bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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 &lt; 0.002), poor differentiation (P &lt; 0.001), lymphatic infiltration (P &lt; 0.005), and lymph node metastasis (P &lt; 0.006). TC1 also correlated with poor survival in diffuse type carcinomas (P &lt; 0.0001), and even in patients with lymph node metastasis (P &lt; 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

Abstract
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 &lt; 0.001) and age at diagnosis of &gt;2.5 years (P &lt; 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 &lt; 0.001) and in different subsets: neuroblastoma without MYCN amplification (MNA) (event-free survival and overall survival, P &lt; 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 &lt; 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 &lt; 0.001; hazard ratio, 3.534). Moreover, 11q alterations were strongly correlated with the occurrence of metastatic relapses (P &lt; 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

AbstractPurpose: 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

Abstract
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 &lt; 0.05) in both types of rat leukemia, n-3 PUFA had no significant effect compared with controls. Only TTA inhibited (P &lt; 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

Abstract
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

AbstractPurpose: 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

AbstractPurpose: 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.