\ntensor-vector-scalar (TeVeS) theory, we consider the slowly rotating\\nrelativistic stars with a uniform angular velocity. As a result, we find that\\nsimilar to the case in general relativity (GR), the angular momentum is\\nproportional to the angular velocity. Additionally, as the value of coupling\\nconstant becomes higher, the frame dragging in TeVeS becomes quite\\ndifferent distribution from that in GR, where we can also see the deviation\\neven in the interior of star. While with smaller value of , although the\\nframe dragging approaches to that expected in GR, the induced vector field due\\nto the rotation does not vanish and still exists. Thus, through the\\nobservations associated with relativistic object, one could be possible to\\ndistinguish the gravitational theory in strong field regime even in the case\\nthat the value of coupling constant is quite small.\\n
Mechanical stress-induced reactive gliosis in the auditory nerve and cochlear nucleus
2010-04-02

Object Hearing levels following microsurgical treatment gradually deteriorate in a number of patients treated for vestibular schwannoma (VS), especially in the subacute postoperative stage. The cause of this late-onset deterioration of hearing is not completely understood. The aim of this study was to investigate the possibility that reactive gliosis is a contributory factor. Methods Mechanical damage to nerve tissue is a feature of complex surgical procedures. To explore this aspect of VS treatment, the authors compressed rat auditory nerves with 2 different degrees of injury while monitoring the compound action potentials of the auditory nerve and the auditory brainstem responses. In this experimental model, the axons of the auditory nerve were quantitatively and highly selectively damaged in the cerebellopontine angle without permanent compromise of the blood supply to the cochlea. The temporal bones were processed for immunohistochemical analysis at 1 week and at 8 weeks after compression. Results Reactive gliosis was induced not only in the auditory nerve but also in the cochlear nucleus following mechanical trauma in which the general shape of the auditory brainstem response was maintained. There was a substantial outgrowth of astrocytic processes from the transitional zone into the peripheral portion of the auditory nerve, leading to an invasion of dense gliotic tissue in the auditory nerve. The elongated astrocytic processes ran in parallel with the residual auditory neurons and entered much further into the cochlea. Confocal images disclosed fragments of neurons scattered in the gliotic tissue. In the cochlear nucleus, hypertrophic astrocytic processes were abundant around the soma of the neurons. The transverse diameter of the auditory nerve at and proximal to the compression site was considerably reduced, indicating atrophy, especially in rats in which the auditory nerve was profoundly compressed. Conclusions The authors found for the first time that mechanical stress to the auditory nerve causes substantial reactive gliosis in both the peripheral and central auditory pathways within 1–8 weeks. Progressive reactive gliosis following surgical stress may cause dysfunction in the auditory pathways and may be a primary cause of progressive hearing loss following microsurgical treatment for VS.