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Adenosina Desaminasa/genética , Secuencia de Bases , Eritema Pernio/genética , Trastornos de la Pigmentación/congénito , Proteínas de Unión al ARN/genética , Eliminación de Secuencia , Eritema Pernio/complicaciones , Niño , Motivo de Unión al ARN Bicatenario/genética , Femenino , Humanos , Linaje , Trastornos de la Pigmentación/complicaciones , Trastornos de la Pigmentación/genética , Trastornos de la Pigmentación/patologíaAsunto(s)
Adenosina Desaminasa/genética , Trastornos de la Pigmentación/congénito , Edición de ARN/genética , Proteínas de Unión al ARN/genética , Degeneración Estriatonigral/congénito , Adenosina Desaminasa/metabolismo , Alelos , Niño , Análisis Mutacional de ADN , Femenino , Heterocigoto , Homocigoto , Humanos , Imagen por Resonancia Magnética , Linaje , Fenotipo , Trastornos de la Pigmentación/diagnóstico , Trastornos de la Pigmentación/genética , Proteínas de Unión al ARN/metabolismo , Degeneración Estriatonigral/diagnóstico , Degeneración Estriatonigral/genéticaAsunto(s)
Fucosiltransferasas/genética , Hiperpigmentación/diagnóstico , Mutación/genética , Enfermedades Cutáneas Genéticas/diagnóstico , Enfermedades Cutáneas Papuloescamosas/diagnóstico , Adolescente , Adulto , Edad de Inicio , Diagnóstico Diferencial , Glucosiltransferasas/genética , Heterocigoto , Humanos , Hiperpigmentación/genética , Persona de Mediana Edad , Linaje , Enfermedades Cutáneas Genéticas/genética , Enfermedades Cutáneas Papuloescamosas/genética , Adulto JovenRESUMEN
Somatic mutations in the gene encoding the catalytic subunit of protein phosphatase 6 (Ppp6c) have been identified in malignant melanoma and are thought to function as a driver in B-raf- or N-ras-driven tumorigenesis. To assess the role of Ppp6c in carcinogenesis, we generated skin keratinocyte-specific Ppp6c conditional knockout mice and performed two-stage skin carcinogenesis analysis. Ppp6c deficiency induced papilloma formation with 7,12-dimethylbenz (a) anthracene (DMBA) only, and development of those papillomas was significantly accelerated compared with that seen following DMBA/TPA (12-O-tetradecanoylphorbol 13-acetate) treatment of wild-type mice. NF-κB activation either by tumor necrosis factor (TNF)-α or interleukin (IL)-1ß was enhanced in Ppp6c-deficient keratinocytes. Overall, we conclude that Ppp6c deficiency predisposes mice to skin carcinogenesis initiated by DMBA. This is the first report showing that such deficiency promotes tumor formation in mice.
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Fosfoproteínas Fosfatasas/genética , Neoplasias Cutáneas/enzimología , 9,10-Dimetil-1,2-benzantraceno , Animales , Carcinogénesis/metabolismo , Células Cultivadas , Queratinocitos/enzimología , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Transgénicos , FN-kappa B/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Transducción de Señal , Piel/enzimología , Piel/patología , Neoplasias Cutáneas/inducido químicamenteRESUMEN
We examined effects of hypocapnia on burst activity in the piriform-amygdala complex and C(4) inspiratory activity in limbic-brainstem-spinal cord preparations from 0- to 1-day-old rats. Hypocapnia (2% CO(2)) increased the burst rate in the piriform-amygdala complex but decreased the C(4) inspiratory burst rate. Since hyperventilation induces hypocapnia, and enhanced amygdala activity may be involved in induction of a sense of anxiety, our findings might explain the neuronal mechanism of a vicious circle between hyperventilation and an increased sense of anxiety.
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Amígdala del Cerebelo/fisiopatología , Hipocapnia/fisiopatología , Animales , Animales Recién Nacidos , Ansiedad/fisiopatología , Ansiedad/psicología , Tronco Encefálico/fisiopatología , Hiperventilación/fisiopatología , Hiperventilación/psicología , Hipocapnia/psicología , Inhalación , Ratas , Ratas Wistar , Médula Espinal/fisiopatologíaRESUMEN
Tumor necrosis factor-alpha (TNF-alpha) inducing protein (Tipalpha) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-alpha and chemokine genes and activation of nuclear factor-kappaB. Since Tipalpha enters gastric cancer cells, the Tipalpha binding molecules in the cells should be investigated. The direct DNA-binding activity of Tipalpha was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tipalpha and DNA, revealed that the affinity of Tipalpha for (dGdC)10 is 2400 times stronger than that of del-Tipalpha, an inactive Tipalpha. This suggests a strong correlation between DNA-binding activity and carcinogenic activity of Tipalpha. And the DNA-binding activity of Tipalpha was first demonstrated with a molecule secreted from H. pylori.
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Proteínas de Unión al ADN/química , ADN/química , Helicobacter pylori/metabolismo , Factor de Necrosis Tumoral alfa/química , Sitios de Unión , Unión ProteicaRESUMEN
To understand the characteristic features of the Mongolian gerbil, Meriones unguiculatus, as an animal model of ascarid infections, the migration behaviour and pathogenesis of larvae were investigated in experimentally infected gerbils. Embryonated eggs from each of Toxocara canis, Baylisascaris procyonis, B. transfuga, Ascaris suum, and A. lumbricoides were orally inoculated into gerbils and larvae were recovered from various organs at designated periods. In T. canis-infected gerbils, larvae were present in the liver 3 days after infection and in the skeletal muscle and brain via the heart and lungs at a similar rate. In B. procyonis- and B. transfuga-infected gerbils, larvae were present in the lungs within 24 h after infection, with some having reached the brain by that time. After 24 h, larvae of B. procyonis tended to accumulate in the brain, while those of B. transfuga accumulated in skeletal muscles. In A. suum- and A. lumbricoides-infected gerbils, larvae remained in the liver on day 5 post-infection and elicited pulmonary haemorrhagic lesions, which disappeared 7 days after initial infection. Thereafter, no larvae of any type were recovered. Ocular manifestations were frequently observed in T. canis- and B. procyonis infected gerbils, but were rare in B. transfuga-infected gerbils. In the cases of A. suum and A. lumbricoides, migration to the central nervous system and eyes was extremely rare, and larvae had disappeared by 2 weeks post-infection. Fatal neurological disturbances were observed in B. procyonis-infected gerbils, whereas irreversible non-fatal neurological symptoms were observed in the case of B. transfuga.
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Infecciones por Ascaridida/parasitología , Ascarídidos/aislamiento & purificación , Gerbillinae/parasitología , Enfermedades de los Roedores/parasitología , Animales , Ascarídidos/parasitología , Infecciones por Ascaridida/veterinaria , Interacciones Huésped-ParásitosRESUMEN
PURPOSE: The effects of cigarette smoking on the association between inflammation and cancer were studied, since some bacteria induce the production of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine and endogenous tumor promoter, in cells. METHODS: Bacteria from a gargled solution from the buccal cavity of 20 individuals were cultured in the presence of 4 mg/ml cigarette-smoke condensates. Although cigarette-smoke condensates inhibited growth of Staphylococcus aureus strongly and that of Staphylococcus warneri weakly, tobacco tar-resistant S. aureus and S. warneri were obtained. RESULTS: One tobacco tar-resistant S. aureus strain (Sa-TA10) induced expression of the TNF-alpha gene in both Bhas 42 cells (v-Ha-ras transfected BALB/3T3 cells) and human lung cancer cell line H226B, while one tobacco tar-resistant S. warneri (Sw-TA75) did not induce it significantly. Moreover, Sa-TA10 induced formation of transformed foci and soft-agar colony in Bhas 42 cells in cooperation with the v-Ha-ras gene. The results suggested that Sa-TA10 has carcinogenic potential, whereas Sw-TA75 does not. CONCLUSION: These data suggest that tobacco tar-resistant S. aureus, with carcinogenic potential, is present in the buccal cavity of some individuals, and that cigarette smoking simultaneously inhibits growth of most of the bacteria and selects carcinogenic bacteria.
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Carcinógenos/efectos adversos , Farmacorresistencia Bacteriana , Mucosa Bucal/microbiología , Staphylococcus aureus/crecimiento & desarrollo , Contaminación por Humo de Tabaco/efectos adversos , Células 3T3/patología , Adulto , Animales , Transformación Celular Neoplásica/efectos de los fármacos , Células Cultivadas , Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , ARN Mensajero/metabolismo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Two unique evidence that cancer incidence rates in Fiji were unusually low, compared with those of another Pacific islands and that green tea beverage is an acknowledged cancer preventive in Japan, allowed us to study a local beverage in Fiji, kawa (kava kava) or yangona (Piper methysticum) belonging to Piperaceae. We isolated five known kawapyrones (kavapyrones) (1-5) and a new additional kawapyrone, 7,8-epoxyyangonin (6), from kawa MeOH extract and subjected them to TNF-alpha (tumor necrosis factor-alpha) release assay from BALB/3T3 cells treated with okadaic acid, a tumor promoter. 5,6-Dehydrokawain (desmethoxyyangonin)(1) and yangonin (4) significantly inhibited TNF-alpha release with IC50 values of 17 microM and 40 microM; a potency as great as (-)-epigallocatechin gallate (EGCG) isolated from green tea extract. Among the experiments with 1-5, dihydrokawain (2) was unique in showing the strongest inhibitory activity against TNF-alpha release in mice, but the weakest activity in the cells. We synthesized 5,6-dehydrokawain (1) and yangonin (4) via three steps from the dianion of ethyl acetoacetate achieving a good yield and determined their conformations by high resolution NMR and x-ray crystallographic analysis.
Asunto(s)
Kava , Fitoterapia , Extractos Vegetales/farmacología , Pironas/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Línea Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas , Pironas/química , Pironas/aislamiento & purificación , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Based on our previous results, which pointed to tumor necrosis factor-alpha (TNF-alpha) as the essential cytokine in tumor promotion in mouse skin, we present here three principal findings related to the specific roles of TNF-alpha, interleukin-1 (IL-1) and IL-6 in tumor promotion (using TNF-alpha- and IL-6-deficient mice) and in BALB/3T3 cell transformation: i) The previously reported residual tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in TNF-/- mice was confirmed by experiments with TNF+/+ and TNF-/- 129/Svj mice of the same strain, using two-stage carcinogenesis experiments. TPA produced tumors in 100% of TNF+/+ and 78% of TNF-/- mice at 20 weeks, and the average number of tumors per mouse was 11.1 in the former group and 2.1 in the latter. Judging from the expression of various inflammatory cytokine genes in TNF+/+ and TNF-/- mice, the residual tumor promoting activity of TPA in TNF-/- mice may be dependent on expression of IL-1alpha and IL-1beta genes. ii) Tumor promotion by TPA and okadaic acid in IL-6+/+ and IL-6-/- C57/BL6 mice was studied, with TPA producing tumors in 57.1% of IL-6+/+ and 40.0% of IL-6-/- mice at 20 weeks, and okadaic acid in 40.0% of IL-6+/+ and 53.3% of IL-6-/- mice. Thus, there was no significant difference between TPA or okadaic acid tumor promotion in either group. In addition, expression of IL-6 gene in skin of both types of mice suggested that IL-6 is not the essential cytokine in tumor promotion, since it can be replaced by other cytokines. iii) In transformed clones of BALB/3T3 cells induced by TNF-alpha alone, IL-1alpha gene expression was induced after transformation by TNF-alpha had occurred, which did not occur in parental cells. Expression patterns of TNF-alpha, IL-1beta, IL-6 and IL-10, along with TGF-beta, were similar in both parental and transformed cells. Considering all these results, we conclude that various cytokines have discrete roles in tumor promotion and cell transformation.
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Transformación Celular Neoplásica/metabolismo , Interleucina-1/fisiología , Interleucina-6/fisiología , Neoplasias Cutáneas/metabolismo , Factor de Necrosis Tumoral alfa/fisiología , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Carcinógenos/toxicidad , División Celular/efectos de los fármacos , Transformación Celular Neoplásica/patología , Cartilla de ADN/química , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ácido Ocadaico/toxicidad , Reacción en Cadena de la Polimerasa , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/patología , Acetato de Tetradecanoilforbol/toxicidad , TransfecciónRESUMEN
Hemorrhagic fevers represent a wide spectrum of viral infectious diseases, out-breaking mostly as epidemics, some of them being highly lethal. They range from those caused by bunyaviridae, associated with renal or pulmonary syndromes and those recently emerging and caused by the filoviridae family of thread-like viruses. Among the latter, Ebola hemorrhagic fever (EHF) bears the highest mortality and morbidity rates. One form of the disease has been documented only in monkeys. The human form, has occurred mainly in areas surrounding rain forests in central Africa. Patients present with signs of hemorrhagic diathesis, fever, diarrhea and neurological disorders, leading sometimes to confusion with local endemic diseases. Fatal victims of the disease die of dehydration. Poor hygienic conditions facilitate the spread of the virus. Biologically, the virus seems to target both the host blood coagulative and immune defense systems. Intensive epidemiologic search have failed to establish the definitive natural host of the virus. Twice, with a 19-year interval, major outbreaks have taken place in the Democratic Republic of the Congo. The second major outbreak in the northwestern city of Kikwit in April 1995 will serve here to elucidate the mechanism of the viral infection.
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Fiebre Hemorrágica Ebola/transmisión , África/epidemiología , Animales , Haplorrinos , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/fisiopatología , HumanosRESUMEN
The success of green tea as a cancer preventive is based on evidence that green tea contains tannins and antioxidants, does not show toxicity in humans and has long traditional use in Asia. In the light of this, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using the inhibition of TNF-alpha release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-alpha release was found in the leaf extract rather than the bark extract, and the main active constituents were identified as geraniin and corilagin, which are present in another Japanese traditional herb, Geranium thunbergii (Genno-shoko). The IC50 values of TNF-alpha release inhibition were 43 microM for geraniin and 76 microM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG) was 26 microM. Treatment with geraniin prior to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-bearing mice from 80.0 to 40.0% and the average numbers of tumor per mouse from 3.8 to 1.1 in week 20. Thus, geraniin has slightly weaker inhibitory activity than EGCG. Since geraniin and corilagin have been well investigated as representative tannins, we discuss here the new possibility of classical herbal medicine in the development of preventive agents for cancer and other life-style related diseases.
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Anticarcinógenos/farmacología , Glucósidos/farmacología , Taninos Hidrolizables , Plantas Medicinales/química , Taninos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Células 3T3 , 9,10-Dimetil-1,2-benzantraceno , Animales , Anticarcinógenos/química , Carcinógenos , Cromatografía Líquida de Alta Presión , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/farmacología , Hojas de la Planta/química , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/prevención & controlRESUMEN
Although retroperitoneal or psoas abscess is an unusual clinical problem, the insidious and occult characteristics of this abscess sometimes cause diagnostic delays, resulting in considerably high morbidity and mortality. In particular, psoas abscess caused by perforated colon carcinoma is uncommon. We report a case of psoas abscess caused by a carcinoma of the cecum. A 72-year-old Japanese woman was admitted to our hospital, with pain in the right groin and buttock. The pain had appeared 6 months before admission, and the symptoms had then been relieved by oral antibiotics. On March 25, 1999, inflammatory signs in the right buttock indicated localized cellulitis, and incision and drainage was performed at a local hospital. The patient was referred to our hospital on the same day. On admission to our hospital, computed tomography (CT) scan revealed a thick right-sided colonic wall and enlargement of the right ileopsoas muscle. Barium enema and colonofiberscopy revealed an ulcerated tumor occupying the entire circumference of the cecum. A retroperitoneal abscess and fistula had been formed by the retroperitoneal perforation of cecum carcinoma: surgical resection was performed after remission of the local inflammatory signs. Operative findings indicated that the cancerous lesion and its surrounding tissues were firmly attached to the right iliopsoas and major psoas muscle, and en-bloc resection, including adjacent muscular tissue, was performed. The fact that carcinoma of the colon could be a cause of psoas abscess and cellulitis in the gluteal region should be considered when an unexplained psoas abscess is diagnosed.
Asunto(s)
Adenocarcinoma/complicaciones , Neoplasias del Ciego/complicaciones , Celulitis (Flemón)/etiología , Absceso del Psoas/etiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirugía , Anciano , Biopsia/métodos , Nalgas , Neoplasias del Ciego/diagnóstico , Neoplasias del Ciego/cirugía , Celulitis (Flemón)/diagnóstico , Celulitis (Flemón)/cirugía , Colonoscopía/métodos , Enema/métodos , Femenino , Humanos , Radioisótopos de Yodo , Absceso del Psoas/diagnóstico , Absceso del Psoas/cirugía , Tomografía Computarizada por Rayos X/métodosRESUMEN
Green tea is the most effective cancer preventive beverage. In the light of this, the mechanisms of action of tea polyphenols were investigated on the molecular levels. We present here the effects of (-)-epigallocatechin gallate (EGCG) on expression of 588 genes in human lung cancer cell line PC-9 cells, using a human cancer cDNA expression array. The levels of gene expression in non-treated control cells, and cells treated with EGCG alone, with the tumor promoter okadaic acid alone, and with EGCG plus okadaic acid, were studied, and their expression levels were classified into down-regulation (under 0.5 fold) and up-regulation (over 2.0 fold) by comparing with the levels of control. Non-treated PC-9 cells expressed 163 genes out of 588, and EGCG-treated cells induced down-regulated expression of 12 genes and up-regulated expression of 4 other genes. From a comparison of gene expression in the cells treated with EGCG and in cells treated with EGCG plus okadaic acid, we found the following genes commonly affected by EGCG: down-regulation of four genes, NF-kappaB inducing kinase (NIK), death-associated protein kinase 1 (DAPK 1), rhoB and tyrosine-protein kinase (SKY); up-regulation of one gene, retinoic acid receptor alpha1. Among them, we think down-regulation of NIK gene expression is significant for cancer prevention, based on evidence that inhibition of NF-kappaB activation is a result of inhibition of NIK/IKK signalling complex.
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Antimutagênicos/farmacología , Catequina/análogos & derivados , Catequina/farmacología , Expresión Génica/efectos de los fármacos , Sondas de ADN , ADN Complementario/biosíntesis , ADN Complementario/genética , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares , FN-kappa B/biosíntesis , FN-kappa B/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Poli A/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The study of green tea polyphenols as a cancer preventative is approaching a new era, with significant results accumulating rapidly. This paper briefly reviews four topics related to mechanisms of action of tea polyphenols: (I) identification of the genes commonly affected by EGCG, as demonstrated by Clontech's Atlas cDNA Expression Array; (II) the significance of heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1) as a new biomarker for early detection of lung cancer, and inhibition of its expression by EGCG; (III) the synergistic or additive effects of EGCG with the cancer preventive agents, sulindac and tamoxifen, on induction of apoptosis in PC-9 cells and on inhibition of intestinal tumor development in multiple intestinal neoplasia (Min) mice; (IV) the results of a 10 year prospective cohort study demonstrating the effectiveness of daily consumption of green tea in preventing cancer, and a prototype study for developing green tea beverage as cancer preventive.
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Anticarcinógenos/administración & dosificación , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/prevención & control , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B , Neoplasias Intestinales/prevención & control , Neoplasias Pulmonares/prevención & control , Ribonucleoproteínas/análisis , Sulindac/administración & dosificación , Té , Animales , Anticarcinógenos/química , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/diagnóstico , Catequina/administración & dosificación , Catequina/análogos & derivados , Catequina/química , Quimioprevención , Estudios de Cohortes , Sinergismo Farmacológico , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ribonucleoproteínas Nucleares Heterogéneas , Humanos , Neoplasias Intestinales/química , Neoplasias Intestinales/diagnóstico , Neoplasias Intestinales/genética , Japón , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Ratones , Ratones Mutantes , Ácido Ocadaico/farmacología , Análisis de Secuencia por Matrices de Oligonucleótidos , Estudios Prospectivos , Té/química , Células Tumorales CultivadasRESUMEN
Considering a suspected link between Helicobacter pylori infection and human stomach cancer, a new H. pylori gene for membrane protein 1 (HP-MP1) was recently cloned. Because HP-MP1 induces release of inflammatory cytokines and tumor necrosis factor-alpha acts as both initiator and tumor promoter, we studied the possible involvement of HP-MP1 in carcinogenesis of H. pylori. Two cell lines, BALB/3T3 cells as control and v-Ha-ras-transfected BALB/3T3 cells (Bhas 42 cells) as putative initiated cells, were each transfected with HP-MP1, urease B genes, or vector alone. All of the Bhas/mpl clones showed strong expression of tumor necrosis factor-alpha gene and produced tumors in 100% of nude mice. Two Bhas/ure clones showed weak tumorigenicity; the other Bhas and BALB clones showed none. Results indicate strong carcinogenic activity of HP-MP1 in cooperation with viral Ras protein and weak activity of urease B.
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Antígenos Bacterianos , Proteínas de la Membrana Bacteriana Externa/fisiología , Transformación Celular Neoplásica/genética , Células 3T3 , Animales , Proteínas de la Membrana Bacteriana Externa/genética , Transformación Celular Neoplásica/metabolismo , Expresión Génica , Vectores Genéticos/genética , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Gástricas/microbiología , Transfección , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/fisiología , Ureasa/genética , Proteínas ras/genética , Proteínas ras/fisiologíaRESUMEN
While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma.
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Adenocarcinoma Papilar/patología , Conducto Colédoco/patología , Neoplasias de la Vesícula Biliar/patología , Anciano , Conductos Biliares Extrahepáticos/patología , Conductos Biliares Extrahepáticos/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Dilatación Patológica , Femenino , Hepatectomía , Humanos , Necrosis , Invasividad Neoplásica , Estadificación de NeoplasiasRESUMEN
To evaluate the relationship among the extracellular matrix (ECM) and mitogen-activated protein kinase (MAPK) family for the vascular damages in hyperglycemia, we injected Mongolian gerbils intravenously with 150 mg/kg streptozotocin (STZ) and observed over the next one year the resulting aortic changes by immunohistochemical techniques. After STZ treatment, hyperglycemia was confirmed. At 4 weeks after STZ administration morphological observation revealed increased stromal components among the vascular smooth muscle cells (SMCs). Immunohistochemically, extracellular matrices such as fibronectin and laminin were localized in the aorta at 4 weeks and one year after STZ administration. The reaction products of MAPK in vascular SMCs were more increased at one year than at 4 weeks after STZ administration. After STZ administration, the increase of ECM and MAPK was observed in the aorta, which suggests these factors play important roles in the pathogenesis of macrovasculopathy in diabetes mellitus.
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Aorta/enzimología , Aorta/patología , Diabetes Mellitus Experimental/enzimología , Diabetes Mellitus Experimental/patología , Matriz Extracelular/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Animales , Gerbillinae , InmunohistoquímicaRESUMEN
Green tea is the most effective beverage for cancer prevention in humans. Looking at the concept of combination cancer chemoprevention, we previously reported the synergistic effects of (-)-epigallocatechin gallate (EGCG) with sulindac, and the additive effects of EGCG with tamoxifen, on cancer-preventive activity in human lung cancer cell line PC-9. This paper reports confirmation of the synergistic effects of EGCG with sulindac on the inhibition of intestinal tumors in multiple intestinal neoplasia (Min) mice. Treatment with both green tea extract and sulindac significantly reduced the number of tumors from 72.3 +/- 28.3 to 32.0 +/- 18.7 tumors per mouse, a decrease of 44.3%, whereas treatment with green tea extract alone or with sulindac alone reduced it to 56.7 +/- 3.5 and 49.0 +/- 12.7, respectively. The results also indicated that green tea extract inhibited tumor growth in Min mice almost as potently as sulindac itself did. The three treated groups did not show any adenocarcinomas, whereas 10.8% of the control group did. Since cancer-preventive agents like sulindac and tamoxifen are associated with adverse effects, we discuss the possibility of non-toxic, combination cancer chemoprevention with green tea, looking at the goal of truly effective cancer prevention.
Asunto(s)
Catequina/análogos & derivados , Neoplasias Intestinales/prevención & control , Extractos Vegetales/farmacología , Sulindac/farmacología , Té , Adenocarcinoma/prevención & control , Animales , Catequina/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones MutantesRESUMEN
The time required in judging if two probes are on the same curve increased monotonically with the separation of the probes along that curve. This process is called "curve tracing" (Jolicoeur, Ullman & Mackay, 1986). In this study we examined whether curve tracing would occur on a three-dimensionally presented curve with depth variation. By comparing the performance on depth varying and no depth varying stimuli, we examined the properties of three-dimensional curve tracing. The mean RT on three-dimensional stimuli increased monotonically as the distance between two probes increased, which indicates that curve tracing also occurs on three-dimensional stimuli. The mean RT on three-dimensional stimuli was longer than that on two-dimensional stimuli. Our results suggest that three-dimensional structure of the stimuli caused additional costs on curve tracing.