Introducing and Validating the Multiphasic Evidential Decision-Making Matrix (MedMax) for Clinical Management in Patients with Intrahepatic Cholangiocarcinoma.

Despite the significant advancements of liver surgery in the last few decades, the survival rate of patients with liver and pancreatic cancers has improved by only 10% in 30 years. Precision medicine offers a patient-centered approach, which, when combined with machine learning, could enhance decision making and treatment outcomes in surgical management of ihCC. This study aims to develop a decision support model to optimize treatment strategies for patients with ihCC, a prevalent primary liver cancer.

Glucosylceramide Synthase Inhibition in Combination with Aripiprazole Sensitizes Hepatocellular Cancer Cells to Sorafenib and Doxorubicin.

Hepatocellular carcinoma () is one of the leading causes of cancer deaths due to its late diagnosis and restricted therapeutic options. Therefore, the search for appropriate alternatives to commonly applied therapies remains an area of high clinical need. Here we investigated the therapeutic potential of the glucosylceramide synthase (GCS) inhibitor Genz-123346 and the cationic amphiphilic drug aripiprazole on the inhibition of Huh7 and Hepa 1-6 hepatocellular cancer cell and tumor microsphere growth.

Integrated Analysis of Cell-Free DNA and Novel Protein Biomarkers for Stratification and Therapy Monitoring in Stage IV Pancreatic Cancer: A Preliminary Study.

Given the poor prognosis of metastatic pancreatic adenocarcinoma (mPDAC), closer disease monitoring through liquid biopsy, most frequently based on serial measurements of cell-free mutated ( cfDNA), has become a highly active research focus, aimed at improving patients' long-term outcomes. However, most of the available data show only a limited predictive and prognostic value of single-parameter-based methods. We hypothesized that a combined longitudinal analysis of cfDNA and novel protein biomarkers could improve risk stratification and molecular monitoring of patients with mPDAC.

Factors affecting pretransplant muscle strength in allogeneic stem cell transplant candidates prior transplantation.

Purpose: Physical performance is crucial for prognosis after allogeneic hematopoietic stem cell transplantation (allo-HCT). Cardiorespiratory fitness has already been shown to have prognostic value, and there is increasing evidence that muscle strength and associated parameters (e.g.

Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology.

Precision oncology offers new cancer treatment options, yet sequencing methods vary in type and scope. In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020. Molecular analyses resulted in a median number of 2.

Ezrin Polarization as a Diagnostic Marker for Circulating Tumor Cells in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide, with no precise method for early detection. Circulating tumor cells (CTCs) expressing the dynamic polarity of the cytoskeletal membrane protein, ezrin, have been proposed to play a crucial role in tumor progression and metastasis. This study investigated the diagnostic and prognostic potential of polarized circulating tumor cells (p-CTCs) in HCC patients.

Inhibiting H3K27 Demethylases Downregulates CREB-CREBBP, Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia.

Background: CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti-tumor effects have previously been demonstrated for GSK-J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.

CT material decomposition with contrast agents: Single or multiple spectral photon-counting CT scans? A simulation study.

Purpose: With the widespread introduction of dual energy computed tomography (DECT), applications utilizing the spectral information to perform material decomposition became available. Among these, a popular application is to decompose contrast-enhanced CT images into virtual non-contrast (VNC) or virtual non-iodine images and into iodine maps. In 2021, photon-counting CT (PCCT) was introduced, which is another spectral CT modality.

How to protect the proximal bronchial tree during stereotactic radiotherapy of ultracentral lung tumors: Lessons from MR-guided treatment.

Purpose: To use imaging data from stereotactic MR-guided online adaptive radiotherapy (SMART) of ultracentral lung tumors (ULT) for development of a safe non-adaptive approach towards stereotactic body radiotherapy (SBRT) of ULT.

Patients And Methods: Analysis is based on 19 patients with ULT who received SMART (10 × 5.0-5.

High Ano1 expression as key driver of resistance to radiation and cisplatin in HPV-negative head and neck squamous cell carcinoma.

Human papilloma virus-negative head and neck squamous cell carcinoma (HNSCC) frequently harbors 11q13 amplifications. Among the oncogenes at this locus, CCND1 and ANO1 are linked to poor prognosis; however, their individual roles in treatment resistance remain unclear. The impact of Cyclin D1 and Ano1 overexpression on survival was analyzed using the TCGA HNSCC dataset and a Charité cohort treated with cisplatin (CDDP)-based radiochemotherapy.

Everolimus with or without mycophenolate mofetil for GVHD prophylaxis after allogeneic HSCT in children with acute kidney injury - a single-center retrospective analysis.

Background: Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants for allogeneic HSCT success. The immunosuppressive agent, ciclosporin A, is most often used to prevent GVHD in pediatric patients, but is known to be nephrotoxic.

A Hitchhiker's Guide Toward CSF Biomarkers for Neuro-Oncology.

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection.

Pretreatment Fatigue in Breast Cancer Patients: Comparison With Healthy Controls and Associations With Biopsychosocial Variables.

Objective: Cancer-related fatigue is one of the most common burdens of cancer patients. To date, most studies focused on fatigue during or after treatment. However, investigation of pretreatment fatigue is crucial to identify causal or risk factors other than cancer therapy and to enable timely fatigue management.

Smad2 Cooperating with TGIF2 Contributes to EMT and Cancer Stem Cells Properties in Pancreatic Cancer via Co-Targeting SOX2.

The underlying mechanisms between cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) remain unclear. In this study, we identified TGIF2 as a target gene of CSC using sncRNA and machine learning. TGIF2 is closely related to the expression of SOX2, EGFR, and E-cadherin, indicating poor prognosis.

The potential of GPT-4 advanced data analysis for radiomics-based machine learning models.

Background: This study aimed to explore the potential of the Advanced Data Analytics (ADA) package of GPT-4 to autonomously develop machine learning models (MLMs) for predicting glioma molecular types using radiomics from MRI.

Methods: Radiomic features were extracted from preoperative MRI of  = 615 newly diagnosed glioma patients to predict glioma molecular types (IDH-wildtype vs IDH-mutant 1p19q-codeleted vs IDH-mutant 1p19q-non-codeleted) with a multiclass ML approach. Specifically, ADA was used to autonomously develop an ML pipeline and benchmark performance against an established handcrafted model using various MRI normalization methods (N4, Zscore, and WhiteStripe).

Role of the tumor board when prescribing mutant isocitrate dehydrogenase inhibitors to patients with isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas, comprising both astrocytomas and oligodendrogliomas, represent a distinct group of tumors that pose an interdisciplinary challenge. Addressing the needs of affected patients requires close collaboration among various disciplines, including neuropathology, neuroradiology, neurosurgery, radiation oncology, neurology, medical oncology, and other relevant specialties when necessary. Interdisciplinary tumor boards are central in determining the ideal diagnostic and therapeutic strategies for these patients.

Development and validation of a molecular classifier of meningiomas.

Background: Meningiomas exhibit considerable clinical and biological heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) that address much of this heterogeneity. Despite the utility of these groups, the stochasticity of clustering methods and the use of multi-omics data for discovery limits the potential for classifying prospective cases.

SarkoLife: quality of life in patients undergoing multimodal soft tissue sarcoma treatment.

Objective: To assess the tolerability of multimodal therapy in soft tissue sarcoma patients, particularly with regard to their quality of life and level of distress.

Materials And Methods: A retrospective cohort study enrolled individuals receiving sarcoma therapy at the sarcoma center of the University of Tuebingen between 2017 and 2022. Participants completed an online survey that included the EORTC's questionnaire (QLQ-C30), coupled with the distress thermometer and demographic inquiries.

Prediction of protein biophysical traits from limited data: a case study on nanobody thermostability through NanoMelt.

In-silico prediction of protein biophysical traits is often hindered by the limited availability of experimental data and their heterogeneity. Training on limited data can lead to overfitting and poor generalizability to sequences distant from those in the training set. Additionally, inadequate use of scarce and disparate data can introduce biases during evaluation, leading to unreliable model performances being reported.

Reversal of Endothelial Cell Anergy by T Cell-Engaging Bispecific Antibodies.

Reduced expression of adhesion molecules in tumor vasculature can limit infiltration of effector T cells. To improve T cell adhesion to tumor endothelial cell (EC) antigens and enhance transendothelial migration, we developed bispecific, T-cell engaging antibodies (bsAb) that activate T cells after cross-linking with EC cell surface antigens. Recombinant T-cell stimulatory anti-VEGFR2-anti-CD3 and costimulatory anti-TIE2-anti-CD28 or anti-PD-L1-anti-CD28 bsAb were engineered and expressed.

Biglycan-driven risk stratification in ZFTA-RELA fusion supratentorial ependymomas through transcriptome profiling.

Recent genomic studies have allowed the subdivision of intracranial ependymomas into molecularly distinct groups with highly specific clinical features and outcomes. The majority of supratentorial ependymomas (ST-EPN) harbor ZFTA-RELA fusions which were designated, in general, as an intermediate risk tumor variant. However, molecular prognosticators within ST-EPN ZFTA-RELA have not been determined yet.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment.