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Cancer Letters

Fengqi Yan, Xia Li, Nan Li, Rui Zhang, Qinhao Wang, Yi Ru, Xiaoke Hao, Jianxin Ni, He Wang, Guojun Wu
Highly efficient target therapy is urgently needed for prostate cancer with overexpression of γ-seminoprotein (γ-SM). Recent studies indicated that mesenchymal stem cells (MSCs) are attractive candidate for cell-based, targeted therapy due to their tumor tropism. Here we designed a dual-target therapeutic system in which MSCs were engineered to produce and deliver scFv-Fdt-tBid, a novel γ-SM-targeted immunoproapoptotic molecule. Such engineered MSCs (MSC.scFv-Fdt-tBid) would home to tumor sites and release the fusion protein to induce the apoptosis of prostate cancer cells...
May 18, 2017: Cancer Letters
Kosuke Mima, Shigeki Nakagawa, Hiroshi Sawayama, Takatsugu Ishimoto, Katsunori Imai, Masaaki Iwatsuki, Daisuke Hashimoto, Yoshifumi Baba, Yo-Ichi Yamashita, Naoya Yoshida, Akira Chikamoto, Hideo Baba
The human intestinal microbiome encompasses at least 100 trillion microorganisms that can influence host immunity and disease conditions, including cancer. Hepatobiliary and pancreatic cancers have been associated with poor prognosis owing to their high level of tumor invasiveness, distant metastasis, and resistance to conventional treatment options, such as chemotherapy. Accumulating evidence from animal models suggests that specific microbes and microbial dysbiosis can potentiate hepatobiliary-pancreatic tumor development by damaging DNA, activating oncogenic signaling pathways, and producing tumor-promoting metabolites...
May 17, 2017: Cancer Letters
Qiuping Liu, Qing Luo, Alexander Halim, Guanbin Song
One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression...
May 17, 2017: Cancer Letters
Jingze Zhang, Li Kong, Qinghua Jiao, Minghuan Li, Jingming Yu
Stereotactic ablative radiotherapy (SABR) has been recognized as a standard alternative treatment to surgery for inoperable early stage non-small cell lung cancer (NSCLC). Guaranteed local control rates over 90% makes oncologists wonder whether SABR is qualified enough to challenge surgery in operable patients. The role of SABR for centrally located lesions would be another question because of the increased risk of severe toxic effect. Plenty of studies suggest that optimization of dose regimen and appropriate case selection would be helpful...
May 16, 2017: Cancer Letters
Ranjani Lakshminarasimhan, Claudia Andreu-Vieyra, Kate Lawrenson, Christopher E Duymich, Simon A Gayther, Gangning Liang, Peter A Jones
The chromatin remodeler AT-Rich Interactive Domain 1A (ARID1A) is frequently mutated in ovarian clear cell carcinoma (OCCC) and endometriosis precursor lesions. Here, we show that knocking down ARID1A in an immortalized endometriosis cell line is sufficient to induce phenotypic changes indicative of neoplastic transformation as evidenced by higher efficiency of anchorage-independent growth, increased propensity to adhere to collagen, and greater capacity to invade basement membrane extract in vitro. ARID1A knockdown is associated with expression dysregulation of 99 target genes, and many of these expression changes are also observed in primary OCCC tissues...
May 6, 2017: Cancer Letters
Benfan Wang, Hong Wu, Chengsen Chai, John Lewis, Flavia Pichiorri, David D Eisenstat, Scott L Pomeroy, Roger P Leng
The p53 protein plays a critical role in preventing tumor development. Although numerous factors have been shown to directly or indirectly regulate p53, the mechanism of how microRNAs (miRNAs) modulate p53 remains unclear. Here, we identified miR-1301, a microRNA that regulates the activity and function of p53, by directly targeting the ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase. Notably, ectopic expression of miR-1301 inhibits dissemination and metastasis of tumor cells in a p53-dependent manner...
May 5, 2017: Cancer Letters
Feiyan Lin, Peili Zhang, Zhigui Zuo, Fule Wang, Ruichun Bi, Wenjing Shang, Aihua Wu, Ju Ye, Shaotang Li, Xuecheng Sun, Jianbo Wu, Lei Jiang
Thioredoxin-1 (Trx-1) is a small redox-regulating protein, which plays an important role in several cellular functions. Despite recent advances in understanding the biology of Trx-1, the role of Trx-1 and its underlying signaling mechanism in colorectal cancer (CRC) metastasis have not been extensively studied. In this study, we observed that Trx-1 expression is increased in CRC tissues compared to the paired non-cancerous tissues and is significantly correlated with clinical staging, lymph node metastasis and poor survival...
May 5, 2017: Cancer Letters
Junyu Xiang, Hui Sun, Li Su, Limei Liu, Juanjuan Shan, Junjie Shen, Zhi Yang, Jun Chen, Xing Zhong, Matías A Ávila, Xiaochu Yan, Chungang Liu, Cheng Qian
Myocyte enhancer factor 2D (MEF2D) is involved in many aspects of cancer progression, including cell proliferation, invasion, and migration. However, little is known about the role of MEF2D in tumor angiogenesis. Using clinical specimens, colorectal cancer (CRC) cell lines and a mouse model in the present study, we found that MEF2D expression was positively correlated with CD31-positive microvascular density in CRC tissues. MEF2D promoted tumor angiogenesis in vitro and in vivo and induced the expression of proangiogenic cytokines in CRC cells...
May 4, 2017: Cancer Letters
Wanqing Chen, Rongshou Zheng, Siwei Zhang, Hongmei Zeng, Changfa Xia, Tingting Zuo, Zhixun Yang, Xiaonong Zou, Jie He
OBJECTIVE: National Central Cancer Registry of China (NCCRC) updated nationwide statistics of cancer incidence and mortality in China using population-based cancer registration data in 2013 from all available cancer registries. METHODS: In 2016, 255 registries' data were qualified and included in this analysis. We estimated numbers of new cancer cases and deaths in China in 2013 using age-specific rates and corresponding national population stratified by area, sex, age group (0, 1-4, 5-9, 10-14…85+) and cancer type...
May 2, 2017: Cancer Letters
Changzheng Du, Dandan Huang, Yifan Peng, Yunfeng Yao, Ying Zhao, Yang Yang, Haiying Wang, Linlin Cao, Wei-Guo Zhu, Jin Gu
Although 5-fluorouracil (5-FU) is known to interfere with the synthesis of ribonucleic acid and deoxyribonucleic acid, the mechanism underlying its therapeutic efficacy in colorectal cancer (CRC) has not been fully elucidated. We aimed to investigate the influence of 5-FU on histone acetylation, a well-established anti-cancer target, to reveal novel pharmacological effects of 5-FU and their significance for CRC therapy. Results demonstrated that 5-FU induces global histone de-acetylation in multiple CRC cell lines...
April 29, 2017: Cancer Letters
Xuan Shi, Hai-Rong Zhu, Tao-Tao Liu, Xi-Zhong Shen, Ji-Min Zhu
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide. However, current strategies curing HCC are far from satisfaction. The Hippo pathway is an evolutionarily conserved tumor suppressive pathway that plays crucial roles in organ size control and tissue homeostasis. Its dysregulation is commonly observed in various types of cancer including HCC. Recently, the prominent role of non-coding RNAs in the Hippo pathway during normal development and neoplastic progression is also emerging in liver...
April 29, 2017: Cancer Letters
Dan Yang, Xin Cao, Fan Wang, Haijing Jiang, Dingding Feng, Hao Guo, Lei Du, Yingliang Jin, Yansu Chen, Xiaoxing Yin, Chenglin Li
Increasing evidence indicates that inflammatory microenvironment facilitates tumor metastasis. Here, we found that LFG-500, a novel synthetic flavonoid, significantly inhibited epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma A549 and H1299 cells co-cultured with LPS-challenged THP-1 cells or cultured in THP-1 cell-derived conditioned medium. Moreover, we found that TNF-α is a direct and decisive factor for promoting EMT and LFG-500 suppressed TNF-α-induced EMT and cell motility. NLRP3 knockdown inactivated NLRP3 inflammasome, which subsequently inhibited EMT and blocked cell migration, indicating that TNF-α-induced EMT requires the NLRP3 inflammasome...
April 29, 2017: Cancer Letters
Ling Li, Lei Kang, Wei Zhao, Yingying Feng, Wenpeng Liu, Tao Wang, Haixing Mai, Jun Huang, Siyu Chen, Yingchun Liang, Juqiang Han, Xiaojie Xu, Qinong Ye
Lactate dehydrogenase A (LDHA), a key enzyme regulating aerobic glycolysis, is overexpressed in many human cancers, and correlates with poor clinical outcomes. Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including LDHA, are being developed. However, the mechanisms of LDHA inhibition and the physiological significance of the LDHA inhibitors in cancer cells are unclear. Here, we show that microRNA-30a-5p (miR-30a-5p) suppresses LDHA expression by directly targeting its 3'-UTR...
April 29, 2017: Cancer Letters
Yongfang Wang, You Zhou, Feng Tao, Shoujie Chai, Xia Xu, Ying Yang, Yiming Yang, Haiyan Xu, Kai Wang
Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC...
April 27, 2017: Cancer Letters
J Luis Espinoza, Mahmoud I Elbadry, Masafumi Taniwaki, Kenichi Harada, Ly Quoc Trung, Noriharu Nakagawa, Akiyoshi Takami, Ken Ishiyama, Takuji Yamauchi, Katsuto Takenaka, Shinji Nakao
Acute myelogenous leukemia (AML) is a clinically heterogeneous disease that is frequently associated with relapse and a poor prognosis. Among the various subtypes, AML with the monosomal karyotype (AML-MK) has an extremely unfavorable prognosis. We performed screening to identify antitumor compounds that are capable of inducing apoptosis in primary leukemia cells harboring the AML-MK karyotype and identified a naturally occurring stilbene, Gnetin-C, with potent anti-tumor activities against AML cells from patients with various cytogenetic abnormalities, including patients with the AML-MK karyotype...
April 26, 2017: Cancer Letters
Junyu Wu, Zhimin He, Xiao-Mei Yang, Kai-Le Li, Da-Liang Wang, Fang-Lin Sun
Lung cancer is one of the most lethal cancers due to its highly metastatic spreading. The motility of lung cancer cells is regulated by paracrine factors, such as TGF-β, in the tumor microenvironment through the induction of epithelial-to-mesenchymal transition (EMT). The stability of microtubules is reported to be associated with the EMT process and the migration of cancer cells. Here, we observed that RCC1 domain-containing protein 1 (RCCD1) is highly expressed in non-small cell lung cancer (NSCLC) patients with poor prognosis, and RCCD1 is much higher expressed in tumor tissues compared with adjacent normal tissues...
April 26, 2017: Cancer Letters
Jaime Abrego, Venugopal Gunda, Enza Vernucci, Surendra K Shukla, Ryan J King, Aneesha Dasgupta, Gennifer Goode, Divya Murthy, Fang Yu, Pankaj K Singh
The increased rate of glycolysis and reduced oxidative metabolism are the principal biochemical phenotypes observed in pancreatic ductal adenocarcinoma (PDAC) that lead to the development of an acidic tumor microenvironment. The pH of most epithelial cell-derived tumors is reported to be lower than that of plasma. However, little is known regarding the physiology and metabolism of cancer cells enduring chronic acidosis. Here, we cultured PDAC cells in chronic acidosis (pH 6.9-7.0) and observed that cells cultured in low pH had reduced clonogenic capacity...
April 26, 2017: Cancer Letters
Jiaxiong Lu, Shan Guan, Yanling Zhao, Yang Yu, Sarah E Woodfield, Huiyuan Zhang, Kristine L Yang, Shayahati Bieerkehazhi, Lin Qi, Xiaonan Li, Jerry Gu, Xin Xu, Jingling Jin, Jodi A Muscal, Tianshu Yang, Guo-Tong Xu, Jianhua Yang
Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling...
April 26, 2017: Cancer Letters
Thibaut Barnoud, M Lee Schmidt, Howard Donninger, Geoffrey J Clark
The Ras genes are the most frequently mutated oncogenes in human cancer. However, Ras biology is quite complex. While Ras promotes tumorigenesis by regulating numerous growth promoting pathways, activated Ras can paradoxically also lead to cell cycle arrest, death, and Oncogene-Induced Senescence (OIS). OIS is thought to be a critical pathway that serves to protect cells against aberrant Ras signaling. Multiple reports have highlighted the importance of the p53 and Rb tumor suppressors in Ras mediated OIS. However, until recently, the molecular mechanisms connecting Ras to these proteins remained unknown...
April 26, 2017: Cancer Letters
Yun Wang, Maoxing Liu, Yanli Jin, Sheng Jiang, Jingxuan Pan
Uveal melanoma (UM) is the most common intraocular malignant neoplasm in adults. Despite the availability of enucleation, radiation and chemotherapy, the prognosis of patients with metastasis remains poor. Therefore, novel effective therapies for patients with metastatic UM are urgently needed. In the present study, we demonstrated that JSL-1, a novel HDAC inhibitor, effectively inhibited the proliferation. JSL-1 induced apoptosis with increased expression of proapoptotic BH3-only protein BIM in UM cells. JSL-1 suppressed migration and invasion of UM cells with MMP-2 decreased...
April 26, 2017: Cancer Letters
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