Association of the I1307K APC mutation with hereditary and sporadic breast/ovarian cancer: more questions than answers

The frequency of the APC I1307K mutation and its association with disease pattern was examined in 996 Ashkenazi women consisting of individuals with either sporadic (n = 382) or hereditary (n = 143) breast and/or ovarian cancer; asymptomatic BRCA1/2 mutation carriers (185delAG, 5382insC and 6174delT) (n = 53) and healthy controls (n = 418). The I1307K allele was equally distributed among women with sporadic (17/382; 4.6%) and inherited (10/143; 7%) breast and/or ovarian cancer irrespective of their being diagnosed before or after 42 years of age and among asymptomatic (7/53; 13.2%) and cancer manifesting BRCA1/2 carriers (10/143; 7%). Taken together, the prevalence of the I1307K allele was significantly higher in BRCA1/2 carriers compared to non-BRCA1/2 carriers (17/196; 8.7% and 40/800, 5%; respectively). The high prevalence of the I1307K allele among BRCA1/2 carriers is not associated with increased cancer risk but seems to be genetically connected because of Jewish ancestry. © 2000 Cancer Research Campaig

Basic and clinical significance of IGF-I-induced signatures in cancer

The insulin-like growth factor (IGF) system mediates growth, differentiation and developmental processes; it is also involved in various metabolic activities. Deregulation of IGF system expression and action is linked to diverse pathologies, ranging from growth deficits to cancer development. Targeting of the IGF axis emerged in recent years as a promising therapeutic approach in cancer and other medical conditions. Rational use of IGF-I-induced gene signatures may help to identify patients who might benefit from IGF axis-directed therapeutic modalities. In the accompanying research article in BMC Medicine, Rajski et al. show that IGF-I-induced gene expression in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients

Heatstroke – providing evidence-based advice to dog owners

With increasing summer temperatures and milder winters, the risk of heatstroke in dogs is growing. Veterinary nurses have a vital role in identifying high risk patients and advising owners of the risks of heatstroke. Nurses are able to recommend preventative measures and first aid necessary to minimise the risk of heatstroke; in addition to increasing the chances of survival where heatstroke does occur. This article will provide an overview of the evidence that can be presented to owners during nursing consultations, and the prognosis of patients presenting with heatstroke

Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer

Introduction: Women with polycystic ovary syndrome (PCOS) have a 3-fold higher risk of endometrial cancer (EC). Insulin resistance and hyperlipidaemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial Sterol Regulatory Element Binding Protein-1 gene (SREBP1) expression in PCOS and EC endometrium, and to correlate endometrial SREBP1 expression with serum lipid profiles. Material and methods: A cross-sectional study was performed at Nottingham University Hospital, United Kingdom. A total of 102 women (PCOS, EC and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time PCR for endometrial SREBP1 and its systemic protein expression were analysed. Results: The BMI of women with PCOS (29.28 (±2.91) kg/m2) and controls (28.58 (±2.62) kg/m2) was not significantly different. Women with EC had a higher mean BMI (32.22 (±5.70) kg/m2). SREBP1 gene expression was significantly increased in PCOS and EC endometrium compared to controls (p<0.0001). SREBP1 gene expression was positively correlated with BMI (r=0.017, p=0.921) and waist-hip ratio (r=0.023, p=0.544) in PCOS, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial SREBP1 gene expression and BMI in EC (r=0.643, p=0.06) and waist-hip ratio (r=0.096, p=0.073). SREBP1 expression was significantly positively correlated with triglyceride in both PCOS and EC (p= 0.028 and p=0.027). Quantitative serum SREBP1 correlated with endometrial gene expression (p<0.05). Conclusions: SREBP1 gene expression is significantly increased in the endometrium of PCOS and EC women compared with controls and positively correlates with serum triglyceride in both PCOS and EC

ZYG11A Is Expressed in Epithelial Ovarian Cancer and Correlates With Low Grade Disease

The insulin-like growth factors (IGF) are important players in the development of gynecological malignancies, including epithelial ovarian cancer (EOC). The identification of biomarkers that can help in the diagnosis and scoring of EOC patients is of fundamental importance in clinical oncology. We have recently identified the ZYG11A gene as a new candidate target of IGF1 action. The aim of the present study was to evaluate the expression of ZYG11A in EOC patients and to correlate its pattern of expression with histological grade and pathological stage. Furthermore, and in view of previous analyses showing an interplay between ZYG11A, p53 and the IGF1 receptor (IGF1R), we assessed a potential coordinated expression of these proteins in EOC. In addition, zyg11a expression was assessed in ovaries and uteri of growth hormone receptor (GHR) knock-out mice. Tissue microarray analysis was conducted on 36 patients with EOC and expression of ZYG11A, IGF1R and p53 was assessed by immunohistochemistry. Expression levels were correlated with clinical parameters. qPCR was employed to assess zyg11a mRNA levels in mice tissues. Our analyses provide evidence of reduced ZYG11A expression in high grade tumors, consistent with a putative tumor suppressor role. In addition, an inverse correlation between ZYG11A and p53 levels in individual tumors was noticed. Taken together, our data justify further exploration of the role of ZYG11A as a novel biomarker in EOC

Prognostic nomogram for progression-free survival in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer on maintenance olaparib therapy following response to chemotherapy

Background: The impact of maintenance therapy with PARP inhibitors (PARPi) on progression-free survival (PFS) in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer (PSROC) varies widely. Individual prognostic factors do not reliably distinguish patients who progress early from those who have durable benefit. We developed and validated a prognostic nomogram to predict PFS in these patients. / Methods: The nomogram was developed using data from a training patient cohort with BRCA mutations and high-grade serous PSROC on the placebo arm of two maintenance therapy trials, Study 19 and SOLO2/ENGOT-ov21. We performed multivariable Cox regression analysis based on pre-treatment characteristics to develop a nomogram that predicts PFS. We assessed the discrimination and validation of the nomogram in independent validation patient cohorts treated with maintenance olaparib. / Results: The nomogram includes four PFS predictors: CA-125 at randomisation, platinum-free interval, presence of measurable disease and number of prior lines of platinum therapy. In the training (placebo) cohort (internal validation C-index 0.64), median PFS in the model-predicted good, intermediate and poor-risk groups was: 7.7 (95% CI 5.3–11.3), 5.4 (4.8–5.8) and 2.9 (2.8–4.4) months, respectively. In the validation (olaparib) cohort (C-index 0.71), median PFS in the model-predicted good, intermediate and poor-risk groups was: not reached, 16.6 (13.1–22.4) and 8.3 (7.1–10.8) months, respectively. The nomogram showed good calibration in the validation cohort (calibration plot). / Conclusions: This nomogram can be used to predict PFS and counsel patients with BRCA mutations and PSROC prior to maintenance olaparib and for stratification of patients in trials of maintenance therapies

Feasibility and Safety of Extensive Upper Abdominal Surgery in Elderly Patients with Advanced Epithelial Ovarian Cancer

We performed a retrospective study to evaluate the feasibility and safety of extensive upper abdominal surgery (EUAS) in elderly (≥65 yr) patients with advanced ovarian cancer. Records of patients with advanced epithelial ovarian cancer who received surgery at our institution between January 2001 and June 2005 were reviewed. A total of 137 patients including 32 (20.9%) elderly patients were identified. Co-morbidities were present in 37.5% of the elderly patients. Optimal cytoreduction was feasible in 87.5% of the elderly while 95.2% of young patients were optimally debulked (P=0.237). Among 77 patients who received one or more EUAS procedures, 16 (20.8%) were elderly. Within the cohort, the complication profile was not significantly different between the young and the elderly, except for pleural effusion and pneumothorax (P=0.028). Elderly patients who received 2 or more EUAS procedures, when compared to those 1 or less EUAS procedure, had significantly longer operation times (P=0.009), greater blood loss (P=0.002) and more intraoperative transfusions (P=0.030). EUAS procedures are feasible in elderly patients with good general condition. However, cautious peri-operative care should be given to this group because of their vulnerability to pulmonary complications and multiple EUAS procedures

Validation of mobile phone use recall in the multinational MOBI‐kids study

Potential differential and non‐differential recall error in mobile phone use(MPU) in the multinational MOBI‐Kids case–control study were evaluated.We compared self‐reported MPU with network operator billing record data up to 3 months, 1 year, and 2 years before the interview date from 702subjects aged between 10 and 24 years in eight countries. Spearman rankcorrelations, Kappa coefficients and geometric mean ratios (GMRs) wereused. No material differences in MPU recall estimates between cases andcontrols were observed. The Spearman rank correlation coefficientsbetween self‐reported and recorded MPU in the most recent 3 monthswere 0.57 and 0.59 for call number and for call duration, respectively. Thenumber of calls was on average underestimated by the participants(GMR = 0.69), while the duration of calls was overestimated (GMR = 1.59).Country, years since start of using a mobile phone, age at time of interview,and sex did not appear to influence recall accuracy for either call number orcall duration. A trend in recall error was seen with level of self‐reportedMPU, with underestimation of use at lower levels and overestimation of useat higher levels for both number and duration of calls. Although bothsystematic and random errors in self‐reported MPU among participantswere observed, there was no evidence of differential recall error betweencases and controls. Nonetheless, these sources of exposure measurementerror warrant consideration in interpretation of the MOBI‐Kids case–controlstudy results on the association between children's use of mobile phonesand potential brain cancer risk