bluuebunny/crossref_metadata_2025_split huggingface dataset:
A laboratory strategy for genotyping haemoglobin H disease in the Chinese
Authors: Chan Amy Yuk-Yin , So Chi-Chiu , Ma Edmond Shiu-Kwan , Chan Li-Chong 
Published: October 2006

Background:The thalassaemias are the commonest blood disorders worldwide, with South East Asia and southern China as areas of high prevalence. Accurate diagnosis of these disorders helps in clinical management with improved outcome.Methods:The α-globin genotypes of 100 Chinese patients in Hong Kong with haemoglobin H (Hb H) disease were characterised. Single-tube multiplex gap-PCR was used to detect −−SEA, −α3.7and −α4.2, while Hb CS, Hb QS and codon 30 (ΔGAG) were identified by single-tube multiplex amplification refractory mutation system (ARMS). Automated direct nucleotide sequencing of the amplified α2- and α1-globin genes was performed to characterise other non-deletional α-thalassaemia determinants.Results:In the 100 cases studied, 99 cases had −−SEAin combination with deletional α+-thalassaemia or non-deletional α-globin gene mutation involving the α2-globin gene. In 70 cases of the deletional form, 43 cases showed the genotype of (−−SEA/−α3.7) and 27 cases of (−−SEA/−α4.2). Three of the 27 cases of (−−SEA/−α4.2) were found to have Hb Q-Thailand linkedin-ciswith −α4.2. The remaining 30 cases were of non-deletional form with the following genotypes: 11 cases of (−−SEA/αHbCSα), 9 cases of (−−SEA/αHbQSα), 3 cases of (−−SEA/αcd30 (ΔGAG)α), 3 cases of (−−SEA/αcd31α), 2 cases of (−−SEA/αpoly-Aα), 1 case of (−−SEA/αHbWestmeadα) and 1 case of (−−non-SEA/αHbQSα).Conclusions:Based on two rapid diagnostic tests, multiplex gap-PCR and multiplex ARMS, more than 90% of the cases were genetically characterised. This laboratory strategy should be widely applicable for genetic diagnosis of α-thalassaemia.
Hay fever and asthma symptoms in conventional and organic farmers in The Netherlands
Authors: Smit Lidwien A M , Zuurbier Moniek , Doekes Gert , Wouters Inge M , Heederik Dick , Douwes Jeroen 
Published: October 2006

Background:Farming has been associated with respiratory symptoms and with protection against atopy. To date, effects of organic farming on respiratory health have not been studied.Aims:To (1) compare hay fever and asthma-like symptoms in organic and conventional farmers and (2) assess associations between current and childhood farm exposures and respiratory health effects by conducting a survey.Methods:Questionnaire data from 1205 conventional and 593 organic farmers were evaluated. Associations between health effects and farm exposures were assessed by logistic regression analyses.Results:Organic farmers reported less wheezing with shortness of breath and slightly more hay fever than conventional farmers. However, organic farming was not an independent determinant of hay fever when adjusted for farming practices and potential confounders. Livestock farmers who grew up on a farm had a threefold lower prevalence of hay fever than crop farmers without a farm childhood (odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1 to 0.5). Both crop farmers who grew up on a farm and livestock farmers who did not grow up on a farm had a reduced prevalence, although less pronounced and not statistically significant. Use of disinfectants containing quaternary ammonium compounds was positively related to hay fever (OR 2.1, 95% CI 1 to 4.4). No effects of farming practices were found for asthma.Conclusions:Our study adds to the evidence that a farm childhood in combination with current livestock farming protects against allergic disorders. This effect was found for both organic and conventional farmers.
Randomized Study of Paclitaxel and Tamoxifen Deposition into Human Brain Tumors: Implications for the Treatment of Metastatic Brain Tumors
Authors: Fine Robert L. , Chen Johnson , Balmaceda Casilda , Bruce Jeffrey N. , Huang May , Desai Manisha , Sisti Michael B. , McKhann Guy M. , Goodman Robert R. , Bertino Joseph S. , Nafziger Anne N. , Fetell Michael R. 
Published: October 2006

Abstract
Purpose: Drug resistance in brain tumors is partially mediated by the blood-brain barrier of which a key component is P-glycoprotein, which is highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This trial assessed, in primary and metastatic brain tumors, the differential deposition of paclitaxel and whether tamoxifen could increase paclitaxel deposition.
Experimental Design: Patients for surgical resection of their primary or metastatic brain tumors were prospectively randomized to prior paclitaxel alone (175 mg/m2/i.v.) or tamoxifen for 5 days followed by paclitaxel. Central and peripheral tumor, surrounding normal brain and plasma, were analyzed for paclitaxel and tamoxifen.
Results: Twenty-seven patients completed the study. Based on a multivariate linear regression model, no significant differences in paclitaxel concentrations between the two study arms were found after adjusting for treatment group (tamoxifen versus control). However, in analysis for tumor type, metastatic brain tumors had higher paclitaxel concentrations in the tumor center (1.93-fold, P = 0.10) and in the tumor periphery (2.46-fold, P = 0.039) compared with primary brain tumors. Pharmacokinetic analyses showed comparable paclitaxel areas under the serum concentration between treatment arms.
Conclusions: Paclitaxel deposition was not increased with this tamoxifen schedule as the low plasma concentrations were likely secondary to concurrent use of P-450-inducing medications. However, the statistically higher paclitaxel deposition in the periphery of metastatic brain tumors provides functional evidence corroborating reports of decreased P-glycoprotein expression in metastatic versus primary brain tumors. This suggests that metastatic brain tumors may respond to paclitaxel if it has proven clinical efficacy for the primary tumor's histopathology.
Intralymphatic Dendritic Cell Vaccination Induces Tumor Antigen–Specific, Skin-Homing T Lymphocytes
Authors: Grover Amelia , Kim Grace J. , Lizée Gregory , Tschoi Mary , Wang Gang , Wunderlich John R. , Rosenberg Steven A. , Hwang Sam T. , Hwu Patrick 
Published: October 2006

AbstractPurpose: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen–specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo.Experimental Design: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100.Results: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen–specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash.Conclusions: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are “imprinted” in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease.
Most Early Disseminated Cancer Cells Detected in Bone Marrow of Breast Cancer Patients Have a Putative Breast Cancer Stem Cell Phenotype
Authors: Balic Marija , Lin Henry , Young Lillian , Hawes Debra , Giuliano Armando , McNamara George , Datar Ram H. , Cote Richard J. 
Published: October 2006

AbstractPurpose: The presence of disseminated tumor cells (DTC) in the bone marrow of breast cancer patients is an acknowledged independent prognostic factor. The biological metastatic potential of these cells has not yet been shown. The presence of putative breast cancer stem cells is shown both in primary tumors and distant metastases. These cells with a CD44+CD24−/low phenotype represent a minor population in primary breast cancer and are associated with self-renewal and tumorigenic potential. Recognizing the potential effect of prevalence of putative stem cells among DTC, we evaluated the bone marrow DTC.Experimental Design: We employed the double/triple-staining immunohistochemistry protocol and modified the established bone marrow cytokeratin (CK) staining protocol by adding steps for additional antigens, CD44 and/or CD24. We evaluated 50 bone marrow specimens, previously categorized as CK+ from early breast cancer patients. CK+ cells were examined for CD44 and CD24 expression by light microscopy, fluorescence microscopy, and spectral imaging.Results: We detected the putative stem cell–like phenotype in all CK+ specimens. The mean prevalence of putative stem/progenitor cells was 72% and median prevalence was 65% (range, 33-100%) among the overall DTC per patient, compared with primary tumors where this phenotype is reported in &lt;10% of cells.Conclusions: This is the first evidence of the existence of the putative stem-like phenotype within the DTC in bone marrow in early breast cancer patients. All patients had a putative stem cell phenotype among the DTC and most individual DTC showed such phenotype. Future molecular characterization of these cells is warranted.
The GNAS1 T393C Polymorphism Is Associated with Disease Progression and Survival in Chronic Lymphocytic Leukemia
Authors: Frey Ulrich H. , Nückel Holger , Sellmann Ludger , Siemer Dörte , Küppers Ralf , Dürig Jan , Dührsen Ulrich , Siffert Winfried 
Published: October 2006

Abstract
Purpose: B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of monoclonal mature B cells. The G protein Gαs subunit has been linked to proapoptotic processes in cancer cell lines. The TT genotype of the GNAS1 T393C polymorphism is associated with increased Gαs transcript levels and a more favorable clinical course in different solid cancers.
Experimental Design: We retrospectively genotyped 144 patients with B-CLL to examine a potential association between T393C genotypes with progression-free survival (time from diagnosis to initiation of chemotherapy) and overall survival.
Results: The C-allele frequency in the patient group was 0.57 and not significantly different from that of healthy blood donors. Median progression-free survival was significantly different between genotypes (TT 130 months; TC 100 months; CC 31 months; P = 0.0066). Multivariable analysis showed that besides of ZAP-70 (P = 0.005) and Binet stage (P &lt; 0.001), the T393C polymorphism was an independent prognostic factor for progression-free survival [hazard ratio (HR) CC versus TT 2.7; P = 0.010]. In Binet A stages, ZAP-70–positive patients with CC genotypes had a HR of 4.4 to receive first therapy compared with ZAP-70–negative patients with T-alleles (P = 0.0001). Regarding overall survival, CC genotypes (median overall survival, 197 months) were at highest risk for death compared with T-alleles (median overall survival, 310 months) in both univariate (HR, 4.8; P &lt; 0.0001) and multivariable analysis (HR, 5.6; P = 0.002).
Conclusions: Here, we show that the GNAS1 T393C status is a novel independent prognostic marker in patients with B-CLL. These results could help to define patients who could benefit from an early individualized therapy.
Monitoring Tumor Glucose Utilization by Positron Emission Tomography for the Prediction of Treatment Response to Epidermal Growth Factor Receptor Kinase Inhibitors
Authors: Su Helen , Bodenstein Claudia , Dumont Rebecca A. , Seimbille Yann , Dubinett Steven , Phelps Michael E. , Herschman Harvey , Czernin Johannes , Weber Wolfgang 
Published: October 2006

AbstractPurpose: The mechanisms underlying the sensitivity of non–small cell lung cancer to epidermal growth factor receptor (EGFR) kinase inhibitors are complex, and there are no established markers to accurately predict treatment outcome in individual patients.Experimental Design: We investigated whether tumors responding to EGFR inhibitors can be identified by measuring treatment-induced changes in glucose utilization by positron emission tomography with the glucose analogue fluorodeoxyglucose (FDG-PET). We studied a panel of cell lines with a spectrum of sensitivity to EGFR kinase inhibitors. After incubation with the EGFR kinase inhibitor gefitinib for various time points, FDG uptake, glucose transport rates, and hexokinase activity were determined. FDG uptake in vivo was assessed by microPET imaging of tumor xenografts in mice.Results: In gefitinib-sensitive cell lines, there was a dramatic decrease in FDG uptake as early as 2 hours after treatment. Immunoblots showed the translocation of glucose transporters (GLUT3) from the plasma membrane to the cytosol; glucose transport rates were reduced 2.6-fold at this time. There was also a modest reduction of hexokinase activity. These metabolic alterations preceded changes in cell cycle distribution, thymidine uptake, and apoptosis. MicroPET studies showed an up to 55% decrease of tumor FDG uptake in sensitive xenografts within 48 hours. In contrast, gefitinib-resistant cells exhibited no measurable changes in FDG uptake, either in cell culture or in vivo.Conclusion: Glucose metabolic activity closely reflects response to gefitinib therapy. FDG-PET may be a valuable clinical predictor, early in the course of treatment, for therapeutic responses to EGFR kinase inhibitors.
Sensitization by Dietary Docosahexaenoic Acid of Rat Mammary Carcinoma to Anthracycline: A Role for Tumor Vascularization
Authors: Colas Séverine , Mahéo Karine , Denis Fabrice , Goupille Caroline , Hoinard Claude , Champeroux Pascal , Tranquart François , Bougnoux Philippe 
Published: October 2006

Abstract
Purpose: To investigate whether dietary docosahexaenoic acid (DHA), a peroxidizable polyunsaturated ω-3 fatty acids, sensitizes rat mammary tumors to anthracyclines and whether its action interferes with tumor vascularization, a critical determinant of tumor growth.
Experimental Design: Female Sprague-Dawley rats were initiated by N-methylnitrosourea to develop mammary tumors and then assigned to a control group (n = 18), receiving a supplementation of palm oil, or to a DHA group (n = 54), supplemented with a microalgae-produced oil (DHASCO, 1.5 g/d). The DHA group was equally subdivided into three subgroups with addition of different amounts of α-tocopherol. Epirubicin was injected weekly during 6 weeks after the largest tumor reached 1.5 cm2, and subsequent changes in the tumor surface were evaluated. Tumor vascularization was assessed by power Doppler sonography before and during chemotherapy.
Results: DHA and α-tocopherol were readily absorbed and incorporated into rat tissues. Epirubicin induced a 45% mammary tumor regression in the DHA-supplemented group, whereas no tumor regression was observed in the control group. In the DHA group, before chemotherapy was initiated, tumor vascular density was 43% lower than in the control group and remained lower during chemotherapy. Enhancement of epirubicin efficacy by DHA was abolished in a dose-dependent manner by α-tocopherol, and the same trend was observed for DHA-induced reduction in tumor vascular density.
Conclusions: Dietary DHA supplementation led to a reduction in tumor vascularization before the enhancement of any response to anthracyclines, suggesting that DHA chemosensitizes mammary tumors through an inhibition of the host vascular response to the tumor.
Peripheral Blood Stem Cell Tumor Cell Contamination and Survival of Neuroblastoma Patients
Authors: Corrias Maria Valeria , Haupt Riccardo , Carlini Barbara , Parodi Stefano , Rivabella Lucia , Garaventa Alberto , Pistoia Vito , Dallorso Sandro 
Published: October 2006

Abstract
Purpose: Contribution of peripheral blood stem cell (PBSC) contaminating tumor cells to subsequent relapse and overall survival of neuroblastoma patients remains controversial.
Experimental Design: Neuroblastoma cell contamination of 27 PBSC harvests from stage IV neuroblastoma patients was assessed by quantitative RT-PCR for both tyrosine hydroxylase (TH) and GD2 synthase (GD2-s). The effect of PBSC contamination on survival was then analyzed.
Results: Seven PBSC tested negative for both markers; 19 were positive for GD2-s, 6 for TH, with 5 positive for both. Survival of the 20 patients with positive PBSC did not differ from that of the patients with negative PBSC (log-rank test, P = 0.134 and 0.218 for event-free survival and overall survival, respectively). By considering the TH and GD2-s results independently, a borderline (P = 0.053) negative effect on event-free survival was observed in patients reinfused with GD2-s-positive PBSC. When the status at transplant was taken into account, only the event-free survival of the patients rescued when in complete remission with GD2-s-negative PBSC was better, although not significantly, than that of patients infused with GD2-s-positive PBSC.
Conclusions: Our results obtained in a small cohort of homogeneously treated stage IV patients suggest that patient survival is not affected by PBSC contamination with the exception of a borderline negative effect on event-free survival in patients rescued when in complete remission.
Inhibition of Tumor Growth with Antiangiogenic Cancer Vaccine Using Epitope Peptides Derived from Human Vascular Endothelial Growth Factor Receptor 1
Authors: Ishizaki Hidenobu , Tsunoda Takuya , Wada Satoshi , Yamauchi Mai , Shibuya Masabumi , Tahara Hideaki 
Published: October 2006

AbstractPurpose: Antiangiogenic therapy is now considered to be one of promising approaches to treat various types of cancer. In this study, we examined the possibility of developing antiangiogenic cancer vaccine targeting vascular endothelial growth factor receptor 1 (VEGFR1) overexpressed on endothelial cells of newly formed vessels in the tumor.Experimental Design: Epitope-candidate peptides were predicted from the amino acid sequence of VEGFR1 based on their theoretical binding affinities to the corresponding HLAs. The A2/Kb transgenic mice, which express the α1 and α2 domains of human HLA-A*0201, were immunized with the epitope candidates to examine their effects. We also examined whether these peptides could induce human CTLs specific to the target cells in vitro.Results: The CTL responses in A2/Kb transgenic mice were induced with vaccination using identified epitope peptides restricted to HLA-A*0201. Peptide-specific CTL clones were also induced in vitro with these identified epitope peptides from peripheral blood mononuclear cells donated by healthy volunteers with HLA-A*0201. We established CTL clones in vitro from human peripheral blood mononuclear cells with HLA-A*2402 as well. These CTL clones were shown to have potent cytotoxicities in a HLA class I–restricted manner not only against peptide-pulsed target cells but also against target cells endogenously expressing VEGFR1. Furthermore, immunization of A2/Kb transgenic mice with identified epitope peptides restricted to HLA-A*0201 was associated with significant suppression of tumor-induced angiogenesis and tumor growth without showing apparent adverse effects.Conclusions: These results strongly suggest that VEGFR1 is a promising target for antiangiogenic cancer vaccine and warrants further clinical development of this strategy.
The Combination of the Rexinoid, LG100268, and a Selective Estrogen Receptor Modulator, Either Arzoxifene or Acolbifene, Synergizes in the Prevention and Treatment of Mammary Tumors in an Estrogen Receptor–Negative Model of Breast Cancer
Authors: Liby Karen , Rendi Mara , Suh Nanjoo , Royce Darlene B. , Risingsong Renee , Williams Charlotte R. , Lamph William , Labrie Fernand , Krajewski Stan , Xu Xiaochun , Kim Heetae , Brown Powel , Sporn Michael B. 
Published: October 2006

AbstractPurpose: We tested whether a selective estrogen receptor modulator (SERM) and a rexinoid are active for prevention and treatment in the mouse mammary tumor virus-neu mouse model of estrogen receptor–negative breast cancer.Experimental Design: For prevention, mice were fed a powdered control diet, the SERM arzoxifene (Arz, 20 mg/kg diet), the rexinoid LG100268 (268, 30 mg/kg diet), or the combination for 60 weeks. In a second prevention study, mice were fed Arz (6 mg/kg diet), 268 (30 mg/kg diet), the combination of Arz and 268, the SERM acolbifene (Acol, 3 mg/kg diet), or the combination of Acol and 268 for 52 weeks. For the treatment studies, mice with tumors were fed combinations of a SERM and 268 for 4 weeks.Results: The rexinoid 268 and the SERMs Arz and Acol, as individual drugs, delayed the development of estrogen receptor–negative tumors. Moreover, the combination of a SERM and 268 was strikingly synergistic, as no tumors developed in any mouse fed the combination of 268 and a SERM. Moreover, this drug combination also induced significant tumor regression when used therapeutically. These drugs did not inhibit transgene expression in vitro or in vivo, and the combination of Arz and 268 inhibited proliferation and induced apoptosis in the tumors.Conclusion: The combination of a rexinoid and SERM should be considered for future clinical trials.
On “Field Significance” and the False Discovery Rate
Authors: Wilks D. S. 
Published: October 2006

AbstractThe conventional approach to evaluating the joint statistical significance of multiple hypothesis tests (i.e., “field,” or “global,” significance) in meteorology and climatology is to count the number of individual (or “local”) tests yielding nominally significant results and then to judge the unusualness of this integer value in the context of the distribution of such counts that would occur if all local null hypotheses were true. The sensitivity (i.e., statistical power) of this approach is potentially compromised both by the discrete nature of the test statistic and by the fact that the approach ignores the confidence with which locally significant tests reject their null hypotheses. An alternative global test statistic that has neither of these problems is the minimum p value among all of the local tests. Evaluation of field significance using the minimum local p value as the global test statistic, which is also known as the Walker test, has strong connections to the joint evaluation of multiple tests in a way that controls the “false discovery rate” (FDR, or the expected fraction of local null hypothesis rejections that are incorrect). In particular, using the minimum local p value to evaluate field significance at a level αglobal is nearly equivalent to the slightly more powerful global test based on the FDR criterion. An additional advantage shared by Walker’s test and the FDR approach is that both are robust to spatial dependence within the field of tests. The FDR method not only provides a more broadly applicable and generally more powerful field significance test than the conventional counting procedure but also allows better identification of locations with significant differences, because fewer than αglobal × 100% (on average) of apparently significant local tests will have resulted from local null hypotheses that are true.