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1.
AJNR Am J Neuroradiol ; 41(8): 1405-1413, 2020 08.
Article in English | MEDLINE | ID: mdl-32675335

ABSTRACT

BACKGROUND AND PURPOSE: Phase imaging helps determine a lesion's susceptibility. However, various inhomogenous phase patterns could be observed in the serial phase images of a lesion and render image interpretation challenging. We evaluated the diagnostic accuracy of differentiating cerebral microbleeds and calcifications from phase patterns in axial locations. MATERIALS AND METHODS: This study retrospectively enrolled 31 consecutive patients undergoing both CT and MR imaging for acute infarction exhibiting dark spots in gradient-echo magnitude images. Six patients had additional quantitative susceptibility mapping images. To determine their susceptibility, 2 radiologists separately investigated the phase patterns in the border and central sections and quantitative susceptibility mapping of dark spots. Sensitivity and specificity were compared using the McNemar test. Interobserver reliability and correlation analysis were determined using the κ coefficient and Pearson correlation coefficient, respectively. RESULTS: Among 190 gradient-echo dark spots, 62 calcifications and 128 cerebral microbleeds were detected from CT. Interobserver reliability was higher for the border phase patterns (κ = 1) than for the central phase patterns (κ = 0.77, P < .05). The sensitivity and specificity of the border phase patterns in identifying calcifications were higher than those of the central phase patterns (98.4% and 100% versus 79% and 83.6%), particularly for lesions >2.5 mm in diameter (100% and 100% versus 66.7% and 61.1%). The same values were obtained using quantitative susceptibility mapping for identification (100% and 100%). A high correlation between the size and susceptibility of cerebral microbleeds and calcifications suggested that greater phase changes may be caused by larger lesions. CONCLUSIONS: The border phase patterns were more accurate than the central phase patterns in differentiating calcifications and cerebral microbleeds and was as accurate as quantitative susceptibility mapping.


Subject(s)
Calcinosis/diagnostic imaging , Cerebral Hemorrhage/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Neuroimaging/methods , Aged , Aged, 80 and over , Cerebral Hemorrhage/pathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed
2.
Cell Death Differ ; 26(1): 196, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30185823

ABSTRACT

Following publication of their article "CCN2 inhibits lung cancer metastasis through promoting DAPK-dependent anoikis and inducing EGFR degradation", the authors reported an error in Fig.6b. α-Tubulin image of rCCN2 treatment  (upper panel in CL1-5) only showed eight lanes, when there should be nine.

3.
J Chem Phys ; 149(22): 224303, 2018 Dec 14.
Article in English | MEDLINE | ID: mdl-30553240

ABSTRACT

This paper reports observations and analysis of the Rb2 31Π g state. A total of 323 rovibrational term values spanning the range of the rotational quantum number J = 7 through 77 and the vibrational quantum number v = 2 through 23 (about 1/3 of the potential well depth) were measured using the optical-optical double resonance technique. The term values are simulated within a model of a piece-wise multi-parameter potential energy function based on the generalized splines. This function not only enables a reproduction of the experimental data with a reasonable quality but also approximates the available ab initio function in its whole range with a uniform accuracy.

4.
Br J Dermatol ; 171(5): 1073-7, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24890286

ABSTRACT

BACKGROUND: Trichilemmoma is a benign follicular epithelial tumour exhibiting outer root sheath differentiation. It is associated with Cowden syndrome and naevus sebaceus (NS), but the pathogenesis of sporadic tumours is poorly understood. Recently, NS was found to be caused by postzygotic HRAS or KRAS mutations. OBJECTIVES: We sought to determine whether NS-related and NS-unrelated trichilemmomas harbour RAS mutations. METHODS: Formalin-fixed and paraffin-embedded blocks of 12 NS-related and 15 NS-unrelated trichilemmomas from 26 individuals were retrieved and analysed to determine the presence of mutations in exons 1 and 2 of the HRAS, KRAS and NRAS genes by polymerase chain reaction and direct sequencing. Mutational hotspots of the FGFR3 and PIK3CA genes were also analysed for NS-unrelated cases. RESULTS: Among the 27 cases, mutually exclusive HRAS c.37G>C and c.182A>G mutations were observed in 17 and three tumours, respectively. Of the 12 NS-related tumours, 11 (92%) harboured the HRAS c.37G>C substitution. Of the 15 sporadic tumours, nine (60%) harboured HRAS mutations, including six c.37G>C and three c.182A>G. An HRAS c.182A>G mutation was observed only in sporadic tumours. No mutations were observed in the other genes that were tested. CONCLUSIONS: The high frequency of HRAS activating mutations, including the c.182A>G substitution, which was rather rare in NS, suggests that most trichilemmomas are authentic neoplasms.


Subject(s)
Genes, ras/genetics , Mutation/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Skin Neoplasms/genetics , Class I Phosphatidylinositol 3-Kinases , Exons/genetics , Genotype , Hair Diseases/genetics , Hair Follicle , Humans , Mutation Rate , Neoplasms, Basal Cell/genetics , Phosphatidylinositol 3-Kinases/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics
5.
Oncogene ; 33(23): 2968-77, 2014 Jun 05.
Article in English | MEDLINE | ID: mdl-23851503

ABSTRACT

Gain of function of membrane receptor was a good strategy exploited by cancer cells to benefit own growth and survival. Overexpression of HER2 has been found to serve as a target for developing trastuzumab to treat 20-25% of breast cancer. However, little or none of the other membrane receptor was found to be useful as a potential target for breast cancer treatment since then. Here, we showed that amplified signaling of interleukin-17 receptor B (IL-17RB) and its ligand IL-17B promoted tumorigenicity in breast cancer cells and impeded acinus formation in immortalized normal mammary epithelial cells. External signal transmitted through IL-17RB activated nuclear factor-κB to upregulate antiapoptotic factor Bcl-2 and induced etoposide resistance. Elevated expression of IL-17RB had a stronger correlation with poor prognosis than HER2 in breast cancer patients. Interestingly, breast cancer patients with high expression of IL-17RB and HER2 had the shortest survival rate. Depletion of IL-17RB in trastuzumab-resistant breast cancer cells significantly reduced their tumorigenic activity, suggesting that IL-17RB and HER2 have an independent role in breast carcinogenesis. Furthermore, treatment with antibodies specifically against IL-17RB or IL-17B effectively attenuated tumorigenicity of breast cancer cells. These results suggest that the amplified IL-17RB/IL-17B signaling pathways may serve as a therapeutic target for developing treatment to manage IL-17RB-associated breast cancer.


Subject(s)
Breast Neoplasms/pathology , Carcinogenesis , NF-kappa B/metabolism , Receptors, Interleukin-17/antagonists & inhibitors , Receptors, Interleukin-17/metabolism , Animals , Apoptosis/drug effects , Autocrine Communication , Breast Neoplasms/metabolism , Carcinogenesis/drug effects , Cell Line, Tumor , Etoposide/pharmacology , Female , Gene Expression Regulation, Neoplastic , Humans , Interleukin-17/immunology , Interleukin-17/metabolism , MCF-7 Cells , Mammary Neoplasms, Experimental , Mice , Mice, Inbred NOD , Mice, SCID , NF-kappa B/antagonists & inhibitors , Paracrine Communication , Receptor, ErbB-2/metabolism , Signal Transduction/drug effects , Xenograft Model Antitumor Assays
6.
J Dent Res ; 92(7): 655-60, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23648741

ABSTRACT

Topical fluoride treatment prevents dental caries. However, the resulting calcium-fluoride-like deposits are soft and have poor wear resistance; therefore, frequent treatment is required. Lasers quickly heat surfaces and can be made portable and suitable for oral remedies. We examined the morphology, nanohardness, elastic modulus, nanowear, and fluoride uptake of fluoride-treated enamel followed by CO2 laser irradiation for 5 and 10 sec, respectively. We found that laser treatments significantly increased the mechanical properties of the calcium-fluoride-like deposits. The wear resistance of the calcium-fluoride-like deposits improved about 34% after laser irradiation for 5 sec and about 40% following irradiation for 10 sec. We also found that laser treatments increased fluoride uptake by at least 23%. Overall, laser treatment significantly improved fluoride incorporation into dental tissue and the wear resistance of the protective calcium-fluoride layer.


Subject(s)
Cariostatic Agents/radiation effects , Dental Enamel/radiation effects , Fluorides/radiation effects , Lasers, Gas/therapeutic use , Low-Level Light Therapy/methods , Calcium Fluoride/chemistry , Calcium Fluoride/radiation effects , Cariostatic Agents/chemistry , Cariostatic Agents/pharmacokinetics , Crystallography , Dental Enamel/metabolism , Dental Enamel/ultrastructure , Elastic Modulus , Electron Probe Microanalysis , Fluorides/chemistry , Fluorides/pharmacokinetics , Hardness , Humans , Mechanical Phenomena , Microscopy, Electron, Scanning , Sodium Fluoride/chemistry , Sodium Fluoride/pharmacokinetics , Sodium Fluoride/radiation effects , Stress, Mechanical , Time Factors , Tooth Wear/pathology
7.
Oncogene ; 32(4): 431-43, 2013 Jan 24.
Article in English | MEDLINE | ID: mdl-22410781

ABSTRACT

Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , MicroRNAs/genetics , Stilbenes/pharmacology , Animals , Cell Line , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/genetics , Disease Progression , Down-Regulation/drug effects , Epithelial-Mesenchymal Transition/drug effects , Epithelial-Mesenchymal Transition/genetics , Female , HEK293 Cells , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mice , Mice, SCID , MicroRNAs/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Protein Phosphatase 2/genetics , Protein Phosphatase 2/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Resveratrol , Xenograft Model Antitumor Assays
8.
Cell Death Differ ; 20(3): 443-55, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23175185

ABSTRACT

CCN family protein 2 (CCN2), also known as connective tissue growth factor, is a secreting protein that modulates multiple cellular events. We previously demonstrated the metastasis-suppressive effect of CCN2 in lung cancer cells. In this study, we investigate the role of CCN2 in anoikis, a form of programmed cell death that is critical in suppressing cancer metastasis. CCN2 binds to the epidermal growth factor receptor (EGFR) and triggers ubiquitination by inhibiting the formation of the ß-pix/Cbl complex, resulting in the degradation of EGFR. Binding of CCN2 to EGFR suppresses the phosphorylation of c-Src and extracellular signal-regulated kinase but increases the expression of death-associated protein kinase, which leads to anoikis. Overall, our findings provide evidence validating the use of CCN2 as an anti-metastatic therapy in lung cancer patients, and prospect a potential therapeutic synergy between CCN2 and the anti-EGFR antibody for the treatment of lung cancer.


Subject(s)
Anoikis , Apoptosis Regulatory Proteins/metabolism , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Connective Tissue Growth Factor/metabolism , ErbB Receptors/metabolism , Amino Acid Sequence , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/genetics , CSK Tyrosine-Protein Kinase , Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Cell Line, Tumor , Cell Movement , Death-Associated Protein Kinases , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Molecular Sequence Data , Phosphorylation , Protein Binding , Protein Structure, Tertiary , Proto-Oncogene Proteins c-cbl/metabolism , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Rho Guanine Nucleotide Exchange Factors , Signal Transduction , Ubiquitination , src-Family Kinases/metabolism
9.
Pathology ; 44(7): 605-10, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22990279

ABSTRACT

AIMS: Focal nodular hyperplasia (FNH) has characteristic histological features which may not be seen in needle biopsy specimens. We investigate the diagnostic role of glutamine synthetase (GS) in needle biopsy specimens. METHODS: Sixty-one hepatic tumours were categorised into 20 'definite' FNHs, 13 'probable' FNHs, and 28 cases without specific diagnosis. Needle biopsy specimens of 92 non-tumourous lesions, 25 well-differentiated hepatocellular carcinomas (WDHCCs), and 4 high-grade dysplastic nodules (HGDNs) and resection specimens of 10 macroregenerative nodules were also selected for immunohistochemical stain of GS for comparison. RESULTS: All 20 'definite' FNHs, nine 'probable' FNHs, and five cases without specific diagnosis expressed typical map-like staining pattern of GS. The demographic data of these five cases were similar to those of FNH. All cases of chronic hepatitis B and C, cirrhosis, macroregenerative nodule and peritumourous liver tissue showed normal pericentral/periseptal pattern. Fifteen of 25 WDHCCs and one HGDN showed diffuse pattern. Ten WDHCCs and two HGDNs showed negative staining. One HGDN showed mosaic pattern. CONCLUSIONS: Immunohistochemical staining of GS increases the diagnostic sensitivity of FNH in needle biopsy, especially in those without typical morphology. It also helps in differentiating FNH from other tumourous and non-tumourous lesions.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/enzymology , Focal Nodular Hyperplasia/enzymology , Glutamate-Ammonia Ligase/metabolism , Liver Neoplasms/enzymology , Precancerous Conditions/enzymology , Adult , Aged , Biopsy, Needle , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/pathology , Diagnosis, Differential , Female , Focal Nodular Hyperplasia/diagnosis , Focal Nodular Hyperplasia/pathology , Humans , Immunohistochemistry , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Male , Middle Aged , Precancerous Conditions/pathology , Young Adult
10.
Oncogene ; 31(19): 2401-11, 2012 May 10.
Article in English | MEDLINE | ID: mdl-21927029

ABSTRACT

Connective tissue growth factor (CTGF) is a multi-functional secreted protein, and it has been shown either to promote or suppress tumor progression among different kinds of cancers. Here, we investigated the role of CTGF in oral squamous cell carcinoma (OSCC) invasion and metastasis. In five OSCC cell lines, endogenous CTGF negatively correlated with invasiveness. Exogenous CTGF protein or forced expression of CTGF gene in the oral cancer cell line SAS significantly decreased their invasive and migratory abilities. MicroRNA (miRNA) microarray analysis was performed in CTGF-overexpressed SAS cells (SAS/CTGF-M3) versus control cells to investigate the mechanism of CTGF-mediated inhibition of OSCC invasion. Among the miRNAs regulated by CTGF, miR-504 and miR-346 were the top two miRNAs downregulated in CTGF transfectants, and the result was confirmed by quantitative reverse transcriptase-PCR. Ectopic miR-504 increased migration and invasion in SAS/CTGF-M3, however, miR-346 did not have such impact on migration/invasion. Furthermore, we identified FOXP1, a member of forkhead transcription factors, as a target gene that takes part in the miR-504-induced cellular invasion. Knockdown of FOXP1 increased invasiveness in SAS/CTGF-M3, confirming the signal axis of CTGF/miR-504/FOXP1 in OSCC. Animal experiments showed that SAS/CTGF-M3-formed orthotopic tumors were associated with a lesser invasive phenotype than control cells. Expression of miR-504 in SAS/CTGF-M3 increased lymph node metastasis, and co-expression of FOXP1 in miR-504-transfected SAS/CTGF-M3 alleviated miR-504-induced metastasis. In OSCC samples, high CTGF was associated with a lower clinical stage and a better outcome. A reverse correlation between CTGF and miR-504, miR-504 and FOXP1, and a positive correlation between CTGF and FOXP1 were shown. Our study discovers a novel signal pathway involving the regulation of miRNA machinery by a secreted cytokine, which will be beneficial for developing therapeutic strategy against advanced OSCC.


Subject(s)
Carcinoma, Squamous Cell/pathology , Connective Tissue Growth Factor/metabolism , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , Mouth Neoplasms/pathology , Repressor Proteins/genetics , Animals , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Connective Tissue Growth Factor/genetics , Female , Gene Knockdown Techniques , Humans , Lymphatic Metastasis , Mice , Mice, SCID , MicroRNAs/genetics , Mouth Neoplasms/genetics , Neoplasm Invasiveness , Neoplasm Staging , Signal Transduction
11.
J Viral Hepat ; 16(11): 796-801, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19413696

ABSTRACT

The significance of hepatitis C viral (HCV)-RNA levels in long-term clinical outcomes of children with chronic HCV infection is not well understood. We conducted a long-term follow-up study of 42 children with chronic HCV infection that included clinical evaluation, biochemical tests, HCV genotyping and repeated quantitative HCV-RNA detection. Patients were divided into low and high viraemia groups according to RNA levels at enrollment (below/above 4.5 x 10(4) IU/mL), and clinical, biochemical and virological factors were evaluated. Overall, 14.3% (6/42) of patients developed spontaneous viral clearance during a median 10.1 years of follow-up. HCV-RNA levels at enrollment and mean RNA levels during follow-up for each patient were significantly correlated (R = 0.9018, 95% CI: 0.6637-0.9038, P < or = 0.001). HCV-RNA level fluctuation was within two log units in 76% of patients. Cumulative viraemia probability during follow-up could be predicted by viraemia levels at enrollment (P = 0.0092). Chronic HCV-infected children, with an RNA level below 4.5 x 10(4) IU/mL at enrollment, have a higher spontaneous viral clearance rate.


Subject(s)
Hepacivirus/physiology , Hepatitis C, Chronic , RNA, Viral/blood , Viral Load/physiology , Viremia , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/virology , Humans , Infant , Male , Taiwan/epidemiology , Time Factors , Viremia/epidemiology , Viremia/immunology , Viremia/virology
12.
Mol Cancer Ther ; 8(1): 36-44, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19139111

ABSTRACT

Pancreatic carcinoma is the fourth leading cause of death from cancer. Novel targets and therapeutic options are needed to aid in the treatment of pancreatic cancer. The compound UA62784 is a novel fluorenone with inhibitory activity against the centromere protein E (CENP-E) kinesin-like protein. UA62784 was isolated due to its selectivity in isogenic pancreatic carcinoma cell lines with a deletion of the DPC4 gene. UA62784 causes mitotic arrest by inhibiting chromosome congression at the metaphase plate likely through inhibition of the microtubule-associated ATPase activity of CENP-E. Furthermore, CENP-E binding to kinetochores during mitosis is not affected by UA62784, suggesting that the target lies within the motor domain of CENP-E. UA62784 is a novel specific inhibitor of CENP-E and its activity suggests a potential role for antimitotic drugs in treating pancreatic carcinomas.


Subject(s)
Chromosomal Proteins, Non-Histone/antagonists & inhibitors , Kinesins/antagonists & inhibitors , Oxazoles/pharmacology , Xanthones/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Chromosomal Proteins, Non-Histone/metabolism , Humans , Kinesins/classification , Kinesins/metabolism , Microtubules/drug effects , Microtubules/metabolism , Molecular Structure , Oxazoles/chemistry , Protein Binding , Tubulin/metabolism , Xanthones/chemistry
13.
Br J Surg ; 96(1): 66-73, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19109797

ABSTRACT

BACKGROUND: Insulin-like growth factor II mRNA-binding protein (IMP) 3 is expressed in embryonic tissues and multiple cancers. The aim was to establish the prognostic value of IMP-3 expression in gastric adenocarcinoma. METHODS: IMP-3 expression in resected gastric adenocarcinomas was analysed by immunohistochemistry. RESULTS: IMP-3 was expressed in 183 (58.1 per cent) of 315 tumours. Expression was associated with older age (P < 0.001), larger tumour size (P = 0.009), deep tumour invasion (P < 0.001) and lymph node metastasis (P < 0.001). IMP-3-positive tumours were associated with poorer 5-year survival than negative tumours at all stages (stage I, 82 versus 97 per cent; stage II, 55 versus 78 per cent; stage III and IV, 11 versus 25 per cent; P = 0.005, P = 0.033 and P = 0.036 respectively). Multivariable analysis identified IMP-3 (hazard ratio (HR) 1.93), depth of tumour invasion (HR 3.69, 9.77 and 10.69 for pathological tumour stage (pT) 2, pT3 and pT4 respectively versus pT1), and lymph node metastasis (HR 1.57, 3.29 and 3.40 for pathological node stage (pN) 1, pN2 and pN3 respectively versus pN0) as independent prognostic factors. CONCLUSION: IMP-3 expression correlates with the metastatic potential of gastric adenocarcinoma and is an independent prognostic factor.


Subject(s)
Adenocarcinoma/metabolism , Insulin-Like Growth Factor Binding Protein 2/metabolism , Insulin-Like Growth Factor Binding Protein 3/metabolism , Stomach Neoplasms/metabolism , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , RNA, Messenger/metabolism , Risk Factors , Stomach Neoplasms/mortality
14.
J Dent Res ; 87(4): 381-5, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18362324

ABSTRACT

Calcium-fluoride-like deposits play a key role in caries prevention by topical fluoride. Previous microhardness analyses have introduced errors due to a substrate effect, and thereby could not substantiate the early loss of these deposits. To address this question, we applied Atomic Force Microscopy (AFM) and a nano-indentation technique in this study to characterize the nano-mechanical properties and topographic structure of enamel surfaces following topical fluoride treatment. The deposits were found to have a low nano-hardness and a high nano-wear depth, which explains the early loss of calcium-fluoride-like deposits. However, a 22% increase in the fluoride concentration could still be detected on the treated enamel surface following the removal of the surface deposits, justifying the long-term effectiveness of topical fluoride treatment.


Subject(s)
Cariostatic Agents/pharmacology , Dental Enamel/drug effects , Fluorides, Topical/pharmacology , Nanotechnology , Biomechanical Phenomena , Calcium Fluoride/chemistry , Dental Enamel/ultrastructure , Electron Probe Microanalysis , Hardness , Humans , Materials Testing , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Stress, Mechanical , Surface Properties
15.
J Clin Pathol ; 61(3): 268-71, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17693578

ABSTRACT

BACKGROUND: Pulmonary sclerosing haemangioma (PSH) is an uncommon tumour that is composed of glandular/papillary lining cells and polygonal cells. The biological behaviour of this tumour has been investigated; however, the molecular pathogenesis of PSH remains unknown. AIMS: To characterise the role of the Wnt/beta-catenin pathway in the genesis of PSH. METHODS: 37 PSH samples were investigated immunohistochemically for detection of the beta-catenin protein and direct sequencing of exon 3 of the beta-catenin gene. RESULTS: Nuclear expression of beta-catenin was found in the lining component of 23 tumours (62%) and in the polygonal component of 11 tumours (30%). The expression of beta-catenin was stronger in the lining component, but weaker in the polygonal component. Interestingly, all the tumours with expression of beta-catenin in the polygonal component also expressed beta-catenin in the lining component. However, mutation of exon 3 of the beta-catenin gene was detected in only one tumour that expressed nuclear beta-catenin in lining and polygonal components. CONCLUSIONS: The Wnt/beta-catenin pathway is involved in the genesis of PSH, but mutation of exon 3 of the beta-catenin gene rarely contributes to the activation of the Wnt/beta-catenin pathway in PSH.


Subject(s)
Mutation , Pulmonary Sclerosing Hemangioma/genetics , beta Catenin/genetics , Adult , Aged , Cell Nucleus/chemistry , Codon , DNA Primers/genetics , Exons , Female , Humans , Immunohistochemistry , Male , Middle Aged , Pulmonary Sclerosing Hemangioma/metabolism , Sequence Analysis, DNA , beta Catenin/analysis
16.
Mol Cell Endocrinol ; 274(1-2): 1-7, 2007 Aug 15.
Article in English | MEDLINE | ID: mdl-17601655

ABSTRACT

Nongenomic estrogenic mechanisms offer an opportunity to explain the conundrum of environmental estrogen and plant estrogen effects on cells and animals at the very low concentrations which are prevalent in our environments and diets. Heretofore the actions of these compounds have not been adequately accounted for by laboratory tests utilizing assays for actions only via the genomic pathway of steroid action and the nuclear forms of estrogen receptor alpha and beta. Membrane versions of these receptors, and the newly described GPR30 (7TMER) receptor protein provide explanations for the more potent actions of xenoestrogens. The effects of estrogens on many tissues demand a comprehensive assessment of the receptors, receptor levels, and mechanisms that might be involved, to determine which of these estrogen mimetic compounds are harmful and which might even be used therapeutically, depending upon the life stage at which we are exposed to them.


Subject(s)
Estrogens/metabolism , Phytoestrogens/metabolism , Xenobiotics/metabolism , Animals , Dose-Response Relationship, Drug , Environmental Exposure , Estrogens/chemistry , Humans , Molecular Structure , Phytoestrogens/chemistry , Receptors, Estrogen/metabolism , Xenobiotics/chemistry
17.
Oncogene ; 26(42): 6160-6, 2007 Sep 13.
Article in English | MEDLINE | ID: mdl-17420720

ABSTRACT

BRCA1 mutation carriers have an 85% lifetime risk of breast cancer and 60% for ovarian cancer. BRCA1 facilitates DNA double-strand break repair, and dysfunction of BRCA1 leads to hypersensitivity to DNA damaging agents and consequently genomic instability of cells. In this communication, we have examined the tumor incidence and survival of Brca1 heterozygous female mice. Brca1 heterozygotes appear to have a shortened life span with 70% tumor incidence. Lymphoma, but not ovarian and mammary gland tumors, occurs commonly in these mice. After a whole-body exposure to ionizing radiation, Brca1 heterozygous mice have a 3-5-fold higher incidence specific to ovarian tumors, but not lymphoma, when compared with the Brca1+/+ mice. All the tumors from heterozygous mice examined retain the wild-type allele and the cancer cells express Brca1 protein, precluding the chromosomal mechanism for loss of heterozygosity of Brca1 locus. Although the manifestation of BRCA1 haploinsufficiency may be different between human and mouse, this study suggests that women carrying Brca1 mutations may be more prone to ovarian tumor formation after IR exposure than nonmutation carriers.


Subject(s)
BRCA1 Protein/genetics , Genetic Carrier Screening , Genetic Predisposition to Disease , Longevity/genetics , Neoplasms, Radiation-Induced/genetics , Ovarian Neoplasms/genetics , Animals , BRCA1 Protein/biosynthesis , Female , Gamma Rays , Loss of Heterozygosity , Mice , Mice, Inbred C57BL , Mice, Knockout , Neoplasms, Radiation-Induced/epidemiology , Ovarian Neoplasms/epidemiology
18.
J Pathol ; 209(4): 549-58, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16739096

ABSTRACT

Stathmin, a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. This study aimed to elucidate its role in the progression, early tumour recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). Stathmin mRNA was overexpressed in 88/156 (56%) resected, unifocal, primary HCCs, while p53 mutation was present in 72 (46%) and osteopontin mRNA overexpression in 79 (51%). Stathmin mRNA expression exhibited high concordance (93%) with protein expression in 107 cases examined by immunohistochemistry. Stathmin overexpression correlated with high alpha-fetoprotein (>200 ng/ml, p = 0.02), larger tumour size (>5 cm, p = 0.012), high tumour grade (p < 0.0002), high tumour stage (stage IIIA-IV) with vascular invasion and various degrees of intrahepatic metastasis (p < 1 x 10(-8)), ETR (p = 0.003), and lower 5-year survival (p = 0.0007). Stathmin protein expression was often more intense in the peripheral regions of tumour trabeculae, tumour borders, and portal vein tumour thrombi. Stathmin overexpression correlated with p53 mutation (p = 0.017) and osteopontin overexpression (p = 1 x 10(-8)), both of which were associated with vascular invasion (both p < 0.0001) and poorer prognosis (p < 0.0004 and p = 0.0004, respectively). Regardless of the status of p53 mutation or osteopontin expression, stathmin overexpression was associated with higher vascular invasion (all p < 0.0001). Approximately 90% of HCCs harbouring stathmin overexpression with concomitant p53 mutation or osteopontin overexpression exhibited vascular invasion, and hence the lowest 5-year survival, p = 0.00018 and p = 0.0009, respectively. However, we did not find that stathmin overexpression exerted prognostic impact independent of tumour stage. In conclusion, stathmin expression correlates with metastatic potential, is an important prognostic factor for HCC, and may serve as a useful marker to predict ETR.


Subject(s)
Carcinoma, Hepatocellular/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Neoplasm Recurrence, Local/genetics , Sialoglycoproteins/genetics , Stathmin/genetics , Biomarkers, Tumor , Carcinoma, Hepatocellular/chemistry , Carcinoma, Hepatocellular/pathology , Chi-Square Distribution , DNA Mutational Analysis , Disease Progression , Female , Genes, p53 , Humans , Immunohistochemistry/methods , Liver Neoplasms/chemistry , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/chemistry , Neoplasm Recurrence, Local/pathology , Osteopontin , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Stathmin/analysis
19.
J Pathol ; 209(3): 317-27, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16639692

ABSTRACT

Glucocorticoid receptor (GR) is a steroid hormone receptor that has been shown to play important roles in mammary development and differentiation, and has been implicated in breast tumourigenesis, but its precise biological significance in mammary pathophysiology remains unclear. In order to generate a comprehensive expression profile for GR in normal versus neoplastic breast tissues, GR expression was investigated in situ in 400 human breast tissue samples, comprising normal tissue and a range of benign, pre-invasive, and invasive lesions, using immunohistochemical assays. The novel expression of GR in myoepithelium, not observed in luminal epithelium, not only demonstrates expression patterns exclusive to the alpha form of oestrogen receptor and progesterone receptor and suggests distinctive functions between GR and these two important steroid hormone receptors in the breast, but may also indicate unique physiological and perhaps pathological roles for the myoepithelium in mediating the effects of glucocorticoid hormones in the breast. The strong expression of GR in metaplastic carcinomas (94.4%) and malignant phyllodes tumours (92.3%) suggests a pathogenetic role for GR, and implies that targeting GR in these tumours may have potential therapeutic application. However, studies on the roles of GR in mammary carcinogenesis should be interpreted with great caution, based on the lack of GR expression in cancer cells in the great majority (98.2%) of non-metaplastic carcinomas, which has gone unnoticed in previous studies. This marked discrepancy warrants a re-examination of the biological roles of GR in the pathophysiology of breast malignancy. The lack of methylation in the promoter region of the GR gene in all 118 non-metaplastic carcinomas, as demonstrated by methylation-specific PCR and bisulphite DNA sequencing analysis, indicates that methylation is less likely to play a role in the reduction of GR expression in non-metaplastic carcinoma of the breast.


Subject(s)
Breast Neoplasms/metabolism , Breast/metabolism , Receptors, Glucocorticoid/metabolism , Base Sequence , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Lobular/genetics , Carcinoma, Lobular/metabolism , DNA Methylation , DNA, Neoplasm/genetics , Epithelial Cells/metabolism , Female , Gene Expression , Humans , Immunoenzyme Techniques , Molecular Sequence Data , Neoplasm Invasiveness , Phyllodes Tumor/genetics , Phyllodes Tumor/metabolism , Promoter Regions, Genetic/genetics
20.
Ann Oncol ; 16(2): 314-21, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15668290

ABSTRACT

BACKGROUND: Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB. PATIENTS AND METHODS: Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings. RESULTS: Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (< or =1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan-Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions. CONCLUSIONS: CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.


Subject(s)
Biomarkers, Tumor/analysis , Calreticulin/biosynthesis , Gene Expression Profiling , Neuroblastoma/genetics , Neuroblastoma/pathology , Cell Differentiation , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Immunohistochemistry , Infant , Infant, Newborn , Male , Polymerase Chain Reaction , Prognosis , Survival Analysis
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