Effect of Alveolar Bone Mass on Mechanical Stress in Calcium-sufficient and -deficient Rats

It is clinically important to check whether sufficient supporting bone mass is maintained in subjects with a low calcium diet. In this study, alveolar and femoral bone mass were measured after tooth movement in calcium-sufficient and -deficient rats, and the correlation between mechanical stress and bone mass was examined using the serum level and histological observation. Seventy rats were divided into 2 groups : normal (NDG) and low calcium diet (LCG) groups. After feeding for 28 days, the distance of tooth movement and the alveolar and femoral bone mass were observed on days 1, 3, 5 and 7 after fitting the appliance. Tooth movement distance was large in LCG. Alveolar bone mass in NDG and LCG showed a different tendency than tooth movement ; the former was increased and the latter was decreased. Body weight decreased from the start of the experiment until day 3 in both groups, and increased gradually thereafter. Femoral bone mass in NDG slightly decreased and then recovered at day 7, but such a result was not observed in LCG. These results suggest that the tooth was able to move when an orthodontic force was applied in rats, even in cases of low alveolar bone mass, although various physical influences were present.     

Combined antitumor effects of TNF and G-CSF on a human medulloblastoma xenograft line

Summary The antitumor effects of TNF and G-CSF on a xenograft line of human medulloblastoma were examined. (Method): 1) A human medulloblastoma xenograft line was transplanted into nude mice. Tumor bearing nude mice were divided into the following eight groups: untreated controls (C); those receiving a subcutaneous injection of G-CSF for one week (G1); for four weeks (G2); those receiving an intratumoral injection of TNF for four weeks (Tit); an intravenous injection of TNF (Tiv); those receiving a combination of G1 and Tit (G1 + Tit); a combination of G2 and Tit (G2 + Tit); and a combination of G2 and Tiv (G2 + Tiv). The relative tumor weight in each group was calculated and any antitumor effects were examined by calculating a tumor growth inhibition ratio. 2) Tumor bearing nude mice were divided into the following two groups: those receiving a subcutaneous injection of G-CSF and an intravenous injection of TNF (G + T); and only an intravenous injection of TNF (T). We evaluated the pathological findings from the tumors at 0 h, 0.5 h, 1 h, 3 h, 6 h, 12 h, 24 h and 48 h after the TNF injection. Routine H.E. staining and immunostaining using antigranulocyte and antimacrophage antibodies were performed. (Results): 1) The tumor growth inhibition ratio was 0.112, 0.190, 0.287, 0.451, 0.347, 0.635, and 0.622 at G1, G2, Tit, Tiv, G1 + Tit, G2 + Tit, G2 + Tiv group. A combined antitumor effect was clearly seen in the G2 + Tit and the G2 + Tiv groups. 2) The tumor was fragmented by the infiltration of many inflammatory cells 24 hours after TNF injection. Many more macrophages were observed in the tumors of G + T mice than in the T mice. Granulocytes were observed only in the tumors of the G + T mice.     

Absorption of horseradish peroxidase in the endolymphatic sac: ultrastructural cytochemistry using a new electrophoretic technique.

Using a newly developed injection technique, the absorption of horseradish peroxidase (HRP) in the endolymphatic sac (ES) of the guinea pig was examined by light and electron microscopy. HRP (molecular weight: 40,000; molecular diameter: about 5-nm) was directly injected into the lumen of the ES by electrophoresis after the recording of a direct current potential in the ES lumen. Both the macrophages floating in the ES lumen and the epithelial cells in the intermediate portion of the ES absorbed intraluminal HRP. The macrophages internalized the intraluminal HRP at a higher rate than the epithelial cells, suggesting that macrophages play a major role in macromolecular absorption in the ES. It was considered that the macrophages took up intraluminal HRP by phagocytosis, while the epithelial cells of the intermediate portion took it up by pinocytosis. In contrast, the epithelial cells in the proximal portion of the ES absorbed little HRP. No penetration through the junctional complexes between epithelial cells was observed in either the intermediate or the proximal portion at any interval after the injection of HRP. This finding indicates that these junctional complexes are impermeable to intraluminal HRP.     

Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-β

In our previous study on liposome-mediated transfection of the human interferon-β (HuIFN-β) gene into subcutaneously implanted human gliomas in nude mice, we found that HuIFN-β was produced and secreted by the tumor cells and that the growth of solid tumors was completely inhibited. The present study investigated the growth-inhibitory effect of liposomes containing the HuIFN-β gene inserted into a vector (PSV2IFN-β) on T9 rat glioma implanted into the brains of rats. Tumor cells and liposomes containing pSV2IFN-β or other additives were simultaneously injected into the brains of rats. HuIFN-β was detected in solid gliomas growing in the brains of rats injected with liposomes and magnetic resonance imaging (MRI) showed that tumor growth was inhibited. In addition, the latent period until the appearance of neurological symptoms was significantly prologed in rats treated with liposomes containing pSV2IFN-β. However, the survival time of the treated rats was not significantly increased. © 1995 Wiley-Liss, Inc.     

Augmentation of the activity of an immunotoxin,anti-Tac(Fv)-PE40KDEL,in T cell lines infected with human T cell leukemia virus type-I

Therapy with an immunotoxin, anti-Tac(Fv)-PE38, which is a conjugate of the variable domains of an anti-Tac monoclonal antibody and Pseudomonas exotoxin, was reported to be useful for adult T cell leukemia (ATL) patients but a considerable amount of the immunotoxin is needed for the therapy and some side effects were also observed. We have previously demonstrated that an immunotoxin, anti-Tac(Fv)-PE40KDEL, showed strong cytotoxic effects on malignant cells from ATL patients. Therefore, we searched for agents that enhance the effects of the immunotoxin. PAK-200, FK-506, quinidine, cepharanthine and cyclosporine A (CsA) augmented the ability of the immunotoxin to inhibit protein synthesis in two human T cell leukemia virus type-I infected T cell lines, KUT-1 and KUT-2. CsA was the most potent agent in both the cell lines. Augmentation of the cytotoxic effect of the immunotoxin by these agents, especially CsA, may be useful in the immunotoxin therapy of ATL.     

Analysis and Distribution of Etoposide in Rat Brain Tumor Model: Intracarotid Versus Intracarotid with Angiotensin II—Induced Hypertension

The brain tissue distribution of etoposide has been investigated in 9L gliosarcoma-bearing rats with or without hypertension induced by angiotensin II (AT II). The rat brain tumor models were divided into the following two groups according to etoposide administration route: intracarotid injection (IC) group and intracarotid injection with hypertension induced by AT II (IHIC) group. Ten mg/kg of etoposide was given, and 30 min and 2, 4, 8, and 24 hr later the rats were sacrificed. The drug concentrations in the serum, tumor, and normal brain tissue were analyzed by high-pressure liquid chromatography. The etoposide concentration in the serum, tumor, and normal brain tissue peaked at 30 min in both groups. The serum concentration was similar between the two groups. The etoposide concentration in the tumor was at least 2.2 times higher in the IHIC group than in the IC group at 30 min and 2 hr. The area under drug concentration curve (AUC) in the tumor in the IHIC group was about 2.2 times higher than that in the IC group. The etoposide concentration in the normal brain on the drug injection side changed only slightly from 0.5 hr to 4 hr and was about 3 times higher in the IHIC group than in the IC group. The etoposide concentration in the contralateral normal brain was very low in both groups at 30 min and disappeared thereafter.

Intracarotid injection of anticancer drugs with AT II-induced hypertension further increases the drug concentration and AUC in the tumor compared with intracarotid injection alone and can be useful in treatment of malignant brain tumors.     

Induction of S100A4 gene expression inhibits in vitro invasiveness of human squamous cell carcinoma, KOSC-3 cells

S100A4 is considered functionally involved in metastasis and invasiveness of rodent and human mammary tumors. We screened the expression of S100A4 in human squamous cell carcinoma cell lines, and found 2 cell lines which were highly invasive, but did not express any noticeable extent of S100A4. To examine whether the expression of S100A4 regulated invasiveness of squamous cell carcinoma, we transfected S100A4 cDNA into KOCS-3 and HSC-4 squamous cell carcinoma cells. The transfectants from KOSC-3 cells expressing sense S100A4 decreased invasiveness by 80% compared with cells of the wild type or those with the vector only.     

Arsenic trioxide and the growth of human T-cell leukemia virus type I infected T-cell lines

A novel therapeutic potential for acute promyelocytic leukemia using arsenic trioxide (As(2) O(3) ) has been reported. Recent in vitro studies demonstrated that As(2) O(3) effectively inhibits the growth of some cell lines derived from patients with malignant lymphoma, chronic lymphocytic leukemia and multiple myeloma. Adult T-cell leukemia (ATL) is an aggressive neoplasm of mature T-cell origin caused by human T-cell leukemia virus type-I (HTLV-I) the prognosis of which still remains very poor. A possible role of As(2) O(3) for the treatment of ATL is demonstrated from evidence that As(2) O(3) significantly inhibits the growth of HTLV-I infected T-cell lines and induces apoptosis in fresh ATL cells at clinically achievable concentration of the agent. The growth inhibition of As(2) O(3) treated HTLV-I infected T-cell lines was induced by both apoptosis and G(1) phase accumulation. Cleaved bcl-2 protein and an enhanced expression of bak protein in the cells were coincidentally observed during As(2) O(3) treatment. A broad spectrum caspase inhibitor, z-Val-Ala-DL-Asp-fluoromethylketone inhibited the apoptosis induced by As(2) O(3). Increased expression of p53, Cip1/p21 and Kip1/p27, and dephosphorylation of retinoblastoma protein (pRb) were detected in the As(2) O(3) treated cells. In conclusion, As(2) O(3) might become a new therapeutic tool in the treatment of ATL as As(2) O(3) induces apoptosis by destruction of the bcl-2 protein and enhancement of the bak protein production proceeding to activate caspases, and also induces G(1) phase accumulation by enhancement of p53, Cip1/p21, Kip1/p27 and dephosphorylation of pRb to HTLV-I infected T-cell lines.