Terbium (lithium zinc) distannide, TbLi1–xZnxSn2 (x = 0.2)

The new terbium (lithium zinc) distannide, TbLi1–xZnxSn2 (x = 0.2) crystallizes in the ortho­rhom­bic CeNiSi2 structure type with space group Cmcm and Pearson symbol oS16. Of the four independent 4c atom positions (m2m site symmetry), three are fully occupied by individual atoms (two by Sn and one by Tb atoms) and the fourth is occupied by Li and Zn atoms with a statistical distribution. The Tb coordination polyhedron is a 21-vertex pseudo-Frank–Kasper polyhedron. One Sn atom is enclosed in a tricapped trigonal prism, the second Sn atom is in a cubocta­hedron and the statistically distributed (Li,Zn) site is in a tetra­gonal anti­prism with one added atom. Electronic structure calculations were used for the elucidation of reasons for and the ability of mutual substitution of lithium and transition metals. Positive charge density was observed around the rare earth atom and the Li and Zn atoms, the negative charge density in the proximity of the Sn atoms

Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide

Aims: Monocytes play an important role in hypertension. Circulating monocytes in humans exist as classical, intermediate and non-classical forms. Monocyte differentiation can be influenced by the endothelium, which in turn is activated in hypertension by mechanical stretch. We sought to examine the role of increased endothelial stretch and hypertension on monocyte phenotype and function. Methods and Results: Human monocytes were cultured with confluent human aortic endothelial cells undergoing either 5% or 10% cyclical stretch. We also characterized circulating monocytes in normotensive and hypertensive humans. In addition, we quantified accumulation of activated monocytes and monocyte-derived cells in aortas and kidneys of mice with Angiotensin II-induced hypertension. Increased endothelial stretch enhanced monocyte conversion to CD14++CD16+ intermediate monocytes and monocytes bearing the CD209 marker and markedly stimulated monocyte mRNA expression of interleukin (IL)-6, IL-1β, IL-23, chemokine (C-C motif) ligand 4 and tumor necrosis factor α. STAT3 in monocytes was activated by increased endothelial stretch. Inhibition of STAT3, neutralization of IL-6 and scavenging of hydrogen peroxide prevented formation of intermediate monocytes in response to increased endothelial stretch. We also found evidence that nitric oxide inhibits formation of intermediate monocytes and STAT3 activation. In vivo studies demonstrated that humans with hypertension have increased intermediate and non-classical monocytes and that intermediate monocytes demonstrate evidence of STAT3 activation. Mice with experimental hypertension exhibit increased aortic and renal infiltration of monocytes, dendritic cells and macrophages with activated STAT3. Conclusions: These findings provide insight into how monocytes are activated by the vascular endothelium during hypertension. This is likely in part due to a loss of nitric oxide signaling and increased release of IL-6 and hydrogen peroxide by the dysfunctional endothelium and a parallel increase in STAT activation in adjacent monocytes. Interventions to enhance bioavailable nitric oxide, reduce IL-6 or hydrogen peroxide production or to inhibit STAT3 may have anti-inflammatory roles in hypertension and related conditions

Impact of Selected Signaling Proteins on SNAIL 1 and SNAIL 2 Expression in Ovarian Cancer Cell Lines in Relation to Cells’ Cisplatin Resistance and EMT Markers Level

It has been increasingly recognized that SNAIL1 and SNAIL2, as major EMT-inducers, might also be involved in drug resistance of cancer cells. We sought to determine a relation between SNAIL1/2, E-cadherin and N-cadherin expression, as well as ovarian cancer cells’ resistance to cisplatin and EMT markers’ level. Thus, four ovarian cancer cell lines, were used: A2780, A2780cis, SK-OV-3 and OVCAR-3. We assessed the impact of ERK1/2, AKT and STAT3 proteins (chosen by the profiling activity of over 40 signaling proteins) on SNAIL1/2 expression, along with E-cadherin and N-cadherin levels. We showed that expression of SNAIL1 and N-cadherin are the highest in cisplatin-resistant A2780cis and SK-OV-3 cells, while high SNAIL2 and E-cadherin levels were observed in cisplatin-sensitive A2780 cells. The highest E-cadherin level was noticed in OVCAR-3 cells. SNAIL1/2 expression was dependent on ERK1/2 activity in cisplatin-resistant and potentially invasive SK-OV-3 and OVCAR-3 cells. STAT-3 regulates expression of SNAIL1/2 and leads to the so-called “cadherin switch” in cancer cells, independently of their chemoresistance. In conclusion, SNAIL1, but not SNAIL2, seems to be involved in ovarian cancer cells’ cisplatin resistance. STAT3 is a universal factor determining the expression of SNAIL1/2 in ovarian cancer cells regardless of their chemoresitance or invasive capabilities

Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases. Chemotherapeutics, radiotherapy and photodynamic therapy induce intracellular stress response pathways in tumor cells, leading to a secretion of various factors belonging to a family of damage-associated molecular patterns molecules, capable of inducing the adaptive immune response. One of them is calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on the surface of dying tumor cells serves as an “eat me” signal for antigen presenting cells (APC). Engulfment of tumor cells by APCs results in the presentation of tumor’s antigens to cytotoxic T-cells and production of cytokines/chemokines, which activate immune cells responsible for tumor cells killing. Thus, the development of ICD and the expression of CRT can help standard therapy to eradicate tumor cells. Here, we review the physiological functions of CRT and its involvement in the ICD appearance in malignant disease. Moreover, we also focus on the ability of various anti-cancer drugs to induce expression of surface CRT on ovarian cancer cells. The second aim of this work is to discuss and summarize the prognostic/predictive value of CRT in ovarian cancer patients

Calreticulin—Multifunctional Chaperone in Immunogenic Cell Death: Potential Significance as a Prognostic Biomarker in Ovarian Cancer Patients

Immunogenic cell death (ICD) is a type of death, which has the hallmarks of necroptosis and apoptosis, and is best characterized in malignant diseases. Chemotherapeutics, radiotherapy and photodynamic therapy induce intracellular stress response pathways in tumor cells, leading to a secretion of various factors belonging to a family of damage-associated molecular patterns molecules, capable of inducing the adaptive immune response. One of them is calreticulin (CRT), an endoplasmic reticulum-associated chaperone. Its presence on the surface of dying tumor cells serves as an “eat me” signal for antigen presenting cells (APC). Engulfment of tumor cells by APCs results in the presentation of tumor’s antigens to cytotoxic T-cells and production of cytokines/chemokines, which activate immune cells responsible for tumor cells killing. Thus, the development of ICD and the expression of CRT can help standard therapy to eradicate tumor cells. Here, we review the physiological functions of CRT and its involvement in the ICD appearance in malignant disease. Moreover, we also focus on the ability of various anti-cancer drugs to induce expression of surface CRT on ovarian cancer cells. The second aim of this work is to discuss and summarize the prognostic/predictive value of CRT in ovarian cancer patients

E-Cadherin Expression in Relation to Clinicopathological Parameters and Survival of Patients with Epithelial Ovarian Cancer

It is generally accepted that loss/reduction of E-cadherin expression on tumor cells promotes their migration, invasiveness, and metastasis. It is also an indicator of cancer cells’ aggressiveness. The aim of this study was to assess how the expression of E-cadherin varies in primary ovarian cancer tissue in regard to overall survival of patients; FIGO stage; grade; histopathological type of tumor; and potential factors discriminating malignant and nonmalignant ovarian tumors. Our analysis was based on literature research (1 January 2000–8 November 2021) conducted according to the PRISMA guidelines. Most studies support the assumption that loss/reduced expression of E-cadherin results in shorter overall survival of EOC patients. Moreover, most research has shown that there is a correlation between the low level of E-cadherin and the advancement stage of disease, especially in high-grade serous ovarian carcinoma type. However, E-cadherin expression seems to not be helpful to distinguish malignant and nonmalignant tumors. In conclusion, reduced E-cadherin expression in primary ovarian cancer tissue may indicate a less favorable disease outcome and is associated with high advancement of the disease

Antitumoral Activity Of Nitric Oxide-Releasing Compounds

Background: Despite significant improvements in the conventional anti-ovarian cancer therapies, tumor cell resistance to various cytostatic drugs remains a relevant problem. Therefore, the new cancer treatment strategies are being developed. Among many agents that have been studied for their potential anti-cancer activity, the most promising are the nitric oxide (NO) donors-syntethic compounds that release NO in vivo and/or in vitro. Aim: We have evaluated the effect of NO donors on the SK-OV-3 and OVCAR-3 ovarian cancer cell lines. We assessed some of the cancer cells’ specific features: the uncontrolled proliferation, over-activation of particular signaling proteins, high resistance to therapeutics and elevated expression and secretion of invasiveness/metastatic factors. Methods: Two members of NONOates family were used: SPER/NO and DETA/NO. Cancer cell lines were cultured with different concentrations of NO donors. The cytotoxic, pro-apoptotic activity of NO donors and their impact on the phosphorylation status of STAT-3 and AKT in cells were determined. The expression of VEGF-A, MMPs and TGF-β was also evaluated. Results: NO donors inhibited ovarian cancer cells growth making them also more susceptible to the cisplatin cytotoxic activity. Moreover, both NO donors induced apoptosis of cells and decreased activity of signaling proteins (STAT3 and AKT). Similarly, SPER/NO and DETA/NO lowered the secretion of pro-metastatic factors, responsible for cancer cells invasiveness. Conclusions: The obtained results show that both NO donors demonstrated a wide range of action on both ovarian cancer cell lines. Therefore, they have a high potential of being a supporting compounds in the cancer therapies