Alfalfa supplementation timing changes the rumen archaeal and fungal community composition and colonization in pre-weaning lambs.

The establishment of the rumen microbiota plays an important role in the rumen development. However, little is known about the effects of alfalfa supplementation time on rumen microbiota establishment. Here, a total of 42 Hu lambs, seven-day-old, were chosen for the study. After a week of adjustment, six lambs were sacrificed to establish a baseline. The remaining 36 lambs were randomly split into two groups: one receiving alfalfa hay at 14 days (EAF), the other at 42 days (LAF), both groups received milk replacer and starter pellets. Introducing alfalfa at 14 days of age significantly improved total dry matter intake between 28 and 42 days (p = 0.04) and average daily gain from both 14 to 28 days (p = 0.04) and 28 to 42 days (p < 0.01), but this effect disappears from 56 to 70 days (p > 0.05). At 42 days, the abundances of Naganishia, Ascochyta, and Neosetophoma in the EAF group were significantly higher (p < 0.05) than those in the LAF group (17.8% vs. 3.97, 10.89% vs. 1.77, and 1.27% vs. 0.09%, respectively). At 56 days, the abundances of Ascochyta, Wallemia, and Aspergillus in the EAF group were significantly lower (p < 0.05) than in the LAF group (3.53% vs. 16.40, 8.78% vs. 18.89, and 2.14% vs. 4.69%). At 70 days, Aspergillus abundance in the EAF group was significantly higher (p < 0.05) than in the LAF group (2.69% vs. 0.85%). The LEfSe analysis showed that Methanobrevibacter_smithii was the archaeal biomarker at 14 days in both groups. Methanobrevibacter_sp_AbM4 was enriched at 56 days in the LAF group. Compared to the LAF group, the specific fungal biomarkers in the EAF group included Sporobolomyces and Bullera at 14 days, Naganishia, Didymella, Cleistothelebolus, and Alloleptosphaeria at 42 days, Ascochyta, Neoascochyta, and Alfaria at 70 days. Correlation analysis results showed strong patterns of association both within and between archaea and fungi, which were influenced by alfalfa supplementation time. In summary, alfalfa supplementation at 14 days of age promotes the growth performance of lambs before weaning, and alfalfa supplementation timing significantly affects rumen archaeal and fungal communities and dynamical changes.

Hypertension and Risk of Endometrial Cancer: A Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: The incidence rates of endometrial cancer are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for endometrial cancer. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of endometrial cancer remains unclear. In this study, we evaluated hypertension as an independent risk factor for endometrial cancer and whether this association is modified by other established risk factors. METHODS: We included 15,631 endometrial cancer cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate ORs and 95% confidence intervals (CI) to evaluate the association between hypertension and endometrial cancer and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of endometrial cancer (OR, 1.14; 95% CI, 1.09-1.19). There was significant heterogeneity by study design (Phet < 0.01), with a stronger magnitude of association observed among case-control versus cohort studies. Stronger associations were also noted for pre-/perimenopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with endometrial cancer risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for endometrial cancer.

Mismatch repair status and surgical approach in apparent early-stage endometrial cancer.

OBJECTIVE: To test the hypothesis that mismatch repair (MMR) status (as an accurate surrogate marker for microsatellite stability) modifies the effect of surgical approach on oncological outcome for apparent early-stage endometrial cancer. METHODS: Observational data from a large prospective population study on endometrial cancer were analyzed using target trial methodology and doubly robust methods, including propensity score matching and adjusted regression analyses. Laparoscopy was compared with laparotomy, stratified by MMR status on outcomes of recurrence and site, and recurrence-free, overall, and disease-specific survival. RESULTS: After matching, there were 400 patients for analysis, with 200 in each treatment group. The mean age was 62 years and mean body mass index was 32 kg/m2. Most patients had early-stage disease (stage I n=362 (90%)) and endometrioid histology (n=363 (91%)). Adjuvant pelvic radiation was administered to 11%, adjuvant vaginal brachytherapy to 13% and adjuvant chemotherapy to 5% of patients. Five-year recurrence-free survival did not differ significantly between modes of surgery across the cohort (p=0.7) or within MMR strata (MMR-proficient p=0.9, MMR-deficient p=0.6). Similarly, there was no significant difference in overall or disease-specific survival by mode of surgery across the cohort or within MMR strata. There was no significant difference in the HR for recurrence for those treated with laparoscopy stratified by MMR status (MMR-proficient HR=0.99 (95% CI 0.28 to 3.58); MMR-deficient HR=0.83 (95% CI 0.24 to 2.87)), even when restricted to endometrioid subtype. CONCLUSION: In this study, there was no evidence of a difference in survival outcomes according to mode of surgery and MMR status.

Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus.

BACKGROUND AND AIM: People with new-onset diabetes mellitus (diabetes) could be a possible target population for pancreatic cancer surveillance. However, distinguishing diabetes caused by pancreatic cancer from type 2 diabetes remains challenging. We aimed to develop and validate a model to predict pancreatic cancer among women with new-onset diabetes. METHODS: We conducted a retrospective cohort study among Australian women newly diagnosed with diabetes, using first prescription of anti-diabetic medications, sourced from administrative data, as a surrogate for the diagnosis of diabetes. The outcome was a diagnosis of pancreatic cancer within 3 years of diabetes diagnosis. We used prescription medications, severity of diabetes (i.e., change/addition of medication within 2 months after first medication), and age at diabetes diagnosis as potential predictors of pancreatic cancer. RESULTS: Among 99 687 women aged ≥ 50 years with new-onset diabetes, 602 (0.6%) were diagnosed with pancreatic cancer within 3 years. The area under the receiver operating curve for the risk prediction model was 0.73. Age and diabetes severity were the two most influential predictors followed by beta-blockers, acid disorder drugs, and lipid-modifying agents. Using a risk threshold of 50%, sensitivity and specificity were 69% and the positive predictive value (PPV) was 1.3%. CONCLUSIONS: Our model doubled the PPV of pancreatic cancer in women with new-onset diabetes from 0.6% to 1.3%. Age and rapid progression of diabetes were important risk factors, and pancreatic cancer occurred more commonly in women without typical risk factors for type 2 diabetes. This model could prove valuable as an initial screening tool, especially as new biomarkers emerge.

Risk Factors for Ovarian Cancer by BRCA Status: A Collaborative Case-Only Analysis.

BACKGROUND: Women with an inherited pathogenic variant in BRCA1 or BRCA2 have a greatly increased risk of developing ovarian cancer, but the importance of behavioral factors is less clear. We used a case-only design to compare the magnitude of associations with established reproductive, hormonal, and lifestyle risk factors between BRCA mutation carriers and noncarriers. METHODS: We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4,289 noncarriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRR) and 95% confidence intervals (CI), with BRCA (carrier vs. noncarrier) as the response variable. RESULTS: IRRs were above 1.0 for known protective factors including ever being pregnant (IRR = 1.29, 95% CI; 1.00-1.67) and ever using the oral contraceptive pill (1.30, 95% CI; 1.07-1.60), suggesting the protective effects of these factors may be reduced in carriers compared with noncarriers. Conversely, the IRRs for risk factors including endometriosis and menopausal hormone therapy were below 1.0, suggesting weaker positive associations among BRCA carriers. In contrast, associations with lifestyle factors including smoking, physical inactivity, body mass index, and aspirin use did not appear to differ by BRCA status. CONCLUSIONS: Our results suggest that associations with hormonal and reproductive factors are generally weaker for those with a pathogenic BRCA variant than those without, while associations with modifiable lifestyle factors are similar for carriers and noncarriers. IMPACT: Advice to maintain a healthy weight, be physically active, and refrain from smoking will therefore benefit BRCA carriers as well as noncarriers.

Association between unstable diabetes mellitus and risk of pancreatic cancer.

BACKGROUND: Deterioration of glycaemic control in people with long-standing diabetes mellitus (diabetes) may be a possible indicator of pancreatic cancer. However, the magnitude of the association between diabetes deterioration and pancreatic cancer has received little attention. METHODS: We conducted a matched cohort study, nested within a population-based cohort of Australian women with diabetes. Women with unstable diabetes, defined as a change in medication after a 2-year period of stable medication use, were matched by birth year to those with stable diabetes, in a 1:4 ratio. We used flexible parametric survival models to estimate hazard ratios (HRs) and 95% confidence intervals (CI). RESULTS: We included 134,954 and 539,789 women in the unstable and stable diabetes cohorts, respectively (mean age 68 years). In total, 1,315 pancreatic cancers were diagnosed. Deterioration of stable diabetes was associated with a 2.5-fold increased risk of pancreatic cancer (HR 2.55; 95% CI 2.29-2.85). The risk was particularly high within the first year after diabetes deteriorated. HRs at 3 months, 6 months and 1 year were: 5.76 (95% CI 4.72-7.04); 4.56 (95% CI 3.81-5.46); and 3.33 (95% CI 2.86-3.89), respectively. The risk was no longer significantly different after 7 years. CONCLUSIONS: Deterioration in glycaemic control in people with previously stable diabetes may be an indicator of pancreatic cancer, suggesting investigations of the pancreas may be appropriate. The weaker longer-term (3-7 years) association between diabetes deterioration and pancreatic cancer may indicate that poor glycaemic control can be a risk factor for pancreatic cancer.

Vitamin D status during and after treatment and ovarian cancer survival.

PURPOSE: Five-year relative survival for ovarian cancer remains below 50%. Strategies to improve outcomes are needed. Higher serum 25-hydroxyvitamin D [25(OH)D] concentrations [measure of vitamin D status] at and before diagnosis have been associated with longer survival in cancer patients; however, data for ovarian cancer are limited. We aimed to determine if 25(OH)D concentrations during and after primary treatment were associated with ovarian cancer-specific survival. METHODS: We used data from a nationwide prospective cohort study of women with ovarian cancer. Among 886 participants treated with chemotherapy, 700 (79%) had a blood sample collected during (n = 591) and/or after (n = 458) primary treatment. These were tested for 25(OH)D. Clinical and survival data were abstracted from medical records. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between 25(OH)D and ovarian cancer-specific survival. RESULTS: Mean 25(OH)D concentrations were lower during than after primary treatment (82 and 91 nmol/L, respectively); only 14% and 8% had concentrations below 50 nmol/L during and after primary treatment, respectively. There was no association between 25(OH)D and ovarian cancer-specific survival during five years of follow-up [HR 1.10 (95% CI: 0.76, 1.61) and 0.95 (0.54, 1.68) for the highest vs. lowest quintile during and after treatment, respectively]. CONCLUSIONS: We did not observe any association between serum 25(OH)D concentration and ovarian cancer-specific survival. Our results suggest that, in the absence of vitamin D deficiency, vitamin D supplementation to improve ovarian cancer survival is not warranted.

The Colonization of Rumen Microbiota and Intervention in Pre-Weaned Ruminants.

In pre-weaned ruminants, the microbiota colonizes rapidly in the rumen after birth and constantly interacts with the host to sustain health and metabolism. The developing microbial community is more malleable, so its manipulation may improve ruminant health and productivity as well as may have long-term effects on ruminants. Hence, understanding the process of rumen microbiota establishment is helpful for nutritional interventions of rumen microbiota in pre-weaned ruminants. This paper reviews the latest advances in the colonization of rumen microbiota while providing insights into the most suitable time for manipulating rumen microbial colonization in early life. In addition, different factors that affect rumen microbiota establishment during the pre-weaned ruminants are discussed in the current manuscript. The purpose of this review is to aid in the development of guidelines for manipulating rumen microbiota to improve animal productivity and health.

Common analgesics and ovarian cancer survival: the Ovarian cancer Prognosis And Lifestyle (OPAL) Study.

BACKGROUND: Most women with ovarian cancer (OC) are diagnosed with advanced disease. They often experience recurrence after primary treatment, and their subsequent prognosis is poor. Our goal was to evaluate the association between use of nonsteroidal antiinflammatory drugs (NSAIDs), including regular and low-dose aspirin, and 5-year cancer-specific survival after an OC diagnosis. METHODS: The Ovarian cancer Prognosis And Lifestyle study is a prospective population-based cohort of 958 Australian women with OC. Information was gathered through self-completed questionnaires. We classified NSAID use during the year prediagnosis and postdiagnosis as none or occasional (<1 d/wk), infrequent (1-3 d/wk), and frequent (≥4 d/wk) use. We measured survival from the start of primary treatment: surgery or neoadjuvant chemotherapy for analyses of prediagnosis use, or 12 months after starting treatment (postdiagnosis use) until the earliest of date of death from OC (other deaths were censored) or last follow-up to 5 years. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and applied inverse-probability of treatment weighting to minimize confounding. We also calculated restricted mean survival times. RESULTS: Compared with nonusers and infrequent users, we observed better survival associated with frequent NSAID use prediagnosis (HR = 0.73, 95% CI = 0.55 to 0.97) or postdiagnosis (HR = 0.65, 95% CI = 0.45 to 0.94). Estimates were similar for aspirin and nonaspirin NSAIDs, new and continuous users and in weighted models. These differences would translate to a 2.5-month increase in mean survival by 5 years postdiagnosis. There was no association with acetaminophen. CONCLUSIONS: Our findings confirm a previous study suggesting NSAID use might improve OC survival.

The association between diabetes mellitus of different durations and risk of pancreatic cancer: an Australian national data-linkage study in women.

AIMS: The bidirectional association between diabetes mellitus (DM) and pancreatic cancer (PC) is established; however, the strength of association between duration of DM and risk of PC needs further investigation. METHODS: We conducted a case-control study nested within a population-based cohort of Australian women established using record linkage. Women diagnosed with PC from July 2007 to December 2013, were matched to five controls based on age and state of residence. DM was defined according to prescription of anti-diabetic medication from administrative prescription data. We used conditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusted for area-level socioeconomic status, rurality of residence, weighted comorbidity score, and predicted probability of obesity. RESULTS: The analyses included 7,267 cases and 35,978 controls. The mean age at the time of DM diagnosis was 71 years whereas the mean age at the time of diagnosis of PC was 76 years. A history of DM of any duration was associated with a 2-fold increase in risk of PC (OR=2.12; 95%CI:1.96-2.29) compared to having no history of DM. The risk decreased with increasing duration of DM. The highest risk was in those who had recent-onset DM (OR=8.08; 95%CI:6.88-9.50 for <12 months of DM), but the risk remained elevated with ≥5 years of DM (OR=1.40; 95%CI:1.27-1.55). CONCLUSION: The markedly increased risk of PC in those with recent-onset DM emphasises the need for further research to distinguish patients for whom new-onset DM is a manifestation of PC from those with type-2 DM. The elevated risk associated with long-standing DM suggests that preventing DM may contribute to a reduction in the incidence of PC.

Predicting obesity and smoking using medication data: A machine-learning approach.

PURPOSE: Administrative health datasets are widely used in public health research but often lack information about common confounders. We aimed to develop and validate machine learning (ML)-based models using medication data from Australia's Pharmaceutical Benefits Scheme (PBS) database to predict obesity and smoking. METHODS: We used data from the D-Health Trial (N = 18 000) and the QSkin Study (N = 43 794). Smoking history, and height and weight were self-reported at study entry. Linkage to the PBS dataset captured 5 years of medication data after cohort entry. We used age, sex, and medication use, classified using anatomical therapeutic classification codes, as potential predictors of smoking (current or quit <10 years ago; never or quit ≥10 years ago) and obesity (obese; non-obese). We trained gradient-boosted machine learning models using data for the first 80% of participants enrolled; models were validated using the remaining 20%. We assessed model performance overall and by sex and age, and compared models generated using 3 and 5 years of PBS data. RESULTS: Based on the validation dataset using 3 years of PBS data, the area under the receiver operating characteristic curve was 0.70 (95% confidence interval [CI] 0.68-0.71) for predicting obesity and 0.71 (95% CI 0.70-0.72) for predicting smoking. Models performed better in women than in men. Using 5 years of PBS data resulted in marginal improvement. CONCLUSIONS: Medication data in combination with age and sex can be used to predict obesity and smoking. These models may be of value to researchers using data collected for administrative purposes.

Clinical pathways and outcomes of patients with Barrett's esophagus in tertiary care settings: a prospective longitudinal cohort study in Australia, 2008-2016.

BACKGROUND: Clinical services for Barrett's esophagus have been rising worldwide including Australia, but little is known of the long-term outcomes of such patients. Retrospective studies using data at baseline are prone to both selection and misclassification bias. We investigated the clinical characteristics and outcomes of Barrett's esophagus patients in a prospective cohort. METHODS: We recruited patients diagnosed with Barrett's esophagus in tertiary settings across Australia between 2008 and 2016. We compared baseline and follow-up epidemiological and clinical data between Barrett's patients with and without dysplasia. We calculated age-adjusted incidence rates and estimated minimally and fully adjusted hazard ratios (HR) to identify those clinical factors related to disease progression. RESULTS: The cohort comprised 268 patients with Barrett's esophagus (median follow-up 5 years). At recruitment, 224 (84%) had no dysplasia, 44 (16%) had low-grade or indefinite dysplasia (LGD/IND). The age-adjusted incidence of esophageal adenocarcinoma (EAC) was 0.5% per year in LGD/IND compared with 0.1% per year in those with no dysplasia. Risk of progression to high-grade dysplasia/EAC was associated with prior LGD/IND (fully adjusted HR 6.55, 95% confidence interval [CI] 1.96-21.8) but not long-segment disease (HR 1.03, 95%CI 0.29-3.58). CONCLUSIONS: These prospective data suggest presence of dysplasia is a stronger predictor of progression to cancer than segment length in patients with Barrett's esophagus.

Statin use and survival following a diagnosis of ovarian cancer: A prospective observational study.

Most women with ovarian cancer have a poor prognosis, but studies have reported an association between statin use and improved survival. We investigated the potential survival benefit of statins in women with ovarian cancer using data from the Ovarian cancer Prognosis and Lifestyle study, a prospective study of Australian women aged 18 to 79 years, diagnosed with ovarian cancer from 2012 to 2015 and followed for 5 to 8 years. We obtained information from patient-completed questionnaires and medical records. We defined exposure based on prediagnosis use, as most women used statins continuously (prediagnosis and postdiagnosis) and few started using statins postdiagnosis. We measured survival from date of first treatment (surgery or neoadjuvant chemotherapy) until date of death or last follow-up. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for potential confounders. To reduce bias due to confounding by indication, we also applied inverse probability of treatment weighting (IPTW). Of 955 eligible women, 21% reported statin use before diagnosis. Statin users had a slightly better survival (HR = 0.90, 95% CI = 0.70-1.15) that was driven by lipophilic statin use (HR = 0.82, 95% CI = 0.61-1.11), with no association for hydrophilic statins (HR = 1.04, 95% CI = 0.72-1.49). The IPTW model weighted to all women with ovarian cancer also suggested a possible reduction in mortality associated with lipophilic statins (HR = 0.80, 95% CI = 0.54-1.21). In analyses restricted to women with hyperlipidaemia, the HRs were further from the null. Our findings are consistent with previous evidence, suggesting that lipophilic statins might improve ovarian cancer survival. Further investigation, in larger cohorts, or preferably in a randomised trial, is required.

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.

TWIRLS, a knowledge-mining technology, suggests a possible mechanism for the pathological changes in the human host after coronavirus infection via ACE2.

Faced with the current large-scale public health emergency, collecting, sorting, and analyzing biomedical information related to the "SARS-CoV-2" should be done as quickly as possible to gain a global perspective, which is a basic requirement for strengthening epidemic control capacity. However, for human researchers studying viruses and hosts, the vast amount of information available cannot be processed effectively and in a timely manner, particularly if our scientific understanding is also limited, which further lowers the information processing efficiency. We present TWIRLS (Topic-wise inference engine of massive biomedical literatures), a method that can deal with various scientific problems, such as liver cancer, acute myeloid leukemia, and so forth, which can automatically acquire, organize, and classify information. Additionally, this information can be combined with independent functional data sources to build an inference system via a machine-based approach, which can provide relevant knowledge to help human researchers quickly establish subject cognition and to make more effective decisions. Using TWIRLS, we automatically analyzed more than three million words in more than 14,000 literature articles in only 4 hr. We found that an important regulatory factor angiotensin-converting enzyme 2 (ACE2) may be involved in host pathological changes on binding to the coronavirus after infection. On triggering functional changes in ACE2/AT2R, the cytokine homeostasis regulation axis becomes imbalanced via the Renin-Angiotensin System and IP-10, leading to a cytokine storm. Through a preliminary analysis of blood indices of COVID-19 patients with a history of hypertension, we found that non-ARB (Angiotensin II receptor blockers) users had more symptoms of severe illness than ARB users. This suggests ARBs could potentially be used to treat acute lung injury caused by coronavirus infection.

Common medications and survival in women with ovarian cancer: A systematic review and meta-analysis.

OBJECTIVES: Ovarian cancer is usually diagnosed at an advanced stage when five-year relative survival is <50%. Therefore, strategies to improve survival are required. Studies suggest associations between common chronic disease medications such as metformin, statins, beta-blockers, aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) and improved cancer survival. We aimed to review the evidence for a possible relation between these medications and survival among women with ovarian cancer. METHODS: We conducted four systematic reviews and evaluated the risk of bias in the included studies. Where possible, we calculated pooled hazard ratios (pHR) and 95% confidence intervals (CI), excluding studies considered to have the potential for immortal time bias (ITB) which, in practice, was the major source of bias. RESULTS: We identified 36 studies evaluating one or more of the medications (metformin n = 8, statins n = 12, beta-blockers n = 11, aspirin and/or NA-NSAIDs n = 9). We rated 21 studies as ITB-free. The meta-analysis of the ITB-free studies suggested improved survival in statin users compared to non-users (pHR: 0.76, 95%CI: 0.68-0.85), but no overall survival benefit associated with use of metformin, beta-blockers, aspirin or NA-NSAIDs. The pooled result of two studies did, however, suggest a possible association between perioperative beta-blocker use and improved survival. Studies considered to have potential ITB were more likely to report survival benefits associated with these medications. CONCLUSION: Statin use is associated with better ovarian cancer survival but further study, preferably a clinical trial, is required. There are insufficient data to draw conclusions regarding metformin, beta-blockers, aspirin and NA-NSAIDs.

LncRNA WT1-AS up-regulates p53 to inhibit the proliferation of cervical squamous carcinoma cells.

BACKGROUND: It has been reported that the development of cervical squamous cell carcinoma (CSCC) requires the involvement of a large number of lncRNAs. In a recent study lncRNA, WT1-AS was been characterized as a tumor-suppressive lncRNA in gastric cancer. In our study we aim to explore the involvement of WT1-AS in CSCC. METHODS: Seventy-six CSCC patients (20 to 63 years, 40.1 ± 6.1 year) from the 233 CSCC patients who were admitted by the Affiliated Tumour Hospital of Xinjiang Medical University between august 2010 and January 2014. RT-qPCR, cell proliferation rate measurement, cell transfection, and western blot were carried out to analyze the samples. RESULTS: We found that HPV infection failed to affect WT1-AS expression in CSCC tissues, while WT1-AS was down-regulated in CSCC tissues compared with non-cancer tissues. P53 was also down-regulated in CSCC tissues and positively correlated with WT1-AS. Analysis of the survival of CSCC patients revealed that low levels of WT1-AS were accompanied by poor survival. Significantly up-regulated p53 was observed after WT1-AS over-expression in CSCC cells, while p53 over-expression failed to affect WT1-AS. P53 and WT1-AS over-expression resulted in the inhibited proliferation of CSCC cells. CONCLUSION: Therefore, WT1-AS is down-regulated in CSCC and it may inhibit CSCC cell proliferation at least partially by up-regulating p53.

Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal Adenocarcinoma and Surveillance of Barrett's Esophagus.

Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett's esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance of BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker candidate panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and the United States (1 clinic) using previously established lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay. The area under receiver operating characteristic curve (AUROC) was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance. Complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarkers in lectin pull-down samples for EAC across both cohorts. A panel of 10 serum glycoprotein biomarker candidates discriminated BE patients not requiring intervention (BE± low grade dysplasia) from those requiring intervention (BE with high grade dysplasia (BE-HGD) or EAC) with an AUROC value of 0.93. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed toward EAC, levels of serum C9 were significantly (p < 0.05) increased with disease progression in EPHA (erythroagglutinin from Phaseolus vulgaris) and NPL (Narcissus pseudonarcissus lectin) pull-down samples. The results confirm alteration of complement pathway glycoproteins during BE-EAC pathogenesis. Further prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted, prior to development of a first-line BE surveillance blood test.

Breastfeeding and Endometrial Cancer Risk: An Analysis From the Epidemiology of Endometrial Cancer Consortium.

OBJECTIVE: To investigate the association between breastfeeding and endometrial cancer risk using pooled data from 17 studies participating in the Epidemiology of Endometrial Cancer Consortium. METHODS: We conducted a meta-analysis with individual-level data from three cohort and 14 case-control studies. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the association between breastfeeding and risk of endometrial cancer using multivariable logistic regression and pooled using random-effects meta-analysis. We investigated between-study heterogeneity with I  and Q statistics and metaregression. RESULTS: After excluding nulliparous women, the analyses included 8,981 women with endometrial cancer and 17,241 women in a control group. Ever breastfeeding was associated with an 11% reduction in risk of endometrial cancer (pooled OR 0.89, 95% CI 0.81-0.98). Longer average duration of breastfeeding per child was associated with lower risk of endometrial cancer, although there appeared to be some leveling of this effect beyond 6-9 months. The association with ever breastfeeding was not explained by greater parity and did not vary notably by body mass index or histologic subtype (grouped as endometrioid and mucinous compared with serous and clear cell). CONCLUSION: Our findings suggest that reducing endometrial cancer risk can be added to the list of maternal benefits associated with breastfeeding. Ongoing promotion, support, and facilitation of this safe and beneficial behavior might therefore contribute to the prevention of this increasingly common cancer.

Iatrogenic immunosuppression and risk of non-Hodgkin lymphoma in solid organ transplantation: A population-based cohort study in Australia.

Iatrogenic immunosuppression is a strong risk factor for non-Hodgkin lymphoma (NHL) but the dose-related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population-based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984-2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (<1 year after transplantation; n = 29) and late (≥1 year; n = 61) NHL using the Fine and Gray proportional subdistribution hazards model that accounted for death as a competing risk. After adjustment for immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21-4·01] and late NHL (HR 1·78, 95% CI: 1·12-2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk.