tbuckley/cabot-search huggingface dataset:
Abstract 1459: Proteomic identification of a novel antitumor protein from myeloid-derived suppressor cells in breast cancer
Authors: Angela Boutte, Charles Lin
Journal: Cancer Research (2010)

Abstract Myeloid derived suppressor cells (MDSCs) are significantly increased in hematopoietic organs of cancer patients and animals bearing tumors. The number of MDSCs is directly proportional to tumor malignancy. MDSCs infiltrate into tumors and facilitate tumor progression and metastasis. In searching for molecular mediators responsible for tumor metastasis, we used proteomics and mass spectrometry in combination with a mammary tumor model that includes two distinct tumor cell lines, 67NR and 4T1, which are derived from a single mammary tumor. While these cell lines form primary tumors with equivalent growth kinetics, they differ dramatically in their metastatic potential. MDSCs were isolated from spleens of tumor-bearing mice and compared for protein expression profiles using 2D-DIGE-MS. There was a significant reduction of a novel protein, neutrophilic granule protein (NGP), in MDSCs from 4T1- compared to 67NR- tumor-bearing mice. Further analysis showed that NGP was expressed in myeloid cells, but not in epithelial tumor cells. Addition of 4T1 tumor cell conditioned media decreased the gene expression in promyelocyte cells. Computational analysis of NGP indicates presence of a putative cystatin domain, a known cathepsin inhibitor site. Indeed, forced expression of NGP in cultured cells inhibited endogenous cathepsin B activity. Since cathepsins have been linked to tumor invasion and metastasis, we postulated that NGP has an anti-tumor role. To test this hypothesis, we generated 4T1 cells stably expressing NGP (4T1-NGP) or empty vector (4T1-Vec), and found that expression of NGP in tumor cells inhibited Matrigel invasion, but not cell proliferation. Furthermore, implantation of 4T1-NGP cells in mammary pad of syngeneic Balb/c mice resulted in a significant reduction of primary tumor growth and lung metastasis. Histological examination reveals reduced tumor angiogenesis and increased apoptosis. Collectively, this study identified a novel protein, NGP, in MDSCs acts as a negative mediator of tumor growth and metastasis, likely through inhibition of cathepsin activity. Down-regulation of NGP in the tumor microenvironment contributes to tumor growth and metastasis. NGP may act as a novel protease inhibitor and may be a therapeutic target for breast cancer. 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 1459.
P441 PREDICTION OF PORTAL HYPERTENSION AND ESOPHAGEAL VARICES IN CIRRHOTIC PATIENTS WITH APPARENT DIFFUSION COEFFICIENT OF THE SPLEEN
Authors: A.A.K. Abdel Razeka, M. El-Bendary, E. Motawea, S.M. Massoud, M.R. Abdel-Aziz, K. Zalata
Journal: Journal of Hepatology (2014)
Enhancement of Mammary Carcinogenesis by High Levels of Dietary Fat and its Association With Ad Libitum Feeding
Authors: L. S. FREEDMAN
Journal: JNCI Journal of the National Cancer Institute (1991)

Enhancement of Mammary Carcinogenesis by High Levels of Dietary Fat and Its Association With Ad Libitum FeedingWe have read with interest the article by Welsch et al (7).The authors compared four groups of Sprague-Dawley rats fed different diets following a single dose of 7,12-dimethylbenz[a]anthracene.The diets for the four groups were as follows: 5% com oil diet fed ad libitum (group I), 20% corn oil diet fed ad libitum (group II), 5% corn oil diet fed 12% less than group I (group III), and 20% corn oil diet fed 12% less than group II (group IV).The mean numbers of mammary carcinomas per rat (±SE) in groups I to IV were 4.1 ± 0.6, 6.8 ± 0.7, 3.0 ± 0.3, and 4.1 ± 0.5, respectively.The mean weights of mammary carcinomas per rat (g ± SE) were 3.5 ± 0.7, 8.0 ± 1.3, 3.0 ± 1.1, and, 4.6 ± 1.3, respectively.A second experiment involved the restricted diets fed to groups III and IV and yielded results comparable to those obtained in the first experiment.The mean numbers of mammary carcinomas per rat (±SE) in groups III and IV were 3.1 ± 0.4 and 3.7 ± 0.3, and the mean weights of tumors were (g ± SE) 4.3 ± 1.2 and 4.0 ± 1.1, respectively.The authors note that both the number and the total weight of
Traumatic Diaphragmatic Hernia
Authors: Edoardo Picetti, Mario Mergoni
Journal: New England Journal of Medicine (2011)

A 6-year-old boy presented to the hospital after several hours of vomiting and dyspnea. He had been in a motor-vehicle accident 6 months earlier and had sustained a seatbelt injury that necessitated surgical repair of a right diaphragmatic hernia.
Bevacizumab as adjuvant therapy for lung cancer does not help patients over 65
Authors: B. Roehr
Journal: BMJ (2012)

There is no substantial benefit for patients over 65 in adding bevacizumab (Avastin) to the standard treatment of carboplatin and paclitaxel for non-small cell lung cancer, a study shows ( JAMA 2012;307:1593). 

Bevacizumab gained that additional indication in 2006 based on a trial where two thirds of the patients were younger than 65, despite the …
Paying hospitals for all patients' visits increases activity without necessarily improving quality, report shows
Authors: M. Limb
Journal: BMJ (2012)

The NHS can learn from recent attempts elsewhere in Europe to reform healthcare payment systems but it will take time to create the “optimal blend” of strategies that works best in the United Kingdom, a new report has concluded.

The health policy think tank the Nuffield Trust has studied trends in payment reorganisation across Europe and considered what lessons may apply for healthcare systems such as the NHS. The trust’s report was published on 23 August.1

Its director, Jennifer Dixon, who co-wrote the report, said that it was clear from the review that payment reform in England was “going in the right direction.”

The report says that the search for efficiencies in healthcare is wide ranging and that, although national payment systems can be used …
Abstract 1905: Influence of serum and oxygen on lipid biosynthesis and energy metabolism in murine glioblastoma.
Authors: Nathan Ta, Thomas Seyfried
Journal: Cancer Research (2013)

Abstract Glucose and glutamine are essential energy metabolites for brain tumor growth and survival under both normoxic and hypoxic conditions. Carbons derived from either metabolite can be used for lipid synthesis. Here, we used uniformly labeled C14-glucose and C14-glutamine to examine de novo lipid synthesis in the VM-M3 murine glioblastoma cells. The major lipids synthesized included phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), sphingomyelin (SM), phosphatidic acid (PA), cholesterol (Chol), and cardiolipin (CL). De novo lipid synthesis was greater with glucose than with glutamine as the metabolic substrate under normoxia. Conversely, glutamine was the preferred substrate for lipid synthesis under anoxia. Lactate was produced largely from glucose carbons with minimal lactate derived from glutamine. Total lipid synthesis, using either glucose or glutamine, was greater in media without serum than in media containing 10% FBS under normoxia. Significant triglyceride accumulation was observed only under anoxia. Our findings show that lipid biosynthesis using glucose or glutamine is dependent on the type of growth environment, and that the VM-M3 glioblastoma cells can grow under anoxia only through acquisition of lipids, especially cholesterol, from serum. Supported in part from Boston College Res. Expense Fund. Citation Format: Nathan Ta, Thomas Seyfried. Influence of serum and oxygen on lipid biosynthesis and energy metabolism in murine glioblastoma. [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 1905. doi:10.1158/1538-7445.AM2013-1905
Autoimmune Adrenal Insufficiency Mimicking Bilateral Adrenal Metastases From Adenocarcinoma of the Lung on PET/CT
Authors: John K. Blazak, Frank Fiumara
Journal: Clinical Nuclear Medicine (2011)

A 49-year-old woman presented for investigation of a chronic cough. Computed tomography (CT) demonstrated a 12-mm diameter lobulated mass in the right middle lobe of the lung. There was no evidence of metastases on computed tomography and, particularly, no masses were demonstrated in the adrenal glands. Subsequent bronchoscopic biopsy demonstrated a poorly differentiated adenocarcinoma. A staging F-18 fluorodeoxyglucose positron emission tomography/computed tomography scan revealed uptake in the right middle lobe malignancy and in bilateral adrenal glands. Two weeks later the patient presented to hospital following a syncopal episode. Addison disease was subsequently diagnosed on the basis of hyponatremia, hyperkalemia, and positive antiadrenal antibodies.
The “Dawn Phenomenon” — A Common Occurrence in Both Non-Insulin-Dependent and Insulin-Dependent Diabetes Mellitus
Authors: Geremia B. Bolli, John E. Gerich
Journal: New England Journal of Medicine (1984)

The dawn phenomenon is a condition recently described in patients with insulin-dependent diabetes mellitus (IDDM) that is characterized by abrupt increases in fasting levels of plasma glucose or insulin requirements or both between 5 and 9 a.m., in the absence of antecedent hypoglycemia. To determine its potential clinical relevance, we assessed its frequency and reproducibility in 20 patients with IDDM and in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM) during overnight closed-loop (feedback-controlled) intravenous insulin infusion. After 6 a.m., plasma glucose levels increased similarly in NIDDM (89 +/- 2 mg per deciliter, midnight to 6 a.m., vs. 98 +/- 2 mg per deciliter, 6 to 9 a.m.; P less than 0.01). Insulin requirements increased at least 50 per cent for 1 1/2 hours in 77 per cent of patients with NIDDM and in 75 per cent of patients with IDDM. In five patients with IDDM who were studied on four occasions, the phenomenon occurred during 17 of the 20 observation periods, with insulin requirements after 6 a.m. increasing 225 +/- 34 per cent; coefficients of variation in individual patients ranged from 4 to 25 per cent. Thus, the dawn phenomenon occurs commonly in both NIDDM and IDDM, but its potential variability must be taken into consideration when one is attempting to adjust insulin doses.
MB-09 * AGGRESSIVE MEDULLOBLASTOMA SUBVERTS THE PHOTORECEPTOR SPECIFIC TRANSCRIPTION FACTOR NRL
Authors: A. Garancher, M. Morabito, N. Rocques, M. Larcher, C. Micquel, S. Puget, F. Doz, O. Delattre, O. Ayrault, A. Eychene, F. Bourdeaut, C. Pouponnot
Journal: Neuro-Oncology (2015)

Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising in the cerebellum. Although multimodal treatments have significantly increased the survival, 20% to 30% of patients remain incurable. Transcriptomic studies identified four MB subgroups. Among those, the group 3 is of poorer prognosis, frequently metastatic and refractory to current therapies. It is characterized by a photoreceptor differentiation program composed of genes expressed in the retina in physiological conditions. Cancer cells often express such aberrant differentiation programs unrelated to their tissue of origin. They result, in some instances, from cancer cell plasticity but are not thought to contribute to cancer progression. Our work established that the retina-specific photoreceptor differentiation program is instrumental to MB progression. Using transcriptomic data from patient samples and different models including patient-derived xenografts, we showed that group 3 MBs subvert NRL, a major transcription factor of this program, to its profit and thus, identified one key driver event of this poorly characterized MB subgroup. We further demonstrated that NRL protects MB from apoptosis by controlling the expression of the anti-apoptotic BCL-XL gene. Accordingly, we also showed that anti-BCL therapies could represent an alternative therapeutic strategy for this pediatric tumor.
Abstract 1777: Genome-wide identification of replication-associated breakpoints.
Authors: Yu-Chen Tsai, Nishita Shastri, Kevin D. Smith, Jonathan Schug, Rafael Casellas, Eric J. Brown
Journal: Cancer Research (2013)

Abstract Previous studies have defined sequences that are difficult to replicate and, consequently, are more vulnerable to replication-associated breaks and recombination events. However, many of these sequences have been identified through indirect and biased approaches. To identify genomic sequences that contribute to replication-associated breakpoints, we have performed genome-wide screens to determine the location, sequence, and frequency of replication perturbations within the mammalian genome. To convert these transient pause sites in S phase into longer-lived intermediates, asynchronous ATR-inhibited cells were treated with a low dose of polymerase inhibitor (0.2 μM aphidicolin) to promote selective replication fork collapse at difficult-to-replicate sequences. Affected regions were then isolated by chromatin immunoprecipitation of RPA (RPA-ChIP) and by a recently developed novel DNA breakpoint isolation method. Following deep sequencing, these sites were mapped within 1-5 kb regions and sequences at the center of these peaks were binned to quantify the overall frequency of replication fork collapse at such sites. Surprisingly, sequences that have long been thought to be among the most difficult to replicate, such as CGG repeats, were overshadowed by distinct repetitive sequences that are relatively uncharacterized. These sites were greater than 50-fold enriched over background, and were more common as replication-troubled regions than other well characterized sequences (e.g. triplet repeats, fragile sites, etc). In total, over 100 independently confirmed sites were identified, with most sequences observed in multiple locations across the genome. Notably, common fragile sites, which have been speculated to harbor such replication slow zones, were not observed to be particularly enriched in RPA-ChIP samples, consistent with recent observations that these sites are fragile for reasons other than impeded DNA replication rates. These findings and others indicating a larger role of chromatin structure in common fragile site breakage will be discussed. Citation Format: Yu-Chen Tsai, Nishita Shastri, Kevin D. Smith, Jonathan Schug, Rafael Casellas, Eric J. Brown. Genome-wide identification of replication-associated breakpoints. [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 1777. doi:10.1158/1538-7445.AM2013-1777 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Relation between Exposure to Asbestos and Mesothelioma
Authors: Irving J. Selikoff, Jacob Churg, E. Cuyler Hammond
Journal: New England Journal of Medicine (1965)

IN 1960 Wagner, Sleggs and Marchand1 reported 33 cases of diffuse pleural mesothelioma from the North Western Cape Province of South Africa. The collection of such a large number of cases of a rare tumor within a short time (1956–1960) in one area was considered unusual enough. Even more striking was the fact that close questioning and investigation revealed that 32 patients had evidence, admittedly circumstantial in most cases, of some potential or actual contact with asbestos by virtue either of residence in mining areas or in industry twenty to forty years before.This remarkable concentration of cases in one . . .
Abstract 1504: Characterization of the murine oral squamous cell carcinoma cell line AT84 stably overexpressing uPAR
Authors: Synnove Magnussen, Robert Hanes, Elin Hadler-Olsen, Lars Uhlin-Hansen, Gunbjorg Svineng
Journal: Cancer Research (2011)

Abstract Cancers of the oral cavity are associated with poor prognosis, and almost half of the patients diagnosed with oral squamous cell carcinoma (SCC) will die from the disease. Compared to its counterpart in skin, one main differing feature is the ability of oral SCC to metastasize. A prerequisite for metastasis is the capability to invade the surrounding tissue and penetrate into the nearest blood- or lymphatic vessel. This initial step in metastasis requires several extracellular matrix degrading enzymes. One such enzyme is uPA (urokinase-type plasminogen activator), involved in pericellular proteolysis, where high levels are correlated with poor prognosis in several cancers. Upon binding of pro-uPA to its extracellular receptor uPAR, the enzyme is cleaved and activated. uPA further activates matrix metalloproteases (MMP's), also needed for matrix degradation. In addition, ample evidence shows that binding of uPA to uPAR triggers receptor-mediated cellular signaling. uPAR lacks a membrane spanning domain hence signal transduction has to be mediated through one or several membrane partners. uPARs role in the regulation of cell adhesion, migration and proliferation has been linked to its interplay with membrane partners such as integrins, EGFR, caveolin and G-protein coupled receptors (e.g. FPRL1). To better understand the role of uPAR in the invasive growth and metastasis of oral SCCs, the mouse oral SCC cell line, AT84 [1, 2], was stably transfected with uPAR. Overexpression of uPAR resulted in down regulation of epithelial marker E-cadherin and the cells display a more mesenchymal appearance, indicating epithelial-mesenchymal transition (EMT). In addition, elevation of uPAR expression increased migration in a wound healing assay. In contrast to previous reports, an increase in MMP-9 activity was not observed in these cells, although an increase in overall proteolytic activity could be found using gelatin as substrate. The cells were reintroduced into the C3H mouse to observe the role of uPAR in cancer progression in vivo. Results from the analysis of the host-tumor interactions within this syngenous mouse model will be presented. 1. Lou, E., et al., Clinical and pathological features of the murine AT-84 orthotopic model of oral cancer. Oral Dis, 2003. 9(6): p. 305-12. 2. Schultz-Hector, S. and S. Haghayegh, Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation. Cancer Res, 1993. 53(6): p. 1444-9. 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 1504. doi:10.1158/1538-7445.AM2011-1504
Combination Regimens of <i>nab</i>-Rapamycin (ABI-009) Effective Against MDA-MB-231 Breast-Tumor Xenografts.
Authors: N. Desai, O. D'Cruz, V. Trieu
Journal: Cancer Research (2009)

Abstract Background: The mammalian target of Rapamycin (mTOR) is a key intracellular kinase integrating cell proliferation and survival and is an attractive target for cancer therapy. Nab-rapamycin (ABI-009) was developed using proprietary nab-technology and showed dose-linear pharmacokinetics, safety up to 90 mg/kg and effective antitumor activity at 40 mg/kg in the human-tumor-xenograft panel. The goal of this study was to test the effectiveness of different combination regimens for ABI-009 against MDA-MB-231 breast-tumor xenografts.Materials and methods: Subcutaneous human-breast (MDA-MB-231) tumors were grown in athymic nude mice and treated intravenously (IV) with ABI-009 alone at 40 mg/kg (3xwkly/4wks) and in combination with Erlotinib (50 and 100 mg/kg/day/4wks, IP), Cetuximab (20 and 40 mg/kg, 3xwkly/4wks, IP), Doxorubicin (2 and 5 mg/kg, wkly/10 wks, IV), Oxaliplatin (5 and 10 mg/kg wkly/4 wks, IV), SAHA (50 mg/kg, qdx7 or qdx14, IP), and Perifosine (30 and 60 mg/kg, 3xwkly/4wks, PO). The animal weights and tumor measurements were recorded three times weekly and adverse observations recorded.Results: ABI-009 was highly effective as a single agent against MDA-MB-231 breast tumor xenografts with 75% tumor-growth inhibition (TGI). Combination with Erlotinib resulted in TGI of 85% and 95% (50 and 100 mg/kg, respectively), 83% and 87% for Cetuximab (20 and 40 mg/kg, respectively), 83% and 90% for Doxorubicin (2.5 and 5 mg/kg, respectively), 82% and 85% for Oxaliplatin (5 and 10 mg/kg, respectively), 82% and 90% for SAHA (7 and 14 day treatment, respectively), and 92% and 96% for Perifosine (30 and 60 mg/kg, respectively). Notably, Erlotinib and Perifosine were found to synergize with ABI-009 resulting in maximum TGI and tumor growth delay.Discussion: ABI-009 (nab-rapamycin) alone was highly effective against MDA-MB-231 human-breast-tumor xenografts. Antitumor activity of ABI-009 was significantly increased in combination with kinase inhibitors, Erlotinib (EGFR-kinase inhibitor) and Perifosine (AKT inhibitor). Antitumor activity of ABI-009 was also significantly increased in combination with Doxorubicin – a topoisomerase inhibitor, and SAHA – an HDAC inhibitor, but not in combination with Oxaliplatin – a DNA crosslinker. In contrast, combination of ABI-009 with anti-EGFR monoclonal antibody, Cetuximab was not effective. The synergy of these combinations confirmed that rapamycin is active only on TORC1 and that suppression of TORC2 via AKT or PI3K pathways is a means of increasing activity of mTOR inhibitors with potential relevance to breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6106.