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Topic Review
Adenocarcinoma of the Colon
Adenocarcinoma of the colon is the most common malignant neoplasia of the gastrointestinal tract and is a major contributor to mortality worldwide. Invasiveness and metastatic behavior are typical of malignant tumors and, because of its portal drainage, the liver is the closest capillary bed available in this case, hence the common site of metastatic dissemination. Current therapies forecast total resection of primary tumor when possible and partial liver resection at advanced stages, along with systemic intravenous therapies consisting of chemotherapeutic agents such as 5-fluorouracil. These cures are definitely not exempt from drawbacks and heavy side effects. Biocompatible polymeric networks, both in colloids and bulk forms, able to absorb large quantities of water and load a variety of molecules-belong to the class of innovative drug delivery systems, thus suitable for the purpose and tunable on each patient can represent a promising alternative. Indeed, the implantation of polymeric scaffolds easy to synthesize can substitute chemotherapy and combination therapies scheduling, shortening side effects. Moreover, they do not require a surgical removal thanks to spontaneous degradation and guarantees an extended and regional cargo release, maintaining high drug concentrations.
  • 524
  • 22 Jan 2021
Topic Review
Adenoids and Tonsils: Immune System's Tireless Gatekeepers
Within the intricate realm of the mucosal immune system resides a captivating duo: the adenoids (or pharyngeal tonsils) and the tonsils (including palatine, tubal, and lingual variations), which harmoniously form the Waldeyer’s ring. As they are strategically positioned at the crossroads of the respiratory and gastrointestinal systems, these exceptional structures fulfill a vital purpose. They function as formidable “gatekeepers” by screening microorganisms—both bacteria and viruses—with the mission to vanquish local pathogens via antibody production. However, under specific circumstances, their function can take an unsettling turn, inadvertently transforming them into reservoirs for pathogen incubation.
  • 436
  • 28 Jun 2023
Topic Review
Adenomyoma
The term ‘adenomyoma’ was coined around the year 1880 to designate the majority of mucosa-containing lesions related to the female genital tract. Currently, the term is more commonly applied to localised adenomyosis of the uterus.
  • 662
  • 07 May 2021
Topic Review
Adenomyosis
Adenomyosis is defined as an invasion of the endometrium into the uterine myometrium, which results in an enlargement of the uterus, formation of adenomyotic tumours, profuse menstrual and inter-menstrual bleeding and recurrent pain. Microscopically ectopic nonneoplastic, endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium are noted. It is estrogens' dependent disease so that the hormonal treatment is the first line treatment in adenomyotic patients.
  • 513
  • 16 Feb 2021
Topic Review
Adenomyosis and Infertility
Adenomyosis (the presence of ectopic endometrial glands and stroma below the endometrial–myometrial junction) is a benign condition which is increasingly diagnosed in younger women suffering from infertility. Adenomyosis is a common gynecological disorder, affecting women of reproductive age. It negatively affects in vitro fertilization, pregnancy and the live birth rate, as well as increases the risk of miscarriage. With the advent of non-invasive diagnoses with MRI and TVUS, the role of adenomyosis in infertility has been better recognized.
  • 180
  • 31 Aug 2023
Topic Review
Adenosine and COVID-19
Coronavirus disease 2019 (COVID-19) patients can develop interstitial pneumonia, which, in turn, can evolve into acute respiratory distress syndrome (ARDS). This is accompanied by an inflammatory cytokine storm. severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has proteins capable of promoting the cytokine storm, especially in patients with comorbidities, including obesity. Since currently no resolutive therapy for ARDS has been found and given the scientific literature regarding the use of adenosine, its application has been hypothesized. Through its receptors, adenosine is able to inhibit the acute inflammatory process, increase the protection capacity of the epithelial barrier, and reduce the damage due to an overactivation of the immune system, such as that occurring in cytokine storms. These features are known in ischemia/reperfusion models and could also be exploited in acute lung injury with hypoxia. Considering these hypotheses, a COVID-19 patient with unresponsive respiratory failure was treated with adenosine for compassionate use. The results showed a rapid improvement of clinical conditions, with negativity of SARS-CoV2 detection.
  • 1.8K
  • 23 May 2022
Topic Review
Adenosine Deaminase
Adenosine deaminase (ADA, EC 3.5.4.4) - the enzyme engaged in purine metabolism that irreversibly converts adenosine or 2′deoxyadenosine to inosine or 2′deoxyinosine, respectively. In human tissues, it occurs as two isoenzymes: ADA1 and ADA2. ADA1 constitutes the majority of ADA activity and it is present in virtually all tissues, while ADA2 has been found with ADA1 only in monocytes/macrophages. Both ADA isoenzymes are present in cytosolic form, soluble fraction that can be located away from the originating cell, or as ecto-enzymes binding to the cell surface by dedicated proteins. Intracellularly, ADA plays a significant role counteracting high concentrations of 2'deoxyadenosine. When intracellular ADA activity is lowered, e.g. during severe combined immunodeficiency disease (SCID), 2′deoxyadenosine accumulates and is converted to 2′-deoxyadenosine-5′-triphosphate (dATP), which inhibits ribonucleotide reductase (RNR), a crucial enzyme in DNA synthesis that follows disrupted T-cell development. Intracellular concentration of adenosine, the second substrate for ADA, is maintained inside the cell on the low level by adenosine kinase with Km value ~ 1 µM. Under conditions of low energy charge, adenosine-5′-monophosphate (AMP) that originates from adenosine-5′-triphosphate (ATP) degradation, is rapidly transformed to adenosine, which is not immediately deaminated to inosine due to high Km of ADA (25–100 µM). This results in temporary accumulation of adenosine that is vigorously exported out the cell via equilibrative nucleoside transporters (ENTs). Therefore, transmembrane adenosine transport, together with the activities of ecto-ADA and soluble ADA are important regulators of extracellular adenosine concentration. Except enzymatic function, ecto-ADA plays a significant extra-enzymatic role in the interactions between cells that expressed ADA-anchoring proteins on their surfaces. This co-stimulatory and cell-to-cell connecting actions along with its activity regulate many cellular processes related to proliferation and differentiation, which affect pathological conditions associated with cardiovascular diseases such as endothelial activation and dysfunction, inflammation, myocardial ischemia-reperfusion injury, or coagulation disorders. Since these pathologies are associated with ADA overexpression, the inhibition of its activity as well as binding to the surface proteins exhibit an attractive therapeutic potential in cardiovascular diseases.
  • 1.8K
  • 30 Oct 2020
Topic Review
Adenosine Targeting Strategy for Glioblastoma Aggressiveness
Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. 
  • 520
  • 05 Sep 2022
Topic Review
Adenoviral Gene Therapy Vectors
Adenoviral vectors are commonly used in clinical gene therapy. Apart from oncolytic adenoviruses, vector replication is highly undesired as it may pose a safety risk for the treated patient. Thus, careful monitoring for the formation of replication-competent adenoviruses (RCA) during vector manufacturing is required.
  • 283
  • 07 Dec 2023
Topic Review
ADGRG1/GPR56 in Tumor Progression
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. 
  • 542
  • 16 Dec 2021
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