A Tale of Two Medicines
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A Tale of Two Medicines
Natural Medicine, Pharmaceuticals and GMO’s, the Good, the Bad and the OMG! - (The information provided is not intended to be a substitute for professional medical advice, diagnosis or treatment.  Never disregard professional medical advice, or delay in seeking it, because of something you have read on this scoopit page.)
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Northeastern lichens may yield drug against breast cancer

Northeastern lichens may yield drug against breast cancer | A Tale of Two Medicines | Scoop.it

Abundant in the lush hills of northeast India, a variety of plant-like organisms called lichens may hold the key to a potential drug against breast cancer that affects one in 28 women in India, according to a discovery by scientists here.

Attached to rocks and tree trunks and seen on the ground, these dual organisms are made up of a symbiotic association of fungus and alga and are known reservoirs of dyes and drugs.

India is home to more than 2,400 species of lichens - also included in the lower plants category along with mosses and ferns - or almost 16 percent of its global distribution.

 

Now, a team of five scientists at the Kolkata-based Bose Institute's Division of Molecular Medicine have shown that an extract of the tropical lichen species Parmotrema reticulatum (PRME) can "specifically" halt duplication of cancerous cells and trigger their death without harming normal cells.

Their medicinal properties have been attributed to the active compounds generated as a result of their mutually beneficial relationship, said Nripendranath Mandal, Associate Professor of the Division and leader of the research group involved in the study.

"The 70 percent methanolic extract PRME which we used possesses significant anti-cancer activity against breast cancer cells in the laboratory, that is, in vitro.

 

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The Emerging Role of MicroRNAs in the Regulation of Gene Expression by Nutrients.

The Emerging Role of MicroRNAs in the Regulation of Gene Expression by Nutrients. | A Tale of Two Medicines | Scoop.it

MicroRNAs (miRNAs) are a class of evolutionarily conserved, small non-coding RNAs of 19-24 nucleotides in length that regulate gene expression mostly at the posttranscriptional level. They are known to be involved in the control of different processes such as cell cycling, programmed cell death, cell differentiation, tumor development, metastasis, and sensing of nutrient stress. This review summarizes the evidence regarding the changes in miRNA expression that are caused by diets with a deficiency or augmented intake of nutrients such as amino acids, carbohydrates, fatty acids, vitamins, and phytochemicals. As diet is known to influence the expression of miRNAs, miRNA profiling has the potential to be useful in the assessment of nutritional status in dietary intervention studies. Additionally, as it can change miRNA expression, diet may be used as a therapeutic agent to treat many different diseases. Also, we explored here some ideas on therapeutics based on the manipulation of miRNA expression levels for dietary-derived diseases as well as the putative effect of food-derived miRNAs on host gene expression.

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Christian Yamashiba Kasongo's curator insight, February 23, 2014 12:20 AM

The Emerging Role of MicroRNAs in the Regulation of Gene Expression by Nutrients

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Epigallocatechin-3-Gallate Inhibits IGF-I-Stimulated Lung Cancer Angiogenesis through Downregulation of HIF-1α and VEGF Expression

Epigallocatechin-3-Gallate Inhibits IGF-I-Stimulated Lung Cancer Angiogenesis through Downregulation of HIF-1α and VEGF Expression | A Tale of Two Medicines | Scoop.it
Numerous studies have shown that epigallocatechin-3-gallate (EGCG), a polyphenol component extracted from green tea, can inhibit the growth and induce apoptosis of various types of human tumor cells. In this study, we evaluated the inhibitory effects of EGCG on the proangiogenic capabilities of A549 cells. Methods: A549 cells starved in serum-free culture medium for 24 h were pretreated with EGCG at various concentrations (0, 10, 25, 50, and 100 μmol/l) for 1 h, followed by the addition of insulin-like growth factor-I (IGF-I) at the final concentration of 40ng/ml and continued culturing for an additional 16 h. The in vitro angiogenesis analyzing test kit with ECMatrix™ gel was used to detect the formation of capillary tube-like structures. The mRNA expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) was determined by real-time PCR. The protein expression of HIF-1α and VEGFwas detected by Western blotting and ELISA, respectively. Results: EGCG significantly inhibited the formation of capillary tube-like structures on the surface of ECMatrix induced by IGF-Iboth in vitro and in vivo and reduced the level of hemoglobin in Matrigel plugs. In addition, EGCG was shown to significantly inhibit the IGF-I-induced upregulation of HIF-1α protein expression. Meanwhile, EGCG at the concentration of 25 and 100 μmol/l exhibited obvious inhibitory effects on IGF-I-induced VEGF expression (p < 0.01). Conclusion: Our results suggest that EGCG has potent inhibitory effects on tumor angiogenesis induced by IGF-I in human non-small cell lung cancer cells, which may possibly contribute to the downregulation of HIF-1α and VEGFexpression.
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Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial

The role of nutrition in the treatment of attention-deficit hyperactivity disorder (ADHD) is gaining international attention; however, treatments have generally focused only on diet restriction or supplementing with one nutrient at a time.

 

To investigate the efficacy and safety of a broad-based micronutrient formula consisting mainly of vitamins and minerals, without omega fatty acids, in the treatment of ADHD in adults.

 

This double-blind randomised controlled trial assigned 80 adults with ADHD in a 1:1 ratio to either micronutrients (n = 42) or placebo (n = 38) for 8 weeks (trial registered with the Australian New Zealand Clinical Trials Registry: ACTRN12609000308291).

 

Intent-to-treat analyses showed significant between-group differences favouring active treatment on self- and observer- but not clinician-ADHD rating scales. However, clinicians rated those receiving micronutrients as more improved than those on placebo both globally and on ADHD symptoms. Post hoc analyses showed that for those with moderate/severe depression at baseline, there was a greater change in mood favouring active treatment over placebo. There were no group differences in adverse events.

 

This study provides preliminary evidence of efficacy for micronutrients in the treatment of ADHD symptoms in adults, with a reassuring safety profile.

 

 

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Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells

Luteolin is a flavonoid commonly found in fruit and vegetables. This compound has been shown in laboratory conditions to have anti-inflammatory, anti-oxidant and anti-cancer properties but results from epidemiological studies have been less certain. New research published in BioMed Central’s open access journal BMC Gastroenterology shows that luteolin is able to inhibit the activity of cell signaling pathways (IGF and PI3K) important for the growth of cancer in colon cancer cells.

Colon cancer is the second most frequent cause of cancer-related death in the Western World. Colon cancer cells have elevated levels of IGF-II compared to normal colon tissues. It is thought that this is part of the mechanism driving uncontrolled cell division and cancer growth. Researchers from Korea showed that luteolin was able to block the secretion of IGF-II by colon cancer cells and within two hours decreased the amount of receptor (IGF-IR) precursor protein. Luteolin also reduced the amount of active receptor (measured by IGF-I dependent phosphorylation).

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Revealed: Big Pharma's hidden links to NHS policy, with senior MPs saying medical industry uses ‘wealth to influence government’

Revealed: Big Pharma's hidden links to NHS policy, with senior MPs saying medical industry uses ‘wealth to influence government’ | A Tale of Two Medicines | Scoop.it
NHS bosses allowed a lobbying company working for some of the world’s biggest drugs and medical equipment firms to write a draft report which could help shape future health policy. NHS England commissioned a group called the Specialised Healthcare Alliance (SHCA) to consult with patients’ groups, charities and health organisations and produce a report feeding into its future five-year strategy for commissioning £12bn of services.

 

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The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor–related apoptosis-inducing ligand

Dietary flavonoid apigenin is expected to have preventive and therapeutic potential against malignant tumors. In this report, we show for the first time that apigenin markedly induces the expression of death receptor 5 (DR5) and synergistically acts with exogenous soluble recombinant human tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) to induce apoptosis in malignant tumor cells. TRAIL is a promising candidate for cancer therapeutics due to its ability to selectively induce apoptosis in cancer cells. The combined use of apigenin and TRAIL at suboptimal concentrations induces Bcl-2-interacting domain cleavage and the activation of caspases-8, -10, -9, and -3. Furthermore, human recombinant DR5/Fc chimera protein and caspase inhibitors dramatically inhibit apoptosis induced by the combination of apigenin and TRAIL. On the other hand, apigenin-mediated induction of DR5 expression is not observed in normal human peripheral blood mononuclear cells. Moreover, apigenin does not sensitize normal human peripheral blood mononuclear cells to TRAIL-induced apoptosis. These results suggest that this combined treatment with apigenin and TRAIL might be promising as a new therapy against malignant tumors.

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Vitamin E Levels Given to Mice in New Cancer Study Far Exceed Safe Levels Found in Dietary Supplements

In response to a study, “Antioxidants Accelerate Lung Cancer Progression in Mice,” published yesterday in Science Translational Medicine, the Council for Responsible Nutrition (CRN), the leading trade association representing the dietary supplement industry, issued the following statement:


Statement by Duffy MacKay, N.D., vice president, scientific and regulatory affairs, CRN:


“This animal study used mega-doses of vitamin E on mice that were genetically modified to be predisposed to fast-growing cancer, generating what should have been another hypothesis worthy of discussion among scientists, but instead resulted in a rash of scare-mongering headlines that don’t reflect the weight of the study’s findings.

 

To put the study into context and what it means for the typical vitamin E supplement user, consider this. The mice were genetically engineered to develop fast-growing tumors and then given the equivalent of human doses of vitamin E that ranged between approximately 1,950 IU to 10,000 IU, which translates to approximately 90 to 450 times the recommended amount for consumers to avoid deficiency. Typical multivitamins target the Recommended Dietary Allowance (RDA) and typical single letter vitamin E supplements contain 200 IU to 400 IU daily, all well within the safety range between the RDA and the Tolerable Upper Levels (UL) established by the government.*

 

 

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Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation

Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation | A Tale of Two Medicines | Scoop.it

A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways.

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Inconclusive Findings: Now You See Them, Now You Don’t!

Inconclusive Findings: Now You See Them, Now You Don’t! | A Tale of Two Medicines | Scoop.it

The environmental health literature is rife with controversial papers that evoke criticism, support, and, most importantly, a desire to better understand the findings put forth by the authors. A research article by Séralini and colleagues (Séralini et al. 2012), published in the journal Food and Chemical Toxicology (FCT), is one such article resulting in considerable discourse (Arjó et al. 2013; Barale-Thomas 2013; Grunewald and Bury 2013; Ollivier 2013; Wagner et al. 2013; Sanders et al. 2013; Schorsch 2013; Séralini et al. 2013) and a call for new research (European Commission 2013). This is all part of the scientific process in a modern research environment. However, the retraction of the article by Séralini et al. from FCT sets a new precedent in the management of peer-reviewed publications that we believe has serious implications for environmental public health. The retraction announcement by the Editor-in-Chief specifically states, “Ultimately, the results presented (while not incorrect) are inconclusive, and therefore do not reach the threshold of publication for Food and Chemical Toxicology” (FCT 2013). The Editor-in-Chief also was very clear that he “found no evidence of fraud or intentional misrepresentation of the data.”

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Apple flavonoids inhibit growth of HT29 human colon cancer cells and modulate expression of genes involved in the biotransformation of xenobiotics

Apple flavonoids inhibit growth of HT29 human colon cancer cells and modulate expression of genes involved in the biotransformation of xenobiotics | A Tale of Two Medicines | Scoop.it
Flavonoids from fruits and vegetables probably reduce risks of diseases associated with oxidative stress, including cancer. Apples contain significant amounts of flavonoids with antioxidative potential. The objectives of this study were to investigate such compounds for properties associated with reduction of cancer risks. We report herein that apple flavonoids from an apple extract (AE) inhibit colon cancer cell growth and significantly modulate expression of genes related to xenobiotic metabolism. HT29 cells were treated with AE at concentrations delivering 5–50 µM of one of the major ingredients, phloridzin (“phloridzin-equivalents,” Ph.E), to the cell culture medium, with a synthetic flavonoid mixture mimicking the composition of the AE or with 5–100 µM individual flavonoids. HT29 cell growth was inhibited by the complex extract and by the mixture. HT29 cells were treated with nontoxic doses of the AE (30 µM, Ph.E) and after 24 h total RNA was isolated to elucidate patterns of gene expression using a human cDNA-microarray (SuperArray®) spotted with 96 genes of drug metabolism. Treatment with AE resulted in an upregulation of several genes (GSTP1, GSSTT2, MGST2, CYCP4F3, CHST5, CHST6, and CHST7) and downregulation of EPHX1, in comparison to the medium controls. The enhanced transcriptional activity of GSTP1 and GSTT2 genes was confirmed with real-time qRT-PCR. On the basis of the pattern of differential gene expression found here, we conclude that apple flavonoids modulate toxicological defense against colon cancer risk factors. In addition to the inhibition of tumor cell proliferation, this could be a mechanism of cancer risk reduction
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Christian Yamashiba Kasongo's curator insight, February 9, 2014 9:33 AM

Apple flavonoids inhibit growth of HT29 human colon cancer cells and modulate expression of genes involved in the

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Dormant Prostate Cancer Cells May be Reawakened by Factors Commonly Produced in Inflammatory Cells

Researchers in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute discovered in pre-clinical models that dormant prostate cancer cells found in bone tissue can be reawakened, causing metastasis to other parts of the body. Understanding this mechanism of action may allow researchers to intervene prior to disease progression.

 

"Understanding how and why dormant cells in bone tissue metastasize will aid us in preventing the spread of disease, prolonging survival and improving overall quality of life," said Chia-Yi "Gina" Chu, PhD, a researcher and postdoctoral fellow in the Uro-Oncology Research Program and lead author of the study published in the journal Endocrine-Related Cancer.

 

In the study, investigators found that cancerous cells in the bone were reawakened after exposure to RANKL, a signaling molecule commonly produced by inflammatory cells. Researchers then genetically engineered cells to overproduce RANKL and found that these cells could significantly alter the gene expression of surrounding dormant cells in lab studies and in laboratory mice, causing them to transform into aggressive cancer cells.

 

Researchers then injected these engineered RANKL cells directly into the blood circulation of laboratory mice, which caused dormant cells within the skeleton to reawaken, creating tumors within the bone. When the RANKL receptor or its downstream targets were blocked, tumors did not form.

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Christian Yamashiba Kasongo's curator insight, February 3, 2014 12:39 PM

Dormant Prostate Cancer Cells May be Reawakened by Factors Commonly Produced in Inflammatory Cells

Christian Yamashiba Kasongo's curator insight, February 5, 2014 3:59 PM

Dormant Prostate Cancer Cells May be Reawakened by Factors Commonly Produced in Inflammatory Cells

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Silibinin reverses drug resistance in human small-cell lung carcinoma cells

Silibinin reverses drug resistance in human small-cell lung carcinoma cells | A Tale of Two Medicines | Scoop.it

Small-cell lung carcinoma (SCLC) has a dismal prognosis in part because of multidrug resistance (MDR). Silibinin is a flavonolignan extracted from milk thistle (Silybum marianum), extracts of which are used in traditional medicine. We tested the effects of silibinin on drug-sensitive (H69) and multi-drug resistant (VPA17) SCLC cells. VPA17 cells did not show resistance to silibinin (IC50=60μM for H69 and VPA17). Flow cytometry analysis after incubation in 30μM silibinin showed no changes in cell cycle phases in VPA17 or H69 cells compared with untreated cells. Silibinin (30μM) incubation was pro-apoptotic in VPA17 cells after >3days, as measured by ELISA of BUdR labeled DNA fragments. Apoptosis was also indicated by an increase in caspase-3 specific activity and decrease in survivin in VPA17 MDR cells. VPA17 cells had increased Pgp-mediated efflux of calcein acetoxymethyl ester (calcein AM); however, this was inhibited in cells pre-incubated in silibinin for 5days. Pre-incubation of VPA17 cells in 30μM silibinin for 5days also reversed resistance to etoposide (IC50=5.50 to 0.65μM) and doxorubicin (IC50=0.625 to 0.035μM). The possible synergistic relationship between silibinin and chemotherapy drugs was determined by exposure of VPA17 cells to 1:1 ratios of their respective IC50 values, with serial dilutions at 0.25 to 2.0×IC50 and calculation of the combination index (CI). Silibinin and etoposide showed synergism (CI=0.46 at ED50), as did silibinin and doxorubicin (CI=0.24 at ED50). These data indicate that in SCLC, silibinin is pro-apoptotic, reverses MDR and acts synergistically with chemotherapy drugs. Silibinin, a non-toxic natural product may be useful in the treatment of drug-resistant SCLC.

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Christian Yamashiba Kasongo's curator insight, February 2, 2014 4:17 AM

Silibinin reverses drug resistance in human small-cell lung carcinoma cells

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Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study | A Tale of Two Medicines | Scoop.it

The results of this study, which is the largest to date and one of the first based on European populations, show that, compared with a mid-range concentration of 50 to 75.0 nmol/l, circulating 25-(OH)D levels lower than 50.0 nmol/l are associated with an increased risk of colorectal cancer. Although levels higher than 75.0 nmol/L were associated with a reduced colorectal cancer risk, the association was not significant compared with the mid-range concentration. Analyses by quintile of 25-(OH)D concentration, showed a dose-response decrease in colorectal cancer risk with increasing 25-(OH)D concentration. Participants in the highest quintile had a significant 40% lower risk of colorectal cancer than did those in the lowest quintile. Additionally, higher consumption of dietary calcium, but not dietary vitamin D, was found to be associated with a reduced risk of colorectal cancer.

 

Since the first suggestion that vitamin D may have a role in colorectal cancer risk, the association has been evaluated pre-diagnostically by only a few small studies.Most of these studies have shown inverse associations with colorectal cancer risk but the results have been based mainly on North American populations with different dietary and lifestyle habits than their western European counterparts. The strong inverse associations of the present study suggest that further research efforts should concentrate less on observational findings and more on clinically relevant studies to determine whether vitamin D has a causal role in colorectal cancer prevention or whether it is a marker of other events.

 

An important consideration for circulating 25-(OH)D levels is what concentration should be deemed sufficient for colorectal cancer protection. Results of a recent review and meta-analysis, which included around half as many cases as in our study suggest that a blood 25-(OH)D level of about 80.0 nmol/l results in a colorectal cancer risk reduction of roughly 50%

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Christian Yamashiba Kasongo's curator insight, February 23, 2014 12:19 AM

Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control studyajouter votre point de vue ...

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More Evidence Shows Whooping Cough Evolving In Response To Its Vaccine.

More Evidence Shows Whooping Cough Evolving In Response To Its Vaccine. | A Tale of Two Medicines | Scoop.it

Whooping cough is evolving in response to its vaccine. Want proof? In a new study, researchers found 30 percent of whooping cough bacteria in Australia have evolved.

 

We've reported on the evolution of whooping cough before. Researchers have found evolved pertussis, as whooping cough is scientifically known, in Finland, France, Italy, Japan and the U.S. As we previously reported, the evolved bacteria don't seem to be more dangerous than their predecessors. Nevertheless, the U.S. Centers for Disease Control and Prevention are keeping an eye on whooping cough's evolution. It could help explain another recent pertussis phenomenon: The newest pertussis vaccines seem to wear off much faster than older ones, leaving kids vulnerable at age 8 or 10 unless they get booster shots.

 

In Australia, researchers from several universities and hospitals examined samples of pertussis dating back to 1997. What they saw happening there mirrored what's happened in the U.S.

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Christian Yamashiba Kasongo's curator insight, February 23, 2014 12:24 AM

aj Plus éléments probants, de la coqueluche évolution en réponse à ses vaccins. Votre point de vue externe de ...

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Traditional Chinese Medicine May Be Beneficial in Diabetes Prevention

Traditional Chinese Medicine May Be Beneficial in Diabetes Prevention | A Tale of Two Medicines | Scoop.it

 

A recent randomized controlled trial in China suggests that giving pre-diabetic patients a medicinal herb mixture three times daily may help prevent a future diagnosis of type 2 diabetes. This trial was conducted over 11 sites in China and involved 389 pre-diabetic participants.

 

The patients were randomized to take either a placebo capsule three times daily before meals or a capsule containing a mixture of traditional Chinese herbs three times daily before meals. The herb mixture is called Tianqi and contains 10 herbs which have long been thought to improve blood glucose control. In addition to taking the capsules, both groups received diabetes education for a month and met with a nutritionist multiple times throughout the course of the study. The trial lasted for a year.

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Luteolin is effective in the non-small-cell lung cancer model with L858R/T790M EGFR mutation and erlotinib resistance

Luteolin is effective in the non-small-cell lung cancer model with L858R/T790M EGFR mutation and erlotinib resistance | A Tale of Two Medicines | Scoop.it

Non-small-cell lung cancer (NSCLC) is one of the most commonly diagnosed malignancies all over the world. The small-molecule tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) including gefitinib and erlotinib have been used widely for treating NSCLC. Unfortunately, nearly all patients eventually progress by acquired resistance after experiencing marked improvement on these drugs. Because there is no effective therapeutic strategy to treat NSCLC with acquired resistance to EGFR TKIs, we mainly evaluated the effects of luteolin on T790M mutant NSCLC cells.

 

The effect of luteolin on the viability of NSCLC cell and normal cells lines was investigated using the Cell Counting Kit-8 (CCK-8) assay. Luteolin-induced apoptosis was assessed by Bivariate FITC-Annexin V/ PI assay, and Western blot assay was used to test the apoptotic proteins. Co-immunoprecipitation was used to test the luteolin effect between Hsp90 and mutant EGFR. The effect of luteolin on the Akt/mTOR pathway was studied using Western blotting analysis, and the in vivo anti-tumour efficacy was examined in an xenograft model.

 

We found that luteolin exerted remarkable anti-tumorigenic effects on EGFR L858R/T790M mutation and erlotinib-resistant NSCLC both at cell and animal levels. Mechanistically, luteolin induced EGFR degradation through inhibiting the association of Hsp90 and mutant EGFR and therefore obviously prevented PI3K/AKT/mTOR signalling and led to NSCLC cell apoptosis.

 

Our investigation suggests that luteolin may act as a potential candidate for NSCLC therapy especially for treatment to acquired erlotinib-resistant NSCLC patients.

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Christian Yamashiba Kasongo's curator insight, February 23, 2014 12:30 AM

aLuteolin is effective in the non-small-cell lung cancer model with L858R/T790M EGFR mutation and erlotinib resistancejouter votre point de vue ...

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Inhibition of Lung Cancer Growth in Mice by Dietary Mixed Tocopherols

Inhibition of Lung Cancer Growth in Mice by Dietary Mixed Tocopherols | A Tale of Two Medicines | Scoop.it

Tocopherols are lipophilic antioxidants found in vegetable oils. Here, we examined the growth inhibitory effect of a γ-tocopherol-enriched tocopherol mixture (γTmT) against CL13 murine lung cancer cells grown in culture and as subcutaneous tumors in A/J mice. We found γTmT had no effect after 2 d and weakly inhibited the growth of CL13 in culture after 5 d (28% growth inhibition at 80 µM). Dietary treatment with 0.1% and 0.3% γTmT for 50 d inhibited the growth of CL13 tumors in A/J mice by 53.9 and 80.5%, respectively. Histopathological analysis revealed an increase in tumor necrosis compared to control tumors (80% and 240% increase by 0.1% and 0.3% γTmT, respectively). Dietary treatment with γTmT dose-dependently increased γ- (10.0 – 37.6-fold) and δ-tocopherol (8.9 – 26.7-fold) in the tumors of treated mice compared to controls. Dietary treatment with γTmT also increased plasma γ- (5.4 – 6.7-fold) and δ-tocopherol (5.5 – 7-fold). Whereas others have demonstrated the cancer preventive activity of γTmT against mammary and colon cancer, this is the first report of growth inhibitory activity against lung cancer. Further studies are needed to determine the underlying mechanisms for this anticancer activity, and to determine if such activity occurs in other models of cancer.

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Inactivation of Pathogenic Viruses by Plant-Derived Tannins: Strong Effects of Extracts from Persimmon (Diospyros kaki) on a Broad Range of Viruses

Inactivation of Pathogenic Viruses by Plant-Derived Tannins: Strong Effects of Extracts from Persimmon (Diospyros kaki) on a Broad Range of Viruses | A Tale of Two Medicines | Scoop.it

Tannins, plant-derived polyphenols and other related compounds, have been utilized for a long time in many fields such as the food industry and manufacturing. In this study, we investigated the anti-viral effects of tannins on 12 different viruses including both enveloped viruses (influenza virus H3N2, H5N3, herpes simplex virus-1, vesicular stomatitis virus, Sendai virus and Newcastle disease virus) and non-enveloped viruses (poliovirus, coxsachievirus, adenovirus, rotavirus, feline calicivirus and mouse norovirus). We found that extracts from persimmon (Diospyros kaki), which contains ca. 22% of persimmon tannin, reduced viral infectivity in more than 4-log scale against all of the viruses tested, showing strong anti-viral effects against a broad range of viruses. Other tannins derived from green tea, acacia and gallnuts were effective for some of the viruses, while the coffee extracts were not effective for any of the virus. We then investigated the mechanism of the anti-viral effects of persimmon extracts by using mainly influenza virus. Persimmon extracts were effective within 30 seconds at a concentration of 0.25% and inhibited attachment of the virus to cells. Pretreatment of cells with the persimmon extracts before virus infection or post-treatment after virus infection did not inhibit virus replication. Protein aggregation seems to be a fundamental mechanism underlying the anti-viral effect of persimmon tannin, since viral proteins formed aggregates when purified virions were treated with the persimmon extracts and since the anti-viral effect was competitively inhibited by a non-specific protein, bovine serum albumin. Considering that persimmon tannin is a food supplement, it has a potential to be utilized as a safe and highly effective anti-viral reagent against pathogenic viruses.

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Flavonoid apigenin modified gene expression associated with inflammation and cancer and induced apoptosis in human pancreatic cancer cells through inhibition of GSK-3β/NF-κB signaling cascade

Flavonoid apigenin modified gene expression associated with inflammation and cancer and induced apoptosis in human pancreatic cancer cells through inhibition of GSK-3β/NF-κB signaling cascade | A Tale of Two Medicines | Scoop.it

The objective was to examine the inhibitory effects of citrus fruit bioactive compounds on BxPC-3 and PANC-1 human pancreatic cancer cells, focusing on the antiproliferative mechanism of action of the flavonoid apigenin related to the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway.

 

Flavonoids, limonoids, phenolic acids, and ascorbic acid were tested for cytotoxic effects on BxPC-3 and PANC-1 cells; apigenin was the most potent (IC50 = 23 and 12 μM for 24 and 48 h for BxPC-3 and IC50 = 71 and 41 μM for 24 and 48 h for PANC-1). Apigenin induced pancreatic cell death through inhibition of the glycogen synthase kinase-3β/nuclear factor kappa B signaling pathway. Apigenin arrested cell cycle at G2/M phase (36 and 32% at 50 μM for BxPC-3 and PANC-1, respectively) with concomitant decrease in the expression of cyclin B1. Apigenin activated the mitochondrial pathway of apoptosis (44 and 14% at 50 μM for BxPC-3 and PANC-1, respectively) and modified the expression of apoptotic proteins. Apigenin highly upregulated the expression of cytokine genes IL17F (114.2-fold), LTA (33.1-fold), IL17C (23.2-fold), IL17A (11.3-fold), and IFNB1 (8.9-fold) in BxPC-3 cells, which potentially contributed to the anticancer properties.

 

Flavonoids have a protective role in pancreatic cancer tumorigenesis.

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Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation

Genome-wide analysis discloses reversal of the hypoxia-induced changes of gene expression in colon cancer cells by zinc supplementation | A Tale of Two Medicines | Scoop.it

Hypoxia-inducible factor 1 (HIF-1), the major transcription factor specifically activated during hypoxia, regulates genes involved in critical aspects of cancer biology, including angiogenesis, cell proliferation, glycolysis and invasion. The HIF-1a subunit is stabilized by low oxygen, genetic alteration and cobaltous ions, and its over-expression correlates with drug resistance and increased cancer mortality in various cancer types, therefore representing an important anticancer target. Zinc supplementation has been shown to counteract the hypoxic phenotype in cancer cells, in vitro and in vivo, hence, understanding the molecular pathways modulated by zinc under hypoxia may provide the basis for reprogramming signalling pathways for anticancer therapy. Here we performed genome-wide analyses of colon cancer cells treated with combinations of cobalt, zinc and anticancer drug and evaluated the effect of zinc on gene expression patterns. Using Principal Component Analysis we found that zinc markedly reverted the cobalt-induced changes of gene expression, with reactivation of the drug-induced transcription of pro-apoptotic genes. We conclude that the hypoxia pathway is a potential therapeutic target addressed by zinc that also influences tumor cell response to anticancer drug.

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Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells

Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells | A Tale of Two Medicines | Scoop.it

Retinoic acid (RA) is a small molecular derivative of vitamin A that is stored in quiescent stellate cells in pancreas stroma. Cancer associated fibroblasts (CAFs) are activated fibroblast cells in pancreatic ductal adenocarcinoma tumor microenvironment. We treated CAFs with RA and found that these cells became static due to the low expression of α-SMA, FAP, and IL-6 and decreased production of extracellular matrix (ECM). Furthermore, we verified that the low secretion of IL-6 from CAFs was related to RA-induced inhibition of migration and epithelial-mesenchymal transition (EMT) of tumor cells. However, RA could not inhibit the migration and EMT of tumor cells directly. Therefore, our study showed that one of the therapeutic effects of RA on tumor cells is through its modulation of CAFs in tumor microenvironment. The tumor microenvironment plays an important role in promoting tumor migration and might be a promising target of biological treatment.

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Freeze-Dried Black Raspberry Gel Induces Clinical and Histologic Regression and Reduces Loss of Heterozygosity Events in Premalignant Oral Intraepithelial Lesions.

Approximately 30% higher-grade premalignant oral intraepithelial neoplasia (OIN) lesions will progress to oral cancer. While surgery is the OIN treatment mainstay, many OIN lesions recur which is highly problematic for both surgeons and patients. This clinical trial assessed the chemopreventive efficacy of a natural-product based bioadhesive gel on OIN lesions.

 

This placebo-controlled multicenter study investigated the effects of topical application of bioadhesive gels that contained either 10% w/w freeze dried black raspberries (BRB) or an identical formulation devoid of BRB placebo to biopsy-confirmed OIN lesions (0.5 gm x q.i.d., 12 weeks). Baseline evaluative parameters (size, histologic grade, LOH events) were comparable in the randomly assigned BRB (n=22) and placebo (n=18) gel cohorts. Evaluative parameters were: histologic grade, clinical size and loss of heterozygosity (LOH).

 

Topical application of the BRB gel to OIN lesions resulted in statistically significant reductions in lesional sizes, histologic grades and LOH events. In contrast, placebo gel lesions demonstrated a significant increase in lesional size and no significant effects on histologic grade or LOH events. Collectively, these data strongly support BRB's chemopreventive impact. A cohort of very BRB-responsive patients-as demonstrated by high therapeutic efficacy-was identified. Corresponding protein profiling studies, which demonstrated higher pretreatment levels of BRB metabolic and keratinocyte differentiation enzymes in BRB-responsive lesions, reinforce the importance of local metabolism and differentiation competency.

 

Results from this trial substantiate the LOH reductions identified in the pilot BRB gel study and extend therapeutic effects to significant improvements in histologic grade and lesional size.

Jonathan Middleton's insight:

Interesting that the black Raspberry gel reduces "Loss of heterozygosity (LOH)" an event that results in loss of a gene and the surrounding chromosomal region.

 

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Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes

Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue. Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, (b) increased ceramide levels, and (c) up-regulated mRNA levels of the stress protein p8. These effects were prevented by blockade of the CB2 cannabinoid receptor or by pharmacologic inhibition of ceramide synthesis de novo. Knockdown experiments using selective small interfering RNAs showed the involvement of p8 via its downstream endoplasmic reticulum stress–related targets activating transcription factor 4 (ATF-4) and TRB3 in Δ9-tetrahydrocannabinol–induced apoptosis. Cannabinoids also reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue. In conclusion, results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress–related genes ATF-4 and TRB3. These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer.

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Christian Yamashiba Kasongo's curator insight, February 5, 2014 3:57 PM

Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes

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Dietary Supplements: Harmful or Essential? Cutting Through the Unrelenting Rhetoric

Dietary Supplements: Harmful or Essential? Cutting Through the Unrelenting Rhetoric | A Tale of Two Medicines | Scoop.it

What a firestorm! Ever since Dr. Paul Offit's book, "Do you Believe in Magic: The Sense and Nonsense of Alternative Medicine" was released last summer, there's been a burst of new negative dietary supplement study results and position papers. Editorials, featuring provocative headlines such as: Enough is Enough: Stop Wasting Money on Vitamin and Mineral Supplements and Don't Take Your Vitamins, have been published in prominent medical journals and major media outlets, many authored or co-authored by the omnipresent Offit, himself.

 

In response to the loud and growing chorus of conventional and academic physicians opposing dietary supplementation, The Council for Responsible Nutrition, Natural Products Association and Life Extension Foundation have released their own statements.

 

This article attempts to break through the din and unremitting confusion sown by the media whir around dietary supplements, the industry that champions their use and public health in general.

 

First, a few disclosures: FON Therapeutics currently consults and collaborates with several nutraceutical companies. I also admit to personally ingesting a significant amount of supplements ever since working at a mom and pop health food store in 1980, and in even greater quantities when diagnosed with 'incurable' leukemia in 1991.

Can I objectively write on this topic? You be the judge.

 

My success achieving complete remission of chronic lymphocytic leukemia without traditional intervention and using quality nutraceuticals as part of a comprehensive, personalized integrative cancer therapy regimen has been well-documented by my oncologist, Lee Nadler, MD, a Harvard Medical School dean and one of the World's largest NIH funded investigators for cancer and HIV/AIDS.

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Christian Yamashiba Kasongo's curator insight, February 2, 2014 4:14 AM

Dietary Supplements: Harmful or Essential? Cutting Through the Unrelenting Rhetoric

Christian Yamashiba Kasongo's curator insight, February 9, 2014 9:38 AM

Dietary Supplements: Harmful or Essential? Cutting Through the Unrelenting Rhetoric