Oral recombinant methioninase (o-rMETase) is superior to injectable rMETase and overcomes acquired gemcitabine resistance in pancreatic cancer
Recombinant methioninase (rMETase) was administered as an injectable drug to target methionine dependence of cancer. Recently, we observed that rMETase could be administered orally (o-rMETase) in a patient-derived orthotopic xenograft (PDOX) mouse model of melanoma. Here, we determined the efficacy of o-rMETase on a pancreatic cancer PDOX model. Forty pancreatic cancer PDOX mouse models were randomized into four groups of 10 mice each. o-rMETase was significantly more effective than i.p.-rMETase, but combination of both was significantly more effective. (Source: Cancer Letters)
Source: Cancer Letters - June 18, 2018 Category: Cancer & Oncology Authors: Kei Kawaguchi, Kentaro Miyake, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Tasuku Kiyuna, Masuyo Miyake, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Sahar Razmjooei, Sintawat Wangsiricharoen, Michael Bouvet, Shree Ram Singh, Michiaki Unn Tags: Original Articles Source Type: research
CISD2 inhibition overcomes resistance to sulfasalazine-induced ferroptotic cell death in head and neck cancer
Sulfasalazine has been repurposed to induce ferroptotic cancer cell death via inhibition of xc--cystine/glutamate antiporter (xCT). However, cancer cells are capable of developing mechanisms to evade cell death. Therefore, we sought to determine the molecular mechanisms underlying resistance to sulfasalazine-induced ferroptosis in head and neck cancer (HNC). The effects of sulfasalazine and pioglitazone were tested in various HNC cell lines. The effects of these drugs and inhibition and overexpression of CISD2 gene were determined by evaluating viability, cell death, lipid ROS production, mitochondrial iron, and mouse tumo...
Source: Cancer Letters - June 18, 2018 Category: Cancer & Oncology Authors: Eun Hye Kim, Daiha Shin, Jaewang Lee, Ah Ra Jung, Jong-Lyel Roh Tags: Original Articles Source Type: research
Rational design and development of a peptide inhibitor for the pd-1/pd-l1 interaction
We report here the rational design and validation of a peptide inhibitor to the PD-1/PD-L1 interaction as an attempt to develop a viable alternative to current inhibitory antibodies. We demonstrated, by biolayer interferometry and in silico docking simulations, that a PD-L1 peptide mimetic (PL120131) can interfere with the PD-1/PD-L1 interaction by binding to PD-1. We show that PL120131 is capable of inhibiting PD-1 mediated apoptotic signaling pathway and rescuing Jurkat cells and primary lymphocytes from apoptosis. (Source: Cancer Letters)
Source: Cancer Letters - June 16, 2018 Category: Cancer & Oncology Authors: Rebecca J. Boohaker, Vijaya Sambandam, Isaac Segura, James Miller, Mark Suto, Bo Xu Tags: Original Articles Source Type: research
Novel tumor necrosis factor- α induced protein eight (TNFAIP8/TIPE) family: Functions and downstream targets involved in cancer progression
The tumor necrosis factor (TNF)- α- induced protein 8 (TNFAIP8/TIPE) family is a death effector domain (DED)-containing protein family with four identified members: TNFAIP8 (TIPE), TNFAIP8L1 (TIPE1), TNFAIP8L2 (TIPE2), and TNFAIP8L3 (TIPE3). These proteins were found to play crucial roles in the regulation of immune homeostasis, i nflammation, and cancer development. Intensive research in the past two decades revealed a strong correlation of TIPE proteins with development of various cancers including cancers of the bladder, blood, bone, breast, cervix, colon, esophagus, endometrium, stomach, liver, lung, ovary, pancreas, ...
Source: Cancer Letters - June 16, 2018 Category: Cancer & Oncology Authors: Ganesan Padmavathi, Kishore Banik, Javadi Monisha, Devivasha Bordoloi, Shabnam Bano, Frank Arfuso, Gautam Sethi, Fan Lu, Ajaikumar B. Kunnumakkara Tags: Mini-review Source Type: research
Loss of Linc01060 induces pancreatic cancer progression through vinculin-mediated focal adhesion turnover
There is currently limited knowledge regarding the involvement of long non-coding RNAs (lncRNAs) in cancer development. We aimed to identify lncRNAs with important roles in pancreatic cancer progression. We screened for lncRNAs that were differentially expressed in pancreatic cancer tissues. Among 349 differentially expressed lncRNAs, Linc01060 showed the lowest expression in pancreatic cancer tissues compared with normal pancreatic tissues. Lower Linc01060 expression in pancreatic cancer tissues was significantly associated with a poor prognosis. (Source: Cancer Letters)
Source: Cancer Letters - June 15, 2018 Category: Cancer & Oncology Authors: Xiuhui Shi, Xingjun Guo, Xu Li, Min Wang, Renyi Qin Tags: Original Articles Source Type: research
ABT-263-induced MCL1 upregulation depends on autophagy-mediated 4EBP1 downregulation in human leukemia cells
The present study aimed to investigate the pathway related to MCL1 expression in ABT-263-treated human leukemia U937 cells. ABT-263 upregulated MCL1 protein expression but did not affect its mRNA level and protein stability. Notably, ABT-263 increased 4EBP1 mRNA decay and thus reduced 4EBP1 expression. Overexpression of 4EBP1 abrogated ABT-263-induced MCL1 upregulation. ABT-263-induced activation of IKK α/β-NFκB axis elicited autophagy of U937 cells, leading to reduced mRNA stability of 4EBP1. Inhibition of the IKKα/β-NFκB axis or autophagy mitigated the effect of ABT-263 on 4EBP1 and MCL1 expression. (Source: Cancer Letters)
Source: Cancer Letters - June 15, 2018 Category: Cancer & Oncology Authors: Yuan-Chin Lee, Liang-Jun Wang, Chia-Hui Huang, Yi-Jun Shi, Long-Sen Chang Tags: Original Articles Source Type: research
Targeting Orai1-mediated store-operated calcium entry by RP4010 for anti-tumor activity in esophagus squamous cell carcinoma
Esophageal cancer (EC) is the 6 t h leading cause of cancer mortality worldwide with poor prognosis, hence more effective chemotherapeutic drugs for this deadly disease are urgently needed. We previously reported that high expression of Orai1, a store-operated Ca2+entry (SOCE) channel was associated with poor survival rate in EC patients and Orai1-mediated intracellular Ca2+ oscillations regulated cancer cell proliferation. Previous studies suggested that Orai1-mediated SOCE is a promising target for EC chemotherapy. (Source: Cancer Letters)
Source: Cancer Letters - June 14, 2018 Category: Cancer & Oncology Authors: Chaochu Cui, Yan Chang, Xiaoli Zhang, Sangyong Choi, Henry Tran, Kumar V. Penmetsa, Srikant Viswanadha, Liwu Fu, Zui Pan Tags: Original Articles Source Type: research
The TGF β-induced lncRNA TBILA promotes non-small cell lung cancer progression in vitro and in vivo via cis-regulating HGAL and activating S100A7/JAB1 signaling
Long non-coding RNAs (lncRNAs) play critical roles in multiple cellular processes in non-small cell lung cancer (NSCLC); however, the involvement of lncRNAs in the transforming growth factor-beta (TGF β) signaling pathway, the critical tumor cell epithelial-mesenchymal transition (EMT) and metastasis pathway, remains poorly understood. To address this issue, we compared the lncRNAs expression patterns of NSCLC cells treated with and without TGFβ1 treatment. We observed that one of the most prom inent hits, TGFβ-induced lncRNA (TBILA), promoted NSCLC progression and was upregulated in tumor tissues. (Source: Cancer Letters)
Source: Cancer Letters - June 13, 2018 Category: Cancer & Oncology Authors: Zhiliang Lu, Yuan Li, Yun Che, Jianbing Huang, Shouguo Sun, Shuangshuang Mao, Yuanyuan Lei, Ning Li, Nan Sun, Jie He Tags: Original Articles Source Type: research
Roles of microRNA in the immature immune system of neonates
Neonates have an immature immune system; therefore, their immune activities are different from the activities of adult immune systems. Such differences between neonates and adults are reflected by cell population constitutions, immune responses, cytokine production, and the expression of cellular/humoral molecules, which contribute to the specific neonatal microbial susceptibility and atopic properties. MicroRNAs (miRNAs) have been discovered to modulate many aspects of immune responses. Herein, we summarize the distinct manifestations of the neonatal immune system, including cellular and non-cellular components. (Source: Cancer Letters)
Source: Cancer Letters - June 13, 2018 Category: Cancer & Oncology Authors: Hong-Ren Yu, Lien-Hung Huang, Sung-Chou Li Tags: Mini-review Source Type: research
Nrf2-activated Expression of Sulfiredoxin Contributes to Urethane-induced Lung Tumorigenesis
In this study, we found that cigarette smoke condensate and urethane significantly stimulated the expression of sulfiredoxin (Srx) at the transcript and protein levels in cultured normal lung epithelial cells, and such stimulation was mediated through the activation of nuclear related factor 2 (Nrf2). To study the role of Srx in lung cancer development in vivo, mice with Srx wildtype, heterozygous or knockout genotype were subjected to the same protocol of urethane treatment to induce lung tumors. (Source: Cancer Letters)
Source: Cancer Letters - June 12, 2018 Category: Cancer & Oncology Authors: Murli Mishra, Hong Jiang, Hedy A. Chawsheen, Matthieu Gerard, Michel B. Toledano, Qiou Wei Tags: Original Articles Source Type: research
Deferoxamine suppresses esophageal squamous cell carcinoma cell growth via ERK1/2 mediated mitochondrial dysfunction
Deferoxamine (DFO) was found to modulate multiple cellular pathways involved in the growth of breast cancer, hepatocellular carcinoma, lung cancer and bladder cancer. However, the effect of DFO on esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we report that DFO-treated ESCC cells show strong anti-tumorigenic properties, such as inhibition of cell proliferation, induction of cell cycle arrest, and promotion of apoptosis. Mechanistically, DFO significantly activated ERK1/2 signaling, which is reactive oxygen species (ROS)-dependent. (Source: Cancer Letters)
Source: Cancer Letters - June 12, 2018 Category: Cancer & Oncology Authors: Linhua Lan, Wei Wei, Ying Zheng, Lili Niu, Xiaoling Chen, Dawei Huang, Yang Gao, Shouyong Mo, Jin Lu, Miaomiao Guo, Yongzhang Liu, Bin Lu Tags: Original Articles Source Type: research
Editorial Board
(Source: Cancer Letters)
Source: Cancer Letters - June 10, 2018 Category: Cancer & Oncology Source Type: research
HDAC1-induced epigenetic silencing of ASPP2 promotes cell motility, tumour growth and drug resistance in renal cell carcinoma
Renal cell carcinoma (RCC) is highly resistant to chemotherapies. The lack of efficacious treatment for metastatic RCC has led to a poor 5-year survival rate. Here, we found that Apoptosis-stimulating protein of p53-2(ASPP2) was frequently decreased in primary RCC tissues in comparison with non-tumoural kidney controls. Decreased ASPP2 was correlated with high grades and poor outcomes of RCC. Further studies revealed that ASPP2 downregulation promoted EMT and increased resistance to 5-Fluorouracil (5-FU)-induced apoptosis. (Source: Cancer Letters)
Source: Cancer Letters - June 8, 2018 Category: Cancer & Oncology Authors: Huayi Li, Xingwen Wang, Cheng Zhang, Yiwei Cheng, Miao Yu, Kunming Zhao, Wenjie Ge, Anyong Cai, Yao Zhang, Fengtong Han, Ying Hu Tags: Original Articles Source Type: research
The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma
Inducing DNA damage is known to be one of the mechanisms of cytotoxic chemotherapy agents for cancer such as cisplatin. The endogenous DNA damage response confers chemoresistance to these agents by repairing DNA damage. The initiation and transduction of the DNA damage response (DDR) signaling pathway, which is dependent on the activation of ATM (ataxia-telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related), is essential for DNA damage repair, the maintenance of genomic stability and cell survival. (Source: Cancer Letters)
Source: Cancer Letters - June 8, 2018 Category: Cancer & Oncology Authors: Qi Shi, Luyan Shen, Bin Dong, Hao Fu, Xiaozheng Kang, Yongbo Yang, Liang Dai, Wanpu Yan, Hongchao Xiong, Zhen Liang, Keneng Chen Tags: Original Articles Source Type: research
Does metronomic chemotherapy induce tumor angiogenic dormancy? A review of available preclinical and clinical data
Tumor dormancy is the ability of cancer cells to survive in a non-proliferating state. This condition can depend on three main mechanisms: cell cycle arrest (quiescence or cell dormancy), immunosurveillance (immunologic dormancy), or lack of functional blood vessels (angiogenic dormancy). In particular, under angiogenic dormancy, cancer cell proliferation is counterbalanced by apoptosis owing to poor vascularization, impeding tumor mass expansion beyond a microscopic size, with an asymptomatic and non-metastatic state. (Source: Cancer Letters)
Source: Cancer Letters - June 6, 2018 Category: Cancer & Oncology Authors: Gianfranco Natale, Guido Bocci Tags: Mini-review Source Type: research
