tbuckley/cabot-search huggingface dataset:
Pituitary-Ovarian Responses to Nafarelin Testing in the Polycystic Ovary Syndrome
Authors: Randall B. Barnes, Robert L. Rosenfield, Stephen Burstein, David A. Ehrmann
Journal: New England Journal of Medicine (1989)

To investigate the basis of polycystic ovary syndrome, we examined the responses of patients to nafarelin, a specific gonadotropin-releasing-hormone agonist, given to stimulate pituitary and gonadal secretion. We compared 16 normal women in the follicular phase, 5 normal men, 8 women with polycystic ovary syndrome, and 1 woman with polycystic ovary syndrome caused by a 3β-hydroxysteroid dehydrogenase deficiency. After 100 μg of nafarelin was given subcutaneously, serum follicle-stimulating hormone and luteinizing hormone increased rapidly to peak levels within four hours. The women with polycystic ovary syndrome had a pattern similar to that of the men, with greater early luteinizing-hormone responses (30 minutes to 1 hour) and lower peak follicle-stimulating-hormone responses than normal women (P<0.05). Patients with polycystic ovary syndrome responded to gonadotropin stimulation with normal to increased production of plasma estrogens and increased levels of androstenedione at 16 to 24 hours (P<0.05). Elevated production of 17α-hydroxyprogesterone was found in all the women with polycystic ovary syndrome and in the men. These abnormal responses were unchanged by pretreatment with dexamethasone to suppress adrenal function. In the patient with the 3β-hydroxysteroid dehydrogenase deficiency, both basal and stimulated plasma levels of Δ5-3β-hydroxysteroids before the enzymatic block were elevated, whereas plasma levels of 17α-hydroxyprogesterone and androstenedione — the steroids immediately beyond the block — were low. We conclude that women with polycystic ovary syndrome have masculinized pituitary and ovarian responses to stimulation by nafarelin. Our findings suggest that the regulation of the ovarian 17-hydroxylase and C-17,20-lyase activities is abnormal in such women. (N Engl J Med 1989;320:559–65.)
P17.29 * IDENTIFICATION OF NOVEL MOLECULAR TARGETS FOR TEMOZOLOMIDE-BASED THERAPIES AGAINST GLIOBLASTOMA: A COMPREHENSIVE SHRNA-BASED SCREEN OF DNA REPAIR FACTORS
Authors: H. Erasimus, S. Fritah, S. Haan, S. P. Niclou, E. Van Dyck
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis (the median survival of GBM patients is 14.6 months). Current GBM treatment, which consists of surgical resection followed by radiation therapy and temozolomide (TMZ) chemotherapy, is faced with the development of resistance. The DNA-alkylating agent TMZ exerts its cytotoxic function by damaging DNA and inducing tumor cell death. However, efficient repair and/or tolerance of TMZ-induced DNA lesions can mediate resistance to chemotherapy. One such important factor is the O-6-methylguanine-DNA methyltransferase (MGMT). In addition to mediating the cellular response to anti-cancer therapeutics, DNA repair pathways also help cancer cells to cope with the extra load of endogenous DNA damage that occurs as a consequence of the tumorigenic process. Which DNA repair molecules are important for GBM survival in the absence of chemotherapeutic treatment and/or in response to anti-cancer genotoxics remains, however, vastly unknown. In this project, we have addressed this question by developing a large-scale differential shRNA screen specifically targeting components of the DNA-damage response (DDR). This includes not only DNA repair genes, but also genes involved in cell cycle checkpoints, DNA damage tolerance pathways and chromatin factors that facilitate DNA repair. Pooled shRNAs will be introduced in selected GBM-derived, cancer stem like cells (GSCs), as well as control non-cancer cells. Genes that appear essential to the survival of GSCs, but dispensable to non-cancer cells, either in the absence of treatment, or following exposure to TMZ, will be selected. Subsequently, promising candidates will be validated individually in vitro, and the best candidates will be further validated in vivo, using patient derived xenograft animal models developed in the laboratory. This will allow us to monitor, in a pre-clinical setting, the impact of depleting selected DDR factors, on tumor formation and response to TMZ. Long-term perspectives include determining the potential of the selected DDR components as druggable, therapeutic targets in the treatment against GBM.
Calcified Substernal Goiter Seen on Bone Scan
Authors: KOUROSH NOURISAMIE, ORHAN KONEZ
Journal: Clinical Nuclear Medicine (2000)

A Tc-99m MDP scan of a 59-year-old man diagnosed with prostate carcinoma was obtained to rule out metastatic bone disease, which showed a focal intense uptake within the upper sternal region. Subsequent SPECT scan of the chest showed that this scintigraphic abnormality was located in the upper mediastinum and did not involve the sternum. Chest radiographs were obtained and showed a mass with a subtle eggshell calcification in the retrosternal superior mediastinum. Review of previous bone scans and clinical and laboratory data revealed the diagnosis of substernal thyroid with dystrophic calcification. Follow-up bone scans obtained because of the patient’s increased prostate-specific antigen levels have shown neither significant change in appearance of the scintigraphic abnormality nor evidence of bony metastases.
Abstract 1189: Discovery of RPS25-MDM2/MDMX-p53 regulatory feedback loop
Authors: Xu Zhang, Wei Wang, Wenrong Xu, Ming-hai Wang, Hui Wang, Ruiwen Zhang
Journal: Cancer Research (2012)

Abstract There is an increasing interest in elucidation of ribosomal proteins (RPs) in cancer development and progression. Ribosomal proteins have extraribosomal functions and participate in a surveillance network for cell growth, division, and apoptosis. Accumulating evidence suggests that the p53 protein, together with ribosomal proteins, takes part in a surveillance mechanism for genome integrity and protein translation, and is activated by nucleolar stress. We herein identified a regulatory role of RPS25 in p53-mediated cellular response to ribosomal stress. We demonstrated that RPS25 bound to MDM2 by using immunoprecipitation and GST pull-down assays. RPS25 inhibited the E3 ligase activity of MDM2, resulting in the stabilization and activation of p53. Overexpression of RPS25 induced cell cycle arrest and apoptosis through p53. The MDM2-binding and nucleolar location domains of RPS25 were critical for regulating p53 stability and activity. Knockdown of RPS25 by siRNA attenuated the activation of p53 induced by ribosomal stress. Furthermore, we found that MDMX was involved in the regulation of the E3 ligase activity of MDM2 by RPS25, suggesting that RPS25 modulates p53 in an MDM2 and MDMX-dependent manner. Finally, RPS25 was identified to be a transcriptional target of p53. Ribosomal stress-induced p53 activation inhibited RPS25 protein level, while knockdown of p53 restored RPS25 expression. In conclusion, these results demonstrate that RPS25 is a novel regulator of p53 in ribosomal stress and define a unique S25-MDM2/MDMX-p53 regulatory feedback loop in ribosomal stress. (This work was supported by NIH/NCI grants R01 CA112029 and R01 CA121211 and a Susan G Komen Foundation grant BCTR0707731.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1189. doi:1538-7445.AM2012-1189
Abstract 3172: Methylation portraits discriminate between hepatocellular carcinoma cases and controls
Authors: Rafael Guerrero-Preston, Ethan Soudry, Andrew Jaffe, Carmen Ili-Gangas, Priscilla Brebi-Mieville, Jimena Pérez, Xiaoli Zhong, Quiang Yang, Stephen J. Meltzer, Manel Esteller, David Sidransky
Journal: Cancer Research (2011)

Abstract Background: Most genome-wide methylation studies have focused on technology to profile and identify therapeutic biomarkers in HCC. However, attempts to integrate these technologies to clinical and population based studies are still lacking. Objective: Our aim was to identify existing methylation profiling technologies that can be used in translational epigenomic efforts. Methods: We examined Quantitative Methylation specific PCR, oligonucleotide methylation tiling arrays (MeDIP-chip), and Methylation BeadChip arrays and their ability to distinguish between HHC cases and controls, a key goal in Phase I biomarker development trials. Scatterplots, histograms and heat maps of genome-wide DNA methylation array data were used to provide a snapshot of the differences in methylation patterns between tumor and normal samples. Results: The representative tumor sample had a lower methylation score median and less significant genome-wide methylated probes (1,503) than either normal liver tissue samples (2,585 and 2,2887 respectively). RASSF1A and B4GALT1 had a sensitivity of 52%, a specificity of 100% and an AUC of 0.73 (RASSF1A) and 0.75 (B4GALT1). SSBP2 had a sensitivity of 38%, a specificity of 100% and an AUC of 0.58. A panel combining these genes with HCC risk factors had a sensitivity of 87%, a specificity of 100% and an AUC of 0.91. Conclusions: We have shown that genome-wide and gene-specific methylation platforms, which interrogate gene promoter regions, can be used to examine novel biomarkers and differentiate HCC from normal liver tissue. Additional studies will confirm the value of using methylation-profiling technologies to evaluate these new markers as we move forward. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3172. doi:10.1158/1538-7445.AM2011-3172
Abstract 1165: Measuring telomere length for the early detection of precursor lesions of esophageal squamous cell carcinoma.
Authors: Shih-Wen Lin, Christian C. Abnet, Neal D. Freedman, Rosana Risques, Donna Prunkard, Peter Rabinovitch, Ning Lu, You-Lin Qiao, Sanford M. Dawsey
Journal: Cancer Research (2013)

Abstract Objectives: Esophageal cancer is the fifth leading cause of cancer death worldwide. The five-year survival is approximately 16%. Patients can be successfully treated if diagnosed early, but current early detection screening tests are inadequate. Balloon cytology is a simple and inexpensive method of retrieving esophageal cells, but traditional cytologic examination of these cells has poor sensitivity and specificity. We examined whether telomere length, a marker for chromosomal instability, in DNA extracted from balloon cytology-collected esophageal cells is associated with precursor lesions of esophageal squamous cell carcinoma. Methods: The Cytology Sampling Study 2, a population-based esophageal cancer early detection screening study, recruited over 700 healthy subjects from a high-risk population in Linxian, China. The screening study used a mesh-covered balloon to collect esophageal cells. All subjects underwent endoscopy, and precursor lesions were diagnosed by biopsy. Using a nested case-control study design, we examined the association between telomere length and dysplasia in 37 low-grade dysplasia cases, 52 high-grade dysplasia cases, and 92 matched controls. DNA was extracted from cells collected by balloon cytology, and telomere length was measured in triplicate by a quantitative PCR assay. Logistic regression models adjusted for age, sex, smoking tobacco, alcohol intake, and hypertension were used to examine the association between telomere length and risk of low-grade dysplasia and high-grade dysplasia, compared with normal controls. Results: Telomere lengths were comparable among the low-grade dysplasia cases, high-grade dysplasia cases, and controls, with a median of 0.93 [interquartile range (IQR), 0.84-1.06], 0.94 (IQR, 0.82-1.09), and 0.93 (IQR, 0.78-1.05), respectively. Overall, telomere length was not associated with risk of low-grade dysplasia or high-grade dysplasia, with an odds ratio [OR, 95% confidence interval (CI)] of 1.16 (0.87-1.54) and 1.20 (0.92-1.56), respectively. Conclusions: Given that esophageal cancers have very poor prognoses, it is of utmost importance to improve early detection. In this study, esophageal cell telomere length was not associated with esophageal precursor lesions and cannot serve as an early detection marker. Citation Format: Shih-Wen Lin, Christian C. Abnet, Neal D. Freedman, Rosana Risques, Donna Prunkard, Peter Rabinovitch, Ning Lu, You-Lin Qiao, Sanford M. Dawsey. Measuring telomere length for the early detection of precursor lesions of esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1165. doi:10.1158/1538-7445.AM2013-1165
Necrotizing Renal Papillitis: A Form of Acute Pyelonephritis
Authors: Stanley L. Robbins, G. Kenneth Mallory, Thomas D. Kinney
Journal: New England Journal of Medicine (1946)

NECROSIS of the renal papillae, sometimes termed "papillitis necroticans"1 or "necrotizing pyelonephritis,"2 is an infrequently recognized and severe type of suppurative renal infection that is usually encountered in diabetic patients although it is occasionally found in nondiabetic persons.3 , 4 The lesion, which has been a well recognized pathologic entity for many years, was recently well described by Günther.5 It remains, however, a poorly defined clinical entity that is usually found as an unexpected lesion at autopsy. Recent publications emphasize the fact that the problem of acute pyelonephritis — in particular that of necrotizing papillitis — is of greater magnitude than its . . .
Abstract 542: TGF-β inhibitors enhance chemotherapeutic efficacy via abrogation of autocrine and paracrine signaling in a triple negative breast cancer model
Authors: Tanuka Biswas, LuZhe Sun
Journal: Cancer Research (2011)

Abstract Triple negative breast cancer (TNBC) accounts for approximately 15-20% of total invasive breast cancers. This subtype of cancer is often correlated with poor prognosis, visceral metastases and relapse. Molecular characterization reveals that these tumors are negative for hormone receptors and they often develop chemo resistance. Tumor microenvironment, among other factors, has emerged as a definite player in the progression of breast cancer and may also confer chemo resistance. In the current study, we demonstrate that MDA-MB-231 cells show greater resistance to paclitaxel in heterotypic culture with RMF/EG-hTERT (reduction mammary fibroblast with enhanced GFP) as compared to homotypic culture. Further, we show that RMF/EG-hTERT cells can enhance the motility of MDA-MB-231 cells in trans well migration assays, which could be attenuated by the TGF-β inhibitor sRIII (soluble receptor type III). TGF-β signaling was shown to activate pro-survival pathways like PI3K/Akt and MAPK/ERK pathways in mammary fibroblasts suggesting that they may mediate the paracrine tumor-promoting activity of TGF-β. Autocrine TGF-β signaling has been shown to promote EMT and cancer stem cell-like features in TNBC cells and appears to be a potential therapeutic target. We show that paclitaxel in combination with sRIII was more effective in inhibiting the growth of MDA-MB-231 cells than either agent alone. The combination of a TGF-β inhibitor with paclitaxel was also more effective in inhibiting tumor sphere formation than either agent alone. Our future research will be focused on the mechanisms of autocrine and paracrine TGF-β signaling in mediating chemo resistance and the tumor-promoting activity of mammary stromal cells. Our research will reveal the potential use of TGF-β inhibitors as novel therapeutics in combination with chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 542. doi:10.1158/1538-7445.AM2011-542
Re: Lung Cancer Incidence Among Patients With Beryllium Disease
Authors: MERRIL EISENBUD
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Re: Lung Cancer Incidence Among Patients With Beryllium Disease Get access MERRIL EISENBUD MERRIL EISENBUD Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 20, 20 October 1993, Pages 1697–1698, https://doi.org/10.1093/jnci/85.20.1697 Published: 20 October 1993
THU0235 Identifying and quantifying prognostic factors in systemic sclerosis-related interstitial lung disease using a time-varying covariate survival model
Authors: O.A. Moore, N. Goh, T. Corte, H. Rouse, O. Hennessy, V. Thakkar, J. Byron, J. Sahhar, J. Roddy, P. Youssef, P. Nash, J. Zochling, S.M. Proudman, W. Stevens, M. Nikpour
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Interstitial lung disease (ILD) is a leading cause of mortality in systemic sclerosis (SSc). We have shown that total extent of lung disease on high-resolution CT (HRCT) lung, reported using a simple grading system,[1] can determine prognosis in SSc-ILD. <h3>Objectives</h3> We assessed factors that predicted deterioration in ILD using a time varying covariate model. <h3>Methods</h3> SSc patients with a baseline HRCT around the time of diagnosis of ILD were identified through the Australian Scleroderma Cohort Study (ASCS). All HRCTs and pulmonary function tests (PFTs) performed during follow-up were retrieved. Demographic and disease-related data were prospectively collected in the ASCS database. HRCTs were reported by three blinded raters (two respiratory physicians, one radiologist) following a training session. Scans were graded according to the percentage of lung disease seen; &gt;20% - extensive, &lt;20% - limited, unclear - indeterminate. Indeterminate results were converted to limited or extensive using an FVC threshold of 70%. The composite outcome variable was deterioration (defined as need for home oxygen or lung transplantation) or death. Demographic and disease related data including HRCT grade was compared to outcome using a Weibull hazards regression model with time-varying covariates. <h3>Results</h3> Among 172 patients followed for mean±SD of 3.47±2.93 years, there were 33 outcome events. In time-varying covariate models (based on 1309 serial PFTs and 353 serial HRCTs in the 172 patients), serial DLCO/VA (ml/min/mmHg/L) (adjusted hazards ration (aHR) =0.4, 95% CI: 0.3-0.7, p=0.001), FVC (dL) (aHR =0.9, 95% CI: 0.8-0.97, p=0.008) and extensive disease score (aHR =3.3, 95% CI: 1.1-9.9, p=0.03), were strongly predictive of outcome. <h3>Conclusions</h3> In follow-up of patients with SSc-ILD findings of extensive disease according to this simple staging system or lower DLCO/VA or FVC are indicative of increased risk of poor disease outcome. Considering the cost and radiation risk of HRCT-lung we would suggest the use of PFTs in the follow-up of these patients. <h3>References</h3> Goh NSL, Desai SR, Veeraraghavan S, et al. Interstitial Lung Disease in Systemic Sclerosis: A Simple Staging System. American Journal of Respiratory and Critical Care Medicine 2008;177:1248–1254. <h3>Disclosure of Interest</h3> None Declared
AB0689 Association between MRI Inflammation and Bone Loss in Early Axial Spondyloarthritis
Authors: E. Gubar, A. Botchkova, A. Smirnov, T. Dubinina, A. Diomina, O. Rumyantseva, S. Shubin, E. Tukchova, S. Glukhova, A. Godzenko, S. Erdes
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The association between MRI inflammation and bone loss in early axial spondyloarthritis (axSpA) patients is not sufficiently studied. <h3>Objectives</h3> Establishing the association between MRI inflammation of sacroiliac joints (SIJs), lumbar spine (LS) and hip joints (HJs) and bone loss in the nearby bone-joint system in early axial axSpA patients. <h3>Methods</h3> 73 patients (33 men and 40 women) with early axSpa were examined: mean disease duration 19.9±14.4 months. Patients fulfilled ASAS criteria. Mean age 28.3±6.4 years, mean BASDAI 4.1±1.9; mean ASDAS-CRP 2.7±1.3; mean ESR 21.9±17.6; mean CRP 29.0±38.5; 66 (90.4%) patients were HLA-B27 positive. MRI of SIJs, LS and HJs (in case of hip joint involvement) was performed on Signa Ovation 0.35 T scanner (matrix 288x192). BMD was measured using dual energy x-ray absorptiometry (DXA) of the femoral neck (FN) and lumbar spine (LS) (L2–4). BMD reduction was defined as T score ≤−1. <h3>Results</h3> MRI inflammation of SIJs and/or LS and/or HJs has been found in 62 (84.9%) patients. Among the 62 patients of this group 44 (71.0%) had BMD reduction in FN and/or LS. And in the group of patients without MRI inflammation (n=11) nobody had bone loss (p=0.0001). MRI sacroiliitis (SI) was observed in 53 (72.6%) patients: 37 (69.8%) of them had BMD reduction in FN and/or LS, and 16 (30.2%) patients of this group had normal BMD values (p=0.007). MRI SI has been found in 32 out of 37 (86.5%) patients that had BMD reduction in the LS; in the group of patients without bone loss in the LS (n=36) MRI SI was observed in 21 (58.3%) patients (p=0.007). MRI SI has been found in 21 out of 27 (77.8%) patients that had BMD reduction in the FN; in the group of patients without bone loss in the FN (n=46) MRI SI was observed in 32 (69.6%) patients (p=0.45). <h3>Conclusions</h3> Correlation has been detected between inflammatory lesions in SIJs and/or LS and/or HJs and bone loss in FN and/or LS. There is an association between existence of active MRI SI and BMD reduction in the LS. This demonstrates that in patients with early axSpA bone loss is a result of inflammation. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2435
Health Care Reform Stages a Comeback in Massachusetts
Authors: John E. McDonough, Christie L. Hager, Brian Rosman
Journal: New England Journal of Medicine (1997)

Since the demise of efforts to reform the national health care system in the fall of 1994, there have been few new initiatives to address the problems faced by the more than 40 million Americans who lack health insurance. Even state governments that were at the forefront of efforts to deal with this problem in the early 1990s saw their initiatives stalled, scaled back, or repealed.1 As the focus of debates on health policy shifted to issues such as controlling Medicare and Medicaid costs and protecting the rights of already insured consumers enrolled in managed-care plans, the public turned its . . .