tbuckley/cabot-search huggingface dataset:
Abstract ES3-3: Management of Women with a High Predisposition to Breast Cancer: Standard of Care
Authors: SM Domchek
Journal: Cancer Research (2010)

Abstract Women who have inherited germ line mutations in BRCA1 and BRCA2 are at significantly increased risk for breast and ovarian cancer. Fortunately, our understanding of the management of BRCA1 and BRCA2 mutation carriers has increased significantly in the 15 years since these genes were identified. There have been improvements in genetic testing techniques resulting in fewer “missed” BRCA1 and BRCA2 mutations, as well as a better understanding of the risks of these mutations. Incorporating breast MRI into screening results in earlier detection of breast cancer. Prophylactic mastectomy significantly reduces breast cancer risk, while improvements in reconstructive surgery allow women more options. Risk reducing salpingo-oophorectomy in BRCA1/2 mutation carriers decreases breast cancer risk, ovarian cancer risk and improves breast cancer specific-, ovarian cancer specific-and overall survival. Emerging data suggest that BRCA1/2 mutation testing can play a role in newly diagnosed breast cancer, particularly from the standpoint of surgical decision making. Finally, knowledge of BRCA1 and BRCA2 mutation status has the potential to impact decisions on systemic therapy as will be reviewed. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES3-3.
P56 * CONVECTION-ENHANCED DELIVERY (CED) OF CARBOPLATIN NANOSPHERES FOR THE TREATMENT OF GLIOBLASTOMA
Authors: A. Arshad, B. Yang, A. Bienemann, N. Barua, S. Gill
Journal: Neuro-Oncology (2014)

INTRODUCTION: We are currently investigating CED of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioma in adults and children. Although initial results show significant promise, our current treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. Furthermore, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations. We sought to encapsulate carboplatin in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system with improved safety and persistence within the brain and increased cancer cytotoxicity. METHOD: We compared the neuronal and tumour cytotoxicity of free carboplatin with encapsulated carboplatin in primary neuronal and GBM cultures. We studied distribution, tissue clearance and toxicity of carboplatin nanospheres following intrastriatal CED in rats. RESULTS: Encapsulation of carboplatin in PLGA nanospheres conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life compared with the free drug. CONCLUSION: Encapsulation of carboplatin in PLGA onfers increased safety, with significant increases in tumour cytotoxicity and persistence within the brain. Further investigation is required to determine the translational potential of using PLGA encapsulated-carboplatin as a novel anti-glioma treatment strategy.
Case 66-1962
Authors: Frank C. Wheelock, Benjamin Castleman
Journal: New England Journal of Medicine (1962)

Presentation of CaseA forty-four-year-old man was referred to the hospital because of hematemesis.Weakness of insidious onset began three months previously, and two weeks before admission the patient stopped working because of weakness and faintness. Later in the day he passed a large, tarry stool and subsequently experienced two episodes of hematemesis. He entered another hospital, where examination revealed marked hepatomegaly and a hemoglobin of 5 gm. per 100 ml. He continued to pass tarry stools, unaccompanied by hematemesis, for several days; after four transfusions of blood the hemoglobin rose to 7.7 gm. per 100 ml.The patient stated . . .
Case 43-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, H.C. Meissner, M.S. Pasternack
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 3 1/2-year-old boy was admitted to the hospital because of pharyngitis, fever, rash, and cervical lymphadenopathy.The child was born to a 21-year-old woman by spontaneous vaginal delivery after a full-term second pregnancy; the pregnancy and delivery were uncomplicated; the birth weight was 4.3 kg. The child's early growth and development were normal. He had recurrent bouts of otitis media during the first year of life, but drainage tubes were not required. He was otherwise well until 1 1/2 years before entry, when he was admitted to another hospital for treatment of pneumonia of the right . . .
SAT0275 Almost 40% of patients with chronic back pain starting before the age of 45 fulfill the asas axial spondyloarthritis criteria:
Authors: M. de Hooge, R. van den Berg, F. van Gaalen, M. Reijnierse, T. Huizinga, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chronic back pain is a very prevalent complaint in the general population but only a small proportion of these patients suffer from spondyloarthritis (SpA). Unfortunately, it is not clear when primary care or other physicians should refer a patient with chronic back pain to a rheumatologist. Many rheumatologists fear their practices will be overloaded with patients not having SpA if they have to see all patients with chronic back pain. Some have recommended inflammatory back pain (IBP) as the referral symptom but this is not an ideal criterion since many patients with SpA do not have IBP<sup>1</sup>. <h3>Objectives</h3> To describe how many patients with chronic back pain referred to the rheumatology outpatient clinic fulfill at least one of the classification criteria sets for spondyloarthritis (SpA). <h3>Methods</h3> We started the SpondyloArthritis Caught Early (SPACE)-project and included all (n=157) patients with chronic back pain (almost daily ≥3 months), starting before the age of 45 years of short duration (≤2 years). Patients were classified according to the modified New York (mNY), European SpA Study Group (ESSG), Amor and ASAS axial SpA classification criteria sets. <h3>Results</h3> In total, 93 (59.2%) patients fulfilled any of the criteria sets. Twelve (7.6%) patients fulfilled the mNY criteria; 68 (43.3%) patients fulfilled the ESSG criteria, 44 (28.0%) the Amor criteria and 60 (38.2%) the ASAS criteria for axial SpA. The overlap of the criteria is presented in the table. Eight of the 12 patients who fulfill the mNY criteria also fulfilled all the other criteria sets. The one patient only fulfilling the mNY criteria and no other criteria sets has "night pain" as only SpA feature. <h3>Conclusions</h3> Approximately 60% of the patients included in the SPACE-cohort fulfill at least one of the SpA criteria sets; 38% fulfill the ASAS axial SpA criteria. The selection criteria as used in the SPACE-project are easily applicable and work very well. Almost daily chronic back pain of short duration starting before the age of 45 years (in accordance with the entry criterion of the ASAS axial SpA criteria) appears to be a very good and simple referral strategy at a rheumatology department, with a high yield of patients with SpA. <h3>References</h3> van den Berg R. Submitted to EULAR2012 under identifier EULAR12-1485 <h3>Disclosure of Interest</h3> None Declared
UEGW 2011 Report: Putting endoscopy into perspective
Authors: I. Papanikolaou, T. Rösch
Journal: Endoscopy (2012)

The 18th United European Gastroenterology Week (UEGW), held in Barcelona in October 2010, marked a return to the traditional "stand-alone" UEGW meeting after the previous year's combined congress format of GASTRO 2009. Various abstracts on endoscopic subjects were presented, providing a unique opportunity for those interested in gastrointestinal endoscopy to not only become acquainted with the latest advancements and research in the field, but also to meet and exchange experiences with colleagues from all over the world. This report will focus mainly on oral presentations, with a few selected poster presentations, which will be reviewed briefly in the context of recent literature in the respective fields of gastrointestinal endoscopy.
Peristaltic Waves in Pyloric Stenosis
Authors: Gabriel Altit, Marcel Milot
Journal: New England Journal of Medicine (2013)

A 5-week-old full-term male infant presented to our institution with a history of multiple episodes of projectile, nonbilious vomiting. Laboratory investigations revealed a hypokalemic, hypochloremic metabolic alkalosis. On physical examination, an olive-shaped mass that was 2 cm long was palpated in the lower inner aspect of the right upper quadrant, and abdominal peristaltic waves were observed (see Video). Ultrasonography showed pyloric stenosis. Infantile pyloric stenosis causes gastric-outlet obstruction caused by hypertrophy of the pylorus. The diagnosis is currently made on the basis of the clinical history and ultrasonographic measurements of pyloric thickness. The classic pathognomonic signs of this disorder (a . . .
PSYCHOPHARMACOLOGIC STUDY OF SCHIZOPHRENIA AND DEPRESSION
Authors: J. S. GOTTLIEB, J. R. KNOTT, L. L. KIMBLE
Journal: American Journal of Psychiatry (1948)

1. Nine patients, 4 with depression, 5 with schizophrenia, were studied with respect to changes in the beta activity of the EEG induced by the intravenous injection of sodium amytal mg. 250 (with racemic amphetamine sulfate mg. 20). These changes were measured on 5 consecutive days prior to a course of electric convulsive therapy. They were again studied in a single session, after this course of treatment. 2. There was observed to be a striking increase in beta activity after the injection. This increase was greatest in the frontal EEG, least in the occipital EEG, forming an anterior-posterior per cent time gradient, which was an accentuation of the preinjection gradient. 3. There was no systematic electrocortical tolerance developed in either group, to the drug, over a 5-day period. The schizophrenic group, however, developed the usual psychological tolerance. 4. After a course of electric convulsive therapy there was a decrease in percent time beta; the response of beta to sodium amytal was greatly reduced, particularly in the fronral area. 5. These data suggest that the electrocortical response measured (per cent time beta) and the psychologic state are reflections of the activity of different neural systems.
Abstract 2588: Affitoxin - A novel approach to HER2-targeted therapy
Authors: Rafal J. Zielinski, Ilya Lyakhov, Monika Kuban, Jacek Capala
Journal: Cancer Research (2010)

Abstract Expression of the human epidermal growth factor receptor 2 (HER2) is amplified in 25 −30% of breast cancers and has been associated with unfavorable prognosis. In spite of the development of new HER2-targeted therapies, such as trastuzumab (Herceptin®; Genentech, Inc., South San Francisco, CA), which has revolutionized the treatment of HER2-overexpressing breast cancers, there is a significant number of patients with HER2-positive tumors who do not respond or acquire resistance to these therapies. An alternative treatment maybe constituted by immunotoxins. Immunotoxins are hybrid proteins composed of a targeting moiety such as an antibody, antibody fragment or ligand directed to an antigen or a receptor on the surface of tumor cells, and a toxic domain derived form plant (ricin) or bacteria (diphtheria toxin or Pseudomonas aeruginosa exotoxin A). The targeting moiety directs the toxin moiety to the tumor cell and, then, the active domain induces apoptosis by inhibition of protein synthesis. The PE38, which is a truncated version of Pseudomonas exotoxin A (PE), is preferred for construction of immunotoxin because its high toxic potential has been well documented and cytotoxic pathways described and understood. Affitoxins are immunotoxin derivatives containing Affibody molecule as a targeting moiety instead of antibodies or antibodies fragments. Affibody molecules are a new class of relatively small (∼7-kDa) affinity proteins. Structurally, they are based on a 58-amino-acid scaffold, derived from the Z domain of the Staphylococcus aureus protein, and were obtained by combinatorial protein engineering. Previously we reported construction, overxpression and characterization of Affitoxin targeting tumors with HER2 overexpression. Receptor-dependent binding and tumorocidal activity was confirmed on cell lines varying with receptor number. Both binding and toxicity was reverted when excess of Affibody molecules (acting as a competitor) was applied. Here we report in vivo characterization of HER2 -Affitoxin. First we show that Affitoxin is well tolerated in athymic mice. Pharmacokinetic analysis indicates relatively short half-life of Affitoxin in the circulation most probably due to rapid renal clearance which seems to be compatible with fast binding of Affitoxin to HER2. Finally we show that HER2-Affitoxin is potent agent that leads to elimination of breast and ovarian xenografts (BT474 and SKOV3 s.c. tumors), while no such an effect was observed for off-target Affitoxin applied in the same concentration. Immunogenic potential of HER2 Affitoxin was also evaluated. We conclude that our HER2-Affitoxin has potential to become an attractive alternative in treatment of tumors associated with expression of HER2 receptors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2588.
Focal Hepatic 11C-Acetate Activity on PET/CT Scan Due to Lymphoid Hyperplasia
Authors: Li Huo, Yonghong Dang, Ruie Feng, Jingqiao Lv, Fang Li
Journal: Clinical Nuclear Medicine (2014)

A 69-year-old woman complaining of abdominal bloating underwent ultrasonography, which revealed a small lesion in the left lobe of the liver. The lesion had elevated activity of both 18F-FDG and 11C-acetate on PET/CT scan and was suspected of being malignant. Postresection pathological examination demonstrated that this lesion was a focal intrahepatic lymphoid hyperplasia.
Abstract 3942: Novel mechanism for inactivation of the DNA damage response during apoptosis
Authors: Stéphanie Solier, Yves Pommier
Journal: Cancer Research (2010)

Abstract Apoptosis, programmed cell death, is required in multicellular organisms for various physiological processes. Disruption of the equilibrium between cell death and proliferation is one of the mechanisms of tumor formation. Therefore, one of the challenges and one of the ongoing approaches for cancer therapy is to develop pro-apoptotic agents. One such agent is TRAIL (Tumor necrosis factor-Related Apoptosis-Inducing Ligand), a promising therapy in development because it induces apoptosis preferentially in cancer cells compared to normal cells. We recently identified the “apoptotic ring”, a previously unnoticed process of cellular apoptosis by the nuclear peripheral staining of phosphorylated DNA damage response (DDR) proteins including γ-H2AX, ATM, DNA-PK and Chk2. The γ-H2AX apoptotic ring forms in the early phase of the apoptotic response to a broad range of stimuli including TRAIL in different cell types. It differs from the focal pattern response (DDR nuclear foci) to DNA damaging agents. Because γ-H2AX is a fundamental chromatin modification in response to DNA double-strand breaks and serves as a molecular platform for the docking of DDR protein complexes and for amplifying the DDR, we were particularly interested to determine whether the apoptotic γ-H2AX response led to the full recruitment of the DDR factors. Here we looked at MDC1 (mediator of DNA damage checkpoint 1) which normally binds to γ-H2AX in response to DNA damage and amplifies the DDR. We will report that during TRAIL-induced apoptosis, MDC1 does not exhibit an apoptotic ring. Lately a new phosphorylation of histone H2AX on tyrosine 142 (P-Y142-H2AX) has been described, thereby preventing the binding of MDC1 to γ-H2AX. However, we find that Y142 phosphorylation is reduced in response to TRAIL and uncovered a novel mechanism to explain the inactivation of MDC1-mediated transduction of the DDR during apoptosis. Indeed, we demonstrate for the first time that MDC1 is cleaved by caspase-3 during apoptosis, separating the FHA (forkhead-associated) and the BRCT (breast cancer C-terminal) domains, and consequently disrupting the linkage to γ-H2AX and other DNA damage responsive proteins. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3942.
SAT0423 Benefits of Rehabilitation Program in Patients with L5-S1 Degenerative Foraminal Stenosis
Authors: M. R. Traistaru, O. Rogoveanu, R. Popescu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Degenerative foraminal stenosis (DFS) is one the three anatomically locations of degenerative lumbar spinal stenosis (1) and more frequently involves the L5 nerve root (L5 – S1 foramen is the one with the smaller foramen / root area ratio) (2). The treatment options are adapted to clinical and functional status, generated by the severity of pressure on the nerve root complex by the degenerative changes (1, 3). <h3>Objectives</h3> The purpose of our randomized controlled study was to compare outcomes between the conservative therapies (activity modifications, medications and physical treatments) and the pharmacotherapy in patients with moderate symptomatic DFS (L5-S1 foramen). <h3>Methods</h3> 66 patients with L5 – S1 DFS were randomly assigned to a conservative treatment group – CG (n=36; 23 males, 13 females; mean age [±SD] = 54 ± 8 years) or a pharmacotherapy group – PG (n=28, 15 males, 13 females; mean age [±SD] = 56 ± 7 years). All patients were completely assessed (patient’s description of their symptoms - Konno self-administered diagnostic tool, physical and radiological examinations and functional assessment - The Roland-Morris Disability Questionnaire). Subjects in the CG received activity modifications, medications (similar to PG) and physical therapy (supervised exercise - twice daily stretching and adapted strengthening for lumbar spine, over a 6-week period; in addition we recommended lumbar bracing and performed ultrasounds, TENS and hot packs for 2 weeks). Measured outcomes were the generic QoL scale SF-MOS (Short Form Medical Outcomes Study) and the Roland-Morris Disability Questionnaire (RMDQ) score. Differences parameter values between groups were tested by ANOVA test. <h3>Results</h3> Both groups showed clinically and statistically significant improvements in SF-MOS and RMDQ scores at 6 weeks (SF-MOS scores had improved by 43% in the CG and by 21% in the PG; RMDQ scores had improved over 25% in both groups). At 3 months, patients in the CG clinic were more satisfied with the overall outcome of their rehabilitative treatment compared with subjects in the PG. <h3>Conclusions</h3> Although both groups improved by 6 weeks, subjects in the CG achieved about twice as much improvement in SF-MOS scores than subjects in PG. The results indicate that a conservative treatment in moderate symptomatic DFS patients had not only effect on pain and function lumbar status but also a long term effect on perceived recovery. More randomly studies investigating conservative an surgical treatments in all degenerative spinal stenosis are required. <h3>References</h3> Genevay S., Atlas S.J., Best Practice and Research Clinical Rheumatology 24 (2010): 253 – 265. Jenis L.G., An H.S., Spine 2000; 25 (3):389 – 394. Konno S., Kikuchi S., tanaka Y., et.al., BMC Musculoskeletal Disord 2007; 8:102 <h3>Disclosure of Interest</h3> None Declared
Abstract 2377: Variation in the BRCT1 domain of the DNA repair gene XRCC1 delays invasive breast cancer in mice
Authors: Christina Pettan-Brewer, John Morton, Rebecca Coil, Jorming Goh, Warren C. Ladiges
Journal: Cancer Research (2011)

Abstract The breast cancer susceptibility protein BRCA1 C-terminal (BRCT) domain coordinates protein interactions in DNA repair and cell cycle control, and comprises over 100 member proteins. One of these, XRCC1, is involved in base excision repair and single strand break repair. In order to investigate the role of the XRCC1-BRCT1 domain in breast cancer, we generated a mouse line with a variation of leucine (L) from arginine (R) at position 360, and crossed it with PyMT transgenic mice with a highly penetrant metastatic breast cancer phenotype. PyMT mice with advanced tumors expressing the L360R variant (N=20) had an average tumor volume of 360±57 mm3 compared to an average tumor volume of 730±69 mm3 for PyMT/wild type littermates (N=20), significant at p less than 0.01. In addition, the L360R variant was associated with a significant decrease in metastatic foci in the lungs of PyMT mice, an increase in tumor cell apoptosis as measured by caspase 3 immunohistochemistry, a decrease in tumor cell proliferation as measured by ki-67 immunohistochemistry, and a decrease in PARP binding as determined by NADH depletion. These preliminary observations suggest that the XRCC1/BRCT1 domain is involved in invasive breast cancer, and that genetic variation of this domain can suppress the invasive phenotype by decreasing tumor cell proliferation and increasing apoptosis of tumor cells possibly in association with altered PARP binding and activity. The XRCC1 L360R mouse is a promising animal model to further investigate the potential of targeting the XRCC1/BRCT1 domain for adjunctive treatment of invasive breast cancer. 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 2377. doi:10.1158/1538-7445.AM2011-2377
Extracellular Visfatin-Promoted Malignant Behavior in Breast Cancer Is Mediated Through c-Abl and STAT3 Activation
Authors: Amos C. Hung, Steven Lo, Ming-Feng Hou, Yi-Chen Lee, Chun-Hao Tsai, Yuan-Yin Chen, Wangta Liu, Yu-Han Su, Yi-Hsuan Lo, Chie-Hong Wang, Shiou-Chen Wu, Ya-Ching Hsieh, Stephen Chu-Sung Hu, Ming-Hong Tai, Yun-Ming Wang, Shyng-Shiou F. Yuan
Journal: Clinical Cancer Research (2016)

Visfatin is an adipocytokine involved in cellular metabolism, inflammation, and cancer. This study investigated the roles of extracellular visfatin in breast cancer, and explored underlying mechanisms in clinical and experimental settings.Associations of serum visfatin with clinicopathologic characteristics and patient survival were assessed with Cox regression models and Kaplan-Meier analyses. Effects of extracellular visfatin on cultured breast cancer cells were examined, followed by in vivo investigation of tumor growth and metastasis in xenograft animal models. Imatinib and Stattic were used to inhibit c-Abl and STAT3 activation, respectively.Breast cancer patients with high serum visfatin levels were associated with advanced tumor stage, increased tumor size and lymph node metastasis, and poor survival. Elevated phosphorylation of c-Abl and STAT3 in breast tumor tissues were correlated with high serum visfatin levels in patients. Visfatin-promoted in vitro cell viability and metastatic capability were suppressed by imatinib (c-Abl inhibitor) and Stattic (STAT3 inhibitor). Increased in vivo cell invasiveness was observed in zebrafish xenografted with visfatin-pretreated breast cancer cells. Tumor growth and lung metastasis occurred in visfatin-administered mice xenografted with breast cancer cells. Tail vein-injected mice with visfatin-pretreated breast cancer cells showed increased lung metastasis, which was suppressed by imatinib.Serum visfatin levels in breast cancer patients reveal potential prognostic values, and our findings that visfatin promoted breast cancer through activation of c-Abl and STAT3 may provide an important molecular basis for future design of targeted therapies that take into account different serum visfatin levels in breast cancer. Clin Cancer Res; 22(17); 4478-90. ©2016 AACR.