tbuckley/cabot-search huggingface dataset:
ROBUST INDUCTION OF TYPE-1 CD8+ T-CELL RESPONSES IN WHO GRADE II LOW-GRADE GLIOMA PATIENTS RECEIVING PEPTIDE-BASED VACCINES IN COMBINATION WITH POLY-ICLC
Authors: H. Okada, L. H. Butterfield, R. L. Hamilton, A. Hoji, M. Sakaki, B. J. Ahn, G. Kohanbash, J. Drappatz, J. Engh, N. Amankulor, M. O. Lively, M. D. Chan, A. M. Salazar, D. M. Potter, E. G. Shaw, F. S. Lieberman
Journal: Neuro-Oncology (2014)

BACKGROUND: WHO grade II low-grade gliomas (LGGs) with high risk factors for recurrence are mostly lethal despite current treatments, and novel approaches are needed. We conducted a phase I study to evaluate the safety and immunogenicity of subcutaneous vaccinations with synthetic peptides for glioma-associated antigen (GAA) epitopes in human leukocyte antigen (HLA)-A2+ adults with high-risk LGGs in the following three cohorts: 1) newly diagnosed patients without prior radiation therapy (RT); 2) newly diagnosed patients with prior RT, and 3) recurrent patients. METHODS: GAAs were interleukin-13 receptor (IL-13R)α2, EphA2, Wilms Tumor (WT)1, and Survivin, and synthetic peptides were emulsified in Montanide-ISA-51 and given every 3 weeks for 8 courses with intramuscular injections of Toll-like receptor 3 agonist Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose (poly-ICLC), followed by q12-week booster vaccines. Primary endpoints were safety and CD8+ T-cell responses against vaccine-targeted GAAs. RESULTS: Cohorts 1, 2, and 3 enrolled 12, 1, and 10 patients, respectively. No regimen-limiting toxicity has been encountered except for one case with Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 fever (Cohort 1). Enzyme-linked Immuno-SPOT (ELISPOT) assays demonstrated robust and sustained interferon (IFN)-γ responses against at least 3 of the 4 GAA epitopes in 10 and 4 cases of Cohorts 1 and 3, respectively. Cohort 1 patients demonstrated significantly higher IFN-γ ELISPOT responses than Cohort 3 patients, suggesting newly diagnosed patients have superior vaccine-responsiveness to recurrent patients. IFN-γ ELISPOT response levels in this study is significantly higher than those observed in our previous phase I/II study in high-grade glioma patients (Okada et al. JCO 2011). Furthermore, IFN-γ ELISPOT response levels were significantly higher than those for IL-5, indicating effective type-1 skewing by the current regimen. Median progression-free survival (PFS) periods are 21 months (Cohort 1; since diagnosis; range 10-42) and 12 months (Cohort 3; since the 1st vaccine; range 3-26). The only patient with large astrocytoma in Cohort 2 has been progression-free for over 58 months since diagnosis. There was a positive trend between IFN-γ ELISPOT responses and progression-free survival (PFS) in Cohort 3 patients (P = 0.08 by The Cox proportional hazards model). CONCLUSIONS: The current regimen is well tolerated and induces robust GAA-specific responses in WHO grade II LGG patients. These results suggest these patients may be suitable populations for vaccine therapy and warrant further evaluations of this approach. SECONDARY CATEGORY: Clinical Neuro-Oncology.
POP Surprise
Authors: R Renner
Journal: Environmental Health Perspectives (2002)

Science SelectionsOpen AccessPOP Surprise R Renner R Renner Search for more papers by this author Published:1 April 2002https://doi.org/10.1289/ehp.110-a204bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit "POP Surprise." Environmental Health Perspectives, 110(4), pp. A204–A205FiguresReferencesRelatedDetails Vol. 110, No. 4 April 2002Metrics About Article Metrics Publication History Originally published1 April 2002Published in print1 April 2002 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.
AB0814 Cross Sectional Study of Hypovitaminosis D in among Rheumatology Patients in Brunei
Authors: M.C.L. Wang, S. Shim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Vitamin D deficiency is increasingly recognised as a global health problem. The important role of vitamin D in skeletal health is well established. Studies have shown vitamin D deficiency in many autoimmune rheuamtic disorders. These patients are commonly treated with corticosteroids which is an important risk factor for osteoporosis. Therefore detection of hypovitaminosis D is important. <h3>Objectives</h3> The aim of this study is to determinine the prevalence of vitamin D deficiency in a cohort of patients attending the Rheumatology clinic at RIPAS hospital which is a tertiary hospital in Brunei and to compare between different gender, ethnic groups and disease groups. <h3>Methods</h3> A cross sectional study was conducted among patients attending Rheumatology clinic from Jan 2000 to Dec 2010. Demographic and clinical data was abstracted from case notes. Quantitative determination of 25(OH) vitamin D is a direct, competitive chemiluminescence immunoassay. Vitamin D deficiency was defined as 25(OH) vitamin D &lt;50 nmol/L and severe deficiency &lt;25 nmol/L. <h3>Results</h3> This study comprised 292 patients, 251 female and 41male. Their mean age is 49.9 (±SD 15.57) ranging from 15-95 yrs. The main racial groups were Malays (78.4%) and Chinese (19.2%). The mean vitamin D level is 49.57 (±SD 22.22) nmol/l. The overall prevalence of Vitamin D deficiency is 57.0% and severe deficiency is 8.2%. Deficiency is more common in female than male, 60.6% vs 39% (p&lt;0.001). Malay has the highest prevalence of vitamin D deficiency at 63.7% compared to Chinese and others groups at 32.1% and 42.8% respectively (p&lt;0.001). Severe deficiency was found in 9.6% Malays but not among other racial groups. An analysis of variance showed significant variation among the racial groups; a post-hoc Tukey test indicated that Malay differed significant from the Chinese but not the others. There is a very weak correlation of age with vitamin D serum concentration (Spearman9s rho r=0.285, p&lt;0.05). No correlation of vitamin D level with body mass index was found. <h3>Conclusions</h3> Hypovitaminosis D is common among Rheumagology patients in Brunei. Differences in gender and ethnic groups were found with higher prevalence among females and ethnic Malays. SLE patients have higher prevalence than those with RA. There is weak correlation of vitamin D level with age but no correlation was detected with body mass index. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3883
AB1455-HPR The effects of low back pain on quality of life and functional disability in nurses with low back pain
Authors: R.N. Demirtas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Low back pain (LBP) is a major public health concern and there is a high prevalence of among nurses. <h3>Objectives</h3> The aim of this study was to identify the effects of LBP on general health related quality of life(HRQOL)and functional disability in nurses with LBP. <h3>Methods</h3> A total of 122 nurses from Medical Practice and Research Hospital completed a demographic questionnaire. HRQOLwas assessed by the Medical Outcomes Study 36-Item Short Form Health Survey questionnaire (SF-36). It was used Visual Analogue Scala (VAS) and the Oswestry Low Back Pain Disability Questionnaire to assess the self-perceived pain and functional disability. HRQOLand functional disability between the nurses who had less pain intensity (VAS scores &lt;, =5) and more pain intensity (VAS scores =,&gt;6) were compared. <h3>Results</h3> The age, body mass index, daily and weekly working hours, total working duration (years) and the number of patients given in care of nurses with LBP in two groups (who had less pain intensity and more pain intensity) were similar (p&gt;0.05). Pain intensity was 3.77±1.29 in group I and 7.66±1.13 in group II and it was different between the groups (p&lt;0.001). The nurses who had more pain intensityhad significantly worse scores of functional disability (p&lt;0.001) and general health (p&lt;0.05), physical function (p&lt;0.001), role physical (p&lt;0.001), social function (p&lt;0.05), bodily pain (p&lt;0.001) domains of SF-36 compared to nurses who had less pain intensity. <h3>Conclusions</h3> The findings of this study suggest that HRQOLis more seriously affected and becomes worsewith the increment of LBP intensity. LBP also causes functional disability in nurses. Therefore, comprehensive interventions aimed at minimizing the risk of LBP and improving HRQOL and functional status among nurses are needed. <h3>References</h3> Videman T, Ojajärvi A, Riihimäki H, Troup JD. Low back pain among nurses: a follow-up beginning at entry to the nursing school. Spine. 2005 Oct 15;30(20):2334-41. Yip VY. New low back pain in nurses: work activities, work stress and sedentary lifestyle. J Adv Nurs. 2004 May;46(4):430-40. Cooper JE, Tate RB, Yassi A. Components of initial and residual disability after back injury in nurses. Spine. 1998 Oct 1;23(19):2118-22. <h3>Disclosure of Interest</h3> None Declared
High-Resolution Chromosomes as an Independent Prognostic Indicator in Adult Acute Nonlymphocytic Leukemia
Authors: Jorge J. Yunis, Richard D. Brunning, Robert B. Howe, Michael Lobell
Journal: New England Journal of Medicine (1984)

Using high-resolution chromosomes of bone-marrow specimens from 105 consecutive adult patients with de novo acute nonlymphocytic leukemia, we found an unusually high degree of complexity in this disorder, which may explain previous difficulties in identifying useful prognostic indicators. Specimens from 99 of the 105 patients were successfully analyzed, and 92 (93 per cent) had a chromosomal defect. Seventeen categories were identified, 12 representing a specific recurrent defect. Three of them have been found to have independent prognostic importance. Patients with an inversion 16 (9 per cent), diagnosed as having M2, M4, or M5b disease according to the morphologic classification of the French-American-British Acute Leukemia Cooperative Study Group, had a uniform and sustained complete remission and a median survival of 25 months. In contrast, 14 patients (14 per cent) with complex chromosomal abnormalities and a diagnosis of M1, M2, M4, M5a, or M6 disease had a very poor prognosis. In 12 of the 14 patients efforts to achieve induction of remission failed, and the group had a median survival of 2.5 months. A third group with a trisomy 8 as the single defect (11 per cent) had an intermediate prognosis and a median survival of 10 months. With the different types of treatment for acute nonlymphocytic leukemia that are now available, we suggest that high-resolution chromosome analysis will become an important tool in selecting specific types of therapy for groups of patients with differing prognoses.
Abstract 5409: Cetuximab downregulates lactate dehydrogenase-A, leading to inhibition of glycolysis and reversal of the Warburg effect in HNSCC cells.
Authors: Haiquan Lu, Xinqun Li, Zhen Fan
Journal: Cancer Research (2013)

Abstract Cetuximab is an anti-human epidermal growth factor receptor (EGFR) monoclonal antibody currently approved for treatment of patients with head and neck squamous cell carcinoma (HNSCC) in combination with conventional radiotherapy and chemotherapy. Previous studies showed that cetuximab downregulates the alpha subunit of the transcription factor hypoxia-inducible factor-1 (HIF-1α) through inhibition of EGFR-mediated downstream cell signaling and that downregulation of HIF-1α is required for cetuximab-induced antiproliferative effects; however, the underlying mechanism has not been established. In this study, we explored the mechanism from the perspective of cancer metabolism. HIF-1 plays a critical role in reprogramming cancer metabolism towards aerobic glycolysis (i.e., the Warburg effect), which is critically important for supplying cancer cells with the biomass needed for cell proliferation. We found that cetuximab downregulated lactate dehydrogenase A (LDH-A) and inhibited glycolysis in cetuximab-sensitive cells in a HIF-1α downregulation-dependent manner. HNSCC cells with acquired resistance to cetuximab expressed a high level of HIF-1α and were highly glycolytic. Overexpression of a HIF-1α mutant conferred resistance to cetuximab-induced G1-phase cell cycle arrest, which could be overcome by knockdown of LDH-A expression. Addition of a small molecule LDH-A inhibitor markedly enhanced the response of cetuximab-resistant cells to cetuximab. Cetuximab had no noticeable inhibitory effect on glycolysis in nontransformed cells, in which glycolysis is followed by oxidative phosphorylation in the mitochondria. These findings provide novel mechanistic insights into cetuximab-induced antitumor effects from the perspective of cancer metabolism and suggest novel strategies for enhancing the response of cancer patients to cetuximab therapy. Citation Format: Haiquan Lu, Xinqun Li, Zhen Fan. Cetuximab downregulates lactate dehydrogenase-A, leading to inhibition of glycolysis and reversal of the Warburg effect in HNSCC cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5409. doi:10.1158/1538-7445.AM2013-5409
PTH-092 Interval Scanning with Magnetic Resonance Enterography Demonstrates Response to Anti-Tnf Therapy and has Utility in Reassessment of Crohn’S Disease
Authors: R Dart, N Griffin, V Goh, K Taylor, S Anderson, J Sanderson, P M Irving
Journal: Gut (2013)

<h3>Introduction</h3> NICE guidelines mandate yearly reassessment of disease activity for those treated with anti-TNF therapy (ATT). Magnetic resonance enterography (MRE) is established in the assessment of small bowel Crohn’s disease, however, there is little data to support its utility in disease monitoring. We examined MRE prior to treatment and after at least 6 months treatment with ATT, observing for radiological remission or change in disease burden. <h3>Methods</h3> We identified 27 patients (infliximab n = 23 adalimumab n = 4) who underwent pre-treatment and reassessment MRE from a local database of patients treated with ATT. MRE scans were assessed by a consultant radiologist, measuring location of lesions, number of skip lesions, length of affected small bowel and skip lesion wall thickness. <h3>Results</h3> Median time to MRE post initiation of ATT was 12 months (range 6–20). All patients were ATT naïve prior to treatment; all but 2 were treated with concomitant immunosuppression. In 63% (n = 17) of patients, there was small bowel disease noted in &gt; 1 location; terminal ileum 74% (20), distal ileum 37% (10), mid ileum 22% (6), proximal ileum 18% (5), distal jejunum 15% (4), mid jejunum 4% (1) and duodenum 4% (1). In no instances had disease spread to a new location on interval scanning. Total length of involvement (cm) improved post-treatment from median 15cm (range 3–50) to 6.8cm (0–33) p = 0.012, as did length of the dominant lesion 6.5cm (2.5–30) vs 3cm (0–30) p = 0.001. Lesion bowel wall thickness also improved 7mm (4–12) vs 5mm (2–10) p = 0.0006. Disease burden, calculated by total stricture length x bowel wall thickness, also improved, 80 (12–400) vs 32 (0–264) p = 0.001. Improvement in number of skip lesions per-patient was not significant 2 (1–6) vs 1 (0–5) p = 0.2; in 2 cases the number of skip lesions increased. In no cases was the total length of involvement greater; however in 27% (7) cases this was static, and in 11% (3) bowel wall thickness was greater. Total disease burden was greater in 2 patients. Complete radiological remission was demonstrated in only 2 patients. <h3>Conclusion</h3> Response of Crohn’s disease to ATT is well documented, and we are able to demonstrate quantifiable interval improvement using MRE. Recording the disease burden by way of stricture length and bowel wall thickness is a mode of measuring MRE response to treatment in Crohn’s disease and may be used for disease reassessment as required by NICE. <h3>Disclosure of Interest</h3> None Declared.
Abstract 501: Characterization of lung cancer stem/initiating cells from non-small-cell lung cancer patients
Authors: Wan-Jiun Chen, Huei-Wen Chen, Chao-Chi Ho, Hsuan-Yu Chen, Pan-Chyr Yang
Journal: Cancer Research (2011)

Abstract Cancer stem cells (CSCs) have been proposed to be responsible for chemoresistant, tumor recurrent, and metastasis. To culture and characterize the CSCs become urgent and may be helpful to develop novel diagnostic and therapeutic strategies. Accumulated evidences indicated the importance of CSCs in tumor formation and successfully isolated the CSCs from patients or cell lines with different cancer types; however, this has not been well explored in lung cancer. Not alike previous isolation through specific markers and quiescent condition, we cultured the lung cancer stem/initiating cells from patient with lung adenocarcinoma and the CSCs formed tumor sphere as fed by the surrounding stroma cells. These lung cancer stem/initiating cells were characterized with highly expressed levels of the stemness makers, nanog, oct4, sox2, and klf4 (53.3-, 37.7-, 13.0, and 4.4-folds changes) as comparing to the feeder cells, also, showed relative higher percentages of side population (27.4%), ALDH activity (14%), higher tumorigenesity compared to other lung cancer cell lines including adenocarcinoma (A549, H522, H23, Hop62, and EKVX), large cell carcinoma (Hop92), squamous cell carcinoma (H226), and bronchi alveolar carcinoma (H322M). These lung CSCs also showed higher drug resistance capacity represented by IC50 to chemotherapy drugs including docetaxel, cisplatin, vinorelbine distrate, and etoposide (13.0-, 1.55, 27.2- and 103.3-folds increased). Furthermore, we found that as less as 100 cells could generate adenocarcinoma formation both in orthotropic or subcutaneous models in severe combined immunodeficient (NOD/SCID) mice. Interestingly, the lung CSCs could spontaneous differentiate into epithelial types of cancer cells as removing the feeder cells in vitro or different phenotypes of adenocarcinoma cells in vivo. Transcriptomic analysis indicated that the Wnt, Notch, TGF-β and HGF signaling pathways are highly expressed in the lung CSCs and quickly down-regulated as removing the feeder cells. The gene expression profiles also provide the novel markers for selection CSCs from lung cancer cell lines and lung cancer patients. To sum up, we have cultured the cancer stem/initiating cells from lung cancer patient with the feeder cells, which providing the tumor microenvironment to maintain the stemness of the cancer stem cells. This model should be helpful not only for isolating and cultured the lung CSCs from patients, but also in developing the anti-cancer strategy targeting on lung CSCs. 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 501. doi:10.1158/1538-7445.AM2011-501
Changes in biologic features between primary and recurrent breast cancers
Authors: Seika Tei, Naoki Aomatsu, Soichiro Hiramatsu, Takehiko Iwauchi, Junya Morimoto, Takafumi Nishii, En Wang, Kinshi Kosaka, Yasutake Uchima, Kazuhiro Takeuchi
Journal: Annals of Oncology (2015)
Abstract ADV03: My breast cancer yellow brick road.
Authors: Susan Axler
Journal: Cancer Research (2013)

Abstract From DCIS, stage 0 breast cancer, to invasive recurrence four years later, to Stage IV spread eight years after that, and now living with advanced breast cancer since 2000, I have traveled the winding path of researching, support groups, consultations, treatment and therapies. My road is not one solid concrete walkway. One organization cannot do it all: research innovative technologies and signaling cellular pathology; provide funding for research grants; support patients and families; meet financial needs as they arise. I started on this winding road when I questioned my route and I tiptoed gingerly at first, then raced along, often stumbling, to physicians and organizations that could make a difference and help me with my decisions. ACS's Reach to Recovery mission "…dedicated to eliminating cancer…by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy and service" and "to assist people with breast cancer throughout the continuum of their disease experience." Linda Creed Foundation, working hand and hand with the National Breast Cancer Coalition whose mission has become curing breast cancer by 2020, lobbies full force making yellow bricks stronger, funding major innovative and costly research, for consumer-advocate input on review panels for grants from Department of Defense. Metastic Breast Cancer Network's mission "to raise awareness of metastatic breast cancer by putting a public face on the metastatic experience (and) give those living with Stage IV disease a greater voice and visibility in the breast cancer and research communities as well as the public at large," provides education and information on treatments and coping. My road includes other organizations that lovingly mold beautiful yellow bricks. The Cancer Support Community (formerly Gilda's Club and the Wellness Community) provides educational and emotional resources. The S.J. Cancer Fund's patient assistance mission addresses financial needs such as paying utility bills, transportation and medical co-pay bills, and Living Beyond Breast Cancer does anything and everything they can to help the breast cancer patient, from phone support for first timers or recurrent "survivors," to conferences, to special events providing companionship and letting women know they are not alone. Citation Format: Susan Axler. My breast cancer yellow brick road. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr ADV03. doi:10.1158/1538-7445.AM2013-ADV03