tbuckley/cabot-search huggingface dataset:
A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.
Authors: Lynn Mara Schuchter, Lawrence E. Flaherty, Omid Hamid, Gerald P. Linette, Sigrun Hallmeyer, Rene Gonzalez, Charles Lance Cowey, Anna C. Pavlick, Fred J. Kudrik, David H. Lawson, Kim Allyson Margolin, Antoni Ribas, David F. McDermott, James L. Khatcheressian, Keith T. Flaherty, Bann-Mo Day, Rolf Gerhard Linke, John D. Hainsworth
Journal: Journal of Clinical Oncology (2012)

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAF V600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAF V600E mutation as detected by the cobas 4800 BRAF V600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.
Silica Nanoparticles Target a Wnt Signal Transducer for Degradation and Impair Embryonic Development in Zebrafish
Authors: Hongyang Yi, Zhuyao Wang, Xiaojiao Li, Min Yin, Lihua Wang, Ali Aldalbahi, Nahed Nasser El-Sayed, Hui Wang, Nan Chen, Chunhai Fan, Haiyun Song
Journal: Theranostics (2016)

Many types of biocompatible nanomaterials have proven of low cytotoxicity and hold great promise for various applications in nanomedicine. Whereas they generally do not cause apparent organ toxicity or tissue damage in adult animals, it is yet to determine their biological consequences in more general contexts. In this study, we investigate how silica nanoparticles (NPs) affect cellular activities and functions under several physiological or pathological conditions. Although silica NPs are generally regarded as "inert" nanocarriers and widely employed in biomedical studies, we find that they actively affect Wnt signaling in various types of cell lines, diminishing its anti-adipogenic effect in preadipocytes and pro-invasive effect in breast cancer cells, and more significantly, impair Wnt-regulated embryonic development in Zebrafish. We further demonstrate that intracellular silica NPs block Wnt signal transduction in a way resembling signaling molecules. Specifically, silica NPs target the Dvl protein, a key component of Wnt signaling cascade, for lysosomal degradation. As Wnt signaling play significant roles in embryonic development and adipogenesis, the observed physiological effects beyond toxicity imply potential risk of obesity, or developmental defects in somitogenesis and osteogenesis upon exposure to silica NPs. In addition, given the clinical implications of Wnt signaling in tumorigenesis and cancer metastasis, our work also establishes for the first time a molecular link between nanomaterials and the Wnt signaling pathway, which opens new door for novel applications of unmodified silica NPs in targeted therapy for cancers and other critical illness.
Investigation of First Identified<i>mcr-1</i>Gene in an Isolate from a U.S. Patient — Pennsylvania, 2016
Authors: Kelly E. Kline, Jordan Shover, Alexander J. Kallen, David R. Lonsway, Sharon Watkins, Jeffrey R. Miller
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In 2015, scientists reported the emergence of the plasmid-encoded mcr-1 gene conferring bacterial resistance to the antibiotic colistin (1), signaling potential emergence of a pandrug-resistant bacterium. In May 2016, mcr-1-positive Escherichia coli was first isolated from a specimen from a U.S. patient (2) when a Pennsylvania woman was evaluated for a urinary tract infection. The urine culture and subsequent testing identified the gene in an extended-spectrum beta-lactamase (ESBL)-producing E. coli with reduced susceptibility to colistin. The patient had no international travel for approximately 1 year, no livestock exposure, and a limited role in meal preparation with store-bought groceries; however, she had multiple and repeated admissions to four medical facilities during 2016.
To assess the effect of smoking on cardiovascular system
Authors: Anupama Gupta, Sushma Sood, Rajesh Gupta, Joshil Behra
Journal: European Respiratory Journal (2012)

Background: Smoking alters autonomic functions and increases adrenergic activity that predisposes to cardiovascular morbidity and mortality. Heart rate Variability (HRV) is a measurement of autonomic activity.

Method: Study included 60 subject in total, of which 30(Test group-A) were chronic smokers with history of at least 10 pack years and 30(Group-B) non smoker controls. The HRV was recorded in the supine posture in relaxed state. We recorded the frequency domain analysis [low frequency domain (LF), high frequency domain (HF) and LF/HF ratio] for which five minute recordings were taken and data was generated by the Polyrite D system.

Results: In group-A a significant (P<0.001) increase in heart rate with decreased RR interval was recorded as compared to control group-B. Along with, there was a decrease (P<0.05) in high frequency domain (HF) where as there was a increase (P<0.05) in LF/HF ratio. In the sub group with more than 15 pack years smoking history, a significant increase in heart rate (P<0.05) and LF/HF ratio (P<0.001) was recorded compared to less than 15 pack years sub group. Also there was a significant decrease (P<0.05) in RR interval, LF and HF values.

Conclusion: Study of heart rate variability in smokers clearly indicates that cardiac autonomic functions are affected due to smoking, which increases with number of pack years. So the HRV determination should be included in routine investigations to access the severity of cardiac involvement in chronic smokers.
The Prognostic Impact Of Complex Gene Mutation In The Intermediate Risk Karyotype Acute Myeloid Leukemia
Authors: Satoshi Wakita, Hiroki Yamaguchi, Takeshi Ryotokuji, Tuneaki Hirakawa, Ikuko Omori, Tomoaki Kitano, Kunihito Arai, Yoshio Mitamura, Fumiko Kosaka, Kazuo Dan, Koiti Inokuchi
Journal: Blood (2013)
P1079 : PNPLA3 variant p.I148M improves response to bariatric surgery in obese patients with fatty liver disease
Authors: M. Krawczyk, R. Jiménez-Agüero, J.M. Aluztiza, J.I. Emparanza, F. Lammert, J.M. Banales
Journal: Journal of Hepatology (2015)
Tumor necrosis factor ? gene expression and the response to interferon in chronic hepatitis C
Authors: E Larrea, N Garcia, C Qian, M P Civeira, J Prieto
Journal: Hepatology (1996)

Tumor necrosis factor α (TNF-α) is a cytokine with pleiotropic properties that is induced in a variety of pathological situations including viral infections. In this work, we analyzed the expression of TNF-α gene in patients with chronic hepatitis C. Serum TNF-α levels were found to be elevated in all chronic hepatitis C patients including those cases presenting sustained biochemical remission of the disease after interferon therapy. Untreated patients with chronic hepatitis C showed increased TNF-α messenger RNA (mRNA) levels in the liver and mononuclear cells as compared with healthy controls. After completion of treatment with interferon, patients experiencing sustained complete response showed values of TNF-α mRNA, both in the liver and in peripheral mononuclear cells, within the normal range, significantly lower than patients who did not respond to interferon and than those with complete response who relapsed after interferon withdrawal. Pretreatment values of TNF-α mRNA were lower in long-term responders to interferon than in cases who failed to respond to the treatment. Values of TNF-α mRNA in the liver or in mononuclear cells were higher in specimens with positive hepatitis C virus (HCV) RNA than in those samples where the virus was undetectable. Neither the intensity of the liver damage nor the amount of HCV RNA in serum or in cells showed correlation with the levels of TNF-α transcripts in peripheral mononuclear cells but it was found that high TNF-α values were associated with genotype 1b. In conclusion, there is an enhanced expression of TNF-α in HCV infection. High levels of this cytokine may play a role in the resistance to interferon therapy.
Genetic Factors Associated With Severe Cutaneous Adverse Reactions
Authors: Roberto Lozano
Journal: JAMA (2014)

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
Hyperoxaluria Requires TNF Receptors to Initiate Crystal Adhesion and Kidney Stone Disease
Authors: Shrikant R. Mulay, Jonathan N. Eberhard, Jyaysi Desai, Julian A. Marschner, Santhosh V.R. Kumar, Marc Weidenbusch, Melissa Grigorescu, Maciej Lech, Nuru Eltrich, Lisa Müller, Wolfgang Hans, Martin Hrabě de Angelis, Volker Vielhauer, Bernd Hoppe, John Asplin, Nicolai Burzlaff, Martin Herrmann, Andrew Evan, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2016)

Intrarenal crystals trigger inflammation and renal cell necroptosis, processes that involve TNF receptor (TNFR) signaling. Here, we tested the hypothesis that TNFRs also have a direct role in tubular crystal deposition and progression of hyperoxaluria-related CKD. Immunohistochemical analysis revealed upregulated tubular expression of TNFR1 and TNFR2 in human and murine kidneys with calcium oxalate (CaOx) nephrocalcinosis-related CKD compared with controls. Western blot and mRNA expression analyses in mice yielded consistent data. When fed an oxalate-rich diet, wild-type mice developed progressive CKD, whereas Tnfr1-, Tnfr2- , and Tnfr1/2- deficient mice did not. Despite identical levels of hyperoxaluria, Tnfr1-, Tnfr2- , and Tnfr1/2 -deficient mice also lacked the intrarenal CaOx deposition and tubular damage observed in wild-type mice. Inhibition of TNFR signaling prevented the induced expression of the crystal adhesion molecules, CD44 and annexin II, in tubular epithelial cells in vitro and in vivo , and treatment with the small molecule TNFR inhibitor R-7050 partially protected hyperoxaluric mice from nephrocalcinosis and CKD. We conclude that TNFR signaling is essential for CaOx crystal adhesion to the luminal membrane of renal tubules as a fundamental initiating mechanism of oxalate nephropathy. Furthermore, therapeutic blockade of TNFR might delay progressive forms of nephrocalcinosis in oxalate nephropathy, such as primary hyperoxaluria.
Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection
Authors: Luca Arcaini, Caroline Besson, Marco Frigeni, Hélène Fontaine, Maria Goldaniga, Milvia Casato, Marcella Visentini, Harrys A. Torres, Veronique Loustaud-Ratti, Jan Peveling-Oberhag, Paolo Fabris, Roberto Rossotti, Francesco Zaja, Luigi Rigacci, Sara Rattotti, Raffaele Bruno, Michele Merli, Céline Dorival, Laurent Alric, Arnaud Jaccard, Stanislas Pol, Fabrice Carrat, Virginia Valeria Ferretti, Carlo Visco, Olivier Hermine
Journal: Blood (2016)
Short-term low-volume hydration in cisplatin-based chemotherapy: a feasibility study in lung cancer (OLCSG1201)
Authors: Kiichiro Ninomiya, Katsuyuki Hotta, Hiroko Gotoda, Daisuke Morichika, Eiki Ichihara, Akiko Sato, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Annals of Oncology (2015)
Treatment of Patients with Autoimmune Cytopenia and Progressive CLL Using Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP).
Authors: Clive S. Zent, Deborah Bowen, Timothy G Call, Tait D. Shanafelt, Neil E. Kay, Susan L Slager, Susan Schwager, Kari Rabe, Megan Reinalda
Journal: Blood (2009)
Novel tubulin inhibitor ALB 109564(a) in patients with solid tumors: A phase I trial.
Authors: M. S. Clancy, J. M. Cleary, S. Mani, E. Choy, M. Wolf, M. H. Silverman, S. C. Gad, M. H. Parkman, G. Shapiro, B. J. Dezube
Journal: Journal of Clinical Oncology (2010)

e13119 Background: ALB 109564(a) [ALB] is a vinca alkaloid, which functions as a tubulin inhibitor, interfering with microtubule polymerization resulting in metaphase arrest. In preclinical studies, ALB was active in a wide variety of tumor types (e.g., colon, NSCLC, prostate) at concentrations comparable to those of approved vinca alkaloids. Methods: This study sought to determine the maximum tolerated dose based upon first cycle toxicity in 3-6 patients at each dose level, as well as to evaluate the pharmacokinetics of ALB when administered intravenously every three weeks. The starting dose was 1.2 mg/m2, and escalation proceeded according to a modified Fibonacci scheme. Results: 28 patients have been administered ALB across eight dose levels (1.2 to 12 mg/m2). No dose-limiting toxicities as well as no serious adverse events specifically attributed to ALB were observed. Through seven cohorts, adverse events reported to be at least possibly related to study drug were constipation (n=5), anemia (n=2), fatigue (n=2), blurred vision (n=1), decreased appetite (n=1), flushing (n=1), paresthesia (n=1), and rash (n=1); all were either grade 1 or 2. The overall half-life of ALB was 19.05 ± 8.80 hours, which is comparable to that of approved vinca alkaloids. Of 21 patients evaluable for clinical activity, one alveolar small part sarcoma patient, who had marked progression prior to enrollment, has received 21+ cycles of study drug with stable disease. An additional four patients have had stable disease after two or more cycles; one anal (7+ cycles), one pancreatic (5+ cycles), one colon (4 cycles), and one NSCLC (4 cycles). Conclusions: ALB is well tolerated and has shown preliminary activity in disease types not typically associated with approved vinca alkaloids. Further trials in soft tissue sarcoma are in development. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Albany Molecular Research, Inc. Albany Molecular Research, Inc. Albany Molecular Research, Inc. Albany Molecular Research, Inc.
Avelumab (MSB0010718C; anti-PD-L1) in patients with recurrent/refractory ovarian cancer from the JAVELIN Solid Tumor phase Ib trial: Safety and clinical activity.
Authors: Mary L. Disis, Manish R. Patel, Shubham Pant, Erika Paige Hamilton, Albert C. Lockhart, Karen Kelly, J. Thaddeus Beck, Michael S. Gordon, Glen J. Weiss, Matthew H. Taylor, Jorge Chaves, Alain C. Mita, Kevin M. Chin, Anja von Heydebreck, Jean-Marie Cuillerot, James L. Gulley
Journal: Journal of Clinical Oncology (2016)

5533 Background: Avelumab* is a fully human anti-PD-L1 IgG1 antibody under clinical investigation in multiple cancers. We report safety and clinical activity of avelumab in patients (pts) with recurrent/refractory ovarian cancer (OC; NCT01772004). Methods: Pts with advanced OC unselected for PD-L1 expression received avelumab 10 mg/kg IV Q2W until progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 wks (RECIST 1.1). Unconfirmed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Adverse events (AEs) were graded by NCI-CTCAE v4.0. PD-L1 expression was assessed by immunohistochemistry. Results: As of Oct 23, 2015, 124 pts were treated with avelumab (median 12 wks [range 2-54]) and followed for a median of 54 wks (range 11-101). Median age was 62 y (range 27-84), ECOG PS was 0 (47.6%) or 1 (52.4%), and median number of prior therapies was 4 (range 1-13). Treatment-related (TR) AEs occurred in 82 pts (66.1%); most common (≥10%) were fatigue (13.7%), infusion-related reaction (12.1%), and diarrhea (11.3%), all of grade 1/2. Grade 3/4 TRAEs were reported in 8 pts (6.5%); of these, only increased lipase occurred in > 1 pt (n = 2). There were no treatment-related deaths. ORR was 9.7% (95% CI: 5.1-16.3) based on 12 partial responses; 6 were ongoing. Stable disease was observed in 55 pts (44.4%); disease control rate was 54.0%. PD-L1 expression was evaluable in 74 pts (59.7%). Using a ≥1% cutoff for tumor cell staining, 57/74 (77.0%) were PD-L1+ and ORR was 12.3% in PD-L1+ (7/57; 95% CI: 5.1, 23.7) vs 5.9% in PD-L1− pts (1/17; 95% CI: 0.1, 28.7). Overall, median PFS was 11.3 wks (95% CI: 6.1, 12.0) and median OS was 10.8 mos (95% CI: 7.0, 16.1). Conclusions: Single-agent avelumabshowed an acceptable safety profile and clinical activity in heavily pretreated pts with OC. These data represent the largest study of anti-PD(L)1 agents in pts with OC to date. The potential relationship between biomarkers, such as germline BRCA mutational status, and the probability of response is being investigated. Randomized phase 3 trials of avelumab in OC are underway. *Proposed INN. Clinical trial information: NCT01772004.
Validation of the Spanish version of the QODD questionnaire (QODDq-ESP) in a home-based cancer palliative care program and development of the QODDq-ESP-12.
Authors: Pedro Emilio Perez-Cruz, Oslando Padilla Pérez, Pilar Bonati, Oliva Thomsen Parisi, Laura Tupper Satt, Marcela Gonzalez Otaiza, Diego Ceballos Yanez, Armando Maldonado Morgado
Journal: Journal of Clinical Oncology (2015)

70 Background: Improving quality of death (QOD) is a key goal in palliative care. No instruments to measure QOD have been validated in Spanish. The goal of this study was to validate the Spanish version of the quality of death and dying questionnaire (QODD) and to develop a shortened version of this instrument suitable to be completed by phone interview. Methods: Translation/back-translation and adaptation of the QODD was performed following established standards. One question was removed due to cultural inadequacy. We enrolled caregivers (CGs) of consecutive deceased cancer patients from a single palliative care clinic in Santiago, Chile. CGs were contacted by phone between 4 and 12 weeks after patients’ death. Participating CGs completed the adapted QODD (QODD-ESP) by phone interview. A global rating question assessing quality of life (QOL) during the last week of life was included. A shortened version of the QODD (QODD-ESP-12) based on the model by Downey et al. (J Pain Sympt Manage 2010;39) was created. Measures of reliability (Cronbach-alpha), convergent validity (correlation with global rating question) and construct validity (factorial analysis [FA]) were estimated for both versions of the instrument. Results: 150 (50%) out of 302 CGs completed the QODD-ESP. Patients mean (standard deviation [SD]) age was 67 (14), 71 (47%) female and 131 (87%) died at home. CGs mean (SD) age was 51 (13), 128 (85%) female. Mean QODD-ESP score was 69 (range 35-96) with an alpha = .829. Correlation with last week QOL was .434 (p &lt; .01). Kaiser-Meyer-Olkin measure of sampling adequacy was .585, not supporting the existence of a unique underlying construct. Mean QODD-ESP-12 score was 69 (range 31-97) with a alpha = .728. Correlation with last week QOL was .306 (p &lt; .01). Confirmatory FA of QODD-ESP-12 showed that data fitted well Downey’s model (Chi2 4.85 (60), p = .311 Comparative Fit ndex = .98; Tuker-Lewis Index = .977 and root mean square error of approximation (RMSEA) = .023 (CI: 0-.056). Conclusions: QODD-ESP-12 is a reliable and valid instrument with good psychometric properties and can be used to assess QOD in a Spanish speaking cancer palliative care population by phone interview.
Use of Higher Doses of rFVIIa in Individuals with Congenital Hemophilia Complicated by Alloantibody Inhibitors: Analysis of Data Capture from the Hemophilia and Thrombosis Research Society (HTRS) Registry (2004–2008)
Authors: Craig M. Kessler, Joan Cox Gill, Caitlyn T. Wilke, David L. Cooper
Journal: Blood (2008)
Recent Developments in Melanoma Therapy
Authors: Alexander M. Menzies, Georgina V. Long
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Wilm’s Tumor 1 Gene Expression Is a Useful Marker for Minimal Residual Disease in Acute Myeloid Leukemia.
Authors: Jack W. Hsu, Hong Liu, Katarzyna Jamieson, Wei Hou, Myron N. Chang, Kim P. Ahrens, Raul C. Braylan, John R. Wingard
Journal: Blood (2007)