Journals
2009 EN
Marcalee Alexander · Kimberly D. Anderson · Fin BieringSørensen
+29 more
Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations.
Journals
2009 EN
Brodie M. Sakakibara · William C. Miller · Steven Orenczuk
+1 more
A systematic review.
Journals
2009 EN
Gerd Gigerenzer · Wolfgang Gaissmaier · Elke KurzMilcke
+2 more
When might a positive HIV test be wrong? Are your chances of surviving cancer better in the U.S. or in England? Learn how to put aside unjustified fears and hopes and how to weigh your real risk of illness—or likelihood of recovery
Journals
2009 EN
Lauren Fischer · Paula Glitman · Norman J. Pastorek
+53 more
The BDJ editorial team would like to thank all the people who help maintain the quality of scientific papers in the BDJ by acting as referees. By November this year, we had received over 700 manuscripts, an unprecedented number. The following list contains the referees who have worked on scientific papers during 2009.
Journals
2009 EN
Xuan Bich Trinh · Wiebren Tjalma · Peter Vermeulen
+7 more
Vascular endothelial growth factor (VEGF)-A inhibitors exhibit unseen high responses and toxicity in recurrent epithelial ovarian cancer suggesting an important role for the VEGF/VEGFR pathway. We studied the correlation of VEGF signalling and AKT/mTOR signalling. Using a tissue microarray of clinical samples (N=86), tumour cell immunohistochemical staining of AKT/mTOR downstream targets, pS6 and p4E-BP1, together with tumour cell staining of VEGF-A and pVEGFR2 were semi-quantified. A correlation was found between the marker for VEGFR2 activation (pVEGFR2) and a downstream target of AKT/mTOR signalling (pS6) (R=0.29; P=0.002). Additional gene expression analysis in an independent cDNA microarray dataset (N=24) showed a negative correlation (R=-0.73, P<0.0001) between the RPS6 and the VEGFR2 gene, which is consistent as the gene expression and phosphorylation of S6 is inversely regulated. An activated tumour cell VEGFR2/AKT/mTOR pathway was associated with increased incidence of ascites (chi(2), P=0.002) and reduced overall survival of cisplatin-taxane-based patients with serous histology (N=32, log-rank test, P=0.04). These data propose that VEGF-A signalling acts on tumour cells as a stimulator of the AKT/mTOR pathway. Although VEGF-A inhibitors are classified as anti-angiogenic drugs, these data suggest that the working mechanism has an important additional modality of targeting the tumour cells directly.
Journals
2009 EN
Richard Trauger · Eva Corey · Damon A. Bell
+5 more
Androst-5-ene-3beta, 17beta-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hormones such as AED, and thus provide a cell line useful for identifying compounds capable of inhibiting AED-stimulated cell growth. We sought to determine whether structurally related steroids could inhibit AED-stimulated LNCaP cell growth in vitro and tumour growth in vivo. We report here the identification of a novel androstane steroid, HE3235 (17alpha-ethynyl-5alpha-androstan-3alpha, 17beta-diol), with significant inhibitory activity for AED-stimulated LNCaP proliferation. This inhibitory activity is accompanied by an increase in the number of apoptotic cells. Animal studies have confirmed the cytoreductive activity of HE3235 on LNCaP tumours. The results suggest that this compound may be of clinical use in castration-resistant prostate cancer.
Journals
2009 EN
Leia M. Smith · Albiesterova · Maureen C. Ryan
+8 more
Sir, The preliminary data presented by Boegl and Prinz reflect CD133 mRNA by RT–PCR rather than protein profiling measurements by IHC as in Smith et al (2008). In our study, we used two independent, commercially available antibodies (AC133 and ab5558) to assess the expression of CD133 in formalin-fixed paraffin-embedded samples of various solid tumours, including gastric cancer. The concordance of the data between these antibodies together with numerous positive and negative controls described in Smith et al (2008) support the notion that the staining detected in gastric cancer and other samples reflected the presence of the CD133 protein as reported. In contrast, Boegl and Prinz reported that they were not successful in establishing specific antibody binding for CD133. Unfortunately, no details were provided as to which antibodies were evaluated, nor the methodology used, including controls. We are therefore not able to provide any concrete insights into the discrepancy with our own work. It is interesting that although Boegl and Prinz suggest that the level of expression is reduced in gastric cancer, there appears to be a significant number of outliers that may suggest significant expression in a subpopulation of tumours. From the data in Smith et al, the highest IHC staining is in a similar percentage of tumours to the outliers from the Boegl and Prinz experiment. Lack of agreement between protein-based and mRNA-based profiling measurements is commonplace in the literature (Chen et al, 2002; Smith et al, 2002; Souchelnytskyi 2002). It appears that CD133 may fall into this category. The RT–PCR approach will potentially miss splice variants and will also not measure changes in protein stability leading to increased levels of protein. In both of these cases, changes in expression can be detected by a protein-based method, such as IHC. In addition, due to heterogeneity of CD133 expression in tumours, RT–PCR can underestimate CD133 expression if no tumour microdissection was applied. Discordance of protein and mRNA is important to note but ultimately protein expression is required for function and determines its potential as a therapeutic target.
Journals
2009 EN
Ilse Van der Auwera · Hilde Elst · Steven Van Laere
+6 more
Circulating tumour cells (CTC) and tumour-related methylated DNA in blood have been separately assessed for their utility as a marker for subclinical metastasis in breast cancer. However, no studies have looked into the relation between the both molecular markers in this type of cancer. In this study, we investigated the correlations between total/methylated DNA and CTC in the blood from metastatic breast cancer patients. We simultaneously obtained whole blood, plasma and serum samples from 80 patients and 20 controls. The CellSearch System was used to enumerate CTC in blood samples. Plasma total DNA levels were determined by a QPCR method. Sera were analysed by methylation-specific QPCR for three markers: adenomatous polyposis coli (APC), ras association domain family protein 1A (RASSF1A) and oestrogen receptor 1 (ESR1). Total DNA levels in patients were significantly increased when compared with controls (P<0.001) and correlated with the number of CTC (r=0.418, P<0.001). Hypermethylation of one or more genes was detected in 42 (53%) serum samples from breast cancer patients and in three (16%) serum samples from controls (P=0.003). APC was hypermethylated in 29%, RASSF1A in 35% and ESR1 in 20% of breast cancer cases. Detection of a methylated gene in serum was associated with the detection of CTC in blood (P=0.03). The detection of large amounts of circulating total/methylated DNA correlated with the presence of CTC in the blood from patients with breast cancer. This can be interpreted in two ways: (a) CTC are a potential source of circulating tumour-specific DNA; (b) high numbers of CTC and circulating methylated DNA are both a phenotypic feature of more aggressive tumour biology.
Journals
2009 EN
Jacek Gronwald · Cezary Cybulski · W Piesiak
+11 more
It is important to have accurate knowledge of the range of cancers associated with various CHEK2 mutations, and of the lifetime risks of cancer associated with each. We wished to establish the relationship between family history, mutation type and cancer risk in families with a CHEK2 mutation. We obtained a blood sample and pedigree information from 2012 unselected women with breast cancer, from 2007 men with prostate cancer and from 1934 patients with colon cancer, from hospitals throughout Poland. Genetic testing was carried out for four founder CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to be 22.3%. After adjusting for mutation type, the risk of breast cancer was much higher among relatives of probands with breast cancer than among relatives of patients with prostate or colon cancer (HR=3.6; 95% CI=2.1-6.2; P=0.0001). Similarly, the risk of prostate cancer was higher among relatives of probands with prostate cancer than among relatives of patients with breast or colon cancer (HR=4.4; 95% CI=2.2-8.7; P=0.0001) and the risk of colon cancer was higher among relatives of probands with colon cancer than among relatives of patients with prostate or breast cancer (HR=4.2; 95% CI=2.4-7.8; P=0.0001). These analyses suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on the family history of cancer.
Journals
2009 EN
P Britton · S W Duffy · R. Sinnatamby
+8 more
The aim of this study was to estimate the number of patients discharged from a symptomatic breast clinic who subsequently develop breast cancer and to determine how many of these cancers had been 'missed' at initial assessment. Over a 3-year period, 7004 patients were discharged with a nonmalignant diagnosis. Twenty-nine patients were subsequently diagnosed with breast cancer over the next 36 months. This equates to a symptomatic 'interval' cancer rate of 4.1 per 1000 women in the 36 months after initial assessment (0.9 per 1000 women within 12 months, 2.6 per 1000 women within 24 months). The lowest sensitivity of initial assessment was seen in patients of 40-49 years of age, and these patients present the greatest imaging and diagnostic challenge. Following multidisciplinary review, a consensus was reached on whether a cancer had been missed or not. No delay occurred in 10 patients (35%) and probably no delay in 7 patients (24%). Possible delay occurred in three patients (10%) and definite delay in diagnosis (i.e., a 'missed' cancer) occurred in only nine patients (31%). The overall diagnostic accuracy of 'triple' assessment is 99.6% and the 'missed' cancer rate is 1.7 per 1000 women discharged.