Differential miRNA and Protein Expression Reveals miR-1285, Its Targets TGM2 and CDH-1, as Well as CD166 and S100A13 as Potential New Biomarkers in Patients with Diabetes Mellitus and Pancreatic Adenocarcinoma.

Early detection of PDAC remains challenging due to the lack of early symptoms and the absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics signatures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening.

Fibroblast Activation Protein α-Directed Imaging and Therapy of Solitary Fibrous Tumor.

Fibroblast activation protein α (FAPα) is expressed at high levels in several types of tumors. Here, we report the expression pattern of FAPα in solitary fibrous tumor (SFT) and its potential use as a radiotheranostic target. We analyzed FAPα messenger RNA and protein expression in biopsy samples from SFT patients using immunohistochemistry and multiplexed immunofluorescence.

Histology-Based Prediction of Therapy Response to Neoadjuvant Chemotherapy for Esophageal and Esophagogastric Junction Adenocarcinomas Using Deep Learning.

Purpose: Quantifying treatment response to gastroesophageal junction (GEJ) adenocarcinomas is crucial to provide an optimal therapeutic strategy. Routinely taken tissue samples provide an opportunity to enhance existing positron emission tomography-computed tomography (PET/CT)-based therapy response evaluation. Our objective was to investigate if deep learning (DL) algorithms are capable of predicting the therapy response of patients with GEJ adenocarcinoma to neoadjuvant chemotherapy on the basis of histologic tissue samples.

Clinical Outcome and Treatment Sequences of Patients with Advanced Pancreatic Cancer Treated with Contemporary Chemotherapy Protocols.

Introduction: Systemic therapy is firmly established in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). Clinical efficacy is still modest and options are limited. Combination therapy protocols such as FOLFIRINOX and gemcitabine/nab-paclitaxel (Gem/NP) define standard-of-care.

PET-directed combined modality therapy for gastroesophageal junction cancer: Results of the multicentre prospective MEMORI trial of the German Cancer Consortium (DKTK).

Background: Positron emission tomography (PET) may differentiate responding and non-responding tumours early in the treatment of locally advanced gastroesophageal junction adenocarcinomas. Early PET non-responders (P-NR) after induction CTX might benefit from changing to chemoradiation (CRT).

Methods: Patients underwent baseline F-FDG PET followed by 1 cycle of CTX.

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype.

Objective: Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.

Design: Targeted and whole-genome low-coverage sequencing, genome-wide methylation and transcriptome analyses were applied on a final collective of 122 morphologically well-characterised low-grade and high-grade PDAC precursors, including intestinal and gastric intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasias (PanIN).

MCL1 as putative target in pancreatoblastoma.

Pancreatoblastoma (PB) is a rare tumor of the pancreas. In case of metastases, the treatment options are sparse and targeted approaches are not developed. We here evaluate MCL1 amplification as a putative target in PB.

Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression.

Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC.

Localized Angiosarcoma, Not One Disease: A Retrospective Single-Center Study on Prognosis Depending on the Primary Site and Etiology.

Background: Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology.

Methods: We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018.

Image-Based Identification and Genomic Analysis of Single Circulating Tumor Cells in High Grade Serous Ovarian Cancer Patients.

In Ovarian Cancer (OC), the analysis of single circulating tumor cells (sCTCs) might help to investigate genetic tumor evolution during the course of treatment. Since common CTC identification features failed to reliably detect CTCs in OC, we here present a workflow for their detection and genomic analysis. Blood of 13 high-grade serous primary OC patients was analyzed, using negative immunomagnetic enrichment, followed by immunofluorescence staining and imaging for Hoechst, ERCC1, CD45, CD11b and cytokeratin (CK) and sCTC sorting with the DEPArray NxT.

Serial Circulating Tumor DNA Mutational Status in Patients with KRAS-Mutant Metastatic Colorectal Cancer from the Phase 3 AIO KRK0207 Trial.

Background: We assessed the usefulness of circulating tumor DNA (ctDNA) pre- or post-treatment initiation for outcome prediction and treatment monitoring in metastatic colorectal cancer (mCRC).

Methods: Droplet digital PCR was used to measure absolute mutant V-Ki-ras2 Kirsten rat sarcoma viral oncogene ((mut)KRAS) ctDNA concentrations in 214 healthy controls (plasma and sera) and in 151 tissue-based mutKRAS positive patients with mCRC from the prospective multicenter phase 3 trial AIO KRK0207. Serial mutKRAS ctDNA was analyzed prior to and 2-3 weeks after first-line chemotherapy initiation with fluoropyrimidine, oxaliplatin, and bevacizumab in patients with mCRC and correlated with clinical parameters.

Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to virtually all chemo- and targeted therapeutic approaches. Epigenetic regulators represent a novel class of drug targets. Among them, BET and HDAC proteins are central regulators of chromatin structure and transcription, and preclinical evidence suggests effectiveness of combined BET and HDAC inhibition in PDAC.

TFEB-mediated lysosomal biogenesis and lysosomal drug sequestration confer resistance to MEK inhibition in pancreatic cancer.

Oncogenic mutations are encountered in more than 90% of pancreatic ductal adenocarcinomas. MEK inhibition has failed to procure any clinical benefits in mutant RAS-driven cancers including pancreatic ductal adenocarcinoma (PDAC). To identify potential resistance mechanisms underlying MEK inhibitor (MEKi) resistance in PDAC, we investigated lysosomal drug accumulation in PDAC models both in vitro and in vivo.

Notch-Induced Myeloid Reprogramming in Spontaneous Pancreatic Ductal Adenocarcinoma by Dual Genetic Targeting.

Despite advances in our understanding of the genetics of pancreatic ductal adenocarcinoma (PDAC), the efficacy of therapeutic regimens targeting aberrant signaling pathways remains highly limited. Therapeutic strategies are greatly hampered by the extensive desmoplasia that comprises heterogeneous cell populations. Notch signaling is a contentious pathway exerting opposite roles in tumorigenesis depending on cellular context.

MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer.

Decreased expression of the microRNA miR-205 has been observed in multiple tumour types due to its role in the epithelial to mesenchymal transition, which promotes metastasis. We determined the expression of miR-205 in 111 archival samples of prostate carcinoma and found it to be strongly reduced in most samples, with a median expression level of 16% in comparison to benign tissue from the same patient. Lower miR-205 expression correlated significantly with tumour size and miR-205 levels decreased with increasing Gleason score from 7a=3+4 to 8=4+4.

Salinomycin induces autophagy in colon and breast cancer cells with concomitant generation of reactive oxygen species.

Background: Salinomycin is a polyether ionophore antibiotic that has recently been shown to induce cell death in human cancer cells displaying multiple mechanisms of drug resistance. The underlying mechanisms leading to cell death after salinomycin treatment have not been well characterized. We therefore investigated the role of salinomycin in caspase dependent and independent cell death in colon cancer (SW480, SW620, RKO) and breast cancer cell lines (MCF-7, T47D, MDA-MB-453).

Site- and grade-specific diversity of LINE1 methylation pattern in gastroenteropancreatic neuroendocrine tumours.

Background: Recent data indicate that gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have a hypomethylated long interspersed element (LINE1) promoter. To answer the question, of whether LINE1 may be of value in assessing the malignant potential of GEP-NETs, we analysed LINE1 methylation in different organs.

Materials And Methods: A total of 58 GEP-NETs of gastric (n=14), pancreatic (n=15), small intestine (n=17), appendix (n=8), colorectal (n=4) and non-neoplastic tissues were analysed using DNA isolation, bisulphite-treatment and pyrosequencing.

Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis.

The gene encoding the miR-34a microRNA is a transcriptional target of the p53 tumor suppressor protein and subject to epigenetic inactivation in colorectal cancer and numerous other tumor types. Here, we combined pulsed SILAC (pSILAC) and microarray analyses to identify miR-34a-induced changes in protein and mRNA expression. pSILAC allowed to quantify the de novo protein synthesis of 1206 proteins after activation of a conditional miR-34a allele in a colorectal cancer cell line.

Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas.

The microRNA encoding genes miR-34a and miR-34b/c represent direct p53 target genes and possess tumor suppressive properties as they mediate apoptosis, cell cycle arrest, and senescence. We previously reported that the miR-34a gene is subject to epigenetic inactivation by CpG methylation of its promoter region in primary prostate cancer and melanomas, and in 110 different cancer cell lines of diverse origin. Here we analyzed the methylation status of miR-34a and miR-34b/c in additional primary tumors of divergent sites.