Topic Review
HMGA Proteins in Hematological Malignancies
The high mobility group AT-Hook (HMGA) proteins are a family of nonhistone chromatin remodeling proteins known as “architectural transcriptional factors”. By binding the minor groove of AT-rich DNA sequences, they interact with the transcription apparatus, altering the chromatin modeling and regulating gene expression by either enhancing or suppressing the binding of the more usual transcriptional activators and repressors, although they do not themselves have any transcriptional activity. Their involvement in both benign and malignant neoplasias is well-known and supported by a large volume of studies.
  • 843
  • 26 Oct 2020
Topic Review
LncRNAs in Cervical Cancer
Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the etiology of the disease, genetic and epigenetic factors are also required for its progression. Among the epigenetic factors are included the long noncoding RNAs (lncRNAs), transcripts of more than 200 nucleotides (nt) that generally do not code for proteins and have been associated with diverse functions such as the regulation of transcription, translation, RNA metabolism, as well as stem cell maintenance and differentiation, cell autophagy and apoptosis. Recently, studies have begun to characterize the aberrant regulation of lncRNAs in CC cells and tissues, including Homeobox transcript antisense RNA (HOTAIR), H19, Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), Cervical Carcinoma High-Expressed 1 (CCHE1), Antisense noncoding RNA in the inhibitors of cyclin-dependent kinase 4 (ANRIL), Growth arrest special 5 (GAS5) and Plasmacytoma variant translocation 1 (PVT1). They have been associated with several disease-related processes such as cell growth, cell proliferation, cell survival, metastasis and invasion as well as therapeutic resistance, and are novel potential biomarkers for diagnosis and prognosis in CC.
  • 842
  • 13 Jan 2021
Topic Review
Proteoglycans in the hormone-dependent cancers
The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Notably, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and its' PG components crucially mediate these processes including cancer metastasis, angiogenesis, immunobiology, autophagy, and response to therapy. Hormone-dependent cancers exhibit high morbidity and mortality. In spite of advances in therapy, the treatment  of hormone-dependent cancers remains an unmet health need. The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. A plethora of deregulated signaling pathways contributes to the growth, dissemination, and angiogenesis of hormone-dependent cancers. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Importantly, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and the PG components crucially mediate these processes.
  • 842
  • 31 Aug 2020
Topic Review
Gender Differences and NPS
Sex and gender deeply affect the subjective effects and the pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse.
  • 842
  • 26 Oct 2020
Topic Review
14-3-3σ and Its Modulators
14-3-3σ is an acidic homodimer protein with more than one hundred different protein partners associated with oncogenic signaling and cell cycle regulation. 
  • 842
  • 18 May 2021
Topic Review
Left Ventricular Hypertrophy Pathophysiology
Left ventricular hypertrophy (LVH) can be adaptive, as arising from exercise, or pathological, most commonly when driven by hypertension. The pathophysiology of LVH is consistently associated with an increase in cytochrome P450 (CYP)1B1 and mitogen-activated protein kinases (MAPKs) and a decrease in sirtuins and mitochondria functioning. The pathoetiology of LVH is intimately associated with increased blood pressure and therefore with the array of different factors associated with hypertension, including the various manifestations and consequences of stress, obesity and diabetes. 
  • 841
  • 15 Nov 2021
Topic Review
Diffuse Large B-Cell Lymphoma
The most common type of non-Hodgkin lymphoma in adults is diffuse large B-cell (DLBCL). There is a historical unmet need for more effective therapies in the 2nd and 3rd line setting. Emerging immunochemotherapies have shown activity in small studies of heavily pre-treated patients with prolonged remissions achieved in some patients. Anti-CD19 CAR (chimeric antigen receptor) T cells are potentially curative in the 3rd line and beyond setting and are under investigation in earlier lines of therapy. Antibody-drug conjugates (ADC’s) such as polatuzumab vedotin targeting the pan-B-cell marker CD79b has proven effectiveness in multiply-relapsed DLBCL patients. Tafasitamab (MOR208) is an anti-CD19 monoclonal antibody producing prolonged remissions when combined with Lenalidomide (LEN) in patients who were not candidates for salvage chemotherapy or autologous stem cell transplant. Selinexor, an oral, small-molecule selective inhibitor of XPO1-mediated nuclear export (SINE), demonstrated prolonged activity against heavily-pretreated DLBCL without cumulative toxicity and is being investigated as part of an oral, chemotherapy-free regimen for relapsed aggressive lymphoma. This article reviews current strategies and novel therapies for relapsed/refractory DLBCL.
  • 841
  • 24 Nov 2020
Topic Review
Oligonucleotide Therapies in Treating Arthritis
Oligonucleotide therapeutics represent an emerging but highly promising class of therapeutics to treat inflammatory joint disease. Although yet to be successfully tested in clinical trials for arthritis treatment, data from preclinical experimental models of arthritis provide evidence that the intra-articular delivery of oligonucleotides can modify OA disease pathology, by reducing synovitis, preventing sclerotic bone formation and protecting from cartilage damage. Importantly, since oligonucleotide therapeutics are based on gene sequences, they are expected to act specifically on the target gene, and thus may be considered less likely to have off-target effects and to elicit adverse side effects.
  • 841
  • 23 Aug 2021
Topic Review
Electrochemical Biosensing of Dopamine Neurotransmitter
Neurotransmitters are biochemical molecules that transmit a signal from a neuron across the synapse to a target cell, thus being essential to the function of the central and peripheral nervous system. Dopamine is one of the most important catecholamine neurotransmitters since it is involved in many functions of the human central nervous system, including motor control, reward, or reinforcement. It is of utmost importance to quantify the amount of dopamine since abnormal levels can cause a variety of medical and behavioral problems. 
  • 841
  • 17 Jun 2021
Topic Review
Belantamab Mafodotin and Multiple Myeloma
Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed
  • 841
  • 24 Feb 2021
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