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Cancer system biology

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https://www.readbyqxmd.com/read/29792692/small-molecule-targeted-recruitment-of-a-nuclease-to-rna
#1
Matthew G Costales, Yasumasa Matsumoto, Sai Pradeep Velagapudi, Matthew D Disney
The choreography between RNA synthesis and degradation is a key determinant in biology. Engineered systems such as CRISPR have been developed to rid a cell of RNAs. Here, we show that a small molecule can recruit a nuclease to a specific transcript, triggering its destruction. A small molecule that selectively binds the oncogenic microRNA(miR)-96 hairpin precursor was appended with a short 2'-5' poly(A) oligonucleotide. The conjugate locally activated endogenous, latent ribonuclease (RNase L), which selectively cleaved the miR-96 precursor in cancer cells in a catalytic and sub-stoichiometric fashion...
May 24, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29789637/the-proton-pump-inhibitor-pantoprazole-disrupts-protein-degradation-systems-and-sensitizes-cancer-cells-to-death-under-various-stresses
#2
Yu Cao, Min Chen, Dehua Tang, Hongli Yan, Xiwei Ding, Fan Zhou, Mingming Zhang, Guifang Xu, Weijie Zhang, Shu Zhang, Yuzheng Zhuge, Lei Wang, Xiaoping Zou
Proton pump inhibitors (PPIs) play a role in antitumor activity, with studies showing specialized impacts of PPIs on cancer cell apoptosis, metastasis, and autophagy. In this study, we demonstrated that pantoprazole (PPI) increased autophagosomes formation and affected autophagic flux depending on the pH conditions. PPI specifically elevated SQSTM1 protein levels by increasing SQSTM1 transcription via NFE2L2 activation independent of the specific effect of PPI on autophagic flux. Via decreasing proteasome subunits expression, PPI significantly impaired the function of the proteasome, accompanied by the accumulation of undegraded poly-ubiquitinated proteins...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29786742/a-novel-alendronate-functionalized-nanoprobe-for-simple-colorimetric-detection-of-cancer-associated-hypercalcemia
#3
Abhishek Sahu, Youngmin Hwang, Cristian Vilos, Jong-Min Lim, Sunghyun Kim, Won Il Choi, Giyoong Tae
The calcium (Ca2+) ion concentration in the blood serum is tightly regulated, and any abnormalities in the level of serum calcium ions are associated with many potentially dangerous diseases. Thus, monitoring of the Ca2+ ion concentration in the blood serum is of fundamental importance. Gold nanoparticle (GNP)-based colorimetric biosensors have enormous potential in clinical diagnostic applications due to their simplicity, versatility, and unique optical properties. In this study, we have developed an alendronate functionalized gold nanoparticle (GNP-ALD) system for the measurement of Ca2+ ion concentration in biological samples...
May 22, 2018: Nanoscale
https://www.readbyqxmd.com/read/29785006/the-era-of-immunogenomics-immunopharmacogenomics
#4
REVIEW
Makda Zewde, Kazuma Kiyotani, Jae-Hyun Park, Hua Fang, Kai Lee Yap, Poh Yin Yew, Houda Alachkar, Taigo Kato, Tu H Mai, Yuji Ikeda, Tatsuo Matsuda, Xiao Liu, Lili Ren, Boya Deng, Makiko Harada, Yusuke Nakamura
Although germline alterations and somatic mutations in disease cells have been extensively analyzed, molecular changes in immune cells associated with disease conditions have not been characterized in depth. It is clear that our immune system has a critical role in various biological and pathological conditions, such as infectious diseases, autoimmune diseases, drug-induced skin and liver toxicity, food allergy, and rejection of transplanted organs. The recent development of cancer immunotherapies, particularly drugs modulating the immune checkpoint molecules, has clearly demonstrated the importance of host immune cells in cancer treatments...
May 21, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29784056/biomarker-micrornas-for-prostate-cancer-metastasis-screened-with-a-network-vulnerability-analysis-model
#5
Yuxin Lin, Feifei Chen, Li Shen, Xiaoyu Tang, Cui Du, Zhandong Sun, Huijie Ding, Jiajia Chen, Bairong Shen
BACKGROUND: Prostate cancer (PCa) is a fatal malignant tumor among males in the world and the metastasis is a leading cause for PCa death. Biomarkers are therefore urgently needed to detect PCa metastatic signature at the early time. MicroRNAs are small non-coding RNAs with the potential to be biomarkers for disease prediction. In addition, computer-aided biomarker discovery is now becoming an attractive paradigm for precision diagnosis and prognosis of complex diseases. METHODS: In this study, we identified key microRNAs as biomarkers for predicting PCa metastasis based on network vulnerability analysis...
May 21, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29783070/cdh17-alters-mmp-2-expression-via-canonical-nf-%C3%AE%C2%BAb-signalling-in-human-gastric-cancer
#6
Xiao-Jie Jiang, Jing Lin, Qing-He Cai, Jian-Feng Zhao, Hui-Jiao Zhang
Gastric cancer (GC), one of the most common cancers of the digestive system, results in high morbidity and mortality, but the molecular mechanisms underlying GC remain largely unknown. Cadherin-17 (CDH17) is a nonclassical member of the cadherin (CDH) superfamily of calcium-dependent proteins. Despite recent advances in the understanding of CDH17 biology, the mechanism of CDH17 in GC proliferation, migration, and invasion has not been extensively studied. In the present study, we observed that CDH17 expression was increased in GC tissues compared with para-carcinoma tissues and was correlated with lymph node metastasis and the AJCC stage...
May 18, 2018: Gene
https://www.readbyqxmd.com/read/29782706/biological-stimulus-driven-assembly-disassembly-of-functional-nanoparticles-for-targeted-delivery-controlled-activation-and-bioelimination
#7
REVIEW
Xi Hu, Fangyuan Li, Shuying Wang, Fan Xia, Daishun Ling
Nanoassembly technology has emerged as a powerful tool for targeted drug delivery and provides a basis for fabricating medical theranostic nanosystems. However, it is extremely difficult to concentrate nanoparticles at tumor sites, and the poor target-to-background ratio undoubtedly obstructs the accurate diagnosis and effective therapy of cancerous tissues. Importantly, the addition of biological stimulus-responsive groups to nanoassembly systems can enable a biological stimulus-driven assembly-disassembly mutual switch or structural composition/conformation change, thereby amplifying the imaging signal and/or enhancing the therapeutic effect...
May 21, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29782246/precision-medicine-and-radiogenomics-in-breast-cancer-new-approaches-toward-diagnosis-and-treatment
#8
Katja Pinker, Joanne Chin, Amy N Melsaether, Elizabeth A Morris, Linda Moy
Precision medicine is medicine optimized to the genotypic and phenotypic characteristics of an individual and, when present, his or her disease. It has a host of targets, including genes and their transcripts, proteins, and metabolites. Studying precision medicine involves a systems biology approach that integrates mathematical modeling and biology genomics, transcriptomics, proteomics, and metabolomics. Moreover, precision medicine must consider not only the relatively static genetic codes of individuals, but also the dynamic and heterogeneous genetic codes of cancers...
June 2018: Radiology
https://www.readbyqxmd.com/read/29782142/projection-based-3d-printing-of-cell-patterning-scaffolds-with-multi-scale-channels
#9
Dai Xue, Yancheng Wang, Jiaxin Zhang, Deqing Mei, Yue Wang, Shaochen Chen
To fully actualize artificial, cell-laden biological models in tissue engineering, such as 3D organoids and organs-on-a-chip systems, cells need to be patterned such that they can precisely mimic natural microenvironments in vitro. Despite increasing interest in this area, patterning cells at multiscales (~10 μm - 10 mm) remains a significant challenge in bioengineering. Here we report a projection-based 3D printing system that achieves rapid and high-resolution fabrication of hydrogel scaffolds featuring intricate channels for multi-scale cell patterning...
May 21, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29781276/light-induced-hypoxia-triggered-living-nanocarriers-for-synergistic-cancer-therapy
#10
Wenliang Wang, Lin Lin, Xiaojing Ma, Bo Wang, Sanrong Liu, Xinxin Yan, Shengran Li, Huayu Tian, Xifei Yu
Living drug delivery system has been proposed as new concept materials since it is able to communicate with biological system, sense subtle changes of body microenvironment caused by disease and then make rapid response to cure in early stage of disease. Herein, taking full advantage of the tumor hypoxia physiology and successive effects of photodynamic therapy (PDT), we designed a new living delivery system via combining the PDT and hypoxia-responsive chemotherapy, abbreviated as Ce6-PEG-Azo-PCL. Then, according to the facts that oxygen can be converted into reactive oxygen species during irradiation of the photosensitizer, tumor cells could be killed after the poly(ethylene glycol) (PEG) conjugated photosensitizer chlorine e6 were irradiated at tumor site...
May 21, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29781033/microarray-analysis-of-circular-rna-expression-profiles-associated-with-gemcitabine-resistance-in-pancreatic-cancer-cells
#11
Chao Xu, Yue Yu, Fei Ding
Pancreatic cancer (PC) is one of the most malignant tumors of the digestive system due to its rapid progression, metastasis and resistance to chemotherapy. Gemcitabine (GEM) chemotherapy is the first‑choice treatment for advanced PC. However, the effect of GEM‑based chemotherapy on PC is limited due to the development of chemoresistance, and the molecular mechanisms underlying this resistance have yet to be investigated. Circular RNAs (circRNAs), which can function as microRNA sponges, have been found to be involved in the development of several types of cancer...
May 17, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29779447/development-of-postmeiotic-cells-in-vitro-from-spermatogonial-cells-of-prepubertal-cancer-patients
#12
Maram Abofoul-Azab, Ali AbuMadigem, Eitan Lunenfeld, Joseph Kapelushnik, Qinghua Shi, Haim Pinkas, Mahmoud Huleihel
Aggressive chemotherapy in childhood often results in testicular damage and consequently jeopardizes future fertility. The presence of spermatogonial cells (SPGCs) in the testes of prepubertal cancer patient boys (PCPBs) can be used to develop future strategies for male fertility preservation. In the present study, we examined the presence of SPGCs in testes of chemotherapy-treated PCPBs and their ability to develop spermatogenesis in vitro using a three-dimensional (3D) culture system. Seven testicular biopsies were obtained from chemotherapy-treated PCPBs and one from a patient with β-thalassemia major...
May 19, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29779307/-application-of-perihilar-surgical-techniques-in-perihilar-biliary-tract-tumours
#13
J Wang
Perihilar biliary tract tumours include hilar cholangiocarcinoma, gallbladder cancer invading the hepatic hilum and intrahepatic cholangiocarcioma invading the hepatic hilum.The tumours have the special characteristics such as strong invasion capability, the anatomic variant, the pathophysiological complexity, the biological behavior diversity and the difficulty of preoperative evaluation which result in low R0 resection rate, more postoperative complications, more mortality and poor prognosis.The perihilar surgical techniques system aims to set a reasonable and individual operation procedure on the principle of precision surgery by taking the key technique of hilar dissection and exposing, evaluting the hilar anatomy by the means of three-dimensional digital medical image evaluation system, evaluting the relationship between the tumour and hepatic artery and portal vein under the condition of hepatic hilum complete exposure by combining anterograde and retrograde route from intra and extra-hepatic direction to hepatic hilum...
May 1, 2018: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29777862/revealing-a-raf-functions-through-its-interactome
#14
Xin-Yu Zhang, Hui Guo, Bing Han, Xu-Min Zhang, Ying Huang, Yang Yang, Ying Liu, Xiao-Xi Guo, Qian Hao, Su An, Tian-RuiXu
A-Raf is a member of the Raf kinase family. Unlike B-Raf and C-Raf, the functions of A-Raf remain obscure. To gain more insight into the biological functions of A-Raf, we investigated the A-Raf interactome using proteomics. We found 132 proteins that interact with A-Raf and confirmed the interaction of 12 of these proteins with A-Raf by western blotting. Our data suggested that A-Raf regulates apoptosis, RNA catabolism, GTPase activity, and cell adhesion by interacting with proteins located in different cellular compartments...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777721/pentraxins-crp-i-and-crp-ii-are-post-translationally-deiminated-and-differ-in-tissue-specificity-in-cod-gadus-morhua-l-ontogeny
#15
Bergljót Magnadóttir, Polly Hayes, Berglind Gísladóttir, Birkir Þór Bragason, Mariya Hristova, Anthony P Nicholas, Sigríður Guðmundsdóttir, Sigrun Lange
Pentraxins are fluid phase pattern recognition molecules that form an important part of the innate immune defence and are conserved between fish and human. In Atlantic cod (Gadus morhua L.), two pentraxin-like proteins have been described, CRP-I and CRP-II. Here we show for the first time that these two CRP forms are post-translationally deiminated (an irreversible conversion of arginine to citrulline) and differ with respect to tissue specific localisation in cod ontogeny from 3 to 84 days post hatching. While both forms are expressed in liver, albeit at temporally differing levels, CRP-I shows a strong association with nervous tissue while CRP-II is strongly associated to mucosal tissues of gut and skin...
May 16, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29776629/clinical-implication-of-micrornas-in-molecular-pathology-an-update-for-2018
#16
REVIEW
Seema Sethi, Sajiv Sethi, Martin H Bluth
MicroRNAs (miRNAs) are poised to provide diagnostic, prognostic, and therapeutic targets for several diseases including malignancies for precision medicine applications. The miRNAs have immense potential in the clinical arena because they can be detected in the blood, serum, tissues (fresh and formalin-fixed paraffin-embedded), and fine-needle aspirate specimens. The most attractive feature of miRNA-based therapy is that a single miRNA could be useful for targeting multiple genes that are deregulated in cancers, which can be further investigated through systems biology and network analysis that may provide cancer-specific personalized therapy...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29776351/a-computational-study-of-hedgehog-signalling-involved-in-basal-cell-carcinoma-reveals-the-potential-and-limitation-of-combination-therapy
#17
Antoine Buetti-Dinh, Rebecca Jensen, Ran Friedman
BACKGROUND: The smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations. METHODS: We investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29776156/realizations-of-highly-heterogeneous-collagen-networks-via-stochastic-reconstruction-for-micromechanical-analysis-of-tumor-cell-invasion
#18
Hanqing Nan, Long Liang, Guo Chen, Liyu Liu, Ruchuan Liu, Yang Jiao
Three-dimensional (3D) collective cell migration in a collagen-based extracellular matrix (ECM) is among one of the most significant topics in developmental biology, cancer progression, tissue regeneration, and immune response. Recent studies have suggested that collagen-fiber mediated force transmission in cellularized ECM plays an important role in stress homeostasis and regulation of collective cellular behaviors. Motivated by the recent in vitro observation that oriented collagen can significantly enhance the penetration of migrating breast cancer cells into dense Matrigel which mimics the intravasation process in vivo [Han et al...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775845/toward-innovative-combinational-immunotherapy-a-systems-biology-perspective
#19
REVIEW
Xue-Tao Li, Jin-Ji Yang, Yi-Long Wu, Jun Hou
The treatment of non-small-cell lung cancer (NSCLC) has advanced significantly in the last decades. Especially immune checkpoint inhibitors have shown inconceivable effect on enhancing host anti-tumor activity in NSCLC. However, the limitation of checkpoint blockade monotherapy seems unavoidable in most of the NSCLC patients and only ∼20% of them achieved response to monotherapy with immune checkpoint inhibitors. Thus combining immune checkpoint inhibitors with other agents with different action mechanisms holds a promise to revitalize NSCLC treatment, such as the combination of checkpoint inhibitors with angiogenesis inhibitors, or with chemotherapy, as well as the combination of two checkpoint inhibitors...
May 8, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29775783/ocimum-basilicum-mirnome-revisited-a-cross-kingdom-approach
#20
Maulikkumar Patel, Shanaya Patel, Naman Mangukia, Saumya Patel, Archana Mankad, Himanshu Pandya, Rakesh Rawal
O. basilicum is medicinally important herb having inevitable role in human health. However, the mechanism of action is largely unknown. Present study aims to understand the mechanism of regulation of key human target genes that could plausibly modulated by O. basilicum miRNAs in cross kingdom manner using computational and system biology approach. O. basilicum miRNA sequences were retrieved and their corresponding human target genes were identified using psRNA target and interaction analysis of hub nodes. Six O...
May 15, 2018: Genomics
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