bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triggers in the pathway from lung cell damage to malignancy: The glycans.
Authors: Saeed Anwaar Mohammed , Alkhazna Ammar Ali , Herndon Betty , Dim Daniel 
Published: March 2020

e22189 Background: It has been reported that carbon nanoparticles (CN) produce mesothelioma as readily as do asbestos fibers. We have studied early CN damage in experimental animals, quantifying toxicity by release from cells of the nuclear chaperone HMGB1. Damage-released HMGB1 binds to receptors (RAGE, CD24) to upregulate cytokines and produce regulatory signals that control cell homeostasis. Further, HMGB1 has recently been shown to form a complex with P53, one of the most commonly mutated genes in human cancers, and HMGB1 is the controlling factor in autophagy, an important new field in translational cancer research. Methods: One HMGB1 receptor, CD24, is the source of a whole-receptor antibody used to determine extent of malignancy during surgery. CD24 is highly glycosylated. We hypothesized that carbohydrate vs protein specificity would show differences in tumor character. Would antibodies to the CD24 carbohydrate moiety reflect a tumor glycan character, and how would this relate to the tumor profile such as metastasis? With cooperation of TMC pathology Dept, blocks (N=15 each) of lung squamous cell, adenocarcinoma, and small cell cancer were sectioned and stained with mouse monoclonals to CD24, IgM –glycan, IgG-protein fraction. Results: Small cell and adenocarcinoma lung tumors showed mostly similar staining by CD24 protein vs CD24 glycan antibodies. Squamous cell CA showed elevated carbohydrate CD24 staining with negative or low protein stain in over half of the cases, and examination of patient records are being studied to determine metastatic character, lung- damage history and tumor chemotherapy response. Conclusions: Squamous cell tumors demonstrate significantly more staining by antibody to the glycan moiety of CD24, p=0.02. There was no relationship between numbers of positive nodes and staining, although other chart information awaits analysis. Research continues into the significance of this glycan CD24 receptor for HMGB1, our marker for nanoparticle lung damage, and its relationship to malignant transformation. [Table: see text]
The value of promoter methylation of the MGMT gene and IDH mutations in secondary glioblastomas.
Authors: Bie Li , Li Qian Yun 
Published: March 2020

e22193 Background: Several studies have observed a change in MGMT silencing and IDH1 mutation in secondary glioblastomas (sGBMs). However, reports about the prognostic value of promoter methylation of the MGMT gene and IDH mutations in secondary glioblastomas (sGBMs) are few in number. Methods: The study involved primary and secondary tumor tissue samples from 89 GBMs pts (P/S: 42/47) diagnosed and treated within the First Hospital of Jilin University from Jan 2006 to Nov 2011. After surgical treatment, all GBM pts were subjected to radiotherapy with concomitant administration of TMZ. Pts with GBM were screened for promoter status of MGMT gene, by the methylation-speciﬁc polymerase chain reaction (MSP), and, for IDH mutations by direct sequencing. Results: A total of 42 of 89 pts (47.2%) had primary GBMs (pGBMs) (Group 1), while 47 pts (52.8%) had secondary GBMs (Group 2). In Group 2, 23 pts (21/47, 44.7%) developed a sGBM through progression from a low grade glioma (LGG) WHO grade II and a secondary anaplastic gliomas (sAG) (Group 2a), whereas 26 pts (26/47, 55.3%) showed a direct malignant transformation from a LGG to a sGBM (Group 2b). MGMT methylation was observed in 38 (42.7%) GBMs, with a higher frequency in sGBMs than pGBMs (24/14, 51.1 vs. 33.3%; p = 0.008). MGMT methylation status was associated with increased median survival time in pGBMs and sGBMs pts. IDH1 mutations are present in the majority of sGBMs but rare in pGBMs (31/5, 66.0 vs. 11.9%; p < 0.001). Group 2a had a higher frequency with IDH1 mutation than group 2b (18/12, 78.3 vs. 46.2%; p < 0.01). The median survival time after malignant progression of all sGBMs pts with an IDH mutation was longer than in pts with wild-type IDH (3.2 vs. 1.1ys; p < 0.01). IDH1 mutation had an improved outcome in group2a, which is compared with group 2b (3.9 ys vs. 2.1 ys; p < 0.05). Conclusions: In our population, pts with sGBM and IDH mutation had a signiﬁcantly improved outcome. In addition, MGMT methylation is also a powerful prognostic marker in sGBM pts.
Immune-phenotype assessment of ovarian cancer stem cells.
Authors: Martinez Maria Jose , Caballero Miguel , Martinez-Serrano Sergio , Vidal Laura , Fernandez Aranzazu , del Pino Marta , Vilella Ramon 
Published: March 2020

e22200 Background: Current evidence suggests the presence of cancer stem cells (CSC) in epithelial ovarian cancer (EOC) and their role in chemoresistance and relapse. CD44+/CD24-, CD117+ and CD133+ expression have been reported as potential markers for CSC. Methods: Tumor cells from 5 patients with chemo-naive EOC and cells of ovarian and tubal epithelium from 5 healthy menopausal women undergoing surgery for benign pathology were cultured in standard medium (mediumA) and medium for embrionic cells (mediumB).Cells forming non-adherent spheres where considered CSC-like, and adherent cells as non-CSC-like. The percentages of CD24+, CD44+, CD117+, CD133+ and VEGF-R+ cells were determined by flow-cytometry. Results: After 1-7 week sphere formation was observed in all EOC-cells cultured in mediumB but in none of the healthy controls. Mean percentages of markers expression are shown below. Conclusions: Contrary to published data, expression of CD44+/CD24- was lower in CSClike; in Non-CSClike CD133+ was higher in EOC-cells compared to controls. Inmunophenotype of CSClike is still lacking and further investigation is warranted. [Table: see text] [Table: see text]
Immune checkpoint targets on circulating epithelial cells in early and late breast cancer.
Authors: Habets Leo , Frenken Bettina , El Ghali Ilham , Koerber Wolfgang , Danaei Mahmoud , Kusche Manfred , Kroll Torsten , Pachmann Katharina 
Published: March 2020

e22201 Background: Our ongoing investigation of circulating epithelial cells(CEC) in early and late breast cancer with the MAINTRAC method (1ml blood, RBC lysis and fluorometric detection) has shown that CEC evade by hypoxia driven EMT (epithelial mesenchymal transition).We saw CEC with EMT and stemcellmarkers in early and late breast cancer. These cells can be found also in non cancer conditions. So far no differences in marker expression of CEC in cancer and noncancer conditions were found. This underlines the need for extended(e.g four color) analysis and allows searching for new promising targets like the immune checkpoint target PD-L1. Methods: We slightly adapted the basic MAINTRAC methodology to allow four color detection on the AMNIS FlowSight device.The IDEAS software allows comprehensive analysis of the populations. Beside four color analysis of single cells, TCA (tumor cell aggregates ) can be detected and characterized. The basic panel (EPCAMAF660.CD45PE,ALDH1FITC,DAPI) allows detection of living and death CEC and expression of the stemcell marker ALDH1. A second panel allows detection of other targets like PD-L1. Results: With the three color based original method the blood of 188 patients with early and 62 with late breast cancer were examined. No differences between conventional subgroups nor molecular subtype groups were found. In a large non cancer (n=256) control group we found high CEC counts in a group of patients with liver affections (mostly NAFLD). In these patients CEC showed the same marker ecpression .In late breast cancer only 60% of patients showed detctable cell counts.In patients with agressive disease (triple negative or HER2 enriched) mostly none or small CEC numbers were detectable.With our recently started (so far n=48) four color assay we detected coexpression of ALDH1 and PD-L1 which are more specific markers then CD44high or vimentin. Conclusions: Extended four color analysis on CEC allows monitoring of living CEC with stemcellmarker expression. Detection of immune checkpoint determinants like PD-L1on CEC is possible, further unraveling the biology of early and late breast cancer.
Abnormalities in cancer patients' coagulation system.
Authors: Gonzalez Florez Hector Alirio , Rojas M. , Quiroz J. , Mancera Y. 
Published: March 2020

e22207 Background: It is well known cancer patients may present both hemorrhagic and thrombotic abnormalities and these phenomena are difficult to diagnose and treat. Thrombotic phenomena are developed clinicly in 15% in cancer patients and it’s higher in adenocarcinomas and myeloprolipherative disorders. These complications can be the consequence of coagulations factor direct activation or chronic DIC, because of the acquired capacity of neoplastic cells for starting coagulation cascade. Methods: In this study an untreated cancer patients group were compared with another healthy controls group, older than 14 years. Patients before treatment and controls were laboratory tested. A t – test for independent samples was employed. Results: Number: patients group: 66, control group: 73. Median age: patients: 50 (17-78). Controls: 52 (18 -93). Sex: Patients: men: 35%, women: 65%. Controls: men: 52%, women: 48%. Malignancies: breast cancer 9.7%; gastric carcinoma 8.1%; cervical carcinoma 6.5%; NH lymphomas 6.5%, unknown origen metastatic carcinoma 4.8%; oral carcinoma 4.8%. Clinical stages: I: 6.3%; II: 6.3%; III: 22.9%; IV: 62.5% (metastatic) 47.9%. Thrombotic antecedents in patients group: 19.7%. There were significant differences in: Platelets count: patients: 281121, controls: 307745 (p<0.001). Protein C: 0.87 and 3.81 UI/mL, respectively (p < 0.001). Antithrombin III: 97 and 101% (p<0.001). Plasminogen: 92.9 and 101.1% (p < 0.001). Lupus anticoagulant (RVV time): 27 and 25.6” (p<0.001). There were no significant differences in PT: 18.3 and 16.9” and PTT: 31 and 34”. The same significant differences were got when the patients of every clinical stage were compared with control patients. There were no differences when the patients of every clinical stage were compared among themselves, nor between sex. Conclusions: This study shows cancer patients may have many coagulation abnormalities: anticoagulant system defects and fibrinolytic system hipoactivity, demonstrated by the significant differences found in antithrombin III, protein C and plasminogen levels between patients and controls groups. It is suggested to practice these tests to cancer patients, even without clinical coagulation disorders, to stablish prophylactic measures.
Spontaneous and cyclophosphamide-enhanced metastasis inhibited by traditional Chinese medicine (TCM) herbal mixture LQ.
Authors: Zhang Lei , Wu Chengyu , Zhang Yong , Hoffman Robert M. 
Published: March 2020

e22209 Background: Cyclophosphamide pretreatment of mice enhances metastatsis of HT1080 human fibrosarsoma cells (Cancer Res. 68, 516-520, 2008). Methods: HT1080 human fibrosarsoma cells were injected into the footpad or were injected into the epigastric cranialis vein of mice pre-treated with cyclophosphamide (CYC) or a combination of CYC and the herbal mixture LQ. The efficacy was monitored through dynamic subcellular imaging of trafficking of cancer cells in lymph nodes and blood vessels in live mice. Results: LQ significantly inhibited HT1080 spontaneous metastases to local lymph nodes in the foot-pad-injection model. In the control group, 100% of mice had lymph node metastasis, compared to 12.5% of the mice in the LQ treatment group. LQ also significantly inhibited CYC-enhanced experimental metastasis in the epigastric cranialis vein injection model. LQ prolonged the overall survival of mice in the spontaneous-lymph-node metastatic footpad-injection model. Conclusions: The TCM herbal mixture LQ shows promis to inhibit metastasis and will be further tested in other metastatic models.
Comparisons of RNA-seq results for cryopreserved (CRYO) and formalin fixed, paraffin-embedded (FFPE) samples.
Authors: Farooq Umar , Singh Prashant , Gooch Michael , Burian Linda , Sanders M. Melinda , Everson Richard Bernard 
Published: March 2020

e22211 Background: FFPE is the worldwide clinical standard for preservation of tissue samples. Although CRYO tissues are widely used for research, most gene expression assays in clinical use analyze FFPE by RT-PCR. Use of RT-PCR limits numbers of transcripts that can be studied with material available. Next Generation Sequencing promises to overcome those limitations, but for FFPE, there are concerns related to its accuracy including bias associated with RNA truncated at the 3’ end. Little data is available illustrating the extent of truncation or considering implications for bioinformatics analysis of sequencing results. Methods: Total RNA was extracted from patient consented specimens of tumor and normal bladder tissue split with matching halves processed by CRYO and FFPE. Paired end sequencing libraries 100 bp in length were generated using Illumina TruSeq RNA sample kits with minor modifications for FFPE samples. Sequencing was performed on the Illumina HiSeq 2000, aligned with TopHat using the hg19 reference sequence, and further analyzed using open source bioinformatics tools. Results: Comparing Cryo and FFPE reads for a representative specimen, the proportion of reads that mapped to the reference genome were 69% and 63% for normal, and 66% and 63% for tumor specimens. Mapped reads yielded over 25,000 significantly expressed transcripts, isoforms, and splice variants. The extent of 3’ bias was investigated by viewing data in the Integrated Genome Viewer and using Picard tools. Preliminary estimates of 3’ bias in FFPE showed 2.22 for normal and 1.48 for tumor. After accounting for bias, transcripts in CRYO vs FFPE were significantly correlated for both normal tissue and tumor (R2 = 0.76 and 0.95, respectively). Mutations previously identified in these samples by SureSelect hybrid capture system (Agilent) were also observed in the RNA-seq data. Conclusions: FFPE samples can be successfully analyzed by RNA-Seq, allowing the analysis of standard clinical samples and vast quantities of richly annotated archival specimens. Results from CRYO and FFPE analyses are similar when performed using minor modifications to sequencing library preparation and careful attention to appropriate analysis.
Association of PARP inhibitors and docetaxel resistance through suppressing a tumor microenvironment-associated secretory program.
Authors: Zhao Song , Coleman Ilsa , Coleman Roger , Nelson Peter 
Published: March 2020

e22212 Background: Acquired resistance to therapeutics accounts for the majority of treatment failures in metastatic cancer. In response to genotoxic stress induced by therapeutics such as radiation and chemotherapy, tumor microenvironment (TME) undergoes marked molecular alterations manifested by increased secretion of cytokines and growth factors, which in turn promote tumor growth, facilitate epithelial-mesenchymal transition, and ultimately result in resistance to chemotherapy. Fibroblasts are a major component of TME and a primary source of cytokines and growth factor secretion following damage. Preliminary results from our lab indicated PARP1 may be involved in regulating this secretory program. We hypothesized that PARP inhibition would suppress the TME-associated secretory program and thereby overcome chemotherapy resistance. Methods: Transcript profiles of cytokines and growth factors were analyzed with quantitative real-time PCR and cDNA microarrays in prostate fibroblasts after treatment with radiation or docetaxel, in combination with one of three PARP inhibitors (PARPi). We evaluated the effects of the docetaxel-induced fibroblast secretory program, in the absence or presence of PARPi, on the proliferation and drug sensitivity of prostate cancer cell lines. Results: Similar to radiation, docetaxel induced the secretion of cytokines and growth factors in prostate fibroblasts. PARP1 was activated by docetaxel treatment. Exposure to PARPi suppressed the docetaxel-induced secretory program. Further analysis suggested that PARPi abrogates activation of p38MAPK pathway. While conditioned medium from docetaxel-treated prostate fibroblasts stimulated growth and chemotherapy resistance, the addition of PARPi attenuated these effects. Conclusions: Docetaxel induces extracellular secretion of pro-tumorigenic cytokines and growth factors by components of the TME. PARP inhibitors attenuated docetaxel resistance through suppression of this secretory program, supporting a new mechanism of action for this class of drugs. Combinatorial use of cytotoxic agents and microenvironment-directed therapies may reduce treatment resistance.
A phase III trial of personalized chemotherapy based on serum tumor marker decline in poor-prognosis germ-cell tumors: Results of GETUG 13.
Authors: Fizazi Karim , Pagliaro Lance C. , Flechon Aude , Mardiak Jozef , Geoffrois Lionnel , Kerbrat Pierre , Chevreau Christine , Delva Remy , Rolland Frederic , Theodore Christine , Roubaud Guilhem , Gravis Gwenaelle , Eymard Jean-Christophe , Malhaire Jean-pierre , Linassier Claude , Habibian Muriel , Journeau Florence , Logothetis Christopher , Culine Stephane , Laplanche Agnes 
Published: March 2020

LBA4500 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Randomized, open-label, phase III study of pemetrexed plus carboplatin followed by maintenance pemetrexed (Arm A) versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab (Arm B) in patients with advanced nonsquamous (NS) non-small cell lung cancer (NSCLC).
Authors: Zinner Ralph , Ross Helen J. , Weaver Robert , Govindan Ramaswamy , Holden Viran R. , Chowhan Naveed Mahfooz , Beck J. Thaddeus , Waterhouse David Michael , Modiano Manuel , Rao Vijay Phooshkooru , Liu Jingyi , Koustenis Andrew , Melemed Symantha , Guba Susan C. , Ortuzar Waldo Feliu , Desaiah Durisala , Spigel David R. , Obasaju Coleman K. 
Published: March 2020

LBA8003 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Randomized proteomic stratified phase III study of second-line erlotinib (E) versus chemotherapy (CT) in patients with inoperable non-small cell lung cancer (PROSE).
Authors: Lazzari Chiara , Novello Silvia , Barni Sandro , Aieta Michele , De Marinis Filippo , De Pas Tommaso , Grossi Francesco , Mencoboni Manlio , Bearz Alessandra , Floriani Irene , Torri Valter , Bulotta Alessandra , Grigorieva Julia , Roder Joanna , Doglioni Claudio , Roder Heinrich , Righi Luisella , Foti Silvia , Bachi Angela , Gregorc Vanesa 
Published: March 2020

LBA8005 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Digoxin as an inhibitor of global hypoxia inducible factor-1α (HIF1α) expression and downstream targets in breast cancer: Dig-HIF1 pharmacodynamic trial.
Authors: Bardia Aditya , Santa-Maria Cesar Augusto , Jacobs Lisa K. , Cimino-Mathews Ashley , Huang Peng , Russell Stuart , Camp Melissa , Habibi Mehran , Lange Julie R. , Jeter Stacie , Powers Penny , Slater Shannon , Gabrielson Edward , Carducci Michael Anthony , Semenza Gregg , Stearns Vered 
Published: March 2020

TPS1144 Background: Unlike normal cells, tumor cells thrive in a hypoxic microenvironment, and intratumoral hypoxia correlates with increased tumor invasiveness, metastasis, and poor prognosis in cancer. The hypoxic microenvironment is primarily mediated through HIF1α, a transcription factor for over 200 genes involved in cellular metabolism, proliferation, and angiogenesis. In pre-clinical models, cardiac glycosides, including digoxin, act as potent inhibitors of HIF1α protein synthesis and expression of HIF1α target genes (Zhang et al, PNAS 09). Methods: Trial design: The proposed study is a randomized, controlled, two arm, pre-surgical study. Eligible patients include women with stage I-III carcinoma of the breast scheduled to undergo definitive surgery, tumor size ≥ 1cm, grade 2/3 or Ki-67 ≥ 10%, normal organ function, and no known cardiac arrhythmias. Participants will receive oral digoxin daily, or no therapy, for 14 days (±4 days) prior to scheduled surgery. Trial Objectives: 1) To evaluate whether daily oral digoxin therapy, as compared to no study drug, reduces HIF1α expression by IHC and mRNA or its target genes (VEGF, CA-9, and GLUT1) in breast cancer tissue. 2) To evaluate whether daily oral digoxin therapy, as compared to no study drug, reduces levels of serum VEGF & PAI-1, reduces tissue Ki-67 expression, and modulates proteomic profiles of breast cancer tissue. 3) To assess safety and tolerability of digoxin therapy in the pre-surgical setting. Statistical methods: The primary hypothesis is that 2 weeks of digoxin therapy will reduce the level of HIF1α expression in breast cancer tissue assessed by pathologists blinded to the treatment assignment. Our preliminary study shows the mean HIF1α expression level is 2.43. A 33% reduction would be considered clinically relevant. Allowing for up to 20% attrition, a total sample size of 64 will provide more than 85% power to detect 33% reduction with a two-sided significance level of 0.05. Target accrual: 64 (32 each arm). Funding and Acknowledgement: Dept. of Defense, Commonwealth Foundation, ASCO YIA. Contact Person: Dr. Vered Stearns, Email: vstearn1@jhmi.edu .ClinicalTrials.gov Identifier: NCT01763931. Clinical trial information: NCT01763931.