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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/28315854/mutation-of-n-linked-glycosylation-in-epcam-affected-cell-adhesion-in-breast-cancer-cells
#1
Xue Liu, Jiujiao Gao, Yan Sun, Dandan Zhang, Tingjiao Liu, Qiu Yan, Xuesong Yang
EpCAM expression is elevated in breast cancer tissue, and correlates with the cancer metastasis and cell adhesion. Although EpCAM glycosylation is supposed to be associated with its function, the contribution of N-glycosylation to its function remains unclear. Here we analyzed cell adhesion ability of EpCAM in breast cancer cells. The results showed that EpCAM expression was associated with cell adhesion and N-glycosylation mutation of EpCAM decreased adhesion capacity. N-glycosylation mutation of EpCAM was correlated with lower levels of integrin β1 and fibronectin...
March 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28302921/deciphering-the-acute-cellular-phosphoproteome-response-to-irradiation-with-x-rays-protons-and-carbon-ions
#2
Martin Winter, Ivana Dokic, Julian Schlegel, Uwe Warnken, Jürgen Debus, Amir Abdollahi, Martina Schnölzer
Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive. Here, we present the first comprehensive proteomic and phosphoproteomic study applying stable isotope labeling by amino acids in cell culture (SILAC) in combination with high-resolution mass spectrometry to decipher cellular response to irradiation with X-rays, protons and carbon ions...
March 16, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28302680/genomic-and-epigenomic-heterogeneity-of-hepatocellular-carcinoma
#3
De-Chen Lin, Anand Mayakonda, Huy Q Dinh, Pinbo Huang, Lehang Lin, Xiaoping Liu, Ling-Wen Ding, Jie Wang, Benjamin Berman, Erwei Song, Dong Yin, H Phillip Koeffler
Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28300784/the-molecular-basis-of-toxins-interactions-with-intracellular-signaling-via-discrete-portals
#4
REVIEW
Adi Lahiani, Ephraim Yavin, Philip Lazarovici
An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking...
March 16, 2017: Toxins
https://www.readbyqxmd.com/read/28281569/treating-triple-negative-breast-cancer-cells-with-erlotinib-plus-a-select-antioxidant-overcomes-drug-resistance-by-targeting-cancer-cell-heterogeneity
#5
Bin Bao, Cristina Mitrea, Priyanga Wijesinghe, Luca Marchetti, Emily Girsch, Rebecca L Farr, Julie L Boerner, Ramzi Mohammad, Greg Dyson, Stanley R Terlecky, Aliccia Bollig-Fischer
Among breast cancer patients, those diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or the HER2 oncogene; therefore, TNBC lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against TNBC has been put forth based on estimates that 30-60% of TNBC express high levels of EGFR. However, results from clinical trials testing EGFR inhibitors, alone or in combination with cytotoxic chemotherapy, did not improve patient outcomes...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28281524/mir-216b-increases-cisplatin-sensitivity-in-ovarian-cancer-cells-by-targeting-parp1
#6
Y Liu, Z Niu, X Lin, Y Tian
Cisplatin resistance hinders the efficacy of chemotherapy in ovarian cancer. MicroRNAs (miRs) have been implicated in drug resistance in anti-cancer chemotherapy. We compared the expression profiles of miRs between cisplatin-resistant and cisplatin-sensitive ovarian cancer cells, and found that miR-216b was significantly downregulated in cisplatin-resistant ovarian cancer cells. To investigate its molecular mechanism, we performed cell viability and apoptosis assays in cisplatin-resistant ovarian cells, and found that miR-216b reduced cell viability and promoted apoptosis...
March 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28280819/microchip-based-single-cell-functional-proteomics-for-biomedical-applications
#7
REVIEW
Yao Lu, Liu Yang, Wei Wei, Qihui Shi
Cellular heterogeneity has been widely recognized but only recently have single cell tools become available that allow characterizing heterogeneity at the genomic and proteomic levels. We review the technological advances in microchip-based toolkits for single-cell functional proteomics. Each of these tools has distinct advantages and limitations, and a few have advanced toward being applied to address biological or clinical problems that traditional population-based methods fail to address. High-throughput single-cell proteomic assays generate high-dimensional data sets that contain new information and thus require developing new analytical frameworks to extract new biology...
March 10, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28280620/potential-actionable-targets-in-appendiceal-cancer-detected-by-immunohistochemistry-fluorescent-in-situ-hybridization-and-mutational-analysis
#8
Erkut Borazanci, Sherri Z Millis, Jeffery Kimbrough, Nancy Doll, Daniel Von Hoff, Ramesh K Ramanathan
BACKGROUND: Appendiceal cancers are rare and consist of carcinoid, mucocele, pseudomyxoma peritonei (PMP), goblet cell carcinoma, lymphoma, and adenocarcinoma histologies. Current treatment involves surgical resection or debulking, but no standard exists for adjuvant chemotherapy or treatment for metastatic disease. METHODS: Samples were identified from approximately 60,000 global tumors analyzed at a referral molecular profiling CLIA-certified laboratory. A total of 588 samples with appendix primary tumor sites were identified (male/female ratio of 2:3; mean age =55)...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28275089/the-microtubule-network-and-cell-death-are-regulated-by-a-mir-34a-stathmin-1-betaiii-tubulin-axis
#9
Nancy S Vetter, E Anders Kolb, Valerie B Sampson, Christopher Mills
MicroRNA-34a (miR-34a) is a master regulator of signaling networks that maintain normal physiology and disease and is currently in development as a miRNA-based therapy for cancer. Prior studies have reported low miR-34a expression in osteosarcoma (OS); however, the molecular mechanisms underlying miR-34a activity in OS are not well defined. Therefore, this study evaluated the role of miR-34a in regulating signal transduction pathways that influence cell death in OS. Levels of miR-34a were attenuated in human OS cells and xenografts of the Pediatric Preclinical Testing Consortium (PPTC)...
March 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28274767/copper-sulfide-nanoparticle-based-localized-drug-delivery-system-as-an-effective-cancer-synergistic-treatment-and-theranostic-platform
#10
Lin Hou, Xiaoning Shan, Lisha Hao, Qianhua Feng, Zhenzhong Zhang
Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy...
March 5, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28273930/peptide-au-clusters-induced-tumor-cells-apoptosis-via-targeting-glutathione-peroxidase-1-the-molecular-dynamics-assisted-experimental-studies
#11
Meiqing Liu, Liang Gao, Lina Zhao, Jian He, Qing Yuan, Peng Zhang, Yawei Zhao, Xueyun Gao
The original motivation of the article is to give a systematic investigation on the protocol of combining computer simulation and accurate synthesis of serial peptide protected gold clusters for potent tumor targeting therapy. Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant selenoenzyme that regulates cellular redox level, thus becomes a potential target in cancer treatment. We firstly utilize molecular dynamic (MD) simulation to rationally design and screen serial peptide-Au cluster compounds with special peptide sequences and precise gold atoms, which can recognize and bind specific domain of GPx-1 with high affinity...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28272969/prohibitin-promotes-androgen-receptor-activation-in-er-positive-breast-cancer
#12
Pengying Liu, Yumei Xu, Wenwen Zhang, Yan Li, Lin Tang, Weiwei Chen, Jing Xu, Qian Sun, Xiaoxiang Guan
Prohibitin (PHB) is an evolutionarily conserved protein with multiple functions in both normal and cancer cells. Androgen receptor (AR) was reported to act as a different role in the ER-positive and ER-negative breast cancer. However, little is known about the role of PHB and whether PHB could regulate AR expression in the ER-positive breast cancer. Here, we determined the expression and clinical outcomes of PHB in breast cancer samples using 121 breast cancer tissues and published databases, and investigated the role of PHB in breast cancer cell growth, apoptosis and cell cycle arrest in the ER-positive breast cancer cells...
March 8, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28270142/dynamic-proteomics-reveals-bimodal-protein-dynamics-of-cancer-cells-in-response-to-hsp90-inhibitor
#13
Anat Zimmer, Shlomit Amar-Farkash, Tamar Danon, Uri Alon
BACKGROUND: Drugs often kill some cancer cells while others survive. This stochastic outcome is seen even in clonal cells grown under the same conditions. Understanding the molecular reasons for this stochastic outcome is a current challenge, which requires studying the proteome at the single cell level over time. In a previous study we used dynamic proteomics to study the response of cancer cells to a DNA damaging drug, camptothecin. Several proteins showed bimodal dynamics: they rose in some cells and decreased in others, in a way that correlated with eventual cell fate: death or survival...
March 7, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28268231/mir-1-3p-suppresses-the-proliferation-invasion-and-migration-of-bladder-cancer-cells-by-up-regulating-sfrp1-expression
#14
Anquan Shang, Man Yang, Fujun Shen, Jun Wang, Jun Wei, Weiwei Wang, Wenying Lu, Chunbin Wang, Chunlei Wang
BACKGROUND: Bladder cancer is of compelling morbidity and mortality due to its high recurrence rate. Little development has been made in the last decades in the therapy methods. Thus, the mechanism of its growth and invasiveness involving novel molecular targets are needed. OBJECTIVE: Our research objective is to confirm the hypothesis that miR-1-3p suppresses the proliferation, invasion and migration of bladder cancer cells. METHODS: The expression levels of miR-1-3p and SFRP1 were evaluated using RT-qPCR in bladder cancer tissues and cells as well as in normal tissues and cells...
March 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28268169/role-of-runx2-in-breast-cancer-mediated-bone-metastasis
#15
REVIEW
M Vishal, R Swetha, G Thejaswini, B Arumugam, N Selvamurugan
Breast cancer is one of the most prevalent forms of cancer in women. The currently available treatment for breast cancer is mostly curative except when it becomes metastatic. One of the major sites for metastasis of breast cancer is the bone. Homing of the circulating tumor cells is tightly regulated including a number of factors present in the cells and their microenvironment. Runx2, a transcription factor plays an important role in osteogenesis and breast cancer mediated bone metastases. One of the recent advances in molecular therapy includes the discovery of the small, non-coding microRNAs (miRNAs) and they target specific genes to reduce their expression at the post-transcriptional level...
March 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28264478/crosstalk-of-the-androgen-receptor-with-transcriptional-collaborators-potential-therapeutic-targets-for-castration-resistant-prostate-cancer
#16
REVIEW
Daisuke Obinata, Kenichi Takayama, Satoru Takahashi, Satoshi Inoue
Prostate cancer is the second leading cause of death from cancer among males in Western countries. It is also the most commonly diagnosed male cancer in Japan. The progression of prostate cancer is mainly influenced by androgens and the androgen receptor (AR). Androgen deprivation therapy is an established therapy for advanced prostate cancer; however, prostate cancers frequently develop resistance to low testosterone levels and progress to the fatal stage called castration-resistant prostate cancer (CRPC)...
February 28, 2017: Cancers
https://www.readbyqxmd.com/read/28263969/activated-mek-cooperates-with-cdkn2a-and-pten-loss-to-promote-the-development-and-maintenance-of-melanoma
#17
H Yang, D A Kircher, K H Kim, A H Grossmann, M W VanBrocklin, S L Holmen, J P Robinson
The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical outcome for melanoma patients with BRAF(V600E) mutations. Although the initial response to these inhibitors can be dramatic, sometimes causing complete tumor regression, the majority of melanomas eventually become resistant. Mitogen-activated protein kinase kinase (MEK) mutations are found in primary melanomas and frequently reported in BRAF melanomas that develop resistance to targeted therapy; however, melanoma is a molecularly heterogeneous cancer, and which mutations are drivers and which are passengers remains to be determined...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28260110/inhibitory-effect-of-emodin-on-fatty-acid-synthase-colon-cancer-proliferation-and-apoptosis
#18
Kyung Ha Lee, Myung Sun Lee, Eun Young Cha, Ji Young Sul, Jin Sun Lee, Jin Su Kim, Jun Beom Park, Ji Yeon Kim
Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit‑8 assay. The apoptosis rate of cells was quantified via flow cytometry following Annexin V/propidium iodide staining...
February 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28260023/silencing-bmi1-radiosensitizes-human-breast-cancer-cells-by-inducing-dna-damage-and-autophagy
#19
James Griffith, Daniel Andrade, Meghna Mehta, William Berry, Doris M Benbrook, Natarajan Aravindan, Terence S Herman, Rajagopal Ramesh, Anupama Munshi
Overexpression of BMI1 in human cancer cells, a member of the polycomb group of repressive complexes, correlates with advanced stage of disease, aggressive clinico-pathological behavior, poor prognosis, and resistance to radiation and chemotherapy. Studies have shown that experimental reduction of BMI1 protein level in tumor cells results in inhibition of cell proliferation, induction of apoptosis and/or senescence, and increased susceptibility to cytotoxic agents and radiation therapy. Although a role for BMI1 in cancer progression and its importance as a molecular target for cancer therapy has been established, information on the impact of silencing BMI1 in triple-negative breast cancer (TNBC) and its consequence on radiotherapy have not been well studied...
February 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259911/reduced-klotho-expression-contributes-to-poor-survival-rates-in-human-patients-with-ovarian-cancer-and-overexpression-of-klotho-inhibits-the-progression-of-ovarian-cancer-partly-via-the-inhibition-of-systemic-inflammation-in-nude-mice
#20
Youliang Yan, Yifeng Wang, Yi Xiong, Xiufeng Lin, Ping Zhou, Zhiying Chen
Klotho is a recently discovered anti‑aging gene, which has been reported as a tumor suppressor in numerous human malignancies; however, the role of Klotho in human ovarian cancer remains to be elucidated. The aim of the present study was to detect the expression of Klotho and evaluate its association with the progression of human ovarian cancer. A clinical follow‑up study of 120 patients with ovarian cancer and 78 normal controls was conducted. The expression levels of Klotho were determined by western blotting and immunohistochemistry...
February 7, 2017: Molecular Medicine Reports
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