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Targeted cancer therapy molecular level

Stefania Ferrari, Leda Severi, Cecilia Pozzi, Antonio Quotadamo, Glauco Ponterini, Lorena Losi, Gaetano Marverti, Maria Paola Costi
Human thymidylate synthase (hTS) has an important role in DNA biosynthesis, thus it is essential for cell survival. TS is involved in the folate pathways, specifically in the de novo pyrimidine biosynthesis. Structure and functions are intimately correlated, account for cellular activity and, in a broader view, with in vivo mechanisms. hTS is a target for anticancer agents, some of which are clinical drugs. The understanding of the detailed mechanism of TS inhibition by currently used drugs and of the interaction with the mechanism of action of other anticancer agents can suggest new perspective of TS inhibition able to improve the anticancer effect and to overcome drug resistance...
2018: Vitamins and Hormones
Paul J Choi, Joe Iwanaga, R Shane Tubbs, Emre Yilmaz
Owing to its rarity, rhabdomyosarcoma of the head and neck (HNRMS) has seldom been discussed in the literature. As most of the data is based only on the retrospective experiences of tertiary healthcare centers, there are difficulties in formulating a standard treatment protocol. Moreover, the disease is poorly understood at its pathological, genetic, and molecular levels. For instance, 20% of all histological assessment is inaccurate; even an experienced pathologist can confuse rhabdomyosarcoma (RMS) with neuroblastoma, Ewing's sarcoma, and lymphoma...
January 9, 2018: Curēus
Laura Rosenberg, Charles H Yoon, Gaurav Sharma, Monica M Bertagnolli, Nancy L Cho
Desmoid tumors (DTs) are unusual neoplasms of mesenchymal origin that exhibit locally invasive behavior. Surgical resection is the initial treatment of choice for DTs. For patients with recurrent or unresectable disease, however, medical options are limited. Sorafenib is a multikinase inhibitor with known anti-tumor activity in various cancers via suppression of the PI3K/Akt/mTOR pathway. Here, we examined the effects of sorafenib on patient-derived DT cell lines, with the aim of characterizing the efficacy and molecular mechanism of action...
March 10, 2018: Carcinogenesis
Decai Ji, Lining Jiang, Yingjie Li
Bladder cancer has been identified as one of the most malignant cancers with high incidence and mortality. The underlying mechanisms by which regulate the tumorigenesis of bladder cancer deserve further investigation. Here, we found that miR-192-5p was downregulated in human bladder cancer cell lines and tissues. Overexpression of miR-192-5p significantly inhibited the growth of bladder cancer cells, while depletion of miR-192-5p exerted opposite effect. Bioinformatics analysis and molecular mechanism study identified that miR-192-5p targeted the transcription factor Yin Yang 1 (YY1) and decreased the expression level of YY1...
March 13, 2018: Human Cell
Ye Liang, Wenhua Xu, Shihai Liu, Jingwei Chi, Jisheng Zhang, Aihua Sui, Liping Wang, Zhijuan Liang, Dan Li, Yuanbin Chen, Haitao Niu
BACKGROUND/AIMS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL. METHODS: In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo...
March 7, 2018: Cellular Physiology and Biochemistry
Jinho Lee, Gary K Geiss, Gokhan Demirkan, Christopher P Vellano, Brian Filanoski, Yiling Lu, Zhenlin Ju, Shuangxing Yu, Huifang Guo, Lisa Y Bogatzki, Warren E Carter, Rhonda K Meredith, Savitri Krishnamurthy, Zhiyong Ding, Joseph M Beechem, Gordon Mills
Molecular analysis of tumors forms the basis for personalized cancer medicine and increasingly guides patient selection for targeted therapy.  Future opportunities for personalized medicine are highlighted by the measurement of protein expression levels via immunohistochemistry, protein arrays, and other approaches; however, sample type, sample quantity, batch effects, and "time to result" are limiting factors for clinical application.  Here, we present a development pipeline for a novel multiplexed DNA-labeled antibody platform which digitally quantifies protein expression from lysate samples...
March 12, 2018: Molecular & Cellular Proteomics: MCP
Priscila E Kobayashi, Carlos E Fonseca-Alves, Luis G Rivera-Calderón, Márcio Carvalho, Hellen Kuasne, Silvia R Rogatto, Renée Laufer-Amorim
Prostate cancer is a heterogeneous disease with high levels of clinical and gene heterogeneity, consequently offering several targets for therapy. Dogs with naturally occurring prostate cancer are useful models for molecular investigations and studying new treatment efficacy. Three genes and proteins associated with the WNT pathway (β-catenin, APC and E-cadherin) and Caveolin-1 (CAV-1) were evaluated in canine pre-neoplastic proliferative inflammatory atrophy (PIA), prostate cancer and metastatic disease. The APC gene methylation status was also investigated...
March 5, 2018: Research in Veterinary Science
Shayna E Thomas-Jardin, Mohammed S Kanchwala, Joan Jacob, Sana Merchant, Rachel K Meade, Nagham M Gahnim, Afshan F Nawas, Chao Xing, Nikki A Delk
BACKGROUND: In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance...
March 11, 2018: Prostate
Tian Zhou, Wenbin Cai, Hengli Yang, Huizhong Zhang, Minghua Hao, Lijun Yuan, Jie Liu, Li Zhang, Yilin Yang, Xi Liu, Jianling Deng, Ping Zhao, Guodong Yang, Yunyou Duan
In vivo assessment of apoptotic response to cancer therapy is believed to be very important for optimizing management of treatment. However, few noninvasive strategies are currently available to monitor the therapeutic response in vivo. Ultrasonography has been used to detect apoptotic cell death in vivo, but a high-frequency transducer is needed. Fortunately, the capability of ultrasound contrast agents (UCAs) to exit the leaky vasculature of tumors enables ultrasound-targeted imaging of molecular events in response to cancer therapy...
March 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xiao-Hong Pu, Qing Ye, Jun Yang, Hong-Yan Wu, Xi-Wei Ding, Jiong Shi, Liang Mao, Xiang-Shan Fan, Jun Chen, Yu-Dong Qiu, Qin Huang
Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer rarely curable by surgery that is increasing rapidly in incidence. Chromosomal translocations and amplifications of the fibroblast growth factor receptor 2 (FGFR2) locus are present in several kinds of tumors including ICC, but their incidence has not been assessed in Chinese patients. Using break-apart probes and by determining the ratios of FGFR2/chromosome enumeration probe (CEP) 10 double-color probes, we evaluated 122 ICCs for the presence of FGFR2 translocations and amplifications, respectively, by fluorescence in situ hybridization (FISH)...
March 4, 2018: Human Pathology
Shijuan Zhan, Chunfeng Wang, Fangqing Yin
Non-small cell lung cancer (NSCLC) is a primary sub-type of lung cancer with a high incidence rate and poor prognosis. The primary therapeutic treatment for NSCLC is chemotherapy, which is considered to be ineffective and excessively toxic. Novel therapeutic methods, particularly molecular targeted therapy, have attracted considerable attention. MicroRNAs (miRs) are reported to be potential biomarkers and targeted agents with roles in various types of tumors. Herein, the present study presented the observation of aberrant low expression of miR‑29c and associated overexpression of vascular endothelial growth factor A (VEGFA) in NSCLC tumor tissues...
March 5, 2018: Molecular Medicine Reports
N-N An, J Shawn, J-P Peng, M-D Wu, L-G Huang
OBJECTIVE: Wilms' tumor (WT) is the most common malignant tumor in the children's urogenital system. MiR-190b was found to participate in the development and progression of several cancers. However, the molecular mechanism of miR-190b in WT is still unclear. PATIENTS AND METHODS: We detected the miR-190b in WT tissue samples compared to adjacent normal samples as well as in WT patients' blood sample compared to normal volunteers using qRT-PCR. With over-expression and knockdown of miR-190b in WT-derived cell line SK-NEP-1, we next studied cell proliferation, cell circle, apoptosis, invasion and migration abilities change caused by miR-190b ectopic expression...
February 2018: European Review for Medical and Pharmacological Sciences
N Garmpis, C Damaskos, A Garmpi, E Spartalis, E Kalampokas, T Kalampokas, G-A Margonis, D Schizas, N Andreatos, A Angelou, A Lavaris, A Athanasiou, K G Apostolou, M Spartalis, Z Damaskou, A Daskalopoulou, E Diamantis, K Tsivelekas, A Alavanos, S Valsami, M M Moschos, A Sampani, A Nonni, E A Antoniou, D Mantas, G Tsourouflis, K Markatos, K Kontzoglou, D Perrea, N Nikiteas, A Kostakis, D Dimitroulis
OBJECTIVE: Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies...
February 2018: European Review for Medical and Pharmacological Sciences
Freddy E Escorcia, Jeffrey M Steckler, Dalya Abdel-Atti, Eric W Price, Sean D Carlin, Wolfgang W Scholz, Jason S Lewis, Jacob L Houghton
PURPOSE: Tumor-specific molecular imaging is an important tool for assessing disease burden and treatment response. CA19.9 is an important tumor-specific marker in several malignancies, including urothelial carcinoma. [89 Zr]DFO-HuMab-5B1 (MVT-2163) is a CA19.9-specific antibody-based construct that has been validated in preclinical animal models of lung, colorectal, and pancreatic malignancies for positron emission tomography (PET) imaging and is currently in a phase I trial for pancreatic cancer (NCT02687230)...
March 5, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Qianping Zhou, Lanshan Huang, Yongyao Gu, Huiping Lu, Zhenbo Feng
BACKGROUND: Molecular target therapy has become a hot spot in cancer treatment, finding effective targets for diffuse large B cell lymphoma (DLBCL) is an urgent problem. OBJECTIVE: To detect the expression level of C-C motif chemokine ligand 18 (CCL18) in DLBCL and clarify its potential role in the progression of DLBCL. METHODS: Gene expression datas of DLBCL were obtained from TCGA and GEO databases. The relationship between CCL18 and clinicopathologic information of DLBCL was assessed using meta-analysis method...
February 9, 2018: Cancer Biomarkers: Section A of Disease Markers
Yilong Wang, Shuyang Sun, Zhiyuan Zhang, Donglu Shi
Medical science has recently advanced to the point where diagnosis and therapeutics can be carried out with high precision, even at the molecular level. A new field of "precision medicine" has consequently emerged with specific clinical implications and challenges that can be well-addressed by newly developed nanomaterials. Here, a nanoscience approach to precision medicine is provided, with a focus on cancer therapy, based on a new concept of "molecularly-defined cancers." "Next-generation sequencing" is introduced to identify the oncogene that is responsible for a class of cancers...
March 5, 2018: Advanced Materials
Eva Sipos, Nikoletta Dobos, David Rozsa, Klara Fodor, Gabor Olah, Zsuzsanna Szabo, Lorant Szekvolgyi, Andrew V Schally, Gabor Halmos
Introduction: Uveal melanoma (UM) is the most common primary intraocular malignancy with very poor prognosis. Conventional chemotherapy only rarely prolongs the survival, therefore patients require novel treatment modalities. The discovery of specific receptors for hypothalamic hormones on cancer cells has led to the development of radiolabeled and cytotoxic hormone analogs. Materials and methods: In the present study, our aim was to investigate the expression of mRNA for receptors of luteinizing hormone-releasing hormone type I (LH-RH-I) and LH-RH ligand in OCM-1 and OCM-3 human uveal melanoma cell lines...
2018: OncoTargets and Therapy
Michael Stahl, Annett Maderer, Florian Lordick, Andre L Mihaljevic, Stefan Kanzler, Thomas Hoehler, Peter Thuss-Patience, Stefan Mönig, Volker Kunzmann, Sebastian Schroll, Andreas Sandermann, Andrea Tannapfel, Hans-Joachim Meyer, Christoph Schuhmacher, Hansjochen Wilke, Markus Moehler
BACKGROUND: Perioperative chemotherapy significantly improves survival in patients with locally advanced oesophagogastric cancer (EGC). However, as approximately 60% of patients will die from their disease, new therapeutic agents such as molecular-targeted drugs are needed. PATIENTS AND METHODS: To evaluate the role of panitumumab with perioperative chemotherapy, previously untreated patients with locally advanced EGC received, in an open-label randomised phase II study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy with or without panitumumab...
March 1, 2018: European Journal of Cancer
Chunhui Ruan, Lisha Liu, Qingbing Wang, Xinli Chen, Qinjun Chen, Yifei Lu, Yu Zhang, Xi He, Yujie Zhang, Qin Guo, Tao Sun, Chen Jiang
An ideal gene-carrying vector is supposed to exhibit outstanding gene condensing capability with positively charged macromolecules to protect the carried gene during in vivo circulation, and a rapid dissociation upon microenvironmental stimuli at the aimed sites to release the escorted gene. Currently, it still remains a challenge to develop an ideal gene carrier with efficient transfection ability and meanwhile low toxicity for clinical applications. Herein, we innovatively introduced a ROS-biodegradable boric acid ester linkage in elaborating the design of gene carrier...
March 2, 2018: ACS Applied Materials & Interfaces
Erin J Howden, André La Gerche, Jane F Arthur, Julie R McMullen, Garry L Jennings, David W Dunstan, Neville Owen, Sharon Avery, Bronwyn A Kingwell
Hematological cancer survivors are highly vulnerable to cardiometabolic complications impacting long-term health status, quality of life and survival. Elevated risk of diabetes and cardiovascular disease arises not only from the effects of the cancers themselves, but also from the toxic effects of cancer therapies, and deconditioning arising from reduced physical activity levels. Regular physical activity can circumvent or reverse adverse effects on the heart, skeletal muscle, vasculature and blood cells, through a combination of systemic and molecular mechanisms...
February 21, 2018: Blood Reviews
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