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American Journal of Cancer Research

Logan C DeBord, Ravi R Pathak, Mariana Villaneuva, Hsuan-Chen Liu, Daniel A Harrington, Wendong Yu, Michael T Lewis, Andrew G Sikora
Patient-derived xenografts (PDX) are an increasingly valuable tool in oncology, providing biologically faithful models of many different cancer types, and potential platforms for the development of precision oncology approaches. However, PDX have primarily been established in immunodeficient rodent models, with accompanying cost and efficiency constraints that pose barriers to more widespread adoption. The chicken egg chorioallantoic membrane (CAM) is an alternative in vivo PDX model. We provide here a comprehensive review of studies that grafted primary human tissue, as opposed to cell lines, onto the CAM...
2018: American Journal of Cancer Research
Ana Livia Silva Galbiatti-Dias, Glaucia Maria Mendonça Fernandes, Marcia Maria Urbanin Castanhole-Nunes, Luiza Fernandes Hidalgo, Carlos Henrique Viesi Nascimento Filho, Rosa Sayoko Kawasaki-Oyama, Leticia Antunes Muniz Ferreira, Patricia Matos Biselli-Chicote, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo
Recent evidence suggests that cancer stem cells (CSCs), a small population of cancer cells that are highly tumourigenic, capable of self-renewal and have the ability to differentiate into cells that constitute the tumor, are the "drivers" of local recurrence and metastatic spread and may be associated with resistant to conventional therapy. The objectives of the study are to identify and characterize two head and neck cancer cell lines with regard CD44high /CD133high /CD117high profile (CSCs) and CD44low /CD133low /CD117low profile (Non-CSCs); to investigate the influence of chemotherapy treatment in CSCs and compare with Non-CSCs; to evaluate CD44 and EGFR gene expression in CSCs...
2018: American Journal of Cancer Research
Naijin Xu, Xiezhao Li, Masami Watanabe, Hideo Ueki, Hao Hu, Na Li, Motoo Araki, Koichiro Wada, Abai Xu, Chunxiao Liu, Yasutomo Nasu, Peng Huang
Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent stem cells (miPSCs) into prostate cancer stem-like cells with carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9, a mouse prostate cancer cell line. These transformed cells, termed as miPS-RM9CM, displayed CSCs properties, including spheroids morphology and expression of both stemness genes and cancer stem cells surface markers, such as Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44, and CD133...
2018: American Journal of Cancer Research
Matteo Figini, Xifu Wang, Tianchu Lyu, Zhanliang Su, Bin Wang, Chong Sun, Junjie Shangguan, Liang Pan, Kang Zhou, Quanhong Ma, Vahid Yaghmai, Daniele Procissi, Andrew C Larson, Zhuoli Zhang
The purpose of this work is to explore the potential contribution of diffusion MRI to predict the effects of irreversible electroporation (IRE) in a pancreatic ductal adenocarcinoma (PDAC) mouse model. Thirteen mice were injected with Panc-02 PDAC cells in both flanks. One tumor was treated with IRE when it reached a diameter of about 5 mm. T2- and diffusion-weighted MRI sequences were acquired before IRE treatment and 1, 3 and 7 days later. The mice were euthanized 1 day (n = 6) or 2 weeks (n = 7) after treatment...
2018: American Journal of Cancer Research
Ying He, Zhousan Zheng, Yi Xu, Huiwen Weng, Ying Gao, Kai Qin, Jian Rong, Cui Chen, Miao Yun, Jiaxing Zhang, Sheng Ye
Inosine monophosphate dehydrogenase type II (IMPDH2) has been found to play critical roles in the development and progression of several human cancers. However, the expression of IMPDH2 and its clinical significance in hepatocellular carcinoma (HCC) is little known. The expression of IMPDH2 in HCC cell lines and tissues were evaluated by Western blotting (WB), quantitative real-time PCR (q-PCR) and immunohistochemistry (IHC). We found that the expression of IMPDH2 was significantly up-regulated in HCC tissues than in adjacent non-tumorous tissues, and this was correlated with several clinicopathological features, including tumor multiplicity (P=0...
2018: American Journal of Cancer Research
Jingfeng Luo, Jiali Zhou, Fengnan Xie, Yali Zhu, Fei Zhou, Shuanglin Zhang, Shaojie Jiang, Jie He, Jiaxin Liu, Xia Wu, Yanhua Zhang, Jihong Sun, Xiaoming Yang
Cholangiocarcinoma is a most lethal malignancy frequently resistant to chemotherapy. Herpes simplex virus thymidine kinase/Ganciclovir (HSV-TK/GCV) suicide gene therapy is a promising approach to treat different cancers, including cholangiocarcinoma. However drawbacks including low therapeutic gene expression and lack of precise targeted gene delivery limit the wide clinical utilization of the suicide gene therapy. We attempted to overcome these obstacles. We established the "proof-of-principle" of this concept via serial in-vitro experiments using human cholangiocarcinoma cells and then validated the new interventional oncology technique in vivo using mice harboring the same patient derived cholangiocarcinomas...
2018: American Journal of Cancer Research
Zhuo Wang, Mahui Si, Ning Yang, Haibin Zhang, Yong Fu, Kai Yan, Yi Zong, Nan Zhu, Yongpeng Wei
MicroRNAs (miRNAs) have been reported to be involved in tumor metastasis. In this study, we investigated the function of miR-506 in the metastasis of human hepatocellular carcinoma (HCC). We found that miR-506 is significantly downregulated in the primary tissue of metastatic HCC and in highly metastatic HCC cell lines. Overexpression of miR-506 suppressed HCC cell migration, invasion, and metastasis both in vitro and in vivo . Furthermore, miR-506 was found to specifically target the 3' untranslated region (3'-UTR) of interleukin 8 ( IL8 ) mRNA...
2018: American Journal of Cancer Research
Dongjun Dai, Hongchuan Jin, Xian Wang
Triple-negative breast cancer (TNBC) represents around 15%-20% of newly diagnosed breast cancer and is more aggressive than other breast cancer sub-types. Infiltrating duct carcinoma (IDC) is the most common type of TNBC. Nomogram is a valuable tool for prognosis prediction by integrating different biological and clinical variables. The purpose of current study was to evaluate the prognostic value of clinical factors of TNBC patients with IDC histology type and construct nomograms for their outcome prediction...
2018: American Journal of Cancer Research
Xu Lu, Jingwei Liu, Peilin Cui, Tao Liu, Chunmei Piao, Xianghong Xu, Qike Zhang, Man Xiao, Xuesong Liu, Yue Wang, Lin Yang
Dendritic cell (DC) vaccines have been shown to stimulate tumor antigen-specific CD8+ T cells; however, this strategy has demonstrated variable clinical efficacy likely due to immune escape mechanisms that can induce tumor-specific CD8+ T cell dysfunction. Herein, we evaluated the functional characteristics of DC vaccine-induced CD8+ T cells with regard to immune checkpoint inhibitors in gastric cancer patients who were administered Wilms tumor protein-1 (WT1)-targeted DC vaccine. We observed the upregulation of the inhibitory molecule, TIGIT and the inhibitory T cell co-receptors PD1 and Tim3 in limiting WT1-specific CD8+ T cell growth and function in GC patients...
2018: American Journal of Cancer Research
Ziwei Fang, Jiandong Wang, Leslie H Clark, Wenchuan Sun, Yajie Yin, Weimin Kong, Stuart R Pierce, Lindsay West, Stephanie A Sullivan, Arthur-Quan Tran, Varun V Prabhu, Chunxiao Zhou, Victoria Bae-Jump
Uterine serous carcinoma (USC) represents an aggressive histologic subtype of endometrial cancer. It is associated with a poor prognosis, and improved therapies for women battling USCs are greatly needed. ONC201 is an orally bioavailable, first-in-class small molecule that induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) independent of p53. ONC201 has demonstrated anti-tumorigenic activity in pre-clinical models of solid tumors through induction of apoptosis and inactivation of the AKT/MAPK pathways...
2018: American Journal of Cancer Research
Lei Wang, Mingzhao Gao, Mengya Tong, Chengying Xie, Ye He, Li Fu, Yun Li, Haoyu Fu, Liguang Lou
Anaplastic lymphoma kinase (ALK) is a validated molecular target for patients harboring ALK rearrangement, which triggers the development of ALK inhibitors. However, the activation of mesenchymal-epithelial transition factor (c-Met) has emerged as a common cause of acquired resistance induced by selective ALK inhibitors. Herein, we report the first preclinical characterization of CT-711, a novel dual inhibitor of ALK and c-Met. CT-711 demonstrates potent inhibitory activity against ALK kinase activity. Moreover, CT-711 profoundly inhibits ALK signal transduction and thereby induces G1 phase arrest and apoptosis, and results in remarkable anti-proliferative activity against ALK-driven cancer cells...
2018: American Journal of Cancer Research
Xixi Zhao, Jingkun Qu, Xu Liu, Jizhao Wang, Xingcong Ma, Xiaoyao Zhao, Qian Yang, Wanjun Yan, Zitong Zhao, Yuxin Hui, Haocheng Bai, Shuqun Zhang
Tumor associated macrophages (TAMs) are the main infiltrating component in the tumor microenvironment and play an important role in cancer progression. Baicalein has a wide range of pharmacological properties. This study explores the potential effect of baicalein on macrophages polarization and epithelial-mesenchymal transition (EMT) of breast cancer. Co-culture system was established to evaluate the interaction between TAMs and breast cancer cells. Then the role of baicalein in modulating TAMs function was assessed...
2018: American Journal of Cancer Research
Tian Ye, Ke Jiang, Liwen Wei, Martin P Barr, Qing Xu, Guirong Zhang, Chan Ding, Songshu Meng, Haozhe Piao
In addition to direct oncolysis, oncolytic viruses trigger immunogenic cell death (ICD) and primes antitumor immunity. We have previously shown that oncolytic Newcastle disease virus (NDV), strain FMW (NDV/FMW), induces apoptosis and/or autophagy in cancer cells. In this study, we investigated whether oncolytic NDV can induce ICD in lung cancer cells and whether apoptosis or autophagy plays a role in NDV-triggered ICD. To this end, we examined cell surface expression of calreticulin (CRT) on NDV-infected lung cancer cells and measured ICD determinants, high mobility group box 1 (HMGB1), heat shock protein 70/90 (HSP70/90) and ATP in supernatants following viral infection...
2018: American Journal of Cancer Research
Aya Osanai-Sasakawa, Kenta Hosomi, Yoshiki Sumitomo, Takuya Takizawa, Shiho Tomura-Suruki, Minami Imaizumi, Noriyuki Kasai, Tze Wei Poh, Kazuya Yamano, Wei Peng Yong, Koji Kono, Satoshi Nakamura, Toshihiko Ishii, Ryuichiro Nakai
Glutamine is a major nutrient for cancer cells during rapid proliferation. Alanine-serine-cysteine (ASC) transporter 2 (ASCT2; SLC1A5) mediates glutamine uptake in a variety of cancer cells. We previously reported that KM8094, a novel anti-ASCT2 humanized monoclonal antibody, possesses anti-tumor efficacy in gastric cancer patient-derived xenografts. The aim of this study was to investigate the molecular mechanism underlying the effect of KM8094 and to further substantiate the preclinical feasibility of using KM8094 as a potential therapeutic agent against gastric cancer...
2018: American Journal of Cancer Research
Jihang Yao, Zhenghong Li, Ziwei Yang, Hui Xue, Hua Chang, Xue Zhang, Tianren Li, Kejun Guo
Cervical cancer is one of the most common cancers in females, accounting for a majority of cancer-related deaths in worldwide. Long non-coding RNAs (lncRNAs) have been identified as critical regulators in many tumor-related biological processes. Thus, investigation into the function and mechanism of lncRNAs in the development of cervical cancer is very necessary. In this study, we found that the expression of TOB1-AS1 was significantly decreased in cervical cancer tissues compared with the adjacent normal tissues...
2018: American Journal of Cancer Research
Fangfang Chen, Qiaoling Song, Qiang Yu
R428 (BGB324) is an anti-cancer drug candidate under clinical investigation. It inhibits the receptor tyrosine kinase Axl and induces apoptosis of many types of cancer cells, but the relationship between the two has not been well established. We investigated the molecular mechanisms of the R428-induced apoptosis and found that R428 induced extensive cytoplasmic vacuolization and caspase activation, independent of its inhibitory effects on Axl. Further analyses revealed that R428 blocked lysosomal acidification and recycling, accumulated autophagosomes and lysosomes, and induced cell apoptosis...
2018: American Journal of Cancer Research
Lan Mi, Kai Hu, Xianzi Wen, Jing Sun, Aiwen Wu, Mingliang Wang, Minhua Zheng, Lu Zang, Jiafu Ji
The function and clinical implication of transcription factor CCAAT/enhancer-binding protein α (C/EBPα) in colorectal cancer (CRC) still remains undefined. In fact, C/EBPα has long been considered as a tumor suppressor in hematopoietic system and also found lowly expressed in numerous solid tumors. However, our results here for the first time showed that C/EBPα was unexpectedly upregulated and was an independent prognostic marker for patients with CRC. We therefore aimed to explore the detailed role and mechanisms of C/EBPα in CRC...
2018: American Journal of Cancer Research
Zeming Liu, Wen Zeng, Lei Huang, Zhaoyuan Wang, Min Wang, Ling Zhou, Danyang Chen, Haifeng Feng, Wei Zhou, Liang Guo
The significance of prognosis of follicular thyroid cancer (FTC) compared to other subtypes of thyroid cancer, based on large cohort data has only been addressed in a few studies, and the results remain controversial. In this study, we investigated the prognosis of FTC compared to papillary thyroid carcinoma (PTC) and follicular variant PTC (FVPTC) based on Surveillance, Epidemiology, and End Results database (SEER) Program data using propensity score matching. We evaluated data from 128,703 patients with thyroid cancer who were included in the SEER database between 2004 and 2013...
2018: American Journal of Cancer Research
Fei Li, Qianyun Zhang, Yange Gong, Jinxiang Yu
Non-small lung cancer (NSCLC) is one of the most common causes of cancer-associated death worldwide. Long noncoding RNAs (lncRNAs) regulate cancer initiation and progression through different mechanisms. In the present study, we characterized a novel lncRNA named lncKLF6, which was upregulated in NSCLC and associated with poor clinical outcomes. lncKLF6 inhibited Kruppel-like factor 6 (KLF6) transcription and then facilitated NSCLC growth. lncKLF6 is associated with the epigenetic repressor BMI1 and regulates its stability via recruiting deubiquitinase USP22...
2018: American Journal of Cancer Research
Xiao Dong, Chuize Kong, Xiankui Liu, Jianbin Bi, Zhenhua Li, Zeliang Li, Yuyan Zhu, Zhe Zhang
Several studies have shown that low expression of hZIP1 is closely associated with many human cancers, including clear cell renal cell carcinoma (ccRCC). In this study, we aimed to explore the potential mechanism responsible for hZIP1 silencing and revealed a novel regulatory pathway in the pathogenesis of ccRCC. Here, miR-223 was predicted and experimentally validated to be a regulator of hZIP1, and its expression was negatively correlated with the mRNA levels of hZIP1 in primary tumors. Upregulation of hZIP1 inhibited cell proliferation, cell cycle progression, and invasion and induced apoptosis, while inhibition of miR-223 showed the opposite effect on cellular processes...
2018: American Journal of Cancer Research
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