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1.
Curr Med Chem ; 29(42): 6463-6478, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34789121

RESUMEN

BACKGROUND: Members of the α-thymosin family have long been studied for their immunostimulating properties. Among them, the danger-associated molecular patterns (DAMPs) prothymosin α (proTα) and its C-terminal decapeptide proTα(100-109) have been shown to act as immunomodulators in vitro, due to their ability to promote T helper type 1 (Th1) responses. Recently, we verified these findings in vivo, showing that both proTα and proTα(100-109) enhance antitumor-reactive T cell-mediated responses. METHODS: In view of the eventual use of proTα and proTα(100-109) in humans, we investigated their safety profile in silico, in human leukocytes and cancer cell lines in vitro, and in immunocompetent mice in vivo, in comparison to the proTα derivative thymosin alpha 1 (Τα1), a 28-mer peptide extensively studied for its safety in clinical trials. RESULTS: In silico prediction via computational tools showed that all three peptide sequences likely are non-toxic or do not induce allergic regions. In vitro, pro- Tα, proTα(100-109) and Tα1 did not affect the viability of human cancer cell lines and healthy donor-derived leukocytes, did not promote apoptosis or alter cell cycle distribution. Furthermore, mice injected with proTα, proTα(100-109) and Tα1 at doses equivalent to the suggested dose regimen of Tα1 in humans, did not show signs of acute toxicity, whereas proTα and proTα(100-109) increased the levels of proinflammatory and Th1- type cytokines in their peripheral blood. CONCLUSION: Our preliminary findings suggest that proTα and proTα(100-109), even at high concentrations, are non-toxic in vitro and in an acute toxicity model in vivo; moreover, we show that the two peptides retain their immunomodulatory properties in vivo and, eventually, could be considered for therapeutic use in humans.


Asunto(s)
Neoplasias , Timosina , Humanos , Ratones , Animales , Timosina/toxicidad , Péptidos/uso terapéutico , Citocinas , Factores Inmunológicos/uso terapéutico , Neoplasias/tratamiento farmacológico
2.
Mol Immunol ; 46(5): 784-92, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18976813

RESUMEN

Prothymosin alpha (ProTalpha) is a small acidic polypeptide with important immunostimulatory properties, which we have previously shown to be exerted by its carboxyl (C)-terminus. It exerts immunoenhancing effects through stimulation of monocytes via toll-like receptor (TLR) triggering. Here, we assayed the activity of synthetic peptides homologous to ProTalpha's C-terminus to stimulate lymphocyte functions, in particular natural killer cell cytotoxicity of peripheral blood mononuclear cells isolated from healthy donors. A synthetic decapeptide TKKQKTDEDD was identified as the most potent lymphocyte stimulator. The activity of this peptide was sequence-specific and comparable to that of the intact molecule, suggesting that ProTalpha's immunoactive segment encompasses the nuclear localization signal sequence of the polypeptide. Because ProTalpha stimulates immune responses in a monocyte-dependent manner, we further investigated whether the entire molecule and its peptide TKKQKTDEDD specifically act on monocytes and show that both can promote maturation of monocyte-derived dendritic cells (DC). Finally, knowing that, under specific conditions, ProTalpha forms amyloid fibrils, we studied the amyloidogenic properties of its C-terminal peptide segments, utilizing ATR FT-IR spectroscopy and transmission electron microscopy (negative staining). Although the peptide TKKQKTDEDD adopts an antiparallel beta-sheet conformation under various conditions, it does not form amyloid fibrils; rather it aggregates in globular particles. These data, in conjunction with reports showing that the peptide TKKQKTDEDD is generated in vivo upon caspase-cleavage of ProTalpha during apoptosis, strengthen our hypothesis that immune response stimulation by ProTalpha is in principle exerted via its bioactive C-terminal decapaptide, which can acquire a sequence-specific beta-sheet conformation and induce DC maturation.


Asunto(s)
Células Dendríticas/inmunología , Linfocitos/inmunología , Monocitos/inmunología , Péptidos/farmacología , Precursores de Proteínas/farmacología , Timosina/análogos & derivados , Amiloide/inmunología , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Caspasas/inmunología , Células Cultivadas , Células Dendríticas/citología , Humanos , Linfocitos/citología , Monocitos/citología , Péptidos/química , Péptidos/inmunología , Precursores de Proteínas/química , Precursores de Proteínas/inmunología , Estructura Secundaria de Proteína/fisiología , Timosina/química , Timosina/inmunología , Timosina/farmacología , Receptores Toll-Like/inmunología
3.
J Cell Mol Med ; 13(9B): 3929-38, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19220577

RESUMEN

Phenoxodiol (PXD) is a synthetic analogue of the plant isoflavone genistein with improved anticancer efficacy. Various properties and mechanisms of action have been attributed to the drug, the most important being its ability to sensitize resistant tumour cells to chemotherapy, which led to its fast track FDA approval for phase II/III clinical trials. In this study, we examined the effects of PXD on human peripheral blood mononuclear cells (PBMC) and its potential role in regulating immune responses. We show that PXD, at concentrations >or=1 microg/ml (4 microM), inhibited proliferation and reduced the viability of healthy donor-derived PBMC. In contrast, lower PXD concentrations (0.05-0.5 microg/ml) augmented, upon 3-day incubation, PBMC cytotoxicity. Experiments with purified CD56(+) lymphocytes revealed that PXD enhanced the lytic function of natural killer (NK) cells by directly stimulating this lymphocytic subpopulation. Furthermore, in an in vivo colon cancer model, Balb/C mice administered low-dose PXD, exhibited significantly reduced tumour growth rates and prolonged survival (in 40% of the animals). Ex vivo results showed that PXD stimulated both NK and tumour-specific cell lytic activity. We conclude that PXD, when administered at low concentrations, can act as an immunomodulator, enhancing impaired immune responses, often seen in cancer-bearing individuals.


Asunto(s)
Antineoplásicos/farmacología , Factores Inmunológicos/farmacología , Isoflavonas/química , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antígeno CD56/biosíntesis , Línea Celular Tumoral , Supervivencia Celular , Femenino , Humanos , Técnicas In Vitro , Isoflavonas/farmacología , Células Asesinas Naturales/citología , Leucocitos Mononucleares/citología , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad
4.
Phytochemistry ; 68(11): 1587-94, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17475293

RESUMEN

From the aerial parts of Marrubium cylleneum, one labdane nor-diterpene has been isolated together with two labdane diterpenes, hitherto not known as natural products. The structures of the isolated compounds were established by means of NMR [(1)H-(1)H-COSY, (1)H-(13)C-HSQC, HMQC-TOCSY, HMBC, NOESY] and MS spectral analyses. Several diterpenoids from M. cylleneum and M. velutinum were tested for their cytotoxic effect against various cancer cell lines and their immunomodulating potential in human peripheral blood mononuclear cells in standard in vitro assays. Our results show a differential cytotoxicity of some compounds as well as their ability to improve selected lymphocyte functions.


Asunto(s)
Antineoplásicos Fitogénicos/toxicidad , Diterpenos/farmacología , Factores Inmunológicos/farmacología , Marrubium/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Linfocitos/efectos de los fármacos , Resonancia Magnética Nuclear Biomolecular
5.
Artículo en Inglés | MEDLINE | ID: mdl-17347009

RESUMEN

Most recent molecular studies revealed the phylogeny of Greek Podarcis species, which for years remained elusive, due to discordant data produced from various chromosomal, complement fixation and protein studies. In this report, we analyzed cellular immune responses of spleen-derived lymphocytes from six allopatric Podarcis species encountered in Greece, by assessing two-way mixed lymphocyte reaction (MLR)-induced proliferation. On the basis of stimulation indices (S.I.) as determined from cultures set up from xenogeneic splenocytes coincubated in pairs, we generated a phylogenetic tree, fully consistent with the phylogenetic relationships of Podarcis as determined by parallel analyses based on partial mitochondrial (mt) DNA sequences. Although the exact mechanisms triggering lymphocyte responses in lizard two-way xenogeneic MLR are not fully understood, our results show the potential use of cell-mediated immune responses as an additional approach to mtDNA analysis, for species delimitation within specific lizard taxa.


Asunto(s)
Lagartos/genética , Lagartos/inmunología , Filogenia , Animales , Secuencia de Bases , Proliferación Celular , Supervivencia Celular , ADN Mitocondrial/genética , Geografía , Grecia , Lagartos/clasificación , Prueba de Cultivo Mixto de Linfocitos , Linfocitos/citología , Masculino , Bazo/citología , Factores de Tiempo
6.
Peptides ; 27(1): 183-93, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16150512

RESUMEN

Since conserved mammalian polypeptides are believed to exhibit enhanced immunogenicity in avian species, hens were immunized against the poorly immunogenic, highly conserved mammalian polypeptide prothymosin alpha (ProTalpha), i.e. against either non-conjugated ProTalpha (isolated from bovine thymus) or ProTalpha conjugated to keyhole limpet hemocyanin (ProTalpha/KLH). The antibodies Y were isolated from the egg yolk and evaluated through suitable dot-blot and ELISA systems in parallel with antibodies G isolated from the antiserum of rabbits immunized against the same immunogens. As revealed, antibodies Y and G of low titer and/or affinity were obtained against non-conjugated ProTalpha, while antibodies Y against ProTalpha/KLH had a better apparent titer, could better discriminate between ProTalpha and the closely related bioactive peptide thymosin alpha 1, and were obtained at much larger quantities than the corresponding antibodies G.


Asunto(s)
Pollos/inmunología , Inmunoglobulinas/química , Precursores de Proteínas/inmunología , Timosina/análogos & derivados , Secuencia de Aminoácidos , Animales , Bovinos , Femenino , Células HeLa , Hemocianinas/inmunología , Hemocianinas/metabolismo , Humanos , Immunoblotting , Inmunoglobulina G/biosíntesis , Inmunoglobulina G/química , Inmunoglobulina G/aislamiento & purificación , Cadenas Pesadas de Inmunoglobulina/aislamiento & purificación , Cadenas Ligeras de Inmunoglobulina/aislamiento & purificación , Inmunoglobulinas/biosíntesis , Inmunoglobulinas/aislamiento & purificación , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Precursores de Proteínas/metabolismo , Conejos , Timalfasina , Timosina/inmunología , Timosina/metabolismo
7.
Anticancer Res ; 36(7): 3373-82, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27354596

RESUMEN

BACKGROUND/AIM: Peripheral blood mononuclear cells (PBMCs) activated with immobilized monoclonal antibody against cluster of differentiation 3 (CD3) secrete cytokines in their culture supernatant (termed ACD3S). We examined the antitumor efficacy of ACD3S-activated NK-92 cells in vitro and in vivo. MATERIALS AND METHODS: Interleukin (IL) 2-depleted NK-92 cells were reactivated with ACD3S, analyzed for their phenotype and tested for cytotoxicity, and perforin and interferon γ (IFNγ) production. Severe combined immunodeficient (SCID) mice xenografted with human melanoma and breast cancer cells were treated with ACD3S-activated NK-92 cells and tumor growth was monitored. RESULTS: Brief activation of IL2-depleted NK-92 cells with ACD3S fully restored their in vitro cytotoxicity towards tumor cells. ACD3S-activated NK-92 cells were phenotypically similar to standard NK-92 cells, but exhibited prolonged cytotoxicity and produced higher levels of IFNγ. When adoptively transferred to tumor-bearing SCID mice, these cells retarded the growth of melanoma and breast tumors. CONCLUSION: Stimulation of NK-92 cells with ACD3S may be useful in clinical cancer therapy, as an alternative method for ex vivo natural killer cell activation.


Asunto(s)
Neoplasias de la Mama/terapia , Citocinas/inmunología , Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/trasplante , Melanoma/terapia , Animales , Anticuerpos Inmovilizados/inmunología , Anticuerpos Monoclonales/inmunología , Neoplasias de la Mama/inmunología , Complejo CD3/inmunología , Citocinas/administración & dosificación , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Linfoma no Hodgkin/patología , Células MCF-7 , Melanoma/inmunología , Ratones , Ratones SCID , Distribución Aleatoria , Ensayos Antitumor por Modelo de Xenoinjerto
8.
Anticancer Res ; 35(3): 1543-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25750309

RESUMEN

AIM: To investigate the effect of serum from patients with non-small cell lung cancer (NSCLC) on in vitro cytotoxicity of the clonal cell line NK-92. MATERIALS AND METHODS: Twenty-six patients with NSCLC were included in this study. NK-92 cells were incubated in medium supplemented with 25% of each patient's serum (before and after chemotherapy) for 24 h, then washed and tested for cytotoxicity against NK-sensitive K562 targets. RESULTS: The cytotoxicity of NK-92 cells exposed to serum from patients with NSCLC before chemotherapy initiation was significantly reduced compared to that upon incubated with serum from healthy individuals (p<0.001). NK-92 cytotoxicity was further reduced upon exposure to patient's serum after the first and third chemo therapy cycles (p<0.001). CONCLUSION: The results of our in vitro study suggest that serum of patients with NSCLC may exert per se an inhibitory effect on the cytotoxicity of NK-92 cells and this negative regulation may be enhanced with chemotherapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/sangre , Neoplasias Pulmonares/sangre , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad
9.
Eur J Cancer ; 49(7): 1706-14, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23276721

RESUMEN

BACKGROUND: Tumour-associated lymphocytes (TALs) present in effusions of ovarian cancer patients exhibit impaired activities, due to the immunosuppressive environment of the ascites. Means to enhance their cytotoxicity against autologous tumour cells are of clinical importance. The immunomodulator prothymosin alpha (proTα) increases the specific lysis of tumour cells by activated CD8(+) T-lymphocytes and its immunoreactivity is exerted by the carboxy-terminal decapeptide, proTα(100-109). These two molecules were studied on TALs in vitro, and in SCID mice bearing human ovarian tumours. METHODS: TALs and tumour cells were isolated from 41 ovarian cancer patients and co-cultured in the presence of proTα or proTα(100-109). The cytotoxicity of peptide-stimulated TALs was tested against autologous tumour cells and K562. Ex vivo peptide-stimulated TALs from three patients were adoptively transferred intraperitoneally in SCID mice, previously inoculated with each patient's autologous tumour cells. RESULTS: ProTα and its immunoreactive peptide proTα(100-109), enhanced the cytotoxic activity of TALs against autologous tumour cells in vitro, but marginally affected the lysis of K562. The effect of proTα and proTα(100-109) was higher after 7-14 days of stimulation, whereas TAL cytotoxicity was significantly decreased after 21 days. Mice administered TALs, ex vivo activated with proTα or proTα(100-109) for 7 days, showed a relatively lower tumour increase rate and a prolongation of their survival, compared to controls. CONCLUSION: Our data demonstrate that, in the presence of tumour antigens, proTα and proTα(100-109) enhance the depressed cytotoxicity of TALs against autologous tumour cells in vitro and retard tumour growth in vivo.


Asunto(s)
Citotoxicidad Inmunológica/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Oligopéptidos/farmacología , Neoplasias Ováricas/terapia , Precursores de Proteínas/farmacología , Timosina/análogos & derivados , Adulto , Anciano , Animales , Ascitis/inmunología , Ascitis/patología , Células Cultivadas , Técnicas de Cocultivo , Citotoxicidad Inmunológica/inmunología , Femenino , Humanos , Inmunoterapia Adoptiva/métodos , Células K562 , Estimación de Kaplan-Meier , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/trasplante , Ratones , Ratones SCID , Persona de Mediana Edad , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/patología , Precursores de Proteínas/química , Timosina/química , Timosina/farmacología , Carga Tumoral/efectos de los fármacos , Carga Tumoral/inmunología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
10.
Proteomics ; 7(11): 1814-24, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17474146

RESUMEN

Prothymosin alpha (ProTalpha) is an acidic polypeptide associated both with cell proliferation and immune regulation. Although ProTalpha's immunomodulating activity is well established at cellular level, limited information is available regarding the signaling pathways triggered by ProTalpha. Using 2-DE proteomic technology, we investigated changes in protein expression of ProTalpha-stimulated peripheral blood mononuclear cells (PBMC) in the course of a 3-day incubation. Using healthy donor- and cancer patient-derived PBMC, 12 gels were studied, identifying 53 differing protein spots via PMF comparison analysis. Among others, we identified interleukin-1 receptor-associated kinase 4, heat-shock protein 90, lipocalin 2, ribophorin 1, eukaryotic elongation factor 2, 14-3-3 protein, L-plastin, and MX2 protein, all of which were found to be overexpressed upon ProTalpha activation. Based on the physiological role of upregulated proteins, we propose the following model for ProTalpha's immunological mode of action: on day 1, ProTalpha triggers monocyte activation, possibly via toll-like receptor signaling, and enhances antigen presentation, consequently promoting and stabilizing monocyte-T-cell immune synapse; on day 2, activated monocytes produce interleukin (IL)-1, while T-cell receptor triggering promotes T-cell proliferation and IL-2 production; finally, on day 3, ProTalpha-activated PBMC express proteins related to adhesion and cytotoxic effector functions, both contributing to the increase of their lytic activity.


Asunto(s)
Leucocitos Mononucleares/inmunología , Activación de Linfocitos/inmunología , Neoplasias Ováricas/inmunología , Precursores de Proteínas/fisiología , Proteínas/análisis , Proteómica , Timosina/análogos & derivados , Electroforesis en Gel Bidimensional , Femenino , Humanos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Neoplasias Ováricas/sangre , Precursores de Proteínas/farmacología , Proteínas/metabolismo , Valores de Referencia , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Timosina/farmacología , Timosina/fisiología
11.
Cancer Immunol Immunother ; 55(10): 1247-57, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16453152

RESUMEN

Prothymosin alpha (proTalpha) is a 109 amino acid long polypeptide presenting distinct immunoenhancing activity in vitro and in vivo. Recent reports suggest that in apoptotic cells, proTalpha is cleaved by caspases at its carboxy(C)-terminus generating potentially bioactive fragments. In this study, we identified the peptide segment of proTalpha presenting maximum immunomodulatory activity. Calf thymus proTalpha was trypsinised, and the five fragments produced (spanning residues 1-14, 21-30, 31-87, 89-102 and 103-109) were tested for their ability to stimulate healthy donor- and cancer patient-derived peripheral blood mononuclear cell (PBMC) proliferation in autologous mixed lymphocyte reaction (AMLR), natural killer and lymphokine-activated killer cell activity, intracellular production of perforin, upregulation of adhesion molecules and CD25 expression. ProTalpha(89-102) and proTalpha(103-109) significantly fortified healthy donor-lymphocytes' immune responses to levels comparable to those induced by intact proTalpha. These effects were more pronounced in cancer patients, where peptides proTalpha(89-102) and proTalpha(103-109) partly, however significantly, restored the depressed AMLR and cytolytic ability of PBMC, by simulating the biological activity exerted by intact proTalpha. ProTalpha(1-14), proTalpha(21-30) and proTalpha(31-87) marginally upregulated lymphocyte activation. This is the first report showing that proTalpha's immunomodulating activity can be substituted by its C-terminal peptide(s). Whether generation and externalization of such immunoactive proTalpha fragments occurs in vivo, needs further investigation. However, if these peptides can trigger immune responses, they may eventually be used therapeutically to improve some PBMC functions of cancer patients.


Asunto(s)
Neoplasias/inmunología , Fragmentos de Péptidos/inmunología , Precursores de Proteínas/química , Precursores de Proteínas/inmunología , Timosina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Animales , Sitios de Unión , Bovinos , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Inmunofenotipificación , Técnicas In Vitro , Leucocitos Mononucleares/inmunología , Prueba de Cultivo Mixto de Linfocitos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Fragmentos de Péptidos/genética , Precursores de Proteínas/genética , Homología de Secuencia de Aminoácido , Timosina/química , Timosina/genética , Timosina/inmunología
12.
Oncology ; 67(5-6): 403-10, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15713997

RESUMEN

OBJECTIVES: We investigated the immune profile of patients with resected Dukes' stage C colorectal cancer (CRC), receiving adjuvant therapy with edrecolomab (Mo17-1A) or first-line 5-fluorouracil (5-FU)-based chemotherapy. PATIENTS AND METHODS: Patients received either 5 doses of Mo17-1A over 13 weeks, or 5-FU/leucovorin, or 5-FU/levamisole over 6 and 12 months, respectively. Peripheral blood was collected postoperatively and 4 months after therapy initiation. Peripheral blood mononuclear cells were tested in the autologous mixed lymphocyte reaction (AMLR), for natural killer (NK) and lymphokine-activated killer (LAK) cell activity. Serum cytokines were quantified by ELISA. RESULTS: Fifty-two patients entered the study. Postoperatively, they exhibited decreased levels of interleukin (IL)-2, interferon-gamma, IL-12, granulocyte-macrophage colony-stimulating factor and IL-15, low cellular immune responses (AMLR, NK- and LAK-cytotoxicity) and increased levels of IL-1beta, tumor necrosis factor-alpha, IL-6, IL-10 and prostaglandin E(2). After four months of therapy, patients receiving edrecolomab demonstrated enhanced AMLR, NK, LAK activity, increased serum levels of cytokines regulating such responses and reduced levels of acute-phase cytokines and immune suppressors, compared to patients treated with conventional chemotherapy. CONCLUSIONS: Postoperative adjuvant therapy with edrecolomab restores the in vivo deficient immune responses of patients with resected Dukes' C CRC despite its clinical ineffectiveness in recent randomized adjuvant trials. These results suggest that further immunological studies with the combination of edrecolomab and chemotherapy are required.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Citocinas/sangre , Fluorouracilo/farmacología , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia Adyuvante , Colectomía , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Dinoprostona/sangre , Esquema de Medicación , Ensayo de Inmunoadsorción Enzimática , Femenino , Fluorouracilo/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Humanos , Interferón gamma/sangre , Interleucinas/sangre , Células Asesinas Activadas por Linfocinas/inmunología , Células Asesinas Naturales/inmunología , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Factor de Necrosis Tumoral alfa/metabolismo
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