In-Situ Alumina/Aluminate Platelet Composites

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66294/1/j.1151-2916.1992.tb05623.x.pd

Effect of Ta 2 O 5 , Nb 2 O 5 , and HfO 2 Alloying on the Transformability of Y 2 O 3 -Stabilized Tetragonal ZrO 2

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65528/1/j.1151-2916.1990.tb05100.x.pd

Lineage analysis of early and advanced tubular adenocarcinomas of the stomach: continuous or discontinuous?

<p>Abstract</p> <p>Background</p> <p>Eradication of early gastric carcinoma (GC) is thought to contribute to reduction in the mortality of GC, given that most of the early GCs progress to the advanced GCs. However, early GC is alternatively considered a dormant variant of GC, and it infrequently progresses to advanced GC. The aim of this study was to clarify the extent of overlap of genetic lineages between early and advanced tubular adenocarcinomas (TUBs) of the stomach.</p> <p>Methods</p> <p>Immunohistochemical staining for p53 was performed using 28 surgically resected stomachs with 13 intramucosal and 15 invasive TUBs. By chromosome- and array-based comparative genomic hybridization (CGH), genomic copy number constitution was compared between the mucosal and invasive parts of the invasive TUBs and between the mucosal parts of the invasive and intramucosal TUBs, using 25 and 22 TUBs, respectively. <it>TP53 </it>mutation in exons 5-8 was examined in 20 TUBs.</p> <p>Results</p> <p>Chromosomal CGH revealed that 4q+ and 11q+ were more common in advanced and early TUBs, respectively, whereas copy number changes in 8q and 17p showed no significant differences between early and advanced TUBs. However, array CGH revealed that, of the 13 intramucosal TUBs examined, loss of <it>MYC </it>(<it>MYC</it>-) and gain of <it>TP53 </it>(<it>TP53</it>+) was detected in 9 TUBs and <it>MYC</it>+ and/or <it>TP53</it>- was detected in 3 TUBs. Of the mucosal samples of 9 invasive TUBs, 7 showed <it>MYC</it>-/<it>TP53</it>+ and none showed <it>MYC</it>+ and/or <it>TP53</it>-. Of the 9 samples from the invasive parts, 1 (from submucosal cancers) showed <it>MYC</it>-/<it>TP53</it>+ and 6 (1 from submucosal and 5 from advanced cancers) showed <it>MYC</it>+ and/or <it>TP53</it>-. The latter 6 tumours commonly showed a mutant pattern (diffuse or null) in p53 immunohistochemistry, and 4 of the 6 tumours assessable for <it>TP53 </it>sequence analysis revealed mutations. The overall array CGH pattern indicated that, between the mucosal and invasive parts, genetic lineage was found discontinuous in 5 advanced cancers and continuous in 3 submucosal cancers.</p> <p>Conclusions</p> <p>Genetic lineages often differed between early and advanced TUBs. <it>MYC</it>-/<it>TP53</it>+ and <it>MYC </it>+ and/or <it>TP53</it>- may be the signatures of dormant and aggressive TUBs, respectively, in the stomach.</p

Relevance of circulating nucleosomes and oncological biomarkers for predicting response to transarterial chemoembolization therapy in liver cancer patients

<p>Abstract</p> <p>Background</p> <p>Transarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers predicting therapy response are urgently required.</p> <p>Methods</p> <p>Here, sera of 50 prospectively and consecutively included HCC patients undergoing 71 TACE therapies were taken before and 3 h, 6 h and 24 h after TACE application to analyze concentrations of circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), alpha fetoprotein (AFP), C-reactive protein (CRP) and several liver biomarkers, and to compare these with radiological response to therapy.</p> <p>Results</p> <p>While nucleosomes, CYFRA 21-1, CRP and some liver biomarkers increased already 24 h after TACE, percental changes of nucleosome concentrations before and 24 h after TACE and pre- and posttherapeutic values of AFP, gamma-glutamyl-transferase (GGT) and alkaline phosphatase (AP) significantly indicated the later therapy response (39 progression versus 32 no progression). In multivariate analysis, nucleosomes (24 h), AP (24 h) and TACE number were independent predictive markers. The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC) curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity.</p> <p>Conclusion</p> <p>Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.</p

TRAIL receptor I (DR4) polymorphisms C626G and A683C are associated with an increased risk for hepatocellular carcinoma (HCC) in HCV-infected patients

<p>Abstract</p> <p>Background</p> <p>Tumour surveillance via induction of TRAIL-mediated apoptosis is a key mechanism, how the immune system prevents malignancy. To determine if gene variants in the TRAIL receptor I (<it>DR4</it>) gene affect the risk of hepatitis C virus (HCV)-induced liver cancer (HCC), we analysed <it>DR4 </it>mutations C626G (rs20575) and A683C (rs20576) in HCV-infected patients with and without HCC.</p> <p>Methods</p> <p>Frequencies of <it>DR4 </it>gene polymorphisms were determined by LightSNiP assays in 159 and 234 HCV-infected patients with HCC and without HCC, respectively. 359 healthy controls served as reference population.</p> <p>Results</p> <p>Distribution of C626G and A683C genotypes were not significantly different between healthy controls and HCV-positive patients without HCC. <it>DR4 </it>variants 626C and 683A occurred at increased frequencies in patients with HCC. The risk of HCC was linked to carriage of the 626C allele and the homozygous 683AA genotype, and the simultaneous presence of the two risk variants was confirmed as independent HCC risk factor by Cox regression analysis (Odds ratio 1.975, 95% CI 1.205-3.236; p = 0.007). Furthermore HCV viral loads were significantly increased in patients who simultaneously carried both genetic risk factors (2.69 ± 0.36 × 10⁶ IU/ml vs. 1.81 ± 0.23 × 10⁶ IU/ml, p = 0.049).</p> <p>Conclusions</p> <p>The increased prevalence of patients with a 626C allele and the homozygous 683AA genotype in HCV-infected patients with HCC suggests that these genetic variants are a risk factor for HCC in chronic hepatitis C.</p

Plasticity-Induced Fatigue Damage in Ceria-Stabilized Tetragonal Zirconia Polycrystals

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65141/1/j.1151-2916.1994.tb07093.x.pd

Transgenic Expression of Entire Hepatitis B Virus in Mice Induces Hepatocarcinogenesis Independent of Chronic Liver Injury

Hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide, is most commonly caused by chronic hepatitis B virus (HBV) infection. However, whether HBV plays any direct role in carcinogenesis, other than indirectly causing chronic liver injury by inciting the host immune response, remains unclear. We have established two independent transgenic mouse lines expressing the complete genome of a mutant HBV (“preS2 mutant”) that is found at much higher frequencies in people with HCC than those without. The transgenic mice show evidence of stress in the endoplasmic reticulum (ER) and overexpression of cyclin D1 in hepatocytes. These mice do not show any evidence of chronic liver injury, but by 2 years of age a majority of the male mice develop hepatocellular neoplasms, including HCC. Unexpectedly, we also found a significant increase in hepatocarcinogenesis independent of necroinflammation in a transgenic line expressing the entire wildtype HBV. As in the mutant HBV mice, HCC was found only in aged—2-year-old—mice of the wildtype HBV line. The karyotype in all the three transgenic lines appears normal and none of the integration sites of the HBV transgene in the mice is near an oncogene or tumor suppressor gene. The significant increase of HCC incidence in all the three transgenic lines—expressing either mutant or wildtype HBV—therefore argues strongly that in absence of chronic necroinflammation, HBV can contribute directly to the development of HCC

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis