tbuckley/cabot-search huggingface dataset:
THU0331 Outcome of Pregnancy in Patients with Systemic Lupus Erythematosus, Prevalence of Maternal, Obstetric, and Fetal Complications
Authors: H. Alkoky, N. Baghdadi, J. Al Saleh
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic disease affecting mainly women in childbearing age. Studies have shown that pregnancy in SLE women puts the mother and the fetus at risk of serious adverse events [1]. The prevalence of these events is under reported in the Arab countries. This study is to examine the pregnancy outcomes in patients with SLE. <h3>Methods</h3> We have retrospectively analyzed the medical files, and electronic medical records of all pregnant patients with SLE attended our Rheumatology Clinic between 2007 to 2014. All patients met ACR classification criteria for SLE. We have excluded patients diagnosed with DM, hypertension, chronic kidney disease before the onset of lupus. We captured the following data: patient demographic number of pregnancies after the onset of SLE, pregnancy outcomes, maternal complications during and after pregnancy. <h3>Results</h3> We identified 150 pregnancies in 64 patients with lupus, and 57 (89%) patients were Arabs. The total number of live birth was 105 (70%). An adverse fetal event was observed in 48 (32%) pregnancies. Total number of miscarriages was seen 43 (28.6%), six (4%) were induced abortions. Two died in utero (1%) and there was one neonatal death (1%). 44 (29%) were born below 2,500g, four were premature (less than 37 weeks) (3%), intrauterine growth retardation was observed in 19 (12.6%) and four born with malformation (3%). Obstetric complications occurred in 30 (20%) pregnancies, 5 (3%) had pre-eclampsia, 5 (3%) had gestational diabetes, and one had postpartum hemorrhage (1%). Maternal complications were detected in 20 (13.3%) pregnancies, lupus flare was observed in 18 (12%), five had thrombosis (3%), and no death. <h3>Conclusions</h3> Pregnancy in lupus is often associated with an adverse maternal and fetal outcome independent by disease activity. <h3>References</h3> Josephine Patricia Dhar, and Robert J. Sokol, Lupus and Pregnancy: Complex Yet Manageable. Clin Med Res. 2006; 4(4): 310–321. <h3>Disclosure of Interest</h3> None declared
Aberrant Expression of the MLL5, BAALC, ID1, and WT1 Genes Is Associated with Higher Induction Mortality and Poorer Overall Survival in Acute Promyelocytic Leukemia Patients Treated with ATRA and Anthracycline-Based Chemotherapy: An International Consortium On Acute Promyelocytic Leukemia Study
Authors: Antonio R Lucena-Araujo, Rafael Henriques Jacomo, Haesook T Kim, Raul A Melo, Rosane Bittencourt, Ricardo Pasquini, Katia B. Pagnano, Evandro Fagundes, Maria de Lourdes L. F. Chauffaille, Carlos S Chiattone, Hau C. Kwaan, Robert E. Gallagher, Charlotte M Niemeyer, Stanley L. Schrier, Martin S Tallman, David Grimwade, Arnold Ganser, Nancy Berliner, Raul Ribeiro, Roberto P. Falcao, Francesco Lo-Coco, Bob Löwenberg, Miguel Angel Sanz, Eduardo M Rego
Journal: Blood (2012)
Pregnancy Outcomes in Women With Diabetes—Lessons Learned From Clinical Research: The 2015 Norbert Freinkel Award Lecture
Authors: Elisabeth R. Mathiesen
Journal: Diabetes Care (2016)

Among women with diabetes, the worst pregnancy outcome is seen in the subgroup of women with diabetic nephropathy. Development of severe preeclampsia that leads to early preterm delivery is frequent. Predictors and pathophysiological mechanisms for the development of preeclampsia among women with diabetes and observational studies that support antihypertension treatment for pregnant women with microalbuminuria or diabetic nephropathy preventing preeclampsia and early preterm delivery are presented here. Obtaining and maintaining strict glycemic control before and during pregnancy is paramount to prevent preterm delivery. The cornerstones of diabetes management are appropriate diet and insulin, although the risk of severe hypoglycemia always needs to be taken into account when tailoring a diabetes treatment plan. Pathophysiological mechanisms of the increased risk of hypoglycemia during pregnancy are explored, and studies evaluating the use of insulin analogs, insulin pumps, and continuous glucose monitoring to improve pregnancy outcomes and to reduce the risk of severe hypoglycemia in pregnant women with type 1 diabetes are reported. In addition to strict glycemic control, other factors involved in fetal overgrowth are explored, and restricting maternal gestational weight gain is a promising treatment area. The optimal carbohydrate content of the diet is discussed. In summary, the lessons learned from this clinical research are that glycemic control, gestational weight gain, and antihypertension treatment all are of importance for improving pregnancy outcomes in pregnant women with preexisting diabetes. An example of how to use app technology to share the recent evidence-based clinical recommendations for women with diabetes who are pregnant or planning pregnancy is given.
Impact Of p53 Impaired Function On Outcomes Of Multiple Myeloma Patients Carrying Deleted TP53 and/Or Amplified MDM4
Authors: Carolina Terragna, Marina Martello, Enrica Borsi, Lucia Pantani, Elena Zamagni, Paola Tacchetti, Brioli Annamaria, Beatrice Anna Zannetti, Flores Dico, Nicoletta Testoni, Giulia Marzocchi, Katia Mancuso, Serena Rocchi, Giovanni Martinelli, Michele Cavo
Journal: Blood (2013)
Decline in Sexual Functioning Over a 3-Year Period after Hematopoietic Cell Transplantation (HCT): Gender-Specific Impact of Total Body Irradiation (TBI) and Chronic Graft-Versus-Host Disease (cGvHD)
Authors: F. Lennie Wong, Stephen J. Forman, Liton Francisco, Mitzi Gonzales, Melanie Sabado, Cara Hanby, Smita Bhatia
Journal: Blood (2008)
PTU-020 Post Endoscopy Missed Gastrointestinal Cancer at a Local DGH - Implications for Practice
Authors: S Sultan, I Salehi, G Williams, I Jaly, H Khadim, MI Yahya, A El-Sayed, M Mirzaali, J Rademaker
Journal: Gut (2016)

<h3>Introduction</h3> Upper gastroenterology tract cancers (UGIT) are the 4 th commonest malignancy worldwide. The best treatment remains early detection allowing for prompt intervention. Oesophagogastroduodenoscopy (OGD) is the gold standard of diagnosing UGIT cancers however it remains imperfect. There is still a substantial rate of missed UGIT cancers at endoscopy. It is estimated that in the UK the national rate of missed UGIT cancers is 7.2%. It is important that endoscopic techniques undergo regular review ensuring a process of continuous quality improvement. Our aim is to review the missed rate of cancers after a negative OGD examination and to explore the reasons behind this and to propose methods of reducing the rate of missed cancers. <h3>Methods</h3> A retrospective case analysis over a five year period (2010–2015) investigating patients who received a diagnosis of UGIT cancer at our local district general hospital. We used our local clinical databases in identifying relevant patients who had been investigated with a negative endoscopy in the prior year but then went on to receive a diagnosis of colorectal cancer. <h3>Results</h3> 415 patients (F 143; M 272) were audited with an average age of 76 (range 31–102). 31 patients were excluded as cancer diagnosis was discovered by other means (CT, ERCP and emergency operations). Of the 415 patients audited 54 (14%) were investigated with an OGD in the prior year which was negative. We also investigated the presenting pathway and found that the majority of patients (166; 28%) were presenting through the urgent suspected cancer pathway. <h3>Conclusion</h3> Our results show a high rate of missed lesions on initial endoscopy. This has serious implications for practice and suggested published reasons for this are largely thought to be the variability in experience of the endoscopist. To that end it is our recommendation that training for OGD be prolonged. There is also a large variability in reporting of the procedure therefore following a more standardised approach is advocated. Also operators are strongly encouraged to take multiple biopsies of lesions that appear suspicious. Finally we would like to implement a strict, rigorous follow up system whereby patients presenting with alarm symptoms and a negative OGD can be followed up with repeat procedures to ensure no cancers are missed. <h3>References</h3> 1 Yalamarthi S, Witherspoon P, McCole D, Auld CD. Missed diagnosis with upper gastrointestinal cancers. <i>Endoscopy</i> 2004;<b>36</b>(10):874–9. 2 Gado A, Ebeid B. Gastric cancer missed at endoscopy. <i>Alexandria Journal of Medicine</i> 2013;<b>49</b>(1):25–27. 3 Enns R. Missed cancers in the upper gastrointestinal tract after esophagogastroduodenoscopy. <i>Gastroenterol Hepatol</i> 2010;<b>6:</b>691–693. <h3>Disclosure of Interest</h3> None Declared
Inhibition of Retinoic Acid Receptor Signaling by SKI in Acute Myeloid Leukemia.
Authors: Markus Ritter, Magnus Samuelsson, Oliver Hartmann, Andreas Burchert, Theo D. Kim, Christian Thiede, Micheal J. Hayman, Nobuhide Ueki, Martin Eilers, Andreas Neubauer
Journal: Blood (2004)
Bcr strongly inhibits the tumorigenic effects of Bcr-Abl but mutant Bcr proteins lack inhibitory effects and enhance Bcr-Abl oncogenic effects.
Authors: Bastianella Perazzona, Ralph Arlinghaus
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5281 

BCR-ABL oncoprotein is responsible for causing chronic myeloid leukemia (CML). BCR-ABL transforming ability is acquired through its up-regulated Abl tyrosine kinase activity. Bcr is a 160,000 phosphoprotein with a serine/threonine kinase activity localized in its first exon. Perturbation of normal Bcr functions by oncogenic Bcr-Abl protein is important in the generation of CML (Arlinghaus, Oncogene 2002). We have shown that over-expression of BCR interferes with BCR-ABL oncogenic effects. Bcr-Abl phosphorylates endogenous Bcr protein on various tyrosine residues reducing its serine/threonine kinase activity (Liu et al. Mol. Cell. Bio., 1996). However, when in molar excess Bcr is resistant to tyrosine phosphorylation and it is mostly in the phosphoserine form (Wu et al, Oncogene 1999). We studied BCR activity in the TonB210 cell line in which BCR-ABL expression is tightly regulated and under the control of a tetracycline-dependent expression system. GFP alone or BCR/GFP were transduced into TonB210 cells by using a bi-cistronic lentivirus system. In a nude mouse tumor model, we showed that single clones of BCR-ABL/BCR-GFP TonB210 cells injected in nude mice produced tumors at a very low frequency. Appearance of tumors was much delayed and they were 50% smaller compared to the BCR-ABL/GFP only group. TonB210/BCR-ABL/BCR-GFP cells had little colony forming ability in soft agar compared to GFP only expressing cells. Two different BCR point mutants were created: S354A and Y360F. These disrupt the ability of Bcr to be in the hyper-phosphorylated form, required for its inhibitory function (Hawk et al., Cancer Res., 2002), or to function as a kinase, respectively. These mutants showed dramatic effects on TonB210 cells when injected in doxicycline fed mice to induce Bcr-Abl. Tumors developed in eighty five percent of the injected sites as early as ten days after injection at time when controls formed no tumors and despite the fact that lower amounts of Bcr-Abl protein were detected by western in these mutants. It seems that the S354A BCR mutant is involved in the degradation of most but not all the Bcr-Abl protein yet the remaining Bcr-Abl is highly active, as evident from its pTyr content and its ability to maintain TonB210 cells without IL-3. These results indicate that these Bcr mutants lack inhibitory activity against Bcr-Abl, and that the mutant proteins are functioning as dominant-negative (DN) forms of Bcr. We hypothesize that these DN Bcr proteins block the inhibitory effects of endogenous Bcr. Our previous findings have shown that Bcr functions as an inhibitor of Bcr-Abl oncogenic effects in the phosphoserine form but tyrosine-phosphorylated BCR is neutralized as an inhibitor of BCR-ABL effects (Lin et al., Oncogene 2001). Surprisingly the DN forms of Bcr unleash what appears to be the full oncogenic potential of P210 BCR-ABL.
Abstract #1014: Concordance of plasma and tumor DNA methylation in Egyptian patients with hepatocellular carcinoma
Authors: Priyanka Thummalapally, Abdel-Rahman Zekri, Kadry Ismail, Ahmed Hablas, Ibrahim Seifeldin, Hoda Omar, Amr Soliman
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Hepatocellular carcinoma (HCC) is the fifth most common solid malignancy in the world and the fourth leading cause of cancer-related mortality. The age-adjusted worldwide annual incidence is between 5.5 and 14.9/100,000, resulting in approximately 600,000 to 1,000,000 deaths annually. The burden of HCC has been increasing in Egypt with the incidence rate doubling in the past 10 years, and HCC is now the second highest cause of cancer incidence and mortality in men. The high HCC rates in Egypt are attributed to the high prevalence of Hepatitis C virus (HCV). Hepatitis B virus (HBV) rates have declined after the introduction of the vaccine in 1992. Recent studies have shown that aberrant DNA methylation may play an important role in hepatocarcinogenesis. Liver biopsy tissue is the current gold standard for detecting methylation events; however, imaging techniques often suffice for diagnostic purposes making tissue samples increasingly scarce. Large-scale epidemiological and molecular studies are needed to understand the role of methylation in carcinogenesis, so non-invasive detection techniques are urgently needed to feasibly conduct these studies. The efficacy of conducting DNA methylation studies using plasma DNA is still unknown. The objective of this study was to compare the tumor methylation profile in tumor tissues and plasma to test the concordance between the two types of samples from the same HCC patient. The methylation profiles for the following tumor suppressor genes were compared: APC, FHIT, p15, p16, and E-cadherin. Twenty eight HCC cases with matching tissue and plasma DNA were recruited from an ongoing case-control study in Garbiah, Egypt. Concordance between the tissue and plasma were statistically significant in all five genes: APC (P=.001), FHIT (P=.001), p15 (P=.045), p16 (P=.037), and E-cadherin (P=.0008). The average specificity was: 90%, 86%, 96%, 86%, 100%, for the 5 genes respectively. No difference in methylation status was observed by viral status. In conclusion, plasma DNA can be reliable for testing the methylation profile in liver cancer patients. Future studies on a larger sample size should investigate the methylation profile in populations with higher rates of HBV, HCV, and other risk factors. Supported by R-25 CA112383 grant from the National Cancer Institute.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1014.
AB0139 Interleukin-21 Is Overexpressed in Kidney Tissue from Lupus Nephritis Patients and Its Serum Levels Are Correlated with Systemic Lupus Erythematosus Disease Activity
Authors: J.-M. Kim, H.-J. Jeong, S.-H. Kim, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Interleukin-21 (IL-21) has various effects on a number of immune cells including B cells, T cells, natural killer (NK) and NKT cells. One of the essential roles of IL-21 is to contribute to autoantibody production as a result of promoting hyperactivity of B cells. Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by pathogenic autoantibody production and systemic organ damage. A few studies have been conducted for investigating the contribution of IL-21 to the pathogenesis of murine SLE. However, only limited studies have been performed concerning the role of IL-21 in human SLE and the results are still controversial. <h3>Objectives</h3> The aim of this study was to evaluate whether IL-21 participates in the pathogenesis of human SLE. <h3>Methods</h3> Serum IL-21 levels were measured in SLE, osteoarthritis (OA) patients and healthy controls (HC). Serum IL-21 levels were analyzed for revealing the correlation with laboratory data or a disease activity index for SLE. Kidney tissues from patients with lupus nephritis and controls were used for evaluating the expression of IL-21 and IL-21R. Normal portions of human kidneys removed for renal carcinoma were used as normal controls. <h3>Results</h3> Serum levels of IL-21 were increased in the patients with SLE as compared to the patients with OA or HC. Serum IL-21 levels of the patients with SLE were positively correlated with serum levels of IgG, the titers of anti–double-stranded DNA antibodies and the scores of SLE Disease Activity Index. SLE patients with low C4 concentrations had higher serum IL-21 levels than those with normal C4 concentrations. The expression of IL-21 was higher in renal tubular epithelial cells of the patients with lupus nephritis than in those of controls. <h3>Conclusions</h3> This study reveals the association between IL-21 and disease activity in the patients with SLE. We also first demonstrate IL-21 expression in renal tissue of the patients with lupus nephritis. These findings suggest that IL-21 is critically implicated in the pathogenesis of SLE. <h3>References</h3> Ettinger R, Kuchen S, Lipsky PE: Interleukin 21 as a target of intervention in autoimmune disease. Annals of the rheumatic diseases 2008, 67 Suppl 3:iii83–86. Herber D, Brown TP, Liang S, Young DA, Collins M, Dunussi-Joannopoulos K: IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. Journal of immunology 2007, 178(6):3822–3830. <h3>Disclosure of Interest</h3> None declared
PTU-147 Regulation of MMP-7 Expression in The Progression to Oesophageal Adenocarcinoma
Authors: HM Garalla, N Lertkowit, L Tiszlavicz, Z Reisz, G Dockray, A Varro
Journal: Gut (2016)

<h3>Introduction</h3> The incidence of oesophageal adenocarcinoma (AC) has increased at an alarming rate in the past few decades; the most important risk factor is Barrett’s oesophagus (BO). Matrix metalloproteinase (MMP)-7 has been linked to progression in this and many other epithelial cancers; expression of MMP-7 is typical associated with epithelial cells but the regulatory mechanisms remain uncertain. Our aim was to evaluate the pattern of expression of MMP-7 in AC and the mechanisms regulating its expression in an AC cell line. <h3>Methods</h3> Surgically resected tumours and adjacent tissue from 14 patients with AC were stained with a mouse monoclonal anti-human MMP-7 antibody. Stromal and epithelial compartments were scored separately for staining intensity on a four point scale (0–3) and the percentage of stained cells at each intensity recorded. Western blot and indirect ELISA were applied to an oesophageal adenocarcinoma cell line (OE33 cells). Data are expressed as mean ± SE and comparisons were made by ANOVA or t test as appropriate. <h3>Results</h3> MMP-7 was localised to carcinoma cells in all AC cases (80 ± 3% cells scored 2 for intensity), and was strongest in tumour cells at the invasive front (93 ± 1% cells scored 3). There was also expression in epithelial cells in adjacent premalignant lesions of BO (78 ± 4% cells scored 1), but &lt;50% of normal epithelial cells were MMP-7 positive. In the stroma, putative myofibroblasts identified as spindle-shaped cells that expressed MMP-7 were abundant in the invasive part of the tumour (75 ± 7% cells scored 3) whereas they were scarce or absent in adjacent tissue. In OE33 cells, there was high constitutive secretion of MMP-7 that was inhibited by blocking vesicular trafficking with brefeldin A, but not by inhibitors of protein kinase C or MAP kinase activation. However, the phosphatidylinositol (PI) 3 kinase inhibitor, LY294002, significantly inhibited MMP-7 secretion detected by both Western blot and ELISA (secretion in 6 h: 0.7 ± 0.1 nM vs 0.40 ± 0.1 nM, p &lt; 0.002). MMP-7 secretion was similarly inhibited by another PI 3 kinase inhibitor, TG100713 and by MK2206 which inhibits the downstream mediator of PI 3 kinase, Akt. However, the mTOR inhibitor, rapamycin, had no significant effect on MMP-7 expression. <h3>Conclusion</h3> MMP-7 expression increases at the invasive front in AC where it is also expressed in stromal spindle-shaped cells. High constitutive expression of MMP-7 in an AC cell line is partly attributable to activation of PI 3 kinase and Akt. <h3>Disclosure of Interest</h3> None Declared
The Histone Deacetylase-8 (HDAC8) Selective Inhibitor PCI-34051 Decreases Interleukin-1 Beta Secretion in Vitro and Reduces Inflammation in Vivo
Authors: Sriram Balasubramanian, Susanne Steggerda, Mint Sirisawad, Marshall Schreeder, Luke Doiron, Joseph J Buggy
Journal: Blood (2008)
Novel DNA Copy Number Changes in Hematological Malignancies: A cDNA-Based CGH Microarray Screening of CML, AML and CLL Cases without Chromosomal Imbalances in G-Banding.
Authors: Tuija Lundan, Anne Oikarainen, Lena Hafren, Maija Wolf, Erkki Elonen, Juhani Vilpo, Kimmo Porkka, Sakari Knuutila
Journal: Blood (2004)
Cbl and TET2 Mutations Are Present in Refractory Ph+ Disorders Including Accelerated and Blast Crisis CML and ALL.
Authors: Hideki Makishima, Anna M. Jankowska, Heather Cazzolli, Bartlomiej P Przychodzen, Courtney Prince, Siddaiah Harish, Heesun J. Rogers, Eric D. Hsi, Michael A McDevitt, Anjali Advani, Ronald Paquette, Jaroslaw P. Maciejewski
Journal: Blood (2009)