Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and malignant human breast, and comparison with other normal tissues.

The expression of basic fibroblast growth factor (bFGF) and two of its receptors, FGFR1 and FGFR2, was detected using the polymerase chain reaction, and quantified by comparison to the relative amount of product obtained following co-amplification of the ubiquitous glyceraldehyde phosphate dehydrogenase transcript. Varying levels were found in the vast majority of both cancer and non-malignant breast biopsies as well as in samples of several other normal human tissues. Significantly less bFGF was present in cancers (P less than 0.0001). Similarly, FGFR2 product was also much less in cancer tissues (P = 0.0078), as was FGFR1 (P = 0.002). FGFR1 levels in cancers tended to be higher in those which were oestrogen receptor positive (P less than 0.06). Amplification of different coding regions showed evidence of variant forms of FGFR1 RNA. Cancers appeared to have a significantly greater proportion of PCR product corresponding to the region between the third immunoglobulin like domain and the tyrosine kinase domain (P = 0.046). Differential expression was observed in breast cell lines, with bFGF in the normal derived HBL100, HBR SV1.6.1 and 184A1 but little or none in ZR-75-1, MCF-7, T47D and MDA-MB-231. FGFR1 was present in most of these but FGFR2 was absent from T47D, MDA-MB-231 and HBL100. ZR-75-1 cells had a marked preponderance of FGFR1 variants lacking part of the coding sequence. Aberrant receptor processing may provide clues concerning the role of FGF's and their potential involvement in malignancy

Transcripts for transforming growth factors in human breast cancer: clinical correlates.

The levels of mRNA for transforming growth factors (TGF alpha and beta) and the epidermal growth factor receptor (EGFR) were determined in 69 human breast carcinomas and 20 biopsies of non-neoplastic breast tissue by dot blot hybridisation analysis. TGF alpha mRNA was detected in 42% of cancers and 44% of non-neoplastic breast tissue at low levels. TGF beta mRNA was found in all breast cancers and non-neoplastic breast tissues, but the levels of TGF beta mRNA were found to be higher in breast cancers (P = 0.01). EGFR mRNA was detected in 55% of breast cancers and in all non-neoplastic breast tissue tested. The presence of EGFR mRNA was inversely related to oestrogen receptor (ER) status (P = 0.0001). Coexpression of TGF alpha and EGFR was observed in 28% of the carcinomas, and significantly more commonly in ER negative tumours (P = 0.01). No significant relationship was found between histological grade, tumour cellularity or tumour desmoplasia and expression of either the TGFs or of EGFR mRNA. High levels of TGF beta were, however, associated with the absence of lymph node metastases at presentation (P = 0.05). Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients. Longer clinical follow-up and larger numbers of patients are required to determine whether TGFs will prove a useful marker for prognosis in breast cancer patients

Effects of Soil Conservation Practices on Sediment Yield from Forest Road Ditches in Northern Iran

The fine-textured soil in forest road ditches is very susceptible to water erosion especially in rainy seasons in Hyrcanian forest. This study examined the yield of ditch segment-scale sediment after releasing two flow rates of 5 l s-1 and 10 l s-1 in segments treated by riprap (RR), grass cover by Festuca arundinacea L. (GC), compacted cotton geotextile (CG) and wooden wattle by local slash (WW). Sediment sampling from the runoff was carried out at the end of each segment every minute. Runoff flow velocity in different treatments was measured using an electromagnetic flow meter. Sediment concentration and runoff velocity in treatments of RR, GC, CG, WW was significantly lower than that of the control plot (Ctl). Increasing flow rate from 5 l s-1 to 10 l s-1 caused no significant change in sediment concentration (except for Ctl and RR) and runoff velocity (except for Ctl and CG), which means that some water might have penetrated into treated soil by RR, GC and WW and this is not acceptable in forest road maintenance practices. Sediment yield from RR (0.36 g l-1) and Ctl (0.50 g l-1) under the flow rate of 10 l s-1 was significantly higher than that of 5 l s-1 with values of 0.21 g l-1 and 0.38 g l-1, respectively. Minimum amount of sediment concentration was observed for CG (0.20 g l-1) with compacted ditch bed. Moreover, runoff velocity in CG and Ctl under the flow rate of 10 l s-1 was significantly higher than that of 5 l s-1. For a forest road with dimension 30×50 cm, slope of 5%, and clay soil with porosity of 57%, treatments of compacted CG can be used in ditch with low flow rates (5 l s-1) and high flow rate (10 l s-1) because of their high efficiency in reducing sediment yield

Development of a score for assessment of radiologic damage in large-vessel vasculitis (Combined Arteritis Damage Score, CARDS)

OBJECTIVES: Outcome assessment in large-vessel vasculitis (LVV) remains challenging and this impairs patient management and the conduct of clinical studies. Previous proposals for outcome tools have not included imaging. This study aimed to develop an imaging score to quantify damage in LVV and to assess the difference between Takayasu (TAK) and giant cell arteritis (GCA). METHODS: Ninety-six patients (41 TAK, 55 GCA) were identified from local registries at two University Hospitals in the UK. Radiologic lesions including stenosis, occlusion and aneurysm were evaluated in 25 arterial regions by enhanced computed tomography or magnetic resonance angiography. Lesion correlation with combined damage assessment scores was employed in a multiple regression analysis to define the weight of individual lesions and develop a damage index. RESULTS: A numerical damage index was developed: the “Combined Arteritis Damage Score (CARDS)”. The index was derived from a formula: number of regions with mild stenosis × 0.6 + number of regions with moderate to severe stenosis × 1.2 + number with occlusions × 1.6 + number with aneurysms × 0.8 in 25 arterial regions. The median CARDS was higher in TAK than GCA (4.1 and 0.6, interquartile range 1.3-5.7 and 0-3, p<0.001). CONCLUSIONS: We have developed a damage assessment tool, CARDS, based on imaging in LVV of potential value to clinical studies and patient management. TAK and GCA differ in the radiologic severity of disease.Dr. Daiki Nakagomi is supported by the Japan College of Rheumatology and Shimoshizu Hospital, National Hospital Organization. This project was supported by the Cambridge Biomedical Research Centre

The prognostic significance of transforming growth factors in human breast cancer.

Transforming growth factor alpha (TGF alpha) and Transforming growth factor beta-1 (TGF-beta 1) are growth regulatory for breast cancer cell lines in vitro and several studies have suggested that levels of the receptor for TGF alpha, the epidermal growth factor (EGFR) in tumour biopsies predict relapse and survival. We have examined the prognostic significance of TGF alpha, TGF-beta 1 and EGFR mRNA expression in a series of patients with primary breast cancer with a median follow up period of 60 months. In 167 patients the expression of TGF-beta 1 was inversely correlated with node status (P = 0.065) but not ER status, tumour size or menopausal status. Patients with high levels of TGF-beta 1 had a longer disease free interval with a significantly longer probability of survival at 80 months although the overall relapse free survival was not increased. EGFR mRNA expression was measured in 106 patients and was inversely correlated with ER status (P = 0.018). EGFR levels did not predict for early relapse or survival. TGF alpha mRNA levels were measured in 104 patients, no correlation was seen tumour size, node status, Er status, or clinical outcome