tbuckley/cabot-search huggingface dataset:
A 10-year update of CHOP-Bleo in the treatment of diffuse large-cell lymphoma.
Authors: R Lee, F Cabanillas, G P Bodey, E J Freireich
Journal: Journal of Clinical Oncology (1986)

Long-term follow-up results of two studies using cyclophosphamide, doxorubicin, vincristine, and prednisone plus bleomycin (CHOP-Bleo) for the treatment of diffuse large-cell lymphoma are presented. Twenty-eight patients were treated with conventional-dose CHOP-Bleo and 36 patients with maximally tolerated doses of CHOP-Bleo. The maximal duration of follow-up was 10.5 years. The minimum follow-up was 5.7 years. Seventy-five percent of the conventional-dose group achieved a complete remission (CR) with a 10-year actuarial survival of 53% and a corresponding relapse-free survival (RFS) of 69% for CRs. Eighty-one percent of the high-dose group achieved CR, and the 10-year actuarial survival for all patients and RFS for CRs were 48% and 63%, respectively. The combined actuarial survival and RFS for both groups were 51% and 66%, respectively, at 10 years. For 11 patients with stage III disease, 91% achieved CR, 52% survived at 10 years, and the RFS was 67% for CRs. Seventy-five percent of 44 patients with stage IV disease achieved CR, 50% survived at 10 years, and the RFS was 67% for CRs. Three of the 16 relapses occurred late, between 30 to 65 months after initiation of therapy. Neuropathy occurred in 14 patients (22%). Five patients (8%) died of complications related to treatment. Five (8%) had clinically apparent, but nonfatal cardiopulmonary complications. The CHOP-Bleo regimen is an effective treatment for diffuse large-cell lymphoma, and is moderately well tolerated. The use of high-dose CHOP-Bleo for induction therapy did not result in any advantage after long-term follow-up.
Laparoscopic resection for rectal cancer is not supported by studies
Authors: Jacqui Wise
Journal: BMJ (2015)

Minimally invasive laparoscopic resection for colorectal cancer does not provide better outcomes than open resection, two randomised controlled trials published in JAMA have found.

In the first study, conducted at 35 institutions in the United States and Canada, 462 patients with clinical stage II or III rectal cancer were randomly assigned to laparoscopic or open pelvic resection.1 Successful resection was defined by a number of measures including the completeness of the total mesorectal excision, uninvolved circumferential resection margin, and uninvolved distal resection margin.

Successful resection occurred in 82% of …
The empty chair
Authors: Colin Douglas
Journal: BMJ (2000)

Sir Henry Raeburn (1756-1823) was an Edinburgh painter whose output reflected his role in the Scottish Enlightenment. Agreeably, fluently, and for a decent fee, he painted everyone who was anyone, leaving hundreds of portraits, most of them unremarkable but for the distinction of their sitters.

A few are memorable. His skating clergyman glided briefly across the nation's postage stamps a few years ago. His portrait of Mrs Scott-Moncrieff is also widely reproduced. Once, in a frigate in the South China Sea …
Atrasentan (ABT-627, ATN) pharmacokinetics (PK) and endothelin-1 (ET-1) pharmacodynamics (PD) in a phase 2 study of patients with asymptomatic hormone-refractory prostate cancer (HRPC)
Authors: R. A. Carr, B. Hosmane, A. Andre, T. Yanke, K. Hamel, A. Allen
Journal: Journal of Clinical Oncology (2004)

4721 Background: ATN, an oral ET antagonist with high selectivity for ETA receptor, is in phase 3 clinical development for the treatment of HRPC. ETA receptors are primarily responsible for ET-1 mediated vasoconstriction and cell proliferation. ET-1 is the main ET isoform in mammalian tissues and fluids. Methods: ATN PK and ET-1 PD were assessed in a phase 2, randomized, double-blind, placebo-controlled, multicenter study (M96–594). 288 HRPC patients (mean±SD 71±8 yrs, 81±13 kg) were assigned to receive PO QD: ATN 2.5 mg, ATN 10 mg, or placebo, along with continued hormone ablation therapy. Predose blood samples were collected starting Day 14, every 2 weeks for 6 months, and monthly thereafter. For a PK subset (N=9), blood samples for ATN and ET-1 assay were collected over 24 h on Day 28. ATN and ET-1 plasma concentrations were determined using validated methods. Mixed model statistical analysis of ATN and ET-1 predose data included effects for day, dose, age, race, body weight and day*dose. Results: Predose ATN (N=1214 from 173 subjects) and ET-1 (N=1876 from 257 subjects) concentrations did not vary with time, body weight or race, but were positively correlated with age. Only 3% of variability in ATN concentration was explained by age. ATN modestly increased average predose ET-1 levels: 2.8, 3.8 and 4.5 pg/mL for 0, 2.5 and 10 mg dose groups, respectively. ATN and ET-1 results for the PK subset (Day 28): Conclusions: ATN PK were approximately linear and time-independent. No dose adjustment for age or body weight is warranted. ATN modestly increased plasma ET-1 levels. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis
Authors: Zhongwei Cao, Raphael Lis, Michael Ginsberg, Deebly Chavez, Koji Shido, Sina Y Rabbany, Guo-Hua Fong, Thomas P Sakmar, Shahin Rafii, Bi-Sen Ding
Journal: Nature Medicine (2016)
Abstract 281: Loss of Krueppel-like Factor 15 (KLF15) Leads to Altered Wnt-dependent Gene Regulation in Hearts With Systolic Dysfunction
Authors: Claudia Noack, Lavanya M Iyer, Maria-Patapia Zafiriou, Wolfram-Hubertus Zimmermann, Laura C Zelarayán
Journal: Circulation Research (2015)

Background &amp; Aim: Developmentally conserved pathways, such as the Wnt/β-catenin pathway, are upregulated in adult heart diseases. Here, we aimed to elucidate the role of Wnt regulation via KLF15 for adult heart homeostasis. Results: We identified the transcription factor KLF15, a factor previously identified to contribute to cardiac fibrosis and hypertrophy, as a cardiac specific Wnt/β-catenin inhibitor. Accordingly, a constitutive Klf15 KO mouse model revealed specific cardiac upregulation of the Wnt target genes Tcf7l2 and cMyc (n=6, p&lt;0.001). Serial echocardiography showed reduced systolic function starting at 16 weeks in the Klf15 KO hearts (n=10, p&lt;0.05). Genome-wide sequencing studies of Klf15 KO vs. WT hearts at the postnatal age day P10, week 4 and 20 showed that gene expression differs increasingly at 4 and 20 weeks of age, respectively. This is in line with the increasing KLF15 expression after birth, reaching significant level at P13 (n=3/embryonal, fetal, and neonatal stage; each 5-8 pooled hearts). Accordingly, gene set enrichment analysis revealed activation of the Wnt signaling in Klf15 KO hearts at 4 and 20 weeks but not at P10 (p&lt;0.001). This activation was milder in 20 weeks vs. 4 weeks, which may be explained by a concomitant upregulation of Wnt repressors, as Shisa3 and Dact3 with so far unknown function in the mammalian heart (n=9, p&lt;0,01). Wnt activation was accompanied by upregulation of developmental genes and transcriptional regulators at 4 weeks and followed by upregulation of stress factors such as ANP, BNP, and Ankrd1 at 20 weeks. Moreover, we found the Wnt targets TCF7L2 and AXIN2 significantly upregulated in human ventricular biopsies from dilated (n≥5, p&lt;0.05) and ischemic cardiomyopathy (n≥5, p&lt;0.001) vs. non-failing, further underscoring the relevance of the Wnt pathway for human cardiac cellular homeostasis as well. Conclusion: A Wnt-dependent gene signature may precede the expression of stress factors and functional deterioration due to deletion of its cardiac repressor KLF15. Our data indicate that KLF15 is an important regulator of the Wnt pathway and is relevant for cardiac homeostasis and function in the postnatal heart.
Abstract 11802: Coronary Artery Calcification is the Strongest Predictor of Abnormal Duke Prognostic Coronary Artery Disease Index
Authors: Aman M Shah, Iosif Kelesidis, Naeema Hasan, Ainhoa Torrens, Valentin Fuster, Erling Falk, Pieter Muntendam, Henrik Sillesen, Lawrence Boxt, Dan Wang, Abdissa Negassa, Mario Garcia
Journal: Circulation (2014)

Background: Cardiac CT angiography (CCTA) is a useful non-invasive tool to assess coronary artery disease (CAD). The CCTA derived modified Duke prognostic CAD index (MDS) has been shown to predict coronary events in symptomatic patients. No prior study has investigated MDS in asymptomatic patients or the relationship of conventional biomarkers of CAD with MDS. Objective: We sought to determine the ability of clinical, serologic, and imaging biomarkers of CAD to predict abnormal MDS in asymptomatic patients. Methods: There were 374 asymptomatic patients in the High Risk Plaque Study who were evaluated by clinical, serologic, and imaging biomarkers of CAD that underwent CCTA. MDS was calculated from CCTA using a 16-segment convention for coronary tree (high MDS defined as ≥3). The association of MDS with clinical, serologic, and imaging biomarkers was assessed. Results: There were 58 patients identified with high MDS. These patients had lower HDL-C (44 v. 53, p&lt;0.001) and higher CACS (899 v. 26, p&lt;0.001), Framingham risk score (17.5 v. 11, p&lt;0.001), carotid intima-media thickness (0.82 v. 0.74, p=0.001), and triglycerides (150 v. 136, p = 0.011). In multivariate analysis, only CACS≥400 (OR = 15.3, 95% CI: 7.4-31.5, p&lt;0.001) and CACS overall (OR = 6.02, 95% CI: 3.58 - 10.09, p&lt;0.001) independently predicted MDS. Receiver operating characteristic curve analysis revealed improved prediction of MDS with addition of CACS: from AUC = 0.7531 to 0.8951. Conclusion: In asymptomatic patients, CACS is the strongest independent predictor of MDS when compared to conventional biomarkers of CAD.
Effect of tolfenamic acid on ovarian cancer cell growth, targeting of specificity protein transcription factors, and expression of c-Met and survivin.
Authors: R. M. Basha, S. B. Ingersoll, S. Ahmad, C. H. Baker, J. R. Edwards, R. W. Holloway, M. Abdelrahim
Journal: Journal of Clinical Oncology (2010)

e15516 Background: The aberrant expression of hepatocyte growth factor (HGF) and its receptor c-Met are associated with poor prognosis in malignancies including ovarian cancer (OC). Survivin that belongs to inhibitor of apoptosis gene family, plays important role in OC resistance to chemo/radiotherapy. Specificity protein (Sp) transcription factors regulate the expression of c-Met and survivin. Tolfenamic acid (TA), an NSAID, inhibits Sp proteins in some cancer cells/tumors. We tested the anti-cancer activity of TA for its therapeutic applications in OC. Methods: We developed three OC cancer cell-lines (SKOV3-AF1, SKOV3-AF2 and SKOV3-AF3), which express red fluorescent protein (RFP), derived from the original SKOV-3 line. The AF1 and AF2 lines are more resistant to IFNα-2b and are more tumorigenic in nude mice than the parental SKOV-3 cells. The inhibitory effects of TA on OC cells were tested using these cells. Cells were grown in the presence of DMSO (vehicle) or TA at increasing concentrations (25, 50 and 100 μM) and cell viability assay was performed using the Cell Titr Glo kit (Promega) at 24, 48 and 72 h, posttreatment. Lysates were prepared from cells exposed to DMSO or 50 μM TA for 48 h and the expression of Sp proteins (Sp1 and Sp3), c-Met and survivin was analyzed using Western blots. Results: SKOV-3-derived cells showed marked inhibition with TA treatment and this effect was dose- and time-dependent. At 100 μM, TA treatment showed significant inhibitory response (RFP = 67%, AF1 = 96%, AF2 = 88% and AF3 = 92%) at 48 h posttreatment, while the response at 50 μM TA was 30%-60% (RFP = 34%, AF1 = 58%, AF2 = 59% and AF3 = 60%). TA treatment resulted in decreased expression of Sp1 (30%-40%), Sp3 (40%-50%) and c-Met (40%-70%). This decreased expression was associated with TA-induced cell proliferation arrest, suggesting that TA targets c-Met through degradation of Sp proteins. Interestingly, TA also inhibited survivin expression (40%-60%) that could enhance tumor response to chemo/radiotherapy. Conclusions: These data show potent effect of TA on OC cells and suggest that using small molecules like TA to target key transcription factors associated with OC can be a promising treatment option. No significant financial relationships to disclose.
The SH3 Domain Contributes to BCR/ABL-Dependent Leukemogenesis In Vivo: Role in Adhesion, Invasion, and Homing
Authors: Tomasz Skorski, Malgorzata Nieborowska-Skorska, Pawel Wlodarski, Mariusz Wasik, Rossana Trotta, Palanisamy Kanakaraj, Paolo Salomoni, Mark Antonyak, Robert Martinez, Miroslaw Majewski, Albert Wong, Bice Perussia, Bruno Calabretta
Journal: Blood (1998)
Automated data base screening of a population-based cohort of stage 1 colon cancer patients for eligibility in NSABP P-3, a polyp prevention study with celecoxib at Kaiser Permanente Northern California (KPNC)
Authors: C. P. Somkin, R. Gross, H. Liu, L. Fehrenbacher
Journal: Journal of Clinical Oncology (2006)

1021 Background: Adjuvant/Prevention approaches should be designed to have broad applicability for maximum effectiveness. Celecoxib had generated interest as a polyp/colon cancer (CC) preventive agent. We used KPNC electronic data bases to identify consecutive Stage I CC patients and determine their eligibility for NSABP P-3, a polyp prevention study utilizing celecoxib in resected stage I CC. Methods: After IRB approval of both the P-3 study and use of KP data bases for recruitment, we prospectively screened all newly diagnosed CC patients within KPNC (1120 new patients a year) for stage I CC and P-3 eligibility. We identified 121 Stage I CC patients from 9/1/04 to 8/1/05 and using electronic data we screened these patients for 10-year life expectancy and other eligibility criteria. We confirmed each pathology diagnosis and stage by direct review. Results: Without chart review or patient history and exam, we found 65% of the patients were ineligible (IE) for any or multiple reasons. The average patient age was 68.9 years. 133 IE criteria were met by the 121 patients. 32% of patients were IE by age, though for only 11% was age the only criteria met. Other IE included 11% prior invasive CA, 19% coronary disease, 11% sulfa allergy, 8% coumadin usage, 7% prior CVA/TIA, 22% other GI or thrombotic criteria. It is likely that in-person history and examination would increase these IE numbers and reveal other barriers. Conclusions: Population-based automated eligibility analysis may be helpful in evaluating feasibility of chemoprevention and adjuvant trials and more importantly in determining their applicability to the whole population at risk. No significant financial relationships to disclose.
Intermediate-dose intravenous methotrexate and mercaptopurine therapy for non-T, non-B acute lymphocytic leukemia of childhood: a Pediatric Oncology Group study.
Authors: B Camitta, B Leventhal, S Lauer, J J Shuster, S Adair, J Casper, C Civin, M Graham, D Mahoney, L Munoz
Journal: Journal of Clinical Oncology (1989)

Methotrexate (MTX) and mercaptopurine (MP) are the mainstays of continuation therapy for acute lymphocytic leukemia (ALL). These drugs are stored in tissues as active metabolites. Relapse in ALL might reflect failure to achieve adequate intracellular drug levels. Assured (parenteral) delivery of higher doses of MTX and MP should maximize tissue levels of these drugs by overcoming individual variations in absorption, metabolism, clearance, and compliance. Fifty-nine children with ALL at lower risk of relapse received 12 intensive MTX/MP courses immediately after 4 weeks of standard vincristine, prednisone, and asparaginase induction. Each 2-week intensive course included: MTX, 200 mg/m2 intravenous (IV) push then 800 mg/m2 IV over 24 hours on day 1; MP, 200 mg/m2 IV push then 800 mg/m2 IV over 8 hours on day 2; MTX, 20 mg/m2 intramuscularly on day 8; and MP, 50 mg/m2 orally daily on days 8 to 14. After the 6 months of intensive therapy, continuation therapy was weekly MTX/MP (as on days 8 to 14) for 1 or 2 years. Age-based MTX was given intrathecally (IT) for CNS prophylaxis. All patients entered remission. Three patients relapsed: bone marrow (at 24 and 37 months), and bone marrow and CNS (at 34 months). There were no isolated CNS relapses or deaths in remission. Event-free survival at 4 years is 94% (SE, 7%) by Kaplan-Meier analysis. Toxicities (infection, mucositis) occurred in less than 10% of intensive MTX/MP courses. However, a child with Down's syndrome withdrew after three courses because of recurrent severe mucositis. Further studies of this regimen are in progress.
Impact of Body Mass Index, Age, Prostate Volume, and Genetic Polymorphisms on Prostate-specific Antigen Levels in a Control Population
Authors: Jean-Nicolas Cornu, Geraldine Cancel-Tassin, David G. Cox, Morgan Roupret, Nicolas Koutlidis, Pierre Bigot, Antoine Valeri, Valerie Ondet, Cécile Gaffory, Georges Fournier, Abdel-Rahmene Azzouzi, Luc Cormier, Olivier Cussenot
Journal: European Urology (2016)
Repeated anti-CEA-radioimmunotherapy (RAIT) with 131iodine-labetuzumab (phase II study) versus single dose RAIT after salvage resection of colorectal liver metastases (CRC-LM)
Authors: T. Liersch, J. Meller, C. Sahlmann, M. Ghadimi, H. Becker, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2008)

4080 Background: Within a phase-II study a single dose RAIT (40–60 mCi/m2131iodine-labetuzumab, Immunomedics, Inc., Morris Plains, NJ/USA) after salvage resection of CRC-LM has been well tolerated. Compared with a control group (OP±CTX) the RAIT-patients showed an improved overall survival (Ann Surg Oncol 2007, 14 (9): 2577–2590). The aim of the ongoing phase-II-study was to evaluate the toxicity and efficacy (DFS, OS) in pts who received a repeated RAIT with 50 mCi/m2 131iodine-labetuzumab after R0-resection of CRC-LM. Methods: 32 consecutive pts (age 61 years; 8x rectal cancer, 24x colon cancer; CRC-LM: 16x syn-, 16x metachroneous) were re-staged with CT/MRT and FDG-PET after R0-resection of extended CRC-LM prior to RAIT. On account of established risk scores (Nordlinger-, Fong- and Gayowski-Scores) 87% of the pts had an intermediate or high risk of recurrence of CRC-LM within the next 2 years (after R0- resection). During staging procedures 16 pts showed no suspect lesions (adjuvant), while 16 pts showed lesions suspicious of residual or new malignant disease (nonadjuvant). All pts were treated with 40–50mCi/m2 131iodine-labetuzumab (humanized monoclonal antibody against CEA). 24 pts were treated a second time after re-staging (CT/MRT, FDG-PET) prior to second RAIT. Results: 8/32 (25%) of the pts developed hematologic toxicity WHO-grade 4 (leukocytes or thrombocytes). After the second cycle of RAIT no cumulative toxicity could be observed. Complete bone marrow regeneration in all cases was noted. The pts’ compliance was 100% during follow-up of 21 months. The adjuvant pts had a enhanced median DFS of 18 months in comparison to the non-adjuvant patients (DFS: 6 months) and the control group (DFS: 12 months). The OS in pts with repeated RAIT is 96% until now. Conclusions: Repeated Anti-CEA-RAIT with 40- 50mCi/m2 131iodine-labetuzumab is safe and feasible. The side effects are acceptable and the pts’ compliance is high. The DFS and OS data of the adjuvant pts are very encouraging considering their bad prognosis. The efficacy of 2xRAIT will be evaluated versus a combination of RAIT + CTX within the prospectively randomized, multicentric ARC-08 trial which will be initiated in 2008. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Garden State Cancer Center, Immunomedics, Inc. Immunomedics, Inc.
Trends of MBT drug resistance
Authors: Liudmila Pankratova, Inna Volchkova
Journal: European Respiratory Journal (2013)

We conducted 2182 MBT sensitivity tests in the tuberculosis hospital, Saratov (Russia), for assessment of mycobacterium tuberculosis (MBT) drug resistance (DR).  From 2006 to 2012, MBT DR increased from 67.6% to 87.1%, primary MBT DR doubled - from 36.6% to 71.4%, secondary DR increased from 82.1 to 89.7%. By 2012, multiple drug resistance (MDR) reached 67.2%, including the increase of primary MDR from 16.8% to 40.0, and of secondary MDR from 53.8% to 71.1%.  There is a first-line drug DR increase from 2008 to 2012:  • DR to H has gone up from 44.1% to 76.8% (primary from 16.8% to 57.1%; secondary from 57.0% to 79.7%)  • DR to R increased from 44.4% to 70.9% (primary from 16.8% to 40.0%; secondary from 57.3% to 75.4%)  • DR to E increased from 24.2% to 57.9% (primary from 5.6% to 37.1%; secondary from 32.5% to 61.6%)  • DR to S increased from 69.2% to 80.1% (primary reached 65.7%, secondary 82.3%, DR among the chronically ill was 93.4%)  In 2012, second-line drug DR was 67.5%, primary DR - 40.0%, secondary DR - 72.4%. From 2008 to 2012  • DR to PAS increased from 15.2% to 37.3% (primary 8.6%, secondary 42.2%)  • DR to Ofl increased from 18.7% to 29.2% (among new patients - 14.3%, secondary is 31.9%)  • DR to Capr remained stable - 23.3% (primary increased from 5.9% to 20.0%, secondary did not change - 24.1%)  • DR to K has doubled from 26.3% to 50.2% (primary 22.9%, secondary 54.7%)  CONCLUSIONS  The DR reduction trend that emerged in 2011 has been replaced with further DR growth, mainly to the first-line drugs where it has reached alarming proportions. It is vitally important to introduce rapid sensitivity testing methods, as standard chemotherapy regimens (I, II, III) require the use of first-line drugs.
Structural insights into ubiquitin-like protein transfer cascades
Authors: Brenda A. Schulman, Danny Huang, Helen Walden, Dave Duda, Min Zhuang
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

SY16-4 

There are over a dozen ubiquitin-like proteins in higher eukaryotes that function by covalently modifying myriad substrates. The best understood functional consequence of ubiqutin-like protein conjugation is ubiquitin-mediated proteolysis. however, different ubiquitin-like proteins alter the functions of their targets in different ways, for example by changin the target’s subcellular localization, enzymatic activity or protein-protein interactions. Ubiquitin’s closest relative, NEDD8, does not direct its targets to the proteasome. Rather, NEDD8 is conjugated to the cullin subunits of SCF and related ubiquitin ligases to alter their activity. We have uncovered a role for an enzyme in the NEDD8 pathway in cell proliferation. The structural and mechanistic basis for specificity of NEDD8 and ubiquitin activation and conjugation will be discussed.
Filamentous Particles in Human Alveolar Cell Carcinomas: Electron Miscroscopy Studies of Six Cases (Preliminary Report)
Authors: James C. Stinson, Albert Leibovitz, G. V. Brindley, Ronald H. Hayward, Robert A. Turner, William B. McCombs
Journal: JNCI Journal of the National Cancer Institute (1972)

Over a 10-month period we observed 6 cases of human alveolar cell carcinoma, a relatively uncommon human tumor. Electron microscopy study of freshly excised tumor tissue revealed intracytoplasmic vacuoles with dense osmophilic inclusions containing filaments in 4 cases. The filamentous structures were about 90 nm in diameter, with a central core about 15 nm in diameter. Spherical bodies about 90–130 nm in diameter in the vacuolar space had a double membrane, and electrondense particles randomly dispersed in their matrices.
구연 : 바이러스 돌파현상 전후 다약제 내성 B형간염바이러스 검출을 위한 DNA Chip의 임상적 유용성 평가
Authors: 허정, 정홍렬, 윤기태, 조몽, 김광하, 강대환, 송근암, 김철민, 김현주, 한지성
Journal: Clinical and Molecular Hepatology (2009)