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.
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.
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.
What country in the world condones rape of a child age two?
Category: Australian Antipaedophile Party
Created: Tuesday, 20 November 2018 10:34
Written by Dr Russell Pridgeon - Family Court Hero
The answer is Australia.
It is important that Australians understand the de facto reality that has arisen in Australia, without being noticed or commented upon by anybody: incest is no longer considered to be a crime by the Child Protection authorities, the courts, or the parliaments of this country.
It is the nearest thing to an impossibility to have a child’s allegations of sexual abuse by a family member competently investigated: the authorities will make any excuse not to prosecute the offender.
The letter below was sent to a Federal MP who was reported in the media as being deeply opposed to child sexual abuse: there was no effective response: only a form letter from a secretary:
Guardianship prisoner June Lynne Lacey Bill has Do Not Resuscitate orders taken out against her and her families will.
Category: US public guardian corruption
Created: Sunday, 29 December 2019 07:56
Written by Administrator
June Lynne Lacey Bill - Guardianship prisoner with Do Not Resuscitate orders against her will - killed by by guardian who placed another 100 victims on DNR orders against their will.
June was put into guardianship when her daughter (and Power of Attorney) refused to sign a Do Not Resuscitate order at the hospitalist's request. June Lynne Lacey was taken prisoner due to a petition by social services and the hospital to remove her rights.
'She was forced into a nursing home against her will and against her family's wishes. When she protested, she was drugged and forced to take a 210 mile ambulance ride to a nursing home far from her home. She was not permitted to have a phone, not allowed to use a commode (forced to use only a bed pan), not allowed outside and given only day old food.
Within less than a month, she developed pneumonia, a staph infection, septic blood, a urinary tract infection, bedsores and a fever of 102! With an extraordinary will to live and with many prayers and faith in God, June miraculously recovered, only to be put in hospice by social services. She was forced to take oxycodone, which made it hard for her to breathe and swallow, caused an irregular heartbeat, migraines and seizures and gave her intense stomach and chest pain with horrific constipation and nauseousness!
She and her family begged to get rid of the oxycodone, but hospice and social services insisted she take it and refused her medical attention when it made her so sick! Consequently, June died! No one should be forced to die against their will and their families wishes. Health Care Directives should always be upheld and those with Power of Attorney should not be cast aside.
Please support the JUNE LYNNE LACEY BILL to ensure those most vulnerable amongst us are protected and their United States Constitutional rights upheld. (For more info go to junelynnelaceyfoundation.com.) June's rights were stripped from her. She has no right to life, liberty and the pursuit of happiness. Her freedoms were taken away, she was taken prisoner and received NO JUSTICE! PLEASE SPEAK OUT AGAINST THIS INJUSTICE! "-- Joyce Lacey
Source : https://www.facebook.com/397779416964315/posts/2635788203163414/
The Criminal Syndicate of Child Protectors
Category: Australian Antipaedophile Party
Created: Saturday, 06 April 2019 22:48
Written by Alecomm2
Wow. The media certainly didn't do any research before publishing this article. How disappointing. If you had the cohuna's you'd do some and then retract all the wording such as criminal syndicate - and go after the courts and the paedophiles that are running rampant particularly in Brisbane Magistrates Court building.
What a bunch of lying criminal poofters. The only people trafficking children are the federal courts, specifically Federal Magistrates like Jarrett and Coker, the criminal children’s representatives (traffickers) and the all-paedophile supporting court psychologists.