bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 269: The descriptive epidemiology of gynecologic cancers: an international comparison of incidence, survival and mortality
Authors: Zaidi Zoubida , Cherif Mokhtar Hamdi 
Published: July 2017

Abstract
Introduction: Gynecologic Cancers are the most common cancers in women, in 2012, Cervical Cancer (CC) is ranking as the fourth with an estimated 528.000 new cases and Ovarian Cancer (OC) is the seventh most common for females with nearly 239.000 new cases worldwide.
Aim: this communication presents the latest international descriptive epidemiological data for invasive GC, including incidence, survival and mortality in the worldwide.
Methods: -The incidence and mortality statistics presented for GC worldwide were taken from the International Agency for Research on Cancer IARC: * the Cancer Incidence in five Continents Vol X and * GLOBOCAN database, 2012.
-The data of cancer survival are taken from: * Cancer survival in five continents, a worldwide population-based study (CONCORD) version 2, 1995-2009. Estimated five-year net survival, adjusted for background mortality by single year of age, sex, calendar year in each country.
Results: CC is the most common cancer among women in 45 countries mainly in sub-Saharan Africa, part of Asia and some countries in Central and South America, the lowest incidence rates in western Europe, North America, Australia and the eastern Mediterranean. Almost 55% of all new cases of OC occurred in countries very high level of human development mainly northern Europe and America and Oceanic, Africa presents the lowest incidence.
-Data for CC are available for 602 225 women, CC survival was 50% or higher in most countries, except for Libya (Benghazi, 39%) and India (Karunagappally, 46%). During 2005-09, age-standardised 5-year net survival was 70% or higher in Iceland, Mauritius, Norway, South Korea, and Taiwan, for Qatar is also above 70% (based on only 16 cases and is not age-standardised).
-Data for ovarian cancer are available for 779 302 women, during 2005-09, age-standardised 5-year net survival was 40% or higher in Ecuador, the USA, nine countries in Asia, and eight countries in Europe. Survival in other countries was mostly in the range 30-40%, except for Libya (22%).
Conclusions: The evolution of cancers in women shows a consistent and very striking pattern during the epidemiological transition with rapid declines in the incidence of cervical cancer. Comparison of population-based cancer survival CONCORD study 2 showed very wide variations in survival from gynecologic cancer worldwide.
Note: This abstract was not presented at the meeting.
Citation Format: Zoubida Zaidi, Mokhtar Hamdi Cherif. The descriptive epidemiology of gynecologic cancers: an international comparison of incidence, survival and mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 269. doi:10.1158/1538-7445.AM2017-269
Abstract 2690: MK2 pathway blockade inhibits inflammatory cytokine production and colorectal cancer growth and invasion
Authors: Ray Anita L. , Peretti Amanda S. , Johnson Wade , Gan Gregory , Beswick Ellen J. 
Published: July 2017

Abstract
Introduction: Colorectal cancer is the third most common malignancy diagnosed for both men and women in the United States of America. High levels of inflammatory cytokines in colorectal tumors cause increased growth and invasion and carry a higher risk of metastasis. Identifying new targets to control inflammation is important for developing improved treatment approaches. Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a regulator of pro-inflammatory cytokines that may promote colorectal tumor progression. MK2 signaling is known to induce IL-1, IL-6, and TNF-α production. These pro-inflammatory cytokines are associated with CRC development, invasion, and metastasis. We hypothesized that the MK2 pathway could be an important component of CRC growth, invasion and tumor regrowth.
Methods: To investigate this pathway, CT26 CRC cells were examined. Cells were flank-injected into Balb/c mice with and without MK2 inhibitor treatment. At day 19 after tumor injection, tumors were harvested and measured using calipers. Cytokines were quantitated by multiplex bead array in organ culture supernatants and in supernatants from tumor cells plated in fibronectin coated wells. In culture, tumor cell invasion was measured in scratch wound assays containing matrigel.
Results: Treating CT26 cells with MK2 inhibitors markedly reduced tumor growth in mice by a mean of 60% compared to vehicle control treated cells. Inflammatory cytokines were also dramatically decreased with MK2 inhibition compared to controls by up to 80%. Cytokines affected included both known MK2 downstream cytokines (IL-1, IL-6, and TNF-α) and also chemokines such as MIP-1α and MCP-1 in both supernatants from cultured tumor cells and in organ culture supernatants. MK2 inhibition also decreased invasion of tumor cells in a cytokine dependent manner.
Conclusions: The MK2 pathway regulates production of multiple pro-inflammatory cytokines in colorectal tumors, including several previously unreported chemokines. Inhibition of this pathway markedly decreases tumor growth and invasion. Thus, MK2 may be a promising tumor target to prevent colorectal cancer progression.
Citation Format: Anita L. Ray, Amanda S. Peretti, Wade Johnson, Gregory Gan, Ellen J. Beswick. MK2 pathway blockade inhibits inflammatory cytokine production and colorectal cancer growth and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2690. doi:10.1158/1538-7445.AM2017-2690
Abstract 2696: PD-1 antibody treatment induces gut microbiota changes in CT-26 colon cancer syngeneic model
Authors: Ding Jian , Mao Binchen , Shi Qian 
Published: July 2017

Abstract
The gut microbiota plays an important role in shaping systemic immune response. One novel frontier in cancer research is investigating how the gut microbiota change immune response and influence the efficacy of anticancer immunotherapy drugs; this has been reported in CTLA4 and PD-L1 antibody treatment, both in laboratory and clinical settings. One recent study reported that composition of patient`s gut microbes appears to be a determining factor for immunotherapy, at least in melanoma patients. These findings shed light on the potential use of gut microbial as a biomarker for responders in cancer immunotherapy and even as a novel treatment.
Here, we evaluated the gut microbiota profiling upon PD-1 antibody (RMP1-14) treatment in CT-26 colon cancer syngeneic mouse model. Fresh feces were collected at different time points before and after treatment, snap frozen and sent for 16s RNA sequencing for microbiome profiling. Our results identified top 25 abundant taxa in genus level in CT-26 feces. Significant abundance changes were observed in several genera after PD-1 antibody treatment, especially in Akkermansia. These findings indicate that immunotherapy like PD-1 antibody can induce the profile changes of gut microbiota in CT-26 model.
Furthermore, we also investigated the correlation of gut microbiome with immune- microenvironment and the efficacy upon IO therapy, as well as the possibility to utilize microbiota profiling as a quality control step that may help to explain the variability observed in many syngeneic studies.
Citation Format: Jian Ding, Binchen Mao, Qian Shi. PD-1 antibody treatment induces gut microbiota changes in CT-26 colon cancer syngeneic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2696. doi:10.1158/1538-7445.AM2017-2696
Abstract 2697: A role for the membrane type-1 matrix metalloproteinase in the transcriptional regulation of carcinogen-induced inflammasome components
Authors: Sheehy Samuel , Annabi Borhane 
Published: July 2017

Abstract
BACKGROUND : Signal transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-mediated cancer cell functions including migration, proliferation, and survival. Besides the upregulation of the inflammation biomarker cyclooxygenase (COX)-2 expression, MT1-MMP’s role in relaying the signals triggered from pro-inflammatory cues remain poorly understood.
METHODS : Here, we treated HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), a well-known carcinogen and inducer of COX-2 and of MT1-MMP. In order to assess the global transcriptional regulatory role that MT1-MMP may exert on inflammation biomarkers, we combined gene array screens to transiant MT1-MMP gene silencing strategy.
RESULTS : We found that MT1-MMP expression exerted both stimulatory and repressive transcriptional control of several inflammasome-related biomarkers such as IL-1B, IL-6, IL-12A, and IL-33, as well as of transcription factors such as EGR1, ELK1, and ETS1/2 in PMA-treated cells. Among the signal transducing pathways explored, silencing of MT1-MMP prevented PMA from phosphorylating Erk, IκB, and p105 KF-κB intermediates. We also highlight a signaling axis linking MT1-MMP to MMP-9 transcriptional regulation.
CONCLUSIONS : Altogether, our data evidence an important involvement of MT1-MMP in the transcriptional regulation of inflammatory biomarkers consolidating its contribution in signal transducing functions, in addition to its classical hydrolytic activity.
Citation Format: Samuel Sheehy, Borhane Annabi. A role for the membrane type-1 matrix metalloproteinase in the transcriptional regulation of carcinogen-induced inflammasome components [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2697. doi:10.1158/1538-7445.AM2017-2697
Abstract 2706: KRT16 germline mutation associated with familial syndrome of tylosis with esophageal cancer (TOC)
Authors: Young Erin L. , Pflieger Lance , Maese Luke , Fowler Trent , Garfield Kinley , Samadder N. Jewel , Johnson Bella , Mason Clinton C. , Moore Barry , Ryanearson Shawn , Yandell Mark , Kohlmann Wendy , Schiffman Joshua D. 
Published: July 2017

Abstract
Tylosis (palmoplantar keratoderma) with esophageal cancer (TOC) also known as Howel-Evans syndrome has been associated with pathogenic mutations in RHBDF2. A potential TOC family was referred for clinical evaluation at the Family Cancer Assessment Clinic (FCAC) at Huntsman Cancer Institute, Salt Lake City, Utah. Multiple relatives of the proband had hyperkeratosis on the areas of skin associated with pressure and friction, especially the feet, as well as oral leukoplakia. The proband’s father, paternal aunt, paternal grandfather, and paternal great grandfather had been diagnosed with esophageal cancer. Clinical testing was unable to identify a germline mutation in RHBDFR2 that explained the observed phenotype and inheritance pattern. As part of Heritage 1K Project (University of Utah), Pediatric & Adult Cancer Section, we performed whole genome sequencing (WGS) on 5 family members, 4 that were affected with the hyperkeratosis, and 1 unaffected family member, to identify other potential genetic causes for the observed TOC phenotype. We prioritized variants via VAAST (Variant Annotation, Analysis and Search Tool). Reducing our genes of interest to those involved in palmoplantar keratoderma with PHEVOR (Phenotype Driven Variant Ontological Re-ranking Tool), we identified a pathogenic mutation: KRT16 c.379C&gt;T p.Arg127Cys. This mutation is reported in a large palmoplantar keratoderma family (without esophageal cancer) and is listed as pathogenic in Clinvar (www.ncbi.nlm.nih.gov/clinvar). KRT16 c.379C&gt;T p.Arg127Cys was present in each of the affected family members, but not in the unaffected relative. Our analysis is the first of its kind to suggest carriers of pathogenic variants in KRT16 are at-risk for esophageal cancer, and may benefit from esophageal surveillance. Additionally, patients presenting with a family history of esophageal cancer should be considered for germline testing for KRT16 mutations along with RHBDF2 mutations.
Citation Format: Erin L. Young, Lance Pflieger, Luke Maese, Trent Fowler, Kinley Garfield, N. Jewel Samadder, Bella Johnson, Clinton C. Mason, Barry Moore, Shawn Ryanearson, Mark Yandell, Wendy Kohlmann, Joshua D. Schiffman. KRT16 germline mutation associated with familial syndrome of tylosis with esophageal cancer (TOC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2706. doi:10.1158/1538-7445.AM2017-2706
Abstract 2716: A multi-parameter assay for the detection of rare malignant cells in classical Hodgkin lymphoma
Authors: U'Ren Lance , Wu David , Fromm Jonathan R. , Stilwell Jackie , Kaldjian Eric 
Published: July 2017

Abstract
Background: Classical Hodgkin Lymphoma (CHL) ranks among the most frequently occurring lymphomas and is marked by Hodgkin and Reed-Sternberg (HRS) cells, frequently multi-nucleated neoplastic cells that are derived from germinal center B cells. The genetic alterations involved in the pathogenesis of this lymphoma have been difficult to study because HRS cells are rare and are surrounded by robust, non-neoplastic infiltrate, therefore they frequently represent less than 0.1% of cells within involved lymph nodes. Consequently, methods that isolate these rare cells are required to understand pathobiology of this lymphoma. We used the AccuCyte® - CyteFinder® system (RareCyte) to develop a method for detection and isolation of HRS cells.
Methods: A 6-parameter immunofluorescence assay was designed to identify HRS cells that included HRS markers (CD40, CD30, CD15), CD3, combined CD20/CD14 and a cell membrane permeability viability dye. The assay was tested using the KMH2 Hodgkin lymphoma cell line spiked into PBMC and transferred to well slides for imaging by CyteFinder. This instrument utilizes 6-color scanning microscopy coupled with predefined algorithms to identify rare cell populations. The assay was then applied to a frozen fine needle aspirate (FNA) sample taken from the lymph node of a patient with histologically confirmed CHL. The FNA sample was thawed, prepared into a suspension, stained and analyzed as above. Cells identified with HRS phenotype were individually retrieved using the integrated CytePicker module. PCR of framework regions of the immunoglobulin heavy chain gene (IGH) was performed on single HRS cells (InvivoScribe) to assess clonality.
Results: Of ~200 KMH2 cells spiked into blood, the assay identified 180 cells (90%) with the correct HRS phenotype. HRS phenotype cells were identified in the patient lymph node FNA sample. Two individual cells analyzed by IGH framework region PCR demonstrated identical size PCR products, indicating clonality of the B cell receptor rearrangement.
Conclusion: A multi-parameter assay was successfully developed for identifying rare HRS cells with the CyteFinder system. Cells with HRS phenotype in a lymph node FNA sample were demonstrated to have clonal IGH rearrangements, demonstrating that actual HRS cells were identified. This method may be a useful tool for the diagnosis of CHL by identification of rare HRS cells from FNA specimens, as well as to investigate the molecular genomics of CHL.
Citation Format: Lance U'Ren, David Wu, Jonathan R. Fromm, Jackie Stilwell, Eric Kaldjian. A multi-parameter assay for the detection of rare malignant cells in classical Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2716. doi:10.1158/1538-7445.AM2017-2716
Abstract 2719: Accelerated BRAF mutation analysis using a fully automated PCR platform improves the management of patients with metastatic melanoma : MELFAST trial
Authors: Harlé Alexandre , Serre Delphine , Salleron Julia , Husson Marie , Leroux Agnès , Geoffrois Lionnel , Merlin Jean-Louis 
Published: July 2017

Abstract
Background : Molecular diagnosis has become a standard of care in many cancers and BRAF mutations analysis in FFPE tumor specimens is needed to initiate personalized therapy using BRAF tyrosine kinase inhibitor (vemurafenib, dabrafenib) in BRAF-mutated metastatic melanoma. Accelerated BRAF mutation analysis is achievable using CE-IVD fully automated (FA) PCR-based platform (Idylla, Biocartis) and enables the determination of BRAF mutational status in less than 2 hours including sample preparation and proved suitable for routine molecular diagnosis of metastatic melanoma (Harlé et al. PloS ONE 11(4); e0153576).
Patients and methods : MELFAST trial is an observational monocentric study aiming at evaluating the clinical impact of reducing BRAF status determination delay in patients with metastatic melanoma. 40 patients (pts) were included in MELFAST trial, 31 pts were included retrospectively with BRAF mutation analysis being performed according to standard operating procedures (SOP) using conventional PCR, 10 pts were included prospectively with BRAF mutation analysis being performed using FA-PCR.
Results : Among the 40 pts included, 3 pts were excluded because of violation of inclusion criteria. 37 pts that were analyzed (29 pts with retrospective inclusion and 8 pts with prospective inclusion). BRAF mutational status was not known at the time of treatment decision in 11/29 (38%) pts included retrospectively and in all the pts included prospectively. Using FA-PCR enables to provide BRAF mutational status within the same day for most of the samples and the reporting delay was significantly reduced using FA-PCR as compared to SOP (0 vs 7 days, p&lt;0.001) and the delay of initiation of anti-BRAF therapy was subsequently reduced (16 vs 26 days, p=0.035). This reduced delay was found to be consistent with that observed when BRAF mutational status had been anticipated and was already available at the time of treatment line decision (20 days, p=0.798).
Conclusion: As compared to conventional SOP, using FA-PCR accelerates BRAF mutation analysis reporting and significantly reduces the delay before initiation of personalized therapy in pts with metastatic melanoma. This warrants the investigation of the impact on the patients outcome i.e. progression free and overall survival.
Citation Format: Alexandre Harlé, Delphine Serre, Julia Salleron, Marie Husson, Agnès Leroux, Lionnel Geoffrois, Jean-Louis Merlin. Accelerated BRAF mutation analysis using a fully automated PCR platform improves the management of patients with metastatic melanoma : MELFAST trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2719. doi:10.1158/1538-7445.AM2017-2719
Abstract 2723: MET exon 14 skipping mutations in advanced non-small cell lung cancer (NSCLC) are not associated with MET amplification and overexpression
Authors: Gimenez-Capitan Ana , Teixidó Cristina , Aguado Cristina , Rodríguez Sonia , Bertran-Alamillo Jordi , Castellví Josep , Yeste Zaira , Pérez Ana , Rosell Rafael , Molina-Vila Miguel Angel 
Published: July 2017

Abstract
Background: Activating alterations of the mesenchymal epithelial transition (MET) oncogene in NSCLC are potentially actionable with targeted MET inhibitors. MET exon 14 skipping mutations have been described in 3% of patients (p) in NSCLC,.Fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) are currently used for detecting MET amplification and overexpression, respectively, but are not useful to detect MET splicing variants. On the other hand, the reverse transcription-polymerase chain reaction (RT-PCR) technique has the potential to detect this actionable alteration.
Methods: We designed and validated a custom set of 5´and 3´ primers to detect the MET exon 14 splicing variant by RT-PCR. RNA isolation from FFPE samples was performed with Roche High Pure FFPET RNA isolation kit and M-MLV Reverse Transcriptase enzyme was used in the RT-PCR. A panel of cell lines was initially employed to assess the performance of the technique. Subsequently, a total of 232 formalin-fixed paraffin-embedded (FFPE) samples from advanced NSCLC patients were analyzed. Of them, 15 were positive by RT-PCR (n=209) for the MET exon 14 variant. The bands corresponding to the splicing variant were submitted to Sanger sequencing.
Results were compared with FISH (ZytoVision Dual Color probe Z-2087-200) and IHC (Ventana CONFIRM anti-Total c-MET (SP44)). Results: A total of 232 EGFR-wt advanced NSCLC p were analyzed by IHC and 42 (18.1%) were considered as positive (cut-off 3+≥ 50%). Regarding FISH, MET amplification was detected in 13 out of 58 p (22.4%) evaluable while the MET exon 14 skipping variant was detected in 15 (7.2%) out of 209 p . Unexpectedly, only three (21.4%) of the positive MET exon 14 skipping p by RT-PCR were positive for IHC. Finally, of the 15 MET exon 14 positive p, 5 were evaluable for FISH and none of them were positive for MET amplification.
Conclusion: In our cohort of 232 EGFR-wt, advanced NSCLC p, the MET exon 14 skipping mutation had an incidence of 7.2% No correlation was found between the presence of the MET exon 14 variant by RT-PCR and MET overexpression or amplification. Detection of MET exon 14 alterations poses a challenge for diagnostic testing.
Citation Format: Ana Gimenez-Capitan, Cristina Teixidó, Cristina Aguado, Sonia Rodríguez, Jordi Bertran-Alamillo, Josep Castellví, Zaira Yeste, Ana Pérez, Rafael Rosell, Miguel Angel Molina-Vila. MET exon 14 skipping mutations in advanced non-small cell lung cancer (NSCLC) are not associated with MET amplification and overexpression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2723. doi:10.1158/1538-7445.AM2017-2723