Ligands for peroxisome proliferator-activated receptorγ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice

Induction of differentiation and apoptosis in cancer cells through ligands of nuclear hormone receptors (NHRs) is a novel and promising approach to cancer therapy. All-trans-retinoic acid (ATRA), an RA receptor-specific NHR ligand, is now used for selective cancers. The NHR, peroxisome proliferator-activated receptor γ (PPARγ) is expressed in breast cancer cells. Activation of PPARγ through a synthetic ligand, troglitazone (TGZ), and other PPARγ-activators cause inhibition of proliferation and lipid accumulation in cultured breast cancer cells. TGZ (10⁻⁵ M, 4 days) reversibly inhibits clonal growth of MCF7 breast cancer cells and the combination of TGZ (10⁻⁵ M) and ATRA (10⁻⁶ M, 4 days) synergistically and irreversibly inhibits growth and induces apoptosis of MCF7 cells, associated with a dramatic decrease of their bcl-2 protein levels. Similar effects are noted with in vitro cultured breast cancer tissues from patients, but not with normal breast epithelial cells. The observed apoptosis mediated by TGZ and ATRA may be related to the striking down-regulation of bcl-2, because forced over-expression of bcl-2 in MCF7 cells cultured with TGZ and ATRA blocks their cell death. TGZ significantly inhibits MCF7 tumor growth in triple immunodeficient mice. Combined administration of TGZ and ATRA causes prominent apoptosis and fibrosis of these tumors without toxic effects on the mice. Taken together, this combination may provide a novel, nontoxic and selective therapy for human breast cancers.     

Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice

We compared the effects of hematopoietic stem cell and marrow stromal cell transplantation for spinal cord injury in mice. From green fluorescent protein transgenic mouse bone marrow, lineage-negative, c-kit- and Sca-1-positive cells were sorted as hematopoietic stem cells and plastic-adherent cells were cultured as marrow stromal cells. One week after injury, hematopoietic stem cells or marrow stromal cells were injected into the lesioned site. Functional recovery was assessed and immunohistochemistry was performed. In the hematopoietic stem cell group, a portion of green fluorescent protein-positive cells expressed glial marker. In the marrow stem cell group, a number of green fluorescent protein and fibronectin-double positive cells were observed. No significant difference was observed in the recovery between both groups. Both hematopoietic stem cells and marrow stromal cells have the potential to restore the injured spinal cord and to promote functional recovery.     

Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice

Recovery in central nervous system disorders is hindered by the limited ability of the vertebrate central nervous system to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. Cell transplantation to repair central nervous system disorders is an active area of research, with the goal of reducing functional deficits. Recent animal studies showed that cells of the hematopoietic stem cell (HSC) fraction of bone marrow transdifferentiated into various nonhematopoietic cell lineages. We employed a mouse model of spinal cord injury and directly transplanted HSCs into the spinal cord 1 week after injury. We evaluated functional recovery using the hindlimb motor function score weekly for 5 weeks after transplantation. The data demonstrated a significant improvement in the functional outcome of mice transplanted with hematopoietic stem cells compared with control mice in which only medium was injected. Fluorescent in situ hybridization for the Y chromosome and double immunohistochemistry showed that transplanted cells survived 5 weeks after transplantation and expressed specific markers for astrocytes, oligodendrocytes, and neural precursors, but not for neurons. These results suggest that transplantation of HSCs from bone marrow is an effective strategy for the treatment of spinal cord injury.     

Delivery of twins after undergoing adjuvant LHRH analogue and CEF therapy

Chemotherapy is an important part of adjuvant therapy for younger patients with breast cancer, but prevention of ovarian dysfunction due to chemotherapy is important. There are some reports that pretreatment with LHRH analogue can preserve ovarian function. The present patient, who was treated in this way, delivered twins 6 years after surgery. A 33-year-old woman underwent breast conserving surgery for 1 cm carcinoma in the left A region, and pathologic findings were papillotubular carcinoma. t2n1 alpha (2/18) ER (+) PgR (+). LHRH analogue was administrated together with radiation therapy for the preserved breast. Six subsequent courses of CEF therapy were given, and then LHRH analogue was administered for 2 years and tamoxifen for 2 years and six months. Menstruation was recovered 6 months later and twins were delivered 3 years after the last administration of hormone therapy. This case should be referred in the treatment of young patients.     

Percutaneous transhepatic biliary drainage guided by color doppler echography

Percutaneous transhepatic biliary drainage (PTBD) guided by color Doppler echography was performed on nine patients. By color Doppler echography, the segmental and subsegmental branches of both the portal vein and the hepatic artery could be identified and discriminated from the bile ducts because of their color flow mapping. We could select the safe pathway of needle advance, which did not injure the vessels. Thus, complication of bleeding did not occur in any of the patients. Color Doppler echography seems a very useful and safe method for the guidance of PTBD.     

A comparison of prosthetic materials used to repair abdominal wall defects

Large abdominal wall defects may require a prosthesis for closure. The aim of our study was to identify the best material for abdominoplasty in pediatric patients. One hundred twenty-eight Wistar KY strain male rats (3 weeks old) were used. All animals underwent celiotomy via a midline skin incision. They were divided into seven groups as follows: the animals in groups 1 through 6 underwent full-thickness abdominal wall excision 3 cm in diameter. The animals in group 1 underwent primary closure. In groups 2 through 6 the defect was closed with prosthetic material. In Group 7, a sham operation was performed. Daily weights were measured. The animals were killed after 3 and 9 weeks. Adhesion scores were assigned for each group. Vicryl mesh resulted in the fewest adhesions and had no effect on weight gain in the developing rats. Accepted: 11 June 1997     

Effects of long-term administration of vitamin D3 analogs to mice

This study explores the effects of chronic administration of vitamin D(3) compounds on several biological functions in mice. Knowledge of long-term tolerability of vitamin D(3) analogs may be of interest in view of their potential clinical utility in the management of various pathologies such as malignancies, immunological disorders and bone diseases. Four unique vitamin D(3) analogs (code names, compounds V, EO, LH and LA) and 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) were administered i.p. for 55 weeks to Balb/c mice. Each analog had previously been shown to have potent in vitro activities. After 55 weeks of administration, the mice had a profound decrease in their serum levels of interleukin-2 (IL-2). Likewise, several analogs depressed serum immunoglobulin G concentrations (compounds LH and LA), but levels of blood lymphocytes and splenic lymphocyte subsets (CD4, CD8 and CD19) were not remarkably depressed. The percent of committed myeloid hematopoietic stem cells was 4- to 5-fold elevated in the bone marrow of the mice that received analogs LH and V; nevertheless, their peripheral blood white and red cell counts and platelets were not significantly different in any of the groups. The mice that received 1,25(OH)(2)D(3) had a decrease in bone quantity and quality with a decrease in cross-sectional area and cortical thickness, and a 50% reduction in both stiffness and failure load compared with the control group. In contrast, the cohort that received a fluorinated analog (compound EO) developed bones with significantly larger cross-sectional area and cortical thickness as well as stronger mechanical properties compared with the control group. At the conclusion of the study, body weights were significantly decreased in all experimental mice. Their blood chemistries were normal. Extensive gross and microscopic autopsy analyses of the mice at the conclusion of the study were normal, including those of their kidneys. In conclusion, the vitamin D(3) analogs were fairly well tolerated. They did suppress immunity as measured by serum IL-2 and may provide a means to depress the immune response after organ transplantation and for autoimmune diseases. Use of these analogs prevented the detrimental effects of vitamin D(3) administration on mechanical and geometric properties of bone, while one analog (compound EO) actually enhanced bone properties. These results suggest that long-term clinical trials with the analogs are feasible.     

Characterization of varicella-zoster virus-encoded ORF0 gene—Comparison of parental and vaccine strains

The varicella-zoster virus (VZV) Oka vaccine strain (vOka) differs from the parental strain (pOka) at several amino acid positions, but the mutations responsible for the attenuation of vOka have not been clearly defined. The ORF0 of vOka carries some of the mutations. Although we found that the ORF0 of both strains was incorporated into virus particles, the C-terminal region of vOka ORF0 was presented on the virion surface and was N-glycosylated, suggesting that the mutation in vOka ORF0 changes it into a novel envelope glycoprotein. In a mutant virus in which pOka ORF0 was replaced by vOka ORF0, the molecular weight of ORF0 was altered, but the plaque size was not. In addition, a pOka recombinant virus lacking the hydrophobic domain of ORF0 grew equally well as the wild-type virus, indicating that the mutation in ORF0 is not by itself sufficient for the attenuation of the vOka virus.     

Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord

The aim of this study was to evaluate whether transplantation of Schwann cells derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration and functional recovery in completely transected spinal cord in adult rats. Bone marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level. An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap. In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase-immunoreactive nerve fibers was significantly higher compared to the MG group, although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive fibers were rarely detectable in both groups. In the BMSC-SC group, significant recovery of the hindlimb function was recognized, which was abolished by retransection of the graft 6 weeks after transplantation. These results demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of lesioned spinal cord, resulting in recovery of hindlimb function in rats. Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord injury.