tbuckley/cabot-search huggingface dataset:
Abstract A22: Targeting S100p Sensitizes Pancreatic Cancer Cells towards Gemcitabine
Authors: Shing Chun Tang, Yangchao Chen
Journal: Cancer Research (2016)

Abstract Introduction: S100P (S100 Calcium Binding Protein P) is a member of S100 family proteins and plays important roles in cancers. S100p is up-regulated in Pancreatic Ductal Adenocarcinoma (PDAC). There is an up-regulation of S100p in pancreatic intraepithelial neoplasia (PanIN) tissue samples as well as a correlation of its expression with the grade of PanIN. S100p interacts with Receptor for Advanced Glycation End product (RAGE), whose downstream signaling pathways MAPK and NF-kB are responsible for the tumor progression and chemo resistance of PDAC. Thus, abrogation of the RAGE activation may be beneficial towards pancreatic cancer treatment. Therefore, we would like to investigate the growth and chemosensitivity of PDAC cells upon silencing S100p. Methodology: The S100p in PDAC cell lines Capan2 and CFPAC1 was knocked down by lentiviral shRNA. Cell growth, wound healing, colonies formation ability and the tumorigenicity of the S100p knocked down cell lines were evaluated. Moreover, the chemosensitivity of PDAC cells with S100p knockdown towards gemcitabine was evaluated with cell viability assay. Result: Knock-down of S100p inhibited PDAC cell growth and cell migration. RNAi targeting S100p in PDAC cells inhibited cell proliferation. Knock-down of S100p inhibited PDAC tumor growth in nude mice. Enhanced sensitization to gemcitabine on PDAC cells with S100p knock-down was also observed. Conclusion: Our findings suggest that silencing S100p not only can inhibit the in vitro and in vivo growth of PDAC, but also can sensitize PDAC towards gemcitabine treatment. Our result provides a promising alternative by targeting S100p in combinatorial chemotherapy development for pancreatic cancer . Financial support: The work described in this paper was supported by grants from the General Research Fund, Research Grants Council of Hong Kong (CUHK462109, CUHK462713 and 14102714), National Natural Science Foundation of China (81101888) and Direct Grant from CUHK to YC. Citation Format: Shing Chun Tang, Yangchao Chen.{Authors}. Targeting S100p Sensitizes Pancreatic Cancer Cells towards Gemcitabine. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A22.
Abstract 3517: Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis
Authors: Jun Yan, Qing Zhang, Wei Zhao, Changxiao Ye, Cunjie Chang, Xiaojing Huang, Junlong Zhuang, Jiannan Song, Yangyan Cui, Isaac Eliaz, Bing Shen, Ruimin Huang, Hao Ying, Hongqian Guo
Journal: Cancer Research (2015)

Abstract EZH2, a histone H3K27 methyltransferase, plays an essential role in regulation of cell proliferation, survival, invasiveness and cancer stem cell (CSC) maintenance. The upregulation of the histone methyltransferase EZH2 is frequently detected in various cancer types, including urinary bladder cancer (UBC). However, the mechanisms underlying its role in cancer cell are not yet fully understood. Honokiol, a biologically active biphenolic compound isolated from the Magnolia spp, has been linked with anticancer activities; however, its mechanisms is poorly understood. In this study, we investigated the in vitro and in vivo effects of honokiol on UBC cells and whether honokiol can modulate EZH2 mediated network. By employing MTT, colony formation, wound healing, transwell invasion, Western blot, and Aldofluor stem cell detection assays, honokiol was shown to inhibit human UBC cell proliferation, survival, CSC maintenance, migration and invasion. Immunoblotting assay showed that the reduction of EZH2 expression level by honokiol was correlated with the decreases of MMP9, CD44, Sox2, Notch1. Forced expression of EZH2 reversed honokiol induced cell growth arrest and low clonogenicity, indicating that EZH2 is a major downstream target for honokiol in UBC cells. Since EZH2 is essential for gene expression repression, we screened 24 cancer related miRNAs and found that tumor suppressor miR-143 was the most induced miRNA by honokiol treatment. Further quantitative RT-PCR, chromatin immunoprecipitation (ChIP) and functional analysis revealed that EZH2 directly inhibited the expression of miR-143, whereas the inhibition of miR-143 partially rescued the EZH2 knockdown-induced cell growth arrest and reduced clonogenicity. Moreover, in vivo investigation using xenograft analysis in athymic nude mice indicated that honokiol treatment inhibited tumor progression, which was associated with reduced EZH2, CD44, Sox2, Notch1 and MMP9, and increased expression of miR-143. Altogether, our data indicated that honokiol inhibited human UBC tumor growth and aggressiveness through suppression of EZH2 function and induction of its target, miR-143, and that honokiol is promising candidate for chemoprevention and/or therapeutic treatment for bladder cancer. Citation Format: Jun Yan, Qing Zhang, Wei Zhao, Changxiao Ye, Cunjie Chang, Xiaojing Huang, Junlong Zhuang, Jiannan Song, Yangyan Cui, Isaac Eliaz, Bing Shen, Ruimin Huang, Hao Ying, Hongqian Guo. Honokiol inhibits bladder tumor growth by suppressing EZH2/miR-143 axis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3517. doi:10.1158/1538-7445.AM2015-3517
Adult Acute Lymphoblastic Leukemia: A Cost Effective Strategy and Limitations of Intensification of Therapy in India
Authors: Punit Jain, Prashant Deshpande, Anu Korula, Nisham P N, Ansu Abu Alex, Fouzia NA, Kavitha Lakshmi, Aby Abraham, Poonkuzhali Balasubramanian, Alok Srivastava, Biju George, Vikram Mathews
Journal: Blood (2015)
SURG-04. DIFFERENCES BETWEEN INTRAOPERATIVE MRI FLAIR AND T2 TUMOR VOLUMES COMPARED TO POSTOPERATIVE CORRESPONDING VOLUMES IN GLIOMA SURGERY
Authors: Randy Jensen
Journal: Neuro-Oncology (2016)

Intraoperative MRI is a useful tool in the operative management of human gliomas. In non-contrast enhancing gliomas, and to a lesser extent enhancing tumors, the T2 and FLAIR signals are important targets to determine target volumes for resection margins. We hypothesized that intraoperatively (IO) obtained MRI T2 and FLAIR signal volumes might not reflect corresponding post-operative volumes due to tumor edema after resection and brain manipulation. We examined 100 patients, average age 49.5 (range 16-82) 37 females and 63 males, who underwent intraoperative imaging during glioma surgery. We excluded patients with postoperatively diagnosed non-glioma pathology or if a new vascular injury was identified on diffusion-weighted imaging. Volumetric assessment of T2 and FLAIR signals were performed using the OSRIX image analysis program and ratios calculated for intraoperative and post-operative ratios of FLAIR and T2 MRI sequences for each patient. We examined 6 grade I gliomas (DNET, ganglioglioma, JPA) with postop/intraop FLAIR ratios of 3.30 +/-3.16 and T2 ratios of 3.15+/-3.74. In a similar fashion we found that similar ratios of FLAIR and T2 images for 25 Low-grade astrocytomas were 10.85+/-18.34 and T2 of 9.24+/-15.49; 10 oligodendrogliomas of 1.95+/-1.19 for FLAIR and 2.04+/- 1.51 for T2; 8 Anaplastic Astrocytomas with 4.30+/-7.91 for FLAIR and 3.33+/-4.69 for T2; 5 Anaplastic oligodendrogliomas with 2.34+/-3.11 and 2.04 +/-2.43 and 46 Glioblastomas with 2.11+/-2.89 and 2.22 +/-3.28. Postoperative FLAIR and T2 signal volumes are significantly higher than intraoperatively obtained corresponding volumes for all gliomas studied. Further work will be required but this study questions the validity of T2 and FLAIR images obtained intraoperatively.
Targeting Anaplerotic Pathways That Support Fatty Acid Metabolism as a Therapeutic Strategy for Hematological Malignancies: The Achilles’ Heel of the Warburg Effect.
Authors: Ismael J. Samudio, Michael Fiegl, Marina Konopleva, Kumar Kaluarachchi, John S. McMurray, Borys Korchin, Karen Clise Dwyer, Romain Harmancey, Patrick Guthrie, Heinrich Taegtmeyer, Michael Andreeff
Journal: Blood (2008)
R-CHOP Versus (vs) CHOP Followed by Maintenance Rituximab (MR) Vs Observation In Older Diffuse Large B-Cell Lymphoma (DLBCL) Patients (pts): Long-Term Follow-up of Intergroup E4494/C9793
Authors: Vicki A. Morrison, Fangxin Hong, Thomas M. Habermann, Richard I. Fisher, Bruce D. Cheson, Brad Kahl, Sandra J. Horning, Bruce A. Peterson
Journal: Blood (2010)
Robert William Nicholson
Authors: Andrew Evans
Journal: BMJ (2015)

Robert William Nicholson was born in 1948 and educated at Altrincham Grammar School and Manchester University Medical School. He gained the degree of MB ChB in June 1971, passing with distinction in surgery and also winning the Dunville prize in surgery. He secured his fellowship of the Royal College of Surgeons of England in 1976. In 1980 he was awarded an MD from the University of Manchester for his work on hepatobiliary iminodiacetic acid (HIDA) scanning. His postgraduate training took place in Manchester, and it was while working at Manchester Royal Infirmary that he became interested in the subspecialty of coloproctology. He spent a sabbatical period at St Mark’s Hospital in London, where he worked with John Northover and James …
Usefulness of the Quantitative Follow-up of Chimerism in Cell-Free Plasma DNA for the Prediction/Early Diagnosis of Complications After Hematopoietic Stem Cell Transplantation
Authors: Carolina Martinez-Laperche, Victor Noriega, Leyre Bento, Milagros Gonzalez-Rivera, Pascual Balsalobre, Mi Kwon, David Serrano, Jorge Gayoso, Jose L. Diez-Martin, Ismael Buno
Journal: Blood (2012)
Sexual side effects (SSE) reported by adolescent/young adult (AYA) versus older cancer survivors.
Authors: C. E. Hill-Kayser, C. Vachani, M. K. Hampshire, G. A. Di Lullo, J. M. Metz
Journal: Journal of Clinical Oncology (2011)

9120 Background: AYA survivors may experience unique SSE compared to older survivors, and these may be difficult to measure. This Internet based study evaluates patient-reported SSE during cancer survivorship. Methods: Data were gathered via a convenience sample frame from cancer survivors voluntarily utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLink website, it provides customized guidelines for survivor care. During use of the tool, survivors are queried regarding late effects for which they are at risk. All data have been maintained with IRB approval. Results: 3222 cancer survivors answered queries regarding SSE - 392 AYA and 2830 older survivors. Median age of AYA survivors was 30 (range 18–35; median diagnosis age 27). Median age of older survivors was 54 (range 36–93, median diagnosis age 50). AYA survivors were 70% female and older were 76% female. In the AYA cohort, most common cancer diagnoses were hematologic (30%), breast (25%), and genitourinary (GU) (18%), compared to breast (44%), gastrointestinal (11%), and GU (10%) in the older cohort. Among males, erectile dysfunction (ED) was reported by 7% of AYA and 33% of older survivors. Of these, 86% and 94%, respectively, reported no ED prior to treatment; 14% and 93%, respectively, reported that they had not maintained an erection until completion of intercourse since cancer treatment, and 23% and 15%, respectively, reported that they could do so about 50% of the time. Retrograde/dry ejaculation was reported by 53% of AYA and 23% of older survivors. Among females, sexual concerns such as vaginal dryness and shrinkage were reported by 47% of AYA and 59% of older survivors. Conclusions: Male and female cancer survivors using this tool report significant SSE after cancer treatment. SSE reported by AYA versus older male survivors differ, with AYA survivors reporting more retrograde/dry ejaculation and older survivors reporting more ED. SSE appear prominent among female survivors of all ages. This tool offers a unique way for survivors to report their experiences; the data reported here may be of significant impact in future patient counseling and survivor care.
507. AAV-Mini-Agrin for Laminin-alpha2 Deficient CMD
Authors: Chunping Qiao, Yi Dai, Viktoriya Nikolova, Jianbin Li, Juan Li, Sheryl Moy, Xiao Xiao
Journal: Molecular Therapy (2015)

Laminin alpha2 (merosin)-deficient congenital muscular dystrophy (CMD) (MDC1A) is characterized by severe muscle wasting, premature death in early childhood, and lack of effective treatment. The laminin alpha2 gene (around 10kb) is too large to fit into adeno-associated viral (AAV) vectors. Alternatively, a mini-agrin, which has similar function as the laminin alpha2, is utilized as the therapeutic gene. Our previous study with AAV1-mini-agrin gene therapy in dyw/dyw mice showed dramatic therapeutic effects in muscle pathology, but weak on peripheral neuropathy. The objective of the current study was to see whether the nerve pathology in MDC1A mice could be improved by mini-agrin using the AAV9 vector, which has superior ability to transduce nervous system. AAV9-mini-agrin (2 × 10^11vg/pup) was injected into 2 to 3 days old homozygous dyw/dyw pups via the temporal vein. The gene therapy treatment significantly improved mouse body weight (15 ± 45g in treated mice vs. 10.±.09g of untreated homozygous mice at 11 weeks of age, n=6, p< 0.001) and quadrupled life span (41.±0.04 wks of average life span in treated group vs. 10.18±.12 wks in untreated group, n= 9 to 24, p<0.0001, Fig a). In tests for motor function, untreated dyw/dyw mice were hypoactive in an open field and had overt deficits in a marble-burying assay. AAV9-mini-agrin gene therapy led to significant increases in locomotion (p=0.0373) and a marked rescue of marble-burying (Fig b. p=0.0068), an indication of both nerve and muscle functions. Gene therapy also resulted in a significant improvement in nerve pathology vs. the untreated controls shown by toluidine blue staining with more myelinated nerve fibers, and partial restoration of the basal lamina shown by electron microscopy in the treated mice. More importantly, the treated dyw/dyw male and female mice become fertile, which has never been seen before. Genotyping of the unborn pups confirmed that they were all homozygous dyw/dyw mice. This indicates that mini-agrin can partially replace the function of laminin alpha-2 in MDC1A and achieve therapeutic effects in muscle pathology, peripheral neuropathy, and fertility. This study represents a significant advancement in AAV-mediated gene therapy for MDC1A. Fig. Life span extension and functional improvement by the treatment. a. Both AAV9-CMV-mini-agrin and AAV9-CB-mini-agrin treatment resulted in significant improvement in mouse survival. n = 9 to 24, p < 0.0001. b. Treatment led to an overt increase in marble-burying. n=5, * p< 0.01.
Abstract 3785: Cdk1 coordinates telomere replication by regulating the temporal recruitment of telomerase and the CST complex
Authors: Veena Gopalakrishnan, Chang-Ching Liu, Lai Fong Poon, Tingdong Yan, Shang Li
Journal: Cancer Research (2015)

Abstract Telomeres are nucleoprotein structures that cap the ends of linear chromosomes. They ensure genomic stability and complete replication of the genome. The enzyme telomerase mediates telomere elongation. Considering that telomerase is up-regulated in about 90% of human cancers and telomerase-mediated telomere elongation is significantly deregulated in cancers, insights from our study can be used to target the telomere replication machinery for therapeutic intervention in cancer. In our study, we use budding yeast to understand the mechanism of telomere maintenance. In budding yeast, Cdk1 coordinates the cell cycle-dependent elongation of telomere by telomerase. Cdk1 phosphorylates the telomere-specific ssDNA binding protein, Cdc13, which promotes the recruitment of telomerase to the telomere and thereby, telomere elongation. Cdc13 is also an integral part of the CST (Cdc13-Stn1-Ten1) complex, which provides the protective cap at the telomere and inhibits telomere elongation by telomerase. Therefore, the telomere length homeostasis is balanced between these two telomerase-extendable and CST-unextendable states. However, the cellular signaling that regulates the switch between these two states is largely unknown. Here we show that Cdk1 phosphorylates Stn1 sequentially to that of Cdc13. Cdk1-dependant phosphorylation of Stn1 is essential for telomere maintenance in vivo, CST stability and the inhibition of telomerase at the telomeres. By controlling the timing of Cdc13 and Stn1 phosphorylation during cell cycle progression, Cdk1 coordinates the recruitment of telomerase holoenzyme and CST complex to the telomeres respectively and hence the switch between the telomerase-extendable and CST-unextendable states of the telomeres in budding yeast. With increasing evidence of human CST complex being involved in telomere length maintenance, the results from my study will provide insights into telomere homeostasis in humans and its disruption in cancers. Citation Format: Veena Gopalakrishnan, Chang-Ching Liu, Lai Fong Poon, Tingdong Yan, Shang Li. Cdk1 coordinates telomere replication by regulating the temporal recruitment of telomerase and the CST complex. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3785. doi:10.1158/1538-7445.AM2015-3785
Comparative Blood Group Profiling of Human Erythroid Cells (EBs) Generated from Adult Blood (AB), Cord Blood (CB), Human Embryonic Stem Cells (hESC) and Induced Pluripotent Stem Cells (iPS)
Authors: Barbara Ghinassi, Maria Themeli, Kai-Hsin Chang, Gregory Halverson, Ghazala Hashmi, Michel Sadelain, Thalia Papayannopoulou, Anna Rita F Migliaccio, Carolyn Whitsett
Journal: Blood (2011)
Abstract 3691: A chemical therapeutic screen identifies new targets for wt/wt melanoma
Authors: Daniel Verduzco, Keiran Smalley
Journal: Cancer Research (2015)

Abstract Once advanced, melanoma is one of the deadliest forms of cancer. Metastatic melanoma has a 5-year survival rate of about 15%. Treatment of melanoma is based by driver mutation - BRAF-mutant, NRAS-mutant, and melanomas wild-type for BRAF and NRAS, termed “wt/wt melanomas”. While targeted therapies are available for BRAF or NRAS mutant melanomas, no effective targeted therapeutic options are available for wt/wt melanomas. Furthermore, chemotherapy rapidly fails for this third subtype prioritizing the need for novel therapies. We seek to overcome this problem by identifying compounds to target wt/wt melanoma. To this end, we have performed a chemical screen of clinically relevant compounds against 8 wt/wt melanoma cell lines. In our screen, we have identified compounds that specifically target critical proteins, such as ALK, PLK1, and PI3K. Exome sequencing of each wt/wt melanoma line is being performed to uncover specific genetic signatures that would allow for specific susceptibility to each hit from the screen. This work will allow us to develop personalized therapies for the treatment of patients with wt/wt melanoma. Citation Format: Daniel Verduzco, Keiran Smalley. A chemical therapeutic screen identifies new targets for wt/wt melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3691. doi:10.1158/1538-7445.AM2015-3691
Abstract POSTER-THER-1440: Targeted delivery of doxorubicin loaded nanobins to ovarian cancer cells through the urokinase plasminogen activator system
Authors: Yilin Zhang, Elden P. Swindell, Patrick L. Hankins, Hilary A. Kenny, Thomas V. O'Halloran, Andrew P. Mazar, Ernst Lengyel
Journal: Clinical Cancer Research (2015)

Abstract The therapeutic efficacy of antitumor drugs is often limited by non-specific, systematic delivery. Here we report a novel targeted delivery platform designed by coupling liposomal nanobins (NB) with the urokinase plasminogen activator receptor (u-PAR) antibody (ATN-658). The urokinase system is overexpressed in epithelial ovarian cancer (OvCa) cells and is expressed only at low levels in normal cells. Doxorubicin (Dox), a FDA approved antitumor drug, had been loaded into the nanobins as a payload. The size and surface charge of the nanobins were optimized to facilitate specific binding to u-PAR expressing OvCa cells. Confocal and transmission electron microscopy showed that ATN-658-NB(Dox) was internalized in OvCa cells in a receptor-dependent manner and was released from endosomes as a function of time. This uptake could be blocked by stably down-regulating u-PAR expression in the OvCa cells using shRNA. In an orthotopic ovarian cancer model, athymic mice treated with ATN-658-NB(Dox) had a significantly greater reduction in tumor burden (0.06±0.01g versus 0.1±0.01g; p&amp;lt;0.001) than mice treated with NB(Dox), which was corroborated by in vivo fluorescence imaging results. A survival study showed that targeted nanobins prolonged the survival of mice by 3 days (43 days versus 40 days, median survival) as compared to untargeted nanobins. Immunoblot analysis of tumor sections showed that targeted nanobins induced apoptosis (cleaved caspase 3) and inhibited proliferation (Ki-67) more efficiently when compared to untargeted nanobins. Furthermore, tumor-targeted delivery of ATN-658-ND(Dox) was confirmed by ex vivo fluorescence imaging, FACS analysis, and confocal microscopy. Taken together, our findings show that receptor-mediated delivery of targeted nanobins to cancer cells could serve as a novel approach to ovarian cancer treatment. Citation Format: Yilin Zhang, Elden P. Swindell, Patrick L. Hankins, Hilary A. Kenny, Thomas V. O’Halloran, Andrew P. Mazar, Ernst Lengyel. Targeted delivery of doxorubicin loaded nanobins to ovarian cancer cells through the urokinase plasminogen activator system [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1440.
CQC demands improvement at London hospital where mothers “could leave with wrong baby”
Authors: Clare Dyer
Journal: BMJ (2016)

The Royal London Hospital has been ordered to take urgent action after an inspection found that some babies in its maternity unit lacked name tags, putting them at risk of receiving the wrong medicine or going home with the wrong mother.1

The Care Quality Commission (CQC) rated maternity services as “inadequate” at the Royal London, the biggest stand alone hospital in Europe, where 4645 babies were delivered last year.

The regulator’s report said that not enough midwives were in the delivery suite to ensure safe care for all women. It also reported …