tbuckley/cabot-search huggingface dataset:
Abstract 1966: Role of Wnt-Beta-Catenin signals in the control of vascular mimicry in TNBC
Authors: Brian Leyland-Jones, Jennifer H. Carlson, Pradip De, Nandini Dey
Journal: Cancer Research (2015)

Abstract Background: TNBC or basal-like subtype of breast cancer confers poor clinical outcome mostly due to its inherent aggressive nature and its high frequency of metastasis. Malignancy in TNBC is associatedwith micro-vascular proliferations. Vascular Mimicry (VM) of solid tumor is an endothelium-independent matrix-embedded, blood-perfused non-angiogenic micro-circulatory phenomenon. VM of tumor cells refer to the characteristic plasticity of aggressive cancer cells forming de novo vascular networks which perfuse rapidly growing tumors, transporting fluid from leaky vessels and/or connect with the constitutional endothelial-lined vasculature. In a study comparing the VM in three subsets of BC, the presence of VM was more profoundly observed in TNBC than in luminal and HER2+ subtypes. Hypothesis: Recently we have identified a differential activation of Wnt-b-Catenin pathway (WP) in TNBC (Dey et al., PLOSONE; 2014) and demonstrated that Wnt signaling in TNBC is association with metastasis (Dey et al., BMC Cancer 2013). Since TNBC is an aggressive form of BC and VM is associated with the aggressiveness / poor outcome in many solid tumors including BC, we hypothesized that the upregulation of WP in TNBC may have a functional relationship with VM. Methods: Four strategies were used to study the role of WP in VM. They are (1) Wnt-receptor interaction by using WntC59, (2) Wnt cytosolic signaling by using XAV939, (3) Wnt nuclear signaling by using sulindac sulfide and beta-catenin SiRNA and (4) Wnt-regulating pathway by using pan-PI3K inhibitor (LY294002 and SF1126). The signaling of VM was characterized by bevacizumab (HUVEC cell cord formation used as positive control). Results: Using pharmacological and genetic tools, we demonstrated that perturbation of WP (1) at its different nodes and (2) via its upstream regulatory pathway (PI3K) can regulate VM in TNBC cells. Data showed that (1) sulindac sulfide, (2) XAV939 and WntC59 and (3) LY294002 or SF1126 (which decreased pGSK3beta) caused an abrogation of VM in TNBC cell lines while bevacizumab failed to affect the vessel formation. Considering the involvement of VM in mediating the aggressive/metastatic nature of TNBC, we finally tested the effect of downregulation of WP on VM in brain metastasis specific EGFP-tagged MDA-MB231BR cells using a real time recording device (Incucyte) to demonstrate that VM in these cells is regulated by WP. Significance: To our knowledge, this is the first report to demonstrate a direct functional role of WP in the regulation of VM in TNBC. Citation Format: Brian Leyland-Jones, Jennifer H. Carlson, Pradip De, Nandini Dey. Role of Wnt-Beta-Catenin signals in the control of vascular mimicry in TNBC. [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 1966. doi:10.1158/1538-7445.AM2015-1966
Abstract 1478: Development of novel Mi-HTX in vivo platform by reconstituting autologous immune components in patient tumor-derived xenografts
Authors: Saravanan Thiyagarajan, Padhma Radhakrishnan, Vinod D Radhakrishna, Dency D Pinto, Biswanath Majumder
Journal: Cancer Research (2015)

Abstract Developing a clinically relevant in vivo platform for testing novel anti cancer therapeutics is hindered by lack of preservation of several critical components of tumor microenvironments. While syngenic mice model is being used traditionally for understanding action of immunomodulator compounds one major drawback of this model is it does not represent human specific targets therefore exhibit poor translational potential. Patient tumor derived xenograft (PDX) is increasingly appreciated as a surrogate of patient tumors for functional screening of anticancer drugs. However, these models also display limitation of stably maintaining active phenotypes of intra-tumor or tumor infiltrating immune cells in a dynamical setting where mice immune system is also compromised. Recently developed ex vivo CANScript platform (presenting in AACR-2015 Annual meeting) shows promises in realization of a preserved patient immune network in short term culture but have inherent constraints of determining PK/PD correlations. To overcome this limitation and meet the growing need of testing immunomodulator drugs in an immunologically relevant in vivo model here we engineer a novel human tumor xenograft platform called Mi-HTX where patient immune network was reconstituted by implanting suitably primed peripheral blood mononuclear cells from same donor. The data shows the preferential recruitment of several key immune cells (CD8, macrophage and TRegs). The PK/PD/Efficacy correlation of human anti-CTLA-4 in Mi-HTX platform shows the potential application of this model for systematically evaluating immunomodulator drugs. Citation Format: Saravanan Thiyagarajan, Padhma Radhakrishnan, Vinod D Radhakrishna, Dency D Pinto, Biswanath Majumder. Development of novel Mi-HTX in vivo platform by reconstituting autologous immune components in patient tumor-derived xenografts. [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 1478. doi:10.1158/1538-7445.AM2015-1478
Abstract 2403: Biopsy-free comprehensive tumor profiling of 1,000+ consecutive cancer patients using CLIA-certified commercial test and its clinical utility
Authors: Eric Collisson, Stefanie Mortimer, Dragan Sebisanovic, Reza Mokhtari, Somayeh Bakhtiari, Rene Lopez, Devi M. Gadde, Maria M. Vidamo, Heena Patel, Bahram G. Kermani, Helmy Eltoukhy, Richard B. Lanman, AmirAli Talasaz
Journal: Cancer Research (2015)

Abstract Background: Genomic alterations of metastatic cancers may be discordant with alterations in primary tumors due to continuous evolution of disease and tumor heterogeneity. Current NGS approaches based on tissue biopsies can fail to capture a complete picture of the real-time cancer profile. Biopsy-free genomic profiling of circulating tumor DNA (ctDNA) can provide deep insights into the disease when biopsies are not an option. Methods: We developed Guardant360 for comprehensive profiling of ctDNA with high sensitivity (detection in 90%+ of advanced cancer pts) and ultra-high specificity (&amp;gt;99.9999%). Guardant360 has been validated to analyze a 69-oncogene panel covering over 120,000 bases and detects SNVs, gene amplifications, indels and genomic rearrangements, including all NCCN-guidelines recommended biomarkers. We previously reported high concordance of ctDNA profiles with concurrent matched biopsies. Results: In our first 1,000 clinical tests (77% across breast, colorectal and lung and 23% distributed over many other indications), we successfully processed 99.8% of samples. In 3 cases, we canceled the test as we detected secondary genome carry-over (confirmed to be pregnancy or liver transplant cases). Despite the wider range of clinical stages in commercial samples, we detected ctDNA in 78%. Additionally, we identified actionable mutations with associated treatments in 74% of those cases. Clinical benefit of the test was shown in many patients. Examples: A refractory IBC patient with Her2 status change, showed strong response to Her2 TKI. Patients with quantity-not-sufficient biopsy sequencing, showed strong actionable alterations (ERBB2 amplification, BRAF mutation, EGFR activating and resistance mutations, etc) Conclusion: Comprehensive sequencing of a patient's cancer in real -time through a simple blood test can empower oncologists to make better informed treatment decisions, especially when repeat tissue biopsy is not a desirable or viable option. Citation Format: Eric Collisson, Stefanie Mortimer, Dragan Sebisanovic, Reza Mokhtari, Somayeh Bakhtiari, Rene Lopez, Devi M. Gadde, Maria M. Vidamo, Heena Patel, Bahram G. Kermani, Helmy Eltoukhy, Richard B. Lanman, AmirAli Talasaz. Biopsy-free comprehensive tumor profiling of 1,000+ consecutive cancer patients using CLIA-certified commercial test and its clinical utility. [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 2403. doi:10.1158/1538-7445.AM2015-2403
High Expression of Lymphoid Enhancer-Binding Factor 1 (LEF1) Is Related to Ummutated Status of Igvh and Is an Unfavorable Prognostic Marker for Aggressive CLL Patients
Authors: Wei Wu, Huayuan Zhu, Yuan Fu, Jiadai Xu, Wenyi Shen, Wei Xu, Peng Liu, Jianyong Li
Journal: Blood (2012)
Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation
Authors: Zi-Fei Zhou, Tuan-Wei Sun, Feng Chen, Dong-Qing Zuo, Hong-Sheng Wang, Ying-Qi Hua, Zheng-Dong Cai, Jun Tan
Journal: Biomaterials (2016)
PWE-017 Capsule endoscopy in the orofacial granulomatosis/oral Crohn's disease spectrum
Authors: P Patel, D M Borrow, M Escudier, S Challacombe, S Anderson, J D Sanderson
Journal: Gut (2010)

<h3>Introduction</h3> Orofacial granulomatosis (OFG), which includes oral Crohn9s disease (CD) is a chronic inflammatory condition presenting characteristically with lip swelling but also affecting the gingivae, buccal mucosa, floor of the mouth and a number of other sites in the oral cavity. It can occur in combination with systemic conditions however, its true relationship with gut CD remains unclear. Previous studies using conventional endoscopy suggest that at least two-thirds of patients with OFG1 have asymptomatic intestinal inflammation. Capsule endoscopy offers a less invasive means of investigating the gut in these patients and not previously been evaluated in any detail in OFG. The aim was to use capsule endoscopy to determine the presence of gut CD in patients presenting with OFG with active oral inflammation but no gut symptoms. <h3>Methods</h3> 30 consecutive patients with biopsy-proven OFG were recruited from the multidisciplinary Oral Medicine/Gastroenterology out-patient clinic at Guy9s and St Thomas9 NHS Foundation Trust Hospital (London, UK) between January and August 2009. <h3>Result</h3> 26 full capsule endoscopies were performed. Three patients failed to attend three consecutive appointments. One capsule remained in the stomach for the first 24 h and failed to capture any images beyond the pylorus. From the completed recordings, small bowel abnormalities (terminal ileal ulceration and erythema) were only seen in one patient. While waiting for her capsule endoscopy, this patient had in fact developed diarrhoea, rectal bleeding and weight loss. A diagnosis of Crohn9s disease was made at subsequent colonoscopy and biopsy. The remaining recordings were completely normal. <h3>Conclusion</h3> OFG represents a spectrum of disease. Patients can have orofacial manifestations in isolation, but a small proportion have concomitant clinical CD. In patients without intestinal symptoms, a diagnosis of occult CD is very unlikely. GI surveillance using any diagnostic modality should be reserved for patients with GI symptoms or where CD is suspected from history or screening blood tests. Though video capsule endoscopy is attractive and less invasive, ileocolonoscopy with biopsy remains the gold standard in the appropriate patient.
Abstract 3119: miR-296-5p and miR-874-3p control cell proliferation and apoptosis in HCC via regulation of PIN1 expression
Authors: Ka Wai Leong, Chi Wai Cheng, Chun Ming Wong, Oi Lin Irene Ng, Yok Lam Kwong, Eric Wai Choi Tse
Journal: Cancer Research (2015)

Abstract Introduction: PIN1 is a peptidyl-prolyl cis/trans isomerase (PPlase) that regulates multiple signaling pathways to control cell fate. It is found to be up-regulated in hepatocellular carcinomas (HCC), leading to increased cell proliferation and inhibition of apoptosis. However, the regulation of PIN1 remains poorly defined. MicroRNA (miRNA) plays a pivotal role in carcinogenesis by regulating tumor suppressor genes and oncogenes via targeting the 3′UTR of their encoded mRNAs. Therefore, we aimed at identifying miRNAs regulating PIN1 expression, and determining the contributions of these miRNAs to tumorigenesis through PIN1. Methods: Potential miRNAs regulating PIN1 were identified through sequence prediction using the online database TargetScan Release 6.2. Western immunoblotting and qRT-PCR were used to assess PIN1 expression in HCC cells with over-expression of identified miRNAs. Dual-Luciferase reporter assay was conducted to examine the direct interaction between the identified miRNAs and PIN1 3′UTR. The tumor suppressive role of the identified miRNAs in HCC cells was investigated using MTT cell proliferation assay, colony formation assay and Annexin V apoptosis detection assay. To investigate the correlation between the levels of PIN1 and the identified miRNAs, qRT-PCR was used to determine the mRNA levels of PIN1 and the identified miRNAs in 20 pairs of normal liver tissue and HCC. Results: We identified miR-296-5p and miR-874-3p as important negative regulators of PIN1. Consequently, over-expression of miR-296-5p and miR-874-3p enhanced cellular apoptosis, and inhibited cell growth and colony formation in HCC cells. Furthermore, the cellular functions of miR-296-5p and miR-874-3p were abrogated by over-expression of PIN1. Importantly, the expression of PIN1 was negatively correlated with that of miR-296-5p and miR-874-3p in HCC tissues, consistent with the regulatory role of miR-295-5p and miR-874-3p on PIN1 expression. Conclusion: Taken together, our data showed that miR-296-5p and miR-874-3p controlled cell proliferation and apoptosis in HCC by regulating PIN1 expression. Citation Format: Ka Wai Leong, Chi Wai Cheng, Chun Ming Wong, Oi Lin Irene Ng, Yok Lam Kwong, Eric Wai Choi Tse. miR-296-5p and miR-874-3p control cell proliferation and apoptosis in HCC via regulation of PIN1 expression. [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 3119. doi:10.1158/1538-7445.AM2015-3119
Rituximab Reduces the Incidence of Acute Graft Versus Host Disease in an Unselected Series of Twenty-One Patients Undergoing Allogeneic Stem Cell Transplantation at a Single Center.
Authors: M. Christopeit, L. Mueller, W. Grothe, T. Weber, A. Muetherig, S. Theurich, G. Behre
Journal: Blood (2006)
Effect of the Cytochrome P450 3A4 Inducers, Rifampicin and Dexamethasone, on the Pharmacokinetic, Pharmacodynamic and Safety Profile of Bortezomib In Patients with Multiple Myeloma (MM) and Non-Hodgkin's Lymphoma (NHL)
Authors: Andrzej Hellmann, Simon A. Rule, Jan Walewski, Ofer Shpilberg, Huaibao Feng, Helgi van de Velde, Hamina Patel, Donna M Skee, Suzette Girgis, Vernon Louw
Journal: Blood (2010)
Cetuximab (CET)-related hypersensitivity reactions (HSRs): An analysis of timing, demographics, and outcomes from the AGITG/NCIC CTG CO.17 trial.
Authors: E. Elimova, C. J. O'Callaghan, D. Tu, C. S. Karapetis, T. J. Price, L. Zhu, J. R. Zalcberg, J. Simes, D. J. Jonker
Journal: Journal of Clinical Oncology (2011)

3624 Background: The anti-EGFR monoclonal antibody, CET, improved overall (OS) and progression-free survival (PFS) vs.best supportive care (BSC) alone in patients (pts) with KRAS wild-type (WT) status chemotherapy-refractory advanced colorectal cancer (aCRC) on the CO.17 trial. HSRs, while uncommon, were occasionally severe and dose limiting. Methods: The demographics, timing and outcomes of pts with and without HSRs were evaluated. Pts with HSRs by 4 weeks were compared with those without in a landmark analysis excluding pts who died before 4 weeks and adjusting other prognostic factors including performance (PS) and KRAS status. Results: In CO.17, 288 pts were treated by CET+BSC. HSRs occurred in 39 pts (13.5%),all but 2 received prior antihistamines. None received steroid pre-med. More pts with HSRs were female, young and high PS vs. those without HSRs but none was significant. HSRs grades were (1, 2, 3, and 4) in (6.2, 3.5, 2.4, and 1.4%) of pts respectively. First HSR timing was (first dose, week 2-4, and after 1st month) in (9.4, 2.1, and 2.1%) of pts respectively. Late first HSRs occurred at wks 20 (gr3), 29, and 33 in one pt each. Any grade first HSRs occurred (during infusion, within 1hr post, and >1hr post) in (8.0, 2.4, and 3.1%) of pts respectively, and in (2.8, 0.7, and 0.3%) for gr3-4 HSRs. Gr3-4 HSRs were treated with steroids (43%), antihistamines (100%), epinephrine (36%) and ranitidine (93%). Although the protocol specified discontinuation after grade 3-4 reactions, pts were rechallenged with dose reductions (43%), rate reductions (14%) and unchanged with additional pre-medication (7%). No significant difference was found in OS (HR =0.87 with 95% CI 0.53-1.42; p=0.57]) and PFS (HR =1.04 with 95% CI 0.67-1.59, p=0.84) between 33 patients with and without HSRs within 4 weeks of treatment start. Conclusions: No statistically significant difference was found in OS or PFS in 33 patients with HSRs and those without. In a setting without steroid premed the majority of HSRs were mild, occurred within the first month, and within 1 hour of treatment but rare, late, severe reactions occurred. A comparison with dexamethasone premed in the CET arm of the CO.20 trial is planned.
Abstract 1273: Relation between tumor-associated macrophage (TAM) subsets and CD47 expression on squamous cell carcinoma of the head and neck (SCCHN) in tumor microenvironment
Authors: Koichi Sakakura, Hideyuki Takahashi, Kazuaki Chikamatsu
Journal: Cancer Research (2015)

Abstract Introduction: In general, TAM is classified into M1 producing Th1 cytokines and M2 secreting IL-10. Numerous reports have demonstrated that M2 infiltration to tumor microenvironment associates with local immunosuppression and proliferation of cancer cells. In this study, we investigated phagocytic potentials of M1 and M2 in SCCHN in relation to the expression of CD47 molecule, which is known as “Don't eat me” signal against macrophage (Mϕ). Material and Methods: CD68 (pan-Mϕ marker) positive CD163 (M2 marker) negative M1 (derived with GM-CSF and IFN-γ) and CD68+CD163+M2 (derived with M-CSF and IL-10) were induced from positively selected CD14+ cells in PBMC from a healthy donor. Phagocytosis of CD47+/CD47-SCCHN cell lines labeled with CFSE by M1/M2 were assessed using multi-color flow cytometry. Suppressions of the phagocytosis by neutralizing anti-CD47 antibody were also evaluated. Furthermore, we examined CD68, CD163 and CD47 expressions immunohistochemically in 74 cases of oral squamous cell carcinoma, and relation between Mϕ counts or CD47 expression on cancer cells and clinicopathological parameters or prognoses. Results: M1 derived from PBMC showed higher phagocytic potential comparing to M2. Phagocytosis of M1 was dose-dependently inhibited by anti-CD47 neutralizing antibody, however M2 phagocytosis was not suppressed. In immunohistochemical analysis, while CD47 was expressed in almost half cases of oral cancer, CD47 expression did not correlate to the numbers of total Mϕ nor M2. Patients with high CD47 expression on cancer cells, increasing number of total Mϕ or M2 showed significantly shorter overall survival. Conclusion: Only M1 showed CD47-dependent phagocytosis of CD47-expressed cancer cells in vitro. While CD47 expression on patient samples did not correlate with number of total Mϕ or M2, each of them independently showed significant association with prognosis. Various mechanisms were presumed between CD47 expression on SCCHN cells and tumor-infiltrating Mϕ subsets. Citation Format: Koichi Sakakura, Hideyuki Takahashi, Kazuaki Chikamatsu. Relation between tumor-associated macrophage (TAM) subsets and CD47 expression on squamous cell carcinoma of the head and neck (SCCHN) in tumor microenvironment. [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 1273. doi:10.1158/1538-7445.AM2015-1273
SRSF2 Is Essential For Hematopoiesis and Its Mutations Dysregulate Alternative RNA Splicing In MDS
Authors: Yukiko Komeno, Jinsong Qiu, Leo Lin, YiJun Xu, Felicitas Thol, Dora D Monterroza, Russell Dekelver, Liang Chen, Michael Heuser, Xiang-Dong Fu, Dong-Er Zhang
Journal: Blood (2013)
Macrophage Inflammatory Protein (MIP)-1alpha (CCL3) Is a Downstream Target of FGFR3 and RAS Signaling in Multiple Myeloma.
Authors: Esther Masih-Khan, Suzanne Trudel, ZhiHua Li, Vincent Nadeem, Ellen Wei, Joshua Paterson, Jaime O. Claudio, A. Keith Stewart
Journal: Blood (2005)
Abstract 2672: Characterization of the enhanced potency of PI3K inhibitor taselisib (GDC-0032) in PI3K mutant cell lines and models
Authors: Kyle A. Edgar, Michelle Nannini, Rebecca Hong, Charlie Eigenbrot, Stephen Schmidt, Amy Young, Deepak Sampath, Jeffrey J. Wallin, Lori S. Friedman
Journal: Cancer Research (2015)

Abstract Alterations of the phosphoinositide-3 kinase (PI3K)/Akt signaling pathway occur broadly in cancer via multiple mechanisms including mutation of the PIK3CA gene or loss of the tumor suppressor PTEN. The dysregulation of this pathway has been implicated in tumor initiation, cell growth and survival, invasion and angiogenesis; thus PI3K is a promising therapeutic target with multiple inhibitors in clinical trials. The current study investigates preclinical mechanism of action of taselisib (GDC-0032), a novel, oral, selective inhibitor of PI3K alpha sparing inhibition of PI3K beta. In preclinical studies, taselisib demonstrates greater potency in cancer cell lines harboring activating PI3K alpha mutations vs wild-type lines. Taselisib induces tumor growth arrest and regressions at tolerated doses in xenograft and patient-derived xenograft (PDX) tumor models bearing PI3K alpha mutations. Notably, taselisib is distinguished from other PI3K inhibitors by enhanced potency in PI3K alpha mutant isogenic cells compared to parental cells. Pathway inhibition and apoptosis are associated with the enhanced activity of taselisib in PI3K alpha mutant cells. Other PI3K inhibitors, including PI3K alpha selective and pan-PI3K inhibitors, do not achieve the same level of activity in PI3K alpha mutant cell lines. Taselisib is more effective at maintaining suppression of the signaling pathway upon activation of Receptor Tyrosine Kinases (RTKs), such as after alleviation of negative feedback within the pathway. Additionally, a screen to evaluate secreted factors contributing to pan-PI3K inhibitor resistance was carried out in SW48 parental and PI3Kα H1047R isogenic cells. Growth factor ligands for the EGFR family were found to reduce the activity of PI3K inhibitors. Taken together, taselisib offers greater preclinical activity in PI3K alpha mutant cells when compared to other PI3K inhibitors, which may indicate a wider therapeutic index. Citation Format: Kyle A. Edgar, Michelle Nannini, Rebecca Hong, Charlie Eigenbrot, Stephen Schmidt, Amy Young, Deepak Sampath, Jeffrey J. Wallin, Lori S. Friedman. Characterization of the enhanced potency of PI3K inhibitor taselisib (GDC-0032) in PI3K mutant cell lines and models. [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 2672. doi:10.1158/1538-7445.AM2015-2672
A Comparison of Prognostic Models for Chronic Myelomonocytic Leukemia (CMML) in the Era of Hypomethylating Agents
Authors: Eric Padron, Najla H Al Ali, Deniz Peker, Jeffrey E Lancet, Pearlie K Epling-Burnette, Ling Zhang, Alan F. List, Rami S. Komrokji
Journal: Blood (2012)