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Cancer Letters

Kelly M Kreitzburg, Samuel C Fehling, Charles N Landen, Tracy L Gamblin, Rebecca B Vance, Rebecca C Arend, Ashwini A Katre, Patsy G Oliver, Robert C A M van Waardenburg, Ronald D Alvarez, Karina J Yoon
Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. Although most patients respond to frontline therapy, virtually all patients relapse with chemoresistant disease. This study addresses the hypothesis that carboplatin or tamoxifen + FTY720, a sphingosine analogue, will minimize or circumvent drug-resistance in ovarian cancer cells and tumor models. In vitro data demonstrate that FTY720 sensitized two drug-resistant (A2780. cp20, HeyA8. MDR) and two high-grade serous ovarian cancer cell lines (COV362, CAOV3) to carboplatin, a standard of care for patients with ovarian cancer, and to the selective estrogen receptor modulator tamoxifen...
August 15, 2018: Cancer Letters
Xiao Tan, Zhongqiang Zhang, Hongliang Yao, Liangfang Shen
T-cell immunoglobulin domain and mucin domain-4 (Tim-4) is overexpressed in several tumors and is correlated with enhanced tumor development and metastasis. In this study, we investigated the physiological alterations and molecular events related to Tim-4 overexpression in a mouse model of colorectal cancer (CRC). In the current study, we observed that Tim-4 is upregulated in CRC tissues compared with neighboring normal tissues. In addition, statistical analysis revealed that elevated Tim-4 expression was strongly linked to distant metastasis, TNM stage and reduced overall survival duration in CRC patients...
August 14, 2018: Cancer Letters
Yu Wang, Chuanqiang Wu, Chao Zhang, Zhaoqing Li, Tingting Zhu, Jinliang Chen, Yu Ren, Xudong Wang, Lun Zhang, Xuan Zhou
Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is a critical factor that drives the invasion and metastasis of head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of STAT3 overexpression and regulation of HNSCC metastasis remain unknown. In the current study, we demonstrated that upregulated TGF-β may promote epithelial-mesenchymal transition (EMT) through STAT3 activation. In addition, we explored the contributions of STAT3 to HNSCC with a specific focus on its transcriptional regulation and its interaction with the long noncoding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (malat1)...
August 14, 2018: Cancer Letters
Chien-Chi Lin, Murray Korc
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality in the United States, with a 5-year survival of ∼8%. PDAC is characterized by a dense and hypo-vascularized stroma consisting of proliferating cancer cells, cancer-associated fibroblasts, macrophages and immune cells, as well as excess matrices including collagens, fibronectin, and hyaluronic acid. In addition, PDAC has increased interstitial pressures and a hypoxic/acidic tumor microenvironment (TME) that impedes drug delivery and blocks cancer-directed immune mechanisms...
August 14, 2018: Cancer Letters
Yifan Liu, Eun Ju Yang, Baoyuan Zhang, Zhengqiang Miao, Changjie Wu, Junfang Lyu, Kaeling Tan, Terence Chuen Wai Poon, Joong Sup Shim
PTEN is a tumor suppressor found mutated in many cancers. From a synthetic lethality drug screen with PTEN-isogenic colorectal cancer cells, we found that mutant-PTEN cells were resistant to dual inhibitors of FLT3 and aurora kinase-A, including KW2449 and ENMD-2076. KW2449 significantly reduced the viability of wildtype-PTEN cells causing apoptosis, while little effect was observed in mutant-PTEN counterparts. Transcriptome profiling showed that members of PI3K-AKT signaling pathway were strongly changed in cells after KW2449 treatment, indicating a potential role of the pathway in drug resistance...
August 14, 2018: Cancer Letters
Xiaohui Hua, Jiheng Xu, Xu Deng, Jiawei Xu, Jingxia Li, David Q Zhu, Junlan Zhu, Honglei Jin, Zhongxian Tian, Haishan Huang, Qin-Shi Zhao, Chuanshu Huang
ChlA-F is a novel conformation-derivative of Cheliensisin A, styryl-lactone isolates that show potent anti-tumor potential in vivo and vitro. However, the anti-cancer activity and its potential mechanisms underlying ChlA-F action have never been explored. In the present study, we evaluated the potency of ChlA-F on autophagy-mediated anchorage-independent growth inhibition in human high-grade invasive bladder cancer (BC) cells. We found that ChlA-F treatment significantly inhibited anchorage-independent growth of human BC cells by inducing autophagy in a Sestrin-2 (SESN2)-dependent fashion...
August 14, 2018: Cancer Letters
Tao Ma, Wei Chen, Xiao Zhi, Hao Liu, Yue Zhou, Brayant Wei Chen, Liqiang Hu, Jian Shen, Xiaoxiao Zheng, Shufen Zhang, Tingbo Liang
Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective in most patients, development of tumor resistance to gemcitabine can critically limit its efficacy. The mechanisms responsible for this phenomenon remain elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be key regulators in cancer chemo-resistance. The present study aimed to investigate the role of USP9X in gemcitabine resistance using in vitro pancreatic cell lines and a mouse xenograft model. We found that the expression of USP9X in pancreatic cancer cells was positively correlated with gemcitabine resistance, and that inhibition of USP9X by WP1130 sensitized pancreatic cancer cells to gemcitabine...
August 14, 2018: Cancer Letters
Yuehong Wang, Linying Wu, Yinan Yao, Guohua Lu, Liming Xu, Jianying Zhou
The prognosis of small cell lung cancer (SCLC) is poor despite its good initial response to chemotherapy. Polo-like kinase 1 (PLK1) is a crucial mitotic regulator that is overexpressed in many tumors, and its overexpression is associated with tumor aggressiveness and a poor prognosis. However, its role in SCLC is still poorly characterized. Based on immunohistochemistry findings, the PLK1 protein is expressed at higher levels in SCLC tumor samples than in normal lung tissue samples. The selective PLK1 inhibitor BI 6727 significantly induced the inhibition of proliferation and apoptosis in a dose-dependent manner in SCLC cell lines...
August 14, 2018: Cancer Letters
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
Ailiang Zeng, Zhiyun Wei, Wei Yan, Jianxing Yin, Xiaoxu Huang, Xu Zhou, Rui Li, Feng Shen, Weining Wu, Xiefeng Wang, Yongping You
Chemoresistance blunts the effect of Temozolomide (TMZ) in the treatment of glioblastoma multiforme (GBM). Whether exosomal transfer of miRNAs derived from TMZ-resistant GBM cells could confer TMZ resistance remains to be determined. qPCR was used to determine miR-151a expression in two TMZ-resistant GBM cell lines. The direct targets of miR-151a were identified by microarray assays, bioinformatics and further RNA chromatin immunoprecipitation (RNA-ChIP) assay. We characterized exosomes from TMZ-resistant cell lines, serum and cerebrospinal fluid (CSF) and determined the effect of exosomes from TMZ-resistant cells on recipient GBM cells...
August 10, 2018: Cancer Letters
E Peverelli, E Giardino, F Mangili, D Treppiedi, R Catalano, E Ferrante, E Sala, M Locatelli, A G Lania, M Arosio, A Spada, G Mantovani
An efficient intracellular response to somatostatin analogs (SSA) in pituitary tumors requires filamin A (FLNA). Since cAMP pathway plays an important role in GH-secreting pituitary tumors pathogenesis and FLNA is phosphorylated by PKA on S2152, aim of this study was to investigate in tumoral somatotrophs the impact of cAMP pathway activation and SSA stimulation on FLNA phosphorylation and the consequences on SST2 function. We found a PKA-mediated increase (2-fold) and SST2 agonist-induced decrease (-50%) of FLNA phosphorylation in GH3, GH4C1 and primary somatotroph tumor cells...
August 8, 2018: Cancer Letters
Alexey Koval, Constant A Pieme, Emerson Ferreira Queiroz, Simone Ragusa, Kamal Ahmed, Artem Blagodatski, Jean-Luc Wolfender, Tatiana V Petrova, Vladimir L Katanaev
Triple-negative breast cancer (TNBC) and colon cancer (CC) are two stigmatic examples of poorly treatable tumors, whose progression critically depends upon hyperactivation of the Wnt signaling. Development of specific anti-Wnt inhibitors is required to develop drugs against these and other Wnt-dependent cancers. Natural products, especially plants, have been used for the treatment of various diseases from ancient times. We examined extracts from several indigenous Cameroonian herbs and tested their effects on proliferation and Wnt signaling in TNBC and CC cells...
August 8, 2018: Cancer Letters
Xin Chen, Jieru Zhou, Xiaoduan Li, Xinjing Wang, Yingying Lin, Xipeng Wang
Recently, cancer has been considered to be a complex system that includes the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most common immune-related stromal cells in the TME, and communication between cancer cells and TAMs is crucial for the progression of epithelial ovarian cancer (EOC). In this study, we revealed that exosomes derived from EOC cells remodel macrophages to a tumor-promoted phenotype, namely TAMs. In addition, hypoxic microenvironments have been postulated to facilitate this process in the TME, and hypoxia-inducible factors (HIFs) play an important role in this process...
August 8, 2018: Cancer Letters
Yiming Bi, Han Li, Dazhuang Yi, Yang Bai, Sheng Zhong, Qiaochu Liu, Yong Chen, Gang Zhao
Glioblastoma multiforme (GBM) is one of the most aggressive human tumors, and it has a poor prognosis. Temozolomide (TMZ) is the primary alkylating agent used to treat GBM. Nevertheless, a number of GBM patients are resistant to TMZ. Therefore, there is an urgent need for more effective therapeutic options. Cordycepin (COR) is a natural chemical with anti-tumor effects, although its mechanism of action is poorly understood. Several lines of evidence suggest that O6 -methylguanine DNA methyltransferase (MGMT) repairs damaged DNA and contributes to drug resistance to TMZ in gliomas...
August 3, 2018: Cancer Letters
Dannah R Miller, Cherng-Chyi Tzeng, Trey Farmer, Evan T Keller, Steve Caplan, Yu-Shuin Chen, Yeh-Long Chen, Ming-Fong Lin
The standard-of-care treatment for metastatic prostate cancer (PCa) is androgen deprivation therapy (ADT). Nevertheless, most of those tumors eventually relapse and develop into lethal castration-resistant prostate cancer (CRPC). Docetaxel is a FDA-approved agent for the treatment of CRPC; however, the tumor often quickly develops resistance to this drug. Thus, there is an immediate need for novel therapies to treat docetaxel-resistant PCa. In this study, we modified the structure of CIL-102 and investigated the efficacy of the derivatives against CRPC and docetaxel-resistant PCa...
August 2, 2018: Cancer Letters
Hang Gao, Ian Y Zhang, Leying Zhang, Yanyan Song, Shunan Liu, Hui Ren, Huili Liu, Hui Zhou, Yanping Su, Yihang Yang, Behnam Badie
S100B, a member of the multigene family of Ca2+ -binding proteins, is overexpressed by most malignant gliomas but its biological role in gliomagenesis is unclear. Recently, we demonstrated that low concentrations of S100B attenuated microglia activation through the induction of STAT3. Furthermore, S100B downregulation in a murine glioma model inhibited macrophage trafficking and tumor growth. Based on these observations, we hypothesized that S100B inhibitors may have antiglioma properties through modulation of tumor microenvironment...
August 1, 2018: Cancer Letters
Sina Heimer, Gertrud Knoll, Charlotte Steixner, Diana Nicoleta Calance, Dieu Thuy Trinh, Martin Ehrenschwender
Induction of mitochondria-controlled (intrinsic) apoptosis is a mainstay of current anti-neoplastic chemotherapies. Activation of this death pathway is counteracted by BCL-2-like proteins, which functionally set the threshold for apoptosis and determine whether malignant cells are sensitive or resistant to anti-cancer treatments. Hence, unlocking the intrinsic apoptotic cascade and promoting the cell's commitment to undergo apoptosis concordantly promotes efficacy of anti-cancer treatments. Here, we show that hyperosmotic stress enforces addiction of colorectal cancer cells to BCL-XL, thereby exhausting the protective capacity of BCL-2-like proteins and priming mitochondria for death...
July 31, 2018: Cancer Letters
Wen-Su Wei, Xin Chen, Li-Yi Guo, Xiang-Dong Li, Ming-Hui Deng, Gang-Jun Yuan, Le-Ye He, Yong-Hong Li, Zhi-Lin Zhang, Li-Juan Jiang, Ri-Xin Chen, Xiao-Dan Ma, Shi Wei, Ning-Fang Ma, Zhuo-Wei Liu, Jun-Hang Luo, Fang-Jian Zhou, Dan Xie
Clinically, most of human urothelial carcinoma of the bladder (UCB)-related deaths result from tumor metastasis, but the underlying molecular mechanisms are largely unknown. Recently, a growing number of tripartite motif (TRIM) family members have been suggested to be important regulators for tumorigenesis. However, the impact of most TRIM members on UCB pathogenesis is unclear. In this study, TRIM65 was first screened as an important oncogenic factor of UCB from the Cancer Genome Atlas (TCGA) database and was validated by a large cohort of clinical UCB tissues...
July 31, 2018: Cancer Letters
Xi Li, Yanan Wang, Qi Wang, Yinping Liu, Wei Bao, Sufang Wu
Exosomes are nanosized membrane-bound vesicles containing abundant proteins, DNA, mRNA, and non-coding RNAs. Exosomes are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Increasing studies have shown that exosomes play an important role in tumour initiation, growth, progression, metastasis, drug resistance and immune escape. In this article, we review recent advances in the biology of exosomes. We elaborate the specific mechanism by which exosomes affect the communication between tumours and the microenvironment...
July 31, 2018: Cancer Letters
Guoqing Qian, Weilong Yao, Shuo Zhang, Richa Bajpai, Williams D Hall, Mala Shanmugam, Sagar Lonial, Shi-Yong Sun
Agents that inhibit bromodomain and extra-terminal domain (BET) protein have been actively tested in the clinic as potential anticancer drugs. Proteasome inhibitors such as carfilzomib (CFZ) are FDA-approved for the treatment of patients with advanced multiple myeloma and have been tested against other cancers. The current study focuses on the combination of a BET inhibitor (e.g., JQ1) and a proteasome inhibitor (e.g., CFZ) as a novel cancer therapeutic strategy and the underlying mechanisms. The tested combination (JQ1 with CFZ) synergistically decreased cell survival and enhanced apoptosis in vitro and inhibited tumor growth in vivo...
July 29, 2018: Cancer Letters
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