tbuckley/cabot-search huggingface dataset:
Abstract 18503: Barriers to Linkage to Hypertension Care in Rural Western Kenya: A Qualitative Analysis
Authors: Rajesh Vedanthan, Violet Naanyu, Jemima H Kamano, Jackson Rotich, Kennedy K Lagat, Peninah Kiptoo, Claire Hutchinson, Diana Menya, Slyvester Kimaiyo, Valentin Fuster, Carol R Horowitz, Thomas S Inui
Journal: Circulation (2013)

Introduction: Hypertension is the leading global risk factor for mortality and its prevalence is rising in sub-Saharan Africa (SSA). Unless adequately controlled, hypertension will impose large health and economic burdens. Since delays in seeking hypertension care are associated with increased mortality, a critical component of hypertension control is to facilitate early and sustained access of affected individuals to clinical services. However, specific barriers to linkage to hypertension care in SSA are not known. Objective: To evaluate barriers to linkage to hypertension care in rural western Kenya, using a qualitative research approach. Methods: Six mabaraza, or community gatherings (123 men, 119 women), and 17 focus group discussions (88 men, 81 women) were conducted among community health workers, community members, and hypertensive patients, across a spectrum of age, sex, occupation, and distance from health facility. Content analysis was performed with NVivo 10, identifying key themes representing distinct barriers, which were then classified into a modified Health Belief Model. Ranking of identified barriers was performed using triangulation of participant response density, Delphi method of investigator assessments, and published literature. Results: The salient barriers and corresponding proposed solutions are summarized in the Table. Cognitive issues related to knowledge of hypertension and its risks and management were commonly reported by participants. Emotional elements, particularly HIV stigma and fear, were highlighted. Environmental barriers such as finances, distance, and quality of service also featured prominently. Conclusion: Linkage to hypertension care is a critical component to a successful hypertension care delivery program. However, successful execution is contingent upon addressing potential barriers at the cognitive, emotional, and environmental levels.
Association of serum interleukin-7 and interleukin-15 levels with immune reconstitution (IR), graft-versus-host disease (GVHD), and survival after reduced-intensity allogeneic stem cell transplantation (RIST)
Authors: R. M. Dean, F. T. Hakim, T. Fry, S. M. Steinberg, M. Boyiadzis, D. H. Fowler, J. Odom, C. Mackall, R. E. Gress, M. R. Bishop
Journal: Journal of Clinical Oncology (2007)

7107 Background: In laboratory models, interleukin-7 (IL-7) and IL-15 significantly influence IR after allogeneic stem cell transplantation (SCT), thereby affecting immunity, graft-versus-malignancy (GVM) effects, and GVHD. Interleukin-7 (IL-7) is the main homeostatic regulator of naïve CD4+ and CD8+ T cells, and IL-15 is homeostatic for CD8+ memory and effector T cells and NK cells. The contributions of these cytokines to IR after allogeneic SCT are not well characterized in a clinical setting. Methods: We studied serum IL-7 and IL-15 levels in 31 pts with hematologic malignancies undergoing RIST from HLA-matched siblings in a prospective trial. Pts received identical transplant conditioning (fludarabine/cyclophosphamide) and GVHD prophylaxis (CSA/MTX). IL-7 and IL-15 levels and peripheral blood lymphocyte subpopulations (ALC, CD3, CD4, CD8, B, NK, and NKT) were measured before RIST, and post RIST at 1 and 2 weeks; 1, 2, 3, 6, 9, and 12 months. Results: Consistent with their homeostatic effects, IL-7 and IL-15 levels rose from baseline as transplant conditioning induced lymphopenia, and then decreased with lymphocyte recovery. These inverse correlations were strongest within 1 month post RIST. In an exploratory analysis, IL-15 levels at day 0 were correlated with baseline age (r=0.49; p=0.0058) and were higher among patients with CMV reactivation after RIST (p=0.048). At 2 weeks post RIST, higher IL-7 levels were strongly associated with subsequent acute GVHD (p=0.000033), and higher IL-15 levels were associated with inferior survival (p=0.007), mainly from relapse. At 3 months post RIST, superior survival was associated with higher NK cell counts (p=0.0008), and to a lesser extent with higher CD4 counts (p=0.036). Conclusions: These data support preclinical observations that IL-7 promotes GVHD after allogeneic SCT. The association of higher post-RIST IL-15 levels with death from relapse may identify pts with impaired IR leading to inadequate GVM effects. This hypothesis is consistent with the finding that higher NK cell counts after RIST were associated with better survival. Further studies must confirm the hypotheses generated in this setting. No significant financial relationships to disclose.
Social Environmental Moderators of Long-term Functional Outcomes of Early Childhood Brain Injury
Authors: Shari L. Wade, Nanhua Zhang, Keith Owen Yeates, Terry Stancin, H. Gerry Taylor
Journal: JAMA Pediatrics (2016)

Pediatric traumatic brain injury (TBI) contributes to impairments in behavior and academic performance. However, the long-term effects of early childhood TBI on functioning across settings remain poorly understood.
Final analysis of a randomized dosing study of oregovomab in patients with advanced ovarian cancer
Authors: M. W. Method, A. N. Gordon, N. Finkler, J. Cieszynski, C. Nicodemus
Journal: Journal of Clinical Oncology (2005)

5035 Background: OV (oregovomab) is a MAb specific for CA125, currently in Phase III testing as an immunotherapy for consolidation of advanced OC. This study was designed to identify an optimal dosing schedule for OV to maximize immune response and presumed clinical benefit with low toxicity. Methods: 102 pts with stage III/IV OC treated with surgery and chemotherapy were randomized to one of three OV schedules: Group I (N=34): wks 0 and 4 only; Group II (N=34): wks 0, 4, 8, 20 then Q12; Group III (N=34): wks 0, 4, 8, 12, 16, 20 then Q12. Antibody responses (HAMA, Ab2, and anti-CA125) were analyzed serially by ELISAs. Results: There was a statistically significant difference among the treatment groups for the proportion of patients with significant HAMA response ≥3,366 ng/mL by Week 20 (3%, 24% and 39% in Groups I, II and III; p = 0.002), Week 32 (7%, 32% and 39%; p = 0.005), and overall (7%, 47% and 50%; p < 0.001). A statistically significant difference among the treatment groups was observed for the proportion of patients with significant Ab2 response ≥100 ng/mL by Week 20 (10%, 38% and 69% in Groups I, II and III; p < 0.001), Week 32 (10%, 47% and 72%; p < 0.001), and overall (10%, 62% and 75%; p < 0.001). Median time to disease relapse was significantly longer for patients who had a HAMA response≥3366 ng/mL on study compared to those who did not (78 vs 43 weeks; p = 0.0131). Median time to disease relapse was also longer for patients who exhibited a significant Ab2 response at any time on study compared to those who did not (58 vs 33 weeks; p = 0.0507). Analysis of mean changes from baseline in Global QOL and Fatigue scores over time on study revealed no statistically significant differences across groups. OV was well tolerated without significant toxicity in all 3 dosing regimens. Conclusions: Humoral immune response follows a dose response pattern which plateaus after 4 infusions, supporting the dosing regimen used in the ongoing Phase III studies of OV. These data suggest that a strong immune response is correlated with improved clinical outcomes, although this finding will be confirmed in the Phase III studies currently underway. OV was well tolerated without significant toxicity, regardless of dosing regimen. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Unither Unither Unither Unither
Abstract 19764: Cardiac Disease Modeling of Familial Left Ventricular Noncompaction Cardiomyopathy Using Induced Pluripotent Stem Cells
Authors: Yen K Bui, Kimberly R Cordes, Samantha Hastie, Deepak Srivastava
Journal: Circulation (2012)

Left ventricular noncompaction cardiomyopathy (LVNC) is thought to arise from developmental arrest of the normal compaction of ventricular heart muscle, sometime between weeks 4-8 of gestation. In normal heart development, a network of muscle bands (trabeculations) compact fully, resulting in a dense muscle and a smooth inner surface. Failure of trabecular compaction results in a muscle wall consisting of a spongy myocardium with a meshwork of trabeculations that can lead to thin dilated heart muscle and impaired muscle function. Although several disease-causing genes have been implicated in LVNC, the genetic cause remains unknown in more than 50% of patients. We hypothesize that LVNC arises from developmental arrest of the embryonic ventricular myocardial compaction process and that LVNC patients will have expression profiles reflective of this. We have identified a family with LVNC affecting 4 individuals. Through whole exome sequencing we identified a mutation in a cardiac developmental gene that was associated with the LVNC phenotype and was fully penetrant in this family. Using dermal fibroblasts from members of this family, we generated induced pluripotent stem (iPS) cells from affected and unaffected family members to identify transcriptome and functional consequences in cardiomyocytes harboring the genetic mutation. We will present our results from this genetic and cellular approach to LVNC, which allows study of the physiologic consequences of genetic mutations in relevant human cells.
AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study
Authors: G Avvisati, F Lo Coco, D Diverio, M Falda, F Ferrara, M Lazzarino, D Russo, MC Petti, F Mandelli
Journal: Blood (1996)
Anne Louis Margaret Graham
Authors: Joan Carmichael, Oona Scott
Journal: BMJ (2016)

Eldest daughter of Professor and Mrs R J D Graham, Anne Louis Margaret Graham graduated in 1950. Her first appointment was as house surgeon in obstetrics and gynaecology to Professor Margaret Fairlie at the Royal Victoria Infirmary in Dundee. Medical and surgical house jobs followed before she became registrar at the Princess Mary Maternity Hospital in Newcastle upon Tyne. In 1955 she was appointed senior registrar in obstetrics and gynaecology at Dryburn Hospital, Durham.

In 1960, she …
Abstract P6-06-05: Down-regulation of the circadian factor Period 2 by the oncogenic E3 ligase Mdm2: Relevance of circadian components for cell cycle progression
Authors: J Liu, T Gotoh, M Vila-Caballer, CS Santos, J Yang, CV Finkielstein
Journal: Cancer Research (2012)

Abstract Circadian rhythms are mechanisms that measure time on a scale of about 24 h and that adjusts our body to external environmental signals. Core circadian clock genes are defined as genes whose protein products are necessary components for the generation and regulation of circadian rhythms. Circadian proteins also regulate genes involved in either cell division or death; and a perturbation of the balance among these processes leads to cancer development and progression. A key aspect of cancer research is identifying new regulatory pathways involved in proliferation and differentiation of cell. Disruption of circadian rhythm has recently emerged as a new potential risk factor in the development of cancer, pointing to the core gene period 2 (per2) as a tumor suppressor. However, it remains unclear how the circadian network regulates tumor suppression, nor which, if any, of its components is either the ultimate effector that influences the fate of the cell. Initial experiments were devoted to identifying new interacting partners for Per2 using a two-hybrid system. Interestingly, among the positive clones analyzed was the oncogenic protein Mdm2. This result was validated by immunoprecipitation of recombinant and endogenous Per2/Mdm2 complexes from unstressed cells. Pull-down assays using tagged-expressed proteins fragments and labeled proteins were later used to map the interacting regions between Per2 and Mdm2. Our results show Mdm2 binds to the central flexible region of Per2 known to interact with various protein partners. Thus, we hypothesized that binding of Mdm2 to Per2 might act by mediating its ubiquitination and therefore altering Per2 stability. We next examined the formation of the Mdm2/p53/Per2 complex by immunoprecipitation. Our data show anti-p53 antibody is able to co-immunoprecipitate Per2 and Mdm2. Moreover, in vitro and in vivo ubiquitination assays show that binding of Per2 to p53 prevented ubiquitination of p53 by Mdm2 without altering their binding. Immunofluorescence studies using H1299 cells (p53-) confirmed Per2 role in p53 stabilization and for localization. Overall our results suggest that Mdm2 modulates the stability of Per2 and p53 in unstressed cells, and might be responsible for the oscillatory levels of these proteins observed in a 24 h cycle. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-06-05.
Sequential Hepatic Histologic and Histochemical Changes Produced by Diethylnitrosamine in the Rhesus Monkey 2
Authors: B. H. Ruebner, C. Michas, R. Kanayama, P. Bannasch
Journal: JNCI Journal of the National Cancer Institute (1976)

Six young adult male rhesus monkeys were given diethylnitrosamine ip for 3–5 years. Liver biopsies were done monthly. After 6 months, biopsy specimens showed individual hepatocytes and small foci of hepatocytes that were intensely positive for glycogen. During the second and later years, larger foci of such cells developed. In sections stained with hematoxylin and eosin, the glycogen-containing hepatocytes generally appeared unusually clear. Some hepatocytes, however, had eosinophilic or basophilic cytoplasm. Nuclear enlargement and atypia developed, particularly outside the foci. The hepatocytes within most foci were uniform in their histochemical features: glycogen was elevated, glucose-6-phosphatase was decreased, and ATPase activity was present not only along the bile canalicular surface but also along the entire cell membrane. After 3–5 years, neoplastic nodules and hepatocarcinomas developed in 5 of 6 animals. Two nodules and 1 hepatocarcinoma had a histochemical reaction pattern identical to that of the foci. However, most of the nodules and particularly the heptocarcinomas differed from the foci in one or more histochemical parameters. The findings suggested that the glycogen-containing, histochemically altered cells of the foci may be the first step in the development of neoplasia; further steps toward malignancy appeared to be frequently associated with additional alterations, such as loss of sinusoidal ATPase and re-formation of glucose-6-phosphatase.
p28-Mediated Activation of p53 in G2–M Phase of the Cell Cycle Enhances the Efficacy of DNA Damaging and Antimitotic Chemotherapy
Authors: Tohru Yamada, Tapas K. Das Gupta, Craig W. Beattie
Journal: Cancer Research (2016)

p28 is an anionic cell-penetrating peptide of 28 amino acids that activates wild-type and mutated p53, leading subsequently to selective inhibition of CDK2 and cyclin A expression and G2-M cell-cycle arrest. In this study, we investigated the cytotoxic effects of p28 treatment alone and in combination with DNA-damaging and antimitotic agents on human cancer cells. p28 enhanced the cytotoxic activity of lower concentrations (IC20-50) of DNA-damaging drugs (doxorubicin, dacarbazine, temozolamide) or antimitotic drugs (paclitaxel and docetaxel) in a variety of cancer cells expressing wild-type or mutated p53. Mechanistic investigations revealed that p28 induced a post-translational increase in the expression of wild-type or mutant p53 and p21, resulting in cell-cycle inhibition at the G2-M phase. The enhanced activity of these anticancer agents in combination with p28 was facilitated through the p53/p21/CDK2 pathway. Taken together, these results highlight a new approach to maximize the efficacy of chemotherapeutic agents while reducing dose-related toxicity. Cancer Res; 76(8); 2354-65. ©2016 AACR.
Phase I/II trial of the MEK1/2 inhibitor GSK1120212 (GSK212) in patients (pts) with relapsed/refractory myeloid malignancies: Evidence of activity in pts with RAS mutation.
Authors: G. Borthakur, L. Popplewell, M. H. Kirschbaum, J. M. Foran, T. M. Kadia, E. Jabbour, M. Boyiadzis, A. Verma, R. B. Walter, P. S. Wissel, L. Xu, J. W. Bauman, J. Z. Zhu, J. Mazumdar, M. Baccus, J. M. Connor, J. E. Cortes, H. Kantarjian
Journal: Journal of Clinical Oncology (2011)

6506 Background: Signaling through the RAS/RAF/MEK pathway is activated in many human cancers. GSK212 is a potent, selective allosteric inhibitor of MEK1/2 that inhibits proliferation of myeloid cell lines in vitro. A phase I/II study of a single, daily, oral dosing regimen was conducted to define the recommended phase II dose (RP2D) and evaluate pharmacokinetics, toxicity and preliminary activity in pts with previously treated hematologic malignancies. Results reported are from the RP2D; 2mg/day. Methods: Pts with relapsed/refractory AML, MDS, ALL or CMML with WBC <30,000/µL and adequate hepatic, renal and cardiac function were eligible for this study. Pts were prospectively screened for KRAS mutations at amino acids 12 and 13 using a PCR-based kit and for NRAS mutations at amino acids12, 13, and 61 using sequence analysis. Clinical response was assessed using International Working Group (2003 and 2006) criteria for AML and MDS. Results: 45 pts (30 AML, 12 MDS transformed to AML) received 2mg GSK212 daily. 73% were male; median age 62 (range 21–87) and 93% had received prior therapy. GSK212 exhibited long effective half-life with small peak/trough ratios and the exposure profile maintained time above preclinical target threshold for the 24-hour dosing period. Drug-related adverse events (AEs; >10%) were diarrhea 29% (n=13; 24% Grade 1/2, 4% Grade 3), and rash 22% (n=10; 20% Grade 1/2, 2% Grade 3), myelosuppression was not noted. AEs possibly related to inhibition of MEK signaling were blurred vision (n=3; 4% Grade 1, 2% grade 3) and decreased cardiac ejection fraction (n=1; Grade 3). Conclusions: GSK212 demonstrates encouraging signs of clinical activity with manageable AEs in pts with previously treated AML characterized by somatic RAS mutations. Recruitment of pts with N or KRAS mutant AML/MDS and CMML is ongoing. Best response n=39* N or KRAS mutated n=13 RAS wt or unk n=26 CR/CRp 3 (23%) 0 MLFS 1 (8%) 0 PR 0 2 (8%) HI/HI-N/HI-P 1 (8%) 4 (15%) SD# 7 (54%) 9 (35%) PD 1 (8%) 11 (42%) ORR 31% (95% CI 9%, 61%) 8% (95% CI 1%, 25%) * 6 pts not evaluable were RAS wt/unk; 5 had screen assessments only; 1 lacked follow-up. #Investigator assessed. Abbreviation: MLFS, morphologic leukemia-free state.
The Co-Culture Of Primary CLL Cells With Bone Marrow Mesenchymal Cells, CD40 Ligand and CpG ODN Promotes The Proliferation Of Chemoresistant CLL Cells Phenotypically Comparable To Those From The Proliferative Centers
Authors: Noelia Purroy, Pau Abrisqueta, Eva Calpe, Cecilia Carpio, Carles Palacio, Laura Gallur, Marta Crespo, Francesc Bosch
Journal: Blood (2013)
Trends in Giant Cell Tumour of the Bone and Osteosarcoma Incidence in the Sweden (1958-2011)
Authors: A. Liede, J. Sandberg, J. Amelio, R.K. Hernandez, P. Sobocki, H.C.F. Bauer, B. Bach, J. Engellau
Journal: Annals of Oncology (2014)
TRAP1, a novel antiapoptotic gene responsible for multidrug resistance in human colorectal carcinoma cells
Authors: M. Landriscina, E. Costantino, F. Maddalena, A. Piscazzi, A. Fersini, S. Calise, F. Esposito
Journal: Journal of Clinical Oncology (2009)

2541 Background: TRAP1 has been recently described as a component of a mitochondrial pathway selectively up- regulated in tumor cells which antagonizes the proapoptotic activity of cyclophilin D and is responsible for maintenance of mitochondria integrity, thus favoring cell survival. Interestingly, novel TRAP1 antagonists cause sudden collapse of mitochondrial function and selective tumor cell death, suggesting that this pathway may represent a novel molecular target to improve anticancer therapy. Furthermore, we recently observed that TRAP1 is significantly up-regulated in osteosarcoma cells adapted to growth in mild oxidizing conditions and this correlates with a phenotype more resistant to H 2 O 2 -induced DNA damage and apoptosis. This evidence prompted us to investigate the role of TRAP1 as being responsible for multi-drug resistance in human colorectal cancer. Methods and Results: The evaluation of TRAP1 expression by immunoblot and quantitative RT-PCR analysis in a series of 26 human colorectal carcinomas allowed us to observe up-regulation in 17/26 tumors. Accordingly, TRAP1 protein levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Interestingly, HT-29 colorectal carcinoma and Saos-2 osteosarcoma cells transfected with TRAP1 gene exhibited a phenotype resistant to 5-fluorouracil-, oxaliplatin- and irinotecan-induced apoptosis, evaluated by MTT incorporation analysis and annexin V staining. Consistently, the transfection of a dominant negative N-terminal deletion mutant of TRAP1 as well as the inhibition of TRAP1 activity by the TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to apoptosis induced by 5-fluorouracil, oxaliplatin and irinotecan in wild type HT-29 colorectal carcinoma cells and in HT-29 cells resistant to the single agents. Conclusions: These results suggest that the increased expression of TRAP1 in human colorectal carcinomas could be part of a pro-survival pathway responsible for multidrug resistance. Thus, targeting TRAP1 may represent a novel strategy to improve the efficacy of anticancer agents in colorectal cancer. No significant financial relationships to disclose.
Evaluation of the COPD assessment test (CAT) for measuring health-related quality of life in patients with interstitial lung disease
Authors: Kazuma Nagata, Keisuke Tomii, Michio Hayashi, Kojiro Otsuka, Ryo Tachikawa, Kyoko Otsuka
Journal: European Respiratory Journal (2011)

There is a need for a short, simple, and well validated instrument to assess health-related quality of life (HRQL) in patients with interstitial lung disease (ILD). The study was conducted to evaluate the validity of the COPD assessment test (CAT), which is a newly developed short and simple questionnaire for COPD with good measurement properties, in ILD.  52 ILD patients completed the CAT and the St. George9s Respiratory Questionnaire (SGRQ). The patients also completed the MRC dyspnea scale, the Leicester Cough Questionnaire (LCQ), and the Hospital Anxiety and Depression Scale (HADS) and also underwent a six-minute walk test, pulmonary function tests, and arterial blood gas analysis.  The correlation between the CAT score and the SGRQ total score was very strong (r=0.93,  p  p  p  p