RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Circulating tumor cells (CTCs) play an important role in tumor metastasis and may be a target for metastasis prevention. The traditional Chinese medicine Jinfukang functions to improve immunity, prevent metastasis, and prolong lung cancer patient survival periods. Yet, whether Jinfukang prevents metastasis by regulating immune cells to clearance CTCs is still unknown. AIM OF THE STUDY: To explore the anti-metastasis mechanism of Jinfukang from the perspective of regulating NK cells to clear CTCs. MATERIALS AND METHODS: CTC-TJH-01 cell was treated with Jinfukang. Cytokine chip was used to detect cytokines in cell culture supernatant. Lymphocyte recruitment assay was detected by Transwell and flow cytometry. Protein expression was analysis by Western blot. LDH kit was used to detect cytotoxicity. NOD-SCID mice used for tail vein injection to study lung metastasis. RESULTS: Jinfukang could promote the expression and secretion of the chemokine CX3CL1 by CTCs. In addition, Jinfukang could promote the recruitment of natural killer (NK) cells by CTCs and significantly increase the cytotoxic effect of NK cells on CTCs. Moreover, Jinfukang could upregulate the expression of FasL and promote the secretion of TNF-α by NK cells and that NK cells could induce the apoptosis of CTCs through the Fas/FasL signaling pathway. Finally, we confirmed that Jinfukang could promote NK cells to kill CTCs and then inhibit lung cancer metastasis in vivo. The above effects of Jinfukang could be partially reversed by an anti-CX3CL1 mAb. CONCLUSIONS: These results suggest that Jinfukang may prevent lung cancer metastasis by enhancing the clearance of CTCs in the peripheral blood by NK cells, providing evidence for the anti-metastasis effect of Jinfukang.
Asunto(s)
Antineoplásicos/farmacología , Quimiocina CX3CL1/genética , Medicamentos Herbarios Chinos/farmacología , Células Asesinas Naturales/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Metástasis de la Neoplasia/prevención & control , Células Neoplásicas Circulantes/efectos de los fármacos , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Quimiocina CX3CL1/antagonistas & inhibidores , Quimiocina CX3CL1/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Proteínas Ligadas a GPI/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos NOD , Ratones SCID , Metástasis de la Neoplasia/inmunología , Células Neoplásicas Circulantes/inmunología , Células Neoplásicas Circulantes/patología , Receptores de Muerte Celular/metabolismo , Transducción de Señal/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Receptor fas/metabolismoRESUMEN
Galectin3 is expressed in various tissues and plays an important role in the tumor microenvironment (TME). Galectin3 has been found to be overexpressed in a variety of cancers and is associated with tumor progression and metastasis. Over the past decades, emerging evidence has suggested that the TME may induce galectin3 expression to maintain cellular homeostasis and promote cell survival. Furthermore, galectin3 regulates immune cell function to promote tumordriven immunosuppression through several mechanisms. In the TME, intracellular and extracellular galectin3 has different functions. In addition, it has been reported that galectin3 is associated with glycolysis and mitochondrial metabolism in tumors, and it is involved in the regulation of relevant signaling pathways, thus promoting cancer cell survival via adapting to the TME. The aim of the present review was to summarize the current knowledge on galectin3 production and its function in the TME, its effect on TME immunosuppression, its association with tumor metabolism and relevant signaling pathways, and to report common types of cancer in which galectin3 is highly expressed, in order to ensure a comprehensive understanding of the critical effects of galectin3 on tumor progression and metastasis.
Asunto(s)
Galectina 3/metabolismo , Tolerancia Inmunológica/inmunología , Neoplasias/inmunología , Microambiente Tumoral/inmunología , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Movimiento Celular/inmunología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Evaluación Preclínica de Medicamentos , Galectina 3/antagonistas & inhibidores , Glucólisis/efectos de los fármacos , Glucólisis/inmunología , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Ratones , Mitocondrias/metabolismo , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/prevención & control , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Pectinas/farmacología , Pectinas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Cellular communication through gap junctions and hemichannels formed by connexins and through channels made by pannexins allows for metabolic cooperation and control of cellular activity and signalling. These channel proteins have been described to be tumour suppressors that regulate features such as cell death, proliferation and differentiation. However, they display cancer type-dependent and stage-dependent functions and may facilitate tumour progression through junctional and non-junctional pathways. The accumulated knowledge and emerging strategies to target connexins and pannexins are providing novel clinical opportunities for the treatment of cancer. Here, we provide an updated overview of the role of connexins and pannexins in malignant melanoma. We discuss how targeting of these channel proteins may be used to potentiate antitumour effects in therapeutic settings, including through improved immune-mediated tumour elimination.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Conexinas/metabolismo , Melanoma/secundario , Neoplasias Cutáneas/patología , Piel/patología , Animales , Antineoplásicos Inmunológicos/farmacología , Carcinogénesis/efectos de los fármacos , Carcinogénesis/inmunología , Carcinogénesis/patología , Comunicación Celular/efectos de los fármacos , Comunicación Celular/inmunología , Línea Celular Tumoral , Conexinas/agonistas , Conexinas/antagonistas & inhibidores , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/patología , Interacciones Microbiota-Huesped/efectos de los fármacos , Interacciones Microbiota-Huesped/inmunología , Humanos , Melanoma/tratamiento farmacológico , Melanoma/inmunología , Melanoma/mortalidad , Microbiota/inmunología , Invasividad Neoplásica/inmunología , Invasividad Neoplásica/patología , Invasividad Neoplásica/prevención & control , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/prevención & control , Estadificación de Neoplasias , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Piel/citología , Piel/microbiología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
To examine the anti-metastatic activities of polysaccharides in broccoli, purified polysaccharides (BCE-I, -II, and -III) were isolated by fractionation of broccoli enzyme extracts and subsequent ethanol precipitation. BCE-I mainly consisted of galactose and arabinose, whereas BCE-II mainly consisted of galacturonic acid and rhamnose, and BCE-III mainly consisted of rhamnose and galactose. Of the three fractions, stimulation of murine peritoneal macrophages by BCE-I showed the greatest enhancement of tumor necrosis factor-α, interleukin (IL)-12, and IL-6 secretion. In addition, intravenous (i.v.) administration of BCE-I enhanced the lethal activity of natural killer (NK) cells on YAC-1 tumor cells significantly and dose-dependently in an ex vivo experiment of NK cell activity. In an experimental model using lung metastasis of Colon26-M3.1 carcinoma cells, prophylactic i.v. and oral administration of BCE-I significantly and dose-dependently inhibited lung metastatic activity. Furthermore, the inhibitory activity of BCE-1 on lung metastasis partially disappeared when NK cell function was removed through treatment of rabbit anti-asialo GM1. These results indicated that BCE-I has potent antitumor metastatic activity, and that its anti-metastatic activity has relevance to the stimulation of NK and other immune cells.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Brassica/química , Neoplasias del Colon/inmunología , Inmunidad Innata/efectos de los fármacos , Neoplasias Pulmonares/prevención & control , Pectinas/farmacología , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Neoplasias del Colon/patología , Femenino , Humanos , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Activación de Macrófagos/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/prevención & control , Pectinas/química , Pectinas/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polisacáridos/química , Polisacáridos/aislamiento & purificaciónRESUMEN
A polysaccharide fraction, HBE-III, was successfully purified in a high yield (40.4%) from its crude polysaccharide (HBE-0) which was prepared from pectinase hydrolysates of the peels of the Korean Citrus Hallabong. In experimental lung metastasis studies of Colon 26-M3.1 carcinoma cells, prophylactic administration of HBE-III significantly inhibited lung metastasis in a dose-dependent manner. In an in vitro cytotoxicity analysis, HBE-III (up to 1000 µg/mL) did not affect the growth of Colon 26-M3.1 cells and normal cells. HBE-III enhanced production of IL-6 and IL-12 by murine peritoneal macrophages. In an assay for natural killer (NK) cell activity, HBE-III (1000 µg/mouse, i.v.) significantly augmented NK cytotoxicity against Yac-1 tumor cells. The depletion of NK cells by injection of mouse anti-asialo GM1 serum abolished the inhibitory effect of HBE-III on lung metastasis of Colon 26-M3.1 cells. These data suggest that HBE-III may inhibit tumor metastasis via activation of macrophages and NK cells.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Citrus/química , Neoplasias del Colon/patología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Pectinas/química , Pectinas/uso terapéutico , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular , Línea Celular Tumoral , Colon/inmunología , Colon/patología , Neoplasias del Colon/inmunología , Femenino , Hidrólisis , Interleucina-12/inmunología , Interleucina-6/inmunología , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/patología , Metástasis de la Neoplasia/prevención & control , Pectinas/aislamiento & purificación , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/uso terapéuticoRESUMEN
Beta-glucans (ß-glucans), naturally occurring polysaccharides, are present as constituents of the cell wall of cereal grains, mushrooms, algae, or microbes including bacteria, fungi, and yeast. Since Pillemer et al. first prepared and investigated zymosan in the 1940s and others followed with the investigation of ß-glucans in the 1960s and 1970s, researchers have well established the significant role of ß-glucans on the immune system relative to cancer treatment, infection immunity, and restoration of damaged bone marrow. However, information on their biological role in anti-metastatic activity remains limited. As an immunomodulating agent, ß-glucan acts through the activation of innate immune cells such as macrophages, dendritic cells, granulocytes, and natural killer cells. This activation triggers the responses of adaptive immune cells such as CD4(+) or CD8(+) T cells and B cells, resulting in the inhibition of tumor growth and metastasis. Reports have shown that ß-glucans exert multiple effects on cancer cells and cancer prevention. However the mechanisms of their actions appear complex due to differences in source, chemical structure, insufficiently defined preparation, and molecular weight, hence the inconsistent and often contradictory results obtained. This review is focused on the potential of ß-glucans as anti-metastatic agents and the known mechanisms underlying their biological effects.
Asunto(s)
Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , beta-Glucanos/uso terapéutico , Animales , Ensayos Clínicos como Asunto/métodos , Humanos , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/patología , Neoplasias/inmunología , Neoplasias/patología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Resultado del Tratamiento , beta-Glucanos/químicaRESUMEN
BACKGROUND: Psychological studies have documented the presence of a self-punishment profile in cancer patients. Recent immuno-oncological studies have shown that within the group of CD4(+) cells, which play a fundamental role in the generation of anticancer immunity, there is a subtype of cells that in contrast mediates the suppression of the anticancer immunity, the so-called T-regulatory cells (T-reg), which may be identified as CD4(+)CD25(+) cells. PATIENTS AND METHODS: On this basis, we performed a psychoncological study to evaluate CD4(+)CD25(+) cell numbers in relation to the response to Rorschach's test in a group of 30 cancer patients suffering from the most frequent tumor histotypes. RESULTS: Normal values obtained in our laboratory (95% confidence limits) of T-reg lymphocytes and CD4(+)/CD4(+)CD25(+) were <240/mm(3) and >4mm(3), respectively. The psychological profile of self-punishment was found in 18/30 patients (60%). The percentage of patients with abnormally high CD4(+)CD25(+) values observed in the group with self-punishment was significantly higher than that found in patients without self punishment (11/18 vs. 3/12 (25%), p<0.05). In the same way, the percentage of patients with abnormally low CD4(+)/CD4(+)CD25(+) ratios was significantly higher in the group with self-punishment (16/18 vs. 4/12, p<0.01). The mean numbers of T-reg lymphocytes observed in the group with self-punishment was significantly higher than that found in patients who had no self-punishment (314+/-39 vs. 173+/-27, p<0.05). In addition, the mean CD4(+)/ CD4(+)CD25(+) ratio was significantly lower in patients with self-punishment than in the other group (2.6+/-0.2 vs. 5.2+/-0.8, p<0.025). On the contrary, no significant difference was seen in the mean number of CD4(+) lymphocytes. CONCLUSION: The study suggests that self-punishment may inhibit the generation of an effective anticancer immune response by stimulating the activation and proliferation of T-reg lymphocytes, which in turn stimulate tumor dissemination by suppressing anticancer immunity. The abnormally high number of T-reg lymphocytes in patients with self-punishment would suggest a specific immune alteration, as suggested by the evidence of a normal profile for other immune parameters, such as total CD4(+) lymphocytes.
Asunto(s)
Oncología Médica , Neoplasias , Psiquiatría , Psiconeuroinmunología , Castigo/psicología , Linfocitos T Reguladores/inmunología , Adaptación Psicológica/fisiología , Adulto , Anciano , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/inmunología , Neoplasias/inmunología , Neoplasias/psicología , Prueba de Rorschach , Autoeficacia , Adulto JovenRESUMEN
Successful avoidance of the immune surveillance system is critical for the development of a blood-borne metastasis. Previous findings suggest that experimental tumor metastasis was enhanced in senescence-accelerated mice prone 10 (SAMP10) due to a reduction in immune surveillance potential with age. In the present study, water containing green tea (GT)-catechins was freely given to SAMP10 mice, and the chemopreventive effect of GT-catechin intake on tumor metastasis was examined. Natural killer cell activity, which is an indicator of immune surveillance potential and is reduced in control mice with age, was maintained by GT-catechin intake. The early accumulation of lung-metastatic K1735M2 melanoma cells in lungs after intravenous injection of the cells and subsequent experimental lung metastasis was investigated in mice given GT-catechins. The accumulation at 6 and 24 h after injection of K1735M2 cells was significantly suppressed, and the number of lung-metastatic colonies was significantly reduced, in comparison with those in control mice. The results suggest that GT-catechin intake prevented the experimental tumor metastasis in aged SAMP10 mice via its inhibition of a reduction in immune surveillance potential with age.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Camellia sinensis/química , Catequina/uso terapéutico , Vigilancia Inmunológica/efectos de los fármacos , Melanoma/secundario , Metástasis de la Neoplasia/prevención & control , Extractos Vegetales/uso terapéutico , Envejecimiento/inmunología , Animales , Antineoplásicos Fitogénicos/farmacología , Catequina/análogos & derivados , Catequina/farmacología , Línea Celular Tumoral , Células Asesinas Naturales/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Melanoma/tratamiento farmacológico , Ratones , Ratones Endogámicos , Metástasis de la Neoplasia/inmunología , Trasplante de Neoplasias , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/secundario , Fitoterapia , Extractos Vegetales/farmacologíaRESUMEN
OBJECTIVE: To study the effect of yiqi bushen koufiuye (oral liquid for invigorating qi and tonifying the kidney) combined with chemotherapy on postoperative metastasis of stomach cancer. METHODS: The 47 cases of postoperative stomach cancer with the syndrome of deficiency of both the spleen and kidney were divided randomly into the treatment group (28 cases), and the control group (19 cases). The control group was treated simply by chemotherapy; while the treatment group, was treated with Yiqi Bushen Koufuye in addition to chemotherapy. The effect was observed 12 months later on local relapse and distal metastasis, the life quality, peripheral hemogram, and immunologic function. RESULTS: The rates of postoperative relapse and metastasis of the treatment group were obviously lower than those of the control group (P < 0.05). The Karnofasky scores, peripheral hemogram and immunologic function of the treatment group were obviously improved in comparison with the control group (P < 0.01 or P < 0.05). CONCLUSION: Yiqi bushen koufuye combined with chemotherapy is effective in preventing postoperative metastasis of stomach cancer, increasing sensitivity and decreasing toxins, and improving the life quality and immunologic function of the patient.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Metástasis de la Neoplasia/prevención & control , Complicaciones Posoperatorias/prevención & control , Neoplasias Gástricas/cirugía , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/inmunología , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/inmunología , Periodo Posoperatorio , Calidad de Vida , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
One of the functions of macrophages is to provide a defense mechanism against tumor cells. In contrast, tumor-associated macrophages (TAMs), which represent the major inflammatory component of the stroma of many tumors, are associated with tumor progression and metastasis. TAMs, in contrast with normal macrophages, exhibit the M2 phenotype, and thereby exhibit pro-tumoral functions, including angiogenesis and matrix remodeling. This review will discuss the role of TAMs in tumor progression and provide an overview of their significant part in tumor metastasis and angiogenesis.
Asunto(s)
Macrófagos/inmunología , Metástasis de la Neoplasia/inmunología , Neoplasias/inmunología , Productos Biológicos/efectos adversos , Productos Biológicos/uso terapéutico , Progresión de la Enfermedad , Sistemas de Liberación de Medicamentos , Humanos , Invasividad Neoplásica/inmunología , Neovascularización Patológica/inmunologíaRESUMEN
An aqueous plant extract from Azadirachta indica and its chromatographic fraction F1 (neem extract) exerted immunomodulating and antimetastatic activities in BALB/ c-mice. Regular subcutaneous administration of neem extract yielded significantly increased spleen weight and significant enhancement of peritoneal macrophage activity in the chemiluminescence assay, and activation marker CD-44 expression. The thymus weight and thymocyte counts did not show significant differences in the control and neem extract-treated groups, however, determination of peripheral blood cells revealed significant up-regulations of leukocyte subsets, the lymphocytes and monocytes. Flow cytometric analaysis of lymphocyte supopulations documented increased counts of CD-4 and CD-8 cells and an inreased activation marker expression on lymphocytes (CD-25) and monocytes (MAC-3) in neem-treated mice compared to the control animals. To evaluate the antimetastatic activity of neem extract, sarcoma L-1 cells and lymphosarcoma RAW cells were intravenously inoculated into BALB/c-mice. In these model systems the number of experimental lung and liver metastases decreased relevantly, however, biometrically non-significantly in neem extract-treated animals, as compared to the control mice which received injections of saline solutions. Neem extract can be regarded as an immunomodulating and antimetastatic substance which holds promise for further experimental and clinical investigation.
Asunto(s)
Antineoplásicos/uso terapéutico , Azadirachta , Sistema Inmunológico/efectos de los fármacos , Neoplasias Experimentales/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Animales , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Citometría de Flujo , Sistema Inmunológico/patología , Inyecciones Subcutáneas , Subgrupos Linfocitarios/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/patología , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/patología , Tamaño de los Órganos/efectos de los fármacos , Hojas de la Planta/química , Timo/efectos de los fármacos , Timo/inmunología , Timo/patologíaRESUMEN
The pectic polysaccharide (angelan) of Angelica gigas Nakai is an immunostimulator that activates the immune functions of B cells and macrophages. Here we investigated the effect of angelan on tumor growth and metastasis. Angelan was found to significantly prolong the survival rate of B16F10-implanted mice and to reduce the frequency of pulmonary metastasis of B16F10 melanoma. Moreover, the combined treatment of angelan and doxorubicin (a cytotoxic anticancer agent) more effectively inhibited tumor growth and metastasis than either compound alone. In the present study, we found that angelan directly inhibited cancer cell adhesion and invasion through the extracellular matrix, in addition to activating the immune functions of B cells and macrophages. These results suggest that angelan can inhibit tumor growth and metastasis by stimulating host immunity and directly inhibiting cancer cell adhesion.
Asunto(s)
Angelica/química , Proliferación Celular/efectos de los fármacos , Melanoma Experimental/prevención & control , Metástasis de la Neoplasia/prevención & control , Polisacáridos/farmacología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Adhesión Celular/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Femenino , Inyecciones Intraperitoneales , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Melanoma Experimental/mortalidad , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/patología , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/farmacología , Polisacáridos/administración & dosificación , Tasa de Supervivencia , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunologíaRESUMEN
After many years, hyperthermia (HT) is experiencing a new resurgence as seen by the positive results of many randomized trials all over the world. Tumour immunity similarly is suggested as the fourth modality of therapy for metastatic tumours from renal carcinoma and melanoma. An overwhelming amount of data from animal models and human patients indicate that whole body and locoregional hyperthermia exerts many biological and therapeutic effects on immune competent cells and cytokines. Among these effects, hyperthermia has recently been demonstrated to enhance the antigen presentation and consequently the activity of dendritic cells. This improvement is obtained through several mechanisms: a) increased lymphocyte recruitment and trafficking into the tumour area; b) increased immunogenicity of heat treated tumour cells; and c) increased production of the heat-shock proteins and costimulatory molecules. The effects and mechanisms of HT on immunity, lymphocyte recruitment and dendritic cell stimulation by heat shock proteins are reviewed here. Moreover the use of HT as an innate immunity booster in association with biological response modifiers is suggested.
Asunto(s)
Hipertermia Inducida , Inmunidad , Metástasis de la Neoplasia/terapia , Neoplasias/terapia , Animales , Presentación de Antígeno , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Humanos , Metástasis de la Neoplasia/inmunología , Neoplasias/inmunologíaRESUMEN
This mini-review emphasizes a psychoneuroimmunology (PNI) perspective of the hypothesis that stress and surgical excision of the primary tumor can promote tumor metastasis. It first establishes the empirical and theoretical basis for control of metastasis by cell-mediated immunity (CMI), as well as the interactive role of non-immunological risk factors. It then describes the various aspects of surgery that suppress CMI, and the neuroendocrine mechanisms mediating suppression by stress and surgery. Last, it briefly reviews the empirical evidence, from animal and human studies, for the promotion of metastasis by stress and surgery, with specific reference to the mediating role of CMI. It is concluded that: (a) Immunological mechanisms most likely play a role in limiting metastasis in patients with solid tumors. (b) Immunosuppression can be deleterious, especially when surgery is conducted early, before the tumor develops insurmountable mechanisms to escape immune destruction. (c) The most sensitive period for the establishment of metastases is the immediate aftermath of surgery. Interventions aiming at reducing stress and immunosuppression should thus strive to start beforehand. (d) 'Psychological and physiological insults activate similar neuroendocrine mechanisms of immunosuppression. Therefore, a multimodal therapeutic approach should be used to prevent tumor metastasis during the perioperative period. (e) Studies employing interventions aimed at reducing the surgical stress response should preferably assess immunological indices with an established clinical relevance, and follow up long-term recurrence provided sample size assure statistical power. (f) The progress toward earlier detection of cancer, and our growing understanding of immunosuppression, continuously improves the chances for successful PNI interventions.
Asunto(s)
Metástasis de la Neoplasia/inmunología , Neoplasias/inmunología , Neoplasias/cirugía , Psiconeuroinmunología , Estrés Fisiológico/inmunología , Animales , HumanosRESUMEN
Há mais de dois mil anos fitoterápicos têm sido usados de maneira empírica no tratamento de diversas doenças, inclusive o câncer de mama com metástase pulmonar que foi submetido a tratamento com o cogumelo comestível Agaricus sylvaticus (marca registrada Cogumelo do Sol) é aqui relatado. O tratamento foi feito como complemento da tradicional quimioterapia, radioterapia e cirurgia. O sucesso evolutivo observado foi atrribuído ao aumento das células "Natural Killer" do paciente. As células CD-56 (Natural Killer Cells) tem sido observadas, em muitos experimentos laboratoriais como elemento imunológico responsável por atividade anticancerígena em animais e humanos.(au)
Asunto(s)
Humanos , Femenino , Adulto , Medicina de Hierbas , Metástasis de la Neoplasia/inmunología , NeoplasiasRESUMEN
The effects of anti-cancer number one (ACNO), a 19-herb Chinese formula used to treat cancer patients, were studied in F344 rats. In the first study, the number and activity of circulating NK cells were evaluated following 18 days of oral consumption of 0.1, 0.5, or 2 g/kg/day. The second study assessed the effect of ACNO on resistance to metastasis of the MADB106 tumor line, a syngeneic mammary adenocarcinoma that metastasizes only to the lungs and is highly sensitive to NK activity (NKA) in vivo. Resistance to metastasis was assessed under baseline conditions and following the administration of a beta-adrenergic agonist, metaproterenol (MP). MP was used to simulate sympathetic response to stressful conditions, and was previously shown to suppress resistance to MADB 106 metastasis. The results of the first study indicated a dose-dependent increase in NKA per ml of blood and per NK cell, with no significant changes in blood concentration of NK cells. In the second study, whereas MP caused a 4.5-fold increase in the number of metastases in untreated rats, only a 2.3-fold increase occurred in rats treated with ACNO. No significant improvement in baseline levels of resistance to metastasis was observed. These findings indicate the importance of studying ACNO under stressful conditions in patients with potentially metastasizing tumors. This may prove particularly important during the perioperative period, spanning from the detection of the primary tumor to postoperative treatment. During this critical period, psychological and physiological stress responses are known to cause massive immunosuppression, which was suggested to promote metastatic development.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Células Asesinas Naturales/efectos de los fármacos , Metástasis de la Neoplasia/prevención & control , Adenocarcinoma/patología , Agonistas Adrenérgicos beta/toxicidad , Animales , Recuento de Células , Pruebas Inmunológicas de Citotoxicidad , Relación Dosis-Respuesta a Droga , Femenino , Citometría de Flujo , Células Asesinas Naturales/inmunología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Metaproterenol/antagonistas & inhibidores , Metaproterenol/toxicidad , Metástasis de la Neoplasia/inmunología , Metástasis de la Neoplasia/patología , Trasplante de Neoplasias , Ratas , Ratas Endogámicas F344 , Células Tumorales Cultivadas , Aumento de Peso/efectos de los fármacosRESUMEN
The immunomodulatory and antimetastatic activity of standardized aqueous mistletoe extracts from plants grown on fir trees (ME-A) and pine trees (ME-P) were evaluated in BALB/c-mice. Regular subcutaneous (s.c.) and intraperitoneal (i.p.) applications (three times per week for 14 consecutive days; 5 and 50 microg per injection and mouse) upregulated thymus weight and peripheral blood leukocyte counts in tumor bearing mice. To check the influence of ME-A and ME-P treatment on growth of experimental metastases, RAW 117 H 10 lymphosarcoma cells and L-1 sarcoma cells were intravenously inoculated into BALB/c-mice to establish liver and lung colonization. ME-A and ME-P were regularly administered starting 24 h after tumor cell challenge. Organ colonization was investigated on day 14 after tumor cell inoculation and demonstrated statistically significant (P<0.05) reductions of experimental liver and lung metastases for ME-A and ME-P treated mice.
Asunto(s)
Muérdago/uso terapéutico , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Fitoterapia , Plantas Medicinales , Adyuvantes Inmunológicos/uso terapéutico , Animales , Ratones , Ratones Endogámicos BALB C , Muérdago/inmunología , Metástasis de la Neoplasia/tratamiento farmacológico , Metástasis de la Neoplasia/inmunología , Neoplasias Experimentales/inmunologíaAsunto(s)
Acetilmuramil-Alanil-Isoglutamina/farmacología , Adyuvantes Inmunológicos/farmacología , Melanoma Experimental/genética , Metástasis de la Neoplasia/genética , Fenotipo , Animales , Antígenos de Neoplasias/inmunología , Antígenos de Superficie/inmunología , Citotoxicidad Inmunológica , Humanos , Melanoma Experimental/inmunología , Melanoma Experimental/patología , Ratones , Ratones Desnudos , Metástasis de la Neoplasia/inmunología , Trasplante de Neoplasias , Trasplante Heterólogo , Células Tumorales Cultivadas , Escape del TumorRESUMEN
The antimetastatic activity (AA) of spleen macrophages and T-lymphocytes of mice bearing four syngeneic tumours were tested in adoptive transfer system. Elimination of phagocytic cells by treatment with carrageenan or by carbonyl iron resulted in a complete (tumours LS, MMT1, MMT-T6I) or partial (MMT-T6I) AA decrease. Spleen macrophages (adherent cells) of tumour-bearers possessed a significant AA. The treatment of spleen cells both by anti-Thy-1-serum and by complement enhanced AA of spleen cells of LS and MMT1 tumour-bearers, but led to a partial AA suppression of spleen cells of MMT-T6I tumour-bearers. Thus, the efficiency of antimetastatic defence may considerably depend on the presence of synergism between macrophages and T-lymphocytes in realization of their AA.