[show abstract][hide abstract] ABSTRACT: The purpose of this work was to develop and validate fully automated methods for uptake measurement of cerebellum, liver, and aortic arch in full-body PET/CT scans. Such measurements are of interest in the context of uptake normalization for quantitative assessment of metabolic activity and/or automated image quality control.
Cerebellum, liver, and aortic arch regions were segmented with different automated approaches. Cerebella were segmented in PET volumes by means of a robust active shape model (ASM) based method. For liver segmentation, a largest possible hyperellipsoid was fitted to the liver in PET scans. The aortic arch was first segmented in CT images of a PET/CT scan by a tubular structure analysis approach, and the segmented result was then mapped to the corresponding PET scan. For each of the segmented structures, the average standardized uptake value (SUV) was calculated. To generate an independent reference standard for method validation, expert image analysts were asked to segment several cross sections of each of the three structures in 134 F-18 fluorodeoxyglucose (FDG) PET/CT scans. For each case, the true average SUV was estimated by utilizing statistical models and served as the independent reference standard.
For automated aorta and liver SUV measurements, no statistically significant scale or shift differences were observed between automated results and the independent standard. In the case of the cerebellum, the scale and shift were not significantly different, if measured in the same cross sections that were utilized for generating the reference. In contrast, automated results were scaled 5% lower on average although not shifted, if FDG uptake was calculated from the whole segmented cerebellum volume. The estimated reduction in total SUV measurement error ranged between 54.7% and 99.2%, and the reduction was found to be statistically significant for cerebellum and aortic arch.
With the proposed methods, the authors have demonstrated that automated SUV uptake measurements in cerebellum, liver, and aortic arch agree with expert-defined independent standards. The proposed methods were found to be accurate and showed less intra- and interobserver variability, compared to manual analysis. The approach provides an alternative to manual uptake quantification, which is time-consuming. Such an approach will be important for application of quantitative PET imaging to large scale clinical trials.
Medical Physics 06/2012; 39(6):3112-23. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the efficacy of endolymphatic sac surgery for Meniere's disease, and compare the effects of endolymphatic sac decompression with endolymphatic-mastoid shunting.
Twelve patients(13 ears) undergoing endolymphatic-mastoid shunting and eleven patients (11 ears) undergoing endolymphatic sac decompression were retrospectively compared for hearing results and vertigo controlled rates. All of them have been followed up for more than two years after surgery.
According to Chinese Meniere's disease diagnosis and curative effect standard evaluation criteria published in 2006, for vertigo symptom of endolymphatic mastoid shunting group, 9 cases (69.2%) achieved grade A(completely controlled), 4 cases (30.8%) achieved grade B (fundamentally controlled). There were 8 cases (72.7%) with grade A, 2 cases (18.2%) with grade B and one case (9%) with grade C among 11 patients who received endolymphatic sac decompression. There was not statistically significant differences in postoperative speech pure tone average and vertigo controlled rate between the two groups.
Endolymphatic sac decompression and endolymphatic-mastoid shunting are effective management with less complication for intractable Meniere's disease. Particularly, the vertigo symptoms were controlled significantly. Patients with Meniere's disease in advanced clinical stages may also be relieved.
Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology 11/2009; 23(22):1020-2.
[show abstract][hide abstract] ABSTRACT: Overexpression of manganese superoxide dismutase (MnSOD), when combined with certain chemicals that inhibit peroxide removal, increases cancer cell cytotoxicity. Elevating MnSOD levels in cells enhances the conversion of superoxide (O(2)(*-)) to hydrogen peroxide (H(2)O(2)), combined with inhibiting the removal of H(2)O(2), further increases H(2)O(2) levels, leading to increased cytotoxicity. We hypothesized that increasing endogenous O(2)(*-) production in cells that were pretreated with adenoviral MnSOD (AdMnSOD) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) would lead to an increased level of intracellular H(2)O(2) accumulation and increased cell killing. The cytotoxic effects of Adriamycin or radiation, agents known to produce O(2)(*-), were determined in MDA-MB-231 breast cancer cells pretreated with AdMnSOD plus BCNU both in vitro and in vivo. In vitro, AdMnSOD plus BCNU sensitized cells to the cytotoxicity of Adriamycin or radiation. In vivo, AdMnSOD, BCNU, and Adriamycin or ionizing radiation inhibited tumor growth and prolonged survival. The results suggest that agents that produce O(2)(*-) in combination with AdMnSOD plus BCNU may represent a powerful new antitumor regimen against breast cancer.
Cancer Research 05/2009; 69(10):4294-300. · 8.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: AP-2alpha and c-MYC are important transcription factors involved in multiple cellular processes. They each display the paradoxical capacities to stimulate both cell proliferation and apoptosis under different conditions. In the present study we found that over expression of c-MYC was associated with accumulation of reactive oxygen species (ROS) and apoptosis in human keratinocytes, both of which were significantly inhibited by co-expression of AP-2. The effects of AP-2 on c-MYC were active at several levels. First, AP-2 and c-MYC were confirmed to interact at the protein level as previously described. In addition, forced expression of AP-2 significantly decreased steady state levels of c-MYC mRNA and protein. These findings suggested that AP-2 may have a direct effect on the c-myc gene. Chromatin immunoprecipitation assays demonstrated that AP-2 proteins bound to a cluster of AP-2 binding sites located within a 2 kb upstream regulatory region of c-myc These results suggest that the negative regulation of AP-2 on c-MYC activity was achieved through binding of AP-2 protein to the c-myc gene. The effects of AP-2 on c-MYC induced ROS accumulation and apoptosis in epidermal keratinocytes are likely to play an important role in cell growth, differentiation and carcinogenesis of the skin.
[show abstract][hide abstract] ABSTRACT: Superoxide dismutases (SODs) have been found to decrease tumor formation and angiogenesis. SOD gene therapy, as with many other gene transfer strategies, may not completely inhibit tumor growth on its own. Thus, concomitant therapies are necessary to completely control the spread of this disease. We hypothesized that intratumoral injection of AdSOD in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) chemotherapy would synergistically inhibit breast cancer growth. Our data indicate that BCNU when combined with SOD overexpression increased oxidative stress as suggested by elevated glutathione disulfide (GSSG) production in one of three breast cancer cell lines tested, at least in part due to glutathione reductase (GR) inactivation. The increased oxidative stress caused by BCNU combined with adenovirally expressed SODs, manganese or copper zinc SOD, decreased growth and survival in the three cell lines tested in vitro, but had the largest effect in the MDA-MB231 cell line, which showed the largest amount of oxidative stress. Delivery of MnSOD and BCNU intratumorally completely inhibited MDA-MB231 xenograft growth and increased nude mouse survival in vivo. Intravenous (iv) BCNU, recapitulating clinical usage, and intratumoral AdMnSOD delivery, to provide tumor specificity, provided similar decreased growth and survival in our nude mouse model. This cancer therapy produced impressive results, suggesting the potential use of oxidative stress-induced growth inhibitory treatments for breast cancer patients.
Free Radical Biology and Medicine 04/2008; 44(5):856-67. · 5.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer.
Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts.
Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct.
Scavenging plasma membrane-generated superoxide may prove beneficial for suppression of pancreatic cancer growth.
Clinical Cancer Research 01/2008; 13(24):7441-50. · 7.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Phospholipid glutathione peroxidase (PhGPx) reduces lipid hydroperoxides generated in biomembranes and also uses a wide range of reducing cofactors in addition to glutathione. PhGPx is synthesized as a mitochondrial PhGPx form (L-form) and as a nonmitochondrial PhGPx form (S-form). Our aims were to determine whether overexpression of PhGPx altered pancreatic tumor cell behavior. Pancreatic cancer cell lines were found by Western blotting to have diminished levels of PhGPx-immunoreactive protein compared with normal human pancreas. To normalize the levels of this protein, PhGPx was overexpressed in MIA PaCa-2 and AsPC-1 human pancreatic cancer cells by infection with an adenovirus-PhGPx L-form construct (AdPhGPx- L-form) (0-200 MOI) or with an adenovirus-PhGPx S-form construct (AdPhGPx-S-form) (0-200 MOI), and cell growth, plating efficiency, and growth in soft agar were determined. Pancreatic cancer cells were also injected subcutaneously into nude mice and tumor volume was calculated. Single direct injections of the adenoviral- PhGPx constructs were made into preestablished tumors. In vitro, AdPhGPx-S-form demonstrated 80% tumor growth inhibition, whereas AdPhGPx-L-form demonstrated 95% tumor growth inhibition. Ad- PhGPx-L-form or AdPhGPx-S-form also decreased plating efficiency and growth in soft agar. AdPhGPx-Lform decreased in vivo tumor growth to a greater extent than did AdPhGPx-S-form. Because of the growthinhibitory effects of PhGPx, lipid hydroperoxides may play an important role in the growth of pancreatic cancer.
Human Gene Therapy 02/2006; 17(1):105-16. · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: A facile method was established using composition-gradient pattern on zeolite surface to guide the deposition and formation of chemical and biomolecular patterns with features as small as five microns.
Chemical Communications 11/2005; · 6.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pancreatic cancer has low levels of antioxidant enzymes including manganese superoxide dismutase (MnSOD), which converts superoxide radical (O(2)(*-)) into hydrogen peroxide (H(2)O(2)), and glutathione peroxidase (GPx), which converts H(2)O(2) into water. Recent studies have demonstrated that overexpression of MnSOD has a tumor-suppressive effect in pancreatic cancer. However, GPx overexpression has been shown to reverse the tumor cell growth inhibition caused by MnSOD overexpression in other types of cancer. Our aims were to determine if overexpression of GPx alters in vitro pancreatic cancer cell behavior and if delivering the GPx gene directly to tumor xenografts alters growth and survival. In vitro, AdGPx slowed tumor growth by 39% and AdMnSOD slowed tumor growth by 35%. AdGPx also decreased plating efficiency and growth in soft agar. The combination of AdGPx and AdMnSOD had the greatest effect on tumor cell growth suppression with a 71% reduction in cell growth compared to controls. In vivo, either AdGPx or AdMnSOD alone slowed tumor growth by 51% and 54%, respectively, while the combination of AdGPx and AdMnSOD potentiated tumor growth suppression by 81% of controls and increased animal survival. GPx may be a tumor suppressor gene in pancreatic cancer. Delivery of the GPx gene alone or in combination with the MnSOD gene may prove beneficial for treatment of pancreatic cancer.
Human Gene Therapy 04/2004; 15(3):239-50. · 4.02 Impact Factor