tbuckley/cabot-search huggingface dataset:
Immunoproteomics strategy for automation of chemoresistance and chemosensitivity array
Authors: Y. Adler, M. J. Adler, L. Weisenthal, J. Reed, M. Krajewska, A. Olson, S. Krajewski
Journal: Journal of Clinical Oncology (2006)

20076 Background: Chemotherapy sensitivity and resistance assays (CSRAs) often guide therapeutic regimen selection based on patient cancer cells response to chemotherapeutics in culture. Current CSRAs rely on highly time- and skill- dependent biochemical and microscopic endpoint assays of apoptosis. Instead, the assay under development uses immunoproteomic array readout of biomarkers. Such automation may broaden the use of CSRAs for guiding clinical use of increasingly costly chemotherapeutic options. Methods: Specimens from 30 ovarian cancer patients were cultured with and without cisplatinum according to established CSRA procedures (http://weisenthal.org/w_ovarian_cp.pdf). Cells pelleted and fixed at experimental points (0 and 96 hrs cisplatin, and 96 hrs non-treated) were paraffin embedded for construction of immunoproteomic microarrays. A panel of 57 NIH cancer cell lines was similarly arrayed. Protein profiling is performed with monospecific antibodies for 35 select markers of cell cycle, apoptosis, cell signalling, and transcription. Immunostaining results, including rate of cell death and marker expression level are quantitated manually (immunoscore assigned for cell core) and automatically (algorithm by Aperio, Inc). Results: Evaluation of readouts differentiates responders from non-responders aiming to predict clinical chemotherapy outcome. For a subset of imunoproteomic markers, observed expression corresponds to either induced apoptosis or to cisplatin resistance. Selected markers were subjected to cytologic analysis and time line westerns; results corroborate protein profiling data. Correspondence to the results of the classic CSRAs and individual patient therapeutic response will be unblinded. Conclusions: Use of immunoproteomic arrays to replicate classic CSRAs by establishing concordant results may allow automated guidance for chemotherapeutic choices. [Table: see text]
Experimental Transmission of Reticuloendotheliosis in Turkeys With the Cell-Culture-Propagated Reticuloendotheliosis Viruses of Turkey Origin 2
Authors: Prem S. Paul, Kenneth H. Johnson, Kem A. Pomeroy, Benjamin S. Pomeroy, Padman S. Sarma
Journal: JNCI Journal of the National Cancer Institute (1977)

Reticuloendotheliosis virus (REV) strains MN67 and MN81, previously isolated from naturally occurring reticuloendotheliosis (RE) of turkeys, were propagated in turkey embryo fibroblast cultures. Cell-culture-propagated REV were inoculated in 1-day-old turkey poults that were subsequently raised in isolation conditions for 18 weeks. Turkey poults were also exposed by contact with RE-inoculated turkeys to study possible horizontal transmission. Both REV strains MN67 and MN81 were pathogenic for turkey poults and were horizontally transmitted in turkeys. The incubation period of the disease was 8–11 weeks. REV produced 10–33% mortality in turkeys, and macroscopic RE lesions were observed in the livers, spleens, intestines, pancreas, and kidneys. Peripheral nerve enlargement was also seen occasionally. Microscopically, the lesions observed were composed of neoplastic lymphoreticular cells. In addition, neoplastic lymphoreticular cell infiltrates were present in the hearts, gonads, muscles, and brains. REV was isolated from the tissues of turkeys experimentally inoculated with REV, and antibodies to REV were detected in these turkeys. Uninoculated controls showed neither RE lesions nor REV infection. Turkeys of all groups were free of Marek's disease virus infection.
Efficacy endpoints of RTOG 0247: A randomized phase II study of neoadjuvant capecitabine (C) and irinotecan (I) or C and oxaliplatin (O) with concurrent radiation therapy (RT) for locally advanced rectal cancer.
Authors: S. J. Wong, J. Moughan, N. J. Meropol, P. R. Anne, L. A. Kachnic, A. Rashid, J. C. Watson, E. P. Mitchell, J. Pollock, M. G. Haddock, B. Erickson, C. G. Willett
Journal: Journal of Clinical Oncology (2011)

3517 Background: The primary endpoint analysis of RTOG 0247 showed that preoperative pelvic RT plus C + O achieved a pathologic complete response rate (pCR) pre-specified threshold (21%) to merit further study, whereas the RT+ C + I arm did not (10%) (ASCO 2008). This current analysis reports on the secondary efficacy endpoints. Methods: A randomized phase II trial evaluated preoperative RT (50.4 Gy in 1.8 Gy fractions) with (1) concurrent C (1,200 mg/m2/d orally M-F during RT) and I (50 mg/m2 IV weekly x 4 doses) (Arm 1), and with (2) concurrent C (1,650 mg/m2/d orally M-F during RT) and O (50 mg/m2 IV weekly x 5 doses) (Arm 2) in patients with clinical stage T3 or T4 rectal cancer ² 12 cm from the anal verge. Surgery was performed 4-8 weeks following completion of chemoradiation. Four to 6 weeks after surgery, adjuvant chemotherapy (O 85 mg/m2; leucovorin 400 mg/m2 IV over 2 hours; 5FU 400 mg/m2 IV bolus; 5FU 2400 mg/m2/46 hr infusion) was administered every 2 weeks x 9 cycles. Disease-free (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Distant failure (DF), and second primary failure (SPF) were estimated by the cumulative incidence method. Results: 104 patients (median age 57, min-max: 27-78); 32% female were treated. Patient characteristics were similar for both arms. Median follow-up for the RT+C+I arm was 3.77 (min-max: 0.19-5.23) and for the RT+C+O arm was 3.97 years (min-max: 0.44-5.15). The 4-year DFS, OS, DF, and SPF estimates for each arm are shown in the table. Conclusions: In addition to achieving the primary endpoint goal of high pCR, RT+C+O exhibited favorable activity as demonstrated by secondary efficacy endpoints. Although RT+C+I failed to achieve the pre-specified pCR goal, this regimen demonstrated a consistent trend of favorable activity by secondary efficacy endpoints. Treatment arm DFS OS DF SPF No. pts TF 4y% TD 4y% TF 4y% TF 4y% RT+C+ I 52 16 66 7 85 12 24 1 2 RT+C+ O 52 25 56 13 75 17 30 4 6 Abbreviations: No. pts, number of patients; TF, total failures; TD, total deaths; 4y, 4-year.
Poly(Limonene Thioether) Scaffold for Tissue Engineering
Authors: Kristin M. Fischer, Kathy Ye Morgan, Keith Hearon, Demetra Sklaviadis, Zachary L. Tochka, Owen S. Fenton, Daniel G. Anderson, Robert Langer, Lisa E. Freed
Journal: Advanced Healthcare Materials (2016)

A photocurable thiol‐ene network polymer, poly(limonene thioether) (PLT32o), is synthesized, characterized, fabricated into tissue engineering scaffolds, and demonstrated in vitro and in vivo. Micromolded PLT32o grids exhibit compliant, elastomeric mechanical behavior similar to grids made of poly(glycerol sebacate) (PGS), an established biomaterial. Multilayered PL32o scaffolds with regular, geometrically defined pore architectures support heart cell seeding and culture in a manner similar to multilayered PGS scaffolds. Subcutaneous implantation of multilayered PLT32o scaffolds with cultured heart cells provides long‐term 3D structural support and retains the exogenous cells, whereas PGS scaffolds lose both their structural integrity and the exogenous cells over 31 d in vivo. PLT32o membrane implants retain their dry mass, whereas PGS implants lose 70 percent of their dry mass by day 31. Macrophages are initially recruited to PLT32o and PGS membrane implants but are no longer present by day 31. Facile synthesis and processing in combination with the capability to support heart cells in vitro and in vivo suggest that PLT32o can offer advantages for tissue engineering applications where prolonged in vivo maintenance of 3D structural integrity and elastomeric mechanical behavior are required.
Patients and doctors play it safe
Authors: M. E Scott, W. F M Wallace
Journal: BMJ (1996)

EDITOR,—C M Sudlow and colleagues draw attention to the need for the planned provision of facilities to monitor the increasing number of patients to be treated,1 in line with current recommendations.2 We wish to make several suggestions in the light of a recent audit of a cardiac anticoagulation clinic that we undertook recently.

A random sample of 151 patients (83 female) was given a questionnaire, and the current international normalised ratio was noted in addition. The mean (SD) age was 63.7 (10.7) years …
Phagocytic Function of Macrophages Is Impaired By Chronic Lymphocytic Leukemia and high–grade Lymphoma Progression and Can be Highly Effectively Restored for Chemo-Immunotherapy
Authors: Janine Schwamb, Nina Reinart, Daniela Vorholt, Thomas Ulas, Vangica Ristovska, Christian J Braun, Michael T Hemann, Joachim Schultze, Michael Hallek, Christian P. Pallasch
Journal: Blood (2014)
Computed virtual chromoendoscopy versus standard colonoscopy with targeted indigocarmine chromoscopy: a randomised multicentre trial
Authors: J Pohl, E Lotterer, C Balzer, M Sackmann, K-D Schmidt, L Gossner, C Schaab, T Frieling, M Medve, G Mayer, M Nguyen-Tat, C Ell
Journal: Gut (2008)

Colonoscopy is the accepted gold standard for screening of neoplastic colorectal lesions, but the substantial miss rate remains a challenge. Computed virtual chromoendoscopy with the Fujinon intelligent colour enhancement (FICE) system is a new dyeless imaging technique that might allow higher rates of adenoma detection.This is a prospective randomised five tertiary care centre trial of colonoscopy in the FICE mode versus standard colonoscopy with targeted indigocarmine chromoscopy (control group) in consecutive patients attending for routine colonoscopy. Histopathology of detected lesions was confirmed by evaluation of endoscopic resection or biopsy specimens.871 patients were enrolled, and 764 patients (344 female, mean age 64 years) were subjected to final analysis (368 in the FICE group, 396 in the control group). In total, 236 adenomas (mean of 0.64 per case) were detected in the FICE group and 271 adenomas (mean of 0.68 per case) in the control group (p = 0.92). There was no statistically significant difference in the percentage of patients with >or=1 adenoma between the control group (35.4%) and the FICE group (35.6%) (p = 1.0). For the differential diagnosis of adenomas and non-neoplastic polyps, the sensitivity of FICE (92.7%) was comparable with that of indigocarmine (90.4%) (p = 0.44).At colonoscopy, adenoma detection rates are not improved by virtual chromoendoscopy with the FICE system compared with white light endoscopy with targeted indigocarmine spraying. However, FICE can effectively substitute for chromoscopy concerning the differentiation of neoplastic and non-neoplastic lesions.
Phase I study of ZEN-008 (AN-152), a targeted cytotoxic LHRH analog, in female patients with cancers expressing LHRH receptors
Authors: G. Emons, M. Kaufmann, A. R. Günthert, M. Hamid-Werner, C. Gründker, S. Loibl, A. V. Schally
Journal: Journal of Clinical Oncology (2006)

13146 Background: Human ovarian, endometrial, and breast cancers commonly express receptors for luteinizing hormone releasing hormone (LHRH-R). LHRH-R can be used for targeted chemotherapy with ZEN-008 (AN-152), in which doxorubicin is linked to [D-Lys(6)]-LHRH. Safety pharmacology and toxicity studies in mice, rats and dogs demonstrated a significantly reduced cardiotoxic potential of ZEN-008 compared with doxorubicin, e.g. no QT prolongation, myocarditis or fibrosis in the appropriate models. The Phase I study assessed dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetics (PK) of ZEN-008 given once every 3 weeks in patients with gynecological and breast cancers. Methods: Patients with tumors proven immunohistochemically to be LHRH-R positive were eligible if prior therapy did not exceed 70% of the recommended maximum lifetime dose for doxorubicin. Starting at 10 mg/m 2 , doses were doubled between patients until occurrence of side effects of CTCAE grade 2 or higher, thereafter escalation would follow a modified Fibonacci scheme, with 3–6 patients/group. Safety monitoring included repeat assessment of pituitary and cardiac function. Response evaluation followed the RECIST criteria. HPLC with fluorescence detection was used for plasma PK of ZEN-008 and free doxorubicin. Results: Five patients entered the study and received ZEN-008 by intravenous infusion over 2 hours at dosages of 10, 20, 40, 80 and 160 mg/m 2 . Patients 1 to 4 received 2 treatment courses 21 days apart and went off study with progressive disease. Infusion of ZEN-008 was well tolerated at all dosages, without supportive treatment. PK analyses showed dose-dependent plasma levels of ZEN-008 and only minor (10–20%) release of doxorubicin. Conclusions: Infusion of ZEN-008 is well tolerated in female patients. No dose-limiting toxicities were seen up to 160 mg/m 2 which is equimolar to a doxorubicin dose of 46 mg/m 2 . Dose escalation is ongoing. The cytotoxic LHRH analog is stable in human plasma, a prerequisite for receptor-mediated uptake by tumor tissue. [Table: see text]
Abstract 10279: Black Race is Associated With an Increased Risk of Sudden Cardiac Death in Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lin Y Chen, Faye L Lopez, Ronald Prineas, Elsayed Z Soliman, Aaron R Folsom, Alvaro Alonso
Journal: Circulation (2013)

Background: We have recently reported that incident atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. We now aim to identify pre...
Developing palliative care capacity in Colombia and Mexico.
Authors: Felicia Marie Knaul, Virginia Townsend LeBaron, Mariana Calderon, Hector Arreola-Ornelas, Afsan Bhadelia, Eric Lewis Krakauer, Marta Ximena Leon, Diederik Lohman, Karla Petersen O'Farrill, Liliana De Lima
Journal: Journal of Clinical Oncology (2014)

103 Background: Access to pain relief and palliative care often is limited or absent in low-and-middle-income countries (LMICs). Consequently, millions of patients with cancer and other serious illnesses in LMICs suffer needlessly. Multiple stakeholders have joined efforts to enhance the delivery of palliative care, develop national plans, and advocate for improved policies and regulations in Colombia and Mexico with applications to other LMICs. Methods: In Mexico and Colombia, efforts to improve access to palliative care focus on regulatory frameworks, finance, delivery, research and capacity-building, as per World Health Organization recommendations. In Colombia, health and educational institutions have partnered with non-governmental organizations to advise the Ministry of Health (MOH) and Senate. In Mexico, a range of governmental, legislative and private institutions are developing a National Palliative Care Plan. Results: Colombia: Laws passed in 2010 and 2013 require palliative care be available for all cancer patients. The allowable length of opioid prescriptions has been extended from 10 to 30 days, strong opioids must be freely available, and the MOH requires at least 1 pharmacy per State be able to dispense opioids 24/7. Mexico: Amendments to the health law introduced palliative care and pain management as a right for people with terminal illness. The government plans a new digital system to make opioid prescribing more efficient and secure, and the pharmaceutical industry is developing systems for monitoring production and supply. Yet, in both countries, palliative care training is mandatory in less than 5% of medical schools and innovative materials are being developed to train practicing primary care personnel. Conclusions: To meet palliative care needs in LMICs, novel approaches are required to develop and implement national plans, train healthcare providers, educate government officials, and advocate for policies that improve equitable access. Exemplary work in Colombia and Mexico illustrate effective strategies to improve palliative care delivery in LMICs.
Health-related quality of life (HQOL) and early survival outcome of the randomized adjuvant dose-dense (dd) FEC<sub>75</sub> versus FEC<sub>90</sub> CECOG study.
Authors: Z. Kahan, S. Spanik, M. Wagnerova, J. Jassem, T. Skacel, K. Elandt, E. Fitzthum, E. Lindner, C. Zielinski, T. Brodowicz
Journal: Journal of Clinical Oncology (2010)

e11058 Background: Adjuvant ddFEC75 and ddFEC90 chemotherapy regimens have been found feasible in operable breast cancer patients (Kahán et al, Breast Cancer Res Treat. 2008;112:557-563). A protocol-specified HQOL data obtained during chemotherapy, and the disease-free survival (DFS) 3 years after the randomisation of 51 patients were analyzed. Methods: The FACT-B HQOL questionnaires completed by the patients 2 weeks after each chemotherapy cycle were evaluated separately both in the whole study population and in the two treatment arms. DFS according to the treatment arm was analyzed by the Kaplan-Meier method and the Cox proportional hazards model. Results: A significant fall became apparent in the FACT-B outcome index after the third cycle of chemotherapy in the entire population, as a consequence of significant reduction of the Physical and Emotional Well-Being scores and the breast cancer subscales. No changes were detected in the scores of the Social/Family and the Functional Well-Being subscales. There was no significant difference in HQOL among the two treatment arms. After a median follow-up time of 3 years, 5 of the patients in the FEC75 arm (20%), and 1 in the FEC90 arm (3.8%) relapsed, all at distant sites. Two patients of those who relapsed in the FEC75 died. The median DFS times were not reached by the time of analysis. In the FEC90 arm, the risk of relapse was reduced (HR = 0.124, 95% CI: 0.014- 1.124). Conclusions: The HQOL outcome of our study further supports the feasibility of ddFEC chemotherapy, and does not suggest the superiority of FEC75 in any of the domains of HQOL. Our results warrant larger studies to investigate survival benefits of dose-dense FEC chemotherapy at the applied doses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen Amgen
Abstract P087: Association of Psychological Well-Being With Cardiac Repolarization
Authors: Amit J Shah, Robert Carney, Elsayed Z Soliman, Viola Vaccarino
Journal: Circulation (2012)

Background: Abnormal frontal T-axis is an independent predictor of mortality, and may be influenced by increased sympathetic tone and cardiovascular disease risk factors. Factors related to poor psychological health, such as depression, are associated with increased risk of CVD morbidity, although the mechanisms are not clear. We tested the hypothesis that: 1) reduced psychological wellness is associated with abnormal T-axis and 2) this association may help to explain the excess risk of CVD morbidity and mortality related to poor psychological health. Methods: We studied 4485 community-based adults aged 25–65 years without a history of CVD from NHANES I (1971–75) who were monitored for CVD hospitalization and death until 1993. Those with ECG evidence of previous MI, left ventricular hypertrophy, and major ventricular conduction defects (QRS interval ≥ 120 ms) were excluded. Frontal T-axis was obtained through 12-lead ECG, and a deviation of ≥ 30° from normal (45°) was considered abnormal. Psychological well-being was measured with the General Well-Being Scale (GWB). Results: The mean ± SD age was 43.1 ± 11.5 years and 55% were women. The mean ± SD GWB score was 80.5 ± 17.3, the median frontal T-axis was 51°, and 13% had an abnormal T-axis. In cross-sectional analysis adjusting for age, sex, and race, a 1-SD decrease in GWB was associated with an OR of 1.12 for abnormal T-axis (p=0.01). This effect was unchanged after adjusting for systolic blood pressure, smoking, diabetes, total cholesterol, and BMI. Abnormal T-axis was associated with CVD hospitalization/death (adjusted HR 1.29, p=0.01), as was GWB (adjusted HR 1.104 per 1-SD decrease, p=0.01). When both factors were included in the model, the HR of GWB decreased by 8% to 1.096 (p=0.02). Conclusion: Abnormal frontal T-axis is modestly but significantly associated with reduced psychological wellness. Although this association may help understand neurocardiac relationships, it does not substantially explain morbidity and mortality associated with reduced psychological wellness.
Scant evidence on the effectiveness of metformin in type 2 diabetes
Authors: T. L. Perry
Journal: BMJ (2015)

Metformin is remarkably safe compared with alternative drugs for type 2 diabetes, although it does cause at least chemical vitamin B12 deficiency.1 2 The “problem” of reduced glomerular filtration can be seen as an advantage for drugs like metformin that are eliminated through the kidney. Reduced …
Combined treatment of patients with incompletely resected invasive thymoma: A retrospective analysis
Authors: D. M. Kowalski, A. Janowicz-Zebrowska, M. J. Krzakowski, P. Jaskiewicz, K. Zajda, T. Denisso, W. Lasota
Journal: Journal of Clinical Oncology (2007)

18193 Background: Although surgery remains the mainstay of therapy for invasive thymoma, complete resection is feasible in only 60% of patients (pts) and adjunctive radiotherapy (RT) or/and chemotherapy (CT) is advocated. Multidisciplinary approach with chemotherapy (CT) and radiotherapy (RT) is an option for unresectable disease. The aim of our study was to evaluate retrospectively the outcome of pts with invasive thymoma submitted to postoperative RT or combined CT and RT. Methods: Pts in our analysis underwent either radical resection followed by RT or they had incomplete resection with subsequent CT and RT. Results: Between March 1996 and September 2005, 32 (18 women; 56.3% and 14 men; 43.7%) pts with invasive thymoma were treated. Median age was 47,8 years (range, 20–75). Clinical stage I, II, III or IVA was diagnosed respectively in 3 (9.4%), 12 (37.5%), 6 (18.7%) and 11 34.4%) pts. Pathologic types of invasive thymoma were as follows: A - 4 pts (12.5%), B - 9 pts (28.1%), AB - 8 pts (25%); pathological type was not specified in 1 pts (3.1%). Type C thymoma was diagnosed in 10 pts (31.3%). Complete resection was performed in 26 pts (81.3%), whereas 1 pt (3.1%) was irradiated only and 5 pts (15.6%) were treated with CT as single modality. Cisplatin-based CT was used in all pts. Twenty pts (62.5%) were irradiated, while RT was not used in 12 pts (37.5%). Median survival time (MST) for all pts was 54.5 months (range: 2–240 months), and median time to progression (MTTP) was 27.5 months (range: 1–221 months). MST for pts on CT was 46.3 months (range: 2–156) in comparison with 54.7 months (range: 2–240) in non-CT group. MTTP for CT group was 35.2 months (range: 2–144) and 51.0 months (range: 2–221) for no CT group. Tolerance of CT was acceptable. Conclusions: Postoperative RT is effective in reducing local recurrence rate and prolonging survival in pts with invasive thymoma. The role of postoperative CT is unclear and deserves further exploration. No significant financial relationships to disclose.
Involve clinicians to avert a digital disaster
Authors: Nigel Edwards
Journal: BMJ (2016)

And other lessons for creating a paperless health system



The UK government’s recent spending review announced £1bn for health technology. “Better connected services for patients,” it promised, and the information that doctors needed “at their fingertips.”

Nobody can argue with the aspiration—but nobody can forget the less than encouraging history of spending on information technology in the NHS.

The lessons of the National Programme for IT, which cost more than £10bn a decade ago, seem to have been learnt. One size does not fit all: the government has now sworn off top-down rollouts, in favour of trying to support and guide initiatives with more local input. But there exist many other potential paths to disaster, as we at the Nuffield Trust found while carrying out research worldwide for our new report.1 …