TY  - JOUR
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with neoadjuvant radio(chemo)therapy failing in approximately 70 % of cases due to high tumor heterogeneity, and intrinsic radioresistance. Patient-derived organoids (PDOs) closely recapitulate appearance, and functionality as the original tissue and have potential to explore novel therapies for personalized radiooncology. In this study, the radioresponse of PDAC PDO lines was determined after irradiation (RT). PDOs were immunohistochemically characterized by γ-H2AX, HIF-1α and Ki-67 staining. RNA sequencing data were analyzed by gene set enrichment analyses to investigate underlying mechanisms of radioresistance. Preclinical findings were correlated with clinical data from the corresponding patients. PDOs showed a significant heterogeneity in response to radiation and were classified into radiosensitive, intermediate, and radioresistant subgroups. A correlation between radiosensitivity and enhanced proliferation and decreased hypoxia was observed. OXPHOS-related gene signatures were significantly overexpressed in the radioresistant phenotype. Translationally, radioresistance in PDOs was associated with significantly poorer survival of patients. Our platform demonstrated heterogeneity in radioresponse reflecting the clinical situation and correlation with clinical outcomes. Immunohistochemical staining and transcriptomic profiling identified molecular signatures, including HIF-1α and OXPHOS-related pathways, associated with radioresistance. Implementing PDO-based radioresponse profiling in clinical workflows may enable patient stratified treatment approaches. Overall, our findings suggest that functionalizing PDOs for radioresponse might extend PDO-informed precision oncology.
AU  - Kessler, C.*
AU  - Cadacio, F.*
AU  - Maurer, C.*
AU  - Schäfer, A.*
AU  - Orben, F.*
AU  - Fischer, J.C.*
AU  - Schilling, D.
AU  - Fricke, L.*
AU  - Rasch, S.*
AU  - Demir, I.E.*
AU  - Steiger, K.*
AU  - Weichert, W.*
AU  - Schmid, R.M.*
AU  - Combs, S.E.
AU  - Reichert, M.*
AU  - Dobiasch, S.
C1  - 75578
C2  - 58225
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - Development of a translational radiobiology platform using pancreatic cancer patient-derived organoids for personalized radiation oncology.
JO  - Transl. Oncol.
VL  - 62
PB  - Elsevier Science Inc
PY  - 2025
ER  - 

TY  - JOUR
AB  - BACKGROUND: Tailoring surveillance and treatment strategies for stage II colon cancer (CC) after curative surgery remains challenging, and personalized approaches are lacking. We aimed to identify a gene methylation panel capable of stratifying high-risk stage II CC patients for recurrence beyond traditional clinical variables. METHODS: Genome-wide tumor tissue DNA methylation data were analyzed from 562 stage II CC patients who underwent surgery in Germany (DACHS study). The cohort was divided into a training set (N = 395) and an internal validation set (N = 131), with external validation performed on 97 stage II CC patients from Spain. DNA methylation markers were primarily selected using the Elastic Net Cox model. The resulting prognostic index (PI), a combination of clinical factors and selected methylation markers, was compared to baseline models using clinical variables or microsatellite instability (MSI), with discrimination and prediction accuracy assessed through time-dependent receiver operating characteristic curves (AUC) and Brier scores. RESULTS: The final PI incorporated age, sex, tumor stage, location, and 27 DNA methylation markers. The PI consistently outperformed the baseline model including age, sex, and tumor stage in time-dependent AUC across validation cohorts (e.g., 1-year AUC and 95 % confidence interval: internal validation set, PI: 0.66, baseline model: 0.52; external validation set, PI: 0.72, baseline model: 0.64). In internal validation, the PI also showed a consistently improved time-dependent AUC compared with a combination of MSI and tumor stage only. Nevertheless, the PI did not improve the prediction accuracy of CC recurrence compared to the baseline model. CONCLUSIONS: This study identified 27 tumor tissue DNA methylation biomarkers that improved the discriminative power in classifying recurrence risk among stage II colon cancer patients. While this methylation panel alone lacks sufficient prediction accuracy for clinical application, its discriminative improvement suggests potential value as part of a multimodal risk-stratification tool.
AU  - Yuan, T.*
AU  - Edelmann, D.*
AU  - Moreno, V.*
AU  - Georgii, E.
AU  - Barros De Andrade E Sousa, L.
AU  - Pelin, H.
AU  - Jiang, X.*
AU  - Kather, J.N.*
AU  - Tagscherer, K.E.*
AU  - Roth, W.*
AU  - Bewerunge-Hudler, M.*
AU  - Brobeil, A.*
AU  - Kloor, M.*
AU  - Bläker, H.*
AU  - Brenner, H.*
AU  - Hoffmeister, M.*
C1  - 74304
C2  - 57429
TI  - Identification and external validation of tumor DNA methylation panel for the recurrence risk stratification of stage II colon cancer.
JO  - Transl. Oncol.
VL  - 57
PY  - 2025
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Small cell lung cancer (SCLC) is mostly diagnosed in stage III-IV patients and associated with poor prognosis. To date, surgery is no gold-standard treatment for any SCLC stage and evidence is lacking whether it is beneficial. Here we investigate the impact of surgery, with special attention to stage III SCLC patients, sub-stages and treatment combinations. METHODS: The overall survival (OS) and cancer-specific survival (CSS) of 33,198 SCLC patients (SEER database) were analyzed retrospectively, using various statistical analyses, including propensity score matching (PSM), recursive partitioning, and sequential landmark analyses. RESULTS: Independent of stage, the OS of patients with surgery-including treatments was almost always better than without surgery. This holds true for stage I-II patients, even after PMS analysis (p < 0.017). The same was found for stage IV patients that underwent surgery plus chemotherapy vs. chemotherapy alone (p = 0.013 after PSM). Stage III patients showed a robust improvement in OS and CSS after surgery (OS: 18 vs.13 months) or surgery plus chemotherapy (OS: 20 vs.15 months) as confirmed by well-balanced PSM and sequential landmark analyses of long-term survivors. More detailed analyses using two independent approaches showed prolonged OS in T3-4/N0-1 and T1-2/N2 stage III patients after surgery or surgery plus chemotherapy. Importantly, primary site surgery had a major survival advantage over surgery at regional sites (p < 0.003). CONCLUSION: Our study demonstrates that selected patients of all stages, including stage III T3-4/N0-1 and T1-2/N2, can benefit greatly from surgery-including treatments. Thus, surgery should be included into hospital treatment recommendations for specifically selected SCLC patients. Condensed abstract Primary resection in patients with stage III SCLC needs re-evaluation. Selected patients with stage III SCLC benefit significantly from surgery. Patients with T3-4/N0-1 and T1-2/N2 stage III SCLC should be considered for surgery.
AU  - Jia, J.
AU  - Trassl, L.
AU  - Kong, F.*
AU  - Deng, B.
AU  - Liu, R.*
AU  - Sun, Z.*
AU  - Lan, X.*
AU  - Yildirim, A.Ö.
AU  - Stathopoulos, G.T.
AU  - Fernandez, I.E.
AU  - Schamberger, A.C.
C1  - 71523
C2  - 56256
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - Improved survival of patients with stage III small-cell lung cancer with primary resection: A SEER-based analysis.
JO  - Transl. Oncol.
VL  - 49
PB  - Elsevier Science Inc
PY  - 2024
ER  - 

TY  - JOUR
AB  - BACKGROUND AND PURPOSE: To determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: For this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years. RESULTS: Proliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively). CONCLUSION: Increased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome.
AU  - Salvermoser, L.*
AU  - Goldberg, S.N.*
AU  - Alunni-Fabbroni, M.*
AU  - Kazmierczak, P.M.*
AU  - Gröper, M.N.*
AU  - Schäfer, J.N.*
AU  - Öcal, E.*
AU  - Burkard, T.*
AU  - Corradini, S.*
AU  - Ben Khaled, N.*
AU  - Petrera, A.
AU  - Wildgruber, M.*
AU  - Ricke, J.*
AU  - Stechele, M.*
C1  - 70032
C2  - 55368
TI  - CT-guided high dose rate brachytherapy can induce multiple systemic proteins of proliferation and angiogenesis predicting outcome in HCC.
JO  - Transl. Oncol.
VL  - 43
PY  - 2024
ER  - 

TY  - JOUR
AB  - INTRODUCTION: Pleural effusions frequently signal disseminated cancer. Diagnostic markers of pleural malignancy at presentation that would assess cancer risk and would streamline diagnostic decisions remain unidentified. METHODS: A consecutive cohort of 323 patients with pleural effusion (PE) from different etiologies were recruited between 2013 and 2017 and was retrospectively analyzed. Data included history, chest X-ray, and blood/pleural fluid cell counts and biochemistry. Group comparison, receiver-operator characteristics, unsupervised hierarchical clustering, binary logistic regression, and random forests were used to develop the malignant pleural effusion detection (MAPED) score. MAPED was validated in an independent retrospective UK cohort (n = 238). RESULTS: Five variables showed significant diagnostic power and were incorporated into the 5-point MAPED score. Age > 55 years, effusion size > 50% of the most affected lung field, pleural neutrophil count 〈 2,500/mm3, effusion protein 〉 3.5 g/dL, and effusion lactate dehydrogenase > 250 U/L, each scoring one point, predicted underlying cancer with the area under curve(AUC) = 0.819 (P < 10-15) in the derivation cohort. The integrated discrimination improvement of MAPED scores showed an increase compared to cytology (p <0.001). Decision curve analysis indicated that the MAPED score generated net clinical benefit. In the validation dataset, the AUC of MAPED scores was 0.723 ( P = 3 × 10-9) for the MAPED score. Interestingly, MAPED correctly identified 33/42(79%) of cytology-negative patients that indeed had cancer. CONCLUSIONS: The MAPED score identifies malignant pleural effusions with satisfactory accuracy and can be used complementary to cytology to streamline diagnostic procedures. CONDENSED ABSTRACT: Diagnostic markers for malignant pleural effusions remain uncertain. The MAPED score identifies malignant pleural effusions and complements cytology and confers no additional risk to the patient or cost to the healthcare system.
AU  - Jia, J.
AU  - Marazioti, A.*
AU  - Voulgaridis, A.*
AU  - Psallidas, I.*
AU  - Lamort, A.-S.
AU  - Iliopoulou, M.*
AU  - Krontira, A.C.*
AU  - Lilis, I.*
AU  - Asciak, R.*
AU  - Kanellakis, N.I.*
AU  - Rahman, N.M.*
AU  - Karkoulias, K.*
AU  - Spiropoulos, K.*
AU  - Liu, R.*
AU  - Kaiser, J.C.
AU  - Stathopoulos, G.T.
C1  - 68651
C2  - 54855
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - Clinical identification of malignant pleural effusions.
JO  - Transl. Oncol.
VL  - 39
PB  - Elsevier Science Inc
PY  - 2023
ER  - 

TY  - JOUR
AB  - Homologous recombination deficiency (HRD) is a predictive marker for response to poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian carcinoma. HRD scores have entered routine diagnostics, but the influence of algorithms, parameters and confounders has not been analyzed comprehensively. A series of 100 poorly differentiated ovarian carcinoma samples was analyzed using whole exome sequencing (WES) and genotyping. Tumor purity was determined using conventional pathology, digital pathology, and two bioinformatic methods. HRD scores were calculated from copy number profiles determined by Sequenza and by Sclust either with or without fixed tumor purity. Tumor purity determination by digital pathology combined with a tumory purity informed variant of Sequenza served as reference method for HRD scoring. Seven tumors had deleterious mutations in BRCA1/2, 12 tumors had deleterious mutations in other homologous recombination repair (HRR) genes, 18 tumors had variants of unknown significance (VUS) in BRCA1/2 or other HRR genes, while the remaining 63 tumors had no relevant alterations. Using the reference method for HRD scoring, 68 tumors were HRD-positive. HRDsum determined by WES correlated strongly with HRDsum determined by single nucleotide polymorphism (SNP) arrays (R = 0.85). Conventional pathology systematically overestimated tumor purity by 8% compared to digital pathology. All investigated methods agreed on classifying the deleterious BRCA1/2-mutated tumors as HRD-positive, but discrepancies were observed for some of the remaining tumors. Discordant HRD classification of 11% of the tumors was observed comparing the tumor purity uninformed default of Sequenza and the reference method. In conclusion, tumor purity is a critical factor for the determination of HRD scores. Assistance by digital pathology helps to improve accuracy and imprecision of its estimation.
AU  - Menzel, M.*
AU  - Endris, V.*
AU  - Schwab, C.*
AU  - Kluck, K.*
AU  - Neumann, O.*
AU  - Beck, S.*
AU  - Ball, M.*
AU  - Schaaf, C.*
AU  - Fröhling, S.*
AU  - Lichtner, P.
AU  - Schirmacher, P.*
AU  - Kazdal, D.*
AU  - Stenzinger, A.*
AU  - Budczies, J.*
C1  - 68505
C2  - 54684
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - Accurate tumor purity determination is critical for the analysis of homologous recombination deficiency (HRD).
JO  - Transl. Oncol.
VL  - 35
PB  - Elsevier Science Inc
PY  - 2023
ER  - 

TY  - JOUR
AB  - In malignant disease, CD4+Foxp3+ regulatory T cells (Tregs) hamper antitumor immune responses and may provide a target for immunotherapy. Although immune checkpoint blockade (ICB) has become an established therapy for several cancer entities including lymphoma, its mechanisms have not been entirely uncovered. Using endogenously arising λ-MYC-transgenic mouse B-cell lymphomas, which can effectively be suppressed by either Treg ablation or ICB, we investigated which mechanisms are used by Tregs to suppress antitumor responses and how ICB affects these pathways. During tumor development, Tregs up-regulated Foxp3, CD25, CTLA-4 and IL-10, which correlated with enhanced immunosuppressive functions. Thus, in contrast to other tumors, Tregs did not become dysfunctional despite chronic stimulation in the tumor microenvironment and progressive up-regulation of PD-1. Immunosuppression was mediated by direct contacts between Tregs and effector T cells and by IL-10. When λ-MYC mice were treated with ICB antibodies, Tregs revealed a less profound up-regulation of Foxp3, CD25 and IL-10 and a decreased suppressive capacity. This may be due to the shift towards a pro-inflammatory milieu fostered by ICB. In summary, an ICB-induced interference with Treg-dependent immunosuppression may contribute to the success of ICB.
AU  - Bauer, V.
AU  - Ahmetlic, F.
AU  - Hömberg, N.
AU  - Geishauser, A.
AU  - Röcken, M.*
AU  - Mocikat, R.
C1  - 62407
C2  - 50846
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
TI  - Immune checkpoint blockade impairs immunosuppressive mechanisms of regulatory T cells in B-cell lymphoma.
JO  - Transl. Oncol.
VL  - 14
IS  - 9
PB  - Elsevier Science Inc
PY  - 2021
ER  - 

TY  - JOUR
AB  - PURPOSE: Here we demonstrate the potential of multispectral optoacoustic tomography (MSOT), a new non-invasive structural and functional imaging modality, to track the growth and changes in blood oxygen saturation (sO) in orthotopic glioblastoma (GBMs) and the surrounding brain tissues upon administration of a vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor cells were longitudinally monitored for the development of orthotopic GBMs up to 15 days and observed for changes in sO upon administration of combretastatin A4 phosphate (CA4P, 30 mg/kg), an FDA approved VDA for treating solid tumors. We employed a newly-developed non-negative constrained approach for combined MSOT image reconstruction and unmixing in order to quantitatively map sO in whole mouse brains. RESULTS: Upon longitudinal monitoring, tumors could be detected in mouse brains using single-wavelength data as early as 6 days post tumor cell inoculation. Fifteen days post-inoculation, tumors had higher sO of 63 ± 11% (n = 5, P < .05) against 48 ± 7% in the corresponding contralateral brain, indicating their hyperoxic status. In a different set of animals, 42 days post-inoculation, tumors had lower sO of 42 ± 5% against 49 ± 4% (n = 3, P < .05) in the contralateral side, indicating their hypoxic status. Upon CA4P administration, sO in 15 days post-inoculation tumors dropped from 61 ± 9% to 36 ± 1% (n = 4, P < .01) within one hour, then reverted to pre CA4P treatment values (63 ± 6%) and remained constant until the last observation time point of 6 hours. CONCLUSION: With the help of advanced post processing algorithms, MSOT was capable of monitoring the tumor growth and assessing hemodynamic changes upon administration of VDAs in orthotopic GBMs.
AU  - Balasundaram, G.*
AU  - Ding, L
AU  - Li, X.*
AU  - Attia, A.B.E.*
AU  - Dean-Ben, X.L.
AU  - Ho, C.J.H.*
AU  - Chandrasekharan, P.*
AU  - Tay, H.C.*
AU  - Lim, H.Q.*
AU  - Ong, C.B.*
AU  - Mason, R.P.*
AU  - Razansky, D.
AU  - Olivo, M.*
C1  - 54133
C2  - 45302
CY  - 360 Park Ave South, New York, Ny 10010-1710 Usa
SP  - 1251-1258
TI  - Noninvasive anatomical and functional imaging of orthotopic glioblastoma development and therapy using multispectral optoacoustic tomography.
JO  - Transl. Oncol.
VL  - 11
IS  - 5
PB  - Elsevier Science Inc
PY  - 2018
ER  - 

TY  - JOUR
AB  - Screening programs are recommended for individuals at risk (IAR) from families with familial pancreatic cancer (FPC). However, reliable imaging methods or biomarkers for early diagnosis of pancreatic ductal adenocarcinoma (PC) or its precursor lesions are still lacking. The ability of circulating microRNAs (miRNAs) to discriminate multifocal high-grade precursor lesions or PC from normal was examined. The presence of miRNA-21, -155, -196a, -196b and -210 was analyzed in the serum of transgenic KPC mice to test their ability to distinguish mice with different grades of pancreatic intraepithelial neoplasia (mPanIN1-3) or PC from control mice. Serum levels of miR-196a and -196b were significantly higher in mice with PanIN2/3 lesions (n = 10) or PC (n = 8) as compared to control mice (n = 10) or mice with PanIN1 lesions (n = 10; P = .01). In humans, miR-196a and -196b were also diagnostic. Patients with PC, sporadic (n = 9) or hereditary (n = 10), and IAR with multifocal PanIN2/3 lesions (n = 5) had significantly higher serum levels than patients with neuroendocrine pancreatic tumors (n = 10) or chronic pancreatitis (n = 10), IAR with PanIN1 or no PanIN lesions (n = 5), and healthy controls (n = 10). The combination of both miR-196a and -196b reached a sensitivity of 1 and specificity of 0.9 (area under the curve = 0.99) to diagnose PC or high-grade PanIN lesions. In addition, preoperative elevated serum levels of miR-196a and -196b in patients with PC or multifocal PanIN2/3 lesions dropped to normal after potential curative resection. The combination of miR-196a and -196b may be a promising biomarker test for the screening of IAR for FPC.
AU  - Slater, E.P.*
AU  - Strauch, K.
AU  - Rospleszcz, S.
AU  - Ramaswamy, A.*
AU  - Esposito, I.*
AU  - Klöppel, G.*
AU  - Mätthai, E.*
AU  - Heeger, K.*
AU  - Fendrich, V.*
AU  - Langer, P.*
AU  - Bartsch, D.K.*
C1  - 31672
C2  - 34708
CY  - New York
SP  - 464-471
TI  - MicroRNA-196a and -196b as potential biomarkers for the early detection of familial pancreatic cancer.
JO  - Transl. Oncol.
VL  - 7
IS  - 4
PB  - Elsevier Science Inc
PY  - 2014
ER  - 

TY  - JOUR
AB  - High-risk individuals of familial pancreatic cancer (FPC) families are considered to be good candidates for screening programs to detect early PC or its high-grade precursor lesions, especially pancreatic intraepithelial neoplasia (PanIN) 2/3 lesions. There is a definite need for diagnostic markers as neither reliable imaging methods nor biomarkers are available to detect these lesions. On the basis of a literature search, the potential serum markers neutrophil gelatinase-associated lipocalin (LCN2), metallopeptidase inhibitor 1 (TIMP1), chemokine (C-X-C motif) ligand 16 (CXCL16), IGFBP4, and iC3a, which were first tested in transgenic KrasLSL.(G12D/+);p53(R172H/+);Pdx1-Cre mice, were identified. ELISA analyses of LCN2, TIMP1, and CXCL16 revealed significantly higher levels in mice with PanIN2/3 lesions or PC compared to mice with normal pancreata or PanIN1 lesions. Analysis of preoperative human serum samples from patients with sporadic PC (n = 61), hereditary PC (n = 24), chronic pancreatitis (n = 28), pancreatic neuroendocrine tumors (n = 11), and FPC patients with histologically proven multifocal PanIN2/3 lesions (n = 3), as well as healthy control subjects (n = 20), confirmed significantly higher serum levels of LCN2 and TIMP1 in patients with PC and multifocal PanIN2/3 lesions. The combination of LCN2 and TIMP1 as a diagnostic test for the detection of PC had a sensitivity, specificity, and positive predictive value of 100% each. Although this preliminary finding needs to be validated in a large series of individuals at high risk for FPC, serum measurement of LCN2 and TIMP1 might be a promising screening tool.
AU  - Slater, E.P.*
AU  - Fendrich, V.*
AU  - Strauch, K.
AU  - Rospleszcz, S.
AU  - Ramaswamy, A.*
AU  - Mätthai, E.*
AU  - Chaloupka, B.*
AU  - Gress, T.M.*
AU  - Langer, P.*
AU  - Bartsch, D.K.*
C1  - 24390
C2  - 31536
SP  - 99-103
TI  - LCN2 and TIMP1 as potential serum markers for the early detection of familial pancreatic cancer.
JO  - Transl. Oncol.
VL  - 6
IS  - 2
PB  - Neoplasia Press
PY  - 2013
ER  - 

TY  - JOUR
AB  - The supporting role of urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) in migration and invasion is well known. In addition, both factors are key components in cancer cell-related signaling. However, little information is available for uPA and PAI-1-associated signaling pathways in primary cancers and corresponding lymph node metastases. The aim of this study was to compare the expression of uPA and PAI-1-associated signaling proteins in 52 primary breast cancers and corresponding metastases. Proteins were extracted from formalin-fixed paraffin-embedded tissue samples of the primary tumors and metastases. Protein lysates were subsequently analyzed by reverse phase protein array for the expression of members of the PI3K/AKT (FAK, GSK3-β, ILK, pGSK3-β, PI3K, and ROCK) and the MAPK pathways (pp38, pSTAT3, and p38). A solid correlation of uPA expression existed between primary tumors and metastases, whereas PAI-1 expression did not significantly correlate between them. The correlations of uPA and PAI-1 with signaling pathways found in primary tumors did not persist in metastases. Analysis of single molecules revealed that some correlated well between tumors and metastases (FAK, pGSK3-β, ILK, Met, PI3K, ROCK, uPA, p38, and pp38), whereas others did not (PAI-1 and GSK3-β). Whether the expression of a protein correlated between tumor and metastasis or not was independent of the pathway the protein is related to. These findings hint at a complete deregulation of uPA and PAI-1-related signaling in metastases, which might be the reason why uPA and PAI-1 reached clinical relevance only for lymph node-negative breast cancer tissues.
AU  - Malinowsky, K.*
AU  - Wolff, C.*
AU  - Berg, D.*
AU  - Schuster, T.*
AU  - Walch, A.K.
AU  - Bronger, H.*
AU  - Mannsperger, H.*
AU  - Schmidt, C.*
AU  - Korf, U.*
AU  - Höfler, H.*
AU  - Becker, K.F.*
C1  - 11206
C2  - 30548
SP  - 98-104
TI  - uPA and PAI-1-related signaling pathways differ between primary breast cancers and lymph node metastases.
JO  - Transl. Oncol.
VL  - 5
IS  - 2
PB  - Neoplasia Press
PY  - 2012
ER  -