tbuckley/cabot-search huggingface dataset:
Abstract 5404: Up-regulation of proliferative and migratory genes in regulatory T cells from patients with metastatic castration-resistant prostate cancer
Authors: Jo A. Tucker, Ngar-Yee Huen, Alan LY Pang, Tin-Lap lee, Matteo Vergati, Chiara Intrivici, Vittore Cereda, Caroline Jochems, Wai-Yee Chan, Owen Rennert, James L. Gulley, Jeffrey Schlom, Kwong-Yok Tsang
Journal: Cancer Research (2012)

Abstract Immune suppression by regulatory T cells (Tregs) is associated with tumor evasion. An increase in the frequency and suppressive function of Tregs has been shown in a variety of solid tumors. The purpose of this study was to determine if the enhanced number and activity of these cells in prostate cancer patients could be due to tumor-induced changes in gene expression. CD4+CD25hiCD127lo Tregs were isolated from the peripheral blood of healthy donors and metastatic castration-resistant prostate cancer (mCRPC) patients. These samples were selected based on similar suppressive activity in a functional assay. A genome-wide expression array of 38, 500 genes was then performed to detect any effects in expression potentially induced by tumor. We found 384 genes had a three-fold or greater difference in expression between the groups. Differentially expressed genes were involved in cell cycle processes, cellular growth and proliferation, immune response, hematological system development and function, as well as the IL-2 and TGF-β pathways. Genes most up-regulated in the Tregs of mCRPC patients included C-FOS, C-JUN, DUSP1 and RGS1, which are crucial for regulation of T cell proliferation, activation and migration. We also observed increased expression of c-Jun protein in patient Tregs by flow cytometry. Patients had a significantly higher percentage of Tregs in their CD4+ population than the healthy donors, but interestingly, there was no difference in FoxP3 expression. These results indicate that tumor-derived factors may contribute to Treg mediated immune suppression by up-regulating genes that increase their proliferative and migratory capacities, allowing them to better home to the tumor and inhibit the host response. 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 5404. doi:1538-7445.AM2012-5404
Endoscopic submucosal dissection assisted by novel “clip fishing method” (with video)
Authors: M. Ueki, Y. Ikebuchi, H. Matsuoka, H. Otani, A. Yasugi, M. Koda, K. Kawaguchi, K. Harada, K. Yashima, M. Koda, Y. Murawaki
Journal: Endoscopy (2010)

Endoscopic submucosal dissection (ESD) requires substantial skill because of the poor visibility in the cutting area. Recently, traction systems for ESD have been reported [1] [2] [3] [4], but these complex methods have not been widely employed. We therefore designed the "clip fishing method", consisting of a threaded sheath clip. The cost is lower than that of "magnetic-anchor-guided" ESD [4].
Gastrointestinal Myoelectrical Activity in Idiopathic Intestinal Pseudo-Obstruction
Authors: Mark A. Sullivan, William J. Snape, Stephen A. Matarazzo, Robert J. Petrokubi, Graham Jeffries, Sidney Cohen
Journal: New England Journal of Medicine (1977)

We evaluated the myoelectrical and motor function of the esophagus, small intestine, colon and anal sphincter in four patients with chronic idiopathic intestinal pseudo-obstruction. All patients had aperistalsis of the esophagus, with incomplete relaxation of the lower esophageal sphincter after swallowing or balloon distension. Duodenal slow-wave frequency was normal at 11.4+/-0.3 (+/-S.E.M.) cycles per minute. The patients did not have a normal increase in duodenal spike or motor activity after intestinal distension, but duodenal activity increased after stimulation with intravenous secretin. Colonic slow-wave activities were present at two frequencies, 6.2+/-0.3 and 3.3+/-0.1 cycles per minute. Neostigmine administration increased both colonic spike and motor activity normally. These studies suggest that in this disorder, physiologic neural responses to swallowing or intestinal distension are impaired but the intestinal smooth-muscle slow-wave activity and the spike and motor responses to exogenous neurohormonal stimulation are intact.
Abstract SY05-03: Mechanisms regulating stemness in skin cancers.
Authors: Cedric Blanpain
Journal: Cancer Research (2013)

Abstract Cancer stem cells (CSCs) have been described in various cancers by their ability to reform secondary tumours upon transplantation into immunodeficient mice. Using different approaches in mice, we have recently shown that squamous skin tumors contain stem cells that present the ability to reform the parental tumor upon transplantation (Lapouge et al. EMBO J 2012) or by their ability to fuel tumor growth using lineage tracing experiments (Driessens et al Nature 2012). To define the mechanisms that regulate skin cancer stem cells, we transcriptionally profiled cutaneous CSCs at different stages of tumor progression. We uncovered a set of genes, which are enriched in CSCs irrespective of the stages of tumor progression and another set of genes, which are upregulated in CSCs only during malignant progression. We used genetic gain and loss of function in mice to unravel how some of these genes regulate tumor stemness and stimulate malignant transition in vivo within their natural environment. I will discuss how the combination of extrinsic factors such as the vascular niche (Beck et al. Nature 2011) and intrinsic factors regulate the renewal and invasive properties of CSCs during skin cancer progression. This work is supported by WELBIO, the FNRS, the European Research Council (ERC) and the EMBO Young Investigator Program. Citation Format: Cedric Blanpain. Mechanisms regulating stemness in skin cancers. [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 SY05-03. doi:10.1158/1538-7445.AM2013-SY05-03
Abstract P3-10-41: Quantitative Immunohistochemical Analysis and Prognostic Significance of TRPS-1, a New GATA Transcription Factor Family Member, in Breast Cancer
Authors: JQ Chen, J Litton, L Xiao, H-Z Zhang, CL Warneke, Y Wu, X Shen, A Sahin, R Katz, JL Murray, L. Radvanyi
Journal: Cancer Research (2010)

Abstract The Trichorhinophalangeal Syndrome-1 gene (TRPS-1) is a novel GATA transcription factor family member expressed in &amp;gt;90% of human breast cancers. In this study, we developed a new quantitative IHC (qIHC) method to study TRPS-1 as a possible indicator ofprognosis in BC. Using this method, a quantitative parameter for TRPS-1 expression called a Quick Score (QS) was derived from the measured Labeling Index (LI) and Mean Optical Density (MOD) after IHC and applied to a set of 152 Stage II/III BC patients from 1993-2006 who did not receive preoperative chemotherapy. Although highly prevalent in BC, a wide range of TRPS-1 QS was found among the sample set with higher TRPS-1 QS significantly associated with tumor ER-alpha (p= 0.023 for QS, and p= 0.028 for Allred score), PR (p= 0.009), GATA-3 (P&amp;lt;0.0001), and E-cadherin (p&amp;lt; 0.001). TRPS-1 QS was also positively associated with HER2 status (p=0.026). Analysis of different ductal structures revealed that TRPS-1 was expressed at low levels in normal ducts and in usual ductal hyperplasia, but showed a marked increase in DCIS and invasive carcinoma lesions. An analysis of TRPS-1 expression in association with overall survival revealed that TRPS-1 QS (≥4.0) was significantly associated with improved survival (p=0.0165). Patients with TRPS-1 QS &amp;lt;4 had a hazard ratio of 2 (p=0.019) after univariate Cox proportional hazards analysis. Further analysis of the patient samples revealed an ER-/lo, HER2+ (amplified) BC subset in which TRPS-1 expression above a critical quantitative threshold was predictive of greatly improved survival (median survival not reached after 10 years), while patients in this subset with TRPS-1 expression below this threshold having a median survival of less than 5 years. In summary, this new qIHC approach revealed critical differences in TRPS-1 expression in primary BC samples and found that this new GATA family member may be a promising positive prognostic marker that may regulate BC progression. In addition, TRPS-1 may also be a relevant new marker in a luminal ER-/low, HER2+ BC subset. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-41.
Superselective Intra-Arterial Radiometabolic Therapy With I-131 Lipiodol in Hepatocellular Carcinoma
Authors: CARLO L. MAINI, MARIA G. SCELSA, CONCETTA FIUMARA, ANNA TOFANI, ROSA SCIUTO, LUIGI TIPALDI, MARCO D'ANNIBALE, EUGENIO SANTORO
Journal: Clinical Nuclear Medicine (1996)

Superselective transcatheter arterial radioembolization with radioiodinated lipiodol and gelatin sponges was evaluated in 11 patients with nodular hepatocellular carcinoma. Thirteen tumor nodules were treated using 3-5 ml of lipiodol labeled with 259 to 2220 MBq of I-131 followed by gelatin sponge with the following results: 1) there was elevated uptake in 12 tumor nodules with high tumor-to-background ratios; 2) there was excellent clinical tolerance to the treatment (stable cirrhosis in 5 patients and cirrhosis progression in 2 cases); 3) there was good disease control with size reduction in five tumor lesions (41%) and no increase in seven lesions (59%) followed for 2 years; 4) there was a 2-year survival rate of 70%; and 5) three deaths due to hepatic failure at 2, 3, and 20 months after therapy. Superselective arterial radioembolization with I-131 lipiodol is a useful palliative approach to inoperable hepatocarcinoma, providing long-term local control without severe complications in the progression of cirrhosis.
Abstract 3526: Inhibition of ABCB1 (MDR1) expression by an siRNA nanoparticulate delivery system to overcome drug resistance in osteosarcoma
Authors: Michiro Susa, Arun K. Iyer, Xianzhe Liu, Edwin Choy, Francis J. Hornicek, Henry Mankin, Lara Milane, Mansoor M. Amiji, Zhenfeng Duan
Journal: Cancer Research (2010)

Abstract Background: Osteosarcoma accounts for approximately 60% of primary malignant bone tumors diagnosed in the first two decades of life. The use of neo-adjuvant chemotherapy in treating osteosarcoma has improved patients’ average 5 year survival rate from 20% to 70% in the past 30 years. However, for patients who progress after chemotherapy, its effectiveness diminishes due to the emergence of multi-drug resistance (MDR) after prolonged therapy. One of the innovative approaches to addressing MDR is to inhibit MDR1 mRNA expression by RNA interference (RNAi). In order to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure resulting from MDR, we designed and evaluated a novel drug delivery system for MDR1 siRNA delivery. Materials and Methods: Novel biocompatible, lipid-modified dextran-based polymeric nanoparticles were used as the platform for MDR1 siRNA delivery; and the efficacy of combination therapy with this system was evaluated. The mean particle size of the MDR1 siRNA loaded nanoparticles as determined by dynamic light scattering (DLS) measurement was 104.4+3.7 nm and the zeta potential was almost neutral (−0.19+1.13 mV). Multi-drug resistant osteosarcoma cell lines (KHOSR2 and U-2OSR2) were treated with the MDR1 siRNA nanocarriers and MDR1 protein (P-gp) expression, drug retention, and immunofluorescence were analyzed. Combination therapy of the MDR1 siRNA loaded nanocarriers with increasing concentrations of doxorubicin was also analyzed. Results: We observed that MDR1 siRNA loaded dextran nanoparticles efficiently suppresses P-gp expression in the drug resistant osteosarcoma cell lines. With the delivery of nanoparticles loaded with MDR1 siRNA, growth inhibition with doxorubicin was substantially more marked than with the administration of 100 fold higher amounts of free drugs. The results also demonstrated that this approach may be capable of reversing drug resistance by increasing the amount of drug accumulation in MDR cell lines. Furthermore, subcellular distribution of doxorubicin in MDR cells mimicked that of the drug sensitive variant when nanoparticles were utilized. Conclusions: Lipid-modified dextran-based polymeric nanoparticles are a promising platform for siRNA delivery. Nanocarriers loaded with MDR1 siRNA are a potential treatment strategy for reversing MDR in osteosarcoma. 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 3526.
Abstract 4275: A prostate cancer spheroid related gene and chemotherapy
Authors: Masatoshi Watanabe, Akimitsu Takagi, Yoshifumi Hirokawa, Taizo Shiraishi
Journal: Cancer Research (2011)

Abstract Spheroid culture is one of the three-dimensional (3-D) culture models. We have constructed a spheroid culture model for prostate cancer therapy and characterized this model. The change of global gene expression profiles in spheroids and solid tumor tissues were also compared with monolayer cultures, leading to extraction of candidate genes in contexts that more closely mimic tumor growth in vitro under different in vitro growth conditions. It is possible that these genes may be specific to the construction of spheroids and reveal the possibilities of new mechanisms of acquiring anticancer drug resistance or sensitivity. The plk-2 was extracted as a candidate e gene related with spheroid formation. A member of the polo-like kinase (PLK) family, PLK2 is one of highly conserved serine/threonine protein kinases. In this study, we analyzed effects of the PLK2 on the spheroid characterization and anticancer drug resistance in DU-145 spheroids by suppressing plk2 with RNAi. When docetaxel (DTX) was exposed for siRNA-transfected spheroids, the viability changed, the volume decreased at each concentration of DTX, and spheroids were collapsed at last. The result indicates that the plk2 may be involved in acquiring anticancer drug resistance. 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 4275. doi:10.1158/1538-7445.AM2011-4275
Case 10-2002
Authors: Lloyd M. Alderson, Ivana Delalle
Journal: New England Journal of Medicine (2002)

Presentation of CaseFirst AdmissionA 52-year-old right-handed woman was admitted to the neurologic clinic because of ataxia and fatigue.The patient had been well until four months earlier, when she had had a “sinus infection” characterized by green nasal discharge. Radiographs of the paranasal sinuses were reported to be unremarkable. At about the same time, while she was performing aerobic exercises, there was a sudden sensation of “tilting,” without diplopia; on walking shortly thereafter, she felt that she was veering to the left. She had an accompanying band of pain around the top of her head.These symptoms persisted, . . .
Children are influenced by tobacco adverts BMA is concerned about management cost savings Specialist medical order should be in place in January 1996 Fewer authorities will mean pounds sterling150m savings, says minister NHS spending and national income
Authors: L. Beecham
Journal: BMJ (1995)

# Children are influenced by tobacco adverts {#article-title-2}

Tobacco advertising has far more effect on children aged 11 to 14 than on adults, according to new data released by the BMA. The data, which compare the top 10 brands advertised with those smoked by children and adults, show that three out of four of the most heavily advertised brands also appear in the top four brands smoked by children. These top four brands account for 77% of the total advertising budget for tobacco. Adults are less sensitive to advertising with only two of the four most heavily advertised brands appearing in their top four favourite brands. They tend to be more influenced by price.

The head of health policy at the BMA, Dr Vivienne Nathanson, says, “This is conclusive evidence that tobacco advertising persuades children to smoke and scuppers any argument from the tobacco industry that advertising is about brand loyalty. With teenage smoking above 10% for the first time in 12 years and smoking on the increase particularly among young girls, the need for a tobacco advertising ban has never been greater.”

# BMA is concerned about management cost savings {#article-title-3}

The BMA has told the health secretary of the association's concern that the insistence on reducing health authorities' management costs by pounds sterling140m (set out in the executive letter EL(95)85) could lead to a reduction in public health establishments. In his letter to Mr Stephen Dorrell the chairman of the BMA council, Dr Sandy Macara, says that in one case a public health department is to …
1323 HYPOLIPIDEMIC THERAPY VS DIET IN HYPERCHOLESTEROLEMIC PATIENTS AFFECTED BY NONALCOHOLIC STEATOHEPATITIS (NASH)
Authors: D. Donnini, A. Carnelutti, G. Nadalutti, L. De Luca, D. Cappello, F. Cugini, S. Parlamento, A. Dibenedetto, D. De Silvestri, L. Sechi, F. Soardo
Journal: Journal of Hepatology (2012)
Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer
Authors: Heath D. Skinner, Uma Giri, Liang Yang, Sang Hyeok Woo, Michael D. Story, Curtis R. Pickering, Lauren A. Byers, Michelle D. Williams, Adel El-Naggar, Jing Wang, Lixia Diao, Li Shen, You Hong Fan, David P. Molkentine, Beth M. Beadle, Raymond E. Meyn, Jeffrey N. Myers, John V. Heymach
Journal: Clinical Cancer Research (2016)

Head and neck squamous cell carcinoma (HNSCC) is commonly treated with radiotherapy, and local failure after treatment remains the major cause of disease-related mortality. To date, human papillomavirus (HPV) is the only known clinically validated, targetable biomarkers of response to radiation in HNSCC.We performed proteomic and transcriptomic analysis of targetable biomarkers of radioresistance in HPV-negative HNSCC cell lines in vitro, and tested whether pharmacologic blockade of candidate biomarkers sensitized cells to radiotherapy. Candidate biomarkers were then investigated in several independent cohorts of patients with HNSCC.Increased expression of several targets was associated with radioresistance, including FGFR, ERK1, EGFR, and focal adhesion kinase (FAK), also known as PTK2. Chemical inhibition of PTK2/FAK, but not FGFR, led to significant radiosensitization with increased G2-M arrest and potentiated DNA damage. PTK2/FAK overexpression was associated with gene amplification in HPV-negative HNSCC cell lines and clinical tumors. In two independent cohorts of patients with locally advanced HPV-negative HNSCC, PTK2/FAK amplification was highly associated with poorer disease-free survival (DFS; P = 0.012 and 0.034). PTK2/FAK mRNA expression was also associated with worse DFS (P = 0.03). Moreover, both PTK2/FAK mRNA (P = 0.021) and copy number (P = 0.063) were associated with DFS in the Head and Neck Cancer subgroup of The Cancer Genome Atlas.Proteomic analysis identified PTK2/FAK overexpression is a biomarker of radioresistance in locally advanced HNSCC, and PTK2/FAK inhibition radiosensitized HNSCC cells. Combinations of PTK2/FAK inhibition with radiotherapy merit further evaluation as a therapeutic strategy for improving local control in HPV-negative HNSCC. Clin Cancer Res; 22(18); 4643-50. ©2016 AACR.
Active bleeding without identifiable lesion on capsule endoscopy
Authors: R. Rerknimitr, S. Aniwan, V. Viriyautsahakul, P. Kullavanijaya
Journal: Endoscopy (2012)

With read with great interest the paper by Lecleire et al. on the role of emergency capsule endoscopy in severe obscure-overt gastrointestinal bleeding (OOGIB) [1]. We agree with the authors that this study has emphasized the benefit of an emergency approach by capsule endoscopy in patients with persistent bleeding despite negative esophagogastroduodenoscopy (EGD) and colonoscopy. However, we question the therapeutic decision-making in those patients (n = 12) in whom capsule endoscopy was only able to locate the active bleeding site but failed to reveal the cause of bleeding. In this group, two patients were moribund and two patients underwent further endoscopy. Without further investigation reported, another five young patients suspected for Meckel’s bleeding underwent surgery directly and another three patients received conservative treatment. In our opinion, these patients deserve further investigation before invasive surgical treatment or conservative treatment can be offered. Repeat capsule endoscopy has been reported to be a good strategy for the approach of OOGIB and resulted in a change in management in 39 % – 63 % of patients [2] [3]. In addition, double-balloon endoscopy, if carried out within 24 hours, has been reported to be useful in OOGIB [4].
Endoscopic ultrasound-guided fine-needle aspiration can differentiate between tuberculosis and sarcoidosis
Authors: J. Yang, E. Linghu
Journal: Endoscopy (2012)

It is very difficult to make a differential diagnosis between tuberculosis and sarcoidosis by considering only mediastinal lymph nodes, as these two diseases often have a high degree of overlapping clinical and diagnostic features. The article by Fritscher-Ravens et al. [1] provided some answers to this challenge. As a prospective study, the design of this investigation was rigorous and the conclusion should be credible. There are some reports of the use of endoscopic ultrasonography-guided fine-needle aspiration (EUS – FNA) in the differential diagnosis of mediastinal lymphadenopathy but most are retrospective studies [2] [3]. We have also performed mediastinal lymph node puncture and believe that EUS – FNA is a safe, minimally invasive, and effective diagnostic method. In the Fritscher-Ravens article, the authors used EUS to guide the endoscope and detect pathological lymph nodes and then used FNA to obtain tissue for cytological and bacteriological analysis. From their precise work, the following positive results were obtained. First, on EUS the node of tuberculosis was significantly smaller than that of sarcoidosis. Second, after biopsy tissue staining with May – Grünwald – Giemsa, cytology revealed epithelioid cell granulomas on a “dirty background” with debris suggesting tuberculosis; a “clear background” was suggestive of sarcoidosis. Third, the sensitivity of cultures from the FNA samples for Mycobacterium tuberculosis was 71 % (95 %CI 0.53 – 0.85). Therefore, follow-up and the typical clinical features of tuberculosis contributed to the final diagnosis.
ROLE OF INFERIOR VENA CAVA FILTERS IN PATIENTS UNDERGOING CATHETER-BASED TREATMENT OF ACUTE PULMONARY EMBOLISM: A COMPREHENSIVE META-ANALYSIS
Authors: Pankaj Arora, Rajat Kalra, Navkaranbir Bajaj, Sameer Ather, Jason Guichard, William Lancaster, Fabio Raman, Garima Arora, Donald Clark, David McGiffin, Mustafa Ahmed
Journal: Journal of the American College of Cardiology (2016)