Cancer

RNA polymerase III (Pol-III) transcribes tRNAs and other small RNAs essential for protein synthesis and cell growth. Pol-III is deregulated during carcinogenesis; however, its role in vivo has not been studied. To address this issue, we manipulated levels of Brf1, a Pol-III transcription factor that is essential for recruitment of Pol-III holoenzyme at tRNA genes in vivo. Knockout of Brf1 led to embryonic lethality at blastocyst stage. In contrast, heterozygous Brf1 mice were viable, fertile and of a normal size.

BACKGROUND: Long intergenic noncoding RNA p21 (lincRNA-p21) is considered a target of wild-type p53, but little is known about its regulation by mutant p53 and its functions during the progression of head and neck squamous cell carcinoma (HNSCC). METHODS: RNAscope was used to detect the expression and distribution of lincRNA-p21. Chromatin immunoprecipitation and electrophoretic mobility shift assays were performed to analyze the transcriptional regulation of lincRNA-p21 in HNSCC cells. The biological functions of lincRNA-p21 were investigated in vitro and in vivo.

BACKGROUND: TNM8 staging for oropharyngeal squamous cell carcinomas (OPSCC) surrogates p16 immunohistochemistry for HPV testing. Patients with p16+ OPSCC may lack HPV aetiology. Here, we evaluate the suitability of TNM8 staging for guiding prognosis in such patients. METHODS: HPV status was ascertained using p16 immunohistochemistry and high-risk HPV RNA and DNA in situ hybridisation. Survival by stage in a cohort of OPSCC patients was evaluated using TNM7/TNM8 staging. Survival of p16+/HPV- patients was compared to p16 status.

Histologic transformation to small cell neuroendocrine prostate cancer occurs in a subset of patients with advanced prostate cancer as a mechanism of treatment resistance. Rovalpituzumab tesirine (SC16LD6.5) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) and was initially developed for small cell lung cancer. We found that DLL3 is expressed in most of the castration-resistant neuroendocrine prostate cancer (CRPC-NE) (36 of 47, 76.6%) and in a subset of castration-resistant prostate adenocarcinomas (7 of 56, 12.5%).

AIMS: To investigate whether genetic or inflammatory pro-oncogenic factors are relevant to the increased risk of gallbladder cancers in patients with pancreaticobiliary maljunction (PBM). METHODS: Mutations in KRAS exon 2 were examined by a highly sensitive, droplet digital PCR platform using surgically resected specimens of PBM-associated (n=31) and non-associated gallbladder cancers (n=49). The tissue expression of IL-6 and IL-33, which are suspected to promote biliary carcinogenesis, was analyzed by quantitative real-time PCR and in situ hybridization.

Chimeric antigen receptor (CAR) T cells, a type of cell-based immunotherapy, have shown some promising results in multiple myeloma, a bone marrow cancer. These earlier CAR T cells targeted a protein called B cell maturation antigen, but some patients’ cancer cells expressed little to none of this antigen and were therefore resistant to the CAR T cells. Smith et al. identified another target antigen for multiple myeloma, called GPRC5D.

Recent studies have revealed a role for macrophages and neutrophils in limiting chemotherapy efficacy; however, the mechanisms underlying the therapeutic benefit of myeloid-targeting agents in combination with chemotherapy are incompletely understood. Here, we show that targeting tumour-associated macrophages by colony-stimulating factor-1 receptor (CSF-1R) blockade in the K14cre;Cdh1(F/F);Trp53(F/F) transgenic mouse model for breast cancer stimulates intratumoural type I interferon (IFN) signalling, which enhances the anticancer efficacy of platinum-based chemotherapeutics.

Background

Oropharyngeal cancers associated with high-risk type human papillomavirus (HR-HPV) infection have better prognosis than virus negative cancers. Similarly, the HPV status in laryngeal cancer (LC) may be associated with better outcome.

Methods

Samples from 88 patients with LC were investigated using the polymerase chain reaction (PCR) and p16 immunohistochemistry for HR-HPV analysis. The cut-off point for p16 overexpression was diffuse (≥75%) tumor expression with at least moderate (+ 2/3) staining intensity.

Results

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient.