tbuckley/cabot-search huggingface dataset:
Imaging instructed standardized treatment for hepatocellular carcinoma with radiofrequency ablation
Authors: M. Chen, W. Yang, K. Yan, Y. Dai, W. Wu, J. Wu
Journal: Journal of Clinical Oncology (2008)

15534 Background: This paper aimed to investigate the role of imaging instructed standardized RFA treatment in HCC. Methods: A total of 350 patients with 476 HCC underwent RFA in our institute. Among them, 297 patients (84.8%) were not candidate for surgery; 265 patients (75.7%) had advanced HCC or recurrent HCC after surgery. These patients were divided into six groups based on different treatment protocols and strategies and there was overlap among different groups: 248 patients with 284 >3.5cm HCC were treated with mathematical optimal protocol (group A); 81 patients with 115 HCC were treated with instruction of contrast enhanced ultrasound (CEUS) which was helpful to select indication and identify ablation range for RFA (group B). 71 patients with 74 hypervascular HCC were treated with new techniques which included color US guided ablation of entrance of feeding artery and then CEUS guided ablation of viable area of tumor (group C). Control group was selected for A, B, C group respectively for comparison. Imaging instructed individual protocols and strategies were developed for peripherally located HCC, including 102 patients with 105 HCC near diaphragm (group D), 56 patients with 59 HCC near bowel (group E) and 52 patients with 54 HCC near gallbladder (group F). Results: The tumor necrosis rate were 90.5 (257/284 tumors) for group A, 52.2% (12/23 tumors) for control group A (P<0.001); 92.2% (106/115 tumors) for group B, 83.0% (93/112 tumors) for control group B (P=0.036); 90.5% (67/74 tumors) for group C, 78.4% (80/102 tumors) for control group C (P=0.046); 92.3%(97/105 tumors) for group D, 91.5%(54/59 tumors) for group E and 94.4% (51/54 tumors) for group F, respectively. The follow-up period ranged from 3 to 84 months with mean period of 24 months. The 1, 3, 5 year survival for these 350 HCC patients were 87.9%, 58.7% and 43.2%, respectively. The major complications rate was 2.3% (12/532 sessions) in this study. Conclusions: standardized treatment of RFA based on imaging information can effectively improve RFA efficacy and safety and will play important roles in expanding indication for mini-invasive therapy in HCC. No significant financial relationships to disclose.
Tolerability and safety of oral neratinib (HKI-272) in Japanese patients with advanced solid tumors
Authors: Y. Ito, K. Hatake, S. Takahashi, M. Yokoyama, M. Suenaga, M. Ota, Y. Onozawa, K. Yamazaki, S. Hironaka, N. Boku
Journal: Journal of Clinical Oncology (2009)

e14505 Background: Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor. In non-Japanese pts, neratinib was found to have clinical activity against solid tumors and dose-limiting toxicity (DLT) of diarrhea. The maximum tolerated dose (MTD) was 320 mg daily and the recommended dose (RD) was 240 mg because of the diarrhea. In this phase 1 study, the MTD was determined and safety and preliminary efficacy were assessed in Japanese pts with advanced solid tumors. Methods: Pts (3- 6/cohort) received 80, 160, 240, or 320 mg oral neratinib. Each pt participated in only 1 dose group and received single doses of neratinib followed by 1 wk of observation; pts then received daily continuous administration at the same dose. DLTs were assessed from the first single dose to the end of 14 days of continuous treatment. Pharmacokinetics (PK) will be analysed via a noncompartmental method. Tumor measurements were made at screening and at the end of every 8 weeks (2 cycles) by RECIST. Results: Preliminary data for 21 pts as of 30 Oct 2008 are presented. Pts had a median age [range] of 61 yrs [39–78], were 62% male, and had all received ≥2 prior chemotherapy regimens. Tumor types at primary diagnosis were advanced colorectal (81%), breast (14%), and gastric (5%) cancer. Median duration of neratinib treatment [range] was 10 wks [3–29].Two patients at the 320-mg dose had DLTs of diarrhea plus anorexia. Therefore the MTD was determined to be 240 mg. Neratinib-related AEs, any grade in ≥25% of pts included diarrhea (95%), fatigue (67%), anorexia (43%), nausea (43%), abdominal pain (38%), decreased hemoglobin (38%), increased AST (33%), and rash (29%). Neratinib-related AEs, grade ≥3 in ≥1 pts were anorexia (3 pts) and diarrhea (2 pts). Two pts had partial response (PR), 8 pts had stable disease (SD) ≥8 wks, 2 had SD≥16 wks, 9 had progressive disease. The 2 pts with PR had ErbB-2+ advanced breast cancer. PK analysis is still ongoing. Conclusions: In Japanese pts, the MTD for neratinb was determined to be 240 mg and the RD will be confirmed as 240 mg. Neratinib is tolerable and demonstrates preliminary antitumor activity in pts with solid tumors. [Table: see text]
Phase I study of intravenous decitabine in combination with oral vorinostat in patients with advanced solid tumors and non-Hodgkin's lymphomas (NHL)
Authors: A. Stathis, S. Hotte, H. Hirte, E. X. Chen, S. Webster, A. Iacobucci, S. McGill, L. Wang, I. Espinoza-Delgado, L. L. Siu
Journal: Journal of Clinical Oncology (2009)

3528 Background: Decitabine (D), a hypomethylating agent, and vorinostat (V), a histone deacetylase inhibitor, belong to two different classes of drugs with an epigenetic effect. The ideal dose scheduling of these drugs remains controversial. This phase I study aims to determine the recommended phase II dose (RPTD) of the combination, their toxicity profile, pharmacokinetic (PK) interaction and preliminary clinical activity. Methods: Patients (pts) with advanced solid tumors or relapsed/refractory NHL are eligible. Two different schedules of D and V are being evaluated: sequential administration of D followed by V and concurrent administration of D and V. Dose escalation of D and V on the sequential schedule is described in Table. Results: To date, 27 pts have been entered into dose levels 1, -1, 1a, 1b, -1b, -2b of the sequential schedule. Demographics: median age 61 (range 31–76), F:M = 13:14, ECOG 0:1:2 = 8:16:3, tumor types: 24 solid tumor and 3 NHL. Pts received a total of 77 cycles with a median of 2 cycles (range 1–8). Adverse events (AE) of grade 3 or higher of at least possible attribution to the study treatment were neutropenia (16 pts), thrombocytopenia (4), febrile neutropenia (2), fatigue (2), and 1 pt each for constipation, dehydration, nasal bleeding, elevated alanine aminotransferase, and hyponatremia. Dose limiting toxicities (DLT) consisted mainly of myelosuppression, constitutional and gastrointestinal symptoms occurred in 7/27 (26%) of pts so far. Disease stabilization for 4 or more cycles was observed in 7 out of 22 (31.8%) evaluable pts (two with breast and one each of thymus, colon, pancreatic, appendix and non-small cell lung cancers). Conclusions: The sequential combination of D and V seems to be tolerable after some adjustments in the doses and duration of drug administration. Prolonged disease stabilization has been observed in multiple tumor types. Accrual is ongoing and RPTD will likely be dose level -1b or -2b. ( Supported by NCI Grant No. U01CA132123.) [Table: see text] No significant financial relationships to disclose.
Metabolic Homeostasis Is Maintained in Myocardial Hibernation by Adaptive Changes in the Transcriptome and Proteome
Authors: Manuel Mayr
Journal: Circulation (2009)

Abstract #1810 Manuel Mayr, Kings Coll London, London, United Kingdom; Dalit May, The Hebrew Univ-Hadassah Univ Hosp, Jerusalem, Israel; Basetti Madhu, John Griffiths, Cancer Res UK, Cambridge, United Kingdom; Anton Horrevoets, VU Univ Medical Ctr, Amsterdam, Netherlands; Eli Keshet, The Hebrew Univ-Hadassah Univ Hosp, Jerusalem, Israel Manuel Mayr, 2009 Finalist and Presenting Author
Pre- and postoperative chemotherapy including bevacizumab in potentially curable metastatic colorectal cancer: A multicenter, single-arm phase II trial—Results of ASSO LM1.
Authors: T. Gruenberger, F. Laengle, J. Thaler, W. Eisterer, D. Tamandl, B. Herberger, A. Lenauer, B. Gruenberger
Journal: Journal of Clinical Oncology (2010)

e14032 Background: Patients with colorectal cancer (CRC) and liver metastases may benefit from perioperative chemotherapy and disease resection. Best treatment sequence, length and combination still needs to be determined. We evaluated bevacizumab and XELOX in a multicenter approach. Methods: Patients with liver metastases from CRC potentially curable by resection were eligible for this trial. Patients received bevacizumab 5 mg/kg (day 1), oxaliplatin 85 mg/m2 (day 1) and capecitabine 3,000 mg/m2/day (days 1–7) of a 2-week cycle, for six cycles. The sixth cycle did not include bevacizumab, resulting in 5 weeks between the last bevacizumab dose and surgery. Therapy with bevacizumab plus XELOX was restarted 5 weeks after surgery for another six cycles. Results: 43 patients (pts) with a median age of 66 years (38-80) were enrolled into this multicenter trial. 78% of these pts had synchronous disease, 51% started neoadjuvant treatment without primary tumor resection. The median number of metastases was 2 (1-10) and the median Fong score was 3 (0-4). Currently available efficacy results confirm an ORR of 59%, 38% SD and 3% PD. Preoperative grade 3/4 adverse events were 17% diarrhoe, 5% HFS, 2% neuropathy and 5% thromboembolic events. All liver resections were curative and consisted of major resection in 43% of the pts, perioperative blood transfusions were required in only 10%. Postoperative morbidity occurred in 22% of the pts, 3 operative revisions were related to the primary tumor resection. Postoperative liver function and regeneration (assessed by CT 4 weeks postOP) were normal in all but one patient (sepsis, anastomotic dehiscence, multiorgan failure). Median length of hospital stay was 11 days (5-41). Conclusions: These data suggest that bevacizumab and XELOX can be safely administered in the neoadjuvant setting and proves its efficacy even in patients with their primary insitu. These multicenter results confirm the uniformity of previous single-center findings. Progression-free and overall survival results are eagerly awaited. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, Roche Merck, Roche, sanofi-aventis Merck, Roche, sanofi-aventis
Abstract 17435: Gender Difference of Nerve Growth Factor Expression in Heart Failure Patients: Preliminary Results from a Single Centre Study
Authors: Emilia D'Elia, Alessia Pascale, Nicoletta Marchesi, Matteo Augello, Calvillo Laura, Andrea Mortara, Stefano Govoni, Emilio Vanoli
Journal: Circulation (2012)

Introduction: Sympathetic nervous system plays a critical role in disease progression and cardiac risk after myocardial infarction and in chronic heart failure (CHF) patients. Cardiac remodeling af...
The dual specific Src/Abl kinase inhibitor AZD0530 inhibits the formation and activity of human osteoclasts
Authors: J. Klein-Nulend, M. A. van Duin, T. P. Green, V. Everts, T. J. de Vries
Journal: Journal of Clinical Oncology (2007)

3602 Background: Gene knockout studies have demonstrated the critical importance of the non-receptor TK Src to osteoclast bone resorptive function. Deregulated Src TK activity is also reported as a hallmark of the invasive cancer cell. Bone metastatic cancer cells interact with and activate osteoclasts in a destructive cycle of bone degradation and stimulation of tumor cell growth. Therefore targeting Src activity would appear to be a rational therapeutic approach in treating metastatic bone disease. We have reported previously (AACR 2005) on the activity of the dual Src/Abl kinase inhibitor AZD0530 in inhibiting the bone resorptive activity of mature rabbit osteoclasts in a bone slice model. Here we tested the effect of AZD0530 in a human co-culture system, examining its activity on i) osteoclast formation by peripheral blood mononuclear cells (PBMCs) co-cultured with osteoblasts, and ii) osteoclastic bone resorption. Methods and Results: PBMC adhesion to osteoblasts and osteoblast morphology was not affected by AZD0530 (0.1–10 μM). However, AZD0530 inhibited the formation of multinucleated osteoclast-like cells dose dependently. PBMC-osteoblast co-cultures were then exposed to 1 μM AZD0530 for different time intervals. AZD0530 was most effective in inhibiting the formation of osteoclast-like cells when added at the onset of osteoclastogenesis, suggesting that Src activity is important during the initial induction of osteoclast formation. Formation of actin rings, to which c-Src co-localizes, is a prerequisite for osteoclastic bone resorption. The effect of AZD0530 on formation of actin rings was analyzed using the co-culture system on cortical bone slices. AZD0530 prevented migration of osteoclast precursors to the bone surface, and the subsequent formation of actin rings. On withdrawal of the drug, this process was reversible. Conclusions: Our data suggest that Src activity is pivotal for the formation, migration and activity of osteoclasts. Data reported elsewhere suggest AZD0530 will also impact on tumor cells directly. AZD0530 is a promising new anti-cancer drug with potential to additionally treat metastatic bone disease through its inhibition of both osteoclast activity and tumor cell invasion into and within the bone micro-environment. No significant financial relationships to disclose.
Effect of Temperature on Cellular Electrophoretic Mobility Phenomena&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Weiss, L.
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Effect of Temperature on Cellular Electrophoretic Mobility Phenomena Get access L. Weiss L. Weiss Department of Experimental Pathology, Roswell Park Memoria/Institute, Buffalo, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 36, Issue 5, May 1966, Pages 837–847, https://doi.org/10.1093/jnci/36.5.837 Published: 01 May 1966 Article history Received: 26 July 1965 Published: 01 May 1966
Heparin-Induced Thrombocytopenia: New Insights Into the Impact of the FcγRIIa-R-H131 Polymorphism
Authors: Lena E. Carlsson, Sentot Santoso, Gudrun Baurichter, Hartmut Kroll, Stephanie Papenberg, Petra Eichler, Nomdo A.C. Westerdaal, Volker Kiefel, Jan G.J. van de Winkel, Andreas Greinacher
Journal: Blood (1998)
Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial
Authors: Marek Trněný, Thierry Lamy, Jan Walewski, David Belada, Jiri Mayer, John Radford, Wojciech Jurczak, Franck Morschhauser, Julia Alexeeva, Simon Rule, Boris Afanasyev, Kamil Kaplanov, Antoine Thyss, Alexej Kuzmin, Sergey Voloshin, Kazimierz Kuliczkowski, Agnieszka Giza, Noel Milpied, Caterina Stelitano, Reinhard Marks, Lorenz Trümper, Tsvetan Biyukov, Meera Patturajan, Marie-Laure Casadebaig Bravo, Luca Arcaini
Journal: The Lancet Oncology (2016)
<i>Phylo.io</i>: Interactive Viewing and Comparison of Large Phylogenetic Trees on the Web
Authors: Oscar Robinson, David Dylus, Christophe Dessimoz
Journal: Molecular Biology and Evolution (2016)

Phylogenetic trees are pervasively used to depict evolutionary relationships. Increasingly, researchers need to visualize large trees and compare multiple large trees inferred for the same set of taxa (reflecting uncertainty in the tree inference or genuine discordance among the loci analysed). Existing tree visualization tools are however not well suited to these tasks. In particular, side-by-side comparison of trees can prove challenging beyond a few dozen taxa. Here, we introduce Phylo.io, a web application to visualize and compare phylogenetic trees side-by-side. Its distinctive features are: highlighting of similarities and differences between two trees, automatic identification of the best matching rooting and leaf order, scalability to very large trees, high usability, multiplatform support via standard HTML5 implementation, and possibility to store and share visualisations. The tool can be freely accessed at http://phylo.io. The code for the associated JavaScript library is available at https://github.com/DessimozLab/phylo-io under an MIT open source license.
Lymphosarcoma Associated With Virus-Like Intranuclear Inclusions in a California King Snake (Colubridae: &lt;italic&gt;Lampropeltis&lt;/italic&gt;)
Authors: E R Jacobson, J C Seely, M N Novilla
Journal: JNCI Journal of the National Cancer Institute (1980)

A laboratory-bred and laboratory-reared male California king snake was submitted for clinical evaluation, and a mass was palpated caudal to the stomach and within the abdominal cavity. The snake was anesthetized and the mass was excised. A constricted atonic section of adjacent small intestine was removed and the ends were subsequently reanastomosed. The snake died 2 days post surgery; after histopathologic examination of all major organs (except muscle and brain), lymphosarcoma was diagnosed. Lymphocytes, approximately 70% of which contained small to large eosinophilic intranuclear inclusions, had infiltrated all major organs. By electron microscopic examination these inclusions were found to be large electron-dense granular structures. Aggregates of circular structures that measured 50 nm were seen in the cytoplasm of several cells.
Recurrence pattern in early-stage breast cancer in a minority cohort.
Authors: S. B. Sreenivasappa, B. Ciobanu, S. Sandhu, F. Feitosa, J. Samuel
Journal: Journal of Clinical Oncology (2010)

1600 Background: The recurrence pattern of women with early stage breast cancer (ESBC) in ethnic minority, treated as per current guidelines is not well known. Methods: Women diagnosed with ESBC in 2000-07 with stages I, II and IIIA, had surgery for unilateral breast cancer, infiltrating ductal cancer and > 6 months of follow up were studied as a retrospective cohort. Clinical data was analyzed by logistic regression and Cox proportional hazard. Results: 455 women were evaluated. Median age at diagnosis was 53 yrs (23-89). 228 (50.1%) were African American (AA), 81 (17.8%) Hispanics, 93 (20.4%) Caucasian, 53 (11.6%) Other. 125 (27.5%) were stage I, 115 (25.3%) stage IIa, 90 (19.8%) were stage IIb and 92 (20.2%) stage IIIa. Median follow up 40 mo (6-119). Median tumor size was 2.5 cm (0.1-10). 38 grade I, 173 grade II, 223 grade III. 255 had no vascular invasion (VI), 95 had VI and 51 had indeterminate. 126 (28%) were triple negative (TN). 196 (85%) of the node negative women, 183 (97%) node positive women received therapy. Median time to recurrence was 18 mo (3-118). 14 (11.2%) in stage I, 15 (13%) in stage IIA, 20(22%) in stage IIB and 24 (26%) in stage IIIA recurred. 50 (61%) has systemic recurrence, 22 (27%) has local recurrence and 9 (11%) had both. 8, 12, 13 and 11 recurrence in stage I, IIa, IIb, IIIa were in AA women. On multivariate analysis tumor size OR 1.81 (p = 0.004), triple negative tumors OR 2.073 (p = 0.021) and vascular invasion OR 2.2 (p = 0.035) increased risk recurrence. Tumor size HR 1.16 (p = 0.002), TN (p = 0.016) and VI HR 1.415 (p = 0.05) had a higher time to recurrence. Conclusions: In this minority cohort the risk of recurrence in adequately treated early breast cancer is about twice that of historic controls at each stage. Recurrence rate at each stage is higher in African American women when compared to women of other ethnic groups. Local breast and systemic recurrence is higher than historic controls. The receptor status, tumor size and vascular invasion influence recurrence and time to recurrence. High recurrence rates due to agressive tumor biology warrant aggressive therapy in early breast cancer in minority groups. Newer therapies and further investigations of disease and healthcare disparities in the underserved minority population are warranted. No significant financial relationships to disclose.
Identification of three potential biomarkers in early resectable hepatocellular carcinoma.
Authors: S. Ang, W. Wang, Y. Soe, C. Tan, W. Chow, A. K. Kwee, H. Toh
Journal: Journal of Clinical Oncology (2010)

4131 Background: Current surveillance programs employing routine serum alpha-fetoprotein and abdominal ultrasound for patients at-risk for HCC have not demonstrated significant improvement in patient clinical outcome due to their low sensitivity and specificity. The aim of this study was to identify novel serum biomarkers that might potentially improve on the current surveillance modalities. Methods: Serum proteins of 58 patients with surgically resected HCC (39 patients stage I and 19 patients stage III) and 11 non-HCC patients with chronic hepatitis B were profiled using RayBio L-Series 507 Antibody Array that simultaneously detects the levels of 507 proteins. To validate the data from the L-Series 507 array analysis, significantly modulated markers in the array analysis were quantified using multiplex sandwich ELISA. All samples were run in triplicates and analysis was repeated at least once. The results were compared with clinico-pathological parameters. Results: We identified three novel biomarkers confirmed by ELISA, namely TIMP-4, MCP-1 and Prolactin, which were all significantly overexpressed in the resected HCC patients compared to the non-HCC group. The lower limit of detection were 2.4 ng/mL (Prolactin), 72 pg/mL (TIMP-4) and 18 pg/mL (MCP-1). The median serum concentrations in non-HCC patients were 14.49 ng/mL, 1.36 ng/mL and 628 pg/mL compared to 47.95 ng/mL (p = 0.0003), 5.73 ng/mlL(p < 0.0001) and 1,099.2 pg/mL (p = 0.002) in the stage I HCC. The concentrations were further elevated to 56.12 ng/mL (p = 0.0001), 6.76 ng/mL (p < 0.0001) and 1240.6 pg/mL (p = 0.001) in the stage III HCC. TIMP-4 and MCP-1 were significantly higher in patients with larger tumors (p = 0.02 and p = 0.009 respectively). Elevated levels of all three novel biomarkers above median cut-off value portend a poorer relapse-free survival in resected HCC patients (p = 0.02). TIMP4 levels above median cut-off was also associated with reduction in relapse-free survival (p = 0.05). No association was noted between serum levels of TIMP- 4, MCP-1 and Prolactin with liver cirrhosis or inflammation. Conclusions: These serum proteins can be useful as complementary biomarkers for early detection of HCC in patients at-risk and may play a role in liver carcinogenesis. No significant financial relationships to disclose.