Computational identification of surface markers for isolating distinct subpopulations from heterogeneous cancer cell populations.

Intratumor heterogeneity reduces treatment efficacy and complicates our understanding of tumor progression and there is a pressing need to understand the functions of heterogeneous tumor cell subpopulations within a tumor, yet systems to study these processes in vitro are limited. Single-cell RNA sequencing (scRNA-seq) has revealed that some cancer cell lines include distinct subpopulations. Here, we present clusterCleaver, a computational package that uses metrics of statistical distance to identify candidate surface markers maximally unique to transcriptomic subpopulations in scRNA-seq which may be used for FACS isolation.

The Effect of Ionizing Irradiation on the Autotaxin-Lysophasphatidic Acid Axis and Interleukin-6/8 Secretion in Different Breast Cancer Cell Lines.

Background: The Autotaxin (ATX)-lysophosphatidic acid (LPA) axis is involved in decreasing radiation sensitivity of breast tumor cells. This study aims to further elucidate the effect of irradiation on the ATX-LPA axis and cytokine secretion in different breast cancer cell lines to identify suitable breast cancer subtypes for targeted therapies.

Methods: Different breast cancer cell lines (MCF-7 (luminal A), BT-474 (luminal B), SKBR-3 (HER2-positive), MDA-MB-231 and MDA-MB-468 (triple-negative)) and the breast epithelial cell line MCF-10A were irradiated.

Deep learning identifies heterogeneous subpopulations in breast cancer cell lines.

Motivation: Cells exhibit a wide array of morphological features, enabling computer vision methods to identify and track relevant parameters. Morphological analysis has long been implemented to identify specific cell types and cell responses. Here we asked whether morphological features might also be used to classify transcriptomic subpopulations within cancer cell lines.

Computational identification of surface markers for isolating distinct subpopulations from heterogeneous cancer cell populations.

Intratumor heterogeneity reduces treatment efficacy and complicates our understanding of tumor progression. There is a pressing need to understand the functions of heterogeneous tumor cell subpopulations within a tumor, yet biological systems to study these processes are limited. With the advent of single-cell RNA sequencing (scRNA-seq), it has become clear that some cancer cell line models include distinct subpopulations.

A concept of dual-responsive prodrugs based on oligomerization-controlled reactivity of ester groups: an improvement of cancer cells neutrophils selectivity of camptothecin.

Many known chemotherapeutic anticancer agents exhibit neutropenia as a dose-limiting side effect. In this paper we suggest a prodrug concept solving this problem for camptothecin (HO-cpt). The prodrug is programmed according to Boolean "AND" logic.

Radiotherapy combined with docetaxel alters the immune phenotype of HNSCC cells and results in increased surface expression of CD137 and release of HMGB1 of specifically HPV-positive tumor cells.

Purpose: Human papilloma virus (HPV) positive head and neck squamous cell carcinoma (HNSCC) tumors respond significantly better to anticancer treatments. It is assumed to be due to a better response to radiotherapy (RT), and presumably to an increased immunogenicity. However, little is known how the immune phenotype of HNSCC tumor cells is modulated by standard treatment, namely by radiochemotherapy (RCT).

Evaluation of intracranial stenting in a simulated training and assessment environment for neuroendovascular procedures.

Purpose: Given the inherent complexity of neurointerventional procedures and the associated risks of ionizing radiation exposure, it is crucial to prioritize ongoing training and improve safety protocols. The aim of this study is to assess a training and evaluation environment using a vascular model of M1 stenosis, within a clinical angiography suite, without relying on animal models or X-ray radiation.

Materials And Methods: Using a transparent model replicating M1 stenosis, we conducted intracranial stenting procedures with four different setups (Gateway & Wingspan, Gateway & Enterprise, Neurospeed & Acclino, and Pharos Vitesse).

DNA as the main target in radiotherapy-a historical overview from first isolation to anti-tumour immune response.

DNA damage is one of the foremost mechanisms of irradiation at the biological level. After the first isolation of DNA by Friedrich Miescher in the 19th century, the structure of DNA was described by Watson and Crick. Several Nobel Prizes have been awarded for DNA-related discoveries.

Tumor-specific radiosensitizing effect of the ATM inhibitor AZD0156 in melanoma cells with low toxicity to healthy fibroblasts.

Purpose: Despite new treatment options, melanoma continues to have an unfavorable prognosis. DNA damage response (DDR) inhibitors are a promising drug class, especially in combination with chemotherapy (CT) or radiotherapy (RT). Manipulating DNA damage repair during RT is an opportunity to exploit the genomic instability of cancer cells and may lead to radiosensitizing effects in tumors that could improve cancer therapy.

Fisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells.

Background: Triple-negative breast cancer (TNBC) is associated with aggressiveness and a poor prognosis. Besides surgery, radiotherapy serves as the major treatment modality for TNBC. However, response to radiotherapy is limited in many patients, most likely because of DNA damage response (DDR) signaling mediated radioresistance.

Effects of dietary polyunsaturated fatty acids on corticosterone concentrations and spatial learning in rats.

Dietary intake of polyunsaturated fatty acids (PUFAs) is crucial for neuronal functions, can positively affect cognition, and reduce glucocorticoid (e.g. corticosterone) concentrations in response to stress.

Quantification of long-term doxorubicin response dynamics in breast cancer cell lines to direct treatment schedules.

While acquired chemoresistance is recognized as a key challenge to treating many types of cancer, the dynamics with which drug sensitivity changes after exposure are poorly characterized. Most chemotherapeutic regimens call for repeated dosing at regular intervals, and if drug sensitivity changes on a similar time scale then the treatment interval could be optimized to improve treatment performance. Theoretical work suggests that such optimal schedules exist, but experimental confirmation has been obstructed by the difficulty of deconvolving the simultaneous processes of death, adaptation, and regrowth taking place in cancer cell populations.

Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells.

(1) Background: Just little is known about the interaction of ALK/ROS1-targeting kinase inhibitors with ionizing radiation (IR), particularly regarding side effects. We investigated the toxicity in two different lung cell lines both ALK/ROS1 wildtype (healthy and tumor origin) as representatives for normal lung tissue; (2) Methods: Human lung cell line BEAS-2B and malignant A549 lung cancer cells (ALK/ROS1 wt) were treated with alectinib or crizotinib, 2 Gy irradiation or a combination of KI and IR. Cell toxicity was analyzed by cell death (Annexin, 7AAD), colony forming, migration assay and live-cell imaging (TMRM, DRAQ7, Caspase3/7).

Influence of Gender on Radiosensitivity during Radiochemotherapy of Advanced Rectal Cancer.

Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas. We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84.

Palbociclib Induces Senescence in Melanoma and Breast Cancer Cells and Leads to Additive Growth Arrest in Combination With Irradiation.

Introduction: Several kinase inhibitors (KI) bear the potential to act as radiosensitizers. Little is known of the radiosensitizing effects of a wide range of other KI like palbociclib, which is approved in ER+/HER2- metastatic breast cancer.

Method: In our study, we used healthy donor fibroblasts and breast cancer and skin cancer cells to investigate the influence of a concomitant KI + radiation therapy.

Kinase Inhibitors of DNA-PK, ATM and ATR in Combination with Ionizing Radiation Can Increase Tumor Cell Death in HNSCC Cells While Sparing Normal Tissue Cells.

(1) Kinase inhibitors (KI) targeting components of the DNA damage repair pathway are a promising new type of drug. Combining them with ionizing radiation therapy (IR), which is commonly used for treatment of head and neck tumors, could improve tumor control, but could also increase negative side effects on surrounding normal tissue. (2) The effect of KI of the DDR (ATMi: AZD0156; ATRi: VE-822, dual DNA-PKi/mTORi: CC-115) in combination with IR on HPV-positive and HPV-negative HNSCC and healthy skin cells was analyzed.

Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model.

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep.

PARP Inhibitors Talazoparib and Niraparib Sensitize Melanoma Cells to Ionizing Radiation.

(1) Background: Niraparib and Talazoparib are poly (ADP-ribose) polymerase (PARP) 1/2 inhibitors. It is assumed that combining PARP inhibitors with radiotherapy could be beneficial for cancer treatment. In this study, melanoma cells were treated with Niraparib and Talazoparib in combination with ionizing radiation (IR).