RESUMEN
Aim: Variation in dental structures is widely accepted as a combination of multiple factors such as gender, environmental effects and genetics. However, the characterization of similarities and differences in dental morphology has been lacking in relation to the factors mentioned. This study aims to assess and compare the variations in traits in mandibular molars and the influence of gender and ethnicity in affecting these traits amongst the Malaysian population of Mongoloid ancestry. Materials and Methods: Our study population was 180 dental casts of patients, from 15 to 40 years old, comprising 56 Malays and 124 Chinese; 60 were males and 120 were females. Traits like groove pattern, number of cusps, protostylids and deflecting wrinkles were observed, scored, and recorded. Results: This study revealed that the most common mandibular first molar (M1) was characterized by 5 cusps and displayed 'Y' groove pattern, while the most common mandibular second molar (M2) had 4 cusps and exhibited a groove pattern that resembled a '+'. Notably, all the traits studied were bilaterally symmetrical, except for the groove pattern of M1, while sexual dimorphism was observed in groove patterns of M2. Conclusions: This study found that M1 had a preponderance of 5 cusps with 'Y' groove pattern, while M2 were typically 4-cusped with '+' groove pattern.
Objetivo: La variación en las estructuras dentales es ampliamente aceptada como el resultado de una combinación de múltiples factores como el género, los efectos ambientales y la genética. Sin embargo, ha faltado la caracterización de similitudes y diferencias en la morfología dental en relación a los factores mencionados. Este estudio tiene como objetivo evaluar y comparar las variaciones en los rasgos de los molares mandibulares y la influencia del género y la etnia al afectar estos rasgos entre la población malaya de ascendencia mongoloide. Materiales y Métodos: Nuestra población de estudio fue de 180 modelos dentales de pacientes, de 15 a 40 años,conformados por 56 malayos y 124 chinos; 60 eran hombres y 120 eran mujeres. Se observaron, puntuaron y registraron rasgos como el patrón de surcos, el número de cúspides, los protostílidos y las arrugas desviadas. Resultados: Este estudio reveló que el primer molar mandibular más común (M1) se caracterizaba por 5 cúspides y mostraba un patrón de ranura en 'Y', mientras que el segundo molar mandibular más común (M2) tenía 4 cúspides y exhibía un patrón de ranura que se parecía a un ' +'. En particular, todos los rasgos estudiados eran bilateralmente simétricos, excepto el patrón de surco de M1, mientras que se observó dimorfismo sexual en los patrones de surco de M2. Conclusión: Este estudio encontró que M1 tenía una preponderancia de 5 cúspides con un patrón de ranura en 'Y', mientras que M2 tenía típicamente 4 cúspides con un patrón de ranura '+'.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Diente Molar/anatomía & histología , Etnicidad , Malasia/etnología , MandíbulaRESUMEN
Long non-coding RNA (lncRNA) is an essential regulator of carcinogenesis and cancer progression. In the study, we explored the role of lncRNA DLGAP1-AS1 in gastric cancer (GC). qRT-PCR was carried out to detect DLGAP1-AS1 expression in GC tissues and cell lines. CCK-8 assay, EdU assay, and transwell experiments were employed to detect the malignant biological behaviors of GC cells with DLGAP1-AS1 knockdown or overexpression. Bioinformatics and dual-luciferase report assay were used to confirm the binding relationship between DLGAP1-AS1 and miR-515-5p. MARK4 expression was detected by western blot after DLGAP1-AS1/miR-515-5p was selectively regulated. DLGAP1-AS1 was up-regulated in GC tissues and cell lines, and its high expression was closely associated with larger tumor size, higher TNM stage, and lymph node metastasis. Furthermore, DLGAP1-AS1 overexpression enhanced cell proliferation, migration, and invasion, and miR-515-5p could reverse these effects. DLGAP1-AS1 participated in the regulation of the MARK4 signaling pathway by targeting miR-515-5p. DLGAP1-AS1 promoted GC progression through miR-515-5p/MARK4 signaling pathway.
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MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Proteínas Serina-Treonina Quinasas , ARN Largo no Codificante/genética , Neoplasias Gástricas/genéticaRESUMEN
Long non-coding RNA (lncRNA) is an essential regulator of carcinogenesis and cancer progression. In the study, we explored the role of lncRNA DLGAP1-AS1 in gastric cancer (GC). qRT-PCR was carried out to detect DLGAP1-AS1 expression in GC tissues and cell lines. CCK-8 assay, EdU assay, and transwell experiments were employed to detect the malignant biological behaviors of GC cells with DLGAP1-AS1 knockdown or overexpression. Bioinformatics and dual-luciferase report assay were used to confirm the binding relationship between DLGAP1-AS1 and miR-515-5p. MARK4 expression was detected by western blot after DLGAP1-AS1/miR-515-5p was selectively regulated. DLGAP1-AS1 was up-regulated in GC tissues and cell lines, and its high expression was closely associated with larger tumor size, higher TNM stage, and lymph node metastasis. Furthermore, DLGAP1-AS1 overexpression enhanced cell proliferation, migration, and invasion, and miR-515-5p could reverse these effects. DLGAP1-AS1 participated in the regulation of the MARK4 signaling pathway by targeting miR-515-5p. DLGAP1-AS1 promoted GC progression through miR-515-5p/MARK4 signaling pathway.
Asunto(s)
Humanos , Neoplasias Gástricas/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proteínas Serina-Treonina Quinasas , Línea Celular TumoralRESUMEN
DNJ, an inhibitor of α-glucosidase, is used to suppress the elevation of postprandial hyperglycemia. In this study, we focus on screening an appropriate microorganism for performing fermentation to improve DNJ content in mulberry leaf. Results showed that Ganoderma lucidum was selected from 8 species and shown to be the most effective in improvement of DNJ production from mulberry leaves through fermentation. Based on single factor and three factor influence level tests by following the Plackett-Burman design, the optimum extraction yield was analyzed by response surface methodology (RSM). The extracted DNJ was determined by reverse-phase high performance liquid chromatograph equipped with fluorescence detector (HPLC-FD). The results of RSM showed that the optimal condition for mulberry fermentation was defined as pH 6.97, potassium nitrate content 0.81% and inoculums volume 2 mL. The extraction efficiency reached to 0.548% in maximum which is 2.74 fold of those in mulberry leaf.
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1-Desoxinojirimicina/aislamiento & purificación , 1-Desoxinojirimicina/metabolismo , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Morus/metabolismo , Reishi/metabolismo , Biotecnología/métodos , Cromatografía Líquida de Alta Presión , Medios de Cultivo/química , Fermentación , Concentración de Iones de Hidrógeno , Hojas de la Planta/metabolismo , Reishi/crecimiento & desarrollo , Tecnología Farmacéutica/métodosRESUMEN
DNJ, an inhibitor of α-glucosidase, is used to suppress the elevation of postprandial hyperglycemia. In this study, we focus on screening an appropriate microorganism for performing fermentation to improve DNJ content in mulberry leaf. Results showed that Ganoderma lucidum was selected from 8 species and shown to be the most effective in improvement of DNJ production from mulberry leaves through fermentation. Based on single factor and three factor influence level tests by following the Plackett-Burman design, the optimum extraction yield was analyzed by response surface methodology (RSM). The extracted DNJ was determined by reverse-phase high performance liquid chromatograph equipped with fluorescence detector (HPLC-FD). The results of RSM showed that the optimal condition for mulberry fermentation was defined as pH 6.97, potassium nitrate content 0.81% and inoculums volume 2 mL. The extraction efficiency reached to 0.548% in maximum which is 2.74 fold of those in mulberry leaf.
Asunto(s)
1-Desoxinojirimicina/aislamiento & purificación , 1-Desoxinojirimicina/metabolismo , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Morus/metabolismo , Reishi/metabolismo , Biotecnología/métodos , Cromatografía Líquida de Alta Presión , Medios de Cultivo/química , Fermentación , Concentración de Iones de Hidrógeno , Hojas de la Planta/metabolismo , Reishi/crecimiento & desarrollo , Tecnología Farmacéutica/métodosRESUMEN
DNJ, an inhibitor of α-glucosidase, is used to suppress the elevation of postprandial hyperglycemia. In this study, we focus on screening an appropriate microorganism for performing fermentation to improve DNJ content in mulberry leaf. Results showed that Ganoderma lucidum was selected from 8 species and shown to be the most effective in improvement of DNJ production from mulberry leaves through fermentation. Based on single factor and three factor influence level tests by following the Plackett-Burman design, the optimum extraction yield was analyzed by response surface methodology (RSM). The extracted DNJ was determined by reverse-phase high performance liquid chromatograph equipped with fluorescence detector (HPLC-FD). The results of RSM showed that the optimal condition for mulberry fermentation was defined as pH 6.97, potassium nitrate content 0.81% and inoculums volume 2 mL. The extraction efficiency reached to 0.548% in maximum which is 2.74 fold of those in mulberry leaf.
Asunto(s)
1-Desoxinojirimicina/aislamiento & purificación , 1-Desoxinojirimicina/metabolismo , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/metabolismo , Morus/metabolismo , Reishi/metabolismo , Biotecnología/métodos , Cromatografía Líquida de Alta Presión , Medios de Cultivo/química , Fermentación , Concentración de Iones de Hidrógeno , Hojas de la Planta/metabolismo , Reishi/crecimiento & desarrollo , Tecnología Farmacéutica/métodosRESUMEN
BACKGROUND: We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. CONCLUSION: Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Carcinoma Lobular/mortalidad , Células Asesinas Inducidas por Citocinas/trasplante , Células Dendríticas/trasplante , Inmunoterapia Adoptiva , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carboplatino/administración & dosificación , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/secundario , Carcinoma Lobular/terapia , Terapia Combinada , Células Asesinas Inducidas por Citocinas/inmunología , Células Dendríticas/inmunología , Docetaxel , Femenino , Estudios de Seguimiento , Humanos , Dosis Máxima Tolerada , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Taxoides/administración & dosificación , Tiotepa/administración & dosificaciónRESUMEN
BACKGROUND: Recent studies suggest that the relationship between cancer stem cells (CSCs) and the vascular niche may be bidirectional; the niche can support the growth and renewal of CSCs, and CSCs may contribute to the maintenance of the niche. There is little knowledge concerning the role of breast cancer stem cells in promoting tumor angiogenesis. AIM: For human breast cancers, CSCs have been shown to be associated with a CD44+/CD24- phenotype. We investigated the potential activities of CD44+/CD24- breast cancer stem cells in promoting tumor angiogenesis. METHODS: The expression of pro-angiogenic genes was determined by quantitative real-time RT-PCR. Endothelial cell migration assays were employed to evaluate effects of conditioned media from CD44+/CD24- on human umbilical vein endothelial cells. A chorioallantoic membrane (CAM) assay was used to study the potential of CD44+/CD24- cells to promote angiogenesis. RESULTS: In our study, CD44+/CD24- cells expressed elevated levels of pro-angiogenic factors compared with CD44+/CD24+ cells. CD44+/CD24- cell-conditioned media significantly increased endothelial cell migration. Breast cancer cell lines enriched with CD44+/CD24- cells were more pro-angiogenic in the CAM assay than those lacking a CD44+/CD24- subpopulation. CD44+/CD24- cells sorted from MCF-7 cell lines were more pro-angiogenic in a CAM assay than CD44+/CD24+ cells. Furthermore, the VEGF concentration was significantly higher in CD44+/CD24- cell-conditioned media than in CD44+/CD24+ cell-conditioned media. The pro-angiogenic effect of CD44+/CD24- cells on endothelial cells was abolished by bevacizumab. CONCLUSION: Our findings demonstrate that CD44+/CD24- breast cancer stem cells have substantial pro-angiogenic potential and activity. This provides new insights to explore in the development of targeted therapies.
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Neoplasias de la Mama/patología , Antígeno CD24/metabolismo , Receptores de Hialuranos/metabolismo , Células Madre Neoplásicas/patología , Neovascularización Patológica/metabolismo , Inhibidores de la Angiogénesis/farmacología , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Bevacizumab , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Movimiento Celular , Embrión de Pollo , Membrana Corioalantoides/irrigación sanguínea , Membrana Corioalantoides/metabolismo , Resistencia a Antineoplásicos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Femenino , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Neovascularización Patológica/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: To ascertain the biologic significance of lung cancer Side population (SP) cells, which represent putative cancer stem cells (CSC) in the absence of consensus biomarkers for tumor-specific CSC. MATERIALS AND METHODS: We sorted and analyzed the angiogenic features of SP cells, isolated from tumor cell lines based on the exclusion of the DNA dye Hoechst 33342, from the NSCLC cell lines A549 and H460. RESULTS: Compared with non-SP cells, mRNA of vascular endothelial growth factor (VEGF)-A, VEGF-B, angiopoietin (ang)-1, ang-2, fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (Cox-2) and interleukin-8 (IL-8) were over-expressed in SP cells accompanied by over-expression of ABCG2 and MDR1 mRNA. The supernatant of cultured SP cells could significantly induce migration of human umbilical vein endothelial cells, while recombinant human endostatin (Endostar 25(®)) could inhibit the migration. CONCLUSIONS: This study revealed that the NSCLC SP cells might represent CSCs and possess pro-angiogenic properties, and antiangiogenesis represent a potential therapy.
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Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Endostatinas/farmacología , Neoplasias Pulmonares/patología , Células Madre Neoplásicas/efectos de los fármacos , Neovascularización Patológica/patología , Células de Población Lateral/efectos de los fármacos , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Humanos , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/patología , Neovascularización Patológica/tratamiento farmacológico , Fenotipo , ARN Mensajero/metabolismo , Proteínas Recombinantes/farmacología , Células de Población Lateral/patologíaRESUMEN
AIM: The aim of the study is to explore the safety of cytotoxic T lymphocytes (CTLs) infusion by transfected dendritic cells (DCs) with recombinant adeno-associated virus vector (rAAV) carrying CEA cDNA among advanced cancer patients. PATIENTS AND METHODS: A total of 27 cancer patients with tumor tissue expression positivity and/or sera-elevated level of CEA were subsequently divided into cohort A and B resulted from the ex vivo expansion number of CTLs generated from co-culture of specific transfected DCs with autologous T lymphocytes. Based on the variations of infused number of specific CTL derived from different yields of individualized patients who had experienced various anti-cancer treatments, we compared the patients of low number of CTL cells (2-8 × 10(8) infused, cohort A, 6 cases) with those of higher number (above 8 × 10(8) infused, cohort B, 21 cases) to testify the possible adverse reactions caused by amount of infused CTLs. This study resembled a phase I study aiming for setting up clinical trial of adoptive cellular therapy that conceptually comes from conventional cytotoxic drugs. RESULTS: The results showed that one case from the each cohort had experienced moderate fever, and four cases with fatigue were seen in cohort B. The symptoms were transient without serious adverse events. For the consideration of clinical response 2 partial remission (8.0 %, 2/25), 1 minor remission, and 9 stable disease (40 %, 10/25) were observed in 25 patients eligible for evaluation. Sera levels of CEA assay were lowered in six patients. During a median follow-up of 8.1 months, we could not observe severe or chronic adverse reactions related to rAAV-DC infusions. Meanwhile, the variation of number of CTLs infused in this setting did not alter the status of peripheral lymphocyte population. CONCLUSIONS: These preliminary data suggest that the rAAV-DC immunotherapy is well-tolerated and showed no severe adverse reactions in cancer patients.
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Vacunas contra el Cáncer/efectos adversos , Células Dendríticas/trasplante , Dependovirus/genética , Neoplasias/terapia , Linfocitos T Citotóxicos/trasplante , Adulto , Anciano , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Vectores Genéticos , Humanos , Inmunoterapia , Masculino , Persona de Mediana Edad , Neoplasias/inmunología , Neoplasias/metabolismo , Fenotipo , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/metabolismo , TransfecciónRESUMEN
BACKGROUND: Increasing evidence shows that bone marrow stromal cells (BMSCs) have antitumor activities both in vitro and in animal models. Further studies fleshed out the supportive data that the antitumor activity of BMSCs could be markedly enhanced by cytokines such as IL-2 and IFN-ß (interferon). However, powerful strategies to activate BMSCs other than by genetically engineering interventions are still required. METHODS: In this study, new methods of generating antitumor activities of murine marrow-originated MSCs pulsed with homologous tumor-derived exosomes (TEX) were explored to yield potent immune effectors against hepatocellular carcinoma cells in vitro. RESULTS: The results showed that BMSCs pulsed with exosomes and IFN-γ exhibited increased migration ability with a result of 163.22 ± 26.90 versus 129.89 ± 29.28 cells/HP by transwell determination (p < 0.05). The inhibition of homologous hepatocellular carcinoma cells line H(22) cells by exosomes pulsed BMSCs was significantly increased by 41.9 % compared with control (p < 0.05), and flow cytometry analysis showed that the cell cycle of H(22) cells was arrested in G(0)/G(1) phase. Meanwhile, western blot analysis showed that PCNA protein expression in the supernatant of H(22) cells was significantly decreased. CONCLUSIONS: This study demonstrated that BMSCs pulsed with TEX could enhance its antitumor activities, which might be regarded as a novel promising antitumor treatment.
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Carcinoma Hepatocelular/patología , Proliferación Celular , Exosomas/fisiología , Neoplasias Hepáticas/patología , Células Madre Mesenquimatosas/fisiología , Animales , Técnicas de Cultivo de Célula , Diferenciación Celular/fisiología , Linaje de la Célula/fisiología , Células Cultivadas , Regulación hacia Abajo , Exosomas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , FenotipoRESUMEN
Pentoxifylline (PTX), a phosphodiesterase inhibitor, is known to downregulate tumor necrosis factor-alpha (TNF-alpha) secretion induced by lipopolysacchride (LPS) and gamma interferon (IFN-gamma). We have had limited success in treating leprosy reactions, including erythema nodosum leprosum (ENL), in which TNF-alpha has been identified as a major proinflammatory cytokine. PTX inhibited production of NO (IC50 approximately equal to 1.0 mg/ml) and TNF-alpha (IC50 approximately equal to 0.05 mg/ml) in a dose-dependent fashion. As little as 0.5 mg/ml of PTX decreased NO production and 0.01 mg/ml of PTX inhibited TNF-alpha production. Western blot analyses demonstrated that iNOS was suppressed by PTX. Northern blot analyses showed significant reduction of TNF-alpha mRNA. We conclude that PTX is an effective inhibitor of lipoarabinomannan (LAM)-induced TNF-alpha production at both the product and transcriptional levels in our macrophage cell line. PTX also showed moderate inhibition of NO at the product level as well as translation of iNOS.