tbuckley/cabot-search huggingface dataset:
E7107, a new 7-urethane derivative of pladienolide D: Discovery of a novel antitumor agent
Authors: Jun Niijima, Yoshihiko Kotake, Regina M. Kanada, Mitsuo Nagai, Yoshio Fukuda, Takashi Sakai, Hiroyuki Ishihara, Masashi Yoshida, Toshio Tsuchida, Masao Iwata, Toshimitsu Uenaka, Yoshiharu Mizui, Shinya Abe, Kentaro Yoshimatsu, Makoto Asada
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2988 

Pladienolides, novel 12-membered macrolides possessing an inhibitory activity of hypoxia-induced vascular endothelial growth factor (VEGF) expression, were isolated from Streptomyces platensis Mer-11107. Some of the pladienolides have been shown to have a strong inhibitory growth activity in various cancer cell lines at nanomolar concentrations and a good in vivo antitumor activity against human tumor xenografts. Further, these macrolides appear to have a different mechanism of action from those of pre-existing anticancer agents in clinical use according to the COMPARE analysis data. In order to enhance the potency of the naturally occurring pladienolides, synthetic derivatives were prepared and evaluated. We describe herein the synthetic approach for the derivatization of pladienolide D that led us to the discovery of E7107, which has a wide tumor spectrum, a high regression rate, and a wide therapeutic window. One of our synthetic approaches was the replacement of the acetoxy group in position-7 with a urethane moiety. Urethane derivatives were synthesized from pladienolide D in 7 steps employing commonly used and simple organic reactions. The replacement of the acetoxy group with a simple urethane moiety decreased the in vitro antiproliferative activity. However, by introducing an amino function onto the urethane moiety, the activity was regained. Many of the derivatives in this series showed a strong in vitro activity as potent as pladienolide D. A correlation between the lipophilicity of these derivatives and their in vitro activity was observed. Detailed data will be presented at the meeting. In the human colon WiDr xenograft model, several of the urethane derivatives showed more potent in vivo tumor regression activity than that of pladienolide D. Among these derivatives, E7107 was found to have an impressive tumor regression activity against WiDr xenograft with a wide dose range. These results suggest that E7107 might be a promising therapeutic agent for the treatment of cancer.
Abstract 16838: Relative Hypochromia is Associated With Increased All-Cause Mortality in Non-Anemic Heart Failure Patients
Authors: Muhammad Hammadah, Marie-Luise Brennan, Stanley L Hazen, W. H. Wilson Tang
Journal: Circulation (2013)

Introduction: Anemia has been associated with increased mortality in heart failure patients, yet recent studies have suggested that functional iron deficiency may be contributing. However, the impa...
Induction Chemotherapy, Chemo-Radiotherapy and Surgery in Locally Advanced Gastric Cancer (Gc) Patients: Long Term Results from a Single Institution
Authors: P. Martin Romano, N. Buil, L. Arbea, J.P. Fusco, E. Castanon Alvarez, L. Zubiri, L. Ceniceros, J. Subtil, A. Chopitea, J.L. Hernandez-Lizoain, J. Rodriguez
Journal: Annals of Oncology (2014)
Guidelines of care for the management of acne vulgaris
Authors: Andrea L. Zaenglein, Arun L. Pathy, Bethanee J. Schlosser, Ali Alikhan, Hilary E. Baldwin, Diane S. Berson, Whitney P. Bowe, Emmy M. Graber, Julie C. Harper, Sewon Kang, Jonette E. Keri, James J. Leyden, Rachel V. Reynolds, Nanette B. Silverberg, Linda F. Stein Gold, Megha M. Tollefson, Jonathan S. Weiss, Nancy C. Dolan, Andrew A. Sagan, Mackenzie Stern, Kevin M. Boyer, Reva Bhushan
Journal: Journal of the American Academy of Dermatology (2016)

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.
An observational study of the impact of ethnicity on patients treated for non-small cell lung cancer (NSCLC) in the second-line setting with pemetrexed: Preliminary results in African Americans
Authors: A. C. Girvan, G. Peltz, E. Pennella, G. Pohl, D. Faries, M. D. Marciniak, C. K. Obasaju, E. J. Stepanski, L. S. Schwartzberg, A. A. Adjei
Journal: Journal of Clinical Oncology (2009)

e20624 Background: African-Americans are more likely to develop and die from lung cancer than persons of any other ethnic group. Historically, African-Americans have been under-represented in oncology clinical research. This prospective, single-arm, observational study evaluates the impact of ethnicity on disease control rate (DCR) (CR + PR + SD)) in patients (pts) with non-small lung cancer (NSCLC) being treated with pemetrexed (Pem) in the second-line setting. Methods: Eligibility criteria include stage IIIB or IV NSCLC pts receiving Pem for second-line therapy with no restrictions on performance status. An accrual of 200 African-Americans, 200 Hispanics, 200 Asian-Americans, and 400 Caucasians is planned to test the hypothesis that subjects from these minority populations with advanced NSCLC will have DCRs that are not inferior to Caucasian subjects during second-line treatment with Pem in routine clinical practice. This report describes observations from an early examination of the data of the Caucasian and African-American pts enrolled. Results: 293 pts have been enrolled in this study including 243 Caucasians and 34 African-Americans. Demographics of Caucasians: M/F (136:107); median age 66 (range 37–88); histology adenocarcinoma/squamous/other/unknown (141:67:33:2). Demographics of African-Americans: M/F (21:13); median age 64 (range 43–80); histology adenocarcinoma/squamous/other/unknown (22:9:3:0). DCR in Caucasians: 38% (CI= 28–47%: 3 CR, 8 PR, and 34 SD in 120 of the 243 pts). DCR in African-Americans: 61% (CI=36–86%: 0 CR, 0 PR, and 11 SD in 18 of the 34 pts). Updated safety and efficacy data will be available. Conclusions: Preliminary results based on limited data do not indicate an inferior response for African-American pts compared to Caucasian pts being treated with Pem for NSCLC in the second-line setting. Additional data are needed to establish a definitive conclusion. [Table: see text]
Abstract 9234: Ventricular Irregularity, but not Ventricular Rate, is Important for Determination of NT-ProBNP Levels in Chronic Atrial Fibrillation: Evidence for Lenient Rate Control in Atrial Fibrillation
Authors: Wonjong Park, Yoon-Jung Choi, Jin-Sung Lee, Min-Kyu Kang, Sang-Hee Lee, Ung Kim, Jong-Sun Park, Dong-gu Shin, Young-Jo Kim
Journal: Circulation (2012)

Background Adequate rate control has been a concern in management of patients with atrial fibrillation(AF). Role of ventricular rate(VR) and its irregularity have not been well studied with respect to the elevation of NT-proBNP level. VR at which NT-proBNP level is lowest would be the optimal heart rate in patients with AF. Methods and Results In 85 patients with AF(69.8±9.0 years, 43 men), NT-proBNP level, indices of VR irregularity(mean VR, standard deviation(SD) of VR, SD of successive differences and SD of 5-minute averages(SDAVR)) derived from 24-hour ambulatory ECG and transthoracic echocardiographic parameters(early mitral inflow velocity(e)/mitral annular velocity(e′), left atrial volume index and left ventricular ejection fraction(LVEF)) were measured. Potential determinants of NT-proBNP level were identified by univariate and multivariate linear analysis. Age, e/e’ and SDAVR were significant univariate predictors of NT-proBNP level, but mean VR did not. e/e′and SDAVR remained as significant predictors after multivariate adjustment(β=0.028, P =0.004, and β=-0.002, P =0.008, respectively). When the patients were stratified with the 33rd and 67th percentile values of e/e′(10.62 and 14.63, respectively), a significant positive correlation between mean VR and NT-proBNP level was present in patients with higher e/e(N=57, β=0.007, P =0.043). Conclusions LV diastolic function and VR irregularity rather than VR were associated with elevation of NT-proBNP level in AF. Key words : Atrial fibrillation, NT-proBNP
MDS-associated cytogenetic abnormalities (MDS-CA) after total therapy (TT) regimens for newly diagnosed multiple myeloma (MM): Apparent surge after introduction of post-transplant consolidation chemotherapy (CONS) in TT2 and TT3
Authors: K. Hollmig, S. Waheed, B. Nair, J. Haessler, N. Petty, M. Pineda-Roman, Y. Alsayed, F. van Rhee, J. Crowley, B. Barlogie
Journal: Journal of Clinical Oncology (2009)

8595 Background: We have previously reported on the variables associated with the development of MDS-CA in the context of autologous transplant-supported high-dose therapy regimens for MM (Barlogie et al, Blood 2008). Methods: Due to a perceived increase in MDS-CA frequency, our MM data base was reviewed again to determine the potential effect of CONS introduced in TT2 and retained in TT3 trials. The frequency of MDS-CA post-transplant was determined, using Kaplan-Meier estimate plots, for 183 patients who received TT1, 554 enrolled in TT2 and 305 receiving TT3. Persistence of MDS-CA implied their documentation on 3 successive occasions. Results: 3-year MDS-CA estimates were 2% for both TT1 and TT2 and 4% for TT3 (TT3 v TT2, p=0.04; TT3 v TT1, p=0.11); persistent MDS-CA were also more frequently observed in TT3 in comparison with TT2 and TT1 (2% v 0% v 0%, both p=0.01). Multivariate analysis of features associated with transient and persistent MDS-CA revealed TT3 as an adverse feature (HR=2.84, p=0.043), along with incomplete platelet recovery of &lt;165,000/uL 3mo after 1 st transplant. Conclusions: Despite reduced induction chemotherapy prior to and CONS after tandem melphalan (200mg/m2)-based autotransplants from 4 in TT2 to 2 in TT3, overall and persistent MDS-CA increased significantly in TT3. Clinical MDS and AML were rarely observed and a full account of hematopathologic findings will be presented. [Table: see text]
Towards European core competencies for training infection control/hospital hygiene professional
Authors: F Coiz, S Brusaferro, B Cookson, S Kelenic, R Gallagher, Gaetano Pierpaolo Privitera, T Cooper, W Popp, J Fabry, P Hartemann, K Mannerquist, E Fabbro, C Ruef, K Weist, C Suetens, C. Varela santos
Journal: Clinical Microbiology and Infection (2011)
Preoperative concomitant chemo-radiotherapy (CT-RT) in superior sulcus tumors (SST): A mono-institutional experience
Authors: A. G. Favaretto, G. Pasello, F. Rea, L. Loreggian, C. Magro, G. Sotti
Journal: Journal of Clinical Oncology (2008)

7578 Background: SST is an uncommon neoplasia, whose optimal treatment remains controversial. Recently preoperative chemo- radiotherapy is arousing interest. Methods: Treatment consisted of a platinum-based CT: carboplatin AUC 5 on days 1 and 22, with mitomycin-C 8 mg/m2, d.1 & 22, and vinblastine 4mg/m2 dd.1, 8, 22 & 29 (MVC), from 1994 to 1999 or combined with vinorelbine 25mg/m2 dd.1, 8, 22 & 29 (NC), from 2000 to 2007. RT was administered 5 dd/week, 30Gy in 10 fractions from dd. 22 to 35 (from 1994 to 1996), or 44Gy in 22 fractions, dd.22 to 52 (from 1997 to 2007). Surgery was planned after 2–3 weeks from the conclusion of RT. Results: Since 1994, 38 pts were treated with induction CT-RT. M/F ratio was: 33/5, median age 61 years/ range (43–77yrs), median PS was 80 (range 50–90). Histology subtypes were as follows: squamous 14 (37%), adeno 16 (42%), NSC 8 (21%); stage: 20 had IIb (53%), 8 IIIa (21%), and 10 IIIb (26%); 5 pts had a weight loss>5% (13%), 4 pts had a weight loss<5% (11%), 29 had no weight loss (76%); 31 pts had shoulder pain (82%), 4 pts had the Horner syndrome (11%). Induction CT: 16 pts had MVC (43%) and 21 CN (57%); Induction RT: 7 patients treated with MVC had 30 Gy/10F, 9 had 44 Gy/22F; all of the patients treated with CN had 44 Gy/22 F, but 2 of them did not complete RT because of early death or toxicity. Hematologic toxicity was mild: out of 94 cycles we observed 6 gr.4 and 3 gr.3 neutropenia; 11 gr.3 leukopenia; 1 gr4 leukopenia; 1 gr.4 and 2 gr.3 thrombocytopenia; 2 gr.3 and 3 gr.2 anemia. Nonhematologic toxicity consisted of constipation in 11 pts, esophagitis in 4 pts. One complete, 18 partial, 7 stable disease and 1 progressive disease were observed; 11 were not evaluable. Surgery: 30 upper lobectomies and 4 segmentectomies, with chest wall resections, were performed (89% resection rate); 4 pts were not operated: 2 for unresectability 1 for early death and 1 for progression during CT-RT. At resection 5 pathologic complete remissions were seen. 24 pts had improvement of shoulder/arm pain. Median progression-free survival was 106 weeks and median survival was 196 weeks. Conclusions: In SST, concurrent carboplatin-based CT plus RT was active and feasible without major toxicities. This resulted in a high resectability rate and favorable progression-free and overall survival rates. No significant financial relationships to disclose.
Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI1 gene in acute myelogenous leukemias with inv(3)(q21q26)
Authors: K Suzukawa, E Parganas, A Gajjar, T Abe, S Takahashi, K Tani, S Asano, H Asou, N Kamada, J Yokota
Journal: Blood (1994)
BCX7353, a Potent Inhibitor of Plasma Kallikrein, Shows Sustained Maximal Enzyme Inhibition When Dosed Orally Once Daily: Results from a Phase I Trial in Healthy Subjects
Authors: Melanie Cornpropst, Sylvia Dobo, Jo Collier, Angela Rose, Ramanda Wilson, Y.S. Babu, Phil Collis, William Sheridan
Journal: Journal of Allergy and Clinical Immunology (2016)
Efficacy of cyclophosphamide, doxorubicin, etoposide and prednisone (CHEP) chemotherapy in previously untreated aggressive non-Hodgkin’s lymphoma (NHL)
Authors: W. S. Lee, Y. D. Joo, J. S. Chung, G. J. Cho, K. T. Park, C. H. Sohn
Journal: Journal of Clinical Oncology (2005)

6721 Background: CHOP regimen has been the standard therapy for NHL for the previous 30 years, but its complete response & long-term survival rates were unsatisfactory. Therefore, more effective chemotherapeutic regimens are required. Methods: Patients with histologically confirmed aggressive NHL were studied. All patients received CHEP chemotherapy as first-line treatment (cyclophosphamide 650mg/m2 i.v. on day 1; adriamycin 50mg/m2 i.v. on day 1; etoposide 80mg/m2 i.v. on days 1–3; prednisolone 80mg p.o. on days 1–7). Courses were repeated every 21 days for at least 4 cycles pending response to treatment. Results: Between March 1997 and April 2003, 36 patients (24 males and 12 females) were enrolled in the study. Median age was 52 (range 15–69) years. Of these patients, 19 patients (53%) had diffuse large B-cell lymphomas. Eighteen patients (50%) had localized disease (Ann Arbor stage I or II) and 18 patients (50%) had advanced disease (Ann Arbor stage III or IV). Median follow-up duration was 15.5 (range 1.0–80.0) months. Thirty one patients (86.1%) responded with 26 CR (72.2%) and 5 PR (13.9%). Among patients with localized disease (stage I, II), all had CR (100%). Of these patients with CR, 2 patients (11.1%) developed recurrence. However, among patients with advanced disease (stage III, IV), 13 patients (72.2%) responded with 8 CR (44.4%) and 5 PR (27.8%). Myelosuppression was the dose-limiting toxicity. Seventeen patients (47%) experienced grade 3–4 neutropenia but no neurologic side effects which frequently occurred after using vincristine. Conclusions: CHEP regimen in patients with aggressive NHL is effective as first-line therapy, and possesses an acceptable toxicity profile. We suggest a trial that adds rituximab to the CHEP regimen as first-line therapy for aggressive NHL in the future. No significant financial relationships to disclose.
Reply Creatine supplementation in chronic heart failure
Authors: A Gordon
Journal: Cardiovascular Research (1996)

Dr. M.L. Field has in a Letter to the Editor pointed out several interesting theoretical aspects on creatinine loading of cardiomyoytes concluding the lack of efficacy of creatine supplementation in treating the failing myocardium. The Letter discusses the possibly important role of the free creatine store as ATP acceptor with simultaneous ADP release at the inner mitochondrial membrane. An increased creatine concentration would amplify the local ADP concentration and stimulate respiration [l]. The creatine concentration in the human diseased heart is 1218 mM [2,3], but in the normal contractile cycle 60-70% of the creatine is phosphorylated [4]. The free creatine available for mitochondrial creatine kinase will thus correspond to approximately 5 mM, which is below the K, value given by Saks et al. [5]. This would indicate a positive role for creatine supplementation as stimulator of respiration in heart tissue in cardiac failure. This will of course not necessarily give an increase of the ejection fraction, but the measurement seemed justified since the hypothesis has never been tested. Furthermore, depressed myocardial total creatine levels were reported from explanted hearts [3] that probably had a more deranged myocardial function than present in our patient group. Perhaps a recruitment of a considerably larger and sicker patient population would be necessary to achieve efficacy.
Reduction of circulating regulatory T cell (Treg) by intravenous high-dose interferon (HDI) treatment in melanoma patients
Authors: P. A. Ascierto, M. Napolitano, E. Celentano, E. Simeone, G. Gentilcore, M. Capone, L. Ciccarelli, G. Palmieri, G. Castello, N. Mozzillo
Journal: Journal of Clinical Oncology (2009)

9040 Background: T regulatory (Treg) cells are an immunoregulatory cell type which express high levels of surface CD25, CTLA-4, and GITR. Tregs have been shown to be present in tumor and tumor-draining lymph nodes, acting as an inhibitory population blocking effector cell function. Depletion or blockade of Tregs might be able to enhance antitumor immunity. Recent evidence has been reported about the possibility of High Dose Interferon (HDI) to act through an indirect immunomodulatory mechanism (Gogas, NEJM 2006; Moschos JCO 2006). We started a study to verify if iv HDI treatment in melanoma patients could be able to reduce the number of Treg cells in peripheral blood. Methods: Analysis was performed on melanoma pts referring to the National Cancer Institute of Naples since July 2006 and who addressed to Neoadjuvant or Adjuvant treatment with iv HDI (20 MUI/m 2 , 5 days per week) for 4 wks. Peripheral blood mononuclear cells (PBMC) were obtained from 22 consecutive melanoma pts. Blood draw was performed at days 0, 8, 15, 22 and 29. PBMC were thawed and labeled with anti-CD4 and anti-CD25hi (BD, San Diego, CA) and anti-FoxP3 (eBioscience, San Diego, CA). Labeled cells were analyzed using a FACScalibur (Becton Dickinson). Results: Fifteen (68.2%) out of 22 pts showed a decrease of Treg cells in peripheral blood. The average value at day 0 for circulating Treg (cTreg) was 2.7%. The average percentage at day 29 was 1.4%. The average reduction was 1,4 (50% reduction in the average value of cTreg). Statistical analysis showed an average decrease of 0.29% per week of treatment. Despite of this clear trend in reducing cTreg by HDI, statistical significance was not reached (probably due to the power of the study). Moreover, it has been observed great differences between the disease status, the prognosis (recurred/not recurred pts, alive/deceased) and an increased basal percentage of cTreg. Our preliminary data are consistent for an effect of HDI on reducing cTreg, although no conclusion about the role of such reduction in terms of response to treatment or as prognostic markers of better/worse disease can be inferred. Further data are awaited in order to verify if the Treg reduction after a HDI treatment may indeed contribute to the antitumor response. [Table: see text]
Effects of Cilazapril on Exercise Tolerance in the Chronic Phase of Acute Myocardial Infarction
Authors: Kazuhiko Tanabe, Noriyuki Suzuki, Naohiko Osada, Akiko Yamamoto, Masaru Nakayama, Yasuhiro Yokoyama, Masayoshi Sakakibara, Haruki Itoh, Masahiro Murayama, Sumio Yamada, Hiroshi Yamasaki
Journal: Circulation (1996)

The present study was conducted to investigate the effects of cilazapril on exercise tolerance and the hormone kinetics of catecholamines, the renin-angiotensin-aldosterone system and alpha-atrial natriuretic peptide (ANP) in patients in the chronic phase of acute myocardial infarction (AMI). The subjects consisted of 19 cases of AMI. Cardiopulmonary exercise testing was performed 1 month after the onset of AMI, and patients were randomly assigned to either a group treated with 1 mg/day of cilazapril (9 cases) and or an untreated group (10 cases). After the completion of 2 months of exercise training at the anaerobic threshold (AT), blood samples were taken during a cardiopulmonary exercise test and various hormones were measured. In comparing the parameters of exercise tolerance before and after the completion of exercise training there were no significant differences between the 2 groups with respect to oxygen uptake, oxygen pulse, or exercise time at AT or at peak exercise. With regard to temporal changes in exercise tolerance, oxygen uptake, oxygen pulse and exercise time all tended to increase in both groups. With regard to hormone kinetics, the alpha-ANP concentration at peak exercise was significantly lower, and the noradrenaline secretions also tended to be lower, in the cilazapril-treated group, even though the peak exercise time was similar in both groups. These results may be support the hypothesis that cilazapril mitigates the left ventricular load during exercise therapy in patients in the chronic phase of AMI. (Jpn Circ J 1996; 60: 831 - 840)
Response to Comment on Bonnet et al. Association Between Handedness and Type 2 Diabetes: The E3N Study. Diabetes Care 2015;38:e199
Authors: Fabrice Bonnet, Aurélie Affret, Marie-Christine Boutron-Ruault, Beverley Balkau, Françoise Clavel-Chapelon, Guy Fagherazzi
Journal: Diabetes Care (2016)

We thank Dr. Selvin (1) for her comments on our article (2). Selvin was concerned about the way age was handled in our analysis and how it …
Epilepsy in glioma patients: mechanisms, management, and impact of anticonvulsant therapy: Table 1.
Authors: Terri S. Armstrong, Robin Grant, Mark R. Gilbert, Jong Woo Lee, Andrew D. Norden
Journal: Neuro-Oncology (2015)

Seizures are a well-recognized symptom of primary brain tumors, and anticonvulsant use is common. This paper provides an overview of epilepsy and the use of anticonvulsants in glioma patients. Overall incidence and mechanisms of epileptogenesis are reviewed. Factors to consider with the use of antiepileptic drugs (AEDs) including incidence during the disease trajectory and prophylaxis along with considerations in the selection of anticonvulsant use (ie, potential side effects, drug interactions, adverse effects, and impact on survival) are also reviewed. Finally, areas for future research and exploring the pathophysiology and use of AEDs in this population are also discussed.