tbuckley/cabot-search huggingface dataset:
Abstract 5184: Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer
Authors: Haruhisa Kitano, Joon-Yong Chung, Jun Hanaoka, Shuhei Inoue, Doki Yoshinori, Junya Fukuoka, Stephen M. Hewitt
Journal: Cancer Research (2015)

Abstract Lymphangiogenesis is a key component for tumor growth and metastasis in non-small cell lung cancer (NSCLC), and is a promising target in cancer therapy strategy. The axis of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGFR-3 is considered to be a major driver of lymphangiogenesis but the detailed mechanism of this process remains unclear. We recently showed that the expression of synaptonemal complex protein 3 (SCP3) is associated with poor prognosis and linked with lymph node metastasis in NSCLC. To investigate the possible lymphangiogenic significance of SCP3 in NSCLC, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expressions in archival tumor tissues from 89 NSCLC patients with lymph node metastasis by immunohistochemical staining. The positive staining of SCP3, VEGF-A, VEGF-B, VEGF-C and VEGF-D expressions were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, we have identified that the SCP3 expression is positively correlated with VEGF-C and VEGF-D (for both, p &amp;lt; 0.001) whereas its expression is negatively correlated with VEGF-A and VEGF-B (p = 0.029 and p = 0.026, respectively). Furthermore, we have also detected the linkage between SCP3 and VEGF-C or VEGF-D expressions in human lung cancer cell lines. In multivariate analysis of patients with lymph node metastasis, SCP3 expression displayed the worse overall survival (HR = 1.86, p = 0.008). These data suggest that SCP3 is linked with lymphangiogenesis and provide insight into the SCP3-VEGF-C/VEGF-D axis based anti-lymphangiogenic therapy strategy. Citation Format: Haruhisa Kitano, Joon-Yong Chung, Jun Hanaoka, Shuhei Inoue, Doki Yoshinori, Junya Fukuoka, Stephen M. Hewitt. Synaptonemal complex protein 3 is associated with lymphangiogenesis in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5184. doi:10.1158/1538-7445.AM2015-5184
Abstract LB-219: Interleukin-8 promotes generation of M2 macrophages and arginase-producing granulocytes: Prognostic significance of interleukin-8 and infiltration of immune cells positive for CD163 and CD66b in tumor tissues in patients with oral squamous cell carcinoma
Authors: Masato Okamoto, Yohei Fujita, Hiroyuki Goda, Koh-ichi Nakashiro, Hiroyuki Hamakawa
Journal: Cancer Research (2015)

Abstract Biomarkers are essential for improving the effectiveness of treatments for patients with cancer. The immunological status in a tumor microenvironment is closely associated with the prognosis of cancer patients. Here we investigated whether serum interleukin (IL)-8 reflects the tumor microenvironment and has prognostic value in 50 patients with resectable oral squamous cell carcinoma (OSCC). We found that the relapse-free survival (RFS) was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001). The tumor expression of IL-8, the infiltration of CD163-positive cells, and of CD66b-positive cells in the tumor tissues were correlated with the serum IL-8 level (p = 0.033, p = 0.038 and p = 0.044, respectively), and they were associated with poor clinical outcome (p = 0.007, p = 0.002 and p = 0.001 respectively, in DFS) in all patients. A multivariate analysis revealed that N status, tumor IL-8 expression, CD163 and CD66b infiltration significantly affected the DFS of the patients. A further analysis suggested that the combination of N status with serum IL-8, tumor IL-8, CD163 and CD66b infiltration in the tumor tissues may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Finally, the in vitro experiments clearly demonstrated that IL-8 enhanced the generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10 which suppress anti-tumor immunity. Furthermore, IL-8 increased the generation of arginase-producing, CD66b-overexpressing cells from peripheral blood polymorphonuclear cells. These findings indicate that IL-8 may be involved in poor clinical outcomes via the generation of CD163-positive M2 macrophages and CD66b-overexpressing, arginase-producing granulocytes, and that these factors may have prognostic value as well as may be new targets for treatment in patients with resectable OSCC. Citation Format: Masato Okamoto, Yohei Fujita, Hiroyuki Goda, Koh-ichi Nakashiro, Hiroyuki Hamakawa. Interleukin-8 promotes generation of M2 macrophages and arginase-producing granulocytes: Prognostic significance of interleukin-8 and infiltration of immune cells positive for CD163 and CD66b in tumor tissues in patients with oral squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-219. doi:10.1158/1538-7445.AM2015-LB-219
P17 A retrospective analysis comparing the use of procore with standard fine needle aspiration in endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA)
Authors: DJ McCracken, TE McManus, A Shamboul
Journal: Thorax (2016)

Endobronchial ultrasound has become first line in the investigation of mediastinal lesions suspicious for malignancy in keeping with NICE guidelines, however needle size and type, along with number of passes required to maximise diagnostic sensitivity remains unclear. Previous meta-analyses, the largest of which included 576 patients,<sup>1</sup> have compared the use of ProCore with standard fine needle aspiration in the assessment of pancreatic masses with differences noted only in the number of passes required. We aim to assess whether a ProCore needle improves diagnostic sensitivity in EBUS-TBNA. Complete follow up data regarding all 235 patients undergoing EBUS-TBNA in a district general hospital has been collected since the service’s inception in 2012. Results were collated and retrospectively analysed allowing for calculation of test sensitivity and specificity. Comparison was then made between procedures where standard fine needle aspiration was performed and those using a ProCore needle. Overall sensitivity of EBUS-TBNA was shown to be 85% with a specificity of 100% in keeping with quoted figures from other centres. Standard fine needle aspiration produced a sensitivity of 77% (85/110) versus ProCore sensitivity of 92% (115/125) with a p value of 0.0016. 30% (33/110) of patients undergoing standard fine needle aspiration required an appropriate crossover technique such as mediastinoscopy or CT guided FNA in order to either obtain or confirm the diagnosis compared with 15% (19/125) of the ProCore group with a p value of 0.0064. Our retrospective analysis shows a statistically significant difference in the diagnostic sensitivity of sampling mediastinal lymphadenopathy using a ProCore needle compared with standard fine needle aspiration. It also shows that a significantly fewer number of patients required further procedures in order to obtain or confirm the diagnosis. This could potentially be confounded by the retrospective nature of the study design, however due to the statistical significance demonstrated, further study is required in the form of a randomised control trial. <h3>Reference</h3> Bang JY, Hawes R, Varadarajulu S. A meta-anlysis comparing ProCore and standard fine-needle aspiration needles for endoscopic ultrasound-guided tissue acquisition. <i>Endoscopy</i> 2016;<b>48</b>(4):229–49.
Meloxicam (M) in combination with paclitaxel (P) and carboplatin (C) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: T. Takahashi, Y. Kogure, S. Ueda, M. Ebisawa, G. Asai, N. Yamamoto
Journal: Journal of Clinical Oncology (2005)

7115 Background: Cyclooxygenase-2 (COX-2) is overexpressed in NSCLC, and COX-2 promotes tumor growth through the production of prostaglandins. P is known to induce COX-2, and induction of COX-2 will decrease the efficacy of P itself. M is a selective COX-2 inhibitor, and shown to inhibit the growth of COX-2 positive lung cancer cells in vitro (Anticancer Res. 20:2867, 2000). Neuropathy is a serious problem after P administration, and COX-2 in infiltrating inflammatory cells in injured nerve plays an important role in the maintenance of neuropathic pain (Neuroscience. 121:691, 2003). We conducted this study to evaluate the hypothesis that the addition of M to P/C will enhance the response and reduce the severity of P induced neuropathy through the inhibition of COX-2. Methods: Eligibility criteria included histologically or cytologically confirmed stage IIIB or IV NSCLC, no previous chemotherapy, adequate organ function, and ECOG PS 0–2. Current use of steroid was not allowed. P(200 mg/m2) and C(AUC 6) was administered on day 1 every 3 weeks, and M (10mg/day) was administered orally once a day from day 0. Primary endpoint was response rate and secondary endpoint were toxicity profile and overall suvial. Results: From June 2003 to May 2004, 49 eligible patients(pts) were treated: gender M/F; 38/11, median age; 63yrs (43–74), stage IIIB/IV; 18/31, PS 0/1/2; 22/23/4, histology AD/SQ/LA;36/11/2, number of treatment cycles 1/2/3/4/5; 2/3/21/21/2. The overall response rate was 49% (24/49; 95%CI35 ∼ 63%) and 20 of 49 had stable disease. Median survival time and median progression free survival were 455 days and 152 days. Grade(G) 3/4 neutropenia, anemia, thrombocytopenia occurred in 42 pts (86%), 7pts (14%), 6pts (12%), respectively. Only 3 (6%) developed neutropenic fever. G2 peripheral neuropathy occurred in only 3 pts (6%). G2/3 skin rash, nausea/vomititng occurred in 7 pts(14%) 18pts(37%), respectively. Conclusions: M will enhance the reponse to P/C in patients with advanced NSCLC, and reduce the severity of P-induced neuropathy, without increasing problematic severe toxicities. No significant financial relationships to disclose.
Abstract LB-197: Circulating rare cells enable highly efficient cancer detection
Authors: Eva Obermayr, Elisabeth Maritschnegg, Paul Speiser, Christian Singer, Eva M. Schuster, Sabine Danzinger, Nina Pecha, Robert Zeillinger
Journal: Cancer Research (2015)

Abstract Objectives of the study We intended to develop a protocol combining a novel micro-fluidic enrichment technology and RT-qPCR for the molecular analysis of CTCs. Recently we identified CTC-specific mRNA markers allowing CTC detection in 29% of breast cancer patients and in 24.5% of ovarian cancer patients at diagnosis. However, the detection of cancer cells was hampered by the large number of contaminating leukocytes. The necessary use of cut-off values for positivity reduced the specificity of the down-stream PCR assay. By improving the purity of cancer cells and PCR analysis we sought to increase both sensitivity and specificity of the diagnostic procedure. Methodology For reducing the blood sample volume (up to 20ml) density gradient centrifugation was used when needed. The samples were passed through a micro-fluidic disposable cassette, which captures tumor cells based on their less deformable nature and larger size compared to blood cells. Lysis of the captured cells was done directly in the cassette and total RNA was extracted. After a cDNA pre-amplification step gene expression levels of leukocyte-specific and CTC-related markers were measured using RT-qPCR. The efficiency of the combined protocol was assessed in blood samples taken from patients with primary and recurrent malignant diseases. Results 7 out of 13 pre-selected RNA markers were not detectable in blood samples from 11 healthy volunteers. In cancer patients we observed measurable gene expression of at least one out of these 7 RNA markers. 5 out of 5 breast cancer (primary disease: N = 1; metastatic: N = 4), 9 out of 10 primary and 4 out of 8 relapsed ovarian cancer patients were classified correctly by the test. The most striking finding is the detection rate of 90% for primary ovarian cancer at a specificity of 100%. Conclusions The enrichment of rare cells from blood samples using micro-fluidics results in a highly pure cell population. This enables the application of extremely sensitive methods, like RT-qPCR to specifically detect rare events. By combining a novel micro-fluidic cell enrichment and molecular analysis we have taken a major step forward, which allows the implementation of ′liquid biopsies′ in cancer detection studies and as a companion diagnostic in clinical trials. Citation Format: Eva Obermayr, Elisabeth Maritschnegg, Paul Speiser, Christian Singer, Eva M. Schuster, Sabine Danzinger, Nina Pecha, Robert Zeillinger. Circulating rare cells enable highly efficient cancer detection. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-197. doi:10.1158/1538-7445.AM2015-LB-197
Kidney cancer: Experience of Centro Oncologico Buenos Aires (COBA) with immunotherapy (It) and targeted therapies (TT).
Authors: A. P. Hunis, L. A. Reuter, M. Hunis, A. Deves
Journal: Journal of Clinical Oncology (2011)

e15024 Background: To review the COBA results obtained in the first-line treatment of patients (pts.) with advanced kidney cancer for the past 10 years, since January 2000 to June 2006 (It) and from July 2006 to October 2010 (sunitinib and other TT). Methods: A descriptive, retrospective, longitudinal, non-comparative study. Results: The study included 150 pts. (106 male and 44 female 71% 29% H ratio: 1.5 - M: 1). Age: 51-60 years: 66 pts. (44%), 61 - 70 years: 34 pts. (23%). Histology: clear cell: 128 pts. (85%), chromophobe 8 pts. (5%), papillary 6 pts. (4%), oncocytoma 2 pts. (2%), sarcomatoid 2 pts. (2%), urothelial 2 pts. (2%), leiomyosarcoma 2 pts. (2%). Stages: stage IV: 88 pts. (59%) metastatic sites: 48 pts. (32%) lung, 30 pts. (20%) bone, 18 pts. (12%) retroperitoneal, 16 pts. (11%) lymph node, stage III: 6 pts. (4%) Stage II: 20 pts. (13%) Stage I: 36 pts. (24%). Surgery: radical nephrectomy: 122 pts. (81%). It.: 44 pts. (30% of 150 pts.) From January 2000 to June 2006: INF-α 2 (10 MU/I three times per week): 38 pts. (86.4%); IL2: 6 pts. (13.6%). From the studies published by Motzer et al. at ASCO 2006 and later began using sunitib as first-line treatment in July 2006. TT: 52 pts. 34.6% of the 150. From July 2006 to October 2010: sunitinib: 42 pts. (80.8%), sorafenib: 4 pts. (7.7%), temsirolimus: 6 pts. (11.5%) Stable disease: TT (16 pts. - 30%): 10 months; It. (10 pts. - 22.7%): 5.5 months. Sunitinib toxicity: fatigue: 42 pts. (100%) arterial hypertension: 6 pts. (14%), hand-foot syndrome: 4 pts. (9%), mucositis: 2 pts. (5%). Conclusions: Treatment with TT proved useful in controlling metastatic renal disease, achieving a statistically significant result of stable disease compared to that obtained with immunotherapy (10 vs. 5.5 months - p <0.001).
OP11ESTABLISHING A DIAGNOSTIC PIPELINE FOR METHYLOME ANALYSIS OF PAEDIATRIC AND ADULT BRAIN TUMOURS IN THE UK USING THE HEIDELBERG CLASSIFIER
Authors: Sebastian Brandner, Zane Jaunmuktane, Shu An, Thomas J. Stone, Jane Chalker, Karolina Pawliczak, Mark Kristiansen, Mike Hubank, Thomas S. Jacques
Journal: Neuro-Oncology (2015)

INTRODUCTION: Characteristic patterns of the DNA methylation are key features in various tumours. A promising tool for DNA methylation studies is the Illumina Infinium 450k array that assesses the DNA methylation status of 450,000 individual CpG sites. An algorithm, developed in Heidelberg, is based on more than 2000 reference brain tumours and is able to distinguish brain tumour entities based on their methylation profile. The aim is to improve the diagnostic accuracy, important for paediatric tumours, and useful for entities with unusual morphology or clinical course. METHOD: We have set up a diagnostic pipeline and have performed a trial run on a set of morphologically well-characterized paediatric and adult brain tumours and of a set of complex, unresolved tumour cases. Unprocessed idat-files of Illumina Infinium Human Methylation 450 BeadChips are uploaded to the Heidelberg v9 classifier. This tool provides a molecular classification, based on the comparison to the reference set as well as a low resolution copy number plot from the array data for assessment of deletions, including 1p19q codeletion and amplifications, and provides reliable information on the MGMT promoter methylation status. RESULTS: We present the feasibility of setting up a 450k array platform in a diagnostic setting including validation steps and interpretation of the classifier results of rare entities and approaches to refining or revising histological diagnosis. CONCLUSION: The molecular classification by Heidelberg classifier is as yet a research tool, but it does show a great potential for improving diagnostic accuracy, risk stratification and a step closer to improved patient-tailored therapy
Abstract 4189: Analgesic effect of quetiapine on the cancer induced bone pain animal model
Authors: Keon Uk Park, Mi Hwa Heo, Jin Young Kim, Ilseon Hwang, Hun Mo Ryoo
Journal: Cancer Research (2015)

Abstract Background: Cancer induced bone pain is one of the most common pain in patients with advanced cancer. Because of treatment associated side effects, it has been reported that more than half of cancer patients have inadequate and undermanaged pain control. Therefore, new mechanism-based therapies need to be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug that has superior therapeutic effects in patients with schizophrenia and other neurological disorders like depression. We reported that a study of anti-inflammatory effect of quetiapine on collagen induced arthritis mouse model. Now we focused on the potential analgesic effects of quetiapine on the cancer induced bone pain (CIBP) animal model and the mechanism of bone pain evaluated by various nociceptors expression. Methods: Fifteen male C3H/HeN mice were randomly divided into five groups: Control, CIBP, CIBP + quetiapine treatment, CIBP + opioid treatment and CIBP + melatonin treatment. Treatments were started when mouse showed positive signs of bone tumor until the day 28, according to the protocol, daily for 12 days. Pain thresholds of CIBP mouse model were measured by aesthesiometer for each group. At the end of the treatment period, tissue of mouse tibia were removed and quantitative and qualitative evaluation of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 expression were done. Results: The data showed that mouse behavior about pain thresholds was marked improved in CIBP + quetiapine treatment group compared with CIBP group. The expression of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 in CIBP + quetiapine treatment group was significantly lower than those in CIBP groups. Conclusions: These results suggest analgesic effect of quetiapine on CIBP animal model and provide the possibility that TRPV and ASICs could be a potential target of cancer pain management. Citation Format: Keon Uk Park, Mi Hwa Heo, Jin Young Kim, Ilseon Hwang, Hun Mo Ryoo. Analgesic effect of quetiapine on the cancer induced bone pain animal model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4189. doi:10.1158/1538-7445.AM2015-4189
Il-10 Polymorphism and TGF-β Haplotypes Are Associated with Rejection of Graft in Children with Beta Thalassemia Major Undergoing Matched Related Bone Marrow Transplantation (BMT).
Authors: Shanmugaapriya Sellathamby, Ryad Tamouza, Kavitha M Lakshmi, Auro Viswabandya, Biju George, Vikram Mathews, Rajagopal Krishnamoorthy, Dominique Charron, Mammen Chandy, Alok Srivastava
Journal: Blood (2006)
318. Targeted Genome Editing of Human Induced Pluripotent Stem Cells Using CRISPR/CAS9 to Generate a Knock-in Type II Collagen Reporter for the Purification of Chondrogenic Cells
Authors: Shaunak S. Adkar, Vincent P. Willard, Jonathan M. Brunger, Kenneth T. Shiao, Charles A. Gersbach, Farshid Guilak
Journal: Molecular Therapy (2016)

INTRODUCTION: Differentiation of human induced pluripotent stem cells (hiPSCs) to articular chondrocytes may provide a strategy for engineering cartilage tissue for therapy and functional characterization of patient-specific cartilage. Development of robust protocols will be particularly important for therapeutic applications. However, the difficulty of generating a pure population of chondrogenic precursors has hindered development of such protocols. We sought to isolate a chondrogenic cell population by engineering a novel hiPSC line to express GFP downstream of the COL2A1 gene using CRISPR/Cas9. METHODS: Reporter hiPSCs lines were generated via transfection of guide RNA/Cas9-T2A-GFP expression vector and COL2A1-P2A-GFP targeting vector (Fig 1A). Targeted clones were identified by junction PCR. Reporter validation was performed with lentiviral SOX9 overexpression and recombinant TGF-β3 treatment to activate COL2A1 expression. Cells were imaged with fluorescence microscopy at Days 4, 7, and 10. GFP+ and GFP− cells were sorted at Day 14 using fluorescence activated cell sorting (FACS). Gene expression from cell populations was analyzed with qRT-PCR. Reporter lines were differentiated to chondrogenic precursors via ectomesenchymal specification and TGF-β3 treatment. RESULTS: COL2A1-P2A-GFP reporter hiPSC lines were generated with CRISPR/Cas9 (Fig 1A/B). Imaging after COL2A1 activation demonstrated the presence of GFP signal only in treated cells (Fig 1C). Clonally derived cell lines displayed varied expression of GFP as measured by FACS (Fig 1D). GFP signal was highly correlated with COL2A1 gene expression (r2=0.95) (Fig 1E). GFP+ cells were enriched for chondrogenic markers such as COL2A1 and ACAN (p<0.05) (Fig 2A). After differentiation to chondrogenic precursors, 4.5% of cells were GFP+ (Fig 2B). This GFP+ population was enriched for COL2A1 transcript (Fig 2C), suggesting isolation of a chondrogenic population. DISCUSSION: We show the characterization of a knock-in COL2A1 hiPSC reporter cell line using CRISPR/Cas9. The reporter functions specifically during COL2A1 upregulation and may be useful as a surrogate metric with wide dynamic range and high specificity for determining COL2A1 expression. The GFP+ population is enriched for chondrocyte-specific markers, namely COL2A1 and ACAN. The reporter enriches for COL2A1 expression after multi-staged differentiation, suggesting its utility for tissue engineering applications.
Suicide strategy has failed, and GPs need better training in assessing risk, say MPs
Authors: Adrian O’Dowd
Journal: BMJ (2016)

National efforts to reduce the number of suicides in England have failed, and a new drive to tackle the problem must be backed by a clear implementation strategy, MPs have said.

Politicians on the parliamentary health committee published an interim report1 into suicide prevention on 19 December in which they also called for better training for GPs in identifying and dealing with suicide risk.

The report said that 4820 people were recorded as having died in 2015 from suicide in England with the true figure likely to be higher. The 2014 suicide rate (10.3 deaths in every 100 000) was the highest since 2004.

This was despite the launch of the government’s 2012 suicide prevention strategy.2 The government said that it would publish …
In Vitro Toxicity of Fludarabine on Normal Bone Marrow (BM) Progenitors Suggests Its Involvement in the Impairment of Hematopoietic Progenitor (HP) Mobilization.
Authors: Céline Richard, Véronique Maguer-Satta, Juliette Berger, Sandrine Jeanpierre, Franck E. Nicolini, Olivier Tournilhac, Mauricette Michallet, Marc G. Berger
Journal: Blood (2007)