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https://www.readbyqxmd.com/read/30302777/the-role-of-the-unfolded-protein-response-in-cancer-progression-from-oncogenesis-to-chemoresistance
#1
REVIEW
Emma Madden, Susan E Logue, Sandra J Healy, Serge Manie, Afshin Samali
Tumour cells endure both oncogenic and environmental stresses during cancer progression. Transformed cells must meet increased demands for protein and lipid production needed for rapid proliferation and must adapt to exist in an oxygen and nutrient deprived environment. To overcome such challenges, cancer cells exploit intrinsic adaptive mechanisms such as the unfolded protein response (UPR). The UPR is a pro-survival mechanism triggered by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), a condition referred to as ER stress...
October 10, 2018: Biology of the Cell
https://www.readbyqxmd.com/read/30257595/a-mitochondrial-based-oncology-platform-for-targeting-cancer-stem-cells-cscs-mito-onc-rx
#2
Federica Sotgia, Bela Ozsvari, Marco Fiorillo, Ernestina Marianna De Francesco, Gloria Bonuccelli, Michael P Lisanti
Here, we wish to propose a new systematic approach to cancer therapy, based on the targeting of mitochondrial metabolism, especially in cancer stem cells (CSCs). In the future, we envision that anti-mitochondrial therapy would ultimately be practiced as an add-on to more conventional therapy, largely for the prevention of tumor recurrence and cancer metastasis. This mitochondrial based oncology platform would require a panel of FDA-approved therapeutics (e.g. Doxycycline) that can safely be used to inhibit mitochondrial OXPHOS and/or biogenesis in CSCs...
September 26, 2018: Cell Cycle
https://www.readbyqxmd.com/read/30223117/discovery-of-novel-human-inosine-5-monophosphate-dehydrogenase-2-himpdh2-inhibitors-as-potential-anticancer-agents
#3
Chetan P Shah, Prashant S Kharkar
The enzyme inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes an essential step in the de novo biosynthesis of guanine nucleotides, and thus regulates the guanine nucleotide pool required for cell proliferation. Of the two isoforms, human IMPDH type 2 (hIMPDH2) is a validated molecular target for potential immunosuppressive, antiviral and anticancer chemotherapy. In search of newer hIMPDH2 inhibitors as potential anticancer agents, three novel series (A: 5-aminoisobenzofuran-1(3H)-one, B: 3,4-dimethoxyaniline and C: benzo[d]-[1,3]dioxol-5-ylmethanamine) were synthesized and evaluated for in vitro and cell-based activities...
September 7, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30209740/in-vitro-antibacterial-and-anticancer-properties-of-helicteres-hirsuta-lour-leaf-and-stem-extracts-and-their-fractions
#4
Hong Ngoc Thuy Pham, Jennette A Sakoff, Danielle R Bond, Quan Van Vuong, Michael C Bowyer, Christopher J Scarlett
Helicteres hirsuta Lour. (H. hirsuta) has been considered as a herbal medicine for the treatment of malaria and diabetes but limited studies have been conducted on its anticancer and antibacterial properties. In this study, the in vitro antibacterial and anticancer properties of the leaf and stem extracts and their two sub-fractions (aqueous and saponin-enriched butanol fractions) prepared from H. hirsuta were elucidated. MTT and CCK-8 assays were employed to assess their in vitro anticancer properties against various cancer cell lines...
September 12, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/30027971/distributions-of-manganese-in-diverse-human-cancers-provide-insights-into-tumour-radioresistance
#5
Philip A Doble, George L Gabor Miklos
Many cancers are variably resistant to radiation treatment: some patients die within months, while others with the same tumour type and equivalent radiation protocol, survive for years. To determine why some tumours are radiosensitive, while others return after radiotherapy, requires new non-traditional approaches to oncology. Herein we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to test the hypothesis that Mn functions as a metabolic radioprotector and is an apex predictor of tumour radioresponsiveness...
September 19, 2018: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/30003999/extracellular-vesicles-and-anti-cancer-drug-resistance
#6
REVIEW
Niamh Mc Namee, Lorraine O'Driscoll
Extracellular vesicles (EVs) including exosomes, microvesicles, oncosomes, and microparticles have been associated with communicating anti-cancer drug-resistance. The in vitro, pre-clinical in vivo and patients' data linking EVs to drug-resistance (and the specific drugs involved) in breast cancer, prostate cancer, lung cancer, ovarian cancer, haematological malignancies, colorectal cancer, gastric cancer, pancreatic cancer, glioblastoma, neuroblastoma, melanoma, kidney cancer and osteosarcoma. Details of the mechanisms by which the resistance seems to be occurring (e...
July 10, 2018: Biochimica et biophysica acta. Reviews on cancer
https://www.readbyqxmd.com/read/29899865/oleanolic-acid-induces-p53-dependent-apoptosis-via-the-erk-jnk-akt-pathway-in-cancer-cell-lines-in-prostatic-cancer-xenografts-in-mice
#7
Gyeong-Ji Kim, Hyeon-Ju Jo, Kwon-Jai Lee, Jeong Woo Choi, Jeung Hee An
We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), U87 (human glioblastoma), normal murine liver cell (BNL CL.2) and human foreskin fibroblast cell lines (Hs 68). The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA did not exhibit toxicity in BNL CL. 2 and Hs 68 cell lines in our experiments. OA, at 100 µg/mL, increased the number of apoptotic cells to 27...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29792360/newer-human-inosine-5-monophosphate-dehydrogenase-2-himpdh2-inhibitors-as-potential-anticancer-agents
#8
Chetan P Shah, Prashant S Kharkar
Human inosine 5'-monophosphate dehydrogenase 2 (hIMPDH2), being an age-old target, has attracted attention recently for anticancer drug development. Mycophenolic acid (MPA), a well-known immunosuppressant drug, was used a lead structure to design and develop modestly potent and selective analogues. The steep structure-activity relationship (SAR) requirements of the lead molecule left little scope to synthesise newer analogues. Here, newer MPA amides were designed, synthesised and evaluated for hIMPDH2 inhibition and cellular efficacy in breast, prostate and glioblastoma cell lines...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29780878/microfluidics-in-malignant-glioma-research-and-precision-medicine
#9
Meghan Logun, Wujun Zhao, Leidong Mao, Lohitash Karumbaiah
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer that has no effective treatments and a prognosis of only 12-15 months. Microfluidic technologies deliver microscale control of fluids and cells, and have aided cancer therapy as point-of-care devices for the diagnosis of breast and prostate cancers. However, a few microfluidic devices are developed to study malignant glioma. The ability of these platforms to accurately replicate the complex microenvironmental and extracellular conditions prevailing in the brain and facilitate the measurement of biological phenomena with high resolution and in a high-throughput manner could prove useful for studying glioma progression...
May 2018: Advanced Biosystems
https://www.readbyqxmd.com/read/29771007/dichlorophenylacrylonitriles-as-ahr-ligands-that-display-selective-breast-cancer-cytotoxicity-in-vitro
#10
Jennifer R Baker, Jayne Gilbert, Stefan Paula, Xiao Zhu, Jennette A Sakoff, Adam McCluskey
Knoevenagel condensation of 3,4-dichloro- and 2,6-dichlorophenylacetonitriles gave a library of dichlorophenylacrylonitriles. Our leads (Z)-2-(3,4-dichlorophenyl)-3-(1H-pyrrol-2-yl)acrylonitrile (5) and (Z)-2-(3,4-dichlorophenyl)-3-(4-nitrophenyl)acrylonitrile (6) displayed 0.56±0.03 and 0.127±0.04 μm growth inhibition (GI50 ) and 260-fold selectivity for the MCF-7 breast cancer cell line. A 2,6-dichlorophenyl moiety saw a 10-fold decrease in potency; additional nitrogen moieties (-NO2 ) enhanced activity (Z)-2-(2,6-dichloro-3-nitrophenyl)-3-(2-nitrophenyl)acrylonitrile (26) and (Z)-2-(2,6-dichloro-3-nitrophenyl)-3-(3-nitrophenyl)acrylonitrile (27), with the corresponding -NH2 analogues (Z)-2-(3-amino-2,6-dichlorophenyl)-3-(2-aminophenyl)acrylonitrile (29) and (Z)-2-(3-amino-2,6-dichlorophenyl)-3-(3-aminophenyl)acrylonitrile (30) being more potent...
July 18, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29736304/the-contrasting-roles-of-inflammasomes-in-cancer
#11
REVIEW
Qin He, Yu Fu, Dean Tian, Wei Yan
Chronic inflammation plays a decisive role at different stages of cancer development. Inflammasomes are oligomeric protein complexes activated in response to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs and DAMPs are released from infected cells, tumors and damaged tissues. Inflammasomes activate and release inflammatory cytokines such as IL-1β and IL-18. The various inflammasomes and inflammatory cytokines and chemokines play contrasting roles in cancer development and progression...
2018: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29718569/grp78-targeted-in-silico-virtual-screening-of-novel-anticancer-agents
#12
Ambily Nath Indu Viswanath, Ji Woong Lim, Seon Hee Seo, Jae Yeol Lee, Sang Min Lim, Ae Nim Pae
Overexpression of GRP78 in a variety of cancers such as glioblastoma, leukemia, lung, prostate, breast, gastric, and colon makes it a prime target for anticancer drug development. Present study reports GRP78-based design of novel anticancer agents using in-silico methods. As a first step toward the work, the interactions between GRP78 and 15 known ligands were modeled by docking simulation. The docked complex, GRP78-13, superior to other compounds with respect to its experimental activity and energy descriptors, was deduced into a structure-based pharmacophore...
August 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29695515/novel-role-of-prostate-apoptosis-response-4-tumor-suppressor-in-b-cell-chronic-lymphocytic-leukemia
#13
Mary K McKenna, Sunil K Noothi, Sara S Alhakeem, Karine Z Oben, Joseph T Greene, Rajeswaran Mani, Kathryn L Perry, James P Collard, Jacqueline R Rivas, Gerhard C Hildebrandt, Roger A Fleischman, Eric B Durbin, John C Byrd, Chi Wang, Natarajan Muthusamy, Vivek M Rangnekar, Subbarao Bondada
Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell-cycle transition...
June 28, 2018: Blood
https://www.readbyqxmd.com/read/29682554/differential-expression-patterns-of-eph-receptors-and-ephrin-ligands-in-human-cancers
#14
REVIEW
Chung-Ting Jimmy Kou, Raj P Kandpal
Eph receptors constitute the largest family of receptor tyrosine kinases, which are activated by ephrin ligands that either are anchored to the membrane or contain a transmembrane domain. These molecules play important roles in the development of multicellular organisms, and the physiological functions of these receptor-ligand pairs have been extensively documented in axon guidance, neuronal development, vascular patterning, and inflammation during tissue injury. The recognition that aberrant regulation and expression of these molecules lead to alterations in proliferative, migratory, and invasive potential of a variety of human cancers has made them potential targets for cancer therapeutics...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29660689/quinonoid-compounds-via-reactions-of-lawsone-and-2-aminonaphthoquinone-with-%C3%AE-bromonitroalkenes-and-nitroallylic-acetates-structural-diversity-by-c-ring-modification-and-cytotoxic-evaluation-against-cancer-cells
#15
Thekke V Baiju, Renata G Almeida, Sudheesh T Sivanandan, Carlos A de Simone, Lucas M Brito, Bruno C Cavalcanti, Claudia Pessoa, Irishi N N Namboothiri, Eufrânio N da Silva Júnior
Morita-Baylis-Hillman acetates and α-bromonitroalkenes have been employed in cascade reactions with lawsone and 2-aminonaphthoquinone for the one-pot synthesis of heterocycle fused quinonoid compounds. The reactions reported here utilized the 1,3-binucleophilic potential of hydroxy- and aminonaphthoquinones and the 1,2/1,3-bielectrophilic potential of bromonitroalkenes and Morita-Baylis-Hillman acetates for the synthesis of pyrrole and furan fused naphthoquinones. The synthesized compounds were evaluated against HCT-116 (human colon carcinoma cells), PC3 (human prostate cancer cells), HL-60 (human promyelocytic leukemia cells), SF295 (human glioblastoma cells) and NCI-H460 (human lung cancer cells) and exhibited antitumor activity with IC50 values as low as < 2 μM...
May 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29621137/trap1-regulation-of-cancer-metabolism-dual-role-as-oncogene-or-tumor-suppressor
#16
REVIEW
Danilo Swann Matassa, Ilenia Agliarulo, Rosario Avolio, Matteo Landriscina, Franca Esposito
Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to tumor outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a molecular chaperone involved in the regulation of energetic metabolism in cancer cells. This protein is highly expressed in several cancers, such as glioblastoma, colon, breast, prostate and lung cancers and is often associated with drug resistance. However, TRAP1 is also downregulated in specific tumors, such as ovarian, bladder and renal cancers, where its lower expression is correlated with the worst prognoses and chemoresistance...
April 5, 2018: Genes
https://www.readbyqxmd.com/read/29529299/the-association-between-copy-number-aberration-dna-methylation-and-gene-expression-in-tumor-samples
#17
Wei Sun, Paul Bunn, Chong Jin, Paul Little, Vasyl Zhabotynsky, Charles M Perou, David Neil Hayes, Mengjie Chen, Dan-Yu Lin
We systematically studied the association between somatic copy number aberration (SCNA), DNA methylation and gene expression using -omic data from The Cancer Genome Atlas (TCGA) on six cancer types: breast cancer, colon cancer, glioblastoma, leukemia, lower-grade glioma and prostate cancer. A major challenge for such integrated study is that the association between DNA methylation and gene expression is severely confounded by tumor purity and cell type composition, which are often unobserved and difficult to estimate...
April 6, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29371271/quality-of-life-of-elderly-patients-with-solid-tumours-undergoing-adjuvant-cancer-therapy-a-systematic-review
#18
REVIEW
Karis Kin-Fong Cheng, Ethel Yee-Ting Lim, Ravindran Kanesvaran
OBJECTIVES: The measurement of quality of life (QoL) in elderly cancer population is increasingly being recognised as an important element of clinical decision-making and the evaluation of treatment outcome. This systematic review aimed to summarise the evidence of QoL during and after adjuvant therapy in elderly patients with cancer. METHODS: A systematic search was conducted of studies published in CINAHL plus, CENTRAL, PubMed, PsycINFO and Web of Science from the inception of these databases to December 2016...
January 24, 2018: BMJ Open
https://www.readbyqxmd.com/read/29369787/the-influence-of-peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-ligands-on-cancer-cell-tumorigenicity
#19
REVIEW
Saghar Yousefnia, Sara Momenzadeh, Farzad Seyed Forootan, Kamran Ghaedi, Mohammad Hossein Nasr Esfahani
Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the nuclear receptor superfamily of PPARs (PPARα, PPARβ/δ, PPARγ). Numerous studies have concentrated on the key role of PPARs in inflammation and a variety of cancers which include prostate, breast, glioblastoma, neuroblastoma, pancreatic, hepatic, leukemia, and bladder and thyroid tumors. This review, specifically deals with anti-tumor and tumorigenicity effects of PPARγ and its natural and synthetic agonists including Troglitazone, Cladosporol A, B, 15-Deoxi-Δ12-14 -Prostaglondin J2 (15-d-PGJ2), Ciglitazon, docosahexaenoic acid, eicosapentaenoic acid Alpha-eleostreac acid, Amorfrutin C, Sphingosine 1-phosphate, Evodiamine, Excavatolide B vs respected antagonists as GW9662, bisphenol-A-diglycidyl-ether...
April 5, 2018: Gene
https://www.readbyqxmd.com/read/29206231/cancer-type-dependent-expression-of-ck2-transcripts
#20
Melissa M J Chua, Migi Lee, Isabel Dominguez
A multitude of proteins are aberrantly expressed in cancer cells, including the oncogenic serine-threonine kinase CK2. In a previous report, we found increases in CK2 transcript expression that could explain the increased CK2 protein levels found in tumors from lung and bronchus, prostate, breast, colon and rectum, ovarian and pancreatic cancers. We also found that, contrary to the current notions about CK2, some CK2 transcripts were downregulated in several cancers. Here, we investigate all other cancers using Oncomine to determine whether they also display significant CK2 transcript dysregulation...
2017: PloS One
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