tbuckley/cabot-search huggingface dataset:
The Effect of Cell Division on the Cellular Dynamics of Microinjected DNA and Dextran
Authors: James J. Ludtke, Magdolna G. Sebestyén, Jon A. Wolff
Journal: Molecular Therapy (2002)

The legend to Figure 1 was printed with duplicate letters for panels “A” and “B.” Below is Figure 1, accompanied by the corrected figure legend. The Effect of Cell Division on the Cellular Dynamics of Microinjected DNA and DextranLudtke et al.Molecular TherapyMay, 2002In BriefGene delivery is a multistep process that is being studied to increase its efficiency, a major hurdle for effective gene therapy. Our study focused on the nuclear entry step by microinjecting a mixture of fluorescent dextran and the pEYFP-Nuc plasmid (encoding a nuclear-targeted, enhanced GFP) into the cytoplasm of nondividing and dividing cells that were selected using non-chemical means. After 10 and 1000 ng/μl of plasmid DNA (pDNA) were cytoplasmically injected, 28% and 50% of the cells that had not divided expressed GFP, respectively, compared with 50% and 90% for the cells that had divided. Full-Text PDF Open Archive
Mdm2 Is Required for Survival and Growth of p53-Deficient Cancer Cells
Authors: Kyle P. Feeley, Clare M. Adams, Ramkrishna Mitra, Christine M. Eischen
Journal: Cancer Research (2017)

Abstract p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with implications for therapeutically targeting Mdm2. Deletion of Mdm2 in T-cell lymphomas or sarcomas lacking p53 induced apoptosis and G2 cell-cycle arrest, prolonging survival of mice with these tumors. p53−/− fibroblasts showed similar results, indicating that the effects of Mdm2 loss extend to premalignant cells. Mdm2 deletion in p53−/− cells upregulated p53 transcriptional target genes that induce apoptosis and cell-cycle arrest. Mdm2 deletion also increased levels of p73, a p53 family member. RNAi-mediated attenuation of p73 rescued the transcriptional and biological effects of Mdm2 loss, indicating that p73 mediates the consequences of Mdm2 deletion. In addition, Mdm2 deletion differed from blocking Mdm2 interaction with p53 family members, as Nutlin-3 induced G1 arrest but did not activate apoptosis in p53−/− sarcoma cells. Our results indicate that, in contrast to current dogma, Mdm2 expression is required for cell survival even in the absence of p53. Moreover, our results suggest that p73 compensates for loss of p53 and that targeting Mdm2 in p53-deficient cancers has therapeutic potential. Cancer Res; 77(14); 3823–33. ©2017 AACR.
MLN51, a novel protein overexpressed in breast cancer
Authors: Sébastien F. Degot, Marie-Christine Rio, Catherine Tomasetto
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4290 

Metastatic Lymph Node 51 (MLN51) is a novel gene over-expressed in human breast cancer that has been isolated using subtractive hybridization. MLN51 codes for a protein of 703 amino acids, that share no homologies with other human proteins. Nevertheless, MLN51 counterparts are found in many species, showing that this protein is well conserved from worm to man. Immunohistochemistry revealed that MLN51 protein is over-expressed in 30% of the breast tumours tested, without association with a specific histological type of tumour or grade. Regardless of the high expression found in epithelial breast cancer cells, MLN51 is expressed at a basal level in all cell-types that were studied, such as normal mammary epithelial cells, endothelial cells and fibroblasts, suggesting that MLN51 is involved in an ubiquitous biological function. MLN51 primary sequence contains several protein-protein interactions motifs. In its amino-terminal half, a coiled-coil domain and two nuclear localisation signals were identified and in its carboxy-terminal half one SH2 and four SH3 potential binding motifs are present. Moreover, the protein is phosphorylated in normal and cancer cells and the coiled-coil domain promotes MLN51 oligomerisation. Recently, using a genetic screen, the counterpart of MLN51 has been identified in Drosophila, named Barentsz. Barentsz is involved in the localisation of Oskar mRNA during development. Accordingly, in transfected cells, MLN51 protein is present in a perinuclear position, a region where proteins involved in mRNA maturation and transport are located. In addition, MLN51 is present in high molecular weight complexes containing RNA. Altogether, these data indicate that MLN51 is a conserved protein involved in an essential biological function probably related to mRNA maturation and/or transport. As MLN51 is overexpressed in 30% of breast cancers, we are curently clarifying its function to assess its contribution in cellular transformation.
An innovative approach to post-treatment cancer care: The After Cancer Treatment Transition Clinic (ACTT).
Authors: Carol A. Townsley, Shari Moura, Barbara Fitzgerald, Gillian Hawker, Jane Mosley, Cris Barrett, Catharine Fox, Malcolm J. Moore
Journal: Journal of Clinical Oncology (2012)

e19522 Background: Improvements in early detection and cancer therapy have led to better survival rates. Integration of cancer survivorship initiatives as part of cancer care is gaining momentum. However, post cancer treatment follow up care may not be best met in acute cancer clinics. Visits to a large urban cancer centre in Canada have increased by 30% in the past 5 years. These increased volumes have lead to prolongation of patient wait times and increased stress for health care providers. This cancer centre is undergoing a transformative change that focuses on improving the patient cancer care experience. Methods: The development of the ACTT clinic has been a partnered initiative between two academic healthcare centres: an urban cancer centre and a community ambulatory hospital with a focus in chronic disease management. It is being managed by an advanced practice nurse and a GP Oncologist. The ACTT clinic delivers high quality, safe specialized physician and advanced nursing patient care, with engagement of patients/families, oncologists and primary care. The target population is patients who have completed cancer therapy, are well and are at moderate to low risk for cancer recurrence. The initial phase of the project involved transitioning patients with Testes, Melanoma, Breast and Colorectal cancers. Each cancer site group identifies the appropriate processes for clinic functioning at the ACTT, and if required, for appropriate linkages back to acute cancer care and primary care. Results: Over 1,000 patients have been transitioned to ACTT since April 2010 with 10-20 additional patients referred weekly. Essential components of the model include: standard surveillance protocols for recurrence or secondary cancers, management of long term and late effects of cancer treatment, monitoring for distress and health promotion. Standard reporting includes patient assessment and a defined plan of care communicated to their oncologist and primary care. Patient experience evaluation of the program is ongoing. Conclusions: The ACTT clinic initiative has been successful in developing a novel clinic model and has successfully transitioned over 1,000 patients from an acute care cancer clinic.
Halofuginone, an Old Anticoccidosis Drug, Induces Apoptosisin Multiple Myeloma Cells, Associated with Down Regulation of MCL1.
Authors: Merav Leiba, Yu-Tzu Tai, Teru Hideshima, Jana Jakubikova, Ikeda Hiroshi, Xian-Feng Li, Peter Burger, Paul Richardson, Nikhil C. Munshi, Arnon Nagler, Kenneth C. Anderson
Journal: Blood (2007)
<i>In vitro</i> Metabolomic Approaches to Investigating the Potential Biological Effects of Phenolic Compounds: An Update
Authors: Úrsula Catalán, Laura Barrubés, Rosa Maria Valls, Rosa Solà, Laura Rubió
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract Dietary phenolic compounds (PCs) have been receiving interest for their presumed roles in disease prevention. However, there is a lack of studies on the underlying molecular mechanisms. In this regard, in vitrometabolomic approaches are suitable for the investigation of the molecular changes in response to PC exposure. Up to date, the biological effects of PCs have only been examined for PCs from rosemary (Rosmarinus officinalis), olive oil, and resveratrol using cell-based metabolomic approach, although transcriptomic and/or proteomic studies have also been conducted in the same in vitro cell experiment in some cases. Our integral analysis of the reviewed studies suggest that PCs may be involved not only in basic cellular processes or macro- and micro-nutrient metabolism, but also in specific metabolic pathways that have been thoroughly investigated. These modulated pathways could have a clinical impact on neurodegenerative diseases, type 2 diabetes, cancer, and cardiovascular diseases. In conclusion, the in vitro metabolomic approaches provide additional information of the molecular mechanisms involved in disease risk reduction of dietary PCs. In order to elucidate the mechanisms of action of PCs, more metabolomic cell-based studies are needed and testing the physiological conjugated forms of PCs in these cell systems could be of special interest.
Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial
Authors: M Hunault-Berger, N Maillard, C Himberlin, C Recher, A Schmidt-Tanguy, B Choufi, C Bonmati, M Carré, M-A Couturier, E Daguindau, J-P Marolleau, F Orsini-Piocelle, J Delaunay, E Tavernier, S Lissandre, M Ojeda-Uribe, L Sanhes, L Sutton, A Banos, L M Fornecker, M Bernard, D Bouscary, A Saad, M Puyade, V Rouillé, I Luquet, M C Béné, J-F Hamel, F Dreyfus, N Ifrah, A Pigneux
Journal: Blood Cancer Journal (2017)

Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial
Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief
Authors: Dane D. Jensen, TinaMarie Lieu, Michelle L. Halls, Nicholas A. Veldhuis, Wendy L. Imlach, Quynh N. Mai, Daniel P. Poole, Tim Quach, Luigi Aurelio, Joshua Conner, Carmen Klein Herenbrink, Nicholas Barlow, Jamie S. Simpson, Martin J. Scanlon, Bimbil Graham, Adam McCluskey, Phillip J. Robinson, Virginie Escriou, Romina Nassini, Serena Materazzi, Pierangelo Geppetti, Gareth A. Hicks, Macdonald J. Christie, Christopher J. H. Porter, Meritxell Canals, Nigel W. Bunnett
Journal: Science Translational Medicine (2017)

Therapeutic targeting of the neurokinin 1 receptor in endosomes provides efficacious and prolonged pain relief.
Abstract 14382: Psoriasis is Associated with Impaired HDL Efflux Despite Normal HDL Levels Compared to Controls
Authors: Nehal N Mehta, YiDing Yu, William T Farver, Amrith Rodrigues, Parasuram Krishnamoorthy, Jules Antigua, Anna Raper, Amanda Baer, Stephanie DerOhannessian, Joel M Gelfand
Journal: Circulation (2011)

Introduction: Psoriasis is a Th-1/17 mediated inflammatory skin disease associated with increased risk of major adverse cardiac events (MACE). Systemic inflammation has been shown to be associated ...
Prenatal Alcohol Exposure
Authors: Megan A. Moreno
Journal: JAMA Pediatrics (2017)

Evelyne Muggli, MPH; Harold Matthews, BPsych(Hons); Anthony Penington, MDBS; Peter Claes, PhD; Colleen O’Leary, PhD; Della Forster, PhD; Susan Donath, MA; Peter J. Anderson, PhD; Sharon Lewis, PhD; Cate Nagle, PhD; Jeffrey M. Craig, PhD; Susan M. White, MBBS; Elizabeth J. Elliott, MD; Jane Halliday, PhD
The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis
Authors: Amirhossein Sahebkar, Maria-Corina Serban, Peter Penson, Camelia Gurban, Sorin Ursoniu, Peter P. Toth, Steven R. Jones, Giuseppe Lippi, Kazuhiko Kotani, Karam Kostner, Manfredi Rizzo, Jacek Rysz, Maciej Banach
Journal: Drugs (2017)

Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen therapy is associated with lower circulating low-density lipoprotein cholesterol and increased triglycerides, but its effects on other lipids are less well studied. We aimed to investigate the effect of tamoxifen on circulating concentrations of lipoprotein(a) [Lp(a)] through a meta-analysis of available randomized controlled trials (RCTs) and observational studies. This study was registered in the PROSPERO database (CRD42016036890). Scopus, MEDLINE and EMBASE were searched from inception until 22 March 2016 to identify studies investigating the effect of tamoxifen on Lp(a) values in humans. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate. Meta-analysis of five studies with 215 participants suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment (SMD −0.41, 95% confidence interval −0.68 to −0.14, p = 0.003). This effect was robust in the sensitivity analysis. Meta-analysis suggested a statistically significant reduction of Lp(a) levels following tamoxifen treatment. Further well-designed trials are required to validate these results.
Caulobacter in cancer immunotherapy
Authors: Mayowa Adeleye, Pravin Bhatnagar, Mavanur Suresh, John Smit
Journal: Clinical Cancer Research (2007)

A60  Purpose: To develop new cancer vaccine formulations using both the wild type (WT) and genetically modified Caulobacter crescentus (CC).Methods: Murine mammary carcinoma (EMT-6) cancer cell line was employed to investigate the anti-tumour effects of CC in two groups. In-vivo comparison of the effect of routes of administration on the antitumor effect of WT CC against EMT-6 was investigated. In-vivo comparison of the antitumor effects of the single and double mutant bacterial strains against EMT-6 was also performed. These include the CB15A KASC which is an S-layer minus strain, but still has the Smooth Lipopolysaccharides (LPS) and CB15A Ca5 KSAC which is a strain that has no S-layer and has a point mutation in the Smooth LPS. This latter strain can be referred to as the “naked” Caulobacter control. Natural killer (NK) cells from mice were isolated using magnetic activated cell separation from splenocytes using anti-NK cellanti-CD49b (DX5)microbead separator. Purified NK cells were co-incubated with WT CC, purified LPS, isolated S-layer protein ormouse interleukin-2 (IL-2).The cell-free supernatants from pooled cultures were collected for Enzyme Linked ImmunoSorbent Assay (ELISA) for interferon-gamma (IFN-γ) secretion. We developed a new active specific immunotherapy approach with high density display of MUC-1 breast cancer tandem peptide repeats on the S-Layer of CC.Results: WT treated mice showed a lower tumour volume with longer survival rate, when compared to the control group. Antitumor efficacy was higher in mice treated with intraperitoneal route than in intratumoral route of treatment. Normal saline treated and the double mutant control treated groups, exhibited high relative tumour volume and short survival rates compared to the WT bacteria and the single mutant strain treated groups. The latter showed a prolonged survival rates as well as reduced tumour volume. Thus, the results suggest that CC smooth LPS might be responsible for the bacteria anti-tumour activity. CC LPS directly stimulates pro-inflammatory cytokine IFN-γ production by NK cells. The in-vitro immunochemical characterization of the new designer high-density expression of multimeric-MUC-1 on CC display of cancer peptides using B27.29 monoclonal antibody against MUC-1 antigen using standard whole cell ELISA and SDS-PAGE analysis were established. Conclusion:CC may be a safe, bacterial immunomodulator for the treatment of tumors. The non-toxic and highly immunogenic CC-LPS play a key role in the inherent antitumor effect of the bacteria. Finally, CC is also valuable as a “platform” for particulate whole cell expression and presentation of MUC-1 peptide. Acknowledgement: The project is supported by the Natural Sciences and Engineering Research Council of Canada Collaborative Health Research Project (NSERC-CHRP).
Rare Variant, Gene-Based Association Study of Hereditary Melanoma Using Whole-Exome Sequencing
Authors: Mykyta Artomov, Alexander J Stratigos, Ivana Kim, Raj Kumar, Martin Lauss, Bobby Y Reddy, Benchun Miao, Carla Daniela Robles-Espinoza, Aravind Sankar, Ching-Ni Njauw, Kristen Shannon, Evangelos S Gragoudas, Anne Marie Lane, Vivek Iyer, Julia A Newton-Bishop, D Timothy Bishop, Elizabeth A Holland, Graham J Mann, Tarjinder Singh, Jeffrey Barrett, David J Adams, Göran Jönsson, Mark J Daly, Hensin Tsao
Journal: JNCI Journal of the National Cancer Institute (2017)

Extraordinary progress has been made in our understanding of common variants in many diseases, including melanoma. Because the contribution of rare coding variants is not as well characterized, we performed an exome-wide, gene-based association study of familial cutaneous melanoma (CM) and ocular melanoma (OM).
Development and characterization of a combination chemotherapy formulation with quercetin and irinotecan
Authors: Man-Yi Wong, Gigi Chiu
Journal: Clinical Cancer Research (2007)

B26  Quercetin is a flavone that exerts cytotoxicity in cancer cells but not in normal cells. However, clinical application of quercetin has been hampered by its low water solubility and potency. The objectives of this study are to develop a formulation to improve the water solubility of quercetin and to encapsulate chemotherapeutic agents exhibiting synergistic activity with quercetin. This could lead to more effective treatments and reduced side effects. In vitro studies of quercetin and irinotecan alone or in combination were conducted on breast cancer cells (MDA-MB-231 and JIMT-1) and ovarian cancer cells (SKOV-3). Quercetin and irinotecan exhibited synergism over a wide range of concentrations. A cholesterol-free liposome formulation was prepared by the thin film hydration method followed by extrusion. Quercetin was incorporated into the lipid bilayer of the liposomes while irinotecan was encapsulated with an ionophore generated transmembrane proton gradient. The encapsulation efficiencies for irinotecan and quercetin were 83% and 97% respectively; providing a 10- fold increase in the water solubility of quercetin. In addition, the liposomes had a unimodal size-distribution (polydispersity = 0.19) with a mean size of 107 nm. The liposomes were stable for up to 12 weeks, without any significant changes in either the mean size (111nm) or size distribution (polydispersity = 0.18). In conclusion, the liposomes encapsulated the two agents efficiently, solubilized quercetin and were stable, demonstrating the potential of this novel formulation to be translated into clinical use for treating breast and ovarian cancers.
Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial
Authors: Jürgen Finke, Claudia Schmoor, Wolfgang Andreas Bethge, Hellmut Ottinger, Matthias Stelljes, Liisa Volin, Dominik Heim, Hartmut Bertz, Olga Grishina, Gerard Socie
Journal: The Lancet Haematology (2017)
Randomized phase II clinical trial of the anti-HER2 (GP2) vaccine to prevent recurrence in high-risk breast cancer patients: A planned interim analysis.
Authors: Francois Trappey, John S. Berry, Timothy J Vreeland, Diane F. Hale, Alan K. Sears, Sathibalan Ponniah, Sonia A. Perez, Guy T. Clifton, Michael Papamichail, George Earl Peoples, Elizabeth Ann Mittendorf
Journal: Journal of Clinical Oncology (2013)

3005 Background: A prospective, randomized, multi-center, placebo-controlled, single-blinded, phase II trial was designed to evaluate the safety and clinical efficacy of GP2, a HER2-derived peptide vaccine, in breast cancer patients. Methods: Clinically disease-free, node-positive or high-risk node-negative patients (pts) with any level of HER2 expression were enrolled after standard of care therapy. HLA-A2+ pts were randomized to receive GP2 + GM-CSF (VG) or GM-CSF alone (CG). HLA A2- controls from a parallel arm of the study were also eligible for evaluation, the extended CG (ECG). Pts receive 6 monthly intradermal inoculations (R0-R6) during the primary vaccine series followed by four boosters every 6 mos. Immune responses (IR) were measured by delayed type hypersensitivity (DTH) at R0 and R6. This planned interim analysis was performed at 24 months median follow-up. Results: We have currently enrolled 172 pts (46, VG; 43, CG; 83 extended CG). There are no differences between groups with respect to age, rate of node positivity, tumor grade, tumor size, ER/PR status, and HER2 over-expression (all p &gt; 0.05). Maximum local toxicity (tox) was similar between the two groups (grade (Gr) 1 and 2: VG 93%, CG 98%; Gr 3: VG 2%, CG 1%). Maximum systemic tox was also similar between the groups (Gr 1 and 2: VG 91%, CG 85%). No Gr 3 systemic tox has been reported. The most frequent systemic reactions are fatigue, headache, and myalgias. IR to GP2 has been robust. DTH is increased from R0 to R6 in the VG (3.0±0.98 to 21.5±4.04 mm, p &lt; 0.01) vs. the smaller increase in CG (2.6±0.89 to 6.0±1.6 mm, p = 0.01). VG DTH at R6 is significantly higher than the CG (21.5 vs 6.0 mm, p &lt; 0.01). The recurrence rate (RR) is decreased in the VG vs CG (4.3% vs. 11.6%, p = 0.41) and VG vs ECG (4.3% vs 9.5%, p = 0.41). In pts with HER2-overexpressing (IHC3+ or FISH+) tumors, the RR is decreased in the VG (0% vs 5% CG, p = 0.28). For TNBC (HER2 low, ER/PR-) pts, the RR is reduced in the VG vs ECG (0% vs 10.6%, p = 0.251). Conclusions: The GP2 vaccine is safe and the minimal toxicity is comparable between the VG and CG, suggesting that it is due to GM-CSF. Robust in vivo immune response has correlated with a &gt;50% reduction in breast cancer recurrences in the VG. Clinical trial information: NCT00524277.
Abstract #5256: Comparative study between liquid based cytology and conventional preparation in respiratory cytology
Authors: Masatoshi Kakihana
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The Thinprep Processor (CYTYC Corp., Boxborough, MA) is a thin-layer preparation device that is designed to improve both sample collection and cytopreparation. The advantages of Thinprep1 (TP) over conventional preparation (CP) include uniform thickness, elimination of air-drying artifacts, better cellular preservation, and elimination of obscuring blood and exudates. Numerous studies have compared TP with CP for use in gynecology cytology and more recently, in fine needle aspiration. However, to the best of our knowledge, there have been few reports comparing TP to CP for examining lung cancer specimens. The purpose of the current study was to evaluate the differences between TP and CP for performing fine needle aspiration, and we examined a variety of parameters, including the diagnostic accuracy, cellularity, and cytomorphology. Furthermore, residual material can be used to either process multiple slides or a cell block (CB), for ancillary tests such as immunochemistry (IC) and molecular tests. We hypothesized that the induction of prohibiting the PI3K/AKT/m-TOR signaling pathway may lead to reduce tumor progression. We demonstrated that the epidermal growth factor receptor tyrosine kinase inhibitor (erlotinib), m-TOR inhibitor (rapamycin), and histone deacethylase inhibitor (MS-275) induced cell growth inhibition in human NSCLCs cells were accompanied by G1/S phase arrest. We successfully performed DNA, RNA, and protein analysis in residual TPmaterial from lung cancer aspirates.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5256.
Effect of dialisys membrane on polymorphonuclear granulocytes phagocytosis and antimicrobial killing
Authors: F. Giacchino, F. Bonello, G. Banche, N.Mandras Nmandras, J. Roana, V. Tullio, P. Belardi, C. Merlino, A Cuffini
Journal: Journal of the American Society of Nephrology (2004)