Body Composition in Cholangiocarcinoma Affects Immune Cell Populations in the Tumor and Normal Liver Parenchyma.

Background: Due to malnutrition and tumor cachexia, body composition (BC) is frequently altered and known to adversely affect short- and long-term results in patients with cholangiocarcinoma (CCA). Here, we explored immune cell populations in the tumor and liver of CCA patients with respect to BC.

Methods: A cohort of 96 patients who underwent surgery for CCA was investigated by multiplexed immunofluorescence (MIF) techniques with computer-based analysis on whole-tissue slide scans to quantify and characterize immune cells in normal liver and tumor regions.

Key Regulatory Elements of the TGFβ-LRRC15 Axis Predict Disease Progression and Immunotherapy Resistance Across Cancer Types.

Transforming growth factor-beta (TGFβ) has dual roles in cancer, initially suppressing tumors but later promoting metastasis and immune evasion. Efforts to inhibit TGFβ have been largely unsuccessful due to significant toxicity and indiscriminate immunosuppression. Leucine-rich repeat-containing protein 15 (LRRC15) is a TGFβ-regulated antigen expressed by mesenchymal-derived cancer cells and cancer-associated fibroblasts (CAFs).

Liver volumetry improves evaluation of treatment response to hepatic artery infusion chemotherapy in uveal melanoma patients with liver metastases.

Background: In uveal melanoma patients, short-term evaluation of treatment response to hepatic artery infusion chemotherapy (HAIC) using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria is challenging due to the diffuse metastatic spread. As liver enlargement can frequently be observed, this study aims to compare RECIST 1.

Minimally invasive determination of pancreatic ductal adenocarcinoma (PDAC) subtype by means of circulating cell-free RNA.

Pancreatic ductal adenocarcinoma (PDAC) comprises two clinically relevant molecular subtypes that are currently determined using tissue biopsies, which are spatially biased and highly invasive. We used whole transcriptome sequencing of 10 plasma samples with tumor-informed subtypes, complemented by proteomic analysis for minimally invasive identification of PDAC subtype markers. Data were validated in independent large cohorts and correlated with treatment response and patient outcome.

Head-to-head comparison of Ga-FAPI-46 PET/CT, F-FDG PET/CT, and contrast-enhanced CT for the detection of various tumors.

Objective: FAPI-PET/CT exhibits high tumor uptake and low background accumulation, enabling high-sensitivity tumor detection. We compared the diagnostic performance of  Ga-FAPI-46 PET/CT plus contrast-enhanced CT (CE-CT), F-FDG PET/CT plus CE-CT, and standalone CE-CT in patients with various malignancies.

Methods: 232 patients underwent  Ga-FAPI-46 PET/CT,F-FDG PET/CT, and CE-CT each within 4 weeks.

Theranostics with somatostatin receptor antagonists in SCLC: Correlation of Ga-SSO120 PET with immunohistochemistry and survival.

Positron Emission Tomography (PET) using the somatostatin receptor 2 (SSTR2)-antagonist satoreotide trizoxetan (Ga-SSO120) is a novel, promising imaging modality for small-cell lung cancer (SCLC), which holds potential for theranostic applications. This study aims to correlate uptake in PET imaging with SSTR2 expression in immunohistochemistry (IHC) and to assess the prognostic value of Ga-SSO120 PET at initial staging of patients with SCLC. We analyzed patients who underwent Ga-SSO120 PET/CT during initial diagnostic workup of SCLC as part of institutional standard-of-care.

Fibroblast Activation Protein-Directed Imaging Outperforms F-FDG PET/CT in Malignant Mesothelioma: A Prospective, Single-Center, Observational Trial.

The fibroblast activation protein (FAP) is highly expressed in tumor and stromal cells of mesothelioma and thus is an interesting imaging and therapeutic target. Previous data on PET imaging with radiolabeled FAP inhibitors (FAPIs) suggest high potential for superior tumor detection. Here, we report the data of a large malignant pleural mesothelioma cohort within a Ga-FAPI46 PET observational trial (NCT04571086).

P-move: a randomized control trial of exercise in patients with advanced pancreatic or biliary tract cancer (aPBC) receiving beyond first-line chemotherapy.

Purpose: Patients with advanced pancreatic and biliary tract cancer (aPBC) frequently suffer from high symptom burden. Exercise can reduce treatment side effects and improve patient-related outcomes (PROMs). However, evidence from prospective studies regarding feasibility and efficacy in advanced settings are sparse.

Histology-Based Radiomics for [F]FDG PET Identifies Tissue Heterogeneity in Pancreatic Cancer.

Radiomics features can reveal hidden patterns in a tumor but usually lack an underlying biologic rationale. In this work, we aimed to investigate whether there is a correlation between radiomics features extracted from [F]FDG PET images and histologic expression patterns of a glycolytic marker, monocarboxylate transporter-4 (MCT4), in pancreatic cancer. A cohort of pancreatic ductal adenocarcinoma patients ( = 29) for whom both tumor cross sections and [F]FDG PET/CT scans were available was used to develop an [F]FDG PET radiomics signature.

Prognostic Implications of Ga-FAPI-46 PET/CT-Derived Parameters on Overall Survival in Various Types of Solid Tumors.

Tumoral fibroblast activation protein expression is associated with proliferation and angiogenesis and can be visualized by PET/CT. We examined the prognostic value of [Ga]Ga-fibroblast activation protein inhibitor (FAPI) (Ga-FAPI)-46 PET/CT for different tumor entities in patients enrolled in 2 prospective imaging studies (NCT05160051, = 30; NCT04571086, = 115). Within 4 wk, 145 patients underwent Ga-FAPI-46 and [F]FDG (F-FDG) PET/CT.

Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment.

5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients.

Ga-Fibroblast Activation Protein Inhibitor PET/CT Improves Detection of Intermediate and Low-Grade Sarcomas and Identifies Candidates for Radiopharmaceutical Therapy.

Fibroblast activation protein-α (FAP) is often highly expressed by sarcoma cells and by sarcoma-associated fibroblasts in the tumor microenvironment. This makes it a promising target for imaging and therapy. The level of FAP expression and the diagnostic value of Ga-FAP inhibitor (FAPI) PET for sarcoma subtypes are unknown.

CellViT: Vision Transformers for precise cell segmentation and classification.

Nuclei detection and segmentation in hematoxylin and eosin-stained (H&E) tissue images are important clinical tasks and crucial for a wide range of applications. However, it is a challenging task due to nuclei variances in staining and size, overlapping boundaries, and nuclei clustering. While convolutional neural networks have been extensively used for this task, we explore the potential of Transformer-based networks in combination with large scale pre-training in this domain.

Development of Potent Dual BET/HDAC Inhibitors via Pharmacophore Merging and Structure-Guided Optimization.

Bromodomain and extra-terminal domain (BET) proteins and histone deacetylases (HDACs) are prime targets in cancer therapy. Recent research has particularly focused on the development of dual BET/HDAC inhibitors for hard-to-treat tumors, such as pancreatic cancer. Here, we developed a new series of potent dual BET/HDAC inhibitors by choosing starting scaffolds that enabled us to optimally merge the two functionalities into a single compound.

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.

Ga-Labeled Fibroblast Activation Protein Inhibitor (Ga-FAPI) PET for Pancreatic Adenocarcinoma: Data from the Ga-FAPI PET Observational Trial.

The fibroblast activation protein (FAP) is highly expressed on carcinoma-associated fibroblasts in the stroma of pancreatic cancer and thus is a promising target for imaging and therapy. Preliminary data on PET imaging with radiolabeled FAP inhibitors (FAPIs) demonstrate superior tumor detection. Here we assess the accuracy of FAP-directed PET in patients with pancreatic cancer.

Protocol of the IntenSify-Trial: An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy.

Expression of CYP3A5 protein is a basal and acquired resistance mechanism of pancreatic ductal adenocarcinoma cells conferring protection against the CYP3A and CYP2C8 substrate paclitaxel through metabolic degradation. Inhibition of CYP3A isozymes restores the cells sensitivity to paclitaxel. The combination of gemcitabine and nab-paclitaxel is an established regimen for the treatment of metastasized or locally advanced inoperable pancreatic cancer.