tbuckley/cabot-search huggingface dataset:
MicroRNA 181a (<i>miR-181a</i>) expression as a prognosticator in cytogenetically normal acute myeloid leukemia (CN AML)
Authors: S. Schwind, G. Marcucci, K. Maharry, M. D. Radmacher, S. P. Whitman, P. Paschka, K. Mrózek, J. E. Kolitz, R. A. Larson, C. D. Bloomfield
Journal: Journal of Clinical Oncology (2009)

7001 Background: We showed recently that CEBPA mutations (mut) in CN AML are associated with better outcome and a unique microRNA expression profile, including miR-181a upregulation. Here we tested if miR-181a expression can predict outcome independently. Methods: We analyzed 187 de novo CN AML adult patients (pts) aged &lt;60 years (y; median 45) similarly treated on CALGB 9621 and 19808. Of these, 122 had molecular high risk [FLT3-ITD or NPM1 wild type (wt)] and 65 low risk (no FLT3-ITD, NPM1 mut) CN AML. FLT3, NPM1, CEBPA, MLL, and WT1 mutations, and ERG and BAALC expression were analyzed centrally. miR-181a expression was measured in pretherapy marrow using OSUCCC v3.0 arrays. The mean of 2 miR-181a probe log intensities was used as a continuous variable for analyses. Results: Higher miR-181a levels (miR-181a↑) were associated with CEBPA mut, NPM1 wt, no FLT3-TKD, lower ERG expression, higher %FAB M1/M2, lower WBC and age, higher blood blasts, and lower % gum hypertrophy. miR-181a↑ tended to associate with more complete remissions (CRs; p = .07) and significantly associated with longer disease-free (DFS; p = .05) and overall (OS; p = .01) survival (median follow-up 6.5 y for pts alive). A stronger prognostic impact of miR-181a was observed in the molecular high risk group, where miR-181a↑ predicted more CRs (p = .03), and longer DFS (p = .0002) and OS (p = .0001). In multivariable analyses of the molecular high risk group, miR-181a↑independently predicted CR, and longer DFS and OS (Table). For descriptive purposes, we dichotomized pts at the median miR-181a expression value. For high v low miR-181a expressers, CR rates were 84% vs 72% and 5 y DFS and OS rates 43% vs 18% and 48% vs 19%, respectively. Conclusions: miR-181a expression is a prognostic marker in CN AML, mainly in the molecular high risk group, where it predicts outcome independently of other variables including CEBPA mutations. As miR-181a↑ confer better treatment response, novel approaches increasing miR-181a levels might benefit not only CN but also other AML pts. [Table: see text] No significant financial relationships to disclose.
Systemic mechanisms and effects of ionizing radiation: A new ⿿old⿿ paradigm of how the bystanders and distant can become the players
Authors: Zacharenia Nikitaki, Ifigeneia V. Mavragani, Danae A. Laskaratou, Violeta Gika, Vadim P. Moskvin, Konstantinos Theofilatos, Konstantinos Vougas, Robert D. Stewart, Alexandros G. Georgakilas
Journal: Seminars in Cancer Biology (2016)
A multicenter phase II randomized study of gemcitabine (G) weekly followed by erlotinib (E) after progression versus E followed by G after progression in advanced non-small cell lung cancer (NSCLC) in vulnerable elderly patients selected with a comprehensive geriatric assessment (CGA) (GFPC*0505).
Authors: H. Jullian, L. Greillier, C. Chouaid, R. Corre, J. Crequit, L. Falchero, C. Dujon, H. Berard, J. B. Auliac, H. Le Caer
Journal: Journal of Clinical Oncology (2010)

e18002 Background: Elderly patients (pts) are a heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and activity of weekly G followed by E after progression versus E following by G after progression in vulnerable elderly advanced NSCLC patients selected on the basis of a CGA and Charlson score (CS). Methods: This multicenter phase II study randomized chemonaive pts with stage IV and IIIB with pleural effusion received G 1,250mg/m2 days 1, 8, for a maximum of 18 weeks or until progression, followed by E until second progression (arm A) versus E in first line followed by G until second progression (arm B).Only vulnerable pts (without dependence for ADL and geriatric syndrome) selected by CGA using a software (EGSK) included in a palm assistant with 10 items: socio-economic conditions, cognitive assessment, depression scale, nutritional risk, quality of life(QOL), ADL, IADL (Lawton), incontinence, falls, pain. Major endpoint was time to second progression (TTP2), secondary endpoints were response, time to first progression (TTP1), safety, QOL. Results: 95 pts (67 available today) were enrolled from Aug 2006 to Dec 2009. Patients: Male/Female 54/13, median age 78.1; PS 0/1/2:22/33/10, median co-morbidity (CS) 1.85 (1-3), median IADL score 3.48 (1-4), median global geriatric index: 17.7/20. Respectively for arm A and B, partial response was 18% and 7%, stable disease 18% and 27%, progressive disease 64% and 67%,TTP1 81 and 63 days, median survival 4.3 and 3.9 months. The main WHO grade 3/4 toxicity was anemia 12.5% and fatigue 12.5% in arm A and fatigue 28.6% and anemia 5.7% in B. Conclusions: Preliminary analysis suggests that either the G followed by E or E followed by G appears to have acceptable toxicity but moderate activity, comparable in terms of efficacy to prior data in this vulnerable elderly NSCLC pts population with significant co-morbidities. Our trial confirms the necessity to identify the better tools in CGA to distinguish frail pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Boehringer Ingelheim, Lilly, Roche Amgen, Lilly, Roche Amgen, Lilly, Roche
Outpatient single dose ceftriaxone and amikacin vs. imipenem/cilastatin monotherapy in the empiric treatment of pediatric patients with high risk fever aneutropenia. A randomized, prospective clinical trial
Authors: N. Ahmed-El Borollosy, A. El Beshlawy, H. El Mahallawy, A. El Haddad
Journal: Journal of Clinical Oncology (2004)

8520 Background: The empiric usage of once daily ceftriaxone plus amikacin (C+A) for febrile neutropenia allows outpatient treatment for selected patients. We hypothesized that patients initially at high risk for sepsis can be candidates for outpatient therapy if at 48 hours satisfy strict "Selection Criteria". Being a well established monotherapy agent, Imipenem was used as control. We compared the efficacy, treatment modification, toxicity, duration of hospitalization and cost between both groups. In addition we assessed risks of early discharge and rate of readmission. Design/Methods: A prospective, randomized crossover clinical trial involving 120 pediatric cancer patients with high-risk fever and neutropenia. Febrile patients at 72 hours were crossed-over together with adding vancomycin. Patients on C+A were assessed using Early Discharge Criteria, and if eligible continued treatment as outpatients. Intention-to-treat analysis was used. Results: We found a statistically significant difference between duration of hospitalization between the C+A [median 4.5 days] and control [9.5 days] (p<0.001), per episode antibiotic cost (p< 0.001) & total episode cost [study median $873 vs. control $1655, p<0.001]. Similar results were obtained using average admission costs in a corresponding North American institution. There was no statistically significant difference in the response to treatment at 72 hours, after crossover or at the end of episode. Cultures grew more Gram-positive bacteria (59%). Overall success rate was 95.8%. Conclusions: Pediatric febrile-neutropenic patients initially at high-risk for sepsis can be risk-assessed at some point in treatment for outpatient therapy. The convenience, less adverse effects and cost benefit of the once daily regimen of ceftriaxone plus amikacin will be particularly useful to reduce the overall treatment costs, and duration of hospitalization. Further studies are needed to clarify the role of risk categorization and outpatient therapy in the context of high-risk febrile neutropenia. No significant financial relationships to disclose.
Production of Carcinoembryonic Antigen by Human Prostate Epithelial Cells In Vitro2
Authors: Richard D. Williams, David L. Bronson, Arthur Y. Elliott, Elwin E. Fraley
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Production of Carcinoembryonic Antigen by Human Prostate Epithelial Cells In Vitro Get access Richard D. Williams, Richard D. Williams Search for other works by this author on: Oxford Academic PubMed Google Scholar David L. Bronson, David L. Bronson Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur Y. Elliott, Arthur Y. Elliott Search for other works by this author on: Oxford Academic PubMed Google Scholar Elwin E. Fraley Elwin E. Fraley Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 4, April 1977, Pages 1115–1116, https://doi.org/10.1093/jnci/58.4.1115 Published: 01 April 1977 Article history Received: 18 June 1976 Accepted: 15 September 1976 Published: 01 April 1977
Development of Biomarker Models to Predict Outcomes in Lupus Nephritis
Authors: Bethany J. Wolf, John C. Spainhour, John M. Arthur, Michael G. Janech, Michelle Petri, Jim C. Oates
Journal: Arthritis & Rheumatology (2016)

Objective The American College of Rheumatology guidelines for the treatment of lupus nephritis recommend change in induction therapy when response to therapy has not occurred within 6 months. Response is not defined, and renal fibrosis can occur while waiting for this end point. Therefore, a decision support tool to better define response is needed to guide clinicians when starting patients on therapy. This study was undertaken to identify biomarker models with sufficient predictive power to develop such a tool. Methods Urine samples from 140 patients with biopsy‐proven lupus nephritis who had not yet started induction therapy were analyzed for a panel of urinary biomarkers. Univariate receiver operating characteristic (ROC) curves were generated for each individual biomarker and compared to the ROC area under the curve values from machine learning models developed using random forest algorithms. Biomarker models of outcome developed with novel markers in addition to clinical markers were compared to those developed with traditional clinical markers alone. Results Models developed with the combined traditional and novel biomarker panels demonstrated clinically meaningful predictive power. Markers most predictive of response were chemokines, cytokines, and markers of cellular damage. Conclusion This is the first study to demonstrate the power of low‐abundance biomarker panels and machine learning algorithms for predicting lupus nephritis outcomes. This is a critical first step in research to develop clinically meaningful decision support tools.
A phase I and pharmacokinetic study of weekly 48-hour infusion of high-dose 5-Fluorouracil and folinic acid in patients with recurrent or metastatic colorectal cancers
Authors: K.-H. Yeh, W.-C. Lu, Y.-F. Ho, Y.-S. Lu, C.-H. Hsu, M.-Y. Liu, R. R. Chen, A.-L. Cheng
Journal: Journal of Clinical Oncology (2004)

3674 Background: We have successfully used weekly 24-hour infusion of high-dose 5-FU (2,600 mg/m2) with leucovorin (LV, folinic acid) (300 mg/m2) (HDFL24) to treat metastatic colorectal cancer (J Clin Oncol 1994;12:875; Anticancer Res 1997;17:3867). Our in-vitro data show that 2.5 μM of 5-FU can suppress free thymidylate synthase, and exposure for more than 24 hours may result in even higher cytotoxicity. Minimal myelosuppression of HDFL24 is attributed to a short half-life of 5-FU and the existence of a “blood-bone marrow (BM) barrier” at low plasma 5-FU concentrations. We further explored the best schedule/dose of 5-FU/LV, and studied the pharmacokinetics (PK) of weekly 48-hour infusion of high-dose 5-FU and LV (HDFL48) regimen. Methods: We escalated 5-FU from 2,500 (level 1), 3,000 (level 2), 3,500 (level 3), to 3,750 mg/m2 (level 4) plus a fixed-dose (300 mg/m2) of LV. The 48-hour infusion was given on Days 1, 8, 15, repeated every 4 weeks. At the end of the 1st dose of the 1st cycle for each patient, one BM aspirate and 3 blood samples (at 0, 20 and 40 minutes after completion) were collected. Plasma 5-FU concentrations were assayed by HPLC. Results: The mean (range) values of half-life, clearance, and volume of distribution were 7.9 (4.3–11.6) min, 3011 (592–7074) ml/min, and 0.52 (0.19–1.04) L/kg, respectively. The mean 5-FU concentrations in plasma/BM at level 1, 2, and 3 were 5.63/2.90, 4.64/2.05, and 23.69/4.73μM. Thirteen patients had been enrolled, and 12 of them had failed HDFL24-based regimens. DLT was not reached until 1 of 3 patients at dose level 4 who had developed Gr3 neutropenia and thrombocytopenia. During a total of 61 cycles (average: 5.1, range: 2–12 cycles/patient), major toxicity was Gr1/2 diarrhea and stomatitis in 28 (45.9%) and 42 (68.9%) cycles. Notably, 3 patients had partial response, including 2 had failed HDFL24. Median time to progression was 4 (2–12) months. Conclusions: The PK study shows 5-FU concentrations in BM were lower than that in plasma by about 2-to-5 folds. Data suggest the MTD of 5-FU/LV in HDFL48 is at least 3,750/300 mg/m2/48-hour, and HDFL48 can be used as the salvage chemotherapy for those who had failed HDFL24. No significant financial relationships to disclose.
Circulating biomarkers of sorafenib efficacy in advanced HCC.
Authors: Leonidas Chelis, Kostantinos Anagnostopoulos, Grigorios Trypsianis, Eleni Kyrillos Hamalidou, Nikolaos Xenidis, Kiriakos Amarantidis, Savas Deftereos, Dimitra Pitsiava, Prodromos Michailidis, Evagelos Christakidis, Dimitrios Michailidis, Dimitrios Matthaios, Filio Koukaki, Alexandros H. Kortsaris, Stylianos Kakolyris
Journal: Journal of Clinical Oncology (2013)

302 Background: Sorafenib represents the only drug with proven efficacy as first-line treatment of hepatocellular carcinoma (HCC). We analyzed 12 cytokines and growth factors related to angiogenesis, inflammation and cell proliferation and evaluated their possible utility as biomarkers of sorafenib efficacy in HCC. Methods: Our study population consisted of 62 HCC patients who received first-line sorafenib and 20 healthy controls. Material was collected at 3 different snapshots: (A) at baseline, (B) after 4 weeks on treatment, (C) at disease progression. Using commercially available ELISA kits we measured the serum levels of: VEGF-A, b FGF, sVEGFR2, Ang2, SDF1, VEGF-C, IL-6, IL-8, AFP, HGF, TSP1, BMP9 (bone morphogenetic protein 9). BMP9, a vascular quiescence factor, was explored for first time in HCC. Results: Patients had significant: (a) higher levels of Ang2, IL-6, IL-8, AFP, HGF, VEGF-A, FGFb , (b) lower levels of SDF1 than controls. At snapshot (B) we found a significant decrease of BMP9 and sVEGFR2 while a trend for significant increase was observed for VEGF-A, bFGF and IL-6. All statistically significant correlations for baseline levels of examined cytokines and their median change at week 4 with overall survival (OS) and progression free survival (PFS) are listed (Table). At disease progression (snapshot C) in comparison with baseline we found statistical significant: (a) increase for AFP, VEGF-A, bFGF, IL-6, (b) decrease for BMP9 and sVEGFR2. Conclusions: The values of circulating cytokines and growth factors examined in the present study showed frequent and statistically significant alterations during the disease course. Whether these factors could serve as potential biomarkers of sorafenib efficacy in HCC is something warranting further exploration and confirmation in bigger studies. [Table: see text]
Erratum: Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro
Authors: J Iqbal, D D Weisenburger, A Chowdhury, M Y Tsai, G Srivastava, T C Greiner, C Kucuk, K Deffenbacher, J Vose, L Smith, W Y Au, S Nakamura, M Seto, J Delabie, F Berger, F Loong, Y-H Ko, I Sng, X Liu, T P Loughran, J Armitage, W C Chan
Journal: Leukemia (2011)
Weekly paclitaxel, carboplatin, and bexarotene for the treatment of patients with advanced non-small cell lung cancer: Efficacy results from a phase I/II study
Authors: W. J. Petty, K. H. Dragnev, W. C. Black, B. F. Cole, S. Hammond, I. Williams, E. Dmitrovsky, J. R. Rigas
Journal: Journal of Clinical Oncology (2005)

7243 Background: The combination of weekly paclitaxel (Taxol) and every 4 week carboplatin (Paraplatin) as first-line therapy for advanced non-small cell lung cancer (NSCLC) has been reported. The study noted a median survival time of 8.8 months and a 1-year survival of 39.5%. The current phase I/II study was designed to evaluate the tolerability and activity of the rexinoid, bexarotene (targretin) in combination with weekly paclitaxel and every 4 week carboplatin. Methods: Patients with confirmed stage IIIB or IV NSCLC and adequate organ function were enrolled. Prior chemotherapy was allowed for the phase I portion of this study. All patients were scheduled to receive paclitaxel 100 mg/m2 weekly for 3 doses every 4 weeks and carboplatin AUC = 6 monthly. Bexarotene oral capsules were administered daily starting on initial day of chemotherapy. Two dose levels of bexarotene were evaluated (300 mg/m2/day and 400 mg/m2/day). The recommended phase II dose of bexarotene was 400 mg/m2/day. Results: As of December 2004, 33 patients were enrolled, 13 patients receiving 300 mg/m2/day and 20 patients at 400 mg/m2/day of bexarotene. Patient characteristics include: age (median 59), gender (female 43%), stage (93% stage IV), Karnofsky performance status (37% with KPS 60–70%), prior chemotherapy (30%), prior radiation (33%), and prior surgery (33%). Hematologic toxicity was mild with grade 3 anemia in 3 pts and grade 3 neutropenia in 4 pts. Non-hematologic toxcities consisted primarily of hyperlipidemia and hypothyroidism which were medically managed. No cases of pancreatitis were observed. With a median follow-up of 15.1 months, the median survival time for all patients is 6.9 months with 1-year survival of 43%. The median survival time for chemotherapy-naive patients (n = 24) is 8.3 months with a 1-year survival of 47%. Conclusions: The 1-yr survival for chemotherapy-naive patients treated with bexarotene in combination with weekly paclitaxel and every 4 week carboplatin is encouraging. Ongoing phase III trials will determine whether adding bexarotene to conventional chemotherapy improves survival as a first line treatment for NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Ligand Bristol-Myers Squibb, Ligand Bristol-Myers Squibb, Ligand
Abstract A39: A platform to assess multiple therapy options simultaneously in a patient's own tumor
Authors: Richard Klinghoffer, Alicia Moreno-Gonzalez, Michael Carleton, Marc Grenley, Beryl Hatton, Jason Frazier, William Kerwin, Ilona Tretyak, Nathan Hedin, Joyoti Dey, Joseph Casalini, Sally Ditzler, James Olson, Nathan Caffo
Journal: Clinical Cancer Research (2015)

Abstract Assessment of anti-cancer drug efficacy is an imprecise and challenging undertaking. Early candidate selection is typically based on results from systemically treated animal models and later by performance in human trials where patients are exposed to often toxic levels of drug, prior to obtaining readouts of tumor response. In both of these testing models, only one drug can be tested at a time. Using these methods, over 90% of candidate new oncology drugs fail to provide benefit for patients in human clinical trials. To improve the predictive value of preclinical candidate selection in animal models and enable a new type of pre-Phase 1 toxicity-sparing comparative drug efficacy study in humans, amenable for use in the solid tumor clinic, we have developed a technology platform called CIVO™. This platform allows for simultaneous assessment of multiple drugs or drug combinations directly in a single solid tumor to assess efficacy, resistance and drug synergies. In this study, precise, controlled delivery of classic chemotherapy drugs vincristine and doxorubicin induced spatially defined (ranging 0.3 – 2.0 mm in diameter), readily detectable, and mechanism-specific cellular changes around sites of tumor microinjection across three xenograft models of lymphoma. The extent of apoptosis induced via CIVO™ microdosing of each drug (&amp;lt;1/100th the effective dose used to treat human patients) correlated with drug effect on tumor growth mediated by conventional systemic drug dosing. Consistent with utility for detecting pre-existing tumor resistance to certain drugs, CIVO™ microdosing predicted diminished responses to both vincristine and doxorubicin in tumors derived from cells that had previously acquired resistance to doxorubicin. This lack of efficacy was confirmed by systemic treatment of the resistant tumors. The CIVO™ platform is concurrently being evaluated for correlation to systemic treatment in immune-intact canine patients with autochthonous tumors. The data presented here generated in drug-responsive and non-responsive solid tumors in the preclinical setting sets the stage for future application of this technology to demonstrate tumor responsiveness to novel drug candidates in the context of human patients. Citation Format: Richard Klinghoffer, Alicia Moreno-Gonzalez, Michael Carleton, Marc Grenley, Beryl Hatton, Jason Frazier, William Kerwin, Ilona Tretyak, Nathan Hedin, Joyoti Dey, Joseph Casalini, Sally Ditzler, James Olson, Nathan Caffo. A platform to assess multiple therapy options simultaneously in a patient's own tumor. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A39.