tbuckley/cabot-search huggingface dataset:
Older adolescents and young adults with acute lymphoblastic leukemia (ALL) in the United States: From the lowest to highest death rate and number of deaths—More rationale for the CALBG-SWOG-ECOG C10403 trial based on COG AALL0232
Authors: A. Bleyer
Journal: Journal of Clinical Oncology (2008)

18034 Background: In the U.S., children with ALL have had a dramatic mortality rate reduction whereas older patients have not (Proc. ASCO 21: 389a, 2002), a difference that has been known since 2000 to be largely attributable to differences in pediatric versus adult treatment regimens (Blood 2000;96:467a,abstr; J Clin Oncol 2003;21:774–80; Leukemia 2004;18:2032–5; Pediat Blood Cancer 2005;45:578,Abstr; J Clin Oncol 2006;24(18S):#9024,abstr; Pediatr Blood Cancer 2006,43:748–56). To ascertain whether there has been any improvement in the U.S. since these reports, national mortality rates were assessed as a function of year of age and year of diagnosis. Methods: National ALL deaths and death rates during 1969–2004 were obtained from the U.S. SEER program (SEERStat, www.seer.cancer.gov accessed 1/8/08). Best fit regressions (linear, polynomial or exponential) were used to determine trends and estimate rates for specific calendar years. Results: Below age 15 the national ALL mortality rate has declined dramatically, from 14.6 to 3.7 deaths per year per million from 1970 to 2004 and from 800+ deaths in 1970 to an average of 220 deaths per year during 2000–2004. In 1970, 15–24 year-olds had one-third the ALL death rate and one-third the number of deaths that occurred in younger patients. Since 1995, 15–19 and 20–24 year-olds have had a greater death rate than younger patients and the highest of all 5-year age groups younger than 55 years. The number of deaths from ALL has become higher in 15–24 year-olds than in any other 10-year age group (Table). Conclusions: The age dependent trend in death rates and number of deaths from ALL is more rationale for the CALBG-SWOG-ECOG C10403 trial, which opens this year in all three cooperative groups and will be preformed in conjunction with COG AALL0232. The upper age limit of this phase II trial is 30 years and should be accessible via the Cancer Trials Support Unit (CTSU). Age (Years) at [upper row] and Number of Deaths from ALL [lower row], U.S. 2000–2004 0–9 5–14 15–24 25- 34 35–44 45–54 55–64 65–74 75–84 85+ 687 834 959 615 677 781 818 885 818 773 No significant financial relationships to disclose.
Safety and tolerability of 1-hour intravenous infusion of tremelimumab (CP-675,206) in patients with surgically incurable stage III or IV melanoma
Authors: J. Chesney, A. Ribas, R. Gonzalez, M. Gordon, J. Gomez-Navarro, M. A. Marshall, B. Huang, P. Hsyu, D. Gernhardt
Journal: Journal of Clinical Oncology (2009)

e20016 Background: In previous tremelimumab clinical trials, monoclonal antibody was infused over 3–5 hours. Shorter infusion times would be more convenient. Therefore, this study assessed safety and tolerability of tremelimumab 1-hr infusion. Methods: This ongoing study is an open-label, multicenter, phase I clinical trial evaluating safety and tolerability of tremelimumab (15 mg/kg 1-hr infusion every 90 days for up to 4 doses) in patients with surgically incurable stage III or IV melanoma. Primary endpoint was any tremelimumab-related adverse events (AEs) that occur from start of infusion to 1 hr post-end of infusion of Dose 1 and either prevented full dose from being administered or were ≥ grade 3. Results: Forty-five patients (71% male; median age, 59 years) were enrolled and received ≥ 1 dose of tremelimumab. Patients experienced no AEs during first infusion that met criteria for the primary endpoint. With a 1-sided exact binomial test at 10% significance level (α=0.10), p value was 0.099 (&lt;0.10). Therefore, the null hypothesis (H 0 : infusion-related reaction rate ≥ 5%) was rejected. Four (9%) patients reported a mild to moderate AE during or within 1 hr after first infusion. These included 1 patient each who experienced grade 2 hypertension (considered unrelated to tremelimumab by the investigator), grade 1 hypotension, grade 2 hypersensitivity, and grade 1 transient flushing. Mean (SD) C max (n=32) was 325 (66) μg/mL, mean (SD) AUC (N=16) was 102,000 (35,000) μg×h/mL, and mean half-life was 20 days. These single-dose PK results were similar to those from previous studies using 3- to 5-hr infusion times, suggesting that 1-hr infusion of tremelimumab did not significantly alter PK. No human-anti-human antibodies were detected in any patients. Conclusions: In patients with advanced melanoma, 1-hr infusion of tremelimumab resulted in a safety profile during infusion that was consistent with tremelimumab studies using longer infusion times, and single-dose PK analysis did not reveal any perturbations in tremelimumab distribution or clearance. Therefore, a more convenient 1-hr infusion is a reasonable option for administration of tremelimumab. [Table: see text]
Dextromethorphan-Quinidine for Agitation in Alzheimer Disease—Reply
Authors: Jeffrey L. Cummings, João Siffert
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 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
Abstract 1998: Deficient expression of oncogenic Wip1 (PPM1D) negatively regulates melanoma progression and metastasis
Authors: Bo-Hyun Moon, Shubhankar Suman, Henghong Li, Qian Yang, Steven J. Strawn, Janine LoBello, Sharlyn J. Mazur, Ettore Appella, Suzie Chen, Albert J. Fornace
Journal: Cancer Research (2014)

Abstract PPM1D belongs to the magnesium-dependent serine/threonine phosphatase family. It is well demonstrated that PPM1D amplification and overexpression is a frequent event in many human cancer types; however, its role in melanoma development and metastasis is not yet defined. The objectives of this study were to evaluate the role of Wip1 in melanoma progression and to evaluate correlations between Wip1 expression and clinical pathological parameters, such as grade and metastasis. In order to investigate the role of Wip1 in melanoma progression, we crossed Grm1 transgenic (TG3) mice, a well-characterized mouse model for melanoma, with Wip1 null mice (PPM1D-/-) to generate TG3:PPM1D-/- mice, and observed the rate of spontaneous melanoma formation. Compared with TG3 mice, TG3:PPM1D-/- mice exhibited dramatic reductions in melanoma incidence and metastasis to lymph nodes, lungs, liver and spleen. In addition, in-vitro down-regulation of Wip1 in Mass20 melanoma cells significantly decreased cellular proliferation and migration. Further, human melanoma tissue microarrays (TMAs) were used to determine PPM1D mRNA and protein expression levels in human tumors at different stages of progression. In situ staining of PPM1D mRNA and its corresponding protein Wip1 in human melanoma TMAs revealed higher expression levels in at least ∼50% of the metastatic tumors analyzed. Overall, our results demonstrate abundant expression of Wip1 in late stage/high grade melanoma and suggest that therapeutic strategies targeting Wip1 in individuals with select tumor subtypes might improve the survival advantage in Wip1-positive melanoma patients. However, further studies are required to elucidate the interactions between Wip1 signaling and established pathways of melanoma progression. Note: This abstract was not presented at the meeting. Citation Format: Bo-Hyun Moon, Shubhankar Suman, Henghong Li, Qian Yang, Steven J. Strawn, Janine LoBello, Sharlyn J. Mazur, Ettore Appella, Suzie Chen, Albert J. Fornace. Deficient expression of oncogenic Wip1 (PPM1D) negatively regulates melanoma progression and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1998. doi:10.1158/1538-7445.AM2014-1998
Management of Advanced Stage Hodgkin Lymphoma
Authors: Ranjana Advani, Weiyun Z. Ai, Sandra J. Horning
Journal: Journal of the National Comprehensive Cancer Network (2006)

Although advanced Hodgkin lymphoma is highly curable, balancing the high cure rate with long-term toxicity is challenging. ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) is the standard chemotherapy regimen, producing a high cure rate with acceptable toxicity. Stanford V and BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) are new regimens with encouraging results and are undergoing randomized clinical trials. The International Prognostic Score provides a clinical tool that may help identify patients with high-risk disease who may require a more aggressive regimen. Consolidative radiation's role in managing advanced Hodgkin lymphoma is still controversial, but it is most accepted for bulky or residual disease or after brief chemotherapy. The development and integration of newer imaging tools, such as fluorodeoxyglucose–positron emission tomography imaging, may allow a more precise evaluation of disease and help define which patients might benefit from consolidative treatment.
Association of<i>CYP2C19</i>*17/*17 Genotype With the Risk of Voriconazole-Associated Squamous Cell Carcinoma
Authors: Kiyanna Williams, Sarah T. Arron
Journal: JAMA Dermatology (2016)

This cohort study investigates whether lung transplant recipients with the ultrarapid-metabolizing *17 allele of CYP2C19 have an increased risk for voriconazole-associated cutaneous squamous cell carcinoma.
Low-grade astrocytoma, anaplastic oligodendroglioma or astrocytoma, and glioblastoma: The clinical trial portfolio of the EORTC Brain Tumor and Radiation Oncology Groups for newly diagnosed patients.
Authors: B. Baumert, R. Stupp, M. J. Van Den Bent, S. Erridge, A. Brandes, G. A. Pesce, D. C. Weber, D. A. Lacombe, T. Gorlia, W. Wick
Journal: Journal of Clinical Oncology (2010)

e12551 Background: Better understanding of underlying molecular mechanisms and alterations have led to substantial improvements in classification and therapy of gliomas. Grouping of patients, based on their histologic grade and on molecular characteristics, aims at tailored treatment strategies for several subtypes of glioma. Methods: The ongoing trials of the groups (http://groups.eortc.be/brain/html/trials.html) reflect this. Grade II glioma patients are stratified by 1p loss. Progressive or poor prognosis patients are then randomized to either radiotherapy 28 x 1.8 Gy (standard arm) or primary temozolomide (TMZ) chemotherapy for up to 1 year. Primary endpoint is PFS. For patients with anaplastic glioma, separate trials are conducted depending on the presence of translocation 1p/19q. In addition patients are stratified for O6-methyl-guanyl-methyl-transferase (MGMT). For non-deleted tumors, standard radiotherapy is compared to concomitant or adjuvant TMZ chemotherapy in the 4-arm CATNON trial. Primary endpoint is OS. The so-called CODEL intergroup trial led by the NCCTG for patients with the translocation will evaluate the role of concomitant and adjuvant temozolomide (TMZ/RT→TMZ) added to standard radiotherapy and has TMZ monotherapy in an observational arm. In glioblastoma, patient selection is based on MGMT methylation. The phase III CENTRIC trial investigates the benefit of the addition of the integrin inhibitor cilengitide, in patients with methylated MGMT with OS as primary endpoint. For patients with unmethylated MGMT, the mTOR inhibitor temsirolimus is added to radiotherapy in a randomized phase II design, primary endpoint being 1-yr survival rate. Prognosis for elderly patients with glioblastoma is less favorable and shortened hypofractionated radiotherapy is often proposed. In a randomized phase III trial this is compared to concomitant or concomitant/adjuvant TMZ/RT, a collaboration led by the National Cancer Institute of Canada. Results: N/A. Conclusions: Continued and collaborative international research has shown to improve the standard of care of glioma patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Essex Chemie Switzerland, Merck KGaA, OncoMethylome Sciences, Roche, Schering-Plough Pfizer GlaxoSmithKline, Merck KGaA, Roche, Schering-Plough Merck KGaA, Schering-Plough Essex Chemie Switzerland
Osteoporosis: cause and management
Authors: D Srivastava
Journal: BMJ (1987)

suggest that they are at high risk of developing leptospirosis, the remarkably low incidence of the disease in such communes argues to the contrary.The clustering of so many cases in the commune, the finding of only a moderate rise in the tempera- ture at the centre of a meatball cooked on a hot plate,2 and the very peculiar interaction of the index case with the commune strongly suggested that food was the common source.
Multiple STAT3 Mutations In Different Lymphocyte Clones Of Large Granular Lymphocytic Leukemia Patients
Authors: Hanna L M Rajala, Thomas Olson, Sonja Lagström, Pekka Ellonen, Syed Arshi Uz Zaman, Emma I Andersson, Michael J. Clemente, Andres Jerez, Kimmo Porkka, Jaroslaw P. Maciejewski, Thomas P. Loughran, Satu Mustjoki
Journal: Blood (2013)
Transarterial chemoembolization with doxorubicin-loaded drug-eluting beads (DEBDOX) in the treatment of breast cancer liver metastases: A pilot study
Authors: G. Bruixola, R. García, F. Gomez, C. Escoín, L. Palomar, H. de la Cueva, J.J. Martínez, A. Santaballa
Journal: Annals of Oncology (2015)
Research With Controlled Drugs: Why and Why Not? Response to Open Peer Commentaries on “An Ethical Exploration of Barriers to Research on Controlled Drugs”
Authors: Michael H. Andreae, Evelyn Rhodes, Tyler Bourgoise, George M. Carter, Robert S. White, Debbie Indyk, Henry Sacks, Rosamond Rhodes
Journal: The American Journal of Bioethics (2016)

We thank the open peer commentary authors for their support for our project and for their insightful and helpful comments on our article, “An Ethical Exploration of Barriers to Research on Controll...
A Phase 2, Randomized, Double-Blind, Multicenter Trial of Denosumab in Combination with Chemotherapy As First-Line Treatment of Metastatic Non-Small Cell Lung Cancer
Authors: D.R. Spigel, F.R. Hirsch, R.H. De Boer, R. Natale, J. Crawford, G.J. Weiss, J. Glaspy, A. Feng, A. Braun, R. Jain
Journal: Annals of Oncology (2014)
Abstract P2-05-02: Clinical significance of microRNA regulator Lin28 expression in patient with early breast cancer
Authors: S Park, YK Shin, BJ Song, BJ Chae, SS Jung, Y-L Choi
Journal: Cancer Research (2012)

Abstract Lin28 is an RNA-binding protein that is highly expressed in human embryonic stem (ES) cells. It can facillatate the reprogramming of human somatic cells to pluripotency with other stem cell marker proteins (Oct4, Nanog and Sox2). Lin28 regulates the processing of microRNAs including let-7 (Mirlet7) and translation of specific subset of cell cycle-related genes such as IGF-2, OCT4. Recently, it has been suggested that Lin28 expression may contribute to breast cancer metastasis in an animal model (Dangi-Garimellaet al., 2009). To define clinical impact of Lin 28 in breast cancer, we investigated Lin28 expression in tumors from patients with early breast cancer who underwent curative resection of tumor. To define prognostic impact of Lin 28 in breast cancer, we investigated Lin28 expression in patients with early breast cancer who underwent curative resection of tumor. In all, 950 slides from paraffin-embedded tissue were available for analysis by Lin28 expression by immunohistochemistry (IHC), and 78 cases (13.2%) were identified as Lin28-positive. Lin28 positivity was significantly associated with more advanced stage (P &amp;lt; .001), lymph node involvement (P&amp;lt; .001), absence of estrogen receptor expression (P = .002), negative progesterone receptor expression (P = .017), HER2 overexpression (P&amp;lt; .001), higher histologic grade (P = .008), and higher tumor grade (P = .012). The Lin28 positive patients with early breast cancer demonstrated substantially poorer relapse free survival (Lin28+ positive vs. Lin28−(P = 0.013) and trends toward poorer overall survival. Taken together, a sub-population of breast cancer with Lin28 expression is significantly associated with aggressive tumor phenotype and poor clinical outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-02.
Small Molecules for Active Targeting in Cancer
Authors: Chin S. Kue, Anyanee Kamkaew, Kevin Burgess, Lik V. Kiew, Lip Y. Chung, Hong B. Lee
Journal: Medicinal Research Reviews (2016)

For the purpose of this review, active targeting in cancer research encompasses strategies wherein a ligand for a cell surface receptor expressed on tumor cells is used to deliver a cytotoxic or imaging cargo. This area of research is more than two decades old, but in those 20 and more years, how many receptors have been studied extensively? What kinds of the ligands are used for active targeting? Are they mostly naturally occurring molecules such as folic acid, or synthetic substances developed in campaigns for medicinal chemistry efforts? This review outlines the most important receptor or ligand combinations that have been used in active targeting to answer these questions, and therefore to address the most important one of all: is research in active targeting affording diminishing returns, or is this an area for which the potential far exceeds progress made so far?
Review of<i>Let Me Heal: The Opportunity to Preserve Excellence in American Medicine,</i>by Kenneth M. Ludmerer
Authors: Joseph J. Fins
Journal: The American Journal of Bioethics (2016)

"Review of Let Me Heal: The Opportunity to Preserve Excellence in American Medicine, by Kenneth M. Ludmerer." The American Journal of Bioethics, 16(4), pp. W14–W15
miR-203 and miR-221 regulate SOCS1 and SOCS3 in essential thrombocythemia
Authors: A Navarro, S Pairet, A Álvarez-Larrán, A Pons, G Ferrer, R Longarón, C Fernández-Rodríguez, L Camacho, M Monzó, C Besses, B Bellosillo
Journal: Blood Cancer Journal (2016)

Abstract The biological basis of essential thrombocythemia (ET) patients lacking known mutations is still unknown. MicroRNAs (miRNA) regulate hematopoietic differentiation and are deregulated in several hematopoietic malignancies. However, miRNA expression in ET patients has been poorly explored. We performed miRNA profiling in platelets from 19 ET patients and 10 healthy controls. Hierarchical cluster analysis showed two well-separated clusters between patients and controls, indicating that ET platelets had a characteristic 70-miRNA signature ( P &lt;0.0001), 68 of which were downregulated. According to the mutational status, three differentially expressed miRNAs, miR-15a ( P =0.045), miR-150 ( P =0.001) and miR-519a ( P =0.036), were identified. A 40-miRNA signature was identified characterizing JAK2V617F-positive ET patients. Eight genes, whose interaction with the miRNAs could activate the JAK/STAT pathway were identified. An inverse correlation was observed between miRNAs expression and their target genes for SOCS1 and miR-221, SOCS3 and miR-221, SOCS3 and miR-203, and PTPN11 and miR-23a. All three miRNAs were upregulated in JAK2V617F-negative ET patients. SOCS1 and SOCS3 were validated as targets of miR-221 and miR-203, respectively. In summary, our study shows that platelets from JAK2V617F-negative ET patients harbor a specific miRNA signature that can participate in the modulation of the JAK/STAT pathway through regulation of key genes as SOCS1 and SOCS3 .
Cervical Cancer Stem Cells Selectively Overexpress HPV Oncoprotein E6 that Controls Stemness and Self-Renewal through Upregulation of HES1
Authors: Abhishek Tyagi, Kanchan Vishnoi, Sutapa Mahata, Gaurav Verma, Yogesh Srivastava, Shashank Masaldan, Bal Gangadhar Roy, Alok C. Bharti, Bhudev C. Das
Journal: Clinical Cancer Research (2016)

Perturbation of keratinocyte differentiation by E6/E7 oncoproteins of high-risk human papillomaviruses that drive oncogenic transformation of cells in squamocolumnar junction of the uterine cervix may confer "stem-cell like" characteristics. However, the crosstalk between E6/E7 and stem cell signaling during cervical carcinogenesis is not well understood. We therefore examined the role of viral oncoproteins in stem cell signaling and maintenance of stemness in cervical cancer.Isolation and enrichment of cervical cancer stem-like cells (CaCxSLCs) was done from cervical primary tumors and cancer cell lines by novel sequential gating using a set of functional and phenotypic markers (ABCG2, CD49f, CD71, CD133) in defined conditioned media for assessing sphere formation and expression of self-renewal and stemness markers by FACS, confocal microscopy, and qRT-PCR. Differential expression level and DNA-binding activity of Notch1 and its downstream targets in CaCxSLCs as well as silencing of HPVE6/Hes1 by siRNA was evaluated by gel retardation assay, FACS, immunoblotting, and qRT-PCR followed by in silico and in vivo xenograft analysis.CaCxSLCs showed spheroid-forming ability, expressed self-renewal and stemness markers Oct4, Sox2, Nanog, Lrig1, and CD133, and selectively overexpressed E6 and HES1 transcripts in both cervical primary tumors and cancer cell lines. The enriched CaCxSLCs were highly tumorigenic and did recapitulate primary tumor histology in nude mice. siRNA silencing of HPVE6 or Hes1 abolished sphere formation, downregulated AP-1-STAT3 signaling, and induced redifferentiation.Our findings suggest the possible mechanism by which HPVE6 potentially regulate and maintain stem-like cancer cells through Hes1. Clin Cancer Res; 22(16); 4170-84. ©2016 AACR.