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https://www.readbyqxmd.com/read/28732326/therapeutic-applications-of-histone-deacetylase-inhibitors-in-sarcoma
#1
REVIEW
Fan Tang, Edwin Choy, Chongqi Tu, Francis Hornicek, Zhenfeng Duan
Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis...
July 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28732112/identifying-mechanisms-for-cancer-cell-chemoresistance
#2
(no author information available yet)
No abstract text is available yet for this article.
September 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28731185/snail-maintains-metastatic-potential-cancer-stem-like-properties-and-chemoresistance-in-mesenchymal-mouse-breast-cancer-tubo%C3%A2-p2j-cells
#3
Sun Young Ma, Jin-Hee Park, Hana Jung, Sung-Min Ha, Yeonye Kim, Dong Hyen Park, Deuk Hee Lee, Sooyong Lee, In-Ho Chu, So Young Jung, Il-Hwan Kim, Il-Whan Choi, Chang Soo Choi, Saegwang Park
Snail, a zinc-finger transcriptional repressor of E-cadherin expression, is one of the key inducers of epithelial-mesenchymal transition (EMT) in epithelial cancer. In breast cancer, EMT has been associated with malignancies, including metastasis, cancer stem-like properties, and resistance to chemotherapy and radiotherapy. In this study, we analysed the role of Snail in the highly metastatic mesenchymal TUBO‑P2J mouse breast cancer cells, by loss of function using short hairpin RNA. Though silencing Snail did not restore the E-cadherin expression or induce morphological changes, Snail silencing significantly ablated in vitro and in vivo metastatic potentials...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731151/meg3-is-a-prognostic-factor-for-crc-and-promotes-chemosensitivity-by-enhancing-oxaliplatin-induced-cell-apoptosis
#4
Lixia Li, Jian Shang, Yupeng Zhang, Shi Liu, Yanan Peng, Zhou Zhou, Huaqing Pan, Xiaobing Wang, Lipng Chen, Qiu Zhao
A major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to oxaliplatin-based chemotherapy. Recently, studies have shown that long non-coding RNAs (lncRNAs) play an important role in drug resistance. Using HiSeq sequencing methods, we identified that lncRNAs show differential expression levels in oxaliplatin-resistant (OxR) and non-resistant CRC patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MEG3 was verified to be downregulated in non-responding patients and to have considerable discriminating potential to identify responding patients from non-responding patients...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731137/phosphorylation-of-bcl-2-plays-an-important-role-in-glycochenodeoxycholate-induced-survival-and-chemoresistance-in-hcc
#5
Maojun Zhou, Qi Zhang, Jinfeng Zhao, Mingmei Liao, Sailan Wen, Manyi Yang
Hepatocellular carcinoma (HCC) is a highly malignant tumor and can evolve rapidly to resistance to chemotherapies. Glycochenodeoxycholate (GCDA), which is toxic and hydrophobic, is the main ingredient in the bile and associated with carcinogenesis of gastrointenstinal tumors. Bcl-2 is the most important anti-apoptotic protein and overexpressed in various human tumors. In the present study, we found that GCDA can induce the chemoresistance of human liver cancer cells and specific depletion of Bcl-2 by RNA interference blocks GCDA-stimulated chemoresistance, which indicate the pivotal role of Bcl-2 in such process...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28729028/micrornas-as-key-effectors-in-the-p53-network
#6
Frauke Goeman, Sabrina Strano, Giovanni Blandino
The guardian of the genome p53 is embedded in a fine-spun network of MicroRNAs. p53 is able to activate or repress directly the transcription of MicroRNAs that are participating in the tumor-suppressive mission of p53. On the other hand, the expression of p53 is under tight control of MicroRNAs that are either targeting directly p53 or factors that are modifying its protein level or activity. Although the most important function of p53 is suggested to be transcriptional regulation, there are several nontranscriptional functions described...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28729023/micrornas-in-dna-damage-response-carcinogenesis-and-chemoresistance
#7
Yuanzhang Fang, Lu Zhang, Zhenghu Li, Yujing Li, Cheng Huang, Xiongbin Lu
In the classical model of tumorigenesis, cancer develops via slowly accumulating mutations that facilitate uncontrolled cell growth and allow cells to escape apoptosis. Oncogenes and tumor suppressor genes regulate the key signaling pathways involved in tumorigenesis and cancer progression. Moreover, studies indicate that MicroRNAs (MiRNAs) are also key parts of these processes. MiRNAs are short, noncoding RNAs that regulate the expression of target genes at the posttranscriptional level. By regulating the expression of numerous cytokines, MiRNAs play crucial roles in cell growth, apoptosis, and stemness maintenance...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28726781/autophagy-inhibition-reduces-chemoresistance-and-tumorigenic-potential-of-human-ovarian-cancer-stem-cells
#8
Anna Pagotto, Giorgia Pilotto, Elena Laura Mazzoldi, Maria Ornella Nicoletto, Simona Frezzini, Anna Pastò, Alberto Amadori
Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as in vitro culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28724889/aptamer-mediated-survivin-rnai-enables-5-fluorouracil-to-eliminate-colorectal-cancer-stem-cells
#9
Hadi AlShamaileh, Tao Wang, Dongxi Xiang, Wang Yin, Phuong Ha-Lien Tran, Roberto A Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Sarah Shigdar, Wei Duan
The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723662/acetyl-lupeolic-acid-inhibits-akt-signaling-and-induces-apoptosis-in-chemoresistant-prostate-cancer-cells-in-vitro-and-in-vivo
#10
Claudia Schmidt, Cornelia Loos, Lu Jin, Michael Schmiech, Christoph Q Schmidt, Menna El Gaafary, Tatiana Syrovets, Thomas Simmet
The triterpenoid acetyl-lupeolic acid (ac-LA) isolated from the oleogum resin of Boswellia carterii reduced the viability of a panel of cancer cell lines more efficiently than lupeol. There was no detectable intracellular conversion of ac-LA to lupeol and vice versa. In contrast to docetaxel, ac-LA did not induce selection of treatment-resistant cancer cells. By various parameters including DNA fragmentation, ac-LA was shown to induce apoptosis in androgen-independent PC-3 cells, whereas in MDA-MB-231 breast cancer cells, ac-LA led to cell accumulation in the G2/M phase of the cell cycle, but not to apoptosis...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723416/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-2-neuroendocrine-tumours-hepatocellular-carcinoma-and-gastro-intestinal-stromal-tumours
#11
REVIEW
Cindy Neuzillet, Louis de Mestier, Benoît Rousseau, Olivier Mir, Mohamed Hebbar, Hemant M Kocher, Philippe Ruszniewski, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28721828/mir-149-as-a-potential-molecular-target-for-cancer
#12
Suet Hui Ow, Pei Jou Chua, Boon Huat Bay
MicroRNAs (miRNAs) are small, non-coding nucleotides that regulate the expression of proteins. They play major roles in fundamental cellular processes. Aberrant expression of miRNAs has been frequently detected in cancers. miR-149 has been implicated in tumor progression by regulating cellular proliferation, migration, invasion, epithelial-mesenchymal-transition and chemoresistance. There have been reports that miR-149 can function both as an oncogene or tumor suppressor, depending on the type of cancer, thereby giving rise to the possibility of utilizing miR-149 mimics and inhibitors for cancer therapy...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28721584/mir-34a-attenuates-glioma-cells-progression-and-chemoresistance-via-targeting-pd-l1
#13
Yi Wang, Li Wang
OBJECTIVE: To investigate the roles of miR-34a in progression and chemoresistance of glioma cells. RESULTS: Quantitative real-time PCR analysis showed that miR-34a level was lower, but PD-L1 expression level was higher in glioma tissue specimens compared with normal brain tissues and their expression levels were negatively correlated. Ectopic expression of miR-34a inhibited glioma cell proliferation, promoted cell cycle arrest in G1/S phase and cell apoptosis. Additionally, miR-34a/PD-L1 axis was again confirmed and co-expression of PD-L1 with miR-34a mimics attenuated the effects of miR-34a on cell proliferation and apoptosis in glioma cells...
July 18, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28720093/solanum-nigrum-unripe-fruit-fraction-attenuates-adriamycin-resistance-by-down-regulating-multi-drug-resistance-protein-mdr-1-through-jak-stat-pathway
#14
Sankar Jagadeeshan, Diana David, S Jisha, S Manjula, S Asha Nair
BACKGROUND: Solanum nigrum, herbal plant that commonly grows in temperate climate zone, has been used as a traditional folk medicine whose ripen fruits were proven to exhibit anti-tumor properties. In traditional Chinese medicine, it has been used for centuries to cure inflammation, edema, mastitis and hepatic cancer and in the Ayurvedic system of traditional medicine in India, S. nigrum is applied against enteric diseases, ulcer, diarrhea and skin diseases. A methanolic glycosidic extract fraction of unripe fruit of S...
July 18, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28719220/egfr-targeted-cationic-polymeric-mixed-micelles-for-co-delivery-of-gemcitabine-and-mir-205-for-treating-advanced-pancreatic-cancer
#15
Goutam Mondal, Saud Almawash, Amit Kumar Chaudhary, Ram I Mahato
Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Since epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer cells, in this study, we aimed to deliver mixed micelles containing GEM and miR-205 decorated with EGFR-targeting cetuximab (C225) monoclonal antibody for targeted therapy...
July 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28718444/tumor-host-cell-interactions-in-ovarian-cancer-pathways-to-therapy-failure
#16
REVIEW
Elke Pogge von Strandmann, Silke Reinartz, Uwe Wager, Rolf Müller
Although most ovarian cancer patients are highly responsive to chemotherapy, they frequently present with recurrent metastatic lesions that result in poor overall survival, a situation that has not changed in the last 20 years. This review discusses new insights into the regulation of ovarian cancer chemoresistance with a focus on the emerging role of immune and other host cells. Here, we summarize the complex molecular pathways that regulate the interaction between tumor and host cells, discuss the limitations of current in vitro and in vivo models for translational studies, and present perspectives for the development of innovative therapies...
February 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718440/selective-targeting-of-rsk-isoforms-in-cancer
#17
REVIEW
Kimberly A Casalvieri, Christopher J Matheson, Donald S Backos, Philip Reigan
The p90 ribosomal S6 kinase family (RSK1-4) is a group of highly conserved Ser/Thr kinases that act as downstream effectors of the Ras/Raf/MEK/ERK signaling pathway. The RSKs phosphorylate a range of substrates involved in transcription, translation, cell cycle regulation, and cell survival. Although the RSKs have a high degree of sequence homology, their functional differences in cancer are of great interest. Current RSK inhibitors target more than one RSK isoform, and this may limit their efficacy as anticancer agents...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718426/targeting-tgf-%C3%AE-signaling-in-cancer
#18
REVIEW
Selcuk Colak, Peter Ten Dijke
The transforming growth factor (TGF)-β signaling pathway is deregulated in many diseases, including cancer. In healthy cells and early-stage cancer cells, this pathway has tumor-suppressor functions, including cell-cycle arrest and apoptosis. However, its activation in late-stage cancer can promote tumorigenesis, including metastasis and chemoresistance. The dual function and pleiotropic nature of TGF-β signaling make it a challenging target and imply the need for careful therapeutic dosing of TGF-β drugs and patient selection...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716816/sphingosine-1-phosphate-receptor-1-promotes-environment-induced-and-acquired-chemoresistance
#19
Veronica Lifshitz, Saul J Priceman, Wenzhao Li, Gregory Cherryholmes, Heehyoung Lee, Adar Makovski-Silverstein, Lucia Borriello, Yves A DeClerck, Hua Yu
Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28714406/role-of-the-immune-component-of-tumor-microenvironment-in-the-efficiency-of-cancer-treatment-perspectives-for-the-personalized-therapy
#20
Marina Stakheyeva, Vladimir Riabov, Irina Mitrofanova, Nikolai Litviakov, Evgeny Choynzonov, Nadezhda Cherdyntseva, Julia Kzhyshkowska
Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones...
July 14, 2017: Current Pharmaceutical Design
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