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Cancer pathways

Changhee Kang, Jong Soo Kim, C-Yoon Kim, Eun-Young Kim, Hyung-Min Chung
Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Extracellular signal-regulated kinase 5 (ERK5) plays a novel role in chemoresistance in some cancer cells and this pathway is a central mediator of cell survival and apoptotic regulation. The aim of this study was to investigate the effect of ERK5 inhibitor, XMD8-92, on proliferation and apoptosis in AML cell lines. Findings showed that XMD8-92 inhibited the activation of ERK5 by G-CSF and decreased the expression of c-Myc and Cyclin D1...
October 31, 2018: International Journal of Stem Cells
Myung Jin Ban, Hyung Kwon Byeon, Yeon Ju Yang, Sojung An, Jae Wook Kim, Ji-Hoon Kim, Da Hee Kim, Jaemoon Yang, Hyunjung Kee, Yoon Woo Koh
Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. The ERK is aberrantly overexpressed and activated in HNSCC. Here, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects combining selumetinib with the fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth...
October 21, 2018: Cancer Science
Mayumi Harada, Masato Morikawa, Takayuki Ozawa, Mai Kobayashi, Yusuke Tamura, Kei Takahashi, Masahiko Tanabe, Keiichiro Tada, Yasuyuki Seto, Kohei Miyazono, Daizo Koinuma
Cyclin-dependent kinase (CDK) 4 and CDK6 inhibitors are effective therapeutic options for hormone receptor (HR)-positive, HER2-negative advanced breast cancer. Although CDK4/6 inhibitors mainly target the cyclin D-CDK4/6-retinoblastoma tumor suppressor protein (RB) axis, little is known about the clinical impact of inhibiting phosphorylation of other CDK4/6 target proteins. Here, we focused on other CDK4/6 targets, SMAD proteins. We showed that a CDK4/6 inhibitor palbociclib and activin-SMAD2 signaling cooperatively inhibited cell cycle progression of a luminal type breast cancer cell line T47D...
October 21, 2018: Cancer Science
Anh Cong, Rafaela M L Pimenta, Hong Bok Lee, Venkatram Mereddy, Jon Holy, Ahmed A Heikal
Most studies using intrinsic NAD(P)H as biomarkers for energy metabolism and mitochondrial anomalies have been conducted in routine two-dimensional (2D) cell culture formats. Cellular metabolism and cell behavior, however, can be significantly different in 2D cultures from that in vivo. As a result, there are emerging interests in integrating noninvasive, quantitative imaging techniques of NAD(P)H with in vivo-like three-dimensional (3D) models. The overall features and metabolic responses of the murine breast cancer cells line 4T1 in 2D cultures were compared with those in 3D collagen matrix using integrated optical micro-spectroscopy...
October 21, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Alfredo I Sagredo, Eduardo A Sagredo, Victor Pola, César Echeverría, Rodrigo Andaur, Luis Michea, Andrés Stutzin, Felipe Simon, Katherine Marcelain, Ricardo Armisén
Transient Receptor Potential Melastatin 4 (TRPM4) is a Ca2+ -activated and voltage-dependent monovalent cation channel, which depolarizes the plasma cell membrane, thereby modulating Ca2+ influx across Ca2+ -permeable pathways. TRPM4 is involved in different physiological processes such as T cell activation and the migration of endothelial and certain immune cells. Overexpression of this channel has been reported in various types of tumors including prostate cancer. In this study, a significant overexpression of TRPM4 was found only in samples from cancer with a Gleason score higher than 7, which are more likely to spread...
October 21, 2018: Journal of Cellular Physiology
Gee Su Yang, Sreelakshmy Kumar, Susan G Dorsey, Angela R Starkweather, Debra Lynch Kelly, Debra E Lyon
PURPOSE: Psychoneurological (PN) symptoms, such as anxiety, cognitive impairment, depression, fatigue, sleep disturbances, and pain, are highly prevalent in breast cancer patients undergoing cancer treatment. Emerging evidence suggests that genetic polymorphisms may contribute to differential symptom susceptibility. We aimed to systematically review associations between genetic polymorphisms and PN symptoms during or after cancer treatment for early-stage breast cancer. METHODS: Twenty-six eligible articles published until October 2017 were identified in PubMed, PsycINFO, Web of Science, and additional records...
October 20, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Christos Christodoulou, Georgios Oikonomopoulos, Georgia Angeliki Koliou, Ioannis Kostopoulos, Vassiliki Kotoula, Mattheos Bobos, George Pentheroudakis, George Lazaridis, Maria Skondra, Sofia Chrisafi, Angelos Koutras, Dimitrios Bafaloukos, Evangelia Razis, Kyriaki Papadopoulou, Pavlos Papakostas, Haralambos P Kalofonos, Dimitrios Pectasides, Pantelis Skarlos, Konstantine T Kalogeras, George Fountzilas
BACKGROUND: Trastuzumab is a monoclonal antibody against HER2-positive breast cancer. Despite improving the natural history of the disease, there is a number of patients who are resistant to it, whereas all patients will eventually develop resistance and disease will progress. Inconsistent preclinical data show that the IGF-R pathway may contribute to either de novo or acquired resistance to trastuzumab. MATERIALS AND METHODS: In total, 227 trastuzumab-treated metastatic breast cancer patients were evaluated for IGF-1, IGF-1R, GLP-1R, Akt1, Akt2 Akt3 mRNA expression, and IGF-1Rα, IGF-1Rβ, IGF-2R protein expression...
November 2018: Cancer Genomics & Proteomics
Xiaonan Wang, Xue Jiao, Yiming Meng, Hao Chen, Noreen Griffin, Xinghua Gao, Fengping Shan
This study was to explore the effect and mechanisms of anti- human gastric cancer by MENK in vitro and in vivo. The results showed in MENK-treated xenograft tissue, the percentage of M2-type macrophages decreased while M1-type macrophages increased. MENK increased the expression of M1-related cytokine TNF-α and attenuated the expression of M2-related cytokine IL-10 expression. MENK upregulated the expression of opioid receptor (OGFr), while it inhibited HGC27 and SGC7901 cells through blocking PI3K/AKT/mTOR signal pathway in vitro and in vivo...
October 18, 2018: International Immunopharmacology
Tongmeng Jiang, Jinmin Zhao, Shan Yu, Zhengwei Mao, Changyou Gao, Ye Zhu, Chuanbin Mao, Li Zheng
How cancer cells and their anchorage-dependent normal counterparts respond to the adhesion ligand density and stiffness of the same extracellular matrix (ECM) is still not very clear. Here we investigated the effects of ECM adhesion ligand density and stiffness on bone tumor cells (osteosarcoma cells) and bone forming cells (osteoblasts) by using poly (ethylene glycol) diacrylate (PEGDA) and methacrylated gelatin (GelMA) hydrogels. By independently changing the PEGDA and GelMA content in the hydrogels, we achieved crosslinked hydrogel matrix with independently tunable stiffness (1...
October 15, 2018: Biomaterials
Nilanjan Mandal, Mitradip Bhattacharjee, Arun Chattopadhyay, Dipankar Bandyopadhyay
Activity of α-amylase enzyme in human serum indicates the onset of pancreatitis, mumps, cancer, stress, and depression. Herein we design and develop a biosensor for the point-of-care-testing (POCT) of α-amylase concentration in serum. The biosensor is composed of a glass substrate coated with an electrically conducting poly-aniline-emeraldine-salt (PANI-ES) film covered with starch-coated gold nanoparticles (SAuNPs). Addition of different dosage of α-amylase on the biosensor selectively depletes starch stabilized on the SAuNPs, which changes the electrical resistance of the sensor...
October 9, 2018: Biosensors & Bioelectronics
Nayanendu Saha, Dorothea Robev, Emilia Mason, Juha P Himanen, Dimitar B Nikolov
The Eph-ephrin signaling pathway mediates developmental processes and the proper functioning of the adult human body. This distinctive bidirectional signaling pathway includes a canonical downstream signal cascade inside the Eph-bearing cells, as well as a reverse signaling in the ephrin-bearing cells. The signaling is terminated by ADAM metalloproteinase cleavage, internalization, and degradation of the Eph/ephrin complexes. Consequently, the Eph-ephrin-ADAM signaling cascade has emerged as a key target with immense therapeutic potential particularly in the context of cancer...
October 18, 2018: International Journal of Biochemistry & Cell Biology
You Fu, Runze Lu, Jian Cui, Hao Sun, Hongbao Yang, Qingtao Meng, Shenshen Wu, Michael Aschner, Xiaobo Li, Rui Chen
Epidemiological studies have associated ambient fine particulate matter (PM2.5 ) exposure with lung cancer, in which epithelial-mesenchymal transition (EMT) is an initial process. Thus, it is important to identify the key molecule or pathway involved in the PM2.5 induced EMT. Human bronchial epithelial (HBE) cells were exposed to PM2.5 (100 or 500 μg/ml) for 30 passages and analyzed by metabolomics to identify the alteration of metabolites related to PM2.5 exposure. The expression levels of EMT markers were evaluated by qRT-PCR and Western blot assays in HBE cells and murine lung tissues...
October 18, 2018: Ecotoxicology and Environmental Safety
Parham Jabbarzadeh Kaboli, Melody Pui-Yee Leong, Patimah Ismail, King-Hwa Ling
BACKGROUND: Berberine is an alkaloid plant-based DNA intercalator that affects gene regulation, particularly expression of oncogenic and tumor suppressor proteins. The effects of berberine on different signaling proteins remains to be elucidated. The present study aimed to identify the effects of berberine against key oncogenic proteins in breast cancer cells. METHODS: Molecular docking and molecular dynamics simulations were used for EGFR, p38, ERK1/2, and AKT...
August 1, 2018: Pharmacological Reports: PR
Jerry Cheng-Yen Lai, Kuan-Ju Lai, Edward Yi-Yung Yu, Sho-Ting Hung, Chia-Ying Chu, Kung-Liahng Wang
The presence of pelvic lymph node metastases is without doubt the most significant prognostic factor that determines recurrences and survival of women with early-stage cervical cancer. To avoid the underdiagnosis of lymph node metastasis, pelvic lymphadenectomy procedure is routinely performed with radical hysterectomy procedure. However, the pelvic lymphadenectomy procedure may not be necessary in most of these women due to the relatively low incidence of pelvic lymph node metastasis. The removal of large numbers of pelvic lymph nodes could also render non-metastatic irreversible damages for these women, including vessel, nerve, or ureteral injuries; formation of lymphocysts; and lymphedema...
October 2018: Taiwanese Journal of Obstetrics & Gynecology
Zhongjie Chen, Zhiqiang Wu, Wen Ning
Radiation-induced pulmonary fibrosis (RIPF) is a common complication in patients with lung cancer and breast cancer after receiving thoracic radiotherapy. The average incidence of RIPF is 16%-28% after radiotherapy. RIPF includes a heterogeneous group of lung disorders characterized by progressive and irreversible destruction of lung architecture and disruption of gas exchange. The clinical signs of RIPF include increasing dyspnea, deteriorating lung function, and accumulation of interstitial fluid, eventually leading to respiratory failure...
October 17, 2018: Translational Oncology
Fang-Jun Cao, Ming-Xuan Xu, Bo-Hang Zhou, Yi-Si Du, Jun-Hu Yao, Le Zhou
Our previous study found that 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines (CATHIQs) have excellent anti-cancer activity and obvious apoptosis induction phenomenon. As our continuing research, this study further explored their underlying molecular mechanism of apoptosis induction in cancer cells. Flow cytometry analysis showed that the NB4 cells treated by 1-cyano-2-(2-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline or the MKN-45 cells treated by 1-cyano-2-(2-trifluoromethylphenyl)-1,2,3,4-tetrahydroisoquinoline for 48 h were at early stage of apoptosis, and the cell cycle arrest was only slightly affected...
October 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Wentong Li, Hongli Yu, Dejun Ding, Zhitong Chen, Yonghong Wang, Saisai Wang, Xujing Li, Michael Keidar, Weifen Zhang
Cold atmospheric plasma (CAP) is an emerging biomedical technique that shows great potential for cancer treatment. On the other hand, magnetic nanoparticles open up a wide field of possible applications in medicine. Here we seek to develop a novel dual cancer therapeutic method by integrating promising CAP and iron oxide-based magnetic nanoparticles (MNPs), and evaluate its underlying mechanism for targeted lung cancer treatment. For this purpose, the synergistic effects of CAP and iron oxide-based MNPs on cellular bioactivity, epidermal growth factor receptor (EGFR) expression, and EGFR downstream signaling pathways were investigated...
October 17, 2018: Free Radical Biology & Medicine
Yuko Omori, Yusuke Ono, Mishie Tanino, Hidenori Karasaki, Hiroshi Yamaguchi, Toru Furukawa, Katsuro Enomoto, Jun Ueda, Atsuko Sumi, Jin Katayama, Miho Muraki, Kenzui Taniue, Kuniyuki Takahashi, Yoshiyasu Ambo, Toshiya Shinohara, Hiroshi Nishihara, Junpei Sasajima, Hiroyuki Maguchi, Yusuke Mizukami, Toshikatsu Okumura, Shinya Tanaka
BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are regarded as precursors of pancreatic ductal adenocarcinomas (PDAs), but little is known about mechanism of progression. This makes it a challenge to assess cancer risk in patients with IPMNs. We investigated associations of IPMNs with concurrent PDAs by genetic and histologic analyses. METHODS: We obtained 30 pancreatic tissues with concurrent PDAs and IPMNs; 168 lesions, including incipient foci, were mapped, microdissected, and analyzed for mutations in 18 pancreatic cancer-associated genes and expression of tumor suppressors...
October 17, 2018: Gastroenterology
Jingxuan Yang, Zicheng Zhang, Yuqing Zhang, Xiaoling Ni, Guohua Zhang, Xiaobo Cui, Mingyang Liu, Can Xu, Qiang Zhang, Huiyun Zhu, Jie Yan, Vivian F Zhu, Yusheng Luo, John P Hagan, Zhaoshen Li, Jing Fang, Aminah Jatoi, Martin E Fernandez-Zapico, Lei Zheng, Barish H Edil, Michael S Bronze, Courtney W Houchen, Yi-Ping Li, Min Li
BACKGROUND & AIMS: Cachexia, which includes muscle wasting, is a frequent complication of pancreatic cancer. There are no therapies that reduce cachexia and increase patient survival, so it is important to learn more about its mechanisms. The zinc transporter ZIP4 promotes growth and metastasis of pancreatic tumors. We investigated its effects on muscle catabolism via extracellular vesicle (EV)-mediated stimulation of mitogen-activated protein kinase 14 (p38MAPK). METHODS: We studied nude mice with orthotopic tumors grown from human pancreatic cancer cell lines (AsPC-1 and BxPC-3); tumors were removed 8 days after cell injection and analyzed by histology...
October 17, 2018: Gastroenterology
Ying-Ju Lai, Wan-Nien Yu, Sheng-Chu Kuo, Chi-Tang Ho, Chao-Ming Hung, Tzong-Der Way, Chiung-Tong Chen
Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer deaths worldwide, especially in male. With poor prognosis, significant portions of patients with HNSCC die due to cancer recurrence and tumor metastasis after chemotherapy and targeted therapies. The HNSCC FaDu cell ectopic expression of Twist, a key transcriptional factor of epithelial-mesenchymal transition (EMT), which triggers EMT and results in the acquisition of a mesenchymal phenotype, was used as the cell model. Our results demonstrated that treatment with newly synthesized 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), a flavonoid derivative, elicited changes in its cell morphology, upregulated E-cadherin messenger RNA and protein expression, downregulated N-cadherin, vimentin, and CD133 (a marker associated with tumor-initiating cells) in FaDu-pCDH-Twist cells...
October 20, 2018: Journal of Cellular Physiology
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