tbuckley/cabot-search huggingface dataset:
Abstract 62: Pim-1 Engineering of Human CPCs Increases Telomere Length from Aged Patients with Heart Failure
Authors: Sadia Mohsin, Mohsin Khan, Kathleen Wallach, Travis Cottage, Michael Mcgregor, Mark Sussman
Journal: Circulation Research (2012)

Rationale: Adoptive transfer of human cardiac progenitor cells (hCPCs) can repair damaged myocardium and improve function in a pathologically challenged heart. Aging can exhaust hCPC pool and pose a challenge to effectively regenerating the damaged myocardium. There is a dire need to reverse the senescent phenotype of these hCPCs isolated from elderly patients to target large segment of population suffering from heart failure. Objective: Demonstrate that Pim-1 engineering of human cardiac progenitor cells (hCPCs) isolated from elderly patients with heart failure can increase the telomere lengths, telomerase activity, population doubling and reverse their senescent phenotype. Methods and Results: hCPCs positive for the putative stem cell marker c-kit were isolated from heart biopsy samples from patients undergoing Left Ventricular Assist Device (LVAD) implantation. hCPCs isolated from patients aged 75-85 years (n=3) with heart failure demonstrate decreased population doubling time concomitant with decreased telomere lengths measured by in situ hybridization and telomerase activity measured by TRAP assay compared to patients aged 60-73 years (n=3). hCPCs were engineered to express Pim-1-GFP (hCPCeP), a fused GFP version of the kinase by using a lentivirus expression system. The cell cycling time measured by population doubling is increased after over expression of Pim-1 in hCPCs isolated from old patients. Pim-1 modification significantly increased telomere lengths and telomerase activity indicative of reversal of senescent characteristics of aged hCPCs. Conclusion: Ex vivo gene delivery of Pim-1 enhances telomere length, telomerase activity and decreases population-doubling time. Modification of aged hCPCs from elderly patients augments their ability to regenerate damaged myocardium, making stem cell engineering a viable option to address current limitations associated with senescent phenotype of aged hCPCs.
Utility of clinical markers to identify patients with high risk cervical dysplasia and cancer
Authors: S. Ueda, M. Carney, J. Killeen, M. Wakabayashi
Journal: Journal of Clinical Oncology (2006)

10055 Background: The natural history of cervical neoplasias appears unpredictable with 1/3 to 1/2 of CIN lesions regressing without intervention; therapeutic targeting aids in screening and selecting patients at risk and elucidating treatment response. This study aimed at determining if a pattern of tumor suppressor, oncogene, and growth factor expression (specifically HER-2/neu, progesterone and estrogen receptors (ER/PR), p53, and Ki67) exists in the progression of cervical cancer utilizing the widely applicable process of immunohistochemistry. Methods: Paraffin sections from 128 cervical biopsy, cone, and hysterectomy specimens collected from 1/00–12/04 were obtained from the surgical pathology repository at a tertiary care center with a primarily Asian and Polynesian patient population. Levels of expression in normal, low and high grade dysplasias, and invasive carcinomas were measured via automated immunohistochemical analysis. Results: 30% of samples came from patients who smoked. Ki-67 index rose with increasing dysplastic change (17–43%) but dropped with invasive carcinomas (&lt;17%). HER-2/neu staining occurred at greater levels in high grade lesions and invasive carcinomas but average intensity measured &lt;1, with &gt;2.2 being of prognostic significance because of candidacy for Herceptin therapy by breast criteria. ER/PR expression generally remained low with a penchant for parabasal cells (2–14%), and p53 levels likewise appeared minimally affected (3–5%). Conclusions: While HPV infection immortalizes cervical cells via a p53/pRb pathway, the equivocal expression of wild-type p53 across pre-invasive and more aggressive lesions suggests the involvement of other environmental toxins and genetic mutations. PR and ER play only a minor role in the development of adenosquamous carcinomas, indicating a lack of hormonal control in cervical tumor growth and proliferation. Her-2/neu, however, participates in the late events of cervical malignancy but at such levels that clinical usefulness proves questionable. Although HER-2/neu perhaps holds limited prognostic value in cervical carcinogenesis, similar molecular pathways independent of HPV need to be investigated as adjuncts to the common Pap smear. No significant financial relationships to disclose.
Epstein-Barr Virus Strains With Latent Membrane Protein-1 Deletions: Prevalence in the Italian Population and High Association With Human Immunodeficiency Virus–Related Hodgkin's Disease
Authors: Riccardo Dolcetti, Paola Zancai, Valli De Re, Annunziata Gloghini, Beatrice Bigoni, Barbara Pivetta, Salvatore De Vita, Antonino Carbone, Mauro Boiocchi
Journal: Blood (1997)
Correction of the auditory phenotype in C57BL/6N mice via CRISPR/Cas9-mediated homology directed repair
Authors: Joffrey Mianné, Lauren Chessum, Saumya Kumar, Carlos Aguilar, Gemma Codner, Marie Hutchison, Andrew Parker, Ann-Marie Mallon, Sara Wells, Michelle M. Simon, Lydia Teboul, Steve D. M. Brown, Michael R. Bowl
Journal: Genome Medicine (2016)

Background: Nuclease-based technologies have been developed that enable targeting of specific DNA sequences directly in the zygote.These approaches provide an opportunity to modify the genomes of inbred mice, and allow the removal of strain-specific mutations that confound phenotypic assessment.One such mutation is the Cdh23 ahl allele, present in several commonly used inbred mouse strains, which predisposes to age-related progressive hearing loss.Results: We have used targeted CRISPR/Cas9-mediated homology directed repair (HDR) to correct the Cdh23 ahl allele directly in C57BL/6NTac zygotes.Employing offset-nicking Cas9 (D10A) nickase with paired RNA guides and a single-stranded oligonucleotide donor template we show that allele repair was successfully achieved.To investigate potential Cas9-mediated 'off-target' mutations in our corrected mouse, we undertook whole-genome sequencing and assessed the 'off-target' sites predicted for the guide RNAs (≤4 nucleotide mis-matches).No induced sequence changes were identified at any of these sites.Correction of the progressive hearing loss phenotype was demonstrated using auditory-evoked brainstem response testing of mice at 24 and 36 weeks of age, and rescue of the progressive loss of sensory hair cell stereocilia bundles was confirmed using scanning electron microscopy of dissected cochleae from 36-week-old mice.Conclusions: CRISPR/Cas9-mediated HDR has been successfully utilised to efficiently correct the Cdh23 ahl allele in C57BL/6NTac mice, and rescue the associated auditory phenotype.The corrected mice described in this report will allow age-related auditory phenotyping studies to be undertaken using C57BL/6NTac-derived models, such as those generated by the International Mouse Phenotyping Consortium (IMPC) programme.
Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer.
Authors: D G Pfister, E Strong, L Harrison, I E Haines, D A Pfister, R Sessions, R Spiro, J Shah, F Gerold, T McLure
Journal: Journal of Clinical Oncology (1991)

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.
Trabectedin in advanced, pretreated soft tissue sarcoma: The Hospital Sírio-Libanês experience in a compassionate use program.
Authors: R. Schmerling, F. C. Maluf, P. M. Hoff, F. Costa, A. C. Buzaid
Journal: Journal of Clinical Oncology (2010)

e20511 Background: There is no established standard therapy for patients (pts) who had disease progression after an anthracycline-based chemotherapy, although some antitumor activity has been reported with single agent ifosfamide and chemotherapy combinations including gemcitabine with docetaxel, and vinorelbine and dacarbazine. Trabectedin is the first compound of a new class of antineoplastic agent with a mechanism of action that involves the transcription-dependent nucleotide excision repair system, approved for use in metastatic sarcomas only in Europe. Methods: We reviewed the clinical data from all pts with metastatic soft tissue sarcoma treated in a Trabectedin Compassionate Use Program. All pts had to have prior therapy with at least one line of an anthracycline-based regimen. Trabectedin was administered in a 24-hour infusion at 1.2–1.5mg/m2 (at the attending physician's discretion), repeated q3 weeks. Results: A total of 35 pts (20 M, 15F), with several soft-tissue sarcoma histologies were included. Five received 1 prior line of chemotherapy; 17 received 2 lines and 13 received 3 or more lines of prior chemotherapy. Three pts have not yet been treated and 5 died before receiving trabectedin. Performance status, according to ECOG criteria, was: zero, 3 pts; one, 16 pts; two, 8 pts; three, 2pts; four, 6pts. Response was evaluated according to RECIST. Among the 26 evaluable patients there were 2 PRs, 13 SD, 11 PD. Median TTP was 128 days (range 2-393). Fourteen patients (54%) had TTP > 120 days and nine patients (35%) > 180 days. Toxicity was manageable, and most frequent events were neutropenia, protracted nausea and fatigue. One patient had severe AST/ALT elevation and 3 patients had G2/3 CPK elevation. Three patients died within 30 days after the first cycle and were labeled as PD. Conclusions: According to EORTC criteria to consider activity of a drug in sarcoma therapy (TTP in 3 months >39% and TTP in 6 months>14%; Van Glabbeke et al.), our data suggest that trabectedin is active, with acceptable toxicity, even in a heavily pretreated patient population. No significant financial relationships to disclose.
Abstract 046: A Potential MicroRNA Biomarker for Atherosclerotic Lesions in Baboons
Authors: G M Karere, J P Glenn, S Birnbaum, N Kuhn, K Lange, C Christensen, K Rice, M Mahaney, L Havill, J L VandeBerg, L A Cox
Journal: Circulation Research (2013)

Introduction: Cardiovascular disease is the leading cause of death in developed countries and commonly due to atherosclerosis. Atherosclerosis is a resultant of interplay of gene and environmental factors including diet. Liver is the primary target for lipid metabolism and circulatory microRNAs (miRNAs) are potential biomarkers for atherosclerosis. However, little information is available on miRNAs for early prediction and diagnosis of severity of atherosclerosis. Hypothesis: We hypothesized that peripheral blood mononuclear cell (PBMCs) miRNA(s) are potential biomarkers for atherosclerosis. We tested this by first identifying PBMCs and liver miRNAs with discordant expression in baboons with low and high serum low density-lipoprotein cholesterol (LDL-C) concentrations and then determined if the miRNAs correlated with atherosclerotic lesions in baboons fed a high fat diet for 2 years. Methods and Results: Using Next Gen methods, we sequenced PBMCs and liver small RNA libraries from baboons discordant for LDL-C concentrations (low LDL-C, n = 3; high LDL-C, n = 3); fed a high-cholesterol, high-fat (HCHF) diet for 7 weeks. We identified 47 and 27 novel baboon miRNAs, and 494 and 490 human homologues in PBMCs and in liver, respectively. Seventy-one and 30 miRNAs showed differential response to HCHF diet in PBMCs and in liver, respectively. Comparison of miRNA expression profiles from PBMCs and liver showed concordant expression for miR-221/222 family; it was down-regulated in high LDL-C baboons in response to HCHF diet. Using qRT-PCR, we quantified miR-221 abundance in PBMCs and in livers of high LDL-C baboons (n = 109) on 2-year HCHF challenge and revealed, for hepatic miR-221, a positive correlation with severity of lesions in descending aorta (Pearson correlation coefficient, r = 0.18, p = 0.05) and aortic arch (r = 0.22, p = 0.03). Conclusions: Liver miR-221 abundance is associated with extent of lesions in baboons fed a HCHF diet for 2 years and may be a biomarker for atherosclerosis.
Recovery position cuts hospital admissions in unconscious children, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Putting an unconscious child in the recovery position is associated with a significant reduction in hospital admission, shows a study that found that many parents carry out potentially dangerous manoeuvres instead.1

Loss of consciousness is common in young children, and as many as 15% of children present with at least one syncopal event before age 19.

European guidelines recommend that an unconscious child whose airway is clear and who is breathing normally should be turned on his or her side into the recovery position, which helps keep the airway …
Colouring books for adults on the cancer ward
Authors: Miriam Rigby, Mark Taubert
Journal: BMJ (2016)

Throughout 2015, colouring books for adults have topped the UK’s bestselling paperback charts.1 In our cancer centre’s inpatient wards, colouring books are next to many beds. This phenomenon began two months ago when one patient started colouring in birds using pencils, felt tips, and glitter pens …
The clinical use of corticosteroids in pregnancy
Authors: M.W. Kemp, J.P. Newnham, J.G. Challis, A.H. Jobe, S.J. Stock
Journal: Human Reproduction Update (2015)

The use of antenatal steroid therapy is common in pregnancy. In early pregnancy, steroids may be used in women for the treatment of recurrent miscarriage or fetal abnormalities such as congenital adrenal hyperplasia. In mid-late pregnancy, the antenatal administration of corticosteroids to expectant mothers in anticipation of preterm birth is one of the most important advances in perinatal medicine; antenatal corticosteroids are now standard care for pregnancies at risk of premature delivery in high- and middle-income countries. The widespread uptake of this therapy is due to a compelling body of evidence demonstrating improved neonatal outcomes following antenatal corticosteroid exposure, stemming most notably from corticosteroid-driven maturation of fetal pulmonary function. As we approach the 50th anniversary of landmark work in this area by Liggins and Howie, it is apparent that much remains to be understood with regards to how we might best apply antenatal corticosteroid therapy to improve pregnancy outcomes at both early and mid to late gestation.Drawing on advances in laboratory science, pre-clinical and clinical studies, we performed a narrative review of the scientific literature to provide a timely update on the benefits, risks and uncertainties regarding antenatal corticosteroid use in pregnancy. Three, well-established therapeutic uses of antenatal steroids, namely recurrent miscarriage, congenital adrenal hyperplasia and preterm birth, were selected to frame the review.Even the most well-established antenatal steroid therapies lack the comprehensive pharmacokinetic and dose-response data necessary to optimize dosing regimens. New insights into complex, tissue-specific corticosteroid signalling by genomic-dependent and independent mechanisms have not been used to inform corticosteroid treatment strategies. There is growing evidence that some fetal corticosteroid treatments are either ineffective, or may result in adverse outcomes, in addition to lasting epigenetic changes in a variety of homeostatic mechanisms. Nowhere is the need to better understand the intricacies of corticosteroid therapy better conveyed than in the findings of Althabe and colleagues who recently reported an increase in overall neonatal mortality and maternal morbidity in association with antenatal corticosteroid administration in low-resource settings.New research to clarify the benefits and potential risks of antenatal corticosteroid therapy is urgently needed, especially with regard to corticosteroid use in low-resource environments. We conclude that there is both significant scope and an urgent need for further research-informed refinement to the use of antenatal corticosteroids in pregnancy.
P0637 : Short-term antiviral prophylaxis is not effective in HBsAg-negative, anti-HBc positive, and/or anti-HBs patients undergoing hematopoietic stem cell transplantation
Authors: Y.J. Kim, M. Lee, Y.Y. Cho, J.-J. Yoo, Y. Cho, D.H. Lee, H. Cho, E.J. Cho, J.-H. Lee, S.J. Yu, J.-H. Yoon, H.-S. Lee
Journal: Journal of Hepatology (2015)
P0320 : Targeting TGF-beta I with the transforming growth factor receptor type I kinase inhibitor, LY2157299, modulates stemness-related biomarkers in hepatocellular carcinoma
Authors: B. Rani, F. Dituri, Y. Cao, U. Engström, L. Lupo, S. Dooley, A. Moustakas, G. Giannelli
Journal: Journal of Hepatology (2015)
Diagnostic and prognostic value of<sup>18</sup>F-DOPA PET and<sup>1</sup>H-MR spectroscopy in pediatric supratentorial infiltrative gliomas: a comparative study
Authors: Giovanni Morana, Arnoldo Piccardo, Matteo Puntoni, Paolo Nozza, Armando Cama, Alessandro Raso, Samantha Mascelli, Michela Massollo, Claudia Milanaccio, Maria Luisa Garrè, Andrea Rossi
Journal: Neuro-Oncology (2015)

(1)H-MR spectroscopy (MRS) and (18)F-dihydroxyphenylalanine (DOPA) PET are noninvasive imaging techniques able to assess metabolic features of brain tumors. The aim of this study was to compare diagnostic and prognostic information gathered by (18)F-DOPA PET and (1)H-MRS in children with supratentorial infiltrative gliomas or nonneoplastic brain lesions suspected to be gliomas.We retrospectively analyzed 27 pediatric patients with supratentorial infiltrative brain lesions on conventional MRI (21 gliomas and 6 nonneoplastic lesions) who underwent (18)F-DOPA PET and (1)H-MRS within 2 weeks of each other. (1)H-MRS data (choline/N-acetylaspartate, choline-to-creatine ratios, and presence of lactate) and (18)F-DOPA uptake parameters (lesion-to-normal tissue and lesion-to-striatum ratios) were compared and correlated with histology, WHO tumor grade, and patient outcome.(1)H-MRS and (18)F-DOPA PET data were positively correlated. Sensitivity, specificity, and accuracy in distinguishing gliomas from nonneoplastic lesions were 95%, 83%, and 93% for (1)H-MRS and 76%, 83%, and 78% for (18)F-DOPA PET, respectively. No statistically significant differences were found between the 2 techniques (P > .05). Significant differences regarding (18)F-DOPA uptake and (1)H-MRS ratios were found between low-grade and high-grade gliomas (P≤.001 and P≤.04, respectively). On multivariate analysis, (18)F-DOPA uptake independently correlated with progression-free survival (P≤.05) and overall survival (P = .04), whereas (1)H-MRS did not show significant association with outcome.(1)H-MRS and (18)F-DOPA PET provide useful complementary information for evaluating the metabolism of pediatric brain lesions. (1)H-MRS represents the method of first choice for differentiating brain gliomas from nonneoplastic lesions.(18)F-DOPA uptake better discriminates low-grade from high-grade gliomas and is an independent predictor of outcome.
Etoposide, leucovorin, 5-fluorouracil (ELF) combination chemotherapy for advanced gastric cancer: Experience with two treatment schedules incorporating intravenous or oral etoposide
Authors: B.G. Taal, F.G.M. Teller, W.W. ten Bokkel Huinink, H. Boot, J.H. Beijnen, R. Dubbelman
Journal: Annals of Oncology (1994)
Growth Factors and Cytokines Upregulate Gelatinase Expression in Bone Marrow CD34+ Cells and Their Transmigration Through Reconstituted Basement Membrane
Authors: Anna Janowska-Wieczorek, Leah A. Marquez, Jean-Marc Nabholtz, Maria L. Cabuhat, Jencet Montaño, Hung Chang, Jacob Rozmus, James A. Russell, Dylan R. Edwards, A. Robert Turner
Journal: Blood (1999)
Phase II study and long-term follow-up of patients treated with taxol for advanced ovarian adenocarcinoma.
Authors: A I Einzig, P H Wiernik, J Sasloff, C D Runowicz, G L Goldberg
Journal: Journal of Clinical Oncology (1992)

PURPOSE Based on the results of our phase I study that demonstrated the antitumor activity of taxol in a previously treated patient with ovarian cancer, a phase II study was conducted to evaluate the efficacy of taxol in patients with metastatic ovarian cancer and to evaluate further the toxicity of taxol in this group of patients. PATIENTS AND METHODS Thirty-four patients with metastatic ovarian cancer received taxol (180 to 250 mg/m2) as a 24-hour continuous infusion. A premedication regimen was used to reduce the likelihood of an acute hypersensitivity reaction. RESULTS Six of 30 assessable patients demonstrated complete responses (one patient) or partial responses (five patients; 20%; 95% confidence interval [CI], 6% to 34%; range, 2 to 30 months). Additionally, one patient had a less than partial objective response (2 months), and two patients had stable disease for 6 and 15 months. Those responders had a median survival of 27 months, and the nonresponders had a median survival of 6 months (P = .0001). Myelosuppression was the most significant toxicity. Other adverse effects included alopecia and peripheral neuropathy. CONCLUSION Taxol has significant activity in ovarian cancer and should be studied in combination with other active agents earlier in this disease.