https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53345 Wed 22 Nov 2023 10:19:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27946 Wed 22 Mar 2023 16:18:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42701 Wed 22 Mar 2023 15:07:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42676 Wed 22 Mar 2023 14:34:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37272 Wed 16 Sep 2020 14:03:32 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49893 A and I157T. Predictors of survival were determined among CHEK2 pathogenic variant carriers using the Cox proportional hazards model. The median follow-up was 17.5 years. Covariates included age (≤60; >61 years), sex (female; male), clinical characteristics (stage: TNM, grade, histopathological type), smoking status (non-smoking; smoking) and cancer family history (negative; positive). Results: We found no impact of CHEK2 mutations on bladder or kidney cancer survival. However, we observed a possible increased survival in the subgroup of patients with stage T1 bladder cancer with CHEK2 mutations but this did not meet statistical significance (HR = 0.14; 95% CI 0.02–1.04; p = 0.055). Moreover, we observed that the missense mutations were more frequent in the low grade invasive bladder cancer patient group (OR = 7.9; 95% CI 1.50–42.1; p = 0.04) and in patients with bladder cancer with stage Ta (OR = 2.4; 95% CI 1.30–4.55; p = 0.006). The different results where missense mutations occurs less often we observed among patients with high grade invasive bladder cancer (OR = 0.12; 95% CI 0.02–0.66; p = 0.04) and those with stage T1 disease (OR = 0.2; 95% CI 0.07–0.76; p = 0.01). Our investigations revealed that any mutation in CHEK2 occurs more often among patients with stage Ta bladder cancer (OR = 2.0; 95% CI 1.19–3.47; p = 0.01) and less often in patients with stage T1 disease (OR = 0.31; 95% CI 0.12–0.78; p = 0.01). In the kidney cancer patients, truncating mutations were present more often in the group with clear cell carcinoma GII (OR = 8.0; 95% CI 0.95–67.7; p = 0.05). The 10-year survival for all CHEK2 mutation carriers with bladder cancer was 33% and for non-carriers 11% (p = 0.15). The 10-year survival for CHEK2 mutation carriers with kidney cancer 34% and for non-carriers 20% (p = 0.5). Conclusion: CHEK2 mutations were not associated with any change in bladder or kidney cancer survival regardless of their age, sex, smoking status and family history. We observed a potentially protective effect of CHEK2 mutations on survival for patients with stage T1 bladder cancer. CHEK2 missense mutations were more common among patients with low grade invasive bladder cancer and in patients with stage Ta diease. The frequencies of the I157T CHEK2 pathogenic variant were less in patients with high grade invasive bladder cancer and those with stage T1 disease. Among patients with bladder cancer with stage Ta disease, the OR for any mutation in CHEK2 was 2.0 but for those with stage T1 disease, the OR was 0.3. We observed truncating CHEK2 mutations were associated with kidney cancer patients with GII clear cell carcinoma.]]> Wed 14 Jun 2023 17:10:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27356  G variant (rs152451) was significantly enriched in cases and may represent a low-penetrance polymorphism (p = 0.002; OR 1.24 (95 % CI 1.09–1.47). Conclusions: Our findings support truncating variants in PALB2 as high-penetrance breast cancer susceptibility alleles, and suggest that a common missense variant may also lead to a low level of increased breast cancer risk.]]> Wed 11 Apr 2018 17:01:50 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14702 Wed 11 Apr 2018 16:44:59 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:6849 Wed 11 Apr 2018 16:39:01 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27053 Wed 11 Apr 2018 16:37:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13672 Wed 11 Apr 2018 16:23:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20669 Wed 11 Apr 2018 15:57:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14356 Wed 11 Apr 2018 15:41:30 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26763 Wed 11 Apr 2018 15:09:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4382 G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and BRCA1 mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression. Results: A comparison of the genotype frequencies between cases and controls revealed no association of the PHB 3'UTR _CT+TT genotypes with ovarian cancer risk (ORadj 1.34; 95% CI, 0.59–3.11). Conclusion: Our data suggest that the PHB 3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish BRCA1 founder mutations.]]> Wed 11 Apr 2018 14:48:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14811 Wed 11 Apr 2018 14:25:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15650 Wed 11 Apr 2018 13:40:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26643 Wed 11 Apr 2018 13:39:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20527 Wed 11 Apr 2018 13:11:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10390 Wed 11 Apr 2018 12:49:05 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13891 Wed 11 Apr 2018 12:00:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13895 Wed 11 Apr 2018 11:47:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4378 A, causes overexpression and supports uncontrollable cellular growth. This polymorphism has been associated with an increased risk of developing many cancers, including endometrial cancer. Methods: The 870 G>A polymorphisms (rs605965) in the cyclin D1 gene was genotyped in an Australian endometrial cancer case-control population including 191 cases and 291 controls using real-time PCR analysis. Genotype analysis was performed using chi-squared (χ²) statistics and odds ratios were calculated using unconditional logistic regression, adjusting for potential endometrial cancer risk factors. Results: Women homozygous for the variant cyclin D1 870 AA genotype showed a trend for an increased risk of developing endometrial cancer compared to those with the wild-type GG genotype, however this result was not statistically significant (OR 1.692 95% CI (0.939-3.049), p = 0.080). Moreover, the 870 G>A polymorphism was significantly associated with family history of colorectal cancer. Endometrial cancer patients with the homozygous variant AA genotype had a higher frequency of family members with colorectal cancer in comparison to endometrial cancer patients with the GG and combination of GG and GA genotypes (GG versus AA; OR 2.951, 95% CI (1.026-8.491), p = 0.045, and GG+GA versus AA; OR 2.265, 95% CI (1.048-4.894), p = 0.038, respectively). Conclusion: These results suggest that the cyclin D1 870 G>A polymorphism is possibly involved in the development of endometrial cancer. A more complex relationship was observed between this polymorphism and familial colorectal cancer.]]> Wed 11 Apr 2018 10:44:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4380 Wed 11 Apr 2018 10:34:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22707 BRCA₂, has a large number of genetic variants of unknown effect. The variant rs11571833, an A > T transversion in the final exon of the gene that leads to the creation of a stop codon 93 amino acids early (K3326*), is reported as a neutral polymorphism but there is some evidence to suggest an association with an increased risk of breast cancer. We assessed whether this variant was enriched in a cohort of breast cancer cases ascertained through familial cancer clinics compared to population-based non-cancer controls using a targeted sequencing approach. We identified the variant in 66/2634 (2.5%) cases and 33/1996 (1.65%) controls, indicating an enrichment in the breast cancer cases (p = 0.047, OR 1.53, 95% CI 1.00–2.34). This data is consistent with recent iCOGs data suggesting that this variant is not neutral with respect to breast cancer risk. rs11571833 may need to be included in SNP panels for evaluating breast cancer risk.]]> Wed 11 Apr 2018 09:55:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9714 Wed 11 Apr 2018 09:43:06 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15118 Wed 11 Apr 2018 09:18:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15464 Wed 10 Jul 2019 15:19:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23842 Wed 09 Mar 2022 16:01:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32347 Wed 09 Mar 2022 15:59:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29559 G and c.3113G > A, CHEK2 c.349A > G, c.538C > T, c.715G > A, c.1036C > T, c.1312G > T, and c.1343T > G and ATM c.7271T > G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10-5), PALB2 c.3113G > A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10-8) and ATM c.7271T > G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A > G OR 2.26 (95% CI 1.29 to 3.95), c.1036C > T OR 5.06 (95% CI 1.09 to 23.5) and c.538C > T OR 1.33 (95% CI 1.05 to 1.67) (p=0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T > G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G > T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.]]> Wed 09 Feb 2022 15:56:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34524 Wed 06 Apr 2022 13:58:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27793 BRCA1 there has only ever been described two bi-allelic mutation carriers, one of whom was subsequently shown to be a mono-allelic carrier. The second patient diagnosed with two BRCA1 mutations appears to be accurate but there remain some questions about the missense variant identified in that patient. In this report we have identified a woman who is a bi-allelic mutation carrier of BRCA1 and provide an explanation as to why this patient has a phenotype very similar to that of any mono-allelic mutation carrier. The splice variant identified in this patient appears to be associated with the up-regulation of a BRCA1 splice variant that rescues the lethality of being a double mutant. The consequences of the findings of this report may have implications for mutation interpretation and that could serve as a model for not only BRCA1 but also for other autosomal dominant disorders that are considered as being embryonically lethal.]]> Wed 06 Apr 2022 13:57:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34158 MLH1, MSH2, MSH6, and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient’s metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient’s known Lynch syndrome and her thyroid cancer. The thyroid cancer tissue showed normal expression of MSH2, suggesting that the tumor was not due to the oncogenic mutation of Lynch syndrome, and molecular analysis confirmed BRAF V600E mutation. Although in this case the thyroid cancer was sporadic, it raises the importance of considering cancer genetics in familial cancer syndromes when other cancers do not fit the criteria of the syndrome. Careful documentation of other malignancies in patients with thyroid cancer and their families would assist in better understanding of any potential association. Appropriate genetic testing will clarify whether a common pathogenic mechanism links seemingly unrelated cancers.]]> Wed 04 Sep 2019 10:04:10 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27801 Wed 04 Apr 2018 17:04:59 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23843 0.999) or in the number of variants predicted to be pathogenic by various in silico tools (Condel, Polyphen2, SIFT, and CADD) in the cases compared to the controls. In addition, there was no difference in the incidence of classic Lynch syndrome cancers in RINT1 rare variant-carrying families compared to RINT1 wild-type families. This study had 90 % power to detect an odds ratio of at least 2.06, and the results do not provide any support for RINT1 being a moderate-penetrance breast cancer susceptibility gene, although larger studies will be required to exclude more modest effects. This study emphasizes the need for caution before designating a cancer predisposition role for any gene based on very rare truncating variants and in silico-predicted missense variants.]]> Wed 02 Mar 2022 14:25:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28231 Wed 01 Aug 2018 14:52:20 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30964 100) epialleles. RNA-polymerase-II (Pol-II) bound only to three particular epialleles in cAMP-stimulated cells, while phospho-cAMP response element-binding protein (pCREB) bound to only one epiallele, which was different from those selected by Pol-II. Binding of TATA-binding protein increased during syncytial differentiation preferentially at epialleles compatible with Pol-II and pCREB binding. Histone-3 acetylation was detected only at epialleles targeted by Pol-II and pCREB, while gene activating histone-4 acetylation and histone-3-lysine-4 trimethylation occurred at CRH epialleles not associated with Pol-II or pCREB. The suppressive histone-3-lysine-27 trimethyl and-lysine-9 trimethyl modifications showed little or no epiallele preference. The epiallele selectivity of activating histone modifications and transcription factor binding demonstrates the epigenetic and functional diversity of the CRH gene in trophoblasts, which is controlled predominantly by the patterns, not the overall extent, of promoter methylation. We propose that conditions impacting on epiallele distribution influence the number of transcriptionally active CRH gene copies in the trophoblast cell population determining the gestational trajectory of placental CRH production in normal and pathological pregnancies.]]> Tue 24 Apr 2018 15:36:22 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30018 Tue 20 Sep 2022 14:49:52 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41878 Tue 16 Aug 2022 10:04:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46235 Tue 15 Nov 2022 08:51:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25559 Tue 13 Nov 2018 09:58:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47243 Tue 10 Jan 2023 15:12:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:43823 Tue 04 Oct 2022 11:04:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48599 Tue 04 Apr 2023 19:22:25 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41379 Tue 04 Apr 2023 19:08:51 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50043 Thu 29 Jun 2023 14:38:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44981 path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. Methods: The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. Results: Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5–2.5, 2.5–3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5–2.5, 2.5–3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). Conclusions: In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.]]> Thu 27 Oct 2022 09:15:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26762 Thu 24 Mar 2022 11:35:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30577 Thu 24 Mar 2022 11:32:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46914 Thu 08 Dec 2022 08:47:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41461 TP53 vary depending on the subtype, such that ER-negative tumours have a high rate, and in ER-positive tumours they are less common. Previous studies have implicated the intronic polymorphism in TP53 (rs17878362; or PIN3) with an increased risk of developing breast cancer, although little has been discerned on its prevalence in different subtypes. In this study, we investigated the prevalence of the PIN3 genotype in the blood of cohorts with ER-positive and the ER-negative subtype TNBC, and assessed its association with outcome. Methods: We genotyped 656 TNBC and 648 ER-positive breast cancer patients, along with 436 controls, and compared the prevalence of polymorphism rs17878362 in these cohorts. Results: We found there to be no differences in the prevalence of the PIN3 genotype between the ER-positive and TNBC cohorts. Furthermore, no statistically significant difference was observed in the outcome of patients in either cohort with respect to their PIN3 genotype. Conclusions: Taken together, our results do not support an association of the PIN3 genotype with increased breast cancer risk, either in ER-positive or ER-negative patients.]]> Thu 01 Sep 2022 11:19:24 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:7293 Sat 24 Mar 2018 08:42:13 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9594 Sat 24 Mar 2018 08:39:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9354 Sat 24 Mar 2018 08:36:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:8177 Sat 24 Mar 2018 08:36:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1921 50 years of age was significantly elevated compared with the control population (odds ratio, 2.23; P = 0.0046). The results indicate that NOD2 may be a predisposing factor to colorectal cancer characterized by an older average age of disease onset in persons who do not harbor any other genetic predisposition to disease.]]> Sat 24 Mar 2018 08:33:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1288 Sat 24 Mar 2018 08:32:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:998 Sat 24 Mar 2018 08:29:50 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1443 Sat 24 Mar 2018 08:28:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14184 1% predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11. Results: Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV₁% predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV₁% predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation. Conclusion: Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.]]> Sat 24 Mar 2018 08:21:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11525 Sat 24 Mar 2018 08:10:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20712 Sat 24 Mar 2018 08:06:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20953 Sat 24 Mar 2018 08:06:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20832 12% change in FEV₁; AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma. Conclusions: A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma.]]> Sat 24 Mar 2018 08:05:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21378 Chlamydia trachomatis infection is increased by oral contraceptives and modulated by sex hormones. We therefore sought to determine the effects of female sex hormones on the innate immune response to C. trachomatis infection. Method of study: ECC-1 endometrial cells, pre-treated with oestradiol or progesterone, were infected with C. trachomatis and the host transcriptome analysed by Illumina Sentrix HumanRef-8 microarray. Primary endocervical epithelial cells, prepared at either the proliferative or secretory phase of the menstrual cycle, were infected with C. trachomatis and cytokine gene expression determined by quantitative RT-PCR analysis. Results: Chlamydia trachomatis yield from progesterone-primed ECC-1 cells was significantly reduced compared with oestradiol-treated cells. Genes upregulated in progesterone-treated and Chlamydia-infected cells only included multiple CC and CXC chemokines, IL-17C, IL-29, IL-32, TNF-α, DEFB4B, LCN2, S100A7-9, ITGAM, NOD2, JAK1, IL-6ST, type I and II interferon receptors, numerous interferon-stimulated genes and STAT6. CXCL10, CXCL11, CX₃CL1 and IL-17C, which were also upregulated in infected secretory-stage primary cells, and there was a trend towards higher levels of immune mediators in infected secretory-phase compared with proliferative-phase cells. Conclusion: Progesterone treatment primes multiple innate immune pathways in hormone-responsive epithelial cells that could potentially increase resistance to chlamydial infection.]]> Sat 24 Mar 2018 08:04:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17308 Sat 24 Mar 2018 08:01:48 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18434 Sat 24 Mar 2018 07:59:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18919 Sat 24 Mar 2018 07:59:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21565 Sat 24 Mar 2018 07:59:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17886 Sat 24 Mar 2018 07:56:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19171 Sat 24 Mar 2018 07:52:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19418 Sat 24 Mar 2018 07:51:57 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5211 Sat 24 Mar 2018 07:47:45 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5341 Sat 24 Mar 2018 07:45:56 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28878 Sat 24 Mar 2018 07:40:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26262 Sat 24 Mar 2018 07:40:14 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25812 postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n = 315) and from ex-vivo blood tissues (n = 578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia.]]> Sat 24 Mar 2018 07:34:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26944 0.05), but cases presented with an excess of rare germline deletions overlapping likely functional genomic regions including genes (P = 8 x 10^-10), CpG islands (P = 1 x 10^-7) and sno/miRNAs regions (P = 3 x 10^-9). On average, at least one additional gene and two additional CpG islands were disrupted by rare deletions in cases compared to controls. The most pronounced difference was that over 30 sno/miRNAs were disrupted by rare deletions in cases for every single disruption event in controls. A total of 13 DNA repair genes were disrupted by rare deletions in 19/1,209 cases (1.6 %) compared to one gene in 1/528 controls (0.2 %; P = 0.007), and this increased DNA repair gene loss in cases persisted after excluding five individuals carrying CNVs disrupting mismatch repair genes MLH1, MSH2 and MSH6 (P = 0.03). There were 34 miRNA regions deleted in at least one case but not in controls, the most frequent of which encompassed hsa-mir-661 and hsa-mir-203. Our study implicates rare germline deletions of functional and regulatory regions as possible mechanisms conferring endometrial cancer risk, and has identified specific regulatory elements as candidates for further investigation.]]> Sat 24 Mar 2018 07:27:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25547 Sat 24 Mar 2018 07:26:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22288 Sat 24 Mar 2018 07:17:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24332 Sat 24 Mar 2018 07:16:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23306 Sat 24 Mar 2018 07:16:19 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22801 Sat 24 Mar 2018 07:12:18 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23994 Sat 24 Mar 2018 07:10:24 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44131 Sat 08 Oct 2022 12:36:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32706 Mon 23 Sep 2019 11:46:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42338 N = 29,125 cases and 34,836 controls), a robust polygenic signal was observed from gene sets based on TCF4, FMR1, upregulation from MIR137 and downregulation from CHD8. Additional analyses revealed a constant floor effect in the amount of variance explained, consistent with the omnigenic model. Thus, we report that putative core gene sets showed a significant effect above and beyond the floor effect that might be linked with the underlying omnigenic background. In addition, we demonstrate a method to quantify the contribution of specific gene sets within the omnigenic context.]]> Mon 22 Aug 2022 14:00:20 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50311 Mon 17 Jul 2023 15:51:54 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50972 Mon 14 Aug 2023 15:19:39 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46970 Mon 12 Dec 2022 16:19:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55070 Mon 08 Apr 2024 13:27:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33670 Mon 01 Jul 2019 09:50:58 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42186 n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.]]> Fri 26 Aug 2022 10:49:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54935 Fri 22 Mar 2024 14:31:53 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53114 Fri 17 Nov 2023 11:41:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35929 MED12 alterations in 39 of 65 fibroids (60%) from 14 patients. Using isobaric tagged-based quantitative mass spectrometry on three selected patients (n = 9 fibroids), we observed a common set of upregulated ( > 1.5-fold) and downregulated ( < 0.66-fold) proteins in small, medium, and large fibroid samples of annotated MED12 status. These two sets of upregulated and downregulated proteins were the same in all patients, regardless of variations in fibroid size and MED12 status. We then focused on one of the significant upregulated ECM proteins and confirmed the differential expression of periostin using western blotting and immunohistochemical analysis. Our study defined the proteome of uterine fibroids and identified that increased ECM protein expression, in particular periostin, is a hallmark of uterine fibroids regardless of MED12 mutation status. This study sets the foundation for further investigations to analyze the mechanisms regulating ECM overexpression and the functional role of upregulated ECM proteins in leiomyogenesis.]]> Fri 17 Jan 2020 11:35:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51723 Fri 15 Sep 2023 17:53:26 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54828 Fri 15 Mar 2024 11:54:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52991 Fri 03 Nov 2023 16:05:35 AEDT ]]>