tbuckley/cabot-search huggingface dataset:
Phase Ib study of eribulin (ERB) and cyclophosphamide (CTX) in metastatic breast cancer (MBC).
Authors: Thach-Giao Truong, Michael Pelayo, Jennifer A. Grabowsky, Michelle E. Melisko, Mark Jesus Mendoza Magbanua, Mark M. Moasser, Anne Reinert, Jimmy Hwang, John W. Park, Pamela N. Munster, Hope S. Rugo
Journal: Journal of Clinical Oncology (2013)

1095 Background: ERB is a non-taxane microtubule inhibitor approved for the treatment (Tx) of taxane (TAX) and anthracycline-treated MBC based on improved OS compared to treatment of physician choice. In the adjuvant setting, docetaxel/CTX (TC) was superior to doxorubicin/CTX for DFS and OS. ERB is active in TAX-resistant disease with a low rate of peripheral neuropathy (PN); its primary dose-limiting toxicity (DLT) is bone marrow suppression. We hypothesized that the combination of ERB and CTX would be well tolerated and active in patients with TAX-resistant disease, with potential applicability to the adjuvant setting. Methods: We designed a 3+3 phase Ib study of ERB, administered in 2 escalating doses on day 1 and 8, with CTX 600 mg/m 2 day 1 every 21 days. Eligibility included PN ≤ grade 1. Correlative studies to identify predictors of response and toxicity included whole blood for SNPs, GWAS, circulating tumor cells (CTC), and archived tumor RNA/protein expression analysis. Toxicity assessment included QoL and evaluation of PN. Results: 6 patients (pts) with MBC, median age 50 (47-63), were enrolled. All pts had prior TAX exposure and 4 pts had baseline grade 1 PN. Tumor characteristics included hormone receptor + (5 pts), HER2+ (2 pts), and triple-negative (1 pt). Median number of prior Tx for MBC was 5 (1-8). No DLTs were observed; the RP2D is eribulin 1.4 mg/m2 on D1 and D8 with CTX D1 600mg/m2. Neutropenia was the only G3/G4 non-DLT observed at this dose, requiring GCSF support in cycle1 in 2 of 3 pts. All grade toxicities included neutropenia (50%), thrombocytopenia, fatigue, nausea, PN, rash, mucositis, alopecia (33% each), and elevated liver enzymes (17%). Pts received a median of 5.5 cycles (range 3-13), with 3 pts still on Tx. Responses included 2PRs (33%) and 4 SD (67%). 2 pts stopped study Tx for QoL and continued ERB alone. Only 2 pts met threshold of &gt;5CTC/7.5ml at baseline; these had a mean decrease of 90.5% at the start of cycle 2. Conclusions: ERB and CTX is a well-tolerated regimen with promising activity in MBC, with the primary toxicity being neutropenia requiring growth factor support. A phase II study in MBC is underway. Additional correlative studies are ongoing including molecular analyses of CTC. Clinical trial information: NCT01554371.
Safety analysis of a phase II study of cyclophosphamide, vincristine, non-pegilated liposomal doxorubicin (Myocet), and prednisone + rituximab in biweekly regimen (R-COMP-14) as primary treatment of non-Hodgkin lymphoma
Authors: F. R. Garcia Arroyo, J. Herrero, M. Provencio, J. Gómez-Codina, A. Rueda, M. Llanos
Journal: Journal of Clinical Oncology (2006)

17532 Background: Gold standard treatment of CD20+ aggressive B-cell non-Hodgkin lymphoma, R-CHOP, has been suggested to improve outcome when administered as dose-dense regimen supported with G-CSF. The non-pegylated liposomal doxorubicin (Myocet) has an improved safety profile compared to standard formulations of doxorubicin. Standard R-CHOP regimen has been modified replacing doxorubicin with Myocet, administered on a biweekly basis (R-COMP-14) looking for an increase in efficacy without impairing tolerability Methods: Single arm, multicentric, 2-step (Simon design) phase II trial. Newly diagnosed, diffuse large B-cell lymphoma, stages III, IV or I, II with IPI ≥ 1, CD20+, eligible patients (Pt) were treated with Myocet 50 mg/m 2 , cyclophosphamide 750 mg/m 2 , vincristine 1.4 mg/m 2 (max. 2 mg), rituximab 375 mg/m 2 and prednisone 100 mg/d d1–5 in biweekly cycles. Pegilated filgastrim (Neulasta™) was administered on day 2 of the cycle. Response was assessed after 3 cycles, and patients with PR or CR received 5 additional cycles. A safety analysis was planned by protocol with data of first patients included Results: The median age of the 13 Pt included was 59 (range 28–64). At baseline 53.9% Pt had III-IV stage and 41.7% had extraganglionar involvement. Median basal LVEF was 66% (range 44–79). A median of 7 cycles of R-COMP were administered. The median relative dose intensity per week for Myocet was 94.9%. 6.2% of the cycles were delayed and 8.6% of the cycles were dose reduced. There were 2 episodes of febrile neutropenia. G3 asthenia, G3 neurotoxicity and G3 related infection were found in one cycle each. One patient had G3 hepatic toxicity resolved with dose reduction. At the end of treatment the median LVEF was 65.52% (range 52–76), there was no cardiac event related to the treatment. 84.6% of Pt had complete or partial response (7 RC, 2 uRC, 2 PR, 1 SD, 1 PD) at the end of the study Conclusions: In this small safety group of Pt that received the dose-dense regimen, the preliminary results suggest that R-COMP-14 supported with Neulasta is a well tolerated and effective regimen. Recruitment will proceed as planned (75 Pt). No significant financial relationships to disclose.
C20orf94 deletion Is Strongly Associated with TEL/AML1 Rearrangement and Links Illegitimate V(D)J Recombination with Gender Bias In Childhood Acute Lymphoblastic Leukemia
Authors: Barbara Meissner, Thies Bartram, Cornelia Eckert, Rolf Koehler, Jan Trka, Ivana Hermanova, Petra Breithaupt, Martin Zimmermann, Gunnar Cario, André Schrauder, Anja Möricke, Giovanni Cazzaniga, Geertruy Kronnie, Renate Kirschner-Schwabe, Arend von Stackelberg, Jochen Harbott, Renate Panzer-Gruemayer, Jean-Pierre Bourquin, Andre Franke, Eva Ellinghaus, Stefan Schreiber, Claus R Bartram, Martin Schrappe, Martin Stanulla
Journal: Blood (2010)
In vivo optical pathology of paclitaxel efficacy on the peritoneal metastatic xenografts of gastric cancer using multiphoton microscopy.
Authors: Koji Tanaka, Tadanobu Shimura, Masato Okigami, Yuji Toiyama, Yuhki Morimoto, Takahito Kitajima, Satoru Kondo, Mikio Kawamura, Susumu Saigusa, Yoshinaga Okugawa, Masaki Ohi, Yasuhiro Inoue, Keiichi Uchida, Toshimitsu Araki, Yasuhiko Mohri, Akira Mizoguchi, Masato Kusunoki
Journal: Journal of Clinical Oncology (2013)

e22205 Background: Peritoneal metastasis shows an extremely poor prognosis in patients with gastric cancer. Clinically, the tumor response to chemotherapeutics depends on anatomical location of metastasis. Metastatic tumor xenografts have been shown to be more resistant to chemotherapy than subcutaneous non-metastatic tumor xenografts in preclinical murine model. We have reported a method of in vivo optical pathology using multiphoton microscopy (MPM) in colorectal liver metastatic tumor xenograft model. Aim: We established a method of time-series in vivo optical pathology of peritoneal metastatic xenografts of gastric cancer using MPM. Then, we imaged and evaluated paclitaxel efficacy in the tumor microenvironment with regard to both tumor cell itself and intravascular change in tumor vessels. Methods: Red fluorescent protein (RFP) expressing human gastric cancer cell line (NUGC4) was inoculated into the peritoneal cavity of green fluorescent protein (GFP) expressing nude mice. Paclitaxel (10 mg/kg) was administered three times a week for more than three weeks. Intravital MPM was performed before and after paclitaxel treatment for the exteriorized peritoneal metastatic lesion in the same living mouse. Results: Four to six weeks later, RFP-NUGC4 cells formed macroscopic peritoneal metastases. Red-colored cancer cells and green-colored surrounding stroma with tumor vessels were clearly imaged at the cellular level (in vivooptical pathology). Their cross-sectional images were obtained from the tissue surface to the area of depth of 200 μm (z-stacks imaging). After paclitaxel treatment, tumor cell fragmentation, condensation, swelling and intracellular vacuoles were observed. Within the tumor vessels, platelet aggregation and platelet adhesion to endothelial cells were observed. Conclusions: In vivo optical pathology using MPM provides histopathological information about three-dimensional tissue microarchitecture without tissue shrinkage by fixation and tissue destruction by microtome-sectioning. Our method may become a powerful tool to evaluate the tumor response to new chemotherapeutics on ‘metastatic site’ in preclinical tumor xenograft model.
Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results
Authors: Richard Pebody, Fiona Warburton, Joanna Ellis, Nick Andrews, Alison Potts, Simon Cottrell, Jillian Johnston, Arlene Reynolds, Rory Gunson, Catherine Thompson, Monica Galiano, Chris Robertson, Rachel Byford, Naomh Gallagher, Mary Sinnathamby, Ivelina Yonova, Sameera Pathirannehelage, Matthew Donati, Catherine Moore, Simon de Lusignan, Jim McMenamin, Maria Zambon
Journal: Eurosurveillance (2016)

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season's adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0-61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6-64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1-68.6) against influenza B. In 2-17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6-94.3) against influenza B and 41.5% (95% CI: -8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.
Finding disease patterns by shining a light on life: A work in progress
Authors: Vinay Dhir, Amit Maydeo
Journal: Endoscopy (2016)

Our expectations about the pretreatment evaluation of malignant diseases have undergone a profound change in the past few years. An ideal situation would be if we could detect, diagnose, and stage the disease with a single procedure. This would save considerable time and patient anxiety arising from waiting for results. In addition to standard histology, we would also prefer to know the cellular and biochemical nature of the disease so that we could personalize the treatment. These expectations are likely to be realized with recent advances in technology.
Clinical Implication of BCR/ABL Fusion Transcript Monitoring in Addition to Ig/TCR Gene Rearrangement-Based Minimal Residual Disease in Philadelphia Chromosome-Positive Childhood Acute Lymphoblastic Leukemia
Authors: Kirsten Bleckmann, Julia Alten, Anja Moericke, Andishe Attarbashi, Andrea Teigler-Schlegel, Christine Damm-Welk, Rolf Koehler, Martin Schrappe
Journal: Blood (2014)
Antidepressant Prescription in the Geriatric Population
Authors: Avash Das, Abhishek Maiti, Shirshendu Sinha
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
Concurrent chemoradiotherapy with cisplatin/vinorelbine and cisplatin/docetaxel in locally advanced stage III NSCLC
Authors: Makoto Nagamata, Yusuke Okuma, Kuniko Sunami, Kageaki Watanabe, Satoshi Takahashi, Yoshiro Nakahara, Makiko Yomota, Yukio Hosomi, Tatsuru Okamura
Journal: Annals of Oncology (2015)
FUNCTIONAL MR IMAGING CAN IMPROVE CHARACTERIZATION OF ANTERIOR MEDIASTINAL LESIONS
Authors: Johan Coolen, Frederik De Keyzer, Erik Verbeken, Christophe Deroose, Johan Vansteenkiste, Dirk De Ruysscher, Walter De Wever, Stephanie Peeters, Christophe Dooms, Paul De Leyn, Kristiaan Nackaerts, Johny Verschakelen, Steven Dymarkowski, Dirk Van Raemdonck
Journal: Journal of Thoracic Oncology (2014)
Pre-existence of invasive cells in breast ductal carcinoma in situ.
Authors: V. A. Espina, R. I. Gallagher, B. D. Mariani, K. Tran, C. Mueller, S. Banks, L. Pastore, K. H. Edmiston, L. A. Liotta
Journal: Journal of Clinical Oncology (2010)

10508 Background: The treatment of DCIS is controversial because its true malignant nature is unclear. Very little is known about factors that promote survival of breast ductal carcinoma in situ (DCIS) neoplastic cells within the duct or induce the emergence of invasive carcinoma. To address this question we have studied the malignant phenotype of fresh living human DCIS lesions. We reproduciblely cultured human epithelial cells and spheroids from pure fresh human DCIS lesions suggesting that invasive cells pre-exist within the ductal niche. Methods: We procured fresh living human DCIS lesions, obtained under consent after surgical therapy as leftover tissue not required for diagnosis. We characterized the DCIS cells by organ culture, xenograft transplantation, full genome molecular cytogenetics (300k SNPs, Illumina HumanCytoSNP profile), and signal pathway profiling (Reverse Phase Protein Microarray). Results: Ex vivo organoid culture of pure DCIS lesions, without enzymatic treatment or sorting, induced the emergence of neoplastic epithelial cells exhibiting the following characteristics: a) spontaneous generation of hundreds of spheroids and duct- like 3-D structures in culture within 2 weeks, b) tumorigenicity in NOD SCID mice, c) cytogenetically abnormal (copy number loss/gain in chromosomes including 1, 5, 6, 8, 13, 17) compared to the normal karyotype of the non-neoplastic cells in the source patient's breast tissue, d) in vitro migration and invasion of autologous breast stroma, and e) up-regulation of signal pathways linked to, and components of, cellular autophagy. Multiple autophagy markers were present in the patient's original DCIS lesion and mouse xenografts. Autophagy is a survival mechanism. Treatment with a lysosomotropic inhibitor (chloroquine phosphate) of autophagy completely suppressed the generation of DCIS spheroids/3-D structures, suppressed invasion of autologous stroma, induced apoptosis, suppressed autophagy and eliminated cytogenetically abnormal cells from the organ culture. Conclusions: These findings support the hypothesis that cytogenetically abnormal invasive cells pre-exist in human DCIS, but are held in check in the duct microenvironment. Autophagy constitutes a novel treatment target for DCIS. No significant financial relationships to disclose.
A phase I trial of GRN163L (GRN), a first-in-class telomerase inhibitor, in advanced solid tumors
Authors: M. J. Ratain, F. M. Benedetti, L. Janisch, S. Khor, R. L. Schilsky, E. E. Cohen, M. L. Maitland, L. Elias, P. M. LoRusso
Journal: Journal of Clinical Oncology (2008)

3581 Background: Telomerase is over-expressed in most malignancies and is the predominant mechanism by which cancer cells maintain adequate telomere length and immortalization. GRN is a 13-mer oligonucleotide direct inhibitor of the telomerase active site, and has demonstrated broad anticancer effects in preclinical models. Methods: This is a phase I dose escalation study of GRN given weekly as a 2 hr infusion to patients (pts) with refractory, advanced solid tumors. Endpoints included safety, tolerability, pharmacokinetics and efficacy. Results: As of 1/3/08, 20 pts with advanced solid tumors (including 6 colorectal, 3 lung, 2 mesothelioma, 2 pancreas, 7 other) have been treated in escalating dose cohorts at 0.4–4.8 mg/kg of GRN/wk. The pts ranged from 50–74 years of age (median 64 years) and had received 1- 10 prior chemotherapies. Most possibly/probably related adverse events have been reversible, Grade 1–2, and include aPTT prolongation, nausea, vomiting, fatigue, diarrhea, anemia, elevated GGT and peripheral neuropathy. At 3.2 mg/kg, a patient who was tolerating therapy well died of unknown cause after the 4th dose, which was considered a dose-limiting toxicity (DLT). Also, at this dose level, one pt had grade 1 thrombocytopenia during cycle 1 and a 2nd patient had cumulative thrombocytopenia (eventually grade 4 after ten doses). At 4.8 mg/kg, one pt developed grade 4 thrombocytopenia subsequent to the first 3 doses (a DLT). There has been no consistent effect upon other hematological parameters. The plasma half-life of GRN163L was approximately 4–5 hrs, without evidence of nonlinear pharmacokinetics. Conclusion: Accrual to the study continues at 4.8 mg/kg/wk. GRN causes thrombocytopenia (possibly mechanism-related) at doses >3.2 mg/kg/wk, but has not demonstrated any other major toxicities. The maximally tolerated dose appears to be >3.2 mg/kg/wk when given by 2 hr infusions. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Geron Geron
N-Acetylcysteine inhibits IL-17-induced IL-8 production from human airway smooth muscle cells - a possible role for anti-oxidant treatment in chronic lung rejection?
Authors: Wim Wuyts, Bart Vanaudenaerde, Lieven Dupont, Dirk Van Raemdonck, Maurice Demedts, Geert Verleden
Journal: European Respiratory Journal (2003)
TCT-164 Causes of Death after Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Complex Coronary Artery Disease: 5-Year follow-up of the SYNTAX trial
Authors: Milan Milojevic, Stuart J. Head, Catalina A. Parasca, Patrick W. Serruys, Friedrich-Wilhelm Mohr, Marie-Claude Morice, Michael Mack, Elisabeth Ståhle, Ted Feldman, Antonio Colombo, Keith D. Dawkins, A. Pieter Kappetein, David R. Holmes
Journal: Journal of the American College of Cardiology (2015)
Prevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activation
Authors: Ismail Çimen, Begüm Kocatürk, Seda Koyuncu, Özlem Tufanlı, Umut I. Onat, Asli D. Yıldırım, Onur Apaydın, Şeyma Demirsoy, Zaliha G. Aykut, Uyen T. Nguyen, Steven M. Watkins, Gökhan S. Hotamışlıgil, Ebru Erbay
Journal: Science Translational Medicine (2016)

A bioactive lipokine promotes metabolic resilience of organelles and limits the progression of atherosclerosis.
P0032 : The impact of Ischemia/Reperfusion injury on liver allografts from deceased after cardiac death versus deceased after brain death donors
Authors: B. Amir Sayed, J. Xu, A.M. Casas-Ferreira, P. Srinivasan, N. Heaton, Y. Ma, C. Legido-Quigley, S. Fuggle, W. Jassem
Journal: Journal of Hepatology (2015)
HMGCoA Reductase Inhibition Reverses Myocardial Fibrosis and Diastolic Dysfunction Through AMPK Activation in a Mouse Model of Metabolic Syndrome
Authors: Nerea Hermida, Andreas Markl, Julien Hamelet, Paul Herijgers, Sandrine Horman, Gauthier Noppe, Cristophe Beauloye, Mark van Bilsen, Chantal Dessy, Jean Luc Balligand
Journal: Circulation (2012)
Delaying conformal radiation therapy in high-risk prostate cancer patients lowers the actuarial distant metastases free survival
Authors: R. A. Nakamura, C. R. Monti, F. A. Trevisan, J. C. Prestes, M. R. Cruz, L. N. Castilho, J. A. Reinato, L. F. Borges
Journal: Journal of Clinical Oncology (2007)

15614 Background: It is not well documented on medical literature the value of time to treat prostate cancer. This study was performed to evaluate the value of treatment time with conformal radiotherapy (3DCRT) in high-risk prostate cancer patients. Methods: From October 1997 to January 2002, 116 patients with high-risk prostate cancer were submitted to 3DCRT and were analyzed retrospectively. The median age was 65 years-old. High risk patients were defined as patients with PSA &gt; 20 ng/ml, and/or T3 clinical stage and/or Gleason score &gt; 7, or two factors of intermediate risk (PSA &gt;= 10 and &lt; 20 ng/ml, T2b-T2c and Gleason score = 7). The median time from diagnosis to 3DCRT was 2.9 months (0.9–134.9). The median doses of radiation on prostate and on seminal vesicles were 81 Gy (72–82.8) and 61.2 Gy (45–77.4), respectively. The neoadjuvant and concomitant androgen suppression therapy were performed on 69 (59.5%) and 79 (68.1%) patients, respectively. Results: On median follow-up of 54.5 months (13.5–93.9), the 5-year actuarial overall survival, the 5-year actuarial biochemical progression-free survival and the 5-year actuarial distant metastases free survival were 84.3%, 64.7% and 88.6%, respectively. The 5-year actuarial distant metastases free survival for patients treated with 3DCRT less than or equal to 5 months was 92.5% versus 72.1% for patients treated with 3DCRT &gt; 5 months (p=0.0076). The 5-year actuarial distant metastases free survival for patients with biochemichal progression was 68.8% versus 100% for patients with no biochemical progression (p 65 years-old (p=0.0160). Conclusions: The study suggests that delaying 3DCRT in high-risk prostate cancer patients lowers the actuarial distant metastases free survival. Biochemical progression may be a strong prognostic factor for distant metastases and, consequently, poor quality of life. No significant financial relationships to disclose.
Mortality of CAP reduced in the UK: is this enough?
Authors: Antoni Torres, Carolina Garcia-Vidal
Journal: Thorax (2016)

In 1930, pneumonia was the third most frequent cause of death in the USA. Now almost a century later, and despite the introduction of antibiotics in the 1950s, pneumonia remains the fourth most common cause of death worldwide.1 Community-acquired pneumonia (CAP) represents a major burden in terms of morbidity, mortality and health cost, as well as days of work lost.

In the last 10 years, guidelines for management of CAP have been published.2–4 One of the objectives of the guidelines is to improve outcomes (including mortality) when implemented. This was demonstrated, for example, by Dean et al ,5 showing a reduction in mortality from 14.2% to 11% in a series of hospitals in the USA after implementation of the 2001 American Thoracic Society CAP guidelines.

The British Thoracic Society (BTS) guidelines were published in 20092 and they advised three key points for CAP quality standards: (1) to perform a chest X-ray within 4 hours of presentation, (2) to perform a mortality risk assessment using the CURB65 score and (3) to administer the first dosage of antibiotics within the first 4 hours after emergency department (ED) arrival. In parallel with the 2009 publication the BTS started a CAP audit programme. The audit was conducted from 2009 to 2012 and then subsequently in 2014.6 A total of 218 institutions …