Search PubMed⌕ Search

Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 415 records · Page 23Linked to original sources
PubMed1984

In vitro cytotoxicity to various human tumor cell lines of a tumor cytotoxic factor(s) produced by human alveolar macrophages.

When human alveolar macrophages (AM) obtained by lavage of the lungs of healthy donors were incubated in medium with or without lipopolysaccharide (LPS) they released a factor(s) with tumor cell killing activity. This tumor cytolytic and/or cytotoxic factor(s) (TCF) was assayed by measuring its effect in inhibiting target cell growth. TCF activity was not observed in the supernatant from cultures of LPS-treated hematopoietic malignant cell lines (monocytic leukemia, B-cell leukemia and T-cell leukemia cell lines). Human TCF was significantly cytotoxic to 13 of 15 solid-tumor cell lines tested and to 7 of 9 hematopoietic malignant cell lines, but not to two different normal, nontumorigenic cell lines. TCF-rich supernatants contained low levels of interferon (IFN) activity that were not significantly cytotoxic to A-375 melanoma cells. Human TCF and IFN-alpha or IFN-beta had additive cytotoxic effects. These data suggest that human TCF released by activated human AM may be of potential use in the treatment of malignant disseminated diseases.

B-Lymphocytes↗
PubMed1984

Establishment of human KB cells resistant to 1-beta-D-arabinofuranosylcytosine, and mechanisms of cellular resistance in isolated clones.

A subline of human KB cells that was resistant to 1-beta-D-arabinofuranosylcytosine (ara-C) was established by continuous exposure of the cells to increasing concentrations of ara-C. Thirteen resistant clones were isolated from the resistant subline (KB/ara-C). KB/ara-C showed 1,300-fold higher resistance than the parent KB cells to ara-C; the most resistant clones, clones 7 and 10, showed 1,330-fold higher resistance. In the absence of ara-C, the resistance of the parent KB/ara-C cells was stable for at least 14 weeks, whereas that of clone 7 was stable for 10 weeks, but was slightly less after 14 weeks. The ara-C kinase and ara-C deaminase activities of the 13 clones and the cellular uptake of ara-C by several clones were measured. In general the clones showed decreased deoxycytidine kinase activity and decreased cellular uptake of ara-C. Most clones had higher cytidine deaminase activity than KB cells, but some had activity similar to that of the KB cells. A clear inverse relationship was found between the ara-C sensitivity of the clones and their kinase activity, but not their deaminase activity or their ara-C uptake. These results clearly demonstrate that a major mechanism of ara-C resistance of these human KB cells was a decrease in the activity of the ara-C activating enzyme deoxycytidine kinase. The parent KB/ara-C cells showed no clear cross-resistance to various antitumor agents other than an ara-C derivative, including metabolic inhibitors, alkylating agents, DNA binders and mitotic spindle poisons.

Antineoplastic Agents↗
PubMed1984

Production of a tumor cytolytic factor(s) by activated human alveolar macrophages and its action.

When human alveolar macrophages (AM) lavaged from healthy donors were incubated in medium with or without lipopolysaccharide (LPS) or muramyl dipeptide, they released a factor(s) responsible for tumor cell killing. The activity of the tumor cytolytic factor(s), called TCF, was determined by radioactive release assay. Human AM released variable amounts of TCF into the culture medium without any stimulation, but the release was stimulated significantly by LPS (0.1 micrograms/ml) or muramyl dipeptide (1 micrograms/ml). Maximal production of TCF by the AM was detected in the supernatant after treatment for 3 hr with LPS, and the extent of TCF release correlated with the density of AM. In cultures with LPS, the ability of activated AM to secrete TCF was maintained for 48 hr but was lost by 96 hr. After its loss, the ability to produce TCF could be restored by a second treatment with LPS. Full expression of lysis by TCF to lyse tumor cells required its interaction with tumor cells for at least 24 hr. TCF destroyed human allogeneic tumor cell lines but did not affect nonneoplastic cell lines. TCF activity was resistant to treatment with protease inhibitors, superoxide dismutase, or catalase and to heating at 70 degrees for 1 hr, but it was labile on heating at 100 degrees for 10 min. The tumoricidal activity in the supernatant of activated human AM indicates a potential effector mechanism by which AM kill neoplastic cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Potentiating effect of muramyl dipeptide and its lipophilic analog encapsulated in liposomes on tumor cell killing by human monocytes.

Human monocytes harvested from healthy donors and separated by discontinuous gradient centrifugation and adherence were highly cytotoxic to allogeneic melanoma cells, but did not affect nontumorigenic cells, as measured by lysis of the cells. After 4 days incubation of these monocytes in medium, they showed little, if any, cytolytic activity. Hydrophilic muramyl dipeptide (MDP) or lipophilic muramyl tripeptide (MTP-PE) was encapsulated within multilamellar (MLV) liposomes composed of phosphatidylserine-phosphatidylcholine. The cultured monocytes were rendered tumoricidal by interaction for 24 hr with MDP or liposomes containing soluble MDP or lipophilic MTP-PE. Moreover, freshly isolated monocytes treated for 24 hr with liposomes containing MDP or MTP-PE remained tumoricidal during culture for up to 5 days. About 1,600-times lower concentration of MDP entrapped in liposomes than of free MDP in the medium was effective for rendering monocytes tumoricidal. Similarly, about 80-times lower concentration of MTP-PE in liposomes than of free MDP was effective for the activation of monocytes. It is concluded that MLV liposomes containing MDP or MTP-PE are far more efficient in potentiating the tumoricidal activity of human monocytes than unencapsulated, free MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Potential value of liposomes containing muramyl dipeptide for augmenting the tumoricidal activity of human alveolar macrophages.

Potentiation of the tumoricidal activity of human alveolar macrophages (AM) by muramyl dipeptide (MDP) and MDP in liposomes (liposome-MDP) was examined. Significant increase in AM-mediated cytotoxicity against allogeneic melanoma cells required the interaction of AM with liposome-MDP for a minimum of 4 h. The uptake by human AM of liposomes containing fluorescent quinacrine was examined. A linear correlation was found between the amount of liposomes added to AM monolayers and their phagocytosis of liposome-entrapped quinacrine. Addition of phosphatidylserine to liposomes composed of phosphatidylcholine enhanced both the phagocytosis of liposomes and the ability of liposome-MDP to potentiate the tumoricidal activity of human AM. In experiments on the dose response of liposomes containing 10 micrograms/ml MDP, 50 nmol of liposomes/10(5) AM caused maximal activation of human AM, and greater than 100 nmol of liposomes was less effective. These results show that multilamellar vesicle liposomes containing MDP are more effective than free MDP in potentiating the tumoricidal activity of human AM during culture for 4 h.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Inhibition of the arrest of hematogenously disseminated tumor cells.

Most metastases in patients occur as a result of hematogenous dissemination of tumor cells. This process of metastasis is complex and consists of several steps, foremost of which is the arrest of circulating emboli in capillary beds and the formation of a thrombus at that site. Thrombus formation in the metastasis of human cancer was described first by Billroth in 1878. It was reported that the organization of tumor cell emboli, and the subsequent penetration of tumor cells into the capillary wall, was the first stage of metastasis. Since then, many investigations and observations have been made clinically as well as experimentally to clarify the process (or mechanisms) of tumor cell arrest and how to inhibit it. Coagulative and fibrinolytic pathways were believed to have a main role in thrombus formation. However, other factors responsible for the relationship between tumor cells and the host must be also considered. Elegant and extensive studies by Fidler and Kripke demonstrated that development of metastasis is not a random process, but a selection process of specialized subpopulations of highly metastatic cells within the primary tumors. Biochemical constituents and ionic properties on cell surfaces, deformability or locomotive activities of tumor cells, as well as thrombo-plastic-fibrinolytic activities, are also important factors determining the arrest patterns of circulating tumor cells. On the other hand, host defense factors against tumor cells in the bloodstream have been attracting much attention recently in tumor immunology. Host defense factors relating the arrest of tumor cells to the establishment of metastatic foci seemed difficult to define, since many studies showed contradictory data concerning the influence of immune response on tumor cell arrest. Hemodynamic abnormality may also influence the arrest of tumor cells in the circulation. Hypercoagulability induced from host tissues is greatly associated with the arrest patterns. Platelet activities might affect thrombus formation. Nevertheless, exact explanations of the process or mechanisms inhibiting or enhancing the arrest of tumor cells after hematogenous dissemination have not been obtained. In any event, for cancer treatment, it is important to determine which substances inhibit the arrest of circulating tumor cells and how to prevent hematogenous metastasis. In this review, we will focus upon coagulative and fibrinolytic processes and then upon substances that inhibit the arrest of circulating tumor cells. Furthermore, some comments on the possible clinical applications of inhibitory substances for prevention of cancer metastasis are added.

Animals↗
PubMed1983

In vivo and in vitro NO2 exposures enhance phagocytic and tumoricidal activities of rat alveolar macrophages.

Rat alveolar macrophages (AM) were exposed in vivo or in vitro to nitrogen dioxide (NO2) and subsequently tested for phagocytic and tumoricidal activities. AM obtained by lavage from Fischer 344/N rats exposed for 4 h to 40 ppm NO2 were significantly more phagocytic to opsonized sheep red blood cells (SRBC), exhibited an increased cytotoxic response toward syngeneic mammary adenocarcinoma cells, and were more sensitive to activation by agents such as lipopolysaccharide, muramyl dipeptide, and macrophage-activating factor, as compared with the response of AM obtained from unexposed control rats. Repeated 4 h/d NO2 exposures over 7-d or 14-d periods usually resulted in AM activity similar to control levels, with some instances of increased phagocytic activity of the AM but not to the extent of that observed for a single 4 h exposure. There were no significant decreases in the cytotoxic or phagocytic activities of the AM during any of the exposure periods. For the in vitro exposures, AM were lavaged from normal rats and then exposed for various periods to 10, 20, or 40 ppm NO2. A dose-related and time-dependent enhanced cytotoxic response of AM was observed. Maximum AM-mediated cytotoxicity occurred after an in vitro exposure to 10 ppm NO2 for 2 h. The cytotoxic response was directed toward syngeneic mammary adenocarcinoma cells but not against syngeneic embryoblast cells, indicating that the AM retained the ability to distinguish between normal and abnormal cells. No inhibitory effects of NO2 on AM-mediated cytotoxicity were observed. These experiments suggest that the host AM-mediated immune defense of the lung may be modulated by host exposure to inhaled chemicals.

Animals↗
PubMed1983

Changes of alveolar macrophages in protein-deficient rats.

Protein malnutrition was achieved by feeding female F344 rats a 5% casein diet for 7 weeks. At appropriate times, animals were killed and their alveolar macrophages (AM) were obtained by broncho-pulmonary lavage of the lung. Functional changes of AM were determined by measuring phagocytosis of latex beads, yeast cells or opsonized sheep red blood cells (SRBC) and the ability to respond to a macrophage-activating factor (MAF) such as lymphokines. After 3 weeks on a low casein diet, the number of AM was much lower than in rats on control diet, but the abilities of the AM to phagocytose latex and yeast cells were the same as those of controls. Phagocytosis of opsonized SRBC was higher than in control rats but could not be enhanced by in vitro treatment with MAF. The most striking ultrastructural feature of these AM was the abundance of finger-like microvilli on the cell surface before phagocytosis; after ingestion of SRBC into phagocytic vacuoles there were only a few short microvilli on the surface. These data suggest that dietary protein malnutrition affects the number and phagocytic functions of AM responsible for host defense in the lung.

Animals↗
PubMed1983

CT anatomy of hilar lymphadenopathy.

The normal distribution of lymph nodes in the pulmonary hili is diagrammatically shown, with a typical computed tomographic (CT) demonstration of hilar lymphadenopathy. On the basis of observations in anatomic cross sections of cadaver lungs, the lymph nodes in the right lung can be divided into four principal groups (right upper lobe, interlobar, middle lobe, and lower lobe) and in the left lung into three principal groups (left upper lobe, interlobar, and lower lobe). Most of the hilar lymph nodes are situated along the bronchi in close relation with the pulmonary vascular branches. Because of this close proximity, contrast-enhanced CT images are indispensable for precise CT interpretation of a hilar lymphadenopathy.

Humans↗
PubMed1983

Ultrastructural changes of alveolar macrophages of protein-deficient rats.

Enhancement of phagocytosis of alveolar macrophages (AM) was examined by cytochemical and electron microscopic studies on macrophages from protein-deficient rats. The macrophages from rats fed on 5% casein diet had longer microvilli, more phagocytic vacuoles and more lysosomes with acid phosphatase activity than those from control rats. Many phagocytic vacuoles were seen close to the site of attachment of opsonized sheep red blood cells (SRBC) and were mainly located in the subplasmalemmal layer which was rich in microfilaments but contained few cytoplasmic organelles. After attachment, opsonized SRBC were engulfed through a hemispherical crater into the phagocytic vacuoles. The phagocytic vacuoles seemed to be formed by invagination of the cell surface because they had membrane ATPase activity continuous with that of the outer surface of the plasma membrane. In the cell, the vacuoles fused with the numerous preexisting lysosomes in the interior of the cell receiving the contents of the latter. The mechanism of enhancement of phagocytosis in protein-deficiency is discussed.

Animals↗