tbuckley/cabot-search huggingface dataset:
Abstract 241: In Vivo Response to Dynamic Hyaluronic Acid Hydrogels
Authors: Jennifer L Young, Jeremy Tuler, Rebecca Braden, Pamela Schup-Magoffin, Jacquelyn Schaefer, Kyle Kretchmer, Karen L Christman, Adam J Engler
Journal: Circulation Research (2013)

Tissue-specific elasticity arises in part from developmental changes in extracellular matrix over time, e.g. ~ 10-fold myocardial stiffening in the chicken embryo. When this time-dependent stiffening is mimicked in vitro with a thiolated hyaluronic acid (HA-SH)/poly(ethylene glycol) diacrylate (PEGDA) hydrogel, improved cardiomyocyte maturation has been observed. However, host interactions, matrix polymerization, and stiffening kinetics remain uncertain in vivo, and each plays a critical role in therapeutic applications using HA-SH. In order to assess in vivo feasibility and biocompatibility of HA-SH/PEGDA hydrogels, subcutaneous injections were first performed. Hematological and histological analysis of subcutaneously injected HA-SH/PEGDA hydrogels showed minimal systemic immune response and host cell infiltration. Most importantly, subcutaneously injected HA-SH/PEGDA hydrogels exhibited time dependent porosity and stiffness changes at a rate similar to hydrogels polymerized in vitro, as measured by atomic force microscopy. When injected intramyocardially, host cells begin to actively degrade HA-SH/PEGDA hydrogels within 1-week post-injection, continuing this process while producing matrix to nearly replace the hydrogel within 1 month post-injection. While non-thiolated HA did not degrade after injection into the myocardium, it also did not elicit an immune response, unlike HA-SH/PEGDA, HA-SH/low concentration PEGDA, or high concentration HA-SH only hydrogels, where visible granulomas and macrophage infiltration were present at 1 month post-injection, as indicated by CD45 (lymphocyte marker) and CD68 (macrophage marker) staining, likely due to reactive thiol groups. Altogether, these data suggest that the HA-SH/PEGDA hydrogel responds appropriately in a less vascularized niche and stiffens as had been demonstrated in vitro, but in more vascularized tissues, in vivo applicability appears limited.
Papovavirus SV40 Transplantation Immunity Conferred by an Adenovirus-SV40 Hybrid2
Authors: Fred Rapp, Satvir S. Tevethia, Joseph L. Melnick
Journal: JNCI Journal of the National Cancer Institute (1966)

Further studies were made of a type 7 adenovirus-SV40 “hybrid” which carries the tumor determinant of papovavirus SV 40 in an adenovirus capsid. Vaccination of weanling hamsters with the hybrid conferred marked protection against cells transformed by papovavirus SV 40. The protection was similar to that afforded by SV40 itself. The number of cells required to induce tumors in 50 percent of the challenged animals rose from less than 100 in the controls to greater than 40,000 cells in animals previously vaccinated with either the adenovirus-SV 40 hybrid or with SV 40. Nonhybridized adenovirus type 7 failed to protect the hamsters. A few tumors occurred in the vaccinated animals, but the appearance of breakthrough tumors in hamsters inoculated with the hybrid virus closely paralleled that observed in hamsters inoculated with SV 40. The results indicate that incorporated in the adenovirus-SV 40 hybrid are the SV 40 determinants responsible for inducing the intranuclear tumor antigen but also for conferring transplantation resistance.
Human growth hormone and insulin-like growth factor-1 enhance the proliferation of human leukemic blasts.
Authors: Z Estrov, R Meir, Y Barak, R Zaizov, Z Zadik
Journal: Journal of Clinical Oncology (1991)

As the number of long-term survivors of childhood leukemia increases, growth retardation has emerged as a significant complication. Treatment of these children with growth hormone (GH) has been suggested and sporadically implemented. We, therefore, studied the effect of human GH (hGH) and its by-product insulin-like growth factor-1 (IGF-1) on the growth of leukemic cells in vitro. Under serum-free conditions hGH and IGF-1 induced a significant dose-dependent proliferative effect on promyelocytic leukemia (HL60) and Burkitt's lymphoma (Daudi) cell lines. Anti-hGH antibodies negated the stimulatory effect of hGH and anti-IGF-1 serum abrogated the growth-promoting effect enhanced by IGF-1. Similar statistically significant stimulatory properties were found when freshly obtained marrow cells from four of five acute lymphoblastic leukemia (ALL) of childhood and four acute myelogenous leukemia (AML) patients were studied in ALL and AML blast-cell clonogenic assays. ALL colonies increased numerically by 72% (P less than .025) and AML colonies by 92% (P less than .01) in the presence of hGH at concentrations of 2.5 x 10(2) and 3.0 x 10(2) ng/mL, respectively. IGF-1 stimulated ALL and AML blast-colony growth at concentrations ranging from 0.05 to 0.5 ng/mL by up to 105% (P less than .025) and 65% (P less than .03), respectively. Our in vitro data suggest that circulating hGH and IGF-1 may promote leukemic blast cell replication in vivo, and the supplemental administration of hGH to leukemia patients in remission must be carefully monitored for early relapse.
Phase I-II clinical and pharmacokinetic study of plitidepsin in children with malignant tumors. On behalf of the European ITCC (Innovative Therapies for Children with Cancer) Consortium
Authors: B. Geoerger, F. Doz, S. Lowis, P. Kearns, E. Estlin, B. Gibson, N. Corradini, P. Lardelli, G. Vassal
Journal: Journal of Clinical Oncology (2008)

10028 Background: Plitidepsin (Aplidin) is a cyclic depsipeptide isolated from the tunicate Aplidium albicans, nowadays manufactured by synthesis. It is a rapid and potent inductor of apoptosis. Phase I trials in adults with solid and hematological malignancies explored 5 different treatment schedules. Muscle and liver toxicities were dose-limiting toxicities (DLTs); hematological DLT was not observed at the recommended dose (RD). Methods: This is a multicentre, open-label, non-randomized phase I-II two-step study in children with solid tumors with a dose finding stage followed by an expanded cohort at the RD. Plitidepsin was administered as a 3-h iv infusion every 2 weeks (1 injection=1cycle). The initial dose level was 4 mg/m2 (80% of the RD in adults), with a classical dose-escalation methodology to 5 and 6 mg/m2. Results: 37 patients (pts) have been enrolled to date. Median age was 9 years (range 2–17). 114 cycles in 33 pts were evaluable for toxicity. During the dose finding stage 8 pts were treated at 4 mg/m2 (1 DLT, G2 myalgia lasting more than 2 weeks), 3 pts at 5 mg/m2 (no DLT) and 7 pts at 6 mg/m2 (2 DLTs, G4 CPK increase and G3 increase of ALT lasting more than 2 weeks). 6 mg/m2 was considered the maximum tolerated dose (MTD). 15 pts were further treated at the expanded cohort at 5 mg/m2. 2 pts had G3 vomiting, 1 pt G3 myalgia and dysesthesia, 1 pt G3 ALT increase for more than 2 weeks, and 2 pts G3 and G4 increases of CPK, respectively. Biochemical DLTs were asymptomatic. Non-hematological toxicities included G1-G2 muscle disorders (myalgia, CPK elevation, muscle weakness) and G1–2 fatigue. 3 G3 hypersensitivity reactions were observed, 1 without adequate prophylactic treatment. Pharmacokinetic data were similar to those reported in adults (extensive tissue distribution, long half-life), however children of the age group 2–11 years appeared to have lower clearance. Clinical activity was observed in pts with neuroblastoma (1PR, 1SD), glioblastoma, pancreatoblastoma, medulloblastoma and hepatoblastoma (1 SD each). Conclusions: Plitidepsin was well tolerated in children, with muscular disorders being the most relevant toxicity observed. 6 mg/m2 was defined as MTD. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration PharmaMar PharmaMar PharmaMar
25 LONG TERM – 8 YEAR FOLLOW UP OF A RANDOMIZED TRIAL OF TACROLIMUS MONOTHERAPY VERSUS TRIPLE THERAPY AFTER LIVER TRANSPLANTATION FOR HCV CIRRHOSIS
Authors: P. Manousou, D. Samonakis, E. Tsochatzis, E. Cholongitas, J. Davidson, D. Patch, K. Rolles, A. Hall, P. Hayes, A. McCormick, A.P. Dhillon, A.K. Burroughs
Journal: Journal of Hepatology (2013)
A phase II study of an adapted CT with oxaliplatin (Oxa) and bolus 5FU in I-line treatment of metastatic CRC in elderly patients not eligible to FOLFOX
Authors: C. Falci, L. M. Pasetto, U. Basso, S. Monfardini
Journal: Journal of Clinical Oncology (2008)

15124 Background: FOLFOX and FOLFIRI have been established to be an effective I-line CT for mCRC. Not all over 70-yrs old pts can receive infusional 5-FU because of cardiac comorbidity, refuse of infusional CT or vulnerability state at the comprehensive geriatric assessment (CGA). Till now no alternative schedules containing Oxa have been assessed in elderly pts. The aim of the present study was to evaluate the feasibility and activity of biweekly Oxa plus bolus 5FU and low dose LV as I-line CT. Methods: pts ≥70 yrs with measurable, chemonaive mCRC, ECOG PS ≤2, not eligible to infusional 5FU, fit or vulnerable at CGA (Balducci et al) received Oxa 85 mg/m2 on d 1 and 15, LV 20 mg/m2 plus bolus 5FU 500 mg/m2 on d 1, 8 and 15 every 28d. Study design was 1 stage, estimated sample size 34. Toxicity was the primary endpoint. Response was evaluated by CT-scan every 2 cy. Results: 35 pts, median age 74 (range 70–84) entered the study. Ten pts (28.6%) had cardiological comorbidities. Median number of comorbidities was 1.3 among 20 vulnerable pts, 0 among 15 fit pts. Toxicity according to CTC v 3.0 (see table), was not related to age or CGA. 46.7% of fit pts and 70% of vulnerable pts received < 6 cycles of CT because of toxicity (7 pts), PD (6 pts) or refuse (8 pts). Out of 28 valuable pts 10 PR were observed for an RR of 35.7% (95% CI 17.9–53.4%). Eleven pts had SD (39.3%) while 7 progressed during treatment (25%). After a median follow up of 29.3 mo 32 pts progressed or died, with a median PFS of 9.4 mo. Totally 24 out of 35 pts died, for a median OS of 16.3 mo. A clinical difference in terms of OS among 15 pts receiving II line CT and the other 20 receiving only best supportive care (13.9 vs 11.4, p=0.19 n.s.) was reported. Conclusions: Biweekly Oxa with bolus 5-FU is a safe and effective alternative in elderly pts not susceptible to FOLFOX because of refuse by pts or vulnerability at CGA. Toxicity Toxicities Grade 2 Grade 3 Grade 4 Number % Number % Number % Anemia 4 11.4 1 2.8 0 0 Neutropenia 3 8.6 3 8.6 1 2.8 Trombocytopenia 3 8.6 0 0 0 0 Diarrhea 2 5.7 5 14.3 1 2.8 Mucositis 2 5.7 0 0 1 2.8 Vomiting 2 5.7 1 2.8 0 0 Neurotoxicity 6 17.1 3 8.6 1 2.8 Fatigue 3 8.6 1 2.8 0 0 No significant financial relationships to disclose.
Clinical experience of itopride in the treatment of postoperative ileus after surgery for GI malignancy
Authors: A. Maseeh
Journal: Journal of Clinical Oncology (2005)

4249 Background: Postoperative ileus follows any operation. We attempted to document effects of new prokinetic drug Itopride hydrochloride is benificial in decreasing the period of postoperative ileus and/or associate symptoms like nausea and vomiting. Methods: Fifteen consecutive patients of either sex, median age of 37 yrs, were treated with 50 mg Itopride once daily -group 1 and twelve patients with placebo group 2. The time (in hours) to first passage of flatus, first liquid meal, first bowel movement, and total length of hospital stay was also recorded. Results: Nausea was found significantly more frequently in placebo group at the day of surgery & on postoperative days 1 and 2 when compared with that of itopride group. There was significant difference between group 1 and group 2 in time to first flatus (44.9 +/- 12 vs. 53. 6 +/- 17), but no significant difference was found in time to first meal (76.4 +/- 48 vs. 72.7 +/- 55), first bowel movement (62.8 +/- 42 vs. 55.2 +/- 38), or length of hospital stay (200.3 +/- 63 vs. 192.1 +/- 63) in hours. Conclusion: Perioperative administration of Itopride accelerates the restoration of bowel movement after abdominal surgery. Itopride was well tolerated and serious adverse effect was not observed during the study. Preliminary clinical experience suggests that Itopride can be a useful accelerator in restoration of bowel movement after major abdominal surgery. However, further research is needed to establish the usefulness of Itopride. No significant financial relationships to disclose.
Primary care physician willingness to provide follow-up care for adult cancer survivors
Authors: M. Del Giudice, S. Verma, E. Piliotis, B. J. Harvey, E. Grunfeld
Journal: Journal of Clinical Oncology (2007)

6562 Background: Routine follow-up of adult cancer survivors is an important clinical and health service issue. Due to a lack of evidence suggesting advantages of long-term follow-up care in oncology clinics, there is increasing support for the locus of this care to be provided by primary care physicians (PCPs). However, views from PCPs on this issue remain to be studied. Methods: A mail survey of a random sample of community based PCPs in Canada, stratified by region and proximity to urban centres was conducted. Views on routine follow-up of adult cancer survivors and modalities to facilitate PCPs in providing this care were determined. Results: 330 PCPs responded (adjusted response rate 52%). PCPs are willing to assume exclusive responsibility for routine follow-up care approximately 2.5 (95 % Confidence Interval [CI], 2.3–2.7;) years after active treatment of colorectal and prostate cancers; 2.8 (95 % CI, 2.5–3.1) years for breast cancer and 3.2 years (95% CI, 2.9–3.5) years for lymphoma. Respondents ranked care shared between cancer specialists and PCPs as their preferred strategy of follow-up, followed equally by exclusive care by cancer specialists or by PCPs. PCPs considered the most useful modalities to assist them in assuming exclusive responsibility for follow-up care were: (1) a patient-specific letter from the specialist; (2) printed guidelines; (3) expedited routes of re-referral; and (4) expedited access to investigations for suspected recurrence. The least useful modalities were: (1) pamphlets; (2) more office staff; and (3) websites. The majority of PCPs recognized that specialist clinics are overcrowded (55.6 %) and that PCPs are better placed to provide psychosocial support (79.8 %). However, they believed that specialist follow-up is important so that patients remain in the cancer centre system (67.2 %) and that patients expect follow-up care by cancer specialists (71.7%). Variations in responses were observed according to current practices and proximity to urban centres. Conclusions: With appropriate information and support in place, PCPs are willing to assume exclusive responsibility for the follow-up care of prevalent adult cancer survivors. Insights gained from this survey may help guide strategies in providing optimal care to cancer survivors. No significant financial relationships to disclose.
Level of troponin needed to rule out MI in patients with chest pain is identified
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Researchers have identified the level of the protein troponin below which it is highly unlikely that someone presenting with chest pain has had a myocardial infarction (MI).

Routine use of the test in the emergency department could rule out a diagnosis of MI in two thirds of patients with chest pain, the authors have estimated—double the number of patients currently suitable for immediate discharge.

A total of 6304 patients presenting with suspected acute coronary syndrome at four emergency departments in Scotland from June 2013 to January 2014 were recruited to the prospective observational cohort study, reported in the Lancet .1 All patients …
Lung Carcinoma of Sheep (Jaagsiekte): Tissue-Bound Precipitating Antibodies
Authors: I Hod, R Milchan
Journal: JNCI Journal of the National Cancer Institute (1979)

Firmly bound IgG was examined and its activity was tested in spontaneous lung carcinoma of sheep (jaagsiekte). High levels of IgG were extracted by acid-glycine buffer (GB) at pH 2.8 from both the tumor tissue and normal lung, which were exhaustively prewashed by phosphate-buffered saline (PBS) at pH 7.4. The first acid-GB eluates of the normal or tumor tissue acted in the immunodiffusion test as precipitating antibodies against antigens of the first PBS eluate of the tumor tissue. In addition, free intracytoplasmic type A particles were observed in cell-free tumor extract.
Mechanism of action of benzydamine in the treatment of oral mucositis
Authors: S. T. Sonis, B. Watkins, E. Fey, M. Yuschak, D. Parenti
Journal: Journal of Clinical Oncology (2005)

8040 Background: BZD has been proposed as a topical intervention for radiation-induced (RT) OM. BZD has been reported to have a range of biological activities that intervere with many of the mechanisms that are thought to be of importance in the pathogenesis of RT-induced OM. The objective of this study was to define the mechanisms by which BZD attenuates RT-induced OM. Methods: The effect of topically applied BZD on selected morphological and biological parameters was studied in temporal fashion to develop a descriptive pattern of events from which suggestions of mechanisms could be derived. 60 golden Syrian hamsters were randomized into 3 groups (G1 placebo n=32, G2 BZD n=32, G3 no treatment n=4). G1 and G2 animals were treated qd on day (d) 0 (day of RT) and then qid for 28d by injection into the left buccal cheek pouch. A single 37Gy radiation dose was administered to the left buccal pouch of all animals on d0. Four animals from G1 and G2 were sacrificed on d1,4,8,12,16,18 and 28, their left buccal pouches removed and the tissue studies for a variety of histological and immunohistochemical outcomes and markers. Results: Topical application of 0.15% BZD resulted in macroscopic attenuation of OM. A biphasic response characterized many study endpoints. Histological outcomes reflected tissue injury. BZD modified epithelial proliferation, but not differentiation. Observed changes correlated with a reduction in tissue levels of interleukin (IL)-1beta and tumor necrosis factor-alpha, but not IL-6. Preferential antiapoptotic activity was seen in epithelium and connective tissue of BZD-treated animals. Endothelial expression of COX-2 was altered by BZD. Conclusions: BZD’s effect in this model correlated with its selective attenuation of pro-inflammatory cytokines and its modification of epithelial and connective tissue apoptosis. These data do not indicate whether these effects are mechanistic drivers of OM or downstream markers of a more fundamental biological effect. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration McNeil Consumer and Specialty Pharmaceuticals Biomodels LLC, McNeil
Innovative Tools and Technology for Analysis of Single Cells and Cell–Cell Interaction
Authors: Tania Konry, Saheli Sarkar, Pooja Sabhachandani, Noa Cohen
Journal: Annual Review of Biomedical Engineering (2016)

Heterogeneity in single-cell responses and intercellular interactions results from complex regulation of cell-intrinsic and environmental factors. Single-cell analysis allows not only detection of individual cellular characteristics but also correlation of genetic content with phenotypic traits in the same cell. Technological advances in micro- and nanofabrication have benefited single-cell analysis by allowing precise control of the localized microenvironment, cell manipulation, and sensitive detection capabilities. Additionally, microscale techniques permit rapid, high-throughput, multiparametric screening that has become essential for -omics research. This review highlights innovative applications of microscale platforms in genetic, proteomic, and metabolic detection in single cells; cell sorting strategies; and heterotypic cell–cell interaction. We discuss key design aspects of single-cell localization and isolation in microfluidic systems, dynamic and endpoint analyses, and approaches that integrate highly multiplexed detection of various intracellular species.
Characteristics Of Chronic Lymphocytic Leukemia (CLL) In Senegal. Clinical Features, Cytology, Immunophenotype, Cytogenetic Abnormalities and Altered Expression Of Micro-RNA
Authors: Abibatou Sall Fall, Tandakha Ndiaye Dieye, Fatou Samba Ndiaye, Saliou Diop, Claire Mathiot, Charles-Henri Gattiolat, Evelyne May, Joëlle Wiels, Saloua Trojani, Awa Toure, Martine Raphael
Journal: Blood (2013)
Abstract 17696: Pulmonary Vein Obstruction: a European Congenital Heart Surgeons Association (ECHSA) Multicentric Study
Authors: David Kalfa, Emre Belli, Emile Bacha, Virginie Lambert, Duccio di Carlo, Heikki Sairanen, Jean Rubay, Martin Kostolny, Christian Schreiber, Matej Nosal, Mark Hazekamp, Hakan Berggren, Illya Yemets, Bohdan Maruszewski, George Sarris, Marco Pozzi, Tjark Ebels, François Lacour-Gayet
Journal: Circulation (2014)

Pulmonary vein obstruction (PVO) still has a poor prognosis and its optimal management and risk factors for pejorative outcomes remain controversial in the absence of large multicentric studies. We assessed the hypothesis that diffuse PVO and postoperative pulmonary hypertension are associated with worse outcomes while the sutureless surgical technique is associated with better outcomes. Methods: One hundred and seven patients treated for native or acquired PVO in 16 European or North-American centers (2000-2012) were included retrospectively. A specific PVO severity score (range:0-16) was developed. Endpoints were 1) PVO-related death, 2) persistence or recurrence of PVO, and 3) PV reintervention or PVO-related death. A univariate and multivariate risk analysis (logistic regression and Cox model) was performed. Mean follow-up was 34±41 months. Results: Patient characteristics, outcomes and risk analyses are summarized in Tables 1, 2 and 3 respectively. In conclusion, both native and acquired PVO still have a poor prognosis. Sutureless repair is significantly associated with lower risks of PVO recurrence and PV reoperation/PVO-related mortality in the univariate analysis. A postoperative pulmonary hypertension and a high degree of severity of the disease evaluated by a new severity score are independent risk factors for pejorative outcomes.
Late-breaking abstract: Ventilation inhomogeneities in children with congenital thoracic malformations
Authors: Matthew Morten, Payal Mandaliya, Rajendra Kumar, Alan James, Aniruddh Deshpande, Vanessa Murphy, Peter Gibson, Bruce Whitehead, Paul Robinson, Joerg Mattes
Journal: European Respiratory Journal (2014)

Background:  Congenital thoracic malformations (CTM) are rare lung lesions that are managed with surgical resection or active surveillance.  Aims and objectives:  To assess large and small airway function in children with CTM by utilising pulmonary function tests that are better suited for the sensitive measure of disease in children.  We hypothesise that more sensitive measures of peripheral airways will more likely demonstrate adverse pulmonary function in post-operative CTM children.  Methods:  Nitrogen lung clearance index (LCI), reactance and resistance (X5Hz and R5Hz) and forced expiratory volume in 1 s (FEV1) were prospectively measured in 10 children with CTM (mean age/SD: 7.6/1.3) who had undergone surgical resection in early life and in 16 healthy children (mean age/SD: 4.8/0.4).  Results:  Mean LCI was 8.0 (95% CI 7.5 to 8.5) in the CTM group and 7.3 (95% CI 7.0 to 7.8) in healthy children (p=0.02). Mean % predicted X5Hz was 175% (95% CI 122 to 228) in the CTM group and 104% (95% CI 89.4 to 118.3) in healthy children (p=0.001). Mean % predicted FEV1 was 83% (95% CI 74 to 92) in the CTM group and 98% (95% CI 87 to 108) in healthy children (p=0.043). Mean LCI was inversely correlated with height z-scores in the CTM group (rs=-0.88, p=0.002) but not in healthy children (rs=-0.19, p=0.49).  Conclusions:  Children with CTM appear to have impaired lung function as demonstrated by the significant differences in X5Hz and LCI scores. These findings are of clinical significance as ventilation inhomogeneities are closely correlated with somatic growth.