tbuckley/cabot-search huggingface dataset:
Abstract 3894: The importance of matched tumor and normal DNA for somatic mutation discovery and clinical interpretation
Authors: Siân Jones, Mark Sausen, Valsamo Anagnostou, Samuel V. Angiuoli, Bryan Chesnick, Kevin Galens, Maura Kadan, Lisa Kann, Karli Lytle, Derek Murphy, Monica Nesselbush, Eniko Papp, Sonya Parpart-Li, David Riley, Manish Shukla, Theresa Zhang, Luis A. Diaz, Victor E. Velculescu
Journal: Cancer Research (2015)

Abstract Massively parallel sequencing approaches are beginning to be used clinically to characterize individual patient tumors and to identify targeted therapies based on mutations identified. A major question in these analyses is the extent to which these methods identify clinically actionable alterations in patients and whether the examination of the tumor tissue alone is sufficient or whether matched normal DNA should also be analyzed to accurately identify tumor-specific (somatic) alterations. To address these issues, we comprehensively evaluated tumor-normal paired samples from 753 cancers from fourteen tumor types. We analyzed somatic alterations using whole exome or targeted next generation sequencing approaches that were validated with high sensitivity and specificity. These analyses revealed an average of 140 and 4.34 somatic changes per exome and targeted analyses, respectively. Approximately 65% of cases had somatic alterations in genes associated with known therapies or current clinical trials. In contrast, a tumor-only sequencing approach followed by bioinformatic removal of common germline variants from existing databases led to a 36% and 58% false discovery rate in alterations identified in targeted and exome analyses, respectively, including in potentially actionable genes. These data suggest that matched tumor-normal sequencing analyses are essential for precise identification and interpretation of somatic alterations and have important implications for the diagnostic and therapeutic management of cancer patients. Citation Format: Siân Jones, Mark Sausen, Valsamo Anagnostou, Samuel V. Angiuoli, Bryan Chesnick, Kevin Galens, Maura Kadan, Lisa Kann, Karli Lytle, Derek Murphy, Monica Nesselbush, Eniko Papp, Sonya Parpart-Li, David Riley, Manish Shukla, Theresa Zhang, Luis A. Diaz, Victor E. Velculescu. The importance of matched tumor and normal DNA for somatic mutation discovery and clinical interpretation. [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 3894. doi:10.1158/1538-7445.AM2015-3894
A phase I study of bortezomib and interferon-alpha-2b in patients with metastatic melanoma
Authors: K. L. Kendra, G. B. Lesinski, T. E. Olencki, W. Carson
Journal: Journal of Clinical Oncology (2008)

20031 Background: Preclinical studies demonstrate synergistic activation of Caspase 3 and enhancement of survival with combination therapy. The primary objective: to determine the safety, tolerability and DLT’s of the combination therapy. Methods: Eligibility: cutaneous melanoma, PS ≤2, normal organ and bone marrow function, unlimited prior therapies. Allowed: Treated brain metastases. Excluded; peripheral neuropathy ≥ grade 2. IFN was administered at a dose of 5 MU/m2 SC on days 1, 3, and 5 (week 0). Combination therapy was given with B (on day 1) (weeks 1–5). Escalating doses were studied. Results: Ten patients were treated. Median age: 61 (40 - 82); 5 females, 5 males. Highly sun exposed areas (10). Clarks level: III (2), IV (8); primary (mitosis/10 HPF): 1 (4), 2 (1), 3 (1). Ave time from diagnosis to recurrence: 5.5 yrs. Metastatic sites: skin (5), LN (4), visceral (3), bone (1), soft tissue (1), brain (2). Median cycles received: 2.4 (cohort 1), 2 (cohort 2), 2 (cohort 3). Gr 3 toxicities: fatigue (4), vomiting (2), anorexia (2), anemia (2), lymphopenia (1), dehydration (1), depression (1), dyspnea (1), neuropathy (1). Gr 2 toxicities: neuropathy (2). Conclusions: B and IFN can be safely administered in patients with treated CNS metastasis. Toxicities: similar to IFN alone. Anti tumor response to these slowly proliferating tumors (lower doses of b) are limited. Accrual continues to the highest dose level. No significant financial relationships to disclose.
Abstract 14197: Cardiac Steatosis Induced by Cardiomyocyte-specific Adipose Triglyceride Lipase Deficiency is Associated with Impaired Oxidative Substrate Metabolism and Hypertrophy
Authors: Petra C Kienesberger, Thomas Pulinilkunnil, Martin E Young, Erin E Kershaw, Jason R Dyck
Journal: Circulation (2011)

Despite the association between myocardial steatosis and cardiac dysfunction it remains unclear whether increased cardiac lipid accumulation in the absence of increased fatty acid uptake or genetic...
Abstract 3771: Tank-binding kinase 1 associates with centrosomes and regulates microtubule dynamics and mitosis
Authors: Smitha R. Pillai, Jonathan Nguyen, Joseph Johnson, Eric Haura, Domenico Coppola, Srikumar Chellappan
Journal: Cancer Research (2015)

Abstract TANK Binding Kinase 1 (TBK1) regulates interferon signaling and NFκB function by acting as a non-canonical IκB kinase. TBK1 also participates in RalB-mediated inflammatory responses and contributes to the survival of non-small cell lung cancers (NSCLC) driven by oncogenic KRAS. In addition, TBK1 could phosphorylate and activate Akt, modulate autophagy and alter the autocrine cytokine network in cancer cells indicating oncogenic roles in addition to its immune regulatory functions. Our studies reveal that TBK1 plays a novel and direct role in promoting mitotic progression of lung cancer cells by phosphorylating multiple substrates during mitosis as well as by modulating microtubule dynamics. Levels of active phospho-TBK1 are elevated in mitotic cells where it localized to centrosomes, mitotic spindles and midbody as seen by confocal microscopy. Inhibition of TBK1 by kinase inhibitors such as BX795, Amlexanox, MRT67037 or depletion of TBK1 by shRNA resulted in mitotic defects and decreased the number of mitotic cells. TBK1 could interact with the centrosomal protein CEP170 and the nuclear mitotic apparatus protein NuMA as seen by GST binding assays, immunoprecipitation-western blot assays and proximity ligation assays. In addition, TBK1 could phosphorylate CEP170 and NuMA in in vitro kinase assays; mass spectrometry analysis revealed that TBK1 phosphorylated 12 serine residues and a threonine residue of CEP170 and five serine residues of NuMA. Inhibition or depletion of TBK1 prevented the centrosomal localization of CEP170 and the association of NuMA with the spindle poles. TBK1 depletion in A549 and H1650 cells resulted in more stable microtubules; further, depletion of TBK1 inhibited the interaction of CEP170 with the microtubule depolymerase Kif2b and the binding of NuMA to Dynein, resulting in mitotic abnormalities or mitotic arrest. In addition, inhibition of specific interaction between TBK1 and CEP170 using a 13 amino acid peptide resulted in inhibition of mitosis, enhanced microtubule stability and mitotic defects. These results are paradigm shifting that suggest TBK1 plays a significant role in regulating microtubule dynamics and mitotic progression of cells and this might have significant relevance to cancer as well as innate immune response. Citation Format: Smitha R. Pillai, Jonathan Nguyen, Joseph Johnson, Eric Haura, Domenico Coppola, Srikumar Chellappan. Tank-binding kinase 1 associates with centrosomes and regulates microtubule dynamics and mitosis. [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 3771. doi:10.1158/1538-7445.AM2015-3771
Effect of Zoledronic Acid on Bone Mineral Density in Thalassemia-Induced Osteoporosis: Results of a Phase II Clinical Trial.
Authors: Ali Taher, Sami Azar, Wael Shamseddeen, Dany Habr, Adlette Inati, Suzane Koussa, Rami Mahfouz, Zaher Otrock
Journal: Blood (2005)
Thymidine Kinase Levels Correlate With Prognosis In High Grade Lymphoma, and Can Discriminate Patients With a Clinical Suspicion Of Low Grade To High Grade Transformation
Authors: Moshe E. Gatt, Neta Goldschmidt, Moran Friedman, Ina Kalichman, Arronson Anne Charlotte, Vivian Barak
Journal: Blood (2013)
Abstract LB-294: Cellular microRNAs whose expression is altered by the oncogenic mouse polyomavirus
Authors: Neethu Chokkalingam, Chang K. Sung
Journal: Cancer Research (2015)

Abstract microRNAs are non-coding small RNAs that regulate expression of many genes and have been proposed as useful biomarkers for diverse diseases including cancer. Studies of the highly oncogenic mouse polyomavirus (Py) have identified many pathways in tumor development. The pathways found altered in Py-induced tumors strongly overlap with those affected in various human cancers, highlighting the Py-mouse systems's broad applicability to oncology. In spite of the resolving power of microRNA expression analysis and the relevance of the oncogenic mouse virus to human cancer, currently there is a lack of systematic profiling analysis on microRNAs in the context of the early phases of Py-induced tumor development and progression. We focused our investigation on cellular microRNAs that may be targeted by Py during viral infection for possible microRNA biomarkers of oncogenesis. To explore the effects of Py infection on the host microRNA expression and to identify those microRNAs that are functionally involved in Py-induced tumorigenesis, microRNA expression in uninfected and Py-infected mouse cells were compared using the microRNA Array kit. This qRT-PCR based screening and further validation assays revealed that the levels of seven murine microRNAs were elevated in Py-infected cells which include miR-let7a, miR-32, miR-124, miR-141, miR-146a, miR-215, and miR-218.Our further research focuses on identification of genes targeted by these microRNAs and their roles during viral infection. This study will bring a better understanding of microRNA involvement in tumor development, progression and possibly prevention. Citation Format: Neethu Chokkalingam, Chang K. Sung. Cellular microRNAs whose expression is altered by the oncogenic mouse polyomavirus. [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-294. doi:10.1158/1538-7445.AM2015-LB-294
Abstract 4042: Kruppel-like factor 5 promotes breast cancer proliferation, migration and invasion partially through upregulating the transcription of TNFα-induced protein 2
Authors: Lin Jia, Rong Liu, Ceshi Chen
Journal: Cancer Research (2015)

Abstract The Krupple-like factor 5 (KLF5) transcription factor is highly expressed in high-grade and basal-like TNBC breast cancers. Our previous studies reported that KLF5 promotes breast cancer cell proliferation and survival through target genes, such as FGF-BP and mPGES1. However, the mechanism by which KLF5 promotes cell migration and invasion is still not completely understood. In this study, we demonstrated that TNFAIP2, a TNFα-induced gene, is a KLF5 direct downstream target gene. The expression of the TNFAIP2 is highly correlated with the expression of the KLF5 protein in breast epithelial cell lines at both mRNA and protein levels. Manipulation of KLF5 expression positively alters TNFAIP2 mRNA and protein expression levels in multiple breast cell lines. KLF5 binds to TNFAIP2 gene promoter and activates its transcription. Functionally, TNFAIP2 promotes cell proliferation and xenograft growth in NOD-SCID mice. Importantly, knockdown of either KLF5 or TNFAIP2 significantly reduces cancer cell migration and invasion. Overexpression of TNFAIP2 rescues KLF5 knockdown-induced migration suppression in HCC1937 cells. TNFAIP2 interacts with two small GTPase Cdc42 and Rac1, increases their activities, and changes actin skeleton and cell morphyology. Finally, KLF5 and TNFAIP2 promote cell migration and invasion through activating Cdc42 and Rac1. These findings collectively suggest that TNFAIP2 is a KLF5 direct target gene and both KLF5 and TNFAIP2 promotes TNBC cell migration and invasion through Cdc42 and Rac1. Citation Format: Lin Jia, Rong Liu, Ceshi Chen. Kruppel-like factor 5 promotes breast cancer proliferation, migration and invasion partially through upregulating the transcription of TNFα-induced protein 2. [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 4042. doi:10.1158/1538-7445.AM2015-4042
Strong Cell Surface Expression of the Toll-Like Receptor Homolog CD180 Identifies Circulating Cells of Marginal Zone Lymphoma From Other B-Cell Malignancies
Authors: Laurent Miguet, Lucile Baseggio, Sarah Lennon, Pascale Felman, Luc Fornecker, Anne-Cecile Galoisy, Caroline Mayeur-Rousse, Raoul Herbrecht, Alice Eischen, Sarah Cianferani, Laurent Mauvieux
Journal: Blood (2012)
The Effect of Interleukin-11 (Oprelvekin, Neumega®) on Thrombocytopenia Associated with Tyrosine Kinase Inhibitors (TKI) in Patients with Chronic Myeloid Leukemia (CML).
Authors: Ahmed M. Aribi, Hagop Kantarjian, Patricia Ault, Charles Asa Koller, Deborah Thomas, Stefan Faderl, Guillermo Garcia-Manero, Jorge Cortes
Journal: Blood (2006)
A Novel FACS Assay for Absolute Quantification of CD20 on B-Cells and Determination of CD20 Occupancy in Whole Blood Samples Shows a Higher Binding Strength of Obinutuzumab (GA101) to CD20 on B-Lymphocytes
Authors: Drifa Beroual, Danièle Boulay-Moine, Carole Badoil, Christian Klein, Maxime Moulard
Journal: Blood (2011)
Retrospective analysis of chemotherapy with S-1 and cisplatin for advanced urachal carcinoma
Authors: Kenjiro Tsuruoka, Shinsuke Sasada, Jun Hashimoto, Makoto Kodaira, Harukaze Yamamoto, Mayu Yunokawa, Kan Yonemori, Chikako Shimizu, Yasuhiro Fujiwara, Kenji Tamura
Journal: Annals of Oncology (2015)
Long-Term Outcomes of Dasatinib Therapy in Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia from Physician’s and Patient’s Perspective
Authors: Tatyana I Ionova, Tatyana P Nikitina, Denis A Fedorenko, Taras A Gritsenko, Valentina L Ivanova, Galina B Kuchma, Tatyana V Shnaider, Inga V Sannikova, Elena I Usacheva, Kira A Kurbatova
Journal: Blood (2014)
Abstract 4125: SSA, a novel sulindac derivative, inhibits breast cancer cell invasion and migration
Authors: Bin Yi, Xingling Feng, Ruixia Ma, Xiaoguo Zhang, Hong Chang, Hongyou Zhao, Ziping Liang, Xi Chen, Xiuhua Hu, Gary Piazza, Yaguang Xi
Journal: Cancer Research (2015)

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs), such as sulindac, have been reported for striking chemopreventive activity in various types of human cancer, including breast cancer. However, few studies have reported that sulindac is able to prevent tumor metastasis. In this study, we aim to study anti-metastatic activity of sulindac in breast cancer and explore the mechanistic basis responsible for this activity, which we hypothesize may involve a cyclooxygenase (COX) independent mechanism. Numerous studies have reported that the anticancer properties of sulindac might involve, at least partially, a non-COX mediated mechanism, which provides an insight into development of safer and more efficacious new derivatives. We have previously described a chemical derivative of sulindac, referred to as sulindac sulfide amide (SSA), which lacks inhibitory effect on COX-1 or -2, yet shows greater potency to inhibit tumor cell growth compared with sulindac sulfide (SS). Our results showed that SSA treatment at a sub-cytotoxic concentration (4μM) for 36 h significantly inhibits both migration and invasion of highly aggressive MDA-MB-231, BT-20 and SK-BR-3 breast tumor cells. When treating non-invasive breast MCF-7 cells with TGF-β1 to induce their motility, we found that SSA could significantly counteract the induced motility of these cells. These results indicate that SSA can suppress breast tumor cell invasion by modulation of TGF-β1 signaling. We further studied Smad-2/3 that are important downstream components in the TGF-β1 signaling pathway and found that SSA could inhibit Smad-2/3 phosphorylation and reduce their translocation to the nucleus. In addition, Smad-2/3 knockdown could mimic the anti-invasive effect of SSA in MDA-MB-231 cells, regardless of the presence of TGF-β1. In summary, we demonstrate that the non-COX inhibitory derivative, SSA can suppress breast cancer cell invasion and migration. These observations suggest that inhibition of TGF-β1/Smad signaling is responsible for the inhibitory effect of SSA on breast tumor cell invasion and migration. Citation Format: Bin Yi, Xingling Feng, Ruixia Ma, Xiaoguo Zhang, Hong Chang, Hongyou Zhao, Ziping Liang, Xi Chen, Xiuhua Hu, Gary Piazza, Yaguang Xi. SSA, a novel sulindac derivative, inhibits breast cancer cell invasion and migration. [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 4125. doi:10.1158/1538-7445.AM2015-4125
Abstract A1-54: Pan-cancer analysis of the etiology and consequences of intratumor heterogeneity
Authors: Noemi Andor, Trevor A. Graham, Claudia Petritsch, Hanlee P. Ji*, Carlo C. Maley*
Journal: Cancer Research (2015)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR03) of the Conference Proceedings. Citation Format: Noemi Andor, Trevor A. Graham, Claudia Petritsch, Hanlee P. Ji*, Carlo C. Maley*. Pan-cancer analysis of the etiology and consequences of intratumor heterogeneity. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-54.
Implant surface roughness and patient factors on long‐term peri‐implant bone loss
Authors: Hugo De Bruyn, Véronique Christiaens, Ron Doornewaard, Magnus Jacobsson, Jan Cosyn, Wolfgang Jacquet, Stijn Vervaeke
Journal: Periodontology 2000 (2016)

Abstract Dental implant placement is a common treatment procedure in current dental practice. High implant survival rates as well as limited peri‐implant bone loss has been achieved over the past decades due to continuous modifications of implant design and surface topography. Since the turn of the millennium, implant surface modifications have focused on stronger and faster bone healing. This has not only yielded higher implant survival rates but also allowed modifications in surgical as well as prosthetic treatment protocols such as immediate implant placement and immediate loading. Stable crestal bone levels have been considered a key factor in implant success because it is paramount for long‐term survival, aesthetics as well as peri‐implant health. Especially during the past decade, clinicians and researchers have paid much attention to peri‐implant health and more specifically to the incidence of bone loss. This could furthermore increase the risk for peri‐implantitis, the latter often diagnosed as ongoing bone loss and pocket formation beyond the normal biological range in the presence of purulence or bleeding on probing. Information on the effect of surface topography on bone loss or peri‐implantitis, a disease process that is to be evaluated in the long‐term, is also scarce. Therefore, the current narrative review discusses whether long‐term peri‐implant bone loss beyond physiological bone adaptation is affected by the surface roughness of dental implants. Based on comparative studies, evaluating implants with comparable design but different surface roughness, it can be concluded that average peri‐implant bone loss around the moderately rough and minimally rough surfaces is less than around rough surfaces. However, due to the multifactorial cause for bone loss the clinical impact of surface roughness alone on bone loss and peri‐implantitis risk seems rather limited and of minimal clinical importance. Furthermore, there is growing evidence that certain patient factors, such as a history of periodontal disease and smoking, lead to more peri‐implant bone loss.
Decreased FPN1 in Myeloma Promotes Malignant Cell Growth and Osteoclast Differentiation
Authors: Zhimin Gu, He Wang, Jiliang Xia, Ivana De Domenico, Ye Yang, Junwei Huang, Hongwei Xu, Zhengdong Jin, Guido J. Tricot, Fenghuang Zhan
Journal: Blood (2014)
Advances in immunotherapeutic strategies for colorectal cancer commentary on: tumoral immune cell exploitation in colorectal cancer metastases can be targeted effectively by anti-CCR5 therapy in cancer patients by Halama et al
Authors: Dustin A. Deming
Journal: Journal for ImmunoTherapy of Cancer (2016)

Colorectal cancer is a leading cause of cancer-related death in the United States, despite recent advances in treatment strategies. The immune system has been implicated in the pathogenesis of colorectal cancer, with numerous studies identifying either antagonistic or pro-tumorigenic effects of infiltrating immune cells. Therapeutic strategies harnessing the immune system to target cancers have evolved expediently over the last 5&nbsp;years, especially the use of checkpoint inhibitors. Recently, a subset of patients whose colorectal cancers harbor a deficiency in mismatch repair proteins have demonstrated dramatic and durable response to checkpoint blockade. Unfortunately, the vast majority of colorectal cancers are mismatch repair proficient and resistant to these inhibitors. The tumor microenvironment has been implicated in the resistance to checkpoint block and ways to overcome these resistance mechanisms would be a major advance for the treatment of colorectal cancer. Here we provide commentary on a manuscript from Halama et al. examining CCL5/CCR5 as an immune biomarker and the potential role of anti-CCR5 agents for the treatment of patients with colorectal cancer.
TET2 SNP rs2454206 (I1762V) Correlates with Improved Survival In Pediatric Acute Myelogenous Leukemia, a Report From the Children's Oncology Group
Authors: Matthew A. Kutny, Todd A. Alonzo, Robert B. Gerbing, Phoenix A. Ho, Daniel Geraghty, Beverly Lange, Nyla A. Heerema, Soheil Meshinchi
Journal: Blood (2010)