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Due to its rapid progression to advanced stages and highly metastatic properties, gastric cancer (GC) is one of the most aggressive malignancies and the fourth leading cause of cancer-related deaths worldwide. The metastatic process includes local invasion, metastasis initiation, migration with colonisation at distant sites, and evasion of the immune response. Tumour growth involves the activation of inhibitory signals associated with the immune response, also known as immune checkpoints, including PD-1/PD-L1 (programmed death 1/programmed death ligand 1), CTLA-4 (cytotoxic T cell antigen 4), TIGIT (T cell immunoreceptor with Ig and ITIM domains), and others. Immune checkpoint molecules (ICPMs) are proteins that modulate the innate and adaptive immune responses. While their expression is prominent on immune cells, mainly antigen-presenting cells (APC) and other types of cells, they are also expressed on tumour cells. The engagement of the receptor by the ligand is crucial for inhibiting or stimulating the immune cell, which is an extremely important aspect of cancer immunotherapy. This narrative review explores immunotherapy, focusing on ICPMs and immune checkpoint inhibitors in GC. We also summarise the current clinical trials that are evaluating ICPMs as a target for GC treatment.
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Inhibidores de Puntos de Control Inmunológico , Proteínas de Punto de Control Inmunitario , Inmunoterapia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunoterapia/métodos , Proteínas de Punto de Control Inmunitario/metabolismo , AnimalesRESUMEN
Lagovirus europaeus/GI.2 causes severe and highly fatal Rabbit Hemorrhagic Disease (RHD). Because of its characteristics, this infection is used as an animal model for acute liver failure (ALF). Apoptosis is one of the key processes underlying ALF and has been described as one of the mechanisms of RHD pathogenesis. Apoptotic cell death has been quite well characterized in infection with different variants of GI.1 strains, but so far, the GI.2 genotype has not been widely studied. In this study, we performed an evaluation of apoptotic cell death in hepatocytes of rabbits infected with Lagovirus europaeus/GI.2. We analyzed the expression of genes involved in apoptotic cell death by real-time PCR and performed immunohistochemical (IHC) assays. We showed a significant increase in the expression of caspase-3 and the proapoptotic Bax and anti-apoptotic Bcl-2 in infected animals. In addition, we recorded increased Bax/Bcl-2 ratios. IHC analyses showed the presence of morphological signs of apoptosis in the hepatocytes of infected rabbits. Our results indicate that caspase-3 and proteins from the Bcl-2 families play a key role in apoptosis induced by Lagovirus europaeus/GI.2 infection.
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Enfermedades Transmisibles , Enfermedades Gastrointestinales , Trastornos Hemorrágicos , Lagomorpha , Lagovirus , Fallo Hepático Agudo , Humanos , Animales , Caspasa 3 , Proteína X Asociada a bcl-2 , Fallo Hepático Agudo/etiología , Apoptosis , Modelos Animales , Proteínas Proto-Oncogénicas c-bcl-2RESUMEN
Interleukin 6 (IL-6) is a pleomorphic pro-inflammatory cytokine that is strongly associated with local as well as systemic inflammatory processes. Its role in physiological and pathogenic processes throughout the human body has been the subject of numerous studies in recent years. Measurements of the IL-6 levels in gingival crevicular fluid (GFC), as well as in serum, can be important diagnostic and prognostic factors in periodontal diseases (PD) and in assessing their impact on a range of related inflammatory diseases. This narrative review explores the significant role of IL-6 in patients with periodontitis and its association with other widespread inflammatory pathologies.
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Interleucina-6 , Periodontitis , Humanos , Citocinas , Líquido del Surco Gingival , Interleucina-6/metabolismoRESUMEN
Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease leading to joint destruction. The causes of RA are not fully known. Most likely, the development of the disease depends on the coexistence of many factors, such as hereditary factors, immune system defects, gender, infectious agents, nicotine, and stress. Various epigenetic changes have been identified and correlated with the aggressive phenotype of RA, including the involvement of sirtuins, which are enzymes found in all living organisms. Their high content in the human body can slow down the aging processes, reduce cell death, counteract the appearance of inflammation, and regulate metabolic processes. Sirtuins can participate in several steps of RA pathogenesis. This narrative review presents, collects, and discusses the role of all sirtuins (1-7) in the pathogenesis of rheumatoid arthritis.
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Artritis Reumatoide , Sirtuinas , Humanos , Artritis Reumatoide/metabolismo , Inflamación/complicacionesRESUMEN
Melanoma is the most serious type of skin cancer, causing a large majority of deaths but accounting for only ~1% of all skin cancer cases. The worldwide incidence of malignant melanoma is increasing, causing a serious socio-economic problem. Melanoma is diagnosed mainly in young and middle-aged people, which distinguishes it from other solid tumors detected mainly in mature people. The early detection of cutaneous malignant melanoma (CMM) remains a priority and it is a key factor limiting mortality. Doctors and scientists around the world want to improve the quality of diagnosis and treatment, and are constantly looking for new, promising opportunities, including the use of microRNAs (miRNAs), to fight melanoma cancer. This article reviews miRNA as a potential biomarker and diagnostics tool as a therapeutic drugs in CMM treatment. We also present a review of the current clinical trials being carried out worldwide, in which miRNAs are a target for melanoma treatment.
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Melanoma , MicroARNs , Neoplasias Cutáneas , Persona de Mediana Edad , Humanos , MicroARNs/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/terapia , Melanoma/diagnóstico , Melanoma/genética , Melanoma/terapia , Biomarcadores , Melanoma Cutáneo MalignoRESUMEN
Gastric cancer is a major health burden worldwide. Among all neoplasms, gastric cancer is the fifth most common and the third most deadly type of cancer. It is known that sirtuins (SIRTs), are NAD+-dependent histone deacetylases regulating important metabolic pathways. High expression of SIRTs in the human body can regulate metabolic processes; they prevent inflammation but also resist cell death and aging processes. The seven members of this family enzymes can also play a fundamental role in process of carcinogenesis by influencing cell viability, apoptosis and metastasis. This review collects and discusses the role of all seven sirtuins (SIRT1-SIRT7) in the pathogenesis of gastric cancer (GC).
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Sirtuinas , Neoplasias Gástricas , Humanos , Sirtuinas/metabolismo , Supervivencia Celular , Muerte Celular , ApoptosisRESUMEN
The oral cavity is inhabited by a wide spectrum of microbial species, and their colonization is mostly based on commensalism. These microbes are part of the normal oral flora, but there are also opportunistic species that can cause oral and systemic diseases. Although there is a strong exposure to various microorganisms, the oral mucosa reduces the colonization of microorganisms with high rotation and secretion of various types of cytokines and antimicrobial proteins such as defensins. In some circumstances, the imbalance between normal oral flora and pathogenic flora may lead to a change in the ratio of commensalism to parasitism. Healthy oral mucosa has many important functions. Thanks to its integrity, it is impermeable to most microorganisms and constitutes a mechanical barrier against their penetration into tissues. Our study aims to present the role and composition of the oral cavity microbiota as well as defense mechanisms within the oral mucosa which allow for maintaining a balance between such numerous species of microorganisms. We highlight the specific aspects of the oral mucosa protecting barrier and discuss up-to-date information on the immune cell system that ensures microbiota balance. This study presents the latest data on specific tissue stimuli in the regulation of the immune system with particular emphasis on the resistance of the gingival barrier. Despite advances in understanding the mechanisms regulating the balance on the microorganism/host axis, more research is still needed on how the combination of these diverse signals is involved in the regulation of immunity at the oral mucosa barrier.
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Interacciones Microbiota-Huesped/inmunología , Inmunidad Mucosa , Microbiota/inmunología , Mucosa Bucal/inmunología , Mucosa Bucal/microbiología , Factores de Edad , Animales , Autoinmunidad , Biodiversidad , Susceptibilidad a Enfermedades , Disbiosis , Humanos , SimbiosisRESUMEN
Melanoma is one of the most aggressive and progressive skin cancers. It develops from normal pigment-producing cells known as melanocytes, so it is important to know the mechanism behind such transformations. The study of metastasis mechanisms is crucial for a better understanding the biology of neoplastic cells. Metastasis of melanoma, or any type of cancer, is a multi-stage process in which the neoplastic cells leave the primary tumour, travel through the blood and/or lymphatic vessels, settle in distant organs and create secondary tumours. MicroRNA (miRNA) can participate in several steps of the metastatic process. This review presents the role of miRNA molecules in the development and progression as well as the immune response to melanoma.
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Melanoma , MicroARNs , Neoplasias Cutáneas , Humanos , MicroARNs/genética , Melanoma/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Melanocitos/patología , Piel/patología , Regulación Neoplásica de la Expresión GénicaRESUMEN
Rhabdomyosarcoma (RMS) is a malignant tumor of soft tissue derived from embryonic mesenchymal and/or neuroectodermal tissues. It is most often associated with other genetic syndromes such as Li-Fraumeni or Bechwith-Wiedeman. RMS cells show morphological similarities to striated muscle and the presence of specific markers of muscle tissue. At the histological level, it is divided into two subtypes (alveolar RMS - ARMS and embryonal RMS - ERMS), which differ in their genetic background, and prognosis. In recent years there has been significant progress in understanding the mechanisms that regulate RMS cell growth and metastasis. Recently, a number of several chemokines, cytokines or growth factors and their receptors were identified involved in RMS pathogenesis as well as animal models of this tumor have been developed. This knowledge is of great importance in the development of potential therapeutic strategies not only in RMS, but also other types of cancer. This paper will discuss the theories of the origin of this rare tumor and the molecular mechanisms involved in its growth and metastasis. The processes and mechanisms described herein, such as chemotaxis, adhesion, proliferation, intracellular signal transduction, seem to universal for number of cancer types.
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Rabdomiosarcoma/patología , Rabdomiosarcoma/secundario , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Rabdomiosarcoma/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Adipose tissue serves as an energy store and is also an active endocrine organ, exerting activity that influences obesity-related processes through the production of regulatory proteins called adipokines or adipocytokines. Adipokines play important direct and indirect roles in the pathogenesis of insulin resistance, the regulation of local and systemic inflammatory processes, and related metabolic complications. There have been an increasing number of studies showing the relationship between some adipokines and carcinogenesis. This work reviews the current literature concerning the effects of omentin-1 on carcinogenesis.
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Pets are inhabiting more and more human homes every year. In 2020, the cat population in Europe was 110 million, including 6.8 million in Poland. Dry food is the most popular dietary model for cats because of its easy storage and efficient satisfaction of pet needs. The high processing temperature of dry food reduces the chance of microbial contamination, but this can occur later, during post-production or storage in the pet's caregiver's home or, in the case of weighed foods, in the store. The purpose of this study was to investigate the microbiological safety of dry feed sold in the original manufacturer's packaging and the same feed from the same manufacturers sold in a retail store by weight. Six discriminants, presence of Salmonella spp., number of coliforms, number of coagulase-positive staphylococci, determination of yeast and mould counts, Enterobacteriaceae count, Listeria monocytogenes and determination of total aerobic microbial count were used for the analysis. Then, cat food was then stored for 45 days according to the manufacturer's recommendations. Based on the samples tested both after opening and after storage, it was concluded that the dry cat food analyzed posed a law microbiological risk to animals and humans.
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Contaminación de Alimentos , Listeria monocytogenes , Humanos , Animales , Gatos , Contaminación de Alimentos/análisis , Microbiología de Alimentos , Alimentación Animal/análisis , Polonia , Recuento de Colonia MicrobianaRESUMEN
The oral mucosa is a mechanical barrier against the penetration and colonization of microorganisms. Oral homeostasis is maintained by congenital and adaptive systems in conjunction with normal oral flora and an intact oral mucosa. Components contributing to the defense of the oral cavity include the salivary glands, innate antimicrobial proteins of saliva, plasma proteins, circulating white blood cells, keratinocyte products of the oral mucosa, and gingival crevicular fluid. General disturbances in the level of immunoglobulins in the human body may be manifested as pathological lesions in the oral mucosa. Symptoms of immunoglobulin-related general diseases such as mucous membrane pemphigoid (MMP), pemphigus vulgaris (PV), linear IgA bullous dermatosis (LABD), Epidermolysis Bullosa Aquisita (EBA), and Hyper-IgE syndrome (HIES) may appear in the oral cavity. In this review, authors present selected diseases associated with immunoglobulins in which the lesions appear in the oral cavity. Early detection and treatment of autoimmune diseases, sometimes showing a severe evolution (e.g., PV), allow the control of their dissemination and involvement of skin or other body organs. Immunoglobulin disorders with oral manifestations are not common, but knowledge, differentiation and diagnosis are essential for proper treatment.
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(1) Background: stromal-derived factor-1 (SDF-1/CXCL12), hepatocyte and vascular-endothelial growth factors (HGF and VEGF) have been shown to facilitate cell motility, proliferation and promote local tumor progression and metastatic spread. Recent research shows the important role of these cytokines in gastric cancer (GC) progression. (2) Methods: 21 gastric cancer patients and 19 healthy controls were included in the study. SDF-1, HGF and VEGF levels were evaluated in sera by ELISA. Patients and control sera were used to stimulate CRL-1739 GC cell line, and chemotaxis, adhesion and proliferation potential were assessed. (3) Results: Concentrations of SDF-1, HGF and VEGF were significantly higher in patients than in controls. Chemotaxis and adhesion assays revealed a significant response of GC cells to patients' serum. Furthermore, significant relationships were seen between chemotactic/adhesion response and tumor stage. Serum from intestinal early GC patients produced significantly stronger chemotactic response when compared to patients with metastatic spread. In turn, serum from patients with distal metastases significantly increased the adhesion of GC cells when compared to sera from the patients with no distal metastases. We also observed that HGF strongly stimulated the proliferation of CRL-1739 cells. (4) Conclusions: We observed that the sera from GC patients, but also SDF-1, HGF and VEGF used alone, have a strong pro-metastatic effect on CRL-1739 cells. We also demonstrated that the concentration of these cytokines is specifically elevated in the sera of patients in an early stage of malignancy. Our results indicate that SDF-1, HGF and VEGF are very important molecules involved in gastric cancer progression.
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Due to the development of molecular diagnostic techniques, the latest research in the diagnosis of cancer diseases, including laryngeal cancer, has been focused on the occurrence of specific types of molecular patterns, including markers expressed on cells of the immune system (e.g., PD-1, PD-L1, and CTLA-4), which may be directly or indirectly involved in the development of neoplastic diseases. Laryngeal cancer is one of the diseases that is diagnosed more often in men than in women, and many factors are involved in its development, including environmental and lifestyle factors, viral infections (e.g., HPV, HHV-1, and EBV), and disorders of the immune system. In this study, we determined the level of PD-1 receptor expression on T and B lymphocytes and their relationships based on the classification of the grade and TNM scale, in turn based on blood, tumor, and lymph node samples from patients diagnosed with laryngeal cancer. In addition, we determined the presence of EBV genetic material in the tested biological materials as well as the degree of cancer advancement and its correlation with the level of PD-1 receptor expression. The results suggested that the level of PD-1 expression on T and B lymphocytes was significantly higher in the tumor samples as compared to the lymph node samples, and their comparison with the immunophenotype results from the blood samples provided statistically significant data on changes in the incidence of individual subpopulations of T and B lymphocytes and the level of PD-1 receptor expression. The analysis of the individual parameters of the TNM scale also showed significant changes between the PD-1 expression and the tested biological material in individual subgroups of the scale. We also found that the expression of PD-1 on the CD4+ T cells from the lymph node samples caused an almost 1.5-fold increase in the risk of death. In the analyses of the presence of EBV, the highest concentration was recorded in the tumor samples, then for the lymph node samples, and followed by the blood samples. Furthermore, we showed that the presence of EBV genetic material was positively correlated with the level of PD-1 expression in the tested biological materials.
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Innate lymphoid cells (ILCs) are a recently described group of immune cells that can regulate homeostasis and protect mammalian organisms, including humans, from infections and diseases. Considering this, ILC research is still ongoing to better understand the biology of these cells and their roles in the human body. ILCs are a multifunctional group of immune cells, making it important for the medical community to be familiar with the latest research about the ILC families and their functions in selected disease states, such as cancer formation, metabolic disorders and inflammation. By discovering the roles of ILC populations and their participation in many disorders, we can improve disease diagnostics and patient healthcare.
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Five years after being discovered in 2003, some giant viruses were demonstrated to play a role of the hosts for virophages, their parasites, setting out a novel and yet unknown regulatory mechanism of the giant viruses presence in an aqueous. So far, 20 virophages have been registered and 13 of them have been described as a metagenomic material, which indirectly impacts the number of single- and multi-cell organisms, the environment where giant viruses replicate.
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Virus Gigantes/fisiología , Virófagos/fisiología , Genoma Viral , Virus Gigantes/clasificación , Virus Gigantes/genética , Metagenómica , Filogenia , Virófagos/clasificación , Virófagos/genética , Replicación ViralRESUMEN
BACKGROUND: Colorectal cancer (CRC) is a leading cause of death in the western world, and its incidence increases with patient age. It is also known that with age there occur changes in the levels of certain hormones, including an increase in the secretion of pituitary gonadotropins (PtGs) as a result of the loss of gonadal hormone feedback. We recently reported that functional PtG receptors are expressed in human lung cancer cells, rhabdomyosarcoma cells, and malignant hematopoietic stem cells. FINDINGS: Here we report for the first time that the receptors for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are expressed in primary tumor samples isolated from CRC patients as well as in the established human CRC cell lines HTC116 and HTB37. Moreover, we also report that PtGs stimulate chemotaxis, adhesion, and proliferation of these cell lines. CONCLUSIONS: Our results suggest that PtGs play an important and underappreciated role in CRC pathogenesis, and we call for further studies to better define their role in gastrointestinal malignancies and their direct effect on putative CRC cancer stem cells.
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Neoplasias Colorrectales/metabolismo , Hormona Folículo Estimulante/metabolismo , Hormona Luteinizante/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Adhesión Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Quimiotaxis/fisiología , Neoplasias Colorrectales/patología , Fibronectinas/metabolismo , Estudios de Seguimiento , Humanos , Masculino , ARN Mensajero/metabolismoRESUMEN
The erythropoietin receptor (EpoR) is expressed by cells from the erythroid lineage; however, evidence has accumulated that it is also expressed by some other non-hematopoietic tissues including several solid tumor cells and proposed candidates for cancer stem cells. This is an important concern, because recombinant erythropoietin (EPO) is frequently employed in cancer patients as a drug to ameliorate anemia related to chemo/radiotherapy. In our studies, we employed three human neuroblastoma (NB) cell lines and found in all of them the expression of EpoR and EPO mRNA. The functionality of EpoR in RMS cell lines was evaluated by chemotaxis, adhesion, and direct cell proliferation assays. We noticed that all three human NB cell lines responded to EPO stimulation by enhanced chemotaxis and cell adhesion. However, at the same time we did not observe any significant effect of EPO on proliferation. Based on this EPO supplementation in NB patients employed because of radio/chemotherapy induced anemias may have an unwanted side effect on tumor metastasis.
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Umbilical cord blood (UCB) is a rich source of stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitors cells (EPCs), and very small embryonic-like stem cells (VSELs). These cells most likely are mobilized into UCB in response to hypoxia and delivery stress. We have hypothesized that they may play a role in repairing certain tissue/organ injuries that occur in the newborn child after delivery. Here we asked whether delivery also mobilizes stem cells into maternal blood, as the mother also experiences hypoxia and several types of internal tissue injuries, particularly in the reproductive tract. We observed that the number of HSCs, MSCs, EPCs, and VSELs increases in maternal blood at 24 h after physiological delivery (n = 17). Based on this observation, we propose that delivery stress is associated with an increase in the number of circulating stem cells, not only on the fetal side but also on the maternal side of the fetal-maternal circulatory barrier.
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Diferenciación Celular/genética , Células Progenitoras Endoteliales/citología , Sangre Fetal/citología , Células Madre de Sangre Periférica , Adulto , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Femenino , Sangre Fetal/metabolismo , Citometría de Flujo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , Relaciones Materno-Fetales , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismoRESUMEN
Evidence has accumulated that sex hormones play an important role in several types of cancer. Because they are also involved in skeletal muscle development and regeneration, we were therefore interested in their potential involvement in the pathogenesis of human rhabdomyosarcoma (RMS), a skeletal muscle tumor. In the present study, we employed eight RMS cell lines (three fusion positive and five fusion negative RMS cell lines) and mRNA samples obtained from RMS patients. The expression of sex hormone receptors was evaluated by RT-PCR and their functionality by chemotaxis, adhesion and direct cell proliferation assays. We report here for the first time that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) receptors are expressed in established human RMS cell lines as well as in primary tumor samples isolated from RMS patients. We also report that human RMS cell lines responded both to pituitary and gonadal sex hormone stimulation by enhanced proliferation, chemotaxis, cell adhesion and phosphorylation of MAPKp42/44 and AKT. In summary, our results indicate that sex hormones are involved in the pathogenesis and progression of RMS, and therefore, their therapeutic application should be avoided in patients that have been diagnosed with RMS.