tbuckley/cabot-search huggingface dataset:
A phase II trial of the multitargeted kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer (MTC).
Authors: Martin Schlumberger, Barbara Jarzab, Maria E. Cabanillas, Bruce Robinson, Furio Pacini, Douglas Wilmot Ball, Judith C McCaffrey, Kate Newbold, Roger Allison, Renato Martins, Lisa F. Licitra, Manisha H. Shah, Donald Bodenner, Rossella Elisei, Lynn A. Burmeister, Yasuhiro Funahashi, Rita Sellecchia, Corina Andresen, James P. O'Brien, Steven I. Sherman
Journal: Journal of Clinical Oncology (2012)

5591 Background: Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ. In phase I studies of lenvatinib partial responses (PR) were observed in thyroid as well as melanoma, endometrial, and renal cancers. Methods: Patients (pts) with unresectable MTC and disease progression demonstrated by RECIST during the prior 12 months were enrolled. Pts may have received prior VEGFR targeted therapy. Pts were treated with a starting dose of lenvatinib 24 mg once daily in 28 day cycles until disease progression or development of unmanageable toxicities. Primary end point was Response Rate (RR) by RECIST. Tumor genetic analysis and circulating cytokine and angiogenic factors (CAF) analysis were performed. Results: 59 pts were enrolled (med age: 52; Male: 63%;) and are evaluable for response. 54% of pts required dose reduction for management of toxicity, and 22% were withdrawn from therapy due to toxicity. The most common treatment-related adverse events were proteinuria 58% (Gr3: 2%), diarrhea 56% (Gr3: 5%), hypertension 48% (Gr3: 7%), fatigue 44% (Gr3: 5%), decreased appetite 41% (Gr3: 5%), nausea 34% (Gr3: 0), and weight decreased 32% (Gr3: 3%). No Gr4 events were reported for these event categories. Confirmed PRs were observed in 21pts (RR: 36%, 95% CI: 24-49) based on independent imaging review (IIR) and 29 pts (RR: 49%, 95% CI: 36-62) based on investigator assessment. For pts who received prior VEGFR-directed treatment (n=26) RR=35% (IIR); with no prior VEGFR-directed treatment (n=33) RR=36 % (IIR). Median PFS by IRR is 9.0 mo (95% CI: 7.0-) (based on minimum 8 mo. f/u, 46% events observed). There was no clear difference in treatment response between RET-mutant (RET-mu) and RET-wild type (RET-wt) patients. Low baseline levels of ANG2, sTie-2, HGF and IL-8 were associated with greater tumor shrinkage and prolonged PFS whereas high baseline levels of VEGF and sVEGFR3 were associated with greater tumor shrinkage. Conclusions: Lenvatinib administered orally at a dose of 24 mg once daily to patients with MTC is associated with manageable toxicity and a RR of 36%, identifying lenvatinib as a promising new potential therapeutic agent for treating patients affected with this disease.
Esomeprazole immediate release tablets: Gastric mucosa ex vivo permeation, absorption and antisecretory activity in conscious rats
Authors: Camillo Benetti, Lisa Flammini, Valentina Vivo, Paolo Colombo, Gaia Colombo, Lisa Elviri, Carmelo Scarpignato, Francesca Buttini, Ruggero Bettini, Elisabetta Barocelli, Alessandra Rossi
Journal: Journal of Controlled Release (2016)
Extrapulmonary small cell carcinoma: University of Miami/Jackson Memorial Hospital experience.
Authors: M. C. Mendoza-Puccini, G. E. Panta, V. Patel, S. Patel, C. A. Quintero, J. E. Gomez, E. S. Santos, L. E. Raez, C. Ikpeazu
Journal: Journal of Clinical Oncology (2010)

e17524 Background: Extra-pulmonary small cell carcinoma (EPSCC) is a heterogeneous group of cancers. The clinical-pathological features of EPSCC remain poorly defined. Because these tumors are uncommon, there is very little published information. Methods: We retrospectively reviewed all medical records for all patients at Jackson Memorial Hospital and Sylvester Comprehensive Cancer Center with a diagnosis of small cell carcinoma whose primary tumor was located outside of the lung. We collected 40 variables regarding demographic, epidemiologic, clinical, and treatment information. Tumors were included if they were poorly differentiated, small cell carcinomas, with at least 1 neuro-endocrine marker (synaptophysin or chromogranin). Results: To date we have collected information on 21 patients. These include 9 head and neck, 7 bladder, and 5 gastrointestinal primary locations. 11 patients had disease limited to the primary organ and 10 patients had extensive disease. 4 patients were female, and 17 male. The age range is 42-88, with a mean of 65.8 and a median of 62 years. 13 patients were current or former smokers, while 8 were never smokers. 1 patient was treated with surgery alone, 3 patients received chemotherapy alone, 13 patients received a combination of 2 modalities, 3 patients received a combination of 3 modalities, and 1 patient expired before treatment. Survival information is currently available for 19 patients. The median survival for these is 19.63 months with a mean of 23.21 months. Conclusions: In our experience, EPSCC has a better survival than pulmonary SCC and is more frequently limited to the primary organ. Chemotherapy plays a significant role in the treatment of EPSCC, but most patients received multi-modality treatment with cisplatin based chemotherapy. Smoking does not appear to be as significant in the etiology of EPSCC as in pulmonary SCC, as 38% of our patients were never smokers. The final report will include 40 patients and will evaluate treatment patterns and the relationship between primary site and survival. No significant financial relationships to disclose.
Gene delivery and immunomodulatory effects of plasmid DNA associated with Branched Amphiphilic Peptide Capsules
Authors: L.A. Avila, L.R.M.M. Aps, N. Ploscariu, P. Sukthankar, R. Guo, K.E. Wilkinson, P. Games, R. Szoszkiewicz, R.P.S. Alves, M.O. Diniz, Y. Fang, L.C.S. Ferreira, J.M. Tomich
Journal: Journal of Controlled Release (2016)
Towards Successful Implementation of Pharmacokinetic-Guided Prophylactic Dosing of Clotting Factor Concentrate in Hemophilia; The Do’s and Don’ts after Discrete Choice Experiment Analysis
Authors: Janske Lock, Esther W. de Bekker-Grob, Gamze Urhan, Saskia Middeldorp, Marjolein Peters, Karina Meijer, Rienk Y.J. Tamminga, Britta Laros-van Gorkum, Paul Brons, Felix J.M. Van der Meer, Mariette H.E. Driessens, Peter W. Collins, Karin Fijnvandraat, Frank W.G. Leebeek, Marjon H. Cnossen
Journal: Blood (2014)
Appropriate Perspective and Context for Newly Approved Medications, Including Flibanserin—Reply
Authors: Steven Woloshin, Lisa M. Schwartz
Journal: JAMA Internal Medicine (2016)

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
Pediatric Emergency Medicine
Authors: Marc Nelson
Journal: JAMA (2005)

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
P1200 : The effect of azathioprine on the risk of malignancy in patients with primary sclerosing cholangitis: A long-term multicenter study
Authors: R. Zenouzi, T.J. Weismüller, K.K. Jorgensen, H. Lenzen, P. Hübener, K. Schulze, M. Bubenheim, T.H. Karlsen, K.M. Boberg, M.P. Manns, A.W. Lohse, C. Schramm
Journal: Journal of Hepatology (2015)
Real-Life Comparison Of Severe Vascular Events and Other Non-Hematological Complications In CML Patients Treated With Second Line Nilotinib Or Dasatinib
Authors: Joanna Gora-Tybor, Ewa Medras, Malgorzata Calbecka, Agnieszka Kolkowska, Edyta Ponikowska-Szyba, Tadeusz Robak, Krzysztof Jamroziak
Journal: Blood (2013)
Day 100 Absolute Lymphocyte Count (ALC) Predicts Risk of Serious Infections in Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation (HCT)
Authors: Arun Singavi, Jonathan Kapke, Adam Levin, Anjishnu Banerjee, Fenlu Zhu, Mehdi Hamadani, Parameswaran Hari, Timothy S. Fenske
Journal: Blood (2015)
MM-005: A Phase 1 Trial Of Pomalidomide, Bortezomib, and Low-Dose Dexamethasone (PVD) In Relapsed and/Or Refractory Multiple Myeloma (RRMM)
Authors: Paul G. Richardson, Craig C. Hofmeister, David Siegel, Sagar Lonial, Jacob P. Laubach, Yvonne A. Efebera, David H. Vesole, Ajay K. Nooka, Jacalyn Rosenblatt, Noopur Raje, Mohamed H. Zaki, Ye Hua, Yan Li, Sheetal Shah, Jianming Wang, Kenneth C. Anderson
Journal: Blood (2013)
Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations
Authors: Laurence Albiges, A. Ari Hakimi, Wanling Xie, Rana R. McKay, Ronit Simantov, Xun Lin, Jae-Lyun Lee, Brian I. Rini, Sandy Srinivas, Georg A. Bjarnason, Scott Ernst, Lori A. Wood, Ulka N. Vaishamayan, Sun-Young Rha, Neeraj Agarwal, Takeshi Yuasa, Sumanta K. Pal, Aristotelis Bamias, Emily C. Zabor, Anders J. Skanderup, Helena Furberg, Andre P. Fay, Guillermo de Velasco, Mark A. Preston, Kathryn M. Wilson, Eunyoung Cho, David F. McDermott, Sabina Signoretti, Daniel Y.C. Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2016)

Purpose Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC. Methods The impact of BMI (high BMI: ≥ 25 kg/m 2 v low BMI: &lt; 25 kg/m 2 ) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors. Results In the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P = .034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P = .002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend = .015). Conclusion High BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway.
Cheyne–Stokes Respiration, Chemoreflex, and Ticagrelor-Related Dyspnea
Authors: Alberto Giannoni, Michele Emdin, Claudio Passino
Journal: New England Journal of Medicine (2016)

We found evidence of ZIKV infection in amniotic epithelial cells and in fetal mesenchymal cells with affinity for perichondrium.Our observation indicates that ZIKV replicates in pluripotent (amniotic stem) cells involved in early-stage embryo development.The observation of prolonged viremia until day 21 in the patient is in concordance with the findings of Driggers et al. 3 and provides further data for consideration in the ongoing development of testing algorithms in pregnant women.These algorithms are currently based on the assumption that ZIKV viremia can be detected only up to 7 days.
Phase I/II trial of IMMU-132 (isactuzumab govitecan), an anti-Trop-2-SN-38 antibody drug conjugate (ADC): Results in patients with metastatic gastrointestinal (GI) cancers.
Authors: Alexander Starodub, Allyson J. Ocean, Wells A. Messersmith, Vincent J. Picozzi, Michael J. Guarino, Sajeve Samuel Thomas, Aditya Bardia, Manish A. Shah, Serengulam V. Govindan, Pius P Maliakal, William A. Wegener, Steven A. Hamburger, Robert M. Sharkey, David M. Goldenberg
Journal: Journal of Clinical Oncology (2015)

703 Background: Trop-2 is a tumor-associated glycoprotein highly expressed in many epithelial cancers. Elevated expression has been linked to more aggressive disease and a poorer prognosis. IMMU-132 is an ADC comprising a humanized mAb binding to Trop-2 and conjugated to SN-38 (drug: Ab ratio = 7.6), the active metabolite of irinotecan. After finding potent activity in human tumor xenografts, a phase I/II trial was undertaken (NCT01631552). Methods: Pts with relapsed/refractory metastatic cancers were enrolled, starting at a dose of 8 mg/kg given on days 1 and 8 of a 3-week cycle. Dose levels of 8 and 10 mg/kg were chosen for phase II (N=47). Results: Sixty pts with advanced GI cancers were enrolled in phase I/II. Neutropenia was the principal dose-limiting toxicity, with fatigue, diarrhea, nausea, and vomiting as other reported toxicities. In the phase II pts with median prior therapies of 3 (range 1-7), the following moderate/severe drug-related toxicities occurred: neutropenia (Gr 3, 18.8%; Gr 4, 10.4%); fatigue (Gr 3, 14.6%; Gr 4, 0%), anemia (Gr 3, 10.4%; Gr 4, 0%); diarrhea (Gr 3, 4.2%; Gr 4, 0%). Of 29 CRC pts (10 mg/kg [N=9], 8 mg/kg [N=20]), 1 had a PR and 14 had SD as the best response by RECIST, with a time to progression (TTP) of 11.5+ months (mo) for the PR (65% shrinkage) and a median of 4.8+ mo for the SD pts (5 ongoing). This is a disease control rate (DCR) of 51.7%. Thirteen CRC pts had KRAS mutations, 7 with SD (median TTP = 4.4+ mo [range, 2.8-7.8 mo; 3 ongoing]). Of 15 pts with pancreatic ca, 8 had SD as best RECIST response (median TTP = 3.4 mo); DCR=53.3%. Among 11 pts with esophageal ca, 7 had CT assessments with 1 PR (TTP, 6.9+ mo), and 4 SD (TTP, 4.0+, 5.0, 6.0, and 6.9 mo) as best response; DCR=62.5%. Of 5 gastric ca pts, only 3 had post-baseline CT assessments, all with SD (1 with 19% target lesion reduction and an ongoing TTP of 6.7+ mo). Conclusions: IMMU-132 is a novel anti-cancer therapeutic, conjugating a topoisomerase I inhibitor to an internalizing, cancer-selective mAb. This ADC can be given safely and repeatedly over many months to heavily pretreated patients. Encouraging activity in pts with several metastatic gastrointestinal tumors has been observed. Clinical trial information: NCT01631552.
Clinical validation of CTC subtype frequency to prognosis OS in mCRPC patients.
Authors: Ryan Vance Dittamore, Jessica Louw, Nicole A. Schreiber, Ryon Graf, Adam Jendrisak, Ann Johnson, Lyndsey Dugan, Brigit McLaughlin, Glenn Heller, Martin Fleisher, Yipeng Wang, Dena C. Marrinucci, Howard I. Scher
Journal: Journal of Clinical Oncology (2016)

302 Background: CellSearch is an FDA cleared assay that enumerates intact CK+, DAPI+, CD45- cells via EpCAM capture. CTC number is prognostic for survival pre- and post- systemic therapy. These cells are a subset of confirmed genomically altered CTC’s in blood. We report the prognostic significance for OS in mCRPC of CTC subtypes not enumerated by CellSearch including apoptotic CTCs, CK- CTCs, small CTCs, and CTC clusters. Methods: 221 blood samples from 179 unique patients were collected from pts about to begin AR directed (n = 150) or taxane (n = 71) therapy for progressive CRPC. Samples were analyzed utilizing the Epic Sciences platform to enumerate traditional (CK+, abnormal morph), apoptotic (CK+, fragmented nuclei), CK- (CK-/abnormal morph), small (CK+, normal morph), and CTC clusters. Patients were followed for up to 2.3 yrs. Paired CellSearch and Epic traditional CTC counts were collected on 173 patient samples. Results: In paired analysis, Epic traditional CTCs were identified in 86% of patients vs. 67% by CellSearch, and any Epic CTC subtype was found in 96% of the patient samples. Increased frequency of any CTC subtype was a univariate predictor of OS (see table). Conclusions: Epic identified CTC subtypes not identified by CellSearch or other technologies that select or sort based upon size or epithelial expression. Cells were detected in 96% of the patient samples and all 5 subtypes were found to be prognostic for survival. The biologic characterization of CTC subtypes as a biomarker of drug sensitivity is ongoing. The increased clinical sensitivity of subtypes and prevalence of CTCs identified on the Epic platform provides a greatly expanded array of clinically relevant biomarkers to develop predictive liquid biopsy signatures in the metastatic setting. [Table: see text]
Evidence-based clinical practice update: practice guidelines for anterior cruciate ligament rehabilitation based on a systematic review and multidisciplinary consensus
Authors: Nicky van Melick, Robert E H van Cingel, Frans Brooijmans, Camille Neeter, Tony van Tienen, Wim Hullegie, Maria W G Nijhuis-van der Sanden
Journal: British Journal of Sports Medicine (2016)

Aim The Royal Dutch Society for Physical Therapy (KNGF) instructed a multidisciplinary group of Dutch anterior cruciate ligament (ACL) experts to develop an evidence statement for rehabilitation after ACL reconstruction. Design Clinical practice guideline underpinned by systematic review and expert consensus. Data sources A multidisciplinary working group and steering group systematically reviewed the literature and wrote the guideline. MEDLINE and the Cochrane Library were searched for meta-analyses, systematic reviews, randomised controlled trials and prospective cohort studies published between January 1990 and June 2015. Eligibility criteria for selecting studies Included literature must have addressed 1 of 9 predetermined clinical topics: (1) preoperative predictors for postoperative outcome, (2) effectiveness of physical therapy, (3) open and closed kinetic chain quadriceps exercises, (4) strength and neuromuscular training, (5) electrostimulation and electromyographic feedback, (6) cryotherapy, (7) measurements of functional performance, (8) return to play and (9) risk for reinjury. Summary Ninety studies were included as the basis for the evidence statement. Rehabilitation after ACL injury should include a prehabilitation phase and 3 criterion-based postoperative phases: (1) impairment-based, (2) sport-specific training and (3) return to play. A battery of strength and hop tests, quality of movement and psychological tests should be used to guide progression from one rehabilitation stage to the next. Postoperative rehabilitation should continue for 9–12 months. To assess readiness to return to play and the risk for reinjury, a test battery, including strength tests, hop tests and measurement of movement quality, should be used.
P-082 Gastric cancer in Moroccan patients aged 45 years or younger: Clinicopathological features and prognosis
Authors: F. Ziani, S.A. Brahmi, L. Amaadour, B. Meryem, K. Rajae, Z.L. Fatima, A. Samia, M. Nawfel
Journal: Annals of Oncology (2015)
Loss Of Canonic Notch Signaling In The Microenvironment Causes a Myeloproliferative Syndrome Via Derepression Of The miR155 Promoter
Authors: Lin Wang, Huajia Zhang, Sonia Rodriguez-Rodriguez, Liyun Cao, Jonathan Parish, Amy Zollman, Malgorzata Kamocka, H. Scott Boswell, Edward F. Srour, Brahmananda Reddy Chitteti, Taghi Manshouri, Srdan Verstovsek, Reuben Kapur, Angelo A. Cardoso, Nadia Carlesso
Journal: Blood (2013)
The Small-Molecule VEGF-Receptor Inhibitor Pazopanib (GW786034B) Targets Both Tumor and Endothelial Cells in Multiple Myeloma.
Authors: Klaus Podar, Giovanni Tonon, Martin Sattler, Yu-Tzu Tai, Steven LeGouill, Hiroshi Yasui, Kenji Ishitsuka, Rakesh Kumar, Lini N. Pandite, Teru Hideshima, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (2006)