Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.     

IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three prospective studies.

Prospective cohort studies on breast cancer risk among premenopausal women and insulin-like growth factor I (IGF-I) concentrations have so far included only few cases, and have shown inconsistent relative risk estimates. We pooled 220 cases of breast cancer diagnosed before age 50, and 434 control subjects, from three prospective studies in New York (USA), Ume? (Northern Sweden) and Milan (Italy), and we measured IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) with common enzyme-linked immunosorbent assays. Overall, IGF-I and IGFBP-3 measurements obtained by the common method showed a positive but not significant relationship with breast cancer risk (odds ratios (ORs) 0.90 [95% confidence intervals (95% CI) 0.50-1.62], 1.63 [0.89-2.97], 1.46 [0.78-2.73] and 1.41 [0.75-2.63] for quintiles of IGF-I, and ORs 0.98 [0.54-1.75], 1.06 [0.59-1.91], 1.04 [0.58-1.87] and 1.77 [0.97-3.24] for quintiles of IGFBP-3). Our results give only moderate support for an association of blood IGF-I with breast cancer risk in young women.     

Fungal Species and Multi-Mycotoxin Associated with Post-Harvest Sorghum (Sorghum bicolor (L.) Moench) Grain in Eastern Ethiopia

Sorghum is the main staple food crop in developing countries, including Ethiopia. However, sorghum grain quantity and quality are affected by contaminating fungi both under field and post-harvest stage. The aim of the current study was to assessed fungal species and multi-mycotoxins associated with sorghum grain in post-harvest samples collected from eastern Ethiopia. Fungal genera of Aspergillus, Alternaria, Bipolaris, Fusarium, Mucor, Penicillium, and Rhizoctonia were recovered in the infected grain. A liquid chromatography-tandem mass spectrometric (LC-MS/MS) was used for quantification of multiple mycotoxins/fungal metabolites. Overall, 94 metabolites were detected and grouped into eight categories. All metabolites were detected either in one or more samples. Among major mycotoxins and derivatives, deoxynivalenol (137 μg/kg), zearalenone (121 μg/kg), ochratoxin A (115 μg/kg), and fumonisin B₁ (112 μg/kg) were detected with maximum concentrations, while aflatoxin B₁ had relatively lower concentrations (23.6 μg/kg). Different emerging mycotoxins were also detected, with tenuazonic acid (1515 μg/kg) occurring at the maximum concentration among Alternaria metabolites. Fusaric acid (2786 μg/kg) from Fusarium metabolites and kojic acid (4584 μg/kg) were detected with the maximum concentration among Fusarium and Aspergillus metabolites, respectively. Unspecific metabolites were recognized with neoechinulin A (1996 μg/kg) at the maximum concentration, followed by cyclo (L-Pro-L-Tyr) (574 μg/kg) and cyclo (L-Pro-L-Val) (410 μg/kg). Moreover, metabolites form other fungal genera and bacterial metabolites were also detected at varying levels. Apparently, the study revealed that sorghum grains collected across those districts were significantly contaminated with co-occurrences of several mycotoxins. Farmers should be the main target groups to be trained on the improved management of sorghum production.     

The Role of Nitrogen Fertilization on the Occurrence of Regulated,Modified and Emerging Mycotoxins and Fungal Metabolites in Maize Kernels

The European Food Safety Authority is currently evaluating the risks related to the presence of emerging mycotoxins in food and feeds. The aim of this study was to investigate the role of soil fertility, resulting from different nitrogen fertilization rates, on the contamination of regulated mycotoxins and emerging fungal metabolites in maize grains. The trial was carried out in the 2012–2013 growing seasons as part of a long-term (20-year) experimental platform area in North-West Italy, where five different N rates, ranging from 0 to 400 kg N ha⁻¹, were applied to maize each year. Maize samples were analyzed by means of a dilute-and-shoot multi-mycotoxin LC-MS/MS method, and more than 25 of the most abundant mycotoxins and fungal metabolites were detected. Contamination by fumonisins and other fungal metabolites produced by Fusarium spp. of the section Liseola was observed to have increased in soils that showed a poor fertility status. On the other hand, an overload of nitrogen fertilization was generally associated with higher deoxynivalenol and zearalenone contamination in maize kernels, as well as a higher risk of other fungal metabolites produced by Fusarium spp. sections Discolor and Roseum. A balanced application of N fertilizer, in accordance with maize uptake, generally appears to be the best solution to guarantee an overall lower contamination by regulated mycotoxins and emerging fungal metabolites.     

Physiological effects of muscarinic vs nicotinic ACh antagonists upon ganglion cell activity in the frog retina

The intravitreal administration of ACh agonists (eserine, carbachol, oxotremorine) or that of ACh muscarinic antagonists (scopolamine, atropine) provoked a reduction of the On-Off ganglion cell discharges. The agonists depressed the Off discharges more than the On discharges, while the ACh muscarinic antagonists depressed the On- more than the Off discharges. These drugs did not modify the ganglion cell receptive field area; thus, the muscarinic cholinergic system seems not to be involved in the spatial organization of the On-Off ganglion cells, but rather seems to play an important part in the separation of On and Off information channels. ACh nicotinic antagonists [hexamethonium, D-tubocurarine (D-TC), alpha-bungarotoxin (alpha-BGTX)] provoked an increase of the receptive field area of On-Off ganglion cells, this enlargement being due to the suppression of the inhibition normally exerted by the surround upon the centre of the field. Moreover D-TC and alpha-BGTX, but but hexamethonium, increased the number of ganglion cell discharges. These data are analogous to those obtained after administration of GABA antagonists and show that through nicotinic receptors, ACh seems to be involved in the spatial organization of the On-Off ganglion cell.     

Regulation of differentiation, proliferation and drug-induced apoptosis in HT58 lymphoma cells

Recently, it has been suggested, that differentiated cells are more resistant to the apoptotic effect of DNA damaging agents possibly due to the decreased activity of “damage detecting/apoptosis triggering” mechanism. Previously, we have shown, that PMA pretreatment reduced etoposide-(ETO) but enhanced staurosporine- (STA) -induced apoptosis in HT58 cells. Data presented here show that the HT58 human, “mature” B-lymphoma cells exposed to PMA secrete more IgM into the supernatant indicating commitment of cells to perform differentiated function. The sensitivity of HT58 cells to ETO- or STA-induced apoptosis is influenced diversely with PMA pre- or posttreatment. Interestingly, the DNA damage (gamma radiation, bleomycin, ETO) or okadaic acic (30 nM) reduced the [PMA+STA] - induced apoptosis.