tbuckley/cabot-search huggingface dataset:
MNGO-17EFFECTS OF LAPATINIB ON MENINGIOMAS IN ADULTS WITH NEUROFIBROMATOSIS TYPE 2 (NF2)
Authors: Diana S. Osorio, Jessica Hu, Joseph Stanek, Mari Hagiwara, Jeffrey Wisoff, John G. Golfinos, Thomas Roland, Carole Mitchell, Jeffrey C. Allen, Matthias Karajannis
Journal: Neuro-Oncology (2015)

BACKGROUND: EGFR and ErbB2 are overexpressed schwannomas and meningiomas. Preclinical and clinical data indicate that lapatinib, an EGFR/ErbB2 inhibitor, has antitumor activity against schwannomas. METHODS: We conducted a single institution, retrospective review of patients with NF2 and progressive vestibular schwannomas treated on a Phase II clinical trial with lapatinib (NCT00973739). We included patients with at least one volumetrically measurable meningioma (>0.5cm3) who received at least five 28-day courses of therapy. Lapatinib was administered in continuous 4-week courses receiving standard adult doses (1,500mg once daily). Meningioma response was assessed using 3-dimensional MRI volumetrics. Progressive meningioma growth and response were defined as +20%/-20%-change from baseline in tumor volume, respectively. Off-treatment defined as any period >5 months without lapatinib. RESULTS: Eight patients (ages: 20-58 years) who met criteria had 17 evaluable meningiomas with a combined volume of 61.35cc baseline, 61.17cc during treatment, and 108.86cc (+77.44%-change) off-treatment. Tumor volume differences were significant (p = 0.0033) using a two-sided Wilcoxon-Signed-Rank test. Median time on-therapy: 15 months and off-therapy: 14 months (both ranged 5-29 months). We calculated a median and mean annual growth rate off-treatment: 10.42% and 20.05%, respectively. The best response to therapy was -26.1% after 23 months on lapatinib. Two of 17 tumors grew >20% on-treatment while 9 of 17 grew >20% off-treatment. CONCLUSIONS: These data suggest that lapatinib has modest growth-inhibitory effects on meningiomas in NF2 patients. Prospective studies of lapatinib for NF2 patients with progressive meningiomas may be warranted.
ERCC1 and XPF protein expression in patients with nasopharyngeal carcinoma (NPC) undergoing curative intent radiation with or without platinum chemotherapy.
Authors: A. Jagdis, T. Phan, A. C. Klimowicz, J. J. Laskin, H. Lau, S. K. Petrillo, J. E. Siever, T. A. Thomson, A. M. Magliocco, D. Hao
Journal: Journal of Clinical Oncology (2011)

5587 Background: Early stage NPC is highly curable by radiation (RT), but higher stage NPC patients often recur locally and/or develop distant metastases despite combination chemoradiotherapy (CRT). The ERCC1-XPF heterodimer is a structure specific endonuclease involved in both nucleotide excision repair and the repair of interstrand crosslinks. Suppression of ERCC1-XPF results in reduced DNA repair capacity which has been associated with sensitivity to chemotherapy and RT. We sought to evaluate the prognostic/predictive value of ERCC1-XPF in 142 consecutive patients with non-metastatic NPC treated with curative intent between Jan 2000-Dec 2007. Methods: 0.6 mm cores from pre-treatment formalin-fixed paraffin-embedded biopsies were assembled into a tissue microarray. ERCC1 and XPF protein expression was evaluated by immunofluorescence combined with automated quantitative analysis (AQUA) using the FL297 and 3F2 antibodies respectively. ERCC1 and XPF protein expression levels were correlated with clinical outcomes. Results: Patient characteristics were as follows: mean age=52 years (range 18-85), 67% male, 79% KPS ≥ 90%, WHO type 1/2/3=12%/28%/60%, stage III/IV=65%. Fifty seven (40%) patients received platinum-based CRT; the remainder was treated with RT alone. The 2-year locoregional control rate=83%. With a median follow-up of 50 months (range 2.9 to 120), the 5 year overall survival (OS) was 70.8%. Both disease free survival (DFS) and OS favoured stage I/II patients (DFS, p=0.036; OS, p=0.015). Median AQUA® scores were used as cutpoints for ERCC1 (n=134) and XPF (n=128) protein expression. Agreement between dichotomized ERCC1 and XPF scores was high at 79% (kappa=0.572, p<0.001). We observed a non-significant trend towards a better RR with low XPF levels. However, neither biomarker predicted locoregional recurrence, DFS or OS after adjustment for age, KPS, and WHO type, irrespective of stratification by stage or treatment. Conclusions: This is the largest series to date evaluating ERCC1 and XPF in NPC. In contrast with smaller NPC biomarker studies, and findings in other tumour types, neither ERCC1 nor XPF were prognostic nor predictive in this cohort.
Obatoclax (GX15-070) Is a Potent Antagonist of Constitutive Mcl-1/Bak Interactions in Intact Mitochondrial Membrane and Synergizes with Bortezomib in Mantle Cell Lymphoma.
Authors: Gordon Shore, Mark Watson, Anne Roulston, Richard Marcellus, Nancy Steenart, Pierre Beauparlant, Sasmita Tripathy, Xavier Billot, Laurent Bélec, Giorgio Attardo, Mai Nguyen, Stephane Acoca, Enrico Purisima, Patricia Pérez-Galan, Dolors Colomer
Journal: Blood (2006)
Abstract 3127: Small but lethal, miR-137 acts as a tumor suppressive microRNA in colorectal cancer
Authors: Amber Rae Smith, Rebecca Marquez, Bryan Tsao, Alexandria Roy, Bailey Wilkerson, Surajit Pathak, Kristi Neufeld, Xiao-Feng Sun, Liang Xu
Journal: Cancer Research (2015)

Abstract Colorectal cancer is the 3rd most common cause of cancer-related deaths for men and women in the United States. Understanding the mechanisms associated with the initiation and progression of colorectal cancer is needed to develop precise therapies. Multiple regulatory processes are responsible for maintaining cellular homeostasis, including microRNA (miRNA) regulation. We previously demonstrated that miR-137 expression was significantly decreased in 84% of tumors as compared to adjacent mucosal tissue from patients with rectal cancer (n = 68). Restoration of miR-137 reduced colon cancer growth, measured by colony formation and tumorsphere assays. Induction of miR-137 expression significantly decreased tumor growth in our xenograft tumor model by approximately 50% (n = 10). To understand the mechanism associated with the tumor suppressive function of miR-137, we transfected miR-137 mimic into HCT-116 cells and performed microarray analysis to identify changes in gene expression and identify key regulatory pathways effected by miR-137 restoration. Multiple miR-137 targets were down regulated, as compared to cells treated with a negative control mimic. The data was validated using quantitative real-time PCR (qPCR). Finally, the expression of miR-137 target genes was analyzed in a panel of colon cancer cell lines using qPCR. In summary, miR-137 acts as a tumor suppressive microRNA by negatively regulating multiple targets that are overexpressed in colorectal cancer. Citation Format: Amber Rae Smith, Rebecca Marquez, Bryan Tsao, Alexandria Roy, Bailey Wilkerson, Surajit Pathak, Kristi Neufeld, Xiao-Feng Sun, Liang Xu. Small but lethal, miR-137 acts as a tumor suppressive microRNA in colorectal cancer. [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 3127. doi:10.1158/1538-7445.AM2015-3127
A phase II study of decitabine and carboplatin in recurrent platinum (Pt)-resistant ovarian cancer (OC).
Authors: D. Matei, C. Shen, F. Fang, J. Schilder, M. Li, A. Arnold, Y. Zeng, J. M. Pilrose, C. Kulesavage, C. Balch, W. Berry, P. Wulfridge, T. H. Huang, K. P. Nephew
Journal: Journal of Clinical Oncology (2011)

5011 Background: Aberrant DNA methylation is a hallmark of cancer. Preclinical studies showed that hypomethylating agents reverse Pt resistance, supporting testing low dose decitabine (D) combined with carboplatin (Cp), in recurrent Pt-resistant OC. Methods: Key eligibility included recurrent OC, Pt-resistant or Pt-refractory, measurable (RECIST) or detectable (GCIC), normal organ function, no limit on prior therapy. Treatment was D 10mg/m2 d1-5 prior to Cb (AUC 5, d8), based on phase I results. Primary endpoint was response rate (RR). Secondary endpoints were clinical benefit rate (CBR), progression free survival (PFS), safety, and overall survival (OS). PBMCs, plasma, and tumor biopsies were collected on d1 and d8 for assessment of biomarkers correlating with PFS. Genome-wide DNA methylation and gene expression profiling of tumors used Infinium and Affymetrix U133A arrays. Global (LINE-1) and gene-specific DNA methylation and expression levels were measured by pyrosequencing and qRT-PCR. Data analysis included linear mixed-effects models, statistical analysis for microarrays (SAM), clustering, functional pathway prediction, and gene ontology. Results: 17 patients were enrolled. Median age was 60 (45-83), median number of prior regimens was 5 (1-10). 15 patients had Pt-resistant and 2 Pt-refractory OC; 16 had measurable, 1, detectable OC. 1CR (GCIC) and 5 PRs (RECIST) were observed (RR=35%, 95% CI: 14%-62%). 6 other patients had stable disease. CBR was 70% and median PFS was 309 days. 9 patients (53%) were free of progression at 6 mos. Most common grade 3-4 AEs were neutropenia (23%), thrombocytopenia, leukopenia, anemia (11% each). LINE-1 methylation was decreased on d8 vs. d1 in PBMC DNA (P<0.05). Demethylation of OC-associated genes MLH1, RASSF1a, HOXA10, and HOXA11,in tumors from d1 to d8 is positively correlated with PFS (P<0.05). Inflammatory response genes were altered in tumors on d8 vs. d1, and expression of pathways involved in proliferation, transformation, survival, and DNA repair were reduced on d1, correlating with PFS (P<0.01). Conclusions: Low-dose D alters DNA methylation restoring sensitivity to Cp in patients with heavily pre-treated OC, resulting in a high RR and prolonged PFS.
Abstract 973: Coordinated regulation of cap-dependent translation and microRNA function by convergent signaling through the PI3K/Akt/mTOR and Jak/Stat/Pim signaling pathways
Authors: Scott H. Olejniczak, Gaspare La Rocca, Megan Radler, Craig B. Thompson
Journal: Cancer Research (2015)

Abstract Growth and proliferation of tumor cells requires coordinated activation of many cellular processes, including cap-dependent mRNA translation. MicroRNAs oppose cap-dependent translation to set thresholds for expression of target proteins. Emerging data suggest that microRNA function, like cap-dependent translation, is enhanced by activation of cancer-associated signaling due, at least in part, to induction of GW182 protein expression. In the current study, we demonstrate that increased expression of GW182 in normal and transformed hematopoietic cells contributes to enhanced microRNA function by increasing overall capacity for microRNA-mediated target repression. Furthermore, expression of GW182 was found to be regulated post-transcriptionally by the translation initiation complex downstream of convergent signaling through the PI3K/Akt/mTOR and Jak/Stat/Pim signaling pathways, both of which are commonly activated in hematopoietic malignancies. PI3K/Akt/mTOR signaling contributed to GW182 expression primarily by stimulating eIF4E binding to GW182 mRNA, while Jak/Stat/Pim signaling enhanced GW182 expression by additionally increasing eIF4A-dependent unwinding of G-quadraplexes in the 5′ untranslated region (UTR) of GW182 mRNA. Inhibition of either eIF4E-dependent translation initiation by treatment with rapamycin or eIF4A-dependent unwinding of the GW182 5′ UTR by treatment with silvestrol led to decreased GW182 expression and microRNA function. Our data provide a mechanism by which microRNA function is linked to cap-dependent translation, allowing thresholds for expression of microRNA targeted proteins to be maintained despite changes in protein synthesis. Citation Format: Scott H. Olejniczak, Gaspare La Rocca, Megan Radler, Craig B. Thompson. Coordinated regulation of cap-dependent translation and microRNA function by convergent signaling through the PI3K/Akt/mTOR and Jak/Stat/Pim signaling pathways. [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 973. doi:10.1158/1538-7445.AM2015-973
Effect of Huangqi On Mesenchymal Stem Cells (MSC) Transplanted Therapy in Spinal Cord Injury: It Promotes the Neural Differentiation of MSC In Vivo.
Authors: Qin Yu, Yueshuang Bai, Jie Lin, Lixian Sheng, Qin Dong, Ying Guo, Xiaobo Xuan
Journal: Blood (2009)
Measurement of baseline serum SDF-1 levels as a predictive biomarker for outcomes in the NCIC CTG MA.14 trial of octreotide, a somatostatin analogue in postmenopausal breast cancer.
Authors: A. Aguilar-Mahecha, M. Basik, J. W. Chapman, K. Jahan, S. Hassan, L. Zhu, C. F. Wilson, K. I. Pritchard, L. E. Shepherd, M. N. Pollak
Journal: Journal of Clinical Oncology (2011)

577 Background: Stromal cell derived-factor 1 (SDF-1) is a chemokine implicated in breast tumor growth and metastasis. Blood SDF-1 levels have a significant prognostic value in primary breast cancers. We have reported that 4 month serum SDF-1 levels had a significant EFS predictive value in the adjuvant breast cancer population of MA.14 (ASCO 2010). Here, we sought to confirm the association with baseline assessments of SDF-1. Methods: NCIC CTG MA.14 is a randomized phase III trial in postmenopausal women of tam 20 mg daily for 5 yr +/- octreotide LAR for 2 yr. Stratification factors were adjuvant chemo, axillary nodal status, and ER status. The primary endpoint was event-free survival (EFS) defined as time from randomization to recurrence, second malignancy, or death due to any cause. Serum was collected at various timepoints throughout the trial. Baseline SDF-1 serum levels were measured with an ELISA kit (R&D). To assess the effect of SDF-1 on EFS in the context of factors considered in the main trial, we used step-wise forward multivariate adjusted Cox modeling, adjusting by the stratification factors, and adding a factor if the likelihood ratio criterion was significant, p ≤ 0.05. Events for the analysis were those reported at ASCO 2008. Results: 667 women were accrued (333 to tam, 334 to tam + oct), and followed for a median 7.9 years. We successfully measured the baseline levels of SDF-1 in 469 (70%) patients, 241 on tamoxifen arm, of whom 80 (33%) experienced an EFS event; and for 228 on tamoxifen and octreotide LAR arm, of whom 70 (31%) had an EFS event.Consistent with our previous findings, we found that in a step-wise multivariate analysis, higher log (SDF-1) (p < 0.0001) was significantly associated with worse EFS. Also, the interaction of treatment and SDF-1 split at median was significantly (p < 0.0001) associated with EFS with inclusion of the significant main trial factors. Conclusions: We have confirmed that baseline SDF-1 levels have a predictive value in the breast cancer population of MA.14 treated with octreotide LAR. Further validation of SDF-1 and investigation of a possible pharmacogenetic effect with octreotide therapy is warranted.
Abstract 1009: Cytotoxic effect of ginsenosides C-K and PPD on glioblastoma cells through cell cycle arrest and down-regulation of cell adhesion proteins
Authors: Eunsoo Kim, Cheryl Wanderi, Chulhee Choi, Kyungsun Choi
Journal: Cancer Research (2015)

Abstract Ginsenosides, pharmacologically active components of ginseng have been shown to have strong anticancer effects; however, their effect on glioblastoma has not been extensively evaluated. Here, we investigated the anticancer effect and the molecular mechanisms of ginsenosides on glioblastoma. Among 12 ginsenosides tested, compound-K (C-K) and protopanaxadiol (PPD), significantly reduced U251MG cell viability in dose- and time-dependent manner. This cytotoxic effect was accompanied by decreased expression of cell adhesion proteins including N-Cadherin and Integrin β1, which led to reduced phosphorylation of focal adhesion kinase. Furthermore, we observed the reduction of Cyclin D1 and subsequent G1-phase cell cycle arrest. We further demonstrated that C-K and PPD inhibited the phosphorylation of Akt and extracellular signal regulated kinase. Conversely, C-K and PPD stimulated phosphorylation of JNK and cleavage of PARP. These results collectively indicate that ginsenosides C-K and PPD may provide a new strategy to treat malignant glioblastoma that are quite resistant to conventional anti-cancer treatment. (This research was supported by a grant of the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea;grant number : HI14C0042) Citation Format: Eunsoo Kim, Cheryl Wanderi, Chulhee Choi, Kyungsun Choi. Cytotoxic effect of ginsenosides C-K and PPD on glioblastoma cells through cell cycle arrest and down-regulation of cell adhesion proteins. [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 1009. doi:10.1158/1538-7445.AM2015-1009
Laparoscopic versus robotic adrenalectomy: A comprehensive meta-analysis
Authors: Konstantinos P. Economopoulos, Konstantinos S. Mylonas, Aliki A. Stamou, Vasileios Theocharidis, Theodoros N. Sergentanis, Theodora Psaltopoulou, Melanie L. Richards
Journal: International Journal of Surgery (2016)
Low Erythrocytic Glutathione Peroxidase-1 Activity Correlates with Hemolytic Rate in Patients with Sickle Cell Disease and Is Elevated on Hydroxyurea.
Authors: Gregory J. Kato, Chun Seok Cho, Seung Ha Yang, Sung Won Bae, Jong Seo Lee, Mark T. Gladwin, Sue Goo Rhee
Journal: Blood (2007)
Abstract POSTER-CTRL-1217: Human placental lactogen-functionalized bimodal imaging probe for human ovarian cancer detection
Authors: Yilin Zhang, Karthik M. Sundaram, Nan-Sheng Li, Joseph A. Piccirilli, Ernst Lengyel
Journal: Clinical Cancer Research (2015)

Abstract The early detection of ovarian cancer (OvCa) is a challenge because the postmenopausal ovaries are hidden in the peritoneal cavity and current imaging technologies lack the ability to differentiate between benign and malignant masses. Our goal is to improve the detection and imaging of OvCa utilizing cancer cell-targeted, bimodal fluorescent and paramagnetic micelles that effectively detect malignant tumors. The human prolactin receptor (PrlR) is expressed in 98% of malignant ovarian tumors, but is not expressed in benign ovarian tumors or fallopian tubes. Therefore, we conjugated the maleimide-functional micelles to a thiol group of human placental lactogen (hPL), a ligand of PrlR, to specifically target OvCa cells. The micelles were 20-nm in diameter with a favorable surface charge (-5.8mV) characterized by dynamic light scattering, zeta potential, and transmission electron microscopy (TEM). After conjugation to hPL, hPL-micelles displayed an increased molecular weight and particle size as assessed by SDS-PAGE, MALDI-TOF, and size exclusion chromatography. Microscopic and cytometric analyses demonstrated that hPL-micelles were more efficiently internalized in human primary OvCa cells and OvCa cell lines than unconjugated micelles. The knockdown of PrlR using shRNA in OvCa cell lines or the triple mutation of hPL significantly inhibited uptake of hPL-fluorophore conjugates, suggesting receptor-mediated endocytosis. Furthermore, the Xenogen IVIS small animal imaging system detected a greater accumulation of hPL-micelles than of unconjugated micelles in the human ovarian tumor xenograft, confirming the enhanced imaging of OvCa through targeted delivery. Given the low prevalence of OvCa and the current unsatisfactory imaging modalities, “receptor-dependent imaging” through hPL-decorated bimodal micelles has the potential to improve detection of OvCa through enhanced specificity. Citation Format: Yilin Zhang, Karthik M. Sundaram, Nan-Sheng Li, Joseph A. Piccirilli, Ernst Lengyel. Human placental lactogen-functionalized bimodal imaging probe for human ovarian cancer detection [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-CTRL-1217.
Prognostic Impact of Splenomegaly on Survival of Chinese with Primary Myelofibrosis
Authors: Jingya Wang, Junqing Xu, Robert Peter Gale, Zefeng Xu, Bing Li, Tiejun Qin, Yue Zhang, Liwei Fang, Hongli Zhang, Lijuan Pan, Shiqiang Qu, Peihong Zhang, Zhijian Xiao
Journal: Blood (2014)
Type 2 Diabetes-Related Variants Influence on the Risk of Developing Multiple Myeloma: Results from the Immense Consortium
Authors: Juan Sainz, Carmen Belén Lupiañez, Daniele Campa, Gabriele Buda, Hernan Jose Moreno, Marek Dudziński, Charles Dumontet, Ramón García-Sanz, Krzysztof Jamroziak, Artur J. Jurczyszyn, Stefano Landi, Fabienne Lesueur, Herlander Marques, Joaquín Martínez-López, Victor Moreno, Mario Petrini, Rui Manuel Reis, Zofia Szemraj-Rogucka, Annette Juul Vangsted, Judit Varkonyi, Ulla Vogel, Marzena Wątek, Federico Canzian, Rafael Rios
Journal: Blood (2014)
Prioritizing Pediatric Surgical Conditions—A Call to Go Beyond Operations, Cost, and Comparative Effectiveness Research
Authors: Peter C. Minneci, Katherine J. Deans
Journal: JAMA Pediatrics (2016)

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Feasibility and Prognostic Value of VO2peak in Patients Undergoing Hematopoietic Cell Transplantation (HCT)
Authors: William A Wood, Allison M Deal, Claudio L Battaglini, Bryce B Reeve, Amy P Abernethy, Yoon Hie Kim, Julia S Whitley, Charlotte Shatten, Robert N Irons, Amber N Essenmacher, Kimberly Wehner, Alicia Pinto, James Coghill, Paul M Armistead, Stefanie Sarantopoulos, Don A. Gabriel, Jonathan S Serody, Thomas C. Shea
Journal: Blood (2012)
Transplant-Related Mortality in Patients ≥50 Years of Age Is No Lower after Transplantation from Young Fully Matched Unrelated Donors (MUD) Than from Matched Siblings When All Patients Are Given the FLUBUP Regimen with Thymoglobulin.
Authors: James A. Russell, M. Ahsan Chaudhry, Diana M. Quinlan, A. Robert Turner, Loree M. Larratt, Michelle Geddes, Jan Storek, Mary Lynn Savoie, Christopher Brown, Nizar J. Bahlis, Douglas A. Stewart
Journal: Blood (2006)