tbuckley/cabot-search huggingface dataset:
Abstract 1298: The effect of adipocyte-derived factors on lung cells: Exploring the protective nature of excess weight on lung cancer risk
Authors: Rosalind B. Penney, Daniel Sappington, Eric Siegel, Gunnar Boysen, Susan Kadlubar
Journal: Cancer Research (2015)

Abstract Lung cancer is the second most common cancer in men and in women (not including skin cancer) and the most common cause of cancer mortality. According to several epidemiologic papers, excess weight, identified as the BMI categories of overweight and obese, lowers lung cancer risk. Despite the numerous studies describing this anomaly, the underlying mechanisms for the protective effects are still unknown. Adipose tissue is known to secrete inflammatory molecules such as IL6, IL1β, and IL12. Activated IL6- and IL1β-associated inflammatory pathways are known to promote tumorigenesis, while the activated IL12-associated pathway inhibits tumorigenesis. We hypothesize that adipocytes create an environment that prevents lung carcinogenesis through activating inflammatory pathways that inhibit tumor growth and through blocking inflammatory pathways that promote tumor growth. To study the effect of adipocyte-derived factors on lung cells, alveolar fibroblasts (MRC5) and lung carcinoma (A549) cells were cultured in standard medium and in a 50:50 standard: adipocyte-conditioned medium (CM). In addition, cells were treated with benzo[a]pyrene (B[a]P), a known lung carcinogen. After 48 hours, mRNA expression levels of inflammatory genes were determined by RT-PCR. The data demonstrate that B[a]P treatment induced expression of IL1β, IL6 and IL12 in both cell lines. CM treatment decreased expression of IL1β and IL6 in MRC5 cells and increased their expression in A549 cells. In contrast, CM treatment decreased expression of IL12 in both cells lines. Cells treated with B[a]P plus CM had increased expression of IL12 in both cell lines, and reduced expression of IL1β and IL6 in MRC5 (2.3-fold and 6.5-fold, respectively) and A549 cells (40-fold and 11.5-fold, respectively) over B[a]P-treated cells. It was demonstrated that combined treatment increased NFκB (a transcription factor for IL1β, IL6 and IL12) mRNA expression 4-fold over control. The data suggest that conditioned medium inhibits B[a]P-induced and NFκB-mediated expression of IL1β and IL6 but increases NFκB-mediated expression IL12. This suggests that excreted factors from an adipocyte-rich environment may lead to the activation of growth-prohibiting inflammatory pathways, as opposed to growth-promoting pathways. Understanding these mechanisms and the possible discovery of biomarkers can be the foundation for new preventive techniques and treatments for lung cancer. Citation Format: Rosalind B. Penney, Daniel Sappington, Eric Siegel, Gunnar Boysen, Susan Kadlubar. The effect of adipocyte-derived factors on lung cells: Exploring the protective nature of excess weight on lung cancer risk. [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 1298. doi:10.1158/1538-7445.AM2015-1298
Outcomes With Rituximab Monotherapy Versus R-CHOP In Post-Transplant Lymphoproliferative Disease Arising After Solid Organ Transplant: A Multicentre UK Study
Authors: David Burns, Katherine Clesham, Joanna Haughton, Michelle Lannon, Hayder Hussein, Jennifer Marsh, Martin Rowe, Anne L Lennard, Roderick J Johnson, Kate Cwynarski, Sridhar Chaganti
Journal: Blood (2013)
Molecular Analysis of the t(2;8)/MYC-IGK Translocation in High-Grade Lymphoma/Leukemia by Long-Distance Inverse PCR
Authors: Hannes Kroenlein, Stefan Schwartz, Richard Reinhardt, Mara Molkentin, Nicola Goekbuget, Dieter Hoelzer, Eckhard Thiel, Thomas Burmeister
Journal: Blood (2011)
Real-World Clinical Experience with Long-Term Miglustat Therapy in Type 1 Gaucher Disease: The ZAGAL Project
Authors: Pilar Giraldo, Pilar Alfonso, MAngeles Fernandez-Galan, Guillermo Martín-Nuñez, Abelardo Barez, Rafael Franco, Dora Alonso, Antonio Acedo, Alejandro Martin, Elvira Martinez-Estefano, Vanessa Roldan, Sol Serrano, Paz Latre, Miguel Pocovi
Journal: Blood (2008)
Abstract 889: Mouse model for chemotherapy-induced alopecia with transplantation of human hair follicles onto immune deficient mouse
Authors: Ohsang Kwon, Ji-Seon Yoon, Mira Choi, Chang Yup Shin, Kyu Han Kim
Journal: Cancer Research (2015)

Abstract Optimized research models of chemotherapy-induced alopecia (CIA) require for further understanding the pathogenesis and protection of CIA. The present study was aimed to develop a new mouse model for CIA by follicular unit transplantation of human hair follicles onto the immune-deficient mice. At 22 weeks after transplantation, single dose of cyclophosphamide (Cph) was treated in mice of Cph100 (100mg/kg) and Cph150 (150mg/kg) groups. On day 6 of treatment, hair follicles showed dystrophic anagen representing with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, up-regulated P53 expression and apoptotic matrix keratinocytes, and down-regulated expression of Ki67 and melanogenic protein in the hair bulb were also noted in both groupsin Cph100 and Cph150. Subsequently, hair follicles in Cph100 appeared to recover as anagen hair follicles after 9 days. Ki67 and melanogenic protein expression returned as the levels analogous to the control. On the other hands, hair follicles of Cph150 prematurely entered dystrophic catagen-telogen phase after 9 days of treatment. Ki67 and melanogenic protein expression in immunofluorescence staining were barely visible. Those findings indicate that this model represented two pathways of dystrophic anagen pathway in Cph100 and dystrophic catagen pathway in Cph150. Our model will be a useful tool for the further understanding of the impact of chemotherapy on the human hair follicle. Citation Format: Ohsang Kwon, Ji-Seon Yoon, Mira Choi, Chang Yup Shin, Kyu Han Kim. Mouse model for chemotherapy-induced alopecia with transplantation of human hair follicles onto immune deficient mouse. [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 889. doi:10.1158/1538-7445.AM2015-889
Late Clearance of Circulating Leukemic Blasts (CBs) During Induction Therapy (IT) Is a predictive of Refractory Adult Acute Myeloid Leukemia (AML)
Authors: Alaa Muslimani, Aya Rifai, Mohammad Muhsin Muhsin Chisti, Jeffery Margolis, Laura Nadeau, Ishmael Jaiyesimi, James Huang
Journal: Blood (2012)
Selective Serotonin Reuptake Inhibitors Influence Agonist-Induced Platelet Aggregation. Preliminary Results from Comorbidity of Depression and Cardiovascular Disease Study
Authors: Omer Iqbal, Cafer Adiguzel, Jawed Fareed, Debra Hoppensteadt, Evangalos Litinas, He Zhu, Angelos Halaris
Journal: Blood (2008)
Abstract 1456: Efficacy of photo-immunotherapy in combination with surgical resection on a pancreatic cancer patient derived orthotopic xenograft (PDOX)
Authors: Yukihiko Hiroshima, Ali Maawy, Takashi Murakami, Nzola De Magalhães, Daisuke Kawaguchi, Kenichi Matsuo, Kuniya Tanaka, Michael Bouvet, Robert M. Hoffman, Itaru Endo
Journal: Cancer Research (2015)

Abstract Complete tumor resection improves overall survival of pancreatic cancer patients. We have previously showed that UVC irradiation in combination with fluorescence-guided surgery (FGS) completely cured metastatic pancreatic cancer by eradicating minimal residual cancer after FGS. Recently, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, demonstrated in vivo tumor shrinkage after irradiation with NIR light without any side effects. In this study, we used a clinically applicable model of pancreatic cancer to examine the use of PIT to eradicate minimal residual cancer of a patient derived orthotopic xenograft (PDOX). We found that anti-CEA-IR700 could label and illuminate PDOX strongly enough for PIT in both subcutaneous and orthotopic models. Furthermore, we succeeded in detecting fluorescence from the minimal residual cancer of the PDOX. The local recurrence rate of BLS only and BLS + PIT group was 85.7% and 28.6%, respectively. BLS + PIT tended to reduce the recurrence rate compared to BLS only, and there was marginally significant difference (p = 0.051). The average recurrent tumor weight of BLS only and BLS + PIT group was 1149.0 ± 794.6 mg and 210.8 ± 336.9 mg, respectively. The average recurrent tumor weight of BLS + PIT group was significantly less than BLS only (p = 0.015). In conclusion, anti-CEA-IR700 is able to label and illuminate the PDOX strongly enough for PIT. PIT reduces recurrence by eradicating microscopic disease undetectable with BLS, and might be applicable to pancreatic cancer patients. Citation Format: Yukihiko Hiroshima, Ali Maawy, Takashi Murakami, Nzola De Magalhães, Daisuke Kawaguchi, Kenichi Matsuo, Kuniya Tanaka, Michael Bouvet, Robert M. Hoffman, Itaru Endo. Efficacy of photo-immunotherapy in combination with surgical resection on a pancreatic cancer patient derived orthotopic xenograft (PDOX). [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 1456. doi:10.1158/1538-7445.AM2015-1456
Exercise-induced biochemical changes and their potential influence on cancer: a scientific review
Authors: Robert James Thomas, Stacey A Kenfield, Alfonso Jimenez
Journal: British Journal of Sports Medicine (2016)

Aim To review and discuss the available international literature regarding the indirect and direct biochemical mechanisms that occur after exercise, which could positively, or negatively, influence oncogenic pathways. Methods The PubMed, MEDLINE, Embase and Cochrane libraries were searched for papers up to July 2016 addressing biochemical changes after exercise with a particular reference to cancer. The three authors independently assessed their appropriateness for inclusion in this review based on their scientific quality and relevance. Results 168 papers were selected and categorised into indirect and direct biochemical pathways. The indirect effects included changes in vitamin D, weight reduction, sunlight exposure and improved mood. The direct effects included insulin-like growth factor, epigenetic effects on gene expression and DNA repair, vasoactive intestinal peptide, oxidative stress and antioxidant pathways, heat shock proteins, testosterone, irisin, immunity, chronic inflammation and prostaglandins, energy metabolism and insulin resistance. Summary Exercise is one of several lifestyle factors known to lower the risk of developing cancer and is associated with lower relapse rates and better survival. This review highlights the numerous biochemical processes, which explain these potential anticancer benefits.
Abstract 2685: Paracrine effect of NRG1 and HGF drives resistance to MEK inhibitors in metastatic uveal melanoma
Authors: Hanyin Cheng, Mizue Terai, Takami Sato, Andrew Aplin
Journal: Cancer Research (2015)

Abstract Metastatic uveal melanoma (UM) patients usually die within one year, emphasizing an urgent need to develop new treatment strategies. Mitogen-activated protein kinase kinase (MEK) small molecule inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in UM patients. In this study, we identified compensatory mechanisms that provide resistance to MEK inhibition in metastatic UM. We screened for growth factors that were able to induce resistance in three newly characterized metastatic UM cell lines to MEK inhibitors, trametinib and selumetinib, with colony formation assay and viability assay. Cellular signaling pathway analysis was carried out to determine the molecular mechanisms of resistance to MEK inhibition in metastatic UM cells. Clinical-grade antibody and inhibitors targeting these pathways were used to determine their capability to overcome the resistance mediated by these growth factors. Conditioned medium collected from fibroblasts were used to evaluate whether stromal effect from fibroblasts could drive resistance to metastatic UM cells. We demonstrate that Neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1, whereas HGF induces sustained activation of AKT in the presence of trametinib. Individually targeting ERBB3 and cMET, the receptors for NRG1 and HGF, overcomes resistance to trametinib provided by these growth factors and by conditioned medium from fibroblasts, which produce NRG1 and HGF. Analysis of metastatic liver biopsies showed that ERBB2, which is the co-receptor for NRG1, and cMET were phosphorylated in some of these clinical specimens. Our data suggest that combination of MEK inhibitors with ERBB3 and cMET targeting agents may provide novel and effective treatment strategies in metastatic UM. Citation Format: Hanyin Cheng, Mizue Terai, Takami Sato, Andrew Aplin. Paracrine effect of NRG1 and HGF drives resistance to MEK inhibitors in metastatic uveal melanoma. [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 2685. doi:10.1158/1538-7445.AM2015-2685
Phase I study of regorafenib sequentially administered with either FOLFOX or FOLFIRI in patients with first-/second-line colorectal cancer.
Authors: B. Schultheis, G. Folprecht, J. Kuhlmann, R. Ehrenberg, U. T. Hacker, C. Kohne, M. Kornacker, O. Boix, T. Lin, J. Krauss, R. Fischer, S. Hamann, D. Strumberg, K. B. Mross
Journal: Journal of Clinical Oncology (2011)

3585 Background: Regorafenib is an oral multikinase inhibitor of angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-β, FGFR), and oncogenic kinases (KIT, RET, B-RAF). Regorafenib resulted in a 74% disease control rate (PR+SD) in a phase I study in patients (pts) with refractory metastatic colorectal cancer (CRC). A phase III monotherapy trial in relapsing CRC pts is ongoing. Methods: The phase Ib study 11656 investigated the safety, PK, and efficacy of sequentially administered regorafenib in combination with mFOLFOX6 (FOLFOX) or FOLFIRI (oxaliplatin 85 mg/m2 or irinotecan 180 mg/m2, 400 mg/m2 D/L-folinic acid, 400 mg/m2 5 FU bolus followed by 5 FU 2400 mg/m2 for 46 h) every 2 wks as 1st or 2nd line treatment for CRC. Regorafenib 160 mg was given once daily on days 4-10 and 18-24 of every 4 wk cycle. Tumor response was evaluated per RECIST 1.0. Results: 45 pts (FOLFOX: n=25 , FOLFIRI: n=20) were enrolled. 12 pts were ongoing at data cutoff Dec 2010. Demographic variables were similar in both groups. The median treatment duration was 107 days in the FOLFOX and 112 days in the FOLFIRI group. The primary reason for discontinuation was PD (n=10), AE (n=12), consent withdrawn/other (n=8), metastasectomy surgery (n=3).The incidence of treatment related AEs is presented in the table below. Regorafenib had no significant effect on the PK of platinum and 5-FU, whereas exposure of SN-38 increased by 32%. Of the 21 pts in the FOLFOX group who were evaluable for efficacy, 4 achieved PR, 15 SD and 2 PD as best response. Of the 17 evaluable pts in the FOLFIRI group, 4 achieved PR, 11 SD and 2 PD. Conclusions: Regorafenib, when administered sequentially with standard chemotherapy, has shown acceptable tolerability and promising activity in 1st and 2nd line pts with CRC. Regorafenib increased the exposure to SN-38 in the FOLFIRI group, but was not associated with a reduced tolerability. Regorafenib combined with mFOLFOX6 or FOLFIRI will be evaluated in phase II CRC trials. Drug-related AEs (%) in ≥ 30% of pts Regorafenib + FOLFOX Regorafenib + FOLFIRI All grades CTC 3-4 All grades CTC 3-4 Diarrhea 48 4 60 10 Neutropenia 40 28 50 40 Mucositis 40 8 35 0 Fatigue 28 0 45 0 Leukopenia 32 8 40 15 Hand-foot skin reaction 36 4 35 15 Nausea 40 4 25 0 Neuropathy 44 4 20 0
NHS services will close unless social care crisis is resolved, warns BMA leader
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

The NHS in England will not be able to cope unless the government gets to grips with the current crisis in social care, the chair of the British Medical Association has warned.

The sustainability and transformation plans (STPs) currently being developed across 44 “footprint” areas in England will need to deliver £26bn (€30bn; $32bn) in cuts by 2020-21 to plug gaps in health and social care budgets, a previous analysis by the BMA has found.1 Of these savings £5bn must come from social care.

A new analysis by the BMA has found evidence of deep financial problems in social care across large swathes of England that almost match the deficits facing the NHS.2

In Staffordshire and Stoke-on-Trent, for example, the local STP predicts a £256m shortfall in social care, which is only slightly …
Green Synthesis of Sub‐10 nm Gadolinium‐Based Nanoparticles for Sparkling Kidneys, Tumor, and Angiogenesis of Tumor‐Bearing Mice in Magnetic Resonance Imaging
Authors: Bingbo Zhang, Weitao Yang, Jiani Yu, Weisheng Guo, Jun Wang, Shiyuan Liu, Yi Xiao, Donglu Shi
Journal: Advanced Healthcare Materials (2016)

Gadolinium (Gd)‐based nanoparticles are known for their high potential in magnetic resonance imaging (MRI). However, further MRI applications of these nanoparticles are hampered by their relatively large sizes resulting in poor organ/tumor targeting. In this study, ultrafine sub‐10 nm and biocompatible Gd‐based nanoparticles are synthesized in a bioinspired, environmentally benign, and straightforward fashion. This novel green synthetic strategy is developed for growing dextran‐coated Gd‐based nanoparticles (GdNPs@Dex). The as‐prepared GdNPs@Dex is not only biocompatible but also stable with a sub‐10 nm size. It exhibits higher longitudinal and transverse relaxivities in water ( r 1 and r 2 values of 5.43 and 7.502 s −1 × 10 −3 m −1 of Gd 3+ , respectively) than those measured for Gd–DTPA solution ( r 1 and r 2 values of 3.42 and 3.86 s −1 × 10 −3 m −1 of Gd 3+ , respectively). In vivo dynamic T 1 ‐weighted MRI in tumor‐bearing mice shows GdNPs@Dex can selectively target kidneys and tumor, in addition to liver and spleen. GdNPs@Dex is found particularly capable for determining the tumor boundary with clearly enhanced tumor angiogenesis. GdNPs@Dex is also found cleared from body gradually mainly via hepatobiliary and renal processing with no obvious systemic toxicity. With this green synthesis strategy, the sub‐10 nm GdNPs@Dex presents promising potentials for translational biomedical imaging applications.
298. Transfection of Neutrophils from X-Linked Chronic Granulomatous Disease Patients with gp91phox mRNA Restores Oxidase Activity with High Efficiency and Viability
Authors: Suk See De Ravin, Linhong Li, Uimook Choi, Jessica Chu, Narda Theobald, Sherry Koontz, Janet Lee, Kol Zarember, Hanh Khuu, Cathy Cantilena, Madhusudan V. Peshwa, Harry L. Malech
Journal: Molecular Therapy (2015)

Chronic granulomatous disease (CGD) is an inherited immune deficiency due to defective phagocyte NADPH oxidase required for production of antimicrobial oxidants. Fungal or bacterial infections in CGD may persist despite intensive and prolonged antibiotic therapy. In settings where conventional antibiotic therapy and/or surgical debridement do not control infection, use of allogeneic unmatched donor granulocyte transfusions has been therapeutic. However, CGD patients treated with granulocyte transfusions may develop high titers of anti-HLA antibodies, restricting use of allogeneic granulocyte transfusions and further complicating potentially curative bone marrow transplant. Using the CGD patient as an autologous donor for granulocyte transfusions would be a helpful solution. Here we demonstrate highly efficient functional correction of the functional defect in CGD by transfection of patient's own granulocytes with mRNA while retaining viability using a scalable, cGMP-compliant MaxCyte® GT™ electroporation system capable of handling clinically relevant numbers of cells (>1010 cells). Freshly collected granulocytes from normal volunteers were electroporated using the MaxCyte electroporation system with eGFP-mRNA on the day of collection. Flow cytometry of demonstrated that >90% of neutrophils expressed eGFP with viability exceeding 90% at 24 hrs after electroporation. Phagocyte NADPH oxidase activity of the normal neutrophils was retained as well as bactericidal activity against Burkolderia cepacia, a CGD bacterial pathogen. Antibacterial activity of electroporated granulocytes was comparable to unmanipulated granulocytes confirming retention of cellular function following the electroporation. Finally, electroporated eGFP positive human neutrophils injected into CGD mice were shown to remain in circulation as well as migrate to the peritoneal cavity following thioglycollate IP injection and there were no adverse effects observed in the mice. Electroporation of gp91phox mRNA into human X-linked CGD (gp91phox-deficient) patient neutrophils resulted in expression of gp91phox protein in >70% of cells with >90% viability at 24 hours after treatment. Using the dihydrorhodamine assay of phagocyte NADPH oxidase activity, >70% of neutrophils remained functionally corrected 2 days after transfection. Other studies of cellular function in vitro and in vivo with electroporated corrected CGD neutrophils are in progress. In summary, we show the feasibility of restoring the function of CGD patient-autologous neutrophils via electroporation of mRNA encoding the defective gene product. This approach may have potential clinical utility in the management of severe chronic bacterial and fungal infections in CGD but also short-term correction of other hematopoietic gene diseases.
Abstract 548: Exosome as biomarkers and diagnostics in bladder cancer
Authors: Yu-Ru Liu, Christopher Silver, Yi-Fen Lee
Journal: Cancer Research (2015)

Abstract Esosomes are small membrane vesicles secreted by most cell types. They are first found in reticulocytes and play important roles in cell-to-cell communication. Recent studies suggest that exosomes secreted by tumor cells containing tumor specific proteins and miRNAs. Previous study shows that exosomes purified from high grade bladder cancer promote cancer progression. This study aims to characterize the genetic contents in bladder cancer exosomes through mass spectrometry and miRNA array. Exosomes were purified from bladder cancers, immortalized bladder cells, and urine of healthy volunteers and muscle invasive bladder cancer patients. Via proteomics analysis, we have identified several cancer associated exosomal proteins that were found only in bladder cancer, including EDIL-3, an anagiogenic protein in our previous report. Functional characterization of those proteins is currently undertaken with a focus on periostin an extracellulear matrix protein. In addition to protein, exosomes also contain miRNAs that regulate cellular behaviors. Thus, we performed miRNA expression profiling microarray on exosomes from high grade bladder cancer cells, and immortalized bladder cells (LC Sciences). The differences in miRNA expression were compared and differences were determined by a student T test (P&amp;lt;0.05). Results showed significant difference miRNAs between cancer cells vs normal cells. Some of cancer-specific miRNAs which have shown to play critical roles in tumorigenesis and cancer progression will be study priority. Ultimately our work should contribute to the understanding of how exosomes contribute to bladder cancer biology and may elucidate novel urine exosomes markers for bladder cancer diagnosis. Note: This abstract was not presented at the meeting. Citation Format: Yu-Ru Liu, Christopher Silver, Yi-Fen Lee. Exosome as biomarkers and diagnostics in bladder cancer. [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 548. doi:10.1158/1538-7445.AM2015-548