tbuckley/cabot-search huggingface dataset:
RT-14 * TIME TO RADIATION THERAPY IN GLIOBLASTOMA MULTIFORME: IS SOONER BETTER?
Authors: H. Kistka, E. Min, L. Chambless
Journal: Neuro-Oncology (2014)

INTRODUCTION: Optimal post-surgical treatment of glioblastoma multiforme (GBM) includes concurrent radiation therapy and temozolomide. However, there is conflicting data regarding the ideal timing of radiation. Proponents of early therapy cite the rapid proliferation rate of WHO grade IV tumors and advocate treatment with minimal delays. Others believe extra time allows the surgical cavity to collapse and tempers the risk of infection, minimizing complications from radiation. METHODS: We retrospectively reviewed records of 97 patients with a pathologic diagnosis of GBM at our institution who underwent postoperative treatment with at least 6 weeks of radiation according to Radiation Therapy Oncology Group guidelines and concurrent temozolomide therapy. Demographic, clinical, radiographic and operative data were reviewed. Analysis of variance(ANOVA) was used to identify differences between surgical and demographic subgroups. Kaplan-Meier survival analysis was used to estimate overall(OS) and progression free survival(PFS). Cox regression analyses were performed to determine the effect of radiation timing on survival. RESULTS: 49 male and 47 female patients had a median age at surgery of 57 years (range 18-77). Sixteen patients underwent biopsy, 64 had a subtotal resection(STR) and 16 had a gross total resection(GTR). One year OS and PFS were 70% and 16%, respectively. The median time to radiation(TTR) was 26 days (range 9-51 days). TTR was significantly longer in patients with resection compared to biopsy (p < 0.001). TTR did not significantly affect OS (p = 0.732) or PFS (p = 0.699) of the entire cohort or the subgroup treated with resection (OS, p = 0.809; PFS, p = 0.812). CONCLUSIONS: The precise timing of radiation initiation does not appear to affect survival of patients with GBM who are optimally treated with radiation and temozolomide. Therefore practitioners may allow extra time within the recommended 6 week window for optimal medical stabilization and wound healing without fear that this may adversely affect patient outcomes.
SP0190 Juvenile Dermatomyositis: Whats New in 2014?
Authors: L. Wedderburn
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> It is increasingly clear that juvenile dermatomyositis (JDM), a rare complex autoimmune disorder that involves autoimmune, vascular and inflammatory mechanisms, is not homogeneous. Rather, the diagnosis of JDM covers a heterogeneous group of patients, with a wide spectrum of outcomes ranging from complete remission through to those with recalcitrant difficult to treat disease, with ongoing active skin rash, calcinosis or vasculopathic complications. In this talk we will consider novel biomarkers that can distinguish these subphenotypes, and the underlying genetics or mechanistic pathways that may drive these disease types. We will also review methods with which to assess and monitor disease and international efforts to standardize the data and samples that are considered minimal to allow the optimal management of patients with JDM. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6355
Spontaneous Perforation of Common Bile Duct in a Pediatric Patient
Authors: Marjan Joodi, Nasim Norouzbeigi, Mohammad Ali Ghodsi Rad, Reza Shojaeian, Vahid Reza Dabbagh Kakhki, Ramin Sadeghi
Journal: Clinical Nuclear Medicine (2012)

We report a case of spontaneous biliary perforation in a 21-month old female pediatric patient with the presenting symptoms of abdominal distension, jaundice, and umbilical hernia. Hepatobiliary scintigraphy showed tracer accumulation in the peritoneal cavity. Preliminary diagnosis of spontaneous biliary perforation was confirmed during surgery. After surgical repair of the biliary leakage, the patient recovered fully. This case shows the importance of hepatobiliary scintigraphy in patients suspicious for this condition.
Abstract 3165: Metastatic tumor evolution delineates clinically important oncogenic drivers in diffuse gastric cancer.
Authors: Lincoln D. Nadauld, Sarah Garcia, Georges Natsoulis, John M. Bell, Erik Hopmans, Hua Xu, Reetesh K. Pai, John F. Regan, James M. Ford, Calvin J. Kuo, Hanlee Ji
Journal: Cancer Research (2013)

Abstract We conducted a detailed genetic and functional analysis of personalized tumor evolution in a case of diffuse gastric cancer. Leveraging the unique genetics of an individual with a confirmed germline mutation in the causative CDH1 tumor suppressor gene, we identified candidate drivers for a primary tumor in the stomach and a metastatic recurrence in the left ovary, referred to as a Krukenberg tumor. Using genome sequencing, we demonstrate that the primary and metastatic tumors share the majority of cancer driver events including biallelic CDH1 and TP53 mutations consistent with a common genetic origin. The primary gastric cancer displayed amplification of FGFR2, a gene that encodes the fibroblast growth factor (FGF) receptor 2 with multiple small molecule inhibitors in clinical therapy development. Tumor evolution and genetic divergence was clearly evident with the ovarian metastasis lacking the FGFR2 amplification and displaying its own subset of mutations and genomic aberrations. Namely, the metastatic tumor had unique biallelic events affecting TGFBR2, a critical gene in the TGF-β (tumor growth factor) signaling pathway that has not previously implicated in diffuse gastric cancer. To determine the independent oncogenic attributes of these separate pathways, we used a diffuse gastric cancer cell line and organoid model system to replicate and study the context of the known and candidate drivers found in the index patient's primary versus metastatic sites. We demonstrated that in the context of biallelic CDH1 and TP53 functional loss, the addition of either FGFR2 or TGFBR2 drivers independently lead to gastric cancer. This result supports the independent cancer driver roles of the FGF and TGF-β signaling pathways in metastatic tumor evolution in diffuse gastric cancer. Our study has implications regarding personalized cancer medicine approaches in patients with metastatic gastric cancer. Citation Format: Lincoln D. Nadauld, Sarah Garcia, Georges Natsoulis, John M. Bell, Erik Hopmans, Hua Xu, Reetesh K. Pai, John F. Regan, James M. Ford, Calvin J. Kuo, Hanlee Ji. Metastatic tumor evolution delineates clinically important oncogenic drivers in diffuse gastric cancer. [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 3165. doi:10.1158/1538-7445.AM2013-3165
Bioresorbable Vascular Scaffolds — Will Promise Become Reality?
Authors: Robert A. Byrne
Journal: New England Journal of Medicine (2015)

All other things being equal, most of us would agree that a coronary-artery stent that disappears after its useful function has been served would be preferable to a permanently indwelling device. Late stent failure occurs at a low but steady rate with the passage of time,1 and an increasing body of evidence implicates an accelerated form of atherosclerosis inside the stent as a common underlying cause.2 Moreover, the presence of a rigid metal scaffold in the vessel wall permanently abolishes physiologic vasomotion in the stented area.With this in mind, researchers have sought to develop self-degrading coronary stents with enough . . .
Services for older people need major change, says report
Authors: J. Wise
Journal: BMJ (2014)

How the United Kingdom manages its ageing population needs to change radically so that care is coordinated around all of a person’s needs rather than being based on single diseases, says a report from the health think tank the King’s Fund.1

The report also calls for care that prioritises prevention and supports independent living. It says that for this to be achieved more integrated working is needed, to ensure that the right mix of services is available.

David Oliver, the report’s lead author and president elect of the British Geriatrics Society, said, “The health and care systems have a …
P623 NCU-G1GT/GT MICE: A LONG-LIVED MODEL FOR LIVER FIBROSIS
Authors: X.Y. Kong, C.K. Nesset, C. Schjalm, E.M. Løberg, A.C. Rustan, G.H. Thoresen, E.T. Kase, W. Eskild
Journal: Journal of Hepatology (2014)
Abstract 4970: Convergence of protein kinase and caspase signaling: A mechanism for pathological rewiring of survival pathways by protein kinase CK2
Authors: Jacob P. Turowec, James S. Duncan, Shawn Li, Greg Gloor, David W. Litchfield
Journal: Cancer Research (2012)

Abstract Crosstalk between protein kinases and caspases has become evident in light of the observation that phosphorylation within the caspase cleavage motif impairs proteolysis. Given that phosphorylation networks and sensitivity to apoptotic cues are altered in cancer signaling, we sought to investigate if the negative regulation of caspase-mediated degradation by protein phosphorylation is a global mechanism that manifests in changes to cancer cell survival. To systematically investigate the extent to which phosphorylation regulates the caspase degradome, we employed a combination of peptide cleavage assays, database mining, and N-terminomics. These studies revealed that phosphorylation could potentially regulate the cleavage of a significant proportion of caspase substrates. One notable example of phosphorylation-regulated caspase cleavage was the observation that pro-caspase-3 itself is phosphorylated in a manner that prevents subsequent cleavage and activation by upstream initiator caspases. To further examine the role of phosphorylation in regulating the activation of caspase-3, we investigated the phosphorylation of pro-caspase-3-FLAG in HeLa cells transfected with each of the catalytic isoforms of protein kinase CK2 in the presence or absence of the regulatory CK2β subunit. These studies suggest that the activation of caspase-3 could be regulated by CK2 in cells. Coupled with the observations that CK2 is constitutively activity and expressed at elevated levels in a number of different cancers, our observations suggest that increased levels of CK2 could lead to a pathological phosphorylation of pro-caspase-3 to prevent its activation and promote cancer cell survival. 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 4970. doi:1538-7445.AM2012-4970
Can nipple-areola-sparing mastectomy be an alternative to mastectomy? Over 10 years of follow up at a Japanese institution.
Authors: T Sakurai, T Umemura, E Jinta, S Shimizu, T Suzuma, G Yoshimura, T Sakurai
Journal: Cancer Research (2009)

Abstract Abstract #22 Introduction: Cosmetic outcome is one of the most important aspects of surgical treatment of breast cancer. Therefore, to maximize the cosmetic outcome for patients who require a mastectomy, what can be done from an oncologically safe perspective must be considered. Recent reports have suggested that nipple-areola-sparing mastectomy (NSM) is oncologically as safe as a classical mastectomy (MT) and provides a better cosmetic outcome than MT. However, little is known about the long-term outcome of NSM.&amp;#x2028; Aim: To determine the oncological and technical outcomes of NSM compared with MT using long term follow-up data.&amp;#x2028; Patients and Methods: We retrospectively analyzed 788 patients, median age 51 years, with primary breast cancer who underwent NSM from 1985 to 2004. The indication of NSM in this study was defined as being for any stage, any tumor size and any tumor-areola distance. Briefly, NAC was preserved when palpation and the outlook of the nipple was normal. Median tumor size and tumor-areola distance were 2.5cm (0-10.0) and 1.8cm (0-9.0), respectively. Our surgical notes for NSM were; (1) a thin flap (approximately 5 mm thick subcutaneous adipose tissue) was placed close to the tumor, and a thick flap (more than 1cm thick subcutaneous adipose tissue) was created more than 2cm away from the tumor to conserve breast volume using subcutaneous fat, and (2) tissue under the NAC was left at 5 mm in thickness, but the major ducts were removed from within its lumen. Eighty-one patients (10%) underwent immediate breast reconstruction (IBR) using implants. We also analyzed 144 patients with breast cancer who underwent MT in the same period as those who underwent NSM. No patient received radiotherapy. We compared the local recurrence rate (LRR), disease-free survival (DFS) and overall survival (OS) between 788 NSM and 144 MT cases.&amp;#x2028; Results: Median follow-up of NSM and MT was 92 (10-252) and 87 (0-231) months, respectively. To our surprise, no complications of NSM including nipple and areola necrosis were recorded (0/788). For NSM, there were 70 patients (8.9%) with local recurrence, including 23 (2.9%) at the nipple, 4 (0.5%) at the areola, 4 (0.5%) at both nipple and areola, and 39 at the skin flap (4.9%). This suggested that the rate of NAC relapse was quite low. There were no significant differences in LLR between NSM and MT, (10y, 8.9% vs. 7.6%, p=0.62), DFS (10y, 83% vs. 83%, p=0.34) and OS (10y, 88% vs. 86%, p=0.34), respectively. Cosmetic outcome of NSM was better than that of MT in the majority of patients.&amp;#x2028; Conclusion: These results suggested that NSM provides a good cosmetic outcome and is as safe oncologically as MT. Our long term follow-up data shows that NSM is a possible alternative to mastectomy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 22.
Loop observe and snare technique for endoscopic resection of a gastric inflammatory fibroid polyp
Authors: M. Ergun, N. Zengin, E. Kayacetin
Journal: Endoscopy (2012)

A 51-year-old woman with epigastric pain and weight loss underwent upper gastrointestinal endoscopy following admission to our hospital. The endoscopy revealed a large polypoid mass with a thick stalk at the gastric antrum. Endoscopic ultrasound showed a 3-cm, hypoechoic, homogeneous lesion with indistinct margins originating from the submucosal layer, without involvement of the muscularis propria ([Fig. 1]). We carried out endoloop (Olympus Optical Company, Tokyo, Japan) ligation and the loop was tightened around the stalk ([Fig. 2]). After 72 hours, a submucosal injection was given and snare excision carried out successfully ([Fig. 3]). The mucosal defect was closed with three hemoclips. Pathologic examination revealed spindle cells arranged in a concentric, onion skin-like formation in the submucosal layer, accompanied by inflammatory cell infiltration ([Fig. 4]). These findings were consistent with the diagnosis of an inflammatory fibroid polyp (IFP). The patient recovered uneventfully.
Abstract 4134: miR1288 in colorectal cancers: Altered expression and its clinicopathological significance
Authors: Vinod Gopalan, Ali Salajegheh, Robert A. Smith, Alfred K-Y Lam
Journal: Cancer Research (2012)

Abstract Introduction: MicroRNA-1288 (miR-1288) is a non-coding RNA located in 17p11.2 and not been studied solely in cancer. We aim to examine the miR-1288 expression in a large cohort of patients with colorectal carcinoma, adenoma and non-neoplastic colorectal tissues. The implications of miR-1288 expression and clinicopathological features were also studied. Methods: Tissues from 102 patients with surgical resection of colorectum (82 adenocarcinomas, 10 adenomas and 10 non-neoplastic tissues), two colon cancer cell lines (SW480 and SW48) and one normal colonic epithelial cell line (FHC) were recruited. miRNA was extracted from all these samples and were converted in to cDNA. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for the detection of miR-1288 expression. The results were correlated with the clinical and pathological data. Results: miR-1288 expression was decreased in majority of colorectal adenocarcinoma when compared to colorectal adenoma and non-neoplastic tissues. Reduced or absence expression of miR-1288 was noted in 78% (n=64) of the cancers. The colon cancer cell lines showed reduced expression of miR-1288 compared to normal colonic epithelial cell line. Distal colorectal cancers showed higher expression levels of miR-1288 than proximal cancers (p= 0.007). The expression levels of miR-1288 were significantly altered in different levels of cancer invasion (T staging) (p= 0.023). Conclusions: Altered expression pattern of miR-1288 in colorectal cancers compare to non-neoplastic tissues was identified. Also, differential regulation of miR-1288 was found to be related to location and pathological staging of colorectal cancers. 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 4134. doi:1538-7445.AM2012-4134
Biomarkers: The Clues to Genetic Susceptibility.
Authors: M Zeiger
Journal: Environmental Health Perspectives (1994)

There are approximately 500,000 cancer-related deaths annually in the United States. Scientists believe as that many as 80% of those deaths could be prevented due to the fact that most malignancies are a result of external factors rather than inherent biological conditions. With recent advances in molecular biology, a new field that combines highly sensitive and specific techniques for detecting early damage associated with cancer has emerged. By combining knowledge about external factors related to lifestyle and environmental or occupational exposure to chemicals with knowledge of how genetic differences cause variations in human responses to environmental pollutants, scientists are developing a better understanding of questions such as why some smokers get cancer but others do not, why certain groups of people have a higher incidence of cancer after exposure to a toxicant and others do not, and why certain women are more prone to develop breast cancer than others. Scientists using biomarkers of susceptibility will be able to identify risks and prevent adverse health effects through prevention and intervention strategies.
Détection de lésions néoplasiques colorectales par sonde endoscopique scintillante miniaturisée: étude de faisabilité in vivo dans un modèle murin de cancérogénèse colique
Authors: S Leblanc, P Anfre, G Burato, F Batteux, C Nicco, A Rouquette, C Chereau, E Noirault, B Hautefeuille, O Tillement, F Prat
Journal: Endoscopy (2012)

Une sonde miniaturisé ecapable de détecter des rayonnements gamma a été récemment développée en vue d'une application endoscopique pour aider à la détection de lésions néoplasiques du tractus digestif. Le but du projet était d'évaluer les performances diagnostiques de la sonde dans la détection radio-isotopique de lésions tumorales dans un modèle murin de cancer colorectal.
p38 MAPK is altered transcriptionally, translationally, and post-translationally in inflammatory breast cancer – significance and implications.
Authors: DT Rosenthal, CR Dambro, JC Brenner, Z Wu, SD Merajver
Journal: Cancer Research (2009)

Abstract Abstract #4061 Inflammatory breast cancer (IBC) is the most lethal form of breast cancer, with a 5-year survival rate below 45%. The disease progresses rapidly, and is typically identified as stage IIIb upon diagnosis. IBC is characterized by widespread invasion of the dermal lymphatics by tumor emboli, which results in lymphatic blockage. It is this blockage that leads to edema, erythema, and the subsequent “peau d'orange” appearance of the breast, and thus the misnomer “inflammatory” breast cancer.&amp;#x2028; Little is known about the mechanisms of IBC metastasis, and as such the treatments available to patients are limited. Our lab identified RhoC GTPase as an oncogenic driver of the IBC phenotype, as overexpression of RhoC in normal human mammary epithelial cells (HME) leads to increased motility, invasion, and secretion of angiogenic factors. Ensuing studies from our lab revealed that p38 is involved in mediating IBC metastasis and invasion, as demonstrated by the effects of p38 inhibitors on RhoC-transfected HMEs. The aim of the current project was to determine the means by which IBC utilizes p38, and elucidate the contributions of the specific p38 isoforms to IBC metastasis and invasion.&amp;#x2028; We demonstrate, for the first time, differences in the transcriptional, translational, and post-translational regulation of specific p38 MAPK isoforms in breast cancer, differences which delineate IBC from other invasive breast cancers, and invasive breast cancer from normal mammary epithelia. Furthermore, we show evidence that this upregulation is driven by RhoC overexpression. The contribution of each isoform to metastasis and invasion was then determined using isoform-specific expression vectors and RNA interference (RNAi). The results of this study will be useful in designing new drugs and therapies specific for IBC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4061.
AB0412 The frequency of metabolic syndrome and insulin resistance in women with rheumatoid arthritis
Authors: N. Aygun Bilecik, N. Samanci Karaman, N. Balci
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Metabolic syndrome (MS) is a multidisciplinary case including classic cardiovascular risk factors especially hypertension, obesity, glycosine tolerance and dyslipidemia. There are contradictory results in the literature about the frequency of MS in patients with Rheumatoid arthritis (RA). The purpose of this study is to study MS frequency and insulin resistance in patients with RA and also to examine the inflammation indicators of MS, disease activity, disease duration as well as the relationship with the medications taken. <h3>Methods</h3> The study included 100 female patients diagnosed with RA according to the diagnosis criteria of American Rheumatism Association that applied to Physical Medicine and Rehabilitation Department of the Faculty of Medicine of Akdeniz University. The control group was formed by 100 female cases without any inflammatory rheumatism disease at similar ages that applied to the same policlinic. All cases within the scope of the study were applied detailed systemic and muscle-skeleton system examination and their fasting blood glucose, triglyceride, HDL cholesterol, insulin, uric acid, fibrinogen, Hs-CRP and erythrocyte sedimentation rate (ESH) were monitored. Disease starting age and duration, medications taken and disease activity (evaluated with DAS-28) of RA patients were recorded. In all cases, MS presence was studied according to NCEP ATP III and IDF 2005 diagnosis criteria and also insulin resistance was studied by HOMA-IR method. <h3>Results</h3> When RA patients and control group was evaluated in respect to MS presence, it was detected that there was MS in 27% of RA patients and 28% of control group according to NCEP ATP III criteria and in 33% of RA patients and 44% of control group according to IDF 2005 criteria. In both methods, there was nostatistically significant difference between RA and control groups in respect of MS frequency. In respect of insulin resistance that was calculated by HOMA-IR, there was no statistically significant difference between RA patients and control group. When RA patients were evaluated by means of certain clinical and laboratory parameters within itself, it was found that ESH, serum uric acid and insulin levels in RA patients as well as the disease activity that was evaluated with DAS-28 and also HOMA-IR values were statistically higher than the ones without MS. Also MTX-treated patients was determined significantly lower in the presence of MS. <h3>Conclusions</h3> In conclusion, it was determined in this study that MS frequency in RA patients was similar to control group. In addition, it was found that serum uric acid and ESH levels and also disease activity was high in RA patients with MS. Consequently, controlling of inflammation and disease activity in RA patients can reduce MS frequency. <h3>Disclosure of Interest</h3> None Declared