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Targeted cancer therapy molecular level

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https://www.readbyqxmd.com/read/28429795/cd200-positive-cancer-associated-fibroblasts-augment-the-sensitivity-of-epidermal-growth-factor-receptor-mutation-positive-lung-adenocarcinomas-to-egfr-tyrosine-kinase-inhibitors
#1
Masayuki Ishibashi, Shinya Neri, Hiroko Hashimoto, Tomoyuki Miyashita, Tatsuya Yoshida, Yuka Nakamura, Hibiki Udagawa, Keisuke Kirita, Shingo Matsumoto, Shigeki Umemura, Kiyotaka Yoh, Seiji Niho, Masahiro Tsuboi, Kenkichi Masutomi, Koichi Goto, Atsushi Ochiai, Genichiro Ishii
Cancer associated fibroblasts (CAFs) play important roles in the chemotherapeutic process, especially through influencing the resistance of tumor cells to molecular targeted therapy. Here we report the existence of a special subpopulation of patient-specific-CAFs that augment the sensitivity of EGFR gene mutation-positive lung cancer to the EGFR-tyrosine kinase inhibitor (EGFR-TKI), gefitinib. When cocultured with EGFR mutation positive lung cancer cells, these CAFs increased the apoptic effect of gefitinib on cancer cells, whereas, in the absence of gefitinib, they did not affect cancer cell viability...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429280/synergistic-anti-cancer-effects-of-epigenetic-drugs-on-medulloblastoma-cells
#2
Juan Yuan, Núria Llamas Luceño, Bjoern Sander, Monika M Golas
PURPOSE: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain...
April 20, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28427860/differential-mtor-pathway-profiles-in-bladder-cancer-cell-line-subtypes-to-predict-sensitivity-to-mtor-inhibition
#3
Andrew M Hau, Manando Nakasaki, Kazufumi Nakashima, Goutam Krish, Donna E Hansel
BACKGROUND: Molecular classification of bladder cancer has been increasingly proposed as a potential tool to predict clinical outcomes and responses to chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR) inhibition as a chemotherapeutic strategy and characterized the expression profile of mTOR signaling targets in representative bladder cancer cell lines from basal, luminal, and either basal/luminal ("non-type") molecular subtypes. MATERIALS AND METHODS: Protein and mRNA expression of mTOR signaling components from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype (T24 and J82) bladder cancer cell line subtypes were determined by Western blot and database mining analysis of the Cancer Cell Line Encyclopedia...
April 18, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28427561/molecular-targets-of-ascochlorin-and-its-derivatives-for-cancer-therapy
#4
Jason Chua Min-Wen, Benjamin Chua Yan-Jiang, Srishti Mishra, Xiaoyun Dai, Junji Magae, Ng Shyh-Chang, Alan Prem Kumar, Gautam Sethi
Cancer is an extremely complex disease comprising of a multitude of characteristic hallmarks that continue to evolve with time. At the genomic level, random mutations leading to deregulation of diverse oncogenic signal transduction cascades and polymorphisms coupled with environmental as well as life style-related factors are major causative agent contributing to chemoresistance and the failure of conventional therapies as well as molecular targeted agents. Hence, there is an urgent need to identify novel alternative therapies based on alternative medicines to combat this dreaded disease...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28427511/role-of-hypoxia-inducible-factors-hif-in-the-maintenance-of-stemness-and-malignancy-of-colorectal-cancer
#5
REVIEW
Ramakrishna Vadde, Sarojamma Vemula, Rajeswari Jinka, Neha Merchant, Pallaval Veera Bramhachari, Ganji Purnachandra Nagaraju
Hypoxia is a condition of insufficient tissue oxygenation, which is observed during normal development as well as tumorigenesis and its response at the cellular level is primarily mediated through hypoxia inducible factors (HIFs). HIFs have a significant role in the maintenance of stemness in both stem cells as well as in cancer stem cells (CSC) by acting as transcription factors. The CSCs are proposed to be the driving force of colon tumorigenesis and malignancy. These HIFs play a significant role in a wide range of diseases including colon cancer...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28414550/expression-of-long-noncoding-rna-urothelial-cancer-associated-1-promotes-cisplatin-resistance-in-cervical-cancer
#6
Bi Wang, Zhi Huang, Rui Gao, Zhu Zeng, Weiming Yang, Yuan Sun, Wei Wei, Zhongqing Wu, Lei Yu, Qinshan Li, Shuai Zhang, Fenghu Li, Guoli Liu, Bingjie Liu, Li Leng, Wei Zhan, Yanlong Yu, Guozhen Yang, Shi Zhou
Cisplatin resistance is still one of the main reasons for failure of clinical therapy for cervical cancer. But the underlying molecular mechanisms involved in cisplatin resistance of cervical cancer have still remained unclear. Recent studies reported that long noncoding RNAs (lncRNAs) are novel nonprotein-coding transcripts, which might play a key role in cancer biogenesis and prognosis. One of the lncRNAs, urothelial cancer associated 1 (UCA1), has been shown to promote different types of cancer cell proliferation, migration, and invasion...
April 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28414093/imbalance-in-leptin-adiponectin-levels-and-leptin-receptor-expression-as-chief-contributors-to-triple-negative-breast-cancer-progression-in-northeast-india
#7
Rizwana Sultana, Amal Ch Kataki, Bibhuti Bhusan Borthakur, Tarun K Basumatary, Sujoy Bose
BACKGROUND: Triple-Negative breast cancer (TNBC), accounts for a large percentage of breast cancer cases in India including Northeast India. TNBC has an unclear molecular aetiology and hence limited targeted therapies. Human breast is comprised of glandular, ductal, connective, and adipose tissues. Adipose tissue is composed of adipocytes. The adipocytes apart from being energy storage depots, are also active sources of adipocytokines and/or adipokines. The role of adipokines in breast cancer including TNBC has been sporadically documented...
April 14, 2017: Gene
https://www.readbyqxmd.com/read/28413468/antitumor-effect-of-sunitinib-in-human-prostate-cancer-cells-functions-via-autophagy
#8
Bangqi Wang, Dongyuan Lu, Min Xuan, Weilie Hu
The aim of the present study was to explore sunitinib-induced autophagic effects and the specific molecular mechanisms involved, in vitro, using PC-3 and LNCaP human prostate cancer cell lines. Cells were exposed to escalating doses of sunitinib treatment and subsequent cell viability and cell cycle analyses were performed to evaluate the inhibitory effect of sunitinib in vitro. Immunofluorescence staining of microtubule associated protein 1A/1B-light chain 3 (LC3) puncta was employed to assess autophagy levels after sunitinib treatment...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412359/potentiation-of-docetaxel-sensitivity-by-mir-638-via-regulation-of-stard10-pathway-in-human-breast-cancer-cells
#9
Ge Zhao, Ying Li, Ting Wang
Acquired resistance to classical chemotherapeutics such as docetaxel (DTX) remains a critical challenge in breast cancer (BCa) treatment. Epigenetic modification by microRNAs (miRNAs) has been shown to play a crucial role in cancer drug resistance. Previous study, using human drug-resistant BCa tissues, has identified miR-638 as one of the most down-regulated miRNAs, but its exact roles and underlying mechanisms during the pathogenesis of chemoresistance remain to be determined. In the current study, we found that miR-638 expression was significantly down-regulated in clinical DTX-resistant BCa tissues compared to that in DTX-sensitive BCa tissues...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28411284/mitochondrial-power-drives-tamoxifen-resistance-nqo1-and-gclc-are-new-therapeutic-targets-in-breast-cancer
#10
Marco Fiorillo, Federica Sotgia, Diego Sisci, Anna Rita Cappello, Michael P Lisanti
Here, we identified two new molecular targets, which are functionally sufficient to metabolically confer the tamoxifen-resistance phenotype in human breast cancer cells. Briefly, ~20 proteins were first selected as potential candidates, based on unbiased proteomics analysis, using tamoxifen-resistant cell lines. Then, the cDNAs of the most promising candidates were systematically transduced into MCF-7 cells. Remarkably, NQO1 and GCLC were both functionally sufficient to autonomously confer a tamoxifen-resistant metabolic phenotype, characterized by i) increased mitochondrial biogenesis, ii) increased ATP production and iii) reduced glutathione levels...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411194/systematic-characterization-of-a-to-i-rna-editing-hotspots-in-micrornas-across-human-cancers
#11
Yumeng Wang, Xiaoyan Xu, Shuangxing Yu, Kang Jin Kang, Zhicheng Zhou, Leng Han, Yiu Huen Tsang, Jun Li, Hu Chen, Lingegowda S Mangala, Yuan Yuan, A Karina Eterovic, Yiling Lu, Anil K Sood, Kenneth L Scott, Gordon B Mills, Han Liang
RNA editing, a widespread posttranscriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here we systematically characterized the miRNA editing profiles of 8,595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines...
April 14, 2017: Genome Research
https://www.readbyqxmd.com/read/28411180/co-expression-of-sall4-with-hdac1-and-or-hdac2-is-associated-with-underexpression-of-pten-and-poor-prognosis-in-patients-with-hepatocellular-carcinoma
#12
Huanlin Wang, Kenichi Kohashi, Tomoharu Yoshizumi, Yukihiko Okumura, Yuki Tanaka, Masahiro Shimokawa, Takeshi Iwasaki, Shinichi Aishima, Yoshihiko Maehara, Yoshinao Oda
Spalt-like transcriptional factor 4 (SALL4), a stem marker, is re-activated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex (NuRD), which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study we investigated the expression status of SALL4, HDAC1 and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the post-hepatectomy specimens of 135 patients with hepatocellular carcinoma (HCC) who were treated at our hospital...
April 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28411172/computational-study-on-human-sphingomyelin-synthase-1-hsms1
#13
Stefano Piotto, Lucia Sessa, Pio Iannelli, Simona Concilio
Human sphingomyelin synthase 1 (hSMS1) is the last enzyme for sphingomyelin (SM) biosynthesis. It has been discovered that in different human tumor tissues the SM levels are lower compared to normal tissues and the activation of hSMS1, to restore the normal levels of SM, inhibits cell cycle proliferation of cancer cells. Since the importance of SM and other lipid metabolism genes in the malignant transformation, we decided to explore the hSMS1 mechanism of action. Enzymes capable to regulate the formation of lipids are therefore of paramount importance...
April 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28405842/egfr-targeting-peptide-coupled-platinum-iv-complexes
#14
Josef Mayr, Sonja Hager, Bettina Koblmüller, Matthias H M Klose, Katharina Holste, Britta Fischer, Karla Pelivan, Walter Berger, Petra Heffeter, Christian R Kowol, Bernhard K Keppler
The high mortality rate of lung cancer patients and the frequent occurrence of side effects during cancer therapy demonstrate the need for more selective and targeted drugs. An important and well-established target for lung cancer treatment is the occasionally mutated epidermal growth factor receptor (EGFR). As platinum(II) drugs are still the most important therapeutics against lung cancer, we synthesized in this study the first platinum(IV) complexes coupled to the EGFR-targeting peptide LARLLT (and the shuffled RTALLL as reference)...
April 12, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28405164/a-dual-mediated-liposomal-drug-delivery-system-targeting-the-brain-rational-construction-integrity-evaluation-across-the-blood-brain-barrier-and-the-transporting-mechanism-to-glioma-cells
#15
Chang Liu, Xiao-Na Liu, Gui-Ling Wang, Yu Hei, Shuai Meng, Ling-Fei Yang, Lan Yuan, Ying Xie
As the global population ages, cancer rates increase worldwide, and degenerative diseases of the central nervous system (CNS), brain tumors, and inflammation threaten human health more frequently. We designed a dual-mediated (receptor-mediated and adsorption-mediated) liposome, named transferrin-cell penetrating peptide-sterically stabilized liposome (TF-CPP-SSL), to improve therapy for gliomas through combining molecular recognition of transferrin receptors (TF-Rs) on the blood-brain barrier (BBB) and glioma cells with the internalization and lysosomal escaping ability of CPP...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#16
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
April 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28401970/integrating-multiple-omics-data-for-the-discovery-of-potential-beclin-1-interactions-in-breast-cancer
#17
Yi Chen, Xuan Wang, Guan Wang, Zhaozhi Li, Jinjin Wang, Lingyu Huang, Ziyi Qin, Xiang Yuan, Zhong Cheng, Shu Zhang, Yiqiong Yin, Jun He
Breast cancer has been reported as one of the most frequently diagnosed malignant diseases and the leading cause of cancer death in women all around the world. Furthermore, this complicated cancer is divided into multiple subtypes which present different clinical symptoms and need correspondingly directed therapy. We took BECN1, a core gene in autophagy performing a tumor inhibitory effect, as a starting point. The study in this paper aims to identify genes related to breast cancer and its multiple subtypes by integrating multiple omics data using the least absolute shrinkage and selection operator (LASSO), which is a statistical method that can integrate more than two types of omics data...
April 12, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28393905/metabolomic-characterisation-of-the-effects-of-oncogenic-pik3ca-transformation-in-a-breast-epithelial-cell-line
#18
Chung-Ho E Lau, Gregory D Tredwell, James K Ellis, Eric W-F Lam, Hector C Keun
Somatic mutations in PIK3CA are frequently found in a number of human cancers, including breast cancer, altering cellular physiology and tumour sensitivity to chemotherapy. This renders PIK3CA an attractive molecular target for early detection and personalised therapy. Using (1)H Nuclear Magnetic Resonance spectroscopy (NMR) and Gas Chromatography - Mass Spectrometery (GC-MS) together with (13)C stable isotope-labelled glucose and glutamine as metabolic tracers, we probed the phenotypic changes in metabolism following a single copy knock-in of mutant PIK3CA (H1047R) in the MCF10A cell line, an important cell model for studying oncogenic transformation in breast tissues...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28391045/luteolin-inhibits-colorectal-cancer-cell-epithelial-to-mesenchymal-transition-by-suppressing-creb1-expression-revealed-by-comparative-proteomics-study
#19
Yuan Liu, Tingyuan Lang, Bingwei Jin, Feng Chen, Yi Zhang, Roger W Beuerman, Lei Zhou, Zhiqi Zhang
The cyclic AMP (cAMP) response element binding protein 1 (CREB1) is a promising target for cancer therapy. Here, we report that luteolin, a natural product, inhibits the expression of CREB1 at the transcriptional level and blocks epithelial-to-mesenchymal transition (EMT) of colorectal cancer cells. Treatment of colorectal cancer cells with luteolin induced mesenchymal-to-epithelial transition, reduced the expressions of mesenchymal markers and inhibited cell mobility in vitro. Through comparison of the proteomic profile of HCT-116 cells with and without luteolin treatment, we identified 366 differentially expressed proteins...
April 5, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28388957/hbxip-overexpression-is-correlated-with-the-clinical-features-and-survival-outcome-of-ovarian-cancer
#20
Yixuan Wang, Jie Sun, Nan Li, Shuanlong Che, Tiefeng Jin, Shuangping Liu, Zhenhua Lin
BACKGROUND: Accumulated evidence has demonstrated that Mammalian hepatitis B X-interacting protein (HBXIP) has broad roles in cancer. Although HBXIP is associated with a variety of cancers, the HBXIP protein expression level and its clinical significance in ovarian cancer have not yet been determined. The aim of this study is to investigate the association between HBXIP expression and the clinicopathological features of ovarian cancer patients to determine whether HBXIP may be correlated with a poor prognosis in ovarian cancer patients...
April 7, 2017: Journal of Ovarian Research
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