bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centrosome amplification in CHO and DT40 cells by inactivation of cyclin‐dependent kinases
Authors: Steere Nathan , Wagner Michael , Beishir Stephen , Smith Ewan , Breslin Loretta , Morrison Ciaran G. , Hochegger Helfrid , Kuriyama Ryoko 
Published: July 2011

AbstractTo study the mechanism of centrosome duplication in cycling cells, we established a novel system of multiple centrosome formation in two types of cells: CHO cells treated with RO3306, a Cyclin‐dependent kinase 1 (Cdk1) inhibitor and DT40 cells, in which Cdks were knocked out by chemical genetics. Cdk1‐inactivated cells initiated DNA replication and centrosome duplication at the onset of S phase. They became arrested at the end of G2, but the centrosome cycle continued to produce supernumerary centrioles/centrosomes without DNA endoreplication in those cells. Centrosomes were amplified in a highly synchronous and reproducible manner: all of them were located next to the nucleus and spread widely apart from each other with several μm in distance. Double knockout of Cdk1 and Cdk2 caused cell cycle arrest at G1/S and centrosomes were no longer duplicated. However, cells continued to grow and increased their volume over 10‐fold during 48 hr of culture. Centrosome components, including γ‐tubulin and Cep135, were synthesized and accumulated during the arrest, allowing rapid centrosome multiplication upon recovery from the cell cycle arrest or expression of exogenous Plk4 in G1/S cells. Thus centrosome amplification results from the discoordination of the centrosome cycle from the progression of other cell cycle events, which is controlled by different levels of Cdk activities. © 2011 Wiley‐Liss, Inc.
Unexpected Opioid Activity Profiles of Analogues of the Novel Peptide Kappa Opioid Receptor Ligand CJ‐15,208
Authors: Aldrich Jane V. , Kulkarni Santosh S. , Senadheera Sanjeewa N. , Ross Nicolette C. , Reilley Kate J. , Eans Shainnel O. , Ganno Michelle L. , Murray Thomas F. , McLaughlin Jay P. 
Published: July 2011

AbstractAn alanine scan was performed on the novel κ opioid receptor (KOR) peptide ligand CJ‐15,208 to determine which residues contribute to the potent in vivo agonist activity observed for the parent peptide. These cyclic tetrapeptides were synthesized by a combination of solid‐phase peptide synthesis of the linear precursors, followed by cyclization in solution. Like the parent peptide, each of the analogues exhibited agonist activity and KOR antagonist activity in an antinociceptive assay in vivo. Unlike the parent peptide, the agonist activity of the potent analogues was mediated predominantly, if not exclusively, by μ opioid receptors (MOR). Thus analogues 2 and 4, in which one of the phenylalanine residues was replaced by alanine, exhibited both potent MOR agonist activity and KOR antagonist activity in vivo. These peptides represent novel lead compounds for the development of peptide‐based opioid analgesics.
Successful recruitment of healthy African American men to genomic studies from high‐volume community health fairs
Authors: Patel Yash R. , Carr Katherine A. , Magjuka David , Mohammadi Yousef , Dropcho Edward F. , Reed Angela D. , Moore Marietta L. , Waddell Mary Jane , Shedd‐Steele Rivienne , Sweeney Christopher J. , Hahn Noah M. 
Published: July 2011

AbstractBACKGROUND:Study of genomic data obtained from patient biospecimens is frequent in research of subjects with prostate and other epithelial malignancies. Understanding of the characteristics of healthy men who participate in genomic research is limited.METHODS:Patients were identified through the Prostate Cancer Genetic Risk Evaluation of SNPs Study and the Indiana University Cancer Biomarker Study, 2 population‐based biomarker and cohort studies. Between 2006 and 2010, healthy Caucasian (n = 774) and healthy African American (n = 381) men were recruited and enrolled at high‐volume free community health fairs. Each participant completed a demographic questionnaire and provided a blood sample for genomic research investigations. Frequency differences between demographic features of healthy African American and Caucasian men were compared and analyzed by 2‐sample t test and multivariate logistic regression after adjusting potential confounding variables with significance at the P < .05 level. Features examined included: age, body mass index (BMI), income, education, marital status, tobacco, alcohol, family history, prostate‐specific antigen (PSA) level, and prior prostate cancer screening history.RESULTS:Significant differences between healthy Caucasian and African American men participating in genomic research included: marital status (married, 69% Caucasian vs 46% African American, P< < .001), mean age (years, 58 Caucasian vs 54 African American, P < .001), mean BMI (kg/m2, 30.9 Caucasian vs 32.3 African American, P = .004), annual income (P = .038), education (P = .002), and mean PSA (ng/mL, 1.2 Caucasian vs 2.0 African American, P = .005).CONCLUSIONS:Significant demographic differences exist between healthy Caucasian and African American men choosing to participate in genomic research. These differences may be important in designing genomic research study recruitment strategies. Cancer 2012;. © 2011 American Cancer Society.
Racial variation in breast cancer treatment among Department of Defense beneficiaries
Authors: Enewold Lindsey , Zhou Jing , McGlynn Katherine A. , Anderson William F. , Shriver Craig D. , Potter John F. , Zahm Shelia H. , Zhu Kangmin 
Published: July 2011

AbstractBACKGROUND:Although the overall age‐adjusted incidence rates for female breast cancer are higher among whites than blacks, mortality rates are higher among blacks. Many attribute this discrepancy to disparities in health care access and to blacks presenting with later stage disease. Within the Department of Defense (DoD) Military Health System, all beneficiaries have equal access to health care. The aim of this study was to determine whether female breast cancer treatment varied between white and black patients in the DoD system.METHODS:The study data were drawn from the DoD cancer registry and medical claims databases. Study subjects included 2308 white and 391 black women diagnosed with breast cancer between 1998 and 2000. Multivariate logistic regression analyses that controlled for demographic factors, tumor characteristics, and comorbidities were used to assess racial differences in the receipt of surgery, chemotherapy, and hormonal therapy.RESULTS:There was no significant difference in surgery type, particularly when mastectomy was compared with breast‐conserving surgery plus radiation (blacks vs whites: odds ratio [OR], 1.1; 95% confidence interval [CI], 0.8‐1.5). Among those with local stage tumors, blacks were as likely as whites to receive chemotherapy (OR, 1.2; 95% CI, 0.9‐1.7) and hormonal therapy (OR, 1.0; 95% CI, 0.6‐1.4). Among those with regional stage tumors, blacks were significantly less likely than whites to receive chemotherapy (OR, 0.4; 95% CI, 0.2‐0.7) and hormonal therapy (OR, 0.5; 95% CI, 0.3‐0.8).CONCLUSIONS:Even within an equal access health care system, stage‐related racial variations in breast cancer treatment are evident. Studies that identify driving factors behind these within‐stage racial disparities are warranted. Cancer 2012;. © 2011 American Cancer Society.
The efficacy of taxane chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers
Authors: Kriege Mieke , Jager Agnes , Hooning Maartje J. , Huijskens Elisabeth , Blom Jannet , van Deurzen Carolien H. M. , Bontenbal Marijke , Collee J. Margriet , Menke‐Pluijmers Marian B. E. , Martens John W. M. , Seynaeve Caroline 
Published: July 2011

AbstractBACKGROUND:We assessed the efficacy of taxane chemotherapy in BRCA1‐ and BRCA2‐associated patients compared with sporadic metastatic breast cancer patients.METHODS:Response rates (RRs) to and progression‐free survival (PFS) after taxane chemotherapy of 35 BRCA1‐associated and 13 BRCA2‐associated metastatic breast cancer patients were compared with those outcomes in 95 matched (1:2) sporadic patients. Matching was performed for age at and year of diagnosis of primary breast cancer, year of metastatic disease, and line of therapy (first vs second or third).RESULTS:Among BRCA1‐associated patients, the RR was worse (objective response [OR], 23% vs 38%; progressive disease [PD], 60% vs 19%; P < 0.001); and the median PFS shorter (2.2 vs 4.9 months; P = 0.04) compared with sporadic patients. In the subgroup of hormone receptor (HRec)‐negative patients, BRCA1‐associated patients (n = 20) had a worse RR (OR, 20% vs 42%, respectively; PD, 70% vs 26%, respectively; P = 0.03) and a shorter PFS (1.8 vs 3.8 months; P = 0.004) compared with sporadic patients (n = 19). These outcomes in HRec‐positive patients were similar in BRCA1‐associated (n = 11) and sporadic (n = 61) patients (OR, 36% vs 38%; PD, 28% vs 20%; median PFS, both 5.7 months). In BRCA2‐associated patients, who were mainly HRec‐positive, the OR was higher than in sporadic patients (89% vs 38%, respectively; P = 0.02), whereas the median PFS was not significantly different (7.1 vs 5.7 months, respectively).CONCLUSIONS:BRCA1‐associated, HRec‐negative metastatic breast cancer patients were less sensitive to taxane chemotherapy than sporadic HRec‐negative patients. HRec‐positive BRCA1‐ and BRCA2‐associated patients had a sensitivity to taxane chemotherapy similar to that of sporadic patients. Cancer 2012;. © 2011 American Cancer Society.
DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node‐negative breast cancer
Authors: Taunk Neil K. , Goyal Sharad , Wu Hao , Moran Meena S. , Chen Sining , Haffty Bruce G. 
Published: July 2011

AbstractBACKGROUND:DEAD box 1 (DDX1) is an RNA helicase with a number of roles, including translation initiation, RNA splicing and modification, and possibly DNA double‐strand break repair. Amplification of DDX1 expression has been implicated in tumors including neuroblastoma, Wilms tumor, retinoblastoma, and testicular carcinoma. The purpose of this study was to evaluate the prognostic significance of DDX1 expression in patients with breast cancer treated with breast‐conserving therapy.METHODS:Paraffin‐embedded specimens from 282 women with node‐negative stage 1 and 2 breast cancer treated with breast‐conserving surgery and radiation therapy were constructed into tissue microarrays and stained for DDX1. The molecular profiles were correlated with clinicopathologic factors and overall, local, and distant metastatic‐free survival.RESULTS:DDX1 positivity was identified in 142 (50%) patients. The median age at diagnosis was 53 years. Eighty percent of the patients had T1 disease; 11% were HER2neu‐positive, and 18% had triple‐negative disease. DDX1 negativity was strongly associated with triple‐negative phenotype (P = .01). DDX1 positivity was found to be associated with improved local relapse‐free survival (96% vs 85%, P = .0233), distant metastatic‐free survival (95% vs 85%, P = .0320), and overall survival (92% vs 84%, P = .0474) at 10 years.CONCLUSIONS:Node‐negative, early stage breast cancer patients with high levels of DDX1 were found to have a significant improvement in local control, distant metastatic‐free survival, and overall survival compared with patients with low levels of DDX1. Cancer 2012;. © 2011 American Cancer Society.
Clinical significance of pretreatment serum C‐reactive protein level in soft tissue sarcoma
Authors: Nakamura Tomoki , Matsumine Akihiko , Matsubara Takao , Asanuma Kunihiro , Uchida Astumasa , Sudo Akihiro 
Published: July 2011

AbstractBACKGROUND:The aim of this study was to determine whether circulating C‐reactive protein (CRP) levels before treatment predict the overall survival and disease‐free survival in soft tissue sarcoma patients.METHODS:A total of 102 primary soft tissue sarcoma patients from 2003 to 2009 were retrospectively reviewed. The CRP levels were obtained before treatment for all patients. The patients who presented with metastases at diagnosis were excluded from this study.RESULTS:Elevated CRP levels were seen in 18 patients. The tumor histological grade and American Joint Committee on Cancer stage in the patients with elevated CRP levels were significantly higher than those in patients with normal CRP levels. Patients with elevated CRP levels before initial treatment had a poorer overall survival than patients with normal CRP levels (P = .01). The overall survival estimates at 3 and 5 years were 75.3% and 53.8%, respectively, versus 90.3% and 81.3%, respectively. Patients with elevated CRP levels before initial treatment had poorer event‐free survival after initial treatment than patients with normal CRP levels (P < .001). The event‐free survival estimates at 2 and 5 years were 53.2% and 33.2%, respectively, versus 83.2% and 81.3%, respectively. A multivariate analysis also showed the preoperative CRP level to be an independent predictor of events.CONCLUSIONS:The pretreatment serum CRP level may be a marker of aggressive tumor characteristics. Pretreatment elevated CRP levels were found to be a poor prognostic factor for overall survival in a univariate analysis, and for disease‐free survival in a multivariate analysis, for soft tissue sarcoma patients. Cancer 2012;. © 2011 American Cancer Society.
Patterns of chemotherapy‐induced toxicities in younger children and adolescents with rhabdomyosarcoma
Authors: Gupta Abha A. , Anderson James R. , Pappo Alberto S. , Spunt Sheri L. , Dasgupta Roshni , Indelicato Daniel J. , Hawkins Douglas S. 
Published: July 2011

AbstractBACKGROUND:Patients aged >10 years with rhabdomyosarcoma have an inferior outcome compared with patients ages 1 to 9 years, which may be explained by toxicities (adverse events [AEs]) that result in chemotherapy dose reductions.METHODS:AEs observed during 1 of 3 randomized chemotherapy regimens (vincristine, dactinomycin, and cyclophosphamide [VAC]; vincristine, dactinomycin, and ifosfamide [VAI]; or vincristine, ifosfamide, and etoposide [VIE]) in the Fourth Intergroup Rhabdomyosarcoma Study were recorded. The incidence of toxicities by age and treatment regimen was determined. The odds of developing AEs in a particular age group (ages 5‐9 years, 10‐14 years, and 15‐20 years) were compared with the odds in the control group of patients ages 1 to 4 years.RESULTS:In total, 657 patients were eligible for analysis. The estimated 5‐year event‐free survival rates were 78%, 83%, 67%, and 58% for the groups ages 1 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 20 years, respectively. Patients ages 15 to 20 years experienced less neutropenia (odds ratio [OR], 0.43; P < .0001), thrombocytopenia (OR, 0.41; P < .0001), anemia (OR, 0.34; P < .0001), and infection (OR, 0.41; P < .0001) compared with younger patients, although they received similar amounts of chemotherapy. In contrast, peripheral nervous system toxicity was higher in adolescents aged >10 years (OR, 4.18; P < .0001). Females experienced more neutropenia (OR, 1.28; P = .05) and thrombocytopenia (OR, 1.26; P = .06) compared with males.CONCLUSIONS:Adolescents who received treatment for rhabdomyosarcoma experienced significantly less hematologic toxicity and more peripheral nervous system toxicity compared with younger children despite receiving similar amounts of chemotherapy. Although outcomes were inferior in adolescents, it was unclear whether the differences in toxicity observed in the current study had an impact on outcome. The authors concluded that future studies examining the age‐related and sex‐related differences in pharmacokinetics of chemotherapy are necessary. Cancer 2012;. © 2011 American Cancer Society.
Spleen deflation and beyond: The pros and cons of Janus kinase 2 inhibitor therapy for patients with myeloproliferative neoplasms
Authors: Quintás‐Cardama Alfonso , Verstovsek Srdan 
Published: July 2011

AbstractThe myeloproliferative neoplasms (MPNs) essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are malignancies that frequently harbor the recurrent somatic point mutation JAK2V617F. The discovery of this mutation has fueled the development of Janus kinase 2 (JAK2) inhibitors. Available results have indicated that JAK2 inhibitors are particularly effective at reducing spleen size. However, the activity of these agents is multifaceted and also involves a marked improvement of systemic symptoms and, for those agents with dual JAK1 and JAK2 inhibitory activity, a marked reduction in the levels of circulating cytokines involved in the pathogenesis of the disease. Because JAK2 inhibitors are not specific for JAK2V617F, responses have also been observed in JAK2V617F‐negative MPNs because of the inhibition of wild‐type JAK2, which is also likely responsible for the induction of cytopenias in patients with MF and for the normalization of peripheral blood counts observed in patients with ET or PV. Given the distinct mortality and morbidity associated with ET, PV, and MF, the use of JAK2 inhibitors appears reasonable for patients with MF as well as for those with ET or PV who have become resistant or intolerant to hydroxyurea. Ongoing randomized, placebo‐controlled, phase 3 trials will further delineate the role of these agents in the management of patients with MPNs. The pros and cons of JAK2 kinase inhibitor therapy are herein discussed. Cancer 2012;. © 2011 American Cancer Society.
Decreased sensitivity of 17p‐deleted chronic lymphocytic leukemia cells to a small molecule BCL‐2 antagonist ABT‐737
Authors: Kojima Kensuke , Duvvuri Seshagiri , Ruvolo Vivian , Samaniego Felipe , Younes Anas , Andreeff Michael 
Published: July 2011

AbstractBACKGROUND:Despite the high complete response rates achieved with fludarabine‐based regimens, relapse is inevitable in chronic lymphocytic leukemia (CLL). Relapsed patients often acquire deletions of the short arm of chromosome 17 (del[17p]), which are closely associated with tumor protein 53 (TP53) mutations. Wild‐type p53 up‐regulates and activates B‐cell CLL/lymphoma 2 (BCL‐2)‐associated X protein (BAX), and it down‐regulates and inactivates BCL‐2. The small‐molecule BCL‐2 inhibitor ABT‐737 induces apoptosis in a BAX‐dependent and BCL‐2 homologous antagonist‐killer (BAK)‐dependent manner. The role of p53 in sensitivity of CLL cells to BCL‐2 inhibition has not been extensively investigated.METHODS:The authors investigated the association of del(17p) with ABT‐737 sensitivity in CLL cells from 50 patients. Stable p53 and BAX knockdown cells were used for mechanistic studies.RESULTS:CLL cells with del(17p) were less sensitive to ABT‐737‐induced BAX activation and apoptosis than CLL cells without del(17p) (39% ± 7.3% vs 63.7% ± 2.9% [specific annexin V induction]; P < .01). A positive correlation between the degrees of apoptosis induced by ABT‐737 and by the p53‐activating binding protein homolog murine double minute (MDM2) antagonist nutlin‐3a (correlation coefficient [r] = 0.75; P < .0001) was observed. CLL cells with del(17p) expressed lower levels of BAX than those without del(17p) (0.67 ± 0.12 vs 1.27 ± 0.10 in relative protein expression levels; P < .01). Knockdown of p53 or BAX in leukemia cells resulted in decreased apoptosis induced by ABT‐737.CONCLUSIONS:The current data indicated that p53 dysfunction may lead to decreased apoptosis induction by ABT‐737. Cancer 2012;. © 2011 American Cancer Society.
Early onset HER2‐positive breast cancer is associated with germline TP53 mutations
Authors: Melhem‐Bertrandt Amal , Bojadzieva Jasmina , Ready Kaylene J. , Obeid Elias , Liu Diane D. , Gutierrez‐Barrera Angelica M. , Litton Jennifer K. , Olopade Olufunmilayo I. , Hortobagyi Gabriel N. , Strong Louise C. , Arun Banu K. 
Published: July 2011

AbstractBACKGROUND:Germline TP53 mutations predispose to early onset breast cancer in women and are associated with Li‐Fraumeni syndrome. Published data on the pathological characteristics of breast cancer among women with TP53 mutations is limited.METHODS:We retrospectively reviewed the clinical records of women who underwent genetic testing for suspected germline TP53 mutations and who were diagnosed with breast cancer between 2000 and 2011. The pathological characteristics of the breast tumors from patients testing positive for a mutation (cases) were compared with those testing negative (controls).RESULTS:Patients who tested positive for germlineTP53 mutations (n = 30) were compared with controls (n = 79). Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared with 25% for the controls (P = .0001). Among patients with a mutation, 70% had estrogen receptor‐ and/or progesterone receptor‐positive tumors, compared with 68% in the control group (P = .87). After adjusting for age at breast cancer diagnosis, having a HER2‐positive tumor increased the odds of testing positive for a germline TP53 mutation (odds ratio, 6.9; 95% confidence interval, 2.6‐18.2). For each yearly increment in age at breast cancer diagnosis, there was decreased likelihood of having a TP53 mutation of 5% (odds ratio, 0.95; 95% confidence interval0.91‐0.99).CONCLUSIONS:This study suggests an association between germline TP53 mutations and early onset HER2‐positive breast cancer. If confirmed in a larger cohort, these results could guide genetic testing strategies, lead to chemoprevention trials incorporating HER2‐targeted therapies, and elucidate some of the molecular pathways involved in breast cancer. Cancer 2012;. © 2011 American Cancer Society.
Anodic coloring of titanium and its alloy for jewels production
Authors: Diamanti M. V. , Del Curto B. , Masconale V. , Passaro C. , Pedeferri M. P. 
Published: July 2011

AbstractAnodized titanium with its interference colors, its appearances and its light, is undoubtedly of great appeal to the field of architecture and to all ramifications of design, to visual communication and to the world of fashion. On its surface, it is possible to create a visionary world of colors, perfectly controlled by the imposition of determined anodizing parameters and surface conditions. This article presents one of the applications of anodized titanium, which most earns general interest nowadays in the designers' world, that is, the production of colored titanium jewels. Since titanium is considered a seminoble metal, its use is mainly directed to small series production: therefore, a good know‐how giving high reliability of the anodic coloring process is required. The chosen procedure will be described, together with a full characterization of the obtained interference colors. © 2011 Wiley Periodicals, Inc. Col Res Appl, 2012