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https://www.readbyqxmd.com/read/28431962/structural-basis-chemical-driving-forces-and-biological-implications-of-flavones-as-cu-ii-ionophores
#1
Fang Dai, Wen-Jing Yan, Yu-Ting Du, Xia-Zhen Bao, Xiu-Zhuang Li, Bo Zhou
A main biochemical property of cancer cells, compared with normal cells, is altered redox status including increased levels of copper to maintain their malignant phenotypes. Thus, increasing copper accumulation, by using ionophores, to disrupt abnormal redox homeostasis of cancer cells may be an important anticancer strategy. Naturally occurring molecules with extraordinarily diverse chemical scaffolds are an important source of inspiration for developing copper ionophores. Dietary flavonoids are well-characterized copper chelators and show cancer chemopreventive potential, but their ionophoric role for redox-active copper and the related biological implications have remained unknown...
April 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28431516/evaluation-of-the-impact-of-disease-prevention-measures-a-methodological-note-on-defining-incidence-rates
#2
Yin-Bun Cheung, Ying Xu, Matthew Cairns, Paul Milligan
BACKGROUND: In studies of recurrent events, it is common to consider a person who has suffered a disease episode and received curative treatment to be not at risk of suffering a new episode for a duration of time. It is a common practice to deduct this duration from the person's observation time in the statistical analysis of the incidence data. METHODS: We examined the concepts of incidence and protective efficacy from a real life point of view. We developed simple formulae to show the relationship between the incidence rate and protective efficacy between analyses with and without deducting the curative treatment time from the observation time...
April 21, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28430653/preventive-effects-of-the-sodium-glucose-cotransporter-2-inhibitor-tofogliflozin-on-diethylnitrosamine-induced-liver-tumorigenesis-in-obese-and-diabetic-mice
#3
Koki Obara, Yohei Shirakami, Akinori Maruta, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Mitsuru Seishima, Masahito Shimizu
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease. In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb obese and diabetic mice. The direct effects of tofogliflozin on human liver cancer cell proliferation were also evaluated. Mice were administered diethylnitrosamine-containing water for 2 weeks and were treated with tofogliflozin throughout the experiment...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430601/growth-suppressive-activity-of-raloxifene-on-liver-cancer-cells-by-targeting-il-6-gp130-signaling
#4
Yina Wang, Haiyan Ma, Chongqiang Zhao, Tianshu Liu, Dan Yan, David Jou, Huameng Li, Cuntai Zhang, Jiagao Lü, Chenglong Li, Jiayuh Lin, Sheng Li, Li Lin
BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer. We reported the discovery of EVISTA (Raloxifene HCl) as novel inhibitor of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428272/hur-small-molecule-inhibitor-elicits-differential-effects-in-adenomatosis-polyposis-and-colorectal-carcinogenesis
#5
Michaela Lang, David Berry, Katharina Passecker, Ildiko Mesteri, Sabin Bhuju, Florian Ebner, Vitaly Sedlyarov, Rayko Evstatiev, Kyle Dammann, Alexander Loy, Orest Kuzyk, Pavel Kovarik, Vineeta Khare, Martin Beibel, Guglielmo Roma, Nicole Meisner-Kober, Christoph Gasche
HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3' untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427863/ros-in-cancer-the-burning-question
#6
REVIEW
Iok In Christine Chio, David A Tuveson
An unanswered question in human health is whether antioxidation prevents or promotes cancer. Antioxidation has historically been viewed as chemopreventive, but emerging evidence suggests that antioxidants may be supportive of neoplasia. We posit this contention to be rooted in the fact that ROS do not operate as one single biochemical entity, but as diverse secondary messengers in cancer cells. This cautions against therapeutic strategies to increase ROS at a global level. To leverage redox alterations towards the development of effective therapies necessitates the application of biophysical and biochemical approaches to define redox dynamics and to functionally elucidate specific oxidative modifications in cancer versus normal cells...
April 17, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28427561/molecular-targets-of-ascochlorin-and-its-derivatives-for-cancer-therapy
#7
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/28427145/uncoupling-genotoxic-stress-responses-from-circadian-control-increases-susceptibility-to-mammary-carcinogenesis
#8
Mingzhu Fang, Pamela A Ohman Strickland, Hwan-Goo Kang, Helmut Zarbl
We previously demonstrated that chemopreventive methylselenocysteine (MSC) prevents N-Nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in the susceptible Fischer 344 (F344) rats by enhancing NAD+-dependent SIRT1 activity, restoring circadian expression of Period 2 (Per2) and circadian controlled genes. Here, we show that compared to the genetically resistant Copenhagen (COP) rat strain, mammary glands of the F344 rats have a 4-hour phase delay in circadian expression of Per2. Consequently, F344 rats failed to increase SIRT1 activity and circadian expression of Per2 and DDRR genes after exposure to NMU...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423681/sulforaphane-for-the-chemoprevention-of-bladder-cancer-molecular-mechanism-targeted-approach
#9
REVIEW
Andrew Leone, Gregory Diorio, Wade Sexton, Michael Schell, Mark Alexandrow, Jed W Fahey, Nagi B Kumar
The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423551/metabolic-reprogramming-of-the-premalignant-colonic-mucosa-is-an-early-event-in-carcinogenesis
#10
Mart Dela Cruz, Sarah Ledbetter, Sanjib Chowdhury, Ashish K Tiwari, Navneet Momi, Ramesh K Wali, Charles Bliss, Christopher Huang, David Lichtenstein, Swati Bhattacharya, Anisha Varma-Wilson, Vadim Backman, Hemant K Roy
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422250/a-novel-nanomissile-targeting-two-biomarkers-and-accurately-bombing-ctcs-with-doxorubicin
#11
Yu Gao, Xiaodong Xie, Fengqiao Li, Yusheng Lu, Tao Li, Shu Lian, Yingying Zhang, Huijuan Zhang, Hao Mei, Lee Jia
Rare circulating tumor cells (CTCs) cause >50% of primary colorectal cancer survivors to develop deadly metastasis at 3-5 years after surgery; the current chemotherapies can do nothing about these cells. Herein, we synthesized a novel doxorubicin (DOX)-entrapped mesoporous silica nanoparticle (MSN), covalently-conjugated with two aptamers, for simultaneously targeting EpCAM and CD44, the typical surface biomarkers of colorectal CTCs. The nanomissile can specifically capture the metastasis-prone CTCs spiked in healthy human blood in a competitive-binding manner...
April 19, 2017: Nanoscale
https://www.readbyqxmd.com/read/28422073/chemopreventive-strategies-for-inflammation-related-carcinogenesis-current-status-and-future-direction
#12
REVIEW
Yusuke Kanda, Mitsuhiko Osaki, Futoshi Okada
A sustained and chronically-inflamed environment is characterized by the presence of heterogeneous inflammatory cellular components, including neutrophils, macrophages, lymphocytes and fibroblasts. These infiltrated cells produce growth stimulating mediators (inflammatory cytokines and growth factors), chemotactic factors (chemokines) and genotoxic substances (reactive oxygen species and nitrogen oxide) and induce DNA damage and methylation. Therefore, chronic inflammation serves as an intrinsic niche for carcinogenesis and tumor progression...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419101/anti-proliferative-effect-of-novel-primary-cetyl-alcohol-derived-sophorolipids-against-human-cervical-cancer-cells-hela
#13
Laxman Nawale, Parul Dubey, Bhushan Chaudhari, Dhiman Sarkar, Asmita Prabhune
Sophorolipids (SLs) are glycolipid biosurfactants that have been shown to display anticancer activity. In the present study, we report anti-proliferative studies on purified forms of novel SLs synthesized using cetyl alcohol as the substrate (referred as SLCA) and their anticancer mechanism in human cervical cancer cells. Antiproliferative effect of column purified SLCA fractions (A, B, C, D, E and F) was examined in panel of human cancer cell lines as well as primary cells. Among these fractions, SLCA B and C significantly inhibited the survival of HeLa and HCT 116 cells without affecting the viability of normal human umbilical vein endothelial cells (HUVEC)...
2017: PloS One
https://www.readbyqxmd.com/read/28418881/aspirin-as-a-potential-modality-for-the-chemoprevention-of-breast-cancer-a-dose-response-meta-analysis-of-cohort-studies-from-857-831-participants
#14
Liming Lu, Leiyu Shi, Jingchun Zeng, Zehuai Wen
BACKGROUND: Previous meta-analyses on the relationship between aspirin use and breast cancer risk have drawn inconsistent results. In addition, the threshold effect of different doses, frequencies and durations of aspirin use in preventing breast cancer have yet to be established. RESULTS: The search yielded 13 prospective cohort studies (N=857,831 participants) that reported an average of 7.6 cases/1,000 person-years of breast cancer during a follow-up period of from 4...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417445/chemopreventive-efficacy-of-curcumin-loaded-plga-microparticles-in-a-transgenic-mouse-model-of-her-2-positive-breast-cancer
#15
Alex E Grill, Komal Shahani, Brenda Koniar, Jayanth Panyam
Curcumin has shown promising inhibitory activity against HER-2-positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth...
April 17, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28416456/licoricidin-inhibits-the-growth-of-sw480-human-colorectal-adenocarcinoma-cells-in-vitro-and-in-vivo-by-inducing-cycle-arrest-apoptosis-and-autophagy
#16
Shuai Ji, Shunan Tang, Kai Li, Ziwei Li, Wenfei Liang, Xue Qiao, Qi Wang, Siwang Yu, Min Ye
Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer activities, but the active ingredients and underlying mechanisms have not been revealed. By screening the cytotoxic activities of 122 licorice compounds against SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD) inhibited SW480 cell viability with an IC50 value of 7.2μM. Further studies indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation of caspase-dependent pro-apoptotic signaling...
April 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28415774/chemoprevention-of-prostate-cancer-in-men-with-high-grade-prostatic-intraepithelial-neoplasia-hgpin-a-systematic-review-and-adjusted-indirect-treatment-comparison
#17
Kang Cui, Xiangnan Li, Yabing Du, Xiance Tang, Seiji Arai, Yiwei Geng, Ying Xi, Han Xu, Yue Zhou, Wang Ma, Tengfei Zhang
BACKGROUND: High-grade prostatic intraepithelial neoplasia (HGPIN) is the precursor or premalignant form of prostate cancer. At least 30% patients with a confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy. HGPIN patients are the appropriate at-risk population for chemoprevention strategies investigation against prostate cancer. However the commonly used chemoprevention agents that targeted on hormonal imbalance or lifestyle-related factors showed varied results in HGPIN patients...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414157/commiphora-molmol-resin-attenuates-diethylnitrosamine-phenobarbital-induced-hepatocarcinogenesis-by-modulating-oxidative-stress-inflammation-angiogenesis-and-nrf2-are-ho-1-signaling
#18
Ayman M Mahmoud, Amr R Zaki, Manal E Hassan, Gomaa Mostafa-Hedeab
The objective of the current study was to investigate the possible chemopreventive activity of Commiphora molmol resin (myrrh) extract using a rat model of diethylnitrosamine (DEN)/phenobarbital (PB)-induced early stage hepatocarcinogenesis. Here, we pointed to the modulatory effect of myrrh on oxidative stress, angiogenesis, inflammation and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Hepatocarcinogenesis was induced in Wistar rats using DEN for initiation and PB as a promoting agent. The rats received 125 or 250 mg/kg C...
April 14, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28413959/chemopreventive-properties-of-tolfenamic-acid-a-mechanistic-review
#19
David Feldman, Elizabeth Leahy, Seong-Ho Lee
Tolfenamic acid is one of the conventional non-steroidal anti-inflammatory drugs (NSAIDs) commonly used for the treatment of inflammation, migraines and pain. There has been a growing body of experimental evidence that tolfenamic acid possesses anti-cancer activity. However, in order to develop a therapeutic strategy using tolfenamic acid for the treatment of cancer, further research is required to highlight reliable cellular and molecular mechanisms of anti-cancer properties. Tolfenamic acid has been shown to alter the expression of several genes that represent cancer hallmarks including apoptosis, growth arrest, angiogenesis and metastasis...
April 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28412747/selenomethionine-and-methyl-selenocysteine-multiple-dose-pharmacokinetics-in-selenium-replete-men
#20
James R Marshall, Raymond F Burk, Rochelle Payne Ondracek, Kristina E Hill, Marjorie Perloff, Warren Davis, Roberto Pili, Saby George, Raymond Bergan
According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast supplement containing selenium, 200 mcg/day, decreased the incidence of total cancer, cancers of the prostate, colon and lung, and cancer mortality. The active agent in the selenized yeast supplement was assumed to be selenomethionine (SEMET), although the supplement had not been well speciated. The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer...
February 17, 2017: Oncotarget
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