Efficacy of nimotuzumab (hR3) conjugated with 131I or 90Y in laryngeal carcinoma xenograft mouse model.

PURPOSE: The humanized monoclonal antibody hR3, both alone and in combination with other chemotherapeutic agents and radiotherapy, can be used to treat head and neck cancers. Substantial progress has been made in the development of targeted radioimmunotherapy using iodine-131 (131I) and yttrium-90 (90Y) radioisotopes in recent years. In the present study, we examined the efficacy of hR3 conjugated with 131I or 90Y to inhibit tumor growth in a laryngeal carcinoma xenograft tumor model. METHODS: hR3 was labeled with 131I or 90Y to generate the conjugates 131I-hR3 or 90Y-hR3. The conjugates were incubated with HEp-2 laryngeal carcinoma cells to evaluate binding capacity. The efficacy of the labeled hR3 conjugates to treat laryngeal cancer was also evaluated in nude mice inoculated with HEp-2 tumors. RESULTS: The purified radioimmunoconjugates with specific activities of 187-191 MBq/mg had radiochemical purity >98% and >80% immunoreactivity with HEp-2 cells. Mice with HEp-2 xenografts treated with 131I-hR3 or 90Y-hR3 showed reduced tumor volume and improved survival rates compared to the untreated control group and the group treated with unlabeled hR3. At equivalent doses, radioimmunotherapeutic hR3 labeled with 90Y had increased tumor inhibition activity compared to hR3 labeled with 131I. CONCLUSIONS: 131I-hR3 and 90Y-hR3 are promising targeted radiopharmaceuticals for treatment of head and neck cancers, especially laryngeal cancers.

Combination of vaccine-strain measles and mumps virus synergistically kills a wide range of human hematological cancer cells: Special focus on acute myeloid leukemia.

Through combining vaccine-derived measles and mumps viruses (MM), we efficiently targeted a wide range of hematopoietic cancer cell lines. MM synergistically killed many cell lines including acute myeloid leukemia (AML) cell lines. Further investigation suggested that enhanced oncolytic effect of MM was due to increased apoptosis induction. In an U937 xenograft AML mouse model, MM displayed greater tumor suppression and prolonged survival. Furthermore, MM efficiently killed blasts from 16 out of 20 AML patients and elicited more efficient killing effect on 11 patients when co-administered with Ara-C. Our results demonstrate that MM is a promising therapeutic candidate for hematological malignancies.

Hippocampal neuronal responses during signaled licking of gustatory stimuli in different contexts.

Neuroanatomical studies suggest that hippocampal formation (HF) receives information from all sensory modalities including taste via the parahippocampal cortices. To date, however, no neurophysiological study has reported that HF neurons encode taste information. In the present study, we recorded CA1 HF neurons from freely behaving rats during performance of a visually-guided licking task in two different triangular chambers. When a cue lamp came on, the rats were required to press a bar to trigger a tube to protrude into the chambers for 3 s. During this period, the rats could lick one of six sapid solutions: [0.1M NaCl (salty), 0.3M sucrose (sweet), 0.01 M citric acid (sour), 0.0001 M quinine HCl (bitter), 0.01 M monosodium L-glutamate (MSG, umami), and a mixture of MSG and 0.001 M disodium-5'-inosinate (IMP) (MSG+IMP)], and distilled water. Of a total 285 pyramidal and interneurons, the activity of 173 was correlated with at least one of the events in the task-illumination of cue lamps, bar pressing, or licking the solution. Of these, 137 neurons responded during licking, and responses of 62 of these cells were greater to sapid solutions than to water (taste neurons). Multivariate analyses of the taste neurons suggested that, in the HF, taste quality might be encoded based on hedonic value. Furthermore, the activity of most taste neurons was chamber-specific. These results implicate the HF in guiding appetitive behaviors such as conditioned place preference.