Daunomycin was coupled to dextrans of various molecular sizes. The binding to the dextran carriers augmented the therapeutic efficacy of the antitumor agent in a murine lymphoma line (YAC). When the treatment with the drug or its conjugates was given concomitantly with the tumor cells at separate sites, the unbound drug was able, at its optimally effective doses, to prevent tumors in 40% of the mice, whereas the drug-dextran was efficient in 80% of the mice. The advantage of the drug-dextran over the free drug was also manifested when the treatment was given 6 days after tumor transplantation. However, a further delay of the treatment resulted in a decrease in the potency of the drug-dextran. Similar behavior was observed when increasing tumor loads were transplanted (10(5)-10(8) cells) and when the treatment was administered immediately. The most favorable effect of the drug-dextran was obtained with 10(7) cells, but against 10(8) cells neither the free drug nor the bound one was effective.
Conjugates of daunomycin covalently coupled, either directly or through a dextran bridge, t o antibodies reacting selectively with tumor cells, were tested for their capacity t o suppress tumor development in mice. The drug-antibody conjugates, or mixtures of drug and antibody, were compared either to the free drug or t o the drug coupled to normal immunoglobulin for their effect on two tumor systems. In the f i r s t case, a plasmacytoma (PCS), both the drug and the tumor cells were administered by the same route, namely, intraperitoneally (IP). The drug bound 'to antibody had no advantage over the free drug, but was better than the drug bound t o normal immunoglobulin. The best results were obtained in this system when daunomycin was given in a mixture with the antitumor antibody. In the second system, a lymphoma (Yac), the treatment and the tumor were administered by different routes-while the tumor was transplanted IP, the treatment was given intravenously (IV). The extent of conjugation was greatly increased in this system by introducing a dextran bridge between the drug and the antibody. In the Yac system, the anti-tumor antibodies were purified for some of the in vivo experiments. A t high doses, the daunomycin-dextran-anti-Yac antibody conjugate was superior t o the free drug but no better than daunomycin bound t o dextran alone or through dextran t o normal immunoglobulin. A t low doses, an advantage for the binding t o specific tumor antibody rather than t o normal immunoglobulin was observed. O n the basis of these data we believe that further improvement in the conjugation techniques, and the development of antibodies with better specificity towards the tumor cells, could lead towards successful use of antibody carriers in chemotherapy.
Stimulation of thymocytes in vitro by spleen cells differing for the entire H-2 complex leads to a significant proliferative response without a significant cell-mediated lympholysis (CML) response. Addition of soluble cell-free supernates (SF), (taken from a 7-day mixed leukocyte culture) enables these cultures to develop CML response. For optimal CML response, the SF has to be added within 48 h of onset of cultures. Although with spleen cells as responding cells, SF could quantitatively replace I-region different stimulating cells for generation of CML responses, with thymocytes as responding cells, stimulation with I-region cells appeared obligatory for the generation of CML responses. The implications of these findings are discussed.
The mobile network operators (MNOs) are looking into economically viable backhaul solutions as alternatives to fiber, specifically the hybrid fiber coaxial networks (HFC). When the latencies from both the wireless and the HFC networks are added together, the result is a noticeable end-to-end system latency, particularly under network congestion. In order to decrease total system latency, we proposed a method to improve upstream userto-mobile core latency by coordinating the LTE and HFC scheduling in previous papers. In this paper, we implement and optimize the proposed method on a custom LTE and DOCSIS end-to-end system testbed. The testbed uses the OpenAirInterface (OAI) platform for the LTE network, along with Cisco's broadband router cBR-8 that is currently deployed in the HFC networks around the world. Our results show a backhaul latency improvement under all traffic load conditions.
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