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Cancer Letters

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https://www.readbyqxmd.com/read/29225052/supersulfated-low-molecular-weight-heparin-synergizes-with-igf1r-ir-inhibitor-to-suppress-synovial-sarcoma-growth-and-metastases
#1
Giuliana Cassinelli, Laura Dal Bo, Enrica Favini, Denis Cominetti, Sabina Pozzi, Monica Tortoreto, Michelandrea De Cesare, Daniele Lecis, Eugenio Scanziani, Lucia Minoli, Annamaria Naggi, Israel Vlodavsky, Nadia Zaffaroni, Cinzia Lanzi
Synovial sarcoma (SS) is an aggressive tumor with propensity for lung metastases which significantly impact patients' prognosis. New therapeutic approaches are needed to improve treatment outcome. Targeting the heparanase/heparan sulfate proteoglycan system by heparin derivatives which act as heparanase inhibitors/heparan sulfate mimetics is emerging as a therapeutic approach that can sensitize the tumor response to chemotherapy. We investigated the therapeutic potential of a supersulfated low molecular weight heparin (ssLMWH) in preclinical models of SS...
December 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222042/antiangiogenic-compounds-well-established-drugs-versus-emerging-natural-molecules
#2
Andreia Ribeiro, Rui M V Abreu, Madalena M Dias, Maria Filomena Barreiro, Isabel C F R Ferreira
Angiogenesis is the natural and physiologic process of growing blood vessels from pre-existing ones. Pathological angiogenesis occurs when the precise balance of all the molecular pathways that regulate angiogenesis is disrupted, and this process is a critical step in many diseases, including cancer. A limited number of antiangiogenic synthetic drugs have been developed. However, due to toxicity and side effects issues, the search for alternative to existing drugs is ongoing. In this sense, natural molecules obtained from plants or macrofungi, have demonstrated extraordinary potential in the treatment of angiogenesis-related pathologies, specially taking into consideration its absence or very low toxicity, when compared to synthetic drugs...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222041/tap73-inhibits-cell-invasion-and-migration-by-directly-activating-kai1-expression-in-colorectal-carcinoma
#3
Woo-Kyun Bae, Chang-Soo Hong, Mi-Ra Park, Eun-Gene Sun, Ji-Hee Lee, Keunsoo Kang, Kyung-Hyun Ryu, Hyun-Jeong Shim, Jun-Eul Hwang, Sang-Hee Cho, Ik-Joo Chung
p73 is a member of the p53 family of transcription factors and, like p53, plays a role as a tumor suppressor. p73 is involved in development, proliferation, apoptosis and metastasis. However, the precise molecular mechanisms underlying its function in inhibiting metastasis remain largely unknown. Here, we show that induction of TAp73 decreased invasion and migration activity of colorectal cancer cells, whereas knockdown of TAp73 led to increased invasion and migration activity. KAI1 was identified as a transcriptional target of TAp73 and its expression is indispensable for TAp73-mediated inhibition of cell invasion and migration...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222040/prohibitin-a-new-player-in-immunometabolism-and-in-linking-obesity-and-inflammation-with-cancer
#4
Yang Xin Zi Xu, Sudharsana Rao Ande, Suresh Mishra
Immunometabolism, which has important implications in cancer biology, has emerged as a major regulator of different immune cell types. Various factors that integrate metabolic switches within immune cells with signal directed program that promote or inhibit their functions remain largely unidentified. Furthermore, sex differences are known to exist in immune functions and cancer incidences in the body and sex steroid hormones are integral component of these differences. However, factors that mediate such differences, and the potential link between the two fundamental aspects of immune cell biology that contributes to sex differences in health and disease remain unexplored...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222039/the-role-of-stat3-in-leading-the-crosstalk-between-human-cancers-and-the-immune-system
#5
Yu Wang, Yicheng Shen, Sinan Wang, Qiang Shen, Xuan Zhou
The development and progression of human cancers are continuously and dynamically regulated by intrinsic and extrinsic factors. As a converging point of multiple oncogenic pathways, signal transducer and activator of transcription 3 (STAT3) is constitutively activated both in tumor cells and tumor-infiltrated immune cells. Activated STAT3 persistently triggers tumor progression through direct regulation of oncogenic gene expression. Apart from its oncogenic role in regulating gene expression in tumor cells, STAT3 also paves the way for human cancer growth through immunosuppression...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222038/hdac6-inhibition-induces-glioma-stem-cells-differentiation-and-enhances-cellular-radiation-sensitivity-through-the-shh-gli1-signaling-pathway
#6
Wei Yang, Yingying Liu, Ruoling Gao, Hongquan Yu, Ting Sun
The existence of small numbers of stem-like cells, called glioma stem cells (GSCs), in human glioblastoma multiforme (GBM) is responsible for recurrence due to resistance to radiotherapy and chemotherapy. Inhibition of histone deacetylase 6 (HDAC6) enhanced radiosensitivity of cancer cells. However, the effect of inhibiting HDAC6 on stemness and radioresistance of GSCs and its molecular mechanism are largely unknown. In the present study, we found that HDAC6 was upregulated in GSCs comparing to non-stem tumor cells...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29222037/diabetes-as-risk-factor-for-pancreatic-cancer-hyperglycemia-promotes-epithelial-mesenchymal-transition-and-stem-cell-properties-in-pancreatic-ductal-epithelial-cells
#7
Sascha Rahn, Vivien Zimmermann, Fabrice Viol, Hendrike Knaack, Kerstin Stemmer, Lena Peters, Lennart Lenk, Hendrik Ungefroren, Dieter Saur, Heiner Schäfer, Ole Helm, Susanne Sebens
Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29217458/imp2-and-imp3-cooperate-to-promote-the-metastasis-of-triple-negative-breast-cancer-through-destabilization-of-progesterone-receptor
#8
Hye-Youn Kim, Huyen Trang Ha Thi, Suntaek Hong
Triple-negative breast cancer (TNBC) is one of the most aggressive malignancies and is associated with high mortality rates due to the lack of effective therapeutic targets. In this study, we demonstrated that insulin-like growth factor-II mRNA-binding protein 2 and 3 (IMP2 and IMP3) are specifically overexpressed in TNBC and cooperate to promote cell migration and invasion. Downregulation of both IMP2 and IMP3 in TNBC cells was found to produce a synergistic effect in suppressing cell invasion and invadopodia formation, whereas overexpression of IMP2 and IMP3 in luminal subtype cells enhanced epithelial-mesenchymal transition and metastasis...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29203251/androgen-receptor-ar-degradation-enhancer-asc-j9%C3%A2-in-an-fda-approved-formulated-solution-suppresses-castration-resistant-prostate-cancer-cell-growth
#9
Max A Cheng, Fu-Ju Chou, Keliang Wang, Rachel Yang, Jie Ding, Qiaoxia Zhang, Gonghui Li, Shuyuan Yeh, Defeng Xu, Chawnshang Chang
ASC-J9® is a recently-developed androgen receptor (AR)-degradation enhancer that effectively suppresses castration resistant prostate cancer (PCa) cell proliferation and invasion. The optimal half maximum inhibitory concentrations (IC50) of ASC-J9® at various PCa cell confluences (20%, 50%, and 100%) were assessed via both short-term MTT growth assays and long-term clonogenic proliferation assays. Our results indicate that the IC50 values for ASC-J9® increased with increasing cell confluency. The IC50 values were significantly decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal prostate cells...
December 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29203250/nfyb-induced-high-expression-of-e2f1-contributes-to-oxaliplatin-resistance-in-colorectal-cancer-via-the-enhancement-of-chk1-signaling
#10
Zejun Fang, Chaoju Gong, Songshan Yu, Weihua Zhou, Waseem Hassan, Hongzhang Li, Xue Wang, Yanyan Hu, Kaipeng Gu, Xixi Chen, Bing Hong, Yuyan Bao, Xiang Chen, Xiaomin Zhang, Hong Liu
As a third-generation platinum drug, oxaliplatin has been widely applied in colorectal cancer (CRC); however, acquired resistance to oxaliplatin has become a major obstacle. In the present study, we found that the nuclear transcription factor Y subunit beta (NFYB) and E2F transcription factor 1 (E2F1) expression levels were significantly higher in oxaliplatin-resistant DLD1 and RKO CRC (OR-CRC) cells than in non-resistant cells. Additionally, highly expressed NFYB transactivated the E2F1 gene, which is important to maintain oxaliplatin resistance in OR-CRC cells...
December 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29199006/lb-100-a-novel-protein-phosphatase-2a-pp2a-inhibitor-sensitizes-malignant-meningioma-cells-to-the-therapeutic-effects-of-radiation
#11
Winson S C Ho, Saman Sizdahkhani, Shuyu Hao, Hua Song, Ashlee Seldomridge, Anita Tandle, Dragan Maric, Tamalee Kramp, Rongze Lu, John D Heiss, Kevin Camphausen, Mark R Gilbert, Zhengping Zhuang, Deric M Park
Atypical and anaplastic meningiomas (AAM) represent 20% of all meningiomas. They are associated with poor outcomes due to their tendency to recur. While surgery and radiation (RT) are first line therapy, no effective systemic medical treatment has been identified. Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase involved in cell cycle regulation and DNA repair. Here, we examined radiosensitizing effects of LB-100, a novel inhibitor of PP2A against AAM as a novel treatment strategy...
November 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29199005/ginsenoside-rg3-sensitizes-hypoxic-lung-cancer-cells-to-cisplatin-via-blocking-of-nf-%C3%AE%C2%BAb-mediated-epithelial-mesenchymal-transition-and-stemness
#12
Jingjing Wang, Lili Tian, Muhammad Noman Khan, Li Zhang, Qun Chen, Yi Zhao, Qiu Yan, Li Fu, Jiwei Liu
Cisplatin is a first line chemotherapy in lung cancer, but decreased susceptibility may limit its application. In solid tumors, hypoxia alters the microenvironment and is associated with proliferation, metastasis, and drug sensitivity. The hypoxia-induced desensitization of cisplatin is not clearly elucidated. 20 (R)-Ginsenoside (Rg3), the traditional Chinese medicine, is extracted from ginseng and has antitumor activities. In this study, we evaluated if Rg3 is effective in improving cisplatin sensitivity by blocking hypoxia...
November 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29199004/dicer-reprograms-stromal-fibroblasts-to-a-pro-inflammatory-and-tumor-promoting-phenotype-in-ovarian-cancer
#13
Zongyuan Yang, Ping Jin, Sen Xu, Taoran Zhang, Xin Yang, Xiaoting Li, Xiao Wei, Chaoyang Sun, Gang Chen, Ding Ma, Qinglei Gao
Inflammation and host stromal activation contribute significantly to ovarian cancer (OC) initiation and malignant progression. However, the complex reciprocal interactions between them are largely unknown. Here, we discovered that the tumor suppressor gene Dicer was paradoxically overexpressed in ovarian tumor stroma, and induced fibroblast activation and stromal inflammation. Dicer transformed normal fibroblasts to a carcinoma-associated fibroblast (CAF)-like state, which was morphologically spread out and functionally activated to fuel tumor invasion and metastasis...
November 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29197615/interplay-between-the-lung-microbiome-and-lung-cancer
#14
Qixing Mao, Feng Jiang, Rong Yin, Jie Wang, Wenjie Xia, Gaochao Dong, Weidong Ma, Yao Yang, Lin Xu, Jianzhong Hu
The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer...
November 29, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29196129/stanniocalcin-1-augments-stem-like-traits-of-glioblastoma-cells-through-binding-and-activating-notch1
#15
Yong Li, Zhi-Cheng He, Xiao-Ning Zhang, Qing Liu, Cong Chen, Zheng Zhu, Qian Chen, Yu Shi, Xiao-Hong Yao, You-Hong Cui, Xia Zhang, Yan Wang, Hsiang-Fu Kung, Yi-Fang Ping, Xiu-Wu Bian
Glioblastoma (GBM) is a fatal tumor and comprises heterogeneous cells in which a subpopulation with stem cell-like properties is included. Cancer cells with stem cell-like properties account for tumor initiation, drug resistance and recurrence. To identify and characterize specific factors in regulating stem-like traits is critical for GBM therapeutic. Here, we showed that Stanniocalcin-1 (STC1), a secretory glycoprotein, functions as a novel stimulator for stem-like traits of GBM cells. We found STC1 was prominently expressed in glioma spheres which are mainly comprised of glioma stem-like cells...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29196128/maintenance-of-stemness-by-mir-589-5p-in-hepatocellular-carcinoma-cells-promotes-chemoresistance-via-stat3-signaling
#16
Jianting Long, Chunlin Jiang, Baoxian Liu, Qiangsheng Dai, Ruixi Hua, Cui Chen, Bing Zhang, Heping Li
The strength and duration of STAT3 signaling are tightly controlled by multiple negative feedback mechanisms under physical conditions. However, how these serial feedback loops are simultaneously disrupted in cancers, leading to constitutive activation of STAT3 signaling in hepatocellular carcinoma (HCC), remains obscure. Here we report that miR-589-5p is elevated in HCC tissues, which is caused by recurrent gains. Overexpression of miR-589-5p correlates with poor overall and relapse-free survival in HCC patients...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29196127/lncrnas-and-circrnas-from-the-same-gene-masterpieces-of-rna-splicing
#17
Ma-Sha Huang, Tao Zhu, Ling Li, Pan Xie, Xi Li, Hong-Hao Zhou, Zhao-Qian Liu
Accumulating evidence has shown that lncRNAs and circRNAs are novel regulators of gene expression. The discovery of numerous lncRNAs and circRNAs, and investigation into their structures and functions will contribute to our understanding of the pathogenesis of diseases as well as better prevention, diagnosis, and treatment of diseases. There is a close relationship between circRNAs and lncRNAs regarding to their origins and functions. Recent studies have shown that non-coding linear and circular transcripts can be transcribed from the same gene and are potential super-enhancers modulating gene transcription...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29196126/oncogenic-kit-signalling-on-the-golgi-is-suppressed-by-blocking-secretory-trafficking-with-m-copa-in-gastrointestinal-stromal-tumours
#18
Yuuki Obata, Keita Horikawa, Isamu Shiina, Tsuyoshi Takahashi, Takatsugu Murata, Yasutaka Tasaki, Kyohei Suzuki, Keita Yonekura, Hiroyasu Esumi, Toshirou Nishida, Ryo Abe
Most gastrointestinal stromal tumours (GISTs) are caused by constitutively active mutations in Kit tyrosine kinase. The drug imatinib, a specific Kit inhibitor, improves the prognosis of metastatic GIST patients, but these patients become resistant to the drug by acquiring secondary mutations in the Kit kinase domain. We recently reported that a Kit mutant causes oncogenic signals only on the Golgi apparatus in GISTs. In this study, we show that in GIST, 2-methylcoprophilinamide (M-COPA, also known as "AMF-26"), an inhibitor of biosynthetic protein trafficking from the endoplasmic reticulum (ER) to the Golgi, suppresses Kit autophosphorylation at Y703/Y721/Y730/Y936, resulting in blockade of oncogenic signalling...
November 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29179998/ell2-regulates-dna-non-homologous-end-joining-nhej-repair-in-prostate-cancer-cells
#19
Yachen Zang, Laura E Pascal, Yibin Zhou, Xiaonan Qiu, Leizhen Wei, Junkui Ai, Joel B Nelson, Mingming Zhong, Boxin Xue, Shaoxiong Wang, Dongrong Yang, Li Lan, Yuxi Shan, Zhou Wang
ELL2 is an androgen-responsive gene that is expressed by prostate epithelial cells and is frequently down-regulated in prostate cancer. Deletion of Ell2 in the murine prostate induced murine prostatic intraepithelial neoplasia and ELL2 knockdown enhanced proliferation and migration in C4-2 prostate cancer cells. Here, knockdown of ELL2 sensitized prostate cancer cells to DNA damage and overexpression of ELL2 protected prostate cancer cells from DNA damage. Knockdown of ELL2 impaired non-homologous end joining repair but not homologous recombination repair...
November 24, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29179997/elevated-cyclic-amp-levels-promote-brafca-pten-mouse-melanoma-growth-but-pcreb-is-negatively-correlated-with-human-melanoma-progression
#20
Carlos I Rodríguez, Edgardo Castro-Pérez, B Jack Longley, Vijayasaradhi Setaluri
Melanocyte development and differentiation are regulated by cAMP, which is produced by the adenylate cyclase (AC) enzyme upon activation of the melanocortin-1-receptor (MC1R). Individuals carrying single amino acid substitution variants of MC1R have impaired cAMP signaling and higher risk of melanoma. However, the contribution of AC to this risk is not clear. Downstream of AC, the phosphorylated transcription factor, cyclic AMP Responsive Element Binding Protein (pCREB), which is activated by protein kinase A, regulates the expression of several genes including the melanocyte master regulator MITF...
November 24, 2017: Cancer Letters
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