BACKGROUND: Osteopontin (OPN) is a cytokine associated with a cell-matrix via integrins. Fibroblast specific protein-1 (FSP-1), known as S100A4, has been implicated in cell migration by non-muscle myosin. We investigated whether the role of OPN and FSP-1/S100A4 expression in their contribution to the podocyte phenotype change to form podocyte bridge and cellular crescent. METHODS: Glomerular expression of OPN and FSP-1/S100A4 in renal biopsies of 16 patients with crescentic glomerulonephritis (CrGN) and 13 normal renal biopsies were studied by immunohistochemistry. RESULTS: The expression of OPN and FSP-1/S100A4 was increased in the podocytes of glomeruli, with and without crescents, in patients with CrGN. Neither OPN nor FSP-1/S100A4 was expressed in glomeruli from the normal controls (p<0.01). A significant positive correlation was found between the expression of OPN in glomerular tufts and cellular crescents, and the expression of OPN and FSP-1/S100A4 in glomerular tufts (p<0.05). CONCLUSIONS: The results suggest that OPN plays a role in early podocyte attachment to Bowman's capsule, and FSP-1/S100A4 potentiate podocyte contribution to cellular crescent formation by inducing cellular migration and growth.
Biopsy ; Bowman Capsule ; Cell Movement ; Fibroblasts ; Glomerulonephritis ; Humans ; Integrins ; Myosins ; Osteopontin ; Phenotype ; Podocytes

BACKGROUND: Osteopontin (OPN) is a cytokine related to cell-matrix adhesion and cell survival and is expressed in the distal convoluted tubules in normal adult kidneys. Only one in vitro study has investigated the role of OPN in mechanically stretched podocytes and their actin cytoskeleton rearrangement. METHODS: Glomerular OPN expression was investigated in biopsies from patients with human idiopathic focal segmental glomerulosclerosis (FSGS) (n = 25) and in normal renal biopsies (n = 16) by immunohistochemistry. RESULTS: OPN was expressed in the podocytes from patients with FSGS. OPN expression increased in podocytes from both non-sclerotic hypertrophic and sclerotic glomerular tufts in patients with FSGS compared to the podocytes in normal controls. CONCLUSIONS: The results suggest that OPN plays a role in the early adaptive response of podocytes to the increased mechanical load caused by glomerular hypertrophy preceding FSGS. OPN was involved in cell-matrix adhesion and influenced the detachment delay of podocytes from the glomerular basement membrane and apoptosis.
Actin Cytoskeleton ; Adult ; Apoptosis ; Biopsy ; Cell Survival ; Glomerular Basement Membrane ; Glomerulosclerosis, Focal Segmental ; Humans ; Hypertrophy ; Immunohistochemistry ; Kidney ; Osteopontin ; Podocytes

Background : CD44 is a transmembranous glycoprotein that participates in cell-cell and cell-matrix interactions, and it also contributes to cell migration. In vitro studies have suggested that the expression of CD44 isoforms is associated with tumor metastasis. Since it is not clear whether the CD44 isoforms play a role in the tumorigenesis, differentiation, progression or metastasis of renal cell carcinomas (RCCs). Methods : We performed immunohistochemistry with primary antibodies for the standard CD44 (CD44s) and the CD44 variant exon 6 (CD44v6) on the archival paraffin-embedded tissue microarray (TMA) specimens from 51 RCC patients. Results : In the normal kidney, the expressions of both CD44s and CD44v6 were negligible. The CD44s expression was increased in accordance with the tumor size (p<0.01), but it was not related to the microvessel density (MVD). No CD44v6 expression was observed in all RCC cases. Univariate analysis indicated that stage, tumor size, lymph node metastasis and distant organ metastasis were the statistically significant prognostic factors for disease free survival (DFS) (p<0.01), and the multivariate analysis proved that stage (p<0.01) and tumor size (p<0.05) were the independent prognostic factors for DFS. Conclusions : Our results suggest that CD44s, but not CD44v6, plays a role in tumor progression and it could be a potential prognostic factor for patients with RCCs.
Antibodies ; Antigens, CD44 ; Carcinogenesis ; Carcinoma, Renal Cell* ; Cell Movement ; Disease-Free Survival ; Exons ; Glycoproteins ; Humans ; Immunohistochemistry ; Kidney ; Lymph Nodes ; Microvessels ; Multivariate Analysis ; Neoplasm Metastasis ; Protein Isoforms*

PURPOSE: The growth, progression, and metastasis of malignant neoplasms are influenced by the environment of the tumor and by proliferation of the tumor itself. Angiogenesis of a malignant neoplasm is a very important environmental factor of tumor growth and metastasis. Also, it is a prognostic factor for malignant neoplasms. The mechanism of angiogenesis, such as the effects of cytokines and angiogenesis-promoting factors, is incompletely understood. METHODS: This study was designed to define the role of tumor necrosis factor-alpha (TNF-alpha) and the vascular endothelial growth factor (VEGF) in angiogenesis induced by lipopolysaccharide (LPS) and thalidomide (anticytokine drug) in CT26 murine colon cancer transplanted to BALB/c mice. RESULTS: The tumor size in the LPS-treated group (n=3, 2.1+/-0.26 cm) was larger than it was in the LPS thalidomide-treated group (n=4, 1.95+/-0.19 cm) and in the control group (n=3, 1.6+/-0.20 cm) (P<0.05). The microvessel density determined by CD31 immunostaining was lowest for the control group and highest for the LPS- treated group, but the differences were not statistically significant. An immunohistochemical study showed that the expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) were higher in the experimental groups than they were in the control group. Also, the LPS thalidomide-treated group had lower expressions of TNF-alpha (P<0.01) and VEGF (P<0.05) than the LPS-treated group. Western blots revealed that the TNF-alpha and the VEGF levels semiquantitatively increased from the control group to the LPS thalidomide-treated group to the LPS-treated group. CONCLUSIONS: Our study revealed that low doses of LPS stimulated angiogenesis through increased expression of TNF-alpha and VEGF. Thalidomide decreased angiogenesis, probably through suppression of TNF-alpha with a decreased expression of VEGF. We conclude that TNF-alpha, suppressed by thalidomide, in the model of transplanted colon cancer may inhibit angiogenesis through coincident decrease in the expression of VEGF.
Animals ; Blotting, Western ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; Cytokines ; Mice* ; Microvessels ; Neoplasm Metastasis ; Thalidomide* ; Tumor Necrosis Factor-alpha* ; Vascular Endothelial Growth Factor A*

BACKGROUND: Osteopontin (OPN) is a glycoprotein and it participates in cell-cell and cell-matrix interactions. In vitro studies suggest that the OPN expression is associated with tumor metastasis, and especially with the metastasis of osteotropic tumors originating in breast, prostate and lungs. Since no human tissue study has suggested the means by which OPN participates in the tumorigenesis, angiogenesis, progression and metastasis of renal cell carcinoma (RCC), we evaluated the expression and prognostic significance of OPN in RCC. METHODS: Immunohistochemistry was performed with using the primary antibody for OPN on the archival paraffin-embedded tissue microarray specimens from 51 RCC patients who underwent radical or simple nephrectomy. RESULTS: In the normal kidney specimens, OPN was expressed in a few compressed distal tubules adjacent to the RCCs. In RCCs, the OPN expression was elevated in larger tumors (p<0.05) and in the tumor with low microvessel density (p<0.01). In the present study, univariate analysis indicated that stage, tumor size, lymph node and distant organ metastasis are significant prognostic factors for disease free survival (DFS) in RCC patients (p<0.01), but OPN is not (p=0.0661). Multivariate analysis indicated lymph node metastasis is the independent prognostic indicator of DFS (p<0.05). CONCLUSION: Though this study has statistical limitations, these results suggest OPN plays a role in tumor progression and metastasis and it may act as a potential prognostic indicator to predict the prognosis of RCC patients.
Anoxia ; Breast ; Carcinogenesis ; Carcinoma, Renal Cell* ; Disease-Free Survival ; Glycoproteins ; Humans* ; Immunohistochemistry ; Kidney ; Lung ; Lymph Nodes ; Microvessels ; Multivariate Analysis ; Neoplasm Metastasis ; Nephrectomy ; Osteopontin* ; Prognosis ; Prostate

Background : Differential diagnoses of intrahepatic adenocarcinomas (IHAC) play an important role in the detecting primary sites and the determining type of treatment and overall prognosis of the patient. However, histopathologic findings alone have limitations of differential diagnoses of IHAC. Methods : To clarify which tumor related proteins (TRP) are useful for differential diagnoses of IHAC, TRP expression were investigated immunohistochemically, using MUC5AC, MUC2, mAb 91.9H, MUC1, and pS2, and by high iron diamine (HID) staining in 61 clinically confirmed IHACs. Results : MUC5AC (9/18, p<0.05) and MUC1 (17/18, p>0.05) displayed the most frequent expression in cholangiocarcinomas, and MUC2 (11/18, p<0.05), mAb 91.9H (16/18, p<0.05), and HID (16/18, p<0.05) in colorectal adenocarcinomas. pS2 (3/11, p>0.05) was expressed more often in pancreatic adenocarcinomas than other IHAC, while MUC2 and 91.9H were not expressed at all in pancreatic adenocarcinomas. The positivity of several TRP did not correlate with tumor differentiation. Conclusions : MUC5AC, MUC2, mAb 91.9H, and HID may be useful in differentiating cholangiocarcinomas from colorectal adenocarcinomas.
Adenocarcinoma* ; Cholangiocarcinoma ; Diagnosis ; Diagnosis, Differential* ; Humans ; Iron ; Prognosis

BACKGROUND/AIMS: TRAIL-induced apoptosis was believed to occur in tumor cell lines, while not in normal cells, which suggested that TRAIL might be safe as an antitumor therapy. Some authors advocate that this exclusive TRAIL-induced apoptosis depended on whether or not TRAIL-R3 mRNA was expressed. In this study we investigated the difference in the expression of TRAIL and its receptors mRNA between human hepatocellular carcinoma (HCC) and surrounding liver tissues. METHODS: Intra-operative sampling of HCC and paired surrounding liver tissue was performed in 12 patients who underwent hepatic resection due to HCC. After RT-PCR, using total RNA extracts from the tissues, amplified RT-PCR, products were analyzed qualitatively for the expression of TRAIL and its receptors mRNA. Both tissues were compared semi-quantitatively for the expression of TRAIL-R3 mRNA with beta-actin using the method of Nicoletti et al. RESULTS: 1) TRAIL mRNA was expressed in HCC and surrounding liver tissues in all cases. 2) TRAIL-R1, -R2, and -R3 mRNA were also expressed in HCC and surrounding liver tissues in all cases. 3) The ratio of the expression of TRAIL-R3 mRNA to beta-actin mRNA was 0.22+/-0.15 in HCC and 0.34+/-0.21 in surrounding liver tissues (p=0.124, paired t-test). 4) TRAIL, TRAIL-R1, -R2 and -R3 mRNA were expressed in all HCC cases irrespective of the degree of tumor cell differentiation. CONCLUSIONS: TRAIL, TRAIL-R1, -R2, and TRAIL-R3 mRNA were expressed in all of the HCC and surrounding liver tissues. There was no quantitative difference in the expression of TRAIL-R3 mRNA between both tissues.
Actins ; Apoptosis ; Carcinoma, Hepatocellular* ; Cell Differentiation ; Cell Line, Tumor ; Humans ; Liver* ; Necrosis* ; RNA ; RNA, Messenger* ; TNF-Related Apoptosis-Inducing Ligand

BACKGROUNDAlthough some studies measured the burden of caregivers and the factors that influenced their feelings of burden, few studies have measured the quality of life (QOL) for primary caregivers of patients with muscular dystrophy (MD). We assessed the QOL for primary caregivers of patients with MD in South Korea and identified factors associated with caregivers' QOL.

METHODSNinety dyads of patients with MD and their primary caregivers were enrolled in this study. The QOL of caregivers of patients with MD was assessed subjectively using the World Health Organization Quality of Life Assessment, Life Brief Form. Caregivers' emotional status was assessed using the Beck Depression Inventory (BDI) and family function level was evaluated using the Family APGAR scale. Patients reported their emotional status using the BDI or the Children's Depression Inventory. The functional levels of patients were evaluated by the modified Barthel Index.

RESULTSCaregivers' QOL was statistically associated with family income, family function, emotional status of patients, level of education, and emotional status of caregivers (P < 0.05). Caregivers who were employed had a significantly higher QOL than those who were not (P < 0.05). In multiple regression analyses, emotional and employment status of caregivers was strongly associated with caregivers' QOL.

CONCLUSIONRehabilitation teams should consider not only the physical factors of patients but also the psychological and demographic factors of primary caregivers of patients with MD.

Adolescent ; Adult ; Caregivers ; statistics & numerical data ; Child ; Female ; Humans ; Linear Models ; Male ; Muscular Dystrophies ; Quality of Life ; Republic of Korea ; Young Adult

Mucormycosis is an uncommon, frequently fatal, opportunistic fungal infection and usually occur in immunocompromised patients. Rhinocerebral and pulmonary disease are the common forms but intestinal infection is an extremely rare form of the disease. Invasive intestinal mucormycosis is usually fatal, therefore, few cases reported survival after early diagnosis and surgical resection combined with antifungal treatment. Because of high mortality after surgery, the healing of ulcers caused by intestinal mucormycosis has not previously observed in immunocompromised host. We reported a case of the intestinal mucormycosis that had been healed the ulcer and symptomatic improvement after only amphotericin B.
Amphotericin B* ; Early Diagnosis ; Immunocompromised Host ; Lung Diseases ; Mortality ; Mucormycosis* ; Ulcer*