tbuckley/cabot-search huggingface dataset:
Effect of p53 gene transfection on human hepatocarcinoma cells' sensitivity to irradiation.
Authors: Zhengchao Tao, Liting Qian
Journal: Journal of Clinical Oncology (2013)

e22018 Background: Several studies demonstrated that p53 gene transfection enhanced the anti-tumor effects of radiotherapy. This study is to investigate whether p53 gene transfection can increase the radiosensitivity of liver tumor cells. Methods: Liver tumor cell lines, HepG2 (with wild type p53 genes) and PLC/PRF/5 (with mutant p53 genes), were separately transfected with recombinant adenoviral human p53 gene (rAdp53) and adenoviral enhance green fluorescent protein gene (AdEGFP), forming 4 types of cells: HepG2 transfected with rAdp53, HepG2 with AdEGFP, PLC/PRF/5 with rAdp53, and PLC/PRF/5 with AdEGFP. The transfected and untransfected HepG2 and PLC/PRF/5 cells were irradiated with 6MV-X at doses of 0, A2, A4, A6, A8, A and 10 Gy. After exposition to radiation, cell survival, clonogenic capacity, and apoptosis were analyzed. The effect differences between cell types were analyzed using statistical methods of pairwise group comparisons and mixed effect model. Results: After exposing irradiation, all the cells’ survival rate and clonogenic capacity decreased, and the proportion of apoptotic cell increased. These effects become stronger with increaseing dose of radiation. Between untransfected cells, radiation had a stronger effect on HepG2 cells than PLC/PRF/5 and the differences were statistically significant for all the 3 measures. The rAdp53 transfection, not the AdEGFP, significantly enhanced radiation effects on both cell lines. The enhanced effects on PLC/PRF/5 cells were significantly stronger then the enhanced effects on HepG2 cells. Conclusions: PLC/PRF/5 cells with mutant p53 genes were more resistant to radiation then HepG2 with wide type of p53 genes. The rAd-P53 transfection could enhance radiosensitivity of both cell lines, but the enhanced effect on PLC/PRF/5 cells with mutant p53 gene was stronger than HepG2 with wide type of p53 genes.
Prognostic Stratification of Patients with Chronic Lymphocytic Leukemia Based on Quantitative Flow Cytometry Evaluation of ZAP-70 Versus Homology of IgVH Plot.
Authors: Marti n Klabusay, Viera Kuhrova, Viera Hrabcakova, Petr Coupek, Jiri Mayer
Journal: Blood (2008)
Evolution and Clinical Impact of EGFR Mutations in Circulating Free DNA in the BELIEF Trial
Authors: Miguel-Angel Molina-Vila, Rolf A. Stahel, Urania Dafni, Núria Jordana-Ariza, Ariadna Balada-Bel, Mónica Garzón-Ibáñez, Beatriz García-Peláez, Clara Mayo-de-las-Casas, Enriqueta Felip, Alessandra Curioni Fontecedro, Oliver Gautschi, Solange Peters, Bartomeu Massutí, Ramon Palmero, Santiago Ponce Aix, Enric Carcereny, Martin Früh, Miklos Pless, Sanjay Popat, Sinead Cuffe, Paolo Bidoli, Roswitha Kammler, Heidi Roschitzki-Voser, Zoi Tsourti, Niki Karachaliou, Rafael Rosell
Journal: Journal of Thoracic Oncology (2019)
Elimination of both cancer stem cells and progenitor cells as essential for tumor eradication.
Authors: Creticus Petrov Marak, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2013)

e22179 Background: Cancer stem cells (CSC) have been identified in several malignancies. Elimination of CSCs requires precise identification of markers and development of mechanisms to target them specifically. It is possible that in spite of elimination of CSCs, the tumor may recur. Dedifferentiation of progenitor cells may help replenish cancer stem cells. Methods: A mathematical model of a cancer stem cell system with four layers has been constructed to reflect the hierarchy of cancer stem cells, progenitor cells and, transit-amplifying cells and pre-differentiated cells. This model is constructed in the lines of the phase space model described by Kirkland. Dedifferentiation parameters were introduced to allow for dedifferentiation when the stem cell pool receded below 40% of its normal size. The effects of stem cell antagonists (SCA) and differentiating agents (DA) were simulated to study the perturbations caused by them on the growth of the tumor. Results: SCAs when used alone result in the establishment of a new equilibrium across different layers within the tumor by de-differentiation. DAs which act only on progenitor cells cause an increase in the number of cells in the subsequent layers and contribute to an increase in the size of the tumor. DAs which act only on the pre-differentiated layer of cells move cells from this layer into a terminally differentiated layer of cells which results in a new but lower equilibrium. DAs which act on the progenitor, transit amplifying and pre-differentiated cells cause the establishment of a new equilibrium which is lower than that of all agents which act on individual layers of cells. A combination of an SCA and a DA which acts on multiple layers eliminates the re-establishment of a new equilibrium and leads to decline in cell populations in all the layers, thus reducing the possibility of recurrence. Conclusions: SCAs when used individually are not effective in eliminating the tumor. DAs which act only on progenitor cells can fuel tumor growth but DAs which act on multiple layers have a profound effect in slowing the growth of the tumor but do not eliminate the tumor. This model implies that a combination of an SCA and a DA which acts on multiple layers may have a better chance at eliminating the tumor.
GATA-1, but Not GATA-2, Antagonizes PU.1 Mediated Transcriptional Activity at the CBFA2T3 (ETO2, MTG16) Promoter through a Mechanism Dependent on GATA DNA Binding.
Authors: Yogenthiran Saunthararajah, SiJun Yang, ShriHari Kadkol, Marie Baraoidan, Vinzon Ibanez, Fariborz Mortazavi
Journal: Blood (2005)
Not all proteinuria is created equal
Authors: Andrew Beenken, Jonathan M. Barasch, Ali G. Gharavi
Journal: Journal of Clinical Investigation (2019)

Albuminuria acts as a marker of progressive chronic kidney disease and as an indicator for initiation of hypertension treatment via modulation of the renin-angiotensin-aldosterone system with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors. However, the true significance of albuminuria has yet to be fully defined. Is it merely a marker of underlying pathophysiology, or does it play a causal role in the progression of kidney disease? The answer remains under debate. In this issue of the JCI, Bedin et al. used next-generation sequencing data to identify patients with chronic proteinuria who had biallelic variants in the cubilin gene (CUBN). Through investigation of these pathogenic mutations in CUBN, the authors have further illuminated the clinical implications of albuminuria.
抗糸球体基底膜(GBM)腎炎におけるインターロイキン(IL)10遺伝子導入によるタンパク尿症の減少
Authors: Fouqueray B, Suberville S, Isaka Y, Akagi Y, Gerard C, Velu T, Imai E, Baud L
Journal: Journal of the American Society of Nephrology (1996)
Abstract 16651: Diuretic Responsiveness and Its Prognostic Importance in Children With Heart Failure
Authors: Jack F Price, Samuel Younan, Antonio Cabrera, Susan Denfield, Hari Tunuguntla, Swati Choudhry, William Dreyer, Ayse Akcan-Arikan
Journal: Circulation (2018)

Introduction: Fluid overload and congestion are common features of acute decompensated heart failure (ADHF) in children. However, response to diuretics is variable and, in adults, may predict outcome. We sought to identify risk factors for and prognostic relevance of decreased diuretic responsiveness (DR) in children hospitalized with ADHF. Hypothesis: We hypothesized that diminished diuretic responsiveness is associated with worse clinical outcomes. Methods: We performed a single center, retrospective cohort study, examining the medical records of 197 consecutive children &lt;21 years of age who were hospitalized with ADHF. Patients receiving thiazide diuretics were excluded. DR was defined as net fluid (mL) output per 1mg of furosemide equivalents during the first 72 hours of treatment with a loop diuretic. Greater and lesser DR was determined by DR values above and below the median, respectively. Multivariable analysis was performed to determine association of DR with the composite end-point of inpatient death or need for mechanical circulatory support (MCS). Results: A total of 119 patients (51% female) met study criteria. Median age at admission was 6.7 years (IQR 1.6 to 14.2 years). Etiologies of ADHF included dilated cardiomyopathy (n=73), congenital heart disease (n=16), acute heart transplant rejection (n=10), myocarditis (n=9), restrictive cardiomyopathy (n=7), hypertrophic cardiomyopathy (n=1), and ischemic cardiomyopathy (n=1). Median ejection fraction was 26% (IQR 18-38%). Median DR was 5.8 ml/mg (IQR -3.6 to 15.3 ml/mg). Thirty-four percent of patients remained in a positive fluid balance after 72 hours of treatment with a loop diuretic. Factors associated with lesser DR included: younger age, the absence of peripheral edema, female sex and the use of inotropes. The composite end-point of death or MCS occurred in 31 (26%) patients. Lesser DR was associated with worse outcomes, even after adjusting for age and total urine output per weight (OR 6.9, p&lt;0.01). Patients with lesser DR also experienced longer length of hospital stay than patients with greater DR (median, 55 vs 27 days, p&lt;0.01). Conclusions: In children hospitalized with ADHF, early diminished DR during decongestion therapy is common and portends a poor prognosis.
Determining the Extent of Disease with Magnetic Resonance Imaging of the Bone Marrow (BM-MRI) in Patients with Multiple Myeloma (MM).
Authors: Sikander Ailawadhi, Lyudmyla Derby, Terry L. Mashtare, Kena C. Miller, Gregory Wilding, Swaminathan Padmanabhan, Ronald Gottlieb, Ronald A. Alberico, Donald L. Klippenstein, Ahmed N. Abdelhalim, Asher A. Chanan-Khan
Journal: Blood (2007)
Individualized intensification of treatment based on tumor marker decline in metastatic nonseminomatous germ cell testicular cancer (NSGCT): A report from the Swedish Norwegian Testicular Cancer Group, SWENOTECA
Authors: S. Olofsson, O. Dahl, M. Jerkeman, G. Cohn-Cedermark, O. Klepp, U. Stierner, M. Törnblom, R. Wahlqvist, E. Cavallin-Ståhl
Journal: Journal of Clinical Oncology (2009)

5015 Background: From July 1995 to December 2003, 602 adult patients from Sweden and Norway with metastatic testicular NSGCT were included in a population-based multicenter SWENOTECA protocol with strict guidelines for staging, treatment and follow-up. Methods: The basic strategy of this protocol was to individualize treatment according to AFP and β-HCG decline (t1/2). Satisfactory response to treatment was defined as a t½ for AFP ≤ 7 days and/or β-HCG ≤ 3 days. Initial treatment for all patients was 2 courses of standard BEP. Tumor markers were analyzed once a week during treatment. Patients with satisfactory response went on with BEP while patients with unsatisfactory t1/2 received intensified treatment in two steps with addition of ifosfamide (BEP-if/PEI) in step 1. If still unsatisfactory response the treatment was intensified according to step 2 involving high-dose chemotherapy with stem cell rescue. Postchemotherapy surgery was performed according to protocol guidelines. Results: 99,7% (602 of 604) of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median FU was 72 months. 75% of the patients were treated with BEP, median 4 courses, without intensification, 19% according to intensification step 1 and 6% according to intensification step 2. Five year progression free survival (PFS), cancer specific survival (CSS) and overall survival (OS) grouped according to IGCCCG prognostic score are given in the Table below. There was no significant difference in PFS between the good and intermediate risk group. Death due to all causes was 10,1% (n=61) and treatment related deaths were 1,3 % (n=8). Conclusions: Our results, in a population based patient material, with individualized treatment based on tumor marker decline, are highly encouraging in all risk groups, but most notably in the intermediate risk group. [Table: see text] No significant financial relationships to disclose.
Screening for Copy Number Alterations and Loss of Heterozygosity in Chronic Lymphocytic Leukemia - A Comparative Study of Four Differently Designed, High Resolution Microarray Platforms.
Authors: Rebeqa Gunnarsson, Johan Staaf, Mattias Jansson, Anne Marie Ottesen, Hanna Göransson, Ulrika Liljedahl, Ulrik Ralfkiaer, Mahmoud Mansouri, Karin Ekström Smedby, Henrik Hjalgrim, Ann-Christine Syvänen, Åke Borg, Anders Isaksson, Jesper Jurlander, Gunnar Juliusson, Richard Rosenquist
Journal: Blood (2007)
Factors influencing prognosis for occupational hand eczema
Authors: C.M. Olesen, T. Agner, N.E. Ebbehøj, T.K. Carøe
Journal: British Journal of Dermatology (2019)

Hand eczema is a common skin disease causing itchy skin patches on the hands, which can have a significant impact on the quality of life of affected individuals. Occupational hand eczema is when the condition is caused or made worse by factors in the workplace. Occupational hand eczema affects up to 30% of people in ‘high risk’ occupations, such as jobs like hairdressing in which the hands stay wet for prolonged periods (known as wet work) or where the hands come into contact with irritants or allergens. In this study the authors, based in Copenhagen, Denmark, looked at factors influencing the prognosis (likely outcome, such as whether or not it will improve) for occupational hand eczema. By using files from the Danish Labor Market Insurance, patients with occupational hand eczema in the period January 2010 to December 2011 were identified and included in the study. Information on gender, age, occupation, wet work, atopic eczema (a common type of eczema in childhood) and contact allergy (skin allergy caused by contact with an allergen) was obtained from the files. In 2015, participants received a questionnaire about lifestyle factors, occupation and persistence of hand eczema. A total of 1491 out of 2703 patients responded to the question regarding persistence of hand eczema and were included in the study. A total of 19.3% of patients reported that their hand eczema had completely healed. Current tobacco smoking and a high level of stress were factors associated with persistence of hand eczema, while a high level of exercise was significantly related to healing of eczema. Change of profession was a favorable prognostic factor (meaning it led to improvement), while age, gender, atopic eczema, contact allergy and education did not significantly influence the prognosis. The study showed that traditionally important risk factors such as atopic eczema and contact allergy had no marked influence on prognosis, while lifestyle factors were of major importance. The findings indicate that risk factors may vary over time, allowing for new perspectives on prevention, with increased focus on lifestyle factors.
Challenges experienced with early introduction and sustained consumption of allergenic foods in the Enquiring About Tolerance (EAT) study: A qualitative analysis
Authors: Paula Voorheis, Sadie Bell, Laura Cornelsen, Matthew Quaife, Kirsty Logan, Tom Marrs, Suzana Radulovic, Joanna Craven, Carsten Flohr, Gideon Lack, Michael R. Perkin, Louise Young, Victoria Offord, Mary DeSousa, Jason Cullen, Katherine Taylor, Anna Tseng, Bunmi Raji, Sarah Byrom, Gillian Regis, Charlie Bigwood, Charlotte Stedman, Sharon Tonner, Emily Banks, Yasmin Kahnum, Rachel Babic, Ben Stockwell, Erin Thompson, Lorna Wheatley, Devi Patkunam, Kerry Richards, Ewa Pietraszewicz, Alick Stephens, Asha Sudra, Victor Turcanu
Journal: Journal of Allergy and Clinical Immunology (2019)

BackgroundThe early introduction group participants of the Enquiring About Tolerance study were asked to undertake a proscriptive regimen of early introduction and sustained consumption of 6 allergenic foods. It was envisaged that this might be challenging, and early introduction group families were presented with an open-text question to express any problems they were experiencing with the regimen in recurring online questionnaires.ObjectiveWe sought to analyze these open-text questionnaire responses with the aim of identifying challenges associated with the introduction and regular consumption of allergenic foods.MethodsThree combinations of interim questionnaire responses were selected for analysis, representing the early period (4, 5, and 6 months), middle period (8 and 12 months), and late period (24 and 36 months) of participation in the Enquiring About Tolerance study. Responses were assigned a code to describe their content and subsequently grouped into themes to portray key messages. A thematic content analysis allowed for conversion of qualitative codes into quantitative summaries.ResultsThree main challenges to allergenic food consumption were identified. First, some children refused the allergenic food, causing a sense of defeat among caregivers. Second, caregivers were concerned that allergenic foods might be causing a reaction, triggering a need for reassurance. Third, practical problems associated with the regimen compromised caregivers' capacity to persist.ConclusionUnderstanding the challenges experienced with allergenic food introduction and sustained consumption is the necessary precursor to developing specific communication and support strategies that could be used by caregivers, practitioners, policymakers, and key stakeholders to address these problems.Graphical abstract
Phase 1 Clinical Trial of NPI-0052, a Novel Proteasome Inhibitor in Patients with Multiple Myeloma
Authors: Paul Richardson, Craig C. Hofmeister, Todd M. Zimmerman, Asher Alban Chanan-Khan, Matthew A. Spear, Michael A. Palladino, Angie M. Longenecker, Gillian Cropp, G. Kenneth Lloyd, Sandra Wear, Alison L. Hannah, Kenneth C Anderson
Journal: Blood (2008)
Cytarabine plus mitoxantrone versus cytarabine plus clofarabine as second-line therapy in AML.
Authors: Zartash Gul, Asheesh Jain, Stacey A. Slone, Ali Raufi, Emily Marie Van Meter, Amber Lawson, John W. Hayslip, Gregory Monohan, Dianna S. Howard, Kevin T. McDonagh, Zaid Alkadhimi
Journal: Journal of Clinical Oncology (2013)

e18001 Background: There are no comparative studies that can provide guidance about the choice of second line therapy in AML patients (pts). Methods: We retrospectively evaluated 30 consecutive pts who underwent reinduction chemotherapy for AML with mitoxantrone and cytarabine (ACM) or cytarabine and clofarabine (ACC). Results: Baseline characteristics of the pts are described in the Table. Ten pts achieved remission after initial induction therapy in ACM group and 4 pts in ACC group (P=0.71). Median length of remission was 314 days (d) (81-874 d) in ACM group and 178.5 d (57-232 d) in ACC group (P=0.13).After reinduction in ACM and ACC groups 9 and 3 patients achieved remission respectively (P=0.4).One pt in each group underwent allogeneic stem cell transplant. After a median follow-up of 11.2 m (ACM) and 10.5m (ACC), 9 and 6 pts had died in ACM and ACC groups respectively. Causes of death were progression (ACM=2pts, ACC= 1pt), end organ failure (3 pts each) and unknown (ACM=4pts, ACC=2 pts). Median Overall survival (OS) was 18.4 months (m) in ACM and 13.1 m in ACC group (P=0.49). After reinduction therapy OS was 8.3 and 6.9 m in ACM and ACC groups (P=0.72). In our patient cohort we did not find any baseline characteristics that were associated with OS or achievement of remission after reinduction therapy. Conclusions: In our pt cohort both ACM and ACC regimens demonstrated the ability to induce remission as a possible bridging strategy to allogeniec stem cell transplant. Larger studies are needed to compare these two regimens as well as evaluate any baseline characteristics which correlate with OS or achievement of remission. [Table: see text]
Chimeric peptide supramolecular nanoparticles for plectin-1 targeted miRNA-9 delivery in pancreatic cancer
Authors: Ying Wu, Yuexiao Tang, Shangzhi Xie, Xiaoxiao Zheng, Shufen Zhang, Jiayan Mao, Baoming Wang, Yuerou Hou, Liqiang Hu, Kequn Chai, Wei Chen
Journal: Theranostics (2019)

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis. Insights into the roles of MicroRNAs (miRNAs) in diseases, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Methods: Here, we employed a novel chimeric peptide supramolecular nanoparticle delivery system for plectin-1 (PL-1)-targeted PDAC-specific miR-9 delivery in vitro and in pancreatic cancer patient-derived xenograft (PDX) model. RT-PCR and immunohistochemistry (IHC) were conducted to detect the expression pattern of eIF5A2. mRFP-GFP-LC3 fluorescence microscopy and Western blot were carried out to determine autophagy. Luciferase reporter assays were performed to elucidate the regulatory role of miR-9/eIF5A2 axis. Results: PL-1/miR-9 nanocomplexes dramatically improve the anticancer effect of doxorubicin through downregulating eIF5A2 expression to inhibit autophagy and induce apoptosis in PDAC therapy in vivo. Mechanistically, miR-9 directly targets the eIF5A2 transcript by binding to its 3'-untranslated region (3'-UTR) to reduce the expression levels and the secreted protein of eIF5A2 in PDAC cells. Conclusion: PL-1/miR-9 nanoparticles can be used as a novel promising anti-cancer strategy with tumor targeting and miR-9/eIF5A2 may serve as a new potential therapeutic target for future synergic therapy against human PDAC.
A Spliced Variant of CXCR3 (CXCR3B) Is Differentially Expressed on CD4+CD25+ Regulatory vs. CD4+CD25− Non-Regulatory T Cells Exposed to Platelet Factor 4 (PF4).
Authors: Chao Yan Liu, Gao Yuan, Qi-Hong Sun, Gian Paolo Visentin
Journal: Blood (2004)
A phase I study of sorafenib in association with docetaxel-prednisone in chemonaive metastatic castration-resistant prostate cancer
Authors: F. Mardjuadi, J. Medioni, J. Kerger, J. L. Canon, L. Duck, S. Oudard, M. Clausse, L. D'Hondt, A. Moxhon, J. P. Machiels
Journal: Journal of Clinical Oncology (2009)

5153 Background: Docetaxel (D)-prednisone (P) is the standard regimen for metastatic castrate-resistant prostate cancer (mCRPC). Sorafenib (S) is a dual-action kinase inhibitor that blocks cell proliferation and angiogenesis with antitumor activity in CRPC. The objectives were dose limiting toxicities (DLTs)/recommended dose (RD) of S in combination with D-P, pharmacokinetics (PK), and safety at the RD in an expanded cohort. Methods: 6 pts were enrolled per dose level (DL). All pts received D 75 mg/m 2 /3 wks in 6 chemotherapy cycles and P 10 mg/d. S dose escalation included 4 DL. DL 1: S 200 mg bid from day 3 to 19 of each chemotherapy cycle. DL 2: S 200 mg bid started at day 3 of the 1st cycle and continued without interruption through the cycles. DL 3: S 400 mg bid from day 3 to 19 of each cycle. DL 4: S 400 mg bid started at day 3 of the 1st cycle without interruption through the cycles. DLTs were determined during the first cycle. Results: 24 chemo-naive mCRPC pts (median age 68) were included in the dose-escalation study. PK analysis showed that mean C max and AUC of D were increased at cycle 2 in cohort 2, 3, and 4 indicating a PK interaction dependent on the exposure to S. For the 24 pts, the main Gr 3–4 toxicities (N pts) were febrile neutropenia (8), uncomplicated neutropenia (5), and hand-foot syndrome (4). No DLT was found. PSA response (&gt; 50% in PSA decrease) was recorded in 15 out of 20 pts. Conclusions: The RD of S in combination with D is 400 mg bid continuously. PK analysis revealed an interaction between D and S that may explain the high rate of febrile neutropenia and Gr4 neutropenia. 14 pts were included in an expanded cohort to further explore the safety of this regimen. Updated data will be presented. [Table: see text] No significant financial relationships to disclose.