TY  - JOUR
AB  - AIMS: Associations of plasma viscosity and plasma Ig levels (a determinant of viscosity) with incident coronary heart disease (CHD) events; and with CHD, cardiovascular disease (CVD: CHD and stroke) and all-cause mortalities. METHODS: Meta-analysis of plasma viscosity levels from the MONitoring of trends and determinants of CArdiovascular (MONICA)/Cooperative Health Research in the Region of Augsburg, MONICA Glasgow and Speedwell Studies; and five other published studies. Meta-analysis of IgA, IgG and IgM levels from the Augsburg, Glasgow and Speedwell studies; and one other published study. RESULTS: Over median follow-up periods of 14-26 years, there were 2270 CHD events, and 4220 all cause deaths in 28 605 participants with baseline plasma viscosity measurements. After adjustment for major risk factors, (HRs; 95% CIs) for a 1 SD increase in viscosity were 1.14 (1.09 to 1.20) for CHD events; and 1.21 (1.17 to 1.25) for all-cause mortality. 821 CHD events and 2085 all-cause deaths occurred in 8218 participants with baseline Ig levels. For CHD events, adjusted HRs for 1 SD increases in IgA, IgG and IgM were, respectively, 0.97 (0.89 to 1.05); 0.95(0.76 to 1.17) and 0.90 (0.79 to 1.03). Corresponding adjusted HRs for all-cause mortality were 1.08 (95% CI 1.02 to 1.13), 1.03 (95% CI 0.94 to 1.14) and 1.01 (95% CI 0.96 to 1.06). CONCLUSIONS: After risk factor adjustment, plasma viscosity was significantly associated with risks of CHD events; and with CHD, CVD and all-cause mortalities. We found no significant association of IgA, IgG or IgM levels with incident CHD events or mortality, except for a borderline association of IgA with all-cause mortality.
AU  - Lowe, G.D.O.*
AU  - Harris, K.*
AU  - Koenig, W.*
AU  - Ben-Shlomo, Y.*
AU  - Thorand, B.
AU  - Peters, A.
AU  - Meisinger, C.
AU  - Imhof, A.*
AU  - Tunstall-Pedoe, H.*
AU  - Peters, S.A.E.*
AU  - Woodward, M.*
C1  - 67532
C2  - 54095
CY  - British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
SP  - 394-401
TI  - Plasma viscosity, immunoglobulins and risk of cardiovascular disease and mortality: new data and meta-analyses.
JO  - J. Clin. Pathol.
VL  - 77
IS  - 6
PB  - Bmj Publishing Group
PY  - 2023
SN  - 0021-9746
ER  - 

TY  - JOUR
AB  - Background Histone deacetylases (HDACs) are enzymes which play a central role in post-translational histone and non-histone protein modification. Deregulation of HDACs has been detected in various human malignancies and may also influence response to chemotherapy. Aims To investigate the expression of class I histone deacetylase (HDAC) isoforms 1 and 2 in oesophageal adenocarcinomas. Methods 132 primary resected tumours and 48 tumours treated by chemotherapy were analysed. Expression of HDAC1 and HDAC2 was determined by immunohistochemistry, applied on a tissue microarray and on pretherapeutic biopsies, and correlated with pathological features and prognosis. Results There was negative or low expression of HDAC1 in 54% of tumours, moderate expression in 41% and high expression in 5%. HDAC2 expression was negative or low in 30% of tumours, moderate in 47% and high in 21%. In primary resected tumours, high HDAC2 levels were associated with lymphatic tumour spread and lower tumour differentiation grade. HDAC1 levels were not associated with pT, pN category or tumour differentiation grade. For neoadjuvant treated tumours, there was only a trend for an association with high pretherapeutic HDAC2 expression and tumour regression after chemotherapy. Pretherapeutic HDAC1 levels were not associated with regression after chemotherapy. Survival analysis failed to show any prognostic impact of HDAC1 or HDAC2 expression. Conclusions High HDAC2 expression is associated with aggressive tumour behaviour in oesophageal adenocarcinomas. No significant prognostic value could be found with respect to overall survival or an association with response to conventional chemotherapy for HDAC expression. Immunohistochemical determination of HDACs may be useful for prediction of response to specific HDAC inhibitors.
AU  - Langer, R.*
AU  - Mutze, K.*
AU  - Becker, K.*
AU  - Feith, M.*
AU  - Ott, K.*
AU  - Höfler, H.
AU  - Keller, G.*
C1  - 6011
C2  - 28009
CY  - London
SP  - 994-998
TI  - Expression of class I histone deacetylases (HDAC1 and HDAC2) in oesophageal adenocarcinomas: An immunohistochemical study.
JO  - J. Clin. Pathol.
VL  - 63
IS  - 11
PB  - BMJ Publishing Group
PY  - 2010
SN  - 0021-9746
ER  - 

TY  - JOUR
AB  - astric carcinoma is characterised by numerous genetic and epigenetic alterations that influence cell cycle progression, apoptosis and DNA repair. These alterations include down-regulation of the cyclin-dependent kinase (CDK) inhibitors p21(WAF1/CIP1) and p27(Kip1), and mutations of the tumour suppressor protein p53 and the cell adhesion molecule E-cadherin. Combined evaluation of the prognostic significance of these alterations has not been reported in Mexican Mestizo patients. AIMS: To evaluate p21(WAF1/CIP1), p27(Kip1), p53 and E-cadherin protein expression, including mutant E-cadherin variants with deletion of exon 8 (del 8) or 9 (del 9), in gastric cancer from Mexican patients. METHODS: Immunohistochemistry for the above-mentioned markers, including mutation-specific E-cadherin antibodies, was carried out in 69 gastric carcinomas; expression levels were correlated with histotype, tumour stage and prognosis. RESULTS: Expression of p21(WAF1/CIP1) alone or in combination with p27(Kip1) or in the absence of p53 was associated with favourable prognosis. Staining of del 8 and del 9 E-cadherin was found exclusively in patients negative for p53 and positive for p21(WAF1/CIP1), suggesting that the p21(WAF1/CIP1) regulatory function of p53 was intact. CONCLUSION: Combined evaluation of the prognostic significance of cell cycle regulators and E-cadherin should be performed. Even though patients negative for p53 and positive for p21(WAF1/CIP1) have a favourable prognosis, it may have a negative influence on prognosis if they acquire in addition E-cadherin mutations which have been shown previously to be associated with poor survival.
AU  - Gamboa-Dominguez, A.*
AU  - Seidl, S.*
AU  - Reyes-Gutierrez, E.*
AU  - Hermannstädter, C.*
AU  - Quintanilla-Martinez, L.
AU  - Busch, R.*
AU  - Höfler, H.
AU  - Fend, F.*
AU  - Luber, B.*
C1  - 4791
C2  - 24456
SP  - 756-761
TI  - Prognostic significance of p21WAF1/CIP1, p27Kip1, p53 and E-cadherin expression in gastric cancer.
JO  - J. Clin. Pathol.
VL  - 60
IS  - 7
PB  - BMJ Publ. Group
PY  - 2007
SN  - 0021-9746
ER  - 

TY  - JOUR
AB  - AIMS: To evaluate mRNA and protein expression of signal transducers and activators of transcription (STAT)3 in colorectal carcinomas (CRCs) and to define the association of STAT3 activity with the STAT3-inducible targets cyclin D1, survivin, Bcl-xl and Mcl-1. MATERIALS AND METHODS: Matching serial sections of normal colonic epithelium and invasive CRCs (n = 32) were subjected to quantitative reverse transcriptase polymerase chain reaction specific to STAT3, cyclin D1, survivin, Bcl-xl and Mcl-1, as well as immunohistochemistry. For STAT3 immunohistochemistry, two antibodies, recognising unphosphorylated (UP-) and phosphorylated (tyr705, P-) STAT3 were used. Ki-67 (MIB-1) staining was included as a proliferation marker. RESULTS: Compared with normal colonic epithelium, UP-STAT3 and P-STAT3 (p = 0.023 and 0.006) protein expression and expression of its associated targets cyclin D1, survivin and Bcl-xl were significantly (all p<0.001) increased in carcinoma. In carcinomas, STAT3 (p = 0.019) and Bcl-xl (p = 0.001) mRNAs were correlated with lymph node status. Moreover, nuclear P-STAT3 protein expression (active state) was associated with the expression of its target genes Bcl-xl (p = 0.038) and survivin (p = 0.01) as well as with Ki-67 (p = 0.017). By contrast, cytoplasmic UP-STAT was significantly linked to Bcl-xl mRNA (p = 0.024) and protein (p = 0.001) as well as to cytoplasmic survivin protein expression (p = 0.019). CONCLUSION: Both inactive (UP-STAT3) and active (P-STAT3) STAT3 proteins are markedly increased in invasive CRCs. This is associated with Bcl-xl and survivin induction, increased proliferation and lymph node metastasis. This study therefore provides the basis for further examination of the prognostic or predictive value of these molecular markers in CRC
AU  - Lassmann, S.*
AU  - Schuster, I.*
AU  - Walch, A.K.
AU  - Göbel, H.*
AU  - Jütting, U.
AU  - Makowiec, F.*
AU  - Hopt, U.*
AU  - Werner, M.*
C1  - 168
C2  - 24526
SP  - 173-179
TI  - STAT3 mRNA and protein expression in colorectal cancer: Effects on STAT3-inducible targets linked to cell survival and proliferation.
JO  - J. Clin. Pathol.
VL  - 60
PB  - BMJ Publ. Group
PY  - 2007
SN  - 0021-9746
ER  - 

TY  - JOUR
AU  - Marquart, K.H.
C1  - 42742
C2  - 36424
SP  - 933
TI  - Weibel-Palade bodies in Kaposi's sarcoma Cells.
JO  - J. Clin. Pathol.
VL  - 40
IS  - 8
PY  - 1987
SN  - 0021-9746
ER  -