bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Study Using the Risk of Ovarian Cancer Algorithm to Screen for Ovarian Cancer
Authors: Menon Usha , Skates Steven J. , Lewis Sara , Rosenthal Adam N. , Rufford Barnaby , Sibley Karen , MacDonald Nicola , Dawnay Anne , Jeyarajah Arjun , Bast Robert C. , Oram David , Jacobs Ian J. 
Published: October 2005

Purpose To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile. Patients and Methods Postmenopausal women, ≥ 50 years were randomly assigned to a control group or screen group. Screening involved serum CA125, interpreted using the ROC algorithm. Participants with normal results returned to annual screening; those with intermediate results had repeat CA125 testing; and those with elevated values underwent transvaginal ultrasound (TVS). Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion. Results Thirteen thousand five hundred eighty-two women were recruited. Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer (EOC). The specificity and positive predictive value (PPV) for primary invasive EOC were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively. Conclusion An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women.
Phase II Trial of Bevacizumab Plus Gemcitabine in Patients With Advanced Pancreatic Cancer
Authors: Kindler Hedy L. , Friberg Gregory , Singh Deepti A. , Locker Gershon , Nattam Sreenivasa , Kozloff Mark , Taber David A. , Karrison Theodore , Dachman Abraham , Stadler Walter M. , Vokes Everett E. 
Published: October 2005

Purpose Vascular endothelial growth factor (VEGF) plays a key role in the biology and prognosis of pancreatic cancer. Inhibitors of VEGF suppress the growth of pancreatic cancer in preclinical models. The objectives of this phase II study were to assess the response rate and overall survival of pancreatic cancer patients who received gemcitabine with the recombinant humanized anti-VEGF monoclonal antibody bevacizumab. Patients and Methods Patients with previously untreated advanced pancreatic cancer received gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Bevacizumab, 10 mg/kg, was administered after gemcitabine on days 1 and 15. Tumor measurements were assessed every two cycles. Plasma VEGF levels were obtained pretreatment. Results Fifty-two patients were enrolled at seven centers between November 2001 and March 2004. All patients had metastatic disease, and 83% had liver metastases. Eleven patients (21%) had confirmed partial responses, and 24 (46%) had stable disease. The 6-month survival rate was 77%. Median survival was 8.8 months; median progression-free survival was 5.4 months. Pretreatment plasma VEGF levels did not correlate with outcome. Grade 3 and 4 toxicities included hypertension in 19% of the patients, thrombosis in 13%, visceral perforation in 8%, and bleeding in 2%. Conclusion The combination of bevacizumab plus gemcitabine is active in advanced pancreatic cancer patients. Additional study is warranted. A randomized phase III trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo is ongoing in the Cancer and Leukemia Group B.
Biologic and Prognostic Significance of Dermal Ki67 Expression, Mitoses, and Tumorigenicity in Thin Invasive Cutaneous Melanoma
Authors: Gimotty Phyllis A. , Van Belle Patricia , Elder David E. , Murry Todd , Montone Kathleen T. , Xu Xiaowei , Hotz Susan , Raines Shane , Ming Michael E. , Wahl Peter , Guerry DuPont 
Published: October 2005

PurposeTumor cell proliferation is a central feature of melanoma progression. In this study, we characterized three biomarkers of proliferation (Ki67 expression, dermal mitotic rate [MR], and tumorigenicity) in thin (≤ 1.00 mm) primary cutaneous melanomas and examined their association with prognosis.Patients and MethodsWe used immunohistochemistry to determine Ki67 expression using the monoclonal antibody MIB-1 in lesions from a prospective cohort that included 396 patients with thin invasive primary melanomas seen between 1972 and 1991. A multivariate Cox proportional hazards model was used to define independent prognostic factors, and recursive partitioning was used to develop a prognostic tree identifying risk groups.ResultsDermal Ki67 expression was lower than epidermal Ki67 expression in radial growth phase (RGP) melanomas (n = 171), and dermal Ki67 expression and MR were higher in tumorigenic vertical growth phase (VGP) melanomas (n = 193) compared with RGP and nontumorigenic VGP melanomas (n = 42). Dermal Ki67 expression, MR greater than 0, growth phase, thickness, ulceration, tumor-infiltrating lymphocytes, and sex were associated with metastasis at 10 years, however, only dermal Ki67 expression, MR greater than 0, and sex were independent prognostic factors. Two high-risk groups were identified: men and women with dermal MR greater than 0 and dermal Ki67 expression ≥ 20% in tumor cells and men with MR greater than 0 and Ki67 expression less than 20%, with 10-year metastasis rates of 39% and 20%, respectively.ConclusionProliferation slows as melanoma cells enter the dermis and then increases with the onset of tumorigenic VGP. Ki67 expression and dermal MR provide independent prognostic information that can potentially be used in risk-based management of patients.
Serial Monitoring of Circulating Melanoma Cells During Neoadjuvant Biochemotherapy for Stage III Melanoma: Outcome Prediction in a Multicenter Trial
Authors: Koyanagi Kazuo , O'Day Steven J. , Gonzalez Rene , Lewis Karl , Robinson William A. , Amatruda Thomas T. , Wang He-Jing , Elashoff Robert M. , Takeuchi Hiroya , Umetani Naoyuki , Hoon Dave S.B. 
Published: October 2005

Purpose Circulating tumor cells (CTCs) in blood may be important in assessing tumor progression and treatment response. We hypothesized that quantitative real-time reverse transcriptase polymerase chain reaction using multimarker mRNA assays could detect CTCs and be used as a surrogate predictor of outcome in patients receiving neoadjuvant biochemotherapy (BC) for melanoma. Patients and Methods Blood specimens were collected at four sampling points from 63 patients enrolled on a prospective multicenter phase II trial of BC before and after surgical treatment of American Joint Committee on Cancer stage III melanoma. Each specimen was assessed by quantitative real-time reverse transcriptase polymerase chain reaction for expression of four melanoma-associated markers: melanoma antigen recognized by T cells 1; β1 → 4-N-acetylgalactosaminyltransferase; paired box homeotic gene transcription factor 3; and melanoma antigen gene-A3 family, and the changes of CTCs during treatment and prognostic effect of CTCs after overall treatment on recurrence and survival were investigated. Results At a median postoperative follow-up time of 30.4 months, 44 (70%) patients were clinically disease free. In relapse-free patients, the number of detected markers significantly decreased during preoperative BC (P = .036), during postoperative BC (P = .002), and during overall treatment (P < .0001). Marker detection after overall treatment was associated with significant decreases in relapse-free and overall survival (P < .0001). By multivariate analysis using a Cox proportional-hazards model, the number of markers detected after overall treatment was a significant independent prognostic factor for overall survival (risk ratio, 12.6; 95% CI, 3.16 to 50.5; P = .0003). Conclusion Serial monitoring of CTCs in blood may be useful for indicating systemic subclinical disease and predicting outcome of patients receiving neoadjuvant BC for metastatic melanoma.
Prognostic Significance of BACH2 Expression in Diffuse Large B-Cell Lymphoma: A Study of the Osaka Lymphoma Study Group
Authors: Sakane-Ishikawa Emiko , Nakatsuka Shin-ichi , Tomita Yasuhiko , Fujita Shigeki , Nakamichi Itsuko , Takakuwa Tetsuya , Sugiyama Haruo , Fukuhara Shirou , Hino Masayuki , Kanamaru Akihisa , Soma Toshihiro , Tsukaguchi Machiko , Igarashi Kazuhiko , Kanakura Yuzuru , Aozasa Katsuyuki 
Published: October 2005

Purpose BACH2, a B-cell–specific transcription repressor, is abundantly expressed in lymphocytes of B-cell lineage as well as B-cell lymphoma cell lines. BACH2 possesses an inhibitory effect on proliferation of Raji cell lines derived from Burkitt's lymphoma. In this study, the prognostic significance of BACH2 expression was examined in diffuse large B-cell lymphoma (DLBCL). Patients and Methods BACH2 expression was immunohistochemically examined on the paraffin-embedded sections obtained by biopsy from 108 patients (62 males and 46 females; age range, 23 to 85 years) with DLBCL. Staining intensity in the cytoplasm of the tumor cells was categorized as equal to or stronger (level 1) or weaker (level 2) than that in the endothelial cells in the same specimens. Results Level 1 and 2 expression of BACH2 was found in 32.4% and 67.6% of patients, respectively. Patients with level 1 expression showed significantly better disease-free and overall survival rate than those with level 2 expression (both P < .05). Multivariate analysis revealed BACH2 expression level together with performance status, elevated serum level of lactate dehydrogenase, and treatment response to be independent factors for prognosis of the patients. Conclusion BACH2 expression level is a useful marker to predict disease-free and overall survival of patients with DLBCL.
Assessment of Cardiac Dysfunction in a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel, With or Without Trastuzumab As Adjuvant Therapy in Node-Positive, Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: NSABP B-31
Authors: Tan-Chiu Elizabeth , Yothers Greg , Romond Edward , Geyer Charles E. , Ewer Michael , Keefe Deborah , Shannon Richard P. , Swain Sandra M. , Brown Ann , Fehrenbacher Louis , Vogel Victor G. , Seay Thomas E. , Rastogi Priya , Mamounas Eleftherios P. , Wolmark Norman , Bryant John 
Published: October 2005

Purpose Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) –positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines. Patients and Methods National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. Results Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for ≥ 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity. Conclusion Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy.
A Population-Based Validation of the American Joint Committee on Cancer Melanoma Staging System
Authors: Gimotty Phyllis A. , Botbyl Jeffrey , Soong Seng-jaw , Guerry DuPont 
Published: October 2005

PurposeA major revision of the American Joint Committee on Cancer (AJCC) stages for melanoma was implemented in 2002 after its validation in multinational cohorts including patients from cancer centers and cooperative groups. This staging system has not been validated in a US population-based cohort.Patients and MethodsWe used 41,417 patients with primary invasive cutaneous melanoma diagnosed between 1988 and 2001 from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer registry to validate the revised AJCC staging system. Survival rates computed from stage-specific Kaplan-Meier curves (time to melanoma-specific death) were compared with the survival rates from 17,600 patients in the original AJCC validation study.ResultsIn the SEER cohort, 65% of reported melanomas were ≤ 1.00 mm in thickness and 8.7% were more than 4.00 mm compared with 39% and 10% in the AJCC cohort (P < .001), respectively. AJCC stages were able to discriminate among SEER patient groups with different prognosis. However, SEER survival rates were significantly higher than those in the AJCC study and notably so in patients with T1a lesions (≤ 1 mm without ulceration). This population-specific effect remained significant after controlling for lesion thickness in all substages except stage IIA.ConclusionAlthough this national population-based study validates the most recent revision of AJCC stages for melanoma, it emphasizes that survival rates are population specific and found them to be generally higher for SEER compared with AJCC patients. Population-specific survival rates should be used in study designs and decisions about patient-specific interventions.
Variates of Survival in Metastatic Uveal Melanoma
Authors: Rietschel Petra , Panageas Katherine S. , Hanlon Christine , Patel Ami , Abramson David H. , Chapman Paul B. 
Published: October 2005

Purpose The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival. Patients and Methods All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy. Results The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis. Conclusion A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.
Thyroid Hormone-Regulated Target Genes Have Distinct Patterns of Coactivator Recruitment and Histone Acetylation
Authors: Liu Ying , Xia Xianmin , Fondell Joseph D. , Yen Paul M. 
Published: October 2005

AbstractThyroid hormone receptors (TRs) are ligand-regulated transcription factors that bind to thyroid hormone response elements of target genes. Upon ligand binding, they recruit coactivator complexes that increase histone acetylation and recruit RNA polymerase II (Pol II) to activate transcription. Recent studies suggest that nuclear receptors and coactivators may have temporal recruitment patterns on hormone response elements, yet little is known about the nature of the patterns at multiple endogenous target genes. We thus performed chromatin immunoprecipitation assays to investigate coactivator recruitment and histone acetylation patterns on the thyroid hormone response elements of four endogenous target genes (GH, sarcoplasmic endoplasmic reticulum calcium-adenosine triphosphatase, phosphoenolpyruvate carboxykinase, and cholesterol 7α-hydroxylase) in a rat pituitary cell line that expresses TRs. We found that TRβ, several associated coactivators (steroid receptor coactivator-1, glucocorticoid receptor interacting protein-1, and TR-associated protein 220), and RNA Pol II were rapidly recruited to thyroid hormone response elements as early as 15 min after T3 addition. When the four target genes were compared, we observed differences in the types and temporal patterns of recruited coactivators and histone acetylation. Interestingly, the temporal pattern of RNA Pol II was similar for three genes studied. Our findings suggest that thyroid hormone-regulated target genes may have distinct patterns of coactivator recruitment and histone acetylation that may enable highly specific regulation.
Torque in Mooring Chain. Part 1: Background and Theory
Authors: Hobbs R. E , L Ridge I. M 
Published: October 2005

Chain in both its forms - common (or stud-less) and stud-link - has many engineering applications. It is widely used as a component in the moorings of offshore floating systems, where its ruggedness and corrosion resistance make it an attractive choice. Chain exhibits some interesting behaviour in that when straight and subject to an axial load it does not twist or generate any torque, but if twisted or loaded when in a twisted condition it behaves in a highly non-linear manner, with the torque dependent upon the level of twist and axial load. Clearly an understanding of the way in which chains may behave and interact with other mooring components (such as wire rope, which also exhibits coupling between axial load and generated torque) when they are in service is essential. However, the sizes of chain that are in use in offshore moorings (typical bar diameters are 75 mm and greater) are too large to allow easy testing. This paper, which is in two parts, aims to address the issues and considerations relevant to torque in mooring chain. The first part introduces a frictionless theory that predicts the resultant torques and ‘lift’ in the links as non-dimensionalized functions of the angle of twist. Fortran code is presented in an Appendix, which allows the reader to make use of the analysis. The second part of the paper presents results from experimental work on both stud-less (41 mm) and stud-link (20.5 and 56mm) chains. Torsional data are presented in both ‘constant twist’ and ‘constant load’ forms, as well as considering the lift between the links.
Torque in Mooring Chain. Part 2: Experimental Investigation
Authors: L Ridge I. M , Hobbs R. E 
Published: October 2005

Chain is a commonly used component in offshore moorings where its ruggedness and corrosion resistance make it an attractive choice. Another attractive property is that a straight chain is inherently torque balanced. Having said this, if a chain is loaded in a twisted condition, or twisted when under load, it exhibits highly non-linear torsional behaviour. The consequences of this behaviour can cause handling difficulties or may compromise the integrity of the mooring system, and care must be taken to avoid problems for both the chain and any components to which it is connected. Even with knowledge of the potential problems, there will always be occasions where, despite the utmost care, twist is unavoidable. Thus it is important for the engineer to be able to determine the effects. A frictionless theory has been developed in Part 1 of the paper that may be used to predict the resultant torques and movement or ‘lift’ in the links as non-dimensional functions of the angle of twist. The present part of the paper describes a series of experiments undertaken on both stud-less and stud-link chain to allow comparison of this theoretical model with experimental data. Results are presented for the torsional response and link lift for ‘constant twist’ and ‘constant load’ type tests on chains of three different link sizes.
Lifetime Predictions For High-Temperature Low-Alloy Ferritic Steel Weldments
Authors: Hayhurst D. R , Goodall I. W , Hayhurst R. J , Dean D. W 
Published: October 2005

The paper reports the finite element creep continuum damage mechanics (CDM) analysis of the creep rupture behaviour of thin-section butt-welded, internally pressurized pipes, and of uniaxial cross-welded tension testpieces made of Cr-Mo-V steels. The CDM analyses are shown to predict accurately lifetimes and failure mechanisms observed from metallographic analyses of sectioned components. The paper then addresses the lifetime prediction of components by comparing predictions made using British Standards BSi PD 5500 with the results of the experiments. Predictions have been based on uniaxial plain bar data for both parent and Type IV materials; both of these have been obtained by integration of constitutive equations. Comparison of predicted and experimental weldment lifetimes has been made using a weld strength reduction factor. It is found that the required factors are very dependent on temperature and the ratio of axial to hoop pipe stresses. Finally, the paper examines the British Energy Generation Limited R5 assessment procedure and compares lifetime predictions with those made using the British Standards BSi PD 5500 approach. It is noted that the stresses in both approaches are in good agreement for the external/internal radius ratio of 1.25 considered in the butt-welded pipe experiments.