bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Factor-κB Signature of Inflammatory Breast Cancer by cDNA Microarray Validated by Quantitative Real-time Reverse Transcription-PCR, Immunohistochemistry, and Nuclear Factor-κB DNA-Binding
Authors: Van Laere Steven J. , Van der Auwera Ilse , Van den Eynden Gert G. , Elst Hilde J. , Weyler Joost , Harris Adrian L. , van Dam Peter , Van Marck Eric A. , Vermeulen Peter B. , Dirix Luc Y. 
Published: June 2006

Abstract
Purpose: Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer with high metastatic potential. In a previous study, we showed that IBC is a different form of breast cancer compared with non-IBC by cDNA microarray analysis. A list of 756 genes with significant expression differences between IBC and non-IBC was identified. In-depth functional analysis revealed the presence of a high number of nuclear factor-κB (NF-κB) target genes with elevated expression in IBC versus non-IBC. This led to the hypothesis that NF-κB contributes to the phenotype of IBC. The aim of the present study was to further investigate the role of NF-κB in IBC.
Experimental Design: Immunohistochemistry and NF-κB DNA-binding experiments were done for all NF-κB subunits (RelA, RelB, cRel, NFkB1, and NFkB2) using IBC and non-IBC specimens. Transcriptionally active NF-κB dimers were identified by means of coexpression analysis. In addition, quantitative real-time reverse transcription-PCR for eight NF-κB target genes, selected upon a significant, 3-fold gene expression difference between IBC and non-IBC by cDNA microarray analysis, was done.
Results: We found a significant overexpression for all of eight selected NF-κB target genes in IBC compared with non-IBC by quantitative real-time reverse transcription-PCR. In addition, we found a statistically elevated number of immunostained nuclei in IBC compared with non-IBC for RelB (P = 0.038) and NFkB1 (P &lt; 0.001). Immunohistochemical data were further validated by NF-κB DNA-binding experiments. Significant correlations between immunohistochemical data and NF-κB DNA binding for RelA, RelB, NFkB1, and NFkB2 were found. Transcriptionally active NF-κB dimers, composed of specific combinations of NF-κB family members, were found in 19 of 44 IBC specimens compared with 2 of 45 non-IBC specimens (P &lt; 0.001). In addition, we found evidence for an estrogen receptor (ER)–mediated inhibition of the NF-κB signaling pathway. NF-κB target genes were significantly elevated in ER− versus ER+ breast tumors. Also, the amount of immunostained nuclei for RelB (P = 0.025) and NFkB1 (P = 0.031) was higher in ER− breast tumors versus ER+ breast tumors.
Conclusions: The NF-κB transcription factor pathway probably contributes to the phenotype of IBC and possibly offers new options for treatment of patients diagnosed with this aggressive form of breast cancer.
Ionizing Radiation Antagonizes Tumor Hypoxia Induced by Antiangiogenic Treatment
Authors: Riesterer Oliver , Honer Michael , Jochum Wolfram , Oehler Christoph , Ametamey Simon , Pruschy Martin 
Published: June 2006

Abstract
Purpose: The combined treatment modality of ionizing radiation with inhibitors of angiogenesis is effective despite the supposition that inhibition of angiogenesis might increase tumor hypoxia and thereby negatively affect radiation sensitivity. To directly assess this still controversial issue, we analyzed treatment-dependent alterations of tumor oxygenation in response to inhibition of angiogenesis alone, ionizing radiation, and combined treatment.
Experimental Design: Serial measurements with high-resolution [18F]fluoromisonidazole positron emission tomography and immunohistochemical detection of the endogenous hypoxia marker glucose transporter-1 were done to determine tumor hypoxia in a murine mammary carcinoma allograft model.
Results: Inhibition of angiogenesis with the clinically relevant vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 reduced microvessel density but had only minimal effects on tumor growth, tumor cell apoptosis, and proliferation. However, PTK787/ZK222584 treatment increased overall and local tumor hypoxia as revealed by extended expression of the hypoxia marker glucose transporter-1 and increased uptake of [18F]fluoromisonidazole. Fractionated irradiation induced a strong growth delay, which was associated with enhanced apoptosis and reduced proliferation of tumor cells but only minor effects on microvessel density and allograft oxygenation. Combined treatment with fractionated irradiation resulted in extended tumor growth delay and tumor cell apoptosis but no increase in tumor hypoxia.
Conclusions: These results show that irradiation antagonizes the increase of hypoxia by vascular endothelial growth factor receptor tyrosine kinase inhibition and abrogates the potential negative effect on tumor hypoxia. Thus, the risk of treatment-induced hypoxia by inhibitors of angiogenesis exists but is kept minimal when combined with a cytotoxic treatment modality.
Effects of 12-O-Tetradecanoylphorbol-13-acetate (TPA) in Combination with Paclitaxel (Taxol) on Prostate Cancer LNCaP Cells Cultured In vitro or Grown as Xenograft Tumors in Immunodeficient Mice
Authors: Zheng Xi , Chang Richard L. , Cui Xiao-Xing , Avila Gina E. , Hebbar Vidya , Garzotto Mark , Shih Weichung Joe , Lin Yong , Lu Shou-En , Rabson Arnold B. , Kong Ah Ng Tony , Conney Allan H. 
Published: June 2006

Abstract
Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice.
Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2).
Results: Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33% in experiment 1 and 100% in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17% and 57% of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression.
Conclusions: TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted.
FAS Death Domain Deletions and Cellular FADD-like Interleukin 1β Converting Enzyme Inhibitory Protein (Long) Overexpression: Alternative Mechanisms for Deregulating the Extrinsic Apoptotic Pathway in Diffuse Large B-Cell Lymphoma Subtypes
Authors: Takahashi Hidenobu , Feuerhake Friedrich , Kutok Jeffery L. , Monti Stefano , Dal Cin Paola , Neuberg Donna , Aster Jon C. , Shipp Margaret A. 
Published: June 2006

Abstract
Purpose: Large B-cell lymphomas (LBCL) arise from normal antigen-exposed B cells at germinal center (GC) or post-GC stages of differentiation. Negative selection of normal low-affinity or self-reactive GC B-cells depends on CD95 (FAS)-mediated apoptosis. FAS mutations that result in deletion of the cytoplasmic death domain destabilize the trimeric receptor and inhibit FAS-mediated apoptosis. This apoptotic pathway is also inhibited when the nuclear factor κB (NFκB) target, cellular FADD-like interleukin 1β converting enzyme inhibitory protein (cFLIP), interacts with the death-inducing signaling complex, assembled around the FAS death domain. Herein, we ask whether FAS death domain mutations and NFκB-mediated overexpression of cFLIP represent alternative mechanisms for deregulating the extrinsic apoptotic pathway in LBCL subtypes defined by gene expression profiling [oxidative phosphorylation, B-cell receptor/proliferation, and host response diffuse LBCLs and primary mediastinal LBCLs].
Experimental Design: The FAS receptor was sequenced, FAS death domain mutations identified, and cFLIP expression assessed in a series of primary LBCLs with gene expression profiling–defined subtype designations and additional genetic analyses [t(14;18) and t(3;v)].
Results: FAS death domain deletions were significantly more common in oxidative phosphorylation tumors, which also have more frequent t(14;18), implicating structural abnormalities of either the extrinsic or intrinsic pathway in this diffuse LBCL subtype. In marked contrast, host response tumors, which have up-regulation of multiple NFκB target genes and increased NFκB activity, express significantly higher levels of cFLIPlong.
Conclusions: These data suggest that the gene expression profiling–defined LBCL subtypes have different mechanisms for deregulating FAS-mediated cell death and, more generally, that these tumor groups differ with respect to their underlying genetic abnormalities.
Phase I/II Trial of an Allogeneic Cellular Immunotherapy in Hormone-Naïve Prostate Cancer
Authors: Simons Jonathan W. , Carducci Michael A. , Mikhak Bahar , Lim Michael , Biedrzycki Barbara , Borellini Flavia , Clift Shirley M. , Hege Kristen M. , Ando Dale G. , Piantadosi Steven , Mulligan Richard , Nelson William G. 
Published: June 2006

Abstract
Purpose: To determine the toxicity, immunologic, and clinical activity of immunotherapy with irradiated, allogeneic, prostate cancer cells expressing granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with recurrent prostate cancer.
Patients and Methods: A single-institution phase I/II trial was done in hormone therapy–naïve patients with prostate-specific antigen (PSA) relapse following radical prostatectomy and absence of radiologic metastases. Treatments were administered weekly via intradermal injections of 1.2 × 108 GM-CSF gene–transduced, irradiated, cancer cells (6 × 107 LNCaP cells and 6 × 107 PC-3 cells) for 8 weeks.
Results: Twenty-one patients were enrolled and treated. Toxicities included local injection-site reactions, pruritus, and flu-like symptoms. One patient had a partial PSA response of 7-month duration. At 20 weeks post first treatment, 16 of 21 (76%) patients showed a statistically significant decrease in PSA velocity (slope) compared with prevaccination (P &lt; 0.001). Injection site biopsies showed intradermal infiltrates consisting of CD1a+ dendritic cells and CD68+ macrophages, similar to previous clinical trials using autologous GM-CSF-transduced cancer cells. Posttreatment, patients developed new oligoclonal antibodies reactive against at least five identified antigens present in LNCaP or PC-3 cells. A high-titer antibody response against a 250-kDa antigen expressed on normal prostate epithelial cells was induced in a patient with partial PSA remission; titers of this antibody decreased when treatment ended, and subsequent PSA relapse occurred.
Conclusions: This non-patient-specific prostate cancer immunotherapy has a favorable safety profile and is immunologically active. Continued clinical investigation at higher doses and with longer boosting schedules is warranted.
Which Cyclin E Prevails as Prognostic Marker for Breast Cancer? Results from a Retrospective Study Involving 635 Lymph Node–Negative Breast Cancer Patients
Authors: Sieuwerts Anieta M. , Look Maxime P. , Meijer-van Gelder Marion E. , Timmermans Mieke , Trapman Anita M.A.C. , Garcia Roberto Rodriguez , Arnold Miranda , Goedheer Anneke J.W. , de Weerd Vanja , Portengen Henk , Klijn Jan G.M. , Foekens John A. 
Published: June 2006

Abstract
Purpose: To evaluate the prognostic value of cyclin E with a quantitative method for lymph node–negative primary breast cancer patients.
Patients and Methods: mRNA transcripts of full-length and splice variants of cyclin E1 (CCNE1) and cyclin E2 (CCNE2) were measured by real-time PCR in frozen tumor samples from 635 lymph node–negative breast cancer patients who had not received neoadjuvant or adjuvant systemic therapy.
Results: None of the PCR assays designed for the specific splice variants of the cyclins gave additional prognosis-related information compared with the common assays able to detect all variants. In Cox multivariate analysis, corrected for the traditional prognostic factors, high levels of cyclin E were independently associated with a short distant metastasis-free survival [hazard ratio (HR), 3.40; P &lt; 0.001 for CCNE1 and HR, 1.76; P &lt; 0.001 for CCNE2, respectively]. After dichotomizing the tumors at the median level of 70% tumor cells, the multivariate analysis showed particularly strong results for CCNE1 in the group of 433 patients with stroma-enriched primary tumors (HR, 5.12; P &lt; 0.001). In these tumors, the worst prognosis was found for patients with estrogen receptor–negative tumors expressing high CCNE1 (HR, 9.89; P &lt; 0.001) and for patients with small (T1) tumors expressing high CCNE1 (HR, 8.47; P &lt; 0.001).
Conclusion: Our study shows that both CCNE1 and CCNE2 qualify as independent prognostic markers for lymph node–negative breast cancer patients, and that CCNE1 may provide additional information for specific subgroups of patients.
Markers of Bone Metabolism and Survival in Men with Hormone-Refractory Metastatic Prostate Cancer
Authors: Cook Richard J. , Coleman Robert , Brown Janet , Lipton Allan , Major Pierre , Hei Yong Jiang , Saad Fred , Smith Matthew R. 
Published: June 2006

Abstract
Purpose: To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer.
Experimental Design: The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status.
Results: Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95% confidence interval, 0.628-0.715; P &lt; 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAP.
Conclusions: Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival.
Activities and Accomplishments of the Cancer and Leukemia Group B Genitourinary Committee
Authors: Small Eric J. , Halabi Susan , Kantoff Phillip , D'Amico Anthony , Stadler Walter , Kelley W. Kevin , Mohler James , Bajorin Dean , Vogelzang Nicholas J. 
Published: June 2006

Abstract
The Cancer and Leukemia Group B Genitourinary (GU) Committee has developed a multidisciplinary approach to treatment of GU cancer and has integrated correlative science research into the major research themes of the GU Committee. In localized prostate cancer, trials have evaluated novel approaches in radiation therapy. For patients with recurrence after local therapy, a trial evaluating local recurrence with salvage prostatectomy and a study of systemic therapy with “peripheral androgen blockade” were undertaken. Major contributions have been made in developing and testing therapeutics for advanced, androgen-independent prostate cancer (ketoconazole, suramin, estramustine/docetaxel, and docetaxel/bevacizumab), and in developing predictive markers and algorithms to assess prognosis in these patients. Contributions in kidney cancer have included the development of novel trial methodology, such as the randomized discontinuation trial design, and the testing of antiangiogenics. In addition to these areas, future work of the committee will include further development of therapy for earlier-stage prostate cancer patients and bladder cancer patients.
The Cancer and Leukemia Group B Pharmacology and Experimental Therapeutics Committee: A Historical Perspective
Authors: Ratain Mark J. , Miller Antonius A. , McLeod Howard L. , Venook Alan P. , Egorin Merrill J. , Schilsky Richard L. 
Published: June 2006

AbstractThe Chemotherapy Committee of Cancer and Leukemia Group B (CALGB) was established in the mid-1970s to assemble a group of experts in cancer chemotherapy and pharmacology who could advise the CALGB disease committees about the optimal use of drugs in the fight against cancer and to provide quality assurance for the chemotherapy section of CALGB protocols. Chaired initially by Edward Henderson and then David Van Echo, the committee was also the repository of studies in diseases for which CALGB did not have a formal committee, such as testis cancer and sarcoma. In 1990, following the appointment of Richard Schilsky as Chair, the name of the committee was changed to the Pharmacology and Experimental Therapeutics (PET) Committee to reflect a more specific focus and scientific agenda (i.e., studies of chemotherapy pharmacology and development of new agents). Three PET Committee reference pharmacology laboratories (led by Merrill Egorin, Tony Miller, and Mark Ratain) were established to measure drug concentrations in biological fluids and to perform pharmacokinetic analyses. In addition, the PET Committee embarked on a number of multi-institution phase I studies. These phase I studies included studies of special populations, including the first prospective study of an anticancer agent (paclitaxel) in patients with hepatic dysfunction. In addition, the Committee studied a number of phase I combinations destined for phase II evaluation in disease-specific committees. Following Dr. Schilsky's election as CALGB Group Chair in 1994, Mark Ratain took over as Chair of the PET Committee and continued to emphasize population pharmacology as the primary theme of the Committee's research agenda. In addition, the PET Committee began to develop novel clinical trial designs, including the first completed randomized discontinuation trial of an antineoplastic agent. Most recently, the PET Committee has launched an ambitious research program in pharmacogenetics, facilitated in large part through the recruitment of Howard McLeod as Vice Chair. This area of research is a collaborative effort with the NIH Pharmacogenetics Research Network and has the potential to definitively address the hypothesis that germ line polymorphisms are a significant determinant of the toxicity and efficacy of anticancer therapy. It is anticipated that the results of the current studies will contribute significantly to the goal of individualizing cancer treatment.
The Cancer and Leukemia Group B Pathology Committee at 50
Authors: Compton Carolyn 
Published: June 2006

Abstract
The Pathology Committee of the Cancer and Leukemia Group B (CALGB) is broadly and deeply integrated into the multidisciplinary clinical and scientific operations of the group. It has five major functions in CALGB. First, it insures the highest possible quality of pathologic data in tissue-based correlative science studies through comprehensive quality control of all tissues collected, banked, and distributed to investigators and of all morphology-based studies done within the CALGB. Within this context, the Pathology Committee has the goal of eliminating, to the greatest degree possible, variation in methodology, interpretation, and reporting of pathologic data that would compromise reproducibility of correlative science results and to assure accuracy, uniformity, and completeness of the pathologic data. Second, the committee provides expert pathologic consultation in the development of clinical trials and correlative science studies that involve pathologic issues and/or materials. Third, it provides high-quality tissue banking and centralized morphology-based technical support services (e.g., histologic sections for immunohistochemistry, tissue microarrays, etc.) for all CALGB investigators. Fourth, it initiates and executes high-quality pathologic research using CALGB and intergroup resources. Lastly, it provides group-wide education on pathology-related issues relevant to trial design, scientific study design, and specimen banking.
Cancer and Leukemia Group B Surgery Committee
Authors: Kohman Leslie J. 
Published: June 2006

Abstract
Surgeons play a vital role in the Cancer and Leukemia Group B by providing patients and specimens for studies of the common solid tumors, and more recently, by serving as investigators who conduct surgically focused research protocols and contribute to the correlative science studies in the Group. Surgical activities encompass thoracic, gastrointestinal, breast, and genitourinary cancers and melanoma. Surgical quality assurance is also an important focus. This article will describe the development and importance of a robust and vigorous surgical component to a strong cooperative group and highlight the many trials conducted by the Cancer and Leukemia Group B surgeons and their contributions to advancement of the care of the patient with solid organ malignancy.
The Cancer and Leukemia Group B Transplant Committee
Authors: Linker Charles , Hurd David 
Published: June 2006

Abstract
The Transplant Committee of the Cancer and Leukemia Group B has a robust portfolio of studies and is poised to make significant contributions to the field. We are working in collaboration with the Cancer and Leukemia Group B Leukemia and Lymphoma Disease Committees and importantly in collaboration with other groups to define the role of both autologous and reduced-intensity allogeneic transplantation in the management of selected hematologic malignancies. Some of our studies have the potential to change the standard of care in areas such as the maintenance therapy for multiple myeloma after autologous transplantation and to generate the data that could lead to acceptance of new approaches to the initial post-remission therapy of older adults with acute myeloid leukemia. The cooperative group setting allows us to advance the transplant field by showing which approaches are successful outside of single institutions and are therefore feasible on a generalized basis.