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Topic Review
Physiopathology of Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is a rare but aggressive B-cell hemopathy characterized by the translocation t(11;14)(q13;q32) that leads to the overexpression of the cell cycle regulatory protein cyclin D1. This translocation is the initial event of the lymphomagenesis, but tumor cells can acquire additional alterations allowing the progression of the disease with a more aggressive phenotype and a tight dependency on microenvironment signaling. To date, the chemotherapeutic-based standard care is largely inefficient and despite the recent advent of different targeted therapies including proteasome inhibitors, immunomodulatory drugs, tyrosine kinase inhibitors, relapses are frequent and are generally related to a dismal prognosis. As a result, MCL remains an incurable disease.
  • 719
  • 18 Sep 2020
Topic Review
Nanoparticles-Based Targeted Drug Delivery
Several organic and inorganic nanoplatforms that have been designed exploiting the distinctive features of the tumor microenvironment and tumor cells offer favorable physicochemical properties and pharmacokinetic profiles of a parent drug, with delivery of higher amounts of the drug to the pathological site and its controlled release, thereby improving the balance between its efficacy and toxicity. Advances to this front have included the design and construction of targeted nanoparticles by conjugating homing devices like peptide, ligand, and Fab on the surface of nanomaterials to navigate nanoparticle drug complexes towards the target tumor cell with minimal destruction of healthy cells. Furthermore, actively targeting nanoparticles can facilitate the delivery and cellular uptake of nanoparticle-loaded drug constructs via binding with specific receptors expressed aberrantly on the surface of a tumor cell. Herein, we present an overview of the principle of targeted delivery approaches, exploiting drug-nanoparticle conjugates with multiple targeting moieties to target specific receptors of breast cancer cells and highlighting therapeutic evaluation in preclinical studies. We conclude that an understanding of the translational gap and challenges would show the possible future directions to foster the development of novel targeted nanotherapeutics. 
  • 718
  • 11 Mar 2021
Topic Review
Metal-Based Chemotherapeutic Treatments
Herein we provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments.
  • 718
  • 25 May 2021
Topic Review
Nanoparticles for Thyroid Cancers
Thyroid cancer (TC) is rare relative to cancers of many other organs (breast, prostate, lung, and colon). The majority of TCs are differentiated tumors that are relatively easy to treat and have a good prognosis. However, for anaplastic TC, a rapidly growing and aggressive tumor, treatment is suboptimal because the effective drugs cause severe adverse effects. Drug delivery by nanocarriers can improve treatment by reducing side effects. This can either be mediated through better retention in the tumor tissue due to size (passive targeting) or through the attachment of specific molecules that zero in on the cancer cells (active targeting). Nanoparticles are already used for diagnosis and imaging of TC. For unresectable anaplastic TC, nanoparticle-based treatments, less suitable for deeply located cancers, could be useful, based on low-intensity focused ultrasound and near-infrared irradiation. All potential applications of nanoparticles in TC are still in the preclinical phase. 
  • 718
  • 23 Aug 2021
Topic Review
Radiometal-Labeled Peptides in Cancer Diagnosis
Radiolabeled biomolecules targeted at tumor-specific enzymes, receptors, and transporters in cancer cells represent an intensively investigated and promising class of molecular tools for the cancer diagnosis and therapy. High specificity of such biomolecules is a prerequisite for the treatment with a lower burden to normal cells and for the effective and targeted imaging and diagnosis. The most impressive outputs in categories of newly developed structures, as well as imaging and diagnosis approaches, and the most intensively studied oncological diseases in this context, are emphasized in order to show future perspectives of radiometal labeled amino acid-based compounds in nuclear medicine.
  • 716
  • 17 Mar 2021
Topic Review
Apigenin Increases SHIP-1 Expression
The bioflavonoid apigenin (API) is used to reduce inflammation in different PC models. Wild type mice harboring heterotopic or orthotopic PC were treated with API, which induced SHIP-1 expression, reduced inflammatory tumor-derived factors (TDF), increased the proportion of tumoricidal macrophages and enhanced anti-tumor immune responses, resulting in a reduction in tumor burden compared to vehicle-treated PC mice. In contrast, SHIP-1-deficient mice exhibited an increased tumor burden and displayed augmented proportions of pro-tumor macrophages. These results provide further support for the importance of SHIP-1 expression in promoting pro-tumor macrophage development in the pancreatic TME. 
  • 716
  • 17 Dec 2020
Topic Review
Chemotherapy-Induced Gastrointestinal Mucositis and Anti-Infective Drugs
Gastrointestinal mucositis (GI-M) is a frequently observed side effect of chemotherapy in patients with cancer that affects the gastrointestinal microenvironment and potentially drug absorption. 
  • 715
  • 15 Oct 2021
Topic Review
Smoothened-Dependent/-Independent Hedgehog Signaling Pathway
The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved among mammals, with crucial roles in regulating embryonic development as well as in cancer initiation and progression. The GLI transcription factors (GLI1, GLI2, and GLI3) are effectors of the Hh pathway and are regulated via Smoothened (SMO)-dependent and SMO-independent mechanisms. The SMO-dependent route involves the common Hh-PTCH-SMO axis, and mutations or transcriptional and epigenetic dysregulation at these levels lead to the constitutive activation of GLI transcription factors. Conversely, the SMO-independent route involves the SMO bypass regulation of GLI transcription factors by external signaling pathways and their interacting proteins or by epigenetic and transcriptional regulation of GLI transcription factors expression. Both routes of GLI activation, when dysregulated, have been heavily implicated in tumorigenesis of many known cancers, making them important targets for cancer treatment. 
  • 714
  • 15 Sep 2021
Topic Review
Ultrasound for the Characterization of Renal Masses
Ultrasound is a widely available, approachable, and relatively inexpensive imaging modality that allows for real-time evaluation of a suspected renal mass without the drawbacks of ionizing radiation and the risk of an MRI. CEUS has several advantages over traditional grayscale ultrasound in the characterization of indeterminate renal masses. It has a distinct value in the characterization of cystic renal masses and has the potential to differentiate benign from malignant renal masses to some extent. Ultrasound molecular imaging could potentially be an extension of the use of CEUS for serial disease monitoring and longitudinal assessment of treatment response, though it remains in preclinical stages of development at this time. While emerging micro-Doppler techniques and elastography have shown some encouraging applications, current evidence is limited, and neither is ready for widespread clinical use.
  • 714
  • 09 Mar 2022
Topic Review
Circadian Rhythms and Glioblastomas
Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I–IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells.
  • 713
  • 15 Aug 2021
Topic Review
Colorectal cancer and bone tissue
Colorectal cancer (CRC) is the third most common cancer worldwide. There is a need for the early diagnosis of CRC for a better prognostic outcome. It is, therefore, crucial to understand the CRC pathogenesis in all its aspects. In many cases, one of the main causes of cancer-related deaths is the presence of metastases. In this context, an often overlooked aspect is the metastatic tropism, since CRC, like other cancers, is more prone to metastasize some organs rather than others. Beyond the liver and lung, and differently from other types of cancers, a not usual site of CRC metastases is the bone. However, it may assume a crucial role in the development and the outcome of the disease. Therefore, this review aims to discuss the complex relations between bone markers and CRC pathogenesis, suggesting the use of these molecules as potential targets for therapeutic purposes. Different osteogenic molecules, some of whom are growth factors and are implicated in the different osteogenic pathways, have been proved to also be involved in CRC progression. Some of them are oncogenes, while others oncosuppressors, and in a future perspective, some of them may represent new potential CRC biomarkers.
  • 712
  • 04 Aug 2020
Topic Review
Delivery vehicles in Veterinary Oncology
Nanomedicine is a recent concept in veterinary oncology and provide the possibility of more specific treatment to the patients. In this critical review, we provided the most updated information regarding the use of nanoparticles in veterinary oncology. 
  • 711
  • 26 Oct 2020
Topic Review
Cold-Shock Domains
The cold-shock domain has a deceptively simple architecture but supports a complex biology. Cold-shock domains in human proteins are often associated with natively unfolded protein segments and more rarely with other folded domains. Human proteins containing cold-shock domains bind single-stranded DNA and/or RNA and serve a large variety of roles in regulating transcription, DNA-damage repair, RNA splicing, translation, stability and sequestration.
  • 711
  • 23 Feb 2021
Topic Review
Synergistically Anti-Multiple: Flavonoid, Non-Flavonoid Polyphenols, and Bortezomib
Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. When two or more medications are combined to improve their therapeutic effects, this is referred to as drug synergism. For various diseases, including MM, appropriate drug combinations can reduce drug resistance or maximize efficacy. Bortezomib (BTZ), as a clinically used protease inhibitor, is a cornerstone of Velcade, Revlimid, and Dexamethasone (VRD).  Flavonoids and non-flavonoid polyphenols are potential supportive therapies to address some of the challenges faced in BTZ treatment. 
  • 711
  • 22 Nov 2022
Topic Review
Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment for a variety of hematologic malignancies, immune disorders and metabolic diseases. Allo-HSCT often represents the only possible curative therapy, however it is hampered by high morbidity and mortality rates for an array of complications, including bloodstream infection and graft-versus-host disease (GvHD).
  • 710
  • 22 Feb 2021
Topic Review
Matrisomal Gene Panel for Head and Neck Cancer
Squamous cell carcinoma of the head and neck (SCCHN) is common worldwide and related to several risk factors including smoking, alcohol consumption, poor dentition and human papillomavirus (HPV) infection. Different etiological factors may influence the tumor microenvironment and play a role in dictating response to therapeutics. Here, we sought to investigate whether an early-stage SCCHN-specific prognostic matrisome-derived gene signature could be identified for HPV-negative SCCHN patients (n = 168), by applying a bioinformatics pipeline to the publicly available SCCHN-TCGA dataset. We identified six matrisome-derived genes with high association with prognostic outcomes in SCCHN. A six-gene risk score, the SCCHN TMI (SCCHN-tumor matrisome index: composed of MASP1, EGFL6, SFRP5, SPP1, MMP8 and P4HA1) was constructed and used to stratify patients into risk groups. Using machine learning-based deconvolution methods, we found that the risk groups were characterized by a differing abundance of infiltrating immune cells. 
  • 710
  • 23 Nov 2021
Topic Review
Genetic and Molecular Basis of Von Hippel-Lindau Disease
Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem neoplastic disorder, stemming from germline disease-associated variants of the VHL tumor suppressor gene. VHL protein is involved in oxygen sensing and adaptive response to hypoxia through the EPO-VHL-HIF signaling axis. In recent years, numerous HIF-independent pathways of VHL have been identified, expanding the role of VHL throughout several cellular processes. In addition to VHL syndrome-associated tumors, VHL variations have also been associated with the development of eythrocytosis. Research indicated that there is a distinction between erythrocytosis-causing VHL variations and VHL variations causing VHL disease with tumor development. Therefore, elucidating the molecular background of the pathogenic effects of VHL variants could help determine the best approach to VHL disease management.  
  • 710
  • 24 Mar 2022
Topic Review
Senescence Induction
Cellular senescence is a process resulting in stable cell cycle arrest, which restricts ability of cells to proliferate. It is considered that this state might be a response to chemotherapy, both genotoxic and oxidative stress, oncogenic activation, shortening of telomeres, irradiation or mitochondrial disorder. Senescence is generally considered as a process of tumor suppression, both by preventing cancer cells proliferation and inhibiting cancer progression. It can also be a key effector mechanism for many types of anticancer therapies such as chemotherapy and radiotherapy, both directly and through bioactive molecules released by senescent cells that can stimulate an immune response. Senescence is characterized by a senescence-associated secretory phenotype (SASP) that can have both beneficial and detrimental impact on cancer progression.
  • 710
  • 11 Oct 2022
Topic Review
Immunoproteasome
Proteasome inhibition is a promising strategy for the treatment of multiple myeloma; unfortunately, this disease is often associated with an increasing chemoresistance. One novel approach may be to target the immunoproteasome, a proteasomal isoform mainly present in cells of hematopoietic origin. We investigated the activity of a panel of amides against immunoproteasome core particles as potential agents for the treatment of multiple myeloma (MM). Amide 6 showed an ideal profile since it was able to inhibit both the chymotrypsin-like activities of the immunoproteasome with Ki values of 4.90 µM and 4.39 µM for β1i and β5i, respectively, coupled with an EC50 =17.8 µM against MM.1R cells. Compound 6 inhibited also ubiquitinated protein degradation and was able to act on different phases of MM cell cycle reducing the levels of cyclin A/CDK1, cyclin B/CDK1 and cyclin D/CDK4/6 complexes, which turns in cell cycle arrest.
  • 709
  • 03 Nov 2020
Topic Review
Ionizing Radiation and Complex DDR
Ionizing radiation is a common tool in medical procedures. Monte Carlo (MC) techniques are widely used when dosimetry is the matter of investigation. The scientific community has invested, over the last 30 years, a lot of effort into improving the knowledge of radiation biology. 
  • 709
  • 23 Jun 2021
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