ABSTRACT
BACKGROUND: The aim of this study was to evaluate the combined effect of low-level laser treatment (LLLT) and recombinant human bone morphological protein-2 (rhBMP-2) applied to hypoxic-cultured MC3T3-E1 osteoblastic cells and to determine possible signaling pathways underlying differentiation and mineralization of osteoblasts under hypoxia. METHODS: MC3T3-E1 cells were cultured under 1% oxygen tension for 72 h. Cell cultures were divided into four groups: normoxia control, low-level laser (LLL) alone, rhBMP-2 combined with LLLT, and rhBMP-2 under hypoxia. Laser irradiation was applied at 0, 24, and 48 h. Cells were treated with rhBMP-2 at 50 ng/mL. Alkaline phosphatase activity was measured at 3, 7, and 14 days to evaluate osteoblastic differentiation. Cell mineralization was determined with Alizarin red S staining at 7 and 14 days. Western blot assays were performed to evaluate whether p38/protein kinase D (PKD) signaling was involved. RESULTS: The results indicate that LLLT and rhBMP-2 synergistically increased alkaline phosphatase (ALP) activity and mineralization. Western blot analyses showed that expression of type I collagen, runt-related transcription factor 2 (RUNX2), and Osterix (Osx), increased and expression of hypoxia-inducible factor 1-alpha (HIF-1α), decreased more in the LLLT and rhBMP-2 combined group than in the rhBMP-2 or LLL alone groups. Moreover, LLLT and rhBMP-2 stimulated p38 phosphorylation and rhBMP-2 and LLLT increased Prkd1 phosphorylation. CONCLUSION: Combined treatment with rhBMP-2 and LLL induced differentiation and mineralization of hypoxiccultured MC3T3-E1 osteoblasts by activating p38/PKD signaling in vitro.
Subject(s)
Humans , Alkaline Phosphatase , Hypoxia , Blotting, Western , Cell Culture Techniques , Collagen Type I , In Vitro Techniques , Low-Level Light Therapy , Miners , Osteoblasts , Oxygen , Phosphorylation , Phosphotransferases , Transcription FactorsABSTRACT
Subject(s)
Bone Density , Cone-Beam Computed Tomography , Dental Implants , Follow-Up Studies , Maxilla , OsseointegrationABSTRACT
PURPOSE: The most important independent prognostic factors of breast cancer have been reported to the tumor size and lymph node metastasis, as well as DNA ploidy, proliferation index, and various receptors, including estrogen receptor (ER) and progesteron receptor (PR) and oncogenes, such as c-erbB-2, and the tumor suppressor gene, p53. However, all these prognostic factors are still unable to exactly estimate distant metastasis for breast cancer. Based on this, our aim was to study for the prognostic factors that associated distant metastasis of breast cancer with cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), which are related to angiogenesis, and Cyclin D1, which participates in cell proliferation in breast cancer. METHODS: A retrospective study was carried out on 95 patients, who has undergone an operation for breast cancer, with or without metastasis between January 1993 and July 2001, at the Department of Surgery, Chungnam National University Hospital. The study was based on the immunohistochemical staining of primary tumors for COX-2, VEGF, Cyclin D1, ER, PR and c-erbB-2, which were obtained from tissue samples of 45 and 50 patients with and with no distant metastatic breast cancer. SPSS for Windows, Version 10.0 was used for the statistical analyses. RESULTS: The expressions of COX-2, VEGF and Cyclin D1 were statistically significant in distant metastatic breast cancer. The clinicopathological parameters associated with distant metastasis were the tumor size and histological grade, and lymph node metastasis, lymphovascular invasion, ER and PR. There were positive correlations between 1) COX-2 and VEGF, 2) COX-2 and Cyclin D1, 3) c-erbB-2 and Cyclin D1 and 4) VEGF and Cyclin D1, COX-2 also had positive relationships with the tumor size and c-erbB-2, VEGF had positive relationships with lymph node metastasis, histological grade and lymphovascular invasion, as well as with ER and PR. The overexpressions of COX-2, VEGF and Cyclin D1 shortened the disease-free survival and survival period. CONCLUSION: The overexpressions of COX-2, VEGF and Cyclin D1 were considered poor prognostic factors for the induction of distant metastasis. Therefore, COX-2, VEGF and Cyclin D1 could be used in the prevention of distant metastasis, and prescribed for the treatment of metastatic breast cancer.
Subject(s)
Humans , Breast Neoplasms , Breast , Cell Proliferation , Cyclin D1 , Cyclins , Cyclooxygenase 2 , Disease-Free Survival , DNA , Estrogens , Genes, Tumor Suppressor , Lymph Nodes , Neoplasm Metastasis , Oncogenes , Ploidies , Retrospective Studies , Vascular Endothelial Growth Factor AABSTRACT
PURPOSE: The objective of this study was to test the efficacy and toxicity of adriamycin plus docetaxel as primary chemotherapy for women with locally advanced breast carcinoma, including patients with inflammatory breast cancer. METHODS: From 2001, April to 2003, July, 18 patients with locally advanced breast cancer were treated with Adriamycin (50 mg/m2; intravenous bolus) followed by docetaxel (75 mg/m2; 1-hour intravenous infusion) on day of each cycle for four cycles. RESULTS: Two of 18 patients (11.8%) had inflammatory breast carcinoma. 17 (94.4%) patients underwent surgery. 14 (82.4%) patients had clinical responses, of them, two (11.8%) patients had complete clinical response in primary tumor. One case showed a pathologic complete response. In the lymph node response, four (23.6%) patients had clinical complete responses and 11 (64.7%) patients had partial clinical responses. Grade 3 or 4 neutropenia was recorded in 21.7% (21/97 cycles) and febrile neutropenia was recorded in 13.4% (13/97 cycles). Grade 3 or 4 anemia was recorded in 4.2% (4/97 cycles), but there was no severe thrombocytopenia. Other side effects were diarrhea, oral mucositis and mild emesis. CONCLUSION: Neoadjuvant chemotherapy with adriamycin plus docetaxel was a feasible and effective threatment in an unfavorable series of patients with locally advanced breast cancer including patients with inflammatory breast cancer.
Subject(s)
Female , Humans , Anemia , Breast Neoplasms , Breast , Diarrhea , Doxorubicin , Drug Therapy , Febrile Neutropenia , Inflammatory Breast Neoplasms , Lymph Nodes , Neoadjuvant Therapy , Neutropenia , Stomatitis , Thrombocytopenia , VomitingABSTRACT
We present 3 cases of fecal incontinence associated with traumatic injury during Duhamel procedure. Three male patients suffered from persistent fecal soiling and incontinence for more than 7 years after definitive surgery for Hirschsprung's disease by a pediatric surgeon. They showed grade 4 frequent major soiling, mild patulous anus, and flattening of the anorectal angle due to traumatic injury of the external sphincter and puborectalis muscle on the posterior midline of the anorectal junction. On Parks postanal pelvic floor repair procedures, the incontinent symptoms were abated, anatomic changes were normalized, and postoperative Kirwan classification scales were markedly improved from grade 4 to grade 1. Patients with fecal incontinence after Duhamel operation for Hirschsprung's disease may have a traumatic injury of the anal sphincter. Careful physical and laboratory examinations should be performed for the confirmation of traumatic injury in these patients, and Parks postanal repair could be the treatment of choice for the correction of incontinence.
Subject(s)
Humans , Male , Anal Canal , Classification , Fecal Incontinence , Hirschsprung Disease , Pelvic Floor , Soil , Weights and MeasuresABSTRACT
PURPOSE: In order to clarify the the role of epidermal growth factor (EGF) in the regulation of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) during liver regeneration, we investigated the EGF-dependent gene expression of PA and PAI-1 in rat hepatocytes in primary culture. METHODS: Hepatocytes were isolated from rats using a two step perfusion technique and cultivated in dishes precoated with rat tail collagen. DNA synthesis of the hepatocytes by EGF treatment was measured with (3)H-thymidine incorporation. Gene expression for PAI-1, uPA and tPA was examined using Northern blot hybridization analysis. RESULTS: EGF treatment increased the (3)H-thymidine incorporation of the hepatocytes up to 36 hours and normal polygonal hepatocyte morphology was achieved simultaneously. tPA and PAI-1 mRNA were detected in the control hepatocytes. With the EGF treatment, the tPA mRNA level increased with time up to 48 hours, however the PAI-1 mRNA level rapidly increased to 1 hour and then decreased quickly to the control level. On the contrary, uPA mRNA was not detected in hepatocytes with or without treatment of EGF. The EGF-dependent induction of tPA and PAI-1 mRNA was a protein synthesis independent process. CONCLUSION: These results suggest that differential expression of tPA and PAI-1 mRNA by EGF in hepatocytes may play an important role in the regulation of liver regeneration. Among PAs, tPA seemed to be more important in EGF dependent growth or regeneration of primary hepatocytes in the rat since uPA mRNA was not induced in primary hepatocyte cultures in spite of EGF treatment.