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1.
J Dairy Sci ; 98(5): 2875-83, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25704969

RESUMEN

The emulsifying components in cream are very important in controlling the physical characteristics of whipped cream. The effects of those components on the stability of fat globules and the physical characteristics of whipped cream were investigated. A low-molecular-weight emulsifier, and protein ingredients such as sodium caseinate and a casein partial hydrolysate (casein peptides), were used as emulsifying components in this investigation. The viscosity of deaerated whipped cream (called the serum viscosity) was measured to evaluate the degree of fat-globule aggregation. Furthermore, the shape-retention ability, which is the degree of reduction in the firmness of whipped cream between immediately after whipping and after 1d of refrigeration, was explored. The addition of the low-molecular-weight emulsifier in the continuous phase of dairy cream, which does not contain added low-molecular-weight emulsifiers, increased the stability of the fat globules and reduced the shape-retention ability of the whipped cream. The addition of protein ingredients (sodium caseinate and casein peptides) to the continuous phase of dairy cream had little effect. However, the addition of casein peptide in the continuous phase of dairy cream together with the low-molecular-weight emulsifier reduced the effect of the low-molecular-weight emulsifier on the stabilization of fat globules and the shape-retention ability of the whipped cream. The addition of casein peptide did not recover the serum viscosity; thus, other mechanisms might underlie this phenomenon.


Asunto(s)
Caseínas/química , Productos Lácteos/análisis , Emulsionantes/química , Glucolípidos/química , Glicoproteínas/química , Animales , Emulsiones/química , Gotas Lipídicas
2.
Int J Cancer ; 135(11): 2528-36, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-24346863

RESUMEN

While statin intake has been proven to reduce the risk of colorectal cancer (CRC), the mechanism of antitumor effects and clinical significance in survival benefits remain unclear. Statin-induced antiproliferative effects and its underlying mechanism were examined using six CRC cell lines. Statins except pravastatin showed antiproliferative effects (simvastatin ≥ fluvastatin > atorvastatin) even though both of simvastatin and pravastatin could activate mevalonate pathways, suggesting the statin-mediated antiproliferative effects depended on non-mevalonate pathway. Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. In the clinical setting, Statin intake (except pravastatin) displayed the downregulated EZH2 expression and inversely upregulated p27(KIP1) expression in the resected CRC by immunohistochemical staining and resulted in the significantly better prognoses both in overall survival (p = 0.02) and disease free survival (p < 0.01) compared to patients without statin intake. Statins may inhibit tumor progression via an EZH2-mediated epigenetic alteration, which results in survival benefits after resected CRC. Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer therapy by their synergistic effects in CRC.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Epigénesis Genética/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Complejo Represivo Polycomb 2/genética , Apoptosis/efectos de los fármacos , Western Blotting , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Progresión de la Enfermedad , Proteína Potenciadora del Homólogo Zeste 2 , Humanos , Técnicas para Inmunoenzimas , Complejo Represivo Polycomb 2/antagonistas & inhibidores , Complejo Represivo Polycomb 2/metabolismo , Pronóstico , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas
3.
Gut ; 58(4): 550-9, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19052021

RESUMEN

OBJECTIVE: Fibroblasts in the area of fibrosis in chronic pancreatitis and of the desmoplastic reaction associated with pancreatic cancer are now recognised as activated pancreatic stellate cells (PSCs). Recent studies have shown strong expression of fibrinogen, the central protein in the haemostasis pathway, in the stromal tissues of pancreatic cancer and chronic pancreatitis, suggesting that PSCs are embedded in and exposed to abundant fibrinogen in these pathological settings. The effects of fibrinogen on cell functions in PSCs were examined here. METHODS: PSCs were isolated from human pancreas tissues of patients undergoing operations for pancreatic cancer, and from rat pancreatic tissues. The effects of fibrinogen on key cell functions and activation of signalling pathways in PSCs were examined. RESULTS: Fibrinogen induced the production of interleukin 6 (IL6), interleukin 8 (IL8), monocyte chemoattractant protein-1, vascular endothelial growth factor, angiopoietin-1 and type I collagen, but not proliferation or intercellular adhesion molecule-1 expression. Fibrinogen increased alpha-smooth muscle actin expression and induced the activation of nuclear factor-kappaB (NF-kappaB), Akt and three classes of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK)). Fibrinogen-induced IL6 and IL8 production was inhibited by antibodies against alpha(v)beta(3) and alpha(5)beta(1) integrins, suggesting that these integrins worked as counter receptors for fibrinogen in PSCs. In addition, fibrinogen-induced production of these cytokines was abolished by an inhibitor of NF-kappaB, and partially inhibited by inhibitors of ERK and p38 MAPK. CONCLUSION: Fibrinogen directly stimulated profibrogenic and proinflammatory functions in PSCs.


Asunto(s)
Colágeno Tipo I/biosíntesis , Citocinas/biosíntesis , Fibrinógeno/farmacología , Páncreas/efectos de los fármacos , Animales , Movimiento Celular/fisiología , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Fibrinógeno/metabolismo , Humanos , Integrina alfa5beta1/fisiología , Integrina alfaVbeta3/fisiología , Interleucina-6/biosíntesis , Interleucina-8/biosíntesis , Masculino , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Páncreas/citología , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/patología , Fragmentos de Péptidos/biosíntesis , Procolágeno/biosíntesis , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología
4.
Gut ; 58(6): 820-4, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19052022

RESUMEN

OBJECTIVE: There is a concept that pancreatitis results from an imbalance of proteases and their inhibitors within the pancreatic parenchyma. It has been recently shown that a loss-of-function variant, c.571G>A (p.G191R), in the anionic trypsinogen (PRSS2) gene protects against chronic pancreatitis in European populations. Here we examined the association of the p.G191R variant with pancreatic disorders in Japan. METHODS: Genomic DNA was prepared from 378 healthy controls and 604 patients with pancreatic disorders (241 patients with chronic pancreatitis, 174 with acute pancreatitis, and 189 with pancreatic neoplasm). Mutational analysis of the PRSS2 gene was performed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. RESULTS: The heterozygous p.G191R variant was found in three of 241 (1.2%) patients with chronic pancreatitis, in seven of 174 (4.0%) patients with acute pancreatitis, and in 12 of 189 (6.3%) patients with pancreatic neoplasm. The p.G191R variant was found in 25 (two were homozygous and 23 were heterozygous) of 378 (6.6%) healthy controls. The p.G191R frequency in patients with chronic pancreatitis was lower than that in healthy controls (p = 0.001; odds ratio (OR) 0.178; 95% confidence interval (CI) = 0.057 to 0.561). The p.G191R frequency was lower in patients with alcoholic (0.9%; p = 0.015; OR, 0.132; 95% CI, 0.022 to 0.779) and idiopathic (1.0%; p = 0.025; OR, 0.144; 95% CI, 0.025 to 0.851) chronic pancreatitis than that in healthy controls. There were no statistical differences in the p.G191R frequency between healthy controls and patients with acute pancreatitis or with pancreatic neoplasm. Patients with alcoholic acute pancreatitis (n = 59) had no variant carrier, and the p.G191R frequency was lower than that in healthy controls (p = 0.035). CONCLUSION: The p.G191R variant protected against alcoholic and idiopathic chronic pancreatitis as well as alcoholic acute pancreatitis in Japan.


Asunto(s)
Mutación , Pancreatitis/genética , Tripsina/genética , Tripsinógeno/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Genotipo , Heterocigoto , Homocigoto , Humanos , Japón , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Pancreatitis/metabolismo , Pancreatitis Aguda Necrotizante/genética , Pancreatitis Aguda Necrotizante/metabolismo , Pancreatitis Crónica/etiología , Pancreatitis Crónica/genética , Pancreatitis Crónica/metabolismo , Tripsina/metabolismo , Tripsinógeno/metabolismo
5.
Science ; 278(5335): 120-3, 1997 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-9311916

RESUMEN

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.


Asunto(s)
Poliposis Adenomatosa del Colon/genética , Marcación de Gen , Genes APC , Proteínas Virales , Proteína de la Poliposis Adenomatosa del Colon , Adenoviridae/genética , Animales , Colon/metabolismo , Proteínas del Citoesqueleto/biosíntesis , Modelos Animales de Enfermedad , Exones , Femenino , Mutación del Sistema de Lectura , Eliminación de Gen , Vectores Genéticos , Mutación de Línea Germinal , Homocigoto , Integrasas/genética , Integrasas/metabolismo , Intrones , Masculino , Ratones , Ratones Endogámicos C57BL , Recombinación Genética
7.
Int J Oral Maxillofac Surg ; 37(5): 481-3, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18367380

RESUMEN

This paper describes a case of vertical distraction osteogenesis of a free vascularized osteocutaneous scapular flap in the reconstructed mandible before implant therapy. The patient was a 67-year-old woman with squamous cell carcinoma of the right lower gingiva. She underwent segmental mandibulectomy for tumor ablation and reconstruction with an osteocutaneous scapular flap. The distraction protocol, clinical course and implant therapy are presented. Through this procedure, the bone height of the scapular graft increased by 10mm. Implants with adequate length could be placed in the distracted area. Two years after masticatory loading, the condition of these implants was stable. Vertical distraction osteogenesis of the scapular flap was considered effective when performed before implant therapy, to facilitate postoperative functional and esthetic restoration after tumor resection.


Asunto(s)
Aumento de la Cresta Alveolar/métodos , Mandíbula/cirugía , Osteogénesis por Distracción , Colgajos Quirúrgicos , Anciano , Trasplante Óseo , Carcinoma de Células Escamosas/cirugía , Implantación Dental Endoósea , Femenino , Neoplasias Gingivales/cirugía , Humanos , Procedimientos de Cirugía Plástica , Escápula/trasplante , Trasplante de Piel , Colgajos Quirúrgicos/irrigación sanguínea , Dimensión Vertical
8.
Transplant Proc ; 39(1): 160-5, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17275496

RESUMEN

To recognize "normal" hepatic hemodynamics after live donor liver transplantation (LDLT), we analyzed Doppler parameters on recipients with a right liver graft and donors after extended left hepatectomy. Theoretically these values should be the same. From April 2000 to October 2004, 20 LDLTs were performed using a right liver graft. The 10 recipients without postoperative complications and their donors were included in this study. Portal venous velocity (PVV; cm/s), hepatic arterial peak systolic velocity (cm/s), and hepatic venous peak velocity (HVPV; cm/s) were measured during the first 2 weeks. In donors PVV and HVPV after LDLT were significantly higher after than before left hepatectomy: 19.2 +/- 4.2 vs. 31.5 +/- 13.0 cm/s (P = .013) and 23.0 +/- 7.2 vs. 41.8 +/- 10.3 cm/s respectively (P = .010). However, there were mild degrees of increased PVV and HVPV. In recipients, a markedly increased PVV (106.3 +/- 45.2 cm/s on day 1) was significantly higher than that in donors on each postoperative day. The hepatic arterial resistive index in recipients was also significantly higher than that in donors on each postoperative day, for example, 0.72 +/- 0.11 vs 0.62 +/- 0.04 on day 1 (P = .0326). In conclusion, we have shown "abnormal" hepatic hemodynamics in even those recipients without complications during the early postoperative period after LDLT.


Asunto(s)
Trasplante de Hígado/fisiología , Donadores Vivos , Periodo Posoperatorio , Adulto , Velocidad del Flujo Sanguíneo , Peso Corporal , Humanos , Hígado/anatomía & histología , Hígado/diagnóstico por imagen , Circulación Hepática , Tamaño de los Órganos , Sistema Porta , Ultrasonografía Doppler
9.
J Psychiatr Ment Health Nurs ; 24(8): 638-647, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28840659

RESUMEN

WHAT IS KNOWN ON THE SUBJECT?: There is a developing body of research on violence in healthcare workplaces. Although psychiatric visiting nurses (PVNs) are an important group of professionals who provide medical services for people with mental disorders live in the community, little is known about the experiences and characteristics of violence exposure among PVNs, or the characteristics and work situations of PVNs related to violence exposure. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE?: Approximately 40% of participants were exposed to violence during the previous 12 months; approximately 50% had been exposed during their PVN careers in PVN settings. The most frequent violence was verbal abuse. Longer career length as a PVN and greater number of visits per month were both positively associated with verbal abuse during the previous 12 months. Twenty-eight of the 34 participants (83%) who completed the IES-R-J survey had some residual psychological distress, and two (6%) had a potentially high risk of posttraumatic stress disorder. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: In devising policies and strategies against violence, PVN organizations and administrators should consider the characteristics of the violence, especially verbal abuse, as well as the characteristics and work situations of PVNs that are related to verbal abuse. Furthermore, they might provide relevant information on violence in PVN settings within their violence-prevention manuals or education. It would be important to provide support and to construct a safe workplace environment for PVNs who are experiencing residual psychological distress. ABSTRACT: Introduction Psychiatric visiting nurses (PVNs) play a crucial role by providing medical services for community-living individuals with mental disorders in Japan. However, little is known about violence towards PVNs. Aim This cross-sectional study investigated violence during visits and the resulting psychological effects for PVNs. Methods PVNs were assessed using a violence exposure questionnaire and the Impact of Event Scale-Revised (IES-R-J); a measure of posttraumatic distress. Result Thirty-eight (41%) of 94 participants had experienced violence during the previous 12 months and 49 (53%) over their entire career. The most frequent violence was verbal abuse. Career length as a PVN and number of visits per month were significantly positively associated with verbal abuse during the previous 12 months. The IES-R-J scores indicated 28 of the 34 participants who completed the questionnaire exhibited psychological distress for the most traumatic violence during their career and two had a potentially high risk of posttraumatic stress disorder. Discussion and Implications Policies and strategies aimed at reducing violence in PVN settings should be developed according to characteristics of the violence, as well as the characteristics and work situation of PVNs. Furthermore, the provision of support and a safe workplace environment would be important for PVNs with residual psychological distress.


Asunto(s)
Exposición a la Violencia/estadística & datos numéricos , Enfermeros de Salud Comunitaria/estadística & datos numéricos , Enfermería Psiquiátrica/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad
10.
Toxicol In Vitro ; 20(5): 767-73, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16311011

RESUMEN

The aim of this study is to optimize the experimental conditions for an in vitro skin sensitization test using the human cell lines THP-1 and U-937. As regards pre-culturing time, the expression of CD86 on DNCB-treated THP-1 cells tended to be higher after 48h and 72h pre-culture compared with other time points evaluated. Next, we investigated the effect of chemical treatment time, and found that induction of CD86 expression on THP-1 cells by DNCB reached a plateau after 24h. Augmentation of CD86 expression is often observed when cells are treated with a subtoxic dose of allergens. To determine the appropriate dose of test samples, the cytotoxicity of test samples to THP-1 and U-937 cells was assessed with MTT assay, and the 50% inhibitory concentration (IC50) of each test sample was calculated. Based on the cytotoxicity assay data, four concentrations in the range between toxic and non-toxic were selected (0.1x, 0.5x, 1x and 2x IC50). Several kinds of antibodies were tested for staining THP-1 and U-937 cells treated with allergens/non-allergens (e.g., DNCB, Ni/SLS), and suitable antibodies for staining CD86 and CD54 were selected. We confirmed that the working dilutions of the selected CD86 and CD54 antibodies were appropriate for use in our method. The effect of an FcR blocking procedure was also evaluated. The mean fluorescence intensity (MFI value) was decreased by the FcR blocking procedure, which indicated that non-specific staining was blocked. Therefore, this procedure should be included in the method. Based on our findings, the protocol for this assay was optimized and the experimental conditions to be used in a future validation study were identified. We propose to call this kind of in vitro skin sensitization test h-CLAT, which is short for human Cell Line Activation Test.


Asunto(s)
Alérgenos/toxicidad , Piel/efectos de los fármacos , Antígenos de Superficie/análisis , Antígeno B7-2/análisis , Línea Celular , Dinitroclorobenceno/toxicidad , Humanos , Molécula 1 de Adhesión Intercelular/análisis , Receptores Fc/fisiología , Piel/inmunología , Pruebas Cutáneas , Factores de Tiempo
11.
Toxicol In Vitro ; 20(5): 774-84, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16337770

RESUMEN

Recent regulatory changes have placed a major emphasis on in vitro safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled "optimization of the h-CLAT protocol" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24h and 48h exposure to six known allergens (e.g., DNCB, pPD, NiSO(4)) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC(50))) were evaluated. IC(50) was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen/non-allergen, especially using THP-1 cells. These results suggest that our method, human Cell Line Activation Test (h-CLAT), using human cell lines THP-1 and U-937, but especially THP-1 cells at 24h treatment, may be a useful in vitro skin sensitization model to predict various contact allergens.


Asunto(s)
Alérgenos/toxicidad , Piel/efectos de los fármacos , Antígeno B7-2/análisis , Antígenos CD4/análisis , Línea Celular , Supervivencia Celular , Humanos , Laboratorios , Fenotipo , Piel/inmunología , Pruebas Cutáneas , Factores de Tiempo , Células U937
12.
J Natl Cancer Inst ; 74(2): 335-9, 1985 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3856047

RESUMEN

A micro-enzyme-linked immunosorbent assay (ELISA) test and an ELISA inhibition test were developed and used to detect 4 monoclonal antibodies potentially useful for serodiagnosis of cancer. The 4 antibodies used in conjunction detected 73% of 71 sera from cancer patients and 8% of 42 sera from normal persons. Separately, the 4 antibodies reacted to tumors from various sites such as lung, breast, colon, stomach, and ovary. The ELISA inhibition assay may be useful for detecting culture supernatants reactive against tumor-associated serum antigens. Eventually, a panel of monoclonal antibodies detecting various tumors may be obtainable.


Asunto(s)
Anticuerpos Monoclonales/análisis , Anticuerpos Antineoplásicos/análisis , Neoplasias/diagnóstico , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antineoplásicos/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Neoplasias/inmunología , Análisis de Regresión
13.
Nat Prod Res ; 20(7): 680-5, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16901812

RESUMEN

From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti-inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4), curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8), dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures were elucidated on the basis of spectroscopic data. The anti-inflammatory effect of isolated components on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears were examined. Compounds 1 and 2 suppressed the TPA-induced inflammation of mouse ears by 75% and 53%, respectively, at a dose of 1.0 micromol. Their activities are comparable to that of indomethacin, the normally used anti-inflammatory agent.


Asunto(s)
Antiinflamatorios/aislamiento & purificación , Curcuma/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Edema/tratamiento farmacológico , Ratones , Resonancia Magnética Nuclear Biomolecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Rizoma/química , Sesquiterpenos/química , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja
14.
Cancer Res ; 52(1): 163-7, 1992 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-1530768

RESUMEN

Annexins are a family of calcium- and phospholipid-binding proteins related by amino acid sequence homology. Annexins I and II are substrates for protein tyrosine kinases. Recent investigations have revealed a possible involvement of annexins I and II in mitogenic signal transduction and cell proliferation. To investigate further the involvement of annexins in cell proliferation, we measured the levels of annexins I and II and the enzyme 3-phosphoglycerate kinase (PGK) (annexin II and PGK are components of the primer recognition protein complex) in normal Syrian hamster pancreas, three hamster pancreatic ductal carcinoma cell lines, and allografts of the three cell lines into hamster pancreas. All three carcinoma cell lines had 5-8-fold higher levels of annexin II compared to normal pancreas. An inverse relationship was seen between level of annexin II and the doubling time of the cell culture. In intrapancreatic allografts, annexin II levels were 3-6-fold higher than in normal pancreas. Annexin I levels were 2-3-fold higher in the allografts. Significant increases (5-6-fold) in specific activity of PGK were seen in all allografts examined. However, the level of PGK, as measured by immunoblotting, was not significantly altered. Immunohistochemical staining revealed heterogeneity in the reactivity of the antiannexin and anti-PGK antibodies with tumor cells. Strikingly, the reactivity and staining intensity were greater in the proliferating regions of the primary tumors and in the metastatic foci. Mitotic cells were either unstained or very weakly stained. We conclude from these findings that annexin II and PGK, as primer recognition proteins, may have a role in cell proliferation.


Asunto(s)
Proteínas de Unión al Calcio/análisis , Carcinoma/química , Células PC12/química , Neoplasias Pancreáticas/química , Fosfoglicerato Quinasa/análisis , Animales , Anexinas , Cricetinae , Trasplante de Neoplasias , Células Tumorales Cultivadas/química
15.
Cancer Res ; 45(12 Pt 1): 6453-6, 1985 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2998602

RESUMEN

One hundred sixty-one sera from lung cancer patients, including 46 samples from patients who had not yet received treatment were screened for tumor-associated antigens with 3 monoclonal antibodies, CSLEX1, CSLEA1, and CLEX5, by a new cell binding inhibition assay. We had previously determined that the antigens recognized by CSLEX1 and CSLEA1 are sialosylated Lewisx and sialosylated Lewisa, respectively. Either of these two antibodies alone reacted with about 65% of the 46 untreated patients' sera. Eighty-seven % of the 46 showed positive results with at least one of the two antibodies. The CLEX5 monoclonal antibody is presented here as recognizing a potential tumor-associated antigen. CLEX5 reacted with 54% of the 46 sera from nontreated lung cancer patients. When the results for all three antibodies were combined, the percentage of positive sera was 89% (of 46). Some interesting patterns in the serum levels of the antigens detected by these antibodies were observed. Levels of sialosylated Lewisx were significantly higher in sera from nontreated advanced stage (III and IV) patients (P less than 0.0003). In addition, levels of the antigens detected by CSLEX1 and CSLEA1 were dependent on whether or not the patient had been receiving treatment. These observations suggest potential applications of monoclonal antibodies to diagnosis and monitoring of therapies.


Asunto(s)
Anticuerpos Monoclonales , Antígenos de Neoplasias/análisis , Neoplasias Pulmonares/inmunología , Adenocarcinoma/inmunología , Adenocarcinoma/patología , Adenocarcinoma/terapia , Carcinoma de Células Pequeñas/inmunología , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/terapia , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia
16.
Cancer Res ; 45(1): 435-7, 1985 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-3965149

RESUMEN

A new monoclonal antibody, CSLEX1, directed against sialylated Lewisx was tested in parallel with a monoclonal antibody, CSLEA1, directed against sialylated Lewisa antigen. In tests with a solid-phase radioimmune sandwich assay, the sialylated Lewisx monoclonal antibody detected sera from certain cancer patients that were negative with the sialylated Lewisa monoclonal antibody. Some sera from cancer patients showed the reverse reaction. We conclude that the combined use of these two monoclonal antibodies detects a wider range of sera from cancer patients than the use of a single antibody alone. It should be possible in the future to use multiple monoclonal antibodies to increase detection.


Asunto(s)
Anticuerpos Monoclonales , Antígenos del Grupo Sanguíneo de Lewis/inmunología , Neoplasias/diagnóstico , Neoplasias de la Mama/diagnóstico , Neoplasias del Colon/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias/inmunología , Radioinmunoensayo , Pruebas Serológicas , Ácidos Siálicos/análisis , Ácidos Siálicos/inmunología , Neoplasias Gástricas/diagnóstico
17.
Cancer Res ; 48(20): 5800-4, 1988 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-3167837

RESUMEN

A new type of phorbol ester, which has a macrocyclic dicarboxylic acid diester structure, was isolated from the seed oil of Jatropha curcas L. (Euphorbiaceae). Based on the results of spectroscopic analyses of the compound and its chemical degradation products, its structure is proposed to be an intramolecular 13,16-diester of 12-deoxy-16-hydroxyphorbol, 12-deoxy-16-hydroxyphorbol-4'-[12',14'-butadienyl]-6'-[16',18',20' - nonatrienyl]-bicyclo[3.1.0]hexane-(13-O)-2'-[carboxylate]-(16-O)-3 '- [8'-butenoic-10']ate (DHPB). DHPB showed slightly weaker biological and biochemical activities than 12-O-tetradecanoylphorbol-13-acetate (TPA). DHPB induced ornithine decarboxylase in mouse skin (2.8 nmol CO2/30 min/mg protein/34 nmol application), inhibited the specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to phorbol ester receptors (50% effective dose, 17.0 nM), and activated protein kinase C in vitro (50% effective dose, 36.0 nM). Also, a weak tumor-promoting activity of DHPB was found in a two-stage carcinogenesis experiment on mouse skin. One week after initiation of mice with 100 micrograms of 7,12-dimethyl-benz(a)anthracene, topical application, twice a week, of 2 micrograms of DHPB until week 17, followed by application of 5 microgram of DHPB until week 30 at the same rate, resulted in 46.7% incidence of tumors by week 30. The groups treated with 7,12-dimethylbenz(a)anthracene alone or DHPB alone did not produce significant numbers of tumors. These results indicate that the new phorbol ester, DHPB, is a tumor promoter with weaker activity than 12-O-tetradecanoylphorbol-13-acetate.


Asunto(s)
Carcinógenos/aislamiento & purificación , Ésteres del Forbol/aislamiento & purificación , Aceites de Plantas/análisis , Animales , Espectroscopía de Resonancia Magnética , Ratones , Ésteres del Forbol/farmacología , Semillas , Neoplasias Cutáneas/inducido químicamente
18.
Cancer Res ; 45(4): 1901-5, 1985 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-3884147

RESUMEN

A new cell-binding inhibition assay to detect tumor-associated antigens in sera was developed. This assay determined that sialosylated Lewisx, as detected by the CSLEX1 monoclonal antibody, is present in the sera of 95% of patients with advanced lung adenocarcinomas. Sera with inhibition titers of 1:16 or higher were presumed to contain sialosylated Lewisx. Tests of over 900 sera samples from both malignant and benign disease patients yielded the following percentages of positive inhibition: lung cancers, 43.8%; stomach cancer, 26.0%; colon cancer, 44.4%; gall bladder and bile duct cancers, 47.8%; pancreas cancer, 37.5%; breast cancer, 26.7%; cancers of the hematopoietic system, 2.9%; benign diseases, 0.9% (332 sera); and normal healthy donors, 0.7% (280 sera). Within the lung cancer group, 95% of the sera from 21 advanced (Stages III and IV) nontreated adenocarcinoma patients gave positive results with high inhibition titers, whereas only 27% of sera from treated advanced adenocarcinoma patients yielded positive results. The sensitivity of the cell-binding inhibition assay is similar to those of the solid-phase radioimmunosandwich and reverse passive-hemagglutination assays. Reproducibility tests yielded an r value of 0.90. These results suggest that this simple cell-binding inhibition assay could be applied with monoclonal antibodies, such as CSLEX1, to monitor cancer.


Asunto(s)
Antígenos de Neoplasias/análisis , Antígenos del Grupo Sanguíneo de Lewis/análisis , Neoplasias/inmunología , Anticuerpos Monoclonales , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Pruebas de Hemaglutinación , Humanos , Neoplasias Pulmonares/inmunología , Radioinmunoensayo
19.
Cancer Res ; 44(9): 3952-6, 1984 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-6744310

RESUMEN

A monoclonal antibody, CSTO-1, has been produced against a stomach adenocarcinoma-associated antigen. The antibody is cytotoxic to stomach, colon, and lung adenocarcinoma lines but is completely noncytotoxic to normal blood elements and leukemic cell lines. The monoclonal antibody reacts with tumor cell membranes in enzyme-linked immunosorbent assay and is negative to cell membranes from various normal tissues. By immunoperoxidase testing, the antibody reacts with 18 of 22 stomach adenocarcinomas, 11 of 16 colon adenocarcinomas, 3 of 4 squamous cell carcinomas of the lung, and 1 of 4 lung adenocarcinomas. In addition, the antibody reacts with the superficial epithelium of normal tissues such as colon, stomach, esophagus, acinar cells and duct epithelium of the pancreas, bronchial epithelium of the lung, and sweat duct epithelium of the skin. Thus, the CSTO-1 antibody reacts to an antigen present in normal superficial epithelia, as well as on various tumors. It is of potential use in detecting these antigens on tumor sections and eventually may be used in immunotherapy.


Asunto(s)
Adenocarcinoma/inmunología , Antígenos de Neoplasias/análisis , Antígenos de Superficie/análisis , Neoplasias Gástricas/inmunología , Anticuerpos Monoclonales , Neoplasias del Colon/inmunología , Reacciones Cruzadas , Citotoxicidad Inmunológica , Ensayo de Inmunoadsorción Enzimática , Humanos
20.
Cancer Res ; 44(11): 5279-85, 1984 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6386148

RESUMEN

A monoclonal antibody CSLEX1 which reacts with sialosyl Lex but not with sialosyl Lea has been produced. The CSLEX1 antigen has a tissue distribution similar to that of Lex, appearing characteristically in the proximal tubules of the kidney and on granulocytes. It is tumor associated in that 14 of 34 (41%) of tumor lines tested reacted with the CSLEX1 antibody, and 50 of 74 (68%) of tumor tissues tested reacted with the antibody. Loss of immunoperoxidase staining of tissues after neuraminidase treatment showed that the antibody is reacting to sialyl derivatives. The antibody reacted in solid-phase radioimmunoassay to sialosyllactofucopentaosyl(III)ceramide and sialosyldifucosylganglioside (6B). These results indicate that the CSLEX1 epitope has the following structure: (formula: see text) This structure had not previously been known to be tumor associated.


Asunto(s)
Antígenos de Neoplasias/análisis , Anticuerpos Monoclonales , Complejo Antígeno-Anticuerpo , Conformación de Carbohidratos , Secuencia de Carbohidratos , Línea Celular , Eritrocitos/inmunología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas para Inmunoenzimas , Leucocitos/inmunología , Neoplasias/inmunología , Neuraminidasa
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