Hiroshi Maeda
Sojo University, Japan
Keynote: Med chem
The HPMA-polymer-conjugated-THP [P-THP] showed sustain drug (pirarubicin) release only at tumor tissue, but no significant delivery to normal tissues was seen. The drug uptake studied by human pancreatic cancer cells showed that THP is taken-up more than 30-40 fold than another anthracyclines, eg. doxorubicin. The conjugate contains about 10% THP/ polymer (w/w), and exhibits about 40 kDa. In vivo evaluation of antitumor activity in experimental tumors reveald excellent delivery to primary and metastatic tumors, and remarkable antitumor activity was found below toxicity level. P-THP is tolerated more than 7-10 time of free THP equivalent in mice. We concludes superiority of P-THP is attributed to three points in regard to tumor selectivity: EPR-effect, tumor pH for drug-release and drug-uptake by transporter. Having these data in hand we applied P-THP to various human cancer patients, mostly from hospice with stage IV cancers, or inoperable and / or refused conventional chemotherapy, and asked present tratment. The dose of P-THP ranged 50 to 100 mg iv once, free-THPequivalent per week to 4 wks. Patients received multiple iv infusions. Patch-tape of isosorbide-dinitrate for NO release or ACEinhibitor (such as verapamil) was used to overcome tumor embolism. After iv-infusion prostate cancer became normal with PSA value in 3/4 pts in 4 wks, and 1 pt showed stabilization. Ovarian cancer pt (2/2) showed great improvement in CA19-9 and CA125 after 2-3 iv-infusion. Metastatic cancer in the bone, lung and lymph nodes were cleared. No toxicity was revealed in blood-counts, liver, kidney and neuronal-functions; no apatite-loss, no hair-loss were seen.
Hiroshi Maeda is a World renowned expert in macromolecular therapeutics. He created the World first polymeric-conjugate drug, SMANCS, approved for treatment of hepatoma in Japan. Consequently, he discovered the concept of EPR effect of macromolecular-drugs, ubiquitous mechanism for solid tumor selective targeting of polymeric drugs. He received MS, University of California, Devis, Fulbright student, PhD, MD, Tohoku University. He has published more than 450 papers in reputed journals. He was awarded Lifetime-Achievement-Award at Royal-Pharmaceutical-Society, Princess-Takamatsu-Award in Cancer Research, Tomizo- Yoshida-Award, highest award of Japan-Cancer-Assoc., and also selected as most cited influential scientist in pharmacology by Thomson Reuters 2014, and H-index of 89.
Email: hirmaeda@ph.sojo-u.ac.jp
Medicinal Chemistry received 6627 citations as per Google Scholar report
Spanish 
Chinese 
Russian 
German 
French 
Japanese 
Portuguese 
Hindi 