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https://read.qxmd.com/read/30776694/revealing-quinquennial-anticancer-journey-of-morpholine-a-sar-based-review
#1
REVIEW
Fatima Arshad, Mohemmed Faraz Khan, Wasim Akhtar, Mohammad Mumtaz Alam, Lalit Mohan Nainwal, Sumit Kumar Kaushik, Mymoona Akhter, Suhel Parvez, Syed Misbahul Hasan, Mohammad Shaquiquzzaman
Morpholine, a six-membered heterocycle containing one nitrogen and one oxygen atom, is a moiety of great significance. It forms an important intermediate in many industrial and organic syntheses. Morpholine containing drugs are of high therapeutic value. Its wide array of pharmacological activity includes anti-diabetic, anti-emetic, growth stimulant, anti-depressant, bronchodilator and anticancer. Multi-drug resistance in cancer cases have emerged in the last few years and have led to the failure of many chemotherapeutic drugs...
February 8, 2019: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30776659/kiss1-in-regulation-of-metastasis-and-response-to-antitumor-drugs
#2
REVIEW
Cristina Corno, Paola Perego
Metastatic dissemination of tumor cells represents a major obstacle towards cancer cure. Tumor cells with metastatic capacity are often resistant to chemotherapy. Experimental efforts revealed that the metastatic cascade is a complex process that involves multiple positive and negative regulators. In this respect, several metastasis suppressor genes have been described. Here, we review the role of the metastasis suppressor KiSS1 in regulation of metastasis and in response to antitumor agents. Physiologically, KiSS1 plays a key role in the activation of the hypothalamic-pituitary-gonadal axis regulating puberty and reproductive functions...
February 11, 2019: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://read.qxmd.com/read/30776468/cyp-enzymes-expressed-within-live-human-suspension-cells-are-superior-to-widely-used-microsomal-enzymes-in-identifying-potent-cyp1a1-cyp1b1-inhibitors-identification-of-quinazolinones-as-cyp1a1-cyp1b1-inhibitors-that-efficiently-reverse-b-a-p-toxicity-and-cisplatin
#3
Vinay R Sonawane, Mohd Usman Mohd Siddique, Linda Gatchie, Ibidapo S Williams, Sandip B Bharate, Venkatesan Jayaprakash, Barij N Sinha, Bhabatosh Chaudhuri
Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in 'suspension' for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50 , >10/1...
February 15, 2019: European Journal of Pharmaceutical Sciences
https://read.qxmd.com/read/30776234/identification-and-characterization-of-aes-135-a-hydroxamic-acid-based-hdac-inhibitor-that-prolongs-survival-in-an-orthotopic-mouse-model-of-pancreatic-cancer
#4
Andrew E Shouksmith, Fenil Shah, Michelle L Grimard, Justyna M Gawel, Yasir Raouf, Mulu Geletu, Angelika Berger-Becvar, Elvin D de Araujo, Hema Artee Luchman, William L Heaton, David Bakhshinyan, Ashley A Adile, Chitra Venugopal, Thomas O'Hare, Michael W Deininger, Sheila K Singh, Stephen F Konieczny, Samuel Weiss, Melissa L Fishel, Patrick Thomas Gunning
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% one-year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC...
February 18, 2019: Journal of Medicinal Chemistry
https://read.qxmd.com/read/30775364/nanoparticles-of-metal-organic-cages-overcoming-drug-resistance-in-ovarian-cancer
#5
Han Wang, Zihan Qiu, He Liu, Amarasooriya M D S Jayawardhana, Zhizhou Yue, Hala Daghlas, David J Bowers, Bansidhar Datta, Yao-Rong Zheng
A long-standing challenge in the treatment of ovarian cancer is drug resistance to standard platinum-based chemotherapy. Recently, increasing attention has been drawn to the use of self-assembled metal-organic complexes as novel therapeutics for cancer treatment. However, high hydrophobicity that is often associated with these structures lowers their solubility and hinders their clinical translation. In this article, we present a proof-of-concept study of using nanoprecipitation to formulate the hydrophobic metal-organic cages and facilitate their use in treating chemoresistant ovarian cancer...
2019: Frontiers in Chemistry
https://read.qxmd.com/read/30775317/targeting-jun-cebpb-and-hdac3-a-novel-strategy-to-overcome-drug-resistance-in-hypoxic-glioblastoma
#6
Yixing Gao, Bao Liu, Lan Feng, Binda Sun, Shu He, Yidong Yang, Gang Wu, Guoji E, Chang Liu, Yuqi Gao, Erlong Zhang, Bo Zhu
Hypoxia is a predominant feature in glioblastoma (GBM) and contributes greatly to its drug resistance. However, the molecular mechanisms which are responsible for the development of the resistant phenotype of GBM under hypoxic conditions remain unclear. To analyze the key pathways promoting therapy resistance in hypoxic GBM, we utilized the U87-MG cell line as a human GBM cell model and the human brain HEB cell line as a non-neoplastic brain cell model. These cell lines were cultured in the presence of 21, 5, and 1% O2 for 24 h...
2019: Frontiers in Oncology
https://read.qxmd.com/read/30775247/current-strategies-for-targeting-the-activity-of-androgen-receptor-variants
#7
REVIEW
Cameron M Armstrong, Allen C Gao
Current therapies for advanced prostate cancer, such as enzalutamide and abiraterone, focus on inhibiting androgen receptor (AR) activity and reducing downstream signaling pathways to inhibit tumor growth. Unfortunately, cancer cells are very adaptable and, over time, these cells develop mechanisms by which they can circumvent therapeutics. One of the many mechanisms that have been discovered is the generation of AR variants. These variants are generated through alternative splicing of the full length AR and often lack the ligand binding domain...
January 2019: Asian Journal of Urology
https://read.qxmd.com/read/30775178/-in-silico-analysis-reveals-a-shared-immune-signature-in-casp8-mutated-carcinomas-with-varying-correlations-to-prognosis
#8
Yashoda Ghanekar, Subhashini Sadasivam
Background: Sequencing studies across multiple cancers continue to reveal mutations and genes involved in the pathobiology of these cancers. Exome sequencing of oral cancers, a subset of Head and Neck Squamous cell Carcinomas (HNSCs) common among tobacco-chewing populations, revealed that ∼34% of the affected patients harbor mutations in the CASP8 gene . Uterine Corpus Endometrial Carcinoma (UCEC) is another cancer where ∼10% cases harbor CASP8 mutations. Caspase-8, the protease encoded by CASP8 gene, plays a dual role in programmed cell death, which in turn has an important role in tumor cell death and drug resistance...
2019: PeerJ
https://read.qxmd.com/read/30774996/mek5-erk5-activation-regulates-colon-cancer-stem-like-cell-properties
#9
Diane M Pereira, Sofia E Gomes, Pedro M Borralho, Cecília M P Rodrigues
Colon cancer has been proposed to be sustained by a small subpopulation of stem-like cells with unique properties allowing them to survive conventional therapies and drive tumor recurrence. Identification of targetable signaling pathways contributing to malignant stem-like cell maintenance may therefore translate into new therapeutic strategies to overcome drug resistance. Here we demonstrated that MEK5/ERK5 signaling activation is associated with stem-like malignant phenotypes. Conversely, using a panel of cell line-derived three-dimensional models, we showed that ERK5 inhibition markedly suppresses the molecular and functional features of colon cancer stem-like cells...
2019: Cell Death Discovery
https://read.qxmd.com/read/30774764/downregulation-of-mir-194-5p-induces-paclitaxel-resistance-in-ovarian-cancer-cells-by-altering-mdm2-expression
#10
Koji Nakamura, Kenjiro Sawada, Mayuko Miyamoto, Yasuto Kinose, Akihiko Yoshimura, Kyoso Ishida, Masaki Kobayashi, Aasa Shimizu, Erika Nakatsuka, Kae Hashimoto, Seiji Mabuchi, Tadashi Kimura
Paclitaxel is a first-line drug for treating epithelial ovarian cancer (EOC). However, prognosis for patients with advanced stage cancer remains poor due to primary or acquired drug resistance. Therefore, overcoming chemoresistance is one of the greatest challenges in treating EOC. In this study, we identified microRNAs (miRNA) that regulate paclitaxel resistance and tested their potential utility as therapeutic targets. Paclitaxel-resistant cell lines were established using two EOC cell lines: SKVO3ip1 and HeyA8...
January 18, 2019: Oncotarget
https://read.qxmd.com/read/30774659/metformin-counteracts-hcc-progression-and-metastasis-enhancing-klf6-p21-expression-and-downregulating-the-igf-axis
#11
Fernanda Vacante, Pamela Senesi, Anna Montesano, Stefano Paini, Livio Luzi, Ileana Terruzzi
Background and Aims: Hepatocellular carcinoma (HCC) is the common tumor of the liver. Unfortunately, most HCC seem to be resistant to conventional chemotherapy and radiotherapy. The poor efficacy of antitumor agents is also due, at least in part, to the inefficient drug delivery and metabolism exerted by the steatotic/cirrhotic liver that hosts the tumor. Thus, novel approaches in chemotherapy may be needed to improve the survival rate in patients with HCC. Metformin (METF) has been found to lower HCC risk; however, the mechanisms by which METF performs its anticancer activity are not completely elucidated...
2019: International Journal of Endocrinology
https://read.qxmd.com/read/30774376/reversing-platinum-resistance-in-ovarian-cancer-multicellular-spheroids-by-targeting-bcl-2
#12
Ya'nan Yang, Song Li, Yiting Sun, Di Zhang, Zeyi Zhao, Lian Liu
Purpose: Peritoneal metastasis is the most common pathway for the spread of ovarian cancer. Ovarian cancer cells in ascites prefer to aggregate into the more chemoresistant multicellular spheroids (MCSs), leading to treatment failure and disease recurrence. We previously established a suspension MCS model of ovarian cancer cells in vitro and found that the MCS cells acquired drug resistance to cisplatin. In the present study, we aimed to uncover the underlying mechanism of the platinum resistance of MCS and the potential targets to reverse the drug resistance...
2019: OncoTargets and Therapy
https://read.qxmd.com/read/30774359/anticancer-activity-of-1-25-oh-2-d-3-against-human-breast-cancer-cell-lines-by-targeting-ras-mek-erk-pathway
#13
Wei Zheng, Lin Cao, Linna Ouyang, Qian Zhang, Bofeng Duan, Wei Zhou, Shan Chen, Wei Peng, Yi Xie, Qing Fan, Daoxing Gong
Purpose: Breast cancer is the most common cancer among women with ~1.67 million cases diagnosed annually worldwide, and ~1 in 37 women succumbed to breast cancer. Over the past decades, new therapeutic strategy has substantially improved the curative effect for women with breast cancer. However, the currently available ER-targeted and HER-2-based therapies are not effective for triple-negative breast cancer patients, which account for ~15% of total breast cancer cases. Materials and methods: We reported that 1,25-(OH)2 D3 , a biologically active form of vitamin D3 , exhibited a strong anticancer effects on the proliferation, migration, invasion, cell cycle arrest, and apoptosis of both ER-positive (MCF-7) and ER-negative breast cancer cells (MDA-MB-453)...
2019: OncoTargets and Therapy
https://read.qxmd.com/read/30773635/the-crucial-role-of-zeb2-from-development-to-epithelial-to-mesenchymal-transition-and-cancer-complexity
#14
REVIEW
Masoumeh Fardi, Mohammadreza Alivand, Behzad Baradaran, Majid Farshdousti Hagh, Saeed Solali
Zinc finger E-box binding homeobox 2 (ZEB2) is a DNA-binding transcription factor, which is mainly involved in epithelial-to-mesenchymal transition (EMT). EMT is a conserved process during which mature and adherent epithelial-like state is converted into a mobile mesenchymal state. Emerging data indicate that ZEB2 plays a pivotal role in EMT-induced processes such as development, differentiation, and malignant mechanisms, for example, drug resistance, cancer stem cell-like traits, apoptosis, survival, cell cycle arrest, tumor recurrence, and metastasis...
February 17, 2019: Journal of Cellular Physiology
https://read.qxmd.com/read/30773204/plasma-androgen-receptor-and-docetaxel-for-metastatic-castration-resistant-prostate-cancer
#15
Vincenza Conteduca, Anuradha Jayaram, Nuria Romero-Laorden, Daniel Wetterskog, Samanta Salvi, Giorgia Gurioli, Emanuela Scarpi, Elena Castro, Mercedes Marin-Aguilera, Cristian Lolli, Giuseppe Schepisi, Antonio Maugeri, Anna Wingate, Alberto Farolfi, Valentina Casadio, Ana Medina, Javier Puente, Mª José Méndez Vidal, Rafael Morales-Barrera, Jose C Villa-Guzmán, Susana Hernando, Alejo Rodriguez-Vida, Aránzazu González-Del-Alba, Begoña Mellado, Enrique Gonzalez-Billalabeitia, David Olmos, Gerhardt Attard, Ugo De Giorgi
Plasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples...
March 2019: European Urology
https://read.qxmd.com/read/30772480/therapeutics-strategies-against-cancer-stem-cell-in-breast-cancer
#16
Faezeh Ghasemi, Parisa Zia Sarabi, Seyyed Shamsadin Athari, Abdulreza Esmaielzadeha
Breast cancer is known as a most prevalent cancer and second deadly cancer, among women worldwide. Due to the high incidence rate of breast cancer and limitations of conventional therapy it seemed essential to look for new targets in cancer cells and directly target them such as target therapy on breast cancer stem cells. In this review we indicate some of therapeutic uses of cancer stem cells in breast cancer. Some strategies are targeting surface specific markers and activated signaling pathways in their microenvironment such as Notch, Hedgehog, Wnt/b-catenin, PI3K/Akt, NF-kB, BMP and TGF-β and their maintenance and drug resistance, using various miRNAs, enhancement of CSCs apoptosis, differentiation therapy, blocking epithelial to mesenchymal transition and using different natural compounds...
February 14, 2019: International Journal of Biochemistry & Cell Biology
https://read.qxmd.com/read/30772464/deep-resp-forest-a-deep-forest-model-to-predict-anti-cancer-drug-response
#17
Ran Su, Xinyi Liu, Leyi Wei, Quan Zou
The identification of therapeutic biomarkers predictive of drug response is crucial in personalized medicine. A number of computational models to predict response of anti-cancer drugs have been developed as the establishment of several pharmacogenomics screening databases. In our study, we proposed a deep cascaded forest model, Deep-Resp-Forest, to classify the anti-cancer drug response as "sensitive" or "resistant". We made three contributions in this study. Firstly, diverse molecular data could be effectively integrated to provide more information than single type of data for the classification...
February 14, 2019: Methods: a Companion to Methods in Enzymology
https://read.qxmd.com/read/30772447/imatinib-inhibits-the-regrowth-of-human-colon-cancer-cells-after-treatment-with-5-fu-and-cooperates-with-vitamin-d-analogue-pri-2191-in-the-downregulation-of-expression-of-stemness-related-genes-in-5-fu-refractory-cells
#18
Agnieszka Kotlarz, Małgorzata Przybyszewska, Paweł Swoboda, Jacek Neska, Joanna Miłoszewska, Monika Anna Grygorowicz, Andrzej Kutner, Sergiusz Markowicz
Conventional cytotoxic drugs preferentially eliminate differentiated cancer cells but spare relatively more resistant stem-like cancer cells capable to initiate recurrence. Due to cancer cell plasticity, the stem-like phenotype can be also acquired by cancer cells refractory to treatment with cytotoxic drugs. We investigated whether drugs inhibiting receptor tyrosine kinases could be used to target human colon cancer cells initiating cancer regrowth following conventional cytotoxic treatment. The moderately differentiated cell line HT-29 and poorly differentiated cell line HCT-116 were exposed to 5-fluorouracil (5-FU)...
February 14, 2019: Journal of Steroid Biochemistry and Molecular Biology
https://read.qxmd.com/read/30771899/cancer-upregulated-gene-cug-2-elevates-yap1-expression-leading-to-enhancement-of-epithelial-mesenchymal-transition-in-human-lung-cancer-cells
#19
Sirichat Kaowinn, Natpaphan Yawut, Sang Seok Koh, Young-Hwa Chung
Although our previous studies have showed that a novel oncogene, cancer upregulated gene (CUG)2 induced epithelial-mesenchymal transition (EMT), the detailed molecular mechanism remains unknown. Because several lines of evidence documented that Yes-Associated Protein (YAP)1 is closely associated with cancer stem cell (CSC)-like phenotypes including EMT, stemness, and drug resistance, we wondered if YAP1 is involved in CUG2-induced EMT. We herein found that the overexpression of CUG2 increased YAP1 expression at the transcriptional as well as protein levels...
February 13, 2019: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/30771616/leveraging-the-medicines-for-malaria-venture-malaria-and-pathogen-boxes-to-discover-chemical-inhibitors-of-east-coast-fever
#20
James Nyagwange, Elias Awino, Edwin Tijhaar, Nicholas Svitek, Roger Pelle, Vishvanath Nene
Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T...
January 25, 2019: International Journal for Parasitology, Drugs and Drug Resistance
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