Integrated miRNA Profiling of Extracellular Vesicles from Uterine Aspirates, Malignant Ascites and Primary-Cultured Ascites Cells for Ovarian Cancer Screening.

Extracellular vesicles (EVs) are of growing interest in the context of screening for highly informative cancer markers. We have previously shown that uterine aspirate EVs (UA EVs) are a promising source of ovarian cancer (OC) diagnostic markers. In this study, we first conducted an integrative analysis of EV-miRNA profiles from UA, malignant ascitic fluid (AF), and a conditioned medium of cultured ascites cells (ACs).

Imbalance between Actin Isoforms Contributes to Tumour Progression in Taxol-Resistant Triple-Negative Breast Cancer Cells.

The widespread occurrence of breast cancer and its propensity to develop drug resistance highlight the need for a comprehensive understanding of the molecular mechanisms involved. This study investigates the intricate pathways associated with secondary resistance to taxol in triple-negative breast cancer (TNBC) cells, with a particular focus on the changes observed in the cytoplasmic actin isoforms. By studying a taxol-resistant TNBC cell line, we revealed a shift between actin isoforms towards γ-actin predominance, accompanied by increased motility and invasive properties.

Actin-Dependent Mechanism of Tumor Progression Induced by a Dysfunction of p53 Tumor Suppressor.

Cancer cell aggressiveness, marked by actin cytoskeleton reconfiguration critical for metastasis, may result from an imbalanced ratio favoring γ-actin. Dysfunctional p53 emerges as a key regulator of invasiveness and migration in various cancer cells, both in vitro and in vivo. P53 inactivation (via mutants R175H, R248W, R273H, or TP53 repression) significantly enhanced the migration, invasion, and proliferation of human lung adenocarcinoma A549 cells in vitro and in vivo, facilitating intrapulmonary xenograft metastasis in athymic mice.

The Role of Aurora B Kinase in Normal and Cancer Cells.

Aurora kinases are essential players in mammalian cell division. These kinases are involved in the regulation of spindle dynamics, microtubule-kinetochore interactions, and chromosome condensation and orientation during mitosis. At least three members of the Aurora family - Aurora kinases A, B, and C - have been identified in mammals.

Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary Mutations.

We showed previously that inhibition of KIT signaling in GISTs activates FGFR-signaling pathway rendering cancer cells resistant to receptor tyrosine kinase inhibitor (RTKi) imatinib mesylate (IM) (Gleevec) despite of absence of secondary mutations and thereby illustrating a rationale for the combined (e.g., KIT- and FGFR-targeted) therapies.

Establishment and Characterization of Multi-Drug Resistant p53-Negative Osteosarcoma SaOS-2 Subline.

Aim: To establish a p53-negative osteosarcoma (OS) SaOS-2 cellular subline exhibiting resistance to specific chemotherapeutic agents, including topoisomerase II inhibitors, taxanes, and vinca alkaloids.

Methods: The OS subline exhibiting resistance to the chemotherapeutic agents indicated above was generated by the stepwise treatment of the parental SaOS-2 cell line with increasing concentrations of doxorubicin (Dox) for 5 months. Half-inhibitory concentrations (IC) for Dox, vinblastine (Vin), and paclitaxel (PTX) were calculated by a colorimetric MTS-based assay.

Dermal Fibroblasts as the Main Target for Skin Anti-Age Correction Using a Combination of Regenerative Medicine Methods.

This article includes the data from current studies regarding the pathophysiological mechanisms of skin aging and the regenerative processes occurring in the epidermis and dermis at the molecular and cellular level, mainly, the key role of dermal fibroblasts in skin regeneration. Analyzing these data, the authors proposed the concept of skin anti-age therapy that is based on the correction of age-related skin changes by stimulating regenerative processes at the molecular and cellular level. The main target of the skin anti-age therapy is dermal fibroblasts (DFs).

Significance of NOTCH1 Expression in the Progression of Human Lung and Colorectal Cancers.

Lung and colorectal cancers are the most common types of cancer characterized by a poor prognosis and a high mortality rate. Mutations in the genes encoding components of the main intra- and extracellular signaling pathways, in particular the NOTCH1 gene (Notch1, a member of the Notch family of receptors), play one of the key roles in progression of these malignancies. Notch signaling is involved in maintaining homeostasis of the intestinal epithelium and structural and functional lung elements.

Correlation of the regenerative potential of dermal fibroblasts in 2D culture with the biological properties of fibroblast-derived tissue spheroids.

In situ 3D bioprinting is a new emerging therapeutic modality for treating human skin diseases. The tissue spheroids have been previously suggested as a powerful tool in rapidly expanding bioprinting technology. It has been demonstrated that the regenerative potential of human dermal fibroblasts could be quantitatively evaluated in 2D cell culture and confirmed after implantation in vivo.

Molecular Mechanisms of Changes in Homeostasis of the Dermal Extracellular Matrix: Both Involutional and Mediated by Ultraviolet Radiation.

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. With age, an impairment of structures, quality characteristics, and functions of the dermal extracellular matrix (ECM) occurs in the skin, which leads to disrupted functioning of dermal fibroblasts (DFs), the main cells supporting morphofunctional organization of the skin. The DF functioning directly depends on the state of the surrounding collagen matrix (CM).

Age-Related Changes in the Fibroblastic Differon of the Dermis: Role in Skin Aging.

Skin aging is a multi-factorial process that affects nearly every aspect of skin biology and function. The processes developing in the skin during aging are based on fundamental molecular mechanisms associated with fibroblasts, the main cellular population of the dermis. It has been revealed that the amount of fibroblasts decreases markedly with age and their functional activity is also reduced.

The Design, Synthesis, and Biological Activities of Pyrrole-Based Carboxamides: The Novel Tubulin Inhibitors Targeting the Colchicine-Binding Site.

Microtubule targeting agents (MTAs) that interfere with the dynamic state of the mitotic spindle are well-known and effective chemotherapeutic agents. These agents interrupt the microtubule network via polymerization or depolymerization, halting the cell cycle progression and leading to apoptosis. We report two novel pyrrole-based carboxamides (CAs) (CA-61 and -84) as the compounds exhibiting potent anti-cancer properties against a broad spectrum of epithelial cancer cell lines, including breast, lung, and prostate cancer.

Impaired Expression of Cytoplasmic Actins Leads to Chromosomal Instability of MDA-MB-231 Basal-Like Mammary Gland Cancer Cell Line.

We have shown previously that two cytoplasmic actin isoforms play different roles in neoplastic cell transformation. Namely, β-cytoplasmic actin acts as a tumor suppressor, whereas γ-cytoplasmic actin enhances malignant features of tumor cells. The distinct participation of each cytoplasmic actin in the cell cycle driving was also observed.

Inhibition of FGF2-Mediated Signaling in GIST-Promising Approach for Overcoming Resistance to Imatinib.

Inhibition of KIT-signaling is a major molecular target for gastrointestinal stromal tumor (GIST) therapy, and imatinib mesylate (IM) is known as the most effective first-line treatment option for patients with advanced, unresectable, and/or metastatic GISTs. We show here for the first time that the inhibition of KIT-signaling in GISTs induces profound changes in the cellular secretome, leading to the release of multiple chemokines, including FGF-2. IM increased migration, invasion, and colony formation of IM-resistant GISTs in an FGF2-dependent manner, whereas the use of blocking anti-FGF2 antibodies or BGJ398, a selective FGFR inhibitor, abolished these effects, thus suggesting that the activation of FGF2-mediated signaling could serve as a compensatory mechanism of KIT-signaling inhibited in GISTs.

Spontaneous γH2AX foci in human dermal fibroblasts in relation to proliferation activity and aging.

We assessed the effects of donor age on clonogenicity, proliferative potential, and spontaneous γH2AX foci in the proliferating (Ki67 +) and senescent (SA β-gal +) cultures of skin fibroblasts isolated from 34 donors of different age (23-82 years). Here, we demonstrated that neither the colony forming effectiveness of proliferating (Ki67+) fraction of the fibroblasts nor the average number of γH2AX foci of the same fraction does not depend on the age of the donor. The correlation between the number of γH2AX foci and the donor's age was reliable in quiescent (Ki67-) cells.

Ethyl-2-amino-pyrrole-3-carboxylates are active against imatinib-resistant gastrointestinal stromal tumors in vitro and in vivo.

We showed recently that ethyl-2-amino-pyrrole-3-carboxylates (EAPCs) exhibit potent antiproliferative activities against a broad spectrum of soft tissue sarcoma and gastrointestinal stromal tumor (GIST) cell lines in vitro. The molecular mechanism of action was owing to inhibition of tubulin polymerization and induction of a robust G2/M cell-cycle arrest, leading to the accumulation of tumor cells in the M-phase and induction of apoptosis. Given that more than 50% of the patients with GISTs develop resistance to imatinib (IM) over the 2 years of IM-based therapy, we examined whether EAPCs exhibit activity against IM-resistant GISTs in vitro and in vivo.

Divergent impact of actin isoforms on cell cycle regulation.

We have shown that cytoplasmic actin isoforms play different roles in neoplastic cell transformation. β-Cytoplasmic actin acts as a tumor suppressor, affecting epithelial differentiation, cell growth, cell invasion and tumor growth of colon and lung carcinoma cells. In contrast, γ-cytoplasmic actin enhances malignant features of tumor cells whose actin network regulation is carried out the γ-actin isoform.

Targeting of FGF-Signaling Re-Sensitizes Gastrointestinal Stromal Tumors (GIST) to Imatinib In Vitro and In Vivo.

Dysregulation of the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling pathway is frequently observed in multiple human malignancies, and thus, therapeutic strategies targeting FGFs and FGFRs in human cancer are being extensively explored. We observed the activation of the FGF/FGFR-signaling pathway in imatinib (IM)-resistant gastrointestinal stromal tumor (GIST) cells. Furthermore, we found that the activation of FGFR signaling has a significant impact on IM resistance in GISTs in vitro.

Mitochondria-targeted antioxidant SkQ1 suppresses fibrosarcoma and rhabdomyosarcoma tumour cell growth.

Unlabelled: Mitochondria are important regulators of tumour growth and progression due to their specific role in cancer metabolism and modulation of apoptotic pathways. In this paper we describe that mitochondria-targeted antioxidant SkQ1 designed as a conjugate of decyl-triphenylphosphonium cation (TPP) with plastoquinone, suppressed the growth of fibrosarcoma HT1080 and rhabdomyosarcoma RD tumour cells in culture and tumour growth of RD in xenograft nude mouse model. Under the same conditions, no detrimental effect of SkQ1 on cell growth of primary human subcutaneous fibroblasts was observed.

γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation.

At high exposure levels ionizing radiation is a carcinogen. Little is known about how human stem cells, which are known to contribute to tumorigenesis, respond to prolonged radiation exposures. We studied formation of DNA double strand breaks, accessed as γH2AX and 53BP1 foci, in human mesenchymal stem cells (MSCs) exposed to either acute (5400 mGy/h) or prolonged (270 mGy/h) X-irradiation.

Diffuse colonies of human skin fibroblasts in relation to cellular senescence and proliferation.

Development of personalized skin treatment in medicine and skin care may benefit from simple and accurate evaluation of the fraction of senescent skin fibroblasts that lost their proliferative capacity. We examined whether enriched analysis of colonies formed by primary human skin fibroblasts, a simple and widely available cellular assay, could reveal correlations with the fraction of senescent cells in heterogenic cell population. We measured fractions of senescence associated β-galactosidase (SA-βgal) positive cells in either mass cultures or colonies of various morphological types (dense, mixed and diffuse) formed by skin fibroblasts from 10 human donors.

Myogenic potential of human alveolar mucosa derived cells.

Difficulties related to the obtainment of stem/progenitor cells from skeletal muscle tissue make the search for new sources of myogenic cells highly relevant. Alveolar mucosa might be considered as a perspective candidate due to availability and high proliferative capacity of its cells. Human alveolar mucosa cells (AMC) were obtained from gingival biopsy samples collected from 10 healthy donors and cultured up to 10 passages.

Interaction of microtubules with the actin cytoskeleton via cross-talk of EB1-containing +TIPs and γ-actin in epithelial cells.

Actin microfilaments and microtubules are both highly dynamic cytoskeleton components implicated in a wide range of intracellular processes as well as cell-cell and cell-substrate interactions. The interactions of actin filaments with the microtubule system play an important role in the assembly and maintenance of 3D cell structure. Here we demonstrate that cytoplasmic actins are differentially distributed in relation to the microtubule system.