Improving the Prognostic and Predictive Value of Circulating Tumor Cell Enumeration: Is Longitudinal Monitoring the Answer?

Circulating tumor cell (CTC) numbers in the blood of cancer patients can indicate the progression and invasiveness of tumors, and their prognostic and predictive value has been repeatedly demonstrated. However, the standard baseline CTC count at the beginning of treatment, while informative, is not completely reliable and may not adequately reflect the state of the disease. A growing number of studies indicate that the long-term monitoring of CTC numbers in the same patient provides more comprehensive prognostic data and should be incorporated into clinical practice, as a factor that contributes to therapeutic decisions.

Circulating Tumor Cells: Pathological, Molecular and Functional Characteristics.

This Special Issue, 'Circulating Tumor Cells: Pathological, Molecular and Functional Characteristics 1 [...

Longitudinal analysis of circulating tumor cell numbers improves tracking metastatic breast cancer progression.

Hormone-responsive breast cancer represents the most common type and has the best prognosis, but still approximately 40% of patients with this type can develop distant metastases, dramatically worsening the patient's survival. Monitoring metastatic breast cancer (mBC) for signs of progression is an important part of disease management. Circulating tumor cell (CTC) detection and molecular characteristics gain importance as a diagnostic tool, but do not represent a clinical standard and its value as a predictor of progression is not yet established.

HAX1: A versatile, intrinsically disordered regulatory protein.

HAX1 is a relatively small, ubiquitously expressed, predominantly mitochondrial, intrinsically disordered protein. It has been implicated in the regulation of apoptosis, cell migration, calcium cycling, proteostasis, angiogenesis, autophagy and translation. A wide spectrum of functions, numerous interactions and still elusive molecular mechanisms of action make HAX1 an intriguing subject of research.

The RNA-Binding Landscape of HAX1 Protein Indicates Its Involvement in Translation and Ribosome Assembly.

HAX1 is a human protein with no known homologues or structural domains. Mutations in the gene cause severe congenital neutropenia through mechanisms that are poorly understood. Previous studies reported the RNA-binding capacity of HAX1, but the role of this binding in physiology and pathology remains unexplained.

New 2-[(4-Amino-6--substituted-1,3,5-triazin-2-yl)methylthio]--(imidazolidin-2-ylidene)-4-chloro-5-methylbenzenesulfonamide Derivatives, Design, Synthesis and Anticancer Evaluation.

In the search for new compounds with antitumor activity, new potential anticancer agents were designed as molecular hybrids containing the structures of a triazine ring and a sulfonamide fragment. Applying the synthesis in solution, a base of new sulfonamide derivatives - was obtained by the reaction of the corresponding esters - with appropriate biguanide hydrochlorides. The structures of the compounds were confirmed by spectroscopy (IR, NMR), mass spectrometry (HRMS or MALDI-TOF/TOF), elemental analysis (C,H,N) and X-ray crystallography.

Overall survival analysis of > 65-year-old patients with breast cancer based on their molecular, clinicopathological and laboratory factors.

Introduction: The objective of the present study was to characterize > 65-year-old patients with breast cancer according to clinicopathological, molecular and laboratory factors.

Methods: A total of 723 breast cancer patients, who had been diagnosed and treated during 2005-2019, were retrospectively reviewed. Patients > 65 years of age (92 patients) were compared with < 50-year-old women (306 patients).

Cell Death by Entosis: Triggers, Molecular Mechanisms and Clinical Significance.

Entosis-a homotypic insertion of one cell into another, resulting in a death of the invading cell-has been described in many reports, but crucial aspects of its molecular mechanisms and clinical significance still remain controversial. While actomyosin contractility of the invading cell is very well established as a driving force in the initial phase, and autophagy induced in the outer cell is determined as the main mechanism of degradation of the inner cell, many details remain unresolved. The multitude of triggering factors and crisscrossing molecular pathways described in entosis regulation make interpretations difficult.

Protein Binding to Cis-Motifs in mRNAs Coding Sequence Is Common and Regulates Transcript Stability and the Rate of Translation.

Protein binding to the non-coding regions of mRNAs is relatively well characterized and its functionality has been described in many examples. New results obtained by high-throughput methods indicate that binding to the coding sequence (CDS) by RNA-binding proteins is also quite common, but the functions thereof are more obscure. As described in this review, CDS binding has a role in the regulation of mRNA stability, but it has also a more intriguing role in the regulation of translational efficiency.

The Influence of Different Pretreatment Methods on Color and Pigment Change in Beetroot Products.

Vegetable processing pomace contains valuable substances such as natural colors that can be reused as functional ingredients. Due to a large amount of water, they are an unstable material. The aim of our research was to assess how the pretreatment method (thermal or nonthermal) affects the properties of powders obtained from beet juice and pomace after the freeze-drying process.

The type III secretion system effector EspO of enterohaemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1.

Many enteric pathogens employ a type III secretion system (T3SS) to translocate effector proteins directly into the host cell cytoplasm, where they subvert signalling pathways of the intestinal epithelium. Here, we report that the anti-apoptotic regulator HS1-associated protein X1 (HAX-1) is an interaction partner of the T3SS effectors EspO of enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium, OspE of Shigella flexneri and Osp1 of Salmonella enterica serovar Typhimurium. EspO, OspE and Osp1 have previously been reported to interact with the focal adhesions protein integrin linked kinase (ILK).

How to Predict Metastasis in Luminal Breast Cancer? Current Solutions and Future Prospects.

Breast cancer metastasis is the main cause of breast cancer mortality. Luminal breast cancer represents the majority of breast cancer cases and, despite relatively good prognosis, its heterogeneity creates problems with a proper stratification of patients and correct identification of the group with a high risk of metastatic relapse. Current prognostic tools are based on the analysis of the primary tumor and, despite their undisputed power of prediction, they might be insufficient to foresee the relapse in an accurate and precise manner, especially if the relapse occurs after a long period of dormancy, which is very common in luminal breast cancer.

The interactome of multifunctional HAX1 protein suggests its role in the regulation of energy metabolism, de-aggregation, cytoskeleton organization and RNA-processing.

HCLS1-associated protein X-1 (HAX1) is a multifunctional protein involved in many cellular processes, including apoptosis, cell migration and calcium homeostasis, but its mode of action still remains obscure. Multiple HAX1 protein partners have been identified, but they are involved in many distinct pathways, form different complexes and do not constitute a coherent group. By characterizing HAX1 protein interactome using targeted approach, we attempt to explain HAX1 multiple functions and its role in the cell.

Clinicopathological characteristics of breast cancer patients with mutation according to age.

Introduction: The purpose of the present study was to characterise patients with breast cancer (BC) and mutation (age ≥ 50 years) according to their clinicopathological factors or family history. Patients aged ≥ 50 years were compared with the control group and with mutation carriers aged < 50 years.

Material And Methods: Prognostic factors were analysed in patients with BC with confirmed c.

Quantification of Cell-Substrate Adhesion Area and Cell Shape Distributions in MCF7 Cell Monolayers.

The methods presented here quantify some parameters of confluent adherent cell monolayers from multiple appropriately stained confocal images: adhesion to the substrate as a function of the number and size of focal adhesions, and cell shape, characterized by the cell shape index and other shape descriptors. Focal adhesions were visualized by paxillin staining and cell-cell borders were marked by junction plakoglobin and actin. The methods for cell culture and staining were standard; images represent single focal planes; image analysis was performed using publicly available image processing software.

Impact of Medium pH on DOX Toxicity toward HeLa and A498 Cell Lines.

The influence of the pH of the multicomponent cell medium on the performance of doxorubicin (DOX), an anticancer drug, was studied on the examples of cervical (HeLa) and kidney (A498) cancer cell lines. The change of pH of the cell medium to more acidic led to a decrease of DOX toxicity on both cell lines due to the change of drug permeability across the cell membrane as a result of drug protonation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) studies and lactate dehydrogenase (LDH) release tests have shown low toxicity of the drug, especially in the case of A498 cells, which are characterized by an extremely high glycolytic metabolism.

Genetic 3'UTR variations and clinical factors significantly contribute to survival prediction and clinical response in breast cancer patients.

The study describes a relationship between the 3'UTR variants, clinicopathological parameters and response to chemotherapy. We analyzed 33 germline polymorphisms in 3'UTRs of ADME genes in 305 breast cancer women treated with FAC regime. Clinical endpoints of this study were: overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS) and overall response defined as treatment failure-free survival (TFFS).

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value.

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients.

HAX1 impact on collective cell migration, cell adhesion, and cell shape is linked to the regulation of actomyosin contractility.

HAX1 protein is involved in the regulation of apoptosis, cell motility and calcium homeostasis. Its overexpression was reported in several tumors, including breast cancer. This study demonstrates that HAX1 has an impact on collective, but not single-cell migration, thus indicating the importance of cell-cell contacts for the HAX1-mediated effect.

RNA-protein interactions: disorder, moonlighting and junk contribute to eukaryotic complexity.

RNA-protein interactions are crucial for most biological processes in all organisms. However, it appears that the complexity of RNA-based regulation increases with the complexity of the organism, creating additional regulatory circuits, the scope of which is only now being revealed. It is becoming apparent that previously unappreciated features, such as disordered structural regions in proteins or non-coding regions in DNA leading to higher plasticity and pliability in RNA-protein complexes, are in fact essential for complex, precise and fine-tuned regulation.

Cytoplasmic HAX1 Is an Independent Risk Factor for Breast Cancer Metastasis.

HAX1 is an antiapoptotic factor involved in the regulation of cell migration and calcium homeostasis, overexpressed in several cancers, including breast cancer. It has been suggested that HAX1 is also implicated in metastasis. Herein we report the results of meta-analysis of expression, based on publicly available data, which confirms its significant overexpression in breast cancer and demonstrates copy number gain and prognostic value of overexpression for metastatic relapse in ER+ tumors.

mutation in breast cancer patients: Analysis of prognostic factors and survival.

The presence of BRCA1 mutations is associated with an increased risk of breast and ovarian cancer. The present study compared clinicopathological characteristics and overall survival (OS) of hereditary and sporadic breast cancer. Using data collected from a previous study conducted between 2007-2016 at the Maria Skłodowska Curie Cancer Center and Institute of Oncology (Gliwice, Poland), the prognostic factors and survival in 60 breast cancer mutation carriers were analyzed.

Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals.

Introduction: The majority of breast cancers (BCs) are characterized by the expression of estrogen receptor alpha (ERα+). ERα acts as ligand-dependent transcription factor for genes associated with cell survival, proliferation, and tumor growth. Thus, blocking the estrogen agonist effect on ERα is the main strategy in the treatment of ERα+ BCs.

mutations and SNPs as prognostic and predictive factors in patients with breast cancer.

Tumor protein 53 () is a tumor suppressor gene that encodes tumor protein p53. Tumor protein p53 regulates the expression of target genes in response to cellular stress. Additionally, p53 participates in the regulation of cell cycle checkpoints, DNA repair and apoptosis.