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Nathan Goodyear

Ivermectin: enigmatic multifaceted 'wonder' drug continues to surprise and exceed expec... - 0 views

www.nature.com/ja201711

Ivermectin cancer

shared by Nathan Goodyear on 19 Mar 18 - No Cached
  • The avermectins are known to possess pronounced antitumor activity
  • Over the past few years, there have been steadily increasing reports that ivermectin may have varying uses as an anti-cancer agent, as it has been shown to exhibit both anti-cancer and anti-cancer stem cell properties
  • In human ovarian cancer and NF2 tumor cell lines, high-dose ivermectin inactivates protein kinase PAK1 and blocks PAK1-dependent growth
  • ...13 more annotations...
  • PAK1 is essential for the growth of more than 70% of all human cancers, including breast, prostate, pancreatic, colon, gastric, lung, cervical and thyroid cancers, as well as hepatoma, glioma, melanoma, multiple myeloma and for neurofibromatosis tumors
  • Ivermectin suppresses breast cancer by activating cytostatic autophagy, disrupting cellular signaling in the process, probably by reducing PAK1 expression
  • Cancer stem cells are a key factor in cancer cells developing resistance to chemotherapies and these results indicate that a combination of chemotherapy agents plus ivermectin could potentially target and kill cancer stem cells, a paramount goal in overcoming cancer
  • Triple-negative breast cancers, which lack estrogen, progesterone and HER2 receptors, account for 10–20% of breast cancers and are associated with poor prognosis
  • Ivermectin addition led to transcriptional modulation of genes associated with epithelial–mesenchymal transition and maintenance of a cancer stem cell phenotype in triple-negative breast cancers cells, resulting in impairment of clonogenic self-renewal in vitro and inhibition of tumor growth and metastasis in vivo
  • Ivermectin-induced cytostatic autophagy also leads to suppression of tumor growth in breast cancer xenografts, causing researchers to believe there is scope for using ivermectin to inhibit breast cancer cell proliferation and that the drug is a potential treatment for breast cancer
  • ivermectin synergizes with the chemotherapy agents cytarabine and daunorubicin to induce cell death in leukemia cells
  • Ivermectin inhibits proliferation and increases apoptosis of various human cancers
  • Activation of WNT-TCF signaling is implicated in multiple diseases, including cancers of the lungs and intestine,
  • A new screening system has found that ivermectin inhibits the expression of WNT-TCF targets
  • It represses the levels of C-terminal β-catenin phosphoforms and of cyclin D1 in an okadaic acid-sensitive manner, indicating its action involves protein phosphatases
  • In vivo, ivermectin selectively inhibits TCF-dependent, but not TCF-independent, xenograft growth without side effects
  • ivermectin has an exemplary safety record, it could swiftly become a useful tool as a WNT-TCF pathway response blocker to treat WNT-TCF-dependent diseases, encompassing multiple cancers.117
  • Nathan Goodyear on 19 Mar 18
     
    Ivermectin shows promise and usefullness in several cancer types.  This is a review article.
Nathan Goodyear

MRI for breast cancer screening, diagnosis, and treatment : The Lancet - 0 views

www.thelancet.com/...abstract

breast cancer MRI

shared by Nathan Goodyear on 18 Nov 11 - No Cached
  • Nathan Goodyear on 18 Nov 11
     
    new study sheds serious doubt on the benefit of breast MRI for breast cancer screening.  NO correlation to improved survival can be drawn.  Conclusion: "...to date do not show clear benefit for MRI."  
Nathan Goodyear

Twenty five year follow-up for breast cancer incidence and mortality of the Canadian Na... - 0 views

www.bmj.com/bmj.g366

mammograms mammogram breast cancer

shared by Nathan Goodyear on 12 Feb 14 - No Cached
  • Nathan Goodyear on 12 Feb 14
     
    Study that followed breast screening for 25 years with mammograms finds that no decrease in mortality from regular mammograms.
Nathan Goodyear

Drug Screening Identifies Niclosamide as an Inhibitor of Breast Cancer Stem-Like Cells - 0 views

journals.plos.org/...article

Niclosamide cancer cancer stem cells breast cancer

shared by Nathan Goodyear on 21 Mar 18 - No Cached
  • cancer stem cells may also contribute to tumor formation, metastasis, and treatment resistance
  • Studies have shown that some agents (such as metformin) can selectively target cancer stem cells and that dietary polyphenols, curcumin, peperine, and sulforaphane, which are derived from broccoli/broccoli sprouts, are able to target breast cancer stem cells via inhibition of the Wnt signaling, which affects mammosphere size and colony formation
  • niclosamide inhibits tumor growth and reduces tumor weight
  • ...8 more annotations...
  • Niclosamide treatment inhibited the expression of cyclin D1, Hes1, and PTCH by 33%, 57%, and 79%, respectively
  • The mechanism via which niclosamide, a protonophoric anthelmintic drug, induces stem-like-cell-specific toxicity in breast cancer is interesting. It is an old drug that has been used to treat tapeworms in animals
  • Niclosamide is known to uncouple mitochondrial oxidative phosphorylation during tapeworm killing
  • A screening of autophagy modulators revealed that niclosamide is a novel inhibitor of mTORC1 signaling
  • A recent work also demonstrated that niclosamide induces the apoptosis of myelogenous leukemic cells via the inactivation of NF-kappaB and reactive oxygen species generation
  • Niclosamide was also reported to inhibit Wnt signaling [31]–[33] in colon cancer cells
  • Our recent work demonstrated that niclosamide disrupts multiple metabolic pathways in ovarian-cancer-initiating cells
  • The present study showed that niclosamide treatment resulted in the downregulation of target genes involved in the self-renewal of cancer stem-like cells and inhibited breast SPS
  • Nathan Goodyear on 21 Mar 18
     
    Old ant-parasitic, niclosamide, found to down-regulate cancer stem cell activity.
Nathan Goodyear

Breast cancer mortality trends in England and the assessment of the effectiveness of ma... - 0 views

jrs.sagepub.com/...234.full

cancer mortality england MMG mammogram mammograms women's health breast screening breast cancer screening

shared by Nathan Goodyear on 11 Jun 13 - No Cached
  • Nathan Goodyear on 11 Jun 13
     
    40 year study out of England finds no mortality benefit from mammograms screening.
Nathan Goodyear

Dangers and Unreliability of Mammography: Breast Examination is a Safe, Effective, and ... - 0 views

www.preventcancer.com/...ijhs_mammography.htm

breast cancer mammograms scientific research evidence screening

shared by Nathan Goodyear on 17 Oct 11 - No Cached
  • Nathan Goodyear on 17 Oct 11
     
    nice review on the evidence surrounding mammograms
Nathan Goodyear

How a charity oversells mammography | BMJ - 1 views

www.bmj.com/bmj.e5132

breast cancer mammograms

shared by Nathan Goodyear on 07 Aug 12 - No Cached
  • Nathan Goodyear on 07 Aug 12
     
    This article reveals how data is massaged to promote a viewpoint. In this case mammograms.  Don't let your passions get the best of you, objectively review the data.  Scientists are not doing that these days. Mammograms do help and are needed in the screening, however, mammograms do cause harm and help to promote the same disease it seeks to detect early.  This is in some cases. Also, remember, mammograms are early detection, not prevention.
Nathan Goodyear

The risks associated with mammography screening may be approximately five times higher ... - 0 views

www.greenmedinfo.com/...ve-times-higher-previously-ass

mammogram risks risk radiation breast cancer

shared by Nathan Goodyear on 21 Oct 11 - No Cached
  • Nathan Goodyear on 21 Oct 11
     
    risks associated with mammogram are approximately 5 X higher than previously reported
Nathan Goodyear

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epitheli... - 0 views

www.pnas.org/E7301

Ivermectin cancer ovarian cancer oncogene oncogenes

shared by Nathan Goodyear on 20 Mar 18 - No Cached
  • we functionally validated a potent EOC oncogene, KPNB1, and showed its clinical relevance to human EOC
  • a well-established antiparasitic drug, ivermectin, has antitumor effects on EOC through its inhibition of KPNB1
  • EOC has high intertumor and intratumor heterogeneity at the molecular and epigenetic levels
  • ...22 more annotations...
  • the mortality rate of EOC has not been significantly changed for several decades
  • Sequencing revealed that almost all tumors (96%) had mutations in TP53, which serves as a major driver of this cancer
  • Low-prevalence but statistically significant mutations in nine other genes including NF1, BRCA1, BRCA2, RB1, and CDK12 were also identified, but the majority of genes were mutated at low frequency, making it difficult to distinguish between driver and passenger mutations
  • KPNB1 inhibition via any of three KPNB1 siRNAs or importazole treatment induced apoptosis in human EOC cell lines (Fig. 3 A–F and Fig. S4), and was accompanied by an increase in the expression levels of the proapoptotic proteins BAX and cleaved caspase-3
  • Stable overexpression of KPNB1 in SKOV3 and OVCAR3 (Fig. S6) significantly accelerated cell proliferation/survival (Fig. 5 A–C), confirming that KPNB1 functions as an oncogene in EOC
  • KPNB1 overexpression significantly decreased caspase-3/7 activity (Fig. 5D), in addition to the expression levels of cleaved caspase-3 and BAX proteins (Fig. 5E). KPNB1 overexpression also decreased p21 and p27 protein levels (Fig. 5E), as opposed to their increase by KPNB1 inhibition
  • KPNB1 functions as an antiapoptotic and proproliferative oncogene in EOC.
  • Patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1
  • KPNB1 acts as an oncogene in human EOC and represents a promising therapeutic target.
  • ivermectin treatment suppressed cell proliferation/viability in a dose-dependent manner (Fig. 7A), indicating that it exerts an antitumor effect on EOC
  • ivermectin also induced apoptosis
  • ivermectin increased the expression levels of BAX, and cleaved PARP, as well as p21 and p27
  • KPNB1 inhibition is responsible for the antitumor effect of ivermectin
  • we found that ivermectin synergistically reduced cell proliferation/viability in combination with paclitaxel in human EOC cells
  • Single treatment of ivermectin or paclitaxel reduced tumor growth in nude mice, but, notably, combination treatment of ivermectin and paclitaxel almost completely suppressed tumor growth
  • ERBB2, is amplified and overexpressed in many cancers, including breast (31), ovary (31), colon (32), bladder (33), non-small-cell lung (34), and gastric cancer (35), and is a poor prognostic factor in certain cancer types
  • KPNB1 was the second-highest-ranked gene identified in our screen
  • Increased KPNB1 protein levels have been reported in several cancers, including cervical cancer (42), hepatocellular carcinoma (43), and glioma (44), suggesting KPNB1’s oncogenic potential in these tumor types
  • our findings suggest that KPNB1 might serve as a master regulator of cell cycle by regulating several cell cycle-related proteins, including p21, p27, and APC/C family members
  • higher and/or more-frequent doses of ivermectin than currently approved for humans are well tolerated in humans
  • none of the mice in this study treated with the effective dosage of ivermectin for in vivo anticancer therapy showed severe adverse event
  • we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC cell lines than either drug alone
  • Nathan Goodyear on 20 Mar 18
     
    Ivermectin found to be pro-apoptotic for the epithelial ovarian cancer oncogene, KPNB1 in in Vivo study.  This effective anti-parasitic drug inhibits the KPNB1 oncogene.
Nathan Goodyear

AroER Tri-Screen™ is a Biologically Relevant Assay for Endocrine Disrupting C... - 0 views

toxsci.oxfordjournals.org/...toxsci.kfu023.abstract

Paxil paroxetine estrogen receptor agonist cancer breast prostate hormone hormones

shared by Nathan Goodyear on 19 Feb 14 - No Cached
  • Nathan Goodyear on 19 Feb 14
     
    Paxil is estrogen receptor agonist.  What is interesting about this is that the FDA just approved this as a non-hormonal way to reduce hot flashes--but it is paxil under a different name.  It is non-hormonal--yeah right.  The organization making the approval doesn't know what they are doing at worse, or like the IOM stated are not up with the latest scientific knowledge.
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