Identification of CD44 as a surface biomarker for drug resistance by surface proteome signature technology

We developed surface proteome signatures (SPS) for identification of new biomarkers playing a role in cancer drug resistance. SPS compares surface antigen expression of different cell lines by immunocytochemistry of a phage display antibody library directed to surface antigens of HT1080 fibrosarcoma cells. We applied SPS to compare the surface proteomes of two epithelial derived cancer cell lines, MCF7 and NCI/ADR-RES, which is drug resistant because of overexpression of the P-glycoprotein (P-gp) drug efflux pump. Surface proteomic profiling identified CD44 as an additional biomarker that distinguishes between these two cell lines. CD44 immunohistochemistry can distinguish between tumors derived from these lines and predict tumor response to doxorubicin in vivo. We further show that CD44 plays a role in drug resistance, independently of P-gp, in NCI/ADR-RES cells and increases expression of the antiapoptotic protein Bcl-xL. Our findings illustrate the utility of SPS to distinguish between cancer cell lines and their derived tumors and identify novel biomarkers involved in drug resistance.     

Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and kidney tissues

Sulfite is a potentially toxic molecule that might enter the body via ingestion, inhalation, or injection. For cellular detoxification, mammalians rely on sulfite oxidase to convert sulfite to sulfate. The purpose of this research was to determine the effect of sulfite on zinc, iron, and copper levels in rat liver and kidney tissues. Forty normal and sulfite oxidase-deficient male albino rats were divided into four groups that included untreated controls (group C), a sulfite-supplemented group that received 70 mg sodium metabisulfite per kilogram per day (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase-deficient group that was also given 70 mg sodium metabisulfite per kilogram per day (group DS). The iron and zinc levels in the liver and kidney in groups S and DS were not affected by sulfite treatment compared to their respective controls (groups C and D). Sulfite exposure led to an increase of kidney copper content in the S group when compared to untreated controls. The kidney copper levels were significantly increased in the unexposed deficient rats, but it was not different than that of the deficient rats that were given oral sulfite treatment. These results suggest that kidney copper levels might be affected by exogenous or endogenous sulfite. An erratum to this article is available at .     

Effects of altered photoperiod due to COVID-19 lockdown on pregnant women and their fetuses

ABSTRACT

Maternal circadian rhythms provide highly important input into the entrainment and programming of fetal and newborn circadian rhythms. The light-dark cycle is an important regulator of the internal biological clock. Even though pregnant women spend a greater part of the day at home during the latter stages of pregnancy, natural light exposure is crucial for the fetus. The current recommended COVID-19 lockdown might dramatically alter normal environmental lighting conditions of pregnant women, resulting in exposure to extremely low levels of natural daylight and high-intensity artificial light sources during both day and night. This article summarizes the potential effects on pregnant woman and their fetuses due to prolonged exposure to altered photoperiod and as consequence altered circadian system, known as chronodisruption, that may result from the COVID-19 lockdown.     

Bistability Analysis of an Apoptosis Model in the Presence of Nitric Oxide

Bistability in apoptosis, or programmed cell death, is crucial for the healthy functioning of multicellular organisms. The aim in this study is to show the presence of bistability in a mitochondria-dependent apoptosis model under nitric oxide effects using chemical reaction network theory. The model equations are a set of coupled ordinary differential equations arising from the assumed mass action kinetics. Whether these equations have a capacity for bistability (cell survival and apoptosis) is determined using a modular approach in which the model is decomposed into modules. Each module contains only a subset of the whole model and is analyzed separately. It is seen that bistability in a module is preserved throughout the whole model after adding the remaining reactions in the pathway on these modules. It is also found that inhibitor effect of some proteins and the appearance of a reacting protein in a later stage as a product is a desired feature but not sufficient for bistability (in the absence of cooperativity effects). On the whole model, two apoptotic and two cell survival states are obtained depending on the initial cell conditions. The results suggest that the antiapoptotic effects of nitric oxide species are responsible for the bistable character of the apoptotic pathway when cooperativity is not assumed in the apoptosome formation.     

Predicting Future Morphological Changes of Lesions from Radiotracer Uptake in 18F-FDG-PET Images

We introduce a novel computational framework to enable automated identification of texture and shape features of lesions on ¹⁸F-FDG-PET images through a graph-based image segmentation method. The proposed framework predicts future morphological changes of lesions with high accuracy. The presented methodology has several benefits over conventional qualitative and semi-quantitative methods, due to its fully quantitative nature and high accuracy in each step of (i) detection, (ii) segmentation, and (iii) feature extraction. To evaluate our proposed computational framework, thirty patients received 2 ¹⁸F-FDG-PET scans (60 scans total), at two different time points. Metastatic papillary renal cell carcinoma, cerebellar hemongioblastoma, non-small cell lung cancer, neurofibroma, lymphomatoid granulomatosis, lung neoplasm, neuroendocrine tumor, soft tissue thoracic mass, nonnecrotizing granulomatous inflammation, renal cell carcinoma with papillary and cystic features, diffuse large B-cell lymphoma, metastatic alveolar soft part sarcoma, and small cell lung cancer were included in this analysis. The radiotracer accumulation in patients'' scans was automatically detected and segmented by the proposed segmentation algorithm. Delineated regions were used to extract shape and textural features, with the proposed adaptive feature extraction framework, as well as standardized uptake values (SUV) of uptake regions, to conduct a broad quantitative analysis. Evaluation of segmentation results indicates that our proposed segmentation algorithm has a mean dice similarity coefficient of 85.75±1.75%. We found that 28 of 68 extracted imaging features were correlated well with SUV_max (p<0.05), and some of the textural features (such as entropy and maximum probability) were superior in predicting morphological changes of radiotracer uptake regions longitudinally, compared to single intensity feature such as SUV_max. We also found that integrating textural features with SUV measurements significantly improves the prediction accuracy of morphological changes (Spearman correlation coefficient = 0.8715, p<2e-16).     

Recovery of bean plants from boron-induced oxidative damage by zinc supply

The effects of zinc on growth, boron uptake, lipid peroxidation, membrane permeability (MP), lypoxygenase (LOX) activity, proline and H₂O₂ accumulation, and the activities of major antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX)) in bean plants were investigated under greenhouse conditions. Treatments consisted of control, 20 mg/kg B, and 20 mg/kg B plus 20 mg/kg Zn. When the plants were grown with 20 mg/kg Zn, B toxicity was less severe. Zinc supplied to soil counteracted the deleterious effects of B on root and shoot growth. Excess B significantly increased and Zn treatment reduced B concentrations in shoot and root tissues. Applied Zn increased the Zn concentration in the roots and shoots. While the concentrations of H₂O₂ and proline were increased by B toxicity, their concentrations were decreased by Zn supply. Boron toxicity increased the MP, malondialdehyde content, and LOX activity in excised bean leaves. Applied Zn significantly ameliorated the membrane deterioration. Compared with control plants, the activity of SOD was increased while that of CAT was decreased and APX remained unchanged in B-stressed plants. However, application of Zn decreased the SOD and increased the CAT and APX activities under toxic B conditions. It is concluded that Zn supply alleviates B toxicity by preventing oxidative membrane damage. Published in Russian in Fiziologiya Rastenii, 2009, Vol. 56, No. 4, pp. 555–562. This text was submitted by the authors in English.