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Topic Review
Chloroquine and Hydroxychloroquine
The chloroquine family of antimalarials has a long history of use, spanning many decades. Despite this extensive clinical experience, novel applications, including use in autoimmune disor-ders, infectious disease, and cancer, have only recently been identified. While short term use of chloroquine or hydroxychloroquine is safe at traditional therapeutic doses in patients without pre-disposing conditions, administration of higher doses and for longer durations are associated with toxicity, including retinotoxicity. Additional liabilities of these medications include pharmacokinetic profiles that require extended dosing to achieve therapeutic tissue concentrations. To improve chloroquine therapy, researchers have turned toward nanomedicine reformulation of chloroquine and hydroxychloroquine to increase exposure of target tissues relative to off-target tissues, thereby improving the therapeutic index.
  • 695
  • 19 Jan 2021
Topic Review
Dual Kinase Targeting in Leukemia
Pharmacological cancer therapy is often based on the concurrent inhibition of different survival pathways to improve treatment outcomes and to reduce the risk of relapses. While this strategy is traditionally pursued only through the co-administration of several drugs, the recent development of multi-targeting drugs (i.e., compounds intrinsically able to simultaneously target several macromolecules involved in cancer onset) has had a dramatic impact on cancer treatment.
  • 695
  • 21 Feb 2021
Topic Review
Tumor Cell Signaling Pathways
Increasing the understanding of carcinogenesis has allowed the delineation of crucial signaling pathways, which have shown essential roles in the regulation of stem cell functions
  • 695
  • 09 Sep 2022
Topic Review
Bone Metastasis and Microenvironment in NSCLC
Patients with non-small cell lung cancer (NSCLC) develop bone metastasis (BoM) in more than 50% of cases during the course of the disease. This metastatic site can lead to the development of skeletal related events (SREs), such as severe pain, pathological fractures, spinal compression, and hypercalcemia, which reduce the patient’s quality of life. Recently, the treatment of advanced NSCLC has radically changed due to the advent of immunotherapy. Immune checkpoint inhibitors (ICI) alone or in combination with chemotherapy have become the main therapeutic strategy for advanced or metastatic NSCLC without driver gene mutations. Since survival has increased, it has become even more important to treat bone metastasis to prevent SRE. The lower efficacy of immunotherapy treatments in BoM+ patients could be induced by the presence of a particular immunosuppressive tumor and bone microenvironment. 
  • 695
  • 27 Jul 2022
Topic Review
Antisense Oligonucleotide-Mediated Splice Switching
Antisense oligonucleotides (AOs) have been developed to inhibit the production of alternatively spliced carcinogenic isoforms through splice modulation or mRNA degradation. AOs can also be used to induce splice switching, where the expression of an oncogenic protein can be inhibited by the induction of a premature stop codon. In general, AOs are modified chemically to increase their stability and binding affinity. One of the major concerns with AOs is efficient delivery. Strategies for the delivery of AOs are constantly being evolved to facilitate the entry of AOs into cells. 
  • 695
  • 25 Nov 2021
Topic Review
Orofacial Cancers
Orofacial cancers result in facial deformities and impairment of vital functions and are often lethal. These aggressive solid tumors exhibit great heterogeneity between them and show distinct and exclusive molecular alterations that deregulate the function of important signaling pathways. The Notch signaling pathway is involved in the initiation and development of orofacial cancers. Increasing evidence suggests that Notch molecules may have a dual function in cancer, acting either as oncogenes or tumor suppressor genes. Crosstalk between Notch and other signaling pathways provides a critical multidirectional control in these cancers. Protein phosphorylation is activated in cancers and therefore novel drugs inhibiting phosphorylation events (kinase inhibitors) are increasingly used in the treatment of cancers. Another pharmacological strategy is the selective targeting of Notch signaling in order to eliminate the cancer stem cells using monoclonal antibodies against specific regions of the Notch molecules. Organoids, “organ-on-a-chip” devices and single-cell genomic analyses could be used for further investigations and preclinical studies in orofacial cancers. Organoids can be used to study complex interactions between the various cells lines in orofacial cancers, as well as for the preclinical screening of novel drugs. Microfluidic culture systems, also called “organs-on-chips”, can be used to model cancer cell behavior within orofacial tissues and their environment. These chips also enable to vary drug delivery and composition in a controlled manner in order to study cancer tissue responses to various pharmaceutical anticancer products. Single-cell RNA-seq analyses allow exploring the genetic and functional heterogeneity of orofacial cancers at a cellular resolution, thus revealing new insights into tumor composition and drug resistance. These important technological developments and the innovative therapeutic strategies demonstrate significant promise and generate enthusiasm and optimism within the oncology community.
  • 694
  • 28 Oct 2020
Topic Review
Non-Coding RNAs in Glioblastoma
Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with glioblastoma onset/progression.
  • 694
  • 28 Oct 2020
Topic Review
Abscopal Effect
The abscopal effect (AbE) is defined as radiation-induced shrinkage of distant, non-treated, neoplastic lesions and it is considered the best clinical picture of the efficient immune stimulation by irradiation.
  • 693
  • 17 Nov 2021
Topic Review
Artificial Intelligence in Lung Cancer
Lung cancer is the leading cause of malignancy-related mortality worldwide. AI has the potential to help to treat lung cancer from detection, diagnosis and decision making to prognosis prediction. AI could reduce the labor work of LDCT, CXR, and pathology slides reading. AI as a second reader in LDCT and CXR reading reduces the effort of radiologists and increases the accuracy of nodule detection. 
  • 693
  • 16 Mar 2022
Topic Review
Mammalian Target of Rapamycin and Cancer
The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Even though mTOR signaling plays a critical role in promoting mitochondria-related protein synthesis, suppressing the catabolic process of autophagy, contributing to lipid metabolism, engaging in ribosome formation, and acting as a critical regulator of mRNA translation, it remains one of the significant signaling systems involved in the tumor process, particularly in apoptosis, cell cycle, and cancer cell proliferation. Therefore, the mTOR signaling system could be suggested as a cancer biomarker, and its targeting is important in anti-tumor therapy research. 
  • 693
  • 21 Nov 2022
Topic Review
Adipose Tissue-Derived Extracellular Vesicles
Extracellular vesicles (EVs) are crucial elements that sustain the communication between tumor cells and their microenvironment, and have emerged as a widespread mechanism of tumor formation and metastasis. In obesity, the adipose tissue becomes hypertrophic and hyperplastic, triggering increased production of pro-inflammatory adipokines, such as tumor necrosis factor α, interleukin 6, interleukin 1, and leptin.
  • 691
  • 11 Aug 2021
Topic Review
Metabolic Anti-Cancer Effects of Melatonin
Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers. 
  • 690
  • 08 Jul 2021
Topic Review
Chloride Intracellular Channel Proteins and Malignant Tumor Progression
Chloride intracellular channel proteins (CLICs are the dimorphic protein present in both soluble and membrane fractions. As an integral membrane protein, CLICs potentially possess ion channel activity. In vertebrates, CLICs are classified into six classes: CLIC1, 2, 3, 4, 5, and 6. CLIC2 is expressed at higher levels in benign tumors than in malignant ones, most likely preventing tumor cell invasion into surrounding tissues. CLIC2 is also expressed in the vascular endothelial cells of normal tissues and maintains their intercellular adhesive junctions, presumably suppressing the hematogenous metastasis of malignant tumor cells. 
  • 690
  • 11 Oct 2022
Topic Review
Tumor Suppressor WT1
The Wilms’ tumor 1 (WT1) gene was originally identified based on its mutational inactivation in Wilms’ tumor (nephroblastoma). This first discovery of WT1 as the responsible gene in an autosomal-recessive condition classified it as a tumor-suppressor gene. Mutations of WT1 were associated with the development of kidney tumors and urogenital defects.
  • 690
  • 26 Jul 2021
Topic Review
Esophageal and Gastric Tumors
Gastric and esophageal tumors are diverse neoplasms that involve mucosal and submucosal tissue layers and include squamous cell carcinomas, adenocarcinomas, spindle cell neoplasms, neuroendocrine tumors, marginal B cell lymphomas, along with less common tumors. The worldwide burden of esophageal and gastric malignancies is significant, with esophageal and gastric cancer representing the ninth and fifth most common cancers, respectively. The approach to diagnosis and staging of these lesions is multimodal and includes a combination of gastrointestinal endoscopy, endoscopic ultrasound, and cross-sectional imaging. Likewise, therapy is multidisciplinary and combines therapeutic endoscopy, surgery, radiotherapy, and systemic chemotherapeutic tools. Future directions for diagnosis of esophageal and gastric malignancies are evolving rapidly and will involve advances in endoscopic and endosonographic techniques including tethered capsules, optical coherence tomography, along with targeted cytologic and serological analyses. 
  • 689
  • 23 Feb 2021
Topic Review
Surgical Approaches to Neuroblastoma
Neuroblastoma (NB) is the most commonly occurring soft-tissue malignancy of childhood. Surgery plays an important role in multidisciplinary treatment and its principal aim is a local control of the disease, respecting the integrity of the surrounding structures. There is no unanimous consensus on the best surgical technique, and the operative approach largely depends on the anatomical location and the extension of the mass. To have a complete overview of the different type of treatment, we made a review of the literature from the last twenty years of all the surgical approaches applied for NBs resection, accordingly to the anatomical site.
  • 689
  • 23 Jun 2021
Topic Review
Dynamic Cancer Cell Heterogeneity
Though heterogeneity of cancers is recognized and has been much discussed in recent years, the concept often remains overlooked in different routine examinations. Indeed, in clinical or biological articles, reviews, and textbooks, cancers and cancer cells are generally presented as evolving distinct entities rather than as an independent heterogeneous cooperative cell population with its self-oriented biology. There are, therefore, conceptual gaps which can mislead the interpretations/diagnostic and therapeutic approaches.
  • 688
  • 07 Feb 2022
Topic Review
Proneural-Mesenchymal Transition
Glioblastoma (GBM) is an extremely aggressive tumor of the central nervous system, with a prognosis of 12–15 months and just 3–5% of survival over 5 years. This is mainly because most patients suffer recurrence after treatment that currently consists in maximal resection followed by radio- and chemotherapy with temozolomide. GBM has been classified into four molecular subgroups namely proneural, neural, classical and mesenchymal. The recurrent tumor shows a more aggressive behavior due to a phenotypic shift from the proneural toward the mesenchymal subtype. Proneural-mesenchymal transition (PMT) may represent for GBM the equivalent of epithelial–mesenchymal transition associated with aggressive carcinomas. 
  • 687
  • 14 Dec 2021
Topic Review
Simultaneous Monitoring of Multi-Enzyme Activity
The use of fluorescent imaging probes that monitor the activity of proteases that experience an increase in expression and activity in tumors is well established. These probes can be conjugated to nanoparticles of iron oxide, creating a multimodal probe serving as both a magnetic resonance imaging (MRI) agent and an indicator of local protease activity. Previous works describe probes for cathepsin D (CatD) and metalloproteinase-2 (MMP2) protease activity grafted to cross-linked iron oxide nanoparticles (CLIO). Herein, we have synthesized a triply labeled fluorescent iron oxide nanoparticle molecular imaging (MI) probe, including an AF750 substrate concentration reporter along with probes for cathepsin B (CatB) sand MMP2 protease activity. The reporter provides a baseline signal from which to compare the activity of the two proteases. The activity of the MI probe was verified through incubation with the proteases and tested in vitro using the human HT29 tumor cell line and in vivo using female nude mice injected with HT29 cells. We found the MI probe had the appropriate specificity to the activity of their respective proteases, and the reporter dye did not activate when incubated in the presence of only MMP2 and CatB. Probe fluorescent activity was confirmed in vitro, and reporter signal activation was also noted. The fluorescent activity was also visible in vivo, with injected HT29 cells exhibiting fluorescence, distinguishing them from the rest of the animal. The reporter signal was also observable in vivo, which allowed the signal intensities of the protease probes to be corrected; this is a unique feature of this MI probe design.
  • 686
  • 30 Oct 2020
Topic Review
Timing of Metastatic Colorectal Cancer
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, where ~50% of patients develop metastasis, despite current improved management. Genomic characterisation of metastatic CRC, and elucidating the effects of therapy on the metastatic process, are essential to help guide precision medicine. Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naïve and treated CRC primary tumours (n = 92 tumour regions) and metastases (n = 99 tumour regions), in 30 patients. Somatic variants were analysed to define the origin, composition, and timing of seeding in the metastatic progression of therapy-naïve and treated metastatic CRC. High concordance, with few genomic differences, was observed between primary CRC and metastases. Most cases supported a late dissemination model, via either monoclonal or polyclonal seeding. Polyclonal seeding appeared more common in therapy-naïve metastases than in treated metastases. Whereby, treatment prompted for the selection of distinct resistant clones, through monoclonal seeding to distant metastatic sites. Overall, this study reinforces the importance of early clinical detection and surgical excision of the CRC tumour, whilst further highlighting the clinical challenges for metastatic CRC with increased intratumour heterogeneity (either due to early dissemination or polyclonal metastatic spread) and the underlying risk of future therapeutic resistance in treated patients.
  • 686
  • 20 Oct 2020
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