Combination Doxorubicin And Pdt For Ovarian Cancerbenefits Of Hpmacopolymer Conjugation

The efficacy of combining doxorubicin with a photosensitizer in the treatment of a human carcinoma (mesothelioma cell line H-MESO-1) was first reported by Brophy and Keller. 53 In vitro studies with the combination of free doxorubicin and using both dose and effect addition isobolographic analysis demonstrated independent activity, cooperativity, synergy and additivity in their combined toxicity against OVCAR- 3 (Figure 5). 54 Figure 5. Panel A. The dose-addition isobole analysis for the MTT...

References

Maeda, H., and Matsumura, Y., 1987, Tumouritropic and lymphotropic principles of macromolecular drugs. CRC Crit. Rev. Ther. Drug Carrier Syst. 6 193-210. 2. Suzuki, F., Pollard, R. B., Uchimura, S., Munakata, T., and Maeda, H., 1990, Role of natural killer cells and macrophages in the nonspecific resistance to tumors in mice stimulated with SMANCS, a polymer-conjugated derivative of neocarzinostatin. Cancer Res. 50 3897-3904. 3. ftjhova, B., Strohalm, J., Kubdfikovd, K., Jelinkova, M., Hovorka,...

Chemistry of Peginterferon alfa2a 40KD

Peginterferon alfa-2a (40KD) contains a 40KD branched PEG chain, each with an average molecular weight of 20KD. The two monomethoxy chains are joined via hydrolytically stable urethane bonds to a lysine linker molecule, one at the lysine group and another at the lysine group20. Linking the two 20KD chains via lysine is achieved in a one-step procedure by reacting lysine with monomethoxy PEG succinimidyl carbonate, and the resulting monomethoxy PEG-disubstituted lysine can then be purified by...

Enhanced Permeability and Retention EPR of HPMA Copolymer Anticancer Agents

Compounding interest in the efficacy of HPMA copolymer delivery is the fact that regardless of the presence or absence of a selective targeting moiety, HPMA copolymer-drug conjugates accumulate preferentially in solid tumors, through the enhanced permeability and retention (EPR) effect conceptualized by Maeda. 13,14,23 The EPR effect is attributed to 1) high vascular density in the tumor secondary to abnormal vascular architecture and angiogenesis 2) increased permeability of tumor vessels due...

PEGPAsp Dox Micelles

PEG-PAsp(Dox) micelles are a first generation of polymeric micellar drug developed in our laboratory (Fig. 2) 8, 50. In this formulation, Dox was covalently linked to the side chain of the PAsp segment via an amide bond between the carboxylic group in PAsp and the primary amino group of the glycosidyl residue in Dox. Chemical conjugation of Dox into the PAsp segment with substitution ratio of approximately 50 provided the PAsp segment with sufficient hydrophobicity to form a stable inner core...

Perspectives Of rMETase

A novel approach to the treatment of brain tumors with the combination of rMETase chemotherapeutic regimens that are currently used against such tumors has recently been carried out. The growth of Daoy, SWB77, and D- 54 xenografts implanted subcutaneously in athymic mice was arrested after the depletion of mouse plasma methionine (MET) with a combination of MET- and choline-free diet and rMETase. The treated tumor-bearing mice were rescued from the toxic effects of MET withdrawal with daily...

Info

Blood urea nitrogen (BUN), 167, 212 Bone marrow-cellularity, 36 Bradykinin, 36 C-26 bearing mive, 168 CA 125, 130, 188 CA 15-3, 130, 131 CA 19-9, 130, 131, 188 CA 72-4, 130, 131 Cancer colon, 95 non-small-cell lung, 95 ovarian, 95, 96 Camptothecin analog, 146 Carboxymethyldextran polyalcohol (CM-Dex-PA), 145 Carcinomatosis, 45 Cathepsins, 146 Cationic polymer, 33 CDDP- complexed PEG-PAsp (PEG-Pasp(CDDP)) block copolymers, 165 CDDP- complexed polymeric micelles, 165 Cisplatin...

Synthesis of PEGAsparaginase

E.coli asparaginase, a 140,000 dalton monomer, is composed of four subunits, each with an active site. PEG-asparaginase Oncaspar is prepared by reacting E. coli EC2 asparaginase with succinimidyl succinate-PEG, essentially as described by Abuchowski et al.16. PEG is attached to 64 of the 88 amino groups, or 14 PEG groups per subunit. The conjugate retains 51 of the original activity. A later paper by Ho et al.11 on the clinical pharmacology of PEG-asparaginase contains footnote data that can be...