Search

Retrospective radiographical review.To evaluate the outcome of selective thoracic fusion (STF) by using the Guan-Din method for the treatment of major thoracic compensatory lumbar (MTCL) curves.Performing STF for MTCL curves is to minimize the loss of lumbar motion and the risk of lumbar degeneration or pain. Surgical treatment of MTCL curves aims to maximize the rate of STF for MTCL curves while optimizing instrumental thoracic and compensatory lumbar correction. The Guan-Din method has been demonstrated to be able to enhance the lumbar curve's capacity for spontaneous correction and broaden the current curve criteria of MTCL curves for STF.Between 2004 and 2010, 510 consecutive surgically treated MTCL curves were reviewed. Of these MTCL curves, who met the criteria of lumbar side bending Cobb 35° or less and without global thoracic hyperkyphosis and/or thoracolumbar kyphosis (T10-L2 ≤20°), were treated with STF using the Guan-Din method. Radiographs were analyzed before surgery, immediately after surgery, and at the most recent follow-up (range, 2-8 yr).Curve types of 510 MTCL curves according to Lenke system were as follows: 1A (n = 91), 2A (n = 74), 3A (n = 6), 4A (n = 2), 1B (n = 93), 2B (n = 34), 3B (n = 8), 4B (n = 5), 1C (n = 84), 2C (n = 26), 3C (n = 72), and 4C (n = 15). Of the 510 MTCL curves, 458 (90%) curves were treated with STF. A mean 73% thoracic correction and 63% lumbar correction was obtained at the most recent follow-up. Of the 197 surgically treated MTCL curves with a lumbar C modifier, 148 (75%) curves that contained 57 Lenke 1C and 2C curves and 40 Lenke 3C and 4C curves that did not meet Lenke curve criteria for STF, were successfully treated with STF. A mean 67% thoracic correction and 57% lumbar correction was obtained at the most recent follow-up. The rate of STF and the magnitude of correction of MTCL curves in this study were significantly greater than those in all other reports. No significant change in global coronal and sagittal imbalance was observed.The rate of STF and the compensatory correction of MTCL curves could be maximized by using the Guan-Din method as the method for STF.4.

Knee osteoarthritis (OA) is one of the most prevalent disorders in elderly population. Among various therapeutic alternatives, we employed stromal vascular fraction (SVF), a heterogeneous cell population, to regenerate damaged knee cartilage. OA patients were classified on the basis of age, gender, body mass index (BMI), and x-ray-derived Kellgren&ndash, Lawrence (KL) grade. They were treated with SVF and followed-up for 24 months. Visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index were used to determine treatment efficacy. Cartilage healing was assessed using the MRI-based Outerbridge score (OS) and evaluation of bone marrow edema (BME) lesions, while a placebo group was used as a control. Time- and KL-dependent changes were also monitored. We observed a decreasing trend in VAS score and WOMAC index in the SVF-treated group up to 24 months, as compared with the placebo group. Besides, a significant increase and decrease in Lysholm and OS, respectively, were observed in the treatment group. Compared with the values before treatment, the greatly reduced WOMAC scores of KL3 than KL2 groups at 24 months, indicate more improvement in the KL3 group. Highly decreased BME in the treated group was also noted. In conclusion, the SVF therapy is effective in the recovery of OA patients of KL3 grade in 24 months.

WISP-1 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of matrix cellular proteins. Osteosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effect of WISP-1 on migration activity in human osteosarcoma cells is mostly unknown. In this study, we first found that the expression of WISP-1 in osteosarcoma patients was significantly higher than that in normal bone and corrected with tumor stage. Exogenous treatment of osteosarcoma cells with WISP-1 promoted cell motility and matrix metalloproteinase (MMP)-2 and MMP-9 expression. In addition, the Ras and Raf-1 inhibitor or siRNA abolished WISP-1-induced cell migration and MMP expression. On the other hand, activation of the Ras, Raf-1, MEK, ERK, and NF-κB signaling pathway after WISP-1 treatment was demonstrated, and WISP-1-induced expression of MMPs and migration activity were inhibited by the specific inhibitor, and mutant of MEK, ERK, and NF-κB cascades. Taken together, our results indicated that WISP-1 enhances the migration of osteosarcoma cells by increasing MMP-2 and MMP-9 expression through the integrin receptor, Ras, Raf-1, MEK, ERK, and NF-κB signal transduction pathway.

Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Integrins are the major adhesive molecules in mammalian cells and have been associated with metastasis of cancer cells. Insulin-like growth factor-I (IGF)-I plays an important role in regulating cell growth, proliferation, survival, and metabolism. However, the effects of IGF-I in migration and integrin expression in chondrosarcoma cells are largely unknown. In this study, we found that IGF-I increased the migration and the expression of α5β1 integrin in human chondrosarcoma cells. Pretreatment of cells with IGF-I receptor antibody reduced IGF-I-induced cell migration and integrin expression. Activations of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor-κB (NF-κB) pathways after IGF-I treatment were demonstrated, and IGF-I-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of PI3K, Akt, and NF-κB cascades. Taken together, our results indicated that IGF-I enhances the migration of chondrosarcoma cells by increasing α5β1 integrin expression through the IGF-I receptor/PI3K/Akt/NF-κB signal transduction pathway. J. Cell. Physiol. 226: 3270–3277, 2011. © 2011 Wiley Periodicals, Inc.

Transforming growth factor-beta1 (TGF-beta1) plays a crucial role in adhesion and migration of human cancer cells. Besides, integrins are the major adhesive molecules in mammalian cells. Here we found that TGF-beta1 increased the migration and cell surface expression of beta1 integrin in human lung cancer cells (A549 cells). TGF-beta1 stimulation increased phosphorylation of p85alpha subunit of phosphatidylinositol 3-kinase (PI3K) and Ser(473) of Akt was determined. Besides, we performed that PI3K inhibitor (Ly294002) or Akt inhibitor suppressed the TGF-beta1-induced migration activities of A549 cells. Treatment of A549 cells with NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) also repressed TGF-beta1-induced cells migration and beta1 integrins expression. In addition, treatment of A549 cells with TGF-beta1 induced IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation, IkappaB phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity. Furthermore, the TGF-beta1-mediated increases in IKKalpha/beta, IkappaBalpha phosphorylation and p65 Ser(536) phosphorylation were inhibited by Ly294002 and Akt inhibitor. Co-transfection with p85alpha and Akt mutants also reduced the TGF-beta1-induced kappaB-luciferase activity. Taken together, our results suggest that TGF-beta1 acts through PI3K/Akt, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of beta1 integrins and contributing the migration of human lung cancer cells.

Mutations in codons 12 and 13 of the K-RAS oncogene are detected at a remarkably high frequency in colorectal adenocarcinoma and are believed to be a critical event in oncogenesis. In the present study, we evaluated colorectal tumor specimens from Taiwan for mutations in K-RAS codons 12 and 13 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and direct DNA sequencing. Mutations were found in 48 of 181 (26.5%) tumors, 30 mutations were G--A transitions (62.5% of all mutations), 14 were G--T transversions (29.2%), and only 4 were G--C transversions (8.3%). Similar relative mutation frequencies and spectra were found regardless of the sex of the patient, the tumor grade, or the tumor stage. The high frequency of transitions among K-RAS mutation suggests that G/T mismatches play an important role in the oncogenesis of colorectal adenocarcinoma, implying that alkylating carcinogens may be involved in the colorectal carcinogenesis. Although the frequency of mutation (26.5%) appears to be lower than those reported in the United States (40%), France (49%), and the Netherlands (34%), the spectrum of point mutations in codons 12 and 13 of the K-RAS gene in the Taiwan Chinese population appears to be similar. The reason for these results may be that diet and ethnicity are not rate limit factors in controlling the spectra of mutations but influence on the frequency of K-RAS mutations in human colorectal adenocarcinomas.

It is believed that human progesterone receptor (PR) contains a ligand binding subunit A (83 kDa) or subunit B (120 kDa) and 2 copies of heat shock proteins (hsp90) of molecular weight 90 kDa. To elucidate the mechanism of hormone binding, we employed radiation inactivation to determine its functional size. The functional masses determined in the presence of glycerol, molybdate and potassium chloride were 120 \pm 14, 124 \pm 13 and 130 \pm 20 kDa, respectively. From scatchard plot analysis, the radiation decreased the binding sites and increased the binding affinity of PR with ligand. The functional masses of PR dissolved in the three variant buffers were similar to the molecular weight of PR subunit B. The results implied that PR subunit B could bind with ligand despite hsp90 and hsp90 was not involved in the PR binding to progesterone.

One hundred and thirty-eight stage II and III colorectal cancer patients were included to evaluate the prognostic significance of genetic markers (including mutations of the p53, K- ras genes, and microsatellite instability) on the response to 5-fluorouracil (FU)-based post-operative adjuvant therapies (PAT). When stratified by PAT and adjusting for other prognostic variables, presence of p53 mutation was associated with a poor outcome (hazard ratio (HR)=3.1, 95% confidence interval (CI), 0.9–11.0) among patients without PAT. Our data confirmed that p53 mutation is an independent pre-treatment factor in stage II and III colorectal cancer after curative resection.

Study design Retrospective radiographical review. Objective To demonstrate that the structural and noncompensatory Lenke 3 and 4C lumbar curves could be nonstructural and compensatory. Summary of background data Historically, Lenke 3 and 4C curves were not recommended for selective thoracic fusion (STF) because the lumbar curve was considered structural and noncompensatory. However, consecutive series of Lenke 3 and 4C curves suggest successful treatment with STF. Methods Between 2001 and 2004, 2005 and 2008, and 2010 and 2012, 3 consecutive series of 108, 134, and 78 surgically treated Lenke 1, 2, 3, and 4C curves were reviewed, respectively. The coronal curve criteria for the curves treated with STF during each period were lumbar side bending Cobb angle less than 25° and meeting the Lenke ratio criteria, lumbar side bending Cobb angle 35° or less, and lumbar side bending Cobb angle 45° or less, respectively. The sagittal curve criteria for STF during each period was absence of junctional thoracolumbar kyphosis 20° or more between T10 and L2. The technique used for STF was the Guan-Din method. Radiographs of all the curves treated with STF were analyzed before and after surgery. Results Optimal instrumented thoracic and compensatory lumbar correction was obtained for all Lenke 1, 2, 3, and 4C curves treated with STF in each period. As the coronal criteria for STF were broadened, the extent of feasibility of STF was expanded and the rate of STF increased. Although Cobb angle, apical vertebral translation, and apical vertebral rotation magnitudes of Lenke 3 and 4C curves were larger and more severe than those of Lenke 1 and 2C curves, optimal compensatory correction could still be obtained for Lenke 3 and 4C curves. Conclusion The structural and noncompensatory Lenke 3 and 4C lumbar curves were proven to be nonstructural and compensatory. Lenke 1, 2, 3, and 4C curves have similar natures and similar responses to the same technique (Guan-Din method) used for STF and could be considered collectively as a single indication for STF. The extent of feasibility of STF could be expanded from Lenke 1 and 2 curves to Lenke 1, 2, 3, and 4 curves. Level of evidence 2.

Positron emission tomography (PET) is an important tool for enabling quantification of human brain function. However, quantitative studies using tracer kinetic modeling require the measurement of the tracer time-activity curve in plasma (PTAC) as the model input function. It is widely believed that the insertion of arterial lines and the subsequent collection and processing of the biomedical signal sampled from the arterial blood are not compatible with the practice of clinical PET, as it is invasive and exposes personnel to the risks associated with the handling of patient blood and radiation dose. Therefore, it is of interest to develop practical noninvasive measurement techniques for tracer kinetic modeling with PET. In this paper, a technique is proposed to extract the input function together with the physiological parameters from the brain dynamic images alone. The identifiability of this method is tested rigorously by using Monte Carlo simulation. The results show that the proposed method is able to quantify all the required parameters by using the information obtained from two or more regions of interest (ROI's) with very different dynamics in the PET dynamic images. There is no significant improvement in parameter estimation for the local cerebral metabolic rate of glucose (LCMRGlc) if the number of ROI's are more than three. The proposed method can provide very reliable estimation of LCMRGlc, which is our primary interest in this study.

Background Si-Wu-Tang (SWT), a Traditional Chinese Medicine (TCM) formula, is widely used for the treatment of gynopathies diseases such as menstrual discomfort, climacteric syndrome, dysmenorrhea, and other estrogen-related diseases. Recent studies have shown that SWT can treat primary dysmenorrhea, have anti-pruritic anti-inflammatory effects, and protect against radiation-induced bone marrow damage in an animal model. It has been reported that anti-inflammatory and anti-oxidant agents have the potential to treat osteoporosis by increasing bone formation and/or suppressing bone resorption. However, the effect of SWT on bone cell function has not yet been reported. Methods Alkaline phosphatase (ALP), bone morphogenetic proteins (BMP)-2, and osteopontin (OPN) mRNA expression was analyzed by qPCR. The mechanism of action of SWT extract was investigated using western blotting. The in vivo anti-osteoporotic effect of SWT extract was assessed in ovariectomized mice. Results Here, we report that SWT increases ALP, BMP-2, and OPN expression as well as bone mineralization. In addition, we show that the PI3K, Akt, and NF-κB signaling pathways may be involved in the SWT-mediated increase in gene expression and bone mineralization. Notably, treatment of mice with SWT extract prevented bone loss induced by ovariectomy in vivo. Conclusion SWT may be used to stimulate bone formation for the treatment of osteoporosis.

Interleukin-11 (IL-11) was originally identified as the cytokine that could induce the proliferation of human cells. Recent studies have shown that IL-11 plays a critical role in tumor growth, angiogenesis, and metastasis. Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. However, the effects of IL-11 on human chondrosarcoma cells are largely unknown. Here, we found that IL-11 increased the migration and expression of intercellular adhesion molecule-1 (ICAM)-1 in human chondrosarcoma cells. We also found that human chondrosarcoma tissues had significant expression of the IL-11 which was higher than that in primary chondrocytes. The phosphatidylinositol 3-kinase (PI3K), Akt, and NF-κB pathways were activated by IL-11 treatment, and the IL-11-induced expression of ICAM-1 and migration activity were inhibited by the specific inhibitors and mutant forms of PI3K, Akt, and NF-κB cascades. Taken together, our results indicate that IL-11 enhanced the migration of the chondrosarcoma cells by increasing ICAM-1 expression through the IL-11Rα receptor, PI3K, Akt, and NF-κB signal transduction pathway. J. Cell. Biochem. 113: 3353–3362, 2012. © 2012 Wiley Periodicals, Inc.

The aim of this study was to investigate whether magnesium ascorbyl phosphate (MAP) and coenzyme Q10 (CoQ10) can protect keratinocytes against ultraviolet (UV)A irradiation by increasing the levels of glutathione (GSH). The cell survival fraction was 89.9% when the keratinocytes were irradiated with UVA at a dose of 4 J/cm2. The cell survival fractions were 48.4, 9.1 and 4.8%, at doses of 8, 16 and 32 J/cm2, respectively. MAP was added to the cells prior to UVA irradiation at a dose of 8 J/cm2 and then the cell viability was assayed. The cell survival fractions were 51.6, 55.5, 64.8 and 76.7%, when MAP was added at concentrations of 125, 250, 500 µM and 1 mM, respectively. The results showed that MAP is capable of protecting keratinocytes against UVA irradiation. The cell survival fractions were 77.2, 89.4 and 90.1%, when CoQ10 was added at concentrations of 2.5, 5 and 10 µM, respectively. The results revealed that CoQ10 is capable of protecting keratinocytes against UVA irradiation. At the same time, the levels of GSH within cells were detected. The level of GSH within cells was 0.3 mmol/g protein when the keratinocytes were irradiated with UVA at a dose of 8 J/cm2. We measured the levels of GSH within the cells after MAP or CoQ10 was added prior to UVA irradiation at a dose of 8 J/cm2. The levels of GSH within the cells were 0.344, 0.388, 0.456 and 0.5 mmol/g protein, when MAP was added at concentrations of 125, 250, 500 µM and 1 mM, respectively. The levels of GSH within the cells were 0.328, 0.35 and 0.394 mmol/g protein, when CoQ10 was added at concentrations of 2.5, 5 and 10 µM, respectively. These results imply that MAP and CoQ10 can protect the keratinocytes against UVA irradiation, possibly via increasing the levels of GSH.

AIM: To investigate how a complex network of CC chemokine ligands (CCLs) and their receptors influence the progression of tumor and metastasis. METHODS: In the present study, we used immunohistochemistry to examine the expression of CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues. We analyzed their correlation with tumor metastasis, clinicopathologic parameters and clinical outcome. RESULTS: We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion, lymph node metastasis and higher tumor node metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis. CONCLUSION: These results suggest that overexpression of these two CC chemokine ligands is associated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.

Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. This study is the first to investigate the anti-cancer effects of the new benzimidazole derivative (5-methyl-2(pyridine-3-yl)-1-(3,4,5-trimethoxybenzyl)benzimidazole; MPTB) in human chondrosarcoma cells. MPTB-induced cell apoptosis in two human chondrosarcoma cell lines, JJ012 and SW1353 but not in primary chondrocytes. MPTB-induced upregulation of Bax and Bak and dysfunction of mitochondria in chondrosarcoma. MPTB triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol calcium levels, and increased glucose-regulated protein (GRP) expression. MPTB also increased calpain expression. Transfection of cells with GRP78 or calpain siRNA reduced MPTB-mediated cell apoptosis in JJ012 cells. Importantly, animal studies have revealed a dramatic 44% reduction in tumor volume after 21 d of treatment. This study demonstrates novel anti-cancer activity of MPTB against human chondrosarcoma cells and in murine tumor models.

Bone morphogenetic protein-2 (BMP-2), a member of transforming growth factor-beta superfamily, plays a crucial role in migration and metastasis of human cancer cells. Integrins are the major adhesive molecules in mammalian cells. Here we found that BMP-2 directed the migration and increased cell surface and mRNA expression of beta1 integrin in human chondrosarcoma cancer cells (JJ012). Pretreated of JJ012 cells with phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002) or Akt inhibitor inhibited the BMP-2-mediated migration and integrin expression. BMP-2 increased the phosphorylation of p85 subunit of PI3K and serine 473 of Akt. In addition, NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) also inhibited BMP-2-mediated cells migration and integrin upregulation. Stimulation of JJ012 cells with BMP-2 induced IkappaB kinase (IKKalpha/beta) phosphorylation, IkappaB phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity. Furthermore, the BMP-2-mediated increasing of IKKalpha/beta phosphorylation, IkappaB phosphorylation, and p65 Ser(536) phosphorylation were inhibited by Ly294002 and Akt inhibitor. Co-transfection with p85 and Akt mutants also reduced the BMP-2-induced kappaB-luciferase activity. Taken together, these results suggest that the BMP-2 acts through PI3K/Akt, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of beta1 integrin and contributing the migration of human chondrosarcoma cells.

Matrix metalloproteinases (MMPs) MMP-2 and MMP-9 can degrade type IV collagen of extracellular matrix and basal membranes. Claudin-4 is a member of a large family of transmembrane proteins, claudins, essential in the formation and maintenance of tight junctions. Claudin-4 has been shown to activate MMP-2, indicating that claudin-mediated increased cancer cell invasion might be mediated through the activation of MMP proteins. To explore the roles of MMP-2, MMP-9 and claudin-4 in gastric cancer, we selected 88 cases and then analyzed the expression of these proteins using immunohistochemistry. We found that all of MMP-2, MMP-9 and claudin-4 expressions were significantly higher in intestinal-type than in diffuse-type gastric cancer. On further analysis, testing the relationship between MMP-2 and MMP-9 expression with claudin-4 expression, claudin-4 expression was significantly associated with MMP-9 expression, but not with MMP-2 expression. The results showed that MMP-2, MMP-9 and claudin-4 expression may be phenotypic features, distinguishing intestinal-type and diffuse-type gastric cancer. Possibly, claudin-4 played a role in determining MMP-9 activity which favored intestinal-type gastric cancer to distal metastasis.

Our previous microarray analysis of gastric cancer found that claudin-4 was differentially expressed between intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC). Claudin-4 is a member of a large family of transmembrane proteins, claudins, essential in the formation and maintenance of tight junctions. To explore the roles of claudin-4 in the two histologically distinct types of gastric cancer, we selected 45 IGC and 48 DGC cases and then analyzed the expression of the protein using immunohistochemistry. We found that the overexpression of claudin-4 was greater in IGC than in DGC. A trend was observed between the overexpression of claudin-4 and lymph node metastasis, however, this association was not statistically significant. The results showed that the expression of claudin-4 was lower in DGC. Possibly it played a role in determining the diffuse phenotype and loose cohesion of cells in DGC in a similar manner as E-cadherin.

To compare the gene expression profiling between intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC), cDNA microarray containing 7334 gene elements was performed on 12 paired IGC specimens/its' normal epithelial tissue and 11 paired DGC specimens/its' normal epithelial tissue. Twenty-seven genes were co-over-expressed in IGC and DGC. These overexpressed genes were related to transcription and translation, DNA replications and mitosis, calcium binding, apoptosis and mitochondria protein. Twelve genes were co-underexpressed in IGC and DGC. These underexpressed genes were associated with cell adhesion and migration, organelle movement and intracellular transport, and matrix metalloproteinase. A clustering dendrogram of IGC and DGC with 27 genes significantly differed between IGC and DGC. Nineteen genes were more overexpressed in DGC than in IGC, including annexin Al (ANXA1), chemokine ligand 7 (CCL7), and chemokine ligand 8 (CCL8). Eight genes were more overexpressed in IGC than in DGC, including claudin 4 (CLDN4). The results of quantitative real-time PCR and immunohistochemical staining confirmed the microarray finding. The gene expression profiling between IGC and DGC suggested that they might have unique genetic pathways which share some of the same and some different genetic alterations.

To explore the relationship between mutations of the p53 gene, p53 protein accumulation in tumor tissues and the presence of anti-p53 antibodies (Ab) in sera, a matched case-control study with 63 colorectal cancer patients positive for p53-Ab was carried out. These control patients were matched for age, gender, as well as tumor site and stage with 63 colorectal cancer patients positive for p53-Ab. The study was designed to analyze their p53 gene mutations in exons 4-9 by the single strand conformation polymorphism (SSCP) followed by direct sequencing, as well as measuring p53 protein accumulation by immunohistochemistry. A significantly higher frequency of p53 mutations in exon 4-9 and positive immunohistochemical staining of p53 protein was observed in tumors from p53-Ab positive patients (55.56 and 84.13%, respectively) than in tumors from p53-Ab negative patients (22.22 and 60.32%, respectively). Using a conditional logistic regression model, the humoral response to p53 was found to be associated with p53 gene mutation (OR = 3.34; 95% CI, 1.31-8.54, p=0.012) and p53 protein accumulation (OR = 3.80; 95% CI, 1.02-14.14, p=0.047). Further analysis showed that the frequency of p53 mutations located in the conserved domains II (codons 112-141) and IV (codons 234-258) was significantly higher in p53-Ab positive patients than in p53-Ab negative patients (50.00% (16/32) vs. 8.33% (1/12), p=0.015, Fisher's exact test). Thus, our study demonstrated that the generation of p53 antibodies was usually correlated with the p53 protein accumulation and p53 gene mutation, especially mutations located in conserved domains II and IV.