tbuckley/cabot-search huggingface dataset:
Abstract 4782: The NEDD8-activating enzyme inhibitor, MLN4924, cooperates with TRAIL to augment apoptosis through JNK-dependent downregulation of c-FLIP in head and neck cancer cells
Authors: Liqun Zhao, Ping Yue, Sagar Lonial, Fadlo R. Khuri, Shi-Yong Sun
Journal: Cancer Research (2011)

Abstract The death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), is a tumor-selective cytokines with potential anticancer activity and is currently being tested in clinical trials. Like other types of cancers, head and neck squamous cell carcinoma (HNSCC) cells posses varied sensitivity to TRAIL. MLN4924 is a newly developed small molecule inhibitor of NEDD8-activating enzyme with potent anticancer activity. Elevated NEDD8 conjugation has been reported in HNSCC cells. However, the effects of MLN4924 on the growth of HNSCC cells and on TRAIL-induced apoptosis in HNSCC cells have not been evaluated. In this study, we showed that MLN4924 effectively inhibited the growth of HNSCC cells (IC50s &amp;lt; 0.4 μM) with potent apoptosis-inducing activity. Moreover, MLN4924 synergized with TRAIL to decrease the survival and to induce apoptosis of HNSCC cells. Interestingly, MLN4924 decreased c-FLIP levels with minimal effects on DR4 and DR5 expression. Enforced expression of c-FLIP substantially attenuated MLN4924/TRAIL-induced apoptosis. These data indicate that c-FLIP reduction plays an important role in mediating cooperative induction of apoptosis by the MLN4924 and TRAIL combination. Furthermore we found that MLN4924 decreased c-FLIP stability, increased c-FLIP ubiqutination and facilitated c-FLIP degradation, suggesting that MLN4924 decreases c-FLIP levels through promoting its degradation via an ubiqutination and proteasome-dependent mechanism. Additionally, MLN4924 potently activated JNK signaling evidenced by increased levels of phospho-c-Jun in MLN4924-treated cells. Blockage of the JNK activation with the JNK inhibitor SP600125 not only prevented MLN4924-induced c-FLIP reduction, but also inhibited MLN4924/TRAIL-induced apoptosis. These results suggest that JNK activation mediates c-FLIP downregulation and subsequent enhancement of TRAIL-induced apoptosis induced by MLN4924. Our findings thus warrant further evaluation of the efficacy of MLN4924 or its combination with TRAIL against the HNSCC in vivo and highlight a novel mechanism by which MLN4924 modulates apoptosis. (This study was supported by the Georgia Cancer Coalition Distinguished Cancer Scholar award, Department of Defense VITAL W81XWH-04-1-0142 and NIH/NCI Head and Neck Cancer SPORE CA128613 awards. FR Khuri and SY Sun are Georgia Cancer Coalition Distinguished Cancer Scholars) 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 4782. doi:10.1158/1538-7445.AM2011-4782
TO TAP OR NOT TO TAP: LEFT VENTRICULAR WALL RUPTURE WITH CARDIAC TAMPONADE TREATED WITH EMERGENT PERICARDIOCENTESIS AND EMERGENT REPAIR
Authors: Osama Tariq Niazi, Hayder Hashim, Tasnim Imran, Umair Tariq, Justin Sambol, Marc Klapholz
Journal: Journal of the American College of Cardiology (2015)
P5-11-10: Reproducibility and Robustness of the FDA Approved INFORM HER2 Dual ISH DNA Probe Cocktail Assay.
Authors: IR Loftin, AS McElhinny, R Miller, C Garcia, I Bai, J Ranger-Moore, J Ostrem, M Padilla, T Grogan
Journal: Cancer Research (2011)

Abstract Background: Amplification and/or HER2 overexpression is associated with poor clinical outcome for patients with invasive breast carcinoma. Determination of HER2 status dictates eligibility of patients for trastuzumab (Herceptin) therapy, which has been shown to improve prognosis. We present data from the inter-observer reproducibility and robustness studies of the FDA approved INFORM HER2 Dual ISH DNA Probe Cocktail (HER2 Dual ISH) assay, which is an alternative to FISH. The assay is fully automated and is scored using light microscopy providing morphological context. Methods: Ninety-five human invasive breast carcinoma specimens (a mix of amplified and non-amplified cases) were stained in a study, using the HER2 Dual ISH assay. The slides were enumerated by two qualified readers. The same cohort was stained using Path Vysion FISH and read by one qualified reader. To verify the robustness of the HER2 Dual ISH assay, customer selectable options for factors known to impact the staining quality and intensity, which can be varied for troubleshooting, were tested on human invasive breast carcinoma cases and xenografts. The slides were evaluated by one qualified reader. For both studies all assay steps were fully automated on a VENTANA BenchMark XT automated slide stainer using silver metallographic and red colorimetric detections for Dual ISH. Results: In the inter-observer study the first pass staining success rate was &amp;gt;93% for the HER2 Dual ISH assay, while the FISH first pass staining success rate was 59%. Some cases were rescued after a second attempt, which yielded a second pass staining success rate of 80% for FISH and 97% for HER2 Dual ISH. The negative, positive and overall agreement rates and 95% confidence intervals for the 61 clinical samples of this cohort that were enumerable with both FISH and the HER2 Dual ISH assay are 94.7 (75.4−99.1), 95.2 (84.2−98.7), 95.1 (86.5−98.3) and 89.5 (68.6−97.1), 97.6 (87.7−99.6), 95.1 (86.5−98.3) for reader A vs. FISH and reader B vs. FISH respectively. The positive and negative agreement rates for the inter-observer reproducibility of the HER2 Dual ISH assay were 94.7 and 97.6 %, respectively. In robustness testing, the recommended staining protocol was shown to be effective. All conditions tested resulted in appropriate staining (except for mildest cell conditioning and protease options). Conclusion: The fully automated FDA approved INFORM HER2 Dual ISH assay is robust, reproducible and concordant with the manual FISH assay in determining HER2 status in invasive breast carcinoma. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-10.
Panel Discussion: Role of High Risk Groups in the Derivation of Environmental Health Standards
Authors: Lawrence Plumlee, Stanton Coerr, Herbert L. Needleman, Roy Albert
Journal: Environmental Health Perspectives (1979)

We have heard a great many points reiterated, and I've tried to figure out some ideas that might have been missed.One thing is that some of us will go back into environments where standards for environmental contaminants are set.We must try to be cautious and not forget how ignorant we are.We have heard the description of a variety of syndromes which lead to hypersusceptibility.These include groups which are especially exposed to high levels of chemicals; groups which are deficient in nutrients; and groups which are genetically predisposed to environmental chemical sensitivities.Thus we have the feeling that we know more-and we probably do-than most of our colleagues back home about hypersusceptibility.I think it is very important for us to remember though that there are enormous numbers of diseases of unknown etiology which may well have at least some etiological basis in environmental chemicals.There is increasing evidence that not only cancer but heart disease and many of the autoimmune diseases like rheumatoid arthritis, ulcerative colitis, regional enteritis, as well as respiratory diseases and even behavioral disorders and serious mental disorders, may be related in part to environmental chemicals.Even with the knowledge that we may have of hypersusceptible groups, I think that you should keep in mind Dr. Barth's opening remarks.We may still not yet know the major causes of environmental diseases.We may not have identified those most susceptible to environmental chemicals, either because they have illnesses which are caused by ubiquitous environmental chemicals or because we fail to realize that specific pre-existing diseases have made certain in- dividuals more susceptible to environmental chemi-
TCTAP A-154 Outcomes of Non-Revascularized Unprotected Left Main Coronary Artery Stenosis
Authors: Jae Hyung Roh, Se Hun Kang, Min Su Kim, Hee-soon Park, Byeong Joo Bae, Sang Soo Cheon, Pil Hyung Lee, Mineok Chang, Hyun Woo Park, Sung Han Yoon, Jung-Min Ahn, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2015)
Effect of tibolone on breast cancer recurrence: LIBERATE trial bone sub-study.
Authors: NJ Bundred, P Kenemans, MW Beckmann, J Foidart, E Kubista, B von Schoultz, P Sismondi, R Vassilopoulou-Sellin, C Yip, J Egberts, JV Planellas Gomez, R el Galta, SC van Os
Journal: Cancer Research (2009)

Abstract Abstract #66 LIBERATE, a randomized, placebo controlled, double blind trial studied the effect of tibolone (Livial), a tissue selective hormone replacement therapy (HRT) on breast cancer (BC) recurrence, aiming to demonstrate non-inferiority of treatment compared to placebo. In the LIFT trial of osteoporotic women, tibolone prevented BC development.&amp;#x2028; Design and Method: Women with surgically treated BC (T1-3, N0-2, M0) within the last 5 years complaining of vasomotor symptoms, were randomly assigned to tibolone 2.5mg daily or placebo treatment for a maximum of 5 years. Adequate sample size was estimated to be &amp;gt;1500 in each arm. A bone mineral density (BMD) sub-study of 724 patients (454 Caucasian; 270 Asian) was enrolled utilizing DXA scanning at baseline and 2 years.&amp;#x2028; Results: Between 2002 and 2004, 3,148 women were randomized in 31 countries; 1579 to tibolone and 1569 to placebo. Mean age at randomization was 52.7 years (28.0-75.0) and mean time since surgery was 2.1 years. In total 58% of women recruited were node positive and 78% ER positive. The trial closed prematurely in July 2007, with a median follow-up of 3.1 years (0.01-4.99) per patient, because an increased risk of BC recurrence occurred on tibolone HR 1.40 (1.14-1.70; p&amp;lt;0.001); 15.2% (237/1556) women on tibolone recurred compared to 10.7% (165/1542) on placebo. Risk for distant recurrence on tibolone was HR 1.38 (95% CI 1.09-1.74 p=0.007).&amp;#x2028; Aromatase inhibitor (AI) users had the highest risk of recurrence on tibolone HR 2.42 (1.01-5.79) compared to tamoxifen treated women HR 1.25 (0.98-1.59). Compared to ER positive cancers HR 1.56 (1.22-2.01), ER negative cancer had no increased risk of recurrence HR 1.15 (0.73-1.80). No differences in mortality occurred between groups.&amp;#x2028; At entry to the bone sub-study, 298 (43%) women had normal BMD, 313 (45%) osteopenia (T-score between -1 and -2.5) and 81 (11.7%) osteoporosis. Low body mass index (&amp;lt;0.001), Asian race (p&amp;lt;0.001) and old age at menarche predicted for low bone mass after 2 years. Tibolone increased BMD by 3.5% at the lumbar spine and 2.9% at the hip compared to placebo (both p&amp;lt;0.001) and reduced fracture rate in the Caucasian (p=0.036) but not the Asian population. Women with normal BMD (before or at day 1) had increased recurrence on tibolone 15.1% (21/139) compared to placebo 6.9% (11/159) p=0.036, whereas no increased BC recurrence was seen in women with low BMD; 7.5% (15/201) on tibolone and 6.7% (13/193) on placebo.&amp;#x2028; Conclusion: HRT after breast cancer treatment increases BC recurrence especially in AI treated patients. Risk of BC recurrence is elevated in BC women with normal BMD (compared to low) who take HRT. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 66.
Metastasis: Moving Closer Toward Blocking the Spread Of Cancers
Authors: L. Fintor
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Metastasis: Moving Closer Toward Blocking the Spread Of Cancers Get access Lou Fintor Lou Fintor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 13, 3 July 1991, Pages 902–904, https://doi.org/10.1093/jnci/83.13.902 Published: 03 July 1991
Abstract 1509: Modulation of stromal reaction by PDGF-R tyrosine kinase inhibitor in an orthotopic mice model of gastric carcinoma
Authors: Yasuhiko Kitadai, Mieko Onoyama, Kei Shinagawa, Mayu Ohnishi, Eiji Ohara, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
Journal: Cancer Research (2012)

Abstract Recent studies in molecular and cellular biology have shown that tumor growth and metastasis are not determined by cancer cells alone but also by a variety of stromal cells. Many human tumors secrete platelet-derived growth factor (PDGF) ligands, and PDGF receptors (PDGF-Rs) are expressed by various stromal cell populations, including carcinoma-associated fibroblasts (CAFs). We reported recently that, in a mice model of colon cancer, bone marrow-derived mesenchymal stem cells (MSCs) traveled to tumor stroma, where they differentiated into CAF-like cells. In the present study, we examined PDGF-B and PDGF-Rβ expression in relation to clinicopathologic features of human gastric carcinomas. We also examined the effects of PDGF-R tyrosine kinase inhibitors (imatinib, nilotinib) on tumor stroma in an orthotopic nude mouse model of human gastric carcinoma. Five gastric carcinoma cell lines and 38 surgical specimens of gastric carcinoma were used. Under culture conditions, gastric cancer cell lines expressed PDGF-B at various levels but not PDGFR-β. When cells from these lines were implanted orthotopically into the gastric wall of nude mice, cells with high PDGF-B expression resulted in tumors with abundant stroma. In contrast, cells with low PDGF-B expression resulted in medullary tumors with little stromal reaction. In surgical specimens, we found PDGF-B expression to be associated with stromal reaction. PDGF-B and PDGF-Rβ mRNA expression was significantly higher in patients with lymph node metastasis than in those without and also significantly higher in diffuse-type carcinoma than in intestinal-type carcinoma. In surgical specimens and orthotopic tumors, tumor cells expressed PDGF-B, but PDGF-Rβ was expressed predominantly by stromal cells, including CAFs, pericytes, and lymphatic endothelial cells. Treatment with PDGF-R tyrosine kinase inhibitors did not inhibit tumor growth but did significantly decrease the stromal reaction, lymphatic invasion, lymphatic vessel area, and pericyte coverage of tumor microvessels. In addition, tumor tropism of MSCs was also inhibited by treatment with PDGF-R inhibitors in vivo and in vitro. The PDGF/PDGF-R signaling pathway appears to regulate cancer-stromal cell interaction, and target molecule-based inhibition of the stromal reaction may hold promise as an effective anti-tumor therapy. 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 1509. doi:1538-7445.AM2012-1509
P853 BERBERINE WITH ALFA LIPOIC ACID (ALA) IN NON ALCOHOLIC STEATO-HEPATITIS (NASH). A RANDOMIZED DOUBLE BLINDED PLACEBO CONTROL TRIAL. A CLINICAL PILOT – THE BANISH TRIAL
Authors: P.P. Basu, N.J. Shah, M. Aloysius, R.S. Brown
Journal: Journal of Hepatology (2014)
THU0549 Meniscal Injuries: Is there a Place for Conservative Management?
Authors: E. Soliman, A. Aldawoudy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Meniscal injuries used to be managed operatively, whether scopically or even through open techniques. We observed that some patients with MRI diagnosed meniscal lesions, who have been surgically treated, did not have satisfactory outcomes regarding their pain and function. Whereas, others who were not surgically treated showed unexpected improved outcomes. <h3>Objectives</h3> To evaluate the outcomes of conservative management of non-sport meniscal injuries through rehabilitation programs, and search for the factors that help in selecting patients who may avoid surgery <h3>Methods</h3> 31 patients with MRI diagnosed meniscal injuries were included. Patients were chosen not to have mechanical symptoms or sport injuries, and optionally agreed on conservative management throughstandard rehabilitation. Patients were followed up for one year. Pain was assessed using the pain fraction of the knee injuries and osteoarthritis outcome score (KOOS). Pain scores were tested in relation to patient’s age, sex, history of trauma, laterality of symptoms and MRI grading of meniscal injury. <h3>Results</h3> Comparison between KOOS at the beginning of the study and after one year revealed significant improvement in function and pain with16/31 patients having KOOS scores values above 80 (where 100 is the completely pain free score), and only 2 patients with scores less than 60. There was no relation between the pain scores and the different studied parameters. <h3>Conclusions</h3> Taking a wait-and-see approach to manage non-sport meniscal injuries produces similar outcomes to surgical management. Conservative rehabilitation management still has a place in non-sport meniscal injuries. Parameters which can predict pain improvement and thus avoid unnecessary surgery need further studies to be clearly defined. <h3>Disclosure of Interest</h3> None Declared
PWE-119 Duodenal bulb biopsies for diagnosing adult coeliac disease: is there an optimal biopsy site?: Abstract PWE-119 Table 1
Authors: M Kurien, K E Evans, A D Hopper, M F Hale, S S Cross, D S Sanders
Journal: Gut (2012)

<h3>Introduction</h3> There has been increasing interest in the role that duodenal bulb biopsies may have in helping to establish the diagnosis of coeliac disease. This study aims to determine whether a targeted duodenal bulb biopsy in addition to distal duodenal biopsies is the optimal strategy when trying to identify villous atrophy, comparing histological findings from different quadrants of the duodenal bulb. <h3>Methods</h3> Patients undergoing oesophogastroduodenoscopy (OGD) were prospectively recruited from a single tertiary referral hospital in the UK between July 2010 and October 2011. Indications for biopsy included positive coeliac serology, family history of coeliac disease, chronic diarrhoea, iron deficiency anaemia, abdominal pain and weight loss. All patients recruited to the study had immunoglobulin A (IgA) endomysial antibody (EMA) and tissue transglutaminase (tTG) antibody measurements prior to undergoing their EGD. At endoscopy, eight duodenal biopsies were taken: four from the second part of the duodenum and four quadrantically from the bulb (3,6,9 and 12 o9clock). Each biopsy was graded according to the modified Marsh Criteria, with the optimal biopsy site in the bulb being evaluated by the ability to detect the presence and severity of villous atrophy. <h3>Results</h3> A total of 77 patients were recruited (27 male (35%), 50 female (65%), median age 45, range 19–79) between July 2010 and November 2011. Of these, 28 (36%) were found to have newly diagnosed coeliac disease and 49 were controls (64%). Bulbar villous atrophy was identified in 96% of the coeliac patients, with five patients having villous atrophy confined to the bulb alone (Abstract PWE-119 table 1). The most severe degree of villous atrophy was detected when distal duodenal biopsies were taken in addition to a duodenal bulb biopsy from either the 9 or 12 o9clock position (sensitivity 96.4%, 95% CI 79.7% to 100%). The difference between the 12 o9clock biopsy and the 3 o9clock biopsy in detecting the most severe villous atrophy was 92% (24/26) vs 65% (17/26) (p=0.04). <h3>Conclusion</h3> This study demonstrates the patchy appearance of villous atrophy that occurs within the duodenum. A targeted duodenal bulb biopsy from either the 9 or 12 o9clock position in addition to distal duodenal biopsies, may improve diagnostic yields by detecting the most severe villous atrophy within the duodenum. <h3>Competing interests</h3> None declared.
Abstract 1234: Erk-dependent phosphorylation of Notch intracellular domain (NIC) correlates with increased NIC-dependent transcription
Authors: Isabelle Tremblay, Marie-Josee Boucher
Journal: Cancer Research (2010)

Abstract Background. Recent studies have suggested that the ability of Ras to transform cells depends on cooperation with the Notch signaling pathway. However, the molecular and cellular mechanisms involved in this cooperation remain unknown. Aim. To evaluate the impact of the Mek/Erk pathway, downstream of Ras, on Notch signaling. Methods. HEK293T and human pancreatic cancer cells MIA PaCa-2 were used. Mek/Erk activity was down-regulated by treatment with the specific inhibitor U0126 (10 µM). Transfections or retroviral infections of a constitutive active form of KRas or Mek (MekCA) were used to increase Mek/Erk activity. NIC-dependent transcription was measured by luciferase assays using a specific (CSL) luciferase reporter gene. Results. 1- Transient transfection of an activated KRas stimulated by 1.7-fold NIC-dependent transcription. Transfection of MekCA increased by 4.3-fold NIC-dependent transcription while a wild-type form of Mek (MekWT) was without effect. In parallel, treatment with U0126 reduced by 60% the basal NIC-dependent transcription and completely blocked the KRas- and MekCA-induced NIC-dependent transcription. This negative effect of U0126 on NIC-dependent transcription correlated with decreased nuclear staining of the NIC target gene Hes1. 2- Western blot analysis revealed higher molecular weight forms of NIC when cells were transfected/infected with MekCA as compared to control MekWT-transfected/infected cells. U0126 treatment prevented the MekCA-induced decreased in mobility shift of NIC suggesting that NIC is subjected to Mek-dependent post-translational modifications in vivo. 3- Immunoprecipitation followed by in vitro phosphatase assay revealed that these MekCA-induced higher molecular weight forms of NIC were phosphorylated forms of NIC. 4- By in vitro kinase assays, we demonstrated that NIC worked as Erk substrate. 5- Finally, following in vivo phospholabeling, we observed that NIC immunoprecipitated from MekCA-transfected cells was more phosphorylated as compared to NIC immunoprecipitated from MekWT-transfected cells. Conclusion. Our results provide the novel discovery that Mek/Erk signaling promotes NIC phosphorylation which correlates with increased NIC-dependent transcription. Our discovery thus provides a possible cellular mechanism by which Ras and Notch cooperate to promote cellular transformation. 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 1234.
Case 4-2004
Authors: Alison M. Friedmann, Nancy J. Tarbell, Pamela W. Schaefer, Benjamin L. Hoch
Journal: New England Journal of Medicine (2004)

Presentation of Case Dr. Torunn Yock (Radiation Oncology): A nine-month-old male infant was referred to this hospital for treatment of an orbital rhabdomyosarcoma. The patient had been well until the age of six months, when excessive tearing developed. Over the next two days, his right eye was noted to be puffy and red. His pediatrician made a diagnosis of conjunctivitis. Topical treatment with a combination of bacitracin and polymixin B sulfate (Polysporin) had no effect, and two days later, proptosis developed (Figure 1A). The infant was referred to an ophthalmologist for evaluation and treatment of a possible orbital infection. A . . .
Diagnosis of Glycosphingolipidoses by Urinary-Sediment Analysis
Authors: Robert J. Desnick, Glyn Dawson, Susan J. Desnick, Charles C. Sweeley, William Krivit
Journal: New England Journal of Medicine (1971)

Abstract Biochemical diagnosis of patients with Krabbe's leukodystrophy, Gaucher's disease, lactosylceramidosis, Fabry's disease, Sandhoff's disease and metachromatic leukodystrophy can be made by ...