tbuckley/cabot-search huggingface dataset:
The Probability of Invasive Fungal Infection Among Children with Persistent Febrile Neutropenia and Respiratory Viral Infection
Authors: Avigail Rein, Nira Arad, Moran Amit, Ayelet Ben-Barak, Yael Shachor- Meyouhas, Imad Kassis, Myriam Weyl Ben-Arush
Journal: Blood (2014)
PTH-097 Are patients with coeliac disease seeking alternative therapies to a gluten-free diet?
Authors: I Aziz, K E Evans, V Papageorgiou, D S Sanders
Journal: Gut (2010)

<h3>Introduction</h3> The cornerstone of treatment for coeliac disease is a gluten-free diet (GFD). However, adherence to a GFD is reported to vary between 50 and 70%. Recently other investigators have been reporting their preliminary findings using novel therapies (anti-zonulin or peptidases). Both these observations suggest that patients with coeliac disease may be seeking an alternative therapy for their disease. In both irritable bowel syndrome and inflammatory bowel disease the incidence of complementary or alternative medicine (CAM) use is reported to be as high as 50%. There has never been any data assessing the use of CAM in patients with coeliac disease. <h3>Methods</h3> We sought to assess whether patients with adult coeliac disease are taking complementary or alternative medicines (CAM) and also questioned this group about their interest in novel therapies. This was a survey conducted in an out-patient setting. We also obtained information from a control group (without any GI disease) about their use of CAM. <h3>Results</h3> 310 patients with coeliac disease completed the survey (83 male and age range 19–97, mean age 56). Patients were classified according to their presenting symptoms with 258 having "typical" symptoms (gastrointestinal presenting symptoms, anaemia or a combination of both) and 52 with neither (described as atypical, for example, osteoporosis). The control group was 477 individuals (228 male, age range 17–88, mean age 45.9). The incidence of CAM in patients with coeliac disease was 21.6% (67/310) and in the control group the incidence of CAM usage was 27% (129/477), p=0.08. There were no statistically significant differences in incidence when comparing the two subgroups of coeliac disease. Patients were also asked if they were satisfied with the GFD using a Likert scale. The outcomes reported were very poor 7.4% (23/310), poor 34.5% (107/310), average 34.8% (108/310), 19.4% good (60/310) and 3.9% excellent (12/310). Finally patients were asked about their preferences for possible novel therapies. Patients were asked to arrange in order of preference 1–4 whether they would like a vaccine, genetically modified wheat, peptidase or anti-zonulin. Universally patients placed genetically modified wheat as the lowest preference. A vaccine was reported to be the first choice in 42% of patients, 35% for Anti- Zonulin and 23% for Peptidases. <h3>Conclusion</h3> More than 40% of patients with coeliac disease are dissatisfied with their GFD. These patients are not taking CAM any more than individuals without coeliac disease. This suggests they do not view CAM as alternative to the GFD. However, all the patients in this survey were keen to consider novel therapies with a vaccine being the most preferred option.
Impact of hospice and palliative home care on chemotherapy use at the end of life (EOL).
Authors: R. Bascioni, F. Giorgi, F. Rastelli, M. di Pietro Paolo, M. Brugni, F. Basirat, S. Mulattieri, L. Giuliodori, G. De Signoribus, R. R. Silva, L. Giustini
Journal: Journal of Clinical Oncology (2011)

e16611 Background: Many cancer patients (pts) receive chemotherapy at the end of life (EOL) with negative effects on quality of life and high economic burden. Palliative care services and hospice facilities became widely available in Italy during the last decade. We analyzed if this had an impact on chemotherapy use at EOL comparing current data with those obtained in a study carried out in year 2002, where we observed 33% of pts treated with chemotherapy in the last month of life (Giorgi et al. Proc ASCO 22: #6081, 2004). Methods: We performed a retrospective chart review of pts died in year 2010 and treated in three oncology divisions in which palliative care and hospice services have been available since 2004. Results were compared with those obtained in year 2002 when there was no palliative care program in the same oncology units. Results: Clinical records of 335 pts dead during 2010 were reviewed (F 156, M 179). The most frequent tumors were: breast 53 pts, NSCLC 53, colorectal 48, gastric 30, pancreas 16, prostate 13. Median age was 71 years (range 22-96). Seventy-one pts (21 %) received chemotherapy and 16 pts (5 %) targeted therapies in the last month of life (aggregate 26 %). In the last week of life 10 pts received chemotherapy and 8 pts targeted therapies (5 %). One hundred ninety-two pts (57%) entered a palliative care/hospice program managed by oncologists of the same unit: 126 pts home palliative care and 66 pts hospice care. Despite the expansion of standard second and third line chemotherapy and targeted therapy in the oncologist's therapeutic arsenal, we observed a 7 % reduction (21% relative reduction) of cancer-directed interventions in the last month of life. Conclusions: We observed a 21% relative reduction in anticancer treatment provided at the EOL between 2002 and 2010. We believe that most of this reduction can be ascribed to the implementation of palliative care services where oncologists ensure continuity of care. Maintaining a stable oncologist-patient relationship may foster better EOL decisions and utilization of health care resources.
Abstract 3310: Targeting MUC1-mediated metabolism sensitizes pancreatic cancer cells to radiation therapy
Authors: Venugopal Gunda, Jaime Abrego, Surendra K. Shukla, Nina V. Chaika, Fang Yu, Tadayoshi Bessho, Chi Lin, Pankaj K. Singh
Journal: Cancer Research (2015)

Abstract Overexpression of MUC1 promotes growth promoting metabolic alterations in pancreatic cancer cells. We investigated the role played by MUC1-mediated metabolic alterations in radiation response of pancreatic cancer cells. Our findings indicate that cell survival and clonogenicity of pancreatic cancer cells upon radiation treatment correlate with MUC1 expression. MUC1 expression reduced radiation-induced reactive oxygen species (ROS) production and DNA damage, whereas, increased glucose uptake and lactate secretion upon irradiation. Metabolomic analysis through liquid chromatography-coupled tandem mass spectrometry approach revealed that pancreatic cancer cells exhibit spontaneous metabolic alterations upon irradiation. MUC1 expression further altered radiation-induced carbon flux especially in glycolysis and pentose phosphate pathway. We further investigated radiation-sensitization of MUC1-expressing cells by targeting glycolysis or pentose phosphate pathway using metabolic inhibitors, and observed that pre-treatment with 3-bromopyruvate (BrPA) effectively abrogates MUC1-mediated radiation-resistance by elevating ROS and DNA damage. BrPA treatment also reduced MUC1-induced carbon flux into glycolysis and pentose phosphate pathway, upon irradiation. Hence, our findings demonstrate that MUC1-mediated radiation-resistance in pancreatic cancer cells can be effectively targeted through inhibition of glycolysis. Citation Format: Venugopal Gunda, Jaime Abrego, Surendra K. Shukla, Nina V. Chaika, Fang Yu, Tadayoshi Bessho, Chi Lin, Pankaj K. Singh. Targeting MUC1-mediated metabolism sensitizes pancreatic cancer cells to radiation therapy. [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 3310. doi:10.1158/1538-7445.AM2015-3310
Abstract 3005: Investigating the impact of hypoxia-induced changes in splicing on tumor microenvironment
Authors: Lauren Brady, Vladimir Popov, Mircea Ivan, MIlan Radovich, Constantinos Koumenis
Journal: Cancer Research (2015)

Abstract Hypoxia is a cellular stress that influences both normal and tumor development. For many types of cancer, including head and neck carcinomas, tumor hypoxia shows a strong positive correlation with poor patient outcome. In order to gain a deeper understanding of the biology of the tumor microenvironment, we are investigating how transcription is differentially regulated in hypoxic compared to normoxic regions of tumors. Previously, we reported that the expression of over 500 genes differs between hypoxic and normoxic tumors. However, there has not yet been a global sequencing analysis of tumors to characterize hypoxia-induced differences in transcriptional regulation at base-pair resolution. To achieve this, we developed a method to isolate RNA from hypoxic regions of tumors in vivo and used this method to carry out deep RNA-sequencing of normoxic and hypoxic regions of human head and neck tumors grown in mice. Corresponding in vitro samples from cells cultured in 0.5% oxygen conditions (in which the only stress was hypoxia) were also sequenced. We used these data to examine which genes showed changes in isoform-level expression and to define hypoxia-mediated changes in splicing. The data revealed more than 1,000 hypoxia-responsive mRNA isoforms. Using a combined informatics approach to analyze both differential expression of alternatively spliced exons and entire isoforms, we observed that many hypoxia-induced isoforms showed changes in alternate last exons, retained introns and 3′ untranslated regions compared to the isoforms expressed in normoxic cells. Moreover, we observed global repression of genes involved in RNA processing and splicing, which may represent one mechanism to shift patterns in splicing and lead to expression of stress-induced isoforms. Differentially expressed isoforms include genes that play critical roles in fundamental processes involved in hypoxic adaptation, such as the translation, glycolysis and cell cycle. Therefore, we propose that alternative splicing plays a role in mediating tumor growth and survival in hypoxic conditions by regulating stress-responsive pathways. Citation Format: Lauren Brady, Vladimir Popov, Mircea Ivan, MIlan Radovich, Constantinos Koumenis. Investigating the impact of hypoxia-induced changes in splicing on tumor microenvironment. [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 3005. doi:10.1158/1538-7445.AM2015-3005
Abstract 5477: MERIT40 is an Akt substrate that promotes resolution of DNA damage induced by chemotherapy
Authors: Kristin K. Brown, Laleh Montaser-Kouhsari, Andrew H. Beck, Alex Toker
Journal: Cancer Research (2015)

Abstract Resistance to cytotoxic chemotherapy agents is a common phenomenon in breast cancer and has a drastic impact on patient survival. Characterization of the mechanisms that contribute to chemotherapy resistance, and identification of strategies to circumvent resistance, would provide more effective therapies for the management of breast cancer. In this study we show that in addition to inflicting DNA damage, the cytotoxic chemotherapy agent doxorubicin triggers rapid and sustained activation of Akt in breast cancer cells. Pharmacological inhibitors of PI 3-K or Akt effectively block Akt signaling downstream of DNA damage and render cells markedly more sensitive to doxorubicin. We sought to identify mechanisms by which Akt promotes resistance to doxorubicin and have identified MERIT40, a component of the nuclear BRCA1-A DNA damage repair complex, as a novel Akt substrate that is phosphorylated when cells are exposed to doxorubicin. We have demonstrated that MERIT40 phosphorylation is necessary for BRCA1-A complex assembly and is required for resolution of DNA damage. We propose that inhibition of MERIT40 phosphorylation contributes to the efficacy of combination therapy with PI 3-K or Akt inhibitors and doxorubicin. We also show that MERIT40 phosphorylation is associated with ER status in breast tumor tissue samples, suggesting that MERIT40 phosphorylation could be used as a biomarker in ER-positive breast cancer patients to predict sensitivity to cytotoxic chemotherapy agents. Our data also indicates that patients with high levels of phosphorylated MERIT40 would likely benefit from combination therapy with Akt inhibitors and doxorubicin. We are currently investigating additional mechanisms by which Akt activation downstream of DNA damage promotes chemotherapy resistance with the aim of identifying novel combination therapy regimens to circumvent chemotherapy resistance. Citation Format: Kristin K. Brown, Laleh Montaser-Kouhsari, Andrew H. Beck, Alex Toker. MERIT40 is an Akt substrate that promotes resolution of DNA damage induced by chemotherapy. [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 5477. doi:10.1158/1538-7445.AM2015-5477
Development and Therapeutic Potential of an Anti-CD79b Antibody-Drug Conjugate, Anti-CD79b-Vc-MMAE, for the Treatment of Non-Hodgkin’s Lymphoma
Authors: Andrew G. Polson, Fiona L Bennett, Yvonne Chen, Mark Dennis, Dan Eaton, Allen Ebens, Kristi Elkins, Dorothy French, Mary Ann T. Go, Andrew S Jack, Jagath Junutula, Hartmut Koeppen, Jeffery Lau, Jacqueline McBride, Lily Shi, Andy Rawston, Shang-Fan Yu, Peng Yue, Bing Zheng, David Dornan
Journal: Blood (2008)
Potent Single Agent Activity and Tumor Selectivity of Bortezomib in Mantle Cell Lymphoma: First Impressions from a Randomized Phase II Study of EPOCH-Rituximab-Bortezomib in Untreated Mantle Cell Lymphoma.
Authors: Adrian Wiestner, Kieron Dunleavy, Edgar G. Rizzatti, Hui Liu, Gerald E. Marti, Therese White, Wyndham Wilson
Journal: Blood (2005)
Erratum for the Research Article: “Gene Therapy for Wiskott-Aldrich Syndrome—Long-Term Efficacy and Genotoxicity” by C. J. Braun, K. Boztug, A. Paruzynski, M. Witzel, A. Schwarzer, M. Rothe, U. Modlich, R. Beier, G. Göhring, D. Steinemann, R. Fronza, C. R. Ball, R. Haemmerle, S. Naundorf, K. Kühlcke, M. Rose, C. Fraser, L. Mathias, R. Ferrari, M. R. Abboud, W. Al-Herz, I. Kondratenko, L. Maródi, H. Glimm, B. Schlegelberger, A. Schambach, M. H. Albert, M. Schmidt, C. von Kalle, C. Klein
Journal: Science Translational Medicine (2014)
Toll-like receptor 2 promiscuity is responsible for the immunostimulatory activity of nucleic acid nanocarriers
Authors: Malvina Pizzuto, Monique Gangloff, Daniel Scherman, Nicholas J. Gay, Virginie Escriou, Jean-Marie Ruysschaert, Caroline Lonez
Journal: Journal of Controlled Release (2016)

Lipopolyamines (LPAs) are cationic lipids; they interact spontaneously with nucleic acids to form lipoplexes used for gene delivery. The main hurdle to using lipoplexes in gene therapy lies in their immunostimulatory properties, so far attributed to the nucleic acid cargo, while cationic lipids were considered as inert to the immune system. Here we demonstrate for the first time that di-C18 LPAs trigger pro-inflammatory responses through Toll-like receptor 2 (TLR2) activation, and this whether they are bound to nucleic acids or not. Molecular docking experiments suggest potential TLR2 binding modes reminiscent of bacterial lipopeptide sensing. The di-C18 LPAs share the ability of burying their lipid chains in the hydrophobic cavity of TLR2 and, in some cases, TLR1, at the vicinity of the dimerization interface; the cationic headgroups form multiple hydrogen bonds, thus crosslinking TLRs into functional complexes. Unravelling the molecular basis of TLR1 and TLR6-driven heterodimerization upon LPA binding underlines the highly collaborative and promiscuous ligand binding mechanism. The prevalence of non-specific main chain-mediated interactions demonstrates that potentially any saturated LPA currently used or proposed as transfection agent is likely to activate TLR2 during transfection. Hence our study emphasizes the urgent need to test the inflammatory properties of transfection agents and proposes the use of docking analysis as a preliminary screening tool for the synthesis of new non-immunostimulatory nanocarriers.
Abstract 3893: Whole-exome sequencing analysis of primary central nervous system lymphoma reveals recurrent MYD88 and PIM1 mutations
Authors: Motoo Nagane, Kazutaka Fukumura, Toshihide Ueno, Jeunghun Lee, Yukiko Shishido-Hara, Mitsuaki Shirahata, Kazuhiko Mishima, Koichi Ichimura, Akitake Mukasa, Yoshitaka Narita, Ryo Nishikawa, Hiroyuki Mano
Journal: Cancer Research (2015)

Abstract Primary central nervous system lymphoma (PCNSL) is defined as diffuse large B-cell lymphoma (DLBCL) confined to the central nervous system. Although PCNSL cannot be histologically distinguished from extracerebral DLBCL, its prognosis is quite poor. To gain insights into the transforming mechanism of PCNSL, we conducted whole-exome sequencing for 44 PCNSL specimens. Genomic DNA was extracted from tumors and their matched normal samples. Exome fragments were captured by using SureSelectXT Human All ExonV5+lncRNA, and subjected to deep sequencing with the HiSeq 2000 system. There were 8 cases with germinal center B-cell-like (GCB) subtype and 34 cases with non-GCB subtype. Whole-exome sequencing of tumor and paired normal yielded sequencing data with a mean coverage of 156X and 80X, with 98% and 99% of the targeted bases covered by ≥20 independent reads, respectively. Of 17,832 somatic mutations identified in the PCNSL specimens, 11,611 (65%) were nonsynonymous single nucleotide variations. Predominant nucleotide substitution was a C&amp;gt;T transition (57%) especially in the context of the sequence GCG. We also identified 798 insertions/deletions. Interestingly, MYD88 mutations were detected in 35 of 44 patients (79.5%), and PIM1 mutations were detected in 42 patients (95.5%). Also, a number of genetic aberrations were shown to activate the NF-κB pathway. These results suggest that MYD88 and PIM1 mutations have important roles in the development of PCNSL and could be the therapeutic targets of this intractable disorder. Citation Format: Motoo Nagane, Kazutaka Fukumura, Toshihide Ueno, Jeunghun Lee, Yukiko Shishido-Hara, Mitsuaki Shirahata, Kazuhiko Mishima, Koichi Ichimura, Akitake Mukasa, Yoshitaka Narita, Ryo Nishikawa, Hiroyuki Mano. Whole-exome sequencing analysis of primary central nervous system lymphoma reveals recurrent MYD88 and PIM1 mutations. [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 3893. doi:10.1158/1538-7445.AM2015-3893
Abstract 5051: Androgen receptor-mediated regulation of p14ARF transcription in prostate tumor cells
Authors: Maria Mudryj, Salma Siddiqui, Stephen J. Libertini, Alan P. Lombard, Benjamin Mooso, Leandro D'Abronzo, Frank Melgoza, Alexander Borowsky, Christiana Drake, LiHong Qi, Paramita M. Ghosh
Journal: Cancer Research (2015)

Abstract The p14ARF tumor suppressor is often deleted or silenced in malignancies. Prostate tumors are an exception, where p14 expression is elevated. To understand this phenomenon, we assessed the expression of p53 pathway members, which are most effected by p14ARF. The expression of androgen receptor (AR), a pivotal prostate cancer regulator, which is also affected by p14arf and MDM2 was analyzed as well. The studies used archival prostate tumor tissues obtained from prostatectomies performed at the Veterans Affairs-Northern California Health Care System in Mather California between 1996 and 2002 to better define the relationship between these interrelated networks. A prostate tumor tissue array consisting of 78 tumors of differing stages and grades was constructed to evaluate correlations between multiple parameters. Immunohistochemical studies assessed expression of the proliferation marker Ki67, p53, MDM2, MDM4, p14ARF, and the AR in the nuclear and cytoplasmic compartments of tumor and adjacent cells. p53, MDM4, p14ARF and AR were detected in nuclear and cytoplasmic compartments of tumor and non-tumor cells, but were predominantly nuclear. MDM2 expression was primarily cytoplasmic in tumor cells. Multivariate analysis of the immunohistochemical markers identified a strong correlation between expression of p14ARF and AR. Studies utilizing the prostate CWR22 xenograft and LNCaP cell line models revealed that castration or androgen deprivation resulted in reduced p14arf levels and that this effect correlated with a precipitous decline in E2F1-3a levels. In a reciprocal analysis, RB ablation enhanced p14ARF transcription, arguing that the E2F/RB pathway mediates AR-dependent p14ARF expression. However, we also identified an AR binding site located ∼40 KB upstream of the p14ARF gene. Chromatin immunoprecipitation (ChIP) studies showed that in prostate cells this site was bound by AR. ChIP studies also revealed E2F1 and E2F3 were present at the p14ARF promoter. Together, the studies argue p14ARF is a direct transcriptional target of AR and that AR and E2F collaborate to promote p14ARF expression. . Citation Format: Maria Mudryj, Salma Siddiqui, Stephen J. Libertini, Alan P. Lombard, Benjamin Mooso, Leandro D'Abronzo, Frank Melgoza, Alexander Borowsky, Christiana Drake, LiHong Qi, Paramita M. Ghosh. Androgen receptor-mediated regulation of p14ARF transcription in prostate tumor cells. [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 5051. doi:10.1158/1538-7445.AM2015-5051
Liver Transient Elastography (FibroScan) Correlates with Liver Iron Concentration and Reflects Liver Fibrosis In Patients with Sickle Cell Disease
Authors: Ersi Voskaridou, Maria Schina, Eleni Plata, Dimitrios Christoulas, Maria Tsalkani, Maria Dimopoulou, Hlectra Dimitrakopoulou, George Mousoulis, Evangelos Terpos
Journal: Blood (2010)