Red Wine Polyphenols for Cancer Prevention

Conventional cancer therapies, the second leading cause of death worldwide, result in serious side effects and, at best, merely extend the patient''s lifespan by a few years. Searching for effective prevention is of high priority in both basic and clinical sciences. In recent decades natural products have been considered to be an important source of cancer chemopreventive agents. Red wine polyphenols, which consisted of various powerful antioxidants such as flavonoids and stilbenes, have been implicated in cancer prevention and that promote human health without recognizable side effects. Since resveratrol, a major component of red wine polyphenols, has been studied and reviewed extensively for its chemopreventive activity to interfere with the multi-stage carcinogenesis, this review focuses on recent progress in studies on cancer chemopreventive activities of red wine polyphenol extracts and fractions as well as other red wine polyphenols, like procyanidin B5 analogues and myricetin.     

甲状腺素T4免疫传感器的研究

报道以甲基丙烯酸羟乙酯与甲基丙烯酸甲酯的共聚物为载体膜材料，研制成非酶标记的Ｔ４免疫传感器，并对载体膜材料的共聚方法及共聚物共聚比与传感器灵敏度的关系进行了探讨。     

Evaluation of rapeseed meals in broiler chicks: Effect of iodine supply and glucosinolate degradation by myrosinase or copper

In rapeseed meals (RSM) of a conventional (c) or a newly bred (n) variety 117 or 44 mmol glucosinolates and glucosinolate degradation products per kg dry matter were detected. Soaking meals in aqueous myrosinase or copper sulphate solution and subsequent drying reduced the content of antinutrients by more than 90%. Broiler chickens were fed (i) a glucosinolate-free diet, or this diet in which half the soybean meal was replaced by RSM of various origins and treatment; (ii) untreated cRSM; (iii) cRSM treated with myrosinase: (iv) cRSM treated with Cu (v) untreated nRSM; or (vi) nRSM treated with myrosinase. These diets were administered with or without supplementary iodine. Chickens receiving the iodine-deficient diets with myrosinase-treated RSM showed growth depression, incomplete feathering, leg injuries and severe goitre. In the serum T⁴ could not be detected. Giving myrosinase-treated RSM plus iodine, or giving other RSM diets irrespective of iodine administration, no growth depression was observed. RSM diets without iodine dosage markedly increased thyroid weight: there were no differences between the RSM variants. In contrast to the treatment with myrosinase, in the sera of the chickens fed on untreated RSM or RSM treated with copper T⁴ could be detected, suggesting that in iodine-deficient conditions differences in serum T⁴ concentration between RSM groups indicate a differing anti-thyroid activity. With iodine supplementation the RSM had a significant effect on thyroid weight. The largest thyroids (five-fold heavier) were in the animals with myrosinase-treated cRSM. The untreated cRSM and the nRSM trebled or doubled the thyroid weight, and the myrosinase-treated nRSM trebled it. The thyroid weight of chicks fed cRSM treated with copper did not differ significantly from the glucosinolate-free control. There was evidence that heating the myrosinase-treated RMS produced anti-thyroid compounds; these should be identified in further investigations.     

Spline-regression estimation of the influence of exposure dose on cancer probability

Spline regression is used to analyze the influence of radiation on the cancer probability in a group of participants of Chernobyl accident mitigation, depending on the exposure dose. A new method is proposed to approximate modified polygons by linear splines with two nodes. An algorithm for the identification of a transition point is outlined. __________ Translated from Kibernetika i Sistemnyi Analiz, No. 3, pp. 168–176, May–June 2006.     

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.     

Molecular Aspects and Prognostic Significance of Microcalcifications in Human Pathology: A Narrative Review

The presence of calcium deposits in human lesions is largely used as imaging biomarkers of human diseases such as breast cancer. Indeed, the presence of micro- or macrocalcifications is frequently associated with the development of both benign and malignant lesions. Nevertheless, the molecular mechanisms involved in the formation of these calcium deposits, as well as the prognostic significance of their presence in human tissues, have not been completely elucidated. Therefore, a better characterization of the biological process related to the formation of calcifications in different tissues and organs, as well as the understanding of the prognostic significance of the presence of these calcium deposits into human tissues could significantly improve the management of patients characterized by microcalcifications associated lesions. Starting from these considerations, this narrative review highlights the most recent histopathological and molecular data concerning the formation of calcifications in breast, thyroid, lung, and ovarian diseases. Evidence reported here could deeply change the current point of view concerning the role of ectopic calcifications in the progression of human diseases and also in the patients’ management. In fact, the presence of calcifications can suggest an unfavorable prognosis due to dysregulation of normal tissues homeostasis.     

MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts

Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior.     

The Chick Chorioallantoic Membrane Model: A New In Vivo Tool to Evaluate Breast Cancer Stem Cell Activity

The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immune-incompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities—in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44⁺/CD24^−/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints.