tbuckley/cabot-search huggingface dataset:
Updated risk stratification model for smoldering multiple myeloma (SMM) incorporating the revised IMWG diagnostic criteria.
Authors: Jesus San Miguel, Maria-Victoria Mateos, Veronica Gonzalez, Meletios A. Dimopoulos, Efstathios Kastritis, Roman Hajek, Carlos Fernández de Larrea Rodríguez, Gareth John Morgan, Giampaolo Merlini, Silvia Mangiacavalli, Hartmut Goldschmidt, Michele Cavo, Charalampia Kyriakou, Ming Qi, Jon Ukropec, Brendan M. Weiss, Chris Cameron, S. Vincent Rajkumar, Brian G. Durie, Shaji Kumar
Journal: Journal of Clinical Oncology (2019)

8000 Background: The diagnostic criteria for MM were revised in 2014, recategorizing ultra-high risk (i.e., 80% at two years) as active myeloma requiring therapy. The removal of patients at the highest risk of progression from the smoldering group requires reassessment of current risk stratification models. Methods: We designed a multicenter, retrospective study of SMM patients to develop a risk stratification model. Patients diagnosed with SMM on/after January 1, 2004 were included if they had no disease progression within 6 months, had baseline data from diagnosis (+/- 3 months), had a follow up of ≥1 year, and did not participate in a therapeutic trial of SMM. Various clinical and laboratory factors were explored to identify factors that predicted progression at 2 years. Univariate Cox regressions were run for each factor. For factors with p-values ≤ 0.25, optimal cut points were identified using Youden’s index. Binary factors were used in stepwise regression to fit multivariable Cox model and significant risk factors were determined (F-test). Results: Overall, 2004 patients were included (ages 26-93, 51% female). Factors independently associated with progression (optimal cutoffs) included: Serum M protein (2 g/dL), involved to uninvolved serum-free light chain ratio (20), and marrow plasma cell % (20%). Patients were stratified using the risk factors: Low- (0 factors), Intermediate- (1), and High-Risk (≥2). Previously used high risk markers such as Bence Jones proteinuria (≥500 mg/24 hours) and severe immunoparesis (50% decrease in uninvolved immunoglobulin levels) were both significant in univariate analysis, but were eliminated on step wise selection. Compared to the low risk group, intermediate- and high-risk groups had significantly higher rate of progression (Table). Within the high-risk group, having all 3 risk factors (n=61) versus 2 did not add to the model, with insufficient separation between 2 and 3 factors. Conclusions: We have developed a risk stratification model for SMM that incorporates revised cutoffs for previously used parameters (20/2/20) that can be universally applied. Additonal analysis are being conducted to develop models that utilize common cytogenetic abnormalities, as well as those without FLC given lack of availability of all tests across the world. [Table: see text]
Abstract 14932: Effects of Cardiac Resynchronization Therapy in Ischemic Cardiomyopathy Patients by Revascularization Procedures in MADIT-CRT
Authors: Mustafa Husaini, Yitschak Biton, Scott McNitt, Wojciech Zareba, Arthur J Moss, Ilan Goldenberg, Alon Barsheshet, Valentina Kutyifa
Journal: Circulation (2015)

Background: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed that patients with ischemic cardiomyopathy (ICM) had similar reductions in clinical events with implanted CRT-D vs. ICD-only when compared to patients with non-ischemic cardiomyopathy (NICM). Frequency of revascularizations may serve as a surrogate for severity of coronary artery disease in patients with ICM and severely reduced left ventricular ejection fraction. However, it is unknown whether the number of revascularizations plays a role in clinical outcomes in ICM patients implanted with CRT-D vs. ICD-only. Methods: Using a multivariable analysis of MADIT-CRT data, we evaluated the effect of CRT-D vs. ICD-only on combined heart failure (HF) or death and combined ventricular tachycardia (VT), ventricular fibrillation (VF) or death in ICM patients by the number of pre-enrollment revascularizations (1 or ≥ 2 revascularizations) compared to those with no need for revascularization. Follow-up over a median period of 5.6 years for HF/death and 4.0 years for VT/VF/death was assessed among 1374 ICM patients with a Left Bundle Branch Block (LBBB). Results: There was a significant and similar risk reduction with CRT-D vs. ICD-only in HF/death in all three sub-groups: ICM with no need for revascularization (HR 0.45 [0.26-0.80]; p &lt; 0.006), ICM with one revascularization (HR 0.46 [0.31-0.69]; p &lt;0.001), and ICM with 2 or more revascularization (HR 0.50 [0.30-0.84]; p = 0.008). However, significant risk reduction of VT/VF/death with CRT-D vs. ICD-only was only observed in patients with no need for revascularization (HR 0.52 [0.30-0.89]; p = 0.017), less so in those with ICM with one revascularization (HR 0.72 [0.49-1.06]; p = 0.10), and no reduction was seen in those with ICM with 2 or more revascularization (HR 0.94 [0.54-1.62]; p = 0.81). Conclusions: In ischemic cardiomyopathy patients, CRT-D vs. ICD-only is associated with a significant risk reduction in heart failure events or death irrespective of the frequency of pre-enrollment revascularization procedures; however, the benefit of CRT-D vs. ICD-only to reduce ventricular tachyarrhythmias is attenuated with the increasing number of revascularization procedures.
The bone marrow stroma capacity to confer resistance to leukemia cells from Ara-C treatment as a prognostic factor for overall survival in AML.
Authors: Patricia Macanas-Pirard, Sergio Vargas-Salas, Richard Broekhuizen, Romina Coronado, Carolina Bizama, Sabrina Muñiz-Muñoz, Vivianne Torres, Viviana Montecinos, Daniel Ernst, Francisco Melo, Juan Carlos Roa, Bruno Nervi
Journal: Journal of Clinical Oncology (2019)

e18500 Background: The interaction of acute myeloid leukemia (AML) with the bone marrow stroma (BMS) determines a protective microenvironment that favors leukemia development and resistance to chemotherapy. We developed an in vitro platform to study leukemia and stroma interaction, and showed that BMS secretes soluble factors protecting AML cells from Ara-C-induced apoptosis, which correlated with clinical patient outcomes. Methods: BMS from AML patients and healthy donors were cultured to perform chemo-sensitivity studies with Ara-C on THP-1 cells. A Resistance Factor was calculated (RF = IC 50 stroma conditioned medium (CM)/IC 50 control medium) to classify BMS as “protective” (PS: confers chemo-resistance) or “non-protective” (NPS: does not confer chemo-resistance). Characterization of myofibroblasts in BMS cultures was performed by WB. Quantification of cytokines from primary BMS CM was performed by Luminex. The differential expression of epithelial-mesenquimal-like (EMT-like) and stem cell-markers in THP-1 cells incubated with primary BMS CM was measured by qPCR. Results: We recruited 90 AML patients and 10 healthy BM donors. AML cohort showed 31 patients with PS and 59 patients with NPS. PS patients had a significant poor overall survival (OS) compared with NPS patients (44% versus 70% OS in 2.5 years, median survival 7.3 months versus 20.7 months, HR 2.36). The stroma from healthy BM donors did not confer resistance to THP-1 cells. BMS in both, PS and NPS have activated myofibroblasts and analysis of cytokine expression showed differential expression between groups. THP-1 cells incubated with PS showed significant expression of EMT- and stem cell-markers like Twist, Vimentin, CD44 and CD34 compared to THP-1 cells incubated with NPS and control medium. Conclusions: The capacity of the BMS from AML patients to modulate chemoresistance is a strong prognostic factor for OS, and PS patients have a worst OS compared with NPS patients. Stroma from healthy donors has a NPS phenotype. We propose that the leukemia is capable of educating the stroma to acquire secondarily the capacity to confer resistance to leukemia cells to favor tumor progression and chemoresistance.
The Second Dimension—Integrating Calculated Tumor Area Into Cancer Diagnosis
Authors: Timothy H. McCalmont
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Abstract 14110: Mitral Annular Calcification and Coronary Artery Calcification are Associated With Mortality in HIV-Infected Individuals
Authors: David Lange, David Glidden, Eric Secemsky, Karen Ordovas, Elaine Nitta, Vanita Mistry, Sophia Hur, Steven Deeks, Jeffrey Martin, Ann Bolger, Priscilla Hsue
Journal: Circulation (2013)

Background: Coronary artery calcification (CAC) identifies patients at risk for cardiovascular disease (CVD). Mitral annular calcification (MAC) on transthoracic echocardiography (TTE) correlates w...
Abstract 4450: Novel transducer array layouts to optimize the treatment of multiple brain metastases with tumor treating fields
Authors: Ofir Yesharim, Ariel Naveh, Ze'ev Bomzon
Journal: Cancer Research (2019)

Abstract Introduction: Tumor Treating Fields (TTFields) is an antimitotic cancer treatment approved for the treatment of Glioblastoma Multiforme (GBM). TTFields are delivered using 2 pairs of transducer arrays positioned on the shaved scalp of the GBM patient to optimize the TTFields dose delivered to the tumor. This results in an increased dose of TTFields to the affected tumor region, whilst reducing the intensity of the fields to other regions. Brain metastases, or secondary brain tumors, occur in 10 to 30 percent of adults with cancer. Cancer types most likely to cause brain metastases are lung, breast, colon, kidney and melanoma. When using TTFields to treat brain metastases, it may be desirable to deliver TTFields at therapeutic intensities to the entire brain, in order to treat multiple rather than a single lesion. We investigated novel transducer array layouts designed to deliver a uniform distribution of TTFields to the entire brain. Methods Computer simulations were used to calculate the field distributions generated by different array layouts. The simulations utilized a realistic computerized head model of a 40+ years old human male prepared in-house from a T1 MRI series. Using Sim4Life v3.0 (ZMT Zürich), we simulated the delivery of TTFields using pairs of array layouts placed at different locations on the head and neck. To analyze the field distributions, the brain was divided into five regions: (1) the cerebellum, brain stem and other infra-tentorial anatomical regions; and (2-5) the four quadrants of the cerebrum. The mean and median field intensities in the five regions generated by each layout were calculated and compared. Results Median intensities between 1.5 V/cm to 1.7 V/cm within all regions were achieved using a layout in which one pair of arrays was placed on the right temple and left scapula, while the second pair was placed on the left temple and right scapula. This layout yielded a uniform intensity distribution within the brain. Conclusion We have identified a novel TTFields array layout that could potentially be used to treat the entire brain with sufficiently high intensity to treat for brain metastases. The ongoing Phase 3 METIS study [NCT02831959 is investigating radiosurgery with TTFields for 1-10 brain metastases from non-small cell lung cancer. Citation Format: Ofir Yesharim, Ariel Naveh, Ze'ev Bomzon. Novel transducer array layouts to optimize the treatment of multiple brain metastases with tumor treating fields [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4450.
Abstract CT165: Phase II open label trial of minnelide™ in patients with chemotherapy refractory metastatic pancreatic cancer
Authors: David Propper, Haiyong Han, Daniel Von Hoff, Erkut Borazanci, Tannishtha Reya, Jonathan Ghergurovich, Irina Pshenichnaya, Corina Antal, Rachel Condjella, Shreya Sharma, Peter O'Dwyer, Trevor Littlewood, Hitendra Patel, Ashok Saluja, Mohana Velagapudi, Lifeng Yang, Michael Downes, Ronald Evans, Gerard Evan
Journal: Cancer Research (2019)

Abstract BackgroundTriptolide and its water-soluble prodrug, Minnelide™, have shown promising activity against pancreatic ductal adenocarcinoma (PDAC) in both in vitro and in vivo experiments. Triptolide induces apoptosis in pancreatic cancer cells by different pathways, including caspase-dependent apoptotic death and caspase -independent autophagic death. It inhibits the activity of the TFIIH general transcription factor complex and modulates the transcriptional landscape of both the stroma and cancer cell compartments. In the epithelial tumour compartment, triptolide down-regulates key transcription factors such as c-MYC. In the phase I clinical trial of Minnelide™ significant activity in highly refractory metastatic pancreatic carcinoma was observed. Hence we undertook this study in patients with chemotherapy refractory metastatic PDAC. MethodsEligibility criteria include stage IV PDAC that has progressed on standard chemotherapy, Karnofsky performance status ≥ 70%, and measurable disease. Planned sample size is up to 35 patients with interim analysis after the first 18 evaluable patients, aiming for at least a 20% difference in DCR (10% v 30%). Minnelide™ 0.67 mg/m2 is administered intravenously over 30 minutes on days 1-21, followed by a 7 day rest period in a 28 day cycle. Exploratory objectives include: analysis of tumor texture on radiologic scans as a non-invasive biomarker for response, as well as analyses of paired tumour biopsies for changes in immune cell infiltration, stromal activation, chromatin accessibility, phopshoproteomics and metabolism. # NCT03117920The trial opened 4/2017 and as of 12/2018, 18 patients have been treated. Supported by SU2C, Cancer Research UK, Lustgarten Foundation Citation Format: David Propper, Haiyong Han, Daniel Von Hoff, Erkut Borazanci, Tannishtha Reya, Jonathan Ghergurovich, Irina Pshenichnaya, Corina Antal, Rachel Condjella, Shreya Sharma, Peter O'Dwyer, Trevor Littlewood, Hitendra Patel, Ashok Saluja, Mohana Velagapudi, Lifeng Yang, Michael Downes, Ronald Evans, Gerard Evan. Phase II open label trial of minnelide™ in patients with chemotherapy refractory metastatic pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT165.
Abstract 19793: Pulsatility Modulates the Acquired Von Willebrand Factor Defect Related to Mechanical Circulatory Support Devices
Authors: Flavien VIncent, Antoine Rauch, Valentin Loobuyck, Christoph Nix, Emmanuel Robin, Mouhamed Moussa, Delphine Corseaux, Hugues Spillemaeker, Gilles Lemesle, Annabelle Dupont, Nicolas Debry, Guillaume Schurtz, Bart Staels, Peter J Lenting, Sophie Susen, Eric Van Belle
Journal: Circulation (2017)

Introduction: Bleeding is the most frequent adverse event observed in patients with continuous-flow mechanical circulatory support (CF-MCS). The main risk factor of bleeding is the acquired Von Wil...
Abstract 4833: Antibody-drug conjugate targeting glypican-1 shows tumor growth inhibition in cholangiocarcinoma
Authors: Keiichiro Yokota, Satoshi Serada, Shigehiro Tsujii, Kosuke Hiramatsu, Tsutomu Namikawa, Ichiro Murakami, Kazuhiro Hanazaki, Tetsuji Naka
Journal: Cancer Research (2019)

Abstract Cholangiocarcinoma is one of the most highly malignant cancers. Many patients need systemic chemotherapy for tumor development and recurrence, but their prognosis is poor. Therefore new treatment options are urgently required. We confirmed that the expression of glypican-1 (GPC1) was enhanced in cholangiocarcinoma. GPC1 is a cell surface membrane protein and has been reported as a poor prognostic factor in pancreatic cancer. In this study, we aimed to develop a new therapy for cholangiocarcinoma by the antibody-drug conjugate (ADC) targeting GPC1. By immunohistochemical analysis, enhanced expression of GPC1 was observed in clinical specimens of cholangiocarcinoma. KKU-055 and KKU-100 cells, which are cell lines of cholangiocarcinoma, had high expression of GPC1. In the KKU-055 xenograft model when we administered fluorescently-labeled GPC1 antibody to mice, it accumulated in tumor tissue. We developed a new anti-GPC1 monoclonal antibody (mAb) with highly internalizing activity. The anti-GPC1 mAb was conjugated with the cytotoxic agent monomethyl auristatin F (MMAF). GPC1-ADC showed potent antitumor effect toward KKU-055 and KKU-100 cells compared with the control ADC. In the KKU-055 xenograft model, GPC1-ADC had significant and potent tumor growth inhibition in a dose-dependent manner. In summary, our newly-developed GPC1-ADC showed significant tumor growth inhibition against GPC1-positive cholangiocarcinoma cell lines. Our preclinical data demonstrated that targeting GPC1 by ADC is a promising therapy for GPC1-positive cholangiocarcinoma. Citation Format: Keiichiro Yokota, Satoshi Serada, Shigehiro Tsujii, Kosuke Hiramatsu, Tsutomu Namikawa, Ichiro Murakami, Kazuhiro Hanazaki, Tetsuji Naka. Antibody-drug conjugate targeting glypican-1 shows tumor growth inhibition in cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4833.
Pediatric patients with acute lymphoblastic leukemia generate abundant and functional neoantigen-specific CD8 <sup>+</sup> T cell responses
Authors: Anthony E. Zamora, Jeremy Chase Crawford, E. Kaitlynn Allen, Xi-zhi J. Guo, Jesse Bakke, Robert A. Carter, Hossam A. Abdelsamed, Ardiana Moustaki, Yongjin Li, Ti-Cheng Chang, Walid Awad, Mari H. Dallas, Charles G. Mullighan, James R. Downing, Terrence L. Geiger, Taosheng Chen, Douglas R. Green, Benjamin A. Youngblood, Jinghui Zhang, Paul G. Thomas
Journal: Science Translational Medicine (2019)

Pediatric acute lymphoblastic leukemia elicits a broad, functional, antitumor T cell response, targeting multiple mutations.
Abstract 17385: Eplerenon Reduces Qtc Time Intervall in Primary Hyperparathyroidism
Authors: Martin R Grubler, Nicolas Verheyen, Johannes Schmid, Astrid Fahrleitner-Pammer, Cristina Catena, Andreas Meinitzer, Helmut Brussee, Winfried März, Burkert Pieske, Stefan Pilz, Andreas Tomaschitz
Journal: Circulation (2016)

Purpose: Clinical and experimental studies indicated that mineralocorticoid receptor (MR) antagonism may affect cardiovascular risk in patients with primary hyperparathyroidism (pHPT). We therefore...
Abstract PL03-03: Taming the beast: Strategies to target the immune-suppressive macrophage to enhance cancer immune therapy
Authors: Judith A. Varner
Journal: Cancer Research (2019)

Abstract Advances in basic, translational and clinical research have revealed the power of cancer immune therapy. Checkpoint inhibitors and adoptive T cell therapies are novel, FDA approved therapeutic strategies that promote recruitment to and activation of tumor-reactive cytotoxic T cells. While promising, these strategies are not effective in all cancer patients, and resistance to therapy often develops. Recent advances in the study of the tumor microenvironment have revealed that tumor-associated myeloid cells accumulate rapidly in tumors where they promote resistance to checkpoint inhibitor therapy and adoptive T cell therapy, inhibit immune responses to tumor cells, and stimulate tumor progression. The most abundant of these myeloid cells, macrophages, usually serve as a first line of defense against pathogenic insults to tissues. These innate immune cells mount pro-inflammatory responses to pathogens and repair damaged tissues. However, in tumors, macrophages (TAMs) accumulate rapidly and potently suppress anti-tumor immunity and promote tumor progression. Preclinical studies have identified crucial pathways that regulate the recruitment, polarization, transcription and metabolism of TAMs during tumor progression. We have found that an isoform of PI3Kinase, PI3Kgamma, controls these pathways by activating mTORC1-mediated transcriptional and metabolic pathways that suppress cytotoxic T cell recruitment and activation. Targeting PI3Kgamma and its downstream effectors inhibits immune suppressive polarization and promotes NFkappaB activation and pro-inflammatory transcription in macrophages, thereby recruiting CD8+ T cells and stimulating T cell activation and memory. Novel therapeutics targeting PI3Kgamma stimulate cytotoxic T cell activation and recruitment and synergize with checkpoint inhibitors and chemotherapy in preclinical studies. Clinical trials with PI3Kgamma inhibitors such as IPI-549 (Infinity Pharmaceuticals) are currently underway and offer the promise of improved cancer outcomes for many tumor types. Citation Format: Judith A. Varner. Taming the beast: Strategies to target the immune-suppressive macrophage to enhance cancer immune therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr PL03-03.