tbuckley/cabot-search huggingface dataset:
P17.49 * TREATMENT STRATEGY FOR WHO GRADE III GLIOMAS: THE LESSONS LEARNED FROM THE RETROSPECTIVE MULTICENTER ANALYSIS OF 243 PATIENTS
Authors: C. Kim, Y. Kim, C. Park, S. Lee, Y. Kim, I. Kim, I. Kim, J. Joo, M. Park, M. Lee
Journal: Neuro-Oncology (2014)

OBJECTIVE: This retrospective analysis was performed to determine the efficacy, safety, and tolerability of treatment protocols including radiation therapy, concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy with temozolomide (TMZ), or PCV chemotherapy based on the status of molecular diagnosis in the treatment of patients with WHO grade III gliomas. MATERIALS: Two hundred forty three adult patients with WHO grade III glioma and aged > 17 years were enrolled from two institutions between 2004 and 2012. The pathological diagnoses were anaplastic astrocytomas (AA) in 150 patients and anaplastic oligodendrogliomas (AO) including anaplastic oliogoastrocytomas in 93 patients. Co-deleted group on 1p19q LOH analysis was 60 of available 183 patients and un-methylated group of MGMT promoter was 64 of available 170 patients. The AA patients received four different treatment protocols in same strategy in two institutions: radiation therapy only, CCRT with temozolomide, radiation therapy followed by PCV or temozolomide adjuvant chemotherapy, and nothing after surgery. The AO patients received also four different treatment protocols in same strategy in two institutions: radiation therapy only, CCRT with temozolomide, radiation therapy combined with PCV (neo- or) adjuvant chemotherapy, and temozolomide chemotherapy only after surgery. RESULTS: Overall survival (OS) and progression free survival (PFS) were superior in AO (98m and 61m) than in AA (34m and 23m) and 1p19q co-deleted group had significantly longer OS (98m vs 42m) and PFS regardless treatment protocols. In AA patients RT only group and CCRT with temozolomide group had the better OS and PFS than other two groups. Methylation status of MGMT promoter in these patients did not affect survival differences. In AO patients RT only group, PCV based chemotherapy group (neoadjuvant or adjuvant PCV), or CCRT with temozolomide groups had no statistically significant differences in survival data. However 1p19q co-deleted group had a much better survival data (OS 98m vs 53; PFS not reached yet vs 38m). CONCLUSION: 1p19q co-deletion (molecular diagnosis) may be more important than morphologic diagnosis in grade III gliomas. The methylation status of MGMT promoter is not important such as in case of grade IV, glioblastoma. Adjuvant PCV might improve OS and PFS in AO regardless of the timing of PCV, either pre-RTx. or post-RTx. CCRTx. with TMZ may improve OS in non co-deleted group and this will be one of good candidate for standard one. A randomized controlled study with a long-term follow-up may be mandatory to evaluate and to make a best treatment protocol for these tumors.
Abstract LB-150: Role of EGFR signaling in an inducible mouse model of astrocytomas
Authors: Yurong Song, Qian Zhang, C. Ryan Miller, David Threadgill, Ken D. McCarthy, Terry Van Dyke
Journal: Cancer Research (2010)

Abstract No effective therapy currently exists for astrocytomas, particularly the most biologically aggressive subtype, glioblastoma multiforme (GBM). Recently, The Cancer Genome Atlas (TCGA) project reported the most extensive genetic analysis of GBMs enhancing our ability to query altered signaling pathways potentially involved. Yet, an understanding of disease etiology requires extensive modeling in mammalian genetic systems coupled with analyses of biological contributions of disease. Here we genetically perturbed the primary molecular pathways (pRb and Ras) reported by TCGA in genetically engineered mouse models (GEM). Alterations were induced specifically in adult GEM astrocytes via a tamoxifen-inducible, human GFAP promoter-driven CreERTM allele. GEM with astrocyte RB pathway inactivation alone (T) developed low-grade astrocytomas (grade II). Constitutive KRAS activation alone (R) did not produce detectable brain pathology. GEM harboring both inactivated RB and constitutively active KRAS (TR) in astrocytes developed high-grade astrocytomas (grade III) with low frequency of GBM development (grade IV). EGFR level and its ligands in TR tumors were elevated compared to T alone, suggesting EGFR signaling pathway may play an important role in tumor progression. We reasoned that tumor progression would be delayed if we knocked out EGFR in TR brain. Surprisingly, we found that addition of EGFR inactivation produced tumors with higher frequency of GBM. These results suggest other pathways other than EGFR may compensate for EGFR loss, which in turn contributes to tumor progression. These highly penetrant, inducible GEM models provide a unique system for delineating the downstream pathways and resulting biological abnormalities critical to astrocytoma pathogenesis and for preclinical drug and biomarker development. Initial studies have begun to define the relative contribution to disease of each disrupted pathway, including potential targets for therapeutic intervention. 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 LB-150.
FRI0103 Smoking cessation advice by rheumatologists; results of an international survey:
Authors: A. Naranjo, N.A. Khan, M. Cutolo, S.-S. Lee, F. Gogus, T. Sokka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Smoking increases cardiovascular morbidity in patients with inflammatory rheumatic diseases, and has been associated with poor response to treatment in rheumatoid arthritis. Advice on smoking cessation is strongly recommended in patients with arthritis. Brief advice versus no advice increases the rate of quitting, thus doctors should aim to advise smokers to quit during routine consultations. <h3>Objectives</h3> To understand the practice of rheumatologists and nurses regarding advice for smoking cessation in patients with arthritis. <h3>Methods</h3> We sent a survey to the Rheumatology department participants in the multinational QUEST-RA group. The following items were included: a) number of rheumatologists in department, b) number of nurses for patient education, c) number of doctors and nurses who smoke, d) advice for smoking cessation by doctor and nurse, e) specific protocol for advice in the department, f) special clinic for quitting smoking in the hospital or primary care, and g) specific clinic for early arthritis and/or inflammatory diseases in the department. <h3>Results</h3> Rheumatologists from 44 departments in 25 countries (16 European) completed the survey. The survey involved 395 rheumatologists of whom 25 (6.3%) smokers, and 199 nurses for patient education of whom 44 (22.1%) smokers. Eight departments (18.1%) had a specific protocol for smoking cessation (Table). 255 (64.5%) Rheumatologists reported giving advice to all or almost all smokers with inflammatory diseases. This advice was more frequent by doctors whose department includes an early arthritis clinic (71% vs 51%; p&lt;0.001). However, advice by doctors was not related to the number of rheumatologists, other inflammatory clinics or having a specific protocol for smokers. The nurse give advice to most of patients (&gt;80%) in 11 of the 35 (31.4%) departments with nurse for patient education. Rheumatologists in 19 of the 20 (95%) hospitals with specific clinic/unit for smoking cessation reported referring patients to these clinics if a patient asks for help or has lung disease or smoking-related comorbidities. <h3>Conclusions</h3> Advice for smoking cessation within rheumatology departments is not homogeneous. Two thirds of rheumatologists give advice to quit smoking to all or almost all patients with inflammatory diseases. Only 1 in 5 departments have a specific protocol for smoking cessation. Our data highlights the need to improve awareness of importance and better practice implementation of smoking cessation advice for inflammatory rheumatic disease patients. <h3>Disclosure of Interest</h3> None Declared
Abstract 5358: Comparison of tumor-forming ability in different fractions of pancreatic ductal adenocarcinoma cells
Authors: Masahito Hagio, Yoko Matsuda, Yoko Kawamoto, Yuji Yanagisawa, Hiroshi Makino, Zenya Naito, Toshiyuki Ishiwata
Journal: Cancer Research (2012)

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is associated with a high mortality rate due to its aggressive growth and high metastatic rate. Recently, cancer stem cells have been reported to play a central role in the proliferation, metastasis, and drug resistance of cancer. Although cancer stem cell-like cells seem to be included very loosely in cancer cells, information is still limited. Furthermore, the appropriate way of detecting cancer stem cells has remained controversial. In the present study, we tried to detect and collect a side population (SP) fraction as pancreatic cancer stem cells using Hoechst staining, and compared the in vivo tumor-forming abilities between the major population (MP) and SP of PDAC cells. Methods: A human pancreatic cancer cell line, KLM-1, was stained with Hoechst 33342. We distinguished between MP and SP of cells by the positivity of Hoechst, and then each fraction was isolated using a flow cytometer. Different numbers (1.0×102, 103, 104, and 105) and fractions (MP and SP) of cells were subcutaneously injected into the left and right sides of the back of NOD.CB17-Prkdcscid/J (NOD/SCID) mice. During a 5-week test period, the tumor size was measured regularly. Results: After 5 weeks, tumors were formed in mice injected with above 1.0×104 cells of both fractions. Especially, with the injection of 1.0×105 cells, the tumor-forming rate was 100% in the SP group, whereas it was 66.7% in the MP group. Furthermore, tumors were generated at about 1 week after the injection of the SP fraction (1.0×105 cells); however, in the MP group, it took about 3 weeks to generate a tumor after the injection of the same number of cells. Totally, the tumor volumes of the SP group were bigger than those of the MP group. Even with the injection of 1.0×104 cells of the SP fraction, the tumor volume was bigger than that on the injection of 1.0×105 cells of the MP fraction. Subcutaneous tumor tissues derived from SP and MP cells showed similar histological features. Conclusion: The malignancy of the SP fraction in PDAC cells was confirmed. This fraction might include cancer stem like-cell properties, and may be a candidate for therapeutic target in malignant PDAC. 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 5358. doi:1538-7445.AM2012-5358
A New Multidrug-Resistant Strain of <i>Neisseria gonorrhoeae</i> in Australia
Journal: New England Journal of Medicine (2015)

To the Editor: In 2013, the Centers for Disease Control and Prevention identified Neisseria gonorrhoeae antimicrobial resistance as being an urgent threat. Ceftriaxone monotherapy or dual therapy with azithromycin is now the mainstay of treatment for gonorrhea, and no ideal alternatives have been identified. There have been three sporadic reports of two ceftriaxone-resistant strains of N. gonorrhoeae in the past 5 years: H041 and F89 (Table 1).1-3 H041 was identified in only a single case involving a female sex worker in Japan in 2009.1 F89 was initially reported in France in 2010 in a man who has sex with men2 and subsequently was detected in Spain in two sexually related men who have sex with men.3 Neither H041 nor F89 has since been reported. Here we report a third gonococcal strain that is a cause for public health concern. The A8806 strain, which was identified in Australia in late 2013, was shown to have a minimum inhibitory concentration (MIC) of ceftriaxone of 0.5 mg per liter (Table 1) when measured according to the calibrated dichotomous sensitivity method. The isolate was obtained from a genital swab obtained from a young female European traveler with vaginal discharge who presented to a medical clinic in central Australia in December 2013. She was tested for sexually transmitted infection and treated with metronidazole. She had reported sex with a new partner, who was a fellow European traveler, 1 week previously in Sydney. The patient then traveled from central to northeastern Australia, where she presented with ongoing vaginal discharge to a second clinic and indicated that she had by then received a telephone call from the first clinic confirming a positive test result for gonorrhea. She was treated with ceftriaxone at a dose of 500 mg administered by means of intramuscular injection and azithromycin 1 g orally, and she was reportedly culture-negative for gonorrhea approximately 2 months later. Genetic analyses showed that the A8806 isolate had key similarities to H041 (Table 1). Notably, A8806 had a mosaic penicillin-binding protein 2 with two of three key substitutions4 leading to ceftriaxone resistance in H041 (A311V and T483S, but not T316P) (Table 1). The A8806 strain also shared the same multilocus sequence type as H041 but differed from H041 in the N. gonorrhoeae multiantigen sequence type (Table 1). Previous pharmacodynamic analyses have predicted that treatment failures are likely for strains with an MIC of 0.5 mg per liter with the use of ceftriaxone monotherapy at doses of 250 mg and 500 mg.5 Thus, this isolate arouses new concerns over the ongoing efficacy of ceftriaxone monotherapy for treatment of gonorrhea. Data are lacking to determine the prevalence and spread of the A8806 strain in Australia and elsewhere.
Abstract 4354: Mesenchymal stem cells loaded with paclitaxel inhibit tumor growth and angiogenesis
Authors: Giulio Alessandri, Arianna Bonomi, Valentina Coccè, Loredana Cavicchini, Gloria Invernici, Silvia Cristini, Francesca Sisto, Maura Ferrari, Emilio Ciusani, Graziella Cappelletti, Daniele Cartelli, Eugenio Parati, Augusto Pessina
Journal: Cancer Research (2011)

Abstract Background: Mesenchymal stem cells (MSCs) may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that simple exposure of bone marrow (BM) derived MSCs to high doses of Doxorubicin, led them to acquire anti-proliferative potential towards co-cultured haematopoitic stem cells (HSCs). We thus hypothesized whether MSCs, once primed in vitro with anti-cancer drugs and then localized near cancer cells, can inhibit proliferation. Methods: Paclitaxel (PTX) was used to prime culture of mouse and human MSCs. Incorporation of PTX into MSCs (MSCsPTX) was studied by using FICT-labelled-PTX and analyzed by FACS and confocal microscopy. Release of PTX in culture medium by MSCsPTX was investigated by HPLC. Culture of Endothelial cells (ECs) and aorta ring assay were used to test the anti-angiogenic activity of MSCsPTX, while anti-tumor activity was tested in vitro on the proliferation of different tumor cell lines and in vivo by co-transplanting MSCsPTX with cancer cells in mice. Results: MSCs were able to rapidly incorporate PTX and could slowly release PTX in the culture medium in a time dependent manner. Primed MSCsPTX acquired a potent anti-tumor and anti-angiogenic activity in vitro that was dose dependent, and demonstrable by using their conditioned medium or by co-culture assay. Finally, MSCsPTX co-injected in immunodeficient mice with DU145 and B16 cancer cells, significantly delayed tumor takes and reduced tumor growth. Conclusions: These data demonstrate that, without any genetic manipulation, MSCs can uptake and subsequently slowly release PTX, becoming a potential new tool for cancer therapy. 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 4354. doi:10.1158/1538-7445.AM2011-4354
PTH-031 Polyp Size, Location and Risk of Advanced Neoplasia in a Bowel Screening Population in North-East Scotland
Authors: U Basavaraju, M Glaire, P S Phull
Journal: Gut (2013)

<h3>Introduction</h3> Colonoscopic screening for colorectal cancer (CRC) reduces CRC-associated mortality; however, there is some evidence that this effect applies to mainly left-sided, rather than right-sided, CRC. It is postulated that this might be because polyps with advanced pathology are smaller in the right colon and therefore more easily missed (Gupta <i>et al Clin Gastroenterol Hepatol 2012; 10:1395–1401)</i>. Our aim was to evaluate the relationship between the size and location of polyps with advanced neoplasia in a population undergoing bowel screening in North-East Scotland. <h3>Methods</h3> Analysis of prospectively collected data collected for all screening colonoscopies performed in NHS Grampian region between January 2009 and January 2011. Subjects who had complete colonoscopy were included in the study. Lesions in the rectum, sigmoid or descending colon were considered left sided and lesions proximal to the splenic flexure considered right sided. Advanced neoplastic lesions (ANLs) were defined as polyps with cancer, high grade dysplasia or tubulovillous histology. Lesion size was defined as ≥1cm or &lt; 1 cm <h3>Results</h3> Of the total 1415 subjects undergoing screening colonoscopy during the 2 year period, 1320 (93.3%) had a complete colonoscopy and were included in the analysis. Of these, 606 (45.9%) subjects had a total of 1366 polyps; of these, 213 (35%) subjects had ANLs. Median patient age was 64yrs, and 157 (74%) were males. ANLs were located in the left colon in 169 (79.3%) subjects, in the right colon in 31 (14.6%) of subjects, and in both sides in 13 (6.1%) subjects. There was no significant difference between the proportion of subjects with small ANLs (&lt; 1 cm size) in the right colon (n = 3, 9.7%) compared to the left colon (n = 24, 14.2%; Fisher’s exact test). <h3>Conclusion</h3> In subjects undergoing bowel cancer screening in North-East Scotland, small ANLs were not more common in the right colon. Further studies are required to clarify the pathogenesis of right-sided colonic cancer. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Gupta<i> et al. Clin Gastroenterol Hepatol 2012; 10:1395–1401</i>
P536 IMPACT ON EMERGENCY ADMISSIONS OF AN INTEGRATED MANAGEMENT PATHWAY FOR CIRRHOSIS-RELATED COMPLICATIONS
Authors: V. Andreu, M. Llusa, C. Pons, A. Vega, D. Osuna, L. Martos, A. Perello, A. Abad, M. Arranz, M. Barenys
Journal: Journal of Hepatology (2014)
IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IN CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA
Authors: Fernando Wangüemert Pérez, Pablo Ruiz Hernandez, Guillermo Pérez, Oscar Campuzano Larrea, Julio Hernandez, Josep Brugada, Ramon Brugada
Journal: Journal of the American College of Cardiology (2016)
New Syndrome of Neonatal Hypoglycemia
Authors: Jerome T. Combs, Jerome A. Grunt, Ira K. Brandt
Journal: New England Journal of Medicine (1966)

SYMPTOMATIC hypoglycemia in the newborn infant occurs approximately once in 500 live births.1 Over 80 per cent of these infants are small for their gestational age.2 The occurrence of symptomatic hypoglycemia in the smaller infant of twin births has been emphasized.3 A survey of all admissions to a premature nursery has shown that 4 to 6 per cent of all premature infants have significant hypoglycemia and that approximately 15 per cent of all symptomatic infants who are small for their gestational age have hypoglycemia.4 This has led to the concept that idiopathic hypoglycemia in the newborn infant is often a . . .
PMO-023 Assessment of quality of life, coping strategies and personal beliefs in neuroendocrine tumour patients
Authors: J Garcia-Hernandez, M Khan, J Goodhand, C Toumpanakis, M Caplin
Journal: Gut (2012)

<h3>Introduction</h3> Medical research is focused on the developing of treatments and improving survival outcomes. In recent years, quality of life (QoL) measurements have been included in clinical trials as a relevant outcome variable; however, other psychological variables might have an impact on QoL. This study aims to determine: H1. Whether NET symptoms have a greater impact on QoL than disease severity. H2. Whether coping strategies influence QoL. H3 Whether internal control beliefs in the potential of control cancer growth are associated with QoL. <h3>Methods</h3> 74 patients completed a web survey involving: QoL (EORTC C.30 and GI.NET21), a coping styles (Brief cope) and an illness perception measurements. All questionnaires were counterbalanced. <h3>Results</h3> Endocrine and gastrointestinal symptoms, were negatively associated with self-reported measures of QoL, r=−46, N=73, p.05. Problem focus strategies such as acceptance, active coping and planning were not associated with QoL. Interestingly, emotion focus strategies such as behavioural disengagement, venting and self-blame were negatively associated with QoL, r=−0.48, N=73. Neuroendocrine patients considered that, keeping a positive attitude, not smoking and limiting alcohol intake would prevent cancer from spreading and progressing; however none of them were correlated with QoL. <h3>Conclusion</h3> Disease severity is not associated with to QoL, whereas specific neuroendocrine symptoms, flushing and diarrhoea are. Active coping, acceptance, seeking emotional or instrumental support, were not correlated to QoL. In contrast, behavioural disengagement, denial and self-blame were negatively associated to self reported measures of QoL. Most of our patients endeavour on active or problem focus strategies where there is agreement of being more adaptive long term than avoidant or emotional strategies. This study has shown the relationship between neuroendocrine symptoms and coping strategies with QoL. Prospective and randomised trials will clarify the causal relationship among these constructs. Future research should include the relationship of psychosocial variables and neuroendocrine biomarkers. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Carver CS</b>. You want to measure coping but your protocol is too long: Consider the Brief COPE. <i>Int J Behav Med</i> 1997;<b>4</b>:92–100. 2. <b>Larsson G</b>, Sjoden PO, Oberg K, <i>et al.</i> Importance-satisfaction discrepancies are associated with health-related quality of life in five year survivors of endocrine gastrointestinal tumours. <i>Ann Oncol</i> 1999;<b>10</b>:1321–7. 3. <b>Miles A</b>, Simon A, Wardle J. Answering patient questions about the role lifestyle factors play in cancer onset and recurrence. <i>J Health Psychol</i>. 2010;<b>15</b>:291–8.