i miss victor h auerbach & his. cousin ej ratner

in answer to your question i think you will find both aspirin and metformin to be useful to person of interest. as to dosing aspirin bottle has dosing range although one may likely exceed as desired particularly in view of  glioblastoma as target of  interest

World Neurosurg. 2018 Dec;120:e380-e391. doi: 10.1016/j.wneu.2018.08.080. Epub 2018 Aug 23.

Aspirin Affects Tumor Angiogenesis and Sensitizes Human Glioblastoma Endothelial Cells to Temozolomide, Bevacizumab, and Sunitinib, Impairing Vascular Endothelial Growth Factor-Related Signaling.

Navone SE1, Guarnaccia L1, Cordiglieri C2, Crisà FM1, Caroli M1, Locatelli M1, Schisano L1, Rampini P1, Miozzo M3, La Verde N4, Riboni L5, Campanella R1, Marfia G6.

Author information

1

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

2

Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy.

3

Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

4

Oncology Unit, Fatebenefratelli and Oftalmico Hospital, Milan, Italy.

5

Department of Medical Biotechnology and Translational Medicine, LITA-Segrate, University of Milan, Milan, Italy.

6

Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: giovanni.marfia@unimi.it.

Abstract

BACKGROUND:

Glioblastoma (GBM) is the most common and fatal human brain tumor, with the worst prognosis. The aberrant microenvironment, enhanced by the activation of proangiogenic mediators such as hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and their downstream effectors, sustain GBM malignancy. Proangiogenic signaling represents an attractive chemotherapeutic target. Recent evidence suggests a therapeutic benefit from aspirin (acetylsalicylic acid, or ASA) intake in reducing risk and cancer progression.

METHODS:

In the present study, human primary GBM-endothelial cells (ECs) were used to ascertain whether ASA could inhibit angiogenesis and improve cell sensitivity to drugs. The impact of ASA was observed by measuring cell viability, tube-like structure formation, migration, VEGF production, and proliferative, proangiogenic, and apoptotic modulators expression, such as HIF-1α/VEGF/vascular endothelial growth factor receptor/(VEGFR)-1/VEGFR-2, Ras/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase, phosphoinositide 3-kinase/AKT signaling axis, and Bcl-2-associated X protein/B-cell lymphoma 2 (BCL-2) ratio. Furthermore, we evaluated the effect of ASA alone or in combination with temozolomide (TMZ), bevacizumab (BEV), and sunitinib (SUN).

RESULTS:

Our data reported that ASA affected GBM-EC viability, tube-like structure formation, cell migration, and VEGF releasing in a dose-dependent manner and that combined treatments with TMZ, BEV, and SUN synergized to counteract proangiogenic cell ability. mRNA expression analysis displayed a marked effect of ASA in reducing VEGF, VEGFR-1, HIF-1α, RAS, mitogen-activated protein kinase kinase, AKT, and BCL-2, as well a combined anticancer effect of ASA together with TMZ, BEV, and SUN. Levels of HIF-1α, VEGFR-2, Bcl-2-associated X protein, and BCL-2 protein expression confirmed a positive trend.

CONCLUSIONS:

ASA and antiangiogenic therapies showed synergetic anticancer efficacy in human primary GBM-ECs. Thus, the combination of conventional chemotherapy with ASA may offer a new strategy to counteract tumor malignancy.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS: 

Angiogenesis; Aspirin; Endothelial cells; Glioblastoma; HIF-1α; VEGF

PMID:

 

30144594

 

DOI:

 

10.1016/j.wneu.2018.08.080