Dear Leonard Lauder:
I am writing to commend to your attention the work of Dr. Denise L. Faustman. See faustmanlab.org, pubmed.org faustman dl, and pubmed.org ristori + bcg. I believe that BCG should be freely available to all in the US.
I commend to your attention the literature on metformin as a warning to you to not be narrow minded in your reading and analysis of science and art. With each disease having its own foundation, a narrow and myopic view of the world is created to the detriment of many. While drinking at the Quarter Mile, a local bar,
I debated the usefulness of metformin and aspirin with one afflicted with breast cancer. With the aid of a cell and pubmed.org I produced a list of publications supporting the mechanism for metformin selectively killing cancer cells.
Breast Cancer Res. 2015 Dec;17(1):540. doi: 10.1186/s13058-015-0540-0. Epub 2015 Mar 3.
Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study.
Dowling RJ1, Niraula S, Chang MC, Done SJ, Ennis M, McCready DR, Leong WL, Escallon JM, Reedijk M, Goodwin PJ, Stambolic V.
Abstract
INTRODUCTION:
The anti-diabetic drug metformin exhibits potential anti-cancer properties, which are believed to involve both direct (insulin-independent) and indirect (insulin-dependent) actions. Direct effects are linked to activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and an inhibition of mammalian target of rapamycin (mTOR) signaling, while indirect effects are mediated by reductions in circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling. However, the in vivo impact of metformin on cancer cell signaling, and the factors governing sensitivity in patients remain unknown.METHODS:
Therefore, we conducted a neoadjuvant, single arm, "window of opportunity" trial examining the clinical and biological effects of metformin on breast cancer patients. Non-diabetic women with untreated breast cancer were given 500 mg of metformin three times a day for ≥2 weeks post diagnostic biopsy until surgery. Fasting blood and tumour samples were collected at diagnosis and surgery. Blood glucose and insulin were assayed to assess the physiologic effects of metformin, while immunohistochemical analysis of tumours was used to characterize cellular markers before and after treatment.RESULTS:
Levels of IR expression decreased significantly in tumours (P = 0.04) as did the phosphorylation status of protein kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase (ERK1/2, T202/Y204), AMPK (T172), and acetyl coA carboxylase (ACC, S79) (P = 0.0001, P <0.0001, P <0.005, and P = 0.02, respectively). All tumours expressed organic cation transporter 1 (OCT1), with 90% (35/39) exhibiting an Allred score of 5 or higher.CONCLUSIONS:
Reduced PKB/Akt and ERK1/2 phosphorylation, coupled with decreased insulin and IR levels, suggest insulin-dependent effects are important in the clinical setting. These results are consistent with beneficial anti-cancer effects of metformin and highlight key factors involved in sensitivity, which could be used to identify breast cancer patients who may be responsive to metformin based therapies.TRIAL REGISTRATION:
ClinicalTrials.gov NCT00897884 , May 8(th), 2009.Edward Spike Jr. See Ratner EJ The Lancet p.106 Jan. 14, 1978. Before Ratner's death he asserted orally and in writing the location of a previously unknown ALS pathology. I would like to see this published and explored as a fitting memorial to my friend.
Result Filters
Open Biol. 2013 Jan 8;3(1):120144. doi: 10.1098/rsob.120144.
Oxidants, antioxidants and the current incurability of metastatic cancers.
Watson J1.
Abstract
The
vast majority of all agents used to directly kill cancer cells
(ionizing radiation, most chemotherapeutic agents and some targeted
therapies) work through either directly or indirectly generating
reactive oxygen species that block key steps in the cell cycle. As
mesenchymal cancers evolve from their epithelial cell progenitors, they
almost inevitably possess much-heightened amounts of antioxidants that
effectively block otherwise highly effective oxidant therapies. Also key
to better understanding is why and how the anti-diabetic drug metformin
(the world's most prescribed pharmaceutical product) preferentially
kills oxidant-deficient mesenchymal p53(- -) cells. A much faster
timetable should be adopted towards developing more new drugs effective
against p53(- -) cancers.
Wall Street Journal
By
Melanie Grayce West
March 18, 2015 9:14 p.m. ET
2 COMMENTS
Cosmetics executive Leonard Lauder is giving future nurses a boost.
On Thursday, Hunter College will announce a $10 million gift from Mr. Lauder in support of its school of nursing. The gift will fund salaries and research to attract academics, provide scholarships for students, and enable the purchase and maintenance of equipment needed for instruction.
It is Mr. Lauder’s largest gift to Hunter and one of the biggest to any school of nursing, according to Hunter’s president, Jennifer Raab. The gift is named in memory of Mr. Lauder’s first wife, Evelyn, who died in 2011 from nongenetic ovarian cancer.
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The late Mrs. Lauder went to Hunter College, part of the City University of New York, graduating in 1958 with a degree in anthropology. She also attended Hunter’s high school. That education served as the foundation for her careers as a public-school teacher and an executive at Estée Lauder Cos., the cosmetics firm founded by Mr. Lauder’s parents.
In 1993, after she was diagnosed with breast cancer, Evelyn Lauder founded the Breast Cancer Research Foundation, a New York-based group that has become a national powerhouse for funding study of the disease.
In a recent interview, Mr. Lauder, 81 years old, said he was motivated to support nursing because of the care his late wife received from intuitive, skilled nurses during her many years in and out of hospitals. “I was hugely impressed with the nursing care, but also impressed with the fact that there weren’t that many young people entering nursing from New York or even from America,” Mr. Lauder said.
With the Affordable Care Act, he said, more people will be able to receive medical attention. To serve that demand, more nurses are needed.
“I have a long-term dream that we should and must have, over the next five to 10 years, more storefront walk-in clinics run by physician’s assistants, the highest level of nursing,” said Mr. Lauder. “If we want to be able to care for our population in the long-run and not skyrocket the cost of medical care, we need to eventually have far more of the services handled by people who are graduates of nursing schools.”
The gift follows several others to Hunter, including donations in support of the arts and regular grants in support of breast-cancer researchers. Mr. Lauder credits Hunter with setting his late wife on a road that has ultimately saved “many thousands of lives” through the work of the BCRF. And, he said, the late Mrs. Lauder, the product of the public education system, was also one of its biggest champions.
This type of gift is something of a departure for Mr. Lauder, who in recent years has earned headlines for his donation of $1 billion in artwork to the Metropolitan Museum of Art and for his support of the Whitney Museum of American Art.
Mr. Lauder said he was now turning more of his focus to two areas that need more attention: breast cancer and Alzheimer’s disease.
In response to a question about whether he has accelerated his giving in recent years, Mr. Lauder said: “Yeah. You can’t take it with you, can you?”
Write to Melanie Grayce West at melanie.west@wsj.com
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