High expression of H2AX/γ-H2AX is associated with distinct biological pathway alterations and shorter survival in oropharyngeal squamous cell carcinoma.

Background: The histone gene H2AX and its phosphorylated protein γ-H2AX play a crucial role in the DNA damage response. This study investigates the expression of H2AX mRNA and its phosphorylated γ-H2AX protein in oropharyngeal squamous cell carcinoma (OPSCC), its association with distinct biological pathway alterations and its potential as a biomarker.

Materials And Methods: Expression of H2AX mRNA in 76 OPSCC from The Cancer Genome Atlas (TCGA) cohort was analyzed.

Exploration of histone protein γ-H2AX as a prognostic factor in soft tissue sarcomas and its association with biological behavior, immune cell environment and survival in leiomyosarcoma.

This study evaluates the H2AX/γ-H2AX expression in soft tissue sarcomas (STS), its implications for biological behavior and immune environment, and its potential as a prognostic biomarker. RNA-Seq data from 237 STS were obtained from The Cancer Genome Atlas project. Patients were stratified by H2AX mRNA expression using a survival-associated cutoff.

Hexokinase 2 as an independent risk factor for worse patient survival in esophageal adenocarcinoma and as a potential therapeutic target protein: A retrospective, single‑center cohort study.

Cancer cells exhibit a distinct metabolic profile that features an upregulation of less efficient glycolysis accompanied by lactate production for energy generation, in contract to the characteristic metabolism of normal cells. Consequently, cancer research has focused on the enzymes that participate in these cancer metabolic pathways. Among them, hexokinase 2 (HK2) has an important position as the initial enzyme in the glycolytic pathway.

Extent and clinical significance of the therapy-relevant tight junction protein Claudin 18.2 in pancreatic ductal adenocarcinoma - real-world evidence.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, wherefore targeted therapies have experienced increasing interest. Zolbetuximab is a novel targeted therapy under investigation in patients with PDAC and targets Claudin 18.2 (CLDN18.

Upregulation of the histone γ-H2AX correlates with worse patient survival and basal-like subtype in pancreatic ductal adenocarcinoma.

Purpose: Patients with pancreatic ductal adenocarcinoma (PDAC) have yet to experience significant benefits from targeted therapy. Olaparib is currently the only active substance in BRCA-mutated PDACs that successfully influences the DNA repair of carcinoma cells. H2AX belongs to the histone family and is known as a part of the DNA repair system.

An anti-CD19/CTLA-4 switch improves efficacy and selectivity of CAR T cells targeting CD80/86-upregulated DLBCL.

Chimeric antigen receptor T cell (CAR T) therapy is a potent treatment for relapsed/refractory (r/r) B cell lymphomas but provides lasting remissions in only ∼40% of patients and is associated with serious adverse events. We identify an upregulation of CD80 and/or CD86 in tumor tissue of (r/r) diffuse large B cell lymphoma (DLBCL) patients treated with tisagenlecleucel. This finding leads to the development of the CAR/CCR (chimeric checkpoint receptor) design, which consists of a CD19-specific first-generation CAR co-expressed with a recombinant CTLA-4-linked receptor with a 4-1BB co-stimulatory domain.

Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration.

Copy-number-gain of telomerase reverse transcriptase (hTERT) is associated with an unfavorable prognosis in esophageal adenocarcinoma.

Esophageal adenocarcinoma exhibits one of the highest mortality rates among all cancer entities. Multimodal therapy strategies have improved patients' survival significantly. However, patients in early stages are currently limited to receiving only local therapies, even though some patients within this group showcase short survival periods.

The tight junction protein claudin 6 is a potential target for patient-individualized treatment in esophageal and gastric adenocarcinoma and is associated with poor prognosis.

Background: The prognosis of esophageal adenocarcinoma (EAC) and gastric adenocarcinoma (GAC) remains poor, and new therapeutic approaches are urgently needed. Claudin 6 (CLDN6) is an oncofetal antigen that is largely absent in healthy tissues and upregulated in several cancers, making it a promising therapeutical target. In this study, the expression of CLDN6 was assessed in an large Caucasian EAC and GAC cohort.

High NANOG expression correlates with worse patients' survival in esophageal adenocarcinoma.

Background: Patients diagnosed with esophageal cancer demonstrate a low overall survival even despite the established multimodal therapy as the current standard of care. Therefore, further biomarkers for patients with high-risk and additional therapy options are needed. NANOG is a transcription factor, which can be found in stem cells and is known to support tumorigenesis.

Dissecting the inflammatory tumor microenvironment of esophageal adenocarcinoma: mast cells and natural killer cells are favorable prognostic factors and associated with less extensive disease.

Purpose: Esophageal adenocarcinoma (EAC) remains a challenging and lethal cancer entity. A promising target for new therapeutic approaches, as demonstrated by the success of immune checkpoint inhibitors, are tumor-associated immune cells and the tumor microenvironment (TME). However, the understanding of the TME in esophageal cancer remains limited and requires further investigation.

RNA Sequencing Reveals Alterations and Similarities in Cell Metabolism, Hypoxia and Immune Evasion in Primary Cell Cultures of Clear Cell Renal Cell Carcinoma.

The treatment of advanced renal cell carcinoma remains a challenge. To develop novel therapeutic approaches, primary cell cultures as an model are considered more representative than commercial cell lines. In this study, we analyzed the gene expression of previously established primary cell cultures of clear cell renal cell carcinoma by bulk (3'm)RNA sequencing and compared it to the tissue of origin.

Overexpression of Parkin in clear cell renal cell carcinoma decreases tumor aggressiveness by regulating CKS2 levels.

Low expression levels of the E3 ubiquitin‑protein ligase Parkin (PARK2) are exhibited in several cancer entities, including clear cell renal cell carcinoma (ccRCC), and are associated with poor prognosis; however, PARK2 can also function as a tumor suppressor gene. The aim of the present study was to thoroughly investigate the effects of PARK2 overexpression in ccRCC cell lines and to determine its effects on malignancy by conducting functional assays such as cell cycle analysis, apoptosis analysis, migration and invasion assays. Furthermore, liquid chromatography‑mass spectrometry was used to decipher potential targets of PARK2 that may influence the behavior of ccRCC tumor cells.

Mitophagy-associated genes PINK1 and PARK2 are independent prognostic markers of survival in papillary renal cell carcinoma and associated with aggressive tumor behavior.

The aim of this study was to investigate the mitophagy-related genes PINK1 and PARK2 in papillary renal cell carcinoma and their association with prognosis. In silico data of PINK1 and PARK2 were analyzed in TCGA cohorts of papillary renal cell carcinoma comprising 290 tumors and 33 corresponding non-neoplastic renal tissues. Protein expression data from a cohort of 95 papillary renal cell carcinoma patients were analyzed and associated with clinical-pathological parameters including survival.

Cultivation of Clear Cell Renal Cell Carcinoma Patient-Derived Organoids in an Air-Liquid Interface System as a Tool for Studying Individualized Therapy.

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer accounting for 80% of all renal cancers as well as the majority of renal cancer-associated deaths. During the last decade, the treatment paradigm for ccRCC has radically changed. In particular, the recent development of immune checkpoint inhibitors (ICI) has led to an increased overall survival in the metastatic setting.

Targeting glycolysis with 2-deoxy-D-glucose sensitizes primary cell cultures of renal cell carcinoma to tyrosine kinase inhibitors.

Purpose: To investigate the synergistic effect of glycolysis inhibition on therapy answer to tyrosine kinase inhibitors in renal carcinoma.

Methods: Primary cell cultures from 33 renal tumors including clear cell RCC (ccRCC), papillary RCC and the rare subtype chromophobe RCC as well as two metastases of ccRCC were obtained and cultivated. The patient-derived cells were verified by immunohistochemistry.