bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining EGFR and mTOR Blockade for the Treatment of Epithelioid Sarcoma
Authors: Xie Xianbiao , Ghadimi Markus P.H. , Young Eric D. , Belousov Roman , Zhu Quan-sheng , Liu Juehui , Lopez Gonzalo , Colombo Chiara , Peng Tingsheng , Reynoso David , Hornick Jason L. , Lazar Alexander J. , Lev Dina 
Published: August 2011

Abstract
Purpose: Molecular deregulations underlying epithelioid sarcoma (ES) progression are poorly understood yet critically needed to develop new therapies. Epidermal growth factor receptor (EGFR) is overexpressed in ES; using preclinical models, we examined the ES EGFR role and assessed anti-ES EGFR blockade effects, alone and with mTOR inhibition.
Experimental Design: EGFR and mTOR expression/activation was examined via tissue microarray (n = 27 human ES specimens; immunohistochemistry) and in human ES cell lines (Western blot and quantitative reverse transcriptase PCR). Cell proliferation, survival, migration, and invasion effects of EGFR and mTOR activation treated with erlotinib (anti-EGFR small-molecule inhibitor) alone and combined with rapamycin were assessed in cell culture assays. In vivo growth effects of erlotinib alone or with rapamycin were evaluated using severe combined immunodeficient mouse ES xenograft models.
Results: EGFR was expressed and activated in ES specimens and cell lines. EGFR activation increased ES cell proliferation, motility, and invasion and induced cyclin D1, matrix metalloproteinase (MMP) 2, and MMP9 expression. EGFR blockade inhibited these processes and caused significant cytostatic ES growth inhibition in vivo. mTOR pathway activation at varying levels was identified in all tissue microarray–evaluable ES tissues; 88% of samples had no or reduced PTEN expression. Similarly, both ES cell lines showed enhanced mTOR activity; VAESBJ cells exhibited constitutive mTOR activation uncoupled from EGFR signaling. Most importantly, combined erlotinib/rapamycin resulted in synergistic anti-ES effects in vitro and induced superior tumor growth inhibition in vivo versus single agent administration.
Conclusions: EGFR and mTOR signaling pathways are deregulated in ES. Preclinical ES model–derived insights suggest that combined inhibition of these targets might be beneficial, supporting evaluations in clinical trials. Clin Cancer Res; 17(18); 5901–12. ©2011 AACR.
ABT-737 Induces Apoptosis in Mantle Cell Lymphoma Cells with a Bcl-2high/Mcl-1low Profile and Synergizes with Other Antineoplastic Agents
Authors: Touzeau Cyrille , Dousset Christelle , Bodet Linda , Gomez-Bougie Patricia , Bonnaud Stéphanie , Moreau Anne , Moreau Philippe , Pellat-Deceunynck Catherine , Amiot Martine , Le Gouill Steven 
Published: August 2011

Abstract
Purpose: Mantle cell lymphoma (MCL) is considered to be incurable. ABT-737 is a BH3 mimetic that targets Bcl-2, which is overexpressed in MCL and implicated in drug resistance. The present work investigated the antitumor effect of ABT-737.
Experimental Design: Six MCL cell lines and primary MCL cells (n = 13) were used. Sensitivity to ABT-737 was assessed, and expression levels of Bcl-2 and Mcl-1 were analyzed. Finally, ABT-737 was combined with other cytotoxic agents to promote tailored therapy.
Results: MINO and GRANTA-519 cell lines were highly sensitive to ABT-737 [the median lethal dose (LD50) = 20 and 80 nmol/L, respectively], whereas other cell lines were resistant. In primary MCL cells, 46% of patients' samples were sensitive to ABT-737. The analysis of protein expression levels revealed that both sensitive cell lines and primary MCL cells could be characterized by a Bcl-2high/Mcl-1low profile, whereas resistant MCL cells contained high levels of Mcl-1. ABT-737 induced a rapid disruption of both Bcl-2/Bax and Bcl-2/Bik complexes. In addition, silencing of Mcl-1 by siRNA sensitized MCL cell lines to ABT-737. Similarly, flavopiridol, which induces Mcl-1 downregulation, in combination with ABT-737 led to a synergistic anti-MCL effect in ABT-737–resistant cell lines. This synergy was also observed when ABT-737 was combined with either bortezomib or cytarabine.
Conclusions: The present work shows that ABT-737 induces strong apoptosis in MCL cells expressing a Bcl-2high/Mcl-1low profile. In ABT-737–resistant MCL cells, downregulation of Mcl-1 overcomes Mcl-1–induced resistance and synergizes ABT-737 effects. Our results strongly support the use of ABT-737 according to the Bcl-2/Mcl-1 tumor cell profiles in the treatment of MCL. Clin Cancer Res; 17(18); 5973–81. ©2011 AACR.
IKKβ Overexpression Leads to Pathologic Lesions in Stratified Epithelia and Exocrine Glands and to Tumoral Transformation of Oral Epithelia
Authors: Page Angustias , Cascallana José L. , Casanova M. Llanos , Navarro Manuel , Alameda Josefa P. , Pérez Paloma , Bravo Ana , Ramírez Angel 
Published: August 2011

Abstract
Alterations in nuclear factor kappaB (NFκB) signaling have been related with several diseases and importantly also with cancer. Different animal models with increased or diminished NFκB signaling have shown that NFκB subunits and their regulators are relevant to the pathophysiology of different organs and tissues. In particular, both the deletion of the regulatory subunit β of the kinase of the inhibitor of NFκB (IKKβ) and its overexpression in epidermis lead to the development of skin inflammatory diseases not associated with tumoral lesions. In this work, we have studied the consequences of IKKβ overexpression in other organs and tissues. We found that elevated IKKβ levels led to altered development and functionality of exocrine glands (i.e., mammary glands) in transgenic female mice. In oral epithelia, increased IKKβ expression produced lichenoid inflammation with abundant granulocytes, macrophages, and B cells, among other inflammatory cells. This inflammatory phenotype was associated with high incidence of tumoral lesions in oral epithelia, contrary to what was found in skin. Moreover, IKKβ also increased the malignant progression of both spontaneous and experimentally induced oral tumors. These results highlight the importance of IKKβ in epithelial and glandular homeostasis as well as in oral tumorigenesis and open the possibility that IKKβ activity might be implicated in the development of oral cancer in humans. Mol Cancer Res; 9(10); 1329–38. ©2011 AACR.
Positive body image: Inter-ethnic and rural–urban differences among an indigenous sample from Malaysian Borneo
Authors: Swami Viren , Kannan Kumaraswami , Furnham Adrian 
Published: August 2011

Background: Previous studies examining body image from a cross-cultural perspective have tended to neglect samples from different ethnic groups or along a rural–urban continuum. To overcome this limitation, the present study examined positive body image among rural and urban women from three major indigenous ethnic groups in Sabah, Malaysia. Method: A total of 202 women completed the Body Appreciation Scale, as well as measures of media exposure and financial security, and provided their demographic details. Results: Results showed that there were significant rural–urban differences in body appreciation, with rural participants having significantly higher body appreciation than urban participants. A comparison with a previous data set of West Malaysian women (Swami & Chamorro-Premuzic, 2008) showed that the current urban sample had significantly lower body appreciation and that the rural group had significantly higher body appreciation. Further results showed that research site (urban vs rural) explained 11.0% of the variance in body appreciation. Participant body mass index and exposure to western forms of media explained an additional 2.0% of the variance. Conclusion: These results suggest that there are differences in body image between rural and urban women. Results are discussed in relation to the promotion of positive body image, particularly in developing societies where health care resources may be limited.
RETRACTED: Money and Mimicry
Authors: Liu Jia (Elke) , Vohs Kathleen D. , Smeesters Dirk 
Published: August 2011

The following article has been retracted by the Editor and publishers of Psychological Science: Liu, J. (E.), Vohs, K. D., & Smeesters, D. (2011). Money and mimicry: When being mimicked makes people feel threatened. Psychological Science, 22, 1150–1151. doi: 10.1177/0956797611418348 The retraction follows the results of an investigation into the work of author Dirk Smeesters. The Smeesters Follow-Up Investigation Committee of Erasmus University Rotterdam has determined the following in regard to the retracted article: The paper indicates that the variable Liking of the confederate consists of two items with α = 0.91, whereas a reconstruction of the data proves that three items were used with α = 0.90. The authors state that respondents were randomly assigned to the different experimental conditions. However a test of independence of gender with the experimental conditions shows that this is not the case ( p < 0.001). In a response, Smeesters acknowledged this observation. The Committee considers this to be a major methodological mistake that can affect the interpretation of the paper referring to Criterion 7: committing imputable inaccuracies when undertaking research. As Smeesters was in charge of data collection the Committee holds him solely responsible. The Committee recommends retraction of this paper. ( Smeesters Follow-Up Investigation Committee, 2014 , p. 7) The committee found no blame on the part of Smeesters’s coauthors, who have seen and agreed to this retraction.
Influence of internal parallel and v-shaped ribs on the discharge coefficient of a cylindrical film cooling hole
Authors: Heneka C , Schulz A , Bauer H-J 
Published: August 2011

An experimental study has been conducted to investigate the discharge behaviour of cylindrical film cooling holes with the main focus on the effects of rib arrangement and crossflow velocity inside the internal cooling passage of a gas turbine blade. Two straight flow channels of rectangular cross-section simulate the crossflow situations present at the inlet and outlet of a filmcooling hole. The two channels are connected by a single scaled-up film cooling hole with adiameter of 10 mm, an inclination angle of 30°, and a length-to-diameter ratio of 6. Measurements have been performed at various internal crossflow Mach numbers and rib geometries for both parallel and perpendicular orientations of internal and external crossflows. Parallel and v-shaped ribs with quadratic cross-section and four different angles with respect to the internal crossflow direction (45°, 60°, 75°, and 90°) have been placed upstream and downstream of the entrance of the hole at one wall of the cooling passage. The rib height equals the hole diameter, the rib pitch to height ratio is 10. The internal crossflow Mach number has been varied between 0 and 0.37. The data show that placing ribs onto the wall of the coolant passage may result in reduced, unchanged, or even increased discharge coefficients. Internal crossflow Mach number and orientation of the coolant passage in respect to the hole axis have been identified as major influencing parameters.
Tales from the sequestered room: Client experiences of social work in Norway and Sweden
Authors: Ylvisaker Signe 
Published: August 2011

• Summary: This article focuses on accounts made by clients and social workers about their encounters with one another at social welfare agencies in Norway and Sweden. These are drawn from interviews conducted with 24 women and men asked about their experiences of being social welfare clients. Additional data drawn from interviews conducted with 14 social workers in Norway about their experiences with clients are also explored. In interviewing clients, a main concern was with discussing their recollections of these meetings. Interviews with social workers, too, focused on their recollections, both positive and negative, of encounters with clients. • Findings: The main patterns revealed by analyses of transcribed accounts show that social work is experienced by clients as being extremely beneficial when it provides them with space and opportunities to bring forth aspects of their lives and life stories often not properly acknowledged in other arenas. Conversely, social work is experienced as least beneficial by clients when they feel their concerns are being belittled, redefined and/or ignored. Both social workers and clients agree that good social work involves empathy, sensitivity and opportunities allowing clients to voice their own concerns. • Applications: This study’s findings indicate that one rich source of knowledge about the possibilities as well as limitations of social work practice at welfare agencies is represented by what can be gained by listening attentively to and recording exactly what clients and social workers tell of their encounters in these special sequestered arenas.
IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells
Authors: Huynh HoangDinh , Zheng Junke , Umikawa Masato , Zhang Chaozheng , Silvany Robert , Iizuka Satoru , Holzenberger Martin , Zhang Wei , Zhang Cheng Cheng 
Published: August 2011

AbstractThe role of IGF binding protein 2 (IGFBP2) in cell growth is intriguing and largely undefined. Previously we identified IGFBP2 as an extrinsic factor that supports ex vivo expansion of hematopoietic stem cells (HSCs). Here we showed that IGFBP2-null mice have fewer HSCs than wild-type mice. While IGFBP2 has little cell-autonomous effect on HSC function, we found decreased in vivo repopulation of HSCs in primary and secondary transplanted IGFBP2-null recipients. Importantly, bone marrow stromal cells that are deficient for IGFBP2 have significantly decreased ability to support the expansion of repopulating HSCs. To investigate the mechanism by which IGFBP2 supports HSC activity, we demonstrated that HSCs in IGFBP2-null mice had decreased survival and cycling, down-regulated expression of antiapoptotic factor Bcl-2, and up-regulated expression of cell cycle inhibitors p21, p16, p19, p57, and PTEN. Moreover, we found that the C-terminus, but not the RGD domain, of extrinsic IGFBP2 was essential for support of HSC activity. Defective signaling of the IGF type I receptor did not rescue the decreased repopulation of HSCs in IGFBP2-null recipients, suggesting that the environmental effect of IGFBP2 on HSCs is independent of IGF-IR mediated signaling. Therefore, as an environmental factor, IGFBP2 supports the survival and cycling of HSCs.
Dual-functional capability of CD3+CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity
Authors: Pievani Alice , Borleri Gianmaria , Pende Daniela , Moretta Lorenzo , Rambaldi Alessandro , Golay Josée , Introna Martino 
Published: August 2011

AbstractCD3+CD56+ cytokine-induced killer (CIK) cells display a potent cytolytic activity. The adhesion molecule lymphocyte function-associated antigen-1 plays a crucial role in binding as well as in cytolytic activity of CIK cells against tumor target cells expressing the corresponding ligands. CIK cells express activating natural killer (NK) receptors, including NKG2D, DNAX accessory molecule-1 (DNAM-1), and low levels of NKp30. Cell signaling not only through TCR/CD3 but also through NKG2D, DNAM-1, and NKp30 leads to CIK cell activation resulting in granule exocytosis, cytokine secretion, and cytotoxicity. Antibody blocking experiments showed that DNAM-1, NKG2D, and NKp30 are involved in the TCR-independent tumor cell recognition and killing. Anti–CMV-specific CIK cells could be expanded in standard CIK cultures and mediate both specific, MHC-restricted recognition and TCR-independent NK-like cytolytic activity against leukemic cell lines or fresh leukemic blasts. Antibody blocking of lymphocyte function-associated antigen-1 and DNAM-1 led to significant reduction of both CTL and NK-cell functions, whereas blocking of NKG2D and NKp30 only inhibited NK-like cytotoxicity. Their dual-effector function suggests that CIK cells, when used in a clinical setting, may control both neoplastic relapses and viral infections, 2 frequently associated complications in patients who received a transplant.
Follicular lymphoma tumor–infiltrating T-helper (TH) cells have the same polyfunctional potential as normal nodal TH cells despite skewed differentiation
Authors: Hilchey Shannon P. , Rosenberg Alexander F. , Hyrien Ollivier , Secor-Socha Shelley , Cochran Matthew R. , Brady Michael T. , Wang Jyh-Chiang E. , Sanz Iñaki , Burack W. Richard , Quataert Sally A. , Bernstein Steven H. 
Published: August 2011

AbstractThe follicular lymphoma (FL) T-cell microenvironment plays a critical role in the biology of this disease. We therefore determined the lineage, differentiation state, and functional potential of FL-infiltrating CD4+ T-helper cells (TH) compared with reactive and normal lymph node (NLN) TH cells. Relative to NLNs, FL cells have decreased proportions of naive and central memory but increased proportions of effector memory TH cells. We further show differences in the distribution and anatomical localization of CXCR5+ TH populations that, on the basis of transcription factor analysis, include both regulatory and follicular helper T cells. On Staphylococcus enterotoxin-B stimulation, which stimulates T cells through the T-cell receptor, requires no processing by APCs, and can overcome regulator T cell-mediated suppression, the proportion of uncommitted primed precursor cells, as well as TH2 and TH17 cells is higher in FL cells than in reactive lymph nodes or NLNs. However, the proportion of TH1 and polyfunctional TH cells (producing multiple cytokines simultaneously) is similar in FL cells and NLNs. These data suggest that, although TH-cell differentiation in FL is skewed compared with NLNs, FL TH cells should have the same intrinsic ability to elicit antitumor effector responses as NLN TH cells when tumor suppressive mechanisms are attenuated.
KLF1 gene mutations cause borderline HbA2
Authors: Perseu Lucia , Satta Stefania , Moi Paolo , Demartis Franca Rosa , Manunza Laura , Sollaino Maria Carla , Barella Susanna , Cao Antonio , Galanello Renzo 
Published: August 2011

Abstract
Increased hemoglobin A2 (HbA2; ie, levels > 3.9%) is the most important feature of β-thalassemia carriers. However, it is not uncommon to find persons with borderline HbA2 (levels, 3.3%-3.8%), who pose a relevant screening problem. Several genotypes have been associated with borderline HbA2, but sometimes the reasons for this unusual phenotype are unknown. In this paper, we report, for the first time, that mutations of KLF1 result in HbA2 levels in the borderline range. Six different KLF1 mutations were identified in 52 of 145 subjects with borderline HbA2 and normal mean corpuscular volume and mean corpuscular hemoglobin. Two mutations (T327S and T280_H283del) are here reported for the first time. The prevalent mutation in Sardinians is S270X, which accounts for 80.8% of the total. The frequent discovery of KLF1 mutations in these atypical carriers may contribute significantly to the thalassemia screening programs aimed at identification of at risk couples.
Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia
Authors: Ravandi Farhad , O'Brien Susan , Jorgensen Jeffrey , Pierce Sherry , Faderl Stefan , Ferrajoli Alessandra , Koller Charles , Challagundla Pramoda , York Sergernne , Brandt Mark , Luthra Rajyalakshmi , Burger Jan , Thomas Deborah , Keating Michael , Kantarjian Hagop 
Published: August 2011

Abstract
We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the vari-ant form (HCLv). Cladribine 5.6 mg/m2 given IV over 2 hours daily for 5 days was followed ∼ 1 month later with rituximab 375 mg/m2 IV weekly for 8 weeks. Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated including 5 with HCLv. Median age was 57 years (range, 37-89). All patients (100%) have achieved complete response (CR), defined as presence of no hairy cells in BM and blood with normalization of counts (absolute neutrophil count [ANC]> 1.5 × 109/L, hemoglobin [Hgb] > 12.0 g/dL, platelets [PLT] > 100 × 109/L), as well as resolution of splenomegaly. There were no grade 3 or 4 nonhematologic adverse events directly related to the treatment. Only 1 patient (with HCLv) has relapsed; median CR duration has not been reached (range,1+-63+ months). Three patients with HCLv died including 1 with relapsed disease and 2 from unrelated malignancies. Median survival duration has not been reached (range, 2+-64+ months). Treatment with clad-ribine followed by rituximab is effective tk;4and may increase CR rate. This study was registered at www.clinicaltrials.gov as NCT00412594.
Impact of severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density in men
Authors: El Hadidy El Hadidy M , Ghonaim Mohamed , El Gawad Soma Sh Abd , El Atta Mohamed Abou 
Published: August 2011

Abstract

Background
Hyperthyroidism is accompanied by osteoporosis with higher incidence of fracture rates. The present work aimed to study bone status in hyperthyroidism and to elucidate the impact of severity, duration, and etiology of hyperthyroidism on biochemical markers of bone turnover and bone mineral density (BMD).

Methods
Fifty-two male patients with hyperthyroidism, 31 with Graves' disease (GD) and 21 with toxic multinodular goiter (TNG), with an age ranging from 23 to 65 years were included, together with 25 healthy euthyroid men with matched age as a control group. In addition to full clinical examination, patients and controls were subjected to measurement of BMD using dual-energy X-ray absorptiometery scanning of the lower half of the left radius. Also, some biochemical markers of bone turnover were done for all patients and controls.

Results
Biochemical markers of bone turnover: included serum bone specific alkaline phosphatase, osteocalcin, carboxy terminal telopeptide of type l collagen also, urinary deoxypyridinoline cross-links (DXP), urinary DXP/urinary creatinine ratio and urinary calcium/urinary creatinine ratio were significantly higher in patients with GD and TNG compared to controls (P < 0.01). However, there was non-significant difference in these parameters between GD and TNG patients (P > 0.05). BMD was significantly lower in GD and TNG compared to controls, but the Z-score of BMD at the lower half of the left radius in patients with GD (-1.7 ± 0.5 SD) was not significantly different from those with TNG (-1.6 ± 0.6 SD) (>0.05). There was significant positive correlation between free T3 and free T4 with biochemical markers of bone turnover, but negative correlation between TSH and those biochemical markers of bone turnover. The duration of the thyrotoxic state positively correlated with the assessed bone turnover markers, but it is negatively correlated with the Z-score of BMD in the studied hyperthyroid patients (r = -0.68, P < 0.0001).

Conclusion
Men with hyperthyroidism have significant bone loss with higher biochemical markers of bone turnover. The severity and the duration of the thyrotoxic state are directly related to the derangement of biochemical markers of bone turnover and bone loss.