Neoplastic diseases are still a major medical challenge, requiring a constant search for new therapeutic options. A serious problem of many cancers is resistance to anticancer drugs and disease progression in metastases or local recurrence. These characteristics of cancer cells may be related to the specific properties of cancer stem cells (CSC). CSCs are involved in inhibiting cells’ maturation, which is essential for maintaining their self-renewal capacity and pluripotency. They show increased expression of transcription factor proteins, which were defined as stemness-related markers. This group of proteins includes OCT4, SOX2, KLF4, Nanog, and SALL4. It has been noticed that the metabolism of cancer cells is changed, and the demand for iron is significantly increased. Iron chelators have been proven to have antitumor activity and influence the expression of stemness-related markers, thus reducing chemoresistance and the risk of tumor cell progression. This prompts further investigation of these agents as promising anticancer novel drugs. The article presents the characteristics of stemness markers and their influence on the development and course of neoplastic disease. Available iron chelators were also described, and their effects on cancer cells and expression of stemness-related markers were analyzed.
Nociplastic pain is a recently distinguished type of pain, distinct from neuropathic and nociceptive pain, and is well described in the literature. It is often mistaken for central sensitization. Pathophysiology has not been clearly established with regard to alteration of the concentration of spinal fluid elements, the structure of the white and gray matter of the brain, and psychological aspects. Many different diagnostic tools, i.e., the painDETECT and Douleur Neuropathique 4 questionnaires, have been developed to diagnose neuropathic pain, but they can also be applied for nociplastic pain; however, more standardized instruments are still needed in order to assess its occurrence and clinical presentation. Numerous studies have shown that nociplastic pain is present in many different diseases such as fibromyalgia, complex regional pain syndrome type 1, and irritable bowel syndrome. Current pharmacological and nonpharmacological treatments for nociceptive and neuropathic pain are not entirely suitable for treating nociplastic pain. There is an ongoing effort to establish the most efficient way to manage it. The significance of this field has led to several clinical trials being carried out in a short time. The aim of this narrative review was to discuss the currently available evidence on pathophysiology, associated diseases, treatment possibilities, and clinical trials. It is important that physicians widely discuss and acknowledge this relatively new concept in order to provide optimized pain control for patients.
RNA-binding protein 3 (RBMS3) plays a significant role in embryonic development and the pathogenesis of many diseases, especially cancer initiation and progression. The multiple roles of RBMS3 are conditioned by its numerous alternative expression products. It has been proven that the main form of RBMS3 influences the regulation of microRNA expression or stabilization. The absence of RBMS3 activates the Wnt/β-catenin pathway. The expression of c-Myc, another target of the Wnt/β-catenin pathway, is correlated with the RBMS3 expression. Numerous studies have focused solely on the interaction of RBMS3 with the epithelial–mesenchymal transition (EMT) protein machinery. EMT plays a vital role in cancer progression, in which RBMS3 is a new potential regulator. It is also significant that RBMS3 may act as a prognostic factor of overall survival (OS) in different types of cancer. This review presents the current state of knowledge about the role of RBMS3 in physiological and pathological processes, with particular emphasis on carcinogenesis. The molecular mechanisms underlying the role of RBMS3 are not fully understood; hence, a broader explanation and understanding is still needed.
The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan–Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(−) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.
Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs’ main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs’ potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.
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