tbuckley/cabot-search huggingface dataset:
SP0098 Ultrasound in Lung Fibrosis
Authors: L. Gargani
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Promising data have recently been obtained by lung ultrasound (LUS), which allows the detection of pulmonary fibrosis by the evaluation of B-lines (previously called ultrasound lung comets). B-lines are the sonographic sign of pulmonary interstitial involvement, including increased thickness of the pulmonary septa. Traditionally, B-lines have been employed in patients with heart failure to detect the location and quantification of extravascular lung water, but many data suggest their use also in assessing interstitial lung disease. Assessment of B-lines by LUS would represent an attractive biomarker for the frequent evaluation of pulmonary involvement in patients with rheumatic disease, since it is non-ionising, inexpensive and easy to perform and interpret. <h3>Image/graph</h3> <h3>Disclosure of Interest</h3> None Declared
Paraganglioma and Pancreatic Neuroendocrine Tumor With Rare Metastatic Sites Detected on 68Ga-DOTATATE PET/CT Imaging
Authors: Rahul Vithalrao Parghane, Bhagwant Rai Mittal, Jaya Shukla, Pranab Dey, Anish Bhattacharya, Rakesh Kochhar
Journal: Clinical Nuclear Medicine (2014)

Pancreatic neuroendocrine tumors (PNETs) represent a small percentage of all pancreatic malignancies, and most of these present as metastatic disease. Somatostatin receptor scintigraphy had been used successfully for the assessment of patients with NET. Somatostatin receptor scintigraphy is indispensable for localization of ectopic NET and the distribution of NET throughout the body.
Assays of circulating tumor cells and outcome in the triple-negative breast cancer trial TBCRC001.
Authors: HS Rugo, LA Carey, E Mayer, PK Marcom, M Liu, C Ma, AM Storniolo, A Forero, FJ Esteva, AC Wolff, T Hobday, M Ferraro, NE Davidson, EP Winer, D Moore, J Scott, JW Park
Journal: Cancer Research (2009)

Abstract Abstract #6048 Introduction. Basal-like breast cancer (BBC) has low expression of ER, PR, and HER2, and is often called triple negative (TN) BrCa. TBCRC 001 is a multicenter randomized phase II study of cetuximab (C) alone or combined with carboplatin (P) in TN BrCa. Pts randomized to Arm 1 received C alone (400 mg/m2, then 250 mg/m2 weekly) with P (AUC 2, 3 of 4 weeks) added upon progression (PD). Pts on Arm 2 received C+P throughout. The primary endpoint was objective response. To explore markers of activity and response, we measured circulating tumor cells (CTCs) in pts on study and directly compared two methods of CTC enumeration; CellSearch (Veridex) and immunomagnetic enrichment followed by flow cytometry (IE/FC). A subset of samples were isolated for molecular profiling.&amp;#x2028; Methods. Blood was obtained from consenting pts at baseline, 7 to 14 days after the first infusion, then monthly until the end of the study. CellSearch assay was performed as previously described using 7.5 cc blood in a CellSave tube and the CellSpotter analyzer, and the percent of CTCs staining for EGFR was also measured. For IE/FC, 20 ml of blood was subjected to IE using anti-EpCAM MAb-conjugated iron particles, followed by multiparameter FC for EpCAM, CD45, and nucleic acid content. CTC results were correlated by method, and to time on study treatment. In this preliminary analysis, the endpoint is time on study treatment (to progression/toxicity, TST).&amp;#x2028; Results: Safety and efficacy data from arms 1 and 2 have been presented (Carey et al; SABCS 2007, ASCO 2008). Of 102 TN pts enrolled in this study, 65 had CTC measurements by both methods on at least one time point. CTC levels by the two assays were highly correlated at all time points. At baseline, Spearman's rank correlation coefficient was 0.67 (p&amp;lt;0.0001). Using the cutoffs shown below, CTC by IE/FC or CellSearch at baseline and first follow-up correlated with TST. This relationship was observed in both arm 1 and 2.&amp;#x2028; &amp;#x2028; Conclusion: In this phase II trial of C or C+P in pts with TN metastatic BrCa, CTCs measured by two different techniques were highly correlated. CTC levels at baseline and 7-14 days predicted longer vs. shorter TST, suggesting that CTCs may be an early marker of response to targeted therapy. Additional molecular data on CTCs will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6048.
Abstract P3-01-01: Cyfra 21-1 Is Correlated with Circulating Tumor Cells Detection and Patient Outcome in Metastatic Breast Cancer: Results of a Substudy of the Prospective IC 2004-06 Trial
Authors: F-C Bidard, D Hajaje, T Bachelot, E Brain, M Campone, S Delaloge, C. Mathiot
Journal: Cancer Research (2010)

Abstract Background: The Cyfra 21-1 epitope is a polypeptide originating from cytokeratin-19 fragments possibly released by cell death and was an interesting serum marker in small and/or retrospective studies in breast cancer. On the back of circulating tumor cell (CTC) detection, the prospective IC 2006-04 study planned serum markers (CEA, Ca15.3, Cyfra 21-1) measurements. Methods: Metastatic breast cancer patients were included in a multicentric non-interventional study before the start of the 1st line chemotherapy. Blood biomarkers, including CTC detection (CellSearch®, ≥5CTC/7.5ml), were analyzed at 4 different times: before the start of the chemotherapy, before cycle 2 (ie mostly at day 21), at first tumor evaluation (ie before cycle 3/4) and at tumor progression. Results: 191 of the 267 patients included had Cyfra 21-1 assessed at inclusion. CTC level was ≥5CTC/7.5ml in 44% of the cases. Cyfra 21-1&amp;gt;ULNV (in 65% of pts) was not correlated with tumor ER/PR/HER2 status but strongly correlated with PS (p=8e-04), number of metastatic sites (p=0.0001), Ca15.3 (p=0.009), CEA (p=0.005), LDH (p=7e-08) and CTC detection (p=2e-06). CTC (≥5CTC/7.5ml) and Cyfra21-1 (&amp;gt;ULNV) correlation (N patients) The effectiveness of curcumin in the treatment of HER-2 overexpressed breast cancer was further confirmed through in vivo BT-474 xenograft model. The comparable ability of curcumin to inhibit cell proliferation, mobility, and angiogenesis as herceptin, combined with the potential ability to overcome the herceptin resistance, curcumin may be a novel agent in the treatment of HER-2 overexressed breast cancer. Logistic regression showed that LDH (p=0.0005) and CTC (p=0.0004) were the two independent predictors of Cyfra 21-1 elevation. Baseline Cyfra 21-1 &amp;gt;ULNV was associated with early tumor progression (RECIST, p=0.03). In multivariate analysis including standard biomarkers (without CTC), baseline Cyfra 21-1 was independently associated with PFS (p=0.008, RR), together with PS (P&amp;lt;0.001), triple-negativity (P&amp;lt;0.001) and CEA (p=0.02). Multivariate analysis with CTC, subsequent Cyfra 21-1 analyses (cycles 2, 3-4 and progression) and correlation with tumor response and PFS will be will be shown at the meeting. Conclusion: Cyfra 21-1 is a commonly elevated serum marker in metastatic breast cancer and has an independent prognostic value. Although highly correlated, Cyfra 21-1 appears to be more frequently positive in metastatic breast cancer patients than CTC count. Multivariate analyses comparing CTC and Cyfra 21-1 at different time points will be shown at the meeting. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-01-01.
Abstract 3181: The combined use of urine and serum biomarkers in early detection strategies for pancreatic cancer
Authors: Brian M. Nolen, Aleksey Lomakin, William E. Grizzle, Nirag Jhala, Mohamad A. Eloubeidi, John D. Christein, Juan P. Arnoletti, Denise K. Oelschlager, Selwyn M. Vickers, Anna E. Lokshin
Journal: Cancer Research (2011)

Abstract The devastatingly high level of mortality associated with pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death in the United States, has remained virtually unchanged over the past 50 years due to an inability to effectively detect and treat the disease at an early stage. Currently used imaging techniques including CT and MRI have demonstrated an inability to distinguish benign from malignant pancreatic lesions resulting in both a low sensitivity for pancreatic cancer and a high degree of unnecessary referral for highly invasive endoscopic ultrasound (EUS). A biomarker-based test that could effectively rule out the possibility of malignancy in patients presenting with an abnormal finding by CT or MRI would greatly reduce the number of unnecessary EUS procedure and the associated risk of complication as well as lead to an optimization of resources for more effective early detection of the disease. Serum biomarkers such as CA 19-9 have been under investigation in pancreatic cancer for a number of years. Recently, the use of urine in biomarker studies has garnered considerable interest based on its ease of sampling, high stability, and relative simplicity as a testing matrix. In order to evaluate the use of urine and serum biomarkers in pancreatic cancer screening, we analyzed 77 cancer-associated biomarkers in urine obtained from 55 patients diagnosed with PDAC and 44 patients diagnosed with benign pancreatic conditions. Twenty of the most relevant biomarkers were also tested in sera obtained from the same patient cohort. Forty of the 77 urine biomarkers as well as nine of the twenty serum biomarkers were significantly altered between the benign and malignant groups. Of the twenty biomarkers measured in both urine and serum, seven were more significantly altered in urine, while seven others were more significantly altered in serum. A multivariate analysis of the results identified a four-biomarker panel comprised of both serum and urine biomarkers which could discriminate PDAC from benign disease with optimal levels of sensitivity and specificity. Our results indicate a promising role for the combined use of urine and serum biomarkers in the development of improved screening strategies for pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3181. doi:10.1158/1538-7445.AM2011-3181
AB0604 Soluble adhesion molecules (ICAM-1, VCAM-1, and E-selectin) in patients with early rheumatoid arthritis
Authors: P.A. Klimiuk, S. Sierakowski, M. Fiedorczyk, J. Chwiecko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cell adhesion molecules (CAMs) play an important role in the pathogenesis of rheumatoid arthritis (RA). Mononuclear cells activation, circulation and migration to inflammatory sites are regulated by adhesion molecules like intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin. <h3>Objectives</h3> The aim of the study was to analyse serum concentrations of soluble adhesion molecules in patients with early RA before, and after 6 months treatment with methotrexate (MTX). <h3>Methods</h3> We studied 32 RA patients, untreated with disease modifying anti-rheumatic drugs (DMARDs) or corticosteroids, with disease duration less than 3 years. Twenty osteoarthritis (OA) patients constituted a control group. The analysis of serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) was based on a quantitative sandwich ELISA. <h3>Results</h3> In compassion with OA patients higher serum concentrations of sICAM (p&lt;0.01), sVCAM-1 (p&lt;0.01) and sE-selectin (p&lt;0.05) were observed in untreated patients with early RA. Six months treatment with MTX down-regulated serum concentrations of sICAM-1, sVCAM-1 and sE-selectin (in all cases p&lt;0.001) in studied RA patients. Furthermore, MTX treatment was followed by the decrease in the clinical markers of the RA activity such as the number of painful and swollen joints, ESR, disease activity score (DAS) and CRP levels. <h3>Conclusions</h3> Patients with early RA are characterized by high serum concentrations of sICAM-1, sVCAM-1 and sE-selectin. Therapy with MTX resulted in clinical improvement and diminished serum levels of soluble adhesion molecules in studied RA patients confirming effectiveness of MTX in early stages of the disease. <h3>Disclosure of Interest</h3> None Declared
A phase I/II trial of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in combination with either temozolomide or lomustine for patients with recurrent glioblastoma multiforme (GBM)
Authors: D. Reardon, H. Friedman, W. K. A. Yung, M. Brada, C. Conrad, J. Provenzale, E. Jackson, H. Serajuddin, B. Chen, D. Laurent
Journal: Journal of Clinical Oncology (2004)

1513 Background: VEGF-mediated signaling through VEGF receptors is integral to GBM neovascularization and therefore an attractive therapeutic target. PTK/ZK is an oral, once-daily inhibitor of all known VEGF receptors. The primary objective of this trial was to determine the safety profile and maximum tolerated dose (MTD) of oral once-daily PTK/ZK in combination with either temozolomide (TMZ) or lomustine (CCNU) in patients (pts) with GBM. Antitumor activity was also assessed. Methods: The starting dose of PTK/ZK was 500 mg/day, escalating to 1,000, 1,250, and 1,500 mg/day in cohorts of 3 to 6 pts with dose expansion at 1,500 mg/day in the TMZ treatment arm. Concurrently, pts also received either TMZ (200 mg/m2/day for 5 days every 28 days) or CCNU (130 mg/m2 every 6 weeks). Results: Among 60 pts enrolled, median age was 53 years (range, 28 - 80 years), median KPS was 90 (range, 70 - 100), and the median number of prior regimens was 1 (range, 1 - 9). In 37 pts treated with PTK/ZK + TMZ, 1 dose-limiting toxicity (DLT) (grade 3 dizziness) was reported at 1,500 mg/day, and the MTD was not reached. Among 23 pts treated with PTK/ZK + CCNU, DLTs included grade 3 febrile neutropenia in 1 pt each at the 500- and 1,000-mg levels and grade 4 transaminase elevation in 1 pt treated at the 1,000-mg level, which may be related to CCNU. The PTK/ZK dose level was reduced to 750 mg/day plus CCNU; accrual is ongoing. Among 51 pts evaluable for response, 4 had a partial response (3 with PTK/ZK + TMZ and 1 with PTK/ZK + CCNU) and 27 had stable disease (19 with PTK/ZK + TMZ and 8 with PTK/ZK + CCNU) as best response. Median time to progression was 15.7 weeks (95% CI = 8.6, 17.3 weeks) for PTK/ZK + TMZ and 10.4 weeks (95% CI = 8.1, 18.7 weeks) for PTK/ZK + CCNU. The median TTP for PTK/ZK + TMZ compares favorably with historical reports with TMZ alone (Br J Cancer 2000;83:588). Conclusions: Continuous daily dosing of oral PTK/ZK was well tolerated and demonstrated encouraging antitumor activity when combined with either TMZ or CCNU, warranting further study. Accrual is ongoing, and the respective MTDs have yet to be determined. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp.; Schering AG Novartis Pharmaceuticals Corporation
Microbiota
Authors: Ting Feng, Charles O. Elson, Yingzi Cong
Journal: Gut Microbes (2010)

We have recently demonstrated that microbiota stimulation of innate immune pathways is required for T cell spontaneous proliferation and chronic intestinal inflammation. Microbiota promoted spontaneous proliferation of T cells by activating dendritic cells to produce interleukin (IL)-6 via a TLR/MyD88-dependent pathway. Although both CBir1-specific TCR transgenic (CBir1 Tg) T cells, which are specific for an immunodominant microbiota antigen, and OT-II T cells, which are specific for the model antigen ovalbumin, underwent spontaneous proliferation, only CBir1 Tg T cells but not OT-II T cells induced colitis in specific pathogen-free RAG-/- mice. Blockade of IL-6 or IL-6-mediated spontaneous proliferation of CBir1 Tg T cells abrogated colitis induction in this adoptive transfer model. Our data reveal that microbiota serves as a natural adjuvant for T cell spontaneous proliferation and development of chronic intestinal inflammation, and that both microbiota stimulation of innate immune cells with subsequent T cell spontaneous proliferation and microbiota antigen activation of antigen-specific TCR are required for the induction of experimental colitis
Abstract 5724: HER2-mediated resistance of breast cancer stem cells in HER2-negative/low breast cancer
Authors: Demet Candas, Ming Fan, Nadire Duru, Cheikh Menaa, Yunfei Wen, Kai Xiao, Angela Eldridge, Brett A. Chromy, Shiyong Li, Douglas R. Spitz, Kit S. Lam, Max S. Max, Jian Jian Li
Journal: Cancer Research (2012)

Abstract Despite a recent trend toward improvement, breast cancer (BC) mortality remains high due to resistance of recurrent tumors. A major cause of recurrence is likely a micro-metastatic seeding of cells that developed resistance by activating intrinsic or acquired survival pathways. In this regard, HER2 expression and cancer stem cells (CSCs) are the major cause for recurrence and targeting HER2 is well considered in therapeutic regiments. However, clinical data showed that anti-HER2 also benifit HER2−/low BC patients, suggesting that tumor cells may acquire HER2 gene activation to survive. We have previously reported that NF-κB mediates radioresistance by controlling HER2 gene. Herein, we identified HER2-expressing BC stem cells (HER2+/CD44+/CD24−/low) in radiation-resistant HER2−/low BC cells, MCF7/C6. Matrigel invasion, tumor sphere formation and radioresistance were enhanced in the HER2 mediating radioresistant cells. About 10% of the CD44+/CD24−/low cells sorted from MCF7/C6 cells or irradiated xenografts showed co-expression of HER2/CD44, ALDH and high tumorigenicity compared to HER2−/CD44+/CD24−/low cells, suggesting that the induction of HER2 expression further increased the BCSC aggressiveness. In fact, clinical data indicates that cells co-expressing HER2/CD44 were increased in recurrent tumors (84.6%) compared to the primary tumors (57.1%). Proteomics analysis identified a unique profile of proteins including DNA repair, mitochondrial function, redox, mTOR pathways that may govern the resistance of HER2+/CD44+/CD24−/low CSCs. These results demonstrate that HER2-mediated BC resistance can develop at the level of BCSC. Thus, HER2-expressing BCSCs may serve as an effective target to treat BC recurrence even from primary HER2−/low tumors. 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 5724. doi:1538-7445.AM2012-5724
India considers allowing expatriate doctors to practise back home
Authors: J. Elliott
Journal: BMJ (2012)

A proposal to lure back from overseas doctors with Indian backgrounds to solve the country’s chronic shortage of trained staff has run into opposition.

India has a desperate need for more medical staff, with rural areas in particular struggling to recruit and retain medical staff.

The country needs another 600 000 doctors, a million more nurses, and 200 000 more dental surgeons.

To fill the shortfall India’s government wants to relax the rules so that doctors with the status of “overseas citizenship of India” (OCI) can also practise there. OCI is the term the government uses for people …
Retrospective Analysis of Efficacy and Optional Treatment with Lapatinib Plus Capecitabine Therapy
Authors: Y. Mizuno, N. Kurata, M. Tsutsuyama, S. Umeda, H. Teramoto, T. Shikano, T. Hachisuka, T. Mori, M. Shinohara, M. Miyauchi
Journal: Annals of Oncology (2013)
Abstract 4526: Suppression of Alox5 gene is involved in DZNep induced apoptosis in multiple myeloma cells
Authors: Zhigang Xie, Chonglei Bi, Lip Lee Cheong, Wee Joo Chng
Journal: Cancer Research (2010)

Abstract The 3-Deazaneplanocin A (DZNep), one of S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors, has shown antitumor activities in a broad range of solid tumors and acute myeloid leukemia. It was found that DZNep effectively depletes EZH2 levels and inhibits trimethylation of lysine 27 on histone H3. Here, we examined its effects on multiple myeloma (MM) cells and found that, at 500 nM, it potently inhibited growth and induced apoptosis in 2 of 8 MM cell lines(8226, H929, KMS11, KMS12BM, KMS18, MM1S, OPM-2 and U266). We then attempted to identify molecular mechanisms of sensitivity to DZNep. RNA from un-treated and DZNep treated cells was profiled by Affymetrix HG-U133 Plus 2.0 microarray and genes with a significant change in gene expression were determined by significance analysis of microarray (SAM) testing. ALOX5 was the most down-regulated gene (5.8-fold) in sensitive cells and was expressed at low level in resistant cells. The results were corroborated by qRT-PCR. Western-blot analysis indicated ALOX5 was highly expressed only in sensitive cell line H929 and greatly decreased upon DZNep treatment. Furthermore, down-regulation of ALOX5 by RNA interference can also induce apoptosis in H929. Since it was reported ALOX5 can regulate IL-6 mRNA level, we also determined IL-6 and IL-6R expression by qRT-PCR. As expected, IL-6 and IL-6R mRNA levels were decreased (&amp;gt;2-fold) in H929 upon DZNep treatment. May-Grunwald-Giemsa staining demonstrated that treatment with DZNep also dose dependently induced nuclear and cytoplasmic morphologic features of apoptosis in H929. These findings in vitro warrants further investigation of DZNep for the treatment of MM in vivo. 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 4526.
Abstract 1114: IGF-II regulates the expression of estrogen receptor beta 5: Role in the survival disparity between African-American and Caucasian women with breast cancer
Authors: Chane’ O'Bannon, Nalo Hamilton, Daisy De Leon
Journal: Cancer Research (2011)

Abstract African American (AA) women with breast cancer are more likely to be diagnosed at a more advanced stage of the disease, have a higher recurrence rate and a poorer prognosis than Caucasian (CA) women. African American women are more often diagnosed with high-grade breast tumors at an earlier age most of which are negative for the estrogen and progesterone receptors. These factors result in a higher mortality rate among AA patients. This survival disparity can be attributed to socieconomic status and other related factors, however there are biological factors that may also be involved. The insulin-like growth factor II (IGF-II) plays a crucial role in fetal and cancer development by signaling through the IGF-I receptor (IGF-IR), the insulin receptor (InsR) and crosstalk with the estrogen receptor alpha (ER-α). Compared to CA women, AA women have an increased level of proIGF-II expression in breast tissues and higher signaling activation through the IGF-1 and InsRs. Since the estrogen receptor beta (ER-β) is also expressed in a majority of breast cancers we propose that IGF-II may also activate the ER-β signaling pathway. ER-β has 5 isoforms of which ER-β5 is the most abundantly expressed among AA women with breast cancer and it is associated with a poor prognosis and decreased survival. Thus, our hypothesis is that IGF-II activation of the ER-β5 contributes to the survival disparity between AA women and CA women. To test this hypothesis we analyzed the expression of ER-β5 in AA and CA breast cancer cell lines by western blot, siRNA analysis and IGF-II stimulation. IGF-II not only modulated the phosphorylation of ER-β5, but it also promoted the translocation of ER-β5 to different organelles. Thus, we conclude that ER-β5 may contribute to the survival disparity among AA breast cancer patients since ER-β5 impairs the inhibitory effect of other ER-β isoforms. 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 1114. doi:10.1158/1538-7445.AM2011-1114