tbuckley/cabot-search huggingface dataset:
Abstract 3260: Identification of a novel signaling axis that leads to co-induction of two major actin-regulatory proteins with anti-migratory properties in breast cancer cells
Authors: Marion Joy, Partha Roy
Journal: Cancer Research (2015)

Abstract Dysregulation of actin-regulatory proteins is a hallmark feature of tumor malignancy. Along this line, recent studies have established causal relationships between downregulation of expression of actin-binding proteins profilin-1 and -2 (Pfn1, Pfn2 - genes located on chromosomes 17 and 3, respectively) and increasing invasive ability of breast cancer cells. Conversely, genetically elevating expression of these Pfn isoforms suppresses aggressiveness of breast cancer cells. Therefore, identification of a common signaling pathway linking to regulation of these two Pfn isoforms may lead to a novel conceptual strategy to suppress metastatic potential of breast cancer cells in Pfn-dependent manner. We found that hyperactivating RhoA, a member of Rho-family GTPases, causes a marked depletion of cellular Pfn1 and Pfn2 expression, suggesting that a pathway downstream of activated RhoA is one of the major signaling axes for regulating Pfn1 and Pfn2 expression. Through overexpression and knockdown experiments, we further identified MKL1 (megakaryoblastic leukemia-1), a transcriptional co-factor that activates serum-response factor (SRF)-mediated gene transcription downstream of activated Rho, to be a major regulator of expression of Pfn isoforms. However, SRF does not appear to play a role in Rho-dependent Pfn regulation and furthermore, Rho-dependent Pfn regulation occurs post-transcriptionally suggesting that a non-canonical MKL1-linked pathway is involved in co-regulation of Pfn isoforms. Finally, MKL1-dependent induction of Pfn isoforms involves STAT1 and this pathway can be activated pharmacologically resulting in inhibition of breast cancer cell motility. In conclusion, we have identified a novel MKL1-STAT1 signaling axis for co-induction of the two major cellular isoforms of Pfn. This study could open up promising pharmacological points of attack in the context of metastatic breast cancer. Citation Format: Marion Joy, Partha Roy. Identification of a novel signaling axis that leads to co-induction of two major actin-regulatory proteins with anti-migratory properties in breast cancer cells. [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 3260. doi:10.1158/1538-7445.AM2015-3260
Abstract 3238: Taiwanin A targets against nonsteroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma
Authors: Hong-Meng Chuang, Horng-Jyh Harn
Journal: Cancer Research (2015)

Abstract Taiwanin A (α,β-bis(piperonylidene)-γ-butyrolactone) is isolated from Taiwania cryptomerioides. Similar to paclitaxel, Taiwanin A also extracted from tree barks and have anti-tumor activity in breast, liver, and lung cancer cell lines. The objective of this study is to demonstrate the cytotoxicity of Taiwanin A against tumor cells by increasing the expression of Non-steroidal anti-inflammatory drug-activated gene (NAG-1). NAG-1 has been reported to have antitumor and pro-apoptotic activity, suggesting potential target for cancer therapy. Silencing NAG-1 mRNA expression in A549 reduces the cytotoxicity caused by Taiwanin A. Furthermore, the c-Jun-N-terminal kinase/Ste20-related protein proline/alanine-rich kinase (JNK/SPAK) pathway played a key role in the action of NAG-1 on cell viability, whereas the addition of the JNK pathway inhibitor, SP600125, resulted in the inhibitory effect of NAG-1 and recovery of Taiwanin A treated cells. Xenograft tumor model showed that Taiwanin A dose-dependently significantly decreases tumor mediated growth in nude mice by increasing NAG-1 expression accompanied tumor apoptosis. These data support the conclusion that Taiwanin A inhibits lung carcinoma growth by increasing NAG-1 expression via the JNK pathway both in vivo and in vitro. This result might be contributed to compound design for increasing cytotoxicity activity in the future. Citation Format: Hong-Meng Chuang, Horng-Jyh Harn. Taiwanin A targets against nonsteroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma. [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 3238. doi:10.1158/1538-7445.AM2015-3238
Abstract LB-182: Improved survival among lung cancer patients taking antidepressants
Authors: Adriana Zingone, Derek Brown, Elise Bowman, Oscar Vidal, Joel Neal, Julien Sage, Brid M. Ryan
Journal: Cancer Research (2015)

Abstract In recent years, the anti-cancer properties of several commonly used drugs have been explored, with drugs such as aspirin and beta-blockers associated with improved cancer outcomes. Emerging evidence suggests that the antidepressant family of drugs may target key pathways in cancer cells, raising the possibility that such drugs could be re-purposed for cancer treatment. Here, using the NCI-MD lung cancer study, we assessed antidepressant use in 1,098 lung cancer patients. Strikingly, antidepressant use was associated with a significant extension of lung cancer-specific survival (HR = 0.78, 95% C.I. = 0.63 - 0.97, P = 0.027) (model adjusted for age, gender, race, smoking status, pack-years of smoking, tumor stage and histology). When assessing distinct classes of antidepressants, we observed that NDRIs (norepinephrine and dopamine reuptake inhibitors) and TCAs (tricyclic antidepressants) were specifically associated with extended survival: TCA HR = 0.40, 95% C.I. = 0.18 - 0.91, P = 0.028 and NDRI HR = 0.61, 95% C.I. = 0.39 - 0.95, P = 0.027). In contrast, SRIs (serotonin reuptake inhibitors) were linked with worse survival (HR 1.94 95% C.I. 1.10 - 2.42, P = 0.023). Importantly, the extended survival time associated with antidepressants was not associated with the typical indications for these drugs, suggestive of a direct effect on lung cancer cells. In addition, as we assessed lung cancer-specific survival we conducted a competing risks analysis, the results of which showed that both NDRIs and TCAs were associated with lung cancer survival (fully adjusted model NDRI, HR: 0.63, 95% C.I. 0.40 - 1.00, P = 0.05) (fully adjusted model TCA, HR: 0.36, 95% C.I. 0.17 - 0.76, P = 0.007). We provide strong evidence that lung cancer patients taking antidepressants, particularly NDRIs and TCAs, have a significantly prolonged survival. Considering the manageable and largely tolerable side effects of antidepressants, and the low cost of these drugs, these results indicate that repositioning antidepressants as adjunct therapeutics with chemotherapy may have a rapid and significant translational impact for lung cancer patients. Citation Format: Adriana Zingone, Derek Brown, Elise Bowman, Oscar Vidal, Joel Neal, Julien Sage, Brid M. Ryan. Improved survival among lung cancer patients taking antidepressants. [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-182. doi:10.1158/1538-7445.AM2015-LB-182
Abstract 4333: Association of TP53 mutation status with clinical outcomes in patients with EGFR mutated non-small cell lung cancer (NSCLC)
Authors: Saman Ahmed, Charu Aggarwal, Rosemarie Mick, Joshua Bauml, Roger Cohen, Stephan Kadauke, Trisha Sterlicchi, Tracey L. Evans, John C. Kucharczuk, Charu Desphande, Jennifer J D Morrissette, Robert Daber, Corey J. Langer
Journal: Cancer Research (2015)

Abstract Introduction: Molecular characterization of tumors is critical in the modern treatment of NSCLC. Epidermal Growth Factor Receptor (EGFR) and p53 are commonly mutated genes in NSCLC with independent prognostic implications, but the significance of the co-existence of these mutations inpatients (pts) with Stage IV NSCLC is not well established. Herein, we describe the relationship of EGFR and TP53 mutations (MT) in pts with Stage 4 or recurrent NSCLC and their correlation with pt demographics and therapeutic outcomes. Study Design: We conducted a retrospective analysis of Stage 4 and recurrent EGFR MT (+) NSCLC pts with TP53 MT status determined by the Gene Sequence Analysis Panel obtained at the Abramson Cancer Center between 6/1/2012 and 2/1/2014. Overall survival (OS) and progression-free survival (PFS) were estimated for the TP53 MT (+) and wild type (WT) cohorts from the date of diagnosis. Results: Thirty-six EGFR (+) pts were identified, of whom 26 (72%) were TP53 MT (+). Pt characteristics were similar between cohorts, except for a higher rate of bone metastasis in pts with p53 WT (p = 0.07, Table 1). Median potential follow-up for OS was 15.1 mos. 60% of patients in TP53 WT group received TKI compared to 69% in TP53 MT (+). Of the 36 pts, 9 (25%). have died. A trend towards shorter median OS was seen in pts with p53 MT. (p = 0.08). PFS did not correlate with p53 MT status (p = 0.53). Conclusion: Coexistence of p53 MT and EGFR MT may be associated with shorter survival. Larger sample size and longer clinical follow up will be necessary to determine if these differences are statistically significant and whether TP53 MT status is an independent prognostic factor in EGFR MT NSCLC. Citation Format: Saman Ahmed, Charu Aggarwal, Rosemarie Mick, Joshua Bauml, Roger Cohen, Stephan Kadauke, Trisha Sterlicchi, Tracey L. Evans, John C. Kucharczuk, Charu Desphande, Jennifer J D Morrissette, Robert Daber, Corey J. Langer. Association of TP53 mutation status with clinical outcomes in patients with EGFR mutated non-small cell lung cancer (NSCLC). [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 4333. doi:10.1158/1538-7445.AM2015-4333
Mechanisms of Heme Oxygenase 1-Induced Resistance to Imatinib In CML Cells.
Authors: Daniele Tibullo, Ignazio Barbagallo, Antonio Branca, Cesarina Giallongo, Piera La Cava, Nunziatina Parrinello, Giovanni Li Volti, Angelo Vanella, Fabio Stagno, Giuseppe A Palumbo, Francesco Di Raimondo
Journal: Blood (2010)
The importance of network intervention for cancer patient welfare. the ccm 2012 project: the molise experience
Authors: L. Di Lullo, M.A. Viglione, C. Spina, C. Franchella, M. Bellomo, P. Antonecchia, T. Manfredi Selvaggi, P. Santella, G. Marra, M. Musacchio, G. Antuzzi, A. Silvestri, M. Specchia, S. Piano, G. Giglio, G. Fabrizio, F. Carrozza
Journal: Annals of Oncology (2015)
Cognitive, Behavior and Academic Problems in Adolescent Survivors of Childhood Acute Lymphoblastic Leukemia (ALL): A Report from the Childhood Cancer Survivor Study
Authors: Lisa M Jacola, Kim Edelstein, Wei Liu, Ching-Hon Pui, Robert J. Hayashi, Nina Kadan-Lottick, Deokumar Srivastava, Tara O Henderson, Leslie L. Robison, Gregory T. Armstrong, Kevin R. Krull
Journal: Blood (2015)
Making Molecular Imaging a Clinical Tool for Precision Oncology
Authors: David A. Mankoff, Michael D. Farwell, Amy S. Clark, Daniel A. Pryma
Journal: JAMA Oncology (2016)

Individualized cancer treatment, tailored to a particular patient and the tumor's biological features (precision oncology), requires a detailed knowledge of tumor biology. Biological characterization is typically performed on biopsy material, but this approach can present challenges for widespread and/or heterogeneous disease and for performing serial assays to infer changes in response to therapy. Molecular imaging is a complementary approach that provides noninvasive and quantitative measures of the in vivo biology of the full disease burden and is well suited to serial assay.Molecular imaging can provide unique information to guide precision oncology that includes measuring the regional expression of therapeutic targets, measuring drug pharmacokinetics, measuring therapy pharmacodynamics, and providing a marker of therapeutic efficacy that is highly indicative of outcome. Thus far, most trials of novel molecular imaging in oncology have been small, single-center trials. Only a few methods have progressed to multicenter trials and even fewer have become part of clinical practice.Molecular imaging holds great promise for precision oncology, complementing tissue-based markers to guide more effective, less toxic, and more cost-effective cancer treatments. Beyond logistical and technical challenges, moving new imaging tests from the laboratory to the clinic requires a compelling use case that will benefit patients and/or improve cost-effectiveness, and it requires the collaboration of imagers, oncologists, and industry to reach its true clinical potential.
Disease Subtype–Independent Biomarkers of Breast Cancer Chemoprevention by the Ayurvedic Medicine Phytochemical Withaferin A
Authors: Suman K. Samanta, Anuradha Sehrawat, Su-Hyeong Kim, Eun-Ryeong Hahm, Yongli Shuai, Ruchi Roy, Subrata K. Pore, Krishna B. Singh, Susan M. Christner, Jan H. Beumer, Nancy E. Davidson, Shivendra V. Singh
Journal: JNCI Journal of the National Cancer Institute (2016)

A nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study was undertaken to determine the efficacy of an Ayurvedic medicine phytochemical (Withaferin A, [WA]) for chemoprevention of breast cancer and to elucidate its mode of action.Chemopreventive efficacy of WA (4 and 8 mg/kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU; n = 14 for control group, n = 15 for 4 mg/kg group, and n = 18 for 8 mg/kg group). The mechanisms underlying breast cancer chemoprevention by WA were elucidated by immunoblotting, biochemical assays, immunohistochemistry, and cytokine profiling using plasma and tumors from the MNU-rat (n = 8-12 for control group, n = 7-11 for 4 mg/kg group, and n = 8-12 for 8 mg/kg group) and/or mouse mammary tumor virus-neu (MMTV-neu) models (n = 4-11 for control group and n = 4-21 for 4 mg/kg group). Inhibitory effect of WA on exit from mitosis and leptin-induced oncogenic signaling was determined using MCF-7 and/or MDA-MB-231 cells. All statistical tests were two-sided.Incidence, multiplicity, and burden of breast cancer in rats were decreased by WA administration. For example, the tumor weight in the 8 mg/kg group was lower by about 68% compared with controls (8 mg/kg vs control, mean = 2.76 vs 8.59, difference = -5.83, 95% confidence interval of difference = -9.89 to -1.76, P = .004). Mitotic arrest and apoptosis induction were some common determinants of breast cancer chemoprevention by WA in the MNU-rat and MMTV-neu models. Cytokine profiling showed suppression of plasma leptin levels by WA in rats. WA inhibited leptin-induced oncogenic signaling in cultured breast cancer cells.WA is a promising chemopreventative phytochemical with the ability to inhibit at least two different subtypes of breast cancer.
Trimethylamine <i>N</i>-Oxide, the Microbiome, and Heart and Kidney Disease
Authors: Steven H. Zeisel, Manya Warrier
Journal: Annual Review of Nutrition (2017)

Trimethylamine N-oxide (TMAO) is a biologically active molecule and is a putative promoter of chronic diseases including atherosclerosis in humans. Host intestinal bacteria produce its precursor trimethylamine (TMA) from carnitine, choline, or choline-containing compounds. Most of the TMA produced is passively absorbed into portal circulation, and hepatic flavin-dependent monooxygenases (FMOs) efficiently oxidize TMA to TMAO. Both observational and experimental studies suggest a strong positive correlation between increased plasma TMAO concentrations and adverse cardiovascular events, such as myocardial infarction, stroke, and death. However, a clear mechanistic link between TMAO and such diseases is not yet validated. Therefore, it is debated whether increased TMAO concentrations are the cause or result of these diseases. Here, we have tried to review the current understanding of the properties and physiological functions of TMAO, its dietary sources, and its effects on human metabolism. Studies that describe the potential role of TMAO in the etiology of cardiovascular and other diseases are also discussed.
Mechanism Research of Reversal of Multidrug Resistance by the Application of 5-Bromotetrandrine and Magnetic Nanoparticle of Fe3O4 Combined with Daunorubicin in a Human-Nude Mice Xenograft Model
Authors: Bao-An Chen, Ya-nan Wu, Jian Cheng, Feng Gao, Wen-lin Xu, Hui-lin Shen, Jia-hua Ding, Chong Gao, Yun-Yu Sun, Jun Wang, Gang Zhao, Hui-hui Song, Wen Bao, Xin-chen Sun, Hong-yan Cheng, Yu-xia Deng, Guo-hong Li, Li-jie Liu, Wen-ji Chen, Jue-qiong Wang, Peng Yuan, Xiao-ping Pei, Ning-na Chen, Xue-mei Wang
Journal: Blood (2008)
OC-010 Phenotyping<i>Trichuris</i>colitis reveals innate and adaptive immunological commonalities to human Crohn's disease
Authors: S E Levison, J T McLaughlin, L Zeef, J L Pennock
Journal: Gut (2010)

<h3>Introduction</h3> <i>Trichuris muris</i>, an intestinal dwelling nematode, induces chronic colitis in susceptible mouse strains. Pathology is characterised by patchy, full thickness colonic inflammation, similar to Crohn9s disease (CD). Conversely, resistant mouse strains exhibit transient acute infection (&lt;14 days) with quick and full resolution. Although not an aetiological trigger for CD, the similar histology and strain-dependent response to Trichuris may permit identification of immuno-genetic mechanisms which initiate or perpetuate chronic colitis/resolution. Accurate mechanistic and clinical phenotyping relevant to outcome is essential, and permits biological comparison between <i>T muris</i> colitis and human colitides. <h3>Aims</h3> (1) Characterise colonic mucosal gene expression in resistant and susceptible mouse strains following <i>T muris</i> infection. (2) Phenotype and compare the clinical and immunological profiles of <i>T muris</i> chronic colitis with available CD data. <h3>Method</h3> Susceptible (AKR) and resistant (BALB/c) mice were administered 300 <i>T muris</i> ova by oral gavage. Naïve, resistant and susceptible mice were compared at day 35 post-infection. Wellbeing, body weight and stools were assessed throughout. Worm count, serum IgG, macroscopic and microscopic colonic changes were determined. Pooled colonic mRNA (n=5) was applied to Affymetrix GeneChip Mouse Exon 1.0 ST arrays. 3 replicate GeneChips were processed per study group. Bio-informatic and ANOVA statistical analysis, qPCR replication, and in silico data mining was performed. <h3>Results</h3> Resistant BALB/c exhibited “normal” macroscopic and microscopic appearances and a strong Th2 immune response post-infection. Diarrhoea, weight loss, and colonic shortening were seen in susceptible infected AKR, with moderate-to-severe focal, transmural colonic inflammation and fat hypertrophy. Consistent with clinical and histological findings, infected AKR demonstrated differentially upregulated innate pattern-recognition and autophagy transcripts (eg, TLR4, MyD88, Ripk2, NFkB, NOD2, IRGM) (&gt;×1.2-fold upregulation cf. naïve, p&lt;0.05). Similarly significant upregulated expression of adaptive Th1 and Th17/IL-23R pathway cytokines, receptors and transcription factors was found in colitic AKRs post-infection (eg, IFNg, TNFa, IL23a, IL-12b, IL-12Rb1, TGFb, Stat3, IL-17F, IL-6, IL-21). Mechanistic gene expression patterns with parallels to CD were demonstrated. <h3>Conclusion</h3> With clinical, histological, and immunological commonalities with human Crohn9s disease, chronic Trichuriasis offers a validated, immuno-competent and reproducible tool for colitis research. The exploration and translation of resistance and susceptibility phenotypes/genotypes in this model of colonic inflammation may be far reaching.
NIH Charts a Path for Nutrition Science
Authors: Jennifer Abbasi
Journal: JAMA (2016)

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Abstract 3348: Tumor irradiation induced a phenotype change of monocytes to facilitate vascular regrowth
Authors: Lei Deng, Jason Stafford, Sophia Chernikova, Shie-chau Liu, Jianguo Sun, J. Martin Brown
Journal: Cancer Research (2015)

Abstract We and others have previously shown that tumor irradiation mobilizes CD11b+ myeloid cells from bone marrow into the tumor thereby facilitating vascular regrowth and tumor recurrence. However, how these CD11b+ cells promote vasculature growth remains largely undefined. In this study, we found that CD11b+ cells in a 12Gy-irradiated U251 glioblastoma tumor model were largely Ly6g negative, suggesting that these cells are not in the granulocyte lineage, but rather are monocyte/macrophages (CD11b+Ly6g-). Interestingly, we found that the proportion of Ly6c+ monocytes in the irradiated tumor remained unchanged compared to that in the pre-irradiate tumor. However, the proportion of Ly6c- monocytes rose, driving the increase of total CD11b+ cells post-irradiation. Compared to Ly6c+ monocytes, Ly6c- cells in irradiated tumors were the major cells expressing VEGF. In vitro culture of murine bone marrow enriched Ly6c+ monocyte with colony stimulating factor-1 (CSF-1) downregulated Ly6c expression and increased in vitro angiogenic capability as demonstrated by the tube formation assay. Adding PLX3397, a CSF-1 receptor inhibitor to irradiation, which has been shown to delay tumor growth previously, decreased the Ly6c- monocytes more than the Ly6c+ monocytes. Given that we and others have previously shown that CSF-1 expression was increased in irradiated tumors, we conclude that tumor irradiation induced a phenotype change of monocytes from Ly6c+ to Ly6c- and that the latter, which are more pro-angiogenic, promote tumor vascular regrowth and recurrence post-irradiation. Citation Format: Lei Deng, Jason Stafford, Sophia Chernikova, Shie-chau Liu, Jianguo Sun, J. Martin Brown. Tumor irradiation induced a phenotype change of monocytes to facilitate vascular regrowth. [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 3348. doi:10.1158/1538-7445.AM2015-3348