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Topic Review
Breast carcinoma eukaryotic initiation factors
Breast cancer is the most frequent neoplasm in females. It is a heterogenous entity, classified into intrinsic subtypes based on gene expression data and in corresponding clinical subtypes based on the determination of hormone receptor expression and proliferative activity estimated from ki67 by immunohistochemistry. As for other tumors, the metabolism of breast tumors depends on aerobic glycolysis ("Warburg-effect") and the capability for effective biosynthesis of proteins. Quantity and quality of protein biosynthesis is mainly controlled in the initiation phase of translation, which is characterized by a complex interaction of eucaryotic initiation factors with the mRNA and ribosomal proteins to form a translationally active ribosome. Thus the eIF subunit composition varies from cancer to cancer and is a key factor for determining the cancer cell´s proteome. eIFs can therefore become a suitable anti-cancer drug target. We here summarize the current knowledge on eIF expression and prognostic impact in breast cancer.
  • 946
  • 11 Aug 2020
Topic Review
Repurposing Nelfinavir for Cancer Therapy
Nelfinavir is an anti-infective agent that has extensively been used to treat acquired immunodeficiency syndrome (AIDS) in adult and pediatric patients. In addition to its anti-infective properties, nelfinavir has demonstrated potent off-target anti-cancer effects, suggesting that it could be a suitable candidate for drug repurposing for cancer.
  • 946
  • 07 Dec 2020
Topic Review
Brain-Gut Axis
The brain-gut axis represents a complex bi-directional system comprising multiple interconnections between the neuroendocrine pathways, the autonomous nervous system and the gastrointestinal tract. Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract with a multifactorial etiology. 
  • 946
  • 25 Feb 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.
  • 946
  • 28 Sep 2021
Topic Review
Genetic Therapy in Oncology
The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes—mainly targeted therapy, immunomodulatory therapy, and gene therapy. 
  • 946
  • 03 Nov 2023
Topic Review
β-Catenin in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the deadliest human cancers. Activating mutations in the telomerase reverse transcriptase (TERT) promoter (TERTp) and CTNNB1 gene encoding β-catenin are widespread in HCC (~50% and ~30%, respectively). TERTp mutations are predicted to increase TERT transcription and telomerase activity. 
  • 945
  • 02 Sep 2021
Topic Review
Estrogen Receptors in Non Small Cell Lung Cancer
This entry highlights that exogenous and endogenous sources of estrogens in the human body.  Estrogen associated receptors ERs, GPERs, EGFRs and orphan nuclear receptors ERRs. Role of estrogens and associated receptors in normal lung physiology and NSCLC complications. Potential of using anti-estrogen molecules, alone or in combination with ER/GPER/ EGFR/ERR inhibitors as NSCLC treatment regimen.
  • 945
  • 10 Jan 2022
Topic Review
Atherosclerosis, Diabetes Mellitus, and Cancer
The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer.
  • 944
  • 26 Jul 2023
Topic Review
Androgen Receptor in Lung Development and Lung Cancer
Sex hormones (SHs) and their receptors (SHRs) play a crucial role in human sexual dimorphism and have been traditionally associated with hormone-dependent cancers like breast, prostate, and endometrial cancer. Research has broadened the understanding by revealing connections with other types of cancers, such as lung cancer (LC), where the androgen receptor (AR) plays a significant role. 
  • 944
  • 26 Dec 2023
Topic Review
Polyphenols in Leukaemia
Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Here we discuss the potential therapeutic use of polyphenols in leukaemia. We outline the molecular mechanism of action of polyphenol in leukaemia cell lines, and discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism is essential to evaluate their clinical use. 
  • 943
  • 22 Sep 2021
Topic Review
Chemokines in the cholangiocarcinoma
Cholangiocarcinoma (CCA), a heterogeneous tumor with poor prognosis, can arise at any level in the biliary tree. It may derive from epithelial cells in the biliary tracts and peribiliary glands and possibly from progenitor cells or even hepatocytes. Several risk factors are responsible for CCA onset, however an inflammatory milieu nearby the biliary tree represents the most common condition favoring CCA development. Chemokines play a key role in driving the immunological response upon liver injury and may sustain tumor initiation and development. Chemokine receptor-dependent pathways influence the interplay among various cellular components, resulting in remodeling of the hepatic microenvironment towards a pro-inflammatory, pro-fibrogenic, pro-angiogenic and pre-neoplastic setting. Moreover, once tumor develops, chemokine signaling may influence its progression.
  • 942
  • 24 Aug 2020
Topic Review
EDCs function in tumor microenvironment
Endocrine disruptors (EDCs) can display estrogenic and androgenic effects, and their exposure has been linked to increased cancer risk. EDCs have been shown to directly affect cancer cell regulation and progression, but their influence on tumour microenvironment is still not completely elucidated. In this context, the signalling hub protein RACK1 (Receptor for Activated C Kinase 1) could represent a nexus between cancer and the immune system due to its roles in cancer progression and innate immune activation. Since RACK1 is a relevant EDCs target that responds to steroid-active compounds, it could be considered a molecular bridge between the endocrine-regulated tumour microenvironment and the innate immune system.
  • 942
  • 17 Dec 2020
Topic Review
Ferrocifen Loaded Lipid Nanocapsules
Resistance of cancer cells to current chemotherapeutic drugs has obliged the scientific community to seek innovative compounds. Ferrocifens, lipophilic organometallic compounds composed of a tamoxifen scaffold covalently bound to a ferrocene moiety, have shown very interesting antiproliferative, cytotoxic and immunologic effects. The formation of ferrocenyl quinone methide plays a crucial role in the multifaceted activity of ferrocifens. Lipid nanocapsules (LNCs), meanwhile, are nanoparticles obtained by a free organic solvent process. LNCs consist of an oily core surrounded by amphiphilic surfactants and are perfectly adapted to encapsulate these hydrophobic compounds. The different in vitro and in vivo experiments performed with this ferrocifen-loaded nanocarrier have revealed promising results in several multidrug-resistant cancer cell lines such as glioblastoma, breast cancer and metastatic melanoma, alone or in combination with other therapies. 
  • 942
  • 23 Jun 2021
Topic Review
FOXO3 as a Novel Biomarker in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) represents one of the main causes of cancer-related death worldwide. The transcription factor forkhead box O3 (FOXO3) has been related to hepatic diseases and tumor progression, but the exact role played by FOXO3 on HCC still remains unclear. Recently, a novel systematic review with meta-analysis revealed the potential diagnostic and prognostic value of FOXO3 in this primary liver cancer type.
  • 942
  • 05 Nov 2021
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. 
  • 942
  • 27 Jul 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. 
  • 942
  • 21 Aug 2023
Topic Review
Associations of Leptin and Adiponectin with Tumor Microenvironment
Hormones produced by adipocytes, leptin and adiponectin, are associated with the process of carcinogenesis. Both of these adipokines have well-proven oncologic potential and can affect many aspects of tumorigenesis, from initiation and primary tumor growth to metastatic progression. Involvement in the formation of cancer includes interactions with the tumor microenvironment and its components, such as tumor-associated macrophages, cancer-associated fibroblasts, extracellular matrix and matrix metalloproteinases.
  • 942
  • 29 Aug 2023
Topic Review
Metastatic Castration-Resistant Prostate Cancer
Although most prostate cancers are localized, and the majority are curable, recurrences occur in approximately 35% of men. Among patients with prostate-specific antigen (PSA) recurrence and PSA doubling time (PSADT) less than 15 months after radical prostatectomy, prostate cancer accounted for approximately 90% of the deaths by 15 years after recurrence. An immunosuppressive tumor microenvironment (TME) and impaired cellular immunity are likely largely responsible for the limited utility of checkpoint inhibitors (CPIs) in advanced prostate cancer compared with other tumor types. Thus, for immunologically “cold” malignancies such as prostate cancer, clinical trial development has pivoted towards novel approaches to enhance immune responses. Numerous clinical trials are currently evaluating combination immunomodulatory strategies incorporating vaccine-based therapies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T cells. Other trials evaluate the efficacy and safety of these immunomodulatory agents’ combinations with standard approaches such as androgen deprivation therapy (ADT), taxane-based chemotherapy, radiotherapy, and targeted therapies such as tyrosine kinase inhibitors (TKI) and poly ADP ribose polymerase (PARP) inhibitors.
  • 941
  • 01 Feb 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.
  • 941
  • 29 Mar 2022
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.
  • 939
  • 30 Oct 2020
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