bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A83: Genes of epithelial-mesenchymal transition (EMT) reveal impact on progression and metastasis of neuroendocrine lung carcinomas: A preliminary study
Authors: Prieto Tabatha Gutierrez , Sá Vanessa Karen de , Olivieri Eloisa Helena Ribeiro , Silva Eduardo Caetano Albino da , Reis Rui Manuel , Carraro Dirce Maria , Capelozzi Vera Luiza 
Published: May 2019

Abstract
Background: Metastasis are responsible for the death of 90% of patients with lung cancer, indicating the need to know the multiple signaling pathways involved. Neuroendocrine lung carcinomas (NELC) encompass a wide spectrum of tumors, from the low-grade typical carcinoid (TC) and atypical carcinoid (AC), to the high-grade large cell neuroendocrine carcinoma (LCNEC) and the small-cell lung carcinoma (SCLC). Low-grade NELC are indolent, while high-grade NELC invade and metastasize rapidly. Biomarkers of NELC aggressiveness remain to be determined. Epithelial to mesenchymal transition (EMT) genes profile show promise as indicator of invasion and metastasis. Our aim was to evaluate: (1) EMT gene expression in NELC, (2) its relationship with the histologic subtypes, and (3) its impact on behavior of the tumors.
Methods: Patients with SCLC (n = 10), LCNEC (n=5), AC (n=2) and TC (n=7) were included. EMT gene expression was quantified with a quantitative real-time (RT)-PCR carried out on StepOnePlus™ Real-Time PCR System (Applied Biosystems) with RT2 Profiler PCR Array System (Qiagen, Dusseldorf, Germany). Associations of the gene signature and clinicopathologic features, as well as prognostic factors were evaluated.
Results: A 13-gene signature (AHNAK, COL3A1, DSP, IL1RN, MSN, PDGFRB, SNAI1, SNAI3, TCF3, TGF-beta 1, TGF-beta 2, TGF-beta 3, and VIM) that was related to EMT was upregulated in tumor-tissue from all NELC patients, mainly in those with high-grade NELC. An increased expression of DSP, TCF3, and TGF-beta 2 genes were shown in high-grade when compared to low-grade NELC and associated with lymph node metastasis with statistical significance respectively for DSP (p&lt;0.05), TGF-beta 3 (p&lt;0.05), and marginal significance for TCF3 (p=0.08). TCF3 was also associated with tobacco history (p=0.04).
Conclusion: The EMT analysis identified genes involved in cell proliferation, motility, invasion, and metastasis of NELC. We further inferred DSP, TCF3, and TGF-beta 3 as target against lung cancer metastasis and invasion, thus arising as a promising therapeutic agent.
Citation Format: Tabatha Gutierrez Prieto, Vanessa Karen de Sá, Eloisa Helena Ribeiro Olivieri, Eduardo Caetano Albino da Silva, Rui Manuel Reis, Dirce Maria Carraro, Vera Luiza Capelozzi. Genes of epithelial-mesenchymal transition (EMT) reveal impact on progression and metastasis of neuroendocrine lung carcinomas: A preliminary study [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A83.
Abstract B04: The effects of saliva exosome-like extracellular vesicles from locally advanced OSCC patients on OSCC cell lines
Authors: Bispo Karina A. , Garcia Fabyane O.T. , Carvalho Tárcia A.C.B. , Mak Milena P. , Castro Gilberto de , Pasini Fatima S. 
Published: May 2019

Abstract
Microvesicles (MV) and exosomes (Ex) are extracellular vesicles (EV) differentiated by size and biogenesis pathway but sharing similar mechanisms of released and fusion with recipient cells. The EVs' tumor cellular derived are implicated in mediating interactions with the cellular environment and are rich sources of biomarkers for noninvasive diagnosis, prognosis, and tumor monitoring. In this work we analyzed the effects of EVs like-exosomes derived from cell-free saliva of locally advanced and unresectable oral squamous cell cancer (OSCC) patients at different stages of disease progression: treatment naive (G1), after treatment and disease free for at least 2 years (G3), and healthy volunteers (G0). EVs were isolated by ultracentrifugation and analyzed by transmission electron microscopy (MET) and Nanosight quantification. The EVs effects on proliferation and migration upon SCC-4 and SCC-25 cell lines were investigated by MTT and scratch-wound assays. EVs exosomes-like were detected in saliva of all groups analyzed without differences in quantity and size distribution. The motility of the SCC-4 cell line was significantly modulated by the vesicles of the different groups analyzed after 12 h of treatment (P&lt;0.05 – ANOVA test). Both SCC-4 and SCC-25 showed similar sensitivity to cisplatin and the addition of EVs apparently decreased this sensitivity. Our preliminary data showed a possible effect of the EVs from OSCC saliva patients on the motility and sensitivity to cisplatin of the oral cell lines. Supported by Fundação de Amparo a Pesquisa (FAPESP 2013/253970).
Citation Format: Karina A. Bispo, Fabyane O.T. Garcia, Tárcia A.C.B. Carvalho, Milena P. Mak, Gilberto de Castro Jr, Fatima S. Pasini. The effects of saliva exosome-like extracellular vesicles from locally advanced OSCC patients on OSCC cell lines [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B04.
Abstract B07: CTC and CTM detection in sarcoma patients
Authors: Braun Alexcia C. , Mello Celso A L , Corassa Marcelo P. , Vanessa Alves S. , Abdallah Emne A. , Ulisses Nicolau R. , Díaz Mônica T. M. , Flores Bianca T. C. P. , Fanelli Marcelo F. , Paterlini-Brechót Patrizia , Chinen Ludmilla T. D. 
Published: May 2019

Abstract
Background: Sarcomas represent 1% of all cancers in adults, 8% in adolescents and young people, and 10% in children. Even though it is a rare cancer, it contributes to a significant loss of years of life in comparison with other types of cancer (Amankwah et al., 2013). The presence of isolated circulating tumor cells (CTCs) or circulating tumor microemboli (CTM) in the blood of patients with sarcoma may be early markers of tumor invasion, because it is known that these cells circulate in the blood for months or years before the development of metastases (Paterlini-Brechot and Benali, 2007; Klain, 2009; Rhim et al., 2012).
Objective: To isolate and quantify CTCs and CTM from sarcoma patients, evaluating their presence and correlation with progression-free survival (PFS).
Methods: Blood (approximately 8 mL) was prospectively collected from patients with different types of high-degree sarcoma. Blood was collected before the beginning of chemotherapy. The samples were processed and filtered on ISET (Isolation by Size of Epithelial Tumor Cells, Rarecells, France) system for the isolation and quantification of CTCs and CTMs. Immunocytochemistry (ICC) was later performed with anti-CD45 antibody and counterstained with hematoxylin-eosyn for leucocytes population exclusion. The cutoff was estimated using the maximum of the standardized log-rank statistic proposed by Lausen and Schumacher (1992).
Results: We analyzed 11 high-degree sarcoma patients after metastasis diagnosis, before the beginning of treatment. The median age was 53 years (18-77) and 54.5% were male. The median CTCs number was 2.0 CTCs/mL (1.0-11.0) at baseline. By Kaplan-Meier test, we observed that patients with CTC number below the established cutoff (4.5 CTCs/mL) had better PFS compared to those above the cutoff (7.4 vs. 1.0 months, respectively; P= 0.006). Moreover, patients without CTM had also better PFS compared to those patients with the presence of CTM (7.6 vs. 2.7 months, respectively; P= 0.13).
Conclusion: This is the first study to demonstrate, besides the CTC and CTM presence in sarcoma patients, its real prognostic value, even in a limited sample. Our next step is to characterize these cells to better understand its capability to promote tumor progression.
Citation Format: Alexcia C. Braun, Celso A L Mello, Marcelo P. Corassa, Alves S. Vanessa, Emne A. Abdallah, Nicolau R. Ulisses, Mônica T. M. Díaz, Bianca T. C. P. Flores, Marcelo F. Fanelli, Patrizia Paterlini-Brechót, Ludmilla T. D. Chinen. CTC and CTM detection in sarcoma patients [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B07.
Abstract B18: Metabolic signature characterization in prostate cancer mediated by Heme-oxygenase 1
Authors: Arciuch Valeria G. Antico , Anselmino Nicolas , Paez Alejandra , Cascardo Florencia , Cotignola Javier , Gueron Geraldine , Vazquez Elba 
Published: May 2019

Abstract
Prostate cancer (PCa) is the second leading cause of cancer-associated death in men, with bone metastases being the main cause of mortality. Energetic metabolism alterations have become a new hallmark of cancer, since variations in a single gene can orchestrate changes in metabolic pathways and confer an adaptive advantage. Heme-oxygenase 1 (HO-1) exerts an antitumoral role in PCa inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this work was to assess the role of HO-1 in the metabolic signature of PCa.
Through RNA-Seq we found a set of metabolic genes deregulated under pharmacologic induction (hemin treatment) or genetic induction of HO-1 in PC3 cells. STAR and ATP5L2 were found upregulated, while HMGCS2, PRODH and ACOT12 were downregulated. These genes encode for steroid hormone metabolism, ATP synthesis, ketogenesis, proline and lipid metabolism. The analysis of the deregulated genes (2-fold) under HO-1 modulation by Gene Ontology revealed alterations in several metabolic pathways such as steroid, tyrosine and lipid metabolism, and ion transport. Bone is the only site of PCa progression, and bone cells are able to produce factors that increase the growth and survival of tumor cells favoring progression. However, the molecular nature of this interaction remains to be elucidated. Our preliminary results performed on cocultures of PC3 cells (treated or not with hemin) with Raw264.7 (pre-osteoclastic) or MC3T3 (preosteoblastic) cells demonstrate that HO-1 is able to direct the metabolic fate of bone precursor cells due to the deregulation of glycolytic genes. HO-1 induction in PC3 cells downregulated the expression of PKM2 and LDHA in cocultured Raw264.7 and MC3T3 cells (p&lt; 0.05).
Based on our results, we propose HO-1 as a key regulator of the metabolic status of PCa cells and a powerful mediator capable of redefining the metabolic signature of bone precursor cells, thus favoring the establishment of a less aggressive phenotype.
Citation Format: Valeria G. Antico Arciuch, Nicolas Anselmino, Alejandra Paez, Florencia Cascardo, Javier Cotignola, Geraldine Gueron, Elba Vazquez. Metabolic signature characterization in prostate cancer mediated by Heme-oxygenase 1 [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B18.
Abstract B32: Translational potential of a small-molecule silibinin in colorectal cancer: Targeting cancer stem cells and their inflammatory niche
Authors: Agarwal Rajesh , Agarwal Chapla 
Published: May 2019

Abstract
The inflammatory milieu of colon cancer stem cell (CSC) niche is also an important growth regulator for both CSC and progenitor cell population. Inflammatory signals, e.g., cytokines arising in CSC niche, due to inflammatory cells in microenvironment, also network with other regulatory pathways to influence the expansion of both cell types. With this background, we aimed to assess whether silibinin, a nontoxic, naturally occurring chemopreventive agent with established preclinical efficacy against growth and progression of colorectal cancer (CRC), has the potential to target colon CSC and associated inflammatory niche during CRC inhibition. Our results found that silibinin strongly decreases the percentage of colonosphere formation (a stem cell characteristic) of CRC cells, and that this effect on colon CSC is mediated via blocking IL-4/6 signaling in CRC cell lines. Silibinin also strongly decreased IL-4/6 induced activation of STAT-3 and NF-kB transcriptional activity, which is associated with decreased mRNA levels of various CSC regulatory molecules, and CSC-associated markers. In other studies, silibinin significantly reduced the booster signals of macrophages towards colon CSC, resulting in decreased colonosphere numbers under both normoxic and hypoxic conditions. Furthermore, we used a colitis-related AOM/DSS-induced colon tumorigenesis model to assess the role of inflammatory conditions on colon CSC generation and expansion, and their modulation by silibinin. Our data indicated the protective effect of oral silibinin feeding in this model in terms of an absence of large macroadenomas (&gt;2-3 mm) in the colon. This effect was accompanied by minimal colonic inflammation (decrease in recruitment of inflammatory cells); tissue analysis indicated a decrease in the expression of proinflammatory cytokines, and associated transcription factors: STAT-3 and NF-kB in the colonic tissues from silibinin group. A decrease in transformed stem cell population (for CSC pool expansion) was also identified by dual staining for BMI-1 and CD44 in the colonic tissues. Together, these results highlight silibinin's potential to interfere with CSC pool expansion by targeting both colon CSC and their inflammatory niche, as well as associated signals involved with the survival and multiplication of colon CSC pool. These findings further support the translational potential and clinical usefulness of silibinin in CRC intervention and therapy. (Supported by R01 CA112304.)
Citation Format: Rajesh Agarwal, Chapla Agarwal. Translational potential of a small-molecule silibinin in colorectal cancer: Targeting cancer stem cells and their inflammatory niche [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B32.
Abstract B38: Molecular mechanisms and therapeutic implications of argininosuccinate synthesis 1 regulation in targeted arginine- and glutamine-starvation cancer therapy
Authors: Kuo Macus Tien , Tsai Wen-Bin , Long Yan 
Published: May 2019

Abstract
Argininosuccinate synthetase 1 (ASS1) is the rate-limiting enzyme that catalyzes the biosynthesis of arginine (Arg). Many malignant human tumors are auxotrophic for Arg because ASS1 is silenced. We previously demonstrated that ASS1 is a sensor of Arg auxotrophic response and a chemosensitivity marker for Arg starvation therapy. Upregulation of ASS1 is the primary mechanism of resistance to Arg starvation therapy using Arg-depleting recombinant protein, pegylated arginine deiminase (ADI-PEG20). We will present in this conference that ASS1 is also a sensor for glutamine (Gln)-deprivation response, and that upregulation of ASS1 expression is associated with resistance to Gln-starvation treatments. Knockdown of ASS1 expression resulted in increased sensitivity to both Arg- and Gln-starvation, whereas increased ASS1 expression by ectopic transfection is associated with resistance to both Arg- and Gln-starvation. The addition of permeable fumarate, a metabolite that bridges the tricarboxylic acid and urea cycles, resulted in downregulation of ASS1 expression and increased sensitivity to both Arg- and Gln-deprivation treatments. Metabolically, ASS1 sits in the middle of several metabolic pathways linking Gln and ASS1 metabolism. This may explain how ASS1 can sense both Gln- and Arg-starvation from opposite directions. Mechanistically, the Gln-deprivation response, like the Arg-auxotrophic response, downregulates HIF-1α resulting in de-repression of ASS1. In the meantime, an activator, c-Myc, is upregulated; and the upregulated c-Myc transcriptionally turns on ASS1 expression. We further also demonstrate that Arg starvation-induced c-Myc activation is regulated by the signaling transduction pasthway involving Gas/Axl → PI3 kinase → Akt → GSK3beta → cMyc. Collectively, our results have revealed the molecular basis of auxotropic responses to Arg- and Gln-deprivation, and provided preclinical implications for improving the treatment efficacy of Arg- and Gln-starvation therapies which have been in several current clinical trials. (Supported by NCI grant R01 CA149260.)
Note: This abstract was not presented at the conference.
Citation Format: Macus Tien Kuo, Wen-Bin Tsai, Yan Long. Molecular mechanisms and therapeutic implications of argininosuccinate synthesis 1 regulation in targeted arginine- and glutamine-starvation cancer therapy [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B38.
Abstract B42: Safer approaches to colorectal cancer chemoprevention
Authors: Rao Chinthalapally V. , Mohammed Altaf , Janakiram Naveena B. 
Published: May 2019

Abstract
Colorectal cancer (CRC) protective effects of NSAIDs and COX-2 inhibitors are well established; however, they are associated with gastrointestinal (GI) bleeding and enhanced cardiovascular risk. Mechanistic studies suggest that upregulation of 15-PGDH, sparing COX-1/2 and prostaglandin (PG)I2 synthase and/or selectively targeting mPGES-1 and 5-LOX, would reduce the cardiovascular side effects and may improve the chemopreventive efficacy. One unexplored area in colorectal cancer chemoprevention towards safer drug development is limited or no studies on targeting mPGES-1/5LOX. To design and develop selective inhibitors of dual mPGES-1/5-LOX, we used in silico small-molecular docking simulations approaches, and identified LFA-9 as a novel dual mPGES-1/5-LOX inhibitor among &gt;35 analogs. Azoxymethane (AOM)-induced rat colonic tumors were utilized to assess pharmacodynamic inhibitory effects of LFA-9 on mPGES-1 and 5-LOX by Radio-HPLC. At low μM LFA-9 inhibited the mPGES-1 and 5-LOX activities by ~57% and ~68%, respectively. We tested five different doses (100-1,600 ppm) of LFA-9 by modified AIN-76A diet on male C57 mice and observed that &lt;1,600 ppm dietary LFA-9 was found to be safer and free from the liver and GI toxicities. In AOM/DSS-induced colonic inflammation in F344 rat, 200 ppm and above LFA-9 completely abolishes the colonic inflammation and suppresses mPGES-1 and 5-LOX in dose-response manner. Potential CRC preventive efficacy of LFA-9 was assessed AOM-rat carcinogenesis (Aberrant Crypt Foci, (ACF) as surrogate marker in male F344 rats and intestinal tumor inhibition in APCMin/+ mice. In rats, colonic ACF were induced by AOM/DSS treatment, dietary LFA-9 (200, 400, and 600 ppm) showed dose-response (P&lt;0.0001) inhibitory effects on ACFs formation. In APCMin/+ mice study, diet containing 0, 350, and 700 ppm LFA-9 for 14 weeks administration significantly (p&lt;0.0001) reduced total intestinal tumor multiplicity and size dose-dependently in both male and female mice. At high dose both male and female mice showed &gt; 80% suppression of colonic polyps with &gt;2 mm size. Importantly, mice fed with 350-ppm LFA9 showed colon tumor inhibition of 60% (male) and 90% (female). It is noteworthy that both male and female mice fed with 700-ppm LFA-9 showed 91% inhibition of colon tumors. Overall, the above results show that LFA-9 is a novel dual mPGES-1/5-LOX inhibitor, a safer agent and potential for prevention of CRC in high-risk patients. (Grant support: NCI N01-CN 25001-26 and 1R01CA213987-01.)
Citation Format: Chinthalapally V. Rao, Altaf Mohammed, Naveena B. Janakiram. Safer approaches to colorectal cancer chemoprevention [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B42.
Abstract B43: Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy
Authors: Tilli Tatiana Martins , Carels Nicolas , Tuszynski Jack Adam , Pasdar Manijeh 
Published: May 2019

Abstract
Network-based strategies provided by systems biology are attractive tools for cancer therapy. Modulation of cancer networks by anticancer drugs may alter the response of malignant cells and/or drive network reorganization into the inhibition of cancer progression. Previously, using systems biology approach and cancer signaling networks, we identified the top 5 highly expressed and connected proteins (HSP90AB1, CSNK2B, TK1, YWHAB, and VIM) in the invasive MDA-MB-231 breast cancer cell line. Here, we have knocked down the expression of these proteins, individually or together using siRNAs. The transfected cell lines were assessed for in vitro cell growth, colony formation, migration, and invasion relative to control transfected MDA-MB-231, the noninvasive MCF-7 breast carcinoma cell line, and the nontumoral mammary epithelial cell line MCF-10A. The knockdown of the top-5 upregulated connectivity hubs successfully inhibited the in vitro proliferation, colony formation, anchorage independence, migration, and invasion in MDA-MB-231 cells, with minimal effects in the control transfected MDA-MB-231 cells or MCF-7 and MCF-10A cells. The in vitro validation of bioinformatics predictions regarding optimized multitarget selection for therapy suggests that protein expression levels together with protein-protein interaction network analysis may provide an optimized combinatorial target selection for a highly effective antimetastatic precision therapy in triple-negative breast cancer. This approach increases the ability to identify not only druggable hubs as essential targets for cancer survival, but also interactions most susceptible to synergistic drug action. The data provided in this report constitute a preliminary step toward the personalized clinical application of our strategy to optimize the therapeutic use of anticancer drugs.
Citation Format: Tatiana Martins Tilli, Nicolas Carels, Jack Adam Tuszynski, Manijeh Pasdar. Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B43.