bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRAF, a target in melanoma
Authors: Flaherty Keith T. , McArthur Grant 
Published: July 2010

AbstractThe successful translation of therapies targeting signal‐transduction pathways that are activated by oncogenes has provided a model for molecularly targeted therapy, and the identification of mutations in v‐raf murine sarcoma viral oncogene homolog B1 (BRAF), a serine/threonine kinase, has turned the attention of the melanoma field toward this concept. The current review indicated that BRAF represents an important target in cancer, in part because it is present in 7% of all cancers and also because it represents the first intracellular signaling molecule that is activated by point mutations for which single‐agent therapy appears to have efficacy. Therapy for advanced melanoma has progressed slowly over the past 3 decades, although significant advances have been made in other cancers with the application of cytotoxic chemotherapy and targeted therapies. However, in melanoma, cytotoxic chemotherapies have severe limits, chemotherapy does not convincingly improve on the natural history of metastatic disease and has no role in the adjuvant setting, and cytokine therapy may have a niche in both the adjuvant and metastatic settings but confers only a modest benefit to a small proportion of patients at the cost of severe toxicity. Thus, there are few other cancers in which completely novel therapies are so highly prioritized in clinical research. Understanding network of signal‐transduction pathways and how that network may adapt to BRAF inhibition or mitogen‐activated protein kinase kinase inhibition will point to the next generation of clinical trials investigating rational combination regimens. The current investigations in melanoma will create a set of hypotheses to be tested in each cancer that harbors BRAF mutations. Cancer 2010. © 2010 American Cancer Society.
African ancestry and higher prevalence of triple‐negative breast cancer
Authors: Stark Azadeh , Kleer Celina G. , Martin Iman , Awuah Baffour , Nsiah‐Asare Anthony , Takyi Valerie , Braman Maria , E. Quayson Solomon , Zarbo Richard , Wicha Max , Newman Lisa 
Published: July 2010

AbstractBACKGROUND:The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple‐negative disease.METHODS:African American and white American women with invasive cancer diagnosed at the Henry Ford Health System comprised the primary study population, and Ghanaian patients diagnosed and/or treated at the Komfo Anokye Teaching Hospital in Kumasi, Ghana constituted the comparison group. Formalin‐fixed, paraffin‐embedded specimens were transported to the University of Michigan for histopathology confirmation, and assessment of estrogen and progesterone receptors and HER‐2/neu expression.RESULTS:The study population included 1008 white Americans, 581 African Americans, and 75 Ghanaians. Mean age at diagnosis was 48.0 years for Ghanaian, 60.8 years for African American, and 62.4 for white American cases (P = .002). Proportions of Ghanaian, African American, and white American cases with estrogen receptor‐negative tumors were 76%, 36%, and 22%, respectively (P < .001), and proportions with triple‐negative disease were 82%, 26%, and 16%, respectively (P < .001). All Ghanaian cases were palpable, locally advanced cancers; 57 (76%) were grade 3. A total of 147 American women were diagnosed as stage III or IV; of these, 67.5% (n = 46) of African Americans and 44.6% (n = 29) of white Americans were grade 3. Among palpable, grade 3 cancers, Ghanaians had the highest prevalence of triple‐negative tumors (82.2%), followed by African Americans (32.8%) and white Americans (10.2%).CONCLUSIONS:Our study demonstrates progressively increasing frequency of estrogen receptor‐negative and triple‐negative tumors among breast cancer patients with white American, African American, and Ghanaian/African backgrounds. This pattern indicates a need for additional investigations correlating the extent of African ancestry and high‐risk breast cancer subtypes. Cancer 2010. © 2010 American Cancer Society.
Chromosome 9p deletions identify an aggressive phenotype of clear cell renal cell carcinoma
Authors: La Rochelle Jeffrey , Klatte Tobias , Dastane Aditi , Rao Nagesh , Seligson David , Said Jonathan , Shuch Brian , Zomorodian Nazy , Kabbinavar Fairooz , Belldegrun Arie , Pantuck Allan J. 
Published: July 2010

AbstractBACKGROUND:The authors investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease‐specific survival (DSS) and recurrence‐free survival (RFS) and whether it was associated with more aggressive behavior in small renal masses.METHODS:In total, 703 ccRCC tumors were analyzed using fluorescence in situ hybridization (316 tumors) and cytogenetics (388 tumors). Tumor grade, classification, and size; 9p status; Eastern Cooperative Oncology Group performance status (ECOG PS); lymph node involvement; and the presence of metastasis were recorded. Outcomes were stratified by 9p status, and a Cox proportional hazards models was constructed using TNM staging, ECOG PS, tumor size, tumor grade, and 9p status.RESULTS:Deletions of 9p were detected in 97 tumors (13.8%). At presentation, 9p‐deleted tumors were larger and were more likely to be high grade (grade 3 or 4), to have a high tumor (T) classification (T3‐T4), and to have lymph node or distant metastases (P < .01). The median DSS for patients with and without 9p deletions was 37 months and 82 months, respectively (P < .01). In patients with localized disease, the median RFS in those who had 9p deletions was 53 months and was not reached in those without 9p deletions (P < .01). In patients who had localized lesions that measured ≤4 cm in greatest dimension, 9p‐deleted tumors were more likely to recur (19% vs 2%; P = .01).CONCLUSIONS:Deletion of chromosome 9p in ccRCC occurred in 14% of patients and was associated with higher grade and T classification, and the presence of lymph node and distant metastases. In addition, 9p deletion independently conferred a worse prognosis for patients with localized ccRCC, and most noteworthy, in patients with localized, small renal masses. Preoperatively identifying patients with 9p deletions will improve risk stratification and will help to select appropriate patients for surveillance protocols or aggressive treatment. Cancer 2010. © 2010 American Cancer Society.
Phase 1‐2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma
Authors: Yau Thomas , Chan Pierre , Pang Roberta , Ng Kelvin , Fan S. T. , Poon Ronnie T. 
Published: July 2010

AbstractBACKGROUND:This phase 1‐2 trial assessed the efficacy and tolerability of an oral angiogenesis inhibitor—PTK787/ZK222584 (PTK)—in combination with intravenous doxorubicin for the treatment of advanced hepatocellular carcinoma (HCC) patients.METHODS:In phase 1, advanced HCC patients received PTK at escalating doses together with doxorubicin 60 mg/m2 given as an intravenous bolus every 3 weeks to establish the maximum tolerated dose (MTD). Subsequently, in phase 2, all patients received the same regimen with oral PTK at the MTD dose every 3 weeks for a maximum of 6 cycles.RESULTS:Nine patients were recruited in phase 1, with the MTD established as 750 mg daily. Overall, 27 patients received the regimen with PTK at 750 mg daily. The median age was 52 years (range, 23‐73 years), and 63 percent of patients were chronic hepatitis B carriers. Notably, the majority of patients had Child‐Pugh B cirrhosis. The overall response rate was 26.0%, with all the responding patients having partial response. Another 20% of patients achieved stable disease for at least 12 weeks. The median progression‐free survival was 5.4 months (range, 0.27‐23.6 months), and overall survival was 7.3 months (range, 0.8‐23.6 months). The commonest grade 3 or 4 nonhematological toxicities were mucositis (11%) and alopecia (7%), respectively. Grade 3 or 4 neutropenia was observed in 7 (26%) patients; 2 had neutropenic sepsis.CONCLUSIONS:The combination of PTK with intravenous doxorubicin shows encouraging activity in treating advanced HCC patients. Cancer 2010. © 2010 American Cancer Society.
Complementary therapies for children undergoing stem cell transplantation
Authors: Phipps Sean , Barrera Maru , Vannatta Kathryn , Xiong Xiaoping , Doyle John J. , Alderfer Melissa A. 
Published: July 2010

AbstractBACKGROUND:Children undergoing stem cell transplant (SCT) experience high levels of somatic distress and mood disturbance. This trial evaluated the efficacy of complementary therapies (massage, humor therapy, relaxation/imagery) for reducing distress associated with pediatric SCT.METHODS:Across 4 sites, 178 pediatric patients scheduled to undergo SCT were randomized to a child‐targeted intervention involving massage and humor therapy, the identical child intervention plus a parent intervention involving massage and relaxation/imagery, or standard care. Randomization was stratified by site, age, and type of transplant. The interventions began at admission and continued through SCT Week +3. Primary outcomes included patient and parent reports of somatic distress and mood disturbance obtained weekly from admission through Week +6 using the Behavioral, Affective, and Somatic Experiences Scales. Secondary outcomes included length of hospitalization, time to engraftment, and usage of narcotic analgesic and antiemetic medications.RESULTS:A mixed model approach was used to assess longitudinal trends of patient and parent report outcomes and to test differences between groups on these measures. Significant changes across time were observed on all patient and parent report outcomes. However, no significant differences between treatment arms were found on the primary outcomes. Similarly, no significant between‐group differences were noted on any of the medical variables as secondary outcomes.CONCLUSIONS:Results of this multisite trial failed to document significant benefits of complementary interventions in the pediatric SCT setting. Cancer 2010. © 2010 American Cancer Society.
The tyrosine kinase c‐Abl promotes proliferation and is expressed in atypical teratoid and malignant rhabdoid tumors
Authors: Koos Björn , Jeibmann Astrid , Lünenbürger Henning , Mertsch Sonja , Nupponen Nina N. , Roselli Annariikka , Leuschner Ivo , Paulus Werner , Frühwald Michael C. , Hasselblatt Martin 
Published: July 2010

AbstractBACKGROUND:Atypical teratoid/rhaboid tumors (AT/RTs) and extracranial malignant rhabdoid tumors are highly malignant neoplasms with a dismal prognosis. These tumors predominantly affect infants and targeted, adjuvant treatment approaches would be highly desirable.METHODS:In the current study, the authors investigated the expression and functional role of tyrosine kinases in 2 malignant rhabdoid tumor cell lines (A204 and G401) and in a series of 5 AT/RTs and 18 malignant rhabdoid tumors (13 rhabdoid tumors of the kidney and 5 extrarenal rhabdoid tumors).RESULTS:Both cell lines consistently expressed the tyrosine kinase c‐Abl, which promoted proliferation as assessed by small interfering RNA knockdown. Blockage of c‐Abl using the tyrosine kinase inhibitor imatinib resulted in reduced cellular growth in both cell lines. Furthermore, c‐Abl was expressed in all rhabdoid tumors, whereas expression of platelet‐derived growth factor receptor subtypes alpha and beta was infrequent and c‐Kit expression was absent.CONCLUSIONS:The current data pointed toward a role for c‐Abl in the biology of malignant rhabdoid tumors and provided a rationale for the investigation of tyrosine kinase inhibitors that target c‐Abl for the treatment of these aggressive tumors. Cancer 2010. © 2010 American Cancer Society
Dasatinib induces autophagic cell death in human ovarian cancer
Authors: Le Xiao‐Feng , Mao Weiqun , Lu Zhen , Carter Bing Z. , Bast Robert C. 
Published: July 2010

AbstractBACKGROUND:Dasatinib, an inhibitor of Src/Abl family kinases, can inhibit tumor growth of several solid tumors. However, the effect and mechanism of action of dasatinib in human ovarian cancer cells remains unknown.METHODS:Dasatinib‐induced autophagy was determined by acridine orange staining, punctate localization of GFP‐LC3, LC3 protein blotting, and electron microscopy. Significance of beclin 1, AKT, and Bcl‐2 in dasatinib‐induced autophagy and growth inhibition was assayed by small interfering RNA (siRNA) silencing and/or overexpression of the gene of interest.RESULTS:Dasatinib inhibited cell growth by inducing little apoptosis, but substantial autophagy in SKOv3 and HEY ovarian cancer cells. In vivo studies showed dasatinib inhibited tumor growth and induced both autophagy and apoptosis in a HEY xenograft model. Knockdown of beclin 1 and Atg12 expression with their respective siRNAs diminished dasatinib‐induced autophagy, whereas knockdown of p27Kip1 with specific siRNAs did not. Small hairpin RNA knockdown of beclin 1 expression reduced dasatinib‐induced autophagy and growth inhibition. Dasatinib reduced the phosphorylation of AKT, mTOR, p70S6K, and S6 kinase expression. Constitutive expression of AKT1 and AKT2 inhibited dasatinib‐induced autophagy in both HEY and SKOv3 cells. Dasatinib also reduced Bcl‐2 expression and activity. Overexpression of Bcl‐2 partially prevented dasatinib‐induced autophagy.CONCLUSIONS:Dasatinib induces autophagic cell death in ovarian cancer that partially depends on beclin 1, AKT, and Bcl‐2. These results may have implications for clinical use of dasatinib. Cancer 2010. © 2010 American Cancer Society.
Critical role of surgery in patients with gastroesophageal carcinoma with a poor prognosis after chemoradiation as defined by positron emission tomography
Authors: Patnana Srikrishna V. , Murthy Santosh B. , Xiao Lianchun , Rohren Eric , Hofstetter Wayne L. , Swisher Stephen G. , Liao Zhongxing , Lee Jeffrey H. , Bhutani Manoop S. , Macapinlac Homer A. , Wang Xuemei , Ajani Jaffer A. 
Published: July 2010

AbstractBACKGROUND:The prognosis of patients with localized gastroesophageal carcinoma (LGC) can be defined after chemoradiation by the standardized uptake value (SUV) of positron emission tomography (PET). High SUV (HSUV) after chemoradiation portends a poor prognosis. The authors retrospectively examined the role of surgery in patients with HSUV after chemoradiation.METHODS:The authors analyzed the postchemoradiation PET scans of 204 LGC patients. One hundred twenty‐nine patients had HSUV. Two postchemoradiation variables were evaluated: SUV and surgery and their association with overall survival (OS) and event‐free survival (EFS). The log‐rank test, multivariate Cox proportional hazards model, and Kaplan‐Meier survival plots were used to assess the association between OS or EFS and the dichotomized SUV (using the median SUV as the cutoff) and surgery.RESULTS:The median SUV was 4.6. The OS of the 52 patients who had an SUV above the median and did not undergo surgery (HSUV‐NS) (median OS, 1.22 years; 95% confidence interval [95% CI], 1.02‐2.16 years) was much shorter than that of the 77 patients with an SUV above the median who underwent surgery (HSUV‐S) (median OS, 2.7 years; 95% CI, 2.43 years to not reached [P<.0001]). Similarly, the EFS for patients with HSUV‐NS was significantly shorter than that for patients with HSUV‐S (P= .001). In the multivariate analyses, patients who underwent surgery (irrespective of SUV) had a lower risk of death (P= .0001) and disease progression (P= .002).CONCLUSIONS:The data from the current study suggest that surgery may prolong OS and EFS in patients with a poor prognosis after chemoradiation as defined by PET. However, these data need confirmation. Cancer 2010. © 2010 American Cancer Society.
Breastfeeding in survivors of Hodgkin lymphoma treated with chest radiotherapy
Authors: McCullough Laura , Ng Andrea , Najita Julie , Janov Abbe , Henderson Tara , Mauch Peter , Diller Lisa 
Published: July 2010

AbstractBACKGROUND:Female survivors of therapeutic chest radiation often question whether they will have difficulty with breast feeding, given their prior exposure to breast radiation. In the current study, the rates of successful breastfeeding in long‐term survivors who received chest radiotherapy (CXRT) as a treatment for Hodgkin lymphoma (HL) were examined.METHODS:A survey study of survivors of HL who were treated at the Joint Center for Radiation Therapy in Boston from 1969 through 1996 was performed. Patients were queried about childbearing and breastfeeding. The authors analyzed self‐reported breastfeeding success in women who reported live births after CXRT and compared them with a sibling control group.RESULTS:Overall, 83 female survivors of HL who were treated with CXRT reported at least 1 birth after treatment. There were a total of 141 post‐HL pregnancies resulting in births. In these women, the median age at the time of the HL diagnosis was 23 years (range, 14‐40 years) and the median radiation dose was 41 grays (Gy) (range, 27‐46 Gy). For survivors, 57 of the 94 (61%) breastfeeding attempts were successful, whereas within the control group, 74 of the 94 (79%) attempts were successful (P = .044). Accounting for maternal age at first birth and birth era, multivariable analysis suggested that HL survivors treated with CXRT may be less likely to breastfeed successfully than their siblings (odds ratio, 0.42; 95% confidence interval, 0.2‐1.0 [P = .06]).CONCLUSIONS:The majority of female HL survivors who were treated with CXRT report being able to breastfeed successfully. However, the results of the current study indicate a trend toward less successful breastfeeding in survivors as a previously unreported late effect of radiation. Cancer 2010. © 2010 American Cancer Society.
The 2006 consensus guidelines for the management of women with abnormal cervical screening tests
Authors: Colgan Terence J. 
Published: July 2010

AbstractThe American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines for the management of women with abnormal cervical screening test results is a powerful, evidence‐based document representing an advance in the consistent treatment of women with cervical abnormalities. Nevertheless, the complexity of the guidelines is an outstanding issue, compliance with the guidelines is problematic in some areas, and there is a growing recognition of the deficiencies of colposcopy. In light of these challenges, the cytopathology community has an opportunity to play an active role in integrating data, defining risk, and recommending proper management for women screened for cervical cancer. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
Molecular regulation of the developing commissural plate
Authors: Moldrich Randal X. , Gobius Ilan , Pollak Thomas , Zhang Jiangyang , Ren Tianbo , Brown Lucia , Mori Susumu , De Juan Romero Camino , Britanova Olga , Tarabykin Victor , Richards Linda J. 
Published: July 2010

AbstractThe commissural plate of the developing mouse brain showing all telencephalic midline commissures in single plane of tissue. The Journal of Comparative Neurology, Volume 518, Number 18, 3645–3661.
NIC‐assisted cache‐efficient receive stack for message passing over Ethernet
Authors: Goglin Brice 
Published: July 2010

AbstractHigh‐speed networking in clusters usually relies on advanced hardware features in the NICs, such as zero‐copy capability. Open‐MX is a high‐performance message‐passing stack tailored for regular Ethernet hardware without such capabilities. We present the addition of a multiqueue support in the Open‐MX receive stack so that all incoming packets for the same process are handled on the same core. We then introduce the idea of binding the target end process near its dedicated receive queue. This model leads to a more cache‐efficient receive stack for Open‐MX. It also proves that very simple and stateless hardware features may have a significant impact on message‐passing performance over Ethernet. The implementation of this model in a firmware reveals that it may not be as efficient as some manually tuned micro‐benchmarks. But our multiqueue receive stack generally performs better than the original single queue stack, especially on large communication patterns where multiple processes are involved and manual binding is difficult. Copyright © 2010 John Wiley & Sons, Ltd.
On the Reliability of the AMBER Force Field and its Empirical Dispersion Contribution for the Description of Noncovalent Complexes
Authors: Kolář Michal , Berka Karel , Jurečka Petr , Hobza Pavel 
Published: July 2010

AbstractThe reliability of the AMBER force field is tested by comparing the total interaction energy and dispersion energy with the reference data obtained at the density functional theory–symmetry‐adapted perturbation treatment (DFT–SAPT)/aug‐cc‐pVDZ level. The comparison is made for 194 different geometries of noncovalent complexes (H‐bonded, stacked, mixed, and dispersion‐bound), at the equilibrium distances as well as at longer distances (up to a relative distance of two). The total interaction energies agree very well with the reference data and only the strength of H‐bonded complexes is slightly underestimated. In the case of dispersion energy, the overall agreement is even better, with the exception of the stacked aromatic systems, where the empirical dispersion energy is overestimated. The use of AMBER interaction energy and AMBER dispersion energy for different types of noncovalent complexes at equilibrium as well as at longer distances is thus justified, except for a few cases, such as the water molecule, where the dispersion energy is highly inaccurate.
Ion Interactions with the Carbon Nanotube Surface in Aqueous Solutions: Understanding the Molecular Mechanisms
Authors: Frolov Andrey I. , Rozhin Alex G. , Fedorov Maxim V. 
Published: July 2010

AbstractWe study the molecular mechanisms of alkali halide ion interactions with the single‐wall carbon nanotube surface in water by means of fully atomistic molecular dynamics simulations. We focus on the basic physical‐chemical principles of ion–nanotube interactions in aqueous solutions and discuss them in light of recent experimental findings on selective ion effects on carbon nanotubes.
Room‐temperature synthesis and characterization of cross‐like Pr2(C2O4)3·10H2O micro‐particles
Authors: Yin Xiaobin , Zhang Youjin , Fang Zhiyong , Xu Zhenyu , Zhu Wei , He Hongmei 
Published: July 2010

AbstractCross‐like Pr2(C2O4)3·10H2O micro‐particles were synthesized through a simple precipitation method at room temperature. The products were characterized by X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), field‐emission scanning electron microscopy (FESEM), thermogravimetry–differential thermal analysis (TG‐DTA) and photoluminescence (PL). The possible formation mechanism of the cross‐like Pr2(C2O4)3·10H2O micro‐particles was discussed, and Pr6O11 with similar morphology was obtained by calcining the oxalate precursor. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)