bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 422: Functional analysis of family with sequence similarity 83, member B in lung adenocarcinoma
Authors: Yamaura Takumi , Okabe Naoyuki , Takagi Hironori , Owada Yuki , Inoue Takuya , Watanabe Yuzuru , Fukuhara Mitsuro , Muto Satoshi , Matsumura Yuki , Hasegawa Takeo , Yonechi Atsushi , Hoshino Mika , Osugi Jun , Shio Yutaka , Higuchi Mitsunori , Ezaki Junji , Waguri Satoshi , Gotoh Mitsukazu , Suzuki Hiroyuki 
Published: July 2016

Abstract
Background:
We have reported the usefulness of Family with sequence similarity 83, member B (FAM83B) as a novel biomarker for diagnosis and prognosis of lung squamous cell carcinoma. FAM83B expresses not only in lung cancer but also in several types of solid cancer such as breast, esophageal, and so on. More recently, novel finding showing FAM83B involve to the resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in breast cancer cell lines has been shown. EGFR signaling pathway also plays an important role in lung adenocarcinoma, therefore we hypothesize that FAM83B associates to the tumor proliferation in lung adenocarcinoma, and its results in the resistance to EGFR TKI and in a novel therapeutic target in lung adenocarcinoma.
Materials and methods:
Sixty-four paired tumor and corresponding normal tissue samples obtained from patients with lung adenocarcinoma who underwent surgical resection since 2008 to 2011 were subjected. FAM83B mRNA expression were examined and analyzed relationship between the level of FAM83B and clinicopathological variables. Then, FAM83B knock down study was performed in several types of cancer cell lines (PC-14, H820, H1650, H1975, HLC-1, H2347) to understand whether FAM83B involve to cell proliferation.
Results:
Multivariate analysis show that smaller cancer(≦3cm vs &gt;3cm, p = 0.044), and wild type EGFR(wild type vs. mutant, p = 0.004) tend to express higher FAM83B mRNA. There is no significant difference between FAM83B expression and progression-free survival. FAM83B knock down results in suppression of proliferation in HLC-1, H1650, which express high level of FAM83B protein.
Conclusions:
FAM83B could involve to tumor proliferation of lung adenocarcinoma in part, and could be the novel therapeutic target.
Citation Format: Takumi Yamaura, Naoyuki Okabe, Hironori Takagi, Yuki Owada, Takuya Inoue, Yuzuru Watanabe, Mitsuro Fukuhara, Satoshi Muto, Yuki Matsumura, Takeo Hasegawa, Atsushi Yonechi, Mika Hoshino, Jun Osugi, Yutaka Shio, Mitsunori Higuchi, Junji Ezaki, Satoshi Waguri, Mitsukazu Gotoh, Hiroyuki Suzuki. Functional analysis of family with sequence similarity 83, member B in lung adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 422.
Abstract 4222: Usefulness of VE1 immunohistochemical detection of BRAFV600E in aggressive thyroid cancers (PDCs and UCs)
Authors: Feás-Rodríguez Noa , Costa Angela M. , Alvarez Gago Tomás , Mateos Otero Juan José , Cameselle Teijeiro Jose Manuel , Muñoz Raquel , Garcia-Rostan Ginesa Maria 
Published: July 2016

Abstract
Activating BRAF mutations are frequent in thyroid follicular cell carcinogenesis. The BRAFV600E point mutation represents the most common oncogenic event in sporadic papillary thyroid cancer (PTC). Although at a much lower frequency the BRAFV600E mutation is also present among less differentiated, more aggressive, I131 resistant forms of thyroid cancer as poorly differentiated carcinomas (PDCs) and undifferentiated carcinomas (UCs). Small molecule inhibitors targeting either the BRAF V600E protein or upstream or downstream kinases involved in MAPK signalling are currently under pre-clinical or clinical investigation in advanced, metastatic, I131 resistant thyroid cancers. Recently, immunohistochemical (IHC) studies on PTCs, using the VE1 mouse anti-human BRAF V600E antibody have shown to be a reliable means for detecting the BRAFV600E mutation in a clinical setting without molecular genotyping units. In this study we sought to determine the usefulness of the VE1 antibody for detecting the BRAF V600E mutant protein in a series of 103 aggressive thyroid cancers (59 PDCs and 44 UCs) previously characterized by PCR-SSCP for the presence of BRAF mutations in exons 11 and 15. The BRAFV600E mutation was present in 10/59 PDCs (17%) and 11/44 UCs (25%). Immunohistochemistry revealed 9 mutated PDCs (sensitivity 90%) and 9 mutated UCs (82% sensitivity). The staining intensity in BRAF V600E mutated samples ranged from weak to strong. Non valuable results were found in 3 PDCs and 4 UCs. Overall the results indicate that immunohistochemistry with VE1 antibody may be an alternative to molecular biology approaches for the routine detection of BRAFV600E point mutations in clinical settings without molecular genotyping facilities. It may help clinicians in targeted therapy decision making.
Citation Format: Noa Feás-Rodríguez, Angela M. Costa, Tomás Alvarez Gago, Juan José Mateos Otero, Jose Manuel Cameselle Teijeiro, Raquel Muñoz, Ginesa Maria Garcia-Rostan. Usefulness of VE1 immunohistochemical detection of BRAFV600E in aggressive thyroid cancers (PDCs and UCs). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4222.
Abstract 4223: Novel strategy for diagnosis of solid tumors by visualization of fusion transcripts
Authors: Badiane Markey Fatu , Batish Mona 
Published: July 2016

Abstract
The discovery of chromosomal translocations as one major cause of cancers has led to the introduction of numerous diagnostic techniques to detect these chromosomal abnormalities. Chromosomal banding, DNA fluorescence in situ hybridization (DNA FISH), and RT PCR are all techniques used for the diagnosis of cancers. Despite the advancement these techniques have brought to the field, they are primarily optimized for the detection of blood cancers and are not very efficient for the detection of solid tumors which are very heterogeneous. One such cancer, Ewing's sarcoma (ES), is a prevalent pediatric, bone and soft tissue tumor that is caused by a chromosomal translocation between Ewing's sarcoma breakpoint region 1 (EWSR1) on chromosome 22 and various members of the ETS protein family. The most common fusion partner, in 85% of cases, is Friend leukemia integration 1 (FLI1) on chromosome 11 which leads to the formation of the fused EWS/FLI1 gene that codes for an aberrant transcription factor. However, even within this single translocation there are multiple breakpoint-fusion scenarios that can occur which results in heterogeneity and increases the chances of a faulty diagnosis with standard techniques. Considering the diversity that exists within the molecular abnormalities that result in Ewing's sarcoma and other solid tumors, there is a need for an alternative and more robust method of detection. The technique of single molecule fluorescence in situ hybridization (smFISH) has been modified by our group to target the EWS/FLI1 transcript that results from the chromosomal fusion; this new technique is referred to as “Fusion FISH”. In Fusion FISH, two differently labeled probe sets are designed to target each half of the EWS/FLI1 fusion transcript. A co-localization of the two probe sets indicates the presence of the EWS/FLI1 translocation and a positive test for Ewing's sarcoma. Preliminary data has established the success of Fusion FISH in detecting both type 1 and type 2 translocations in several Ewing's sarcoma cell lines. The fusion transcript is expressed at similar levels in all cell lines and clearly distinct from the signal of wild type EWS and FLI1 mRNA. Additional studies will examine this new technique in other solid cancers, patient tumor samples, and for validation of additional relevant mRNA biomarkers.
Citation Format: Fatu Badiane Markey, Mona Batish. Novel strategy for diagnosis of solid tumors by visualization of fusion transcripts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4223.
Abstract 4226: The rodent eye as a non-invasive window for understanding cancer nanotherapeutics
Authors: Wang Xinlei , Xiao Wenwu , Li Yuanpei , Zhang Pengfei , Goswami Mayank , Zawadzki Robert J. , Pugh Edward N. , Lam Kit S. 
Published: July 2016

Abstract
We have successfully used the mouse eye as a non-surgical window for highly efficient, optical investigation of xenograft models, using a state-of-the-art ocular imaging facility, the UC Davis “EyePod”. The EyePod employs single-cell resolution intravital confocal microscopy and optical coherence tomography, performed completely non-invasively through the natural optics of the eye (1). This technology enables repeatable in vivo imaging over days, weeks and even months, quantitative tracking of tumor development and delivery of theranostic nanoparticles, and the measurement of tumor and tumor microenvironment responses. Moreover, the retina is a highly “approachable part of the brain”, so that non-invasive study of ocular tumors provides a platform for examining such critical issues as drug delivery across the blood retinal barrier (BRB) and blood brain barrier (BBB). Clinical metastasis of solid tumor to the uvea is not uncommon. Therefore, uvea/subretinal xenograft implant, even though not orthotopic, is clinically relevant.
To visualize and photo-manipulate nanoparticle delivery to intraocular xenograft, we have used our recently reported nanoporphyrin (2) as the model system. This novel multifunctional porphyrin-based micellar nanoplatform allows (i) efficient encapsulation of hydrophobic chemotherapeutic drugs or fluorescent dyes, (ii) near-infra red fluorescent (NIRF) detection of the tumor via the intrinsic fluorescence of porphyrins, (iii) photodynamic therapy (PDT) and photothermal therapy (PTT) via efficient free radical and heat generation at the tumor site, respectively. Thorough understanding of how this nanocarrier distributes within the tumor microenvironment, and how it responds to controlled optical stimulation will enable us to maximize its therapeutic potential as a nano-theranostic agent. Preliminary FRET study with doxorubicin-loaded nanoporphyrin has allowed us to visualize in vivo and in real time the release of doxorubicin at the tumor site upon illumination with 680nm laser. In addition, the EyePod has enabled us to follow the tumor response over a period of 35 days. Work is currently underway to (i) develop patient-derived xenograft (PDX) model in the eye of NSG mice, and (ii) use EyePod to study the effect of tumor targeting and brain endothelial cell targeting peptides, recently developed in our laboratory, for nanodelivery into the tumor cells and across the BRB.
Citation Format: Xinlei Wang, Wenwu Xiao, Yuanpei Li, Pengfei Zhang, Mayank Goswami, Robert J. Zawadzki, Edward N. Pugh, Kit S. Lam. The rodent eye as a non-invasive window for understanding cancer nanotherapeutics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4226.
Abstract 4233: Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small lung cancer with FLT-PET imaging
Authors: Chen Xiao , Berger Ian , Khalid Urooj , Cai Jenny , Patel Akash , Katz Sharyn I. 
Published: July 2016

Abstract
Introduction: Successful inhibition of thymidylate synthase (TS) can be imaged with FLT ([18F]thymidine)-positron emission tomography (PET) thereby providing a measure of therapy response on day 1 of therapy. Here we characterize this imaging strategy for implementation into 1st line therapy with pemetrexed and cisplatin for NSCLC.
Materials and Methods: The kinetics of pemetrexed-mediated TS inhibition mediated DNA salvage pathway “flare” in DNA was first characterized in vitro using 3H-thymidine DNA incorporation assays, analysis of TK1 protein expression and mobilization of the equilibrative nucleoside transporter 1 to the cell surface membrane. Kinetics of the pemetrexed-mediated “flare” in the salvage pathway was then confirmed in an in vivo mouse model of NSCLC. Finally, a proof-of-principle clinical trial was performed to demonstrate feasibility of imaging of pemetrexed-mediated TS inhibition in human subjects with NSLC.
Results: In vitro examination of pemetrexed-induced changes in the salvage pathway revealed a burst in DNA activity that peaked at 2 hrs following the administration of pemetrexed. The addition of cisplatin did not impact the amplitude or timing of the pemetrexed-induced “flare” in the salvage pathway. In vivo imaging of TS inhibition with FLT-PET confirmed a peak in salvage pathway activity at 2 hrs. Imaging of pemetrexed-induced TS inhibition in a human clinical trial demonstrated feasibility with imaging at the 2 hr time point.
Conclusion: FLT-PET measured efficacy of pemetrexed-induced TS inhibition is optimal at 2 hrs from the start of therapy. This timing of FLT-PET imaging is feasible in human clinical trials.
Citation Format: Xiao Chen, Ian Berger, Urooj Khalid, Jenny Cai, Akash Patel, Sharyn I. Katz. Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small lung cancer with FLT-PET imaging. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4233.
Abstract 423A: A tumor-associated mRNA localizing in circulating exosomes as a novel serological marker for pancreatic cancer: the retrospective clinical study
Authors: Taniuchi Keisuke 
Published: July 2016

Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the Western world. Early diagnosis of PDAC is difficult, and no biomarkers in blood can identify patients with pancreatic cancer at an early stage. Serum cancer antigen 19-9 (CA19-9) remains the gold standard serum marker for patients with PDAC; however, inadequate sensitivity and specificity limit the use of CA19-9 in the early diagnosis of PDAC. Therefore, the discovery of biomarkers derived from blood that facilitate the distinction of PDAC would greatly affect patient management. Exosomes are extracellular lipid microvesicles, secreted by nearly all cells in body fluids such as peripheral blood. The exosome-associated RNA is called exosomal shuttle RNA that includes microRNAs and messenger RNAs (mRNAs).
Methods: The aims of the present study are to assess if the mRNA that we found in the intracellular exosomes of PDAC cells is secreted from PDAC cells, and it is useful as a serum diagnostic marker for differentiating PDAC from individuals without pancreatic disorders compared with CA19-9. 20 PDAC patients (stage III: n = 5, stage IVa: n = 7 and stage IVb: n = 8 according to the classification of pancreatic carcinoma of the Japan Pancreas Society) and 30 control individuals without pancreatic diseases were analyzed in a retrospective cohort study. Circulating exosomes were isolated from serum, and then the mRNA localizing in exosomes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
Results: We confirmed that the mRNA was localized in secreted exosomes from cultured PDAC cells: a moderately differentiated PDAC cell line (S2-013) by the use of condition media real-time RT-PCR. Furthermore, the retrospective clinical study showed that the area under the curve (AUC) of reciever operating characteristic curves (ROC curves) was 0.805 (95%CI 0.691-0.9199) for this RNA and 0.8 (95%CI 0.675-0.926) for CA19-9. If the mRNA was combined with serum CA19-9, the AUC increased (0.921 [95%CI 0.851-0.991]).
Conclusions: Our data suggest that measuring the level of this exosome-associated mRNA has the potential to improve detection of PDAC. Further research is necessary to understand whether this mRNA has clinical implications for early detection of PDAC (stage I and II) and how much this information adds to serum CA19-9.
Citation Format: Keisuke Taniuchi. A tumor-associated mRNA localizing in circulating exosomes as a novel serological marker for pancreatic cancer: the retrospective clinical study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 423A.
Abstract 4245: BLZ-100 provides optical contrast in animal models of breast cancer
Authors: Hansen Stacey , Fidel Janean , Kennedy Katie , Dernell William , Fransson Boel , Ramsay Josh , Wiss Valorie , Stroud Mark , Parrish-Novak Julia E. 
Published: July 2016

Abstract
Over 230,000 new breast cancer cases occur in the US annually. Complete surgical removal of tumor tissue is critical to reduce the risk of local recurrence. About 24% of patients who undergo breast conservation surgery require a second surgery due to positive margins. Second surgeries can be psychologically and financially costly to patients. BLZ-100, a peptide-fluorophore conjugate, is a Tumor Paint product candidate being developed to provide real-time, high resolution, intraoperative optical contrast between tumor and normal tissue, potentially helping surgeons accomplish more complete and accurate tumor resections. Intraoperative imaging with BLZ-100 may potentially improve the percentage of breast cancer patients achieving a complete resection and negative margins at their first surgical procedure. To better define the relationship between tumor pathology and BLZ-100 fluorescence, data from mouse models and canine mammary cancer cases were evaluated. Human breast cancer was modeled in mice using cell lines and xenograft models using patient-derived tumors. Review of histopathology was also conducted for each dog case. Animals received a single IV dose of BLZ-100, and tumors were excised one day after dosing. Excised tumor and normal tissues were imaged using the Odyssey Clx (LI-COR) to determine the ratio of signal in tumor compared to normal (background) tissue (TBR). Detailed histopathology reports for the dog cases were also analyzed to determine factors potentially associated with fluorescence intensity and TBR. A significant BLZ-100 TBR was observed. Histopathologic features potentially associated with TBR in dogs included cellularity and the degree of infiltration and demarcation. The studies supported the concept that BLZ-100 might potentially serve as an intraoperative optical imaging agent for breast cancer surgery.
Citation Format: Stacey Hansen, Janean Fidel, Katie Kennedy, William Dernell, Boel Fransson, Josh Ramsay, Valorie Wiss, Mark Stroud, Julia E. Parrish-Novak. BLZ-100 provides optical contrast in animal models of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4245.
Abstract 4254: Dynamic change of differentiation in spheroids derived from mixed small cell carcinoma/adenocarcinoma of the uterine cervix
Authors: Kubota Satoshi 
Published: July 2016

Abstract
Small cell carcinoma of the uterine cervix (SCCC) occurs mainly in young women with poor prognosis. Clear treatment algorithm remains difficult to develop for its rarity. Herein, we report a case of SCCC with adenocarcinoma component, and analyzed the mechanism of differentiation using a spheroid culture method.
CTOS (cancer tissue-originated spheroid) is a primary culture system by which highly purified and viable cancer cells are cultivated. The principle of this method is maintaining cell-cell contact throughout the preparation and culture process. CTOS preserves characters of original tumors, especially their differentiation status.
We generated a panel of CTOSs from 9 SCCCs. The success rate of CTOS preparation in SCCC was 100%, indicating SCCC is one of the most suitable cancers for CTOS method.
We focused on SCCCs with adenocarcinoma component. These admixed tumors have been reported in other organs, such as lung, ovary, stomach, and so on. However, the mechanism underlying mixed tumor remains unclear. One of the CTOSs retained the characteristics of mixed tumor in original tumor.
Immunostaining revealed that CD99 was positive in the region of small cell carcinoma region, and CK7 in that of adenocarcinoma. CTOSs were sorted by CD99 and EpCAM (a possible stem cell marker) expression levels, and transplanted into NOD-Scid mice. Xenotumors derived from both CD99lowEpCAMlow cells and CD99lowEpCAMhigh cells showed mixed cell type in H&E staining. Immunohistochemistry revealed that CD99 was positive in the region of small cell carcinoma, and CK7 in that of adenocarcinoma. On the other hand, CD99highEpCAMhigh cells-derived xenotumor consisted of only small cell carcinoma. The tumors were positive for CD99, but negative for CK7.
Next, we searched for the key factor of differentiation. It has been reported that hypoxia induced adenocarcinoma in lung adenosquamous cell carcinoma. When CTOSs were incubated in hypoxia (3%O2), FACS analysis revealed that proportion of CD99low cells increased (20.6% in normoxia, 40.2% in hypoxia). Immunostaining of CTOSs showed similar results. Thus differentiation status of a mixed type SCCC showed dynamic change of differentiation in spheroids depending on culture conditions.
The research can provide insight into the origin of mixed tumor of SCCC, and may be useful for developing treatment strategy.
Citation Format: Satoshi Kubota. Dynamic change of differentiation in spheroids derived from mixed small cell carcinoma/adenocarcinoma of the uterine cervix. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4254.