tbuckley/cabot-search huggingface dataset:
Abstract 5067: Preadipocyte exosomes promote early stage breast cancer formation by enhancing cancer stem cell renewal signaling
Authors: Benjamin Wolfson, Ramkishore Gernapudi, Nadire Duru, Qun Zhou
Journal: Cancer Research (2015)

Abstract The tumor microenvironment plays a critical role in regulating breast cancer progression. Adipocytes differentiate from preadipocytes, which possess mesenchymal stem cell properties. Preadipocytes and adipocytes are essential components of the tumor microenvironment, and signaling between preadipocytes and breast cancer cells has been found to promote breast tumor formation and metastasis. Exosomes secreted from preadipocytes are also important components of the cancer stem cell niche. The primary goal of our studies is to examine how preadipocyte-derived exosomes can regulate early-stage breast cancer formation via regulating stem cell renewal. We use human and mouse preadipocytes and early-stage breast cancer cells (ductal carcinoma in situ, DCIS), as well as xenografts in immunodeficient mice to determine the role of preadipocyte secreted exosomes in DCIS stem cell behavior and tumor formation. By using protein arrays, we reveal CD81 and FLOT-1 as key exosomal protein markers and SOX2 and SOX9 as exosomal secretion of stem cell renewal regulators. We identify a key miR-140/SOX2/SOX9 axis that regulates differentiation, stemness, and migration in the tumor microenvironment. Next, we find that the natural antitumor compound shikonin can suppress preadipocyte signaling, inhibiting nearby DCIS cells. Through co-culture experiments we show that shikonin treated preadipocytes secrete exosomes containing high levels of miR-140 that can impact nearby DCIS cells through targeting SOX9 signaling. We demonstrate that preadipocyte-derived exosomes promote tumorigenesis in vivo, providing strong support for the importance of exosomal signaling in the tumor microenvironment. Finally, our data also show that targeting the tumor microenvironment may assist in blocking tumor formation. Citation Format: Benjamin Wolfson, Ramkishore Gernapudi, Nadire Duru, Qun Zhou. Preadipocyte exosomes promote early stage breast cancer formation by enhancing cancer stem cell renewal signaling. [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 5067. doi:10.1158/1538-7445.AM2015-5067
B-Cell-Specific Transcription Factor BACH2 Involved in the Clinical Behavior Heterogeneity of Waldenström Macroglobulinemia
Authors: Charles Herbaux, Guillemette Marot, Elisabeth Bertrand, Natacha Broucqsault, Sylvie Zouitna-Galiègue, Christophe Roumier, Nicolas Poret, Valérie Soenen, Olivier Nibourel, Catherine Roche-Lestienne, Aline Renneville, Eileen Boyle, Guillemette Fouquet, Sabine Tricot, Claude Preudhomme, Bruno Quesnel, Stephanie Poulain, Xavier Leleu
Journal: Blood (2012)
P22 Application of the recent bts guidelines to a population of nodule patients
Authors: AJ Morgan, D Rosewarne, A Bapusamy, K Tanner, J Hancock, D Reid, S Mathews
Journal: Thorax (2016)

<h3></h3> The BTS nodule guidelines utilise morphological features, volume measurement, and risk modelling to stratify nodule management- potentially time consuming methods which may be offset by the possibility of early discharge Our aim was to identify patients who may be suitable for immediate (volume &lt;80mm<sup>3</sup> or 5mm) or early discharge (stable interval volumetry or VDT &gt;800 days) from our previous Flesichner driven follow-up, and to estimate reduction in future CTs –‘scans saved’, by noting the number of CTs that would have remained in their original schedule. 118 patients were identified. 22 patients had nodules &lt;5 mm, discharge would save 28 future scans. Of 12 patients with 5–5.9mm nodules, 6 patients were dischargeable (4 volume &lt;80 mm<sup>3</sup>, 2 benign morphology), saving 10 future CT scans. For patients with larger nodules and CT scans at least a year apart, serial volumetry identified 17 patients with nodules 6–7.9mm of which 15 were either morphologically benign, &lt;80 mm<sup>3</sup>, static in volume or VDT &gt;800 days, and thus dischargeable saving 15 future CT scans; and 9 patients with &gt;8 mm nodules of which static volumetry was noted in 6, saving 8 future scans. All patients with a CT follow up period of between 3 months and 1 year (n = 44) had static linear measurements and volumetry was not retrospectively performed on these. Total discharges were 51 (see table), with a saving of 61 scans compared to historical protocol. Discharge of patients with nodules &lt; 5 mm is a one off gain as these will not enter follow up in the future. Excluding these, results in an ongoing saving of 33 scans if 34 patients undergo either paired or one off volume measurements, taking an average of 5 minutes to perform. Additional volumetry at 3 months would add a further 5minutes to analysis of these patients CTs. We believe the ‘trade off’ between time for volumetry versus reduced CTs (radiology time, radiation exposure and patient inconvenience) is favourable and should provide an incentive for units to offer volume measurements, performed as in this study by either chest radiologist or trained chest physician, if they are not already doing so.
Integrated Single-Cell Detection of Genotype and Phenotype in SF3B1-Mutated Chronic Lymphocytic Leukemia Cells
Authors: Lili Wang, Dylan Kotliar, Jean Fan, Shuqiang Li, Jonna Grimsby, Dan A. Landau, Jennifer R. Brown, Niall Lennon, Donna Neuberg, Kenneth J Livak, Catherine J. Wu
Journal: Blood (2014)
CC-006 Eosinophilicophilic gastritis due to carbimazole therapy presenting with a history and investigations mimicking gastric carcinoma
Authors: S Patel, A Fleming, D Reffitt
Journal: Gut (2010)

<h3>Introduction</h3> An 82-year-old woman was referred for investigation of a 6-month history of anorexia, progressive weight loss and epigastric discomfort. <h3>Methods</h3> She had a history of hyperthyroidism diagnosed 7 months previously. Currently, she was euthyroid on carbimazole. <h3>Results</h3> On examination there was a palpable tender mass in the left upper quadrant. Abdominal ultrasound demonstrated an irregular mass and CT scan gross gastric wall thickening and lymphadenopathy suggesting probable gastric malignancy. An OGD confirmed an ulcerated mass in the posterior wall, however, biopsies failed to confirm malignancy and therefore treatment was commenced with Lanzoprazole. Subsequent OGD showed persistence of the mass. Repeat histology showed no evidence of malignancy but demonstrated an inflammatory cell infiltrate within the gastric mucosa with a predominance of eosinophils. Review of the previous biopsy confirmed a similar eosinophilic infiltrate was present. A diagnosis of eosinophilic gastritis rather than malignancy was made. As both biopsies demonstrated eosinophils we reviewed her medication. The literature reports one case of carbimazole induced eosinophilic granulomatous vasculitis localised to the stomach presenting similarly but no cases of eosinophilic gastritis.1 Hence, we hypothesised that carbimazole may be aetiological here and the drug was discontinued. In view of her significant weight loss and anorexia a reducing course of prednisolone was simultaneously commenced. Over the next 6 weeks, there was an improvement in the patient9s clinical condition: her appetite returned and she regained the weight loss. She remained well after discontinuing the prednisolone with no recurrence. Subsequent CT scan demonstrated no evidence of the previous mass or lymphadenopathy and a repeat gastroscopy demonstrated no mucosal thickening or ulceration. <h3>Conclusion</h3> Eosinophilic gastritis is a rare condition that usually presents between the second and th decades of life.2 The mainstay of treatment is corticosteroids. Our patient was treated with a short course of prednisolone and withdrawal of carbimazole. She remained symptom free off carbimazole with no recurrence suggesting that carbimazole was the cause of the Eosinophilic Gastritis. This is the first reported case of Eosinophilic Gastritis due to carbimazole therapy. The clinical presentation, endoscopic and histological findings mimic the presentation of gastric cancer and highlight the importance of histological confirmation in the diagnosis of gastric cancer.
Abstract 1917: Targeting wildtype and L858R/T790M mutant EGFR by isoliquiritigenin induces apoptosis and Inhibits tumor growth of NSCLC
Authors: Mee-Hyun Lee, Sung Keun Jung, Do Young Lim, Yong-Yeon Cho, Cheol-Jung Lee, Ji-Hong Song, Myoung Ok Kim, Sung-Hyun Kim, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2015)

Abstract Genetic alteration of epidermal growth factor receptor (EGFR) is a high risk factor of non-small-cell lung cancer (NSCLC). Isoliquiritigenin (ILQ), a chalcone derivative, reported anti-cancer activities. In this study, we investigated the effects of ILQ on the growth of tyrosine kinase inhibitor -sensitive and -resistant NSCLC cells and elucidated its molecular mechanisms. Treatment with ILQ inhibited growth and induced apoptosis in both tyrosine kinase inhibitor-sensitive (HCC827, H1650; delE746-A750 EGFR) and -resistant (H1975; L858R/T790M EGFR) NSCLC cells. However, ILQ didn't showed the inhibitory effects of cell growth and induction of apoptosis in Met amplified-HCC827GR or K-ras mutated-A549 cells. ILQ induced apoptotic markers, the cleavage of caspase-3 and poly-(ADP ribose)-polymerase, increased expression of Bim and reduced expression of Bcl-2. ILQ inhibited the catalytic activity of both wildtype and double mutant (L858R/T790M) EGFR by kinase assay. Treatment with ILQ inhibited the anchorage-independent growth of NIH3T3 cells stably transfected with either wildtype or double-mutant EGFR with or without EGF stimulation. ILQ also reduced the phosphorylation of Akt and ERK1/2 in both TKI-sensitive and -resistant NSCLC cells in the western blotting analysis. ILQ directly bound both wildtype and double-mutant EGFR by ATP-competitive manner. Computational docking model expected that ILQ interacted with Glu762 and Met793 sites of wildtype EGFR and Lys745, Met793 and Asp855 of mutant EGFR. ILQ attenuated the tumor growth of H1975 cell xenografted athymic mice in vivo, which was caused by decreased expression of Ki-67 and diminished phosphorylation of Akt and ERK1/2. Taken together, ILQ suppresses NSCLC cell growth by directly targeting wildtype or mutant EGFR. Citation Format: Mee-Hyun Lee, Sung Keun Jung, Do Young Lim, Yong-Yeon Cho, Cheol-Jung Lee, Ji-Hong Song, Myoung Ok Kim, Sung-Hyun Kim, Ann M. Bode, Zigang Dong. Targeting wildtype and L858R/T790M mutant EGFR by isoliquiritigenin induces apoptosis and Inhibits tumor growth of NSCLC. [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 1917. doi:10.1158/1538-7445.AM2015-1917
Abstract 4411: Oral drug formulations containing microspheres
Authors: Duc P. Do, Alexander Kar
Journal: Cancer Research (2015)

Abstract Oral anticancer drug formulations are considerably favorable not only for patient adherence, but also for ease of administration. The main objective of the present research was to develop extended-release capsule formulations containing doxorubicin hydrochloride-encapsulated albumin microspheres. Albumin-based polymeric microspheres were evaluated as a potential platform technology for providing extended-release of oral dosage formulations. Bovine serum albumin microspheres were prepared by spray drying and characterized for their physicochemical properties. Scanning electron microscopy (SEM) was used to analyze the size, surface morphology, and size distribution of the drug-loaded microspheres. Zeta potential measurements were carried out to assess the surface properties and stability of the microsphere formulations. Dissolution studies were conducted to analyze the release profiles of the microspheres and capsule-containing microsphere drug formulations. SEM analysis indicated that microspheres were less than 2-μm in size, which is considered to be optimal for uptake by the enterocytes. The average Zeta potential measurements were approximately -30 mV. Additionally, the data showed that microspheres, which contained 1% BSA and 0.1% glutaraldehyde, provided a drug release profile that is desirable for cancer therapy. Both microsphere and capsule-encapsulating microsphere formulations were shown to provide extended-release of the drug over 36 hours. Thus, capsules containing biodegradable microspheres show potential for effective delivery of oral drug formulations. Citation Format: Duc P. Do, Alexander Kar. Oral drug formulations containing microspheres. [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 4411. doi:10.1158/1538-7445.AM2015-4411
Statin treatment use in diabetic patients with breast cancer: A potential C-reactive protein mediated benefit.
Authors: A. C. Ceacareanu, C. Hong, J. J. Brennan, M. Epstein, E. Kossoff, G. K. Nimako, K. Patel, A. Forrest
Journal: Journal of Clinical Oncology (2011)

173 Background: Statin treatment has not yet been evaluated in relation to breast cancer (BC) prognosis in diabetes mellitus (DM) patients. Reported decreased survival following BC in women with metabolic syndrome, led us to investigate whether specific statin therapy may lead to improved BC survival. Reported associations between elevated C-reactive protein (CRP) levels at the time of diagnosis with worse cancer prognosis, and CRP-lowering properties of statin treatment in non-cancer patients, led us to investigate whether statin use is associated with lower CRP levels at the time of BC diagnosis and with improved BC outcomes. Methods: All DM patients newly diagnosed with BC between 2003 and 2007 (Roswell Park Cancer Institute) were retrospectively reviewed (n = 225). BC pathology, outcomes, existing comorbidities and drug therapy were documented. Follow up began at BC diagnosis and ended with first confirmed recurrence and/or death, or last date of follow-up. Hazard ratios (HR) and 95% confidence intervals (CI)s representing the association between statins, BC and a defined event were computed with Cox proportional hazards model. CRP plasma levels were determined by enzyme-linked immunosorbent assay in specimens donated at the time of BC diagnosis. A total of 98 study patients, DM+BC, and their matched controls, BC only (n = 196) were analyzed. Results: After a median follow up of 30 months, patients receiving statins for cholesterol management were found to have better disease-free survival (HR 0.27, 95% CI: 0.10, 0.71, X 2 = 7.31, p = 0.06), and lower overall mortality (HR 0.23, 95% CI: 0.08, 0.66, X 2 = 7.80, p = 0.05) compared to patients not receiving any cholesterol management medication. CRP levels have ranged between 0.2 and 21 mg/L and clinically relevant levels ( &gt; 3mg/L) were noted in the study group. Conclusions: This study explored for the first time the association between statin therapy and BC prognosis in DM. We observed improved outcomes in statin-treated patients. While we currently analyze statin therapy in relationship with baseline CRP levels and BC prognosis, our existing findings suggest that statins have the potential to improve BC outcomes potentially through lowering overall inflammation.
Abstract 1499: SUPR peptides as novel targeted molecular imaging agents for Her2
Authors: Lindsay Kelderhouse, Amanda Hardy, Terry T. Takahashi, Argentina Ornelas, Seth Gammon, Shannon Howell, Peiying Yang, Pin Wang, Richard W. Roberts, Steve Fiacco, Steven W. Millward
Journal: Cancer Research (2015)

Abstract Ideal molecular imaging agents would combine the affinity and selectivity of monoclonal antibodies with the rapid clearance and pharmacokinetics of small molecules Here we describe the use of directed evolution to design Scanning Unnatural Protease Resistant (SUPR) peptides as novel molecular scaffolds for in vivo optical and PET imaging of the Her2 receptor. SUPR peptides were obtained through selection against Her2-expressing breast cancer cells in culture using focused biological display peptide libraries pre-selected for protease resistance. SUPR peptide libraries were programmed with unnatural amino acids for enhanced stability and chemically cyclized after translation to enhance affinity. Peptides isolated from selection selectively bind the Her2 receptor in vitro with low nanomolar affinity and do not compete with Trastuzumab or Pertuzumab. Cy5-labeled SUPR peptides show rapid and Her2-specific tumor uptake in vivo and minimal retention in non-tumor tissues after 24 hours of washout. SUPR peptides can be efficiently labeled with 18F via the copper-catalyzed azide-alkyne cycloaddtion and the resulting radiotracers used for nuclear imaging of Her2-postive tumors by PET/CT. Unlike antibodies and their derivatives, SUPR peptides are synthesized chemically and show rapid clearance from systemic circulation. SUPR peptides also show dramatically enhanced stability relative to linear peptides obtained from phage display or combinatorial chemistry while still retaining affinities compatible with molecular imaging applications. While SUPR peptides are selected from biological display libraries, they share similar chemical composition and structure with peptides derived from non-ribosomal peptide synthesis. We believe that this combination of affinity, stability, evolvability, and synthetic accessibility make SUPR peptide technology a general approach for generating highly potent compounds for targeted molecular imaging of cancer biomarkers. Citation Format: Lindsay Kelderhouse, Amanda Hardy, Terry T. Takahashi, Argentina Ornelas, Seth Gammon, Shannon Howell, Peiying Yang, Pin Wang, Richard W. Roberts, Steve Fiacco, Steven W. Millward. SUPR peptides as novel targeted molecular imaging agents for Her2. [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 1499. doi:10.1158/1538-7445.AM2015-1499
Raising council tax to pay for social care is not acceptable, say critics
Authors: Matthew Limb
Journal: BMJ (2016)

Ministers’ new measures to boost social care spending in England will create problems and worsen health inequalities, critics have warned.

Local authorities are being allowed to spend more over the next two years by bringing forward rises in council tax precepts ringfenced for social care. Precepts will now be allowed to rise by as much as 3% this year (2016-17) and 3% in 2017-18. This 6% total previously had to be spread over three years.

Sajid Javid, communities secretary, announced the widely trailed measures as he set out the local government finance settlement in the House of Commons on 15 December. He said that the policy would provide a further £208m (€248m; $258m) to spend on adult social care in 2017-18 and £444m in 2018-19.

Javid also announced a £240m adult social care support grant to …
416. Enhanced Oncolytic Effect of Tumor Necrosis Factor Alpha Armed Engineered Oncolytic Measles Virus Therapy for Ovarian Carcinoma Cell Line
Authors: Ahmed M. Al-Shammari, Patrycja J. Lech, Stephen J. Russell
Journal: Molecular Therapy (2016)

Introduction. Tumor necrosis factor alpha (TNFa) has been recognized having anticancer properties, and proposed as a cancer treatment early in the 1980s, But its toxicity lead to limited use. Replication competent oncolytic viruses such as live attenuated measles virus (MV), targeting cancer cells selectively, have shown very promising results in both pre and clinical stages. one of its most useful aspects is their ability to produce high amounts of transgene products locally, resulting in high local tumor microenvironment versus systemic concentrations. Therefore, we developed Gene therapy approach to increase anti-tumor activity results from the combination of oncolytic activity, transgene-mediated direct cytotoxic effect such as TNFa-mediated apoptosis. Methods, we created novel oncolytic MV expressing murine TNFa by cloning TNFa gene into MV genome. the gene was amplified by PCR using primers that introduce restriction sites at either end of the coding sequence. The gene cloned into a plasmid encoding the entire measles genome. The insertion site for the TNFa gene was between H and L in the first version. In the second version, transgene was inserted upstream of N. The resulting full-length plasmids [MV-TNFa1 and MV-TNFa2] used to rescue the corresponding recombinant measles virus on 293-3-46 helper cells that was transfected with the MV plasmids. We evaluated the 2 recombinant versions of the MV expressing TNFa with 2 other viruses of MV, one having the sodium iodide symporter (NIS) between H and L, and the second has GFP upstream of N for oncolytic potential against ovarian carcinoma cell line SKOV-3. Infectivity, syncytium formation and cytotoxicity of recombinant MV-TNFs in SKOV-3 cells were evaluated by inverted microscopy and the MTT assay. Transgene expression in SKOV-3 cells after infection was assessed for TNFa functionality and concentration using cells that are genetically engineered for NF-kB Signaling Pathway and TNFa quantitative ELISA assay. Results, we were successful to generate the two versions of the virus with TNFa in different genome locations for each version. MV-TNFa2 shown to produce more TNFa than MV-TNFa1 (Figure-1a), but both viruses were producing functional TNFa by activating NF-kB Signaling Pathway (Figure-1b). Recombinant MV-TNFs viruses were efficiently infected SKOV-3 cell line, resulting in extensive syncytium formation followed by cell death. There was enhanced killing for the MV-TNFa1 infected cells comparing to all other viruses (Figure-1c). In conclusion, engineered MV-TNFs may be a potent and novel cancer gene therapy system. MV expressing TNFa elicited oncolytic effects in ovarian cancer cells, enhancing the killing effect which depend on the insert location.