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Cell Pathway And Malignancy

Huizi Wu, Lionel Larribère, Qian Sun, Daniel Novak, Sachindra Sachindra, Karol Granados, Viktor Umansky, Jochen Utikal
Recent studies suggest that malignant melanoma heterogeneity includes subpopulations of cells with features of multipotent neural crest (NC) cells. Zebrafish and mouse models have shown that reactivation of neural crest-specific pathways during transformation determines the invasiveness of melanoma cells. In this study, we show that the neural crest-associated transcription factor FOXD1 plays a key role in the invasion and the migration capacities of metastatic melanomas both in vivo and in vitro. Gene expression profiling analysis identified both an upregulation of FOXD1 in NC and melanoma cells, as well as a downregulation of several genes related to cell invasion in FOXD1 knockdown cells, including MMP9 and RAC1B...
August 15, 2018: International Journal of Cancer. Journal International du Cancer
Maria Luisa Gasparri, Zein Mersini Besharat, Ammad Ahmad Farooqi, Sumbul Khalid, Katayoun Taghavi, Raad Aris Besharat, Claudia Sabato, Andrea Papadia, Pierluigi Benedetti Panici, Michael David Mueller, Elisabetta Ferretti
Ovarian cancer is a leading cause of death among gynecologic malignancies. This disappointing prognosis is closely related to intrinsic or acquired resistance to conventional platinum-based chemotherapy, which can affect a third of patients. As such, investigating relevant molecular targets is crucial in the fight against this disease. So far, many mutations involved in ovarian cancer pathogenesis have been identified. Among them, a few pathways were implicated. One such pathway is the P13K/AKT/mTOR with abnormalities found in many cases...
August 14, 2018: Journal of Cancer Research and Clinical Oncology
Haiyang Chen, Peiran Song, Yanyan Diao, Yongjia Hao, Dou Dou, Wanqi Wang, Xiaoyu Fang, Yanling Wang, Zhenjiang Zhao, Jian Ding, Honglin Li, Hua Xie, Yufang Xu
Bruton's tyrosine kinase (BTK) plays a critical role in B cell receptor (BCR)-mediated signaling pathways responsible for the development and function of B cells, which makes it an attractive target for the treatment of many types of B-cell malignancies. Herein, a series of N5-substituted 6,7-dioxo-6,7-dihydropteridine-based, irreversible BTK inhibitors were reported with IC50 values ranging from 1.9 to 236.6 nM in the enzymatic inhibition assay. Compounds 6 and 7 significantly inhibited the proliferation of Ramos cells which overexpress the BTK enzyme, as well as the autophosphorylation of BTK at Tyr223 and the activation of its downstream signaling molecule PLCγ2...
April 1, 2018: MedChemComm
Micah N Sagini, Michael Zepp, Frank Bergmann, Matthias Bozza, Richard Harbottle, Martin R Berger
Pancreatic adenocarcinoma is a highly aggressive malignancy with dismal prognosis and limited curative options. We investigated the influence of organ environments on gene expression in RNU rats by orthotopic and intraportal infusion of Suit2-007luc cells into the pancreas, liver and lung respectively. Tumor tissues from these sites were analyzed by chip array and histopathology. Generated data was analyzed by Chipster and Ingenuity Pathway Analysis (±1.5 expression fold change and p<0.05). Further analysis of functional annotations derived from IPA, was based on selected genes with significant modulation of expression...
March 2018: Genes & Cancer
Fakhredin Saba, Masoud Soleimani, Saeid Abroun
Bone is one of the most common sites of complication in multiple myeloma (MM) progression and bone remodeling gets definitively perturbed during disease progression. Hypoxia and miR-210 play an important role in hematological malignancies. In an attempt to elucidate the specificity of the pathways of hypoxia and miR-210 in suppression of osteoblastic differentiation in MM patients, we examined the effect of miR-210 and hypoxia on expression of important cytokines and genes of myeloma cells. Differentiation of BM-MSCs towards osteoblastic cells in response to microvesicles (MVs) was also investigated...
2018: EXCLI Journal
Peng Lin, Yuanming He, Guodong Chen, Haikuo Ma, Jiyue Zheng, Zubin Zhang, Biyin Cao, Hongjian Zhang, Xiaohu Zhang, Xinliang Mao
The hedgehog-smoothened (HH/SMO) pathway has been proposed as a potential therapeutic target for hematological malignancies. Our previous studies designed a series of HH inhibitors with novel scaffolds distinctive from vismodegib, the first Food and Drug Administration-approved HH inhibitor for the treatment of basal-cell carcinoma and medulloblastoma. In the present study, we evaluated these HH inhibitors against blood cancers and found that HH78 displayed potent activity in suppressing the HH signaling pathway...
August 13, 2018: Anti-cancer Drugs
Pengfei Qiao, Shenglong Li, Haogang Zhang, Lei Yao, Fujing Wang
Colorectal cancer (CRC) is among the most common malignancies of the digestive system. Dysregulation of miRNAs and the farnesoid X receptor (FXR) are involved in the progression of CRC. In the present study, the effects of FXR and miR‑135A1 in CRC were evaluated. Reverse transcription quantitative‑polymerase chain reaction (RT‑qPCR) was used to examine the expression of miR‑135A1 in patient CRC tissues and adjacent non‑tumor tissues, as well as cell lines. The association between miR‑135A1 and clinical characteristics of patients with CRC was also investigated...
August 7, 2018: Oncology Reports
Yanyang Chen, Yunsheng Ou, Yong Tao, Huzhe Liu, Hang Yin, Shenxi Zhong, Haoyang Yu, Zenghui Zhao, Bin He
Osteosarcoma is the most common primary malignant tumor of the bone found predominantly in children and teenagers and results in early metastasis and poor prognosis. The present study primarily focused on the impact of celastrol on apoptosis and autophagy of osteosarcoma HOS cells, as well as the related mechanisms. Following the appropriate treatment, the human osteosarcoma cell line HOS was assessed for viability, Ca2+ in cells, apoptosis and changes in cell morphology using Cell Counting Kit-8, flow cytometry, inverted phase contrast microscope, Hoechst staining and transmission electron microscopy...
August 1, 2018: Oncology Reports
Kalliopi I Pappa, Polyxeni Christou, Amarildo Xholi, George Mermelekas, Georgia Kontostathi, Vasiliki Lygirou, Manousos Makridakis, Jerome Zoidakis, Nicholas P Anagnou
The available therapeutic approaches for cervical cancer can seriously affect the fertility potential of patient; thus, there is a pressing requirement for less toxic and targeted therapies. The membrane proteome is a potential source of therapeutic targets; however, despite the significance of membrane proteins in cancer, proteomic analysis has been a challenging task due to their unique biochemical properties. The aim of the present study was to develop an efficient membrane protein enrichment protocol, and to the best of our knowledge, to compare for the first time the expression pattern of membrane proteins of one normal cell line, HCK1T, and three cervical cancer cell lines, C33A, a human papilloma virus (HPV)-negative cell line, and two HPV-positive cell lines, SiHa (HPV16+) and HeLa (HPV18+)...
August 7, 2018: International Journal of Oncology
Xia Yang, Yun Deng, Rong-Quan He, Xiao-Jiao Li, Jie Ma, Gang Chen, Xiao-Hua Hu
The altered expression of homeobox (HOX)A11 has been observed in various malignant tumor types, but it has remained to be determined in human lung adenocarcinoma (LUAD). In the present study, the expression of HOXA11 in LUAD and the potential associated mechanisms were assessed. Data from The Cancer Genome Atlas and Oncomine microarrays were gathered and in‑house polymerase chain reaction data were produced to investigate the altered expression of HOXA11 in LUAD and its association with various clinicopathological characteristics...
August 14, 2018: International Journal of Molecular Medicine
Dingyuan Luo, Xinke Xu, Junliang Li, Cheng Chen, Wei Chen, Fangyu Wang, Yanping Xie, Fangcheng Li
Glioblastoma multiforme (GBM) is the most common primary malignant tumor affecting the human brain. Despite improvements in therapeutic technologies, patients with GBM have a poor clinical result and the molecular mechanisms responsible for the development of GBM have not yet been fully elucidated. 3-phosphoinositide dependent protein kinase 1 (PDK1) is upregulated in various tumors and promotes tumor invasion. In glioma, transforming growth factor-β (TGF‑β) promotes cell invasion; however, whether TGF‑β directly regulates PDK1 protein and promotes proliferation and invasion is not yet clear...
August 14, 2018: International Journal of Oncology
Jingtao Zhang, Guilan Wen, Longhua Sun, Wenxin Yuan, Ran Wang, Qinghua Zeng, Guangyi Zhang, Bentong Yu
Lung cancer is one of the most commonly diagnosed malignancies worldwide. Cryptotanshinone (CPT) is a diterpene quinone compound extracted from natural plants and has been reported to have anticancer effects in several cancers including human lung cancer. However, the mechanism by which CPT acts to prevent lung cancer cell growth is largely unknown. In the present study, by using MTT assay, colony formation assay, wound healing and western blotting assays, the effects of CPT on the cell proliferation and migration of human lung cancer cells and the potential cellular signaling mechanisms were investigated...
August 10, 2018: Oncology Reports
Zhaohui Dong, Lanying Zhang, Wei Xu, Gensheng Zhang
Lung cancer is one of the most prevalent malignancies worldwide; it has been ranked the most lethal type of cancer. Non‑small cell lung carcinoma (NSCLC) comprises >80% of all types of lung cancer. Although certain achievements have been made in the treatment of NSCLC, including the targeted gene drug epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI), the five‑year survival rate of patients has not significantly increased. A previous study demonstrated that B7‑H5, a novel co‑stimulatory molecule in the B7 molecule family, was negatively correlated with EGFR in pancreatic cancer...
August 8, 2018: Molecular Medicine Reports
Qingsong Zhao, Saiyue Gao, Qingyan Du, Ye Liu
The long non‑coding RNA, small nucleolar RNA host gene 20 (SNHG20), is involved in promoting several common types of human cancer, however, the exact function of SNHG20 in the pathogenesis of bladder cancer remains to be elucidated. The present study aimed to examine the regulatory mechanism of SNHG20 underlying the malignant progression of bladder cancer. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to examine mRNA and protein expression. Cell survival, proliferation, apoptosis, colony formation, migration and invasion were also studied...
August 10, 2018: International Journal of Molecular Medicine
Binyan Lin, Kai Zhao, Dawei Yang, Dongsheng Bai, Yan Liao, Yuxin Zhou, Zhou Yu, Xiaoxuan Yu, Qinglong Guo, Na Lu
Decreasing bone marrow (BM) microvessel density and circulating angiogenic cytokine levels are promising strategies for the treatment of relapsed and resistant acute myeloid leukemia (AML). Previous studies have reported that wogonoside could inhibit the progression of AML and suppress angiogenesis in a solid tumor, but the correlation of these two effects was ignored. In this research, we determined whether wogonoside could inhibit angiogenesis in this hematologic malignancy. We found that wogonoside could inhibit tumor growth and progression, and prolong the survival of nude mice inoculated with U937/MDR...
August 13, 2018: Journal of Cellular Physiology
Y Patel, M Soni, A Awagulerwitsch, M J Kern, S Liu, N Shah, U P Singh, H Chen
Although it has been demonstrated that transformed progenitor cell population can contribute to tumor initiation, factors contributing to this malignant transformation are poorly known. Using in vitro and xenograft-based models, previous studies demonstrated that miR-489 acts as a tumor suppressor miRNA by targeting various oncogenic pathways. It has been demonstrated that miR-489 directly targets HER2 and inhibits the HER2 signaling pathway; however, its role in mammary gland development and HER2-induced tumor initiation hasn't been studied...
August 13, 2018: Oncogene
Daniel Sappington, Scott Helms, Eric Siegel, Rosalind B Penney, Susanne Jeffus, Teka Bartter, Thaddeus Bartter, Gunnar Boysen
BACKGROUND: Treatment of lung cancer is evolving from the use of cytotoxic drugs to drugs that interrupt pathways specific to a malignancy. The field of metabolomics has promise with respect to identification of tumor-specific processes and therapeutic targets, but to date has yielded inconsistent data in patients with lung cancer. Lymph nodes are often aspirated in the process of evaluating lung cancer, as malignant cells in lymph nodes are used for diagnosis and staging. We hypothesized that fluids from lymph node aspirates contains tumor-specific metabolites and are a suitable source for defining the metabolomic phenotype of lung cancers...
2018: Cancer Treatment and Research Communications
Erhao Zhang, Peiwei Yang, Jieyi Gu, Heming Wu, Xiaowei Chi, Chen Liu, Ying Wang, Jianpeng Xue, Weiyan Qi, Qingbo Sun, Shengnan Zhang, Jialiang Hu, Hanmei Xu
BACKGROUND: The therapeutic application of T cells endowing with chimeric antigen receptors (CARs) is faced with "on-target, off-tumor" toxicity against solid tumors, particularly in the treatment of the pancreatic cancer. To our best knowledge, the pancreatic cancer cell line AsPC-1 often highly expressed some distinct tumor-associated antigens, such as carcino-embryonic antigen (CEA) and mesothelin (MSLN). Therefore, in this research, we have characterized dual-receptor CAR-modified T cells (dCAR-T) that exert effective and safe cytotoxicity against AsPC-1 cells...
August 13, 2018: Journal of Hematology & Oncology
Chao-Yuan Huang, Feng-Shu Hsieh, Cheng-Yi Wang, Li-Ju Chen, Shih-Shin Chang, Ming-Hsien Tsai, Man-Hsin Hung, Chiung-Wen Kuo, Chi-Ting Shih, Tzu-I Chao, Kuen-Feng Chen
AIM: Palbociclib is an oral cyclin-dependent kinase 4/6 inhibitor, which is efficacious in treating breast cancer. Currently, there are numerous active clinical trials testing palbociclib alone or in combination with other medications for treating various types of malignancies. Here, we evaluated the anti-cancer effect of palbociclib in combination with radiation therapy (RT) for treating human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) and addressed the molecular mechanism behind the combination therapy...
August 10, 2018: European Journal of Cancer
Yibao Ma, Sarah M Temkin, Adam M Hawkridge, Chunqing Guo, Wei Wang, Xiang-Yang Wang, Xianjun Fang
Cancer cells undergo metabolic reprogramming such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid cycle enzymes, and upregulation of de novo lipid synthesis and glutaminolysis. These alterations are pivotal to the development and maintenance of the malignant phenotype of cancer cells in unfavorable tumor microenvironment or metastatic sites. Although mitochondrial fatty acid β-oxidation (FAO) is a primary bioenergetic source, it has not been generally recognized as part of the metabolic landscape of cancer...
August 10, 2018: Cancer Letters
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