tbuckley/cabot-search huggingface dataset:
The relationship between codon boundaries and multiple reading-frame preferences: coding organization of bacterial insertion sequences.
Authors: D J Galas, T F Smith
Journal: Molecular Biology and Evolution (1984)

Theoretical considerations have shown that the five possible overlapping reading-frame configurations differ significantly in their coding flexibility and thus in their information content (Siegel and Fitch 1980; Smith and Waterman 1980). Contrary to expectation, the overlapping frame configuration allowing the greatest coding flexibility is rarely seen, whereas one of the most constraining is common. We point out here that this overlapping reading-frame paradox and an observed but unexplained preference in coding regions for a pyrimidine-purine at codon boundaries (Shepherd 1981; Jones and Kafatos 1982; Smith et al. 1983) are intimately linked. The codon boundary preference, which may be related to translation efficiency or accuracy, places constraints on the evolution of overlapping coding regions. These considerations may help identify actual coding regions in DNA sequences. We have analyzed five sequenced (enteric) bacterial insertion sequences for codon boundary incidences and reading-frame configurations and find that they are consistent with these proposed constraints.
Incidence of invasive breast cancer following 8 years of raloxifene therapy in postmenopausal women with osteoporosis: Results from the Continuing Outcomes Relevant to Evista (CORE) trial
Authors: S. Martino, J. A. Cauley, E. Barrett-Connor, T. J. Powles, J. L. Mershon, D. Disch, R. J. Secrest, S. R. Cummings
Journal: Journal of Clinical Oncology (2004)

1000 Background: Raloxifene (RLX) is approved for prevention and treatment of postmenopausal osteoporosis. Breast cancer incidence was a secondary outcome of the Multiple Outcomes of Raloxifene (MORE) trial; compared to placebo, invasive breast cancer (IBC) incidence was reduced 72% in postmenopausal women with osteoporosis receiving RLX for 4 yrs. Methods: The primary aim of CORE, a 4-yr double-blind follow-up to MORE, was to examine the effect of long-term (8 yrs) therapy with RLX on incidence of IBC by continuing observation of women randomized in MORE. Time to first IBC was the primary endpoint and time to first estrogen-receptor (ER) positive IBC was a secondary outcome. All MORE participants were eligible for CORE. CORE participants randomized to placebo in MORE continued to receive placebo in CORE. Those randomized to RLX 60mg/d or 120 mg/d during MORE received RLX 60 mg/d in CORE. Comparisons between the two therapy groups were made using a Cox proportional hazards model and a log-rank test. Results: The primary analysis dataset for CORE included 5213 MORE participants (RLX 60 mg/d, n=3510; placebo, n=1703). For the CORE primary analysis, there were 61 cases of adjudicated breast cancer (31 [0.9%] RLX, 30 [1.8%] placebo) and 52 were IBC (24 [0.7%] RLX, 28 [1.6%] placebo). Compared to placebo, a 59% reduction in IBC incidence was reported in the RLX group (hazard ratio [HR] 0.41, 95% CI 0.24, 0.71; p < 0.001). ER status was determined for 46 IBC cases. Compared to placebo, incidence of invasive ER-positive breast cancer was also decreased in the RLX group (HR 0.34, 95% CI 0.18, 0.66; p < 0.001). The incidence of ER-negative breast cancer was not altered by RLX therapy (HR 1.13, 95% CI 0.29, 4.35). Conclusions: When combined with the statistically significant reduction in incidence of IBC observed in the MORE trial, the CORE results provide additional evidence that the incidence of invasive breast cancer, specifically ER-positive invasive breast cancer, continues to be significantly reduced in postmenopausal women with osteoporosis through 8 years of therapy with raloxifene. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co.; Neothermia, Inc. Eli Lilly & Co.; Neothermia, Inc. Eli Lilly & Co. Eli Lilly & Co.; Pfizer; Organon; NIH; DaCosta Fund for Prevention of Breast Cancer; Merck Eli Lilly & Co. Eli Lilly & Co.
Impact of radiotherapy duration on outcomes in patients with esophageal cancer treated with definitive concurrent radiotherapy and chemotherapy on RTOG trials 8501 and 9405.
Authors: Christopher Leigh Hallemeier, Jennifer Moughan, Michael G. Haddock, Arnold M. Herskovic, Bruce D. Minsky, Harold Kim, Pierre Major, Elizabeth Gore, Mitchell D. Schnall, Kenneth Lee Zeitzer, Ritsuko Komaki, David Bush, Rojymon Jacob, Madhur Garg, Christopher H. Crane
Journal: Journal of Clinical Oncology (2015)

119 Background: Radiotherapy (RT) interruptions have a negative impact on outcomes in many epithelial malignancies treated with definitive RT. The purpose of this study was to analyze the impact of RT duration on outcomes in patients (pts) with esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Pts treated with definitive CRT on RTOG trials 8501 and 9405 were included. Separate analyses were performed in pts receiving standard dose (SD-CRT; 50 Gy + 5FU + cisplatin) and high dose (HD-CRT; 64.8 Gy + 5FU + cisplatin) CRT. Local (LF) and regional (RF) failure were estimated by the cumulative incidence method. Disease-free (DFS) and overall (OS) survival were estimated by the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were utilized to examine for correlation between RT duration (&lt; vs. ≥ median) with LF, RF, DFS and OS. Results: In the SD-CRT cohort (n=235), 96 pts (41%) had ≥ 1 RT interruption for a median of 3 (IQR 1-6) days. The median RT duration was 39 (IQR 37-43) days. In UVA and MVA, RT duration was not associated with LF, RF, DFS, or OS. Estimated outcome rates are in the table. In the HD-CRT cohort (n=107), 64 pts (60%) had ≥ 1 RT interruption for a median of 3.5 (IQR 2-7.5) days. The median RT duration was 52 (IQR 50-57) days. In UVA, RT duration ≥ 52 days was associated with a 33% reduction in risk of DFS failure (HR=0.66, 95% CI [0.44-0.98], p=0.039) and a 29% reduction in risk of death (HR=0.71, 95% CI [0.48-1.06], p=0.09). When excluding the 25 pts with RT dose &lt; 64.8 Gy, RT duration was not associated with DFS or OS. Conclusions: In pts with esophageal cancer receiving definitive SD-CRT, an association between RT duration and outcomes was not observed. In pts receiving HD-CRT, longer RT duration was associated with improved DFS, which may have been due to a significant number of deaths at RT dose &lt; 64.8 Gy. Supported by NCI U10 grants CA21661, CA180868, CA180822, CA37422. Clinical trial information: NCT00002631. [Table: see text]
Pharmacokinetic (PK) - pharmacodynamic (PD) study of gemcitabine (G) in a randomised phase II trial of carboplatin (C) combined with G at standard rate infusion or fixed dose rate infusion in patients with advanced non-small-cell lung cancer (NSCLC)
Authors: R. A. Soo, H. L. Lim, L. Z. Wang, L. S. Tham, R. Soong, H. S. Lee, S. Liang, S. C. Lee, M. Boyer, B. C. Goh
Journal: Journal of Clinical Oncology (2005)

2024
Oral metronomic chemotherapy using cyclophosphamide in metastatic patients (pts) after standard treatment: Results of a randomized phase II trial
Authors: S. Clisant, A. Adenis, E. Dansin, C. Desauw, M. Degardin, L. Mortier, C. Fournier, N. Penel
Journal: Journal of Clinical Oncology (2009)

e13519 Background: Oral metronomic chemotherapy (OMC) has antiangiogenic properties and megestrol acetate (MA) is an orexigen used to maintain the general condition in critically ill pts. Anecdotal responses have been reported with each treatment. We hypothesized that each treatment offer disease control without significant severe toxicity. Methods: This multi-center-randomized study was aimed to assess the efficacy and tolerance of both treatments. Primary endpoint was stable disease rate at 2 months: 2mSD (RECIST). Main eligibility criteria were as follows: non-breast cancer, pts with progressive disease refractory to standard therapies or without established standard care, ECOG=0–1, neither hypercalcemia nor hypoalbuminemia. Pts were randomized to receive MA 160 mg b.i.d or OMC 50 mg b.i.d until severe toxicity or progression. The sample size calculation was based on Simon Minimax design (α=10%, β =90%, P0=5%, P1=20%). The second stage was allowed because at least 2mSD were seen among 12 first pts. Results: 88 pts were included from 9/2006 to 12/2008 (44 in each arm). Median age was 61 (22–84). Most common primaries were: colorectal cancer (30 pts), soft tissue sarcoma (17), lung cancer (13), head &amp; neck (8) and unknown primaries (4). The median number of previous lines of treatment was 4 (0–10). As of 28 December 2008, 80 pts are assessable for primary endpoint: 6/40 pts (15%) experienced 2mSD in OMC arm whereas 2/40 pts (5%) in MA arm. Three long-lasting SD (6 months +) are currently being observed in 3 pts receiving OMC (2 sarcomas and 1 RCC). No Grade 3 or 4 toxicity was notified. Treatment was discontinued in 1 case because of MA- induced deep venous thrombosis. Conclusions: OMC and MA offer SD in patients with advanced, refractory and progressive tumors, without any significant toxicity. The non-progression rate with OMC (15%) is in a same range of efficacy that was recently reported with new targeted therapy or anti-angiogenic agents administered in such pts. The accrual is now completed, and a longer follow-up is necessary to better analyze the clinical benefit and the prognostic factors. [Table: see text]
Effect of Different Sera on Growth and “Spontaneous” Neoplastic Transformation of Mouse Fibroblasts In Vitro
Authors: Giusi Carbone, Rita Piazza, Giorgio Parmiani
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Effect of Different Sera on Growth and “Spontaneous” Neoplastic Transformation of Mouse Fibroblasts In Vitro Get access Giusi Carbone, Giusi Carbone Search for other works by this author on: Oxford Academic PubMed Google Scholar Rita Piazza, Rita Piazza Search for other works by this author on: Oxford Academic PubMed Google Scholar Giorgio Parmiani Giorgio Parmiani Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 387–393, https://doi.org/10.1093/jnci/52.2.387 Published: 01 February 1974 Article history Received: 13 April 1973 Revision received: 11 September 1973 Accepted: 12 October 1973 Published: 01 February 1974
Abstract 070: Interaction between Mena, Connexin43, and Rac1 at the Intercalated Disc
Authors: Rashmi Ram, Andrew P Wescott, Tamlyn Thomas, Robert T Dirksen, Burns C Blaxall
Journal: Circulation Research (2013)

Background: We previously reported that Mena, a member of Ena/VASP family of actin regulatory protein, is associated with heart failure (HF). Mena is localized to the intercalated disc (ICD) and interacts with ICD proteins implicated in HF. The ICD mediates force transmission and electrical coupling between cardiomyocytes. Slowed conduction in HF is associated with Cx43 remodeling, the predominant connexin isoform in the heart. Mena-/- mice develop cardiac dysfunction, conduction abnormalities, ICD disorganization, and Cx43 lateralization. We hypothesized that: 1) Mena’s interaction with the cytoskeleton is critical for ICD stabilization and maintenance of electrical function; 2) Mena may modulate signal(s) from the cardiac sarcolemma to the ICD for control of expression and localization of Cx43 through the regulation of the small GTPase Rac1. Methods and Results: Interaction of Mena with Cx43 and Rac1 was evaluated in neonatal rat ventricular myocytes (NRVM), HeLa cells, and in transgenic mice overexpressing constitutively active V12Rac1 (RacET). Pull down assay using GST-PAK1 demonstrated a direct association of Mena with active Rac1-GTP in vitro. In NRVMs, siRNA knockdown of Mena significantly increased activity of Rac1-GTPase by 2-fold (p=0.05, n=5). Western blot analysis revealed increased total Cx43 expression in Mena siRNA (1.11±0.2) compared to scramble (0.33±0.1, p&lt;0.01, n=5). Enhanced Cx43 expression was associated with increased rate of recovery after photobleaching between cardiomyocytes by gap-FRAP analysis (Tau 153.0±4.8 vs. 73.0±1.8 sec, p&lt;0.0001). Ongoing experiments with optical mapping of NRVM monolayers will determine whether conduction velocity may be enhanced after Mena knockdown. Confocal imaging revealed altered Cx43 trafficking and localization with Mena knockdown. Additionally in ventricles of RacET hearts, Mena expression was increased by 59% (p=0.01, n=4) compared to control, along with lateral redistribution of Cx43. Conclusions: Our results suggest that Mena is a critical regulator of the ICD at the intersection of Cx43 and Rac1. Increased Rac1 activation is associated with lateralized Cx43, and enhanced cellular coupling. Mena may modulate Cx43 localization through the regulation of Rac1 activity.
Diagnostic Dilemmas in Oncology
Authors: Efraim Idelevich, Monika Husar, Eyal Fenig, Baruch Brenner, Noa Ben-Baruch, Shani Adi
Journal: Journal of Clinical Oncology (2000)

Article Tools Diagnostic Dilemmas in Oncology Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.17.3188 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10963648 Diagnostic Dilemmas in Oncology Efraim IdelevichxEfraim IdelevichSearch for articles by this author , Monika HusarxMonika HusarSearch for articles by this author , Eyal FenigxEyal FenigSearch for articles by this author , Baruch BrennerxBaruch BrennerSearch for articles by this author , Noa Ben-BaruchxNoa Ben-BaruchSearch for articles by this author , Shani AdixShani AdiSearch for articles by this author Show More Institutes of Oncology, Kaplan Medical Center, Rehovot, and Rabin Medical Center, Beilinson Campus, Petach Tiqva, Israel https://doi.org/10.1200/JCO.2000.18.17.3188 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Margaret McCartney: Who gains from the media’s misrepresentation of science?
Authors: Margaret McCartney
Journal: BMJ (2016)

The Daily Mail said that “770 deaths a year could be avoided,” about weekend childbirth.1 But the study hadn’t said that.2 For this to be true, maternity services would need to be like Groundhog Day , with every day being Tuesday (the weekday with the lowest risk).

In the Mirror it was “good news for the posh” because drinking three glasses of champagne a week could “stave off” dementia,3 although the experiment looked at “aged rodents” trying to find their way in a maze.4

In the Express , meanwhile, rhubarb “can save your life” because it “speedily kills cancer.”5 But this was in mice, not humans, and the pigment parietin was under evaluation, not the whole plant. These facts were …
Interim results of a phase I trial with a novel orally administered synthetic triterpenoid RTA 402 (CDDO-Me) in patients with solid tumors and lymphoid malignancies
Authors: B. J. Dezube, R. Kurzrock, J. P. Eder, J. G. Supko, C. J. Meyer, L. H. Camacho, M. Andreeff, M. Konopleva, L. Lescale-Matys, D. Hong
Journal: Journal of Clinical Oncology (2007)

14101 Background: RTA 402 (CDDO-Me) is a novel synthetic triterpenoid with potent anticancer and anti-inflammatory activity through selective modulation of proteins that respond to changes in oxidative stress, including NF-κB, JNK, and STAT3. Based on preclinical data demonstrating effects on tumors and associated stroma, a Phase 1 dose-finding and pharmacokinetic study was initiated. Methods: RTA 402 is administered orally once a day for the first 21 days of a 28-day cycle. Dose escalation is proceeding according to an accelerated titration design until an MTD is reached. Results: RTA 402 has been administered to 11 patients at 7 dose levels (5 to 300 mg/day). Cycle 1 data are available for 8 patients. No significant drug-related toxicity has been reported and dose escalation continues in 100% increments. The median biological half-life of RTA 402 was 49 h (range, 18–67 h), and all patients receiving doses &gt;20 mg/day were continuously exposed to plasma levels of the drug exceeding 1 ng/mL. Evidence of antitumor and biological activity has been observed in initial patients. A patient with medullary thyroid carcinoma treated at 5 mg/day has received eight cycles of therapy and has had stable disease with a 70% reduction of calcitonin levels. A patient with metastatic melanoma has experienced disease stabilization through four cycles and remains on study. A second melanoma patient has also experienced disease stabilization through two cycles and remains on study. Radiographic evidence of regressing lesions has been observed in both melanoma patients. Additionally, significant reductions in circulating VEGF, MMP-9, TNF, IL-8, and IL-10, up to 65%, 91%, 90%, 73%, and 70%, respectively, have been observed in at least half of patient samples. Cytokine suppression has correlated with improvements in reported pain and fatigue. Conclusions: Orally administered RTA 402 appears well tolerated up to 150 mg/day and with prolonged exposure up to 8 months. Data from initial patients indicate biological activity and suggest clinical benefit, with disease stabilization in several patients who had rapidly progressing disease with high tumor burden. Phase 2 trials are planned. No significant financial relationships to disclose.
Abstract 212: Hydrogen Peroxide Acutely Stimulates Cardiogenic Gene Expression in Cardiac Progenitor Cells
Authors: Karl D Pendergrass, Michael E Davis
Journal: Circulation Research (2012)

Following acute myocardial infarction, billions of myocytes are lost to cell death. The damage is regional and lost cells are replaced with a collagen scar. One potential therapy to delay or prevent progression into heart failure is regeneration of the damaged myocardium through cell therapy with cardiac progenitor cells (CPC). Reactive oxygen species, specifically hydrogen peroxide, elicit varying responses from different stem/progenitor cells. In the present studies, we sought to determine the effect of acute H2O2 treatment on CPC survival and differentiation. CPCs were isolated and cultured with leukemia inhibitory factor (LIF) to retain their stem-like qualities. CPCs were allowed to differentiate in the absence of LIF for up to 5 days + H2O2. H2O2 (100μM) significantly increased expression of the smooth muscle marker, alpha smooth muscle actin (αSM) by Day 2 as compared to time-matched controls (Ctl: 1.8+1.3 vs 100 μM: 8.5+1.1; p&lt;0.001; N=3). We also observed a trend for an increase in smooth muscle 22 alpha (SM 22α) gene expression by Day 2. Interestingly, by Day 5 the stimulatory effect of 100 μM H2O2 treatment on α SM and SM 22α was reversed and significantly decreased compared to Day 2 (D5: α SM: 0.43+0.05, SM 22α: 0.41+0.2 vs. D2: SM 22α: 10.58+2.3; p&lt;0.01; N=3-4). Evaluation of the endothelial marker VEGFR-2 (Flk-1) showed a trend for an increase in gene expression by Day 2 following 100 μM H2O2 treatment compared to the time-matched control. We also observed an anti-apoptotic effect on CPCs following serum removal, in which 2 days of 100μM H2O2 pretreatment lead to approximately a 55% decrease in cell death compared to untreated CPCs (Ctl: 19.1+2.4 vs 100 μM: 10.5+1.7; p&lt;0.05; N=3-4). The protective effect of the H2O2 pretreatment could be attributed to an increase in anti-oxidative enzymatic capacity in CPCs. There was a trend for an increase in catalase gene expression. In conclusion, our results showed that acute H2O2 preconditioning exerted a stimulatory effect on smooth muscle gene expression and an anti-apoptotic effect compared to time-matched Control CPCs. Furthermore, acute H2O2 preconditioning may aid in directing CPC differentiation towards a vascular phenotype and angiogenesis in the infarcted myocardium, which may prevent or delay heart failure.
Tumorigenic Effects of Direct- and Indirect-Acting Chemical Carcinogens in Rats on a Restricted Diet&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Pollard, P H Luckert
Journal: JNCI Journal of the National Cancer Institute (1985)

The influence of diet restriction on induction of intestinal tumors in Sprague-Dawley rats by two unique carcinogenic agents was investigated: methylazoxymethanol acetate [(MAM) CAS: 592-62-1], which requires metabolic activation, and N-methylnitrosourea [(MNU) CAS: 684-93-5], which is a direct-acting carcinogen. Most of the tumors induced by MAM developed in the small intestine and less frequently in the colon, but MNU produced tumors predominantly in the colon. Among rats fed the restricted diet (12 g/day), the production of tumors by MAM was significantly reduced compared to that of counterpart rats on the ad libitum diet. However, dietary restriction did not modify the production of tumors in rats by MNU. The same relationship of diet restriction to tumor induction was demonstrable when MAM and MNU were administered to the same test rats: Numbers of MAM-related tumors, especially in the small intestine, were reduced and numbers of MNU-related tumors in the colon were unchanged. Dietary restriction modified the tumorigenic response of rats to MAM but not to MNU.
Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces
Authors: Chigusa Nakahashi-Oda, Kankanam Gamage Sanath Udayanga, Yoshiyuki Nakamura, Yuta Nakazawa, Naoya Totsuka, Haruka Miki, Shuichi Iino, Satoko Tahara-Hanaoka, Shin-ichiro Honda, Kazuko Shibuya, Akira Shibuya
Journal: Nature Immunology (2016)
Identification of immune evasion strategies of pediatric pre-B acute lymphoblastic leukemia after bone marrow transplantation
Authors: D. Barbaric, K. Schultz, G. Reid
Journal: Journal of Clinical Oncology (2004)

8555 Background: Bone marrow transplantation (BMT) is the only curative option for refractory/relapsed pediatric acute lymphoblastic leukemia (ALL). However, post-BMT relapse remains an important cause of transplantation failure. Immune mechanisms play a critical role in the anti-leukemic efficacy of BMT, suggesting that mechanisms allowing leukemic blasts to evade immune responses are important in leukemia relapse. An improved understanding of the processes underlying post-BMT ALL relapse is required. Methods: In this study several methods were utilised to assess and compare the allogeneic and autologous T cell responses induced by pediatric pre-B ALL cells which had been obtained at various time points from a pediatric patient with pre-B ALL who relapsed following allogeneic BMT. All patient samples were also extensively phenotyped in order to determine the degree of co-stimulatory molecule expression on the leukemic blasts. Results: We observed a dramatic loss of T cell stimulatory capacity by later relapse samples. Also, the autologous anti-leukemic T cell response demonstrated a Th2 shift compared to the Th1 allogeneic response. These immune stimulatory changes induced by ALL cells at relapse were associated with changes in expression of MHC and costimulatory molecules. HLA-ABC expression was increased on all relapse samples. HLA-DR expression was substantially reduced in those relapse samples obtained following immunosuppression cessation. Expression of the costimulatory molecule CD137L was decreased on post-BMT relapse samples whereas B7-H1 expression was increased. Conclusions: These results reveal mechanisms involved in pre-B ALL relapse, and suggest strategies to prevent evasion of the graft-versus-leukemia effect by ALL cells. No significant financial relationships to disclose.