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Lan Luo, Haibo Zhao, Qian Luo
PURPOSE: Ovarian cancer is one of the major causes of death in females around the world. There are several drug regimens available for this type of cancer, but despite initial response to chemotherapy, the disease consistently relapses, showing that there is a need to find more efficient and novel anticancer agents. Plant-derived natural products may prove beneficial in this case due to their lower cytotoxicity. In the present study we evaluated the anticancer activity of swerchirin against human SKOV3 ovarian cancer cell line...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Mengfan Qi, Ye Tian, Wang Li, Dan Li, Tian Zhao, Yuxin Yang, Qiwen Li, Sujun Chen, Yan Yang, Zhixiong Zhang, Liang Tang, Zhonghua Liu, Bo Su, Fei Li, Yonghong Feng, Ke Fei, Peng Zhang, Fan Zhang, Lei Zhang
Gefitinib, an EGFR tyrosine kinase inhibitor, is used to treat non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, the resistance to gefitinib eventually emerges in most of the patients. To understand its mechanism, we generated two acquired gefitinib-resistant NSCLC cell lines. The resistant cells have slower growth rates, but are more resistant to apoptosis in the presence of gefitinib, compared with their sensitive counterparts. In addition, our genome-wide transcriptome analysis reveals unexpected pathways, particularly autophagy, are dysregulated in the gefitinib-resistant cells...
February 23, 2018: Oncotarget
Chao Zeng, Ming Wen, Xiaomei Liu
Although it is established as a marker of cancer-associated fibroblasts, the expression of fibroblast activation protein (FAP) is not restricted to stromal cells; its expression in multiple types of tumor cell and its pro-tumor functions have been reported. However, the role of FAP in angiogenesis in osteosarcoma remains uncharacterized. In the present study, it was identified that the mRNA and protein expression levels of FAP and vascular endothelial growth factor-A (VEGF-A) corresponded to each other in MG63, U2-OS and HOS osteosarcoma cells...
April 2018: Oncology Letters
Yuanyuan Wang, Jiaojiao Gu, Xiangde Lin, Wei Yan, Wenchao Yang, Guoyang Wu
Thyroid cancer is one of the most common types of cancer in the endocrine system. Among all types of thyroid cancer, papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Long non-coding RNA (lncRNA) BRAF-activated non-protein-coding RNA (BANCR) is a 688-bp-long nucleotide transcript, which was first identified in melanoma. The function of BANCR in thyroid cancer remains unclear. The aim of the present study was to investigate whether BANCR is involved in the development of thyroid cancer...
April 2018: Oncology Letters
Yunjie Zhang, Gangcan Li, Xin Liu, Yanping Song, Jia Xie, Guang Li, Jingjing Ren, Hao Wang, Jiao Mou, Jinqian Dai, Feng Liu, Liang Guo
The present study assessed the mechanism underlying the effect of sorafenib on the proliferation and apoptosis of the acute promyelocytic leukemia (APL) cell line NB4. NB4 cells were treated with different concentrations of sorafenib (0, 1.5, 3, 6, and 12 µM) for 24, 48 and 72 h. Cell proliferation, cell cycle, and apoptosis were analyzed using an MTT assay and flow cytometry analysis, respectively. Reverse transcription-semi-quantitative polymerase chain reaction and western blot analysis were performed to assess the expression of caspase-3, caspase-8, myeloid cell leukemia (MCL)1, cyclin D1, mitogen-activated protein kinase (MEK), phosphorylated (P)-MEK, extracellular signal-regulated kinase (ERK) and P-ERK...
April 2018: Oncology Letters
Hua Chen, Junyi Gao, Zhenhua Du, Xuequn Zhang, Fei Yang, Wei Gao
The pathophysiology of colorectal cancer (CRC) has not been fully elucidated. The dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway frequently contributes to the tumorigenesis and progression of human cancer. The aim of the present study was to explore the expression and clinical significance of a number of associated factors and key components of the PI3K signaling pathway, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (p110α), phosphorylated protein kinase B (p-Akt) Ser473, p-mammalian target of rapamycin (mTOR) Ser2448, cyclin D1, cyclin dependent kinase (CDK)4, RELA proto-oncogene, nuclear factor-κβ subunit (p65), Ras and extracellular signal-regulated kinase (ERK)1/2 in human CRC...
April 2018: Oncology Letters
Ping Zhou, Jian Hu, Xiaoqin Wang, Jingyuan Wang, Yong Zhang, Cong Wang
The present study assessed the function of epidermal growth factor receptor (EGFR) and its molecular targets in non-small cell lung cancer. The results of the present study demonstrated that EGFR protein and mRNA expression in the normal adjacent tissue specimens was decreased compared with that in the lung cancer tissue samples. Compared with the BEAS-2B normal bronchial epithelial cells, EGFR and phosphorylated (p)-extracellular signal-regulated kinase (ERK) protein expression in the SW-900 and A549 lung cancer cells was increased and microRNA (miR)200a expression in the SW-900 and A549 cells was inhibited compared with the BEAS-2B cells...
April 2018: Oncology Letters
Xiangpeng Hu, Hongwei Kan, Alex Boye, Yufeng Jiang, Chao Wu, Yan Yang
The transforming growth factor (TGF)-β/Smad signaling pathway is involved in hepatocellular carcinoma development. Smad2 and Smad3 are phosphorylated following TGF-β1 stimulation and subsequently oligomerize with Smad4 to form the Smad2/3/4 complex, which translocates into the nucleus and regulates target genes, including plasminogen activator inhibitor type 1 (PAI1). Importin (Imp)7 and Imp8 are responsible for transporting phosphorylated (p)Smad2/3 and Smad4 into the nucleus. In our previous study, it was demonstrated that mitogen-activated protein kinase (MAPK) inhibitors, including inhibitors of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 could inhibit the transcription of PAI1, but ERK inhibitor had no significant effect on the phosphorylation of Smad2/3, and the formation of Smad2/3/4 complexes, which was different from the effect of JNK or p38 inhibitor...
April 2018: Oncology Letters
Hai-Tao Huang, Zhi-Gang Sun, Hua-Wei Liu, Jun-Tao Ma, Min Hu
Background: The in-vitro study indicated that ERK/MAPK and PI3K/AKT signal channels may play an important role in reparative regeneration process after peripheral nerve injury. But, relevant in-vivo study was infrequent. In particular, there has been no report on simultaneous activation of ERK/MAPK and PI3K/AKT signal channels in facial nerve cell and axon after facial nerve injury. Results: The expression of P-ERK enhanced in nerve cells at the injury side on the 1 d after the rat facial nerve was cut and kept on a higher level until 14 d, but decreased on 28 d...
December 2017: Saudi Journal of Biological Sciences
Qiang Zuo, Jing Liu, Liping Huang, Yifei Qin, Teresa Hawley, Claire Seo, Glenn Merlino, Yanlin Yu
Multiple genetic mutations within melanoma not only cause lesion-specific responses to targeted therapy but also alter the molecular route of resistance to that therapy. Inactivation of PTEN occurs in up to 30% of melanomas, frequently with a concurrent activating BRAF mutation. PTEN loss regulates both acquired and intrinsic drug resistance. Here we show that AXL/AKT axis mediated-resistance to BRAF inhibitor (BRAFi) depends upon PTEN status in melanoma. Hyperactivation of both ERK and AKT pathways was associated with BRAFi resistance in melanoma with wildtype PTEN...
March 19, 2018: Oncogene
Marco A Alfonzo-Méndez, Gabriel Carmona-Rosas, David A Hernández-Espinosa, M Teresa Romero-Ávila, J Adolfo García-Sáinz
Human α1D -adrenoceptors (α1D -ARs) are a group of the seven transmembrane-spanning proteins that mediate many of the physiological and pathophysiological actions of adrenaline and noradrenaline. Although it is known that α1D -ARs are phosphoproteins, their specific phosphorylation sites and the kinases involved in their phosphorylation remain largely unknown. Using a combination of in silico analysis, mass spectrometry and site directed mutagenesis, we identified distinct α1D -AR phosphorylation patterns during noradrenaline- or phorbol ester-mediated desensitizations...
March 15, 2018: Biochimica et Biophysica Acta
Yuqiu Zheng, Wenli Fang, Shengnuo Fan, Wang Liao, Ying Xiong, Shaowei Liao, Yi Li, Songhua Xiao, Jun Liu
Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively...
February 27, 2018: Journal of Pharmacological Sciences
Scott T Eblen
The extracellular-regulated kinases ERK1 and ERK2 are evolutionarily conserved, ubiquitous serine-threonine kinases that are involved in regulating cellular signaling in both normal and pathological conditions. Their expression is critical for development and their hyperactivation is a major factor in cancer development and progression. Since their discovery as one of the major signaling mediators activated by mitogens and Ras mutation, we have learned much about their regulation, including their activation, binding partners and substrates...
2018: Advances in Cancer Research
Sheng Peng, Hong-Zhu Yan, Pei-Rong Liu, Xiao-Wei Shi, Chun-Liang Liu, Qi Liu, Yu Zhang
BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry...
March 13, 2018: Cellular Physiology and Biochemistry
Jeong-Oh Kim, Jung-Young Shin, Min Young Kim, Kyoung Hwa Son, Chan Kwon Jung, Tae-Jung Kim, Su Young Kim, Jae Kil Park, Sook Whan Sung, Sang Ju Bae, Hyun Jung Min, Jin-Hyoung Kang
BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome...
March 2018: Surgical Oncology
Patricia Fernández-Nogueira, Aleix Noguera-Castells, Gemma Fuster, Leire Recalde-Percaz, Núria Moragas, Anna López-Plana, Estel Enreig, Patricia Jauregui, Neus Carbó, Vanessa Almendro, Pedro Gascón, Paloma Bragado, Mario Mancino
Histamine receptor 1 (HRH1) belongs to the rhodopsin-like G-protein-coupled receptor family. Its activation by histamine triggers cell proliferation, embryonic development, and tumor growth. We recently established that HRH1 is up-regulated in basal and human epidermal growth factor receptor 2 (HER2)-enriched human breast tumors and that its expression correlates with a worse prognosis. Nevertheless, the functional role of HRH1 in basal and HER2-targeted therapy-resistant breast cancer (BC) progression has not yet been addressed...
March 13, 2018: Cancer Letters
Masafumi Yoshinaga, Hiromasa Ninomiya, M M Aeorangajeb Al Hossain, Makoto Sudo, Anwarul Azim Akhand, Nazmul Ahsan, Md Abdul Alim, Md Khalequzzaman, Machiko Iida, Ichiro Yajima, Nobutaka Ohgami, Masashi Kato
Chromium (Cr) pollution caused by wastewater from tanneries is a worldwide environmental problem. To develop a countermeasure, we performed a comprehensive study using Hazaribagh, the tannery area in Dhaka City, Bangladesh, as a model. Our environmental monitoring indicated that the soluble form of Cr, but not barium or arsenic, in Buriganga River is derived from Hazaribagh. Our chemical analysis next showed that Cr, the primary pollutant in canal water at Hazaribagh, consisted of ≤0.7 μM hexavalent Cr [Cr(VI)] and ≤1705 μM trivalent Cr [Cr(III)]...
March 5, 2018: Chemosphere
Hiroshi Chadani, Soichiro Usui, Oto Inoue, Takashi Kusayama, Shin-Ichiro Takashima, Takeshi Kato, Hisayoshi Murai, Hiroshi Furusho, Ayano Nomura, Hirofumi Misu, Toshinari Takamura, Shuichi Kaneko, Masayuki Takamura
Selenoprotein P (SeP), a liver-derived secretory protein, functions as a selenium supply protein in the body. SeP has been reported to be associated with insulin resistance in humans through serial analysis of gene expression. Recently, SeP has been found to inhibit vascular endothelial growth factor-stimulated cell proliferation in human umbilical vein endothelial cells, and impair angiogenesis in a mouse hind limb model. In this study, the role of SeP in ischemia/reperfusion (I/R) injury has been investigated...
March 16, 2018: International Journal of Molecular Sciences
Zhenhua Ji, Yuting Xie, Yu Guan, Yujian Zhang, Kin-Sang Cho, Min Ji, Yongping You
Previous studies have demonstrated that activation of P2X7 receptors (P2X7 R) results in the proliferation and migration of some types of tumor. Here, we asked whether and how the activated P2X7 R contribute to proliferation and migration of human glioma cells. Results showed that the number of P2X7 R positive cells was increasing with grade of tumor. In U87 and U251 human glioma cell lines, both expressed P2X7 R and the expression was enhanced by 3'-O-(4-benzoylbenzoyl) ATP (BzATP), the agonist of P2X7 R, and siRNA...
2018: BioMed Research International
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
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