Number of negative points: a novel method for predicting radiosensitivity in head and neck tumor cell lines

The present study was aimed at establishing a method that combines multiple factors of protein and genetic changes that enables prediction of radiosensitivity in the head and neck squamous cell carcinoma (HNSCC) cell lines. In nine HNSCC cell lines, the quantity of protein expression and the type of genetic alterations were translated into a point system, called the Number of Negative Points. The expression of 14 proteins involved in growth control and/or apoptosis was quantified using a densitometric assessment of Western blots. The blots were adjusted to actin and standardised to normal oral keratinocytes classifying them into four groups depending on the amount of protein expressed (0-3 points). Mutations of the p53 gene were classified into three groups and each mutation was given one point. Since the cell lines each had a known intrinsic radiosensitivity, a multivariate statistical calculation could then be performed to select for the combination of factors having the strongest correlation to radiosensitivity. The strongest correlation of the investigated factors was the combination of epidermal growth factor receptor, survivin and splice site/missense p53 mutations (R=0.990 and P<0.0001). No single factor had a significant correlation to the intrinsic radiosensitivity. Since a significant correlation to the intrinsic radiosensitivity was achieved only when two or more factors were combined, we conclude that a method such as the Number of Negative Points is necessary for prediction of treatment response. We present a novel method to combine factors which enables the prediction of radiosensitivity of HNSCC cell lines.     

Multipolar mitotic cells in the human cell line NHIK 3025 following treatment with the mitotic inhibitor NY 4137

Summary Treatment of human NHIK 3025 cells during interphase with the mitotic inhibitor 2-(2-thenyl) sulfonyl-5-bromopyrimidine (NY 4137) induced the formation of multipolar mitotic cells. A 4 h pulse treatment with 0.010 mM NY 4137 induced the formation of such cells regardless of whether treatment occurred in G1 or S phase. Approximately 35% of the cells originating from such multipolar mitotic divisions had less-than-normal G1 DNA content. Recordings of the DNA content of these small cells by means of flow cytometry showed that the amount of DNA per cell varied randomly. Subpopulations were separated by centrifugal elutriation on the basis of differences in cellular volume. Simultaneous two-parametric recordings of DNA versus total cellular protein showed that even though cells contained an amount of DNA less than G1 cells, there was a proportionality between DNA content and protein content despite variations in cell size.Fellow of the Norwegian Cancer SocietyThe author's name was previously: Mina E. Holm Nygaard     

C-Methylated Dihydrochalcones from Myrica gale L: Effects as Antioxidants and as Scavengers of 1,1-Diphenyl-2-Picrylhydrazyl

Abstract: A number of isomeric or chemically closely related C-methylated dihydrochalcones, which is a rare substance class, has been isolated from the fruit exudate of Myrica gale L. and subjected to the following tests: 1) inhibition of lipid peroxidation induced by tert-butyl hydroperoxide or bromotrichloromethane in isolated rat hepatocytes, 2) inhibition of peroxidation induced by Fe²⁺ ions in a cell free system with linolenic acid as substrate, 3) scavenging activity against the diphenylpicrylhydrazyl radical, and 4) inhibition of enzymatic lipid peroxidation in linoleic acid by soybean 15-lipoxygenase. One of the compounds (myrigalone B = MyB; 2′,6′-dihydroxy-4′-methoxy-3′,5′-dimethyldihydrochalcone) showed good activity in all tests, whereas the others were inactive or slightly active, except that myrigalone A (MyA; 3-(1-oxo-3-phenylpropyl)-1,1.5-trimethylcyclohexane-2.4.6-trione)) like its synthetic analogue MyA* (the polar part of MyA) was nearly as active as MyB in 4). The antioxidant properties of MyB are probably due to its radical scavenging activity and may be related to its conformation, which differs from that of the other compounds.     

Back to WHAT? The role of research ethics in pandemic times

Medicine, Health Care and Philosophy - The Covid-19 pandemic creates an unprecedented threatening situation worldwide with an urgent need for critical reflection and new knowledge production, but...     

Docetaxel Versus Surveillance After Radical Prostatectomy for High-risk Prostate Cancer: Results from the Prospective Randomised,Open-label Phase 3 Scandinavian Prostate Cancer Group 12 Trial

Background

Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer.

Comparison of contrast in brightness mode and strain ultrasonography of glial brain tumours

ABSTRACT: BACKGROUND: Image contrast between normal tissue and brain tumours may sometimes appear to be low in intraoperative ultrasound. Ultrasound imaging of strain is an image modality that has been recently explored for intraoperative imaging of the brain. This study aims to investigate differences in image contrast between ultrasound brightness mode (B-mode) images and ultrasound strain magnitude images of brain tumours. METHODS: Ultrasound radiofrequency (RF) data was acquired during surgery in 15 patients with glial tumours. The data were subsequently processed to provide strain magnitude images. The contrast in the B-mode images and the strain images was determined in assumed normal brain tissue and tumour tissue at selected regions of interest (ROI). Three measurements of contrast were done in the ultrasound data for each patient. The B-mode and strain contrasts measurements were compared using the paired samples t- test. RESULTS: The statistical analysis of a total of 45 measurements shows that the contrasts in the strain magnitude images are significantly higher than in the conventional ultrasound B-mode images (P < 0.0001). CONCLUSIONS: The results indicate that ultrasound strain imaging provides better discrimination between normal brain tissue and glial tumour tissue than conventional ultrasound B- mode imaging. Ultrasound imaging of tissue strain therefore holds the potential of becoming a valuable adjunct to conventional intraoperative ultrasound imaging in brain tumour surgery.     

ADAM12 alleviates the skeletal muscle pathology in mdx dystrophic mice

Muscular dystrophy is characterized by muscle degeneration and insufficient regeneration and replacement of muscle fibers by connective tissue. New therapeutic strategies directed toward various forms of muscular dystrophy are needed to preserve muscle mass and promote regeneration. In this study we examined the role of the transmembrane ADAM12, a disintegrin and metalloprotease, which is normally associated with development and regeneration of skeletal muscle. We demonstrate that ADAM12 overexpression in the dystrophin-deficient mdx mice alleviated the muscle pathology in these animals, as evidenced by less muscle cell necrosis and inflammation, lower levels of serum creatine kinase, and less uptake of Evans Blue dye into muscle fibers. These studies demonstrate that ADAM12 directly or indirectly contributes to muscle cell regeneration, stability, and survival.     

ECL‐cell carcinoids and carcinoma in patients homozygous for an inactivating mutation in the gastric H+K+ATPase alpha subunit

A family with a missense variant of the ATP4A gene encoding the alpha subunit of the gastric proton pump (H⁺K⁺ATPase) has recently been described. Homozygous siblings were hypergastrinemic (median gastrin 486 pM) and had gastric tumours diagnosed at a median age of 33 years. In the current histopathological study, we further characterized the tumours found in the gastric corpus. The tumours had the histological appearance of carcinoids (NET G1 or G2) and were immunoreactive for the general neuroendocrine markers chromogranin A (CgA) and synaptophysin as well as the ECL‐cell markers vesicular monoamine transporter 2 (VMAT2) and histidine decarbozylase (HDC). One of the tumours consisted of a NET G2 component, but also had a component with glandular growth, which morphologically was classified as an intestinal type adenocarcinoma. Many glands of the adenocarcinoma contained a large proportion of cells positive for neuroendocrine markers, especially the small vesicle marker synaptophysin and the cytoplasmic enzyme HDC. In conclusion, patients homozygous for an inactivating ATP4A mutation develop gastric ECL‐cell carcinoids in their 3rd or 4th decade. The adenocarcinoma may be classified as neuroendocrine with ECL‐cell differentiation.