Liposome-encapsulated hemoglobin with high O2 -affinity (P50 O2  = 10 mm Hg, h-LEH) was reported to enhance tumor radiosensitivity. We hypothesize that targeted O2 delivery to tumor hypoxia by h-LEH may also enhance chemotherapy to suppress tumor growth and metastasis in mice. Doxorubicin (DXR; 0.5 or 2 mg/kg i.p.) or S-1 (4 or 8 mg/kg orally) alone or in combination with h-LEH (5 mL/kg i.v.) was administered for 2 weeks to C57BL/6N mice inoculated with Lewis Lung Carcinoma (LLC) in the leg. After the 2-week therapy in six treatment groups, mice were sacrificed for quantitative assessment of tumor growth and lung metastasis. The tumor was then evaluated for its expression of hypoxia-inducible factor-1α (HIF-1α) and matrix metallopoteinase-2 (MMP-2) activity. Combined use of h-LEH and chemotherapeutic agents (DXR or S-1) showed no additional enhancement on suppression of the tumor growth over the chemotherapeutic agent alone. However, the combination use of h-LEH significantly suppressed the number and total area of metastatic colonies in the lung compared with each chemotherapeutic agent alone. Although HIF-1α expression and MMP-2 activity in the original tumor was significantly suppressed in the groups of mice treated with either DXR or S-1 alone, the addition of h-LEH to either agent showed further enhancement of oxygen-mediated degradation of HIF-1α and suppression of MMP-2 activity. Although the addition of h-LEH to DXR or S-1 had little effect on original LLC tumor growth, it significantly enhanced suppression of lung metastasis in mice.

We studied the effect of cyclic polylactates ranging in size from a degree of polymerization number of 3 to 13 on pyruvate kinase, lactic dehydrogenase, anaerobic glycolysis, growth of tumor cells and survival of tumor bearing mice. Pyruvate kinase and lactic dehydrogenase activities were both inhibited by cyclic polylactates, and the inhibition mechanism of cyclic polylactates on lactic dehydrogenase was noncompetitive. About half the anaerobic glycolytic activity of FM3A ascites tumor cells was inhibited and tumor cell growth was also effectively inhibited by cyclic polylactates. Mice, which were treated with cyclic polylactates after inoculation of FM3A ascites tumor cells lived significantly longer than mice, which were treated with vehicle or non mice.

ABSTRACT. The stages of the cycle of the seminiferous epithelium in the Japanese macaque are investigated using testes fixed by a mixture of formaldehyde and glutaraldehyde containing picric acid and embedded in a methacrylate resin, Queto1523M. Sections, 1.0-2.0/zm in thickness, were cut with glass knives and stained with periodic acid-Schiff (PAS) and hernatoxylin. Sections from such resin blocks illustrated cellular detail without structural distortion during the polymerization process. Furthermore, staining affinity with PAS and hematoxylin was excellent. In stained sections, typical germ cell associations were described, based on the nuclear morphology of type A (dark and pale) spermatogonium, type B spermatogonium, various developmental stages of primary spermatocytes during meiosis, and the development of the acrosomic system. In the Japanese macaque, two different steps of spermatids (steps 3 and 4) were constantly seen in the same area of the tubular epithelium during stage III. Therefore, a classification into ten stages is proposed for the cycle in this species. Additional characteristics are described based on the observation of the seminiferous epithelium using semithin sections.

No abstract

ABSTRACT. A histological study was undertaken to clarify seasonal changes in the spermatogenic epithelium of Japanese macaques. Testicular tissue samples were excised by biopsies from five adult laboratory-maintained males in mating and non-mating seasons. The samples were fixed with Bouin's solution, embedded in paraffin, and stained with PAS and hematoxylin. Microscopic observations on cross-sections of seminiferous tubules revealed that the seminiferous epithelium in the mating season was thicker than in the non-mating season. PAS-stained granules were found in some of the dark A-type spermatogonia, which significantly increased in the non-mating season. Spermatids of the steps preceding the appearance of the acrosomic cap in stages I to III were observed significantly more often than those in the step coinciding with the formation of the acrosomic cap in stage IV. In stage I, the ratio of mature spermatids or spermatozoa to immature spermatids in the mating season was higher than that in the non-mating season. These findings suggest that spermiogenesis, as well as spermatocytogenesis, is inhibited in the non-mating season.