CA : A Cancer Journal for Clinicians

The antitumor antibiotic, adriamycin, induces severe cardiac toxicity associated with peroxidation of cardiac lipids in mice. Both this lipid peroxidation and cardiac toxicity of adriamycin are reduced by prior treatment of the animals with the free radical scavenger tocopherol. Such treatment with tocopherol does not, however, alter the magnitude or duration of the adriamycin-induced suppression of DNA synthesis in P388 ascites tumor, nor does it diminish the antitumor responsiveness of P388 ascites tumor. These results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which involves binding to DNA, is not antagonized by tocopherol and is responsible for tumor response.

https://science.sciencemag.org/content/sci/197/4299/165.full.pdf

Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response

Clinical examination of voice

The Hippo pathway is an evolutionarily conserved signalling pathway with key roles in organ development, epithelial homeostasis, tissue regeneration, wound healing and immune modulation Many of these roles are mediated by the transcriptional effectors YAP and TAZ, which direct gene expression via control of the TEAD family of transcription factors Dysregulated Hippo pathway and YAP/TAZ–TEAD activity is associated with various diseases, most notably cancer, making this pathway an attractive target for therapeutic intervention This Review highlights the key findings from studies of Hippo pathway signalling across biological processes and diseases, and discusses new strategies and therapeutic implications of targeting this pathway In this Review, Dey and colleagues discuss the key findings from studies of Hippo pathway signalling across biological processes and diseases, and discuss new strategies and therapeutic implications of targeting this pathway

Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.

The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

Acyclovir plus steroid vs steroid alone in the treatment of Bell's palsy.

Objectives/Hypothesis

To determine salivary pepsin levels as a function of collection time.



Study Design

A prospective, case-control study.



Methods

We selected 57 patients with clinical symptoms and signs of laryngopharyngeal reflux who underwent 24-hour multichannel intraluminal impedance-pH (24h MII-pH) monitoring tests, and 12 control subjects without clinical symptoms and signs of laryngopharyngeal reflux. All subjects were instructed to collect saliva samples upon waking, 1 hour after each meal (3 times per day), and upon any occurrence of laryngopharyngeal reflux (LPR) symptoms. The pepsin levels in saliva were measured by using enzyme-linked immunosorbent assay. The Reflux Symptom Index survey was also administered.



Results

A total of 50 patients in whom LPR was diagnosed based on results of 24h MII-pH monitoring test were enrolled in the study. The average pepsin level upon waking was 17.2 ng/mL, which was significantly higher than that measured in samples collected at any other time (P < .005). Pepsin levels were higher in patients with LPR than those in controls. The Reflux Symptom Index scores were statistically different between these groups of subjects.



Conclusions

The levels of total pepsin in saliva collected upon waking were significantly higher in the group of patients presenting with LPR symptoms and who demonstrated at least one episode of proximal esophageal reflux during 24h MII-pH monitoring. Furthermore, the average pepsin level upon waking was higher than that measured at any other time. Measuring pepsin levels in the saliva upon waking may be a useful method in the diagnosis of LPR.



Level of Evidence

3b Laryngoscope, 2016

Optimal timing of saliva collection to detect pepsin in patients with laryngopharyngeal reflux.

In this study we assessed the clinical significance of an epithelial-mesenchymal transition (EMT) gene signature and explored its association with the tumor microenvironment related to immunotherapy in patients with head and neck squamous cell carcinoma (HNSCC). Genes were selected when mRNA levels were positively or negatively correlated with at least one well-known EMT marker. We developed an EMT gene signature consisting of 82 genes. The patients were classified into epithelial or mesenchymal subgroups according to EMT signature. The clinical significance of the EMT signature was validated in three independent cohorts and its association with several immunotherapy-related signatures was investigated. The mesenchymal subgroup showed worse prognosis than the epithelial subgroup, and significantly elevated PD-1, PD-L1, and CTLA-4 levels, and increased interferon-gamma, cytolytic, T cell infiltration, overall immune infiltration, and immune signature scores. The relationship between PD-L1 expression and EMT status in HNSCC after treatment with TGF-β was validated in vitro. In conclusion, the EMT gene signature was associated with prognosis in HNSCC. Additionally, our results suggest that EMT is related to immune activity of the tumor microenvironment with elevated immune checkpoint molecules.

/pdf/epithelial-mesenchymal-transition-gene-signature-is-428voqj0b1.pdf

Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma

The anthracycline antibiotic adriamycin (Ad) induced degradation (single-strand breaks) of cell DNA in vivo in murine L1210 leukemia cells. Measurement was made by alkaline sucrose gradient methods. Exposure of isolated DNA to Ad had little effect; the in vivo DNA strand breaks were probably due to the action of nucleases on DNA distorted by bound Ad. Toxicity of Ad to postmitotic cells such as cardiac cells could be mediated by this mechanism, since it could be demonstrated in periods substantially shorter than the cell generation time and thus could be responsible for interphase death.

Young Chan Lee

Papers

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

Acyclovir plus steroid vs steroid alone in the treatment of Bell's palsy.

Optimal timing of saliva collection to detect pepsin in patients with laryngopharyngeal reflux.

Epithelial-mesenchymal transition gene signature is associated with prognosis and tumor microenvironment in head and neck squamous cell carcinoma

Induction of DNA Degradation In Vivo by Adriamycin