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Biomedical subjects

A I Kassis

Publications and source records attributed to A I Kassis.

13 recordsLinked to original sources
PubMed1992

Intraperitoneal radioimmunotherapy of refractory ovarian carcinoma utilizing iodine-131-labeled monoclonal antibody OC125.

Refractory epithelial ovarian cancer is generally confined to the peritoneal cavity and is thus amenable to intraperitoneal (ip) therapy. Radiolabeled monoclonal antibodies raised to tumor-associated antigens offer the promise of selective tumor irradiation while reducing toxicity to normal tissues. We have conducted a phase I therapeutic trial to examine the feasibility of ip radioimmunotherapy utilizing escalating doses of 131I-labeled OC125 F(ab')2. Twenty-nine patients were each treated with a single dose of radiolabeled antibody. Twenty-eight patients were evaluable for dose-related toxicity. The toxicities most frequently observed were hematologic and gastrointestinal. Hematologic toxicity was noted in 5/14 (36%) patients receiving 18-87 mCi and in 12/14 (71%) receiving 100-144 mCi (P = 0.018). The median white blood cell nadir of 2-3K/microliters (range, 1.4-3.5K/microliters occurred at a median of 4.5 weeks and the median platelet nadir of 41K/microliters (range, 20-78K/microliters) at a median of 6.5 weeks. Mild gastrointestinal toxicity was observed in 4/14 patients (28%) at doses less than 100 mCi whereas at doses greater than or equal to 100 mCi, 11/14 (79%) patients developed nausea, vomiting, or chronic ileus (P = 0.021). This toxicity occurred most frequently in patients with protracted urinary 131I excretion. We conclude that 131I-labeled OC125 can be safely administered ip. Hematologic and gastrointestinal toxicity is predictable and related to the dose and rate of clearance of isotope.

Animals↗
PubMed1992

N-(m-[125I]iodophenyl)maleimide: an agent for high yield radiolabeling of antibodies.

In an effort to radiolabel antibodies, N-(m-[125I]iodophenyl)maleimide (m-[125I]IPM) was prepared by the demetallation of an N-[m-tri-(n-butyl)stannylphenyl]maleimide intermediate. The unlabeled intermediate was synthesized in greater than or equal to 75% yield using a palladium catalyzed reaction of hexabutylditin with m-bromoaniline, followed by reaction with maleic anhydride and ring annulation. All products were confirmed by NMR and elemental analysis. Labeling with 125I was carried out in a biphasic mixture containing chloramine-T (radiochemical yield greater than or equal to 70%). Rabbit IgG modified with the heterobifunctional crosslinking agent N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) and bovine serum albumin were conjugated with m-[125I]IPM (yield: 40 and 80%, respectively). In addition, m-[125I]IPM was conjugated to rabbit IgG subunits (HL) in 70% yield. The in vitro stability of the radiolabeled proteins in serum showed less than 1% deiodination over 24 h.

Animals↗
PubMed1992

m-[125I]iodoaniline: a useful reagent for radiolabeling biotin.

Biotinyl-m-[125I]iodoanilide (BIA) was synthesized by coupling biotin to m-[125I]iodoaniline via a mixed anhydride reaction. m-[125I]Iodoaniline was produced from the tin precursor, which was prepared using a palladium catalyzed reaction of hexabutylditin with m-bromoaniline. The radioiodinated BIA derivative is characterized by a stable amide and/or intact ureido group on the biotin molecule; it may thus be a useful carrier for targeting radionuclides to avidin-conjugated antibodies previously localized on tumors.

Aniline Compounds↗
PubMed1992

DNA damage produced in V79 cells by DNA-incorporated iodine-123: a comparison with iodine-125.

The neutral elution technique (pH 9.6) has been used to compare the damage produced in the DNA of V79 cells following the decay of the Auger-electron emitters 123I and 125I incorporated into DNA in the form of 5-[123I/125I]iodo-2'-deoxyuridine (123IdU, 125IdU) or after 60Co gamma irradiation. Elution profiles of retained radioactivity versus eluted volume were generally found to be nonlinear and partially dependent on the cell treatment prior to elution. Plots of a suitable function of radioactivity retention on the filters versus total decays for 123I or 125I and dose (Gy) for gamma radiation were linear. Assuming that each 125I decay produces one double-strand break (DSB), the 60Co efficiency in DSB production was found to be 53.4 DSBs/Gy/cell (or 17.8 DSBs/Gy/10(12) Da), in agreement with values reported previously. The decay of 123I led to 0.74 DSB/decay/cell if decays occurring only during nonrepair conditions were counted. This DSB production efficiency is in agreement with Monte Carlo semiempirical models of the action of radiation on DNA.

Animals↗
PubMed1979

Mouse antibody-dependent eosinophil and macrophage adherence and damage to schistosomula of Schistosoma mansoni.

The effects of sera from S. mansoni-infected mice together with eosinophil- and macrophage-rich peritoneal exudate cells (PEC) on the schistosomula were examined in vitro. Adherence to and killing of the parasite by PEC is mediated through a complement-independent opsonizing IgG. Destruction of schistosomula was assessed morphologically and by evaluating their infectivity to normal mice. By using ferritin-labeled anti-mouse immunoglobulin, the antibody was localized on the surface of the schistosomula and at the cell-organism areas of contact. The serum antibody activity appears with the onset of egg production, does not correlate well with the duration of infection, and is relatively specific among schistosome species. Eosinophils and macrophages were demonstrated by electron microscopy to adhere firmly to the surface of the organisms; the latter cells were shown invading the schistosomula. Furthermore, depletion of eosinophils by prior incubation of PEC with monospecific anti-eosinophil serum blocked the early adherence phase, but a substantial part of PEC ability to kill the schistosomula was retained.

Animals↗
PubMed1977

Host serum proteins in Echinococcus multilocularis: complement activation via the classical pathway.

The presence of host serum proteins, including IgG and IgM, within the cyst membranes and on the surface of protoscoleces of Echinococcus multilocularis was demonstrated by the use of HRPO-conjugated purified antisera. Viable protoscoleces incubated either in EDTA- or EGTA-fresh human sera were not lysed; the addition of calcium restored the protoscolecidal activity of the EGTA serum. It is concluded that the complement-mediated lysis of this metazoan organism proceeds via the classical pathway of complement activation. The results are discussed in relation to the ability of this parasite to survive in the immunologically hostile environment of the host.

Animals↗