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Topic Review
Neoangiogenesis and Extracellular Matrix of HNSCC
Head and neck squamous cell cancer (HNSCC) is one of the ten most common malignant neoplasms, characterized by an aggressive course, high recurrence rate, poor response to treatment, and low survival rate. This creates the need for a deeper understanding of the mechanisms of the pathogenesis of this cancer. The tumor microenvironment (TME) of HNSCC consists of stromal and immune cells, blood and lymphatic vessels, and extracellular matrix. It is known that HNSCC is characterized by complex relationships between cancer cells and TME components. TME components and their dynamic interactions with cancer cells enhance tumor adaptation to the environment, which provides the highly aggressive potential of HNSCC and resistance to antitumor therapy.
  • 762
  • 30 Nov 2023
Topic Review
Notch in Hematological Malignancies
Notch receptors are single-pass transmembrane proteins that play a critical role in cell fate decisions and have been implicated in the regulation of many developmental processes. The human Notch family comprises of four receptors (Notch 1 to 4) and five ligands. Their signaling can regulate extremely basic cellular processes such as differentiation, proliferation and death. Notch is also involved in hematopoiesis and angiogenesis, and increasing evidence suggests that these genes are involved and frequently deregulated in several human malignancies, contributing to cell autonomous activities that may be either oncogenic or tumor suppressive. It was recently proposed that Notch signaling could play an active role in promoting and sustaining a broad spectrum of lymphoid malignancies as well as mutations in Notch family members that are present in several disorders of T- and B-cells, which could be responsible for altering the related signaling. Therefore, different Notch pathway molecules could be considered as potential therapeutic targets for hematological cancers.
  • 761
  • 12 Jan 2021
Topic Review
MicroRNA Interrelated Epithelial Mesenchymal Transition (EMT) in Glioblastoma
MicroRNAs (miRNA) are small non-coding RNAs that are 20–23 nucleotides in length, functioning as regulators of oncogenes or tumor suppressor genes. They are molecular modulators that regulate gene expression by suppressing gene translation through gene silencing/degradation, or by promoting translation of messenger RNA (mRNA) into proteins. Circulating miRNAs have attracted attention as possible prognostic markers of cancer, which could aid in the early detection of the disease. Epithelial to mesenchymal transition (EMT) has been implicated in tumorigenic processes, primarily by promoting tumor invasiveness and metastatic activity; this is a process that could be manipulated to halt or prevent brain metastasis. Studies show that miRNAs influence the function of EMT in glioblastomas. Thus, miRNA-related EMT can be exploited as a potential therapeutic target in glioblastomas. 
  • 761
  • 16 Mar 2022
Topic Review
Functional Effects of TGF-β3
Transforming growth factor-beta 3 (TGF-β3) is a ubiquitously expressed multifunctional cytokine involved in a range of physiological and pathological conditions, including embryogenesis, cell cycle regulation, immunoregulation, and fibrogenesis. 
  • 761
  • 10 May 2023
Topic Review
Hypoxia-Inducible Factors and Immunosenescence
Hypoxia activates hypoxia-related signaling pathways controlled by hypoxia-inducible factors (HIFs). HIFs represent a quick and effective detection system involved in the cellular response to insufficient oxygen concentration.
  • 760
  • 23 Aug 2023
Topic Review
Oxidative Stress and Laminopathies Caused by LMNA Mutations
Mutations in the genes that encode for lamins, predominantly lamin A/C, cause a wide spectrum of human diseases, referred to as laminopathies, including muscular dystrophy, lipodystrophy, and systemic premature aging syndrome. HGPS, one of the most severe laminopathies, is a rare genetic disorder characterized by multisystem abnormalities, including premature aging. The most frequent mutation causing HGPS is c.1842C>T (p.G608G) in exon 11 of LMNA, resulting in cryptic splicing between an abnormal donor site in the middle of exon 11 and the usual acceptor of exon 12. This change causes a 50-amino acid deletion in the carboxyl-terminal tail of prelamin A, producing a truncated protein referred to as progerin. The 50 missing amino acids include the recognition sites for the prelamin A-cleaving enzyme ZMPSTE24. Consequently, progerin is normally farnesylated but cannot be further processed because of the lack of docking sites for ZMPSTE24. The farnesylated domain of progerin is firmly anchored to the nuclear membrane, leading to nuclear deformation and deleterious effects in HGPS cells. Blocking the farnesylation of progerin with a farnesyltransferase inhibitor (FTI) successfully reduced the cytotoxic effects of progerin in vitro; however, a clinical trial of FTIs did not yield promising results. A study showed that the interaction between progerin and wild-type lamin A/C was also a critical cause of nuclear deformation in HGPS and normal aging cells, providing a new therapeutic target for HGPS. Progerin expression in various cell types induces excessive ROS production and reduces the activities of the antioxidant system. Oxidative stress is also implicated in other types of laminopathies, such as Dunnigan-type familial partial lipodystrophy (FPLD), amyotrophic quadricipital syndrome with cardiac involvement, autosomal dominant Emery–Dreifuss muscular dystrophy (AD-EDMD), and restrictive dermopathy (RD).
  • 759
  • 25 May 2023
Topic Review
Mesenchymal Stem Cells-Based Cell-Free Therapy in Wound Healing
A wound is an interruption of the normal anatomic structure and function of the skin, which is critical in protecting against foreign pathogens, regulating body temperature and water balance. Wound healing is a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, and re-modeling. Factors such as infection, ischemia, and chronic diseases such as diabetes can compromise wound healing, leading to chronic and refractory ulcers. Mesenchymal stem cells (MSCs) have been used to treat various wound models due to their paracrine activity (secretome) and extracellular vehicles (exosomes) that contain several molecules, including long non-coding RNAs (lncRNAs), micro-RNAs (miRNAs), proteins, and lipids. Studies have shown that MSCs-based cell-free therapy using secretome and exosomes has great potential in regenerative medicine compared to MSCs, as there are fewer safety concerns.
  • 758
  • 07 Jun 2023
Topic Review
MiRNAs/lncRNAs as Potential Biomarkers for Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma (NHL) is a heterogeneous malignancy with variable patient outcomes. There is still a lack of understanding about the different players involved in lymphomagenesis, and the identification of new diagnostic and prognostic biomarkers is urgent. MicroRNAs and long non-coding RNAs emerged as master regulators of B-cell development, and their deregulation has been associated with the initiation and progression of lymphomagenesis. They can function by acting alone or, as recently proposed, by creating competing endogenous RNA (ceRNA) networks. The study of miRNAs’ and lncRNAs’ deregulation in NHL, either alone or as ceRNAs networks, offers new insights into the molecular mechanisms underlying lymphoma pathogenesis and opens a window of opportunity to identify potential diagnostic and prognostic biomarkers.
  • 756
  • 20 Jan 2022
Topic Review
Cell Models for Cystic Fibrosis
Cystic fibrosis (CF) is a autosomal recessive, multisystemic disease caused by different mutations in the CFTR gene encoding CF transmembrane conductance regulator.
  • 756
  • 04 Jan 2023
Topic Review
Role of Interleukin-11 in Non-Small Cell Lung Cancer
Interleukin-11 (IL11), a stromal-cell derived pleiotropic cytokine with profibrotic and cellular remodeling properties, as a potential biomarker in non-small cell lung cancer (NSCLC). IL11 is an important tumor-promoting cytokine that that has both diagnostic and prognostic value in patients with NSCLC. Multiple in vitro studies confirm that IL11 activates known tumor-promoting signaling pathways and clinical studies link increased IL11 expression to poorer prognosis. 
  • 756
  • 22 Aug 2022
Topic Review
SHED-Dependent Oncogenic Signaling of the PEAK3 Pseudo-Kinase
The human kinome is composed of about 50 pseudo-kinases with unclear function, because they are predicted to be catalytically inactive; however, they are shown to play an important role in cancer, similar to active kinases. Understanding how these pseudo-kinases promote tumor formation despite their catalytic inactivity is a great challenge, which may lead to innovative anti-cancer therapies. The PEAK1 and 2 pseudo-kinases have emerged as important components of the protein tyrosine kinase pathway implicated in cancer progression. They can signal using a scaffolding mechanism via a conserved split helical dimerization (SHED) module.
  • 755
  • 11 Jan 2022
Topic Review
Angiogenic Properties of Placenta-Derived EVs
Angiogenesis is one of the main processes that coordinate the biological events leading to a successful pregnancy, and its imbalance characterizes several pregnancy-related diseases, including preeclampsia. Intracellular interactions via extracellular vesicles (EVs) contribute to pregnancy’s physiology and pathophysiology, and to the fetal–maternal interaction.
  • 753
  • 26 May 2021
Topic Review
Next-Generation Sequencing in Acute Myeloid Leukemia
Cytological approaches have long been used in the diagnosis, prognosis, and management of acute myeloid leukemia (AML) and myelodysplastic neoplasms. Technological advances in molecular biology, in particular next-generation sequencing (NGS), have made it possible to establish a molecular list of several gene mutations in AML and MDS, within a matter of days.
  • 753
  • 10 Jul 2023
Topic Review
New Vulnerabilities of Melanoma
Melanoma cells are notorious for their high plasticity and ability to switch back and forth between various melanoma cell states, enabling the adaptation to sub-optimal conditions and therapeutics. This phenotypic plasticity, which has gained more attention in cancer research, is proposed as a new paradigm for melanoma progression. Here the researchers present several rational therapeutic approaches, such as exploiting phenotype-specific and metabolic vulnerabilities and targeting components and signals of the tumor microenvironment (TME), to improve the response of melanoma patients to treatments.
  • 752
  • 13 Apr 2022
Topic Review
Biology of NSCLC
The overall prognosis and survival of non-small cell lung cancer (NSCLC) patients remain poor. The immune system plays an integral role in driving tumor control, tumor progression, and overall survival of NSCLC patients. While the tumor cells possess many ways to escape the immune system, conventional radiotherapy (RT) approaches, which are directly cytotoxic to tumors, can further add additional immune suppression to the tumor microenvironment by destroying many of the lymphocytes that circulate within the irradiated tumor environment.
  • 749
  • 26 Feb 2021
Topic Review
BRAF and MEK Inhibitors in Pediatric CNS Tumors
BRAF is a component of the MAPK and PI3K/AKT/mTOR pathways that play a crucial role in cellular proliferation, differentiation, migration, and angiogenesis. Pediatric central nervous system tumors very often show mutations of the MAPK pathway, as demonstrated by next-generation sequencing (NGS), which now has an increasing role in cancer diagnostics.
  • 749
  • 13 Sep 2022
Topic Review
Molecular Mechanisms Involved in Systemic Sclerosis-Related Lung Fibrosis
Systemic sclerosis (SSc), or scleroderma, is an autoimmune connective tissue disease with one of the highest mortality rates among the rheumatic diseases. Fibrosis is recognized to be a defining feature of SSc, affecting the skin and multiple visceral organs. As a result, SSc is considered the prototypic fibrosing disease. 
  • 749
  • 21 Feb 2023
Topic Review
The Functions of NRF2 in Carcinogenesis and Cancer
The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2)-KEAP1 system is the master regulator of cellular redox and metabolic homeostasis. NRF2 has Janus-like roles in carcinogenesis and cancer development. Short-term NRF2 activation suppresses tissue injury, inflammation, and cancer initiation.
  • 749
  • 19 May 2023
Topic Review
ATP12A Proton Pump in Respiratory Diseases
ATP12A encodes the catalytic subunit of the non-gastric proton pump, which is expressed in many epithelial tissues and mediates the secretion of protons in exchange for potassium ions. In the airways, ATP12A-dependent proton secretion contributes to complex mechanisms regulating the composition and properties of the fluid and mucus lining the respiratory epithelia, which are essential to maintain the airway host defense and the respiratory health. Increased expression and activity of ATP12A in combination with the loss of other balancing activities, such as the bicarbonate secretion mediated by CFTR, leads to excessive acidification of the airway surface liquid and mucus dysfunction, processes that play relevant roles in the pathogenesis of cystic fibrosis and other chronic inflammatory respiratory disorders. Here, the researchers summarize the findings dealing with ATP12A expression, function, and modulation in the airways, which led to the consideration of ATP12A as a potential therapeutic target for the treatment of cystic fibrosis and other airway diseases; the researchers also highlight the current advances and gaps regarding the development of therapeutic strategies aimed at ATP12A inhibition.
  • 749
  • 18 Oct 2023
Topic Review
ATF4 Role during HIV-1 Replication
Activating transcription factor 4 (ATF4) is a transcription factor known to regulate genes associated with the sensing of cellular stress such as amino acid deprival, protein misfolding, growth arrest, and cell death. Despite its key role at the crossroads of immune and stress responses, the precise impact of ATF4 during viral infections remains unclear. Thus, ATF4 has a dual role in promoting cell survival or cell death, but also in limiting infection or participating in viral replication.
  • 749
  • 18 Mar 2024
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