tbuckley/cabot-search huggingface dataset:
Abstract P4-03-16: FAPα (fibroblast activation protein-α) analysis in breast tumor cells and stroma after neoadjuvant treatment
Authors: I Calvo, M Prieto, A Suárez-Gauthier, FJ Pérez, E Hernández, D Acosta, JM Cárdenas, F López-Ríos, LG Estévez
Journal: Cancer Research (2017)

Abstract Background: FAPα is a transmembrane serine protease expressed on cancer associated fibroblast that promotes tumour growth and invasion. In patients (pts) with poor outcome and survival FAPα is highly overexpressed. FAPα is also expressed in stroma across all breast cancer subtypes without association with clinicopathological factors. Pts without Complete Pathological Response (pCR) after Neoadjuvant Chemotherapy (NC) had poor outcome. We analysed the relationship between the expression of FAPα in stroma (fibroblast) and in epithelial breast cancer cells of pts without pCR after NC (taxanes, antracyclines and trastuzumab in Her2+). Methods: 60 pts were included. ER, PR and Ki67 were studied by IHQ (Ventana) and Her2 by FISH (PatnVysion). FAPα expression was determined by IHQ (polyclonal, Ventana). St Gallen guidelines for subtype of breast cancer were used. Results: 53 pts had tissue. Median age 47 years (range 29-68). Median tumour size 43mm and 10 (18.9%) were multifocal. 37 (69.8%) had positive axillary nodes. 47 were ductal invasive carcinomas. 33 (62.3%) were grade 2 and 20 (37.7%) grade 3. 44 pts (83%) had ER+ (20 luminal B), 17 (32%) Her2+ and 6 (11%) triple negative(TN). Median Ki67 was 22% (p25-75:15-38%). Miller-Payne response was 1.9% G1 (1pt), 43.4% G2 (23 pts), 41.5% G3 (22 pts) and 13.2% G4 (7 pts). The recurrences were 2 local and 12 distant (26.4%). Median FAPα in residual epithelial breast cancer cells after NC was 85% (p25-75:30-95%) and in the stroma 20% (p25-75:10-62%). Median epithelial FAPα was 55% in TN, 85% Her2, 72.5% luminal A and 92.5% in luminal B. Median stromal FAPα was 52.5% in TN, 20% Her2, 15% luminal A and 15% in luminal B. There is not association between stromal FAPα and clinicopathological features, but a higher epithelial FAPα was found in tumours wih higher ER, PR and Ki67. In luminal B subtype, stromal FAPα was smaller in pts with relapses (median 7.5%) than without relapses (median 30%). Conclusions: Stromal FAPα in residual cancer after NC is higher in TN breast cancer but without association with relapses in our small sample. However, in luminal B subtype stromal FAPα is smaller in pts with relapses. Citation Format: Calvo I, Prieto M, Suárez-Gauthier A, Pérez FJ, Hernández E, Acosta D, Cárdenas JM, López-Ríos F, Estévez LG. FAPα (fibroblast activation protein-α) analysis in breast tumor cells and stroma after neoadjuvant treatment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-16.
Weakened Connectivity in Fetal Brains Prior to Preterm Birth
Authors: Tracy Hampton
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Quantifying US Residency Competitiveness in Different Fields
Authors: Alain Nathan Sahin
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Circulating Cytokines and Markers of Iron Metabolism in Myelofibrosis Patients Treated with Momelotininb: Correlatives from the Ym-387-II Study
Authors: Vikas Gupta, Ruben A. Mesa, Michael W Deininger, Candido E. Rivera, Shireen Sirhan, Srdan Verstovsek, Yafeng Zhang, Yuanyuan Xiao, Helen Collins, Kevin Kwei, Adarsh Joshi, Carrie Baker Brachmann
Journal: Blood (2015)
Abstract 17846: Prognosis of High Sinus Heart Rate After Catheter Ablation for Atrial Fibrillation
Authors: Hee Tae Yu, Tae-Hoon Kim, Jae-Sun Uhm, Jong-Youn Kim, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Circulation (2015)

Introduction: Although radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) increases a sinus heart rate (HR) after rhythm control, its mechanism and prognosis have not yet been clearly elucidated. Hypothesis: We hypothesized that post-procedural high sinus HR is associated with better clinical outcome of AF ablation without hemodynamic adverse effects. Methods: We included 991 AF patients (75% male, 58 ± 11 years old, 70% paroxysmal AF [PAF]) who had analyzable HR variability (HRV) at 3-months and 1-year after RFCA, and pre- and post-1-year echocardiogram. Average HR measured by 24-hour Holter greater than 2SD (≥92bpm) was defined as post-ablation high sinus HR. Results: 1. Average heart rate was increased significantly (68.8±13.1 to 71.4±10.7bpm, p&lt;0.001), and high sinus HR (≥92bpm) was observed in 28 patients (2.8%) at 3-months after AF ablation. All of them tolerated well, 21% (6/28) were taking low dose β-blocker, and 36% (10/28) kept average HR≥92bpm at 1-year after RFCA. 2. High sinus HR was independently associated with pre-procedural high average HR (OR 1.097; 95% CI 1.029 to 1.169, p=0.005), high left atrial (LA) voltage (OR 3.545; 95% CI 1.183 to 10.618, p=0.024), and reduced rMSSD at 3-months HRV (OR 0.959; 95% CI 0.919 to 0.999, p=0.047). 3. At 1-year follow-up echocardiogram, LA reverse remodeling (ΔLA; -1.1±3.7 vs. -3.0±4.6mm, p=0.055) and the improvement of ejection fraction (ΔEF; 0.7±8.4 vs. 1.7±7.7%, p=0.529) were not significantly different between the patients with high sinus HR and those without. 4. During 27±17 months of follow-up, the patients with high sinus HR at 3-months after RFCA showed significantly lower clinical recurrence than those without (log rank, p=0.020). Conclusions: High sinus HR 3-months after AF ablation is observed in patients with less remodeled LA with significant post-procedure vagal modulation. High sinus HR after AF ablation did not show hemodynamic adverse effect and was associated with lower clinical recurrence rate of AF after RFCA.
The Effect of the CXCR4 Inhibitors, AMD3100 and AMD3465, in Multiple Myeloma Cell Homing and Its Interaction with the Bone Marrow Microenvironment.
Authors: Judith M. Runnels, Abdel Kareem Azab, Costas Pitsillides, Jonathan Farag, Juwell Wu, Aldo M. Roccaro, Patricia Maiso, Charles P. Lin, Irene M. Ghobrial
Journal: Blood (2009)
Human regulatory B cells in health and disease: therapeutic potential
Authors: Claudia Mauri, Madhvi Menon
Journal: Journal of Clinical Investigation (2017)

Regulatory B cells (Bregs) modulate immune responses predominantly, although not exclusively, via the release of IL-10. The importance of human Bregs in the maintenance of immune homeostasis comes from a variety of immune-related pathologies, such as autoimmune diseases, cancers, and chronic infections that are often associated with abnormalities in Breg numbers or function. A continuous effort toward understanding Breg biology in healthy individuals will provide new opportunities to develop Breg immunotherapy that could prove beneficial in treating various immune-mediated pathologies. In this Review, we discuss findings regarding human Bregs, including their mechanisms of suppression and role in different disease settings. We also propose several therapeutic strategies targeting Bregs for better management of immune disorders.
Leukemia Risk Models in Primary Myelofibrosis: An International Working Group Study,
Authors: Ayalew Tefferi, Animesh Pardanani, Naseema Gangat, Kebede Begna, Curtis A. Hanson, Daniel L. Van Dyke, Domenica Caramazza, Alessandro M. Vannucchi, Enrica Morra, Mario Cazzola, Arturo Pereira, Francisco Cervantes, Francesco Passamonti
Journal: Blood (2011)
Ex vivo Akt inhibition promotes the generation of potent CD19CAR T cells for adoptive immunotherapy
Authors: Ryan Urak, Miriam Walter, Laura Lim, ChingLam W. Wong, Lihua E. Budde, Sandra Thomas, Stephen J. Forman, Xiuli Wang
Journal: Journal for ImmunoTherapy of Cancer (2017)

Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation. We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model.Various T cell subsets including CD8+ T cells, bulk T cells, central memory T cells and naïve/memory T cells were isolated from PBMC of healthy donors, activated with CD3/CD28 beads, and transduced with a lentiviral vector encoding a second-generation CD19CAR containing a CD28 co-stimulatory domain. The transduced CD19CAR T cells were expanded in the presence of IL-2 (50U/mL) and Akt inhibitor (Akti) (1 μM) that were supplemented every other day. Proliferative/expansion potential, phenotypical characteristics and functionality of the propagated CD19CAR T cells were analyzed in vitro and in vivo after 17-21 day ex vivo expansion. Anti-tumor activity was evaluated after adoptive transfer of the CD19CAR T cells into CD19+ tumor-bearing immunodeficient mice. Tumor signals were monitored with biophotonic imaging, and survival rates were analyzed by the end of the experiments.We found that Akt inhibition did not compromise CD19CAR T cell proliferation and expansion in vitro, independent of the T cell subsets, as comparable CD19CAR T cell expansion was observed after culturing in the presence or absence of Akt inhibitor. Functionally, Akt inhibition did not dampen cell-mediated effector function, while Th1 cytokine production increased. With respect to phenotype, Akti-treated CD19CAR T cells expressed higher levels of CD62L and CD28 as compared to untreated CD19CAR T cells. Once adoptively transferred into CD19+ tumor-bearing mice, Akti treated CD19CAR T cells exhibited more antitumor activity than did untreated CD19CAR T cells.Inhibition of Akt signaling during ex vivo priming and expansion gives rise to CD19CAR T cell populations that display comparatively higher antitumor activity.
Comparison of the Effects on Reversal of Multi-Drug Resistance of 5-Bromotetrandrine and Tetrandrine in K562/A02 Cell Line in Vivo and in Vitro
Authors: Bao-An Chen, Jue-qiong Wang, Jian Cheng, Feng Gao, Wen-lin Xu, Hui-lin Shen, Jia-hua Ding, Chong Gao, Yun-Yu Sun, Jun Wang, Gang Zhao, Hui-hui Song, Wen Bao, Xin-chen Sun, Hong-yan Cheng, Yu-xia Deng, Guo-hong Li, Li-jie Liu, Wen-ji Chen, Ning-na Chen, Xue-mei Wang
Journal: Blood (2008)
Adequate Immune Reconstitution in Recipients of Unrelated Donor Hematopoietic Cell Transplants Given Rabbit Anti-Thymocyte Globulin During Conditioning.
Authors: Devon Fletcher, John M. McCarty, Harold M Chung, Kathryn Candler, Catherine H Roberts, Lisa Shickle, Miriam Rabie, John Lamberta, Richard Edwards, Amir Toor
Journal: Blood (2009)
Abstract A36: Study of stromal mechanoregulation of tumor metabolism and growth dynamics
Authors: Michael Anderson, Jonathan Celli, Hamid El-Hamidi
Journal: Cancer Research (2017)

Abstract As tumors develop and mature they are subjugated to compressive forces and a rigid stroma. This is particularly true in pancreatic cancer where its defining feature is a particularly rigid and fibrous stroma. The mechanical properties of the stroma can have a large influence on the growth behavior and invasiveness of tumors. An intriguing recent example of this is that the PI3K pathway is activated via integrin engagement on a rigid stroma and can affect some metabolic pathways. What makes this exciting is that both the stromal stiffness and reprogrammed metabolism have long been known to be features of cancer and this showed that these features may be intertwined in a feedback loop. From another angle, tumors are subjugated to high compressive forces and many have shown that this force can alter spheroid growth dynamics and shift cells to a more invasive phenotype. While compressive stress on spheroid growth certainly influences its growth dynamics, it is unclear whether it is due to stress or strain on the spheroid. Additionally, it implicates compressive force in altering the cellular metabolism as well. Going a step further, extracellular acidity is a well-known phenotype of solid tumors and is intrinsically linked to an altered metabolism. To study this feedback loop between stromal mechanical properties and metabolism/acidity we will utilize two different models alongside the pH dependent fluorophore, SNARF. The first is a hybrid gel model that is constructed of a base polyacrylamide (PA) layer that is covalently bound to select ECM proteins such as matrix gel and collagen. The second is a spheroid embedded in agarose model in which a base coat of agarose is applied to the bottom of each well in a multiwall plate and after setting, an ungelled mixture of spheroids, agarose and fluorescently labelled latex beads are poured over the base coat and allowed to set. The agarose is bio inert and cannot be broken down by cells. Thus it effectively acts like a compressible, non-integrin activating, isotropic media that completely surrounds the embedded spheroid. To study the cell packing density we will explore a model that predicts strain on an embedded spheroid due to compressive stress drives the cell density in spheroids. To experimentally explore this model, we will use the spheroid embedded in agarose model and vary starting implanted spheroid sizes, but remove them from the agarose at identical stress levels. All of this together will lead us to a better understanding of how the cell metabolism/pHe and tumor cell packing are mechanoregulated by the stroma. Citation Format: Michael Anderson, Jonathan Celli, Hamid El-Hamidi. Study of stromal mechanoregulation of tumor metabolism and growth dynamics. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A36.
First-in-human study of LY3039478, a Notch signaling inhibitor in advanced or metastatic cancer.
Authors: Christophe Massard, Analia Azaro, Christophe Le Tourneau, Jean-Charles Soria, Marie Alt, Claire Smith, Ute Ohnmacht, Gerard Oakeley, Bharvin Patel, Eunice Yuen, Karim A. Benhadji, Jordi Rodon Ahnert
Journal: Journal of Clinical Oncology (2015)

2533 Background: LY3039478 (LY) is an orally bioavailable, potent, and highly selective Notch inhibitor (Notch 1-4). We report on safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of LY. Methods: Eligible pts (ECOG ≤ 1) had relapsed solid tumors, adequate hematologic, renal, and hepatic functions. Using a predictive pre-clinical PK/PD model and non-clinical toxicology data, a dose range of 2.5-100 mg was selected. LY was given three times a week (TIW) on a 28-day cycle until disease progression. Dose escalation used 3+3 design with probability toxicity band modelling. Safety assessments were based on CTCAE V4.0. Primary objective: to define the recommended phase 2 dose of LY; additional objectives: PK, PD (Aβ in plasma and a panel of 46 genes expressed in skin), and preliminary antitumor activity. Results: 55 pts were treated. The most common related toxicities ( ≥ 10% of pts) included diarrhea (42%); vomiting (40%); nausea (36%); asthenia (33%); decreased appetite (25%); hypophosphatemia (18%); mucosal inflammation (16%); weight decreased (15%); hair color changes and dry skin (13% each); dry mouth (11%). 5 dose-limiting toxicities were observed in cycle 1: thrombocytopenia grade 4 in 3 pts (20mg, 30mg, and 60mg), nausea and asthenia grade 3 in one patient (100mg) and colitis grade 3 (100mg). Other observed grade 3/4 toxicities related to LY in > 1 patient included hypophosphatemia (5 pts) and vomiting (2 pts). Maximum tolerable dose (MTD) was defined as 75 mg TIW. AUC and Cmax appeared to increase in a dose proportional manner. There was no accumulation with multiple dosing with an elimination half-life of approximately 6-8h. Dose dependent inhibition of plasma Aβ and target genes (in skin) was observed. At the recommended dose of 75mg TIW, preliminary data indicate approximately 80% inhibition of Aβ, > 50% inhibition of HES1, NRARP, and CCND1. Additional inhibited genes included HES2, HES4, HES5, HEYL and MYC. 6 pts received ≥ 6 cycles (range 6-18). Best observed response is PR in a patient with ER+/PR+ HER2-breast cancer. Conclusions: The recommended dose for LY monotherapy is 75 mg TIW with manageable toxicities and significant target inhibition. Further exploration of LY monotherapy is ongoing. Clinical trial information: NCT01695005.
Pre-Infusion Characteristics of the Predominant Cord Blood Unit Correlate with Hematopoietic Engraftment in the Setting of Non-Myeloablative Double Cord Blood Transplant (DCBT).
Authors: Richard L. Haspel, Grace S. Kao, Beow Yeap, Thomas R. Spitzer, Jerome Ritz, Joseph H. Antin, Karen Ballen
Journal: Blood (2005)
Abstract A25: Systems biology approach to delineating DNA damage response and R-loop dependencies in Ewing sarcoma
Authors: Aparna Gorthi, Eva Loranc, Cao Lin, Alexander JR Bishop
Journal: Cancer Research (2017)

Abstract Ewing sarcoma is a rare, yet highly aggressive family of bone and soft tissue tumors that afflicts children and young adults. It is the prototypical example of mesenchymal tumors driven by a fusion oncogene involving the EWSR1 gene, most frequently EWS-FLI1. Ewing sarcoma is exquisitely sensitive to genotoxic agents, and more recently PARP1 inhibitors, predominantly when detected at an early stage. However, the molecular basis for this sensitivity is relatively under-explored. Further, the long term side effects of these drugs pose a critical barrier to effective treatment. In this study, we proposed to delineate the pathways dictating Ewing sarcoma chemosensitivity and identify alternative avenues for targeted therapy. R-loops are three nucleic acid DNA structures consisting of an RNA:DNA hybrid and a displaced complementary DNA loop. The importance of R-loops in both being causative as well as disruptive in DNA damage as well as DNA damage response has emerged through recent studies. Our previous work has demonstrated that Ewing sarcoma cell lines have high levels of endogenous damage as well as replication stress. We observe that Ewing cell lines have elevated levels of persistent R-loops and impaired homologous recombination repair of double strand breaks. In the present study, we use a multimodal, systems biology approach involving high-throughput RNAi based survival data, time-course RNA-seq in response to two chemotherapeutics, Chromatin immunoprecipitation-seq and DNA:RNA hybrid immunoprecipitation-seq datasets across multiple Ewing sarcoma and control cell lines. Our data led to the identification of a subset of genes whose expression patterns in response to DNA damage is dysregulated in Ewing sarcoma. Predominantly, among these genes is a network of RNA binding proteins that highlights the importance of RNA metabolism in DNA damage response. We also observe a concomitant alteration in damage-dependent transcription. Finally, we identified several compensatory mechanisms that are upregulated in Ewing sarcoma (RNASEH2, FEN1, Fanconi Anemia, etc.) in order to manage the exacerbated genomic stress conditions and targeting any of these pathways leads to severe tumor cell cytotoxicity. We therefore propose the use of these pathways as potential candidates for targeted therapy. Citation Format: Aparna Gorthi, Eva Loranc, Cao Lin, Alexander JR Bishop. Systems biology approach to delineating DNA damage response and R-loop dependencies in Ewing sarcoma. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A25.
Good Safety and Tolerance Profiles of Long Term Treatment of Advanced Multiple Myeloma (MM) with Bortezomib.
Authors: Jean El-Cheikh, Anne-Marie Stoppa, Reda Bouabdallah, Diane Coso, Jean-Marc Schiano de Collela, Therese Aurran, Jean-Albert Gastaut, Didier Blaise, Mohamad Mohty
Journal: Blood (2007)
A postpartum eruption
Authors: Nadia Shad, Masud Haq, Dennis J Barnes
Journal: BMJ (2017)

A 40 year old woman (gravida 2, para 2) presented to the emergency department nine days postpartum with a four day history of progressive pruritic rash. The rash had initially appeared peripherally on the limbs and later progressed to involve the trunk, abdomen, and back. The palms of the hands and soles of the feet were spared, and there was no mucosal involvement. She had no medical history and was not taking any medication. A previous HIV test and herpes simplex virus titres had been negative. She had presented following a spontaneous delivery after an uneventful pregnancy. On examination, she had numerous tense fluid filled blisters affecting her hands, feet (fig 1), and flexor and extensor aspects of all limbs. Diffuse erythematous pruritic plaques were also present over her torso. Some blisters had burst due to positional pressure, however, Nikolsky’s sign was negative. Fig 1 Tense bullae with surrounding erythema over flexural aspect of the lower limbs (coated in calamine lotion due to severe pruritus)