tbuckley/cabot-search huggingface dataset:
Abstract 314: A rapid 3D tumor spheroid analysis method using the Celigo imaging cytometry
Authors: Leo Li-Ying Chan, Scott Cribbes, Maria Vinci, Sarah Kessel, Lisa Patterson, Sue Eccles
Journal: Cancer Research (2015)

Abstract The current 2D methods for cancer drug discovery have had some difficulty in identifying potential drug candidates that can be used for clinical testing. To overcome this challenge, there has been an increase in research of 3D tissue culture that facilitated the development of new in-vitro tumor model assays. Traditional 2D and 3D analysis method relied heavily on visual observation using microscopy. However, the method is time-consuming and has high variations. Automated plate-based imaging cytometer can be employed to rapidly analyze and characterize 3D tumor spheroids, which can be used to generate both quantitative and qualitative results. In this work, we demonstrate a novel 3D tumor spheroid analysis method using the Celigo imaging cytometer for spheroid counting, size analysis, tumor migration and invasion, tumor viability, and dose response of drug induced/inhibited tumor growth. The plate-based imaging cytometer utilizes bright-field and three fluorescence channels (Blue, Green, and Red) for multi-channel analysis. By utilizing the F theta lens technology, uniform bright-field image is captured for more accurate counting of the entire well. In addition, Celigo analysis software is used to report numerous parameters allowing detailed spheroid characterization. In addition to direct spheroid counting in the well, the use of specific fluorescent dyes and probes allow the user to define viable and hypoxic areas within spheroids and monitor migration and invasion on or into supporting cells and/or tissues. The results showed that Celigo imaging cytometer can accurately count and measure spheroid sizes in response to drug induction. Furthermore, tumor migration and invasion were clearly observed and quantified in the captured images. By utilizing the 3D spheroid imaging cytometry method, researchers can quickly characterize and quantify tumor spheroids, which can improve the efficiency of identification of potential cancer drug candidates. Citation Format: Leo Li-Ying Chan, Scott Cribbes, Maria Vinci, Sarah Kessel, Lisa Patterson, Sue Eccles. A rapid 3D tumor spheroid analysis method using the Celigo imaging cytometry. [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 314. doi:10.1158/1538-7445.AM2015-314
First Inactivated Zika Vaccine Trial
Authors: Jennifer Abbasi
Journal: JAMA (2016)

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Prospective study of breast cancer risk in mutation-negative women from <i>BRCA1</i> or <i>BRCA2</i> mutation-positive families in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab).
Authors: S. Harvey, R. L. Milne, K. E. Birch, P. Weideman, S. McLachlan, M. Friedlander, D. Goldgar, J. L. Hopper, K. Phillips
Journal: Journal of Clinical Oncology (2011)

1516 Background: Published studies have reached contradictory conclusions regarding the breast cancer (BC) risk for mutation negative women from families segregating a BRCA1 or BRCA2 mutation. Accurate estimation of BC risk is crucial for appropriate counselling regarding risk management. Aim: To assess prospectively whether BC risk for non-carrier women from families segregating BRCA1 or BRCA2 mutations is greater than that for the general population. Methods: Eligible women were first-, second- or third-degree relatives of a BRCA1 or BRCA2 mutation carrier, had no personal cancer history at entry into the kConFab cohort, and were not carriers of the family mutation. Self-reported family history of cancer, preventive interventions and verified cancer diagnoses were collected at entry, and every 3 years thereafter. Time at risk of BC was censored at cancer diagnosis or risk-reducing surgery. Standardised incidence ratios (SIR) were estimated by comparing observed to population incidences of invasive breast cancer using the Australian Cancer Incidence and Mortality Books. Results: 728 women from 244 mutation positive (128 BRCA1, 96 BRCA2) families were eligible. Median follow-up was 6.1 years (range 0.1-12.4 years). Six cases of invasive BC were observed. The estimated SIRs were: 1.14 (95% CI=0.51-2.53) for all eligible women (n=728); 1.29 (95% CI=0.58-2.88) for eligible 1st and 2nd degree relatives of an affected mutation carrier (n=442) and 0.48 (95% CI=0.12-1.93) for eligible women with no family history of BC in the non-mutation carrying parental lineage (n=424). Conclusions: We observed no evidence that women from families with BRCA1 or BRCA2 mutations who test negative are at increased risk of BC. Nevertheless, despite this being the largest prospective cohort yet studied for this issue, moderately increased breast cancer risk (2-fold) could not be ruled out. Meta-analysis of this and similar recent prospective studies may provide further clarification.
Inhibition of BCL11B Expression Leads to Apoptosis of Malignant T Cells but Not CD34+ Cells.
Authors: Xin Huang, Si Chen, Shaohua Chen, Lijian Yang, Qi Shen, Piotr Grabarczyk, Grzegorz K. Przybylski, Christian A. Schmidt, Yangqiu Li
Journal: Blood (2010)
Abstract 5561: Violacein inhibits matrix metalloproteinase mediated CXCR4 expression: Potential anti-tumor effect in cancer invasion and metastasis
Authors: Venkataswarup Tiriveedhi
Journal: Cancer Research (2015)

Abstract Matrix metalloproteinases (MMP-2 and -9) play an important role in the tumor metastasis through cleavage of proinflammatory chemokines. Violacein a small molecule naturally produced by Chromobacterium violaceum has been implicated with anti-tumor effects. In this study we investigated the molecular basis of violacein mediated downregulation of CXCL12-CXCR4, chemokine-receptor expression. Gelatin zymography analysis demonstrated that violacein significantly inhibited the cytokine (TNFα and TGFβ) mediated MMP-2 activation in MCF-7 breast cancer cell line. MMP-2 plays a critical role in the secretion of inflammatory CXCL12 a cell migration chemokine. ELISA analysis demonstrated that violacein induced significantly decreased secretion of CXCL12 from cytokine induced MCF-7 cells. Further, we show that MMP-2 and MMP-9 act synergistically at two distinct steps towards the membrane expression of the tumor metastasis chemokine receptor, CXCR4. Violacein efficiently downregulated the CXCR4 membrane expression through MMP-9 inhibition. Taken together, these studies demonstrate the unique mechanism of action of violacein towards potential anti-tumor effect through reduction of CXCL12-CXCR4 expression by inhibition of proteolytic MMP activity. Based on these studies violacein could offer a novel therapeutic venue in cancer therapy. Citation Format: Venkataswarup Tiriveedhi. Violacein inhibits matrix metalloproteinase mediated CXCR4 expression: Potential anti-tumor effect in cancer invasion and metastasis. [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 5561. doi:10.1158/1538-7445.AM2015-5561
Bone Marrow Immunophenotyping By Flow Cytometry in Refractory Cytopenia of Childhood
Authors: Anna M. Aalbers, Marry M. van den Heuvel-Eibrink, Irith Baumann, Michael Dworzak, Henrik Hasle, Franco Locatelli, Barbara De Moerloose, Markus Schmugge, Ester Mejstrikova, Michaela Novakova, Marco Zecca, C. Michel Zwaan, Jeroen G. te Marvelde, Anton W Langerak, Jacques J.M. van Dongen, Rob Pieters, Charlotte Niemeyer, Vincent H.J. van der Velden
Journal: Blood (2014)
Hemoglobin San Martin: A New Unstable Variant Associated with Hemoglobin S in an Argentinean Boy.
Authors: Aurora Feliu-Torres, S. Eandi-Eberle, K. Calvo, I. Bragós, M. Ojeda, M. Voss, A. Pratti, A. Milani, H. Targovnik, G. Sciuccati, M. Bonduel, L. Diaz, R. Staciuk, N. Noguera
Journal: Blood (2007)
Abstract 3822: SOX17 gene promoter methylation in high-grade serous epithelial ovarian cancer
Authors: Lydia Giannopoulou, Issam Chebouti, Kitty Pavlakis, Sabine Kasimir-Bauer, Evi S. Lianidou
Journal: Cancer Research (2015)

Abstract Introduction: Impaired DNA methylation patterns hold promise as cancer biomarkers. SOX17, a member of the SOX family of transcription factors, is conserved in many species and plays critical roles in the regulation of development and stem/precursor cell function, at least partly through repression of the canonical Wnt/beta-catenin signaling pathway. Global analysis of CpG island hypermethylation and gene expression in colorectal cancer cell lines revealed that SOX17 gene silencing is associated with DNA hypermethylation. We have already shown that this gene is hypermethylated in circulating tumor cells and circulating tumor DNA of patients with breast cancer (Chimonidou et al, Clin Chem 2011, Chimonidou et al, Clin Chem, 2013). High grade serous ovarian cancer (HGSC) is the most common histological subtype of ovarian cancer, with a worse disease prognosis and overall survival. In this study, we investigated for the first time the status of SOX17 promoter methylation in patients with high grade serous ovarian cancer. Materials and methods: HGSC tumors (FFPEs) from ovarian cancer patients belonging to an independent group (n = 78) and a training group (n = 47) were analyzed. For the evaluation of the specificity of our results, a small group of 10 corresponding normal tissues from the first ten individuals of the training group was also analyzed. Genomic DNA was isolated from all samples, and then was modified by Sodium Bisulfite (SB). All SB converted DNA samples were analyzed by a real time Methylation Specific PCR (MSP) assay, for detecting SOX17 promoter methylation. The IGROV1 ovarian cancer cell line was used as a positive control in all procedures. Results: In the training group, SOX17 promoter methylation was detected in 25/47 ovarian tumor samples (53.2%) and in 5/10 corresponding normal tissues. The same 5/10 matched pathological samples of the training group, were also found methylated for the SOX17 gene. In the independent group, SOX17 promoter methylation was observed in 61/78 tumor samples (78.2%). Conclusion: Our results indicate for the first time that SOX17 promoter methylation is a frequent event in high grade serous ovarian cancer. Further investigation is required to determine the prognostic significance of SOX17 promoter methylation status in ovarian cancer and correlate these findings with patients’ clinicopathological characteristics. Citation Format: Lydia Giannopoulou, Issam Chebouti, Kitty Pavlakis, Sabine Kasimir-Bauer, Evi S. Lianidou. SOX17 gene promoter methylation in high-grade serous epithelial ovarian 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 3822. doi:10.1158/1538-7445.AM2015-3822
Determining Penetration of Prostate-Specific Antigen Screening Recommendations
Authors: Charles R. Thomas, Yu Shyr
Journal: JAMA Oncology (2016)

Jim C. Hu, MD, MPH; Paul Nguyen, MD; Jialin Mao, MD, MSc; Joshua Halpern, MD; Jonathan Shoag, MD; Jason D. Wright, MD; Art Sedrakyan, MD, PhD
504. Targeted Genome Engineering of Induced Pluripotent Stem Cells To Produce Auto-Regulated Inflammation Resistance for Musculoskeletal Regenerative Medicine
Authors: Jonathan M. Brunger, Ananya Zutshi, Vincent P. Willard, Charles A. Gersbach, Farshid Guilak
Journal: Molecular Therapy (2015)

Chronic inflammatory diseases such as arthritis are characterized by aberrant and dysregulated responses to cytokines such as tumor necrosis factor α (TNFα). While exogenous anti-cytokine therapies have been shown to diminish this inflammatory response, they are often used at high, unregulated doses that can induce significant side effects. Here, we propose a novel regenerative medicine approach to treating such chronic inflammatory diseases by generating custom-designed cells that can execute real-time, user-defined responses to environmental cues, including pro-inflammatory cytokines. We designed and deployed gene editing nucleases based on the CRISPR/Cas9 system to create stem cells with the ability to antagonize TNFα-mediated inflammation in an auto-regulated, feedback-controlled manner for musculoskeletal regenerative medicine applications. Specifically, the cytokine-responsive Ccl2 gene was reprogrammed by nuclease-mediated integration of the gene encoding soluble TNFα receptor I (sTNFRI), a TNFα antagonist, immediately downstream of the Ccl2 promoter. Using a combination of qRT-PCR and site-specific integration of luciferase reporters, we observed increased transgene transcription in response to endogenous Ccl2 activation by treatment with TNFα. Transgene expression from engineered cells was feedback-controlled with rapid on/off dynamics (Fig 1 A). Importantly, engineered cells showed the ability to mitigate the inflammatory effects of TNFα in an auto-regulated manner within 48 hr of induction (Fig 1 B). Finally, while cartilage produced from control stem cells showed significant tissue degradation in response to TNFα, cartilage derived from engineered stem cells was protected from a 3-day treatment with 20 ng/ml TNFα, as evidenced by qRT-PCR, biochemical, and histological analyses (Fig 1C-G). This work demonstrates the utility of programmable nucleases for the development of "designer" stem cells with properties customized for regenerative medicine. Using CRISPR/Cas9, we engineered pluripotent stem cells with the user-specified trait of pro-inflammatory cytokine resistance. Our results show that genome engineering facilitated the rewiring of endogenous cell circuits in order to define novel input/output relationships between inflammatory mediators and their antagonists, achieving therapeutic benefit coupled to a rapidly responding, auto-regulated system. The customization of intrinsic cellular signaling pathways in therapeutic stem cell populations, as demonstrated in this work, can transform the landscape of regenerative medicine and open innovative possibilities for safer and more effective treatments applicable to a wide variety of diseases.
Transfusion of S-303 Treated RBCs To Treat Acute Anemia during or Following Cardiac Surgery: Results of a Phase III Trial.
Authors: Richard J. Benjamin, Jeffrey McCullough, Paul D. Mintz, Edward L. Snyder, William D. Spotnitz, David Wages, Lindsey Wood, Jaime Houghton, Jin-Sying Lin, Laurence Corash, Maureen G. Conlan
Journal: Blood (2004)
Abstract LB-035: Hepatitis C virus NS3/4A hijacks the host B-cell receptor signaling pathway
Authors: Bojie Dai, Ari Landon, Simone Houng, Ronald B. Gartenhaus
Journal: Cancer Research (2015)

Abstract B-cell receptor (BCR) signaling is critical for the development of normal B-cells and B-cell lymphoma. Increasing epidemiological evidence indicates an association between chronic hepatitis C virus (HCV) infection and B-cell lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative disorder are still unclear. Herein, we demonstrate the expression of HCV viral proteins in B-cells of HCV-infected patients and show that HCV up-regulates BCR signaling in human primary B-cells. HCV nonstructural protein NS3/4A interacts with CHK2 and down-regulates its activity, modulating HuR posttranscriptional regulation of a network of target mRNAs associated with B-cell lymphoproliferative disorders. Strikingly, the BCR signaling pathway was found to have the largest number of transcripts with increased association with HuR and up-regulated by NS3/4A. Our study reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV infection, lending further insight into the molecular mechanisms underlying HCV-associated B-cell lymphoproliferative disorders. Citation Format: Bojie Dai, Ari Landon, Simone Houng, Ronald B. Gartenhaus. Hepatitis C virus NS3/4A hijacks the host B-cell receptor signaling pathway. [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 LB-035. doi:10.1158/1538-7445.AM2015-LB-035
85. AAV9-Utrophin Prevents Myonecrosis in Dystrophic Mice and Dogs without Immunosuppression
Authors: Yafeng Song, Alock Malik, Andrew Mead, Marilyn Mitchell, Mihail Petrov, Xiangping Lu, Daniel VanBelzen, Maxwell Joffe, Margaret Choi, Leonard Su, Joe Kornegay, Tejvir Tejvir Khurana, Hansell Stedman
Journal: Molecular Therapy (2016)

The majority of mutations causing Duchenne muscular dystrophy (DMD) are multi-exon, frameshifting deletions, complicating therapy with recombinant dystrophin because of the potential for chronic immune recognition of the "non-self" protein. The paralogous protein utrophin is ubiquitously expressed at levels insufficient to prevent myonecrosis in animal models for DMD, but may confer central immunological tolerance through early developmental expression in the thymus. Here we show for a first time histological evidence for the complete prevention of myonecrosis in dystrophin-deficient striated muscles following systemic administration of an AAV9 vector carrying a 3.5 kb synthetic utrophin transgene (AAVµU). The cDNA was miniaturized by removal of domains least conserved in a comprehensive evolutionary comparison, and further optimized for maximal expression in striated muscle by using the codon bias of mammalian genes encoding contractile proteins. Administration of 1015 AAVµU vector genomes (vg) per kg to neonatal mice prevented centronucleation and saturated global recovery of the sarcoglycan complex, despite a subsequent tenfold increase in striated muscle mass with growth. In neonatal dystrophic dogs, intravenous injection of 1013.5 AAVµU vg/kg without immunosuppression restored sarcoglycan levels and normalized the myofiber size-distribution following a fourfold increase in muscle mass. Interferon-gamma ELISpot assays using utrophin-derived peptides revealed no reactivity in injected dogs, consistent with central immunological tolerance. These findings provide a rationale for high dose, neonatal gene therapy using utrophin as a "self" protein to forestall disability and mortality in DMD, while minimizing the risk of chronic immunotoxicity.
Iron Overload Indices In Thalassemia Major Children Cured by Stem Cell Transplantation at Enrollment In a Prospective Randomized Trial Comparing Phlebotomy and Deferasirox
Authors: Adlette C. Inati, Evelyne Khoriaty, Nada Sbeiti, Timothy G St Pierre, Suzanne Koussa, Khaled M Musallam, Ali T Taher
Journal: Blood (2010)
Prophylactic gastrectomy in <i>CDH1</i>-mutation carriers: Psychosocial, physical, and nutritional effect compared with curative gastrectomy for gastric cancer.
Authors: A. Cats, I. Kluijt, M. Ausems, A. Hartig, M. de Boer, R. van Hillegersberg, J. T. Plukker, E. van Riel, R. Sijmons, L. Spruijt, M. Oldenrode-Berends, N. Hoogerbrugge, E. Bleiker
Journal: Journal of Clinical Oncology (2011)

e14616 Background: Carriers of a CDH1 gene mutation have a risk of up to 80% to develop gastric cancer (GC). Prophylactic total gastrectomy is offered to mutation carriers to prevent invasive GC development. In this usually young and asymptomatic population, however, the psychosocial, physical and nutritional consequences are largely unknown. Therefore, the aim of this study was to investigate the impact of preventive gastrectomy in CDH1 mutation carriers. Methods: Questionnaires were sent to individuals with a CDH1 gene mutation, who had undergone a prophylactic gastrectomy. Disease-free sporadic GC patients, who had undergone a total gastrectomy 2-5 years earlier also received these questionnaires and served as a comparison group. The questionnaire assessed psychosocial (quality of life [QLQ C30, STO22], anxiety and depression [HADS], social impairment), physical (fatigue [CIS]) and nutritional variables. Results: Of the 21 CDH1 carriers who had a prophylactic gastrectomy, 20 (95%) participated (45% males). Of 23 addressed GC patients, 20 (87%) participated (70% males). Mean age was 41 years (range 20-68 years) and 59 years (range 37-74), respectively. Mean time since gastrectomy was 34 months (SD= 18 months, range 5-63 months) and 47 months (SD= 22 months; range 15-80 months), respectively. The levels of quality of life, anxiety, depression, and fatigue as reported by the two groups (preventive vs. curative resection) did not differ significantly. All together, 48% reported complaints about fatigue (28% had severe fatigue), and 18-48% of the patients reported (severe) impairment in daily activities (work, hobbies, personal relationships). Mean ±SD weight loss of 15% ± 6% was found. Food and drink products that patients were unable to consume were: dairy products (73%), fried products (25%), and soft drinks (13%). Conclusions: Following total gastrectomy, patients experience fatigue, impairment of everyday life, and weight loss. Patients with a preventive gastrectomy (carriers) did not differ from cancer patients treated by a curative gastrectomy. However, complaints varied widely among participants.