tbuckley/cabot-search huggingface dataset:
Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales
Authors: Shan Liu, Wei Wei, Bo Xie, Hua Yue, Dezhi Ni, Yali Bao, Guanghui Ma, Zhiguo G. Su
Journal: Advanced Healthcare Materials (2016)

In contrast to traditional strategies based on external driving forces, an internal path for intratumoral delivery is explored by degrading the tumor microenvironment component hyaluronan. Natural hyaluronidase PH20 and constructed long‐acting PH20‐Fc have been used to achieve this objective. It has been then evaluated how these agents facilitate the diffusion of the following typical therapeutic agents varying in nanoscales: doxorubicin (≈1.5 × 1.0 × 0.7 nm) chemotherapy, trastuzumab (10–15 nm) biotherapy, and gold nanorod (≈100 × 35 nm) thermotherapy. In traditional 2D cultures, PH20 and PH20‐Fc have little influence on cytotoxicity due to lack of a tumor microenvironment. However, the cytotoxicities of the three therapeutic agents in 3D tumor spheroids are all enhanced by PH20 or PH20‐Fc because hyaluronan degradation facilitates therapeutic penetration and accumulation. Furthermore, in vivo evaluations reveal that the significantly prolonged circulation time of PH20‐Fc leads to accumulation in the tumor and subsequent hyaluronan degradation. Consequently, PH20‐Fc coadministration further inhibits tumor growth. The performance of PH20‐Fc varies for the three therapeutic agents due to their different nanoscales. Trastuzumab benefits most from combination with PH20‐Fc. The results provide here novel insights that can aid in the development of more effective hyaluronidase‐based therapeutic systems.
C1q and HMGB1 reciprocally regulate human macrophage polarization
Authors: Myoungsun Son, Amit Porat, Mingzhu He, Jolien Suurmond, Frances Santiago-Schwarz, Ulf Andersson, Thomas R. Coleman, Bruce T. Volpe, Kevin J. Tracey, Yousef Al-Abed, Betty Diamond
Journal: Blood (2016)
Efficacy and safety of everolimus in maintenance liver transplant recipients: results of a multi-center, randomized, open-label conversion study
Authors: Lionel Rostaing, Frederik Nevens, Paolo De Simone, Herold J Metselaar, Martina R Sterneck, Emiliano Giostra, Evaristo Varo, Jerome Dumortier
Journal: Hepatology (2008)
Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and down-regulates survivin/BIRC5 gene expression
Authors: W. Glienke, L. Maute, E. Milz, N. Bauer, L. Bergmann
Journal: Journal of Clinical Oncology (2007)

15030 The anti-apoptotic gene survivin/BIRC5 plays an important role in cellular proliferation and survival of cancer cells. Regulated by constitutively activated STAT3, Survivin/BIRC5 may be a target for inhibiting cellular proliferation in pancreatic cancer cell lines. The purpose of this study was (a) to determine the effect of curcumin (diferuloylmethane) on survivin/BIRC5 expression and (b) a possible role of STAT3 activation in Survivin/BIRC5 expression in pancreatic cancer cell lines. We have incubated four pancreatic cancer cell lines with different amounts of curcumin. The expression of Survivin/BIRC5 on mRNA and protein level was measured with RT-PCR and western blot analysis. The activation of STAT3 through phosphorylation, contributing to the regulation of survivin was analyzed with western blot analysis. The incubation of the pancreatic cancer cell lines with curcumin resulted in a down-regulation of cellular proliferation in all cell lines tested but with different rates of inhibition. The expression of survivin/BIRC5 on mRNA and protein level was significantly down-regulated after treatment with 30 μM. Curcumin blocked the phosphorylation of STAT3 in a concentration-dependent manner. Treatment of pancreatic cancer cell lines with curcumin resulted in an induction of apoptosis as measured with FacScan analysis. We conclude that curcumin inhibits several key factors in cancer cellular pathways and may have the potential to be investigated in pancreatic cancer. No significant financial relationships to disclose.
Symptomatic skeletal events (SSE) in patients with advanced prostate cancer: Results from a phase III trial of denosumab for the prevention of skeletal-related events.
Authors: Laurence Klotz, Matthew Raymond Smith, Robert E. Coleman, Kenneth B. Pittman, Piotr Milecki, Rachel Wei, Arun Balakumaran, Karim Fizazi
Journal: Journal of Clinical Oncology (2014)

5075 Background: In a randomized controlled trial of men with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid (ZA) for reducing skeletal-related events (SRE, defined as pathological fracture, surgery or radiation to bone [including the use of radioisotopes], or spinal cord compression) (Fizazi, et al. Lancet 2011;377:813-822.). Recently, the composite endpoint of symptomatic skeletal event (SSE, defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression) was introduced as an alternative term/clinical trial endpoint to describe skeletal morbidity. Methods: Men with CRPC, ≥ 1 bone metastasis, and no prior IV bisphosphonate use received either SC denosumab 120 mg or IV ZA 4 mg (adjusted for creatinine clearance) in a blinded fashion every 4 weeks. Oral calcium and vitamin D supplements were recommended. SSEs included pathologic fractures considered symptomatic by the investigator, spinal cord compression and surgery and radiation to bone. Results: As previously reported, fewer men who received denosumab than ZA had confirmed first SREs, and experienced multiple SREs (Table). Similarly, fewer patients in the denosumab group than the ZA group had confirmed first SSE and multiple SSEs. The median (95% CI) estimate of time to first SSE (superiority analysis) for denosumab was not reached (28.8 mo, not estimable), and for ZA it was 24.2 (20.7, 30.2) mo (HR = 0.78 [0.66, 0.93], P < 0.01). Conclusions: Denosumab reduced the risk of skeletal events in men with CRPC regardless of endpoint definition as SRE or SSE. The risk of developing SSEs was reduced by up to 22% when comparing denosumab with ZA. Clinical trial information: NCT00321620. Number of confirmed skeletal events, n (%) Denosumab (N = 950) ZA (N = 951) Hazard or rate ratio (95% CI) First SSE 241 (25.4%) 289 (30.4%) HR = 0.78 (0.66, 0.93) P < 0.01 First SRE 341 (35.9%) 386 (40.6%) HR = 0.82 (0.71, 0.95) P < 0.01 Multiple SSEs 329 409 RR = 0.78 (0.65, 0.92) P < 0.01 Multiple SREs 494 584 RR =0.82 (0.71, 0.94) P < 0.01
A phase II multicentre study of oxaliplatin (Ox) in combination with paclitaxel (Px) in patients (pts) who failed cisplatin (CDDP) based chemotherapy (CT) for germ cell tumors (GCT)
Authors: C. Theodore, A. Flechon, K. Fizazi, C. Chevreau, J. P. Delord, J. P. Lotz, L. Geoffrois, P. Kerbrat, B. Bui, Y. Yataghene
Journal: Journal of Clinical Oncology (2004)

4534 Background: pts with either CDDP refractory (REF) or with a poor prognosis relapse (REL) GCT, defined as progressing less than 2 or between 2 and 6 months (mos) of CDDP administration respectively have dismal prognosis.Px induces 11 to 26% response rates (RR) in a similar pt population.Ox is a platinum compound with a lack of cross resistance with CDDP. Methods: REF and REL pts, who had received at least one line of CT containing Etoposide+CDDP. Treatment: combination of Px (175 mg/m2, 3h infusion) followed by Ox (130 mg/m2, 2h infusion) administered q3 weeks. Endpoints were RR (WHO criteria) and tumor marker decrease (TMD)>90% or >50%.The 2-step modified Gehan design was used for sample size determination. Results: 26 pts were enrolled; median age 31 yrs (range 18–46); PS 0/1:13/13; 18 had non seminoma (among whom 5 mediastinal primaries), 2 seminoma and 6 mixed GCT; 16 pts were REF and 10 pts were REL; 22, 3 and one pts had previously received 2, 3 and 5 lines of CDDP based CT. A total of 87 cycles (median 4,range 1 to 7) were administered. The worst toxicity (NCI-CTC) consisted in: grade (G) 3 and 4 neutropenia (N) in 3 and 4 pts respectively, G 3 anemia in 3 pts, G 3 thrombocytopenia in one pt, G 3 neuropathy in one pt and G3 infection without N in one pt. One Partial Response with normal TM (lasting 18+ mos) and 4 TMD > 90% and 3 TMD > 50% were observed. Median Time to Tumor Progression and Overall Survival (months) were 2.0 [95% CI :1.5 - 2.5] and 8.8 [95% CI : 5 -12] respectively. However 2 pts were eventually salvaged by surgical exeresis of limited disease and are alive free of disease progression at 13+ and 23+ months respectively. Conclusions: Ox-Px Combination is safe and looks active in refractory and relapsed GCT, it warrants further developments within the treatment strategy in these patients. No significant financial relationships to disclose.
Early Clinical and Pharmacokinetic Results of Lower Dose Fludarabine and Cyclophosphamide, and High Dose Rituximab (FCR-Lite) for Patients with Untreated Chronic Lymphocytic Leukemia (CLL).
Authors: Ahmad A. Tarhini, S. Land, D. Meisner, L. Pietragallo, M. Sulecki, F. Lim, Gauri J. Kiefer, R. Pinkerton, J. Obsorn, S. Sukaly, P.M. Schaefer, Kenneth A. Foon
Journal: Blood (2006)
Tumor mutational burden as a potential biomarker for PD1/PD-L1 therapy in colorectal cancer.
Authors: Thomas J. George, Garrett Michael Frampton, James Sun, Kyle Gowen, Mark Kennedy, Joel R. Greenbowe, Alexa Betzig Schrock, Siraj Mahamed Ali, Samuel Jacob Klempner, Aram F. Hezel, Jeffrey S. Ross, Phil Stephens, Vincent A. Miller, David Fabrizio
Journal: Journal of Clinical Oncology (2016)

3587 Background: Biomarkers capable of predicting response to checkpoint inhibitor therapies represent a significant clinical need. Increased tumor neo-antigenic burden has been linked to PD1/PD-L1 therapeutic response in several conditions including metastatic melanoma, non-small cell lung carcinoma and microsatellite instable (MSI-H) colorectal cancer (CRC). However, the challenges and high cost associated with neo-antigen discovery has shifted focus towards more efficient methods of response stratification. As such, mutational burden determination from whole exome sequencing and comprehensive genomic profiling (CGP) has emerged as a potential solution. In CRC, MSI-H may serve as a predictive biomarker for activity of PD1/PD-L1 therapy, reflecting an unquantified immunogenic mutational burden. Herein, we explore the ability to quantify tumor mutational burden (TMB) as a potential predictive biomarker of PD1/PD-L1 therapy in CRC. Methods: Formalin-fixed, paraffin embedded tissue sections from 2013 cases of CRC were sequenced with CGP (FoundationOne assay). MSI status and PD-L1 gene amplification were determined as previously described. TMB was calculated by counting mutations across a 1.25Mb region spanning 315 genes. Patients were classified as TMB high or low using the top quartile threshold and microsatellite instable (MSI-H) or stable (MSS) using a computational algorithm developed by Foundation Medicine. Results: MSS tumors were observed in 1934 of 2013 (95.2%) cases and MSI-H tumors were observed in 79 of 2013 (3.9%) cases. 79 of 79 (100%) MSI-H cases were TMB high (range 16.8-72.7 mut./Mb) and 1510 of 1934 (78.1%) MSS cases were TMB low (range 0.0-8.0 mut./Mb). Consequently, 424 of 1934 (21.9%) MSS cases were confirmed as TMB high (range 8.8-43.1 mut./Mb). Of note, less than 0.1% of cases featured PD-L1 gene amplifications. Conclusions: Tumor mutational burden as estimated by CGP, as opposed to MSI assessment alone, significantly increases the number of patients with metastatic CRC who may benefit from checkpoint inhibitor based therapeutic approaches. Investigations to validate this biomarker are ongoing.
P1-056: The clinical significance of solitary extrathoracic abnormality on whole body FDG-PET in patients with NSCLC
Authors: Heejong Baek, Jae Soo Koh, Jae Cheol Lee, Gi Jeong Cheon, Chang-Woon Choi, Sang Moo Lim
Journal: Journal of Thoracic Oncology (2007)
A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer
Authors: Rana R. McKay, Lillian Werner, Elahe A. Mostaghel, Rosina Lis, Olga Voznesensky, Zhenwei Zhang, Brett T. Marck, Alvin M. Matsumoto, Liran Domachevsky, Katherine A. Zukotynski, Manoj Bhasin, Glenn J. Bubley, Bruce Montgomery, Philip W. Kantoff, Steven P. Balk, Mary-Ellen Taplin
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride. Experimental Design: Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles. After this time, high-dose dutasteride (3.5 mg daily) was added. Patients continued therapy until study withdrawal or radiographic progression. Repeat metastasis biopsy was obtained at progression. The primary endpoint was to assess mechanisms of resistance. Serum hormone and abiraterone levels were assessed. Tissue was assessed for androgen receptor (AR) and AR splice variant-7 (ARV7) expression. Results: Forty patients were enrolled. Sixty percent (n = 24) achieved a ≥50% reduction in prostate-specific antigen (PSA). The median time to radiographic progression was 11 months. Nearly all baseline (n = 29 of 31) and posttreatment (n = 16 of 16) tumors tested for AR nuclear expression were positive. Of those tested, ARV7 expression was present in 48% (n = 10 of 21) of baseline and 42% (n = 5 of 12) of treatment discontinuation specimens. Compared with patients with higher serum abiraterone levels at treatment discontinuation, patients with lower levels had higher circulating androgens. Conclusions: Despite increased androgen synthesis inhibition, we demonstrate that tumor AR axis remains important in disease progression. We highlight that abiraterone metabolism and pharmacokinetics may play a role in resistance. The noncomparative design limits conclusions on the efficacy of dual therapy with abiraterone and dutasteride, but the results support development of further multifaceted approaches toward AR inhibition. Clin Cancer Res; 23(4); 935–45. ©2016 AACR.
BSc2118, a Novel Proteasome Inhibitor, Shows Anti-Tumor Activity in Multiple Myeloma and Mantle Cell Lymphoma.
Authors: Jan Sterz, Christian Jakob, Ulrike Kuckelkorn, Hannes A. Braun, Martin Kaiser, Claudia Fleissner, Lorenz Kleeberg, Ulrike Heider, Kurt Possinger, Peter M. Kloetzel, Orhan Sezer, Ivana Zavrski
Journal: Blood (2006)
Commentary: Diagnostic devices in clinical trials have high stakes for patient care
Authors: Vinay K Rathi, Harlan M Krumholz, Joseph S Ross
Journal: BMJ (2016)

Following concerns around the use of faulty point-of-care diagnostic devices in clinical trials, Joseph Ross and colleagues call on regulators to take action

The widely used anticoagulant rivaroxaban (Xarelto) has become the centre of considerable scientific and regulatory dispute. A key clinical trial supporting US Food and Drug Administration (FDA) approval was recently found to have used faulty point-of-care devices for monitoring international normalised ratio (INR).1 2 This ongoing episode provides important insights into regulation challenges for diagnostic devices and the far reaching effects these devices have on clinical research and patient care.

The FDA defines in vitro devices as devices using human specimens to guide the treatment or prevention of disease, and clears the large majority for use through the 510(k) process for moderate risk devices, which requires only that a device be “substantially equivalent” to another previously cleared device.3

In 2002, the FDA cleared the INRatio model used in the ROCKET trial4 based on substantial equivalence to the CoaguChek S point-of-care monitor. This approval shows several critical challenges that the FDA faces with clearing diagnostic devices:

Predicates— Analytical and clinical validity of predicate devices may be inherently limited. The CoaguChek S was found to underestimate INR compared with laboratory reference methods, with >40% of measurements deviating by ≥15%,5 and in 2006 was subject to a class II (moderate risk) FDA recall because defective testing strips produced falsely raised results. Currently, no restrictions prohibit using voluntarily recalled devices as predicates, and devices with malfunctioning predicates cannot be readily identified for further testing after clearance.

Clinical testing— Diagnostic devices rarely require prospective clinical studies for clearance, and these studies may not be generalisable when …
Heterogeneous Distribution of the JAK2 Val617Phe Activating Mutation in Familial Myeloproliferative Disorders.
Authors: Christine Bellanne-Chantelot, Myriam Labopin, Isabelle Chaumarel, Francois Delhommeau, Gwendoline Leroy, Florence Bellanger, Gilles Thomas, William Vainchenker, Albert Najman
Journal: Blood (2005)
Thrombotic and Embolic Complications Associated With Atrial Arrhythmia After Fontan Operation
Authors: Alexander C. Egbe, Heidi M. Connolly, Christopher J. McLeod, Naser M. Ammash, Talha Niaz, Vidhushei Yogeswaran, Joseph T. Poterucha, Muhammad Y. Qureshi, David J. Driscoll
Journal: Journal of the American College of Cardiology (2016)
Relationship between Prostatic Acid Phosphatase and Prostate-Specific Antigen Serum Levels and Prostatic Volume in Benign Prostate Hyperplasia
Authors: S. Omacini, R. Mione, M. Barichello, U. Santucci Delli Ponti, A. Bolgan, G.P. Contemori, S. Petracco, G.C. Capitanio, P.M. Donisi, M. Gion
Journal: European Urology (1992)
P1176 : Serum autotaxin is associated with significant impairment of health related quality of life, clinical and biochemical factors in primary biliary cirrhosis
Authors: E. Wunsch, A.E. Kremer, J. Trottier, M. Krawczyk, O. Barbier, F. Lammert, P. Milkiewicz
Journal: Journal of Hepatology (2015)
Despite geographical heterogeneity in baseline use, guideline-directed treatments for acute coronary syndromes improve in all regions from 1999 to 2003. The Global Registry of Acute Coronary Events
Authors: RH Mehta, Frans Van de Werf, A Avezum, G Agnelli, KA Eagle, RJ Goldberg, O Dabbous, CB Granger
Journal: Circulation (2005)
Improving Health and Health Care in the United States
Authors: Howard K. Koh
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
Gemcitabine-based polychemotherapy for advanced pancreatic cancer (APC): Is it ready for prime time? A pooled analysis of 3,682 patients (pts) enrolled in 12 phase III trials
Authors: M. Milella, P. Carlini, A. Gelibter, E. Ruggeri, A. Ceribelli, M. Pino, E. Terzoli, F. Cognetti, D. Giannarelli, E. Bria
Journal: Journal of Clinical Oncology (2006)

4118 Background: Since the introduction of gemcitabine (G), attempts have been made to develop G-based combination regimens to improve the dismal outcome of APC pts. Results of randomized trials, however, have been conflicting and single-agent G presently remains the standard of care for such pts. Methods: All prospective phase III trials comparing single-agent G with G-based polychemotherapy regimens (poly-G) were considered eligible. A pooled analysis was performed and event-based relative risk ratios (RR) with 95% CI were derived through both a fixed- and a random-effect model approach, exploring OS as the primary outcome and PFS and ORR as secondary outcomes. Heterogeneity between different trials was also taken into account. Results: Twelve trials involving 3682 pts were identified. The analysis was conducted considering three different subgroups: 1) overall population (3682 patients, 12 trials), 2) platinum-containing poly-G (PG) vs G (768 pts, 5 trials), and 3) fluoropyrimidine-containing poly-G (FG) vs G (1640 pts, 4 trials). As shown in the table, no significant differences in the primary outcome (OS) were observed in any of the three groups analyzed. Conversely, a significant advantage for poly-G was evident with regard to both PFS and ORR in the overall population as well as in the PG vs G subgroup, although with some heterogeneity. A heterogeneous non-significant trend towards a better PFS and ORR outcome was also observed in the FG vs G subgroup. Conclusions: Single-agent G remains the treatment of choice in APC pts. However, the addition of platinum compounds to G appears to significantly improve PFS and ORR, possibly justifying the use of platinum-based poly-G in younger and fit patients. [Table: see text] No significant financial relationships to disclose.
55P Prognostic Role of Palpability in Screen Detected Breast Cancer (BC)
Authors: O. Brouckaert, C. Truyers, E. Kellen, A. Schoneveld, I. Vergote, H. Wildiers, P. Moerman, M. Christiaens, E. Van Limbergen, P. Neven
Journal: Annals of Oncology (2012)
E-Cigarettes, Youth, and the US Food and Drug Administration’s “Deeming” Regulation
Authors: Micah L. Berman, Y. Tony Yang
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal