tbuckley/cabot-search huggingface dataset:
A pilot study of tumor-derived exosomes as diagnostic and prognostic markers in breast cancer patients receiving neoadjuvant chemotherapy.
Authors: R. E. Raab, T. L. Pawlowski, D. Spetzler, M. R. Klass, C. D. Kuslich, L. S. Bellin, J. H. Wong, A. S. Asch
Journal: Journal of Clinical Oncology (2011)

TPS248 Background: Neoadjuvant chemotherapy (NAC) is a common approach to the treatment of women with locally advanced and inflammatory breast cancers. It is becoming utilized in women with palpable and operable tumors >/= 2cm. The rate of response to NAC varies widely and ranges from 2-80%. It may be useful to have markers to determine which patients are most likely to respond to this approach. Tumor derived exosome analysis may be a novel prognostic biosignature in breast cancer. Tumor derived exosomes are membrane-bound endosome-derived vesicles between 50-100 nm which bear protein signatures related to their cell of origin and contain mRNAs and microRNAs. Most cell types including tumor cells secrete them. Exosomes play a role in cell-cell communication and affect target cells by stimulating them directly or by transferring molecules between cells. They have shown promise in early diagnosis in ovarian, colon, prostate and lung cancer but little is known about their role in breast cancer. Methods: Women with palpable and operable breast cancers >/= 2 cm are eligible for this pilot study. The accrual goal is 100 patients. The primary objective is characterization of protein surface markers and RNA profiles of tumor derived exosomes. The secondary objective is correlation of circulating exosome expression with clinical and pathologic response to NAC. Prior to initiation of chemotherapy, patients will undergo collection of 10 ml of whole blood in an EDTA tube for exosome analysis. Exosomes will be extracted from frozen patient plasma. After extraction, half of the extracted sample will be run on the discovery multiplex panel consisting of 45 antibodies. The remaining sample will be used for RNA analysis. Blood collection for exosome analysis will be performed monthly during chemotherapy and following definitive surgery. Subgroup analysis based on tumor size, lymph node status before and after surgery, estrogen, progesterone and HER 2 status are planned.
First Code
Authors: Christos Theophanous
Journal: Annals of Internal Medicine (2015)

On Being a Doctor4 August 2015First CodeChristos Theophanous, BAChristos Theophanous, BAFrom Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-0195 Audio Reading - “First Code” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "First Code," by C. Theophanous. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Every medical student has spent sleepless nights worrying about the “firsts”—the first anatomy dissection, the first delivery, the first lost patient. How will those moments feel? How prepared will I be?I was midsentence in my report on morning labs to my senior resident when a monotonous voice came over the loudspeaker. “Code blue, room 8A-142. Medicine gold D.” It hardly registered with me, like a department store announcement that only staff ever heeded. The fifth day of my internal medicine rotation, I definitely did not feel like staff. But my senior resident froze, eyes widening. “That's—that's us, right? Mr. ... Author, Article, and Disclosure InformationAffiliations: From Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, California.Corresponding Author: Christos Theophanous, BA, 4275 Via Arbolada #201, Los Angeles, CA 90042; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “First Code” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "First Code," by C. Theophanous. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byHealth Care Competition Law in the Shadow of State Action: Minimizing MACsSudden Cardiac Arrest: A Call to Action From the Institute of MedicineThomas Rea, MD, MPH and Mickey Eisenberg, MD, PhDPivoting Accountability in the Criminal Justice System 4 August 2015Volume 163, Issue 3Page: 238-239KeywordsBreathingHeartRibsShockShouldersSpineStable coronary artery diseaseSternumThoraxWalking ePublished: 4 August 2015 Issue Published: 4 August 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Early changes in CSF sTREM2 in dominantly inherited Alzheimer’s disease occur after amyloid deposition and neuronal injury
Authors: Marc Suárez-Calvet, Miguel Ángel Araque Caballero, Gernot Kleinberger, Randall J. Bateman, Anne M. Fagan, John C. Morris, Johannes Levin, Adrian Danek, Michael Ewers, Christian Haass
Journal: Science Translational Medicine (2016)

Emerging evidence supports a role for innate immunity and microglia in Alzheimer's disease (AD) pathophysiology. However, no marker related to microglia has been included in the temporal evolution models of AD. TREM2 is a transmembrane protein involved in innate immunity and is selectively expressed by microglia and genetically linked to AD and other neurodegenerative disorders. Its ectodomain is released by proteolysis as a soluble variant (sTREM2) and can be detected in the cerebrospinal fluid (CSF). In patients with autosomal dominant AD, we tested how many years before the expected symptom onset did CSF sTREM2 increase in mutation carriers (MCs) compared to noncarriers (NCs). We also determined the temporal sequence of changes in CSF sTREM2 and markers for amyloid deposition and neurodegeneration as well as cognitive performance. We included 218 participants consisting of 127 MC and 91 NC siblings from the Dominantly Inherited Alzheimer Network. We observed that CSF sTREM2 increased in MCs compared to NCs 5 years before the expected symptom onset and this difference remained significant until 5 years after the expected symptom onset. Changes in CSF sTREM2 occurred after alterations were observed in markers for brain amyloidosis and neuronal injury. We propose that microglial activation occurs several years before the expected symptom onset, but after amyloidosis and neuronal injury have already occurred.
532. Stable Transcriptional Repression, Gene Excision, and Parastism of HIV by Conditionally Replicating Lentiviral Vectors
Authors: Uriel A. Lopez-Lemus, Amanda Ackley, Sheena Saayman, Heather Embree, Boro Dropulic, Ramesh Akkina, Paige Charlins, Marc S. Weinberg, Kevin V. Morris
Journal: Molecular Therapy (2016)

Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV, as they have the potential for sustained viral inhibition via reduced treatment interventions. One innovative approach developed here involves using conditionally replicating vectors (CR-Vectors), as these vectors utilize HIV-expressed proteins to replicate. These vector payloads can spread along with HIV into the budding viral particles, and co-infect target cells, essentially disseminating to HIV infected cells. We have generated and characterized CR-Vectors carrying therapeutic payloads consisting of various non-coding RNA regulatory expression cassettes, which modulate HIV both transcriptionally and post-transcriptionally, as well as CRISPR directed excision machinery. Notably, we have followed both virus and vector expression in T-cells and in vivo in the presence and absence of mycophenolic acid (MPA) selection. We find here that CR-Vectors functionally suppress HIV expression in a long-term stable and potent manner in both the presence and absence of MPA; and that transcriptional targeting is more potent at modulating stable suppression of HIV than post-transcriptional targeting or CRISPR directed excision of HIV. This suppression may be physiologically relevant, as it appears to drive HIV to a sustained non-pathogenic set point. Our findings suggest that CR-Vectors with modulatory non-coding RNAs may be a viable approach to achieving long-term stable suppression of HIV leading ultimately to a functional cure.
PTH-012 Five-year review of patients presenting with iron deficiency anaemia
Authors: S Pengelly, M Fabricius, D McMenamin, E Wu, M Metzner, S Lewis, K B Hosie
Journal: Gut (2010)

<h3>Introduction</h3> Between 2000 and 2002, 639 consecutive patients referred to the Iron Deficiency Anaemia (IDA) pathway were prospectively collated on a database. We present the 5-year review of outcomes. <h3>Methods</h3> 639 patients presenting to the IDA pathway were prospectively entered onto a database. Initial assessment included haematological review, coeliac screen, OGD and colonic imaging. A 5-year review of outcomes was undertaken using patient medical records and hospital laboratory databases. <h3>Results</h3> A cause for the IDA had been found initially in 267 (42%) of these patients, with 126 (20%) having a GI luminal tumour; 55 (9%) of these were malignant. 93 (15%) had benign UGI bleeding and 23 (4%) had coeliac disease. Complete medical records were available for 595 (93%) of patients. Of the 373 patients in whom a cause was not initially found, over 5 years 6 (1%) of these were ultimately diagnosed with a GI luminal malignancy and 18 (5%) with a non-luminal or non-GI malignancy. 14 patients (4%) had chronic renal disease, often involving haematuria. 12 (3%) of the anaemias were attributed to gynaecological bleeding. 260 patients never had a cause found and 84% of these had documented resolution of their IDA over a median period of 4 months (range 0–60). <h3>Conclusion</h3> Investigation of patients with unexplained IDA consumes a lot of health resources with large numbers of patients never getting a formal diagnosis. This is an effective pathway with a very high yield of tumours: 161 (25%), of which 131 were luminal GI tumours and 30 were non-luminal or non-GI tumours. Where a cause was not found initially, urological and gynaecological problems occurred frequently. In those patients where a cause was never found, either the patient was never anaemic or the anaemia resolved spontaneously.
Mutations of TET2, IDH1, IDH2 and ASXL1 In Chronic Myeloid Leukemia.
Authors: Catherine Roche-Lestienne, Marceau Alice, Elise Labis, Olivier Nibourel, Valérie Coiteux, Joelle Guilhot, Laurence Legros, Franck Nicolini, Philippe Rousselot, Martine Gardembas, Nathalie Helevaut, Cécile Frimat, Francois Guilhot, Claude Preudhomme
Journal: Blood (2010)
Mechanisms Underlying the Synergistic Interaction of Filanesib with Pomalidomide and Dexamethasone (FPD) in Multiple Myeloma
Authors: Susana Hernández-García, Laura San-Segundo, Lorena González-Méndez, Montserrat Martín-Sánchez, Luis A Corchete, Teresa Paíno, Ana Alicia López-Iglesias, Esperanza Macarena Algarín, Mercedes Garayoa, Brian Tunquist, Norma C Gutierrez, Maria-Victoria Mateos, Enrique M Ocio
Journal: Blood (2015)
PTU-067 Hepatic steatosis in patients with autoimmune hepatitis—prevalence, progression and possible significance
Authors: C Salmon, B Hoeroldt, A Dube, E McFarlane, D Gleeson
Journal: Gut (2010)

<h3>Introduction</h3> A link between steatosis and Prednisolone therapy has been suggested, but is poorly documented. In chronic hepatitis C, steatosis has been linked with fibrosis progression. The prevalence and significance of steatosis in autoimmune hepatitis (AIH) are unclear. <h3>Methods</h3> To assess the prevalence, progression and possible significance of steatosis in AIH. We studied 99 patients with AIH, 17 men, median age 48 (9–85) years, 31 probable, 68 definite by IAIHG criteria. We assessed steatosis (grade 1–3 and distribution), Ishak necro-inflammatory (NI) score and Ishak fibrosis score in paired liver biopsies: the initial diagnostic biopsy and a follow-up biopsy when in remission after median 25 (3–115) months Prednisolone. <h3>Results</h3> 24 of the 99 patients had steatosis on the diagnostic biopsy (16 grade 1, 8 grade 2): 8 zone 1, 6 zone 2 and 12 zone 3. Patients with steatosis had lower NI scores than those without, (median 8 vs 13: p=0.003) but a similar prevalence of plasma cells (54.2% vs 64%) and rosettes (62.5% vs 60%). They were older (median 59 vs 45 years, p=0.001) and had a higher prevalence of diabetes (42% vs 12%, p=0.012) than those without steatosis but had similar body weight and BMI values. On follow-up biopsy, 46 of the 99 patients had steatosis, which had appeared or worsened in 31 patients. In six patients steatosis disappeared and 26 patients had developed new steatosis (7 zone 1, 6 zone 2, 24 zone 3). Steatosis grade worsened between diagnostic and follow-up biopsy (p&lt;0.001). Worsening of steatosis was not related to gender, age, diabetes, or body weight or to duration, initial dose or maintenance dose of Prednisolone. Patients with worsening steatosis, compared to those with stable or improved steatosis, had similar falls in median NI score (12 to 3 and 13 to 3: p&lt;0.001) between diagnostic and follow-up biopsy. However, they achieved no improvement in median fibrosis stage (3 to 3: NS), whereas in patients with stable or improving steatosis, median fibrosis score fell from 3 to 2 (p=0.004). In regression analysis worsening of steatosis was significantly associated with severity of fibrosis on follow-up biopsy: p=0.039. <h3>Conclusion</h3> Steatosis is found in 1/4 of patients with AIH and is related to age and diabetes. Steatosis worsens in 1/3 of patients treated with Prednisolone, although an association with dose or duration of Prednisolone was not observed. Patients with worsening steatosis, despite reduction in inflammation, fail to achieve improvement in fibrosis, suggesting that steatosis progression might compromise long-term outcome in AIH.
Bortezomib and vorinostat as antitumor therapy for epithelial ovarian cancer.
Authors: T. Sueblinvong, Y. Iizuka, R. Ghebre, A. Skubitz, P. L. Judson, M. Bazzaro
Journal: Journal of Clinical Oncology (2011)

e15542 Background: Treatment of women with advanced-stage epithelial ovarian cancer (EOC) has limited efficacy. Aberrant expression of ubiquitin-mediated protein degradation pathways occurs in ovarian cancer, thus we sought of determining the potential therapeutic efficacy of proteasome and HDACs inhibitors (Bortezomib and Vorinostat) as combinatorial approach for ovarian cancer treatment. Methods: The synergistic effect of bortezomib and vorinostat was evaluated by XTT assay and expressed as combination index (CI). Primary ovarian cancer cells were obtained by mechanically dissociating solid ovarian cancer specimens into single-cell suspensions and the epithelial nature of the derived cell population was confirmed with Ber-EP4 and MOC-31 markers. Activation of caspase-3 was determined by measuring the levels of PARP cleavage. Results: Isobologram analysis of EOC cell lines and primary EOC cells exposed to combinatorial treatment with bortezomib and Vorinostat revealed a strong synergistic effect with CI as low as 0.43 and no reduction in cell viability in immortalized ovarian surface cells or in normal surface epithelium. Reduction in the cell viability observed in cancer cells following exposure to bortezomib and vorinostat was consistent with onset of apoptosis as determined by morphological analysis and measurements of PARP cleavage levels. Importantly, primary EOC cells derived from borderline and recurrent ovarian carcinoma revealed highly sensitivity to bortezomib and vorinostat combination suggesting that this approach could be a new alternative treatment for recurrent EOC and borderline EOC with advance stage or invasive feature. Conclusions: This study provides the foundation for clinical testing of bortezomib and vorinostat combination as a therapy for ovarian cancer and may lead to an alternative therapeutic approach for patients affected by type of ovarian cancer that typically do not respond to conventional chemotherapy approach or who develop resistant tumor and relapse. Importantly, this combinatorial approach has potential to achieve significant anti-cancer activity using lower doses of the individual compounds, thus reducing “off-target” toxicity.
Intrathecal Liposomal Cytarabine (Depocyt) Is Safe and Effective for Prevention of Meningeal Disease in Patients with Acute Lymphoblastic Leukemia and High-Grade Lymphoma Treated with the HyperCVAD Regimen.
Authors: Brian McClune, Francis Buadi, Naveed Aslam, Donna Przepiorka
Journal: Blood (2005)
Abstract 2117: Epigenetic mechanisms control switching between metastatic and proliferative subtypes in the SW13 adrenal adenocarcinoma cell line
Authors: McKale R. Davis, Elizabeth E. Hull
Journal: Cancer Research (2015)

Abstract The human adrenal carcinoma SW13 cell line can switch between a subtype which expresses the tumor-suppressor gene Brahma (BRM), SW13+, and one that does not, SW13-. Unlike many tumor supressor genes, which are often mutated, loss of BRM expression occurs post-transcriptionally and BRM expression can be restored via histone deacetylase (HDAC) inhibition. However, many of the previously characterized BRM inducing HDAC inhibitors are toxic, broad-spectrum inhibitors which have limited downstream use, and provide little insight into the specificity of BRM epigenetic suppression. In this work we sought to further characterize the oncogenic potential of the two SW13 subtypes, and to investigate the potential epigenetic regulators that contribute to the subtype switching. SW13 subtype morphology and growth rates were assessed by immunofluorescence and standard growth assays. Metastatic potential was characterized by measuring anchorage-independent growth with soft agar assays, collagenase activity with fluorescein-conjugated gelatin, and invasiveness into a 3D extracellular matrix. Differences in gene expression were measured by standard qRT-PCR and pathway-specific qRT-PCR profiling arrays. The capacity of specific HDAC inhibitors for their ability to induce switching between the SW13 subtypes was assessed by immunofluorescence and gene expression analyses. BRM deficient SW13- cells have both a faster doubling time and an increased rate of anchorage-independent growth, while SW13+ cells exhibit higher collagenase activity and invasive capacity. Significant differences in the expression of multiple genes involved in epigenetic chromatin remodeling as well as epigenetic chromatin modification were observed, indicating that these two subtypes also have unique gene expression profiles that could contribute to BRM regulation. Of those tested, inhibition of HDAC1 most efficiently increased the rate of conversion between SW13- and SW13+ cells, and did so in a dose dependent manner. After conversion to SW13+ subtype there is also increased acetylation on histone H3 but not histone H4 when compared to levels in SW13-, suggesting that the role of acetylation on the H3 tail may play an essential role in the subtype switch. These studies provide new insight into the functional consequences of BRM loss in the SW13 cell type and reveal potential targets for the reversal of BRM epigenetic silencing. Citation Format: McKale R. Davis, Elizabeth E. Hull. Epigenetic mechanisms control switching between metastatic and proliferative subtypes in the SW13 adrenal adenocarcinoma cell line. [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 2117. doi:10.1158/1538-7445.AM2015-2117
TBCRC 011: Targeting the androgen receptor (AR) for the treatment of AR+/ER-/PR- metastatic breast cancer (MBC).
Authors: A. Gucalp, S. M. Tolaney, S. J. Isakoff, J. N. Ingle, M. C. Liu, L. A. Carey, K. L. Blackwell, H. S. Rugo, L. Nabell, A. Abbruzzi, J. Gonzalez, D. D. Giri, S. Patil, K. Feigin, G. D'Andrea, M. Theodoulou, P. Drullinsky, N. T. Sklarin, C. Hudis, T. A. Traina
Journal: Journal of Clinical Oncology (2011)

TPS122 Background: Patients with ER-/PR- MBC do not benefit from endocrine therapy. Doane et al. described a subgroup of ER-/PR- breast cancers with a gene expression profile similar to ER+ tumors but characterized by AR expression (Oncogene 2006). Farmer et al. identified an AR+ER-, non-basal-like group of breast tumors in a separate data set and termed them molecular apocrine breast cancer (Oncogene 2005). In vitro studies with the MDA-MB-453 cell-line, which is representative of this subtype, demonstrated AR-dependent growth and supported AR inhibition as a potential therapeutic approach for these patients (Doane et al., Oncogene 2006). We are testing the efficacy of the AR antagonist, bicalutamide (B) for patients with AR+/ER-/PR- MBC in a multicenter Phase II trial. Clinical trial registry #: NCT00468715. Methods: Patients with ER-/PR- (immunohistochemistry (IHC) <10%) MBC consent to AR testing, confirmed centrally at MSKCC. Patients may undergo AR testing while receiving non-protocol therapy and later begin bicalutamide at disease progression if otherwise eligible. If AR+ (IHC ≥ 10%), patients are eligible for treatment with bicalutamide if they have: ECOG performance status (PS) < 2, adequate renal, hepatic and bone marrow function, measurable/non-measurable disease. Any number of prior regimens is permitted. Treatment consists of bicalutamide 150 mg orally daily (cycle length = 28 days). Patients are evaluated for toxicity every 4 weeks and for response every 12 weeks. Primary endpoint: complete response (CR) + partial response (PR) + stable disease >6 months (SD). Secondary endpoints: PFS, toxicity, correlative studies to better characterize this subtype of breast cancer. Using a single-stage design, if ≥4 patients of 28 have CR, PR or SD, then bicalutamide will be considered worthy of further study for patients with AR+/ER-/PR- MBC. As of 12/30/10, 230 patients have consented for AR testing and 27 have AR+ disease. Sixteen of a planned 28 patients have started protocol therapy with bicalutamide. The other 11 patients pre-screened as AR+ will be offered bicalutamide when appropriate. Supported by TBCRC, Breast Cancer Alliance and AstraZeneca.