bluuebunny/crossref_metadata_2025 huggingface dataset:
Feminists re-reading Bourdieu
Authors: McLeod Julie
Published: March 2005

There is a revival of interest in Bourdieu’s work and this article examines dominant trends within feminist re-engagements. It considers the insights into gender identity afforded by ‘habitus’ and ‘social field’, distinguishing between analyses of ‘gender habitus’, and the potential of habitus and social field for feminist analysis of change. Feminist responses to Bourdieu continue to be divided on the extent to which social field structure determines habitus, and there is a tendency to represent the relationship as too seamless and coherent. Drawing on debates within recent feminist sociology, notably the work of Lois McNay and Lisa Adkins, this article argues instead for greater acknowledgement of the instability of gender norms and the contradictory effects of crossing different social fields. A feminist rethinking of the relationship between gender change, habitus and social field is suggested, which arises from a more contextual analysis of the varying degrees of correspondence between habitus and field. This addresses the co-existence of change and continuity in gender relations and identities, and aims to move such debates beyond questions of either freedom or reproduction.
‘Out on the borderlands’
Authors: MacKinnon Alison , Bullen Elizabeth
Published: March 2005

What tools can we use in attempting to understand the recurring patterns of some girls’ early school leaving and consequent exclusion from well-paid employment? From which disciplinary fields can we take them? Using Bourdieu’s concept of the ‘scholastic point of view’ - the inherent intellectual bias of a discipline, in his case sociology - as a springboard, we suggest that if one turns to different ‘fields’, approaches might be found which point towards differing perspectives. This article brings Bourdieu into dialogue with the work of feminist historians and their conceptual tools. Carolyn Steedman’s notion of the politics of envy and Sally Alexander’s appropriation from psychoanalysis of the idea of repetition offer generative ways of exploring the ‘unthought categories of thought which delimit the thinkable and predetermine the thought’ (Bourdieu and Wacquant, 1992: 40). In their focus on gender, they have much in common with feminist sociologists’ responses to Bourdieu’s work, suggesting that a gendered ‘perspective’ offers a way of avoiding the ‘singular viewpoint’ inherent in any one discipline.
Bourdieu, subcultural capital and risky girlhood
Authors: Bullen Elizabeth , Kenway Jane
Published: March 2005

It is a contention of the culturalist strand of underclass theory that the growth of the underclass is not a function of social and economic change, but of features intrinsic to underclass culture. Children born into disadvantaged communities, it is argued, are socialized into the ‘deviant’ culture of their families, families typically headed by single mothers. According to the underclass thesis, daughters of such families will face a heightened risk of leaving school early and teenage pregnancy. An unanticipated correlation between claims of the underclass thesis and the cohort of mothers and daughters with whom we are working on a current project has led us to ask, ‘how do we acknowledge the culture of disadvantaged communities and their generational synergies, whilst avoiding the pernicious implications of the underclass thesis?’ To answer this question, this article assesses the merits of bringing Bourdieu’s ideas on cultural capital together with Sarah Thornton’s concept of subcultural capital. The article concludes with two examples of how we might draw on these ideas as a way of exploring the means by which girls in difficult economic circumstances understand and pursue their school lives.
Capitalizing on Bourdieu
Authors: Allard Andrea C.
Published: March 2005

This article considers Bourdieu’s concepts of ‘social capital’ and ‘social fields’, comparing and contrasting his use of these concepts with that of James Coleman and Robert Putnam. It examines how Bourdieu’s ideas offer a different way of understanding the lives of economically disadvantaged young women designated as ‘at risk’ of leaving school early. A micro-level analysis is made of ‘Bluey’s story’, a narrative derived from data gathered during a three-year research project on young women’s negotiations from the margins of education and work in Australia. Deconstructing Bluey’s narrative reveals how social capital is deployed (sometimes unsuccessfully) in a range of social fields. Such narratives can thus be used to ‘speak back’ to educational policies, to provide alternative insights into the issues and needs of economically disadvantaged young women and to challenge current constructs of ‘at risk’.
Apoptosis-based therapies for hematologic malignancies
Authors: Reed John C. , Pellecchia Maurizio
Published: March 2005

Apoptosis is an intrinsic cell death program that plays critical roles in tissue homeostasis, especially in organs where high rates of daily cell production are offset by rapid cell turnover. The hematopoietic system provides numerous examples attesting to the importance of cell death mechanisms for achieving homeostatic control. Much has been learned about the mechanisms of apoptosis of lymphoid and hematopoietic cells since the seminal observation in 1980 that glucocorticoids induce DNA fragmentation and apoptosis of thymocytes and the demonstration in 1990 that depriving colony-stimulating factors from factor-dependent hematopoietic cells causes programmed cell death. From an understanding of the core components of the apoptosis machinery at the molecular and structural levels, many potential new therapies for leukemia and lymphoma are emerging. In this review, we introduce some of the drug discovery targets thus far identified within the core apoptotic machinery and describe some of the progress to date toward translating our growing knowledge about these targets into new therapies for cancer and leukemia.
Critical role of host γδ T cells in experimental acute graft-versus-host disease
Authors: Maeda Yoshinobu , Reddy Pavan , Lowler Kathleen P. , Liu Chen , Bishop Dennis Keith , Ferrara James L. M.
Published: March 2005

γδ T cells localize to target tissues of graft-versus-host disease (GVHD) and therefore we investigated the role of host γδ T cells in the pathogenesis of acute GVHD in several well-characterized allogeneic bone marrow transplantation (BMT) models. Depletion of host γδ T cells in wild-type (wt) B6 recipients by administration of anti-T-cell receptor (TCR) γδ monoclonal antibody reduced GVHD, and γδ T-cell-deficient (γδ-/-) BM transplant recipients experienced markedly improved survival compared with normal controls (63% vs 10%, P < .001). γδ T cells were responsible for this difference because reconstitution of γδ-/- recipients with γδ T cells restored GVHD mortality. γδ-/- recipients showed decreased serum levels of tumor necrosis factor α (TNF-α), less GVHD histopathologic damage, and reduced donor T-cell expansion. Mechanistic analysis of this phenomenon demonstrated that dendritic cells (DCs) from γδ-/- recipients exhibited less allostimulatory capacity compared to wt DCs after irradiation. Normal DCs derived from BM caused greater allogeneic T-cell proliferation when cocultured with γδ T cells than DCs cocultured with medium alone. This enhancement did not depend on interferon γ (IFN-γ), TNF-α, or CD40 ligand but did depend on cell-to-cell contact. These data demonstrated that the host γδ T cells exacerbate GVHD by enhancing the allostimulatory capacity of host antigen-presenting cells. (Blood. 2005;106:749-755)
Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia
Authors: de Jonge Robert , Hooijberg Jan Hendrik , van Zelst Bertrand D. , Jansen Gerritz , van Zantwijk Christine H. , Kaspers Gert Jan L. , Peters Frits G. J. , Ravindranath Yaddanapudi , Pieters Rob , Lindemans Jan
Published: March 2005

We studied whether common polymorphisms in genes involved in folate metabolism affect methotrexate (MTX) sensitivity. Ex vivo MTX sensitivity of lymphoblasts obtained from pediatric patients with acute lymphoblastic leukemia (ALL; n = 157) was determined by the in situ thymidylate synthase inhibition assay after either continuous (21 hours; TSI50, cont) or short-term (3 hours; TSI50, short) MTX exposure. DNA was isolated from lymphoblasts obtained from cytospin slides. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR 677C>T, MTHFR 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC 80G>A) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time PCR. Patients with the MTHFR 1298AC variant or the MTRR 66 G-allele showed decreased in vitro MTX sensitivity measured under both test conditions. SHMT1 1420TT homozygotes only showed decreased MTX sensitivity in the TSI50, cont. In conclusion, polymorphisms in the folate-related genes MTHFR, MTRR, and SHMT1 are related to MTX resistance in pediatric patients with ALL. (Blood. 2005;106:717-720)
CGMIM: Automated text-mining of Online Mendelian Inheritance in Man (OMIM) to identify genetically-associated cancers and candidate genes
Authors: Bajdik Chris D , Kuo Byron , Rusaw Shawn , Jones Steven , Brooks-Wilson Angela
Published: March 2005

Background

Online Mendelian Inheritance in Man (OMIM) is a computerized database of information about genes and heritable traits in human populations, based on information reported in the scientific literature. Our objective was to establish an automated text-mining system for OMIM that will identify genetically-related cancers and cancer-related genes. We developed the computer program CGMIM to search for entries in OMIM that are related to one or more cancer types. We performed manual searches of OMIM to verify the program results.

Results

In the OMIM database on September 30, 2004, CGMIM identified 1943 genes related to cancer. BRCA2 (OMIM *164757), BRAF (OMIM *164757) and CDKN2A (OMIM *600160) were each related to 14 types of cancer. There were 45 genes related to cancer of the esophagus, 121 genes related to cancer of the stomach, and 21 genes related to both. Analysis of CGMIM results indicate that fewer than three gene entries in OMIM should mention both, and the more than seven-fold discrepancy suggests cancers of the esophagus and stomach are more genetically related than current literature suggests.

Conclusion

CGMIM identifies genetically-related cancers and cancer-related genes. In several ways, cancers with shared genetic etiology are anticipated to lead to further etiologic hypotheses and advances regarding environmental agents. CGMIM results are posted monthly and the source code can be obtained free of charge from the BC Cancer Research Centre website http://www.bccrc.ca/ccr/CGMIM.
BCG skin reaction in Mantoux-negative healthy children
Authors: Singla Mohit , Sahai Vaibhav , Sodhi Sukhbir , Gupta Rakesh Pal
Published: March 2005

Background

Tuberculosis poses a great challenge, especially in children. The response of BCG Test may be different in previously vaccinated children and needs to be considered before interpreting positivity for TB. This study has been carried out to determine the pattern of BCG reaction comparing previously vaccinated with non-vaccinated children.

Methods

The study was conducted in the healthy school children aged 4–6 years. The BCG skin reaction in Mantoux-negative children was compared between children with and without previous BCG scar. After the Mantoux and BCG Test, the analysis of variance was done as per protocol.

Results

Out of 50 children previously BCG vaccinated, 39(78%) showed exaggerated BCG test responses while out of another 50 children who were not vaccinated for TB, only 9(18%) showed exaggerated BCG Test response (p-value < 0.00001). Average induration obtained in children who were immunized with BCG at birth was much greater than those who were not immunized. 80% and 76% males and females respectively in Group I showed exaggerated BCG response while 16% and 20% males and females respectively of Group II showed exaggerated BCG response.

Conclusion

The present study indicates that normal healthy children may have a mild exaggerated BCG Test response i.e. induration up to 8 mm because of prior BCG vaccination. Therefore, BCG Test, though important should not be the only criteria for start of chemotherapy for TB in children as the side effects of drugs may cause much morbidity. An induration up to 8 mm after the BCG Test can be normal in Indian settings due to exposure to Mycobacterium in environment and/or BCG vaccine.
A hypothesis-generating study to evaluate platelet activity in diabetics with chronic kidney disease
Authors: Brophy Donald F , Martin rika J , Gehr Todd WB , Carr Marcus E
Published: March 2005

Background

It is well described that diabetes mellitus is a hypercoagulable state. It is also known that patients with renal dysfunction have impaired platelet aggregation and function. It is not well described how renal dysfunction affects the hypercoagulability associated with diabetes. This post-hoc sub-group analysis compares platelet function, clot structure and thrombin generation time at baseline, and following enoxaparin exposure in three groups of subjects.

Methods

30 total subjects were evaluated in the three groups: Group I: normal controls (n = 10), Group II: subjects with renal dysfunction but without diabetes (n = 13), and Group III: subjects with concomitant diabetes and renal dysfunction (n = 7). For each subject, platelet contractile force (PCF), clot elastic modulus (CEM) and thrombin generation time (TGT) were simultaneously measured in whole blood at baseline, and following increasing enoxaparin antifactor Xa activity exposure. The group means for each parameter were determined and compared using one-way analysis of variance, with post-hoc Tukey-Kramer test.

Results

At baseline, subjects in Group III (diabetics with concomitant renal dysfunction) display significantly enhanced platelet activity, as measured by PCF (p = 0.003) and CEM (p = 0.03), relative to the non-diabetic Groups I and II. Subjects in Group II (renal dysfunction without diabetes) had significantly prolonged TGT values relative to controls when the antifactor Xa activity concentration reached 0.5 (p = 0.007), 1.0 (p = 0.005) and 3.0 IU/mL (p < 0.0001), respectively. There were no differences between Group II and Group III with respect to TGT at these antifactor Xa activity concentrations. When the antifactor Xa activity concentration reached 3.0 IU/mL, Groups II and III formed significantly less rigid blood clots (CEM p = 0.003) and also trended toward reduced PCF (p = 0.06) relative to Group I.

Conclusion

This hypothesis-generating sub-group analysis suggests that at baseline, patients with concomitant diabetes and renal dysfunction have significantly enhanced platelet activity (PCF), and form more rigid blood clots (CEM) compared to controls and subjects with renal dysfunction but no diabetes. This may suggest that the presence of renal dysfunction does not ameliorate the hypercoagulable state associated with diabetes. Secondly, it appears that subjects with renal dysfunction but without diabetes have an enhanced response to enoxaparin relative to controls.
EMBASE search strategies for identifying methodologically sound diagnostic studies for use by clinicians and researchers
Authors: Wilczynski Nancy L , Haynes R Brian ,   the Hedges Team
Published: March 2005

Background

Accurate diagnosis by clinicians is the cornerstone of decision making for recommending clinical interventions. The current best evidence from research concerning diagnostic tests changes unpredictably as science advances. Both clinicians and researchers need dependable access to published evidence concerning diagnostic accuracy. Bibliographic databases such as EMBASE provide the most widely available entrée to this literature. The objective of this study was to develop search strategies that optimize the retrieval of methodologically sound diagnostic studies from EMBASE for use by clinicians.

Methods

An analytic survey was conducted, comparing hand searches of 55 journals with retrievals from EMBASE for 4,843 candidate search terms and 6,574 combinations. All articles were rated using purpose and quality indicators, and clinically relevant diagnostic accuracy articles were categorized as 'pass' or 'fail' according to explicit criteria for scientific merit. Candidate search strategies were run in EMBASE, the retrievals being compared with the hand search data. The proposed search strategies were treated as "diagnostic tests" for sound studies and the manual review of the literature was treated as the "gold standard." The sensitivity, specificity, precision and accuracy of the search strategies were calculated.

Results

Of the 433 articles about diagnostic tests, 97 (22.4%) met basic criteria for scientific merit. Combinations of search terms reached peak sensitivities of 100% with specificity at 70.4%. Compared with best single terms, best multiple terms increased sensitivity for sound studies by 8.2% (absolute increase), but decreased specificity (absolute decrease 6%) when sensitivity was maximized. When terms were combined to maximize specificity, the single term "specificity.tw." (specificity of 98.2%) outperformed combinations of terms.

Conclusion

Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and specificity for retrieving sound diagnostic studies from EMBASE. These search filters will enhance the searching efforts of clinicians.
International Retrovirology Association brings together scientists and clinicians to bridge discoveries about human T-lymphotropic viruses from the laboratory to clinical trials
Authors: Murphy Edward , Jacobson Steven , Franchini Genoveffa , Taylor Graham P , Hanchard Barrie , Morgan Owen , Lairmore Michael
Published: March 2005

Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980's. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http://www.htlvconference.org.jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV.
Is there a dysfunction in the visual system of depressed patients?
Authors: Fountoulakis Konstantinos N , Fotiou Fotis , Iacovides Apostolos , Kaprinis George
Published: March 2005

Background

The aim of the current study was to identify a possible locus of dysfunction in the visual system of depressed patients.

Materials and Methods

Fifty Major Depressive patients aged 21–60 years and 15 age-matched controls took part in the study The diagnosis was obtained with the SCAN v 2.0. The psychometric assessment included the HDRS, the HAS, the Newcastle Scales, the Diagnostic Melancholia Scale and the GAF scale. Flash Electroretinogram and Electrooculogram were performed in all subjects. The statistical analysis included ANCOVA, Student's t-test and Pearson Product Moment Correlation Coefficient were used.

Results

The Electro-oculographic findings suggested that all subtypes of depressed patients had lower dark trough and light peak values in comparison to controls (p < 0.001), while Arden ratios were within normal range. Electroretinographic recordings did not reveal any differences between patients and controls or between subtypes of depression.

Discussion

The findings of the current study provide empirical data in order to assist in the understanding of the international literature and to explain the mechanism of action of therapies like sleep deprivation and light therapy.
Promoter features related to tissue specificity as measured by Shannon entropy
Authors: Schug Jonathan , Schuller Winfried-Paul , Kappen Claudia , Salbaum J Michael , Bucan Maja , Stoeckert Christian J
Published: March 2005

Background

The regulatory mechanisms underlying tissue specificity are a crucial part of the development and maintenance of multicellular organisms. A genome-wide analysis of promoters in the context of gene-expression patterns in tissue surveys provides a means of identifying the general principles for these mechanisms.

Results

We introduce a definition of tissue specificity based on Shannon entropy to rank human genes according to their overall tissue specificity and by their specificity to particular tissues. We apply our definition to microarray-based and expressed sequence tag (EST)-based expression data for human genes and use similar data for mouse genes to validate our results. We show that most genes show statistically significant tissue-dependent variations in expression level. We find that the most tissue-specific genes typically have a TATA box, no CpG island, and often code for extracellular proteins. As expected, CpG islands are found in most of the least tissue-specific genes, which often code for proteins located in the nucleus or mitochondrion. The class of genes with no CpG island or TATA box are the most common mid-specificity genes and commonly code for proteins located in a membrane. Sp1 was found to be a weak indicator of less-specific expression. YY1 binding sites, either as initiators or as downstream sites, were strongly associated with the least-specific genes.

Conclusions

We have begun to understand the components of promoters that distinguish tissue-specific from ubiquitous genes, to identify associations that can predict the broad class of gene expression from sequence data alone.
The microbial selenoproteome of the Sargasso Sea
Authors: Zhang Yan , Fomenko Dmitri E , Gladyshev Vadim N
Published: March 2005

Background

Selenocysteine (Sec) is a rare amino acid which occurs in proteins in major domains of life. It is encoded by TGA, which also serves as the signal for termination of translation, precluding identification of selenoprotein genes by available annotation tools. Information on full sets of selenoproteins (selenoproteomes) is essential for understanding the biology of selenium. Herein, we characterized the selenoproteome of the largest microbial sequence dataset, the Sargasso Sea environmental genome project.

Results

We identified 310 selenoprotein genes that clustered into 25 families, including 101 new selenoprotein genes that belonged to 15 families. Most of these proteins were predicted redox proteins containing catalytic selenocysteines. Several bacterial selenoproteins previously thought to be restricted to eukaryotes were detected by analyzing eukaryotic and bacterial SECIS elements, suggesting that eukaryotic and bacterial selenoprotein sets partially overlapped. The Sargasso Sea microbial selenoproteome was rich in selenoproteins and its composition was different from that observed in the combined set of completely sequenced genomes, suggesting that these genomes do not accurately represent the microbial selenoproteome. Most detected selenoproteins occurred sporadically compared to the widespread presence of their cysteine homologs, suggesting that many selenoproteins recently evolved from cysteine-containing homologs.

Conclusions

This study yielded the largest selenoprotein dataset to date, doubled the number of prokaryotic selenoprotein families and provided insights into forces that drive selenocysteine evolution.
Prospective study of risk factors for attempted suicide among patients with DSM–IV major depressive disorder
Authors: Sokero T. Petteri , Melartin Tarja K. , Rytsälä Heikki J. , Leskelä Ulla S. , Lestelä-Mielonen Paula S. , Isometsä Erkki T.
Published: March 2005

Background

There are few prospective studies on risk factors for attempted suicide among psychiatric out- and in-patients with major depressive disorder.

Aims

To investigate risk factors for attempted suicide among psychiatric out- and in-patients with major depressive disorder inthe city of Vantaa, Finland.

Method

The Vantaa Depression Study included 269 patients with DSM–IV major depressive disorder diagnosed using semi-structured interviews and followed up at 6- and 18-month interviews with a life chart.

Results

During the 18-month follow-up, 8% of the patients attempted suicide. The relative risk of an attempt was 2.50 during partial remission and 7.54 during a major depressive episode, compared with full remission (P<0.001). Numerous factors were associated with this risk, but lacking a partner, previous suicide attempts and total time spent in major depressive episodes were the most robust predictors.

Conclusions

Suicide attempts among patients with major depressive disorder are strongly associated with the presence and severity of depressive symptoms and predicted by lack of partner, previous suicide attempts and time spent in depression. Reducing the time spent depressed is a credible preventive measure.
Predictors of outcome following treatment for chronic fatigue
Authors: Darbishire Lucy , Seed Paul , Ridsdale Leone
Published: March 2005

We explored the role of baseline characteristics of 105 patients who presented with fatigue in primary care in determining outcome following either graded exercise or cognitive–behavioural therapy. Meeting the criteria for chronic fatigue syndrome was the most powerful predictor of poor outcome and this negative effect was enhanced by greater functional impairment or greater perceived negative consequences, but was not further enhanced by both.
Aggression in drug-dependent in-patients
Authors: Rajesh G. S. , Day Ed
Published: March 2005

Aims and Method

Associations have been reported between aggression and psychoactive substance use, and a link with violence has been demonstrated in community samples. This study aimed to assess the prevalence and nature of aggressive incidents and to examine the factors associated with violence in a specialist substance misuse treatment unit. Data were collected about assaults, aggressive patients and the object of their aggression during a 12-month period.

Results

Eighteen of 165 patients admitted during this period were involved in aggressive incidents. Patients dependent on more than one substance were significantly more aggressive than other categories of drug users. Past history of assaultive behaviour, younger age group and shorter duration of use were also significantly associated with incidents of aggression. Socio-demographic variables such as gender, marital and employment status were poor predictors of aggression.

Conclusions

The incidence of serious violence in this substance misuse treatment unit was low when compared with other psychiatric units. The findings suggest that there are differences in levels of aggression among the various types of drug users. The study reinforces the need for an accurate drug history in order to improve the quality of risk assessment.
Chemoradiation With and Without Surgery in Patients With Locally Advanced Squamous Cell Carcinoma of the Esophagus
Authors: Stahl Michael , Stuschke Martin , Lehmann Nils , Meyer Hans-Joachim , Walz Martin K. , Seeber Siegfried , Klump Bodo , Budach Wilfried , Teichmann Reinhard , Schmitt Marcus , Schmitt Gerd , Franke Claus , Wilke Hansjochen
Published: March 2005

Purpose

Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown.

Patients and Methods

Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time.

Results

The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001).

Conclusion

Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.
Low Microsatellite Instability Is Associated With Poor Prognosis in Stage C Colon Cancer
Authors: Kohonen-Corish Maija R.J. , Daniel Joseph J. , Chan Charles , Lin Betty P.C. , Kwun Sun Young , Dent Owen F. , Dhillon Varinderpal S. , Trent Ronald J.A. , Chapuis Pierre H. , Bokey E. Leslie
Published: March 2005

Purpose

The significance of low microsatellite instability (MSI-L) in colorectal cancer is poorly understood. No clear biologic distinction has been found between MSI-L and microsatellite stable (MSS) colorectal cancer, and these two phenotypes are usually combined when analyzed against the well-defined high MSI (MSI-H) phenotype. Evidence is emerging that an O6-methylguanine DNA methyltransferase (MGMT) gene defect is associated with MSI-L. Therefore, to further define this phenotype, we undertook a detailed analysis of the prognostic significance of MSI-L and loss of MGMT expression in colon cancer.

Patients and Methods

The study cohort was 183 patients with clinicopathologic stage C colon cancer who had not received adjuvant therapy. We analyzed MSI status, MGMT, and mismatch repair protein expression, as well as MGMT and p16 promoter hypermethylation.

Results

We showed that MSI-L defines a group of patients with poorer survival (P = .026) than MSS patients, and that MSI-L was an independent prognostic indicator (P = .005) in stage C colon cancer. Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival.

Conclusion

MSI-L characterizes a distinct subgroup of stage C colon cancer patients, including the MSI-L subset of proximal colon cancer, who have a poorer outcome. Neither the MGMT defect nor p16 methylation are likely to contribute to the worse prognosis of the MSI-L phenotype.
Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma
Authors: Dudley Mark E. , Wunderlich John R. , Yang James C. , Sherry Richard M. , Topalian Suzanne L. , Restifo Nicholas P. , Royal Richard E. , Kammula Udai , White Don E. , Mavroukakis Sharon A. , Rogers Linda J. , Gracia Gerald J. , Jones Stephanie A. , Mangiameli David P. , Pelletier Michelle M. , Gea-Banacloche Juan , Robinson Michael R. , Berman David M. , Filie Armando C. , Abati Andrea , Rosenberg Steven A.
Published: March 2005

Purpose

We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma.

Patients and Methods

Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL) -2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m2). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy.

Results

Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 ± 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus–related lymphoproliferation.

Conclusion

Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma.
Randomized Phase II Study of Temozolomide and Radiotherapy Compared With Radiotherapy Alone in Newly Diagnosed Glioblastoma Multiforme
Authors: Athanassiou Helen , Synodinou Maria , Maragoudakis Evagelos , Paraskevaidis Mihalis , Verigos Cosmas , Misailidou Despina , Antonadou Dosia , Saris George , Beroukas Konstantinos , Karageorgis Pantelis
Published: March 2005

Purpose

Surgery remains the standard treatment for glioma, followed by radiotherapy (RT) with or without chemotherapy. Despite multidisciplinary approaches, the median survival time for patients with glioblastoma multiform (GBM) remains at less than 1 year from initial diagnosis. Temozolomide (TMZ), an oral alkylating agent, has shown promising activity in the treatment of malignant gliomas. We conducted a multicenter randomized phase II study comparing the efficacy and safety of TMZ administered concomitantly and sequentially to RT versus RT alone in patients with newly diagnosed GBM.

Patients and Methods

One hundred thirty patients with pathologically confirmed, newly diagnosed GBM were randomly assigned (110 assessable patients) to receive either TMZ 75 mg/m2/d orally, concomitantly with RT (60 Gy in 30 fractions; group A, n = 57), followed by six cycles of TMZ (150 mg/m2 on days 1 through 5 and 15 to 19 every 28 days), or RT alone (60 Gy in 30 fractions; group B, n = 53).

Results

Median time to progression was 10.8 months in group A and 5.2 months in group B (P = .0001). One-year progression-free survival rate was 36.6% in group A and 7.7% in group B. Median overall survival (OS) time was also significantly better in group A versus group B (13.4 v 7.7 months, respectively; P < .0001), as was the 1-year OS at 56.3% v 15.7% (P < .0001), respectively. Toxicity was mainly hematologic. One patient with grade 4 myelotoxicity died as a result of sepsis. The other side effects were mild.

Conclusion

TMZ combined with RT (concomitantly and sequentially) seems to be more effective than RT alone in patients with newly diagnosed GBM. The combined-modality treatment was well tolerated.
Outcome Results of the 1996-1999 Patterns of Care Survey of the National Practice for Patients Receiving Radiation Therapy for Carcinoma of the Esophagus
Authors: Suntharalingam Mohan , Moughan Jennifer , Coia Lawrence R. , Krasna Mark J. , Kachnic Lisa , Haller Daniel G. , Willet Christopher G. , John Madhu J. , Minsky Bruce D. , Owen Jean B.
Published: March 2005

Purpose

A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States.

Methods

A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model.

Results

Adenocarcinoma was diagnosed in 51% of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01; P = .001), whereas those treated with chemoradiotherapy followed by surgery (HR, 0.32; P < .0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P = .03) compared with patients treated at larger facilities.

Conclusion

Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies.
Serial Evaluation of Academic and Behavioral Outcome After Treatment With Cranial Radiation in Childhood
Authors: Mabbott Donald J. , Spiegler Brenda J. , Greenberg Mark L. , Rutka James T. , Hyder Douglas J. , Bouffet Eric
Published: March 2005

Purpose

To evaluate academic and behavioral outcome in radiated survivors of posterior fossa (PF) tumors.

Patients and Methods

Fifty-three patients (36 males) treated for malignant PF tumors were seen for evaluation of academics and/or behavioral functioning. Forty-six patients were treated for medulloblastoma, and seven patients were treated for ependymoma. Fourteen patients were treated with reduced-dose cranial radiation, and 34 patients were treated with standard-dose cranial radiation (dose was not available for four patients). All patients received an additional boost to the PF. One patient was treated with PF radiation only. Standardized achievement tests and behavioral questionnaires were administered at different times after diagnosis for each child. First, the influence of demographic and medical variables on outcome was examined. Second, the rate of change in scores was determined using mixed model regression for patients seen for serial assessment.

Results

The presence of hydrocephalus was related to poorer academics, but outcome was not related to radiation dose, extent of surgery, or treatment with chemotherapy. Younger age predicted poor reading ability and lower parent rating of academic achievement. Children's performance declined for spelling, mathematics, and reading. Significant declines were also evident in parent and teacher's ratings of academic ability. Behavioral functioning was generally not related to medical and demographic variables, and few clinically significant problems in externalizing behavior were evident. Increases in social and attention problems emerged over time.

Conclusion

Cranial radiation is associated with declines in academic ability, social skills, and attention. However, neither psychological distress nor behavior problems were a significant concern for this sample.
Improving Accrual of Older Persons to Cancer Treatment Trials: A Randomized Trial Comparing an Educational Intervention With Standard Information: CALGB 360001
Authors: Kimmick Gretchen G. , Peterson Bercedis L. , Kornblith Alice B. , Mandelblatt Jeanne , Johnson Jeffrey L. , Wheeler Judith , Heinze Robin , Cohen Harvey J. , Muss Hyman B.
Published: March 2005

Purpose

To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group–sponsored treatment trials.

Methods

Main member institutions of the Cancer and Leukemia Group B (CALGB) and its affiliates were randomly assigned to receive standard information (n = 73) or educational intervention (n = 53). Standard information included CALGB Web site access and periodic notification about existing trials. The geriatric educational intervention included standard information plus: (1) an educational seminar; (2) educational materials; (3) a list of available protocols for use on charts; (4) a monthly e-mail and mail reminders for 1 year; and (5) a case discussion seminar. The main outcome was percentage of accrual of older persons to phase II and III treatment protocols after study initiation compared with baseline.

Results

There were 3,032 patients entered onto trials in the baseline year, and 2,160 and 1,239 during the 2 years postintervention, respectively. Overall percentage of accrual of older patients was 37% at baseline, and 33% and 31% during the first and second years after intervention. There was no improvement in accrual in the intervention versus control arm: 36% v 32% in the first year and 31% v 31% in the second year.

Conclusion

Accrual of older patients was not increased by this intervention. Reasons for lack of effect include low intervention intensity, high baseline accrual rates, and closure of several high-accruing protocols during the study. More intense and multifaceted approaches will be needed to change physician (and patient) behavior and to increase accrual of older persons to clinical trials.
Postoperative Adjuvant Therapy With Tamoxifen, Tegafur Plus Uracil, or Both in Women With Node-Negative Breast Cancer: A Pooled Analysis of Six Randomized Controlled Trials
Authors: Noguchi Shinzaburo , Koyama Hiroki , Uchino Junichi , Abe Rikiya , Miura Shigeto , Sugimachi Keizo , Akazawa Kohei , Abe Osahiko
Published: March 2005

Purpose

This article reports the results of a pooled analysis of six randomized trials conducted to study the efficacy of uracil and tegafur (UFT) in the adjuvant treatment of node-negative breast cancer patients.

Patients and Methods

Six randomized controlled trials on node-negative breast cancer patients were conducted from 1992 through 1995 in Japan that included the three, three-arm trials (control [no adjuvant], UFT, and tamoxifen [TAM] groups) and the three, four-arm trials (control, UFT, TAM, and UFT plus TAM groups). Pooled analysis was performed on the data obtained from these six trials (involving 2,934 patients).

Results

Overall survival was compared between the UFT group (including both the UFT group and the TAM plus UFT group) and the non-UFT group (control group and TAM group). A significant difference (P = .04) was observed in 5-year survival rates between the UFT (95.9%) and the non-UFT (94.0%) groups. Overall survival was also compared between the TAM group (TAM group and TAM plus UFT group) and the non-TAM group (control group plus UFT group). The 5-year survival rate (95.2%) in the TAM group was not significantly different from that (93.9%) in the non-TAM group, but the subset analysis showed a significant (P = .01) improvement in the estrogen receptor-positive subset.

Conclusion

Adjuvant UFT improves the overall survival of node-negative breast cancer patients. Given that UFT has milder adverse effects, it is suggested that UFT can be a useful alternative to doxorubicin and cyclophosphamide, or cyclophosphamide, methotrexate, and fluorouracil in the adjuvant treatment for node-negative breast cancer.
Merkel Cell Carcinoma: Prognosis and Treatment of Patients From a Single Institution
Authors: Allen Peter J. , Bowne Wilbur B. , Jaques David P. , Brennan Murray F. , Busam Klaus , Coit Daniel G.
Published: March 2005

Purpose

Merkel cell carcinoma (MCC) is an uncommon cutaneous malignancy. Most reports consist of single-institution experiences of fewer than 30 patients. The natural history of MCC is poorly defined.

Patients and Methods

A review was performed of Memorial Sloan-Kettering Cancer Center's MCC database, identifying 251 patients who had been treated between 1970 and 2002. Patient, tumor, and treatment-related factors were analyzed for their association with recurrence and survival.

Results

The average follow-up for all patients was 40 months and 46 months for patients alive at last follow-up. The 5-year disease-specific survival rate was 64%. Disease stage was the only independent predictor of survival (stage I, 81%; stage II, 67%; stage III, 52%; stage IV, 11%; P = .001). Pathologic staging of the draining nodal basin was performed in 71 (40%) of 177 patients who presented with clinically negative nodes, and 16 of these patients (23%) were found to have node-positive disease. Pathologic nodal staging was associated with improved stage-specific survival probabilities (clinical node-negative, 75% v pathologic node-negative disease, 97%; P = .009) and decreased nodal recurrence (44% v 11%, P < .001). The median time to recurrence was 9 months, and 102 patients (43%) recurred. Local recurrence developed in 8% of patients after margin-negative excision.

Conclusion

These data demonstrate that the natural history of MCC is variable and dependent on the stage of disease at presentation. Pathologic nodal staging identifies a group of patients with excellent long-term survival. After margin-negative excision and pathologic nodal staging, local and nodal recurrence rates are low.