Beta-endorphin cell therapy for cancer prevention.

ß-Endorphin (BEP)-producing neuron in the hypothalamus plays a key role in bringing the stress axis to a state of homeostasis and maintaining body immune defense system. Long-term delivery of BEP to obtain beneficial effect on chemoprevention is challenging, as the peptides rapidly develop tolerance. Using rats as animal models, we show here that transplantation of BEP neurons into the hypothalamus suppressed carcinogens- and hormone-induced cancers in various tissues and prevented growth and metastasis of established tumors via activation of innate immune functions. In addition, we show that intracerebroventricular administration of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) increased the number of BEP neurons in the hypothalamus, reduced the stress response, enhanced the innate immune function, and prevented tumor cell growth, progression, and metastasis. BEP neuronal supplementation did not produce any deleterious effects on general health but was beneficial in suppressing age-induced alterations in physical activity, metabolic, and immune functions. We conclude that the neuroimmune system has significant control over cancer growth and progression, and that activation of the neuroimmune system via BEP neuronal supplementation/induction may have therapeutic value for cancer prevention and improvement of general health.

Precursors of the purine backbone augment the inhibitory action of hypoxanthine and dibutyryl cAMP on mouse oocyte maturation.

In this study we have tested the hypothesis that precursors of the purine base backbone--glutamine, glycine, aspartic acid, and formate--promote meiotic arrest when included in medium containing established meiotic inhibitors and that this occurs in glucose-dependent fashion. An initial experiment established that in medium supplemented with 4 mM hypoxanthine and containing no purine precursors, very little meiotic arrest was maintained in cumulus cell-enclosed oocytes after 17-18 hr (90% germinal vesicle breakdown; GVB). Increasing concentrations of glucose reduced the maturation percentage such that only 57% had matured at 0.55 mM. The addition of 2 mM glutamine (Gln) alone reduced the maturation percentage in the absence of glucose (70% GVB), and the further addition of glucose revealed an additive inhibitory effect between these two supplements. Dose response experiments with Gln, glycine (Gly), aspartic acid and formate showed that in medium supplemented with hypoxanthine, very little inhibitory action was observed in the absence of glucose but that upon addition of this hexose, a dramatic decrease in maturation percentage was observed in the Gln and Gly groups. Results of experiments using combinations of precursors showed that when Gln and Gly were added together, greater augmentation of meiotic arrest maintained by either hypoxanthine or dibutyryl cAMP was achieved in the presence of glucose than with either amino acid alone. The addition of purine precursors significantly increased the extent of purine nucleotide production by oocyte-cumulus cell complexes, and this was accentuated by glucose. It is concluded that the presence of purine precursors can augment the meiosis-arresting action of established meiotic inhibitors in glucose-dependent fashion, and that this is due, at least in part, to their incorporation into purine nucleotides via the de novo synthetic pathway.