Improving Water Quality Through BMPs For Crop Production Systems Whole Farm Soil and Water Management

The major objective of this demonstration project was to assess the usefulness of Global Positioning Systems/Geographic Information Systems (GPS/GIS), water testing, soil testing and yield monitoring in a whole farm water and soil management plan. An important part of this objective was to make recommendations to increase crop productivity and decrease the potential for surface water degradation through erosion and runoff at the farm. The farm was located on 2400 acres in the Bayou de View watershed in Monroe County, Arkansas. The farm lies approximately five miles southwest of the town of Brinkley straddling Highway 17 just south of its intersection with County Road 302 and with U. S. Highway 70. Slightly over 2200 acres were under cultivation and this was generally in a 1 :2 ratio of rice to soybeans, with approximately half of the soybean fields double-cropped with winter wheat each year

Clinical benefit in Phase-I trials of novel molecularly targeted agents: does dose matter?

Phase-I trials traditionally involve dose-escalation to determine the maximal tolerated dose (MTD). With conventional chemotherapy, efficacy is generally deemed to be dose-dependent, but the same may not be applicable to molecularly targeted agents (MTAs). We analysed consecutive patients included in Phase-I trials at the Royal Marsden Hospital from 5 January 2005 to 6 June 2006. We considered only trials of monotherapy MTAs in which the MTD was defined. Three patient cohorts (A, B, and C) were identified according to the dose received as a percentage of the final trial MTD (0–33%, 34–65%, >66%). Potential efficacy was assessed using the non-progression rate (NPR), that is, complete/partial response or stable disease for at least 3 months by RECIST. A total of 135 patients having progressive disease before enrolment were analysed from 15 eligible trials. Median age was 57 years (20–86); male : female ratio was 1.8 : 1. Cohort A, B, and C included 28 (21%), 22 (16%), and 85 (63%) patients; NPR at 3 and 6 months was 21% and 11% (A), 50% and 27% (B), 31% and 14% (C), respectively, P=0.9. Median duration of non-progression (17 weeks; 95% CI=13–22) was not correlated with the MTD level, P=0.9. Our analysis suggests that the potential for clinical benefit is not confined to patients treated at doses close to the MTD in Phase-I trials of MTAs

Inhibitory effect on expression of angiogenic factors by antiangiogenic agents in renal cell carcinoma

Since it has been widely recognised that renal cell carcinoma is refractory to standard therapies such as chemotherapy and radiotherapy, a new modality of treatment is needed. One of the potential alternative therapies for renal cell carcinoma may be inhibition of angiogenesis. In this study, we analysed the inhibitory effects of several potential agents on expression of angiogenic factors such as vascular endothelial growth factor and basic fibroblast growth factor, which are the main mediators in angiogenesis of renal cell carcinoma. We used medroxyprogesterone acetate, interferon-alpha, interferon-gamma, minocycline hydrochrolide and genistein, which are known to be antiangiogeneic. Northern blot analyses revealed that, among the five agents examined, genistein had a strong inhibitory effect on expression of vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA. Medroxyprogesterone acetate and interferon-alpha did not significantly decrease the level of either vascular endothelial growth factor mRNA or basic fibroblast growth factor mRNA. Interferon-gamma and minocycline had mild inhibitory effects on vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression. Genistein also inhibited both vascular endothelial growth factor mRNA and basic fibroblast growth factor mRNA expression after treatment with epidermal growth factor and hypoxia. These findings suggest that one of the mechanisms of the inhibition of angiogenesis by genistein is suppression of the expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor in renal cell carcinoma

PPARα Deficiency in Inflammatory Cells Suppresses Tumor Growth

Inflammation in the tumor bed can either promote or inhibit tumor growth. Peroxisome proliferator-activated receptor (PPAR)α is a central transcriptional suppressor of inflammation, and may therefore modulate tumor growth. Here we show that PPARα deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of the endogenous angiogenesis inhibitor thrombospondin-1 and prevents tumor growth. Bone marrow transplantation and granulocyte depletion show that PPARα expressing granulocytes are necessary for tumor growth. Neutralization of thrombospondin-1 restores tumor growth in PPARα-deficient mice. These findings suggest that the absence of PPARα activity renders inflammatory infiltrates tumor suppressive and, thus, may provide a target for inhibiting tumor growth by modulating stromal processes, such as angiogenesis

Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

<p>Abstract</p> <p>Background</p> <p>Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC).</p> <p>Methods</p> <p>Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor.</p> <p>Results</p> <p>Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated.</p> <p>Conclusion</p> <p>The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials.</p> <p>Trial registration</p> <p>Current Controlled Trials RPCEC00000052.</p

Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2), a beta integrin antagonist, in patients with solid tumours

To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five –amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1–16 mg kg−1), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of blood and urine over 7 h was performed on Day 1. Twenty-six patients received from 1 to 14 4-week cycles of treatment. The total number of cycles administered to all patients was 86, without dose-limiting toxicities. At dose levels above 0.5 mg kg−1, mean total clearance and volume of distribution showed dose-independent pharmacokinetics (PKs). At 8.0 and 16.0 mg kg−1, clearance of ATN-161 was reduced, suggesting saturable PKs. Dose escalation was halted at 16 mg kg−1 when drug exposure (area under the curve) exceeded that associated with efficacy in animal models. There were no objective responses. Six patients received more than four cycles of treatment (>112 days). Three patients received 10 or more cycles (⩾280 days). ATN-161 was well tolerated at all dose levels. Approximately, 1/3 of the patients in the study manifested prolonged stable disease. These findings suggest that ATN-161 should be investigated further as an antiangiogenic and antimetastatic cancer agent alone or with chemotherapy