bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen Receptor β Expression Is Associated with Tamoxifen Response in ERα-Negative Breast Carcinoma
Authors: Gruvberger-Saal Sofia K. , Bendahl Pär-Ola , Saal Lao H. , Laakso Mervi , Hegardt Cecilia , Edén Patrik , Peterson Carsten , Malmström Per , Isola Jorma , Borg Åke , Fernö Mårten 
Published: April 2007

Abstract
Purpose: Endocrine therapies, such as tamoxifen, are commonly given to most patients with estrogen receptor (ERα)–positive breast carcinoma but are not indicated for persons with ERα-negative cancer. The factors responsible for response to tamoxifen in 5% to 10% of patients with ERα-negative tumors are not clear. The aim of the present study was to elucidate the biology and prognostic role of the second ER, ERβ, in patients treated with adjuvant tamoxifen.
Experimental Design: We investigated ERβ by immunohistochemistry in 353 stage II primary breast tumors from patients treated with 2 years adjuvant tamoxifen, and generated gene expression profiles for a representative subset of 88 tumors.
Results: ERβ was associated with increased survival (distant disease-free survival, P = 0.01; overall survival, P = 0.22), and in particular within ERα-negative patients (P = 0.003; P = 0.04), but not in the ERα-positive subgroup (P = 0.49; P = 0.88). Lack of ERβ conferred early relapse (hazard ratio, 14; 95% confidence interval, 1.8-106; P = 0.01) within the ERα-negative subgroup even after adjustment for other markers. ERα was an independent marker only within the ERβ-negative tumors (hazard ratio, 0.44; 95% confidence interval, 0.21-0.89; P = 0.02). An ERβ gene expression profile was identified and was markedly different from the ERα signature.
Conclusion: Expression of ERβ is an independent marker for favorable prognosis after adjuvant tamoxifen treatment in ERα-negative breast cancer patients and involves a gene expression program distinct from ERα. These results may be highly clinically significant, because in the United States alone, ∼10,000 women are diagnosed annually with ERα-negative/ERβ-positive breast carcinoma and may benefit from adjuvant tamoxifen.
Utility of Circulating B-RAF DNA Mutation in Serum for Monitoring Melanoma Patients Receiving Biochemotherapy
Authors: Shinozaki Masaru , O'Day Steven J. , Kitago Minoru , Amersi Farin , Kuo Christine , Kim Joseph , Wang He-Jing , Hoon Dave S.B. 
Published: April 2007

Abstract
Purpose: Somatic B-RAF gene mutation has been identified in many malignancies and detected at a high frequency in cutaneous malignant melanoma. However, the significance of the B-RAF mutation (B-RAFmt) in terms of its prognostic and predictive capabilities for treatment response or disease outcome is not known. We hypothesized that circulating serum B-RAFmt (B-RAFsmt) at V600E, detected in serum, predicts response in melanoma patients receiving concurrent biochemotherapy.
Experimental Design: A real-time clamp quantitative reverse transcription-PCR assay was designed to assess B-RAFsmt by peptide nucleic acid clamping and a locked nucleic acid hybrid probe. Normal (n = 18) and American Joint Committee on Cancer stage I to IV melanoma patients (n = 103) were evaluated. These included stage IV patients (n = 48) with blood drawn before and after biochemotherapy. Patients were classified as biochemotherapy responders or nonresponders. Responders (n = 24) had a complete or partial response following biochemotherapy; nonresponders (n = 24) developed progressive disease.
Results: Of the 103 melanoma patients, 38 (37%) had B-RAFsmt DNA, of which 11 of 34 (32%) were stage I or II, and 27 of 69 (39%) were stage III or IV. Of the 48 biochemotherapy patients, 10 of 24 (42%) patients were positive for the B-RAFsmt in the respective responder and nonresponder groups before treatment. After biochemotherapy, B-RAFsmt was detected in only 1 of 10 patients (10%) in the responder group and 7 of 10 patients (70%) in the nonresponder group. B-RAFsmt is associated with significantly worse (P = 0.039) overall survival in patients receiving biochemotherapy.
Conclusion: These studies show the presence and utility of circulating B-RAFsmt DNA in melanoma patients.
Potent siRNA Inhibitors of Ribonucleotide Reductase Subunit RRM2 Reduce Cell Proliferation In vitro and In vivo
Authors: Heidel Jeremy D. , Liu Joanna Yi-Ching , Yen Yun , Zhou Bingsen , Heale Bret S.E. , Rossi John J. , Bartlett Derek W. , Davis Mark E. 
Published: April 2007

Abstract
Purpose: Ribonucleotide reductase (RR) is a therapeutic target for DNA replication–dependent diseases such as cancer. Here, a potent small interfering RNA (siRNA) duplex against the M2 subunit of RR (RRM2) is developed and shown to reduce the growth potential of cancer cells both in vitro and in vivo.
Experimental Design: Three anti-RRM2 siRNAs were identified via computational methods, and the potency of these and additional “tiling” duplexes was analyzed in cultured cells via cotransfections using a RRM2-luciferase fusion construct. Knockdown of RRM2 by the best duplex candidates was confirmed directly by Western blotting. The effect of potent duplexes on cell growth was investigated by a real-time cell electronic sensing assay. Finally, duplex performance was tested in vivo in luciferase-expressing cells via whole animal bioluminescence imaging.
Results: Moderate anti-RRM2 effects are observed from the three duplexes identified by computational methods. However, the tiling experiments yielded an extremely potent duplex (siR2B+5). This duplex achieves significant knockdown of RRM2 protein in cultured cells and has pronounced antiproliferative activity. S.c. tumors of cells that had been transfected with siR2B+5 preinjection grew slower than those of control cells.
Conclusions: An anti-RRM2 siRNA duplex is identified that exhibits significant antiproliferative activity in cancer cells of varying human type and species (mouse, rat, monkey); these findings suggest that this duplex is a promising candidate for therapeutic development.
A Phase I Pharmacokinetic and Pharmacodynamic Study of PX-12, a Novel Inhibitor of Thioredoxin-1, in Patients with Advanced Solid Tumors
Authors: Ramanathan Ramesh K. , Kirkpatrick D. Lynn , Belani Chandra P. , Friedland David , Green Sylvan B. , Chow H-H. Sherry , Cordova Catherine A. , Stratton Steven P. , Sharlow Elizabeth R. , Baker Amanda , Dragovich Tomislav 
Published: April 2007

Abstract
Purpose: Thioredoxin-1 (Trx-1) is a cellular redox protein that promotes tumor growth, inhibits apoptosis, and up-regulates hypoxia-inducible factor-1α and vascular endothelial growth factor. Objectives of this study were to determine safety, tolerability, pharmacodynamics, and pharmacokinetics of PX-12, a small-molecule inhibitor of Trx-1.
Experimental Design: Thirty-eight patients with advanced solid tumors received PX-12 at doses of 9 to 300 mg/m2, as a 1- or 3-h i.v. infusion on days 1 to 5, repeated every 3 weeks.
Results: At the 300 mg/m2 dose level, one patient experienced a reversible episode of pneumonitis during the first cycle, and a second patient developed pneumonitis after the second cycle. Doses up to 226 mg/m2 were well tolerated, and grade 3/4 events were uncommon (&lt;3% of patients). The limiting factor on this dosing schedule was pungent odor caused by expired drug metabolite, 2-butanethiol. The best response was stable disease in seven patients (126-332 days). Whereas PX-12 was not detectable following the infusion, the Cmax of its inactive metabolite, 2-mercaptoimidazole, increased linearly with dose. PX-12 treatment lowered plasma Trx-1 concentrations in a dose-dependent manner.
Conclusions: PX-12, the first Trx-1 inhibitor to enter clinical trials, was tolerated up to a dose of 226 mg/m2 by a 3-h infusion. Based on pharmacodynamic and pharmacokinetic data, a trial of prolonged infusion schedule of PX-12 has been initiated.
Plasma Matrix Metalloproteinase-9 Level Is Better than Serum Matrix Metalloproteinase-9 Level to Predict Gastric Cancer Evolution
Authors: Wu Chun-Ying , Wu Ming-Shiang , Chiang En-Pei , Chen Yi-Ju , Chen Chien-Jen , Chi Nai-Hui , Shih Ying-Ting , Chen Gran-Hum , Lin Jaw-Town 
Published: April 2007

Abstract
Purpose: Matrix metalloproteinase-9 (MMP-9) in blood is a promising new tumor marker. The aims of the present study are to compare the usefulness of plasma and serum MMP-9 levels for predicting gastric cancer development, invasion, and survival.
Experimental Design: In this nested case-control study, 114 gastric cancer patients and 87 healthy controls were enrolled. MMP-9 levels and activities were quantitatively measured by ELISA assay and zymography. The results were compared with the occurrence, clinicopathologic features, and outcomes of gastric cancer patients. The follow-up time for all patients was at least 5 years.
Results: Serum MMP-9 levels were significantly higher than plasma MMP-9 levels. Both plasma and serum MMP-9 levels correlated significantly with active MMP-9 identified by zymography (P = 0.002 and P = 0.048, respectively). Plasma MMP-9 level was significantly elevated in gastric cancer patients when compared with control subjects (P &lt; 0.001). Serum MMP-9 levels did not differ between the groups. Receiver-operator characteristics analysis showed the values of sensitivity (82.5%) and specificity (65.5%) at the maximum accuracy for plasma MMP-9 at ≥60 ng/mL (P &lt; 0.001). Elevated plasma MMP-9 correlated significantly with lymph node metastasis [odds ratio (OR), 3.43; P = 0.019], lymphatic invasion (OR, 7.58; P = 0.009), and venous invasion (OR, 4.14; P = 0.033). Patients with elevated plasma MMP-9 levels had poorer survival rates than those with normal plasma MMP-9 levels (P = 0.038). Serum MMP-9 level did not correlate well with gastric cancer–invasive phenotypes or survival.
Conclusion: Our results suggest plasma MMP-9 level is a better marker than serum MMP-9 level for predicting gastric cancer development and progression.
Selective Tumor Targeting by the Hypoxia-Activated Prodrug AQ4N Blocks Tumor Growth and Metastasis in Preclinical Models of Pancreatic Cancer
Authors: Lalani Alshad S. , Alters Susan E. , Wong Alvin , Albertella Mark R. , Cleland Jeffrey L. , Henner William David 
Published: April 2007

Abstract
Purpose: The antitumor activities and pharmacokinetics of the hypoxia-activated cytotoxin AQ4N and its metabolites were assessed in several preclinical models of pancreatic cancers.
Experimental Design: The cytotoxic effects of AQ4N prodrug and its bioreduced form, AQ4, were tested against multiple human tumor cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Nude mice bearing s.c. or orthotopically implanted human BxPC-3 or Panc-1 tumor cells were treated with AQ4N. Tumor growth inhibition, time to progression/end point, and liver metastasis were evaluated in treatment versus control groups. Plasma and tumor levels of AQ4N and its metabolites were quantitated by liquid chromatography-tandem mass spectrometry.
Results: In contrast to AQ4N, the bioreduced AQ4 metabolite displayed potent cytotoxicity in many human tumor lines, including those derived from human pancreatic adenocarcinomas. Single-agent administration of AQ4N significantly delayed tumor growth, progression, and survival in a manner comparable with gemcitabine in multiple pancreatic tumor models in vivo. Survival increases were accompanied by a reduction in incidence and spread of liver metastasis. Quantitation of AQ4N and its metabolites in tumor-bearing mice showed that the prodrug is rapidly cleared from the circulation by 24 h and neither of the bioreduced metabolites was detected in plasma. In contrast, AQ4N readily penetrated BxPC-3 tumors and the cytotoxic AQ4 metabolite rapidly accumulated in tumor tissues at high levels in a dose-dependent fashion.
Conclusion: AQ4N undergoes rapid and selective conversion into the potent antineoplastic metabolite AQ4 in tumors in vivo and provides proof of principle for the use of hypoxia-activated prodrugs in the treatment against pancreatic cancers.
Identification of a Highly Effective Rapamycin Schedule that Markedly Reduces the Size, Multiplicity, and Phenotypic Progression of Tobacco Carcinogen–Induced Murine Lung Tumors
Authors: Granville Courtney A. , Warfel Noel , Tsurutani Junji , Hollander M. Christine , Robertson Matthew , Fox Stephen D. , Veenstra Timothy D. , Issaq Haleem J. , Linnoila R. Ilona , Dennis Phillip A. 
Published: April 2007

Abstract
Purpose: Human and murine preneoplastic lung lesions induced by tobacco exposure are characterized by increased activation of the Akt/mammalian target of rapamycin (mTOR) pathway, suggesting a role for this pathway in lung cancer development. To test this, we did studies with rapamycin, an inhibitor of mTOR, in A/J mice that had been exposed to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
Experimental Design: Tumorigenesis was induced by i.p. injection of NNK, and rapamycin was administered 1 or 26 weeks after NNK administration. Biomarkers associated with mTOR inhibition were assessed in lung and/or surrogate tissues using immunohistochemistry and immunoblotting. Rapamycin levels were measured using mass spectroscopy.
Results: Rapamycin was administered on a daily (5 of 7 days) regimen beginning 26 weeks after NNK decreased tumor size, proliferative rate, and mTOR activity. Multiplicity was not affected. Comparing this regimen with an every-other-day (qod) regimen revealed that rapamycin levels were better maintained with qod administration, reaching a nadir of 16.4 ng/mL, a level relevant in humans. When begun 1 week after NNK, this regimen was well tolerated and decreased tumor multiplicity by 90%. Tumors that did develop showed decreased phenotypic progression and a 74% decrease in size that correlated with decreased proliferation and inhibition of mTOR.
Conclusions: Tobacco carcinogen–induced lung tumors in A/J mice are dependent upon mTOR activity because rapamycin markedly reduced the development and growth of tumors. Combined with the Food and Drug Administration approval of rapamycin and broad clinical experience, these studies provide a rationale to assess rapamycin in trials with smokers at high risk to develop lung cancer.
Molecular Characterization of Waldenstrom's Macroglobulinemia Reveals Frequent Occurrence of Two B-Cell Clones Having Distinct IgH VDJ Sequences
Authors: Kriangkum Jitra , Taylor Brian J. , Treon Steven P. , Mant Michael J. , Reiman Tony , Belch Andrew R. , Pilarski Linda M. 
Published: April 2007

AbstractPurpose: Malignant B lineage cells in Waldenstrom's macroglobulinemia (WM) express a unique clonotypic IgM VDJ. The occurrence of biclonal B cells and their clonal relationships were characterized.Experimental Design: Bone marrow and blood from 20 WM patients were analyzed for clonotypic VDJ sequences, clonal B-cell frequencies, and the complementary determining region 3 profile.Results: Two different clonotypic VDJ sequences were identified in 4 of 20 WM. In two cases, partner clones had different VDJ rearrangements, with one clonotypic signature in bone marrow and a second in blood. For both cases, the bone marrow clone was hypermutated, whereas the blood clone was germ line or minimally mutated. In two other cases, partner clones shared a common VDJ rearrangement but had different patterns of somatic mutations. They lacked intraclonal diversity and were more abundant in bone marrow than in blood. VDJ mutation profiles suggested they arose from a common IgM progenitor. Single-cell analysis in one case indicated the partner clones were reciprocally expressed, following rules of allelic exclusion.Conclusions: The existence of two B-cell clones having distinct VDJ sequences is common in WM, suggesting that frequent transformation events may occur. In two cases, the partner clones had distinct tissue distributions in either blood or bone marrow, were of different immunoglobulin isotypes, and in one case exhibited differential response to therapy. The contributions of each clone are unknown. Their presence suggests that WM may involve a background of molecular and cellular events leading to emergence of one or more malignant clones.
Editorial Introduction
Authors: van der Linden Marcel , Stutje Jan Willem 
Published: April 2007

AbstractErnest Mandel theorised the capitalist world economy as an articulated system of capitalist, semi-capitalist and precapitalist relations of production, linked to each other by capitalist relations of exchange and domination by the capitalist world market. This seems to be an interesting starting point for an historically well-founded theory, building on and going beyond Marx's work, of the worldwide expansion of the capitalist mode of production from its origins to the present. In his attempt to formulate his theory, Mandel did not succeed in resolving all difficulties, however. His main works – Marxist Economic Theory and Late Capitalism – show a number of dangling loose ends. The central question is whether these loose ends are merely technical difficulties or whether they reveal fatal flaws in the theory as a whole. In order to come a step closer to answering this question, a conference was organised in Amsterdam, November 2003. This introduction formulates the five, closely interrelated issues that were highlighted at this conference.
From Formal Subsumption to General Intellect: Elements for a Marxist Reading of the Thesis of Cognitive Capitalism
Authors: Vercellone Carlo 
Published: April 2007

AbstractSince the crisis of Fordism, capitalism has been characterised by the ever more central role of knowledge and the rise of the cognitive dimensions of labour. This is not to say that the centrality of knowledge to capitalism is new per se. Rather, the question we must ask is to what extent we can speak of a new role for knowledge and, more importantly, its relationship with transformations in the capital/labour relation. From this perspective, the paper highlights the continuing validity of Marx's analysis of the knowledge/power relation in the development of the division of labour. More precisely, we are concerned with the theoretical and heuristic value of the concepts of formal subsumption, real subsumption and general intellect for any interpretation of the present change of the capital/labour relation in cognitive capitalism. In this way, we show the originality of the general intellect hypothesis as a sublation of real subsumption. Finally, the article summarises key contradictions and new forms of antagonism in cognitive capitalism.
Henry Reaction and 1,4-Addition of Nitroalkanes to α,β-Unsaturated Carbonyl Compounds under the Influence of MS 4 Å in DMSO
Authors: Oriyama Takeshi , Aoyagi Masaru , Iwanami Katsuyuki 
Published: April 2007

Abstract
In the presence of MS 4 Å in DMSO (dimethyl sulfoxide), Henry reaction with various carbonyl compounds and nitroalkanes proceeded smoothly to give the corresponding β-nitroalcohol without a base catalyst. Moreover, 1,4-additon of nitroalkane to α,β-unsaturated ketones was also performed in DMSO.
Can Juvenile Justice Detention Facilities Meet the Call of the American Academy of Pediatrics and National Commission on Correctional Health Care? A National Analysis of Current Practices
Authors: Gallagher Catherine A. , Dobrin Adam 
Published: April 2007

OBJECTIVE. Despite the recommendation of the American Academy of Pediatrics, just 53 of the ∼3500 juvenile justice residential facilities in the United States have received voluntary accreditation for facility health care from the National Commission on Correctional Health Care. This suggests either that facilities do not meet the standards of care or do not seek accreditation. This study describes whether and under what conditions juvenile detention facilities (a narrowly defined subset of all facility types) adhere to some of the standards outlined by the National Commission on Correctional Health Care and promoted by the American Academy of Pediatrics.METHODS. Data from 2 national censuses of juvenile justice residential facilities (n = 726) were used to describe detention facility performance in terms of 10 types of service provision, ranging from health screening to communicable-disease testing. Multivariate models predicting high levels of service provision were estimated.RESULTS. Juvenile detention centers partially meet some of the minimum standards. Most services can be garnered at some level; however, they tend to be provided on an ad hoc basis for portions of the population rather than systematically for the whole population. Detention centers most likely to provide a higher tier of services tend to be those that have longer average lengths of stay, are larger, and are government owned. There are also geographic and racial differences in quality and scope of health services.CONCLUSIONS. Juvenile facilities have been provided a single set of standards for a diverse system with tremendous variation across and within facility types. Detention centers are just one specialized type. Very few detention centers meet a minimum standard of care, which suggests that standards are simply not being met (hence the low levels of accreditation). The findings of this study call into question whether detention facilities with little in the way of health care infrastructure can benefit from National Commission on Correctional Health Care standards as they are currently packaged, regardless of whether accreditation is the ultimate goal.
Masculine Beliefs, Parental Communication, and Male Adolescents' Health Care Use
Authors: Marcell Arik V. , Ford Carol A. , Pleck Joseph H. , Sonenstein Freya L. 
Published: April 2007

OBJECTIVES. Male adolescents frequently become disconnected from health care, especially as they get older, which limits physicians' abilities to address their health needs and results in missed opportunities to connect them to the health care system as they enter adulthood. In this study we tested the ability of modifiable (beliefs about masculinity, parental communication, sex education, and health insurance) and nonmodifiable (age, race/ethnicity, and region of residence) factors to prospectively predict health care use by male adolescents.PATIENTS AND METHODS. We conducted a prospective analysis of data from 1677 male participants aged 15 to 19 years who completed the National Survey of Adolescent Males, a household probability survey conducted throughout the United States in 1988 (wave 1, participation rate: 74%) and in 1990–1991 (wave 2, follow-up rate: 89%). We present percentages and adjusted relative risks of the factors that predict male adolescents' self-report of a physical examination by a regular provider in the past year measured at wave 2.RESULTS. On average, 1067 (66%) of 1677 male adolescents at wave 2 reported having a physical examination within the last year. Factors associated with a lower likelihood of a physical examination included living in the South, Midwest, and West; being older in age; and holding more traditional masculine beliefs. Factors associated with a higher likelihood of a physical examination included communicating about reproductive health with both parents and being insured. Male adolescents who were sexually active or engaged in ≥2 other risk behaviors had neither a higher nor lower likelihood of a physical examination.CONCLUSIONS. Efforts to enhance male adolescents' health through health care should include work to modify masculine stereotypes, improve mothers' and fathers' communication about health with their sons, expand health insurance coverage, and identify interventions to connect male adolescents at increased risk for health problems with health care.