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Cancer Letters

Mengyu Feng, Guangbing Xiong, Zhe Cao, Gang Yang, Suli Zheng, Xujun Song, Lei You, Lianfang Zheng, Taiping Zhang, Yupei Zhao
Therapy that targets programmed death 1 or programmed death 1 ligand 1 (PD-1/PD-L1), which are known as immune checkpoints, has been recently rapidly developing as oncotherapy for various carcinomas. However, this therapy has a poor effect on the treatment of pancreatic cancer with PD-1/PD-L1 blockade monotherapy. In this review, the development and limitations of anti-PD-1/PD-L1 monotherapy in pancreatic cancer are discussed. We then consider the underlying mechanism of anti-PD-1/PD-L1 monotherapy failure, combination strategies overcoming resistance to anti-PD-1/PD-L1 immunotherapy and the prospect of targeting PD-1/PD-L1 for the immunotherapy of pancreatic cancer...
August 18, 2017: Cancer Letters
Jiaqi Chen, Lei Li, Zhao Yang, Jie Luo, Shuyuan Yeh, Chawnshang Chang
Early studies suggested that using the recently developed anti-androgen Enzalutamide (Enz, also named as MDV3100) with ADT could extend castration resistant prostate cancer (CRPC) patients' survival extra 4.8 months. Yet the therapy in most patients might eventually fail due to development of Enz-resistance. Here we found Enz might also increase some unwanted side-effects via increasing the CRPC cell invasion that might involve altering the Enz-androgen receptor (AR)/EPHB6 suppressor/JNK signaling. Results from multiple clinical surveys also indicated that EPHP6 might function as a suppressor of PCa metastasis...
August 18, 2017: Cancer Letters
Ruzzolini Jessica, Peppicelli Silvia, Andreucci Elena, Bianchini Francesca, Margheri Francesca, Laurenzana Anna, Fibbi Gabriella, Pimpinelli Nicola, Calorini Lido
Vemurafenib, a BRAF inhibitor, elicits in ∼80 % of BRAF(V600E)-mutant melanoma patients a transient anti-tumor response which precedes the emergence of resistance. We tested whether an acidic tumor microenvironment may favor a BRAF inhibitor resistance. A375M6 BRAF(V600E) melanoma cells, either exposed for a short period or chronically adapted to an acidic medium, showed traits compatible with an epithelial-mesenchymal transition, reduced proliferation and high resistance to apoptosis. Both types of acidic cells treated with vemurafenib did not change their proliferation, distribution in cell cycle and level of p-AKT, in contrast to cells grown at standard pH, which showed reduced proliferation, cell cycle arrest and ERK/AKT inhibition...
August 18, 2017: Cancer Letters
Xiaojie Li, Changhong Ma, Li Zhang, Na Li, Xiaohong Zhang, Jianya He, Ruiping He, Miaomiao Shao, Junling Wang, Lan Kang, Chuanchun Han
Increasing evidence has revealed the aberrant expression of long non-coding RNAs (lncRNAs) in many cancer types, including oral squamous cell carcinoma (OSCC). However, limited investigations report metastasis-related lncRNAs in OSCC. Herein, we report the identification of dysregulated intergenic lncRNAs in the highly metastatic OSCC cell line, UM-SCC6H. One of the lncRNAs, termed AC132217.4, was remarkably upregulated and promoted cell migration and epithelial-mesenchymal transition (EMT) by upregulating IGF2 expression...
August 17, 2017: Cancer Letters
Rajnee Kanwal, Alexis R Plaga, Xiaoqi Liu, Girish C Shukla, Sanjay Gupta
MicroRNAs (miRNAs) are small endogenous non-coding molecules that alters gene expression through post-transcriptional regulation of messenger RNA. Compelling evidence suggest the role of miRNA in cancer biology having potential as diagnostic, prognostic and predictive biomarkers. This review summarizes the current knowledge on miRNA deregulated in prostate cancer and their role as oncogene, tumor suppressor and metastasis regulators. The emerging information elucidating the biological function of miRNA is promising and may lead to their potential usefulness as diagnostic/prognostic markers and development as effective therapeutic tools for management of prostate cancer...
August 17, 2017: Cancer Letters
Rabea Oberthür, Henning Seemann, Julia Gehrig, Margret Rave-Fränk, Felix Bremmer, Rovena Halpape, Lena-Christin Conradi, Jens-Gerd Scharf, Peter Burfeind, Silke Kaulfuß
Overexpression and activation of receptor tyrosine kinases (RTKs), such as the insulin-like growth factor 1 receptor (IGF1R) and the epidermal growth factor receptor (EGFR), are frequent phenomena in colorectal cancer (CRC). Here, we evaluated the effect and the cellular mechanisms of the simultaneous inhibition of these two RTKs both in vitro and in vivo in addition to a 5-fluoruracil (5-FU)-based radiochemotherapy (RCT), which is a standard treatment scheme for CRC. Using the small molecule inhibitors AEW541 and erlotinib, specific against IGF1R and EGFR, respectively, different CRC cell lines exhibited a reduced survival fraction after RCT, with the highest effect after the simultaneous inhibition of IGF1R/EGFR...
August 17, 2017: Cancer Letters
Takuya Nakagawa, Keisuke Matsusaka, Kiyoshi Misawa, Satoshi Ota, Kiyoko Takane, Masaki Fukuyo, Bahityar Rahmutulla, Ken-Ichi Shinohara, Naoki Kunii, Daiju Sakurai, Toyoyuki Hanazawa, Hisahiro Matsubara, Yukio Nakatani, Yoshitaka Okamoto, Atsushi Kaneda
Oropharyngeal squamous cell carcinoma (OPSCC) incidence has increased dramatically due to human papillomavirus (HPV); however, associated epigenetic alterations are not well studied. We performed genome-wide DNA methylation analysis using an Infinium 450k BeadArray for clinical OPSCC and non-cancerous samples and cancer cell lines with/without 5-aza-2'-deoxycytidine and/or trichostatin A treatment. Frequent promoter hypermethylation and methylation-associated silencing were detected in 144 genes, which included those involved in cell-cell signaling and neuron differentiation...
August 17, 2017: Cancer Letters
Yun Zheng, Li Liu, Girish C Shukla
Non-coding RNAs include many kinds of RNAs that did not encode proteins. Recent evidences reveal that ncRNAs play critical roles in initiation and progression of cancers. But it is not easy for cancer biologists and medical doctors to easily know the potential roles of ncRNAs in cancer and retrieve the information of ncRNAs under their investigations. To make the available web-based resources more accessible and understandable, we made a comprehensive review for 49 web-based resources of three types of ncRNAs, i...
August 17, 2017: Cancer Letters
Yang Kong, Lufei Zhang, Yu Huang, Tianyu He, Linshi Zhang, Xinyi Zhao, Xiaohu Zhou, Dongkai Zhou, Yingcai Yan, Jiarong Zhou, Haiyang Xie, Lin Zhou, Shusen Zheng, Weilin Wang
Pseudogenes are a subclass of long non-coding (lnc) RNAs that arose from protein-coding genes, but have lost the ability to produce proteins. Pseudogenes play an important role in the pathogenesis of various tumors; however, the role of pseudogenes in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated a novel pseudogene, PDIA3P1, which was upregulated in HCC tissues compared with paired normal adjacent tissues. The expression of PDIA3P1 was significantly correlated with tumor size, metastasis, TNM stage, and overall stage...
August 17, 2017: Cancer Letters
Shuying Shen, Kangmao Huang, Yizheng Wu, Yan Ma, Jiying Wang, Feiwei Qin, Jianjun Ma
Transcriptional co-activator with PDZ-binding motif (TAZ) is a WW domain-containing protein that regulates mesenchymal differentiation and organ development. It is also a downstream effector of the Hippo signaling pathway, which has been implicated in epithelial-mesenchymal transition (EMT) and tumorigenesis. However, the molecular mechanisms underlying TAZ function in these processes in the context of osteosarcoma (OS) are not well understood. We addressed this in the present study using U2OS and HOS cell lines...
August 17, 2017: Cancer Letters
Xiaoan Tao, Yang Lu, Songbo Qiu, Yi Wang, Jun Qin, Zhen Fan
In this study, we expanded our recent work showing that ASCT2, a Na+-dependent neutral amino acid transporter that is a major transporter of glutamine uptake in cancer cells, is physically associated with EGFR in human head and neck squamous cell carcinoma cells and in several other types of cancer cells. We found in our current study that ASCT2 can be downregulated by cetuximab, an approved anti-EGFR therapeutic antibody, via cetuximab-induced EGFR endocytosis independently of cetuximab-mediated inhibition of EGFR tyrosine kinase...
August 17, 2017: Cancer Letters
Johanna Ndamwena Amunjela, Steven John Tucker
Breast cancer molecular heterogeneity has resulted in disparities in therapeutic response and targeting of molecular subtypes of breast cancer. This necessitates identification and validation of novel therapeutic targets for breast cancer treatment. Suppression of Popeye domain-containing (POPDC) proteins is hypothesized to promote malignant cell behaviour and poor clinical outcomes in various cancers. We aimed to determine whether POPDC proteins are suppressed in human ductal carcinoma tissues and if this correlates to clinical progression and Her2 status...
August 12, 2017: Cancer Letters
Li Zhou, Tangfeng Lv, Qun Zhang, Qingqing Zhu, Ping Zhan, Suhua Zhu, Jianya Zhang, Yong Song
Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer...
August 12, 2017: Cancer Letters
Gulzar Ahmad, Rana El Sadda, Galina Botchkina, Iwao Ojima, James Egan, Mansoor Amiji
The main aim of this study was to evaluate the therapeutic efficacy of an oil-in-water nanoemulsion formulation encapsulating DHA-SBT-1214, a novel omega-3 fatty acid conjugated taxoid prodrug, against prostate cancer stem cells. Nanoemulsions of DHA-SBT-1214 (NE-DHA-SBT-1214) were prepared and characterized. In vitro delivery efficiency and cytotoxicity of NE-DHA-SBT-1214 was compared with solution formulation in PPT2 cells. In vivo studies included analysis of comparative efficacy of NE-DHA-SBT-1214 with Abraxane(®) and placebo nanoemulsions as well as post-treatment alternations in clonogenic and sphere-forming capabilities of the tumor cells...
August 11, 2017: Cancer Letters
Jinhua Wang, Hajime Hirose, Guanhua Du, Kelly Chong, Eiji Kiyohara, Isaac P Witz, Dave S B Hoon
P-REX1 (PIP3-dependent Rac exchange factor-1) is a guanine nucleotide exchange factor that activates Rac by catalyzing exchange of GDP for GTP bound to Rac. Aberrant up-regulation of P-REX1 expression has a role in metastasis however, copy number (CN) and function of P-REX1 in cutaneous melanoma are unclear. To explore the role of P-REX1 in melanoma, SNP 6.0 and Exon 1.0 ST microarrays were assessed. There was a higher CN (2.82-fold change) of P-REX1 in melanoma cells than in melanocytes, and P-REX1 expression was significantly correlated with P-REX1 CN...
August 10, 2017: Cancer Letters
Xiaojun Shi, Xinji Zhang, Jinlong Li, Hongfan Zhao, Lijun Mo, Xianghua Shi, Zhiming Hu, Jimin Gao, Wanlong Tan
Program death receptor-1 (PD-1)/program death ligand 1 (PD-L1) signaling plays an important role in tumor adaptive immune resistance. The streptavidin-granulocyte-macrophage colony stimulating factor (SA-GM-CSF) surface-modified tumor cells vaccine developed through our novel protein-anchor technology could significantly promote the activation of dendritic cells. Although GM-CSF vaccine could significantly increase the number of tumor-specific CD8(+)T-cells, the majority of these CD8(+)T-cells expressed PD-1...
August 8, 2017: Cancer Letters
Kang-Seo Park, Hannah Yang, Junyoung Choi, Seyoung Seo, Deokhoon Kim, Chang Hoon Lee, Hanwool Jeon, Sang-We Kim, Dae Ho Lee
More than 25% of non-small cell lung cancers (NSCLCs) carry mutations in KRAS, one of the most common oncogenic drivers in this disease. KRAS-mutant NSCLC responds poorly to currently available therapies; therefore, novel treatment strategies are needed. Here, we describe a particularly promising targeted therapeutic strategy against KRAS mutation-harboring NSCLC intrinsically resistant to treatment by PI3K inhibition. We found that intrinsic resistance to PI3K inhibition derived from RAF/MEK/ERK and RSK activation, bypassing blockage of the PI3K/AKT/mTOR pathway...
August 7, 2017: Cancer Letters
Maria Elena Pisanu, Alessia Noto, Claudia De Vitis, Stefania Morrone, Giosuè Scognamiglio, Gerardo Botti, Federico Venuta, Daniele Diso, Ziga Jakopin, Fabrizio Padula, Alberto Ricci, Salvatore Mariotta, Maria Rosaria Giovagnoli, Enrico Giarnieri, Ivano Amelio, Massimiliano Agostini, Gerry Melino, Gennaro Ciliberto, Rita Mancini
Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways β-catenin and YAP/TAZ...
August 7, 2017: Cancer Letters
E Peverelli, R Catalano, E Giardino, D Treppiedi, V Morelli, C L Ronchi, A Vaczlavik, N Fusco, S Ferrero, J Bertherat, F Beuschlein, I Chiodini, M Arosio, A Spada, G Mantovani
cAMP pathway plays a major role in the pathogenesis of cortisol-producing adrenocortical adenomas (CPA). cAMP-induced steroidogenesis is preceded by actin cytoskeleton reorganization, a process regulated by cofilin activity. In this study we investigated cofilin role in mediating cAMP effects on cell morphology and steroidogenesis in adrenocortical tumor cells. We demonstrated that forskolin induced cell rounding and strongly reduced phosphorylated (P)-cofilin/total cofilin ratio in Y1 (-52 ± 16%, p < 0...
August 5, 2017: Cancer Letters
Shu Zhang, Xinyi Cao, Qiang Gao, Yinkun Liu
Protein glycosylation is one of the most frequent and well-known posttranslational modifications, playing important roles in physiopathological processes. Glycosylation is catalyzed by enzymatic additions of heterogeneous glycans with specific linkage of monosaccharides and, in a preformed fashion, to specific amino acids within glycoproteins. Altered glycan macroheterogeneity and microheterogeneity have been reported in glycoproteins produced mainly by the liver, facilitating tumorigenesis, progression, and metastasis...
August 5, 2017: Cancer Letters
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