bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Angiogenesis Is Associated with Plasma Levels of Stromal-Derived Factor-1α in Patients with Multiple Myeloma
Authors: Martin Sally K. , Dewar Andrea L. , Farrugia Amanda N. , Horvath Noemi , Gronthos Stan , To L. Bik , Zannettino Andrew C.W. 
Published: December 2006

Abstract
Purpose: Multiple myeloma is an incurable hematologic malignancy characterized by increased bone marrow angiogenesis and extensive lytic bone disease. We have previously shown that elevated levels of stromal-derived factor-1α (SDF-1α) in peripheral blood plasma are associated with osteolysis in multiple myeloma patients. We have now examined whether SDF-1α levels also correlate with angiogenesis.
Experimental Design: We examined the contribution of multiple myeloma plasma cell–derived SDF-1α in the stimulation of in vitro angiogenesis using a tube formation assay. We also collected trephine and peripheral blood plasma samples from patients with multiple myeloma to analyze microvessel density and SDF-1α levels, respectively.
Results: We show that multiple myeloma plasma cell line–derived conditioned medium containing SDF-1α stimulates in vitro angiogenesis. In addition, in a large cohort of patients with multiple myeloma and its precursor condition monoclonal gammopathy of undetermined significance, we confirm previous findings that plasma cell burden correlates with both angiogenesis and plasma levels of SDF-1α. We now extend these observations and show the novel finding that peripheral blood plasma levels of SDF-1α positively correlate with the degree of bone marrow angiogenesis in multiple myeloma and monoclonal gammopathy of undetermined significance patients.
Conclusions: High levels of SDF-1α produced by multiple myeloma plasma cells promote osteolysis and bone marrow angiogenesis. Therefore, we propose that inhibition of SDF-1α may be an effective mechanism by which angiogenesis and osteolysis can be reduced in multiple myeloma patients.
Chromosome 20q13.2 Gain May Predict Intravesical Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Tumors
Authors: Akao Jumpei , Matsuyama Hideyasu , Yamamoto Yoshiaki , Sasaki Kohsuke , Naito Katsusuke 
Published: December 2006

Abstract
Purpose: Amplification or gain of copy number of chromosome 20q13.2 has been implicated as a causal factor for chromosome instability. We investigated the impact of chromosomal instability and its causative molecular markers, 20q13.2 gain and centrosome amplification, on patient outcome in upper urinary tract transitional cell carcinoma (UUT-TCC).
Experimental Design: The number of centrosomes was assessed by immunohistochemistry. Numerical aberrations of chromosomes 7, 9, and 17 that allowed the estimation of chromosomal instability and 20q13.2 gain were evaluated by fluorescence in situ hybridization in 96 frozen specimens from UUT-TCC and compared with clinicopathologic background and patient outcome.
Results: Chromosomal instability, 20q13.2 gain, and centrosome amplification were detected in 62 of 96 (64.6%), 61 of 96 (63.5%), and 45 of 90 (50.0%) tumors, respectively. 20q13.2 Gain was significantly associated with tumor stage (P = 0.042), chromosomal instability (P &lt; 0.0001), and centrosome amplification (P &lt; 0.0001). Kaplan-Meier analysis showed that 20q13.2 gain was strongly associated with intravesical recurrence-free survival in all patients (P = 0.0050), as well as in patients with grade 2 tumors (P = 0.0011, log-rank test). On multivariate analysis, 20q13.2 gain was found to be the sole independent prognostic factor predicting subsequent intravesical recurrence (hazard ratio, 1.65; 95% confidence interval, 1.03–2.90; P = 0.036).
Conclusions: 20q13.2 gain was strongly associated with a reduced time to intravesical recurrence in all patients. Our data suggest that 20q13.2 gain may be a predictive marker of intravesical recurrence in patients with UUT-TCC.
Correlation between High Vascular Endothelial Growth Factor-A Serum Levels and Treatment Outcome in Patients with Standard-Risk Acute Lymphoblastic Leukemia: A Report from Children's Oncology Group Study CCG-1962
Authors: Avramis Ioannis A. , Panosyan Eduard H. , Dorey Fred , Holcenberg John S. , Avramis Vassilios I. 
Published: December 2006

Abstract
Purpose: Many molecular pathways, including cell cycle control, angiogenesis, and drug resistance, mediate tumor growth and survival. Vascular endothelial growth factor-A (VEGF-A) serum levels &lt;40 and &gt;100 pg/mL have been associated with good and poor prognoses, respectively.
Experimental Design: The hypothesis was that serum VEGF-A levels in standard-risk acute lymphoblastic leukemia pediatric patients at induction are predictive of event-free survival (EFS). One hundred seventeen patients were entered in CCG-1962 study and randomized into the native and polyethylene glycolated asparaginase arms. VEGF-A levels were quantified by an ELISA assay.
Results: All patients had a decrease in VEGF-A levels by day 14 of induction, but they later dichotomized; EFS group levels remained low and event group levels increased. A correlation exists between high VEGF-A levels at entry to induction and time to event. Moreover, 6-year EFS patients have lower end of induction VEGF-A levels (28 ± 6 pg/mL) than event patients (&gt;100 pg/mL; P &lt; 0.01). Kaplan-Meier curves using various VEGF-A values were produced; with ≤30 at entry into induction (day 0) and ≤60 pg/mL at the end of induction (day 28), patients with low VEGF-A levels had superior EFS (P &lt; 1e−4). Furthermore, patients who had an increase in VEGF-A during induction (ΔVEGF-positive, days 0-28) were more likely to have an event (P &lt; 1e−4). Bifurcation by asparaginase treatment arm did not alter these results.
Conclusions: These observations strongly support that high VEGF-A levels in induction are an asparaginase treatment–independent predictive marker for EFS. Hence, an anti-VEGF-A therapy should be tested in acute lymphoblastic leukemia.
Late Toxicity Is Not Increased in BRCA1/BRCA2 Mutation Carriers Undergoing Breast Radiotherapy in the United Kingdom
Authors: Shanley Susan , McReynolds Kate , Ardern-Jones Audrey , Ahern Roger , Fernando Indrajit , Yarnold John , Evans Gareth , Eccles Diana , Hodgson Shirley , Ashley Sue , Ashcroft Linda , Tutt Andrew , Bancroft Elizabeth , Short Susan , Gui Gerald ,   The Breast Unit of the Royal Marsden NHS Foundation Trust, Barr Lester , Baildam Andrew , Howell Anthony , Royle Gavin , Pierce Lori , Easton Douglas , Eeles Rosalind 
Published: December 2006

Abstract
Purpose: To undertake the first substantial clinical study of breast radiotherapy toxicity in BRCA1 and BRCA2 mutation carriers in the United Kingdom.
Experimental Design: Acute and late radiation effects were evaluated in a retrospective study of 55 BRCA1 and BRCA2 mutation carriers treated with radiotherapy for breast cancer at four centers between 1983 and 2002. Individual matching with controls who had sporadic breast cancer was undertaken for age at diagnosis, time since completion of radiation, and treatment variables. Detailed assessments were undertaken by one examiner. Median follow-up was 6.75 years for carriers and 7.75 years for controls. Rates of late events (rib fractures, lung fibrosis, necrosis of soft tissue/bone, and pericarditis) as well as LENT-SOMA scores and clinical photography scores of breast size, shape, and skin telangiectasia were the primary end points.
Results: No increase in clinically significant late toxicity was seen in the mutation carriers.
Conclusions: These data add substantial weight to the evidence that the outcomes in the treated breast from radiotherapy in women with BRCA1 or BRCA2 mutations are comparable with those in women with sporadic breast cancer.
Acute Chemotherapy–Related Toxicity Is Not Increased in BRCA1 and BRCA2 Mutation Carriers Treated for Breast Cancer in the United Kingdom
Authors: Shanley Susan , McReynolds Kate , Ardern-Jones Audrey , Ahern Roger , Fernando Indrajit , Yarnold John , Evans Gareth , Eccles Diana , Hodgson Shirley , Ashley Sue , Ashcroft Linda , Tutt Andrew , Bancroft Elizabeth , Short Susan , Smith Ian , Gui Gerald ,   The Breast Unit of the Royal Marsden NHS Foundation Trust, Barr Lester , Baildam Andrew , Howell Anthony , Royle Gavin , Pierce Lori , Easton Douglas , Eeles Rosalind 
Published: December 2006

Abstract
Purpose: To evaluate acute toxicity induced by chemotherapy for breast cancer in a retrospective study of 62 BRCA1/2 mutation carriers matched 1:1 with women who had treatment for sporadic disease in the United Kingdom between 1983 and 2003.
Experimental Design: All participants were interviewed by one of two researchers using standardized questionnaires, and their medical records were reviewed by one research nurse. The two main regimens received were cyclophosphamide, methotrexate, and fluorouracil and fluorouracil, epirubicin, and cyclophosphamide. The proportion of cases and controls receiving anthracycline-based treatment was equivalent, but fewer BRCA1 cases received this treatment than did BRCA2 mutation carriers. Toxicity was documented using the Eastern Cooperative Oncology Group Common Toxicity Criteria for hematologic, infective, and gastrointestinal toxicities. No increase in toxicity was seen in BRCA1/2 mutation carriers.
Results: The only significant difference was that neutropenia was less evident in BRCA2 mutation carriers than in either BRCA1 mutation carriers or controls. As a result, there was no requirement for dose reduction among BRCA2 mutation carriers, in contrast to 10 of 39 BRCA1 carriers and 16 of 62 controls (P = 0.02).
Conclusions: This result has implications for therapy and indicates that women with mutations in BRCA1 and BRCA2 may be given the same doses of chemotherapy as noncarriers.
Expression of Erythropoietin and Erythropoietin Receptor in Cervical Cancer and Relationship to Survival, Hypoxia, and Apoptosis
Authors: Leo Cornelia , Horn Lars-Christian , Rauscher Cora , Hentschel Bettina , Liebmann Andre , Hildebrandt Guido , Höckel Michael 
Published: December 2006

AbstractPurpose: Physiologically, hypoxia induces the expression of erythropoietin (Epo) in adult kidney cells. Epo, in turn, acts on the Epo receptor (EpoR) in RBC precursors to stimulate growth and prevent apoptosis. Because hypoxia plays a major role in the malignant progression of tumors and Epo and its receptors have also been detected in malignant tumors, we investigated the expression of Epo and EpoR and their relationship with hypoxia, proliferation, apoptosis, and clinicopathologic variables in cervical cancer.Experimental Design: Intratumoral oxygen measurement and needle biopsies of the tumors were done in 48 patients with cervical cancer. The obtained tissue was analyzed by immunohistochemistry with antibodies against Epo, EpoR, and Ki-67 as well as by terminal deoxynucleotidyl transferase–mediated deoxyuracil triphosphate nick-end labeling assays.Results: Epo and EpoR were expressed in 88% and 92% of samples, respectively. Cervical cancers with higher Epo expression showed a significantly reduced overall survival (3 years, 50.0% versus 80.6%; P = 0.0084). Epo and EpoR expression correlated significantly with apoptosis (r = 0.49, P = 0.001 and r = 0.36, P = 0.021). Furthermore, EpoR expression correlated significantly with tumor size (r = 0.32, P = 0.032) and was significantly associated with the presence of lymphovascular space involvement (P = 0.037). However, we observed no correlation between Epo or EpoR expression and intratumoral hypoxia, although in well-oxygenated tumors, EpoR localized significantly more often to the invasion front (P = 0.047).Conclusions: This study analyzes Epo/EpoR expression and their relationship with intratumoral pO2 levels as well as with survival in patients with cervical cancer. The data suggest a critical role of the endogenous Epo/EpoR system in cervical cancer.
A Novel Anticancer Effect of Thalidomide: Inhibition of Intercellular Adhesion Molecule-1–Mediated Cell Invasion and Metastasis through Suppression of Nuclear Factor-κB
Authors: Lin Yi-Chu , Shun Chia-Tung , Wu Ming-Shiang , Chen Ching-Chow 
Published: December 2006

AbstractPurpose: Thalidomide has been reported to have antiangiogenic and antimetastatic effects. Intercellular adhesion molecule-1 (ICAM-1) was shown to be involved in monocyte adherence to epithelial cells and cancer cell invasion. In this study, we further investigated the role of ICAM-1 in tumorigenesis, including tumor formation and metastasis. ICAM-1 as a molecular target for cancer and the anticancer effect of thalidomide were investigated.Experimental Design: Expression of ICAM-1 protein in human lung cancer specimens was assessed by immunohistochemistry. ICAM-1 overexpressing A549 cells (A549/ICAM-1) were established to investigate the direct effect of ICAM-1 on in vitro cell invasion and in vivo tumor metastasis. Transient transfection and luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation were done to assess the activity and binding of nuclear factor-κB to the ICAM-1 promoter. A xenograft model in nude mice was conducted to evaluate the anticancer effect of thalidomide.Results: High expression of ICAM-1 in human lung cancer specimens was correlated with a greater risk of advanced cancers (stages III and IV). A549/ICAM-1 cells were shown to induce in vitro cell invasion and in vivo tumor metastasis. Anti-ICAM-1 antibody and thalidomide had inhibitory effect on these events. Thalidomide also suppressed tumor necrosis factor-α–induced ICAM-1 expression through inhibition of nuclear factor-κB binding to the ICAM-1 promoter. The in vivo xenograft model showed the effectiveness of thalidomide on tumor formation.Conclusion: These studies provide a framework for targeting ICAM-1 as a biologically based therapy for cancer, and thalidomide might be effective in human lung cancer.
Aurora Kinases: New Targets for Cancer Therapy
Authors: Carvajal Richard D. , Tse Archie , Schwartz Gary K. 
Published: December 2006

Abstract
The Aurora kinase family is a collection of highly related serine/threonine kinases that functions as a key regulator of mitosis. In mammalian cells, Aurora has evolved into three related kinases known as Aurora-A, Aurora-B, and Aurora-C. These kinases are overexpressed in a number of human cancers, and transfection studies have established Aurora-A as a bone fide oncogene. Because Aurora overexpression is associated with malignancy, these kinases have been targeted for cancer therapy. This article reviews the multiple functions of Aurora kinase in the regulation of mitosis and the mitotic checkpoint, the role of abnormal Aurora kinase activity in the development of cancer, the putative mechanisms of Aurora kinase inhibition and its antitumor effects, the development of the first generation of Aurora kinase inhibitors, and prospects for the future of Aurora kinase inhibition in the treatment of cancer.
A Phase 2 Study of Rituximab in Combination with Recombinant Interleukin-2 for Rituximab-Refractory Indolent Non-Hodgkin's Lymphoma
Authors: Khan Khuda D. , Emmanouilides Christos , Benson Don M. , Hurst Deborah , Garcia Pablo , Michelson Glenn , Milan Sandra , Ferketich Amy K. , Piro Lawrence , Leonard John P. , Porcu Pierluigi , Eisenbeis Charles F. , Banks Amy L. , Chen Lei , Byrd John C. , Caligiuri Michael A. 
Published: December 2006

Abstract
Purpose: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)–bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted.
Experimental Design: The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting &lt;6 months). I.V. rituximab was given at 375 mg/m2 (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9).
Results: Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcγR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy.
Conclusions: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL.
A Study to Determine the Effects of Food and Multiple Dosing on the Pharmacokinetics of Vorinostat Given Orally to Patients with Advanced Cancer
Authors: Rubin Eric H. , Agrawal Nancy G.B. , Friedman Evan J. , Scott Pamela , Mazina Kathryn E. , Sun Linda , Du Lihong , Ricker Justin L. , Frankel Stanley R. , Gottesdiener Keith M. , Wagner John A. , Iwamoto Marian 
Published: December 2006

Abstract
Purpose: This phase I study, conducted in advanced-stage cancer patients, assessed the safety and tolerability of oral vorinostat (suberoylanilide hydroxamic acid), single-dose and multiple-dose pharmacokinetics of vorinostat, and the effect of a high-fat meal on vorinostat pharmacokinetics.
Experimental Design: Patients (n = 23) received single doses of 400 mg vorinostat on day 1 (fasted) and day 5 (fed) with 48 hours of pharmacokinetic sampling on both days. Patients received 400 mg vorinostat once daily on days 7 to 28. On day 28, vorinostat was given (fed) with pharmacokinetic sampling for 24 hours after dose.
Results: The apparent t1/2 of vorinostat was short (∼1.5 hours). A high-fat meal was associated with a small increase in the extent of absorption and a modest decrease in the rate of absorption. A short lag time was observed before detectable levels of vorinostat were observed in the fed state, and Tmax was delayed. Vorinostat concentrations were qualitatively similar following single-dose and multiple-dose administration; the accumulation ratio based on area under the curve was 1.21. The elimination of vorinostat occurred primarily through metabolism, with &lt;1% of the given dose recovered intact in urine. The most common vorinostat-related adverse experiences were mild to moderate nausea, anorexia, fatigue, increased blood creatinine, and vomiting.
Conclusions: Vorinostat concentrations were qualitatively similar after single and multiple doses. A high-fat meal increased the extent and modestly decreased the rate of absorption of vorinostat; this effect is not anticipated to be clinically meaningful. Continued investigation of 400 mg vorinostat given once daily in phase II and III efficacy studies is warranted.
Diplomacy with Fundamentalists: The United States and the Taliban
Authors: Kleiner Juergen 
Published: December 2006

AbstractAfter the Taliban had become a permanent factor in Afghan politics at the beginning of 1995, the US administration started talking to them, mainly through the American Embassy in Islamabad. Declassified documents about the administration's dealings with the Taliban, which were obtained and published by the National Security Archive, give insight into the relationship between the two unlikely partners. The Americans discussed various issues with the Taliban, such as peace in Afghanistan, the fight against narcotics, human rights, the proposed Unocal gas pipeline from Turkmenistan through Afghanistan, and terrorism. The Taliban demanded recognition as Afghanistan's legitimate government and wanted access to additional revenue. American talks with the Taliban survived the deterioration of the relationship from original friendliness to opposition to the promotion of sanctions and finally to threats. Since the end of summer 1998, a solution to the issue of Osama Bin Laden has been the US administration's top issue. The Americans asked the Taliban with urgency to take Bin Laden into custody or to expel him. The US administration, however, did not offer the Taliban anything in return. Persuasion was not enough to achieve the desired result and the administration's strategy was self-defeating.
Compromis, régulation et bien commun
Authors: Ollagnon Matthieu 
Published: December 2006

English The concept of compromise refers to a symbolic exchange organizing the mutual relationships of parties while recognizing their otherness. It facilitates bringing individual perspectives together, without fusing viewpoints. Thus compromise permits the emergence of an intersubjective organization of the real, while defining the context of that emergence. In this sense, it is at once the creator and the regulator of social reality. The example of a Catholic chaplaincy illustrates the common good that can emerge from a situation of pluralism regulated by compromise. Reflection on the process of the Lebanese civil war shows us that a weak founding compromise leads to a transformation of the common good, headed towards social deconstruction. French Le concept de compromis renvoie à un échange symbolique organisant les rapports mutuels des parties tout en reconnaissant leur altérité. Il permet de lier ensemble des perspectives individuelles, sans fusion des points de vue. Le compromis permet donc l'émergence d'une organisation intersubjective du réel, tout en définissant le cadre de cette émergence. En ce sens, il est à la fois créateur et régulateur de réalité sociale. L'exemple d'une aumônerie catholique illustre le bien commun qui peut émerger d'une situation de pluralisme régulé par un compromis. Une réflexion sur le processus de guerre au Liban montre qu'un compromis fondateur défaillant conduit à une transformation du bien commun tournée vers la déstructuration sociale.
A Note on National Churches: Ethnocultural Distinction, Socio-religious Compromise and State Regulation
Authors: Turcotte Paul-André 
Published: December 2006

English A national Church is characterized by a concentric synthesis of religion, culture and definitions of socio-political reality. As a result there is a strong social coherence which, objectively speaking, pushes dissidence away from public expression. In cases of compromise between agents of regulation, the separation of powers does not imply a separation between the spiritual and temporal spheres in individual and collective life. Care of the body and soul are intertwined at the same time as they are distinct. From this stems the tension between the system and movements, between the production and the reproduction of relations between religion and society of a Church-type. French L'Église nationale se caractérise notamment par une synthèse concentrique de la religion, de la culture et des définitions de la réalité socio-politique. Il s'ensuit une forte cohérence sociale, objectivement parlant, qui repousse la dissidence hors du cadre de l'expression publique. Dans le cas d'un compromis entre les instances de régulation, la séparation des pouvoirs n'implique pas celle entre les sphères spirituelle et temporelle dans la vie individuelle ou collective. Le soin du corps et le soin de l'âme sont imbriqués tout en se distinguant. ¡ ceci se greffe la tension entre le système et le mouvement, la production et la reproduction des rapports entre religion et société de type Église.