tbuckley/cabot-search huggingface dataset:
<i>Anarchy</i>Is a Molecular Signature of Worker Sterility in the Honey Bee
Authors: Isobel Ronai, Benjamin P. Oldroyd, Deborah A. Barton, Guénaël Cabanes, Julianne Lim, Vanina Vergoz
Journal: Molecular Biology and Evolution (2015)

Worker sterility is a defining characteristic of eusociality. The existence of the sterile worker caste remains a fundamental question for evolutionary biology as it requires the existence of genes that reduce personal reproduction. Currently, little is known about the proximate mechanisms underpinning worker sterility. Studies into a mutant "anarchistic" strain (in which workers can activate their ovaries) of honey bee, Apis mellifera, identified a list of candidate genes that regulate ovary activation. We quantified the expression of the four most promising candidate genes (Anarchy, Pdk1, S6k, and Ulk3) in nonactivated and activated ovaries of wild-type workers. Ovarian expression of Anarchy, a peroxisomal membrane protein, predicts the ovary state of workers with 88.2% accuracy. Increased expression of Anarchy in the ovary is strongly associated with suppression of oogenesis and its expression is sensitive to the presence of the queen. Therefore, Anarchy satisfies key criteria for a "gene underlying altruism". When we knocked down expression of Anarchy in the ovary using RNA interference (RNAi) we altered the expression of Buffy, a gene that regulates programmed cell death. Whole-mount multiplex fluorescent in situ hybridization (mFISH) shows Anarchy transcripts localize to degenerating oocytes within the ovary. Our results suggest that Anarchy is involved in the regulation of oogenesis through programmed cell death. The evolution of facultative worker sterility most likely occurred when the conserved mechanism of programmed cell death was co-opted to regulate ovary activation. Anarchy may therefore be the first example of a gene that has evolved through kin selection to regulate worker sterility.
Abstract 16879: Altered Reactivity and Nitric Oxide Signaling in Isolated Thoracic Ducts From an Ovine Model of Congenital Heart Disease With Increased Pulmonary Blood Flow
Authors: Sanjeev A Datar, Peter E Oishi, Wenhui Gong, Stephen Bennett, Christine E Sun, Michael Johengen, Jun Maki, Rebecca C Johnson, Gary W Raff, Jeffrey R Fineman
Journal: Circulation (2013)

Background: Utilizing our ovine model of congenital heart disease (CHD), we have previously demonstrated altered postnatal pulmonary lymphatic development and function in the setting of chronically...
Phase I trial of AP24534 in patients with refractory chronic myeloid leukemia (CML) and hematologic malignancies.
Authors: M. Talpaz, J. E. Cortes, M. W. Deininger, N. P. Shah, I. W. Flinn, M. J. Mauro, T. O'Hare, V. Rivera, H. Kantarjian, F. G. Haluska
Journal: Journal of Clinical Oncology (2010)

6511 Background: AP24534, an oral multiple tyrosine kinase inhibitor (TKI), is a potent pan-BCR-ABL inhibitor, including T315I. A phase I trial to assess its safety, maximum tolerated dose and activity is ongoing. Methods: Patients (pts) with refractory leukemia were enrolled on a dose escalation trial of daily AP24534. Dose levels were 2, 4, 8, 15, 30 and 60mg and a 45mg level is currently open. Results: As of 1/4/10, 48 pts, median age 62 yrs (range 26-85) have been enrolled. There are 42 CML pts (31 chronic [CP], 6 accelerated [AP], 5 blast phase [BP]) and 2 with Ph+ ALL. Prior therapies in CML pts include imatinib (I) (100% of pts), dasatinib (D) (88%), nilotinib (N) (65%); 97% and 81% of the Ph+ pts failed 2 and 3 prior TKIs, respectively and 88% had documented BCR-ABL mutations. Ph+ pts include 18 with T315I and 6 with F317L. 32 (67%) remain on therapy, median duration 61 days (range 5-360). Sixteen (33%) have discontinued; 7 (15%) for PD, 6 (13%) for investigator decision, 2 (4%) for unrelated deaths, and 1 (2%) for toxicity (pancreatitis). Related AEs ≥ 10% are: nausea (20%), fatigue (15%), vomiting (15%), headache (13%), arthralgia (10%), hot flush (10%), incr glucose (10%), incr lipase (10%), muscle spasms (10%), and rash (10%). Grade 3 or 4 thrombocytopenia occurred in 40% pts and neutropenia in 43%. There are 4/12 pts with G3/4 amylase/lipase at 60 mg and 2/12 with G2 reversible pancreatitis. In evaluable CML pts, 11/13 (85%) achieved CHR, 7/21 (33%) achieved CCyR and 10/21 (48%) achieved MCyR. All 7 (100%) evaluable T315I CP CML pts had CHR, 4 (57%) had CCyR, and 1 (14%) MiCyR. Of 11 evaluable AP/ BP CML or Ph+ALL pts, 4 (36%) had MHR, 1 (9%) had CCyR, and 1 (9%) had minimal response. Of 8 T315I pts in this group, 3 (38%) had MHR, 1 (13%) had CCyR, and 1 (13%) had minimal response. There was 1 CCyR and 1 minimal CyR in 2 F317L pts who failed I, D, and N. A F359C pt who failed I and N achieved CHR and CCyR. MMR was achieved in 3 CML pts (M351T, F359C, and F317L) after 3 months (2 at 15 mg and 1 at 60 mg) and 1 T315I pt attained a transcript level of 0.15% after 6 months on 30mg. Conclusions: AP24534 is well tolerated with no DLTs until 60 mg. There is evidence of antileukemia activity in pts resistant to second generation TKIs, including pts with T315I. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ARIAD Pharmaceuticals Novartis ARIAD Pharmaceuticals ARIAD Pharmaceuticals
Inhibition of Human Rhabdomyosarcoma-Cell Growth in Agar by Dibutyryl Cyclic AMP2
Authors: Richard Sandor
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Inhibition of Human Rhabdomyosarcoma-Cell Growth in Agar by Dibutyryl Cyclic AMP Get access Richard Sandor Richard Sandor Division of Virology, Childrens Hospital of Los Angeles, Los Angeles, California 90027 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 257–260, https://doi.org/10.1093/jnci/51.1.257 Published: 01 July 1973 Article history Received: 08 November 1972 Revision received: 02 April 1973 Accepted: 11 April 1973 Published: 01 July 1973
Tumor Incidence in Mice After Oral Painting With Cigarette Smoke Condensate
Authors: Joseph A. Dipaolo, Morton L. Levin
Journal: JNCI Journal of the National Cancer Institute (1965)

The effect of oral painting with cigarette tobacco tar on the incidence of pulmonary tumors in Swiss mice was studied. Compared to the control mice, at 18 to 19 months of age the animals treated with whole tar, heptane, and residue fractions had more than double the incidence of pulmonary tumors and over three times the number of other tumors, chiefly of the leukemia-lymphoma group. The pulmonary tumors were predominantly adenomas, but there were a few papillary adenocarcinomas and one anaplastic carcinoma. Although not strictly comparable, the tar concentrations in whole tar, heptane, and residue fractions produced significant increases in the incidence of pulmonary tumors (64.2, 59.3, and 46.5%, respectively), as compared with untreated controls (22.3%).
Histone Deacteylase Inhibitors (HDACi) Suppress Toll-Like Receptor-Induced Dendritic Cell Maturation and Alter Secretion But Not Gene Expression Of Polarising Cytokines By Dendritic Cells
Authors: Michael J. Dickinson, Alexander Davenport, Pasquale Petrone, H Miles Prince, David Ritchie, Paul Neeson
Journal: Blood (2013)
Abstract B1-52: Analysis of the iCOGS breast cancer GWAS reveals 4 unique signals in the PTHLH region in patients of European origin
Authors: Adam N. Freeman, T John Martin, Michael A. Henderson, Enes Makalic, Miroslaw K. Kapuscinski, Daniel F. Schmidt, John Hopper
Journal: Cancer Research (2015)

Abstract Parathyroid hormone-related protein (PTHrP), the product of the PTHLH gene, has long been implicated in breast cancer. Its expression is thought to favour and, potentially, facilitate metastasis to bone. Paradoxically, a prospective clinical study clinical suggests that its production in primary breast cancers is actually protective, affording a better prognosis than its absence. Multiple recent Genome-Wide Association Studies (GWAS) have confirmed a single susceptibility locus immediately upstream of the PTHLH gene to be associated with breast cancer. This was again reproduced in the recent iCOGS GWAS, which involved over 90,000 European subjects. In spite of a single SNP, rs10771399, being uniquely reported and reproduced by prior studies, we demonstrate 4 discrete overlapping signals by utilising forward selection logistic regression and LASSO techniques. Two of these signals are centred and superimposed around rs10771399, ~40kbp upstream of PTHLH, a third lies a further 100kbp upstream, and the fourth lies a further 250kbp upstream over the next gene, CCDC91. While the causation of this signal remains elusive, multiple putatively contributory variations are captured by these signals. Citation Format: Adam N. Freeman, T John Martin, Michael A. Henderson, Enes Makalic, Miroslaw K. Kapuscinski, Daniel F. Schmidt, John Hopper. Analysis of the iCOGS breast cancer GWAS reveals 4 unique signals in the PTHLH region in patients of European origin. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-52.
A phase II trial of hepatic arterial infusion chemotherapy with cisplatin for advanced hepatocellular carcinoma with portal vein tumor thrombosis
Authors: J. Furuse, M. Ikeda, T. Okusaka, K. Nakachi, C. Morizane, H. Ueno, H. Yamaura, Y. Inaba, M. Satake, Y. Arai
Journal: Journal of Clinical Oncology (2008)

15556 Background: The objective of this study was to evaluate the antitumor, survival, and adverse effects of hepatic arterial infusion chemotherapy using cisplatin in patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). Methods: Twenty-five patients with advanced HCC with PVTT in the main or first branch who had no prior chemotherapy, with measurable lesions, adequate liver and renal function, and adequate bone marrow reserve, were enrolled. A dose of 65 mg/m2 cisplatin was administered from the proper hepatic artery. Treatment was repeated every 4 to 6 weeks for a maximum of six courses, if there was no evidence of tumor progression or unacceptable toxicity. The primary end-point was the tumor response to this regimen, and the secondary end-point was toxicity, survival and progression-free survival. Results: The median number of treatments was 3 (range: 1–6). Among the 25 enrolled patients, 1 (4%) achieved a complete response, 6 (24%) had a partial response, and the response rate was 28% (95% confidence interval: 12–49%). The serum AFP and PIVKA II levels were reduced by more than 50% in 44% and 68% of the patients who had shown a pretreatment level of 100 U/ml or greater and 100 mAU/ml or greater, respectively. The median survival time, 1-year survival rate and median progression-free survival for the patients as a whole were 10.3 months, 40.3%, and 4.4 months, respectively. The main grade 3 and 4 non-hematological toxicities of this treatment were elevation of the aspartate aminotransferase (44%) and alanine aminotransferase (24%) levels, but no grade 4 hematological toxicity was seen. These toxicities were generally brief and well tolerated. Conclusions: Hepatic arterial infusion chemotherapy with cisplatin has moderate activity with mild toxicity in HCC patients with PVTT, and this is expected to be confirmed in a prospective randomized controlled study. No significant financial relationships to disclose.
大量の前治療を受けた慢性リンパ性白血病患者に対するサルベージ療法としてのシクロホスファミド,フルダラビン,アレムツズマブおよびリツキシマブ
Authors: C Badoux Xavier, J Keating Michael, Wang Xuemei, M O’Brien Susan, Ferrajoli Alessandra, Faderl Stefan, Burger Jan, Koller Charles, Lerner Susan, Kantarjian Hagop, G Wierda William
Journal: Blood (2011)
Depolymerized holothurian glycosaminoglycan with novel anticoagulant actions: antithrombin III- and heparin cofactor II-independent inhibition of factor X activation by factor IXa-factor VIIIa complex and heparin cofactor II-dependent inhibition of thrombin
Authors: H Nagase, K Enjyoji, K Minamiguchi, KT Kitazato, K Kitazato, H Saito, H Kato
Journal: Blood (1995)
Progressive disease rate as a surrogate endpoint of phase II trials for non-small-cell lung cancer
Authors: I. Sekine, T. Tamura, H. Kunitoh, K. Kubota, T. Shinkai, Y. Kamiya, N. Saijo
Journal: Annals of Oncology (1999)

Although the potential activity of anticancer agents has been traditionally assessed by the response rate (RR) in phase II trials, there is an increasing need to identify alternative endpoints to evaluate the efficacy of novel types of antineoplastic agents such as cytostatic agents. However, none of the proposed alternatives have been validated.RR, rate of progressive disease (PD), and median survival time (MST) were obtained from 44 treatment arms in 42 single-agent phase II trials for non-small-cell lung cancer (NSCLC). Correlations between these parameters and their significance in selection of promising drugs were evaluated.The median (range) RR and PD rate per treatment arm were 17% (0%-40%) and 41% (8%-93%), respectively. The PD rate correlated more closely with MST (correlation coefficient (r) = 0.80, P < 0.001) than did the RR (r = 0.62, P < 0.001). The RR of active agents against NSCLC ranged broadly from 7% to 40%, whereas their PD rates were all 50% or less. In addition, all treatment arms with a PD rate over 50% had a poor MST of six months or shorter.The PD rate was potentially as good an endpoint as RR, and it may be a good candidate for the primary endpoint of phase II trials for novel types of anticancer agents.
Phase IIb randomized trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, plus best supportive care (BSC) versus BSC alone in patients with advanced hepatocellular carcinoma who have failed sorafenib treatment (TRAVERSE).
Authors: James M. Burke, Caroline Breitbach, Richard H. Patt, Riccardo Lencioni, Michel Homerin, Jean-Marc Limacher, Monika Lusky, Theresa Hickman, Lara Longpre, David H. Kirn
Journal: Journal of Clinical Oncology (2012)

TPS4152 Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus GM-CSF expression stimulates tumor vascular disruption and anti-tumor immunity (Nature Rev Cancer 2009). JX-594 was well-tolerated in Phase 1 trials and was shown to replicate in metastatic tumors following intratumoral (IT) or intravenous (IV) administration (Lancet Oncol 2008 and Nature 2011). A randomized dose-finding Phase 2 trial has been completed with JX-594 in 30 patients with advanced HCC. Treatment with high-dose JX-594 was associated with prolonged survival vs low-dose JX-594 (median survival 14.1 mo vs 6.7 mo; Hazard Ratio 0.39, p=0.02) (AASLD Annual Meeting, 2011, LB1). Methods: TRAVERSE is a Phase 2b randomized, open-label, multi-center trial of JX-594 plus BSC versus BSC in patients with advanced HCC who have failed sorafenib treatment. Approximately 120 patients will be randomized 2:1 to experimental and control arm respectively. Randomization will be stratified by region (Asian vs non-Asian); sorafenib intolerant vs refractory; and presence vs absence of extra-hepatic disease. The primary objective is to determine overall survival in the 2 arms. Assuming a control median overall survival of 4.0 months and a target hazard ratio of 0.57 (corresponding to an experimental arm median survival of 7.0 months), 73 events (deaths) will provide 70% power at 1-sided alpha = 0.05 to detect a difference in overall survival between the treatment groups using a stratified logrank test. Patients randomized to JX-594 will receive a dose of 10 9 plaque forming units (pfu) IV on Day 1 followed by five IT treatments between Day 8 and Week 18. Main inclusion criteria are advanced HCC having failed sorafenib (intolerance or radiographic progression during or &lt; 3 months following last sorafenib), Child-Pugh A-B7 (no ascites), acceptable hematologic function. Enrollment has begun on this study with clinical trial registry number of NCT01387555.
Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma.
Authors: R Pazdur, J A Ajani, Y Z Patt, R Winn, D Jackson, B Shepard, R DuBrow, L Campos, M Quaraishi, J Faintuch
Journal: Journal of Clinical Oncology (1990)

We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.
Role of lymph-node ultrasonography (US) in the follow-up of melanoma patients to detect nodal recurrence after sentinel lymph node biopsy (SNLB): A prospective cohort study.
Authors: P. Saiag, C. Lebbé, N. Basset Seguin, P. Wolkenstein, N. Dupin, V. Descamps, S. Aractingi, P. Aegerter, S. Chagnon
Journal: Journal of Clinical Oncology (2010)

8576 Background: Nodal recurrence occurs in 10% of pts after negative sentinel lymph node biopsy (SNLB), and best follow-up strategy after SNLB has not been established. We studied prospectively the diagnostic value of US, a technique that has been shown in pts without SNLB to be more sensitive and specific than palpation, to detect nodal recurrence after SNLB. Methods: From 9/03 to 12/08, 1256 new melanoma pts from Paris university hospitals were entered prospectively into MelanCohort (33). SNLB procedures have been standardized among participating hospitals. Every clinical and paraclinical nodal examinations were recorded as normal, doubtful, or highly suggestive of recurrence. We analyzed follow-up records of all patients who had SNLB procedure until nodal recurrence or to 1/11/09. Gold standard for nodal status was histology or uneventful follow-up. Results: Follow-up visits were recorded for 80% of the 452 pts who had SNLB procedure (22% with nodal invasion). Average melanoma thickness was 2.7 ± 2.7 mm; 34% were ulcerated. 61% of the pts had ≥ 1 nodal US during follow-up (mean 3.4 ± 2.7/pt). Nodal recurrence occurred in 13% of the pts, synchronous of distant metastasis in 17% only. Using the criteria “highly suggestive of recurrence”, US detected nodal recurrence with 88% sensitivity, 96% specificity; and positive and negative likelihood ratio of 21, and 0.12, respectively. 23% of the pts with US had ≥ 1 doubtful US result, justifying a control (usually negative) within 1-2 m. or cytology. The initial mode of discovery of nodal recurrence was the patient himself (17%), clinical (38%) or paraclinical (30%) exam, or not specified (15%). Pts followed with US had similar melanoma thickness, ulceration or SNLB invasion rate than those without US surveillance. Using a Cox model in pts with negative SNLB, overall survival was better for lower AJCC stages (p < 0.0001) and marginally better when US was used during follow-up (p = 0.1). Conclusions: US detected 30% of nodal recurrences after SNLB. As surgery is indicated in most of these pts, US use may induce better pt survival. This study is not randomized. The impact of US on pt's anxiety was not analyzed. No significant financial relationships to disclose.
Incidence of adverse reactions to post-induction asparaginase (ASP) therapy in children and adolescents with high-risk acute lymphoblastic leukemia (ALL): A report from the Children’s Oncology Group Study CCG-1961
Authors: G. Dhall, N. J. Robison, J. I. Rubin, H. N. Sather, P. S. Gaynon, N. L. Seibel, L. J. Ettinger
Journal: Journal of Clinical Oncology (2008)

10021 Background: Asparagine depletion is an essential component of combination therapy for ALL. We report the incidence of reactions to three forms of ASP in children and adolescents with high-risk ALL enrolled on the Children’s Oncology Group study CCG- 1961. Methods: Between November 1996 and May 2002, 2078 patients with newly diagnosed high-risk ALL were enrolled on CCG- 1961. All were treated with a standard four-drug induction that included native E. coli ASP (native ASP). Rapid early responders randomized to augmented post induction intensification and all slow early responders were assigned 6 or 10 doses of pegylated ASP (PEG, 2500 IU/m2/dose) post-induction. Native ASP was given when PEG was unavailable (6000 IU/m2/dose × 6 per single dose PEG). Patients with adverse reactions to PEG received Erwinia ASP (10,000 IU/m2/dose × 6). Reaction incidence in PEG-assigned patients was analyzed by logistic regression. Results: 1,383 patients were assigned PEG-containing regimens and received 5,652 doses of PEG. Erwinia was substituted for 2,156 doses and native ASP for 912. Severe allergic reaction (respiratory distress ± hypotension) was reported in 188 (14%), pancreatitis in 51 (4%), and ischemic stroke in 9 (1%) of these patients. PEG had a higher incidence of severe allergic reactions; 60% of these reactions occurred during consolidation. Native ASP had a higher incidence of local reactions. Erwinia ASP had a lower incidence of allergic-type reactions, as well as of pancreatitis and liver dysfunction (See Table). Conclusions: Following native ASP in induction, PEG had the highest incidence of severe allergic reactions. Adverse reactions to PEG and native ASP were otherwise similar. Erwinia ASP had less toxicity. This is the largest cohort of ASP-treated patients reported to date. Incidence of adverse reactions per 1,000 dose equivalents* Reaction PEG Native ASP Erwinia ASP P ** Allergy type Any 82 80 28 <0.0001 Isolated local 9 47 9 <0.0001 Urticaria 39 20 14 <0.0001 Severe 31 7 4 <0.0001 Other Pancreatitis 7 9 2 0.03 Liver dysfunction 58 50 24 <0.0001 CNS events 2 3 2 0.73 * Dose-equivalents (see text): PEG x1, native ASP x6, Erwinia ASP x6. ** Wald test of global null hypothesis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Enzon