Background
Discovery and development of novel drugs that are capable of overcoming drug resistance in tumor cells are urgently needed clinically. In this study, we sought to explore whether ivermectin (IVM), a macrolide antiparasitic agent, could overcome the resistance of cancer cells to the therapeutic drugs.
Methods
We used two solid tumor cell lines (HCT-8 colorectal cancer cells and MCF-7 breast cancer cells) and one hematologic tumor cell line (K562 chronic myeloid leukemia cells), which are resistant to the chemotherapeutic drugs vincristine and adriamycin respectively, and two xenograft mice models, including the solid tumor model in nude mice with the resistant HCT-8 cells and the leukemia model in NOD/SCID mice with the resistant K562 cells to investigate the reversal effect of IVM on the resistance in vitro and in vivo. MTT assay was used to investigate the effect of IVM on cancer cells growth in vitro. Flow cytometry, immunohistochemistry, and immunofluorescence were performed to investigate the reversal effect of IVM in vivo. Western blotting, qPCR, luciferase reporter assay and ChIP assay were used to detect the molecular mechanism of the reversal effect. Octet RED96 system and Co-IP were used to determine the interactions between IVM and EGFR.
Results
Our results indicated that ivermectin at its very low dose, which did not induce obvious cytotoxicity, drastically reversed the resistance of the tumor cells to the chemotherapeutic drugs both in vitro and in vivo. Mechanistically, ivermectin reversed the resistance mainly by reducing the expression of P-glycoprotein (P-gp) via inhibiting the epidermal growth factor receptor (EGFR), not by directly inhibiting P-gp activity. Ivermectin bound with the extracellular domain of EGFR, which inhibited the activation of EGFR and its downstream signaling cascade ERK/Akt/NF-κB. The inhibition of the transcriptional factor NF-κB led to the reduced P-gp transcription.
Major Bust: Heroes helping mothers arrested in sting operation
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Category: Australian Antipaedophile Party
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Created: Monday, 08 July 2019 13:38
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Written by Administrator
Judiciary Using Criminal Justice System to Punish Mothers’ Allies
Physician Faces 25 Years; Others Face Long Prison Terms Too
"We do it because we cannot abide the thought of children being raped…If Australians knew about what was happening [in Family Court], they would be revolted by it. The scale is vast, the problem is huge. It is very sinister." - Dr. Russell Pridgeon, facing prison for helping mothers protect their children
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SIGN PETITION: www.change.org/p/attorney-general-christian-porter-dismiss-…
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"Operation Noetic"
Dr. Russell Pridgeon [pictured], Patrick O’Dea were arrested Thursday in “Operation Noetic”, a two-year sting instigated by family court judges to catch mothers in hiding and their supporters who helped them flee exes who were sexually abusing their children. Arthur Doubleday, 83, was indicted along with a 78 year-old woman, and police have threatened more arrests, effectively terrorizing the small community of brave and elderly citizens who help mothers protect their children when Family Court does not.
Coincidental electricity power station blow-ups or planned?
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Category: Blackrock, Vanguard and Statestreet
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Created: Sunday, 17 December 2023 03:09
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Written by Administrator
Why is it that the power plants that are having critical accidents or explosions in the US are owned by Blackrock or Vanguard? Con Edison in New York and the Hawaii electricity company that allegedly caused the Maui fires were also recently acquired by other Blackrock/Vanguard companies.). Coincidence you say? Let's see what blows up next ...
Protected to death in 2014 by the NSW Foster Care System
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Category: Child protection statistics
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Created: Friday, 18 November 2016 18:10
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Written by Administrator
Once again the governments own statistics prove children are at a risk of 8.4 times higher of dying when placed into foster care.
In 2014, 79 children died in NSW. 11 of those children were in out of home care. [1] This means that 7 % of the children who died were removed from parents [alive] and were protected to death by the department [FACS].
There were 1,400,000 children under the age of 15 years in NSW in 2014, [2] leaving a total of 1,373,576 children not in OOHC. And of those children, 68 died. There were 26,424 in out of home care NSW in 2014. [3] And of those children [in care] 11 of them died.
This means that:
- The rate of children dying in foster care is 1 child death per 2,402 children.
- And the rate of children dying not in foster care is 1 child death per 20,199 children.
[1] http://www.abc.net.au/worldtoday/content/2016/s4577393.htm
[2] http://www.abs.gov.au/ausstats/abs@.nsf/Previousproducts/3235.0Main%20Features152014?opendocument&tabname=Summary&prodno=3235.0&issue=2014&num=&view=
[3] https://aifs.gov.au/cfca/publications/child-abuse-and-neglect-statistics
Blackrock, Vanguard and StateStreet investing under 10% threshold in Aussie businesses to keep under capital gains tax threshold
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Category: Blackrock, Vanguard and Statestreet
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Created: Saturday, 16 December 2023 21:27
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Written by Administrator
In discussion with Senator Gerard Rennick in in senate estimates last week, the esteemed senator discussed capital gains taxes - or more specifically, lack thereof. Australian universities do not pay capital gains (CG) taxes on Australian students but they most certainly should be paying CG on international students. Indigenous land councils - who routinely take a whopping 40% in royalties before paying the people, should definitely pay capital gains, as should foreign investors - especially the big 3. (B,V & S, where S = BV).