ABSTRACT
Angiopoietin-like protein 4 (Angptl4), also known as fasting-induced adiopogenic factor (FIAF), has recently been reported to influence bone metabolism. However, there have been few studies on regulatory factors other than hypoxia for Angptl4 in bone, and particularly in osteoblasts. Expression of interleukin-1ß (IL-1ß), a proinflammatory cytokine, is increased in serum or bone microenvironments in inflammatory bone diseases or estrogen deficient-conditions. The present study was conducted to determine whether Angptl4 expression in osteoblasts is affected by IL-1ß and investigate its involvement in MAP kinase signaling pathways. Angptl4 RNA levels were increased by IL-1ß treatment in murine MC3T3-E1 osteoblastic cells. Western blotting and immunofluorescent staining showed a corresponding increase in Angptl4 protein. IL-1ß treatment of osteoblasts induced phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular regulated kinases (ERKs), p38, and c-Jun N-terminal kinase (JNK). Furthermore, SP600125, an inhibitor of JNK, significantly blocked the upregulation of Angptl4 by IL-1ß. In contrast, treatment with an inhibitor of p38 MAP kinase (SB203580) or an ERK inhibitor (PD98059) produced responses similar to those seen with the DMSO control. Taken together, these results suggest that IL-1ß increases Angptl4 expression through a mechanism dependent on the JNK-MAPK signaling pathway in MC3T3-E1 cells.
Subject(s)
Angiopoietins/biosynthesis , Gene Expression Regulation/physiology , Interleukin-1beta/metabolism , MAP Kinase Kinase 4/metabolism , MAP Kinase Signaling System/physiology , Osteoblasts/metabolism , Angiopoietin-Like Protein 4 , Animals , Cell Line , Gene Expression Regulation/drug effects , MAP Kinase Kinase 4/antagonists & inhibitors , MAP Kinase Signaling System/drug effects , Mice , Osteoblasts/cytology , Protein Kinase Inhibitors/pharmacologyABSTRACT
BACKGROUND: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). METHODS: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. RESULTS: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. CONCLUSIONS: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.
Subject(s)
Breast Neoplasms/therapy , Lymph Nodes/pathology , Lymphatic Irradiation/methods , Adult , Aged , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Lymph Nodes/surgery , Lymphatic Metastasis , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Post-radiation pelvic bone sarcoma can result as a long-term sequela of pelvic irradiation for uterine cervical cancer. CASE: A 59-year-old woman who had received pelvic irradiation for Stage IIB uterine cervical cancer 16 years before was diagnosed as having post-radiation osteosarcoma of the sacrum. Another 66-year-old woman who had received pelvic irradiation for Stage IIIB uterine cervical cancer seven years previously was also diagnosed as having pleomorphic sarcoma of the sacrum. CONCLUSION: When a bone lesion is observed at a previously irradiated field, post-radiation sarcoma should be considered and differentiated from bone metastases.
Subject(s)
Bone Neoplasms/secondary , Neoplasms, Radiation-Induced/etiology , Osteosarcoma/secondary , Sacrum/pathology , Uterine Cervical Neoplasms/radiotherapy , Aged , Bone Neoplasms/etiology , Bone Neoplasms/pathology , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Neoplasms, Radiation-Induced/pathology , Osteosarcoma/etiology , Osteosarcoma/pathology , Radiotherapy/adverse effects , Uterine Cervical Neoplasms/pathologyABSTRACT
An unusual case of intraspinal primitive neuroectodermal tumor arising from the sacral spinal nerve root is presented with the first documentation of myelographic, computed tomographic, and magnetic resonance imaging findings.
Subject(s)
Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Peripheral Nervous System Neoplasms/diagnostic imaging , Spinal Nerve Roots , Adult , Female , Humans , Magnetic Resonance Imaging , Myelography , Neoplasms, Germ Cell and Embryonal/diagnosis , Peripheral Nervous System Neoplasms/diagnosis , Tomography, X-Ray ComputedSubject(s)
Adenoma, Chromophobe/complications , Craniocerebral Trauma/complications , Ophthalmoplegia/etiology , Pituitary Neoplasms/complications , Adenoma, Chromophobe/diagnostic imaging , Aged , Cerebral Angiography , Humans , Male , Pituitary Neoplasms/diagnostic imaging , Tomography, X-Ray ComputedSubject(s)
Lipidoses/diagnosis , Adult , Biopsy , Cerebral Cortex/pathology , Humans , Male , SyndromeABSTRACT
A patient with a dominantly inherited form of Kuf's disease and an associated occipital astrocytoma is presented. This is the first reported case in which the diagnosis of Kufs' disease was made by a cortical biopsy several years before its expected clinical onset. The nosology of this disease, and its clinical, genetic, and histopathological characteristics are discussed. The establishment of an early diagnosis by cortical biopsy and its implications are considered.