By analyzing the morpho-physiological features of the Golgi complex, its relationship with the endoplasmic reticulum in different species, and the molecular machineries involved in intracellular transport, we conclude that; (1) all eukaryotic cells have either Golgi complexes or remnants thereof; (2) all eukaryotic cells have a large minimal set of proteins that are involved in intracellular transport; and (3) several indispensable molecular machines are always present in secreting eukaryotic cells. Using this information, our data about mechanisms of intra-Golgi transport and phylogenetic analysis of several molecular machines, we propose a model for the evolution of the Golgi complex and the endoplasmic reticulum.
Segmentectomy of the spinal cord (SC) was performed in 28 rats at the level of the tenth thoracic vertebra. Scar formation at the operation site was studied, along with the completeness of the anatomical integrity of the SC, in control animals (group 1) and after filling of the defect with the neural matrix Spherogel (group 2) and with Spherogel containing embryonic nerve cells (group 3). The defect in the SC in animals of the control group was filled with fibrin masses by 1-2 weeks, while connective tissues scars were already formed by this time in rats of experimental groups 2 and 3. By 10-11 weeks, these animals showed partial recovery of movement in the three lower limb joints. The scar tissue and adjacent zones of the SC showed large quantities of regenerating fine myelinated nerve fibers. These were clearly evident in the zones of the cranial and caudal margins, to the extent of the appearance of typical SC tissue. In preparations obtained from control animals, fine myelinated fibers were noted in the immediate vicinity of SC substance, while nerve fibers were few in number in scar tissue and the cellular bands of the transitional zone.
The hormonal compound with the highest cytostatic activity against MCF-7 tumor cells (human breast cancer, BC) and the lowest activity against normal cells (rat skin fibroblasts) was sought among gestagens, androstenes, and antiestrogencytostatics. It was found that antiestrogencytostatics and androstenes had the highest cytostatic activity against tumor cells whereas gestagens and antiestrogencytostatics were least active against fibroblasts. Studies of the activity of the hormonal compounds in combination with doxorubicin on the viability of MCF-7 and rat skin fibroblasts found that all investigated compounds with the exception of dehydroepiandrosterone (DHEA) intensify the cytostatic activity of doxorubicin against tumor cells, the greatest effect seen for antiestrogencytostatics. A chemoprotective effect of androstenes on normal cells was noted.Treatment regimes for cancerous diseases have not yet been standarized despite the efforts of researchers and clinicians. This is apparently due to the fact that each tumor has its own receptor array and individual genetic profile and responds differently to one or another type of therapy. Agonists or antagonists of various steroidal receptors have turned out in several instances to be highly effective in treating hormone -dependent neoplasms. Depending on the age of the patient (reproductive or menopausal), various combinations of antiestrogens, progestins, and even androgens may be used in hormone therapy of human breast cancer (BC) [1]. Herein we report the screening of new synthetic gestagens, antiestrogencytostatics, and androstenes and the comparison of them with existing clinical drugs for tumor model and normal cells. The existing clinical drugs have several side effects and drawbacks (multidrug resistance and glucocorticoid, mineralocorticoid, and androgen side effects of hormone -therapy). Therefore, there is a continuous search for more effective and safer new compounds. Several new steroidal compounds have been synthesized. We studied the following of these: 1) 17a-Acetoxy-3b-butyloxy-6-methylpregna-4,6-dien-20-one (ABMP), a gestagen that does not have a D 4 -3-ketone and has a structure similar to progesterone but, in contrast with it, can be readily absorbed orally [2]. The reference drugs were progesterone (P) and medroxyprogesterone acetate (MPA).2) Po715 and Po716, antiestrogencytostatics that are estrogens having transformed C rings with substituents containing a bis-b-chloroethylamine moiety (Fig. 1) [3,4].We used 11a-derivatives of ethynylestradiol with the bis-b-chloroethylamine moiety bonded to the 3 -position.3) Dehydroepiandrosterone nitrate (DHEAN), androstendiol nitrate (AEDN), and androstendiol dinitrate (AEDDN), which are nitro derivatives of the endogenous androstenes dehydroepiandrosterone and androstendiol, respectively. The reference drugs were androstendiol (AED) and DHEA [5].
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