tbuckley/cabot-search huggingface dataset:
Phase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC): Study update
Authors: M.J. Morris, N.J. Vogelzang, O. Sartor, A. Armour, D. Petrylak, A. Tolcher, S. Ejadi, H.M. Babiker
Journal: Annals of Oncology (2016)

Prostate-specific membrane antigen (PSMA) is overexpressed by most prostate cancers. EC1169 is a conjugate of a PSMA targeting moiety linked to the cytotoxic agent tubulysin B hydrazide (TubBH). Following internalization of EC1169 by targeted cancer cells, intracellular release of TubBH results in inhibition of tubulin polymerization. In PSMA-positive LNCaP and MDA PCa 2b xenografts, complete responses and cures have been observed following EC1169 treatment. EC1169 does not show activity in PSMA-negative models, demonstrating its specificity. EC0652 is a companion radiodiagnostic conjugate of a 99mTc chelator and a PSMA-targeting moiety designed to characterize PSMA-expressing disease in real time. Rapid tumor uptake of 99mTc-EC0652 and rapid normal tissue clearance result in enhanced tumor: background ratios with SPECT imaging. Key inclusion criteria are age ≥18 years, ECOG PS 0–1, and adequate organ function. Patients (pts) must have failed androgen-deprivation therapy, progressed on abiraterone or enzalutamide, and have been previously treated with a taxane unless contraindicated. Patients are to undergo a 99mTc-EC0652 SPECT scan prior to therapy. PSMA positivity is not a requirement for study entry. EC1169 is administered as an intravenous bolus on Days (D) 1, 8 (QW) every 21 D. Dose escalation is based upon the "3 + 3" method. Study objectives include determination of EC1169 MTD and recommended phase II dose, safety, pharmacokinetics, antitumor activity and its correlation with PSMA expression as identified on 99mTc-EC0652 SPECT imaging. 23 pts have been treated on the QW schedule. Median age is 70 (range: 57-82). The median number of administered EC1169 cycles is 2 (range: 1-11). 12 (52%) treatment related AEs have been reported. Most common Grade 3/4 AEs were anaemia (2; 8.7%) and lymphopenia (2; 8.7%). No DLT, related SAEs or toxicity requiring dose reductions occurred. PSA response (≥50% max decline) has been observed in 2 pts. Data will be updated at the meeting. To date, EC1169 has been well tolerated. There are promising signs of early efficacy in this heavily pre-treated population.
NK-Like Homeodomain Proteins Regulate NOTCH3-Signaling in T-Cells.
Authors: Stefan Nagel, Letizia Venturini, Grzegorz K. Przybylski, Piotr Grabarczyk, Corinna Meyer, Maren Kaufmann, Karin Battmer, Christian A. Schmidt, Hans G. Drexler, Michaela Scherr, Roderick A.F. MacLeod
Journal: Blood (2008)
Anti Hsp70 Antibodies in Untreated Patients with Chronic Lymphocytic Leukaemia
Authors: Jaroslaw Piszcz, Edyta Cichocka, Lukasz Bolkun, Marzenna Galar, Katarzyna Mazgajska-Barczyk, Marek Milewski, Janusz Kloczko
Journal: Blood (2008)
EXTH-22. MESENCHYMAL STEM CELLS AS CELLULAR VEHICLES TO DELIVER A SUICIDE GENE, CYTOSINE DEAMINASE TO NON-BRAIN CANCERS
Authors: Ha Vu Hai, Da-Young Chang, Jin-Hwa Jung, Sung-Soo Kim, Haeyoung Suh-Kim
Journal: Neuro-Oncology (2016)

The robust development of therapeutic strategies for many types of cancer treatment has achieved remarkable outcomes in preclinical and clinical fields. One of the approaches is based on suicide gene therapy using cytosine deaminase (CD) of non-human origin and a prodrug of 5-flurocytosine (5-FC). CD enzymes convert non toxic 5-FC into anticancer drug, 5-flurouracil (5-FU), which induces a cytotoxic bystander effect on tumor cells. Previous studies demonstrated that mesenchymal stem cells show strong tropism toward tumor region because of combined effects of multiple cytokines secreted from tumor microenviroment. We previously reported a potential therapy using human mesenchymal stem cells engineered to express a bacteria CD gene (MSC/CD) exert bystander effect on C6 rat glioma or U87 human glioma cells in orthotopic models (Chang et al., Int. J. Cancer, 2010; Jung et al., Am. J. Cancer Res., 2015). Here, we show preclinical evidence that MSC/CD cells could be utilized for the treatment of non-brain cancers.
Patient-specific circulating tumor DNA detection during neoadjuvant chemotherapy in triple negative breast cancer
Authors: J.-Y. Pierga, F. Riva, A. Houy, A. Saliou, J. Madic, A. Rampanou, C. Hego, M. Milder, P. Cottu, M.-P. Sablin, A. Vincent-Salomon, O. Lantz, M.-H. Stern, C. Proudhon, F.-C. Bidard
Journal: Annals of Oncology (2016)
Risk for Attacks in Hereditary Angioedema (HAE) Population Correlates with C1-inhibitor Functional Activity (C1-INHact)
Authors: Marco Cicardi, Huamin Henry Li, Chevy Chase, John T. Anderson, Jonathan A. Bernstein, Henriette Farkas, Ying Zhang, Dipti Pawaskar, Ingo Pragst
Journal: Journal of Allergy and Clinical Immunology (2017)
248P Substantial RUNX3 expression and co-existence with EZH2 in esophageal cancer: a new finding in Indian esophageal cancer patients
Authors: A.U. Rehman, M.A. Iqbal, S. Saikia, P.K. Mishra, S.S. Saluja, S. Medhi, S.A. Husain
Journal: Annals of Oncology (2016)
572P Cardiotoxicity in Chinese cancer patients treated with 5- fluorouracil or capecitabine: A multicenter prospective observational study
Authors: G. Chen, J.J. Peng, C. Dong, M. Qiu, C. Wang, H.W. Li, H. Yu, M. Zhang, Q. Zhao, B. Zhu, J. Zhang, L.W. Li, H.F. Wang, Q. Wu, Y. Yuan, G.W. Zhou
Journal: Annals of Oncology (2016)
NIMG-10. EARLY PRESENTATION OF FAMILIAL CEREBRAL CAVERNOUS MALFORMATION (FCCM) IN AN INFANT - A CASE REPORT
Authors: Gurcharanjeet Kaur, Louis Manganas
Journal: Neuro-Oncology (2016)

To describe presentation of FCCM in an infant. Cerebral cavernous malformations (CCMs) are rare low-flow vascular malformations; hemorrhage can result in significant morbidity and mortality. Familial cerebral cavernous malformations (FCCM) are defined as the occurrence of CCMs in at least two family members and/or the presence of multiple CCMs and/or the presence of a disease causing mutation in one of the three genes in which mutations are known to cause familial CCM. FCCM typically manifests between 20 to 30 years of age, but clinical manifestations can occur at any age. Our patient is a 6 month old Caucasian baby boy who was the product of full term cesarean section and meeting milestones. He presented to the emergency room with right eye deviation and right hemiparesis over three days. Maternal history was significant for multiple intra-cerebral cavernous angiomas diagnosed at 30 years of age. CT head revealed a hyperdense lesion over the pontine medullary junction. Subsequent MRI brain w/wo contrast revealed multiple cavernomas. There was surrounding edema and hemorrhage in a cavernoma over left anterior medulla which was responsible for his symptoms. MRA head was normal. Genetic work-up is pending for the patient, however, mother has CCM1 mutation. Although surgery has been considered efficient treatment option for CCMs, it was deferred for our patient given location of lesion and age of this patient. In the case report we describe the first infant to present with FCCM. Majority of individuals present with CCMs are symptomatic between the second and fifth decades. In one study, 9% of individuals were symptomatic before age ten years, 62%-72% between ages 10 and 40 years, and 19% after age 40 years. Functional outcome is mostly determined by the location of CCM lesions, with brainstem and basal ganglia lesions having a worse prognosis.
Amid Reports of Infant Deaths, FTC Cracks Down on Homeopathy While FDA Investigates
Authors: Jennifer Abbasi
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
The New Idiopathic Pulmonary Fibrosis Acute Exacerbations Document: One Step Ahead but Still Suspended in the Air
Authors: Spyros A Papiris, Konstantinos Kagouridis, Likurgos Kolilekas, Anna Karakatsani, Ioanna Korbila, Paschalina Giouleka, Georgia Papadaki, Maria Maniati, Demosthenes Bouros, Effrosyni D Manali
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Vital Signs: Noise-Induced Hearing Loss Among Adults — United States 2011–2012
Authors: Yulia I Carroll, John Eichwald, Franco Scinicariello, Howard J. Hoffman, Scott Deitchman, Marilyn S. Radke, Christa L. Themann, Patrick Breysse
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The 2016 National Academies of Sciences report "Hearing Health Care for Adults: Priorities for Improving Access and Affordability" included a call to action for government agencies to strengthen efforts to collect, analyze, and disseminate population-based data on hearing loss in adults.CDC analyzed the most recent available data collected both by questionnaire and audiometric tests of adult participants aged 20-69 years in the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to determine the presence of audiometric notches indicative of noise-induced hearing loss. Prevalence of both unilateral and bilateral audiometric notches and their association with sociodemographics and self-reported exposure to loud noise were calculated.Nearly one in four adults (24%) had audiometric notches, suggesting a high prevalence of noise-induced hearing loss. The prevalence of notches was higher among males. Almost one in four U.S. adults who reported excellent or good hearing had audiometric notches (5.5% bilateral and 18.0% unilateral). Among participants who reported exposure to loud noise at work, almost one third had a notch.Noise-induced hearing loss is a significant, often unrecognized health problem among U.S. adults. Discussions between patients and personal health care providers about hearing loss symptoms, tests, and ways to protect hearing might help with early diagnosis of hearing loss and provide opportunities to prevent harmful noise exposures. Avoiding prolonged exposure to loud environments and using personal hearing protection devices can prevent noise-induced hearing loss.
Flexible trial design in practice: Dropping and adding arms in STAMPEDE (MRC PR08, CRUK/06/019)—A multiarm, multistage randomized controlled trial.
Authors: Matthew Robert Sydes, Nicholas David James, Malcolm David Mason, Noel W Clarke, Claire Amos, John Anderson, Johann Sebastian De Bono, David Paul Dearnaley, John Dwyer, Gordana Jovic, Alastair SW Ritchie, J. Martin Russell, Karen Sanders, George Thalmann, Mahesh Parmar
Journal: Journal of Clinical Oncology (2012)

27 Background: STAMPEDE ( NCT00268476 ) is a multi-centre, RCT using novel multi‐arm, multi‐stage (MAMS) methods. We describe the methodological and practical issues arising with early stopping of recruitment to some arms following an intermediate analysis and the issues in adding new research arms during the trial. Methods: The trial recruits men with locally advanced or metastatic prostate cancer starting standard long-term hormone therapy. There are 5 research and 1 control arm assessed over 3 intermediate activity stages I-III [outcome measure: failure-free survival (FFS)] and a final efficacy stage IV [outcome measure: overall survival]. At the end of each stage, research arms are formally compared to the control arm. Accrual of further patients is discontinued early for research arms not showing sufficient evidence of activity or with adverse safety considerations; accrual continues to the other arms; this interim hurdle is increasingly stringent at each stage. The addition of new research arm(s) can be actively considered when sufficiently interesting agents emerge. New research arms are compared only to contemporaneously-recruited control arm pts using the same intermediate guidelines in a time-delayed manner. Results: (1) After the second intermediate activity analysis (Mar-2011), the IDMC recommended and the Trial Steering Committee ratified discontinuation of recruitment to two research arms for lack-of-sufficient activity. Nearly 100 recruiting centres in UK and Switzerland had to promptly implement changes. Detailed advanced preparation meant that activation was swift and recruitment continued seamlessly into Activity Stage III. (2) An application to add a new research arm, abiraterone, has been agreed by funders, industry partner and ethics committee; regulatory approval awaited. Details on methodological and practical issues and implementation of these changes will be presented. Conclusions: The STAMPEDE experiences shows that recruitment to MAMS trials is achievable and that mid-flow changes to trial design are practicable and encouraged.
Adaptive Immunotherapy In Multiple Myeloma: Epigenetic Modification and Immunomodulation by Sequential Azacitidine and Lenalidomide to Generate Cancer Testis Antigen Specific Cellular Immune Response
Authors: Amir A Toor, Kyle Payne, Harold M Chung, Catherine H Roberts, Roy T Sabo, Maciej Kmieciak, William Clark, Christy McLaughlin, Angela Buskey, Jennifer Anderson, Rose H Manjili, Susan D. Roseff, John M McCarty, Masoud H Manjili
Journal: Blood (2011)
Rituximab Dose-Dense Chemotherapy Followed by Intensified High-Dose Chemotherapy and Autologous Stem Cell Transplantation (HDC+ASCT) Significantly Reduces the Risk of Progression Compared to Standard Rituximab Dose-Dense Chemotherapy As First Line Treatment in Young Patients with High-Risk (aa-IPI 2–3) Diffuse Large B-Cell Lymphoma (DLBCL): Final Results of Phase III Randomized Trial DLCL04 of the Fondazione Italiana Linfomi (FIL)
Authors: Umberto Vitolo, Annalisa Chiappella, Ercole Brusamolino, Emanuele Angelucci, Giuseppe Rossi, Angelo Michele Carella, Andrea Evangelista, Caterina Stelitano, Monica Balzarotti, Francesco Merli, Gianluca Gaidano, Vincenzo Pavone, Luigi Rigacci, Francesco Zaja, Nicola Cascavilla, Alfonso Maria D'Arco, Chiara Rusconi, Amalia De Renzo, Graziella Pinotti, Michele Spina, Patrizia Pregno, Eleonora Russo, Manuel Gotti, Alessandra Tucci, Maria Giuseppina Cabras, Stefano A. Pileri, Alessandro Levis, Maurizio Martelli
Journal: Blood (2012)
The Search for Potent, Small‐Molecule HDACIs in Cancer Treatment: A Decade After Vorinostat
Authors: Chiara Zagni, Giuseppe Floresta, Giulia Monciino, Antonio Rescifina
Journal: Medicinal Research Reviews (2017)

Abstract Histone deacetylases (HDACs) play a crucial role in the remodeling of chromatin, and are involved in the epigenetic regulation of gene expression. In the last decade, inhibition of HDACs came out as a target for specific epigenetic changes associated with cancer and other diseases. Until now, more than 20 HDAC inhibitors (HDACIs) have entered clinical studies, and some of them (e.g., vorinostat, romidepsin) have been approved for the treatment of cutaneous T‐cell lymphoma. This review provides an overview of current knowledge, progress, and molecular mechanisms of HDACIs, covering a period from 2011 until 2015.
Expression of CXCR4 on Intrahepatic Stem Cells from Organ Donors and Patients with Chronic Liver Disease.
Authors: Laura Porretti, Raffaella Lopa, Roberto Gramignoli, Antonella Ambrosone, Annamaria Mosca, Alessandra Cattaneo, Mario Scalamogna, Stefano Gatti, Giorgio Rossi, Agostino Colli, Daniele Prati
Journal: Blood (2004)
Limited Efficacy of Ponatinib in Myeloproliferative Neoplasms Associated with FGFR1 Fusion Genes
Authors: Sebastian Kreil, Lionel Adès, Martin Bommer, Frank Stegelmann, Mark E Ethell, Anna Lubking, Peter Martin, Ekkehard Eigendorff, Wolf-Karsten Hofmann, Nicholas C.P. Cross, Andreas Hochhaus, Andreas Reiter
Journal: Blood (2015)
Regulation of Connective Tissue Growth Factor (CTGF) Ameliorates the Disease Course in a Rodent Model of Reactive Arthritis (RA).
Authors: Joanne M. Manns, Julian L. Castaneda, Mario C. Rico, Fayez F. Safadi, Steven N. Popoff, Mary F. Barbe, Raul A. De La Cadena
Journal: Blood (2004)
325P Preliminary review of computed tomography (CT)-based image-guided brachytherapy (IGBT) in treatment of cervical cancers: The National Cancer Institute (NCI) experience
Authors: N. Salimin, S. Mohammad, H.L. Goh, S.P. Tang, C.T. Chong, S. Mohd Salim, H.Z. Ahmad, N. Abdullah, M.Z. Muzzamer, A.N.A. Ahmad Sayuty, S.H. Abdul Rahman
Journal: Annals of Oncology (2016)
Identification of Eight Surface Molecules with Survival Predictive Power in B Cell Chronic Lymphocytic Leukemia (B-CLL): A Proposal for a Scoring System.
Authors: Valter Gattei, Paolo Sonego, Stefania Russo, Riccardo Bomben, Michele Dal Bo, Maurizio Rupolo, Giovanni Del Poeta, Carlo Pucillo, Alfonso Colombatti, Massimo Degan, Antonella Zucchetto
Journal: Blood (2004)
A Behind-the-Scenes Story of Precision Medicine *
Authors: Maynard V. Olson
Journal: Genomics Proteomics & Bioinformatics (2017)

Mapping and Sequencing the Human Genome (1988) and Toward Precision Medicine (2011).I do not intend to summarize what the reports say.They are both short, well written, and can speak for themselves.I encourage readers who want a quick summary to read these reports the way most policy-makers do: start with the Executive Summaries, particularly the Conclusions and Recommendations.NRC committees write these summaries with great care since they are read far more widely, and by a more influential audience, than the bodies of the reports.With respect to audience, I assume this book will be of greatest interest to scientists and policy-makers interested in how the policy-making apparatus in the United States works and how it shaped two key initiatives in biology and medicine during their formative stages.A scientist myself, now retired from active research, I am the only person who
The different genetic alterations between Western and Chinese prostate cancers and the underlying mechanisms.
Authors: Xueying Mao, Nuria Coll Bastus, Lara Boyd, Yongwei Yu, Guoping Ren, Luis Beltran, R. Oliver, Bryan D Young, Dan Berney, Yong-Jie Lu
Journal: Journal of Clinical Oncology (2012)

184 Background: Prostate cancer shows a wide variation in the clinical incidence and mortality rates of different geographical regions. While it is the most common male cancer in Western countries, it is much less frequent in Asian countries. We investigated genomic changes in prostate cancers from UK and China using microarrays to determine the genetic similarities and differences as well as the underlying mechanisms. Methods: We determined genome-wide genomic alterations using Affymetrix SNP array 6.0, and evaluated data using fluorescence in situ hybridisation (FISH) and immunohistochemistry. In addition, we assess androgen induced TMPRSS2 and ERG co-localization and fusion. Microsatellite analysis was used for AR CAG repeat polymorphism in UK and Chinese population. Results: Genome-wide analysis of 32 UK and 39 Chinese samples revealed that losses of 21q22 (leading to TMPRSS2:ERG fusion) and 10q23.3 (PTEN) were at much higher frequency in Western than Chinese prostate cancers. Using FISH analysis of 160 UK and 143 Chinese samples, we showed that PTEN deletion and ERG rearrangements were at a significantly higher frequency in samples from UK than China (p&lt;0.001 for both). We found that PTEN and ERG protein were also differentially expressed (p&lt;0.001) in the two populations. Investigating this further, we induced TMPRSS2 and ERG gene proximity and TMPRSS2:ERG fusion in two immortalised prostate epithelial cell lines by exposure to high dose of androgen. This androgen treatment did not cause increased global DNA damage but was associated with low expression of PIWIL1, which is involved in repairing double-strand breaks. Overexpression of PIWIL1 by transfection inhibited androgen induced TMPRSS2:ERG fusion. We found that AR CAG repeat lengths, which associated with AR activity, are significantly shorter in the UK than Chinese patients (p&lt;0.05). Conclusions: We revealed genomic differences in prostate cancer comparing the high-risk (Western) and low-risk (Chinese) populations. We further demonstrated that TMPRSS2:ERG fusion can be induced by androgen. The difference of CAG repeat length between the two populations are potentially associated with TMPRSS2:ERG fusion positive prostate cancers.
Rivaraoxaban dosing is based on more than just pharmacokinetic properties
Authors: Amit Aggarwal
Journal: BMJ (2017)

We at Bayer think that Moore’s letter on rivaroxaban is misleading.1 Pharmacokinetic properties are not the sole determinants of the appropriate dosing regimen, and the pharmacodynamic effect of rivaroxaban once daily is evident for the full 24 hours after being taken.2 Furthermore, the efficacy of any intervention can only be demonstrated in large interventional clinical trials.

The terminal elimination half …
Identification of imaging biomarkers using <sup>18</sup>fluorodeoxyglucose-positron emission tomography (FDG-PET) for the prediction of pathologic response in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer.
Authors: Arti Parekh, Shanna Matalon, Rathan Subramaniam, Lisa A. Kachnic
Journal: Journal of Clinical Oncology (2012)

435 Background: Pre- and post-treatment FDG-PET imaging parameters may be useful for predicting pR following neoadjuvant CRT for LARC Methods: Between 2006 and 2010, 18 patients (pts) receiving preoperative CRT (5FU or capecitabine with concurrent 50.4 Gy conformal radiation) for LARC underwent a pre- (0-14 days before) and post-CRT (4 to 6 weeks after) PET/CT. Total mesorectal excision was performed 6 weeks post CRT. pR was dichotomized into complete (pCRs) and partial responders as reference standard. Pts with pathologic microscopic disease were classified as pCRs for this analysis. Changes in FDG metabolic parameters between pre and post-CRT scans, including maximum Standardized Uptake Value (SUVmax), metabolic tumor volume (MTV) and total glycolytic activity (TGA), were investigated as predictive imaging biomarkers for pR. Fixed SUVmax percentage threshold (30%, 40% and 50%) and gradient-based segmentation (PET Edge) were used to calculate the MTV and TGA. Receiver Operator Curve analysis was performed Results: Median pt age was 57.5 years (31-87); 67% M; 61% AJCC 2010 stage II, 33% III and 6% IV. pCR achieved in 44%. The 30% SUVmax threshold MTV best correlated with PET Edge MTV (Pearson r 0.99). Using ROC analysis, % change in SUVmax and PET edge TGA between pre and post-CRT scans were comparable and the most accurate parameters for predicting pR. SUVmax % change yielded an area under the curve (AUC) of 0.7125 (95% CI 0.4318-0.9932), while the AUC for PET Edge TGA % change was 0.7000 (95% CI 0.4209-0.9791). Based on ROC analysis, a cutoff of 78.9% change of PET Edge TGA had a likelihood ratio of 2.4, with a sensitivity of 90% and a specificity of 62.5% for predicting pCR. A cutoff of 88.7% change of PET Edge MTV yielded a likelihood ratio of 2.00 with a sensitivity of 50% and a specificity of 75%. Conclusions: The % change pre- to post-CRT in SUVmax and PET Edge Total Glycolytic Activity appears to be the most suitable FDG metabolic parameters for predicting pR following neoadjuvant CRT for LARC. As such, these PET-FDG biomarkers of CRT response should be validated in future prospective trials.