bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Soluble HLA Class I and Soluble HLA-G in Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance
Authors: Leleu Xavier , Le Friec Gaëlle , Facon Thierry , Amiot Laurence , Fauchet Renée , Hennache Bernadette , Coiteux Valérie , Yakoub-Agha Ibrahim , Dubucquoi Sylvain , Avet-Loiseau Hervé , Mathiot Claire , Bataille Régis , Mary Jean-Yves ,   on behalf of the Intergroupe Francophone du Myélome
Published: March 2006

Abstract
Serum β2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 μg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (≥2.1 μg/mL) was predictive of short survival (P = 0.017). For each given level of β2-microglobulin, the relative risk of death was higher for patients with HLA-Is ≥ 2.1 μg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to β2-microglobulin produced an efficient prognostic score (P &lt; 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to β2-microglobulin.
The Androgen Receptor Is Significantly Associated with Vascular Endothelial Growth Factor and Hypoxia Sensing via Hypoxia-Inducible Factors HIF-1a, HIF-2a, and the Prolyl Hydroxylases in Human Prostate Cancer
Authors: Boddy Jane L. , Fox Stephen B. , Han Cheng , Campo Leticia , Turley Helen , Kanga Suresh , Malone Peter R. , Harris Adrian L. 
Published: March 2006

Abstract
Purpose: Hypoxia regulates key biological processes including angiogenesis via the transcription factor, hypoxia-inducible factor (HIF). In prostate cancer, angiogenesis is also influenced by androgens, and recent cell line studies suggest that this effect is partly mediated by HIF. The study aimed to assess whether a relationship exists in human prostate cancer between expression of the androgen receptor, HIFs, and the key angiogenesis factor, vascular endothelial growth factor (VEGF).
Experimental Design: A tissue microarray comprised of 149 radical prostatectomy specimens was constructed. Semiquantitative immunohistochemical analysis was used to assess the expression of the androgen receptor, VEGF and HIF-1a and 2a, and their regulatory prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3). Statistical analysis compared these factors with each other and with prostate-specific antigen relapse.
Results: There was a significant correlation between HIF-1a and HIF-2a expression (P = 0.02), and with androgen receptor (P = 0.04 and P &lt; 0.001, respectively) and VEGF expression (P = 0.05 and P &lt; 0.001, respectively). VEGF was also significantly related to the androgen receptor (P = 0.05), whereas PHD2 was inversely related to HIF-2a expression. No significant association was shown between HIF-1a or HIF-2a and time to prostate-specific antigen recurrence (P = 0.20 and P = 0.94, respectively).
Conclusions: These findings confirm the relationship between hypoxia and the androgen receptor in prostate cancer, and show for the first time, the role of HIF-2a in this disease process. They provide clinical evidence to support the recent cell line findings that androgens may regulate VEGF levels through the activation of HIF in androgen-sensitive tumors. Inhibition of both the HIF pathways may provide new therapeutic options in the management of this disease.
X-Linked Inhibitor of Apoptosis Protein Expression Level in Colorectal Cancer Is Regulated by Hepatocyte Growth Factor/C-Met Pathway via Akt Signaling
Authors: Takeuchi Hiroya , Kim Joseph , Fujimoto Akihide , Umetani Naoyuki , Mori Takuji , Bilchik Anton , Turner Rod , Tran Andy , Kuo Christine , Hoon Dave S.B. 
Published: March 2006

Abstract
Purpose: The inhibitor of the apoptosis protein (IAP) family members, such as the X-linked IAP (XIAP), survivin, and livin, are essential for cell survival and antiapoptosis in colorectal cancer cells. We hypothesized that the hepatocyte growth factor (HGF) activation in colorectal cancer via c-Met receptor regulates IAP proteins through Akt signaling.
Experimental Design: The level of IAPs and C-Met mRNA expression was assessed using a quantitative real-time reverse transcriptase-PCR (RT-PCR) assay on colorectal normal mucosa (n = 13), adenomas (n = 6), and colorectal cancer tumors (n = 50). The role of HGF/C-Met pathway through Akt and XIAP was investigated by small interfering RNA (siRNA) and quantitative RT-PCR analysis of colorectal cancer lines.
Results: Of the IAPs, only XIAP showed significant correlation to tumor development and progression. XIAP mRNA level in primary colorectal cancer was significantly higher than that in colorectal normal mucosa (P = 0.01); liver metastases was significantly higher than primary colorectal cancer tumors (P = 0.04); and primary colorectal cancer N1/N2 cases were significantly higher than N0 cases (P = 0.008). HGF stimulation of colorectal cancer lines enhanced XIAP mRNA expression but not other IAPs. Activation of XIAP expression by HGF was inhibited by siRNA targeting Akt1 and Akt2.
Conclusions: Activation of C-MET enhances XIAP through the Akt pathway. XIAP up-regulation was shown to be correlated to colorectal cancer tumor progression. The Akt-XIAP pathway may be a potential molecular target for regulating colorectal cancer progression.
Responses to Human CD40 Ligand/Human Interleukin-2 Autologous Cell Vaccine in Patients with B-Cell Chronic Lymphocytic Leukemia
Authors: Biagi Ettore , Rousseau Raphael , Yvon Eric , Schwartz Mary , Dotti Gianpietro , Foster Aaron , Havlik-Cooper Diana , Grilley Bambi , Gee Adrian , Baker Kelty , Carrum George , Rice Lawrence , Andreeff Michael , Popat Uday , Brenner Malcolm 
Published: March 2006

Abstract
Purpose: Human CD40 ligand activates the malignant B-cell chronic lymphocytic leukemia cells and enhances their capacity to present tumor antigens. Human interleukin-2 further potentiates the immunogenicity of human CD40 ligand in preclinical murine models.
Experimental Design: We prepared autologous B-cell chronic lymphocytic leukemia cells that expressed both human CD40 ligand (&gt;90% positive) and human interleukin-2 (median secretion, 1,822 pg/mL/106 cells; range, 174-3,604 pg). Nine patients were enrolled in a phase I trial, receiving three to eight s.c. vaccinations.
Results: Vaccinations were administered without evidence of significant local or systemic toxicity. A B-cell chronic lymphocytic leukemia–specific T-cell response was detected in seven patients. The mean frequencies of IFN-γ, granzyme-B, and IL-5 spot-forming cells were 1/1,230, 1/1,450, and 1/4,500, respectively, representing a 43- to 164-fold increase over the frequency before vaccine administration. Three patients produced leukemia-specific immunoglobulins. Three patients had &gt;50% reduction in the size of affected lymph nodes. Nonetheless, the antitumor immune responses were observed only transiently once immunization ceased. High levels of circulating CD4+/CD25+/LAG-3+/FoxP-3+ immunoregulatory T cells were present before, during and after treatment and in vitro removal of these cells increased the antileukemic T-cell reactivity.
Conclusions: These results suggest that immune responses to B-cell chronic lymphocytic leukemia can be obtained with human CD40 ligand/human interleukin-2–expressing s.c. vaccines but that these responses are transient. High levels of circulating regulatory T cells are present, and it will be of interest to see if their removal in vivo augments and prolongs the antitumor immune response.
Nuclear Estrogen Receptor β in Lung Cancer: Expression and Survival Differences by Sex
Authors: Schwartz Ann G. , Prysak Geoffrey M. , Murphy Valerie , Lonardo Fulvio , Pass Harvey , Schwartz Jan , Brooks Sam 
Published: March 2006

Abstract
Purpose: A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-α and ER-β and the relationship between ER status, subject characteristics, and survival.
Experimental Design: Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-α and ER-β expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status.
Results: Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-α. Nuclear ER-β positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-β–positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ER-β–positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-β–positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-β–negative tumors.
Conclusions: This study suggests differential expression by sex and influence on survival in men of nuclear ER-β in lung cancer, particularly in adenocarcinomas.
Vitamin C Inactivates the Proteasome Inhibitor PS-341 in Human Cancer Cells
Authors: Zou Wei , Yue Ping , Lin Na , He Min , Zhou Zhongmei , Lonial Sagal , Khuri Fadlo R. , Wang Binghe , Sun Shi-Yong 
Published: March 2006

Abstract
Purpose: PS-341 (bortezomib, Velcade), the first proteasome inhibitor approved by the Food and Drug Administration for the treatment of patients with relapsed multiple myeloma, induces apoptosis in human cancer cell lines. Vitamin C (ascorbic acid) is an essential water-soluble vitamin required for many normal physiologic functions and has to be obtained through diet or supplemental tablets in humans. Here we studied the potential effect of vitamin C on the anticancer activity of PS-341 in human cancer cell lines.
Experimental Design: The effects of vitamin C on apoptosis induction by PS-341 alone and by PS-341 combined with tumor necrosis factor–related apoptosis-inducing ligand were studied. In addition, the effects of vitamin C and other antioxidants on PS-341-mediated proteasome inhibition were also examined. Finally, the direct chemical interaction between vitamin C and PS-341 was determined.
Results: Vitamin C abrogated the ability of PS-341 to induce apoptosis in various human cancer cell lines, to induce G2-M arrest, and to augment apoptosis induced by tumor necrosis factor–related apoptosis-inducing ligand. Moreover, vitamin C suppressed PS-341-mediated inhibition of proteasome activity. PS-341 itself did not induce generation of intracellular reactive oxygen species whereas other antioxidants failed to abrogate its biological activity. Importantly, we detected a direct chemical interaction between vitamin C and PS-341.
Conclusion: Vitamin C directly binds to PS-431, thus inactivating PS-341 independent of its antioxidant activity. Our findings suggest that vitamin C may have a negative effect on PS-341-mediated anticancer activity.
Value of 18F-Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography/Computed Tomography in Non–Small-Cell Lung Cancer for Prediction of Pathologic Response and Times to Relapse after Neoadjuvant Chemoradiotherapy
Authors: Pöttgen Christoph , Levegrün Sabine , Theegarten Dirk , Marnitz Simone , Grehl Sara , Pink Roman , Eberhardt Wilfried , Stamatis Georgios , Gauler Thomas , Antoch Gerald , Bockisch Andreas , Stuschke Martin 
Published: March 2006

Abstract
Purpose: To determine the value of combined positron emission tomography/computed tomography (PET/CT) during induction chemotherapy (CTx) followed by chemoradiotherapy (CTx/RTx) for non–small-cell lung cancer to predict histopathologic response in primary tumor and mediastinum and prognosis of the patient.
Experimental Design: Fifty consecutive patients with locally advanced non–small-cell lung cancer received induction therapy and, if considered resectable, proceeded to surgery (37 of 50 patients). Patients had at least two repeated 18F-2-fluoro-2-deoxy-d-glucose (FDG)-PET/CT scans either before treatment (t0) or after induction CTx (t1) or CTx/RTx (t2). Variables from the PET/CT studies [e.g., lesion volume and corrected maximum standardized glucose uptake values (SUVmax,corr)] were correlated with histopathologic response (graded as 3, 2b, or 2a: 0%, &gt;0-10%, or &gt;10% residual tumor cells) and times to failure.
Results: Primary tumors showed a percentage decrease in SUVmax,corr during induction significantly larger in grade 2b/3 than in grade 2a responding tumors (67% versus 34% at t1, 73% versus 49% at t2; both P &lt; 0.005). SUVmax,corr at t2 was significantly correlated with histopathologic response in tumors smaller than the median volume (7.5 cm3; r = −0.54, P = 0.02). In the mediastinal lymph nodes, SUVmax,corr values at t2 predicted an ypN0 status with a sensitivity and specificity of 73% and 89%, respectively (SUVmax,corr threshold of 4.1, r = −0.54, P = 0.0005). Freedom from extracerebral relapse was significantly better in grade 2b/3 patients (86% at 16 months versus 20% in 2a responders; P = 0.003) and in patients with a greater percentage decrease in SUVmax,corr in the primary tumor at t2 in relation to t0 than in patients with lesser response (83% at 16 months versus 43%; P = 0.03 for cutoff points between 0.45 and 0.55).
Conclusions: SUVmax,corr values from two serial PET/CT scans, before and after three chemotherapy cycles or later, allow prediction of histopathologic response in the primary tumor and mediastinal lymph nodes and have prognostic value.
Annexin A8 Is Up-Regulated During Mouse Mammary Gland Involution and Predicts Poor Survival in Breast Cancer
Authors: Stein Torsten , Price Karen N. , Morris Joanna S. , Heath Victoria J. , Ferrier Roderick K. , Bell Alexandra K. , Pringle Marie-Anne , Villadsen René , Petersen Ole W. , Sauter Guido , Bryson Gareth , Mallon Elizabeth A. , Gusterson Barry A. 
Published: March 2006

AbstractPurpose: Microarray studies have linked Annexin A8 RNA expression to a “basal cell–like” subset of breast cancers, including BRCA1-related cancers, that are characterized by cytokeratin 5 (CK5) and CK17 expression and show poor prognosis. We assessed Annexin A8's contribution to the overall prognosis and its expression in normal, benign, and cancerous tissue and addressed Annexin A8's physiologic role in the mammary gland.Experimental Design: Using microarrays and reverse transcription-PCR, the Annexin A8 expression was studied during mouse mammary gland development and in isolated mammary structures. Reverse transcription-PCR on cultured human luminal and basal cells, along with immunocytochemistry on normal and benign breast tissues, was used for cellular localization. Annexin A8's prognostic relevance and its coexpression with CK5 were assessed on tissue arrays of 1,631 cases of invasive breast cancer. Coexpression was further evaluated on a small cohort of 14 BRCA1-related breast cancers.Results: Annexin A8 was up-regulated during mouse mammary gland involution and in pubertal ductal epithelium. Annexin A8 showed preferred expression in cultured basal cells but predominant luminal expression in normal human breast tissue in vivo. Hyperplasias and in situ carcinomas showed a strong staining of basal cells. Annexin A8 expression was significantly associated with grade (P &lt; 0.0001), CK5 (P &lt; 0.0001), and estrogen receptor status (P &lt; 0.0001); 85.7% BRCA1-related breast tumors coexpressed Annexin A8 and CK5.Conclusion: Annexin A8 is involved in mouse mammary gland involution. In humans, it is a luminally expressed protein with basal expression in cell culture and in hyperplasia/ductal carcinoma in situ. Expression in invasive breast carcinomas has a significant effect on survival (P = 0.03) but is not independent of grade or CK5.
Pharmacokinetics and Tolerability of a Single Dose of DN-101, a New Formulation of Calcitriol, in Patients with Cancer
Authors: Beer Tomasz M. , Javle Milind , Lam Gilbert N. , Henner W. David , Wong Alvin , Trump Donald L. 
Published: March 2006

Abstract
Background: Intermittent administration allows substantial dose escalation of calcitriol but limited bioavailability of the commercially available formulations at high doses is limiting. In this dose escalation study, we sought to evaluate the tolerability and pharmacokinetics of a single oral dose of DN-101, a high-dose calcitriol formulation.
Methods: DN-101 doses were escalated in sequential groups of three to six patients with advanced solid tumors. Dose-limiting toxicity was defined as grade ≥2 hypercalcemia or grade ≥3 persistent treatment-related toxicities. Single-dose administration of 15, 30, 60, 75, 90, 105, 135, and 165 μg was tested.
Results: Thirty-eight patients were enrolled in 2002 and 2003. The median age was 70 years (range, 44-91 years). Dose escalation was stopped at the 165 μg level when the number of capsules required at one time reached 11. No dose-limiting toxicities occurred. Transient and self-limited grade 3 toxicities were hyponatremia (2) and proteinuria (1). A dose-proportional increase in peak concentration (Cmax) and area under the concentration curve (AUC) was seen across the full range of DN-101 doses tested. At the 165 μg dose, Cmax was 6.21 ± 1.99 ng/mL, AUC(0-24) was 41.3 ± 9.77 ng h/mL, AUC(0-∞) was 55.4 ± 8.44, and half-life (T1/2) was 16.2 hours.
Conclusions: At doses between 15 and 165 μg, DN-101 exhibits linear pharmacokinetics. At 165 μg, DN-101 achieves systemic exposure that is 5- to 8-fold higher than that achieved with commercial formulations of calcitriol, which makes DN-101 comparable to that required for antitumor activity in vivo in a murine squamous cell carcinoma model.
How ADAM-9 and ADAM-11 Differentially From Estrogen Receptor Predict Response to Tamoxifen Treatment in Patients with Recurrent Breast Cancer: a Retrospective Study
Authors: Sieuwerts Anieta M. , Meijer-van Gelder Marion E. , Timmermans Mieke , Trapman Anita M.A.C. , Garcia Roberto Rodriguez , Arnold Miranda , Goedheer Anneke J.W. , Portengen Henk , Klijn Jan G.M. , Foekens John A. 
Published: March 2006

Abstract
Purpose: To evaluate the predictive value of the disintegrin and metalloproteinases, ADAM-9, ADAM-10, ADAM-11, and ADAM-12, and of the matrix metalloproteinases, MMP-2 and MMP-9, in patients with recurrent breast cancer treated with tamoxifen.
Experimental Design: A retrospective study was done on 259 frozen specimens of estrogen receptor–positive primary breast carcinomas from patients who developed recurrent disease and were treated with tamoxifen as the first line of therapy. The expression levels of the biological factors were assessed by real-time quantitative reverse transcriptase PCR.
Results: Using log-transformed continuous variables, increasing levels of ADAM-9 [odds ratio (OR) = 1.41; P = 0.015] and decreasing levels of MMP-9 (OR, 0.81; P = 0.035) predicted favorable disease control independent from the traditional predictive factors. Furthermore, when tumors were dichotomized at the median level of 70% tumor cell nuclei, our univariate analysis showed particularly strong results for the group of 153 patients with primary tumors containing 30% or more stromal cells. Although estrogen receptor levels lost their predictive power for this group of patients, high levels of ADAM-9 (OR, 1.59; P = 0.007) and ADAM-11 (OR, 1.65; P = 0.001) were significantly associated with a higher efficacy of tamoxifen therapy.
Conclusions: Our results show that especially for primary tumors containing stromal elements, the assessment of mRNA expression levels of ADAM-9 and ADAM-11 could be useful to identify patients with recurrent breast cancer who are likely to benefit or fail from tamoxifen therapy.
Molecular Alterations in Primary Prostate Cancer after Androgen Ablation Therapy
Authors: Best Carolyn J.M. , Gillespie John W. , Yi Yajun , Chandramouli Gadisetti V.R. , Perlmutter Mark A. , Gathright Yvonne , Erickson Heidi S. , Georgevich Lauren , Tangrea Michael A. , Duray Paul H. , González Sergio , Velasco Alfredo , Linehan W. Marston , Matusik Robert J. , Price Douglas K. , Figg William D. , Emmert-Buck Michael R. , Chuaqui Rodrigo F. 
Published: March 2006

Abstract
Purpose: After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent samples from primary and metastatic sites.
Experimental Design: We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering, and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping.
Results: Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors: macromolecule biosynthesis was down-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21.
Conclusions: Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the development of targeted therapeutic intervention.