Expression of Cathepsin D in early-stage breast cancer and its prognostic and predictive value.

PURPOSE: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. There are conflicting results regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. This study aimed to evaluate the expression and prognostic significance of Cathepsin D in early-stage breast cancer. METHODS: Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n = 954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of Cathepsin D expression with clinicopathological parameters and prognosis was evaluated. RESULTS: Cathepsin D expression was positive in 71.2% (679/954) of breast cancer tumours. Positive expression of Cathepsin D was significantly associated with high histological grade (p = 0.007), pleomorphism (p = 0.002), poor Nottingham Prognostic Index (NPI) score (p < 0.002), recurrence (p = 0.005) and distant metastasis (p < 0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer-specific survival (p = 0.001), higher risk of recurrence (p = 0.001) and distant metastasis (p < 0.0001). ER-positive tumours expressing Cathepsin D and treated with tamoxifen demonstrated a significantly higher risk of distant metastasis. CONCLUSION: Cathepsin D expression significantly predicts poor prognosis in breast cancer and is associated with variables of poor prognosis and shorter outcome. The strong association of Cathepsin D with aggressive tumour characteristics and poor outcomes warrants further research of its potential as a therapeutic target The results also suggest a possible interaction between Cathepsin D and tamoxifen therapy in ER-positive breast cancer which needs further investigation to elucidate the underlying mechanisms.

Examining the effectiveness of the Gateway conditional caution on health and well-being of young adults committing low-level offences: a randomised controlled trial.

BACKGROUND: Young adults who commit low-level offences commonly have a range of health and social needs and are significantly over-represented in the criminal justice system. These young adults may need to attend court and potentially receive penalties including imprisonment. Alternative routes exist, which can help address the underlying causes of offending. Some feel more should be done to help young adults entering the criminal justice system. The Gateway programme was a type of out-of-court disposal developed by Hampshire Constabulary, which aimed to address the complex needs of young adults who commit low-level crimes. This study aimed to evaluate the effectiveness and cost-effectiveness of the Gateway programme, issued as a conditional caution, compared with usual process. METHODS: The Gateway study was a pragmatic, parallel-group, superiority randomised controlled trial that recruited young adults who had committed a low-level offence from four sites covering Hampshire and Isle of Wight. The primary outcome was mental health and well-being measured using the Warwick-Edinburgh Mental Well-being Scale. Secondary outcomes were quality of life, alcohol and drug use, and recidivism. Outcomes were measured at 4, 16 and 52 weeks postrandomisation. RESULTS: Due to issues with retention of participants and low data collection rates, recruitment ended early, with 191 eligible participants randomised (Gateway 109; usual process 82). The primary outcome was obtained for 93 (48.7%) participants at 4 weeks, 93 (48.7%) at 16 weeks and 43 (22.5%) at 1 year. The high attrition rates meant that effectiveness could not be assessed as planned. CONCLUSIONS: Gateway is the first trial in a UK police setting to have a health-related primary outcome requiring individual data collection, rather than focusing solely on recidivism. We demonstrated that it is possible to recruit and randomise from the study population, however follow-up rates were low. Further work is needed to identify ways to facilitate engagement between researchers and vulnerable populations to collect data. TRIAL REGISTRATION NUMBER: ISRCTN11888938.

Sociodemographic variations in the uptake of faecal immunochemical tests in primary care: a retrospective study.

BACKGROUND: Faecal immunochemical test (FIT) usage for symptomatic patients is increasing, but variations in use caused by sociodemographic factors are unknown. A clinical pathway for colorectal cancer (CRC) was introduced in primary care for symptomatic patients in November 2017. The pathway was commissioned to provide GPs with direct access to FITs. AIM: To identify whether sociodemographic factors affect FIT return in symptomatic patients. DESIGN AND SETTING: A retrospective study was undertaken in Nottingham, UK, following the introduction of FIT as triage tool in primary care. It was mandated for all colorectal referrals (except rectal bleeding or mass) to secondary care. FIT was used, alongside full blood count and ferritin, to stratify CRC risk. METHOD: All referrals from November 2017 to December 2021 were retrospectively reviewed. Sociodemographic factors affecting FIT return were analysed by multivariate logistic regression. RESULTS: A total of 35 289 (90.7%) patients returned their index FIT, while 3631 (9.3%) did not. On multivariate analysis, males were less likely to return an FIT (odds ratio [OR] 1.11, 95% confidence interval [CI] = 1.03 to 1.19). Patients aged ≥65 years were more likely to return an FIT (OR 0.78 for non-return, 95% CI = 0.72 to 0.83). Unreturned FIT more than doubled in the most compared with the least deprived quintile (OR 2.20, 95% CI = 1.99 to 2.43). Patients from Asian (OR 1.82, 95% CI = 1.58 to 2.10), Black (OR 1.21, 95% CI = 0.98 to 1.49), and mixed or other ethnic groups (OR 1.29, 95% CI = 1.05 to 1.59) were more likely to not return an FIT compared with patients from a White ethnic group. A total of 599 (1.5%) CRCs were detected; 561 in those who returned a first FIT request. CONCLUSION: FIT return in those suspected of having CRC varied by sex, age, ethnic group, and socioeconomic deprivation. Strategies to mitigate effects on FIT return and CRC detection should be considered as FIT usage expands.

Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in England.

BACKGROUND: A faecal immunochemical tests (FIT) cut-off of ≥10 µg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%. AIMS: To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata. METHODS: A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017-2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates. RESULTS: In total, 514 (1.5%) CRCs were diagnosed following 33,694 index FIT requests. Individuals with a FIT ≥ 10 µg Hb/g faeces had a >3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% [95% CI: 0.03%-2.86%]). Non-anaemic patients with a FIT < 100 µg Hb/g faeces had a CRC risk of <3%, except those between the age of 70 and 85 years (5.26% 95% CI: 2.72%-7.73%). Using a ≥3% CRC threshold in patients <55 years calculated using FIT, age and anaemia might allow 160-220 colonoscopies per 10,000 FITs to be re-purposed, at a cost of missing 1-2 CRCs. CONCLUSIONS: FIT alone with a single cut-off is unlikely to be a panacea for optimising CRC diagnosis, as risk varies by FIT, age and anaemia when faecal haemoglobin levels are below 100 µg Hb/g. Tailored FIT cut-offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.

Faecal immunochemical testing reduces demand and improves yield of Leicester's 2-week pathway for change in bowel habit.

AIM: We look at the effect of introducing the faecal immunochemical test (FIT) in the straight-to-test 2-week pathway for change in bowel habit (CIBH). METHOD: The FIT in primary care triages 2-week wait (2WW) colorectal referrals for patients aged 60 years and above for straight-to-test CT colonography (CTC). We compare the impact of the FIT on numbers of 2WW CTCs, in the year before and after FIT, in both colorectal cancer (CRC) detection and cost-effectiveness at both 4 µg Hb/g faeces and 10 µg Hb/g faeces. RESULTS: At a threshold of 4 µg Hb/g faeces, the positive predictive value of the FIT for diagnosis of CRC is 5.0% with a negative predictive value of 99.8% and a polyp detection rate of 25.5%. The introduction of the FIT resulted in a reduction in the number of CTCs performed through the CIBH pathway from a mean of 143.9 per month prior to the FIT to 66.8 CTCs per month once the FIT was well established. Given a FIT threshold of 10 µg Hb/g the number of CTCs would be predicted to fall by 70.4% to 42.6 CTCs per month resulting in higher CRC and polyp detection rate, and an estimated annual cost saving of £238 258 in our institution. CONCLUSION: The FIT use in primary care improves the yield of 2WW referrals for CIBH alone and reduces the burden and cost of investigations to exclude CRC. Improvements may be possible by increasing the cut-off employed, without adversely affecting the risk of missing a cancer.

Including a general practice endorsement letter with the testing kit in the Bowel Cancer Screening Programme: Results of a cluster randomised trial.

OBJECTIVES: To evaluate the effect of general practitioner endorsement accompanying the screening kit rather than with the invitation letter on participation in the NHS Bowel Cancer Screening Programme and on the socioeconomic gradient in participation in the Programme. METHODS: The NHS Bowel Cancer Screening Programme in England is delivered via five regional hubs. In early 2016, we carried out a cluster-randomised trial, with hub-day of invitation as the randomisation unit. We randomised 150 hub-days of invitation to the intervention group, GP endorsement on the letter accompanying the guaiac faecal occult blood testing kit (75 hub-days, 197,366 individuals) or control, usual letter (75 hub-days, 197,476 individuals). The endpoint was participation, defined as return of a valid kit within 18 weeks of initial invitation. Because of the cluster randomisation, data were analysed by a hierarchical logistic regression, allowing a random effect for date of invitation. Socioeconomic status was represented by the index of multiple deprivation. RESULTS: Participation was 59.4% in the intervention group and 58.7% in the control group, a significant difference (p = 0.04). There was no heterogeneity of the effect of intervention by index of multiple deprivation. We found that there was some confounding between date and screening episode order (first or subsequent screen). This in turn may have induced confounding with age and slightly diluted the result. CONCLUSIONS: General practitioner endorsement induces a modest increase in participation in bowel cancer screening, but does not affect the socioeconomic gradient. When considering cluster randomisation as a research method, careful scrutiny of potential confounding is indicated in advance if possible and in analysis otherwise.

Choice of faecal immunochemical test matters: comparison of OC-Sensor and HM-JACKarc, in the assessment of patients at high risk of colorectal cancer.

OBJECTIVES: Currently, NICE recommends the use of faecal immunochemical test (FIT) at faecal haemoglobin concentrations (f-Hb) of 10 µg Hb/g faeces to stratify for colorectal cancer (CRC) risk in symptomatic populations. This f-Hb cut-off is advised across all analysers, despite the fact that a direct comparison of analyser performance, in a clinical setting, has not been performed. METHODS: Two specimen collection devices (OC-Sensor, OC-S; HM-JACKarc, HM-J) were sent to 914 consecutive individuals referred for follow up due to their increased risk of CRC. Agreement of f-Hb around cut-offs of 4, 10 and 150 µg Hb/g faeces and CRC detection rates were assessed. Two OC-S devices were sent to a further 114 individuals, for within test comparisons. RESULTS: A total of 732 (80.1%) individuals correctly completed and returned two different FIT devices, with 38 (5.2%) CRCs detected. Median f-Hb for individuals diagnosed with and without CRC were 258.5 and 1.8 µg Hb/g faeces for OC-S and 318.1 and 1.0 µg Hb/g faeces for HM-J respectively. Correlation of f-Hb results between OC-S/HM-J over the full range was rho=0.74, p<0.001. Using a f-Hb of 4 µg Hb/g faeces for both tests found an agreement of 88.1%, at 10 µg Hb/g faeces 91.7% and at 150 µg Hb/g faeces 96.3%. A total of 114 individuals completed and returned two OC-S devices; correlation across the full range was rho=0.98, p<0.001. CONCLUSIONS: We found large variations in f-Hb when different FIT devices were used, but a smaller variation when the same FIT device was used. Our data suggest that analyser-specific f-Hb cut-offs are applied with regard to clinical decision making, especially at lower f-Hb.

Tumor-associated autoantibodies in combination with alpha-fetoprotein for detection of early stage hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) continues to be a leading challenge in modern oncology. Early detection via blood-based screening tests has the potential to cause a stage-shift at diagnosis and improve clinical outcomes. Tumor associated autoantibodies (TA-AAbs) have previously shown the ability to distinguish HCC from patients with high-risk liver disease. This research aimed to further show the utility of TA-AAbs as biomarkers of HCC and assess their use in combination with Alpha-fetoprotein (AFP) for detection of HCC across multiple tumor stages. METHODS: Levels of circulating G class antibodies to 44 recombinant tumor associated antigens and circulating AFP were measured in the serum of patients with HCC, non-cancerous chronic liver disease (NCCLD) and healthy controls via enzyme-linked immunosorbent assay (ELISA). TA-AAb cut-offs were set at the highest Youden's J statistic at a specificity ≥95.00%. Panels of TA-AAbs were formed using net reclassification improvement. AFP was assessed at a cut-off of 200 ng/ml. RESULTS: Sensitivities ranged from 1.01% to 12.24% at specificities of 95.96% to 100.00% for single TA-AAbs. An ELISA test measuring a panel of 10 of these TA-AAbs achieved a combined sensitivity of 36.73% at a specificity of 89.89% when distinguishing HCC from NCCLD controls. At a cut-off of 200 ng/ml, AFP achieved a sensitivity of 31.63% at a specificity of 100.00% in the same cohort. Combination of the TA-AAb panel with AFP significantly increased the sensitivity for stage one (40.00%) and two (55.00%) HCC over the TA-AAb panel or AFP alone. CONCLUSIONS: A panel of TA-AAbs in combination with AFP could be clinically relevant as a replacement for measuring levels of AFP alone in surveillance and diagnosis strategies. The increased early stage sensitivity could lead to a stage shift with positive prognostic outcomes.

Neuronal antibody detection and improved lung cancer prediction in Lambert-Eaton myasthenic syndrome.

Since approximately 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS) subsequently develop small-cell lung cancer (SCLC), it is important to be able to predict cancer occurrence in these patients at neurological presentation. We aimed to determine whether circulating biomarkers were effective and objective predictors of cancer development in LEMS. We found that the presence of either SOX2, N-type voltage gated calcium channel or GABAb antibodies at LEMS diagnosis was highly sensitive (84%) and specific (87%) for the detection of SCLC. Screening for SOX2 and neuronal antibodies is a useful adjunct to clinical predictive scoring tools in predicting SCLC in LEMS.

The utility of anti-SOX2 antibodies for cancer prediction in patients with paraneoplastic neurological disorders.

Antibodies to SOXB1 proteins in patients with paraneoplastic disorders are associated with small-cell lung cancer (SCLC), particularly in Lambert-Eaton myasthenic syndrome (LEMS). We aimed to establish if SOX2 antibodies could be used to identify SCLC and other tumours found in a range of paraneoplastic disorders and controls. SOX2 antibodies were detectable in 61% of patients with LEMS-SCLC, and in other paraneoplastic disorders, such as opsoclonus-myoclonus and paraneoplastic cerebellar degeneration, only when there was an underlying SCLC. SOX2 antibodies are specific (>90%) markers for SCLC, but are rarely found in patients with other tumours, whether neurological symptoms are present or not.

GLP-1 suppresses glucagon secretion in human pancreatic alpha-cells by inhibition of P/Q-type Ca2+ channels.

Glucagon is the body's main hyperglycemic hormone, and its secretion is dysregulated in type 2 diabetes mellitus (T2DM). The incretin hormone glucagon-like peptide-1 (GLP-1) is released from the gut and is used in T2DM therapy. Uniquely, it both stimulates insulin and inhibits glucagon secretion and thereby lowers plasma glucose levels. In this study, we have investigated the action of GLP-1 on glucagon release from human pancreatic islets. Immunocytochemistry revealed that only <0.5% of the α-cells possess detectable GLP-1R immunoreactivity. Despite this, GLP-1 inhibited glucagon secretion by 50-70%. This was due to a direct effect on α-cells, rather than paracrine signaling, because the inhibition was not reversed by the insulin receptor antagonist S961 or the somatostatin receptor-2 antagonist CYN154806. The inhibitory effect of GLP-1 on glucagon secretion was prevented by the PKA-inhibitor Rp-cAMPS and mimicked by the adenylate cyclase activator forskolin. Electrophysiological measurements revealed that GLP-1 decreased action potential height and depolarized interspike membrane potential. Mathematical modeling suggests both effects could result from inhibition of P/Q-type Ca2+ channels. In agreement with this, GLP-1 and ω-agatoxin (a blocker of P/Q-type channels) inhibited glucagon secretion in islets depolarized by 70 mmol/L [K+ ]o , and these effects were not additive. Intracellular application of cAMP inhibited depolarization-evoked exocytosis in individual α-cells by a PKA-dependent (Rp-cAMPS-sensitive) mechanism. We propose that inhibition of glucagon secretion by GLP-1 involves activation of the few GLP-1 receptors present in the α-cell membrane. The resulting small elevation of cAMP leads to PKA-dependent inhibition of P/Q-type Ca2+ channels and suppression of glucagon exocytosis.

Adrenaline Stimulates Glucagon Secretion by Tpc2-Dependent Ca2+ Mobilization From Acidic Stores in Pancreatic α-Cells.

Adrenaline is a powerful stimulus of glucagon secretion. It acts by activation of ß-adrenergic receptors, but the downstream mechanisms have only been partially elucidated. Here, we have examined the effects of adrenaline in mouse and human α-cells by a combination of electrophysiology, imaging of Ca2+ and PKA activity, and hormone release measurements. We found that stimulation of glucagon secretion correlated with a PKA- and EPAC2-dependent (inhibited by PKI and ESI-05, respectively) elevation of [Ca2+]i in α-cells, which occurred without stimulation of electrical activity and persisted in the absence of extracellular Ca2+ but was sensitive to ryanodine, bafilomycin, and thapsigargin. Adrenaline also increased [Ca2+]i in α-cells in human islets. Genetic or pharmacological inhibition of the Tpc2 channel (that mediates Ca2+ release from acidic intracellular stores) abolished the stimulatory effect of adrenaline on glucagon secretion and reduced the elevation of [Ca2+]i Furthermore, in Tpc2-deficient islets, ryanodine exerted no additive inhibitory effect. These data suggest that ß-adrenergic stimulation of glucagon secretion is controlled by a hierarchy of [Ca2+]i signaling in the α-cell that is initiated by cAMP-induced Tpc2-dependent Ca2+ release from the acidic stores and further amplified by Ca2+-induced Ca2+ release from the sarco/endoplasmic reticulum.

Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy.

Breast carcinoma is a major health issue for millions of women. Current therapies have serious side effects, and are only partially effective in patients with metastatic tumors. Thus, the need for novel and less toxic therapies is urgent. Moreover, hormonal and antibody therapies effective in other subtypes are not effective in Triple Negative Breast Cancer (TNBC). Immunotherapeutic strategies directed against specific tumor-associated antigens (TAAs) and mediated by specific cytotoxic T lymphocytes (CTL) have been largely underexplored in this disease. Cancer-testis antigens (CTA) are a group of TAAs displaying the ideal characteristics of promising vaccine targets, i.e. strong immunogenicity and cancer specificity. The CTA, Sperm Protein 17 (SP17), has been found to be aberrantly expressed in different neoplasms, including ovarian and esophageal cancers, nervous system tumors and multiple myeloma, and has been suggested as a candidate target for immunotherapy. Here, we evaluated SP17 expression levels in breast cancer cell lines, invasive ductal breast carcinoma, including patients with TNBC, and adjacent non-neoplastic breast tissue, and determined whether SP17 was capable of generating SP17-specific cytotoxic T lymphocytes in vitro. We showed that SP17 is expressed in breast cancer cell lines and primary breast tumors and importantly in TNBC subtype, but not in adjacent non-tumoral breast tissue or unaffected tissues, except in male germinal cells. Furthermore, we detected specific anti-SP17 antibodies in patients' sera and we generated SP17-specific, HLA class I-restricted, cytotoxic T lymphocytes capable of efficiently killing breast cancer cells.

Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome.

OBJECTIVE: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). AIM: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. DESIGN AND METHODS: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. RESULTS: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P < .0001). CONCLUSIONS: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.

Autoantibodies: Opportunities for Early Cancer Detection.

Cancer cells can induce an immunological response resulting in the production of tumor-associated (TA) autoantibodies. These serum immunobiomarkers have been detected for a range of cancers at an early stage before the development of clinical symptoms. Their measurement is minimally invasive and cost effective using established technologies. TA autoantibodies are present in a clinically significant number of individuals and could supplement current screening modalities to aid early diagnosis of high-risk populations and assist the clinical management of patients. Here we review their production, discovery, and validation as biomarkers for cancer and their current and future potential as clinical tools.

Prognostic significance of tumour infiltrating B lymphocytes in breast ductal carcinoma in situ.

AIMS: Tumour-infiltrating lymphocytes (TILs) are an important component of the immune response to cancer and have a prognostic value in breast cancer. Although several studies have investigated the role of T lymphocytes in breast cancer, the role of B lymphocytes (TIL-Bs) in ductal carcinoma in situ (DCIS) remains uncertain. This study aimed to assess the role of TIL-Bs in DCIS. METHODS AND RESULTS: Eighty DCIS cases (36 pure DCIS and 44 mixed with invasive cancer) were stained immunohistochemically for B lineage markers CD19, CD20 and the plasma cell marker CD138. TIL-Bs density and localization were assessed, including relation to the in-situ and invasive components. An association with clinicopathological data and patient outcome was performed. Pure DCIS showed a higher number of TIL-Bs and lymphoid aggregates than DCIS associated with invasion. In pure DCIS, a higher number of peri- and paratumoral TIL-Bs was associated significantly with large tumour size (P = 0.016), hormone receptor (ER/PR) negative (P = 0.008) and HER2+ status (P = 0.010). In tumours with mixed DCIS and invasive components, cases with high-density B lymphocytes, irrespective of their location or topographic distribution, were associated significantly with variables of poor prognosis, including larger size, high grade, lymphovascular invasion, lymph node metastases, ER/PR-negative and HER2+ status. Outcome analysis showed that pure DCIS associated with higher numbers of B lymphocytes had shorter recurrence-free interval (P = 0.04); however, the association was not significant with the CD138+ plasma cell count (P = 0.07). CONCLUSION: Assessment of TIL-B cells based on location and topographic distribution can provide prognostic information. Validation in a larger cohort is warranted.

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 have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia 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 expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. MATERIAL AND METHODS: A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer 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 polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. RESULTS: The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m2 ) and controls (28.58 ± 2.62 kg/m2 ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m2 ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p < 0.0001). Sterol regulatory element binding protein-1 gene expression was positively correlated with body mass index (r = 0.017, p = 0.921) and waist-hip ratio (r = 0.023, p = 0.544) in polycystic ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r = 0.643, p = 0.06) and waist-hip ratio (r = 0.096, p = 0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p = 0.028 and p = 0.027, respectively). Quantitative serum sterol regulatory element binding protein-1 gene correlated with endometrial gene expression (p < 0.05). CONCLUSIONS: Sterol regulatory element binding protein-1 gene expression is significantly increased in the endometrium of women with polycystic ovary syndrome and women with endometrial cancer compared with controls and positively correlates with serum triglyceride in both polycystic ovary syndrome and endometrial cancer.

Making hospitals safer at night.

In the middle of the night, when the rest of the country is asleep, ward nurses up and down the UK are calling the Hospital at Night service. They may be looking for a technician to take a blood sample, or calling for medical help as a patient suddenly deteriorates.