RESUMEN
OBJECTIVE: This study aimed to evaluate the impact of early tracheostomy (ET, ≤7 days) versus that of late tracheostomy (LT, >7 days) on outcomes such as hospital length of stay (LOS), intensive care unit (ICU) days, mechanical ventilation (MV) days, and mortality ratio. METHODS: A historical cohort study was undertaken using charts of patients admitted to the Puerto Rico Trauma Hospital who required MV and underwent tracheostomies, from 2000 to 2013. A logistic regression was performed to evaluate the association between timing of tracheostomy and complications and mortality. To estimate the relationship between ET and outcomes related to hospital stay, a binomial-negative regression was performed. A P < 0.05 was considered statistically significant. RESULTS: A total of 1134 patients were evaluated, 313 of whom underwent ET and 821 underwent LT. Early tracheostomy patients had a lower Injury Severity Score compared with their counterparts (P = 0.004) and showed lower complications (respiratory failure: odds ratio [OR], 0.61; 95% confidence interval [CI], 0.45-0.84; acute respiratory distress syndrome: OR, 0.44; 95% CI, 0.30-0.64; pneumonia: OR, 0.53; 95% CI, 0.40-0.71; septicemia: OR, 0.48; 95% CI, 0.33-0.70; bacteremia: OR, 0.59; 95% CI, 0.40-0.86) than LT patients. Those with ET had lower MV days (RRadj, 0.74; 95% CI, 0.68-0.82), ICU days (RRadj, 0.66; 95% CI, 0.59-0.73), and LOS (RRadj, 0.74; 95% CI, 0.69-0.80) compared with those with LT, after adjusting for age, Injury Severity Score, and complications. However, there were no differences in mortality ratio (ORadj, 0.66; 95% CI, 0.44-1.01) among ET and LT patients, after adjusting for confounders. CONCLUSIONS: Our results suggested that ET reduced complications, MV days, ICU days, and LOS, having an indirect effect on mortality ratio. Standardized protocols for ET are recommended to enhance health outcomes in trauma patients.
Asunto(s)
Traqueostomía/métodos , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Puerto Rico , Estudios Retrospectivos , Traqueostomía/mortalidad , Centros TraumatológicosRESUMEN
The aim of the present work was to optimize the main experimental variables of a procedure using HS-SPME/GC-MS as the analytical methodology to establish the profile of the volatile compounds present in aerial parts of Hedeoma multiflorum Benth. The influence of the type of fiber, equilibrium time, extraction time and extraction temperature on the composition of the volatile compounds was determined using response surface methodology (RSM), and the parameters of the models were corroborated by multiple linear regressions. The results showed that the regression models generated adequately explained the data variation and represented the relationships between the parameters and their responses. The optimal analysis conditions from the contour plots were established (DVB/CAR/PDMS fiber, with a 10 min equilibrium time, 10 min extraction time, and 40°C). Under these conditions, 41 volatile components in the whole plant were determined, which represents more than those reported using hydrodistillation.
El objetivo del presente trabajo fue optimizar las principales variables experimentales de un procedimiento HS-SPME/GC para establecer el perfil de compuestos volaÌtiles presentes en la parte aeÌrea de Hedeoma multiflorum Benth. Se determinoÌ la influencia de las variables tipo de fibra, tiempo de equilibrio, tiempo de extraccioÌn y temperatura de extraccioÌn sobre la composicioÌn de los volaÌtiles, utilizando una met odologiÌa de superficie de respuesta (RSM) y los paraÌmetros del modelo se corroboraron por regresioÌn lineal muÌltiple. Los resultados demostraron que los modelos de regresioÌn generados explican adecuadamente la variacioÌn de los datos y representaron significativamente las relaciones reales entre los paraÌmetros y sus respuestas. Las condiciones oÌptimas de anaÌlisis fueron establecidas (DVB/CAR/PDMS, con un tiempo de equilibrio de 10 minutos, un tiempo de extraccioÌn de 10 minutos y trabajando a 40°C). Utilizando esta metodologiÌa, se determinaron 41 componentes volaÌtiles en planta entera, maÌs que los reportados mediante hidrodestilacioÌn.
Asunto(s)
Hedeoma , Microextracción en Fase Sólida/métodos , Compuestos Orgánicos Volátiles/química , Cromatografía de Gases y Espectrometría de Masas/métodosRESUMEN
Numerous molecules have been considered as targets for cancer immunotherapy because of their levels of expression on tumor cells, their putative importance for tumor biology, and relative immunogenicity. In this review we focus on the ganglioside GM3(Neu5Gc), a glycosphingolipid present on the outer side of the plasma membrane of vertebrate cells. The reasons for selecting GM3(Neu5Gc) as a tumor-specific antigen and its use as a target for cancer immunotherapy are discussed, together with the development of antitumor therapies focused on this target by the Center of Molecular Immunology (CIM, Cuba).
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/inmunología , Gangliósido G(M3)/inmunología , Neoplasias/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Antígenos de Neoplasias/química , Antígenos de Neoplasias/metabolismo , Secuencia de Carbohidratos , Modelos Animales de Enfermedad , Gangliósido G(M3)/antagonistas & inhibidores , Gangliósido G(M3)/química , Humanos , Inmunoterapia/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
Atherogenesis is associated with the early retention of low-density lipoproteins (LDL) in the arterial intima by interaction with glycosaminoglycan (GAG)-side chains of proteoglycans. Retained LDL undergo reactive oxygen species-mediated oxidation. Oxidized LDL trigger oxidative stress (OS) and inflammation, contributing to atherosclerosis development. Recently, we reported the preventive anti-atherogenic properties of the chimeric mouse/human monoclonal antibody (mAb) chP3R99-LALA, which were related to the induction of anti-chondroitin sulfate antibody response able to inhibit chondroitin sulfate dependent LDL-enhanced oxidation. In the present work, we aimed at further investigating the impact of chP3R99-LALA mAb vaccination on progressive atherosclerosis in apolipoprotein E-deficient mice (apoE(-/-)) fed with a high-fat high-cholesterol diet receiving 5 doses (50 µg) of the antibody subcutaneously, when ~5% of the aortic area was covered by lesions. Therapeutic immunization with chP3R99-LALA mAb halted atherosclerotic lesions progression. In addition, aortic OS was modulated, as shown by a significant (p<0.05) reduction of lipid and protein oxidation, preservation of antioxidant enzymes activity and reduced glutathione, together with a decrease of nitric oxide levels. chP3R99-LALA mAb immunization also regulated aortic NF-κB activation, diminishing the proinflammatory IL1-ß and TNF-α gene expression as well as the infiltration of macrophages into the arterial wall. The therapeutic immunization of apoE(-/-) with progressive atheromas and persistent hypercholesterolemia using chP3R99-LALA mAb arrested further development of lesions, accompanied by a decrease of aortic OS and NF-κB-regulated pro-inflammatory cytokine gene expression. These results contribute to broaden the potential use of this anti-GAG antibody-based immunotherapy as a novel approach to target atherosclerosis at different phases of progression.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Aterosclerosis/patología , Sulfatos de Condroitina/antagonistas & inhibidores , Glicosaminoglicanos/antagonistas & inhibidores , Vacunación/métodos , Animales , Apolipoproteínas E/deficiencia , Sulfatos de Condroitina/inmunología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Glicosaminoglicanos/inmunología , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados , Oxidación-Reducción , Reacción en Cadena de la Polimerasa , Proteínas Recombinantes de Fusión/inmunologíaRESUMEN
The progression of atherosclerosis is favored by increasing amounts of chondroitin sulfate proteoglycans in the artery wall. We previously reported the reactivity of chP3R99 monoclonal antibody (mAb) with sulfated glycosaminoglycans and its association with the anti-atherogenic properties displayed. Now, we evaluated the accumulation of this mAb in atherosclerotic lesions and its potential use as a probe for specific in vivo detection of the disease. Atherosclerosis was induced in NZW rabbits (n = 14) by the administration of Lipofundin 20% using PBS-receiving animals as control (n = 8). Accumulation of chP3R99 mAb in atherosclerotic lesions was assessed either by immunofluorescence detection of human IgG in fresh-frozen sections of aorta, or by immunoscintigraphy followed by biodistribution of the radiotracer upon administration of (99m)Tc-chP3R99 mAb. Immunofluorescence studies revealed the presence of chP3R99 mAb in atherosclerotic lesions 24 h after intravenous administration, whereas planar images showed an evident accumulation of (99m)Tc-chP3R99 mAb in atherosclerotic rabbit carotids. Accordingly, (99m)Tc-chP3R99 mAb uptake by lesioned aortic arch and thoracic segment was increased 5.6-fold over controls and it was 3.9-folds higher in carotids, in agreement with immunoscintigrams. Moreover, the deposition of (99m)Tc-chP3R99 mAb in the artery wall was associated both with the presence and size of the lesions in the different portions of evaluated arteries and was greater than in non-targeted organs. In conclusion, chP3R99 mAb preferentially accumulates in arterial atherosclerotic lesions supporting the potential use of this anti-glycosaminoglycans antibody for diagnosis and treatment of atherosclerosis.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Aterosclerosis/tratamiento farmacológico , Glicosaminoglicanos/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/farmacología , Administración Intravenosa , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/farmacocinética , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/patología , Aterosclerosis/inducido químicamente , Aterosclerosis/metabolismo , Combinación de Medicamentos , Técnica del Anticuerpo Fluorescente , Glicosaminoglicanos/metabolismo , Humanos , Masculino , Ratones , Compuestos de Organotecnecio , Fosfolípidos , Conejos , Radioinmunodetección/métodos , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/farmacocinética , Sorbitol , Sulfatos/metabolismo , Tecnecio , Factores de Tiempo , Distribución TisularRESUMEN
Surgery, chemotherapy, and radiation therapy are standard modalities for cancer treatment, but the effectiveness of these treatments has reached a plateau. Thus, other strategies are being explored to combine with the current treatment paradigms in order to reach better clinical results. One of these approaches is the active immunotherapy based on the induction of anti-tumor responses by anti-idiotypic vaccination. This approach arose from Jerne's idiotypic network theory, which postulates that B lymphocytes forms a functional network, with a role in the establishment of the immune repertoires, in the regulation of natural antibody production and even in the establishment of natural tolerance. Due to the large potential diversity of the immunoglobulin variable regions, the idiotypes repertoire can mimic the universe of self and foreign epitopes, even those of non-protein nature, like gangliosides. Gangliosides are sialic acid-containing glycolipids that have been considered attractive targets for cancer immunotherapy, based on the qualitative and quantitative changes they suffer during malignant transformation and due to their importance for tumor biology. Although any idiotype could be able to mimic any antigen, only those related to antigens involved in functions relevant for organism homeostasis, and that in consequence has been fixed by evolution, would be able not only to mimic, but also to activate the idiotypic cascades related with the nominal antigen. The present review updates the results, failures and hopes, obtained with ganglioside mimicking anti-idiotypic antibodies and presents evidences of the existence of a natural response against gangliosides, suggesting that these glycolipids could be idiotypically relevant antigens.
RESUMEN
N-glycolylneuraminic acid (NeuGc) is a sialic acid molecule usually found in mammalian cells as terminal constituents of different membrane glycoconjugates such as gangliosides. The NeuGcGM3 ganglioside has been described as a tumor antigen for non-small cell lung cancer (NSCLC) in humans. Racotumomab is an anti-NeuGc-containing gangliosides anti-idiotype monoclonal antibody (mAb) (formerly known as 1E10) that has received attention as a potential active immunotherapy for advanced lung cancer in clinical trials. In this work, we have examined the antitumor activity of racotumomab in combination or not with chemotherapy, using the 3LL Lewis lung carcinoma as a preclinical model of NSCLC in C57BL/6 mice. Vaccination with biweekly doses of racotumomab at 50-200 µg/dose formulated in aluminum hydroxide (racotumomab-alum vaccine) demonstrated a significant antitumor effect against the progression of lung tumor nodules. Racotumomab-alum vaccination exerted a comparable effect on lung disease to that of pemetrexed-based chemotherapy (100 mg/kg weekly). Interestingly, chemo-immunotherapy was highly effective against lung nodules and well-tolerated, although no significant synergistic effect was observed as compared to each treatment alone in the present model. We also obtained evidence on the role of the exogenous incorporation of NeuGc in the metastatic potential of 3LL cells. Our preclinical data provide support for the combination of chemotherapy with the anti-idiotype mAb racotumomab, and also reinforce the biological significance of NeuGc in lung cancer.
RESUMEN
Neu-glycolyl (NeuGc)-containing gangliosides are attractive targets for immunotherapy with anti-idiotype mAbs, because these glycolipids are not normal components of the cytoplasmic membrane in humans, but their expression has been demonstrated in several human malignant tumors. Racotumomab is an anti-idiotype mAb specific to P3 mAb, an antibody which reacts to NeuGc-containing gangliosides, sulfatides, and other antigens expressed in tumors. Preparations containing racotumomab were able to induce a strong anti-metastatic effect in tumor-bearing mice. Different Phase I clinical trials have been conducted in patients with advanced melanoma, breast cancer, and lung cancer. The results of these clinical trials demonstrated the low toxicity and the high immunogenicity of this vaccine. The induced antibodies recognized and directly killed tumor cells expressing NeuGcGM3. A Phase II/III multicenter, controlled, randomized, double blind clinical trial was conducted to evaluate the effect of aluminum hydroxide-precipitated racotumomab vaccine in overall survival in patients with advanced non-small cell lung cancer. The clinical results of this study showed a significant clinical benefit in the patients who were treated with the anti-idiotype vaccine.
RESUMEN
La aterosclerosis representa la primera causa de muerte en el mundo occidental. Aunque existen varias hipótesis que explican su patogénesis, una de las de mayor reconocimiento es la hipótesis autoinmune. La activación del sistema inmunológico frente a diferentes estímulos aterogénicos provoca en el organismo una reacción que puede dañar el endotelio vascular y con ello inducir el desarrollo de una lesión aterogénica. El diseño de nuevas estrategias terapéuticas, entre ellas las vacunas, representan una herramienta con resultados promisorios en el tratamiento de la aterosclerosis. Teniendo en cuenta estos antecedentes, en el presente trabajo se examinó el estado del arte en el campo de la inmunomodulación de esta enfermedad crónica(AU)
Atherosclerosis represents the first cause of death in the western world. Although there are several hypothesis which explain its pathogenesis, one of the most recognized is the autoimmune hypothesis. The activation of the immunological system against different atherogenic stimulus induces a reaction which may affect the vascular endothelium with the consequent atherogenic lesion development. The design of new therapeutic strategies, among them vaccines, represents a tool with promissory result in atherosclerosis treatment. Taking into account these antecedents, in the present work it was examined the state of the art on the immunomodulation of this chronic disease(AU)
Asunto(s)
Humanos , Aterosclerosis/inmunología , Aterosclerosis/terapiaRESUMEN
Racotumomab is a murine anti-idiotype cancer vaccine targeting NeuGcGM3 on melanoma, breast, and lung cancer. In order to characterize the immunogenicity of alum-adsorbed racotumomab in a non-clinical setting, Leghorn chickens were immunized in dose levels ranging from 25 µg to 1600 µg. Racotumomab was administered subcutaneously in the birds' neck with three identical boosters and serum samples were collected before, during and after the immunization schedule. A strong antibody response was obtained across the evaluated dose range, confirming the immunogenicity of racotumomab even at dose levels as low as 25 µg. As previously observed when using Freund's adjuvant, alum-adsorbed racotumomab induced an idiotype-specific response in all the immunized birds and ganglioside-specific antibodies in 60-100% of the animals. In contrast to the rapid induction anti-idiotype response, detection of ganglioside-specific antibodies in responsive animals may require repeated boosting. Kinetics of anti-NeuGcGM3 antibody titers showed a slight decline 2 weeks after each booster, arguing in favor of repeated immunizations in order to maintain antibody titer. Interestingly, the intensity of the anti-NeuGcGM3 response paralleled that of anti-mucin antibodies and anti-tumor antibodies, suggesting that the in vitro detection of anti-ganglioside antibodies might be a surrogate for an in vivo activity of racotumomab. Taken together, these results suggest that Leghorn chicken immunization might become the means to test the biological activity of racotumomab intended for clinical use.
RESUMEN
BACKGROUND: 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method. RESULTS: Here, we present a comprehensive molecular and immunological characterization of 1E10 produced by the two different production processes in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced 1E10 and bioreactor-obtained 1E10. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. CONCLUSIONS: Changes in 1E10 primary structure like glycosylation; asparagine deamidation and oxidation affected 1E10 structural stability but did not affect the immune response elicited in mice and chickens when compared to 1E10 produced in mice.
Asunto(s)
Anticuerpos Antiidiotipos/biosíntesis , Anticuerpos Monoclonales/biosíntesis , Reactores Biológicos , Vacunas contra el Cáncer/biosíntesis , Animales , Anticuerpos Antiidiotipos/genética , Anticuerpos Antiidiotipos/inmunología , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Asparagina/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/inmunología , Pollos , Cromatografía Líquida de Alta Presión , Ciclofosfamida/uso terapéutico , Femenino , Glicosilación , Ratones , Oxidación-Reducción , Conformación Proteica , Estabilidad Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
The use of low doses of cytotoxic agents continuously for prolonged periods is an alternative for the treatment of patients with metastatic breast cancer who have developed resistance to conventional chemotherapy. The combination of metronomic chemotherapy with therapeutic vaccines might increase the efficacy of the treatment. Twenty one patients with metastatic breast cancer in progression and a Karnosky index ≥60%, were treated with metronomic chemotherapy (50 mg of cyclophospamide orally daily and 2.5 mg of methotrexate orally bi-daily), in combination with five bi-weekly subcutaneous injections of 1 mg of aluminum hydroxide-precipitated 1E10 anti-idiotype MAb (1E10-Alum), followed by reimmunizations every 28 days. Five patients achieved objective response, eight showed stable disease and eight had disease progression. Median time to progression was 9,8 months, while median overall survival time was 12,93 months. The median duration of the response (CR+PR+SD) was 18,43 months (12,20-24,10 months), being higher than 12 months in 76,9% of the patients. Overall toxicity was generally mild. Metronomic chemotherapy combined with 1E10-Alum vaccine immunotherapy might be a useful therapeutic option for the treatment of metastatic breast cancer due to its potential impact on survival and patient quality of live, low toxicity and advantages of the administration.
RESUMEN
Conventional treatment of non-small cell lung cancer (NSCLC) has apparently reached a plateau of effectiveness in improving the survival of the patients. For that reason the search for new therapeutic strategies in this type of tumor is justified. 1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to P3 Ab1 MAb, which reacts with NeuGc-containing gangliosides, sulfatides and with antigens expressed in some tumors, including those from the lung. We report the treatment with aluminum hydroxide-precipitated 1E10 MAb of 34 stage IIIb and 37 stage IV NSCLC patients. These patients were treated with the anti-idiotype vaccine, after received standard chemotherapy and radiotherapy, in a compassionate-use basis study. Patients received five bi-weekly injections of 1 mg of 1E10/Alum, other 10 doses at 28-day intervals and later the patients who maintained a good performance status continued to be immunized at this same time interval. No evidence of unexpected or serious adverse effects was reported. The median survival time of the 56 patients who entered the study with partial response or disease stabilization and with a PS 1 after the first line of chemo/radiotherapy, was 11.50 months from starting vaccination. In contrast, the median survival time calculated for patients who started vaccination with progressive disease and/or a PS2 was 6.50 months.
Asunto(s)
Anticuerpos Antiidiotipos/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Adyuvantes Inmunológicos , Adulto , Anciano , Anciano de 80 o más Años , Compuestos de Alumbre , Animales , Anticuerpos Antiidiotipos/inmunología , Antígenos de Neoplasias/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vacunas contra el Cáncer/inmunología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Terapia Combinada , Femenino , Gangliósidos/inmunología , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Masculino , Ratones , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de SupervivenciaRESUMEN
The relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, reasons for considering these molecules as potential targets for cancer immunotherapy and diagnosis. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast tumours. Nevertheless, the lack of a direct evidence of this antigenic display in human breast cancer has kept the subject controversial. For the first time, we described herein the "in vivo" detection of GM3(NeuGc) ganglioside in human breast primary tumours using a radioimmunoscintigraphic technique with 14F7, a highly specific anti-GM3(NeuGc) ganglioside monoclonal antibody, labelled with (99m)Tc. In an open, prospective Phase I/II clinical trial, including women diagnosed in stage II breast cancer, the 14F7 monoclonal antibody accumulation in tumours at doses of 0.3 (n=5), 1 (n=5) and 3 mg (n=4) was evaluated. Noteworthy, the immunoscintigraphic study showed antibody accumulation in 100% of patients' tumours for the 1 mg dose group. In turn, the radioimmunoconjugate injected at doses of 0.3 mg or 3 mg of the antibody, was uptaken by 60 and 33.3% of breast tumours, respectively. "In vivo" immune recognition of GM3(NeuGc) in breast tumours reinforces the value of this peculiar target for cancer immunotherapy.
Asunto(s)
Anticuerpos Monoclonales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Gangliósido G(M3)/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Radioinmunodetección , Tecnecio/administración & dosificaciónRESUMEN
This review shall present an update in anticancer ganglioside-based immunotherapies, with particular emphasis on molecular vaccines and anti-idiotype mAbs produced by the Center of Molecular Immunology (Havana, Cuba). The project comprises vaccines of N-acetyl or N-glycolylneuraminic acid GM3 ganglioside incorporated into very small proteoliposomes and anti-idiotype antibodies to glycolylated gangliosides. Development of these vaccine preparations from preclinical models of melanoma, breast and lung cancer to human investigation is summarized. A brief discussion on the progress and limitations of present-day clinical trials and future prospects is also included.
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Anticuerpos Antiidiotipos/uso terapéutico , Vacunas contra el Cáncer/inmunología , Gangliósidos/inmunología , Neoplasias/terapia , Vacunas/inmunología , Animales , Ensayos Clínicos como Asunto , Humanos , Neoplasias/inmunologíaRESUMEN
En el presente trabajo se informa por primera vez en Cuba, la producción de hibridomas humano-humano secretores de inmunoglobulinas a partir de la fusión de linfocitos de ganglios linfáticos axilares de paciente con cámcer de mama con células de línea celular linfoblastoide B humana W1-L2-729HF2. En 3 de las 4 fusiones realizadas se obtuvieron hibridomas con crecimiento celular en 196 de los 569 pozos sembrados con el producto de las fusiones. Los primeros híbridos se observaron al final de la primera semana, aunque la mayoría se detectó en la segunda y tercera semanas de haberse realizado la fusión. De los 196 pozos con crecimiento celular, 120 eran secretores de inmunoglobulinas. El nivel de secreción de los híbridos clonados fue desde 4,5 hasta 8,0 *g/mL por 10 6 células. La naturaleza híbrida se determinó por análisis cromosómico y por la clase de inmunoglobulina producida. No se detectaron anticuerpos específicos contra los antígenos intracelulares o localizado en la superficie celular de las diferentes líneas celulares tumorales humanas empleadas en el estudio
Asunto(s)
Hibridomas , Inmunoglobulinas , Anticuerpos Monoclonales , Línea CelularRESUMEN
En el presente trabajo se informa por primera vez en Cuba, la producción de hibridomas humano-humano secretores de inmunoglobulinas a partir de la fusión de linfocitos de ganglios linfáticos axilares de paciente con cámcer de mama con células de línea celular linfoblastoide B humana W1-L2-729HF2. En 3 de las 4 fusiones realizadas se obtuvieron hibridomas con crecimiento celular en 196 de los 569 pozos sembrados con el producto de las fusiones. Los primeros híbridos se observaron al final de la primera semana, aunque la mayoría se detectó en la segunda y tercera semanas de haberse realizado la fusión. De los 196 pozos con crecimiento celular, 120 eran secretores de inmunoglobulinas. El nivel de secreción de los híbridos clonados fue desde 4,5 hasta 8,0 *g/mL por 10 6 células. La naturaleza híbrida se determinó por análisis cromosómico y por la clase de inmunoglobulina producida. No se detectaron anticuerpos específicos contra los antígenos intracelulares o localizado en la superficie celular de las diferentes líneas celulares tumorales humanas empleadas en el estudio
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Anticuerpos Monoclonales , Línea Celular , Hibridomas/metabolismo , Inmunoglobulinas/metabolismoRESUMEN
De noviembre de 1985 a diciembre de 1987 se estudiaron 33 pacientes con leismaniasis mucocutánea, que consultaron en el Hospital Santo Tomás o en el Laboratorio Conmemorativo Gorgas con el objeto de determinar su etiología, la epidemiología y sus características clínicas. Diez y siete pacientes eran del sexo masculino y 16 del femenino. Las edades variaban entre los 14 y los 80 años. Procedían de las áreas rurales endémicas de las provincias de Panamá, Colón, Cocle, Darién, Veraguas, Bocas del Toro y la Comarca de San Blas. En 8 pacientes el compromiso de la mucosa respiratoria ocurrió durante la primoinfección cutánea y en 25 se produjo después de un intervalo se produjo de 2 a 30 años. Veintiuno de los 25 casos tenían historia de LC y presentaban una cicatriz característica. La prueba de Montenegro fue positiva en todos los pacientes, la serología en 84%, el frotis directo en 47%, la histopatología en 37% y el cultivo en el 26%. Las cepas fueron identificadas como L. braziliensis panamensis mediante electroforesis de isoenzimas. Como posibles factores de riesgo se mencionan el sexo femenino y la falta de tratamiento de la LC. El compromiso de la mucosa fie leve en la mayoría de los pacientes; la infección (tabique, cornete inferior) en el 91% de los casos y los síntomas más frecuentes fueron epistaxis, obstrucción nasal y rinorrea
Asunto(s)
Adolescente , Adulto , Persona de Mediana Edad , Humanos , Masculino , Femenino , Leishmaniasis Mucocutánea/complicaciones , Panamá , Anciano de 80 o más Años , Leishmaniasis Mucocutánea/epidemiología , Leishmaniasis Mucocutánea/etiologíaRESUMEN
Se estudian 300 pacientes con enfermedad mamaria benigna y maligna. Se revela. en general, que no existe déficit en el número de células B y si alteraciones en la proporción de células T y en la actividad de las células dependientes de anticuerpos (ADCC). Las pruebas de hipersensibilidad retardada a los antígenos de memoria convencionales y al dinitroclorobenzeno (DNCB) mostraron que las pacientes con enfermedad maligna, en su conjunto, manifiestan energia con mayor frecuencia que las que padecen la enfermedad benigna. Se sugiere el seguimiento clínico de las pacientes con vistas a evaluar los resultados, teniendo en cuenta el desarrollo de la enfermedad