Phase II Study of Ifosfamide+Doxorubicin in Patients With Advanced Synovial Sarcomas (E1793): A Trial of the Eastern Cooperative Oncology Group

Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamide+doxorubicin (88%) than from doxorubicin alone (20%) (P = 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study

Phase II study of IfosfamideþDoxorubicin in patients with advanced synovial sarcomas (E1793): a trial of the Eastern Cooperative Oncology Group

Abstract Purpose Because we had observed in the synovial sarcoma subgroup of a broad phase III advanced soft tissue sarcoma study a significantly greater objective regression rate from ifosfamideþdoxorubicin (88%) than from doxorubicin alone (20%) ( P ¼ 0.02), the Eastern Cooperative Oncology Group (ECOG) decided to further assess this two drug combination in a subsequent Phase II study. Patients Between 1994 and 1999, twelve adult patients with advanced synovial sarcomas were enrolled to receive, as their initial chemotherapy, ifosfamide 7.5 gm/m 2 plus doxorubicin 60 mg/m 2 , given intravenously over two consecutive days every 3 weeks. Methods Each day for 2 days doxorubicin 30 mg/m 2 was infused over 5 min through a running i.v., followed by ifosfamide 3750 mg/m 2 over 4 h. Continuous i.v. fluid was infused at 300 mL /h for 3 h on day 1, before chemotherapy was begun; then the infusion was continued at 100 mL /h for a total of 3 days. Mesna 750 mg/m 2 was given 15 min before ifosfamide and at 4 and 8 h after ifosfamide on days 1 and 2 of each treatment cycle. Filgrastim (G-CSF) 5 mg/kg was given subcutaneously each day for 14 days beginning on day 3 of each treatment cycle to limit the severity of neutropenia. Results Five of our 12 patients (42%) experienced partial regression of their advanced synovial sarcomas; however, this first stage result was borderline for proceeding to the second planned stage of accrual and our case accrual was quite poor. Thus, the study was closed after stage one accrual. Our patients received a median of four cycles of chemotherapy (range: 1 to 6). All patients experienced at least grade 3 neutropenia (grade 4 in nine of them), and one patient died of treatment-related sepsis following the initial cycle of chemotherapy. Median survival was 11 months

Uganda’s HIV Prevention Success: The Role of Sexual Behavior Change and the National Response. Commentary on Green et al. (2006)

The paper by Green et al. (vol. 10, this issue

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

Primed acclimation of cultivated peanut (Arachis hypogaea L.) through the use of deficit irrigation timed to crop developmental periods

Water-deficits and high temperatures are the predominant factors limiting peanut production across the U.S., either because of regional aridity or untimely rainfall events during crucial crop developmental periods. In the southern High Plains of west Texas and eastern New Mexico, low average annual rainfall (450. mm) and high evaporative demand necessitates the use of significant irrigation in production systems. In this west Texas study, the primary objective was to develop irrigation schemes that maximized peanut yield and grade while reducing overall water consumption. Therefore, a large-scale field experiment was established in 2005 and 2006 that utilized 15 treatment combinations of differing rates of irrigation (50, 75, and 100% of grower applied irrigation) applied at different periods of peanut development (early, middle, and late season). Precipitation patterns and ambient temperatures showed greater stress levels in 2006 which likely reduced yields across all treatments in comparison to 2005. Yields were reduced 26 (2005) and 10% (2006) in the lowest irrigation treatment (50% full season) compared with full irrigation (100% full season); but early-season water deficit (50 and 75% in the first 45. days after planting) followed by 100% irrigation in the mid- and late-seasons were successful at sustaining yield and/or crop value. Root growth was significantly enhanced at 50% irrigation compared with 100% irrigation, through greater root length, diameter, surface area, and depth, suggesting greater access to water during mid- and late-season periods. These results suggest that early to mid-season deficit irrigation has the potential to maintain peanut yield without altering quality, and to substantially reduce water use in this semi-arid environment

124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of ¹⁸F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized C_H2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaC_H2), radiolabeled with iodine-124 (¹²⁴I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging.</p> <p>Methods</p> <p>HuCC49deltaC_H2 was radiolabeled with ¹²⁴I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of ¹²⁴I-HuCC49deltaC_H2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of ¹⁸F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection.</p> <p>Results</p> <p>At approximately 1 hour after i.v. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, ¹²⁴I-HuCC49deltaC_H2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, ¹²⁴I-HuCC49deltaC_H2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, ¹⁸F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder.</p> <p>Conclusions</p> <p>On microPET imaging, ¹²⁴I-HuCC49deltaC_H2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while ¹⁸F-FDG failed to demonstrate this. The antigen-directed and cancer-specific ¹²⁴I-radiolabled anti-TAG-72 monoclonal antibody conjugate, ¹²⁴I-HuCC49deltaC_H2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.</p

Directing Astroglia from the Cerebral Cortex into Subtype Specific Functional Neurons

Forced expression of single defined transcription factors can selectively and stably convert cultured astroglia into synapse-forming excitatory and inhibitory neurons

A Tale of Two Spills: Novel Science and Policy Implications of an Emerging New Oil Spill Model

The 2010 Deepwater Horizon oil release posed the challenges of two types of spill: a familiar spill characterized by buoyant oil, fouling and killing organisms at the sea surface and eventually grounding on and damaging sensitive shoreline habitats, and a novel deepwater spill involving many unknowns. The subsurface retention of oil as finely dispersed droplets and emulsions, wellhead injection of dispersants, and deepwater retention of plumes of natural gas undergoing rapid microbial degradation were unprecedented and demanded the development of a new model for deepwater well blowouts that includes subsurface consequences. Existing governmental programs and policies had not anticipated this new theater of impacts, which thereby challenged decisionmaking on the spill response, on the assessment of natural resource damages, on the preparation for litigation to achieve compensation for public trust losses, and on restoration. Modification of laws and policies designed to protect and restore ocean resources is needed in order to accommodate oil drilling in the deep sea and other frontiers.Keywords: Ecosystem, Petroleum, Deep water horizon, Gulf of Mexico, BlowoutKeywords: Ecosystem, Petroleum, Deep water horizon, Gulf of Mexico, Blowou