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Topic Review
Wnt Pathway: A Tailored Target
Cancer represents one of the greatest public health challenges. One of the most cancer-driving events embodies the dysregulation of both the canonical and the non-canonical Wnt/β-catenin pathway. The impact of the Wnt/β-catenin pathway has been widely reviewed in colorectal, breast, and ovarian cancers.  Genetic and epigenetic alterations are commonly detected in colorectal cancers (CRCs). As a matter of fact, 70% of CRCs are connoted by the APC mutations and almost all patients display an overactive Wnt/β-catenin pathway also mediated by oncogenic miRNAs. Therefore, miRNAs have been proposed as anti-cancer and/or diagnostic/prognostic tools. Among cancers, breast cancer (BC) is one of the most expensive health care costs with a high rate of diagnosis and deaths per year. The Wnt/β-catenin cascade and in particular the β-catenin content has been correlated with a dismal prognosis, high tumour grade, and metastasis formation. In addition in triple-negative breast cancer (TNBC) both the canonical and the non-canonical Wnt/β-catenin pathways have been reported as drivers of cancer dissemination, aggressiveness, early age of onset, and poor outcome. To add further complexity, the Wnt5a ligand was found to display both anti-tumour and tumour promoting properties depending on the tumour microenvironment (TME), the activation of specific signalling pathways, and the receptor availability in BC.  Likewise, an abnormal Wnt/β-catenin cascade has been shown to strongly contribute to ovarian cancer (OC) growth, stemness, and drug resistance.  In the last decades, particular attention has been dedicated to investigate the role of extracellular vesicles (EVs) released in the TME in cancer growth and progression. EVs are heterogeneous small membrane-bound carriers with a complex cargo contributing to cell-to-cell communication, tumour growth, invasion, and chemoresistance. Since EVs can be detected in the majority of biological fluids and in the TME, EVs have been proposed as diagnostic and/or prognostic tools, as well as useful therapeutic options. Indeed, EVs engineered with specific anti-tumour molecules or loaded with conventional anti-tumour drugs have been proposed as novel anti-cancer options. Based on these notions, in the last decades, Wnt/β catenin targeting approaches have been explored to hinder tumour expansion. However so far, the most relevant limitation relies on the crucial role played by the Wnt/β catenin cascade in tissue homeostasis. Therefore, to develop targeting approaches the identification of the specific EV cargo driving tumour progression and the mechanisms accounting for the unbalanced Wnt/β catenin pathway in cancer should be considered as the most challenging issues.
  • 645
  • 03 Nov 2020
Topic Review
WMHs and Vascular Cognitive Impairment
White matter hyperintensities (WMHs) of presumed vascular origin are one of the imaging markers of cerebral small-vessel disease, which is prevalent in older individuals and closely associated with the occurrence and development of cognitive impairment. The heterogeneous nature of the imaging manifestations of WMHs creates difficulties for early detection and diagnosis of vascular cognitive impairment (VCI) associated with WMHs. Because the underlying pathological processes and biomarkers of WMHs and their development in cognitive impairment remain uncertain, progress in prevention and treatment is lagging. For this reason,this paper reviews the status of research on the features of WMHs related to VCI,as well as mediators associated with both WMHs and VCI,and summarizes potential treatment strategies for the prvention and intervention in WMHs associated with VCI.
  • 435
  • 24 Aug 2021
Topic Review
Wilson’s Disease
Wilson disease (WD) is a rare disorder caused by mutations in ATP7B, which leads to a defective biliary excretion of copper. Subsequent gradual accumulation of copper in different organs produces an extremely variable clinical picture, which comprises hepatic, neurological psychiatric, ophthalmological, and other disturbances. WD has specific treatment, so that early diagnosis is crucial in order to avoid the progression of the disease and its devastating consequences. The clinical diagnosis of WD is based on the Leipzig scale, which considers clinical, histological, biochemical and genetic data. However, even patients with an initial WD diagnosis based on a high Leipzig score result to suffer from other condition that mimics the WD’s phenotype (Wilson-like).
  • 1.1K
  • 22 Sep 2021
Topic Review
Wilms’ Tumor Gene
WT1 was initially identified as a tumor-suppressor gene involved in the pathogenesis of childhood renal Wilms’ tumor. The gene is located on chromosome 11 (band 11p13) and encodes for a zinc finger DNA-binding protein with four major isoforms, each of which plays a significant role in normal gene function.
  • 347
  • 22 Jun 2022
Topic Review
Wilms Tumor (Nephroblastoma)
Wilms tumor (or nephroblastoma) is a malignant and solid neoplasm that derives from the primitive renal bud. It represents the most frequent primary tumor of the urogenital tract in childhood, and treatment consists of surgery and chemo-radiotherapy. 
  • 191
  • 19 Dec 2023
Topic Review
Will
Will, generally, is a faculty of the mind - within philosophy, will is important as one of the parts of the mind, along with reason and understanding. It is considered central to the field of ethics because of its role in enabling deliberate action. One of the recurring questions discussed in the Western philosophical tradition is that of free will - and the related, but more general notion of fate - which asks how the will can be truly free if a person's actions have either natural or divine causes which determine them. In turn, this is directly connected to discussions on the nature of freedom and to the problem of evil.
  • 2.8K
  • 11 Oct 2022
Topic Review
Wild-type IDH Enzymes
Isocitrate dehydrogenases (IDHs) are enzymes that catalyze the oxidative decarboxylation of isocitrate, producing α-ketoglutarate (αKG) and CO2. The discovery of IDH mutations in several malignancies has led to a better characterization of IDHs involvement in tumorigenesis and the approval of drugs targeting IDH1/2 mutants in cancers. Nevertheless, less is known about the impact of IDH mutants in rare pathologies or the relevance of non-mutated IDH enzymes in cancers. Here, we provide a brief overview of the impact of IDHs enzymes as potential therapeutic targets.  
  • 1.4K
  • 30 Oct 2020
Topic Review
Wide Local Excision in Primary Cutaneous Melanoma Management
Surgical wide local excision (WLE) is an elective procedure involving the excision of a larger area of tissue surrounding the scar left after diagnostic excision of a primary cutaneous melanoma. It remains the current standard of care for primary cutaneous melanoma and aims to achieve locoregional disease control with minimal functional and cosmetic impairment. Despite several prospective randomised trials, the optimal extent of excision margin remains controversial, and this is reflected in the persistent lack of consensus in guidelines globally.
  • 140
  • 01 Mar 2024
Topic Review
Wickerhamomyces Yeast Killer Toxins
Bacteriocins are ribosomally synthesized antimicrobial peptides produced from a wide variety of bacteria that inhibit the growth of similar or closely related bacterial strains. A similar phenomenon of competition is present in yeasts, based on the production of killer toxins (KTs, or mycocins) that are secreted proteins or glycoproteins capable of killing susceptible microorganisms with various mechanisms of action, through interaction with specific superficial receptors. Possible implications and applications of the yeast killer phenomenon in the fight against infectious diseases are reviewed in this work, with particular reference to some wide-spectrum killer toxins (KTs) produced by Wickerhamomyces anomalus and other related species. 
  • 644
  • 15 Oct 2021
Topic Review
Whole-Person Approach to Urinary Tract Infection
Urobiome dysbiosis, defined as an imbalance in the microbial composition in the microenvironments along the urinary tract, is found in women with uncomplicated urinary tract infection (UTI). Historically, antibiotics have been used to address UTI. An alternative approach to uncomplicated UTI is warranted as the current paradigm fails to take urobiome dysbiosis into account and contributes to the communal problem of resistance. A whole-person, multi-modal approach that addresses vaginal and urinary tract dysbiosis may be more effective in reducing recurrent UTI.
  • 448
  • 18 Feb 2022
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