tbuckley/cabot-search huggingface dataset:
A phase I dose escalation study of BIBF 1120 combined with FOLFOX in metastatic colorectal cancer (mCRC) patients (pts).
Authors: H. Prenen, G. D'Haens, J. Capdevila, A. Carrato, A. Sobrero, M. Ducreux, E. François, H. Staines, N. Amellal, E. Van Cutsem
Journal: Journal of Clinical Oncology (2010)

e14054 Background: BIBF 1120 is a potent oral triple angiokinase inhibitor targeting VEGFR 1–3, PDGFR α and β and FGFR 1–3. BIBF 1120 has the potential to be an effective treatment for many solid tumors and is currently in phase III clinical development. It was well tolerated at the dose of 200 mg bid when combined with chemotherapies such as pemetrexed, docetaxel, paclitaxel/carboplatin. It has already shown activity in mCRC patients (pts). We report the results of a Phase I study investigating the tolerability of BIBF 1120 at two different dosages combined with a modified FOLFOX 6 regimen in chemotherapy-naïve mCRC pts. Methods: Main eligibility criteria were performance status (PS) ≤ 2, no prior palliative chemotherapy, adequate biological functions and measurable lesions. The first dose cohort received 150 mg bid BIBF 1120. If well tolerated, this dose was escalated to 200 mg bid. A modified FOLFOX 6 regimen was given concomitantly at a fixed dose, on a 2-weekly treatment cycle basis in both cohorts: 5FU at 400 mg/m2 bolus and 2400 mg/m2 continuous infusion over 46 hours, oxaliplatin at 85 mg/m2 over 2 hours and l-leucovorin at 200 mg/m2 or d,l-leucovorin at 400 mg/m2 over 2 hours. BIBF 1120 PK data were collected during the three first cycles. Dose-limiting toxicities (DLTs) were assessed during the first two cycles. Results: In total, 15 mCRC pts (9 male and 6 female) were enrolled. The median age was 62 years (47–76) and the median PS was 0 (0–2). No pts had prior adjuvant chemotherapy and 73% of pts had abnormal LDH at screening. Only 12 pts were evaluable for the determination of the DLTs over the first two cycles. 3 and 9 pts have been treated with 150 mg bid and 200 mg bid, respectively. Two DLTs occurred, one in the low-dose cohort – a reversible grade 3 diffuse maculopapular skin rash – and one in the high-dose cohort – a reversible grade 3 transaminase elevation with a simultaneous reversible grade 1 bilirubin increase. No other NCI-CTCAE grade 3 or 4 adverse events were observed during the first 2 cycles. Conclusions: This study shows that BIBF 1120 at the dose of 200 mg bid can be safely combined with therapeutic doses of a modified FOLFOX 6 regimen; this combination is being further evaluated in a phase II study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Amgen, AstraZeneca, Fresenius, Merck Serono, MSD, Pfizer, Roche, sanofi-aventis Amgen, Merck Serono, Pfizer, Roche Boehringer Ingelheim
From the Congressional Office of Technology Assessment
Authors: J Eden
Journal: JAMA (1989)

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
Elbasvir–Grazoprevir to Treat Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy
Authors: Gregory J. Dore, Frederick Altice, Alain H. Litwin, Olav Dalgard, Edward J. Gane, Oren Shibolet, Anne Luetkemeyer, Ronald Nahass, Cheng-Yuan Peng, Brian Conway, Jason Grebely, Anita Y.M. Howe, Isaias N. Gendrano, Erluo Chen, Hsueh-Cheng Huang, Frank J. Dutko, David C. Nickle, Bach-Yen Nguyen, Janice Wahl, Eliav Barr, Michael N. Robertson, Heather L. Platt
Journal: Annals of Internal Medicine (2016)

Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID).To evaluate elbasvir-grazoprevir in treating HCV infection in PWID.Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688).Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States.301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT).The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks.The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events.The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event.These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID.Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.Merck & Co.
Association of circulating tumor cells are associated with lymph node metastasis in squamous cell carcinoma of the head and neck region (SCCHN).
Authors: I. Tinhofer, T. Hristozova, R. Konschak, A. Fusi, V. Budach, U. Keilholz
Journal: Journal of Clinical Oncology (2010)

5523 Background: Lymph node metastasis frequently occurs in SCCHN and is generally associated with poor prognosis. The molecular mechanisms regulating tumor cell dissemination and thus the potential targets for novel treatment strategies are still largely unresolved. In this study we tested whether circulating tumor cells (CTCs) are associated with lymph node metastasis in SCCHN. We further established a method to characterize CTCs for the expression of potential drug targets and started with their characterization for EGFR expression. Methods: After informed patient consent, 7.5 ml blood was collected into heparinized tubes. After lysis of erythrocytes samples were enriched for CTCs by depletion of CD45+ blood leukocytes. Samples were stained with fluorescence-labeled antibodies to EpCAM, pan-cytokeratin, EGFR and CD45 or the relevant isotype control antibodies. Absolute numbers of EpCAM+Cytokeratin+CD45- CTCs and their EGFR expression profile were determined by flow cytometry. Results: Currently, a total of 40 SCCHN patients mainly with advanced disease (76% T3-4 stage; 70% N1 or beyond), but all without clinically detectable distant metastases, have been enrolled in this study with the most frequent tumor localization being the oropharynx (65%). Two or more CTCs per 3.75 ml of blood were detected in 40 percent of SCCHN patients (mean ± SD: 3.8 ± 2.6; range: 2-10) whereas none were found in peripheral blood samples from normal control subjects (n=10). The frequency of CTCs depended on the extent of lymph node metastasis with significantly lower CTC numbers in cases with none or only one affected lymph node (p=.01) but did not correlate with T stage (p=.69). In 47% of the cases with detectable CTCs these cells expressed EGFR. Conclusions: The presence of CTCs correlated with lymph node metastasis in SCCHN. The frequency of patients with detectable CTCs was within the range of the reported frequency of patients who will also develop distant metastases. Further studies will clarify whether the presence of circulating tumor cells may be a predictive factor for subsequent hematogenous metastases. In addition, EGFR was identified as one of the potential targets in this rare cell population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Serono Merck Serono Merck Serono
Abstract POSTER-BIOL-1329: The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice
Authors: Jaeyeon Kim, Donna M. Coffey, Lang Ma, Martin M. Matzuk
Journal: Clinical Cancer Research (2015)

Abstract The tumor suppressor p53 is the most frequently mutated gene in high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer. It remains unknown, however, whether p53 mutation can cause HGSC. To address this, we have incorporated a p53 activating mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, generating triple-mutant (TKO) mice. Like DKO mice, TKO mice develop metastatic HGSCs originating from the fallopian tube. Besides, even when fallopian tubes are removed in TKO mice, ovaries alone can spur their own metastatic HGSCs, indicating that p53 mutation can drive HGSC arising from the ovary. To further confirm the ability of p53 mutation to induce ovarian HGSC, we have generated p53R172H-Pten double-mutant (DMu) mice, one genetic control line for TKO mice. As anticipated, these DMu mice develop metastatic HGSCs from the ovary, which spread to the abdominal cavity before killing the mice, just like fallopian tube-deficient TKO mice. Our study therefore shows that the ovary, as well as the fallopian tube, can be a source of high-grade serous ovarian cancer. (Grant support: Marsha Rivkin Ovarian Cancer Challenge Grant; Ovarian Cancer Research Fund (OCRF); F32 NCI National Research Service Award (NRSA); and K99/R00 NCI Pathway to Independence Award) Citation Format: Jaeyeon Kim, Donna M. Coffey, Lang Ma, Martin M. Matzuk. The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1329.
Bevacizumab and irinotecan (BI) for gliomatous leptomeningeal disease.
Authors: S. Taillibert, R. Guillevin, C. Dehais, A. Bellanger, A. M. Omuro
Journal: Journal of Clinical Oncology (2010)

e12526 Background: Leptomeningeal metastasis (LM) may develop in high-grade glioma (HGG) and is associated with poor prognosis and rapid clinical deterioration. Treatment with BI has been associated with high response rates and clinical benefit in HGG, but no efficacy data is available in HGG with LM. Methods: We reviewed 9 grade III-IV glioma pts, treated with BI for LM. Diagnosis relied on positive CSF cytology and/or MRI with unequivocal LM signs. BI (standard doses, Vredenburgh, 2007) were delivered every 14 days until progression or major toxicity (1 cycle= 14 days). Results: Nine pts (glioblastoma = 7; grade 3 glioma = 2) previously treated with radiotherapy and 1-3 lines of chemotherapy (no anti-angiogenic agent) received a median of 3 cycles (1-25) of BI. Median KPS was 50 (40-80), median age was 54 (33-62). Eight pts have progressed and died from their disease; one patient is still on treatment after 25 cycles. Median progression-free and overall survival were 73 (5-374+) and 79 days (16-462+), respectively. Response in intra-parenchymal lesions were seen in 6 pts, with improvements in leptomeningeal enhancement in 4 of those. Neurologic deterioration continued in spite of radiographic improvement in 4 pts, including in 2 of the pts with decreased leptomeningeal enhancement. Such deterioration typically represented worsening of multi-radiculopathy or cranial neuropathy symptoms. The other 2 pts with improvement in radiographic LM had minimal initial symptoms (KPS = 80) and remained clinically stable (≥ 1 year). One symptomatic intraparenchymal tumor hemorrhage occurred but no bleeding was observed in subependymal nodules or subarachnoid space. Conclusions: BI was safe in HGG with LM and seems overall more effective than other treatments, especially in pts with good KPS and few early neurological symptoms of LM. Radiographic and clinical improvement of intraparenchymal disease were frequent, but symptoms from LM did not improve, or even progressed despite radiographic improvement. A decrease in VEGF-mediated vascular permeability may be masking radiographic progression of LM, which seems to continue with nonenhancing spread along nerve roots. Alternative treatments are needed to prevent this pattern of disease progression in HGG. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Genentech, Schering-Plough Roche
Immune response to Mycobacterium tuberculosis in young contacts with discordant immunological test results
Authors: Mohamed Jeljeli, Valérie Guérin-El Khourouj, Virginie Pommelet, Sophie Guilmin-Crepon, Myriam Hormi, Pierre Gressens, Albert Faye, Ghislaine Sterkers
Journal: Journal of Infection (2016)
New Lens Helps Patients See Near, Far, and In-between
Authors: Rebecca Voelker
Journal: JAMA (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 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
Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes
Authors: Rabab Nasrallah, Eva M. Fast, Parham Solaimani, Kathy Knezevic, Alexia Eliades, Rahima Patel, Roshana Thambyrajah, Ashwin Unnikrishnan, Julie Thoms, Dominik Beck, Chris S. Vink, Aileen Smith, Jason Wong, Mairi Shepherd, David Kent, Rahul Roychoudhuri, Fabian Paul, Julia Klippert, Annette Hammes, Thomas Willnow, Bertie Göttgens, Elaine Dzierzak, Leonard I. Zon, George Lacaud, Valerie Kouskoff, John E. Pimanda
Journal: Blood (2016)
Polymorphisms in the
Authors: Leslie A. Lange, Ethan M. Lange, Russell P. Tracy, Alexander P. Reine
Journal: JAMA (2007)

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
Genetic Predisposition to Molecular Response in Patients with Myeloproliferative Neoplasms Treated with Hydroxycarbamide
Authors: Anna Angona, Beatriz Bellosillo, Alberto Alvarez-Larrán, Luz Maria Martinez-Aviles, Laura Camacho, Silvia Pairet, Concepción Fernández, Carles Besses
Journal: Blood (2012)
Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation
Authors: Kozo Okada, William F. Fearon, Helen Luikart, Hideki Kitahara, Kyuhachi Otagiri, Shigemitsu Tanaka, Takumi Kimura, Paul G. Yock, Peter J. Fitzgerald, Alan C. Yeung, Hannah A. Valantine, Kiran K. Khush, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2016)
<sup>89</sup>Zr-bevacizumab PET imaging of disease manifestations in patients with Von Hippel-Lindau disease.
Authors: Sjoukje Oosting, Sophie J. Van Asselt, Adrienne H. Brouwers, Alfons H. H. Bongaerts, Julia Steinberg, Johan R. de Jong, Marjolijn N. Lub-de Hooge, Anouk N.A. Van der Horst-Schrivers, Anna Maria Elisabeth Walenkamp, Eelco W. Hoving, Wim J. Sluiter, B. A. Zonnenberg, Elisabeth De Vries, Thera P. Links
Journal: Journal of Clinical Oncology (2014)

11090 Background: Patients withvon Hippel-Lindau (VHL) disease develop benign and malignant vascular tumors. Local vascular endothelial growth factor (VEGF)-A production is likely involved in the development of disease manifestations and is a treatment target for antiangiogenic therapy. Bevacizumab binds VEGF-A. We aimed to assess whether 89Zr-bevacizumab positron emission tomography (PET) can visualize VHL manifestations and differentiate progressive from non-progressive lesions, and to compare PET results with plasma VEGF-A levels. Methods: Adult VHL patients with ≥ 1 measurable hemangioblastoma were eligible. The tracer 89Zr-bevacizumab (37 MBq) was injected 4 days before the PET scan. Maximum standardized uptake values (SUVmax) were calculated. PET scans were fused with routine MRI of the central nervous system (CNS) and abdomen. Progressive lesions were defined as new lesions, lesions that became symptomatic and lesions ≥ 10 mm that increased ≥ 10% and ≥ 4 mm on repeat anatomic imaging within 12 months. Plasma VEGF-A was measured before 89Zr-bevacizumab injection and with follow-up anatomic imaging. Results: Twenty-two patients were enrolled. 89Zr-bevacizumab PET visualized 59 known VHL manifestations (0-17 per patient, 24 in the CNS) with a median SUVmax of 8.5 (range 1.3-35.8) and a detection rate of 30.8% for lesions ≥ 10 mm. Two of 7 hotspots on PET without substrate on baseline anatomic imaging were detected as lesions on MRI during follow-up at 10 and 12 months. Nine out of 25 progressive lesions and 27 out of 175 non-progressive lesions were visible on PET (positive predictive value 25%, negative predictive value 90%). Progressive and non-progressive lesions had similar SUVmax (median 4.8, range 0.9-8.9 versus 6.7, range 1.3-35.8, P= .14). Plasma VEGF-A did not correlate with imaging results and was similar in patients with and without progressive lesions. Conclusions: VHL manifestations can be visualized with89Zr-bevacizumab PET. 89Zr-bevacizumab uptake and plasma VEGF-A cannot be used to predict progression. High SUVmax in VHL lesions proves local bevacizumab accumulation and could potentially be used to select patients for bevacizumab treatment. Supported by the VHL Family Alliance. Clinical trial information: NCT00970970.
Tissue Distribution of a Minor Antigen, but Not PD-1 Expression, Predicts the Antileukemia Efficacy of Adoptively Transferred, Antigen-Specific T-Cells in a Preclinical Model of Allogeneic Transplant
Authors: Jessica C. Shand, Christian M. Capitini, Haiying Qin, Nicole Nasholm, Terry J. Fry
Journal: Blood (2012)
Role of farnesoid X receptor in establishment of ontogeny of phase-I drug metabolizing enzyme genes in mouse liver
Authors: Lai Peng, Stephanie Piekos, Grace L. Guo, Xiao-bo Zhong
Journal: Acta Pharmaceutica Sinica B (2016)

The expression of phase-I drug metabolizing enzymes in liver changes dramatically during postnatal liver maturation. Farnesoid X receptor (FXR) is critical for bile acid and lipid homeostasis in liver. However, the role of FXR in regulating ontogeny of phase-I drug metabolizing genes is not clear. Hence, we applied RNA-sequencing to quantify the developmental expression of phase-I genes in both Fxr-null and control (C57BL/6) mouse livers during development. Liver samples of male C57BL/6 and Fxr-null mice at 6 different ages from prenatal to adult were used. The Fxr-null showed an overall effect to diminish the "day-1 surge" of phase-I gene expression, including cytochrome P450s at neonatal ages. Among the 185 phase-I genes from 12 different families, 136 were expressed, and differential expression during development occurred in genes from all 12 phase-I families, including hydrolysis: carboxylesterase (Ces), paraoxonase (Pon), and epoxide hydrolase (Ephx); reduction: aldoketo reductase (Akr), quinone oxidoreductase (Nqo), and dihydropyrimidine dehydrogenase (Dpyd); and oxidation: alcohol dehydrogenase (Adh), aldehyde dehydrogenase (Aldh), flavin monooxygenases (Fmo), molybdenum hydroxylase (Aox and Xdh), cytochrome P450 (P450), and cytochrome P450 oxidoreductase (Por). The data also suggested new phase-I genes potentially targeted by FXR. These results revealed an important role of FXR in regulation of ontogeny of phase-I genes.