tbuckley/cabot-search huggingface dataset:
Abstract LB-119: Single-cell live imaging of paclitaxel-resistant cancer cell generation
Authors: Na Niu, Jie Zhang, Ning Zhang, Imelda Mercado-Uribe, Fangfang Tao, Zhenbo Han, Sen Pathak, Asha Multani, Jian Kuang, Jun Yao, Robert Bast, Anil Sood, Mien-Chie Hung, Jinsong Liu
Journal: Cancer Research (2016)

Abstract Polyploid giant cancer cells (PGCCs) are abundant in cancers after chemotherapy. PGCCs have generally been considered nonviable because of their inability to execute mitosis. However, our recently reported studies challenged this paradigm by showing that PGCCs were capable of tumor initiation. To understand the role of PGCCs in chemoresistance, we monitored paclitaxel-induced PGCCs by conventional and live-cell fluorescence time-lapse recording. We found that paclitaxel induced massive cell death but also initiated endoreplication to form PGCCs. These PGCCs continued to grow via endoreplication, endomitosis, or cytofission before generating new mononuclear or multinucleated daughter cells via nuclear fragmentation or budding. These daughter cells resumed mitosis with a new stable karyotype and exhibited drug resistance. Budding from PGCCs was also observed in chemotherapy-treated ovarian cancer specimens from patients. On the basis of our findings, we propose the existence of an amitotic giant cell cycle composed of four phases: initiation, maintenance, termination, and speciation. We believe this is the first report of fluorescent live-cell imaging of the birth of resistant cancer cells at the single-cell level in response to paclitaxel treatment. Our findings provide strong evidence that a stress-induced amitotic giant cell cycle may be a programmed event underlying chemotherapy resistance and cancer relapse. Citation Format: Na Niu, Jie Zhang, Ning Zhang, Imelda Mercado-Uribe, Fangfang Tao, Zhenbo Han, Sen Pathak, Asha Multani, Jian Kuang, Jun Yao, Robert Bast, Anil Sood, Mien-Chie Hung, Jinsong Liu. Single-cell live imaging of paclitaxel-resistant cancer cell generation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-119.
Dexamethasone (DEX) versus prednisone (PRED) during induction for children with high-risk acute lymphoblastic leukemia (HR-ALL): A report from the Children’s Oncology Group Study AALL0232.
Authors: N. J. Winick, W. L. Salzer, M. Devidas, J. B. Nachman, E. A. Raetz, M. L. Loh, N. A. Heerema, A. J. Carroll, J. M. Gastier-Foster, M. J. Borowitz, B. L. Wood, C. L. Willman, S. Hunger, W. L. Carroll, E. C. Larsen
Journal: Journal of Clinical Oncology (2011)

9504 Background: When compared to PRED, the administration of DEX during Induction has been associated with improved outcomes in patients with ALL. However, DEX has also been associated with an increased risk of osteonecrosis (ON) and when given in combination with an anthracycline has an increased risk of induction mortality. Methods: AALL0232 was a Phase 3, randomized trial for patients 1-30 years of age with NCI high risk B-precursor ALL that utilized a 2 x 2 factorial design with an augmented intensity BFM backbone. Patients were randomized to receive DEX 10 mg/m2/day for 14 days versus PRED 60 mg/m2/day for 28 days during Induction and high dose methotrexate (HD MTX) versus Capizzi escalating methotrexate plus PEG asparaginase (C-MTX-ASNase) during Interim Maintenance 1, forming four arms: DH, DC, PH, and PC. In June 2008, the study was amended to exclude patients > 10 years of age from the Induction steroid randomization due to an excessive incidence of ON. Results: Between January 2004 and September 2010, 802 patients 1-9 years of age, and prior to June 2008, 1035 patients > 10 years of age were randomized to the four arms. The 5-year event free survival (EFS) for patients 1-9 years of age randomized to receive DH, DC, PH, or PC was 93.7 + 5.4%, 84.1 + 8.4%, 81.2 + 7.7%, and 84.0 + 6.9%, respectively, p=0.03. The 5 year EFS of patients > 10 years of age randomized to DEX versus PRED prior to June 2008 was 74.7 + 4.6% and 76.5 + 4.6%, respectively, p=0.80. The incidence of ON at 36 months for patients 1-9 and > 10 years of age was 3.1 + 0.9% and 19.6 + 1.6%, respectively. For patients > 10 years old, there was a higher rate of ON among those randomized to DEX before June 2008 as compared to PRED (24.3% versus 15.1%, p=0.0007). Induction death rates were similar between the DEX and PRED arms in both age groups. Conclusions: The DH arm was the superior arm for patients 1-9 years of age. There was no EFS advantage for patients > 10 years of age receiving DEX versus PRED during Induction, but there was a significantly higher risk of ON with DEX. We conclude the DH regimen is preferred for patients 1-9 years old and that PRED given during Induction is preferred for those > 10 years old.
Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement
Authors: Debbie Saslow, Kimberly S. Andrews, Deana Manassaram‐Baptiste, Lacey Loomer, Kristina E. Lam, Marcie Fisher‐Borne, Robert A. Smith, Elizabeth T. H. Fontham
Journal: CA A Cancer Journal for Clinicians (2016)

Abstract Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375–385. © 2016 American Cancer Society.
Viability of endothelial cells after ultrasound-mediated sonoporation: Influence of targeting, oscillation, and displacement of microbubbles
Authors: Tom van Rooij, Ilya Skachkov, Inés Beekers, Kirby R. Lattwein, Jason D. Voorneveld, Tom J.A. Kokhuis, Deep Bera, Ying Luan, Antonius F.W. van der Steen, Nico de Jong, Klazina Kooiman
Journal: Journal of Controlled Release (2016)
What’s the plan, Mr Hunt?
Authors: Fiona Godlee
Journal: BMJ (2016)

If Jeremy Hunt had hoped for a respite from being health secretary for England, he’s not letting on. He greeted his return to “the best job in government” with apparent delight (doi:10.1136/bmj.i3946), a sentiment not shared, though, by most of those working in the NHS (doi:10.1136/bmj.i3972). Nor does he have the confidence of fellow MPs. A highly critical report from the health select committee accuses him of misleading the public about how much money the NHS …
Invasive Candida Infections in Pediatric Patients Treated on the Pilot Study of Decitabine and Vorinostat with Chemotherapy for Relapsed ALL: A Report from the Therapeutic Advances in Childhood Leukemia &amp; Lymphoma (TACL) Consortium
Authors: Michael J. Burke, Patrick Brown, Lia Gore, Richard Sposto, Deepa Bhojwani, Bill H Chang, Steven G. Dubois, Paul S Gaynon, Julia Glade-Bender, Kenneth Matthew Heym, Maria Luisa Sulis, Jessica A. Pollard, Anupam Verma, Van Huynh
Journal: Blood (2014)
Expression profiling of peripheral blood (PB) enriched for circulating tumor cells (CTCs) in testicular germ cell tumors (TGCTs).
Authors: Michal Mego, Paulina Gronesova, Vera Miskovska, Jana Obertova, Patrik Palacka, Jan Rajec, Zuzana Sycova-Mila, Bibiana Vertakova-Krakovska, Michal Chovanec, Pavol Janega, Daniela Svetlovska, Vanda Usakova, Peter Bujdak, Stanislav Spanik, Dalibor Ondrus, Jozef Mardiak
Journal: Journal of Clinical Oncology (2013)

4556 Background: CTCs are prognostic in several types of tumors and are easily accessible for repeat examination. TGCTs represent a model for the cure of cancer. Nonetheless, a small proportion of patients develop disease recurrence. We investigated expression profiling of PB enriched for CTCs in TGCTs aimed to identify expression signature associated with treatment resistance. Methods: This prospective study included 30 patients (pt) treated with first line (27 pt) or salvage (3 pt) chemotherapy. CD45 - peripheral mononuclear cells (PBMCs) were isolated from 10mL of PB on day 1 and on day 22 of first cycle of chemotherapy. Isolated PBMC were depleted of cells of hematopoietic origin (CD45 + ) using RossetteSep kit negative selection with anti-CD45 antibody. CD45-depleted PBMC represent compartment enriched for CTCs, as showed previously. RNA was extracted from CD45 - PBMCs and the expression profiles were obtained using Roche NimbleGen microarrays. Data analysis was processed in R using a limma package followed by GO analysis and MetaCore pathway analysis. Results: Six patients achieved unfavorable response to chemotherapy (other than CR or PR with negative serum markers). We identified 1,506 and 211 genes that were expressed at significantly different levels (FDR&lt;0.05) on day 1 and day 22 of chemotherapy, respectively, with 108 overlapping genes. Cluster analysis using principal component analysis showed, that 5 of 6 samples from patients with unfavourable response to chemotherapy form clearly defined cluster opposed to samples from patients with favourable response. Based on pretreatment expression profiling using MetaCore pathway analysis software, we further identified 758 genes, belonging to several critical functional groups such as immune response, signal transduction, cell proliferation, cell cycle progression, or apoptosis, to be significantly differentially expressed in patients with favourable vs. unfavourable response. Conclusions: Our data suggests that expression profiling of PB enriched for CTCs in TGCTs is feasible, and show great promise in identifying new therapeutic targets and gene expression signature associated with treatment resistance.
Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab
Authors: N. Lassau, B. Coiffier, M. Kind, V. Vilgrain, J. Lacroix, M. Cuinet, S. Taieb, R. Aziza, A. Sarran, C. Labbe-Devilliers, B. Gallix, O. Lucidarme, Y. Ptak, L. Rocher, L.M. Caquot, S. Chagnon, D. Marion, A. Luciani, S. Feutray, J. Uzan-Augui, B. Benatsou, J. Bonastre, S. Koscielny
Journal: Annals of Oncology (2016)
Saliva induces expression of antimicrobial peptides and promotes intracellular killing of bacteria in keratinocytes by epidermal growth factor receptor transactivation
Authors: T. Mohanty, P. Alberius, A. Schmidtchen, K. Reiss, J.‐M. Schröder, O.E. Sørensen
Journal: British Journal of Dermatology (2016)

Wounds in the oral cavity, constantly exposed to both saliva and bacteria, heal quickly without infection. Furthermore, during licking of skin wounds, saliva promotes wound healing and plays a role in keeping the wound free of infection.To investigate whether saliva induces expression of antimicrobial peptides (AMPs) in human epidermal keratinocytes and whether saliva promotes clearance of intracellular bacteria in these cells.Expression of AMPs was investigated in the oral mucosa and ex vivo injured skin by immunohistochemistry. Human beta-defensin-3 expression was investigated in epidermal keratinocytes after saliva stimulation, using real-time polymerase chain reaction and immunofluorescence.We found higher expression of AMPs in the oral mucosa than in the epidermis. Saliva accelerated the injury-induced expression of AMPs in human skin ex vivo and was a potent inducer of the expression of AMPs in epidermal keratinocytes. The expression of AMPs was induced by metalloproteinase-dependent epidermal growth factor receptor (EGFR) transactivation mediated by a salivary lipid. Saliva increased the intracellular clearance of Staphylococcus aureus in keratinocytes through EGFR activation.These findings suggest a previously unreported role of saliva in innate immunity and demonstrate for the first time that saliva induces gene expression in epidermal keratinocytes.
Abstract 4754: Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer
Authors: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi
Journal: Cancer Research (2016)

Abstract Objective. To test if hormone or growth factor receptor expression is associated with survival among patients with high grade serous ovarian cancer (HGS OvCa) we analyzed tumor mRNA expression microarray and clinical data from The Cancer Genome Atlas (TCGA). Methods. HGS OvCa patients were surgically staged prior to treatment with IP (n = 90) or IV-only (n = 398) chemotherapy. Multivariate Cox proportional-hazards regression tested associations of expression of 9 hormone or growth factor receptors with progression free survival (PFS) and overall survival (OS). Hazard ratios are hazard per each one standard deviation increase in gene expression. Expression was analyzed as a continuous variable by restricted mean survival analysis. Mean PFS or OS were compared between IP and IV groups by permutation testing stratified by expression. P-values were two-tailed. Results. Expression of ESR1, PGR, FSHR, LHCGR, MET, and EGFR were not associated with PFS or OS. TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and PFS (HR 1.18 (1.05-1.33), p = 0.006) among IV-only treated patients. ERBB2 expression was associated with decreased OS (HR 1.48 (1.05-2.10), p = 0.027) among patients who received IP chemotherapy. Using multigene (ESR2, PGR, TSHR, and ERBB2) analysis, among the IP group, ERBB2 (HR 1.76 (1.11-2.79), p = 0.015) and ESR2 (HR 0.28 (0.08-0.93), p = 0.037) were associated with OS. Only TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and decreased PFS (HR 1.18 (1.05-1.33), p = 0.007) on multigene analysis of IV-only treated patients. OS and PFS decreased steeply at high expression of TSHR and ERBB2. Among patients with upper 10th percentile TSHR expression, no significant difference in mean OS or PFS was observed between patients treated with IP versus IV-only chemotherapy. Patients with lower TSHR expression (&amp;lt; 90% percentile) experienced a mean 13.7-month increased OS and 16.4-month increased PFS associated with IP chemotherapy (p &amp;lt; 0.0001). Conclusions. Among HGS OvCa patients treated with IV-only chemotherapy, increased tumor TSHR expression was associated with decreased OS and PFS. High TSHR expression characterized patients who did not benefit from IP chemotherapy. Citation Format: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi. Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4754.
Abstract 1937: Dysregulation of lincRNAs is a major driver of aberrant epigenomes during tumorigenesis
Authors: Callie R. Merry, Megan E. Forrest, Sanford Markowitz, Ahmad M. Khalil
Journal: Cancer Research (2016)

Abstract It has now been unequivocally demonstrated that the process of tumorigenesis is driven by both genetic and epigenetic alterations, but the mechanisms of epigenetic dysregulations remain to be elucidated. Work in our laboratory has demonstrated that numerous long intergenic non-coding RNAs (lincRNAs) become dysregulated in human cancers, and a significant subset of these lincRNAs are associated with histone-modifying enzymes and DNA methyltransferases in healthy, non-tumor cells. Based on these observations, we tested an exceptionally novel hypothesis that dysregulation of chromatin-associated lincRNAs is a major mechanism driving cancer-associated aberrant epigenomes. To test this novel concept, we have performed experiments to modulate the expression of specific chromatin-associated lincRNAs in cancer cells, and assessed their impact on the epigenome. Consistent with our hypothesis, modulating the expression of lincRNAs in cancer cells resulted in massive reprogramming of their epigenomes. These epigenomic changes impacted the growth of cancer cells and global gene expression. Mapping the genomic occupancy sites of lincRNAs, and intersection of those sites with altered genomic regions in tumors, further supported direct roles of lincRNAs in modulating chromatin structure. These findings demonstrate key roles of chromatin-associated lincRNAs in suppressing tumorigenesis in normal human tissues by regulating the epigenome. Citation Format: Callie R. Merry, Megan E. Forrest, Sanford Markowitz, Ahmad M. Khalil. Dysregulation of lincRNAs is a major driver of aberrant epigenomes during tumorigenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1937.
Abstract 4415: CPAP contributes to HCC malignancy through regulating inflammatory pathways
Authors: Liang-Yi Hung.
Journal: Cancer Research (2016)

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies, and the third most prevalent cause of cancer-related death worldwide. Its curative treatments are limited to liver resection and liver transplantation. In addition, HCC is characterized by hypervascular tumor which is described as a formation of many blood vessels during tumor growth. It has been shown that the transcription factors NF-κB and STAT3, both of which play an important role in the inflammatory pathway, are activated in HCC. Centrosomal P4.1-associated protein (CPAP) plays a vital role in centrosomal function and is identified as a transcriptional co-activator of NF-κB or STAT5. Our studies indicated that CPAP is overexpressed in HCC and involved in regulating the TNF-α-NF-κB and IL-6/STAT3 pathways. By reporter assay, Q-PCR, immunoblotting and ELISA analysis, we found that the activity of NF-κB or STAT3 is increased in HCC cells with CPAP overexpression upon TNF-α or IL-6 stimulation. Overexpressed GFP-CPAP significantly enhances NF-κB or STAT3-driven transcriptional activation and increases the expression of NF-κB or STAT3-targeted genes in response to TNF-α or IL-6 treatment. Furthermore, by immuoprecipitation and in situ PLA, CPAP could form a complex with NF-κB or STAT3. Expression of CPAP and NF-κB or STAT3 had a positive correlation in clinical HCC tissues. Interestingly, overexpression of GFP-CPAP augmented the expressions of pro-inflammatory cytokines and promoted tumor growth and metastasis in the orthotopic and splenic mouse models. The expression of CPAP was positively correlated with plasma proinflammatory cytokines expression in HCC patients. Our results suggest that CPAP participates in activating the TNF-α-NF-κB and IL-6/STAT3 pathways, which contributes to HCC malignancy. Citation Format: Liang-Yi Hung. CPAP contributes to HCC malignancy through regulating inflammatory pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4415.
Abstract 3412: Prognostic significance of plasma ghrelin in patients with gastric cancer
Authors: Saeed Soleyman-Jahi, Kazem Zendehdel, Afshin Abdirad, Amir Afraz Fallah, Sevil Ghasemi, Fatemeh Sadeghi
Journal: Cancer Research (2016)

Abstract Background: Different prognosis observed for patients of the same clinical stage in gastric cancer, emphasizes the fact that new biological prognostic factors are needed to complement clinical staging. We aimed to investigate the prognostic significance of plasma ghrelin in gastric cancer patients. Methods: In this prospective study, we included 83 gastric cancer patients from Cancer institute of Tehran, Iran. All the patients were candidates for gastrectomy with or without preoperative neoadjuvant chemotherapy (PNC). The patients were followed for three years. Demographic, clinical and para clinical data were registered. Using an ELISA based assay plasma levels of total and active ghrelin were assessed prior to and one week after the operation. Univariate and multivariate COX analyses were used to investigate the independent predictors of patients overall survival. Results: The mean (±SD) age of the patients was 60.3±13.6. Sixty-five (78.3%) patients were male. Majority of the patients had gastric adenocarcinoma (95.2%). Thirty-seven (44.6%) patients had TNM stage II or I. Poorly differentiated grade was detected in 29 (34.9%) of the patients. Forty-eight (57.8%) patients received PNC before the operation. Mean (±SD) survival was 529 ± 373 days. Mean level of the plasma total ghrelin was 269.8±268.7 and 108.7±91.2 (pg/ml) before and after the operation, respectively (P&amp;lt;0.001). Mean level of the plasma active ghrelin was 68.0 ± 63.8 and 44.0± 29.6 (pg/ml) before and after the operation, respectively (P&amp;lt;0.001). Patients in the upper half or highest quartile of postoperative total ghrelin had better survival compared to the corresponding subgroups (Log rank test P = 0.02 and P&amp;lt;0.001, respectively). Multivariate COX model revealed that late TNM stage (HR = 2.93, 95% CI: 1.37-6.27), no PNC (HR = 2.18, 95% CI: 1.08-4.37), history of significant weight-loss (HR = 2.32, 95% CI: 1.04-5.00) and lower quartile (≤38 pg/ml) of postoperative plasma total ghrelin (HR = 3.74, 95% CI: 1.45-9.63) predicted poor survival of patients. The level of other ghrelins did not show independent prediction of survival. Conclusion: Our findings showed that low level of plasma total ghrelin after the gastrectomy could independently predict poor survival in gastric cancer patients. This emphasizes both prognostic and therapeutic significance of this biomarker in gastric cancer. Citation Format: Saeed Soleyman-Jahi, Kazem Zendehdel, Afshin Abdirad, Amir Afraz Fallah, Sevil Ghasemi, Fatemeh Sadeghi. Prognostic significance of plasma ghrelin in patients with gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3412.