tbuckley/cabot-search huggingface dataset:
Phase I/II trial of palbociclib in combination with bicalutamide for the treatment of androgen receptor (AR)(+) metastatic breast cancer (MBC): Pharmacokinetics (PK)
Authors: A. Gucalp, A. Corben, S. Patil, L.A. Boyle, C. Hudis, T.A. Traina
Journal: Annals of Oncology (2016)
Improving the efficacy of chemotherapy drugs for the treatment of triple-negative breast cancers.
Authors: Behyar Zoghi, Peter Ravdin
Journal: Journal of Clinical Oncology (2012)

107 Background: Approximately 15-20% of all breast cancers account for triple-negative breast cancers that exhibit aggressive, distinct metastatic pattern and poor prognosis. More than 50% of patients with triple negative breast cancers develop chemoresistance and do not respond to chemotherapeutic drugs, leading to early relapse and shorter survival. Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious cancer drugs. Methods: Through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant triple negative breast cancer cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Results: Through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant triple negative breast cancer cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Since miRNAs are endogenously expressed and can be easily manipulated using synthetic oligoribonucleotides, we believe that they represent more attractive targets than the single gene or gene product that is the target of conventional cancer treatments that are typically prone to drug resistance. Supporting this, we have recently demonstrated that miRNAs can be systemically delivered to treat breast cancer lung metastasis without any hepatotoxicity. In addition to being a potent therapeutic regimen, our preliminary analyses reveal that miRNAs can be bonafide early prognostic markers to monitor treatment response to specific drugs in triple-negative breast cancers. Conclusions: Taken together, these findings suggest that miRNA can serve as potent therapeutic adjuvants and although the data content of miRNA profiles is far less than that of gene expression profiles, by virtue of their ability to modulate entire spectrum of genes and pathways miRNAs have potential to be better classifiers for the prognosis and response to treatment of cancers. We believe that the identification of miRNAs that mediate chemoresistance could lead to more efficient treatment selection at the patient level and an improved response rates at the population level.
Integrative Genome-Wide Analysis of RNA Binding and Splicing Reveals Complex Loss and Gain of Function Alterations By SRSF2 P95 Mutations in Myelodysplasia
Authors: Kai Rejeski, Yang Liang, Toma Tebaldi, Giovanni Stefani, Ashley Taylor, Jamie Maziarz, Yuanbin Song, Kunthavai Balasubramanian, Radovan Vasic, Edo Kapetanovic, Omar Abdel-Wahab, Manoj M Pillai, Stephanie Halene
Journal: Blood (2015)
Alzheimer Outlook Far From Bleak
Authors: Jeff Lyon
Journal: JAMA (2017)

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
Predictors of survival in patients with refractory metastatic colorectal cancer.
Authors: S. Kim, H. Lee, J. Baek
Journal: Journal of Clinical Oncology (2011)

583 Background: The survival of patients (pts) with metastatic colorectal cancer (mCRC) refractory to three active drugs including fluoropyrimidine, oxaliplatin and irinotecan is very limited but highly variable. Since estimating life expectancy is important for palliative intervention and advanced care planning, we aimed to suggest a model for improved prognostication of pts with mCRC. Methods: We retrospectively reviewed 185 pts with mCRC who had been treated with fluoropyrimidine, oxaliplatin and irinotecan with no response to treatment since 2008. Results: Of 185 pts, there were 104 (56.2%) males and 81 (43.8%) females. The median age was 58 years (range, 23-84 years). Additional cetuximab treatment was given in 43 (23.2%) pts. The median overall survival was 4.82 months. There were seven independent variables with a relationship to survival: performance status (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.31 to 2.42; p&lt;0.001), resection of primary tumor (HR, 1.55; 95% CI, 1.04 to 2.31; p=0.033), histologic type (HR, 2.54; 95% CI, 1.59 to 4.06; p&lt;0.001), neutrophil/lymphocyte ratio (HR, 1.62; 95% CI, 1.14 to 2.30; p=0.007), serum hemoglobin level (HR, 1.42; 95% CI, 1.02 to 1.96; p=0.035), serum albumin level (HR, 2.33; 95% CI, 1.38 to 3.92; p=0.001) and sum of metastasis site (HR, 2.00; 95% CI, 1.39 to 2.86; p&lt;0.001). By combining these risk factors, pts with mCRC could be categorized into three different groups (Table). There was a significant difference in survival duration between the groups. (p&lt;0.001). Conclusions: Seven prognostic factors predicting survival were identified and used to categorize mCRC Pts who had been treated with fluoropyrimidine, oxaliplatin and irinotecan into three prognostic groups. [Table: see text] No significant financial relationships to disclose.
Generation of Highly Efficient Recombinant Adeno-Associated Virus (rAAV) Vectors Targeted to Chronic Myelogenous Leukemia (CML) - and CD34+ Progenitor Cells Obtained by the „AAV Random Peptide Library“ Method.
Authors: Leopold Sellner, Marlon Veldwijk, Marius Stiefelhagen, Juergen A. Kleinschmidt, Frederik Wenz, W. Jens Zeller, Stefan Fruehauf
Journal: Blood (2006)
Elimination of Platelet Factor 4 (PF4) from Platelets Reduces Atherosclerosis and Increases HDL Cholesterol in C57Bl/6 and ApoE−/− Mice.
Authors: Bruce S. Sachais, Tiffany Turrentine, Jeanine M. Dawicki-McKenna, Daniel J. Rader, M. Anna Kowalska
Journal: Blood (2006)
Lenvatinib mesilate (LEN) enhanced antitumor activity of a PD-1 blockade agent by potentiating Th1 immune response
Authors: Y. Kato, X. Bao, S. Macgrath, K. Tabata, Y. Hori, S. Tachino, M. Matijevici, Y. Funahashi, J. Matsui
Journal: Annals of Oncology (2016)
A randomized phase II study to determine the efficacy and tolerability of two doses of eribulin plus lapatinib in trastuzumab pre-treated patients with Her2-positive metastatic breast cancer - E-Vita -
Authors: J. Bischoff, J. Barinoff, C. Mundhenke, D. Bauerschlag, S.D. Costa, D. Herr, K. Lübe, F. Marmé, N. Maass, G. von Minckwitz, E.-M. Grischke, V. Müller, M. Schmidt, B. Gerber, S. Kümmel, C. Schumacher, P. Krabisch, M. Thill, V. Nekljudova, S. Loibl
Journal: Annals of Oncology (2016)
BCL2 Is Highly Mutated In Diffuse Large B-Cell Lymphoma
Authors: Johanna M Schuetz, Nathalie A Johnson, Ryan D Morin, Martin Hirst, Yongjun Zhao, Angela Tam, Richard Moore, Thomas Zeng, Marco A Marra, Joseph M. Connors, Angela R Brooks-Wilson, Randy D. Gascoyne
Journal: Blood (2010)
A Good Adherence to ELN 09 Recommendations in Chronic Myeloid Leukemia (CML) Treatment with Imatinib, Is Associated with Better Outcomes in Patients Treated Outside Clinical Trials
Authors: Luis Felipe Casado, Begoña Maestro, J. Valentin García-Gutiérrez, Marie Hélène Dumas, Isabel Massague, Pilar Giraldo, Manuel Perez-Encinas, Raquel de Paz, Joaquín Martínez-López, Guiomar Bautista, Santiago Osorio, Maria José Requena, Luis Palomera, Maria Jesús Peñarrubia, Carmen Calle, Jose Ángel Hernández-Rivas, Carmen Burgaleta, Marcio M Andrade, Nuria García-Ormena, Juan Luis Steegmann
Journal: Blood (2012)
Novel AML-Associated Loss of Function Mutations in the B55 Alpha Subunit of PP2A Are Associated with Increased Phosphorylation and Activation of AKT and Enhanced Sensitivity to AKT Inhibitor Induced Cell Growth Arrest
Authors: Geoffrey P. Shouse, Rosalia de Necochea-Campion, Saied Mirshahidi, Xuan Liu, Chien-Shing Chen
Journal: Blood (2014)
Deficiency of the Angiotensinase Aminopeptidase A Increases Susceptibility to Glomerular Injury
Authors: Juan Carlos Q. Velez, Ehtesham Arif, Jessalyn Rodgers, Megan P. Hicks, John M. Arthur, Deepak Nihalani, Evelyn T. Bruner, Milos N. Budisavljevic, Carl Atkinson, Wayne R. Fitzgibbon, Michael G. Janech
Journal: Journal of the American Society of Nephrology (2017)

Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops. Moreover, BALB/c APA-knockout (KO) mice injected with a nephrotoxic serum showed persistent glomerular hyalinosis and albuminuria 96 hours after injection, whereas wild-type controls achieved virtually full recovery. We then tested the effect of 4-week infusion of AngII (400 ng/kg per minute) in APA-KO and wild-type mice. Although we observed no significant difference in achieved systolic BP, AngII-treated APA-KO mice developed a significant rise in albuminuria not observed in AngII-treated wild-type mice along with increased segmental and global sclerosis and/or collapse of juxtamedullary glomeruli, microcystic tubular dilation, and tubulointerstitial fibrosis. In parallel, AngII treatment significantly increased the kidney AngII content and attenuated the expression of podocyte nephrin in APA-KO mice but not in wild-type controls. These data show that deficiency of APA increases susceptibility to glomerular injury in BALB/c mice. The augmented AngII-mediated kidney injury observed in association with increased intrarenal AngII accumulation in the absence of APA suggests a protective metabolizing role of APA in AngII-mediated glomerular diseases.
RAPID siRNA Screen for Identification of Therapeutic Gene Targets in Patients with Hematologic Malignancies.
Authors: Jeffrey W Tyner, Marc Loriaux, Stephanie G Willis, Bill H Chang, Vincent T Bicocca, Stephen T Oh, Iris H.I.M. Hollink, Stefanie Segers, Monique L. DenBoer, Marry M van den Heuvel-Eibrink, C. Michel Zwaan, Jason R Gotlib, Michael Deininger, Brian J. Druker
Journal: Blood (2009)
P08.69 The role of comorbidity in elderly glioblastoma
Authors: V. Villani
Journal: Neuro-Oncology (2016)

BACKGROUND: Several studies observed that age is the most significant factor associated with poor prognosis in patients with glioblastoma (GBM).Age is not the only factor in the choice of treatment in elderly patients.Recent studies in cancer patients have shown that comorbidities should be considered a contraindication to aggressive approach, as they can influence the treatment compliance and/or patients' survival.Co-morbidities are often underestimated in patients affected by GBM, and their role on the outcome of elderly GBM patients has been poorly explored.This study evaluated the impact of comorbidities on outcomes in elderly GBM patients.METHODS: Patients over 65 years affected by GBM were consecutively enrolled in a prospective observational study.Demographic and clinical characteristics were recorded.For each patient, comorbid conditions were indentified with the modified version of the Cumulative Illness Rating Scale (CIRS) [21].Results Sixty-six elderly patients [36 males and 30 females] with GBM were enrolled in the study.The median age at diagnosis was 73 years.The median PFS was 8 months with a median of OS of 18 months.The univariate analysis demonstrates that the variables useful in predicting disease progression were: a severity of CIRS-CI compared with a slight CIRS-CI (HR=3.78,95% CIs from 1.32 to 10.88 p=0.013) and the CM greater than 2 compared with the CM less or equal to 2 (HR=2.01,95% CIs from 1.03 to 3.93 p=0.040).At the multivariate analysis the severity of CIRS-CI showed a statistical trend (serious vs slight HR=3.01,95% CIs from 0.93 to 9.72 p=0.065) (table 2).Univariate analysis of the whole cohort found that having an age ≥75 years (>75 vs ≤75; HR=3.19, 95% CIs from 1.68 to 6.07 p<0.001), intermediate or high CIRS-CI (intermediate vs slight; HR=2.21, 95% CIs from 1.04 to 4.67 p=0.038 and high vs slight; HR=8.42, 95% CIs from 3.44 to 20.58 p2 vs≤2; HR=2.24, 95% CIs from 1.16 to 4.32 p=0.016) were associated with shorter survival (table 3).The multivariate analysis confirmed the predictive role on survival for age ≥ 75 years (HR=4.20,95% CIs from 1.99 to 8.85 p>0.001), intermediate CIRS-CI (HR=2.26,95% CIs from 1.06 to 4.81 p=0.034) and high CIRS-CI (HR=8.63,95% CIs from 2.98 to 24.94 p<0.001) (table 3).The CM was not confirmed in the multivariate analysis.Discussion: Lastly, our findings need to be replicated in larger samples.If the prognostic role of comorbidity measured by CIRS on the outcome is confirmed, it would be important to add it in the algorithm for treatment choice in elderly GBM patients.Overall survival
Impact of FOLFOXIRI plus bevacizumab on resectability and survival in patients with initially unresectable liver metastases from colorectal cancer.
Authors: M. Shimada, M. Nishioka, J. Hanaoka, H. Mori, T. Ikemoto, S. Imura, Y. Morine, T. Utsunomiya
Journal: Journal of Clinical Oncology (2011)

621 Background: Prognosis in patients with unresectable liver metastases from colorectal cancer is known to be very poor. However, thanks to progress of chemotherapy including molecular-target agents, “conversion” (from unresectable to resectable) has been sometimes seen. The aim of this preliminary study is to clarify the impact of FOLFOXIRI plus bevacizumab (Bev) on conversion and prognosis in patients with initially unresectable liver metastases from colorectal cancer. Methods: Seven patients with initially unresectable liver metastases from colorectal cancer, who received FOLFOXIRI (LOHP 85mg/m 2 D1, CPT-11 150mg/m 2 D1, LV 200mg/m 2 D1, and 5FU 2,400mg/m 2 infusion over 46 hours, D1) plus Bev 5mg/kg bolus every 2 weeks, were included in this study. Resectability, disease-free survival (DFS), and overall survival (OS) after hepatic resection were investigated in detail. In addition, completeness and adverse effects were examined in this regimen. Results: All 7 patients tolerated the regimen well, and no adverse effect of grade 3-4 was observed. Five out of 7 patients (71%) became resectable (conversion), except for 2 with multiple lung metastases and bone metastasis prior to chemotherapy. Our historical conversion rates were, 0% (0/7) in 5FU/LV regimen from 1994 to 2003, 25% (7/27) other regimens such as FOLFIRI and FOLFOX except for FOLFOXIRI plus Bev from 2004. In 5 patients who became resectable, CR was not observed, however, all had PR after 6 cycles of chemotherapy (RR 100%). All 5 patients could undergo curative (R0) hepatic resection, furthermore, all had pathological major response (grade 2). Follow-up period ranged from 8 to 18 months, with a median period of 14 months, and 2 patients relapsed (lung recurrence and peritoneal dissemination), and one died of lung metastases (1.5-year OS and DFS are 80 % and 60%). Conclusions: Our preliminary data suggested the feasibility of this new therapeutic combination in patients with initially unresectable liver metastases from colorectal cancer, and a high conversion rate and better prognosis. [Table: see text]
The Follicular Lymphoma International Prognostic Index (FLIPI) as Part of a Proposed Prognostic Model for Follicular Lymphoma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (ASCT).
Authors: Grant E. Keeney, Theodore A. Gooley, Oliver W. Press, John M. Pagel, Stephen H. Petersdorf, David G. Maloney, Ajay K. Gopal
Journal: Blood (2004)
Re: Schwartz et al.: Intracameral antibiotics and cataract surgery: endophthalmitis rates, costs, and stewardship (Ophthalmology 2016;123:1411-1413)
Authors: Virgilio Galvis, Alejandro Tello, Rubén D. Berrospi, Paul A. Camacho, Juan José Rey
Journal: Ophthalmology (2017)
MNGO-09. PROGNOSTIC SIGNIFICANCE OF PRE-OPERATIVE ANEMIA AND LEUKOCYTOSIS ON RECURRENCE-FREE SURVIVAL IN MENINGIOMA
Authors: Shirin Karimi, Peter Tonge, Lior Gonen, Raha Tabasinejad, Manav Vyas, Gelareh Zadeh, Kenneth Aldape
Journal: Neuro-Oncology (2016)

Definite pretreatment predictors for tumor recurrence in meningioma are not well defined. Several studies in solid malignant tumors from various sites including glioblastoma have indicated the association of pre-treatment anemia and/or changes in number of leukocytes in peripheral blood with patient outcomes. We hypothesized those changes in complete blood count (CBC) before tumor resection can be used as one of the prognostic factors for tumor recurrence in meningioma. We gathered the clinical and pathological data from 226 histologically confirmed meningioma patients as well as results of CBC collected within 1 week before neurosurgical resection conducted at the Toronto Western Hospital between 2001 and 2015. Results were compared with recurrence-free survival (RFS) using univariable and multivariable analyses. Using standard cut-offs in our laboratory, anemia, leukocytosis and neutrophilia were identified in 56 (25%), 59 (26%) and 70 (31%) patients, respectively. These were distributed in patients among all 3 grades. The majority of patients had normocytic anemia (45/56). On univariate analysis, the presence of anemia (P=0.0003), leukocytosis (P=0.0123), and neutrophilia (P=0.0008) correlated with worse RFS. We found combined leukocytosis and anemia in 27/226(12%) patients who had a particularly poor outcome. On multivariable analysis after adjustment for malignancy grade and extent of resection, leukocytosis plus anemia remained independently prognostic for RFS (P<0.0001, HR=5.35). Lymphopenia and monocytosis were observed in 88(39%) and 32 (14%) of patients, respectively and both of them showed a trend toward poorer RFS. The presence of anemia, leukocytosis in the pre-operative CBC may suggest tumor recurrence in patients with meningioma and should be examined in additional cohorts. Further studies to explain the effect of pre-treatment anemia and changes in number of leukocytes, neutrophils and lymphocytes in peripheral blood on tumor progression and risk stratification of these patients are needed.
P08.40 RNAseq of paired primary and recurrent glioblastoma samples
Authors: L. F. Stead, A. Bruns, R. Morton, S. Harrison, A. Chakrabarty, A. Ismail, H. King, K. Ashton, K. Syed, S. Short
Journal: Neuro-Oncology (2016)

PURPOSE: Subventricular zone(SVZ)is a paired brain structure situated throughout the lateral walls of the lateral ventricles,a known site of neurogenesis and self-renewing neurons in the adult brain.Some current theories propose that brain tumour stem cells originating from SVZ play a role in progression of high-grade gliomas.Since almost all glioblastomas(GBM) progress locally despite aggressive surgery and radiotherapy,recur within the high-dose irradiation volume in most cases, the theory of tumor cell migration from SVZ is interesting to explore.Irradiation of SVZ supposed to kill brain tumor stem cells which may alter tumor progression and survival.Evaluating the impact of the radiation dose to SVZ on progression rates and overall survival in GBM is our aim.MATERIAL-METHOD: Study population consisted of 80 GBM patients(23f,57m)with a median age of 55.5(21-75)who were treated from January 2012 to December 2014.All patients underwent surgery followed by adjuvant radiotherapy(60Gy/30fractions)and concomitant/adjuvant temozolomid.Bilateral SVZ were contoured on MRI images and registered to planning CT slices.Target volumes and organs at risk were also contoured.Conformal radiotherapy with 3-4fields or IMRT with1-2volumetric arcs were used for planning.Median doses for ipsilateral, contralateral and bilateral SVZ were recorded and relations with progression and survival were analyzed using two threshold values at 40Gy and 50Gy.Analyses were performed after a median follow-up of 13months.RESULTS: Median progression free survival(PFS)was 10 months(2-36) and overall survival(OS) was 12 months(3-48).The unfavorable prognostic factors affecting PFS were tumor extending to ventricles(p50 Gy(p50 Gy(p<0.05).The unfavorable prognostic factors affecting OS were tumor extending to ventricles(p40Gy(p40Gy(p<0.05).In multivariate analysis of prognostic factors, tumor extending to ventricles was the only unfavorable factor for both PFS(p<0.01)andOS(p<0.01).CONCLUSIONS: PFS and OS were shorter in the patients in whom tumor was extending to ventricles and in those where SVZ received at least 40-50 Gy.The data of this study is supports the previous studies showing an inverse correlation between irradiation of SVZ and prognosis.With the present data we can only speculate that those tumors extending deep into the lateral ventricles likely to be larger in size, closer to nearby sensitive structures, and not amenable to total resection.Radiation volumes should cover some parts of SVZ and lateral ventricles to give the prescribed dose to in those unfavorable tumors, which may explain the inverse correlation with SVZ irradiation and survival.Further research is required to clarify the role of brain tumor stem cells locates at SVZ in the prognosis of high-grade gliomas.