tbuckley/cabot-search huggingface dataset:
Abstract 1398: IFIT2 depletion promotes migration through atypical PKC signaling in oral squamous cell carcinoma
Authors: Kuo Chu Lai, Chung Ji Liu, Te Chang Lee
Journal: Cancer Research (2011)

Abstract Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) is one of most responsive interferon-stimulated genes to interferons, viruses, and a variety of agents. However, the biological functions of IFIT2 are poorly understood. Our previous study showed that IFIT2 overexpression was frequently found in tumor tissues of oral squamous cell carcinoma (OSCC). Besides, enhanced IFIT2 expression was inversely associated with poor patient survival. In cultured cell system, we demonstrated that depletion of IFIT2 expression in OSCC cell lines significantly enhanced the motility of cells. In this study, experiments were conducted to explore the underlying mechanisms by which IFIT2 depletion enhanced migration of OSCC cells. We first established stable IFIT2 knockdown and non-silencing control cells by lentivirus transduction system. Our results showed that stable IFIT2 knockdown cells displayed elongated spindle-like morphology, F-actin reorganization, and loss of epithelial markers, such as E-cadherin and keratin 18, as compared to control cells, suggesting the involvement of IFIT2 in epithelial-mesenchymal transition and F-actin cytoskeleton organization. While stable IFIT2 knockdown cells exhibited enhanced cell motility and invasion as compared to control cells, we found that PI3K/Akt or PKC inhibitors significantly inhibited migration of stable IFIT2 knockdown OSCC cells. Notably, PKCζ pseudosubstract significantly abolished IFIT2 depletion-induced migration. Furthermore, atypical PKC phosphorylation (Thr410/403) was enhanced in IFIT2-silencing cells compared to that of control cells. Furthermore, among 25 metastatic OSCC patients, the median survival was 57.4 months in patients expressed high levels of IFIT2 (IFIT2 ≥ 50), whereas the median survival drastically reduced to 13.6 months in patients expressed low IFIT2 (IFIT2 &amp;lt; 50). Taken together, our results revealed that atypical PKC signaling may involve in enhanced migration of IFIT2 knockdown OSCC cells. 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 1398. doi:10.1158/1538-7445.AM2011-1398
SAT0224 Neopterin – an indicator for lupus activity?
Authors: G. Zeh, F. Haas, M. Schmalzing, I. Koetter
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In recent times, the role of Type I and II interferons in pathogenesis as well as in flares of systemic lupus erythematosus has been emphasized. Neopterin is a marker of interferon- induced activation of macrophages and therefore, as it has been shown in several smaller studies, a possible marker of activity in SLE. <h3>Objectives</h3> We performed a retrospective analysis of our data which addressed the question of a correlation between neopterin and SLEDAI as well as the complement factors C3 and C4. <h3>Methods</h3> Retrospective Analysis of 196 patients with SLE according the revised ACR-criteria of 1982, from our rheumatology outatient clinic since January 1st 2009. We randomly chose one visit of each patient (out of 693 visits totally) in order to avoid statistical bias. The values for SLEDAI, neopterin, C3 and C4 were illustrated graphically and Spearman's correlation coefficient wascalculated. We investigated the correlation between neopterin and SLEDAI, neopterin and C3/C4 as well as for SLEDAI and C3/C4. Patients with chronic kidney disease (GFR &lt;60ml/min) were excluded. <h3>Results</h3> We found a weak correlation between SLEDAI and neopterin (Spearman ρ=0,29; p&lt;0,001) as well as between C3/C4 and neopterin (ρ= -0,19 for neopterin/C3; p=0,0074 and ρ = -0,087 for neopterin/ C4 respectively; p=0,2254). In contrast, correlation between SLEDAI and C3 was stronger with ρ= -0,5 (p&lt;0,001)and SLEDAI/C4 with ρ= -0,36 (p&lt;0,001). <h3>Conclusions</h3> Compared with complement factors C3 and C4, we could not find a stronger correlation between neopterin an SLEDAI index in our patients. Neopterin therefore was not superior in estimating Lupus activity in our patients compared with C3 and C4. These data are limited by the fact, that only few patients with high or very high disease activity were included in the calculation. Therefore further investigation in larger patient cohorts is needed. Our results from the largest patient population examined to date lie between those of previous smaller studies which revealed correlation coefficients for neopterin and lupus acitivity indices between 0,08 and 0,59. Neopterin may be of value as additional marker of disease activity in individual patients, but generally, the correlation of low C3/C4 with disease activity is better. In our cohort, we had 9 patients with high or very high disease activity (SLEDAI &gt;11). Out of these patients, one had an elevated neopterin and normal values for C3/C4. <h3>Disclosure of Interest</h3> None Declared
Outcomes Of Chronic Lymphocytic Leukemia Patients With Richter Syndrome
Authors: Sameer A. Parikh, Ruchi G. Sharma, Timothy G. Call, Thomas M Habermann, Wei Ding, Jose F. Leis, Susan Schwager, Curtis A. Hanson, William R Macon, Renee C. Tschumper, Diane F. Jelinek, Neil E. Kay, Susan L Slager, Kari G. Rabe, Tait D Shanafelt
Journal: Blood (2013)
Abstract 1408: Opposing roles of p53 and autophagy in a model of <i>PALB2</i>-associated hereditary breast cancer.
Authors: Yanying Huo, Hong Cai, Irina R Teplova, Christian Bowman-Colin, Guanghua Chen, Sandy Pricea, Vassiliki Karantzaa, Eileen White, Bing Xia
Journal: Cancer Research (2013)

Abstract Hereditary breast cancers stem from germline mutations in susceptibility genes such as BRCA1, BRCA2 and PALB2. These and the majority of other known susceptibility genes all encode products that function in the repair and response to DNA damage, particularly double strand breaks. The p53 tumor suppressor is frequently mutated in hereditary breast cancer, and results from mouse models also suggest that its inactivation is critical for tumorigenesis induced by loss of BRCA1 and BRCA2. Autophagy is an intracellular waste disposal/recycling and stress mitigation mechanism that that can impact both cancer initiation and progression, but its role in breast cancer is unclear. Here we show that, similar to Brca1 and Brca2, ablation of Palb2 in mouse mammary gland resulted in tumor development with long latency, the majority of the tumors harbored mutations in Trp53, and combined deletion of Palb2 and Trp53 led to efficient tumor formation. Interestingly, partial loss of autophagy, due to mono-allelic loss of the essential autophagy gene Becn1, delayed and reduced Palb2-associated mammary tumorigenesis in mice with Palb2 single deletion but not Palb2;Trp53 double deletion in the mammary gland. These results indicate that, in the face of DNA damage and genome alterations elicited by PALB2 loss, p53 is a barrier to cancer development whereas autophagy facilitates cell survival and tumorigenesis. Our findings also underscore the similarity between PALB2- and BRCA-associated cancers and further suggest that inhibition of autophagy may represent a new avenue to the prevention and/or treatment of hereditary breast cancers. Citation Format: Yanying Huo, Hong Cai, Irina R Teplova, Christian Bowman-Colin, Guanghua Chen, Sandy Pricea, Vassiliki Karantzaa, Eileen White, Bing Xia. Opposing roles of p53 and autophagy in a model of PALB2-associated hereditary breast cancer. [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 1408. doi:10.1158/1538-7445.AM2013-1408
A simple novel endoscopic successive suture device: a validation study for closure strength and reproducibility
Authors: Y. Song, H. Choi, K. Kim, Y. Kim, B. Kim, D. Hong, B. Keum, H. Chun
Journal: Endoscopy (2013)

Endoscopic surgical technology has been developing rapidly. Although several successful endoscopic closure devices have already been introduced, only a few of them have demonstrated improvements in closure strength and reproducibility over conventional endoscopic clip closures or hand sutures. The objective of this study was to test the feasibility of a novel successive suturing device (SSD) by measuring closure strength and reproducibility.Porcine stomach models were used in this study. Endoclips, full-thickness hand sutures, and the novel SSD sutures were used to close a perforation in the stomach wall, with 10 stomachs being tested for each closure method. Endoclips and SSD sutures were performed using a two-channel endoscope, and the hand sutures were performed from outside of the stomach wall. Air leakage pressure was measured to determine the closure strength and reproducibility of each method.The mean air leakage pressure of the SSD closure was 62.7 ± 8.2 mmHg. SSD-treated stomachs exhibited significantly greater air leakage pressure than Endoclip-treated stomachs. The standard deviation of bursting pressure in SSD stomachs was found to be significantly smaller than that of hand-sewn stomachs but was not different from that of Endoclip stomachs.The consistent closure strength of SSD stomachs demonstrated the reliability and reproducibility of this new closure method. These promising results in closure strength and reproducibility suggest the feasibility of the proposed device for clinical applications.
PWE-152 Selective Loss of Oncofoetal Antigen 5T4-Specific T Cell Response Correlates with Progression of Colorectal Cancer
Authors: M Scurr, M Davies, S Phillips, R Hargest, A Christian, T Hockey, G Williams, A Gallimore, A Godkin
Journal: Gut (2013)

<h3>Introduction</h3> The human oncofoetal antigen 5T4 is expressed on many human carcinomas, including colorectal cancer (CRC) cells, but has limited expression on normal tissues making it an ideal target for cancer immunotherapy. Here, a significant loss of T cell response to 5T4 in patients with more advanced CRC has been identified. <h3>Methods</h3> Lymphocyte samples obtained from HLA-typed CRC patients and healthy donor controls were cultured for two weeks with pools of overlapping 20mer 5T4 peptides, spanning the entire protein, before subsequent analysis for antigen specificity, as measured by the highly sensitive IFN-g/IL-10 ELISPOT assay. <h3>Results</h3> Positive 5T4-specific lines were identified in 79% (15/19) of CRC patients and all (11/11) healthy donors tested. Intriguingly, CRC patients respond to significantly fewer candidate epitopes and generate a lower magnitude of IFN-γ responses to 5T4. Furthermore this response diminishes with tumour advancement despite similar responses to the recall antigen PPD. The mechanism of loss of T cell response is independent of HLA-DR type or patient age, but depletion experiments indicate suppression by Foxp3+ regulatory CD4+ T cells. In addition, analysis of peripheral blood and tumour-infiltrating lymphocytes in the same cohort of patients revealed a marked suppressive phenotype in comparison to healthy age-matched controls. <h3>Conclusion</h3> Effective anti-tumour immunotherapy will be reliant upon overcoming such regulation of tumour-specific T cell responses. These data support a rationale for re-stimulating 5T4-specific immune responses in CRC patients, and reducing tumour-induced immunosuppression to enhance immunotherapy. <h3>Disclosure of Interest</h3> None Declared.
Abstract 3398: Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer cells.
Authors: Chung-Pu Wu, Hong-May Sim, Yang-Hui Huang, Yen-Chen Liu, Sung-Han Hsiao, Hsing-Wen Cheng, Yan-Qing Li, Suresh Ambudkar, Sheng-Chieh Hsu
Journal: Cancer Research (2013)

Abstract Melanoma is the most serious type of skin cancer with a high potential for metastasis and very low survival rates. The discovery of constitutive activation of the BRAF kinase caused by activating BRAF(V600E) kinase mutation in most melanoma patients led to the discovery of the first potent BRAF(V600E) signaling inhibitor, vemurafenib. Vemurafenib was effective in treating advanced melanoma patients and was proposed for the treatment of other BRAF(V600E) mutant cancers as well. Unfortunately, the success of vemurafenib was hampered by the rapid development of acquired resistance in different types of BRAF(V600E) mutant cancer cells. It becomes important to identify and evaluate all of the potential mechanisms of cellular resistance to vemurafenib. In this study, we characterized the interactions of vemurafenib with three major ATP-binding cassette (ABC) transporters, ABCB1, ABCC1 and ABCG2. We found that vemurafenib stimulated the ATPase activity and potently inhibited drug efflux mediated by ABCB1 and ABCG2. Vemurafenib also restored drug sensitivity in ABCG2-overexpressing cells. Moreover, we revealed that in the presence of functional ABCG2, BRAF kinase inhibition by vemurafenib is reduced in BRAF(V600E) mutant A375 cells. Taken together, our findings indicate that ABCG2 confers resistance to vemurafenib in A375 cells, suggesting involvement of this transporter in acquired resistance to vemurafenib. Thus, combination chemotherapy targeting multiple pathways could be an effective therapeutic strategy to overcome acquired resistance to vemurafenib for cancers harboring the BRAF(V600E) mutation. Citation Format: Chung-Pu Wu, Hong-May Sim, Yang-Hui Huang, Yen-Chen Liu, Sung-Han Hsiao, Hsing-Wen Cheng, Yan-Qing Li, Suresh Ambudkar, Sheng-Chieh Hsu. Overexpression of ATP-binding cassette transporter ABCG2 as a potential mechanism of acquired resistance to vemurafenib in BRAF(V600E) mutant cancer 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 3398. doi:10.1158/1538-7445.AM2013-3398
A5.10 Give and take: Evidence for transfer of mitochondria via nanotubes in fibroblast-like synoviocytes
Authors: RA Byrne, I Olmos Calvo, F Kartnig, K von Dalwigk, T Karonitsch, G Steiner, J Holinka, P Ertl, JS Smolen, HP Kiener
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The synovial membrane of diarthrodial joints is primarily composed of fibroblast-like synoviocytes (FLS) that form a complex tissue via discrete cell-to-cell connexions with wide intercellular matrix spaces. The distinct synovial tissue function that is crucial to joint homeostasis depends upon integrated activity of individual FLS. Using a in-vitro synovial organ culture system, we explore mechanisms of FLS cellular cooperation with special interest in the cell-to-cell transfer of mitochondria via interconnecting membrane nanotubes. <h3>Methods</h3> Human FLS were prepared from synovial tissues obtained as discarded specimens following joint arthroplasty. Cells were cultured in spherical matrigel micromasses with an average size of 2 mm Ø. Data was acquired by&nbsp;confocal live cell imaging. Analysis of the resulting 4D movies was done with Imaris® software. <h3>Results</h3> To examine whether or not FLS transfer cytoplasmic cargo, we labelled 50% of FLS with red cell tracker dye and loaded the other 50% with green non-degradable microspheres. In a time series (8 days), we found that microspheres appear in red labelled cells. First evidence was found on Day 1 and over the course of the following days microspheres accumulated in red labelled cells with a transfer rate of&nbsp;10% of newly affected cells/day. With special interest in the transfer of mitochondria, we repeated similar experiments with labelled mitochondria. We found that the transfer rate for these organelles is similar to the one for microspheres. Additionally, we were able to capture evidence that FLS indeed use their nanotube connexions for transfer of mitochondria. <h3>Conclusions</h3> Our experiments suggest transfer of cytoplasmic cargo, including organelles such as mitochondria, between FLS. These studies may provide insight into how synoviocytes orchestrate their activity. Further studies will demonstrate the significance of directed cargo exchange for cellular cooperation and the function of the normal as well as the diseased synovium.
A phase II randomized selection trial evaluating concurrent chemotherapy plus cetuximab or chemotherapy followed by cetuximab in patients with advanced non-small cell lung cancer (NSCLC): Final report of SWOG 0342
Authors: R. S. Herbst, K. Chansky, K. Kelly, J. N. Atkins, A. M. Davies, S. R. Dakhil, K. S. Albain, E. S. Kim, J. J. Crowley, D. R. Gandara
Journal: Journal of Clinical Oncology (2007)

7545 Background: Randomized clinical trials have failed to show a survival benefit for small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors plus chemotherapy in unselected patients with metastatic NSCLC. In contrast, pilot trials of EGFR targeted antibodies plus chemotherapy have suggested enhanced anti-tumor activity. This randomized phase II selection trial was designed to select a cetuximab-chemotherapy regimen for future evaluation in a phase III setting. Methods: Untreated patients (pts) with advanced stage NSCLC were randomized to receive paclitaxel (P) 225 mg/m 2 and carboplatin (Cb) AUC=6 every 3 weeks plus concurrent cetuximab (C) 400 mg/m 2 loading dose followed by 250 mg/m 2 , weekly for 4 cycles followed by maintenance C or sequential PCb for 4 cycles followed by C. Treatment was continued until disease progression. Eligible patients were required to have stage IIIB (pleural effusion) or IV (without brain metastases) disease, a performance status of 0–1 and adequate organ function. The primary endpoint was overall survival. The regimen with superior median survival would be considered for further evaluation provided it met a 10-month minimum. Given a true hazard ratio of 1.3, the probability of correctly choosing the superior arm would be &gt; 90%. Results: From July 2004 to June 2005, 242 eligible pts were enrolled onto the study, Final results are described below: Conclusions: Both regimens met efficacy criterion for continued evaluation though the concurrent regimen of PCb + C, had numerically higher survival, and was chosen for further study. Some toxicities were significantly increased with concurrent therapy. A phase II trial of PCb + Cetuximab + Bevacizumab is ongoing (SWOG 0536) in anticipation of a phase III trial. Molecular correlative studies of the EGFR signaling pathway including EGFR IHC, FISH and mutation analysis are underway. No significant financial relationships to disclose. [Table: see text]
Parathyroid Hyperplasia Shown on 99mTc-HYNIC-TOC Scan
Authors: Na Niu, Xinxin Mao, Hongli Jing, Fang Li
Journal: Clinical Nuclear Medicine (2013)

A 99mTc-HYNIC-TOC scintigraphy was performed on a 68-year-old patient with hypercalcemia and borderline hypophosphatemia to assess the source of suspected tumor-induced osteomalacia. The images revealed increased activity in the upper mediastinum and focal activity in the pancreas. The lesion in the upper mediastinum was subsequently proven pathologically as parathyroid hyperplasia in a patient with multiple endocrine neoplasia type 1 (MEN-1 syndrome).
Abstract 3957: Role of miRNA-211 in melanocyte and melanoma cells
Authors: Nityanand D. Maddodi, Shajil Madhavan, Sulochana Devi, Vijayasaradhi Setaluri
Journal: Cancer Research (2011)

Abstract MicroRNAs (miRNAs) are regulatory RNAs that regulate gene expression. Evidence is accumulating that miRNAs are involved in almost all aspects of tumor biology including tumor cell survival, proliferation and migration. Here, we report that miRNA-221, which maps to the sixth intron of TRPM1 gene (a suppressor of melanoma metastasis), is highly expressed in melanocytes and its expression is reduced in primary and metastatic melanoma cell lines. Expression of miRNA-211 correlates with expression of TRPM1, a transient receptor potential family member calcium channel protein that we showed to be involved in regulation of melanocyte calcium homeostasis and melanin pigmentation. TRPM1and miRNA-211 expression are significantly lower in rapidly proliferative melanocytes compared to the slow growing, differentiated melanocytes. Expression of RAB22A (member of the RAS family of small GTPases), a predicted RNA target of miRNA-211is inversely correlated with the expression of miRNA-211and TRPM1 in melanocytes. Inhibition of miRNA-211 expression by anti-miR211 inhibited the growth of rapidly growing melanocytes. Ectopic expression of miRNA-211in melanoma cells inhibit growth and reduced their migration. We propose that activation of endogenous miRNA-211 expression or targeted delivery of miR-211 in melanoma is a potential therapeutic option for treatment of cutaneous melanoma. 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 3957. doi:10.1158/1538-7445.AM2011-3957
Misclassification of Nasopharyngeal Cancer
Authors: L. J. LUCAS
Journal: JNCI Journal of the National Cancer Institute (1994)

ResponseLucas points out a problem with using diagnoses of nasopharyngeal cancer (NPC) from death certificates.As Lucas noted, the quality of diagnosis of NPC on death certificates is poor.The author contends that the "impact of such misclassification is to overestimate NPC incidence among formaldehyde work-