Photo of Amin I. Kassis,  PhD

Amin I. Kassis, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 398-2400
Fax: (617) 398-2469


amin_kassis@hms.harvard.edu

Amin I. Kassis, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Professor, Radiology, Harvard Medical School
  • Director, Radiation Biology and Experimental Radionuclide Therapy Section, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The major objective of the research in my laboratories is the development of radionuclide carrier systems suitable for the specific delivery of diagnostic and therapeutic radioactive moieties to cancerous cells. The goal is to maximize the effectiveness of radiotherapeutic agents while minimizing their toxicity to normal tissues. We have synthesized proprietary radiolabeled thymidine analogs (8 US issued patents) and documented their radiodiagnostic and radiotherapeutic potential following locoregional administration in tumor-bearing animals. These results represent promising observations on a novel approach to cancer treatment with unsealed radioactive sources. Pharmacokinetics studies in cancer patients have shown the approach to be equally effective. More recently, we have been developing a proprietary technology (Enzyme-Mediated Cancer Imaging and Therapy, 4 US issued patents, 7 US/International patents pending) that aim to irreversibly entrap and concentrate diagnostic and therapeutic radionuclides within solid tumors. When labeled with gamma or positron-emitting radionuclides, these molecules enable imaging (SPECT and PET) of solid tumors and their metastases. When labeled with energetic electron- or alpha-particles emitters, these prodrugs deposit therapeutic doses within solid tumors (technology licensed in 2010 by Sabik Medical, Inc.

Most recently, we have also been developing novel proprietary noninvasive blood- (or other bodily fluid) based cancer (and other disease) detection assays (4 issued International patents and 67 US and International pending patents). Using these assays, we have been able to detect cancer-specific signatures (genomic and proteomic) in tumor-bearing mice and in cancer patients. Specifically, these methodologies aim to enable the facile detection of (i) tumors present in an individual prior to the manifestation of pathologic signs and symptoms (screening), (ii) tumors in an individual suspected of having cancer (diagnosis), and (iii) tumor recurrence in an individual undergoing/following various treatments, e.g., radiation/chemo/etc. The results of recent ongoing studies have confirmed the capability of the SNEP blood assay in identifying patients with aggressive prostate cancer (high risk) and those with very low risk(technology licensed in 2011 by CellMDx, Inc.).

Publications

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  • Ngwa W, Korideck H, Kassis AI, Kumar R, Sridhar S, Makrigiorgos GM, Cormack RA. In vitro radiosensitization by gold nanoparticles during continuous low-dose-rate gamma irradiation with I-125 brachytherapy seeds. 2012. PubMed
  • Balagurumoorthy P, Xu X, Wang K, Adelstein SJ, Kassis AI. Effect of distance between decaying (125)I and DNA on Auger-electron induced double-strand break yield. Int J Radiat Biol 2012. PubMed
  • Mamlouk O, Balagurumoorthy P, Wang K, Adelstein SJ, Kassis AI. Bystander effect in tumor cells produced by Iodine-125 labeled human lymphocytes. Int J Radiat Biol 2012. PubMed
  • Pospisil P, Korideck H, Wang K, Yang Y, Iyer LK, Kassis AI. Computational and biological evaluation of quinazolinone prodrug for targeting pancreatic cancer. Chem Biol Drug Des 2012. PubMed
  • Yang Y, Adelstein SJ, Kassis AI. Target discovery from data mining approaches. Drug Discov Today 2012; 17 Suppl:S16-23. PubMed
  • Yang Y, Wang K, Li W, Adelstein SJ, Kassis AI. Human placental alkaline phosphatase-mediated hydrolysis correlates tightly with the electrostatic contribution from tail group. Chem Biol Drug Des 2011. PubMed
  • Balagurumoorthy P, Adelstein SJ, Kassis AI. Novel method for quantifying radiation-induced single-strand-break yields in plasmid DNA highlights 10-fold discrepancy. Anal Biochem 2011; 417:242-6. PubMed
  • Yang Y, Adelstein SJ, Kassis AI. General approach to identifying potential targets for cancer imaging by integrated bioinformatics analysis of publicly available genomic profiles. Mol Imaging 2011; 10:123-34. PubMed
  • Kassis AI. Molecular and cellular radiobiological effects of Auger emitting radionuclides. Radiat Prot Dosimetry 2011; 143:241-7. PubMed
  • Yang Y, Adelstein SJ, Kassis AI. Integrated bioinformatics analysis for cancer target identification. Methods Mol Biol 2011; 719:527-45. PubMed
  • Zhu X, Palmer MR, Makrigiorgos GM, Kassis AI. Solid-tumor radionuclide therapy dosimetry: new paradigms in view of tumor microenvironment and angiogenesis. Med Phys 2010; 37:2974-84. PubMed
  • Yang S Y, Adelstein J, Kassis AI. Putative molecular signatures for the imaging of prostate cancer. Expert Rev Mol Diagn 2009; 10:65-74. PubMed
  • Yang Y,Adelstein SJ,Kassis AI. Target discovery from data mining approaches. Drug Discov Today 2009; 14:147-54. PubMed
  • Rebischung C, Hoffmann D, Stefani L, Desruet MD, Wang K, Adelstein SJ, Artignan X, Vincent F, Gauchez AS, Zhang H, Fagret D, Vuillez J, Kassis AI, Balosso J. First human treatment of resistant neoplastic meningitis by intrathecal administration of MTX plus (125)IUdR. Int J Radiat Biol 2008; 84:1123-9. PubMed
  • Howell RW,Martin RF,Nikjoo H,Pomplun E,Terrissol M,Watanable R,Yasui L,Kassis AI,Adelstein SJ. Meeting overview. Int J Radiat Biol 2008; 84:957-8. PubMed
  • Singh A,Yang Y,Adelstein SJ,Kassis AI. Synthesis and application of molecular probe for detection of hydroxyl radicals produced by Na(125)I and gamma-rays in aqueous solution. Int J Radiat Biol 2008; 84:1001-10. PubMed
  • Balagurumoorthy P,Wang K,Adelstein SJ,Kassis AI. DNA double-strand breaks induced by decay of (123)I-labeled Hoechst 33342: role of DNA topology. Int J Radiat Biol 2008; 84:976-83. PubMed
  • Balagurumoorthy P,Adelstein SJ,Kassis AI. Method to eliminate linear DNA from mixture containing nicked circular, supercoiled, and linear plasmid DNA. Anal Biochem 2008; 381:172-4. PubMed
  • Kassis AI. Therapeutic radionuclides: biophysical and radiobiologic principles. Semin Nucl Med 2008; 38:358-66. PubMed
  • Balagurumoorthy P,Chen K,Adelstein SJ,Kassis AI. Auger electron-induced double-strand breaks depend on DNA topology. Radiat Res 2008; 170:70-82. PubMed
  • Wang K, Adelstein SJ, Kassis AI. DMSO increases radioiodination yield of radiopharmaceuticals. Appl Radiat Isot 2007; 66:50-9. PubMed
  • Yang Y,Pospisil P,Iyer LK,Adelstein SJ,Kassis AI. Integrative genomic data mining for discovery of potential blood-borne biomarkers for early diagnosis of cancer. PLoS ONE 2008; 3:e3661. PubMed
  • Kassis AI, Korideck H, Wang K, Pospisil P, Adelstein SJ. Novel prodrugs for targeting diagnostic and therapeutic radionuclides to solid tumors. Molecules 2008; 13:391-404. PubMed
  • Abdulhathi MB, Al-Salam S, Kassis A, Ghazal-Aswad S. Unusual presentation of cervical cancer as advanced ovarian cancer. Arch Gynecol Obstet 2007; 276:387-90. PubMed
  • Sgouros G, Knox SJ, Joiner MC, Morgan WF, Kassis AI. MIRD continuing education: Bystander and low dose-rate effects: are these relevant to radionuclide therapy? J Nucl Med 2007; 48:1683-91. PubMed
  • Singh A, Chen K, Adelstein SJ, Kassis AI. Synthesis of coumarin-polyamine-based molecular probe for the detection of hydroxyl radicals generated by gamma radiation. Radiat Res 2007; 168:233-42. PubMed
  • Wang K, Kirichian AM, Aowad AF, Adelstein SJ, Kassis AI. Evaluation of chemical, physical, and biologic properties of tumor-targeting radioiodinated quinazolinone derivative. Bioconjug Chem 2007; 18:754-64. PubMed
  • Pospisil P, Wang K, Al Aowad AF, Iyer LK, Adelstein SJ, Kassis AI. Computational modeling and experimental evaluation of a novel prodrug for targeting the extracellular space of prostate tumors. Cancer Res 2007; 67:2197-205. PubMed
  • Chen K, Aowad AF, Adelstein SJ, Kassis AI. Molecular-docking-guided design, synthesis, and biologic evaluation of radioiodinated quinazolinone prodrugs. J Med Chem 2007; 50:663-73. PubMed
  • Yasui LS, Chen K, Wang K, Jones TP, Caldwell J, Guse D, Kassis AI. Using Hoechst 33342 to target radioactivity to the cell nucleus. Radiat Res 2007; 167:167-75. PubMed
  • Chen K, Wang K, Kirichian AM, Al Aowad AF, Iyer LK, Adelstein SJ, Kassis AI. In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase-mediated cancer diagnosis and therapy. Mol Cancer Ther 2006; 5:3001-13. PubMed
  • Urashima T, Nagasawa H, Wang K, Adelstein SJ, Little JB, Kassis AI. Induction of apoptosis in human tumor cells after exposure to Auger electrons: comparison with gamma-ray exposure. Nucl Med Biol 2006; 33:1055-63. PubMed
  • Balagurumoorthy P, Chen K, Bash RC, Adelstein SJ, Kassis AI. Mechanisms underlying production of double-strand breaks in plasmid DNA after decay of 125I-Hoechst. Radiat Res 2006; 166:333-44. PubMed
  • Pospisil P, Iyer LK, Adelstein SJ, Kassis AI. A combined approach to data mining of textual and structured data to identify cancer-related targets. BMC Bioinformatics 2006; 7:354. PubMed
  • Kishikawa H, Wang K, Adelstein SJ, Kassis AI. Inhibitory and stimulatory bystander effects are differentially induced by Iodine-125 and Iodine-123. Radiat Res 2006; 165:688-94. PubMed
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