IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts.

Background: It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due to its stringent expression pattern in healthy tissue and its apparent role in tumor progression in a considerable amount of malignancies.

Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity.

Acquired resistance to the targeted agent cetuximab poses a significant challenge in finding effective anti-cancer treatments for head and neck squamous cell carcinoma (HNSCC). To accurately study novel combination treatments, suitable preclinical mouse models for cetuximab resistance are key yet currently limited. This study aimed to optimize an acquired cetuximab-resistant mouse model, with preservation of the innate immunity, ensuring intact antibody-dependent cellular cytotoxicity (ADCC) functionality.

A Descriptive Study on the Carcass, Muscle, and Offal Yields of the Plains Zebra () Harvested in Two Seasons.

This study presents descriptive data on the meat and offal production of Plains zebras harvested in the winter ( = 8) and summer ( = 12) seasons, at different respective locations in the Western Cape Province of South Africa. The cold dressing percentages were numerically higher for the winter (58.0 ± 0.

The prognostic impact of the immune signature in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that retain their poor prognosis despite recent advances in their standard of care. As the involvement of the immune system against HNSCC development is well-recognized, characterization of the immune signature and the complex interplay between HNSCC and the immune system could lead to the identification of novel therapeutic targets that are required now more than ever. In this study, we investigated RNA sequencing data of 530 HNSCC patients from The Cancer Genome Atlas (TCGA) for which the immune composition (CIBERSORT) was defined by the relative fractions of 10 immune-cell types and expression data of 45 immune checkpoint ligands were quantified.

Prognostic implications of cellular senescence in resected non-small cell lung cancer.

Background: Cure and long-term survival for non-small cell lung cancer (NSCLC) remains hard to achieve. Cellular senescence, an emerging hallmark of cancer, is considered as an endogenous tumor suppressor mechanism. However, senescent cancer cells can paradoxically affect the surrounding tumor microenvironment (TME), ultimately leading to cancer relapse and metastasis.

Expression of SARS-CoV-2-Related Surface Proteins in Non-Small-Cell Lung Cancer Patients and the Influence of Standard of Care Therapy.

In this study, we aimed to study the expression of SARS-CoV-2-related surface proteins in non-small-cell lung cancer (NSCLC) cells and identify clinicopathological characteristics that are related to increased membranous (m)ACE2 protein expression and soluble (s)ACE2 levels, with a particular focus on standard of care (SOC) therapies. ACE2 ( = 107), TMPRSS2, and FURIN ( = 38) protein expression was determined by immunohistochemical (IHC) analysis in NSCLC patients. sACE2 levels ( = 64) were determined in the serum of lung cancer patients collected before, during, or after treatment with SOC therapies.

Volatile organic compound profiling as a potential biomarker in irritable bowel syndrome: A feasibility study.

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder for which no diagnostic tools are currently available. Patients are diagnosed using the Rome IV criteria and subtyped into a diarrhea, constipation, or mixed phenotype based on their dominant stool pattern. A recent development in the biomarker area is the analysis of volatile organic compounds (VOCs).

Auranofin and Cold Atmospheric Plasma Synergize to Trigger Distinct Cell Death Mechanisms and Immunogenic Responses in Glioblastoma.

Targeting the redox balance of malignant cells via the delivery of high oxidative stress unlocks a potential therapeutic strategy against glioblastoma (GBM). We investigated a novel reactive oxygen species (ROS)-inducing combination treatment strategy, by increasing exogenous ROS via cold atmospheric plasma and inhibiting the endogenous protective antioxidant system via auranofin (AF), a thioredoxin reductase 1 (TrxR) inhibitor. The sequential combination treatment of AF and cold atmospheric plasma-treated PBS (pPBS), or AF and direct plasma application, resulted in a synergistic response in 2D and 3D GBM cell cultures, respectively.

Auranofin reveals therapeutic anticancer potential by triggering distinct molecular cell death mechanisms and innate immunity in mutant p53 non-small cell lung cancer.

Auranofin (AF) is an FDA-approved antirheumatic drug with anticancer properties that acts as a thioredoxin reductase 1 (TrxR) inhibitor. The exact mechanisms through which AF targets cancer cells remain elusive. To shed light on the mode of action, this study provides an in-depth analysis on the molecular mechanisms and immunogenicity of AF-mediated cytotoxicity in the non-small cell lung cancer (NSCLC) cell line NCI-H1299 (p53 Null) and its two isogenic derivates with mutant p53 R175H or R273H accumulation.

Combined Effect of Dietary Protein, Ractopamine, and Immunocastration on Boar Taint Compounds, and Using Testicle Parameters as an Indicator of Success.

This study investigates the combined effect of immunocastration, dietary protein level (low, medium or high) and ractopamine hydrochloride supplementation (0 or 10 mg/kg) on the adipose concentrations of androstenone, skatole and indole in pigs, and explores whether body mass, carcass fatness or testicular parameters may be indicators of boar taint in these carcasses. Immunocastration was successful in decreasing testicle functioning, and adipose androstenone and skatole concentrations, in all individuals. Immunocastration decreased testicle weight and length, seminiferous tubule circumference and epithelium thickness.

In vitro study of the Polo-like kinase 1 inhibitor volasertib in non-small-cell lung cancer reveals a role for the tumor suppressor p53.

Polo-like kinase 1 (Plk1), a master regulator of mitosis and the DNA damage response, is considered to be an intriguing target in the research field of mitotic intervention. The observation that Plk1 is overexpressed in multiple human malignancies, including non-small-cell lung cancer (NSCLC), gave rise to the development of several small-molecule inhibitors. Volasertib, presently the most extensively studied Plk1 inhibitor, has been validated to efficiently reduce tumor growth in preclinical settings.

Extending the interval between second vaccination and slaughter: I. Effects on growth, scrotal size and stress responses of immunocastrated ram lambs.

Immunocastration provides a less invasive means of castrating lambs. Considering increasing consumer awareness, the efficacy of this technique on commercial slaughter lambs needs to be further investigated and its effects on growth and stress responses need to be established. This study compared the growth rate, testes size and stress responses of immunocastrated lambs with that of lambs physically castrated with a Burdizzo clamp, as well as intact rams.

Extending the interval between second vaccination and slaughter: II. Changes in the reproductive capacity of immunocastrated ram lambs.

Immunocastration improves the welfare of castrated commercial slaughter lambs; however, the time-point at which this technique influences semen quality and sperm production has not yet been established for various vaccination schedules. Furthermore, the effect of extended intervals between second vaccination and slaughter needs to be investigated regarding continued testosterone suppression in immunocastrated lambs. The effect of extending the interval between second immunocastration vaccination and slaughter from four to six weeks on the reproductive capacity of Dohne Merino lambs was examined.

Influence of extending the pre-slaughter interval after second vaccination on the carcass cutting yield and the quality of meat from immunocastrated lambs.

The influence of extending the vaccination-to-slaughter interval of immunocastrated lambs on carcass cutting yield and meat quality of the Longissimus thoracis (LT) muscle was investigated in forty Dohne Merino lambs (8.5 months old; 53.7 ± 4.

Impact of self-esteem on the relationship between orthodontic treatment need and oral health-related quality of life in 11- to 16-year-old children.

The interest in the psychological aspects of orthodontic treatment increases, but a drawback of many studies is that the psychological characteristics of the children themselves are often ignored. One of these psychological attributes is self-esteem (SE), which is a relatively stable personal resource that might moderate the effects of conditions or events. The aim of this study was to investigate whether there is a relationship between orthodontic treatment need and oral health-related quality of life (OHRQoL) and whether this relationship is influenced by SE.

Retention of the in vitro radiosensitizing potential of gemcitabine under anoxic conditions, in p53 wild-type and p53-deficient non-small-cell lung carcinoma cells.

Purpose: Whereas radiosensitization by gemcitabine is well studied under normal oxygen conditions, little is known about its radiosensitizing potential under reduced oxygen conditions. Therefore, the present study evaluated the impact of anoxia on gemcitabine-mediated radiosensitization.

Methods And Materials: The clonogenic assay was performed in three isogenic A549 cell lines differing in p53 status (24 h, 0-15 nM gemcitabine, 0-8 Gy irradiation, normoxia vs.

In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells.

Background: Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This in vitro study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules.

Methods: The cytotoxicity, radiosensitising potential and cell cycle effect of MTA were investigated in A549 (NSCLC) and CAL-27 (SCCHN) cells.

Counting clonogenic assays from normoxic and anoxic irradiation experiments manually or by using densitometric software.

The clonogenic assay is the method of choice to determine cell reproductive death after in vitro irradiation treatment. Traditionally, colony quantification has been performed by manual counting, a very laborious, time-consuming and rather subjective task. In this study, we compared manual counting by two skilled investigators with automated counting using the freely available ClonoCounter program.

Lip and tongue pressure in orthodontic patients.

The contribution of the force of the lips, cheeks, and tongue is of particular interest in planning treatment. Thus, the aim of this study was to determine if there are differences in lip and tongue pressure as a function of gender, age, Angle classification, characteristics of occlusion, and oral habits. This cross-sectional study comprised 107 subjects (63 females and 44 males), between 7 and 45 years of age (median 15.

The role of apoptotic cell death in the radiosensitising effect of gemcitabine.

Background: The aim of this study was to evaluate the radiosensitising effect of gemcitabine, in terms of cell-cycle progression, induction of apoptosis, and to investigate the molecular events regulating apoptosis.

Methods: Tumour cells were treated with gemcitabine, radiation, or the combination. 0-72 h after treatment, cells were collected for cell-cycle analysis and apoptosis determination.

Feasibility of collecting self-sampled vaginal swabs by mail: quantity and quality of genomic DNA.

Vaginal self-sampling may be valuable as an alternative method of cervical cancer screening in areas of poor resources, to enroll women who, otherwise, would not participate in population-based cervical cancer screening and in epidemiological follow-up studies. We assessed the reliability of mailed vaginal samples by evaluating the quantity and quality of genomic DNA in the samples. Mailed swabs (n = 201) were compared with freshly collected samples (n = 200) for DNA concentration (45.

Chemoradiation interactions under reduced oxygen conditions: Cellular characteristics of an in vitro model.

Hypoxic tumour regions often contain viable cells that are more resistant to chemotherapy and/or radiotherapy, making it of key importance to analyse new combination treatments under both normoxic and hypoxic conditions. In this study, the impact of moderate hypoxia and anoxia on cellular characteristics was investigated in isogenic A549 cells differing in p53 status. VEGF expression, doubling time, cell cycle distribution, induction of apoptosis and p53 protein expression were evaluated.

Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro.

Background: Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitizing and cell cycle effects.

Methods: Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.

The characterization and molecular structure of hepatoproliferin: a liver regeneration factor from rat hepatocytes.

Hepatoproliferin (HPF) was purified from regenerating rat livers as an oligomeric entity (big-HPF) from which the monomeric form (small-HPF) could be obtained using disaggregating conditions. By using a solid-phase ion-exchange method, small-HPF was forced to dissociate into two charged ionic species, namely norepinephrine (NE) and a sulfonated disaccharide with a molecular structure consisting of D-glucuronic acid bound to glucosamine 2,6-disulfate by a beta-glycosidic linkage having a beta, 1 --> 4 configuration. Monomeric HPF stemmed from the formation of three electrostatic bonds between the protonated amine groups of three norepinephrines, of which two bind to the deprotonated sulfonic groups of glucosamine 2,6-disulfate and one to the deprotonated carboxylic group of glucuronic acid, to constitute a tightly associated complex with a molecular mass of 1046 Da.

Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro.

Purpose: Vinflunine is an innovative microtubule inhibitor belonging to the vinca alkaloid class that possesses radiosensitising properties, which could lead to promising activity in chemoradiation studies in the clinic.

Method: In the current study, different incubation times with vinflunine, immediately before radiation and different time intervals between vinflunine treatment and radiation were investigated, in vitro, using four different human tumour cell lines differing in cell type and p53 status. Results were correlated with the cell cycle distribution at the moment of radiation, in order to elucidate the role of cell cycle perturbations caused by vinflunine on its radiosensitising effect.