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1.
Molecules ; 26(15)2021 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-34361636

RESUMEN

Naturally-occurring halloysite nanotubes (HNTs) have many advantages for constructing target-specific delivery of phototherapeutic agents. Here, HNTs were labeled with fluorescein isothiocyanate (FITC) and loaded with the type-II photosensitizer indocyanine green (ICG) for phototherapy. HNTs-FITC-ICG was structurally stable due to presence of HNTs as the nanocarrier and protective agent. The nanocarrier was further wrapped with red blood cell membrane (RBCM) to enhance the biocompatibility. The HNTs-FITC-ICG-RBCM nanocarrier show high cytocompatibility and hemocompatibility. Due to the photothermal effect of ICG, a significant temperature rising was achieved by irradiation of the nanocarrier using 808 nm laser. The photothermal temperature rising was used to kill the cancer cells effectively. The HNTs-FITC-ICG-RBCM nanocarrier was further linked with anti-EpCAM to endow it with targeting therapy performance against breast cancer, and the anti-EpCAM-conjugated nanocarrier exhibited significantly tumor-specific accumulation. The RBCM-coated and biocompatible HNTs nanocarrier is a promising candidate for target-specific therapy of cancer.


Asunto(s)
Membrana Celular/química , Arcilla/química , Materiales Biocompatibles Revestidos , Portadores de Fármacos , Nanotubos/química , Neoplasias , Terapia Fototérmica , Animales , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Conejos
2.
Molecules ; 26(15)2021 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-34361637

RESUMEN

Ganoderma lucidum extract is a potent traditional remedy for curing various ailments. Drying is the most important postharvest step during the processing of Ganoderma lucidum. The drying process mainly involves heat (36 h at 60 °C) and freeze-drying (36 h at -80 °C). We investigated the effects of different postharvest drying protocols on the metabolites profiling of Ganoderma lucidum using GC-MS, followed by an investigation of the anti-neuroinflammatory potential in LPS-treated BV2 microglial cells. A total of 109 primary metabolites were detected from heat and freeze-dried samples. Primary metabolite profiling showed higher levels of amino acids (17.4%) and monosaccharides (8.8%) in the heat-dried extracts, whereas high levels of organic acids (64.1%) were present in the freeze-dried samples. The enzymatic activity, such as ATP-citrate synthase, pyruvate kinase, glyceraldehyde-3-phosphatase dehydrogenase, glutamine synthase, fructose-bisphosphate aldolase, and D-3-phosphoglycerate dehydrogenase, related to the reverse tricarboxylic acid cycle were significantly high in the heat-dried samples. We also observed a decreased phosphorylation level of the MAP kinase (Erk1/2, p38, and JNK) and NF-κB subunit p65 in the heat-dried samples of the BV2 microglia cells. The current study suggests that heat drying improves the production of ganoderic acids by the upregulation of TCA-related pathways, which, in turn, gives a significant reduction in the inflammatory response of LPS-induced BV2 cells. This may be attributed to the inhibition of NF-κB and MAP kinase signaling pathways in cells treated with heat-dried extracts.


Asunto(s)
Antiinflamatorios , Antineoplásicos Fitogénicos , Neoplasias/tratamiento farmacológico , Reishi/química , Metabolismo Secundario , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Desecación , Ratones , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/patología
3.
Nat Commun ; 12(1): 5041, 2021 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-34413299

RESUMEN

In vivo reprogramming provokes a wide range of cell fate conversion. Here, we discover that in vivo induction of higher levels of OSKM in mouse somatic cells leads to increased expression of primordial germ cell (PGC)-related genes and provokes genome-wide erasure of genomic imprinting, which takes place exclusively in PGCs. Moreover, the in vivo OSKM reprogramming results in development of cancer that resembles human germ cell tumors. Like a subgroup of germ cell tumors, propagated tumor cells can differentiate into trophoblasts. Moreover, these tumor cells give rise to induced pluripotent stem cells (iPSCs) with expanded differentiation potential into trophoblasts. Remarkably, the tumor-derived iPSCs are able to contribute to non-neoplastic somatic cells in adult mice. Mechanistically, DMRT1, which is expressed in PGCs, drives the reprogramming and propagation of the tumor cells in vivo. Furthermore, the DMRT1-related epigenetic landscape is associated with trophoblast competence of the reprogrammed cells and provides a therapeutic target for germ cell tumors. These results reveal an unappreciated route for somatic cell reprogramming and underscore the impact of reprogramming in development of germ cell tumors.


Asunto(s)
Células Madre Pluripotentes Inducidas/patología , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias/patología , Factores de Transcripción/metabolismo , Animales , Animales Modificados Genéticamente , Diferenciación Celular/fisiología , Línea Celular Tumoral , Células Cultivadas , Reprogramación Celular/fisiología , Epigénesis Genética , Femenino , Impresión Genómica , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Ratones , Ratones Endogámicos ICR , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/metabolismo , Factores de Transcripción/genética
4.
Molecules ; 26(16)2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34443300

RESUMEN

Frutalin is a plant lectin with beneficial immunobiological action, although the access to its active form is still restricted. Moreover, there is a knowledge gap on isoform activity and glycosylation impact on its bioactivity, and recombinant production protocols were seen as ineffective. Here, a simpler and faster production and purification protocol was developed, attaining a yield of purified frutalin 3.3-fold higher than that obtained previously. Hemagglutination assays confirmed that this frutalin isoform could not agglutinate rabbit erythrocytes, while maintaining the native tetrameric structure, as indicated by DLS analysis, and strong interaction with methyl-alpha-galactose, in fluorescence spectroscopy studies. The cytotoxicity of the recombinant frutalin isoform was shown in a broad panel of human cancer cells: colon (HCT116), melanoma (A375), triple-negative breast cancer (MDA-MB-231), and ovarian (IGROV-1). Treatment with 8.5-11.8 µM TrxFTL reduced proliferation of all cancer cells to half in 48 h. This anti-proliferative effect encompasses the p53 pathway since it was significantly reduced in p53-null colon cancer cells (HCT116 p53-/-; GI50 of 25.0 ± 3.0 µM), when compared to the isogenic p53-positive cells (HCT116 p53+/+; GI50 of 8.7 ± 1.8 µM; p < 0.002). This recombinantly produced frutalin isoform has relevant cytotoxic effect and its biological activity is not dependent on glycosylation. The developed E. coli production and purification protocol generates high yield of non-glycosylated frutalin isoform with potent cytotoxic activity, enabling the development of novel anticancer p53-targeting therapies.


Asunto(s)
Galectinas/farmacología , Neoplasias/patología , Secuencia de Aminoácidos , Animales , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dispersión Dinámica de Luz , Escherichia coli/metabolismo , Galactosa/metabolismo , Galectinas/química , Galectinas/aislamiento & purificación , Glicosilación/efectos de los fármacos , Hemaglutinación/efectos de los fármacos , Modelos Moleculares , Peso Molecular , Conejos , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/farmacología , Espectrometría de Fluorescencia
5.
Molecules ; 26(16)2021 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-34443432

RESUMEN

BACKGROUND: It is well known that more than 90% of cancer deaths are due to metastases. However, the entire tumorigenesis process is not fully understood, and it is evident that cells spreading from the primary tumor play a key role in initiating the metastatic process. Tumor proliferation and invasion also elevate the concentration of regular and irregular metabolites in the serum, which may alter the normal function of the entire human homeostasis and possibly causes cancer metabolism syndrome, also referred to as cachexia. METHODS: We report on the modification of commercially available hemodialysis membranes to selectively capture circulating tumor cells from the blood stream by means of immobilized human anti-EpCAM antibodies on the inner surface of the fibers. All critical steps are described that required in situ addition of the immuno-affinity feature to hemodialyzer cartridges in order to capture EpCAM positive circulating tumor cells, which represents ~80% of cancer cell types. RESULTS: The cell capture efficiency of the suggested technology was demonstrated by spiking HCT116 cancer cells both into buffer solution and whole blood and run through on the modified cartridge. Flow cytometry was used to quantitatively evaluate the cell clearance performance of the approach. CONCLUSIONS: The suggested modification has no significant effect on the porous structure of the hemodialysis membranes; it keeps its cytokine removal capability, addressing cachexia simultaneously with CTC removal.


Asunto(s)
Neoplasias/patología , Neoplasias/terapia , Células Neoplásicas Circulantes/patología , Diálisis Renal , Citometría de Flujo , Fluorescencia , Células HCT116 , Humanos , Membranas , Polímeros/química , Sulfonas/química
6.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34445354

RESUMEN

PURPOSE: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new "target". Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations. CONCLUSIONS: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled "oxygenate, target, use, and digest". In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues.


Asunto(s)
Terapia Molecular Dirigida/métodos , Neoplasias/terapia , Hipoxia Tumoral/fisiología , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Muerte Celular , Humanos , Terapia Molecular Dirigida/tendencias , Neoplasias/patología , Profármacos/farmacología , Profármacos/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Terapias en Investigación/métodos , Terapias en Investigación/tendencias
7.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-34445578

RESUMEN

The phenomenon of how oncogenes and tumor-suppressor mutations can synergize to promote tumor fitness and cancer progression can be studied in relatively simple animal model systems such as Drosophila melanogaster. Almost two decades after the landmark discovery of cooperative oncogenesis between oncogenic RasV12 and the loss of the tumor suppressor scribble in flies, this and other tumor models have provided new concepts and findings in cancer biology that has remarkable parallels and relevance to human cancer. Here we review findings using the RasV12; scrib-/- tumor model and how it has contributed to our understanding of how these initial simple genetic insults cooperate within the tumor cell to set in motion the malignant transformation program leading to tumor growth through cell growth, cell survival and proliferation, dismantling of cell-cell interactions, degradation of basement membrane and spreading to other organs. Recent findings have demonstrated that cooperativity goes beyond cell intrinsic mechanisms as the tumor interacts with the immediate cells of the microenvironment, the immune system and systemic organs to eventually facilitate malignant progression.


Asunto(s)
Carcinogénesis , Proteínas de la Membrana/metabolismo , Mutación , Neoplasias/patología , Microambiente Tumoral , Proteínas Supresoras de Tumor/metabolismo , Proteínas ras/metabolismo , Animales , Humanos , Proteínas de la Membrana/genética , Neoplasias/etiología , Neoplasias/metabolismo , Transducción de Señal , Proteínas Supresoras de Tumor/genética , Proteínas ras/genética
8.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-34445629

RESUMEN

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics.


Asunto(s)
Aptámeros de Nucleótidos/metabolismo , Neoplasias/metabolismo , Receptores de Transferrina/metabolismo , Técnica SELEX de Producción de Aptámeros/métodos , Aptámeros de Nucleótidos/química , Humanos , Ligandos , Neoplasias/patología , Transcitosis , Células Tumorales Cultivadas
9.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-34445633

RESUMEN

Caspases, a family of cysteine-aspartic proteases, have an established role as critical components in the activation and initiation of apoptosis. Alongside this a variety of non-apoptotic caspase functions in proliferation, differentiation, cellular plasticity and cell migration have been reported. The activity level and context are important factors in determining caspase function. As a consequence of their critical role in apoptosis and beyond, caspases are uniquely situated to have pathological roles, including in cancer. Altered caspase function is a common trait in a variety of cancers, with apoptotic evasion defined as a "hallmark of cancer". However, the role that caspases play in cancer is much more complex, acting both to prevent and to promote tumourigenesis. This review focuses on the major findings in Drosophila on the dual role of caspases in tumourigenesis. This has major implications for cancer treatments, including chemotherapy and radiotherapy, with the activation of apoptosis being the end goal. However, such treatments may inadvertently have adverse effects on promoting tumour progression and acerbating the cancer. A comprehensive understanding of the dual role of caspases will aid in the development of successful cancer therapeutic approaches.


Asunto(s)
Apoptosis , Carcinogénesis , Caspasas/metabolismo , Neoplasias/patología , Animales , Drosophila , Humanos , Neoplasias/enzimología , Neoplasias/etiología , Neoplasias/prevención & control
10.
Expert Opin Drug Metab Toxicol ; 17(9): 1065-1074, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34347509

RESUMEN

INTRODUCTION: KRAS is the most frequently mutated oncogenic driver in pancreatic, lung, and colon cancer. Recently, KRAS inhibitors in clinical use show promising activity but most responses are partial and drug resistance develops. The use of therapeutics in combination with KRAS inhibitors are expected to improve outcomes. AREAS COVERED: This review describes the KRAS G12C mutation-specific inhibitors and the SOS1-targeting inhibitors that reduce the GTP-loading of wildtype and mutated KRAS. Both types of compounds reduce tumor cell proliferation in vitro and in vivo. The combinations of the various KRAS inhibitors with downstream signaling effectors, modulators of KRAS-associated metabolic alterations and chemotherapeutics are summarized. EXPERT OPINION: The clinical potency of mutated KRAS-specific inhibitors needs to be improved by suitable drug combinations. Inhibition of downstream signaling cascades increases toxicity and other combinations exploited comprise G12C-directed inhibitors with SOS1 inhibitors, glucose/glutamine metabolic modulators, classical chemotherapeutics, and others. The most suitable inhibitor combinations corroborated in preclinical development await clinical verification.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias/tratamiento farmacológico , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Proliferación Celular/efectos de los fármacos , Humanos , Mutación , Neoplasias/genética , Neoplasias/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Transducción de Señal/efectos de los fármacos
11.
Medicine (Baltimore) ; 100(29): e26202, 2021 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-34397999

RESUMEN

INTRODUCTION: Previous research indicates that the platelet-to-lymphocyte ratio (PLR) may be an indicator of poor prognosis in many tumor types. However, the PLR is rarely described in patients undergoing neoadjuvant chemotherapy (NAC) for solid tumors. Thus, we performed a meta-analysis to investigate the prognostic value of this ratio for patients with solid tumors treated by NAC. METHODS: A comprehensive search of the literature was conducted using the PubMed, EMBASE, Cochrane Library, and Web of Science databases, followed by a manual search of references from the retrieved articles. Pooled hazard ratios (HRs) with 95% confidence interval (CIs) were used to evaluate the association between PLR and 3 outcomes, namely, overall survival, disease-free survival, and pathological complete response rate after NAC. RESULTS: Eighteen studies published no earlier than 2014 were included in our study. A lower PLR was associated with better overall survival (HR = 1.46, 95% CI, 1.11-1.92) and favorable disease-free survival (HR = 1.81, 95% CI, 1.27-2.59). A PLR that was higher than a certain cutoff was associated with a lower pathological complete response rate in patients with cancer who received NAC (Odds ratio = 1.93, 95% CI, 1.40-2.87). CONCLUSION: Elevated PLR is associated with poor prognosis in various solid tumors. PLR may be a useful biomarker in delineating those patients with poorer prognoses who may benefit from neoadjuvant therapies.


Asunto(s)
Recuento de Linfocitos/normas , Terapia Neoadyuvante/métodos , Neoplasias/patología , Recuento de Plaquetas/normas , Pronóstico , Plaquetas/clasificación , Plaquetas/patología , Humanos , Recuento de Linfocitos/métodos , Linfocitos/clasificación , Linfocitos/patología , Neoplasias/fisiopatología , Neoplasias/terapia , Recuento de Plaquetas/métodos
12.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34445468

RESUMEN

In the late 1980s, Paul Primakoff and colleagues showed that fertilization could be blocked in an in vitro sperm-egg fusion assay by inoculating them in the presence of a disintegrin and metalloprotease (ADAM)-specific antibody [...].


Asunto(s)
Proteínas ADAM/metabolismo , Inflamación/patología , Neoplasias/patología , Animales , Humanos , Inflamación/metabolismo , Neoplasias/metabolismo
13.
FASEB J ; 35(9): e21750, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34424568

RESUMEN

Success of adoptive cell therapy mainly depends on the ability of immune cells to persist and function optimally in the immunosuppressive tumor microenvironment. Although present at the cancer site, immune cells become exhausted and/or inhibited, due to the presence of inhibitory receptors such as PD-L1 on malignant cells. Novel genetic strategies to manipulate the PD1/PD-L1 axis comprise (i) PD-1 reversion where the receptor intracellular domain is replaced with an activating unit, (ii) the use of anti-PD-L1 CAR or (iii) the disruption of the PD-1 gene. We here present an alternative strategy to equip therapeutic cells with a truncated PD-1 (tPD-1) to abrogate PD-1/PD-L1 inhibition. We show that engagement of tPD-1 with PD-L1-positive tumor unleashes NK-92 activity in vitro. Furthermore, this binding was sufficiently strong to induce killing of targets otherwise not recognized by NK-92, thus increasing the range of targets. In vivo treatment with NK-92 tPD-1 cells led to reduced tumor growth and improved survival. Importantly, tPD-1 did not interfere with tumor recognition in PD-L1 negative conditions. Thus, tPD-1 represents a straightforward method for improving antitumor immunity and revealing new targets through PD-L1 positivity.


Asunto(s)
Antígeno B7-H1/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Escape del Tumor/inmunología , Animales , Adhesión Celular , Ingeniería Celular , Línea Celular Tumoral , Supervivencia Celular , Ingeniería Genética , Humanos , Ratones , Neoplasias/patología , Receptor de Muerte Celular Programada 1/metabolismo , ARN Mensajero/genética , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Sci Transl Med ; 13(605)2021 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-34349036

RESUMEN

Most patients with advanced solid cancers exhibit features of cachexia, a debilitating syndrome characterized by progressive loss of skeletal muscle mass and strength. Because the underlying mechanisms of this multifactorial syndrome are incompletely defined, effective therapeutics have yet to be developed. Here, we show that diminished bone morphogenetic protein (BMP) signaling is observed early in the onset of skeletal muscle wasting associated with cancer cachexia in mouse models and in patients with cancer. Cancer-mediated factors including Activin A and IL-6 trigger the expression of the BMP inhibitor Noggin in muscle, which blocks the actions of BMPs on muscle fibers and motor nerves, subsequently causing disruption of the neuromuscular junction (NMJ), denervation, and muscle wasting. Increasing BMP signaling in the muscles of tumor-bearing mice by gene delivery or pharmacological means can prevent muscle wasting and preserve measures of NMJ function. The data identify perturbed BMP signaling and denervation of muscle fibers as important pathogenic mechanisms of muscle wasting associated with tumor growth. Collectively, these findings present interventions that promote BMP-mediated signaling as an attractive strategy to counteract the loss of functional musculature in patients with cancer.


Asunto(s)
Caquexia , Neoplasias , Animales , Desnervación , Humanos , Ratones , Músculo Esquelético/patología , Atrofia Muscular , Neoplasias/complicaciones , Neoplasias/patología
15.
Nat Commun ; 12(1): 4746, 2021 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-34362900

RESUMEN

The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT cell-deficient mice have enhanced NK cell-dependent control of metastatic B16F10 tumor growth relative to control mice. Analyses of this interplay in human tumor samples reveal that high expression of a MAIT cell gene signature negatively impacts the prognostic significance of NK cells. Paradoxically, pre-pulsing tumors with MAIT cell antigens, or activating MAIT cells in vivo, enhances anti-tumor immunity in B16F10 and E0771 mouse tumor models, including in the context of established metastasis. These effects are associated with enhanced NK cell responses and increased expression of both IFN-γ-dependent and inflammatory genes in NK cells. Importantly, activated human MAIT cells also promote the function of NK cells isolated from patient tumor samples. Our results thus describe an activation-dependent, MAIT cell-mediated regulation of NK cells, and suggest a potential therapeutic avenue for cancer treatment.


Asunto(s)
Inmunidad Celular , Células Asesinas Naturales/inmunología , Células T Invariantes Asociadas a Mucosa/inmunología , Neoplasias/inmunología , Animales , Antineoplásicos , Línea Celular Tumoral , Citocinas , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Inmunidad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Antígenos de Histocompatibilidad Menor/genética , Metástasis de la Neoplasia , Neoplasias/patología
16.
PLoS One ; 16(8): e0256047, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34379682

RESUMEN

INTRODUCTION: Five months after COVID-19 first occurred and protective regulations were introduced, patients at three outpatient hematological/oncological centers in Bavaria who had received antiproliferative tumor therapy (n = 30) were questioned about the pandemic's impact. PATIENTS, MATERIALS AND METHODS: In recorded semi-structured telephone interviews, the patients answered questions about their quality of life, treatment procedures, their relationship with medical care staff and modern communication technologies. Each interview consisted of 28 questions. The average length of an interview was 30 minutes. The interviews were transcribed and analyzed by means of a qualitative content analysis according to Mayring. RESULTS: The COVID-19 pandemic adds to the burden of patients by decreasing their social contacts. They perceived the new isolation and protective measures in outpatient clinics as mostly positive and said its impact had been only slightly adverse. With the implemented safety measures, they feel adequately protected and looked after and want their antiproliferative therapy to be performed as scheduled. Talking to medical staff provides additional reassurance. CONCLUSION: Although the COVID-19 pandemic has exacerbated the social isolation of tumor patients, it has had only a minor effect on tumor therapy in the surveyed patient population. The benefits of modern communication options to tumor patients remains uncertain and should be investigated further in future studies.


Asunto(s)
COVID-19/epidemiología , Neoplasias/psicología , Adulto , Antineoplásicos/uso terapéutico , COVID-19/patología , COVID-19/virología , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Pandemias , SARS-CoV-2/aislamiento & purificación , Aislamiento Social , Encuestas y Cuestionarios , Teléfono
17.
S Afr Med J ; 111(6): 570-574, 2021 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-34382569

RESUMEN

BACKGROUND: The COVID-19 pandemic has disrupted cancer diagnostic services. A decline in the number of new cancers being diagnosed over a relatively short term implies a delay in diagnosis and subsequent treatment. This delay is expected to have a negative effect on cancerrelated morbidity and mortality. The impact of the pandemic on the number of new cancer diagnoses in our setting is unknown. OBJECTIVES: To assess the impact of COVID-19 on the number of new cancers diagnosed at our institution in the first 3 months following the implementation of lockdown restrictions, by focusing on common non-cutaneous cancers. METHODS: A retrospective laboratory-based audit was performed at a large anatomical pathology laboratory in Western Cape Province, South Africa. The numbers of new diagnoses for six common cancers (breast, prostate, cervix, large bowel, oesophagus and stomach) from 1 April 2020 to 30 June 2020 were compared with the corresponding period in 2019. RESULTS: Histopathological diagnoses for the six cancers combined decreased by 192 (-36.2%), from 531 new cases in the 2019 study period to 339 in the corresponding period in 2020. Substantial declines were seen for prostate (-58.2%), oesophageal (-44.1%), breast (-32.9%), gastric (-32.6%) and colorectal cancer (-29.2%). The smallest decline was seen in cervical cancer (-7%). New breast cancers diagnosed by cytopathology declined by 61.1%. CONCLUSIONS: The first wave of the COVID-19 pandemic and the associated response resulted in a substantial decline in the number of new cancer diagnoses, implying a delay in diagnosis. Cancer-related morbidity and mortality is expected to rise as a result, with the greatest increase in mortality expected from breast and colorectal cancer.


Asunto(s)
COVID-19/epidemiología , Neoplasias/epidemiología , Salud Pública , Anciano , Femenino , Humanos , Laboratorios , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/patología , Estudios Retrospectivos , Sudáfrica/epidemiología
19.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34360564

RESUMEN

In recent decades, studies on the functional features of Se nanoparticles (SeNP) have gained great popularity due to their high biocompatibility, stability, and pronounced selectivity. A large number of works prove the anticarcinogenic effect of SeNP. In this work, the molecular mechanisms regulating the cytotoxic effects of SeNP, obtained by laser ablation, were studied by the example of four human cancer cell lines: A-172 (glioblastoma), Caco-2, (colorectal adenocarcinoma), DU-145 (prostate carcinoma), MCF-7 (breast adenocarcinoma). It was found that SeNP had different concentration-dependent effects on cancer cells of the four studied human lines. SeNP at concentrations of less than 1 µg/mL had no cytotoxic effect on the studied cancer cells, with the exception of the A-172 cell line, for which 0.5 µg/mL SeNP was the minimum concentration affecting its metabolic activity. It was shown that SeNP concentration-dependently caused cancer cell apoptosis, but not necrosis. In addition, it was found that SeNP enhanced the expression of pro-apoptotic genes in almost all cancer cell lines, with the exception of Caco-2 and activated various pathways of adaptive and pro-apoptotic signaling pathways of UPR. Different effects of SeNP on the expression of ER-resident selenoproteins and selenium-containing glutathione peroxidases and thioredoxin reductases, depending on the cell line, were established. In addition, SeNP triggered Ca2+ signals in all investigated cancer cell lines. Different sensitivity of cancer cell lines to SeNP can determine the induction of the process of apoptosis in them through regulation of the Ca2+ signaling system, mechanisms of ER stress, and activation of various expression patterns of genes encoding pro-apoptotic proteins.


Asunto(s)
Antineoplásicos/administración & dosificación , Apoptosis , Citotoxinas/administración & dosificación , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Selenio/química , Antineoplásicos/química , Citotoxinas/química , Humanos , Nanopartículas/química , Transducción de Señal , Células Tumorales Cultivadas
20.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34360563

RESUMEN

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the "modern" Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin-GH-IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin-GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.


Asunto(s)
Envejecimiento/patología , Enfermedades Cardiovasculares/patología , Diabetes Mellitus Tipo 2/patología , Hiperinsulinismo/complicaciones , Resistencia a la Insulina , Neoplasias/patología , Obesidad/patología , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/etiología , Humanos , Neoplasias/etiología
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