bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5131: Differentially expressed proteins in esophageal squamous cell carcinoma tissue
Authors: Si Fuchun 
Published: September 2020

Abstract
Purpose: To identify differentially expressed proteins among the esophageal squamous cell carcinoma(ESCC) carcinoma tissue, adjacent normal tissue, normal esophageal mucosa, in order to look out the protein related to different stages and study the molecular mechanism and occurrence of the esophageal squamous cell carcinoma.
Methods: Tissue specimens of ESCC and the corresponding clinical data database of ESCC patients were established, a total of 69 patients were selected according to distribution of their sex and age. Two-dimensional gel electrophoresis technology to electrophoresis and get the separation protein of cancerous tissues, adjacent tissues and normal esophageal tissues,then ImageMaster 2D Platinum software was used to search, quantify, match and statistical analysise the proteins on the gel image. 4700 Proteomics Analyzer (TOF/TOFTM) was used to analyze protein spots, in which differentially expressed proteins meet standards were further searched in the Matrix Science, London, UK protein database.
Results: Totle 44 and 29 kinds of differentially expressed proteins were screened from esophageal cancer tissues, adjacent noncancerous tissues and normal tissues, among which, there were 13 differentially expressed proteins between esophageal cancer tissues and adjacent noncancerous tissues, 14 differentially expressed proteins between esophageal cancer tissues and normal tissues, 17 between esophageal adjacent noncancerous tissues and normal tissues. These differential expression proteins mainly involved in PKC-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase, nuclear factor of activated T cells(NFAT) pathway, Integrin Signaling Pathway, Cell to Cell Adhesion Signaling, Calmodulin(CaM) nuclear factor of activated T cells, Mineral absorption of calcium binding protein path way(S100), Path way of vascular smooth muscle contraction affe cted by caldesmon, Apoptotic Signaling in Response to DNA Damage path way, which had the function of cytoskeleton structure, protein phosphorylation, acetylation of aminoend, regulation of calcium combination,tumor cell movement, signal transduction, cell differentiation, cell apoptosis, muscle contraction, translation regulation, gene expression, energy metabolism, cell proliferation.
Conclusion: This study study achieved differentially expressed protein in ESCC tissue patients, provides new basis for the study of esophageal cancer carcinogenesis mechanism.
Citation Format: Fuchun Si. Differentially expressed proteins in esophageal squamous cell carcinoma tissue [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5131.
Abstract 5140: The expression and function of LAP2 and its interaction with Chmp1A in pancreatic cancer
Authors: Park Maiyon 
Published: September 2020

Abstract
Introduction: Chromatin modifying protein 1A (Chmp1A) suppresses pancreatic cancer growth by the activation of ATM and p53. To understand the mechanisms underlying the function of Chmp1A in pancreatic cancer, Chmp1A associated proteins were identified using proteomic analysis. Lamina-associated polypeptide 2 (LAP2) protein isoforms were found to interact with Chmp1A. LAP2 has been shown to interact with Retinoblastoma (Rb) tumor suppressor and shown to be up-regulated in most proliferating cancer cells. However, the function of LAP2 in pancreatic cancer has been poorly understood. In this study, we propose that LAP2 protein functions as tumor suppressor by interacting with Chmp1A in pancreatic cancer.
Experimental procedures: LAP2 transcripts were determined by RT-PCR and LAP2 proteins by WB and microscopic analysis in pancreatic cancer cells compared to normal pancreatic cells. We then tested the function of LAP2 by examining the effect of its overexpression on cancer cell growth. We also tested the interaction between Chmp1A and LAP2 by examining LAP2 expression in Chmp1A overexpressing or silenced cells and vice versa.
Results: The level of LAP2 transcripts and proteins was increased in pancreatic cancer, compared to normal cells. Interestingly, LAP2 protein level was increased in cells derived from well, but not poorly differentiated pancreatic cancers. Immunostaining demonstrated an increased and altered cellular expression of LAP2, compared to normal. LAP2 expression was increased in Chmp1A overexpressing cells but decreased in Chmp1A silenced cells. In addition, Chmp1A expression was increased in LAP2 overexpressing cells.
Summary: The expression of LAP2 isoforms were increased in tumor cells, compared to normal pancreatic cells. LAP2 overexpression study suggests its functions as tumor suppressor in pancreatic cancer. Immunocytochemical analysis suggests that the increased and altered expression of LAP2 might be important for its function in pancreatic cancer. Our data also indicates that there is comparable change in the expression between Chmp1A and LAP2 in pancreatic cancer cells.
Citation Format: Maiyon Park. The expression and function of LAP2 and its interaction with Chmp1A in pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5140.
Abstract 5176: A novel, completely human fusion construct containing active Granzyme B efficiently kills Folate Receptor alpha positive tumor cells
Authors: de Cienfuegos Ana Alvarez , Cheung Laurence H. , Mohamedali Khalid A. , Hittelman Walter N. , Rosenblum Michael G. 
Published: September 2020

Abstract
Folate receptor alpha (FRα) is an attractive therapeutic target because it is highly overexpressed on several tumors such as ovarian, breast and lung cancers and demonstrates low or restricted distribution on normal tissues. In addition, FRα has been shown to play a tumor promoting role with its expression associated with poor prognosis of cancer patients. In our laboratory, we have generated two new molecules targeting FRα and containing active granzyme B (GrB) as the cytotoxic payload. We used as binding domains two different scFvs targeting the FRα from antibodies used in clinical trials. These human scFvs (designated mov003 and mov018) were fused to human GrB through an engineered IgG heavy-chain fragment (designated as Fc) which contains a dimerization domain. The constructs were cloned into the pSECTag vector containing an upstream 5 kDa purification tag with an enterokinase (EK) cleavage site for facile removal. The molecules were expressed in transiently-transfected HEK-293E suspension cells over 3 days at 37°C in 5% CO2. The molecules were isolated from culture media and purified by ion-exchange chromatography followed by EK cleavage to remove the free tag. The yields were 12-18 mg/L for both molecules. The assessment of the specific binding of each molecule to the antigen target is ongoing. The cytotoxicity of the constructs against a panel of cell lines expressing various levels of FRα showed a specific cytotoxic effect with an IC50 in the low nanomolar range (5-100 nM), particularly exhibiting very low IC50 values against breast (MDA-MB-231) and ovarian cell lines (IGROV-1). Receptor negative cells demonstrated IC50 levels in the micromolar range. Based on IC50 values, these data demonstrate suggest the fusion constructs targeting FRα are efficiently internalized and effectively deliver the active serine protease to the cytosol, activating the cytotoxic cascade. In vitro stability assays over 96 hours showed that both constructs are highly stable in mouse serum. Immunofluorescence and confocal studies to examine the time course of internalization and the pro-apoptotic events triggered by these agents are under examination and will be presented. Research conducted, in part, by the Clayton Foundation for Research.
Citation Format: Ana Alvarez de Cienfuegos, Laurence H. Cheung, Khalid A. Mohamedali, Walter N. Hittelman, Michael G. Rosenblum. A novel, completely human fusion construct containing active Granzyme B efficiently kills Folate Receptor alpha positive tumor cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5176.
Abstract 5246: Disulfiram anticancer metabolite, dithiocarb-copper complex, demonstrates anti-neoplastic activity against hypermutated colorectal cancers
Authors: Dumut Daciana Catalina , De Sanctis Juan B. , Mistrik Martin , Skrott Zdenek , Dzubak Petr , Bartek Jiri , Hajduch Marian , Radzioch Danuta 
Published: September 2020

Abstract
Introduction: Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the United States. It was responsible for about 51,000 deaths during 2019. Surgical resection and systemic chemotherapy are standard approaches to treat both localized and metastatic CRC (mCRC). However, the effect of the chemotherapy depends on the characteristics of the individual tumor, for instance CRC subtypes with a microsatellite instability (MSI) tend to have better prognosis and response to both chemotherapy and immune check-point inhibition. Recently, Disulfiram's anti-cancer activity was explored and its metabolite ditiocarb-copper complex (CuET) was found to have high anti-cancer activity. The mechanism of action of CuET was proposed to act through p97 segregase adaptor NPL4 and activation of endoplasmic reticulum stress leading to preferential apoptosis of cancer cells. Since altered protein degradation pathway is targeted by CuET, this compound might display high efficacy in highly mutated colorectal cancers.
Methods: To assess CuET anti-cancer activity in vitro, we performed survival curve assays and colony-formation assays in both murine hypermutated colorectal cancer cell line MC-38 as well as in human KRAS mutant and MSI HCT116 cell line. We also evaluated anti-metastatic effect of CuET on both cell lines through migration-invasion assays in Boyden chamber setting. We assessed in vivo efficacy of systemic treatment with CuET alone or in combination with irinotecan, against MC-38 model in immunocompetent C57BL/6 mice. We characterized tumor growth, mice survival and tumor histopathology.
Results: Our results demonstrate that CuET displays cytotoxicity in MC-38 and HCT116 cells at very low doses with respective IC50 of 46nM and 88nM. CuET also significantly reduces the ability of both cell lines to grow and form colonies under sustained treatment. Additionally, CuET is effective in significantly reducing cancer cell migration and invasion through porous membrane in vitro. Furthermore, systemic treatment with CuET significantly reduced tumor growth in mice and prolonged survival when compared to controls.
Conclusion: CuET demonstrates cytotoxic activity against hypermutated colorectal cancer cells both in vitro and in vivo and should be further investigated in clinical trials.
Citation Format: Daciana Catalina Dumut, Juan B. De Sanctis, Martin Mistrik, Zdenek Skrott, Petr Dzubak, Jiri Bartek, Marian Hajduch, Danuta Radzioch. Disulfiram anticancer metabolite, dithiocarb-copper complex, demonstrates anti-neoplastic activity against hypermutated colorectal cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5246.
Abstract 5260: Preclinical studies with ONC201 in combination with clinically approved chemotherapy as a novel treatment strategy against Small Cell Lung Cancer (SCLC)
Authors: Lee Young S. , Zhou Lanlan , Azzoli Christopher , El-Deiry Wafik S. 
Published: September 2020

Abstract
According to the American Cancer Society, about 10-15 percent of all lung cancer diagnoses are small cell lung cancer (SCLC). The median survival rate of limited-stage small cell lung cancer is about 12 to 16 months. Several clinically approved chemotherapy drugs have been used to treat SCLC, with several more currently under clinical trials. However, a novel combination is still needed to increase patient life expectancy. ONC201 is an impridone, currently in clinical trials, that has proven to have proapoptotic effects in multiple tumor types. We hypothesized that treating SCLC cell lines with ONC201 in conjunction with clinically approved chemotherapy drugs, such as etoposide and carboplatin, will have a synergistic effect and serve as a potential novel combination treatment plan. SCLC cell lines H1048 and H1105 were treated for 72 hours with ONC201 and etoposide, or ONC201 and carboplatin. CellTiter-Glo cell viability assay and Western blotting of PARP cleavage and ATF4 were used to check synergy in the combination treatments. The combination of ONC201 and clinically approved chemotherapy drugs, etoposide and carboplatin, revealed that there was an upregulation in cleaved PARP and a synergistic effect on the overall cell samples. When looking at the combination index of the cell proliferation assays, the best index for each combination was 0.867 with an ONC201 dosage of 4 μM and an etoposide dosage of 0.05 μg/mL in H1048, 0.43191 at ONC201 dosage 0.3125 μM and etoposide dosage 2.5 μg/mL in H1105, and 0.20278 at ONC201 dosage 2.5 μM and carboplatin dosage 3.125 μg/mL in H1105. We are currently testing drug combinations including a triple drug combination of ONC201 and two clinically approved drugs and studying the mechanism underlying the synergies, with the potential to translate this novel combination treatment plan of ONC201 and clinically approved drugs into a clinical regimen to improve the outcome of SCLC patients.
Citation Format: Young S. Lee, Lanlan Zhou, Christopher Azzoli, Wafik S. El-Deiry. Preclinical studies with ONC201 in combination with clinically approved chemotherapy as a novel treatment strategy against Small Cell Lung Cancer (SCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5260.
Abstract 5294: Clinical utility of a multigene panel for hematologic malignancies
Authors: Bozdogan Sevcan Tug , Rencuzogullari Cagla , Mujde Cem , Bisgin Atil 
Published: September 2020

Abstract
Molecular profiling helps to diagnose, classify and guide the treatment of hematologic neoplasms. Thus NGS is the most powerful diagnostics tool to serve clinical management needs. In this study, we analyzed a multi-gene panel for genes associated with diagnostic, prognostic and therapeutic utilities for hematologic neoplasms. A total of 37 samples of myeloid and lenfoid were analyzed in GeneReader NGS system through a targeted multi-gene panel consisting of ASXL1, CALR, CBL, CEBPA, CSF3R, DNMT3A, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, RUNX1, SETBP1, SF3B1, SH2B3, SRSF2, TET2, TP53, U2AF1, ZRSR2. QCI-Analyze and QCI-Interpret were used for bioinformatic analyses. Each sample generated 2.176.058 million reads on average, and minimum of 99.5 % mapped reads to the reference reads. Total of 38 reportable variants of 16 genes were detected in 21 patients. The positivity rate was 70.5% (12 of 17) in myeloid group while its 90% (9 of 10 patients) in lymphoid group.In conclusion, our study shows the high sensitivity and specificity of the NGS technology that facilitates the identification of actionable genetic alterations on multiple genes simultaneously to avoid time-consuming multi-step procedures in hematologic malignancies.
Citation Format: Sevcan Tug Bozdogan, Cagla Rencuzogullari, Cem Mujde, Atil Bisgin. Clinical utility of a multigene panel for hematologic malignancies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5294.
Abstract 5306: Clinicopathological significance of KIFC1 in human colorectal cancer
Authors: Akabane Shintaro , Oue Naohide , Fujiki Yuto , Uraoka Naohiro , Sakamoto Naoya , Sentani Kazuhiro , Egi Hiroyuki , Ohdan Hideki , Yasui Wataru 
Published: September 2020

Abstract
Colorectal cancer (CRC) ranks third in terms of incidence and second in terms of mortality, more than 1.8 million new colorectal cancer cases and 881,000 deaths are reported in Global Cancer Statistics 2018. Therefore, there is an urgent need for a new molecular target in considering treatment strategy. In recent years, cancer has been recognized as a stem cell disease. Spheroid colony formation has been demonstrated as an effective method to characterize cancer stem cells (CSCs). Previously, we analyzed the gene expression profile of spheroid colonies from the gastric cancer cell lines by microarray analysis and found that expression of Kinesin Family Member C1 (KIFC1) was upregulated in gastric spheroid colonies. The kinesin superfamily is a group of proteins that share a motor domain and participate in several biological functions. KIFC1 (or HSET) has been reported to play a vital role in centrosome clustering in cancer cells and is related to pathogenesis in several kinds of cancers. However, the expression of KIFC1 in CRC has not been investigated. The aim of this study is to investigate the expression and the biological function of KIFC1 in CRC. We analyzed the expression and distribution of KIFC1 in 129 CRC cases by immunohistochemistry. In contrast to weak or no staining of KIFC1 in non-neoplastic mucosa, CRC tissue showed stronger, more extensive KIFC1 staining. In total, 67 (52%) of 129 CRC cases were positive for KIFC1. KIFC1-positive CRC cases were significantly associated with CD44-positive and aldehyde dehydrogenase 1 (ALDH1)-positive CRC cases. In the CRC cell proliferation analysis, KIFC1 siRNA-transfected cells showed significantly reduced cell growth ability relative to negative control siRNA-transfected cells. The expression level of phosphorylated Akt and Erk were lower in KIFC1 siRNA-transfected cells compared to negative control siRNA-transfected cells. In the sphere formation analysis, the number and the size of spheres from CRC cells were significantly reduced in KIFC1 siRNA transfected cells than in negative control siRNA-transfected cells. These results indicate that KIFC1 plays an important role in CRC pathogenesis and might be involved in cancer stemness. Although further in-depth studies to clarify the biological significance of KIFC1 in colorectal CSCs are needed, KIFC1 may be a promising therapeutic target for the treatment of CRC.
Citation Format: Shintaro Akabane, Naohide Oue, Yuto Fujiki, Naohiro Uraoka, Naoya Sakamoto, Kazuhiro Sentani, Hiroyuki Egi, Hideki Ohdan, Wataru Yasui. Clinicopathological significance of KIFC1 in human colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5306.
Abstract 5308: Genetic characterization of sarcomatoid carcinomas reveals multiple novel actionable mutations and identifies KRAS mutation as a biomarker of poor prognosis
Authors: Ding Ying , Shao Yang W. , Na Chenglong , Yin Jiani C. , Hua Hongjin , Tao Ran , Jiang Yue , Hu Ran , He Xiao , Miao Chen , Zhu Dongqin , Zhang Zhihong 
Published: September 2020

Abstract
Background: Sarcomatoid component occurs in various epithelial malignancies and is associated with an aggressive disease course and poor clinical outcome. As it is largely rare, the molecular events underlying sarcomatoid carcinomas (SCs) remain poorly characterized. Here, we performed targeted next-generation sequencing (NGS) on patients with surgically resected SCs comprising distinct tissues of origin.
Methods: A total of 71 patients with pathological diagnosis of sarcomatoid carcinoma and underwent surgery were retrospectively enrolled in this study. Overall survival was defined as the time from surgery to death from any cause. Patients alive or lost to follow-up were censored. Genomic DNA from formalin-fixed paraffin-embedded samples was extracted for NGS and tumor mutation burden (TMB) analysis.
Results: In general, SCs occurred more commonly in males, except those of the gallbladder. SCs of the lung and the larynx were associated with a higher proportion of smokers (p=0.0015). Alterations in TP53, RB1, TERT and KRAS were highly frequent, with KRAS mutations being a biomarker of poor prognosis (median OS = 8 vs 16 months, p=0.03). Multiple novel alterations in potentially actionable genes, including ROS1 and NTRK1 fusions and ERBB2 amplification, were detected in the extra-pulmonary cohort. A relatively high proportion (30%) of extra-pulmonary SC patients had high TMB, with a median of 5.39 mutations per Mb. Lastly, copy number variations were common in SCs, and were non-overlapping between the primary and metastatic tumors.
Conclusions: Taken together, our results suggest that comprehensive genetic testing may be necessary to inform treatment options and identify prognostic biomarkers.
Citation Format: Ying Ding, Yang W. Shao, Chenglong Na, Jiani C. Yin, Hongjin Hua, Ran Tao, Yue Jiang, Ran Hu, Xiao He, Chen Miao, Dongqin Zhu, Zhihong Zhang. Genetic characterization of sarcomatoid carcinomas reveals multiple novel actionable mutations and identifies KRAS mutation as a biomarker of poor prognosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5308.