TY  - JOUR
AB  - Endoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population "at risk" compared with the normal population are needed. In a cross-sectional analysis, we compared 587 patients with Barrett's esophagus from the multicenter German BarrettNET registry to 1976 healthy subjects from the population-based German KORA cohort, with and without GERD symptoms. Data on demographic and lifestyle factors, including age, gender, smoking, alcohol consumption, body mass index, physical activity, and symptoms were collected in a standardized epidemiologic survey. Increased age, male gender, smoking, heavy alcohol consumption, low physical activity, low health status, and GERD symptoms were significantly associated with Barrett's esophagus. Surprisingly, among patients stratified for GERD symptoms, these associations did not change. Demographic, lifestyle, and clinical factors as well as GERD symptoms were associated with Barrett's esophagus development in Germany, suggesting that a combination of risk factors could be useful in developing individualized screening efforts for patients with Barrett's esophagus and GERD in Germany.
AU  - Schmidt, M.*
AU  - Ankerst, D.P.*
AU  - Chen, Y.*
AU  - Wiethaler, M.*
AU  - Slotta-Huspenina, J.*
AU  - Becker, K.F.*
AU  - Horstmann, J.*
AU  - Kohlmayer, F.*
AU  - Lehmann, A.*
AU  - Linkohr, B.
AU  - Strauch, K.
AU  - Schmid, R.M.*
AU  - Quante, A.S.
AU  - Quante, M.*
C1  - 58826
C2  - 48383
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 377-384
TI  - Epidemiologic risk factors in a comparison of a Barrett Esophagus Registry (BarrettNET) and a case-control population in Germany.
JO  - Cancer Prev. Res.
VL  - 13
IS  - 4
PB  - Amer Assoc Cancer Research
PY  - 2020
SN  - 1940-6207
ER  - 

TY  - JOUR
AB  - The increasing incidence of esophageal adenocarcinoma (EAC) is mirrored by the increasing prevalence of Barrett esophagus, a precursor lesion resulting in a large number of individuals "at risk" for this lethal malignancy. Among patients with Barrett esophagus, only about 0.3% annually will develop EAC. Because large numbers of patients are followed in endoscopic surveillance, there is a need for risk prediction among a growing population of patients with Barrett esophagus. We identified four potential biomarkers from an inflammation (IL1b)-dependent mouse model of Barrett esophagus and tested them in 189 patients with Barrett esophagus with and without high-grade dysplasia (HGD)/ early cancer (T1). The primary goal was to distinguish patients with Barrett esophagus with no evidence of dysplasia from those with dysplasia. Increasing stem cell marker LGR5 and niche cell marker DCLK1 and decreasing differentiation marker (secretory mucus cells, TFF2+ cells) correlated with elevated tumor score in the mouse. Having outlined the origin of those markers in the Barrett esophagus mouse model, we showed the applicability for human Barrett esophagus. We compared 94 patients with nondysplastic Barrett esophagus tissue with 95 patients with Barrett esophagus and HGD or early cancer. Low levels of TFF2 (AUC 87.2%) provided the best discrimination between nondysplastic Barrett esophagus and Barrett esophagus with cancer, followed by high levels of DCLK1 (AUC 83.4%), low goblet cell ratio (AUC 79.4%), and high LGR5 (AUC 71.4%). The goblet cell ratio, rather than the presence of goblet cells per se, was found to be an important discriminator. These findings may be useful in developing future risk prediction models for patients with Barrett esophagus and ultimately to improve EAC surveillance.
AU  - Schellnegger, R.*
AU  - Quante, A.S.
AU  - Rospleszcz, S.
AU  - Schernhammer, M.*
AU  - Höhl, B.*
AU  - Tobiasch, M.*
AU  - Pastula, A.*
AU  - Brandtner, A.*
AU  - Abrams, J.A.*
AU  - Strauch, K.
AU  - Schmid, R.M.*
AU  - Vieth, M.*
AU  - Wang, T.C.*
AU  - Quante, M.*
C1  - 50338
C2  - 42152
CY  - Philadelphia
SP  - 55-66
TI  - Goblet cell ratio in combination with differentiation and stem cell markers in barrett esophagus allow distinction of patients with and without esophageal adenocarcinoma.
JO  - Cancer Prev. Res.
VL  - 10
IS  - 1
PB  - Amer Assoc Cancer Research
PY  - 2017
SN  - 1940-6207
ER  - 

TY  - JOUR
AB  - Relatively high expression of Hsp27 in breast and prostate cancer is a predictor of poor clinical outcome. This study elucidates a hitherto unknown mechanism by which Hsp27 regulates proteasome function and modulates tumor-specific T-cell responses. Here, we showed that short-term silencing of Hsp25 or Hsp27 using siRNA or permanent silencing of Hsp25 using lentivirus RNA interference technology enhanced PA28α mRNA expression, PA28α protein expression, and proteasome activity; abrogated metastatic potential; induced the regression of established breast tumors by tumor-specific CD8(+) T cells; and stimulated long-lasting memory responses. The adoptive transfer of reactive CD8(+) T cells from mice bearing Hsp25-silenced tumors efficiently induced the regression of established tumors in nontreated mice which normally succumb to tumor burden. The overexpression of Hsp25 and Hsp27 resulted in the repression of normal proteasome function, induced poor antigen presentation, and resulted in increased tumor burden. Taken together, this study establishes a paradigm shift in our understanding of the role of Hsp27 in the regulation of proteasome function and tumor-specific T-cell responses and paves the way for the development of molecular targets to enhance proteasome function and concomitantly inhibit Hsp27 expression in tumors for therapeutic gain.
AU  - Nagaraja, G.M.*
AU  - Kaur, P.*
AU  - Neumann, W.*
AU  - Asea, E.E.*
AU  - Bausero, M.A.*
AU  - Multhoff, G.
AU  - Asea, A.*
C1  - 7120
C2  - 29471
SP  - 122-137
TI  - Silencing hsp25/hsp27 gene expression augments proteasome activity and increases CD8+ T-cell-mediated tumor killing and memory responses.
JO  - Cancer Prev. Res.
VL  - 5
IS  - 1
PB  - American Assoc. for Cancer Research
PY  - 2012
SN  - 1940-6207
ER  -