tbuckley/cabot-search huggingface dataset:
Lack of function of an N-ethylmaleimide-sensitive thiol protein in erythrocyte membrane of autosomal dominant polycystic kidney disease.
Authors: K Vareesangthip, R Wilkinson, T H Thomas
Journal: Journal of the American Society of Nephrology (1998)

The polycystic kidney disease 1 (PKD1) gene product polycystin has been predicted to be an integral membrane protein involved in cell-cell and cell-matrix interactions. The erythrocyte membrane fluidity in autosomal dominant polycystic kidney disease (ADPKD) patients is increased, and this may be due to a membrane cytoskeletal abnormality. The abnormal erythrocyte sodium-lithium countertransport kinetics in-ADPKD are related to an altered thiol protein in the cytoskeleton. The possibility that a similar thiol protein abnormality causes the increased erythrocyte membrane fluidity in ADPKD was investigated. The membrane fluidity of intact erythrocytes from 12 ADPKD patients and 12 healthy control subjects was assessed from the fluorescence anisotropies of 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium-diphenyl-hexatriene (TMA-DPH). The effect on membrane fluidity of N-ethylmaleimide (NEM), cytochalasin D, heating at 48 degrees C for 20 min, or more specifically, liposomes containing antibodies to actin or ankyrin, was determined. In erythrocytes from healthy control subjects, the fluorescence anisotropy of DPH (mean +/- SEM: 0.223 +/- 0.001) was decreased after treatment with NEM (0.200 +/- 0.003, P < 0.001), cytochalasin D (0.206 +/- 0.006, P < 0.001), heating (0.199 +/- 0.002, P < 0.001), and antibodies to actin (0.194 +/- 0.002, P < 0.001) or ankyrin (0.196 +/- 0.002, P < 0.001). The TMA-DPH anisotropy (0.279 +/- 0.001) was also decreased after treatment with NEM (0.264 +/- 0.001, P < 0.001), cytochalasin D (0.264 +/- 0.001, P < 0.001), heating (0.265 +/- 0.001, P < 0.001), and antibodies to actin (0.262 +/- 0.002, P < 0.001) or ankyrin (0.262 +/- 0.002, P < 0.001). NEM had no additional effect on the other treatments, suggesting that its target thiol protein was associated with the cytoskeleton. In untreated erythrocytes from ADPKD patients, fluorescence anisotropies of both DPH and TMA-DPH were reduced, and none of the treatments altered the anisotropy of either DPH or TMA-DPH. In ADPKD, a cytoskeletal thiol protein is abnormal and possibly explains abnormal lipid bilayer properties and transport protein function in erythrocytes in this disease.
Update of the NCI multiinstitutional phase II trial of romidepsin, FK228, for patients with cutaneous or peripheral T-cell lymphoma
Authors: R. Piekarz, R. Frye, J. Wright, W. Figg, S. Allen, M. Kirschbaum, J. Zain, L. Hutchins, L. Showe, T. Fojo, S. E. Bates
Journal: Journal of Clinical Oncology (2007)

8027 Background: The histone deacetylase inhibitors (HDIs) are a class of differentiating agents undergoing clinical testing. Like other HDIs, romidepsin (FK228) modulates expression of genes involved in cell cycle regulation and markers of differentiation in cancer cell lines, leading to induction of differentiation or apoptosis. Romidepsin has demonstrated clinical activity in patients with T-cell lymphoma. Methods: Patients with CTCL (42) or PTCL (36) were enrolled in the NCI multi-institutional trial and assigned to cohorts based on extent of prior therapy and pathology. Romidepsin is administered on days 1, 8, and 15 of a 28 d cycle with a starting dose of 14mg/m 2 . Responses for patients with PTCL are measured using Cheson criteria, and CTCL using RECIST criteria. Results: Cohort one, composed of 27 patients who had previously received no more than 2 prior cytotoxic regimens of chemotherapy, has completed enrollment. Responses observed include 3 patients with CR and 7 patients with partial responses, yielding an overall response rate of 37%. Of note, responses were observed independent of stage of disease. Among 18 patients with stage IV disease, 6 patients had a complete or partial response, including 3 patients with Sézary syndrome. When including patients with greater than 2 prior cytotoxic regimens, the overall response rate was 31%. A replicate arm has been opened with the goal of confirming the response rate observed in the first cohort. Response data have not been evaluated from this arm at this time. Responses observed in 36 patients with refractory or relapsed PTCL includes 3 patients with CR and 8 patients with partial responses, comprising an overall response rate of 30%. Responses were observed independent of prior therapy, with some patients having undergone prior stem-cell transplant. Molecular endpoint analysis was performed on peripheral mononuclear cells (PBMNCs) and tumor biopsies from treated patients evaluating histone acetylation and changes in gene expression. Conclusions: Romidepsin as a single agent appears to have significant single agent activity in patients with CTCL and PTCL. Combination therapy with romidepsin may increase efficacy and should be pursued. This protocol remains open to accrual. No significant financial relationships to disclose.
Identification of differentially expressed genes in paediatric ependymoma
Authors: Blanca Suarez-Merino, Mike Hubank, Richard Hayward, William Harkness, Dominic Thompson, Kim Phipps, Tamas Revesz, John L. Darling, David G. Thomas, Tracy Warr
Journal: Neuro-Oncology (2003)

Abstracts from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Duke University Press.
Molecular Remission After Allogeneic or Autologous Transplantation of Hematopoietic Stem Cells for Multiple Myeloma
Authors: Giovanni Martinelli, Carolina Terragna, Elena Zamagni, Sonia Ronconi, Patrizia Tosi, Roberto M. Lemoli, Giuseppe Bandini, Maria Rosa Motta, Nicoletta Testoni, Marilina Amabile, Emanuela Ottaviani, Nicola Vianelli, Antonio de Vivo, Alessandro Gozzetti, Sante Tura, Michele Cavo
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To assess the clinical relevance of minimal residual disease (MRD) in patients with multiple myeloma (MM), 50 patients were monitored while they were in complete clinical remission (CCR) after autologous or allogeneic stem-cell transplantation. PATIENTS AND METHODS: Stringent molecular monitoring using clonal markers based on rearranged immunoglobulin heavy-chain genes was performed in 44 of 50 MM patients in CCR. Molecular clinical remission (MCR) was defined as more than one consecutive negative polymerase chain reaction (PCR) test result. RESULTS: Twelve (27%) of 44 molecularly monitored patients achieved MCR; four of the 12 became PCR-positive, and one of these four relapsed. In comparison with patients who did not achieve MCR, patients who achieved MCR had a significantly lower relapse rate (41% v 16%; P &lt; .05) and longer relapse-free survival (35 v 110 months; P &lt; .005). Fourteen of 26 patients in CCR who had received allografts were evaluated on a molecular basis: seven (50%) of the 14 achieved MCR and did not relapse; one of the seven remaining patients relapsed. Thirty of 47 patients in CCR who received autografts were evaluated on a molecular basis: five (16%) of the 30 achieved MCR; two of these five became PCR-negative, and one of these two relapsed. Ten of the 25 remaining patients later relapsed. For these nonrandomized groups, the higher MCR rate after allograft procedures was statistically significant (P &lt; .01; Fisher’s exact test). CONCLUSION: MCR can be obtained in a relatively high proportion of MM patients who have achieved CCR after undergoing allograft procedures and in a smaller fraction of patients after undergoing autograft procedures. In approximately one fourth of MM patients who achieve CCR after transplantation, it may be possible to keep the disease burden constantly below the PCR threshold. Because MCR was associated with prolonged relapse-free survival, these patients could have a relatively favorable clinical outcome.
Abstract 14706: The Impact of Smoking on Short- and Long-Term Outcomes in NSTEMI Results from 38,628 Patients from the CRUSADE Registry
Authors: Lan Shen, Shuang Li, Laine Thomas, Tracy Y Wang, Karen Alexander, Eric Peterson, Matthew T Roe, Bimal Shah
Journal: Circulation (2012)

Introduction Smoking tobacco is a known risk factor for coronary disease yet prior studies have found that smokers have observed paradoxically favorable short-term outcomes after acute coronary syn...
Phase II study of pemetrexed (P) plus carboplatin (Cb) or cisplatin (C) with concurrent radiation therapy followed by pemetrexed consolidation in patients (pts) with favorable-prognosis inoperable stage IIIA/B non-small cell lung cancer (NSCLC).
Authors: Hak Choy, Lee Steven Schwartzberg, Shaker R. Dakhil, Edward B. Garon, Janak K. Choksi, Ramaswamy Govindan, Guangbin Peng, Andrew Koustenis, Joseph Treat, Coleman K. Obasaju
Journal: Journal of Clinical Oncology (2012)

7002 Background: There is no consensus chemotherapy regimen with concurrent radiation therapy (CRT) for inoperable stage IIIA/B NSCLC. P synergizes with ionizing radiation, as well as with Cb and C in preclinical models. These doublets have shown efficacy and favorable toxicity profiles in phase II/III trials. Methods: In this open-label randomized phase II trial, 98pts with inoperable stage IIIA/B NSCLC (all histologies) were randomized (1:1) to P 500 mg/m 2 plus Cb AUC 5 (PCb) or P 500 mg/m 2 plus C 75 mg/m 2 (PC) intravenously (IV) every 21 days for 3 cycles. All pts received CRT 64–68 Gy (2 Gy/day, 5 days/week, Days 1–45). Consolidation P 500 mg/m 2 IV every 21 days for 3 cycles began 3 weeks after completion of CRT. The primary endpoint was 2-year overall survival (OS); secondary endpoints included median OS, time to progression (TTP), overall response rate (ORR), and toxicity. Results: Since Jun 2007, 98 pts were enrolled (PCb: 46; PC: 52).Pts were followed until Oct 2011. Mean dose compliance was PCb: 95.7% P, 97.1% Cb; PC: 89.7% P, 89.1% C. Mean dose compliance for CRT was PCb: 95.7%; PC: 88.1%. CRT dose interruptions occurred in PCb: 32.6% and PC: 40.4%. Two-year OS was PCb: 45.2% (95% confidence interval [CI], 29.3-59.8); PC: 57.6% (95% CI, 41.6-70.7); p=0.270. Median OS (months) was PCb: 18.7 (95% CI, 12.9-not assessable [N/A]); PC: 27.0 (95% CI, 23.2-N/A). Median TTP (months) was PCb: 8.8 (95% CI, 6.0-10.7); PC: 13.1 (95% CI, 8.3-N/A); p=0.057. The ORR rates were PCb: 52.2% (complete response [CR], 6.5%; partial response [PR], 45.7%); PC: 46.2% (CR, 3.8%; PR, 42.3%). Grade 4 treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia, 6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. No drug-related deaths were reported. Conclusions: While conclusions are limited by the size of the trial, this study suggests OS and TTP advantages for the C-containing arm. Both combinations with CRT appear well tolerated.
Abstract 4535: Graphene/Pectin-NaCl based gel-biosensor for tracing skin cancer and delivery of anticancer drug paclitaxel
Authors: Sharif M. Shaheen, Daniel Gromadzki, Amor Abdelkader, Stanislav Rangelov
Journal: Cancer Research (2015)

Abstract Graphene(GO)/Pectin/NaCl gel-patch was prepared and evaluated for its bio-sensing. Physical and chemical analyses were carried out to focus the properties of new bio-sensing gel. Afterwards paclitaxel was loaded in the graphene based gel and drug delivery was carried out for dermal delivery, using a biomembrane, a fish swim-bladder in vitro. Kinetic studies were evaluated for feasibility as dermal delivery. Getting information from the kinetic parameters, paclitaxel was delivered to the melanoma cell lines from the gel and cell apoptosis was performed by trypan blue staining. FTIR studies were performed to evaluate the IR-signal transmission between the GO/Pectin/NaCl blend gel and Pectin/NaCl gel. And the same signal was evaluated from that of paclitaxel loaded GO/Pectin/NaCl treated melanoma cells and normal endothelial cells. All our data suggests that GO/Pectin/NaCl blend gel might be a future diagnostic as well as curable anticancer carrier for local cancer therapy. Note: This abstract was not presented at the meeting. Citation Format: Sharif M. Shaheen, Daniel Gromadzki, Amor Abdelkader, Stanislav Rangelov. Graphene/Pectin-NaCl based gel-biosensor for tracing skin cancer and delivery of anticancer drug paclitaxel. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4535. doi:10.1158/1538-7445.AM2015-4535
CXCL13 and CXCL12 in central nervous system (CNS) lymphoma patients
Authors: L. Fischer, A. Korfel, S. Pfeiffer, P. Kiewe, H. Volk, H. Cakiroglu, T. Widmann, E. Thiel
Journal: Journal of Clinical Oncology (2009)

2071 Background: Homing of malignant lymphocytes to the CNS may play a role in the pathogenesis of CNS lymphoma. Recently, the expression of the chemokine receptors CXCR4 and CXCR5 as well as their chemokine ligands CXCL12 and CXCL13 by tumor cells in primary CNS lymphoma (PCNSL) has been demonstrated. In this study, we evaluated CXCL12 and CXCL13 in cerebrospinal fluid (CSF) and serum of patients with CNS lymphoma. Methods: Samples from 30 patients with CNS lymphoma (23 with PCNSL and seven with secondary CNS lymphoma) and 40 controls (10 patients with other CNS malignancies and 30 without a malignant CNS disease) were examined. CXCL12 and CXCL13 concentrations were measured using enzyme-linked immunosorbent assays. The grade of blood brain barrier (BBB) disruption was estimated by the CSF/serum albumin ratio. Results: CNS lymphoma patients and controls did not differ in CXCL12 serum and CSF levels. Serum levels of CXCL13 were generally low. CXCL13 CSF levels, however, were high only in CNS lymphoma patients but not in controls (p &lt; 0.0001). Chemokine levels in CSF and serum did not correlate. In CNS lymphoma CXCL13 concentration in CSF correlated with BBB disruption (R = 0.66, p = 0.003). Elevated CSF levels of CXCL12 and CXCL13 measured in seven CNS lymphoma patients decreased in five patients which responded to chemotherapy, and increased in two with lymphoma progression. Conclusions: Our results suggest a production of CXCL13 within the CNS of CNS lymphoma patients which decreases with response to therapy. Thus, CXCL13 may represent a marker for further diagnostic and prognostic studies. No significant financial relationships to disclose.
Safety of peginterferon alpha-2a (40KD) (PEGASYS (R)) [PEG-IFN alpha-2a (40KD)] plus ribavirin (COPEGUS (R)) among pegylated interferon alpha-2b (12KD)/ribavirin non-responders: Interim analysis of the repeat study
Authors: D. Jensen, Yves Horsmans, P. Andreone, Y. Benhamou, M. Diago, A. Olveira Martin, G. Tcuber, D. Rincon, P. Marcellin
Journal: Journal of Hepatology (2006)
A phase I study of ARRY-520 in solid tumors.
Authors: P. H. Goncalves, E. A. Sausville, M. J. Edelman, N. B. Pandya, M. M. Houlehan, B. B. Freeman, H. M. Simmons, J. S. Stallings, A. M. Ptaszynski, P. LoRusso
Journal: Journal of Clinical Oncology (2010)

2570 Background: Antimitotic therapy stabilizes microtubule polymers and inhibits tubulin polymerization, but is nonselective and causes neurotoxicity. Kinesin Spindle Protein (KSP) is responsible for centrosome separation, required for formation and maintenance of a bipolar spindle. As a target, KSP has been validated preclinically and its inhibition avoids negative effects in nontarget cells where KSP is not expressed. Methods: This phase I study is designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ARRY-520, a potent, selective KSP inhibitor, administered intravenously (IV) in 2 dose schedules (S1 and S2). S1: D1 q 21 days (dose levels [DL] 2.5 and 3.3 mg/m2) with an expansion at the maximum tolerated dose (MTD). In the expansion, tumor biopsies were performed post-dose for PD markers. S2: D1 and D2 q 14 days without granulocyte colony stimulating factor (G-CSF) (DL 1.25 and 1.6 mg/m2/day) and with G-CSF support (DL to date: 1.6 mg/m2/day, with an expansion planned at the MTD, including biopsies). Results: A total of 34 patients (pts) have been treated to date. The median age was 61 years (range 40-79), the median number of prior treatments 3 (range 0-12). The MTD for both S1 and S2 without G- CSF was 2.5 mg/m2 per cycle. Dose-limiting toxicities (DLTs) in S1: Grade 3 febrile neutropenia, sepsis, and Grade 4 thrombocytopenia. DLTs in S2: Grade 3 febrile neutropenia, increased aspartate aminotransferase, hyponatremia, and anorexia. Themost common (≥ 10% of pts) adverse events (AEs) considered at least possibly related to ARRY-520 included hematologic AEs (leukopenia, lymphopenia, neutropenia), nausea, vomiting, anorexia and fatigue. One pt each experienced Grade 1 and Grade 2 mucositis at the DL above the MTD in S1. As neutropenia was the most common DLT, dose escalation with G-CSF support was initiated. Three pts (melanoma, ovarian cancer, and mesothelioma) experienced prolonged stable disease at 42, 22, and 13 weeks respectively. Monopolar spindles were observed in tumor biopsies, indicating that systemic exposure sufficient to elicit biological activity was achieved. PK results will be presented. Conclusions: S2 enrollment is ongoing at 2 mg/m2/day with G-CSF. Preliminary data support further disease-directed development of ARRY-520. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Array BioPharma Array BioPharma Array BioPharma Array BioPharma
Fractionated stereotactic radiosurgery for primary hepatocellular carcinoma
Authors: K. Kang, B. Choi, H. Jang, Y. Kang, J. Jang, G. Chai, S. Bae, S. Yoon, I. Choi
Journal: Journal of Clinical Oncology (2008)

15669 Background: Primary hepatocellular carcinoma (HCC) is a poor prognosis tumor. The role of external conventional radiotherapy in HCC has been limited by the inability of the whole liver and its hepatocytes to tolerate a therapeutic dose. Stereotactic irradiation of extracranial targets offers a non-invasive treatment modality for patients with localized tumors, which are not amenable for surgery or other invasive approaches because of age or impaired medical condition. This study evaluated the efficacy and toxicity of fractionated stereotactic radiosurgery (SRS) in patients with primary HCC. Methods: Eligibility criteria for this study were: 1) tumor less than 5 cm; 2) inoperable, or the patient refused operation; 3) ECOG performance status 0–2; 4) no prior radiotherapy or surgery. Prior allowed therapies are ablation, chemoembolization and systemic therapy. All patients were treated with Cyberknife radisurgery system (Accuray, Sunnyvale, CA). The SRS doses treated were 30–36 Gy (median, 36 Gy) to the 75–88% isodose, 3 fractions and the target volume was 1.5–31.9 cc (median, 14.5 cc), every other day in 1 week. Results: From April 2004 to January 2007, twenty five patients who had been histologically diagnosed as primary HCC patients and treated by Cyberknife fractionated SRS. Median follow-up was 21.5 months (range 6–44). There were 15 male and 10 female with a median age of 55 years (range: 41–79 years). Twenty five patients were evaluable for response based on an abdominal computed tomography scan obtained at a minimum of 3 months after completion of fractionated SBS. The overall response rate was 88%, with 7 patients showing complete response (28%), 15 patients showing partial response (60%) and 3 patients showing stable disease (12%). The 1-year and 2-year survival rates were 89.7 and 77.3%, respectively (median: 37 months). No patient experienced Grade 4 toxicity. Conclusions: Cyberknife fractionated SBS provides excellent local control with minimal side effects in selected patients with primary HCC. Thus, fractionated SRS may be suggested as a local treatment of choice for small HCC when the patients are inoperable or when the patients refuse operation. However, additional trials are needed to optimize this technique and formally compare it with the usual curative approaches. No significant financial relationships to disclose.
Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins
Authors: C Baigent, A Keech, P M Kearney, L Blackwell, G Buck, C Pollicino, A Kirby, T Sourjina, R Peto, R Collins, R Simes
Journal: The Lancet (2005)
Efficacy of Soluble TNFα Inhibitor (Etanercept) for Treatment of Steroid Refractory Acute Graft Versus Host Disease (GVHD) Post Allogeneic Stem Cell Transplantation (SCT).
Authors: Glen A. Kennedy, Jason Butler, James Morton, Geoff R. Hill, Robyn Western, Simon Durrant
Journal: Blood (2005)
Correlation of p34cdc2 cyclin-dependent kinase overexpression, CD44s downregulation, and HER-2/neu oncogene amplification with recurrence in prostatic adenocarcinomas.
Authors: B V Kallakury, C E Sheehan, R A Ambros, H A Fisher, R P Kaufman, P J Muraca, J S Ross
Journal: Journal of Clinical Oncology (1998)

PURPOSE To test whether p34cdc2 overexpression, CD44s downregulation, and HER-2/neu amplification correlate with disease recurrence after radical prostatectomy, and to evaluate a possible biologic association between p34cdc2 and HER-2/neu expression. MATERIALS AND METHODS Immunohistochemical (IHC) detection of both p34cdc2 cyclin-dependent kinase (CDK) and CD44s expression and fluorescence in situ hybridization (FISH)-based analysis of HER-2/neu gene status were performed on formalin-fixed, paraffin-embedded sections of 106 prostatic adenocarcinomas (PACs). Findings were correlated with Gleason grade, pathologic stage, DNA ploidy, and postsurgical biochemical disease recurrence. RESULTS CDK overexpression correlated with tumor grade (P = .001), DNA ploidy (P = .001), pathologic stage (P = .04), and disease recurrence (P = .01). CD44s downregulation correlated with grade (P = .03), ploidy (P = .01), and recurrence (P = .02). HER-2/neu amplification correlated with grade (P = .001), ploidy (P = .001), and recurrence (P = .01). On multivariate analysis, CDK overexpression independently predicted recurrence (P = .001) after prostatectomy. CDK expression correlated with HER-2/neu status with 32 of 65 (49%) tumors that overexpressed CDK and showed concomitant HER-2/neu amplification (P = .04). CONCLUSION This study showed that p34cdc2, CD44s, and HER-2/neu are variably expressed or amplified in prostatic carcinoma and that such alteration may affect tumor behavior. In addition, CDK overexpression and HER-2/neu amplification may be biologically related.
Long-Term Results of the Imatinib GRAAPH-2003 Study in Newly-Diagnosed Patients with De Novo Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia..
Authors: Aline Tanguy-Schmidt, Adrienne de Labarthe, Philippe Rousselot, Francoise Huguet, Eric Delabesse, Francis Witz, Sebastien Maury, Delphine Rea, Jean-Michel Cayuela, Marie-Christiane M Vekemans, Reman Oumédaly, Agnes Buzyn, Arnaud Pigneux, Martine Escoffre, Yves Chalandon, Elizabeth Macintyre, Jean-Paul Vernant, Xavier Thomas, Norbert Ifrah, Herve Dombret
Journal: Blood (2009)
Effects of CYT387, a Potent Novel JAK2 Inhibitor on JAK2-V617F Induced MPD
Authors: Thomas G.P. Bumm, Jeffrey W Tyner, Jutta Deininger, Marc Loriaux, Jonathan VanDyke, Brian J. Druker, Christopher J Burns, Emmanuelle Fantino3, Michael W.N. Deininger
Journal: Blood (2008)