bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of a Drug Activity Biomarker that Shows Target Inhibition in Cancer Patients Receiving Enzastaurin, a Novel Protein Kinase C-β Inhibitor
Authors: Green Lisa J. , Marder Philip , Ray Chad , Cook Carolyn A. , Jaken Susan , Musib Luna C. , Herbst Roy S. , Carducci Michael , Britten Carolyn D. , Basche Michele , Eckhardt S. Gail , Thornton Donald
Published: June 2006

Purpose: To evaluate the effects of the novel protein kinase C (PKC) inhibitor enzastaurin on intracellular phosphoprotein signaling using flow cytometry and to use this approach to measure enzastaurin effects on surrogate target cells taken from cancer patients that were orally dosed with this agent.

Experimental Design: The activity of PKC was assayed in intact cells using a modification of published techniques. The U937 cell line and peripheral blood mononuclear cells were stimulated with phorbol ester, fixed, permeabilized, and reacted with an antibody specific for the phosphorylated forms of PKC substrates. The processed samples were quantitatively analyzed using flow cytometry. The assay was validated for selectivity, sensitivity, and reproducibility. Finally, blood was obtained from volunteer cancer patients before and after receiving once daily oral doses of enzastaurin. These samples were stimulated ex vivo with phorbol ester and were assayed for PKC activity using this approach.

Results: Assay of U937 cells confirmed the selectivity of the antibody reagent and enzastaurin for PKC. Multiparametric analysis of peripheral blood mononuclear cells showed monocytes to be the preferred surrogate target cell. Day-to-day PKC activity in normal donors was reproducible. Initial results showed that five of six cancer patients had decreased PKC activity following enzastaurin administration. In a following study, a group of nine patients displayed a significant decrease in PKC activity after receiving once daily oral doses of enzastaurin.

Conclusion: An inhibition of surrogate target cell PKC activity was observed both in vitro and ex vivo after exposure to the novel kinase inhibitor, enzastaurin.
Preclinical Pharmacologic Evaluation of MST-997, an Orally Active Taxane with Superior In vitro and In vivo Efficacy in Paclitaxel- and Docetaxel-Resistant Tumor Models
Authors: Sampath Deepak , Greenberger Lee M. , Beyer Carl , Hari Malathi , Liu Hao , Baxter Michelle , Yang Sharon , Rios Carol , Discafani Carolyn
Published: June 2006

Purpose: Because resistance to paclitaxel and docetaxel is frequently observed in the clinic, new anti-microtubule agents have been sought. The aim of this study was to evaluate the efficacy and oral activity of a novel taxane (MST-997) in paclitaxel- and docetaxel-resistant tumor models in vitro and in vivo.

Experimental Design: Tubulin polymerization assays, immunohistochemistry, and cell cycle analysis was used to evaluate mechanism of action of MST-997. The effect of MST-997 on growth inhibition in a panel of paclitaxel- and docetaxel-resistant cell lines that overexpressed P-glycoprotein (MDR1) or harbored β-tubulin mutations were assayed in vitro and in murine xenografts.

Results: MST-997 induced microtubule polymerization (EC50 = 0.9 μmol/L) and bundling, resulting in G2-M arrest and apoptosis. In addition, MST-997 was a potent inhibitor of paclitaxel- and docetaxel-sensitive tumor cell lines that did not have detectable P-glycoprotein (IC50 = 1.8 ± 1.5 nmol/L). Minimal resistance (1- to 8-fold) to MST-997 was found in cell lines that either overexpressed MDR1 or harbored point mutations in β-tubulin. Most notable, MST-997 displayed superior in vivo efficacy as a single i.v. or p.o. dose either partially or completely inhibited tumor growth in paclitaxel- and docetaxel-resistant xenografts.

Conclusions: MST-997 represents a potent and orally active microtubule-stabilizing agent that has greater pharmacologic efficacy in vitro and in vivo than the currently approved taxanes. Our findings suggest that MST-997, which has entered phase I clinical trials, may have broad therapeutic value.
Phase II Study of Docetaxel and S-1 Combination Therapy for Advanced or Recurrent Gastric Cancer
Authors: Yoshida Kazuhiro , Ninomiya Motoki , Takakura Norihisa , Hirabayashi Naoki , Takiyama Wataru , Sato Yuji , Todo Satoru , Terashima Masanori , Gotoh Mitsukazu , Sakamoto Jyunnichi , Nishiyama Masahiko
Published: June 2006

Purpose: To evaluate the efficacy and toxicity of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 for patients with advanced or recurrent gastric cancer.

Experimental Design: Patients with advanced or recurrent adenocarcinoma of the stomach and up to one previous chemotherapy regimen were treated with i.v. docetaxel 40 mg/m2 on day 1 and oral S-1 80 mg/m2/d on days 1 to 14 every 3 weeks.

Results: Forty-eight patients (median age, 65 years; range, 25-75 years) received a total of 272 treatment cycles (median, 4; range, 1-17). No complete responses and 27 partial responses were observed for an overall response rate of 56.3% [95% confidence interval (95% CI), 38-66%]. Eighteen patients (37.5%) had stable disease and three patients (6.3%) had progressive disease as best response. The tumor control rate (complete response + partial response + stable disease) was 93.8% (95% CI, 83-98%). Median overall survival was 14.3 months (95% CI, 10.7-20.3 months) and median time to tumor progression was 7.3 months (95% CI, 4.3-10.0 months). The most common grade 3 to 4 hematologic toxicities were neutropenia (58.3%), leukopenia (41.7%), febrile neutropenia (8.3%), and anemia (8.3%). The most common grade 3 nonhematologic toxicities included anorexia (14.6%), stomatitis (8.3%), and nausea (6.3%). No grade 4 nonhematologic toxicities were reported and all treatment-related toxicities were resolved.

Conclusion: Docetaxel/S-1 combination is highly active and well tolerated in advanced or recurrent gastric cancer. Further investigation in randomized studies is warranted.
TC1(C8orf4) Correlates with Wnt/β-Catenin Target Genes and Aggressive Biological Behavior in Gastric Cancer
Authors: Kim Byungsik , Koo Hyunlyoung , Yang Seunghee , Bang Seunghyun , Jung Yusun , Kim Youngmi , Kim Jungtae , Park Juhee , Moon Randall T. , Song Kyuyoung , Lee Inchul
Published: June 2006

Purpose: We have recently reported that TC1(C8orf4), a small protein present in vertebrates, functions as a novel regulator of the Wnt/β-catenin pathway. TC1 up-regulates β-catenin target genes that are implicated in the aggressive behavior of cancers. Our aim was to investigate the clinical and pathobiological relevance of TC1 in gastric cancer.

Experimental Design: The expression of TC1 was analyzed using tissue microarray in correlation with clinicopathologic variables and β-catenin target genes in 299 gastric cancers. The biological effects of TC1 on Matrigel invasiveness and the proliferation of cancer cells were analyzed. TC1 expression was analyzed in gastric cancer cells after serial peritoneal implantation in nude mice.

Results: TC1 expression was present in 111 carcinomas (37.1%), correlating with tumor stage (P < 0.002), poor differentiation (P < 0.001), lymphatic infiltration (P < 0.005), and lymph node metastasis (P < 0.006). TC1 also correlated with poor survival in diffuse type carcinomas (P < 0.0001), and even in patients with lymph node metastasis (P < 0.0014). TC1 also correlated with the expression of β-catenin target genes including laminin γ2, metalloproteinase-7 and metalloproteinase-14, cyclin D1, c-Met, and CD44. TC1 enhanced Matrigel invasiveness and proliferation, supporting its role in the aggressive biological behavior of cancers. The expression of TC1 increased in MKN45 cells after serial peritoneal seeding in nude mice.

Conclusions: Our data suggests that TC1 coordinates the up-regulation of Wnt/β-catenin target genes that are implicated in the aggressive biological behavior of cancers. The strong clinical relevance, even in patients with lymph node metastasis, suggested that TC1 could be a potential therapeutic target of advanced gastric cancers.
Loss in Chromosome 11q Identifies Tumors with Increased Risk for Metastatic Relapses in Localized and 4S Neuroblastoma
Authors: Spitz Ruediger , Hero Barbara , Simon Thorsten , Berthold Frank
Published: June 2006

Purpose: To improve risk prediction in neuroblastoma and to specify the type of a possible relapse, alterations in the long arm of chromosome 11 were analyzed.

Experimental Design: A representative cohort of 611 neuroblastomas was investigated for deletion events in distal chromosome 11q using interphase fluorescence in situ hybridization.

Results: Alterations in 11q were found in 159 of 611 tumors in the whole cohort (26%) and were associated with stage 4 disease (P < 0.001) and age at diagnosis of >2.5 years (P < 0.001). Event-free survival and overall survival were significantly poorer for patients with 11q loss in the whole cohort (event-free survival and overall survival, P < 0.001) and in different subsets: neuroblastoma without MYCN amplification (MNA) (event-free survival and overall survival, P < 0.001), with MNA (event-free survival, P = 0.03; overall survival, P = 0.02), and MYCN-nonamplified stage 1, 2, 3, and 4S tumors with and without del 1p (event-free survival and overall survival, P < 0.001). In stage 4, the 11q status did not discriminate outcome. By multivariate analysis, the 11q status proved prognostic for event-free survival in the whole cohort (P = 0.008; hazard ratio, 1.573) and in the subgroup of stages 1, 2, 3, and 4S without MNA (P < 0.001; hazard ratio, 3.534). Moreover, 11q alterations were strongly correlated with the occurrence of metastatic relapses (P < 0.001).

Conclusion: In addition to the current risk stratification, the status of 11q enables the identification of patients with an increased risk for relapses in general and metastatic relapses in particular.
Quantitative Multiplex Methylation-Specific PCR Analysis Doubles Detection of Tumor Cells in Breast Ductal Fluid
Authors: Fackler Mary Jo , Malone Kara , Zhang Zhe , Schilling Eric , Garrett-Mayer Elizabeth , Swift-Scanlan Theresa , Lange Julie , Nayar Ritu , Davidson Nancy E. , Khan Seema A. , Sukumar Saraswati
Published: June 2006

Purpose: The challenges of cytology for accurate diagnosis of breast cancer are well recognized. We previously showed that normal and tumor tissue can be distinguished using a technique called quantitative multiplex methylation-specific PCR (QM-MSP). We hypothesized that quantitative analysis of methylated genes will provide enhanced detection of cancer cells present in cytologic specimens.

Experimental Design: QM-MSP was done on ductal lavage cells from a set of 37 ductal lavage samples from women undergoing mastectomy (27 with cancer and 3 without). Duct histology information was available for each lavaged duct. QM-MSP data was assessed by measuring cumulative methylation index and by receiver operating characteristic threshold analysis. To determine the baseline level of methylation for each gene in this population, cells from 60 ducts of women at high risk of developing breast cancer were analyzed.

Results: QM-MSP findings on a panel of nine genes were correlated to duct histology and ductal lavage cytology. Cytology detected cancer in 33% (7 of 21 ducts) with a specificity of 99% (92 of 93). QM-MSP detected cancer as calculated by cumulative methylation index with a sensitivity of 62% (13 of 21) and specificity of 82% (62 of 76) and by receiver operating characteristic threshold analysis with a sensitivity of 71% (15 of 21) and specificity of 83% (63 of 76).

Conclusions: Compared with cytology, QM-MSP doubled the sensitivity of detection of cancer. This study provides proof of principle by showing the advantages of using methylation analyses to query cytologic specimens and indicates its potential use in diagnosis and in stratifying risk.
A Bioactively Modified Fatty Acid Improves Survival and Impairs Metastasis in Preclinical Models of Acute Leukemia
Authors: Iversen Per O. , Sørensen Dag R. , Tronstad Karl J. , Gudbrandsen Oddrun A. , Rustan Arild C. , Berge Rolf K. , Drevon Christian A.
Published: June 2006

Purpose: Polyunsaturated fatty acids (PUFA) and the sulfur-substituted fatty acid tetradecylthioacetic acid (TTA) inhibit proliferation and induce apoptosis in lymphoma and leukemic cell lines, but it is unknown if they can modify leukemogenesis in the intact organism.

Experimental Design: We now examined the effects of PUFA and TTA in rats transplanted with either acute promyelocytic leukemia or acute T-cell leukemia. The rats were randomized to isoenergetic diets containing either lard (control), ω3 (n-3) PUFA, or TTA.

Results: Whereas TTA prolonged survival (P < 0.05) in both types of rat leukemia, n-3 PUFA had no significant effect compared with controls. Only TTA inhibited (P < 0.05) leukemic infiltration in the bone marrow and spleen, probably due to apoptosis of the leukemic cells. Plasma metalloproteinase activity, a marker of metastatic activity, was significantly reduced in TTA-fed rats only.

Conclusions: Dietary intake of TTA, but not of n-3 PUFA, in rats with acute leukemia, prolonged their survival. TTA intake was also associated with reduced leukemic cell burden as well as diminished extramedullar dissemination. TTA represents a modified fatty acid that exerts unique effects on malignant hematopoietic cells, and the present study indicates that TTA may have a therapeutic potential in patients with acute leukemias.
Decreased Pigment Epithelium–Derived Factor Expression in Human Breast Cancer Progression
Authors: Cai Jun , Parr Christian , Watkins Gareth , Jiang Wen G. , Boulton Mike
Published: June 2006

Purpose: The aim of this study was to correlate the expression of pigment epithelium–derived factor (PEDF), a potent endogenous antiangiogenic molecule, with severity and prognosis in breast cancer.

Experimental Design: To investigate the gene expression profile of PEDF in human breast cancer in relation to a patient's clinical variables, we examined human breast cancer tissue (n = 119), background breast tissue (n = 33), and a range of cell lines for mRNA and protein levels of PEDF by using reverse transcription PCR, real-time quantitative PCR, immunohistochemistry, and ELISA.

Results: By using reverse transcription PCR, real-time quantitative PCR, immunohistochemistry, and ELISA, PEDF expression was found to be dramatically decreased in breast cancer. An overall outlook for the patients inversely correlated with PEDF mRNA levels. Exogenous PEDF inhibits endothelial tubule formation induced by breast cancer cell–conditioned medium, in vitro.

Conclusion: These observations collectively support the hypothesis that a lack of PEDF expression is a potent factor for the enhancement of tumor growth and angiogenesis in breast cancer.
CIITA-Induced MHC Class II Expression in Mammary Adenocarcinoma Leads to a Th1 Polarization of the Tumor Microenvironment, Tumor Rejection, and Specific Antitumor Memory
Authors: Mortara Lorenzo , Castellani Patrizia , Meazza Raffaella , Tosi Giovanna , De Lerma Barbaro Andrea , Procopio Francesco A. , Comes Alberto , Zardi Luciano , Ferrini Silvano , Accolla Roberto S.
Published: June 2006

Purpose: We have shown previously that the MHC class II–negative murine TS/A adenocarcinoma is rejected in vivo if induced to express MHC class II molecules by transfection of the MHC class II transactivator CIITA. In this study, we explored the immunologic basis of tumor rejection and the correlation between histopathology of tumor tissue and immune rejection.

Experimental Design: Stable TS/A-CIITA transfectants were generated and injected into mice. In vivo cell depletion, immunohistochemistry of tumor tissues, and immune functional assays were done to assess the cellular and immunologic basis of rejection.

Results: Ninety-two percent of mice injected with TS/A-CIITA rejected the tumor and were completely resistant to challenge with parental TS/A. Only CD4+ and CD8+ cells were required for rejection. The tumor microenvironment in TS/A-CIITA-injected mice changed dramatically when compared with the TS/A parental-injected mice. Rapid infiltration with CD4+ T cells followed by dendritic cells, CD8+ T cells, and granulocytes was observed. Importantly, TS/A-CIITA cells could act as antigen-presenting cells because they process and present nominal antigens to CD4+ T cells. Tumor-specific CD4+ T cells of TS/A-CIITA-injected mice had the functional characteristics of Th1 cells and produced IFN-γ and this was relevant for generation and maintenance of protective antitumor response, because IFN-γ knockout mice were no longer rejecting TS/A-CIITA tumor cells.

Conclusion: CIITA-dependent MHC class II expression confers to TS/A tumor cells the capacity to act as a protective vaccine against the tumor by triggering tumor antigen presentation to T helper cells, antitumor polarization of cellular and soluble components of the tumor microenvironment, and establishment of antitumor immune memory.
Anti-CD26 Monoclonal Antibody–Mediated G1-S Arrest of Human Renal Clear Cell Carcinoma Caki-2 Is Associated with Retinoblastoma Substrate Dephosphorylation, Cyclin-Dependent Kinase 2 Reduction, p27kip1 Enhancement, and Disruption of Binding to the Extracellular Matrix
Authors: Inamoto Teruo , Yamochi Tadanori , Ohnuma Kei , Iwata Satoshi , Kina Shinichiro , Inamoto Sakiko , Tachibana Masaaki , Katsuoka Yoji , Dang Nam H. , Morimoto Chikao
Published: June 2006

Purpose: CD26 is a 110-kDa cell surface glycoprotein with a role in tumor development through its association with key intracellular proteins. In this report, we show that binding of soluble anti-CD26 monoclonal antibody (mAb) inhibits the growth of the human renal carcinoma cells in both in vitro and in vivo experiments.

Experimental Design: Growth inhibition by anti-CD26 mAb was assessed using proliferation assay and cell cycle analysis. Anti-CD26 mAb, chemical inhibitors, dominant-negative, or constitutively active forms of specific signaling molecules were used to evaluate CD26-associated pathways. The in vivo growth-inhibitory effect of anti-CD26 mAb was also assessed in a human renal carcinoma mouse xenograft model.

Results: In vitro experiments show that anti-CD26 mAb induces G1-S cell cycle arrest associated with enhanced p27kip1 expression, down-regulation of cyclin-dependent kinase 2, and dephosphorylation of retinoblastoma substrate. Moreover, our data show that enhanced p27kip1 expression is dependent on the attenuation of Akt activity. Anti-CD26 mAb also internalizes cell surface CD26, leading to decreased binding to collagen and fibronectin. Experiments with a mouse xenograft model involving human renal carcinoma cells show that anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival.

Conclusions: Taken together, our data strongly suggest that anti-CD26 mAb treatment may have potential clinical use for CD26-positive renal cell carcinomas.
Dual Epidermal Growth Factor Receptor and Vascular Endothelial Growth Factor Receptor Inhibition with NVP-AEE788 for the Treatment of Aggressive Follicular Thyroid Cancer
Authors: Younes Maher N. , Yazici Yasemin D. , Kim Seungwon , Jasser Samar A. , El-Naggar Adel K. , Myers Jeffrey N.
Published: June 2006

Purpose: Patients with radioiodine-resistant follicular thyroid cancer (FTC) have a poor prognosis, if metastasized, with currently available treatment modalities. Epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) and their receptors (EGFR and VEGFR) have been reported to be overexpressed in FTC and have been implicated in FTC development. We hypothesized that inhibiting the phosphorylation of EGFR and VEGFR by treatment with NVP-AEE788 (AEE788), a novel dual specific EGFR and VEGFR inhibitor, either alone or in combination with paclitaxel, would inhibit the growth of FTC xenografts in an orthotopic nude mouse model.

Experimental Design: To confirm previous reports, EGF and EGFR expression and vascularity were analyzed in human samples of FTC, Hürthle cell carcinoma, and normal thyroid tissues. EGFR expression in four FTC cell lines was measured using Western blotting. The antitumor effect of AEE788 on FTC cells in vitro was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and Western blotting. The effect of AEE788, alone and in combination with paclitaxel, on FTC tumor growth in an orthotopic nude mouse model was also investigated. Immunohistochemical analysis of EGFR and VEGFR signaling status, cell proliferation, apoptosis, and microvessel density was done.

Results: EGF, EGFR, and vascularity were increased in human thyroid tumor samples and EGFR was increased in FTC cells. AEE788 inhibited FTC cell growth in vitro and reduced the phosphorylation status of EGFR, VEGFR, and two downstream targets, AKT and mitogen-activated protein kinase, in FTC cells. AEE788 alone and, to a greater extent, AEE788 plus paclitaxel suppressed FTC tumor growth in the thyroids of nude mice.

Conclusion: Dual inhibition of EGFR and VEGFR by AEE788 could represent a novel approach to the treatment of radioiodine-resistant FTC.
Fifty Years of Clinical Research by the Leukemia Committee of the Cancer and Leukemia Group B
Authors: Larson Richard A. , Stone Richard M. , Mayer Robert J. , Schiffer Charles A.
Published: June 2006

Progress in the care of patients with leukemia has been one of the great success stories in the field of oncology, and clinical research in leukemia has been the “flagship” of the Cancer and Leukemia Group B since the inception of this organization. Lessons learned from the founders' emphasis on childhood and adult leukemia have been extended broadly over the past 50 years to virtually all types of malignant diseases, and the Leukemia Committee has continued to provide leadership and key contributions. The Leukemia Committee is focused on the individualization of treatment based on distinctive biological and clinical characteristics with the aim of increasing efficacy and decreasing nonspecific toxicity. Our clinical trials in leukemia and myeloma have shifted from primarily empirically derived comparisons of different chemotherapeutic regimens to testing novel concepts such as the role of dose intensity, inhibition of specific mechanisms of drug resistance, the use of hematopoietic growth factors and monoclonal antibodies, and the utility of targeted agents. The Cancer and Leukemia Group B was the pioneer among the cooperative groups in the creation of centralized tissue repositories and the incorporation of correlative laboratory studies as an integral feature of clinical trials, a practice now termed “translational research.” Considerable effort has focused on the identification of important pretreatment characteristics, such as morphologic features, immunophenotype, chromosomal abnormalities, and molecular defects, which are significantly associated with outcome in multivariable analyses and which enhance our understanding for the complex biology of these diseases.
Cancer and Leukemia Group B Leukemia Correlative Science Committee: Major Accomplishments and Future Directions
Authors: Bloomfield Clara D. , Mrózek Krzysztof , Caligiuri Michael A.
Published: June 2006

The Cancer and Leukemia Group B (CALGB) Leukemia Correlative Science Committee (LCSC) has a remarkable history of outstanding productivity and has been at the cutting edge of correlative science for adult leukemia for almost 25 years. Its work, initially focused on the use of immunophenotyping for diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia, has, for the last 15 years, focused on the clinical use of cytogenetic and molecular genetic markers in acute myeloid leukemia and acute lymphoblastic leukemia as well as in chronic lymphocytic leukemia. Numerous CALGB LCSC studies have had a major effect on the way we currently diagnose, predict outcome, select appropriate treatment, document complete remission, and monitor residual disease in adults with acute leukemia. In part as a result of the work of the CALGB LCSC, we are increasingly moving toward molecularly targeted therapy in acute and chronic leukemias. In this report, we briefly review those contributions from the CALGB LCSC that have had, or are likely to have in the future, a major effect on how we currently manage leukemia and outline directions of ongoing and future research conducted by the CALGB LCSC.
The Cancer and Leukemia Group B Lymphoma Committee
Authors: Cheson Bruce D. , Canellos George P.
Published: June 2006

The malignant lymphomas include at least 30 entities that are distinct with respect to histology, immunology, genetics, clinical features, and outcome following therapy. The clinical behavior of these diseases ranges from indolent but generally incurable to aggressive and frequently fatal yet potentially curable with appropriate chemotherapy or chemotherapy-antibody regimens. Over the past 50 years, the Cancer and Leukemia Group B (CALGB) Lymphoma Committee has conducted a series of clinical trials that have contributed to an improvement in outcome for patients with a number of the more common lymphoma subtypes. The World Health Organization has classified approximately 30 neoplastic diseases of the hematopoietic and lymphoid tissues (1). The Cancer and Leukemia Group B (CALGB) Lymphoma Committee highlight below clinical trials that have resulted in improved patient outcome for the more frequent lymphoma subtypes.
Cancer and Leukemia Group B Gastrointestinal Cancer Committee
Authors: Goldberg Richard M. , Niedzwiecki Donna , Bertagnolli Monica , Blackstock A. William , Tepper Joel E. , Mayer Robert J.
Published: June 2006

The Cancer and Leukemia Group B Gastrointestinal Cancer Committee was organized in the late 1970s under the leadership of Michael Perry and Philip Schein and began full-scale operations in the mid-1980s. Today, it is a multidisciplinary team of surgeons, radiation and medical oncologists, statisticians, quality-of-life experts, pharmacogeneticists, basic scientists, and community oncologists who design studies that are conducted across the United States. The Committee has done trials in patients with esophageal, gastric, pancreatic, colon, rectal, and anal cancers. New initiatives are under way in hepatocellular cancer, cholangiocarcinoma, and neuroendocrine tumors originating in the gastrointestinal tract. The Committee has increasingly concentrated on translational studies using tumor blocks, germ-line DNA, and plasma to evaluate biological correlates of tumor response and clinical outcomes. A broad program of pharmacogenomics has been incorporated for virtually all studies, including trials that prospectively use polymorphisms in drug-metabolizing genes to assign treatments. Future efforts aim to evolve new standards of care, evaluate new therapies, and answer relevant biological questions in gastrointestinal cancer.
Cancer and Leukemia Group B Cancer Control and Health Outcomes Committee: Origins and Accomplishments
Authors: Paskett Electra D. , Schrag Deborah , Kornblith Alice , Lamont Elizabeth B. , Weeks Jane C. , Marshall James R. , Shapiro Charles , Holland Jimmie
Published: June 2006

Cancer and Leukemia Group B (CALGB) has conducted protocols in cancer prevention and control, psycho-oncology, and health services for many years. Significant findings from the studies have emerged and have helped shape the practice of medicine and the direction of future research in these areas. This article describes the origins of the Cancer Control and Health Outcomes Committee within CALGB and briefly describes significant findings and future work. The success CALGB has had with psycho-oncology and health services research has paved the way for other cooperative groups to develop these modalities. Cancer control research is growing and continues to gather momentum. This type of research is integral to providing quality care to patients and healthy populations.
The Cancer and Leukemia Group B Cancer in the Elderly Committee: Addressing a Major Cancer Need
Authors: Cohen Harvey Jay , Muss Hyman B.
Published: June 2006

Cancer is a disease of aging, and the majority of cancers occur in persons over 65 years of age. In spite of this, few elders have been represented in clinical trials, and the need for information regarding the treatment of elders with cancer remains great. Recognizing these needs, the Cancer and Leukemia Group B (CALGB) formed an elderly Working Group in 1995, and after initial success in developing clinical studies focused on elders, a Cancer in the Elderly Committee. The Committee's objective is to focus attention on issues specifically relevant to the treatment of cancer in the older patient. Two strategies were developed to achieve this objective: (a) to initiate projects and protocols within the Committee and (b) to foster the initiation of studies by other CALGB committees. The research themes of the Committee and the main thrust of committee's research activities are (a) understanding and overcoming barriers to clinical trials participation; (b) treatment efficacy and pharmacokinetic/pharmacologic issues related to chemotherapy and hormone therapy in the older cancer patient; and (c) improving the quality of life for older cancer patients. The Cancer in the Elderly Committee has been successful in developing, implementing, and completing trials in all these areas and serves as a major resource for clinical trials development for the CALGB.
Radiation Oncology Research in the Cancer and Leukemia Group B
Authors: Bogart Jeffrey A. , Seagren Stephen L. , Glicksman Arvin
Published: June 2006

Radiation oncology initiatives have been an integral component in the evolution of multidisciplinary research in the Cancer and Leukemia Group B. Although early studies in the Group primarily focused on chemotherapy for hematologic and pediatric malignancies, the Radiation Oncology Committee was established in 1972, reflecting the broadening scope of clinical investigation with an increased emphasis on solid tumor research. A major early contribution of the Radiation Oncology Committee was the recognition of the importance of formalized radiation quality review, which led to the development of the Quality Assurance Review Center. The committee has been instrumental in designing trials, in conjunction with our medical oncology and surgical oncology colleagues, to assess multimodality therapy. The results of many of these studies have had important implications for clinical practice. Recent efforts have explored our major research theme of treatment intensification via radiotherapy dose modulation and novel combinations of radiotherapy with sensitizing agents, with an emphasis on safely implementing advanced technologies in the cooperative group setting.
Cancer and Leukemia Group B Clinical Research Associates Committee
Authors: Price Kandie C. , Barrett Barbara K. , Roark Jean M.
Published: June 2006

The Cancer and Leukemia Group B is dedicated to developing and implementing training programs that will enhance the skills and abilities of Clinical Research Associates (CRA) involved in all aspects of data collection and research. Training programs not only improve overall knowledge and professionalism but also improve the integrity of study data. The CRA roles and responsibilities include the following: collect, analyze, and monitor data; collaborate with other members of the health care team; insure regulatory mandates are followed; manage the care of research participants; assist in the recruitment and enrollment of human subjects; protect subjects rights by adhering to Institutional Review Board guidelines, the Code of Federal Regulations; prepare and submit timely adverse event experience reports; maintain case report forms and drug accountability records; educate other health care professionals, patients, and families regarding clinical trials; participate in research audits; and function as a team member with the research team. In addition, CRAs may also be responsible for writing reports, grant, and budget development and the development of protocols, forms, and informed consent documents.
Cancer and Leukemia Group B Breast Committee: Decades of Progress and Plans for the Future
Authors: Hudis Clifford A. , Winer Eric P.
Published: June 2006

The Breast Committee of the Cancer and Leukemia Group B was formed in 1969 under the direction of James Holland. Initial studies examined combination chemotherapy for advanced disease. Although the committee has continued to conduct studies in patients with advanced disease, adjuvant therapy has been an even more important focus for the past 30 years. Over the past 20 years, studies have focused on optimization of chemotherapy through the testing of dose and schedule, the value of adding novel agents, and the role of biological agents. Current and future projects are aimed at exploiting and increasing our growing knowledge of the molecular biology of breast cancer by developing targeted therapies.
Efficient FPGA Implementation of Novel Cryptographic Hashing Core
Authors: Michail H. , Kakarountas A. , Milidonis A. , Goutis C.
Published: June 2006

Hash functions are utilized in the security layer of every communication protocol and in signature authentication schemes for electronic transactions. As time passes more sophisticated applications arise that address to more users-clients and thus demand for higher throughput. Furthermore, due to the tendency of the market to minimize devices size and increase their autonomy to make them portable, power issues should also be taken into consideration. Long rumored and now official, the popular and widely used SHA-1 hashing algorithm has been attacked successfully by researchers in China and the US. It is obvious that sometime in the near future the demand for more secure hash functions will arise but these hash functions should also fulfill industry’s expectations as long as the throughput ,the area and the power of these new implementations are concerned. In this paper, an implementation of SHA-256 is presented in which the achieved throughput exceeds the limit of 2 Gbps. Furthermore, power dissipation is kept low in such way that the proposed implementation can be characterized as low-power.
Sex Differences in Response to Sexual and Emotional Infidelity Among Spanish and Chilean Students
Authors: Fernandez Ana Maria , Sierra Juan Carlos , Zubeidat Ihab , Vera-Villarroel Pablo
Published: June 2006

This study evaluates sex differences in response to sexual and emotional infidelity in two Spanish-speaking samples. An extension of previous findings with Anglo, European, and Asian students leads to the prediction that men report being more distressed by sexual than by emotional infidelity, and women report the reverse. Five hundred and eleven students from Spain and Chile respond to a questionnaire consisting of forced-choice-scenarios. Significant sex differences in jealousy as a function of type of infidelity emerges and this is consistent with previous research on jealousy.
A Fluency of Feeling
Authors: Mortenson Steve , Liu Meina , Burleson Brant R. , Liu Yan
Published: June 2006

The present study presents a multilevel analysis of cultural level and individual level differences in the evaluation of emotional support message strategies and interactive support goals. This is done in an effort to distinguish cultural norms regarding social support (i.e., recognizing what counts as an effective message) from a sense of cultural efficacy in social support (i.e., the motivation to provide effective support) and furthermore, to link social support efficacy to individual differences associated with mental wellbeing and effective emotional management. Analyses indicate that evaluations of message sensitivity are predicted by cultural differences but not individual differences. In contrast, valuing specific interactive support goals was associated both with differences in distinction and belonging and the interaction between individual and cultural differences. The pattern of findings supports the conceptual distinctions between culturally appropriate and culturally efficacious dimensions of emotional support.
Are Cultural Differences in Emotion Regulation Mediated by Personality Traits?
Authors: Matsumoto David
Published: June 2006

This article reports a study that documents United States–Japan differences in emotion regulation and demonstrates that those differences are entirely accounted for by individual differences in personality. These findings raise questions about studies that merely document cross-national differences in a psychological variable yet attribute the source of the observed differences to cultural variables without empirical justification to do so. Such differences may be accounted for by aggregate differences in personality.
Stories We Love by
Authors: Jackson Todd , Chen Hong , Guo Cheng , Gao Xiao
Published: June 2006

This research examines conceptions of love among dating and married couples from China and the United States. Sixty-one dating and 81 married American couples and 46 dating and 94 married Chinese couples completed portions of Sternberg's (1998) Love Stories Scale and measures of demographics, stress, and relationship satisfaction. Factor analyses revealed several love story components (objectification-threat, devotion-caring, pragmatism, pornography) common to both cultures, albeit there were subtle differences in their specific elements. Culturally unique components included “love as war” and “love as fairy tale” for the Americans and “love as current tending” and “incomprehensibility of lover” for the Chinese. Devotion–care was the strongest predictor of relationship satisfaction within each culture, independent of demographics and perceived stress. In sum, the research suggests that although Chinese and American views of love overlap somewhat, subtle cultural differences and culturally unique metaphors are also apparent.
Reverence for Mothers in Ecuadorian and Euro-American Culture
Authors: Mealy Marisa , Stephan Walter G. , Abalakina-Paap Marina
Published: June 2006

Two studies examine differences between Ecuadorians and Euro-Americans in levels of reverence for their mothers. Data collected from college students in Ecuador and the United States show that Ecuadorians display higher levels of mother reverence than Euro-Americans. Ecuadorians also score higher on measures of maternal power, similarity of mothers to the cultural ideal of women, and uncertainty avoidance. However, levels of independence are significantly higher in the Euro-American sample than in the Ecuadorian sample. High levels of maternal power, idealization of mothers, and interdependent self-construals are found to predict mother reverence in both cultures. The implications of these findings for interpersonal and intercultural relations are discussed.
A Chinese View of the Western Nursing Metaparadigm
Authors: Kao Hsueh-Fen Sabrina , Reeder Francelyn M. , Hsu Min-Tao , Cheng Su-Fen
Published: June 2006

The purpose of this article is to reveal Chinese-rooted meanings present within the Western nursing metaparadigm and to illustrate some similarities with Rogers’s Science of Unitary Human Beings. Confucian and Taoist beliefs have the potential to illuminate the basic constructs inherent in holistic nursing. The Western nursing metaparadigm of four concepts—person, nursing, health, and environment—was explored through the lens of a Chinese worldview and led to the presentation of a broadened view for an integrated model of nursing. Asian and Western worldviews of human beings and health are not mutually exclusive. The Chinese holistic worldview of Taoism and Confucianism resonates theoretically and cosmically with the dynamic nature of the human-environment mutual relationship basic to Rogers’ unitary view. This strong, theoretical link, when elaborated for its similarities and implications, can broaden the knowledge base to guide contemporary nursing practice, education, and research, particularly relevant for holistic nursing.
Appreciation of Holistic Nursing
Authors: Smith Kelly L.
Published: June 2006

The author’s appreciation for holistic nursing has stemmed from working as a nurse for several years and coming to the realization that although patients may have the same illness or symptoms, their plan of care must be as unique as the individual. During the process of obtaining her Holistic Nursing Certification, she learned the importance of assessing the integrated dimensions of a person. She is discovering there are many ways to care for and nurture an individual. And what works well for one person may not work for the next. Nurses who incorporate the holistic philosophy into their practice will most definitely improve the outcome of the patient’s care as well as the care of themselves.
A Student Reflects
Authors: Cronan Adrienne
Published: June 2006

This short response to research performed on the art of nursing was written by an undergraduate nursing student at the University of Massachusetts, Dartmouth. In it, the author uses an original article, “Sarah’s Story” (also in this issue) and an accompanying poem, “Sarah’s Insight,” to explore her own interpretation of the art of nursing. The art of nursing is “a feeling, a privilege, heartache, a passion, a love, and an art.” Sarah, who was interviewed by the researcher, feels that, during her hospital stay, her nurses found joy in caring for her. Firsthand experience shadowing an experienced nurse showed a similar expression of nursing’s art. Nursing is an art form not taught in the classroom.
Another Student Reflects
Authors: McNeill Laura Ashley
Published: June 2006

This short response to research performed on the art of nursing was written by an undergraduate nursing student at the University of Massachusetts, Dartmouth. In it, the author uses personal experience, an original research article, “Sarah’s Story,” and an accompanying poem, “Sarah’s Insight,” to explore her own interpretation of the art of nursing. The art of nursing was learned firsthand by the author following surgery, and it encompasses “the enthusiasm of a nurse to care for patients.” Similarly, the interviewee, Sarah, learned that nursing is not merely a paycheck. The poem includes words like “surprised,” “amazed,” and “grateful” to explain Sarah’s response. The author concludes that one nurse can inspire others to practice the art of nursing and become successful nurses.
Reinventing Honorable Masculinity
Authors: George Annie
Published: June 2006

This article argues that, contrary to received notions in Indian communities about women’s bodies and actions being the primary sites of male honor, women, too, hold men responsible for male honor and that men’s honor is also shaped by women’s discourses on men’s actions. Additionally, the forms of masculinities men seek to shape have to be considered contemporaneously with the forms of femininities that are emerging around them. Traditional male authority, which rested on the axes of men’s economic provisioning, control over wives, and violence against women, is eroding in newer social conditions in which women are more autonomous. In this fluid situation, men and women, respectively, use concepts of sexual control and understanding to describe and normalize an emerging form of masculinity that allows for men to claim honor when practicing nontraditional gendered actions.
Perceptions of teachers’ positive feedback and perceived threat to sense of self in physical education: a longitudinal study
Authors: Koka Andre , Hein Vello
Published: June 2006

This study examined the direction of causal flow between perceived positive general teacher feedback and perceived threat to sense of self in physical education (PE). The stability effect and stationarity of the relationship between these variables over the two-year period was tested. Students ( N = 302) were administered questionnaire during class time in Grades 6 and 8 and two years later in Grades 8 and 10. The perceived threat to sense of self subscale from the Physical Education Learning Environment Scale (PELES), and perceived positive general feedback subscale from the Perceived Teacher’s Feedback (PTF) questionnaire were used. Results using structural equation modelling showed the high stability of perceived threat and low stability of perceived teacher feedback in PE over the two-year period, and suggest that low level of perceived threat is a significant determinant of high level of perceived positive teacher feedback. In addition, the model showed that relationship between perceived threat and perceived positive feedback within time points differed significantly over time.
Incompatible? Compulsory mixed-sex Physical Education Initial Teacher Training (PEITT) and the inclusion of Muslim women: a case-study on seeking solutions
Authors: Benn Tansin , Dagkas Symeon
Published: June 2006

This article addresses the tensions between Islamic requirements and state provision in physical education initial teacher training (PEITT). Physical education has a firm place in teacher training in England because of its status as a National Curriculum foundation subject which guarantees entitlement for all children. The recruitment and retention of ethnic minority teachers have been a national concern for many years and yet remain an under-researched area. Rising numbers of young Muslims, the majority of whom are of South Asian heritage, led to initiatives for attracting more trainees from this group into higher education. In England, the century-old provision of single-sex specialist physical education secondary training (for 11-18-year-olds) finally disappeared by the mid-1980s. Primary PEITT (for 5-11-year-olds) has traditionally been organized in mixed-sex groups. Therefore the current higher education training system for intending teachers provides only compulsory mixed-sex provision in PEITT at every level. The authors argue that the current situation excludes Muslim women who wish to enter the teaching profession and adhere to Islamic requirements. They recount a case study in one university that tracks policy development to make single-sex physical education available to Muslim women on a tradition ally mixed-sex primary course.
The other revisited
Authors: Fabian Johannes
Published: June 2006

The article is based on a lecture contributing to a series titled ‘Speaking of Others’. It briefly reviews the concept's history in anthropology but the main focus is on a re-examination of the author's contribution in his Time and the Other. The aim of an account of its prehistory and the current state of the question is to reaffirm the ‘other’ as a productive, critical idea in the face of inflationary talk about other, others, and othering.
Estranged belongings
Authors: Newell Sasha
Published: June 2006

Arguing that ethnographies of cities must do more than highlight their fluid, boundless nature, this article seeks forms of social order produced in tension with forces of dissolution. I argue that even in the society of thieves I worked with in Abidjan, theft was ruled by relationships of exchange and obligation and social relationships were prioritized over financial gain. I discovered a tenuous moral community regulating the arbitration of justice in cases of social crisis, a process built upon the tracing of social networks and the determination of who really ‘belongs’. Using my own experience of being robbed and its social aftershocks as an example, I trace the processes through which social networks constrain the interpretation of an event, while at the same time redefining their identities (as group and individual) through this interaction. The juncture of stranger and community is the axis through which such negotiations are carried out.