tbuckley/cabot-search huggingface dataset:
Location analysis of E2F4 binding sites by high-density oligonucleotide human promoter arrays.
Authors: Sunny Song
Journal: Clinical Cancer Research (2007)

C58   Regulatory proteins bind to genomic DNA to control chromosome replication and gene activity, thereby functioning as switches in the regulatory circuitry of cells. This network of circuits is uncharted in many instances and its understanding will aid researchers and companies in identifying new target genes and therapeutics capable of modulating these pathways. ChIP-on-chip (chromatin immunoprecipitation-on-chip) also known as Location Analysis (LA), is a powerful technology to analyze how regulatory proteins interact with the genome of living cells using microarrays (Boyer, L.A. et al., Cell, v122, 947-956). This advanced technology provides insight into the mechanisms of DNA methylation and histone modification, as well as DNA replication and repair. The E2F4 family is a ubiquitous family of transcription factors involved in regulating basic cellular processes. Here we take an unbiased, sensitive, and comprehensive approach towards identifying E2F4 target genes by examining localization of E2F4 binding sites using high-density oligonucleotide human promoter arrays and integrated ChIP analytics software.
Toll-like receptor 4 stimulation with monophosphoryl lipid A ameliorates motor deficits and nigral neurodegeneration triggered by extraneuronal α-synucleinopathy
Authors: Serena Venezia, Violetta Refolo, Alexia Polissidis, Leonidas Stefanis, Gregor K. Wenning, Nadia Stefanova
Journal: Molecular Neurodegeneration (2017)

Alpha-synuclein (α-syn) aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Toll-like receptors (TLRs) are a family of highly conserved molecules that recognize pathogen-associated molecular patterns and define the innate immunity response. It was previously shown that TLR4 plays a role in the clearance of α-syn, suggesting that TLR4 up-regulation in microglia may be a natural mechanism to improve the clearance of α-syn. However, administration of TLR4 ligands could also lead to dangerous adverse effects associated with the induction of toxic inflammatory responses. Monophosphoryl lipid A (MPLA) is a TLR4 selective agonist and a potent inducer of phagocytosis which does not trigger strong toxic inflammatory responses as compared to lipopolysaccharide (LPS). We hypothesize that MPLA treatment will lead to increased clearance of α-syn inclusions in the brain of transgenic mice overexpressing α-syn in oligodendrocytes under the proteolipid protein promoter (PLP-α-syn mouse model of MSA), without triggering toxic cytokine release, thus leading to a general amelioration of the pathology.Six month old PLP-α-syn mice were randomly allocated to four groups and received weekly intraperitoneal injections of MPLA (50 or 100 μg), LPS or vehicle. After a 12-week treatment period, motor behavior was assessed with the pole test. Brains and plasma samples were collected for neuropathological and immunological analysis.Chronic systemic MPLA treatment of PLP-α-syn mice led to increased uptake of α-syn by microglial cells, a significant motor improvement, rescue of nigral dopaminergic and striatal neurons and region-specific reduction of the density of oligodendroglial α-syn cytoplasmic inclusions in the absence of a marked systemic inflammatory response.Our findings demonstrate beneficial effects of chronic MPLA treatment in transgenic PLP-α-syn mice. MPLA appears to be an attractive therapeutic candidate for disease modification trials in MSA and related α-synucleinopathies.
Is histology (His) relevant in adjuvant (Adj)/neoadjuvant (NA) therapy of breast cancer (BC)?
Authors: A. Katz, E. D. Saad, L. Pusztai
Journal: Journal of Clinical Oncology (2006)

10541 Background: Invasive lobular carcinoma (ILC) constitutes 10–15% of cases of invasive BC. In ongoing NCI-sponsored, randomized trials (RT) of early BC, His is not a stratification factor, despite the suggestion that ILC might have distinct clinical behavior and gene expression profile. Compared with invasive ductal carcinoma (IDC), ILC is more frequently of lower grade and positive for estrogen receptor (ER). Methods: We reviewed the literature to evaluate the effect of His on outcome of Adj and NA therapy, by quantifying its impact on the pathologic response (pCR) rate to NA chemotherapy (CT), and on the results of adjuvant trials. We also compiled retrospective series analyzing pCR to NA CT according to His. Results: We retrieved 16 RT (8 phase III, 8 phase II) of NA therapy; 11 compared CT regimens, 3 regimens that contained CT and hormone therapy (HT), and 2 HT only. None of the RT used His for stratification; 5 studies described His at randomization, but only 1 provided information on pCR rate to CT according to His (Dieras et al, 4.0% for ILC, 8.3% for IDC). Compiled results of 6 retrospective series which included nearly 3,000 patients (PTS) showed a pCR rate of 1.7% (6 of 354) in ILC PTS and of 11.6% (300 of 2584) in IDC PTS (P &lt; 0.01). Of 39 phase III RT of Adj CT, 7 compared CT vs HT, 14 CT vs CT + HT, 11 HT vs HT + CT, and 7 CT vs HT vs CT + HT. Of the 39 RT, only 4 described His in demography (9%, 9%, 10% and 12% of PTS participating in these 4 RT were ILC), but none analyzed results according to His. Conclusions: We suggest that the role of CT in early ILC is not clear. The pCR rate is significantly lower in ILC PTS treated with NA CT. It is also not clear if His is an independent predictive factor or a marker of grade/ER expression. The specific value of CT in the Adj treatment of ILC PTS has not been adressed in the Adj RT. Past and current, ongoing RT of Adj CT do not stratify PTS according to His neither evaluate the results according to His. Given the potential therapeutic implications, we suggest that the role of His should be more thoroughly investigated in future RT in order to define the appropriate effectiveness of CT and HT in the treatment of ILC PTS, so that possible overtreatment of ILC PTS with CT might be avoided. No significant financial relationships to disclose.
Management of Relapsed Acute Promyelocytic Leukemia Post ATO Upfront Therapy: Open-Labeled Phase II Study Evaluating Role of Proteasome Inhibition
Authors: Vikram Mathews, Anu Korula, Uday Kulkarni, Saravanan Ganesan, Sachin David, Ansu Abu Alex, Nisham PN, Aby Abraham, Alok Srivastava, Kavitha M Lakshmi, Poonkuzhali Balasubramanian, Biju George
Journal: Blood (2016)
Enzymatic Hydrolysis of Homologous Amino Acid Amides in Normal and Neoplastic Tissues
Authors: Maurice Errera, Jesse P. Greenstein
Journal: JNCI Journal of the National Cancer Institute (1947)

Enzymatic Hydrolysis of Homologous Amino Acid Amides in Normal and Neoplastic Tissues Get access Maurice Errera, Maurice Errera research fellow Search for other works by this author on: Oxford Academic PubMed Google Scholar Jesse P. Greenstein Jesse P. Greenstein chief biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 8, Issue 2, October 1947, Pages 71–75, https://doi.org/10.1093/jnci/8.2.71 Published: 01 October 1947 Article history Published: 01 October 1947 Received: 06 October 1947
Eribulin plus trastuzumab in pretreated HER2-positive advanced breast cancer (ABC) patients: Results on safety and efficacy—An Italian multicenter experience.
Authors: Stefania Eufemia Lutrino, Laura Orlando, Caterina Fontanella, Antonio Febbraro, Marianna Giampaglia, Claudio Zamagni, Claudio Scavelli, Guido Giordano, Enrico Basso, Sara Quercia, Annamaria Quaranta, Claudia Corbo, Rosangela Romano, Daniela Rubino, Chiara Caliolo, Serena Campidoglio, Domenico Bilancia, Elena Barbieri, Antonella Marino, Saverio Cinieri
Journal: Journal of Clinical Oncology (2016)

e12087 Background: Chemotherapy (CT) plus targeted therapy is the established treatment for HER2 overexpressing breast cancer (BC) patients (pts). The debate about anti-HER2 combination beyond standard therapies is still unresolved. Limited data regarding the safety and activity of the combination of eribulin and trastuzumab (E/T) in pretreated HER2-positive advanced breast cancer (ABC) are available. The aim of this observational, retrospective, multicenter study was to examine the tolerability and the clinical activity of eribulin plus trastuzumab in this setting. Methods: Pts treated with eribulin mesylate (1.23 mg/m2 administered via intravenous infusion on Days 1 and 8 each 21-day cycle) plus standard dose of trastuzumab (16 pts received 3-week schedule: 8 mg/kg load, 6 mg/kg q 3 weeks; 3 pts received weekly schedule: 4 mg/kg load, 2 mg/kg q week) were included. Data on overall response rate (ORR), progression free survival (PFS), post-progression survival (PPS), overall survival (OS) and safety were reported. Results: Between January 2012 and May 2015, 19 pts with HER2-positive ABC were included. Median age was 53 years (32 to 74). All pts were heavily pretreated: the median number of prior CT regimens for ABC was 3 (range 2-9). ECOG PS was 0-1 in 84%, visceral metastases were present in most pts (58%). The median number of cycles with E/T was 9 (range 2-26). Neutropenia was the most common grade 3/4 clinical adverse event (15.8%); no febrile neutropenia was observed. Pts also reported grade 3/4 fatigue (5.3%), peripheral neuropathy (5.3%) and nausea (5.3%). Alopecia was observed in the majority of pts (63.1%). The ORR was 48%, with 1 complete response (CR) and 8 partial responses (PR); 5 pts had stable disease (SD), and 4 had progressive disease (PD). Median PFS was 4.4 months (range 1- 9.5), median PPS was 5.4 months (range 4.4-6.3) and median OS was 8 months (range 1.3-14.8) Dose reduction was applied in 6 pts (31.6%); no pts interrupted the treatment prematurely. Conclusions: Tolerability and clinical activity of E/T combination schedule are encouraging . The results of this study indicate that this combination might be considered for future studies.
Frequency of exacerbations in patients with chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort
Authors: MeiLan K Han, Pedro M Quibrera, Elizabeth E Carretta, R Graham Barr, Eugene R Bleecker, Russell P Bowler, Christopher B Cooper, Alejandro Comellas, David J Couper, Jeffrey L Curtis, Gerard Criner, Mark T Dransfield, Nadia N Hansel, Eric A Hoffman, Richard E Kanner, Jerry A Krishnan, Carlos H Martinez, Cheryl B Pirozzi, Wanda K O'Neal, Stephen Rennard, Donald P Tashkin, Jadwiga A Wedzicha, Prescott Woodruff, Robert Paine, Fernando J Martinez, Neil E Alexis, Wayne H Anderson, R Graham Barr, Eugene R Bleecker, Richard C Boucher, Russell P Bowler, Elizabeth E Carretta, Stephanie A Christenson, Alejandro P Comellas, Christopher B Cooper, David J Couper, Gerard J Criner, Ronald G Crystal, Jeffrey L Curtis, Claire M Doerschuk, Mark T Dransfield, Christine M Freeman, MeiLan K Han, Nadia N Hansel, Annette T Hastie, Eric A Hoffman, Robert J Kaner, Richard E Kanner, Eric C Kleerup, Jerry A Krishnan, Lisa M LaVange, Stephen C Lazarus, Fernando J Martinez, Deborah A Meyers, John D Newell, Elizabeth C Oelsner, Wanda K O'Neal, Robert Paine, Nirupama Putcha, Stephen I. Rennard, Donald P Tashkin, Mary Beth Scholand, J Michael Wells, Robert A Wise, Prescott G Woodruff
Journal: The Lancet Respiratory Medicine (2017)
French comment on article Endoscopic ultrasound-guided gallbladder drainage reduces adverse events compared with percutaneous cholecystostomy in patients who are unfit for cholecystectomy1 Etude randomisée comparant le drainage de la vésicule biliaire sous échoendoscopie versus un drainage percutané chez des patients présentant une cholécystite aiguë contre-indiquée pour une cholécystectomie
Journal: Endoscopy (2017)

Il s’agit d’une étude randomisée 1 – 1 portant sur 118 patients entre novembre 2011 et aout 2014 présentant une cholécystite aiguë et une contre-indication chirurgicale (âge > 80 ans, score ASA > 3, comorbidité score > 4 et/ou Karnofsky < 50 %).
Abstract 161: Induced Pluripotent Stem Cell-based Model of Cardiac Arrhythmia: New Platform for Drug Screen
Authors: LouJin Song, Masayuki Yazawa
Journal: Circulation Research (2015)

Human induced pluripotent stem cell (iPSC)-based model of cardiac diseases has been proved to be useful and valuable for identifying new therapeutics. However, the use of human iPSC-based model of cardiac diseases for drug screen is hampered by the high-cost and complexity of methods used for reprogramming, in vitro differentiation, and phenotyping. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free iPSCs from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from Timothy syndrome patients into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared to controls, which were consistent with previous reports using a retroviral method for reprogramming and using an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to test potential therapeutics. With those new approaches in hand, next we plan to use the iPSC-based model of Timothy syndrome to investigate novel molecules involved in the pathogenesis of Timothy syndrome and to screen and identify new therapeutic compounds for Timothy syndrome patients.
Definition of specific protein patterns in advanced bladder cancer for individual prognosis
Authors: Rico Pilchowski, Robert Stoehr, Arndt Hartmann, Ferdinand von Eggeling, Joerg Schubert, Susanne Fuessel, Kerstin Junker
Journal: Cancer Research (2008)

4498    Introduction:  Until now, prognostic parameters for prediction of metastatic risk in bladder cancer patients are not available. Therefore, the aim of this study was the identification of specific protein patterns associated with tumor progression in invasive tumors concerning metastasis.   Materials and methods:  We analyzed 31 metastasized bladder tumors and 19 non-metastasized ones by ProteinChip Technology SELDI-TOF-MS. Cell lysis was performed using buffer containing mercaptoethanol after laser capture microdissection of tumor-positive areas of histological sections. SELDI-TOF-MS was completed with three different chip surfaces (Q10, CM10 and IMAC30). For data analysis we employed the software XL-miner containing a modified algorithm and a relevance index of Kindl for evaluation of automatically generated rules.    Results:  The rule base was generated with a significance level of 0.8 by combination of data from different chip surfaces (Q10, CM10 and IMAC30), which showed sensitivity of 87% and specificity of 83%, respectively. Eight relevant protein peaks were included in the rule base. The protein peaks with the molecular mass of 6651, 11820, 14681, 16047, 16144 and 165647 kDa appeared particularly relevant, since they exhibit the highest relevance index and most frequently appear in the samples.     Discussion:  The results indicate clearly that the ProteinChip Technology, including the bioinformatic evaluation software, is suitable to define relevant protein patterns for metastasized bladder cancer. Using this technique specific protein peaks were identified. Based on these data, we expect the identification of clinically usable biomarkers, which allow the identification of patients at high metastatic risk even in a clinically localized stage leading to an individual therapy decision.
Use of Urine Dipsticks in Spontaneous Bacterial Peritonitis (SBP): Benefit for the Busy Junior Physician
Authors: A Koulaouzidis, E Said, A Saeed
Journal: Endoscopy (2006)

Aims: Recent studies demonstrated the potential of using urine dipsticks to diagnose SBP. We aimed to assess the essential time saved if diagnosis of SBP was based on dipstick result.
Gemtuzumab ozogamicin in infants with AML: results from the Children’s Oncology Group trials AAML03P1 and AAML0531
Authors: Erin M. Guest, Richard Aplenc, Lillian Sung, Susana C. Raimondi, Betsy A. Hirsch, Todd A. Alonzo, Robert B. Gerbing, Yi-Cheng Jim Wang, Samir B. Kahwash, Amy Heerema-McKenney, Soheil Meshinchi, Alan S. Gamis
Journal: Blood (2017)
Cognitive support program for patients with brain metastases.
Authors: Nadine M. Richard, Lori J. Bernstein, David Shultz, Normand Laperriere, Paul N. Kongkham, Alejandro Berlin, Tatiana Deirdre Conrad, Barbara-Ann Millar, Mark Bernstein, Gelareh Zadeh, Kim Edelstein
Journal: Journal of Clinical Oncology (2017)

TPS2086 Background: Brain metastases occur in ~30% of cancer patients. While treatment options continue to evolve, prognosis remains poor in both morbidity and survival, and quality of life (QOL) is increasingly emphasized. Most patients will experience cognitive dysfunction. Deficits in executive and self-regulatory functions, memory, and communication interfere with patients’ functional independence, participation in valued activities, relationships and QOL; they also affect families and caregivers. There are currently no established interventions for oncology and supportive care teams to address cognitive dysfunction and its impact on patient and family QOL. This study targets this gap in knowledge and clinical practice through development and piloting of a novel cognitive support program (CSP) for brain metastasis patients and their primary caregivers. Methods: Building on relevant neuroscience and behavioral research in other cognitively-impaired populations, we designed the CSP as a brief, structured, client-centered program. Using a prospective longitudinal design, 24 cognitively-impaired patients are being recruited from an outpatient multidisciplinary brain metastasis clinic. Each patient, together with their primary caregiver, attends 3 weekly individual sessions to learn strategies for memory, communication and executive functions. At-home practice between sessions applies the strategies in daily activities. Feasibility will be assessed through retention and adherence. Preliminary efficacy will be assessed by reliable change on cognitive, functional and QOL measures completed by patients pre-, post-, and 3 months following the CSP intervention. Caregivers will complete ratings of patient functioning and their own QOL at the same intervals. Analyses of variance will examine CSP intervention effects, with regression analyses to explore moderating effects of participant demographics, baseline levels of cognitive impairment, disease and treatment factors (e.g., volume and location of brain lesions, CNS-directed treatments received). Results of this pilot trial will lay the groundwork for a future randomized trial and further development of cognitive supports for brain metastasis patients and their families.
Characterization of Factors Determining the Kinetics of Disease Relapse after Allogeneic Stem Cell Transplantation (allo-SCT) or Chemotherapeutic Consolidation for Acute Myeloid Leukaemia (AML) in First CR: A Survey from HOVON-SAKK and the Acute Leukaemia Working Party of the EBMT
Authors: Charles Craddock, Jurjen Versluis, Myriam Labopin, Gerard Socie, Anne Huyn, Eric Deconinck, Liisa Volin, Noel Milpied, Jean Henri Bourhis, Alessandro Rambaldi, Patrice Chevallier, Didier Blaise, Manz Markus, Edo Vellenga, Marie Christiane Vekemans, Johan Maertens, Jakob R. Passweg, Christoph Schmid, G J. Ossenkoppele, Paresh Vyas, Bob Löwenberg, Mohamad Mohty, Jan J. Cornelissen, Arnon Nagler
Journal: Blood (2016)
Prognostic Value of BCR-ABL1 Transcript Type in Chronic Myeloid Leukemia Patients Treated Frontline with Nilotinib
Authors: Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Fabio Stagno, Mariella D'Adda, Luciano Levato, Angelo Michele Carella, Bruno Martino, Mario Tiribelli, Carmen Fava, Gianni Binotto, Paolo Avanzini, Monica Bocchia, Micaela Bergamaschi, Antonella Russo Rossi, Francesco Cavazzini, Elisabetta Abruzzese, Simona Soverini, Giuliana Alimena, Michele Cavo, Giovanni Martinelli, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Gianantonio Rosti
Journal: Blood (2016)
Interference of PG2 TATA BOX region with the serum PG2 level in gastric cancer
Authors: Renato Cannizzaro, Raffaella Magris, Mariangela De Zorzi, Stefania Maiero, Laura Caggiari, Mara Fornasarig, Ombretta Repetto, Valli De Re
Journal: Annals of Oncology (2017)
No Perfect Choice
Authors: Emily C. Dossett, Lavanya Wusirika, Vivien Burt
Journal: JAMA (2017)

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Predicted V/S Actual Mortality in Colorectal Cancer: A DGH Experience
Authors: N Kulkarni, A Amir, P Haray, A Joseph, A Masoud
Journal: Endoscopy (2006)

Aims: To compare the 30 day operative mortality figures for colorectal surgery from a DGH catering to a poor socio economic population (20% most deprived in Wales according to the Welsh Index of multiple deprivation figures published by the Welsh assembly in 2005) with the predicted mortality from the ACPGBI online risk prediction models.