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Topic Review
STAT3 in Cell Cycle Arrest and Regulation
There are seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) that are intracellular proteins which function as signal messengers and transcription factors. They transmit signals from cytokines, growth factors, intracellular kinases, mutated oncoproteins, and other signaling pathways to the nucleus. STAT3 play critical roles within neoplastic cells, immune cells, and other stromal cells, such as cancer-associated fibroblasts (CAFs).
  • 916
  • 09 Mar 2023
Topic Review
Extracellular Vesicles Surfaces for Cancer Immunotherapy
Extracellular vesicles are small membranous particles secreted by cells. Extracellular vesicles facilitate the transportation of biomolecules, such as protein, RNA, and DNA fragments, to communicate with neighboring and distant cells. Cancer cells use extracellular vesicles to hijack the immune system and induce cancer-promoting signals. Modifying extracellular vesicles using surface engineering tools allows the addition of biomolecules for targeted delivery, thus modulating the hijacked tumor immune microenvironment to improve therapeutic efficacy.
  • 916
  • 31 May 2023
Topic Review
Chimera and Tandem-Repeat Type Galectins
In humans, a total of 12 galectins have been identified. These galectins play important roles in controlling immune responses within the tumour microenvironment (TME) and the infiltration of immune cells, including different subsets of T cells, macrophages, and neutrophils, to fight against cancer cells. However, these infiltrating cells also have repair roles and are hijacked by cancer cells for pro-tumorigenic activities. Upon a better understanding of the immunomodulating functions of galectin-3 and -9, their inhibitors, namely, GB1211 and LYT-200, have been selected as candidates for clinical trials. The use of these galectin inhibitors as combined treatments with current immune checkpoint inhibitors (ICIs) is also undergoing clinical trial investigations. Through their network of binding partners, inhibition of galectin have broad downstream effects acting on CD8+ cytotoxic T cells, regulatory T cells (Tregs), Natural Killer (NK) cells, and macrophages as well as playing pro-inflammatory roles, inhibiting T-cell exhaustion to support the fight against cancer cells.
  • 916
  • 19 Jun 2023
Topic Review
Solitary Fibrous Tumor
Solitary fibrous tumor (SFT) is a malignant condition that exhibits different clinical behaviors ranging from low to high aggressive SFT. Even when surgery alone provides curation rates above 60%, recurrences do occur in a fraction of patients where surgery is unable to provide disease control. Among the systemic therapeutic options, antiangiogenic compounds have shown higher efficacy than chemotherapy by indirect comparisons. 
  • 915
  • 22 Jun 2021
Topic Review
Mycobacteria and Cancer
Although the therapeutic effect of mycobacteria as antitumor agents has been known for decades, recent epidemiological and experimental studies have revealed that mycobacterium-related chronic inflammation may be a possible mechanism of cancer pathogenesis. Mycobacterium tuberculosis and non-tuberculous Mycobacterium avium complex infections have been implicated as potentially contributing to the etiology of lung cancer, whereas Mycobacterium ulcerans has been correlated with skin carcinogenesis. The risk of tumor development with chronic mycobacterial infections is thought to be a result of many host effector mechanisms acting at different stages of oncogenesis.
  • 915
  • 28 Sep 2021
Topic Review
Oral Mucositis in Cancer
Oral mucositis (OM) is a pathological condition with several oral manifestations, originate from cytotoxic effects of non-surgical cancer therapies. The clinical manifestation ranges from diffuse erythematous areas to necrotic ulcers lesions in the mucosa. The oral mucosa presents confluent, deep, and devastatingly painful ulcerations in the most advanced clinical form. Almost all oral or oropharyngeal mucosa areas undergoing radiation will develop this side effect, however, the patients undergoing chemotherapy regiment develop the condition depending on the dose and cytotoxicity of the drug used. Usually, incidence goes around 20 to 40% for solid tumors, while in the therapies with a high dose of cytotoxic drugs, like hematopoietic stem cell transplant, the incidence is around 80%. The patients that develop OM during the cancer treatment can manifest alterations in physical, mental, emotional, and social health factors, proving an unhealthy state. Patients present diet modifications and weight loss, necessitate opioid analgesics, require supplemental nutrition, increase the risk of bacteremia and sepsis, disrupt optimal cancer therapy, and increase healthcare costs. It is common the association of head and neck cancer and OM in medical care however, the frequency in other cancers has long been overlooked and underreported.  For this reason, a multidisciplinary team composed of other health professionals, as dentists, can identify and treat pathologies in advance during oncological treatment. The OM development is described in a five-step pathogenesis model with several biological factors’ combinations. The lesion occurs with the damage of basal epithelial cells due to the radio-chemotherapy. The cascade of events starts with severe alterations in the environment that involves the generation of reactive oxygen species (ROS), activation of transcription factors (NF-kB) and inflammatory pathways (COX), and up-regulation of proinflammatory cytokines (TNF-a, IL1b, and IL-6). The clinical diagnosis can be made in the early stages. The mucosa presents erythema, the patients complain of burning and intolerance of some specific foods. After two weeks, the ulcerated lesions can be detected in one or more areas of the oral cavity. The patient refers to slight discomfort and inconvenience to severe pain, dysphagia, and difficulty in eating that lead to the opioid intervention. As a result of the cancer treatment, it is common to occur salivary alterations in composition and quantity, leading to the exasperation of OM development and impairment in the patient’s quality of life. The lesions recover depending on the patient's immune compromise, however, heal spontaneously for at least 2 weeks following the completion of the therapeutic regimen. Medical and scientific community discourse about effective management of OM in cancer patients due to its high incidence and clinical significance in patient prognosis. Several scientific studies are carried out to discover a well-defined strategy that provides improved management of OM that may allow more aggressive therapeutic doses and more effective cancer treatment, improved patient survival, and wellbeing. All guidelines for the management of OM agree OM management can be divided into three basic components: general oral care, prevention, and palliative cares. The oral care purpose is to reduce some host-related risk factors for stomatitis, including lowering the impact of oral microbial flora. Therefore, a simple care protocol must be suggested, as brushing teeth, daily flossing, and mouth rinsing. In addition, spicy food, alcoholic beverages, and alcohol-based mouthwashes must be avoided. Prevention is the second most important factor in addressing oral mucositis. The combination of agents and physical strategies can provide anti-inflammatory, analgesic, and anti-microbial more effective effects in OM management. The preventive use of oral cryotherapy and photobiomodulation (PBM) therapy showed a reduction in the impact of the treatment toxicity in the oral mucosa. The OM treatment effectivity increase can be noted with the use of several pharmacological agents (pentoxifylline, benzydamine hydrochloride, thalidomide, and simvastatin) and natural products such as Omega-3 FFA, essential oils from manuka (Leptospermum scoparium), vitamins, glutamine, chamomile, aloe vera, and curcumin. The OM palliative care has focused on symptom control using topical or systemic analgesics and the application of barrier agents to cover injured mucosa. In conclusion, OM is a painful and wasting consequence of anticancer chemotherapy and/or radiotherapy.  The occurrence of this pathology increases the risk of treatment interruption and a decrease in quality of life. A multidisciplinary team can provide global attention during the treatment, detecting early necessary interventions to manage the side effects of the cytotoxic therapeutic and providing wellbeing for cancer patients.
  • 915
  • 29 Mar 2022
Topic Review
Extracellular Vesicles in Pancreatic Cancer
Pancreatic cancer (PC) is among the most devastating digestive tract cancers worldwide. This cancer is characterized by poor diagnostic detection, lack of therapy, and difficulty in predicting tumorigenesis progression. In recent years, the attention of many researchers has been concentrated on the role of extracellular vesicles and of a particular subset of extracellular vesicles, known as exosomes. These nanovesicles are able to deliver their cargos to recipient cells playing key roles in the pathogenesis and progression of many pancreatic precancerous conditions. 
  • 914
  • 29 Jun 2021
Topic Review
Transforming Growth Factor-Beta Signaling Activation in Cancer-Induced Cachexia
Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage inhibitory cytokine 1 (MIC-1/GDF15) and transforming growth factor-beta (TGF-β). Besides its double-edged role as a tumor suppressor and activator, TGF-β causes muscle loss through myostatin-based signaling, involved in the reduction in protein synthesis and enhanced protein degradation.
  • 914
  • 09 Sep 2022
Topic Review
Mechanism of Action of Lymphocyte Activation Gene 3
Lymphocyte activation gene 3 (LAG-3) (CD223) is a CD4-related activation-induced cell surface inhibitory receptor that binds to major histocompatibility complex (MHC) class II molecules with high affinity and negatively regulates T cell effector functions. 
  • 914
  • 21 Aug 2023
Topic Review
Targeted Strategies for Degradation of Key Transmembrane Proteins in Cancer
Targeted protein degradation is an attractive technology for cancer treatment due to its ability to overcome the unpredictability of the small molecule inhibitors that cause resistance mutations. Various targeted protein degradation strategies have been developed based on the ubiquitin–proteasome system in the cytoplasm or the autophagy–lysosomal system during endocytosis. Here describe technologies for the targeted inhibition and targeted degradation of the epidermal growth factor receptor (EGFR), one of the major transmembrane proteins responsible for the onset and progression of many types of cancer.
  • 914
  • 21 Sep 2023
Topic Review
Radiotherapy of Soft tissue sarcomas
       Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patients.ty.
  • 913
  • 26 Aug 2020
Topic Review
Homotrimeric P2X7 Receptor Imaging Tracers
The homotrimeric P2X7 receptor (P2X7R) is expressed by virtually all cells of the innate and adaptive immune system and plays a crucial role in various pathophysiological processes such as autoimmune and neurodegenerative diseases, inflammation, neuropathic pain and cancer. Consequently, the P2X7R is considered a promising target for therapy and diagnosis. As the development of tracers comes hand-in-hand with the development of potent and selective receptor ligands, there is a rising number of PET tracers available in preclinical and clinical studies. P2X7R antagonists can be broadly subdivided into two categories: those able to penetrate the blood-brain barrier (BBB) and enter the central nervous system, or those remaining peripherally. Commonly linked central nervous system (CNS) P2X7R applications are diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD) or multiple sclerosis (MS), as well as the formation of different types of cancer, i.e., glioblastoma multiforme (GBM). On the other hand, peripherally bioavailable P2X7R antagonists that are not BBB-permeable are attractive candidates for the treatment/diagnosis of lung and breast cancer.
  • 913
  • 20 Jan 2023
Topic Review
Dendrimers Integration in Cancer Imaging and Theranostics
Cancer is a result of abnormal cell proliferation. This pathology is a serious health problem since it is a leading cause of death worldwide. Anti-cancer therapies rely on surgery, radiation, and chemotherapy. However, these treatments still present major associated problems, namely the absence of specificity. Nanoparticles, particularly dendrimers, have been paving their way to the front line of cancer treatment, mostly for drug and gene delivery, diagnosis, and disease monitoring. This is mainly derived from their high versatility, which results from their ability to undergo distinct surface functionalization, leading to improved performance. 
  • 913
  • 13 Apr 2023
Topic Review
Capmatinib in Treatment of Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) is a leading cause of death. Capmatinib is a Type Ib MET Tyrosine Kinase Inhibitor (TKI) first discovered in 2011 and was Food and Drug Administration (FDA) approved in August 2022 for advanced NSCLC with MET exon 14 skipping mutation. Clinical trials now involve combination therapy with capmatinib, including amivantamab, trametinib, and immunotherapy. Furthermore, new drug agents, particularly antibody–drug conjugates, are being developed to help treat patients with acquired resistance from capmatinib and other tyrosine kinase inhibitors (TKIs).
  • 913
  • 01 Aug 2023
Topic Review
Delta Radiomics in Head and Neck Cancers
Delta (Δ) radiomics, a concept based on the variation of parameters extracted from medical imaging using artificial intelligence (AI) algorithms, demonstrates its potential as a predictive biomarker of treatment response in head and neck cancers (HNC). The concept of image-guided radiotherapy (IGRT), including computer tomography simulation (CT) and position control imaging with cone-beam-computed tomography (CBCT), now offers new perspectives for radiomics applied in radiotherapy. The use of Δ features of texture, shape, and size, both from the primary tumor and from the tumor-involved lymph nodes, demonstrates the best predictive accuracy. If, in the case of treatment response, promising Δ radiomics results could be obtained, even after 24 h from the start of treatment, for radiation-induced xerostomia, the evaluation of Δ radiomics in the middle of treatment could be recommended. 
  • 913
  • 30 Jun 2023
Topic Review
Human Glioblastoma Multiforme Cells
Glioblastoma multiforme is one of the most deadly neurooncological diseases due to its prominent drug resistance and pronounced potential to reccurence. Both surgical interventions and tumor invasion within brain tissue causes local mechanical disruption of healthy tissues and may be related to enhancement of epidermal growth factor (EGF) secretion by numerous non-neuronal cells (e.g glioma associated microglia and macrophages; GAMs). Thus, in our research we examined the effect of EGF on human glioblastoma T98G cells, especially in the field of the ROS-dependent mechanisms which regulate cytoskeleton architecture rearrangements and their implications for invasive potential enhancement. IMC and DIC contrast microscopy coupled with time-lapse module were applied for visualization of cellular morphology changes and motile activity modulation. Transwell® assay was applied for estimation of cellular transmigration potential. Cell cycle activity was examined with ImageStreamX image flow cytometry (PI/RNAse staining). Moreover, detailed immunocytochemical analysis of cytoskeleton architecture changes (F-actin and vinculin distribution) and determination of ROS production (CellROX probe) were performed with epi-fluorescence and TIRF microscopy coupled with 2D deconvolution. Additional measurements of chosen proteins levels were confirmed with Western blot technique. Finally, estimation of the changes in cellular bioenergetic  status (ATP and lactate levels) which is crucial for effective invasion, was conducted with bioluminescence and spectrophotometric methods. Exposition of GBM cells to EGF resulted in considerable enhancement of cells proliferation accompanied by cell cycle acceleration. Such effect was followed by remarkable augmentation of cellular motility and transmigration potential correlated with noticeable F-actin filaments rearrangements with simultaneous re-distribution of vinculin towards leading edges. Moreover, increase in cellular ROS production and changes in ATP/lactate production were noticeable, pointing the undoubted role of cellular bioenergetic homeostasis modulation in response to EGF. It is worth emphasizing, that erlotinib (EGFR inhibitor) admittedly inhibited cellular invasive potential and cytoskeleton rearrangements during incubation both with or without EGF. Additionally, in our hands, application of antioxidant N-acetyl-L-cysteine prominently endured the EGF-induced up-regulation of cellular motility. Our research indicates strong pro-mitotic and pro-migratory effect of EGF on human GBM cells. Such effect is accompanied by considerable cytoskeleton rearrangements induction and bioenergetic homeostasis modulation. Collectively, we suppose that collaborative EGFR/ROS signaling is one of the key players within EGF-induced invasiveness of GBM cells.
  • 912
  • 27 Oct 2020
Topic Review
UM-EVs involved in tumor progression
Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis.
  • 911
  • 04 Apr 2021
Topic Review
Xenoestrogens and Phytoestrogens in Cancers
According to Global Cancer Statistics 2020, the burden of cancer incidence and mortality is rapidly growing worldwide. The epidemiological features of cancer reflect both the aging and growth of the population and the changes in the prevalence and distribution of the main cancer risk factors, several of which are particularly associated with the environment. Exogenous estrogens, such as synthetic industrial estrogenic compounds (xenoestrogens) and estrogenic molecules from plants (phytoestrogens), are environmental factors that potentially cause various cancers through their interactions with cellular signaling processes involving estrogen signaling pathways.
  • 911
  • 25 Aug 2021
Topic Review
MicroRNAs as Biomarkers for Exercise-Based Cancer Rehabilitation
Expression and functions of microRNAs (miRNAs) have been widely investigated in cancer treatment-induced complications and as a response to physical activity, respectively, but few studies focus on the application of miRNAs as biomarkers in exercise-based cancer rehabilitation. Research has shown that certain miRNA expression is altered substantially due to tissue damage caused by cancer treatment and chronic inflammation. MiRNAs are released from the damaged tissue and can be easily detected in blood plasma. Levels of the miRNA present in peripheral circulation can therefore be used to measure the extent of tissue damage. Moreover, damage to tissues such as cardiac and skeletal muscle significantly affects the individual’s health-related fitness, which can be determined using physiologic functional assessments. These physiologic parameters are a measure of tissue health and function and can therefore be correlated with the levels of circulating miRNAs.
  • 911
  • 29 Mar 2022
Topic Review
A Theranostic Approach in Selective Internal Radiation Therapy
Selective internal radiation therapy (SIRT) is one of the treatment options for liver tumors. Microspheres labelled with a therapeutic radionuclide (90Y or 166Ho) are injected into the liver artery feeding the tumor(s), usually achieving a high tumor absorbed dose and a high tumor control rate. This treatment adopts a theranostic approach with a mandatory simulation phase, using a surrogate to radioactive microspheres (99mTc-macroaggregated albumin, MAA) or a scout dose of 166Ho microspheres, imaged by single photon emission computed tomography (SPECT)/CT.
  • 911
  • 03 Jan 2023
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