RESUMO
Tumor-associated macrophages (TAMs) are abundant population of inflammatory cells which play an essential role in remodeling tumor microenvironment and tumor progression. Previously, we found the high density of TAMs was correlated with lymph node metastasis and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Therefore, this study was designed to investigate the mechanisms of interaction between TAMs and PDAC. THP-1 monocytes were the exposure to conditioned media (CM) produced by PDAC cells; then, monocyte recruitment and macrophage differentiation were assessed. CM from PDAC attracted and polarized THP-1 monocytes to tumor-driven like macrophages. mRNA expression cytokine profiling and ELISA identified the IL-8 secretion was increasing in tumor-driven like macrophages, and STAT3 pathway was involved. Addition of exogenous recombinant human IL-8 promoted PDAC cells motility in vitro and metastasis in vivo via upregulating Twist expression, which mediated epithelial-mesenchymal transition in cancer cells. What is more, IL-8 expression level in tumor stroma by immunohistochemical analysis was related to lymph node metastasis, the number of tumor CD68 but not CD163 positive macrophages and patient outcome. Taken together, these findings shed light on the important interplay between cancer cells and TAMs in tumor microenvironment and suggested that IL-8 signaling might be a potential therapeutic target for PDAC.
Assuntos
Carcinoma Ductal Pancreático/patologia , Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/metabolismo , Monócitos/citologia , Neoplasias Pancreáticas/patologia , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Macrófagos/patologia , Camundongos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Metástase Neoplásica , Transplante de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células THP-1 , Microambiente Tumoral , Regulação para Cima , Neoplasias PancreáticasRESUMO
INTRODUCTION: Pancreatic cancer is an aggressive carcinoma of the digestive system and radical resection, which is available to very few patients, is the only possibility for cure. Since therapeutic choices are limited at the advanced stage, screening and early diagnostic tools are indispensable for a better prognosis. Areas covered: This review illustrates serologic and imaging examinations, and carbohydrate antigens, microRNAs, methylation biomarkers, molecules in exosomes, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and endoscopic retrograde cholangiopancreatography, among other topics. No matter which approach is used, the accuracy of early diagnosis is extremely low. Combining different methods greatly improves the accuracy of early diagnosis. This review was conducted utilizing PubMed with key search words pancreatic cancer, early diagnosis, biomarkers and imaging. Expert commentary: Appropriate combination of biomarkers and imaging technologies will become standard practice in the future. Because the incidence of and mortality from pancreatic cancer is rising, further study of new approaches for the early detection of pancreatic tumors is essential.
Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pancreáticas/diagnóstico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Metilação de DNA , Exossomos/metabolismo , Humanos , MicroRNAs/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/genética , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos TestesRESUMO
It is critical to understand the pathogenesis of preinvasive stages of pancreatic duct adenocarcinoma (PDAC) for developing novel potential diagnostic and therapeutic targets. The polycomb group family member B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi1) is overexpressed and involved in cancer progression in PDAC; however, its role in the multistep malignant transformation of human pancreatic duct cells has not been directly demonstrated. In this study, we stably expressed Bmi1 in a model of telomerase-immortalized human pancreatic duct-derived cells (HPNE) and showed that Bmi1 promoted HPNE cell proliferation, migration, and invasion but not malignant transformation. We then used mutant KRASG12D as a second oncogene to transform HPNE cells and showed that it further enhanced Bmi1-induced malignant potential. More importantly, coexpression of KRASG12D and Bmi1 caused anchorage-independent growth transformation in vitro but still failed to produce tumors in nude mice. Finally, we found that mutant KRASG12D induced HPNE-Bmi1 cells to undergo partial epithelial-mesenchymal transition (EMT) likely via upregulation of snail. Knockdown of KRASG12D significantly reduced the expression of snail and vimentin at both the messenger RNA (mRNA) and protein level and further impaired the anchorage-independent growth capability of invasive cells. In summary, our findings demonstrate that coexpression of Bmi1 and KRASG12D could lead to transformation of HPNE cells in vitro and suggest potential new targets for diagnosis and treatment of PDAC.
Assuntos
Carcinoma Ductal Pancreático/patologia , Transformação Celular Neoplásica/genética , Neoplasias Pancreáticas/patologia , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: The long-term effectiveness and safety of lamivudine in patients with decompensated hepatitis B virus-related cirrhosis are still not clear. The present study attempted to describe the clinical outcomes of lamivudine therapy in these special patients over three years. METHODS: This study was a retrospective, controlled cohort study which involved 153 patients with decompensated hepatitis B virus-related cirrhosis. Of these, 86 patients received lamivudine 100 mg daily accompanied with general internal treatment, and the other 67 were given general internal treatment only. Significant clinical responses were recorded after years of antiviral treatment. RESULTS: The patients in both groups were matched in terms of age, sex and laboratory results at baseline. After years of therapy, the Child-Pugh-Turcotte scores and laboratory values of the patients receiving lamivudine were remarkably improved compared to the patients in the control group. The mortality rate and the incidence of cirrhosis-related complications were much lower in the lamivudine group than in the control group. Genotypic resistance tyrosine, methionine, aspartate, aspartate mutations developed in 26.7 percent of the patients during 3-year lamivudine treatment, and cirrhosis-related death and the hepatocellular carcinoma were more likely to occur in patients with these mutations than in the other patients who were treated with lamivudine. CONCLUSIONS: Continuous long-term lamivudine treatment in patients with decompensated hepatitis B virus-related cirrhosis delays clinical progression, and significantly improves hepatic function and prognosis. However, the use of a retrospective control cohort precludes drawing definitive conclusions.
Assuntos
Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Lamivudina/uso terapêutico , Cirrose Hepática/mortalidade , Adulto , Idoso , Estudos de Coortes , Feminino , Hepatite B/complicações , Vírus da Hepatite B/genética , Humanos , Lamivudina/efeitos adversos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The Child-Pugh score, the model for end-stage liver disease (MELD) score, and the occurrence of cirrhosis-related complications are independent prognostic predictors used in the assessment of chronic liver diseases. OBJECTIVES: The objectives of this study were to determine the best prognostic scoring system, and to create a combined method to predict the prognosis of liver cirrhosis more accurately. METHODS: We retrospectively reviewed 435 cirrhotic patients from January 2009 to June 2010 and evaluated their short- and medium-term survival. Child-Pugh, MELD and its advanced scoring systems were computed for each patient. The sensitivity and specificity of these scoring systems were analyzed and their validity was assessed using concordance (c)-statistics in predicting the prognosis of cirrhotic patients. RESULTS: Overall, 107 patients died within 6 months and 150 patients died within 1 year. The clinical and biochemical characteristics, cirrhosis-related complications, and the scores were significantly different among the survivors and patients who died. The largest area under the receiver operating characteristic curve was 0.741 for the integrated MELD (iMELD) at 6 months and 0.713 for iMELD at 12 months, indicating that iMELD was the best scoring system tested. Given this result, we created a new scoring system that combined iMELD and an index of cirrhosis-related complications, called iMELD-C. This novel system had c indexes of 0.758 for the 6-month survival and 0.746 for the 1-year survival. CONCLUSIONS: The iMELD-C score is a better predictor of both short- and medium-term survival in patients with cirrhosis.
Assuntos
Doença Hepática Terminal/complicações , Cirrose Hepática/complicações , Modelos Teóricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To review the development, mechanism, necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis. DATA SOURCES: Most information was pulled from a literature search (Pubmed 2000 to 2011) using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis. Relevant book chapters were also reviewed. STUDY SELECTION: Well-controlled, prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected. RESULTS: Specific antiviral agents not only control viral replication, which permits liver transplantation, but also improve liver function so significantly that patients could be removed from the transplant waiting list. However, the emergence of drug-resistant mutants can result in treatment failure. Combination therapy is a save-strategy in drug-resistant. CONCLUSIONS: Although the treatment of end-stage liver disease is still a challenge worldwide, antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis. The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance. A combination of antivirals may be one of the future strategies for fulfilling these goals.
Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/patogenicidade , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Vírus da Hepatite B/efeitos dos fármacos , HumanosRESUMO
BACKGROUND: Purifying stem cells is an inevitable process for further investigation and cell-therapy. Sorting side population (SP) cells is generally regarded as an effective method to enrich for progenitor cells. This study was to explore whether sorting SP could enrich for the Musashi1 (Msi1) positive cells from Msi1 high expression cells (Msi1(high) cells) derived from mouse embryonic stem cells (ESCs) in vitro. RESULTS: In this study, Msi1(high) cell population derived from ESCs were stained by Hoechst 33342, and then the SP and non-SP (NSP) fractions were analyzed and sorted by fluorescence activated cell sorter. Subsequently, the expressions of Msi1 and other markers for neural and intestinal stem cells in SP and NSP were respectively detected. SP and NSP cells were hypodermically engrafted into the backs of NOD/SCID mice to form grafts. The developments of neural and intestinal epithelial cells in these grafts were investigated. SP fraction was identified and isolated from Msi1(high) cell population. The expression of Msi1 in SP fraction was significantly higher than that in NSP fraction and unsorted Msi1(high) cells (P< 0.05). Furthermore, the markers for neural cells and intestinal epithelial cells were more highly expressed in the grafts from SP fraction than those from NSP fraction (P< 0.05). CONCLUSIONS: SP fraction, isolated from Msi1(high) cells, contains almost all the Msi1-positive cells and has the potential to differentiate into neural and intestinal epithelial cells in vivo. Sorting SP fraction could be a convenient and practical method to enrich for Msi1-positive cells from the differentiated cell population derived from ESCs.
Assuntos
Separação Celular/métodos , Células-Tronco Embrionárias/citologia , Citometria de Fluxo/métodos , Proteínas do Tecido Nervoso/análise , Proteínas de Ligação a RNA/análise , Animais , Diferenciação Celular , Células Cultivadas , Células-Tronco Embrionárias/metabolismo , Camundongos , Camundongos SCID , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
BACKGROUND: Embryonic stem cells have great plasticity. In this study, we repaired impaired small intestine by transplanting putative intestinal epithelial stem cells (Musashi1 and hairy and enhancer of split 1 high expression cells) derived from embryonic stem cells. METHODS: The differentiation of definitive endoderm in embryoid bodies, derived from male ES-E14TG2a cells by the hanging-drop method, was monitored to define a time point for maximal induction of putative intestinal epithelial stem cells by epidermal growth factor. Furthermore, to evaluate the regenerative potential of intestinal epithelium, these putative stem cells were engrafted into NOD/SCID mice and female mice with enteritis. Donor cells were located by SRY DNA in situ hybridization. RESULTS: The results revealed that definitive endodermal markers were highly expressed in 5-day embryoid bodies. These embryoid body cells were induced into putative intestinal epithelial stem cells on the 5th day of epidermal growth factor administration. Grafts from these cells consisted of adenoid structures and nonspecific structural cells with strong expression of small-intestinal epithelial cell markers. In situ hybridization revealed that the donor cells could specifically locate in damaged intestinal epithelium, contribute to epithelial structures, and enhance regeneration. CONCLUSIONS: In conclusion, the Musashi1 and hairy and enhancer of split 1 high expression cells, derived from mouse embryonic stem cells, locate predominantly in impaired small-intestinal epithelium after transplantation and contribute to epithelial regeneration.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células-Tronco Embrionárias/metabolismo , Proteínas de Homeodomínio/metabolismo , Intestino Delgado/lesões , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transplante de Células-Tronco , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células Cultivadas , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Proteínas de Homeodomínio/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição HES-1RESUMO
OBJECTIVE: To prepare arsenic trioxide (As2O3)-loaded biodegradable polylactic-co-glycolic acid (PLGA) nanoparticles (NPS) and evaluate the glomeration ability, appearance, structure, surface and release characteristics of the NPs. METHODS: With PLGA as the carrier material, As2O3 NPs (As2O3-NPS) were prepared with the method of matrix and ultrasound emulsification. According to the criteria of the diameter of the NPs, drug loading (DL) and embedding ratio (ER), the process of NP preparation was optimized by scanning electron microscopy (SEM), ultraviolet spectroscopy (UV), and XPS. RESULTS: The As2O3-NPS prepared were uniformly spherical with an average diameter of 210-/+23 nm, DL of 29.6% and ER of 82.1%. The drug release assay in vitro showed a sustained drug-release capacity of the preparation. CONCLUSION: As2O3-NPS may serve as a carrier of As2O3 to change the pharmacokinetics of As2O3 in vivo, allow slow drug release, and prolong the drug circulation time after intravenous injection, thereby producing better antitumor effects.
Assuntos
Arsenicais/síntese química , Arsenicais/farmacocinética , Portadores de Fármacos , Óxidos/síntese química , Óxidos/farmacocinética , Trióxido de Arsênio , Arsenicais/administração & dosagem , Nanopartículas , Óxidos/administração & dosagem , Tamanho da Partícula , Ácido PoliglicólicoRESUMO
Msi1 (Musashi 1) is regarded as a marker for neural and intestinal epithelial stem cells. However, it is still unclear whether Msi1-positive cells derived from mouse embryonic stem cells have the ability to differentiate into neural or intestinal epithelial cells. A pMsi1-GFP (green fluorescent protein) reporter plasmid was constructed in order to sort Msi1-positive cells out of the differentiated cell population. The GFP-positive cells (i.e. Msi1-positive cells) were sorted by FACS and were hypodermically engrafted into the backs of NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice. The presence of neural and intestinal epithelial cells in the grafts was detected. Msi1 was highly expressed in the GFP-positive cells, but not in the GFP-negative cells. The markers for neural cells (Nestin and Tubulin ß III) and intestinal epithelial cells [FABP2 (fatty acid binding protein 2), Lyz (lysozyme) and ChA (chromogranin A)] were more highly expressed in the grafts from Msi1-positive cells than those from Msi1-negative cells (P<0.05). The grafts from the Msi1-negative cells contained more mesodermal-like tissues than those from the Msi1-positive cells. The pMsi1-GFP vector can be used to sort Msi1-positive cells from a cell population derived from mouse embryonic stem cells. The Msi1-positive cells can differentiate into neural and intestinal epithelial-like cells in vivo.
Assuntos
Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/fisiologia , Mucosa Intestinal/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/fisiologia , Proteínas de Ligação a RNA/metabolismo , Animais , Diferenciação Celular/genética , Células Cultivadas , Células-Tronco Embrionárias/transplante , Regulação da Expressão Gênica no Desenvolvimento , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas do Tecido Nervoso/genética , Neurogênese/genética , Neurogênese/fisiologia , Neurônios/metabolismo , Proteínas de Ligação a RNA/genética , TransfecçãoRESUMO
OBJECTIVE: To investigate the clinical features and management of pancreatic disease-associated portal hypertension. METHODS: A retrospective analysis was carried out in patients with portal hypertension and concurrent pancreatic diseases. The medical records of these patients were reviewed including the data of demographics, etiologies, venous involvement, clinical presentations, laboratory tests, imaging studies, therapeutic modalities and outcomes. RESULTS: Fifty-two patients with portal hypertension resulting from pancreatic diseases were found in our hospital, accounting for 4% of all the patients with portal hypertension in 11 years. The underlying pancreatic diseases were chronic pancreatitis (21 cases, 35.6%), pancreatic carcinoma (20 cases, 33.9%), acute pancreatitis (8 cases, 13.6%), pancreatic pseudocyst (3 cases, 5.1%). Of the 40 patients whose venous involvement was identified, splenic vein obstruction occurred in 27 cases (67.5%) and portal vein obstruction in 16 cases (40.0%). Mild or moderate splenomegaly was present in 48 cases (81.4%), with leukocytopenia as the most common manifestation of the 31 cases (52.5%) with concomitant hypersplenism. Forty-five patients (76.3%) developed gastroesophageal varices (including 35 with isolated gastricvarices), and among them 22 experienced bleeding (42.3%). Conservative treatment was effective in controlling acute bleeding, but could not prevent re-bleeding. Splenectomy was performed in 18 patients mainly due to gastrointestinal hemorrhage. No postoperative bleeding occurred during the follow-up ranging from 8 months to 9 years. CONCLUSION: Pancreatic diseases may compromise portal vein and its tributaries, leading to generalized or regional portal hypertension. Pharmacological therapy can effectively control acute variceal bleeding, while surgical treatment is the appropriate procedure of choice in case of hemorrhagic recurrence.
Assuntos
Hipertensão Portal/etiologia , Neoplasias Pancreáticas/complicações , Pancreatite Crônica/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: To investigate the incidence of pancreatic cancer-related depression and the relationship between symptoms of depression and the quality of life (QoL) of patients. METHODS: 262 inpatients with cancer of the digestive system (pancreatic cancer, liver cancer, esophageal cancer, gastric cancer, and colorectal cancer) from four Guangzhou hospitals were enrolled into the study between June 2007 and June 2009. The Hamilton Rating Scale for Depression-24 questionnaire was used to assess the degree of depression. QoL of all patients was evaluated by EORTC QLQ-C30. Additionally, EORTC QLQ-PAN-26 was used for patients with pancreatic cancer. RESULTS: The incidence of depression among pancreatic cancer patients was significantly higher than among other digestive cancers. More pancreatic cancer patients suffered severe depression than those with liver cancer and gastric cancer. Compared with other groups with depression, QoL of pancreatic cancer patients in each functioning scale was significantly worse, while the symptoms of fatigue and pain were significantly severe. QoL of pancreatic cancer patients with depression in role, emotional, and social functioning were sharply poorer than those without depression. The symptoms of fatigue, pain and appetite loss in cancer patients with depression were significantly more frequent than those without depression. CONCLUSION: Compared with other cancers of the digestive system, depressive symptoms are common psychological disturbances in pancreatic cancer patients. Moreover, depression significantly lowers QoL in pancreatic cancer patients.
Assuntos
Depressão/psicologia , Neoplasias Pancreáticas/psicologia , Qualidade de Vida , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Distribuição de Qui-Quadrado , China/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Neoplasias do Sistema Digestório/psicologia , Feminino , Humanos , Incidência , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de RiscoRESUMO
AIM: To investigate the preparation, physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS: The nanovesicle carriers were prepared from the amphiphilic block copolymer of PEG-PDLLA by a double emulsion technique, and gemcitabine was used as the model drug. The morphology of the nanovesicles was determined by scanning and transmission electron microscopy, and the drug content, drug entrapment and drug-release curve in vitro were detected by UV-Vis-NIR spectrophotometry. Cytotoxicity in the human pancreatic cancer cell line SW1990 was tested by 3-(4,5-dimethyl) ethiazole (MTT) assay. RESULTS: The gemcitabine-loaded nanovesicles were hollow nanospheres with a mean size of 200.6 nm, drug loading of 4.14% and drug embedding ratio of 20.54%. The nanovesicles showed excellent controlled release that was characterized by a fast initial release during the first 72 h, followed by a slower and continuous release. The MTT assay demonstrated that gemcitabine-loaded nanovesicles exhibited dose-dependent and time-delayed cytotoxicity in the human pancreatic cancer cell line SW1990. CONCLUSION: Gemcitabine-loaded PEG-PDLLA nanovesicles prepared by a double emulsion technique exhibited good performance for controlled drug release, and had similar cytotoxic activity to free gemcitabine.
Assuntos
Antimetabólitos Antineoplásicos , Linhagem Celular Tumoral/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Portadores de Fármacos , Poliésteres/química , Polietilenoglicóis/química , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/farmacologia , Materiais Biocompatíveis/química , Preparações de Ação Retardada , Desoxicitidina/química , Desoxicitidina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Emulsões/química , Humanos , Teste de Materiais , Nanoestruturas , Tamanho da Partícula , Poliésteres/farmacologia , Polímeros/química , GencitabinaRESUMO
BACKGROUND: Stem cells must be located and positively identified to elucidate their role in disease pathogenesis and therapy. In this study the expression patterns of the small intestinal stem cell (SISC) markers Musashi-1 (Msi1) and hairy and enhancer of split 1 (Hes1) were identified and the relationship between their expression and epithelial proliferation in the whole mouse small intestine was examined. MATERIAL/METHODS: Mouse small intestines were separated into four segments. Msi1 and Hes1 expression levels were quantified in each intestinal segment by immunohistochemistry, real-time reverse-transcription polymerase chain reaction, and Western blot. Small intestinal epithelial proliferation was examined using the bromodeoxyuridine (BrdU) method and proliferating cell nuclear antigen (PCNA) immunostaining. RESULTS: Msi1- and Hes1-positive cells were predominantly detected at the crypt bases. Msi1 and Hes1 protein expression values were significantly higher in the jejunal segment than in the ileal (P<0.05) and mRNA was directly associated with protein expression values. Greater numbers of proliferative cells were detected in jejunal crypts with BrdU and PCNA labeling (P<0.05). CONCLUSIONS: Expression of the Msi1 and Hes1 SISC markers in the small intestine was not homogenous and the markers were more highly expressed in jejunal tissues. This expression pattern correlated with the small intestinal epithelial proliferation pattern measured by BrdU- and PCNA-labeling methods.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Homeodomínio/metabolismo , Jejuno/citologia , Jejuno/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Biomarcadores/metabolismo , Proliferação de Células , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Camundongos , Microvilosidades/metabolismo , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Fatores de Transcrição HES-1RESUMO
OBJECTIVE: To investigate the relationship between symptoms of pancreatic cancer-related depression and quality of life of patients. METHODS: Fifty inpatients with pancreatic cancer from 3 Guangzhou hospitals between June 2007 and October 2008 were enrolled. Hamilton rating scale for depression-24 (HAMD-24) questionnaire was used to assess the degree of depression. Quality of Life (QoL) was evaluated by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) and QLQ-PAN-26 respectively. RESULTS: Thirty-nine (78.0%) of these patients reported depression and 12 patients (30.8%) had severe depression. The incidence of depression in pancreatic cancer patients with chemotherapy was 92.3% (24/26), which was significantly higher than that of patients with surgical therapy (62.5%, 15/24) (P = 0. 011). The QoL of pancreatic cancer patients with depression in role functioning, emotional functioning and social functioning was significantly worse than that of patients without depression. The symptoms of fatigue, pain and appetite loss in pancreatic cancer patients with depression were significantly more than those without depression (P < 0.05). CONCLUSIONS: Depressive symptoms are common psychological disturbance in pancreatic cancer patients. Moreover, depression significantly lowers quality of life for pancreatic cancer patients.
Assuntos
Depressão/psicologia , Neoplasias Pancreáticas/psicologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/etiologia , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Prospectivos , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the inhibitive effects of 5-fluorouracil-loaded polylactic acid nanoparticles (5-FU-PLA-NPs) on human Tenon's capsule fibroblasts in vitro. METHODS: This paper was experimental study. MTT assay was performed to estimate the effects of 0.1 mg/L, 1.0 mg/L, 10.0 mg/L, 100.0 mg/L, 1000.0 mg/L unloaded polylactic acid nanoparticles (PLA-NPs) on fibroblasts proliferation on 48 h, 72 h. MTT assay was performed to estimate the effects of 0.1 mg/L, 1.0 mg/L, 10.0 mg/L, 100.0 mg/L, 1000.0 mg/L original 5-FU and 5-FU-PLA-NPs on fibroblasts' proliferation on 7 consecutive days respectively. The inhibitory rate of the two drugs against the fibroblasts was calculated. Cells were exposed to 100 mg/L original 5-FU and 5-FU-PLA-NPs respectively for 7 days. Semi-quantitative RT-PCR was used to observe the mRNA expression of type III procollagen at the 1st day, 5th day and 7th day. RESULTS: PLA-NPs had no cytotoxicity on the fibroblasts. Both 5-FU-PLA-NPs and original 5-FU could inhibit the proliferation of the fibroblasts and make the expression of type III procollagen mRNA lower in dose-dependent and time-dependent manner. The inhibitive effect of original 5-FU was more effective than 5-FU-PLA-NPs in the initial period, but the inhibitive effect of 5-FU-PLA-NPs was more effective than original 5-FU in long time. CONCLUSION: PLA has good biocompatibility and safety, and can be used as a carrier of ophthalmic drugs. 5-FU-PLA-NPs shows slow-releasing function. 5-FU-PLA-NPs can be proposed as a potential controlled and targeted ophthalmic delivery system for the treatment of antifibrosis after glaucoma filtering surgery.
Assuntos
Fáscia/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fluoruracila/farmacologia , Proliferação de Células , Células Cultivadas , Olho/citologia , Fáscia/citologia , Fibroblastos/citologia , Fibroblastos/metabolismo , Fluoruracila/administração & dosagem , Humanos , Ácido Láctico , Nanopartículas , Poliésteres , PolímerosRESUMO
OBJECTIVE: To prepare gemcitabine-loaded nanovesicles and to observe its morphology, structure, particle size, and drug-release performance in vitro. METHODS: Diemulsion technique was used to prepare nanovesicles as carrier from amphiphilic block copolymer of poly (ethylene glycol)-block-poly (D, L-lactide), and gemcitabine was used as the model drug. The morphology of vesicles was determined by scanning electron microscope (SEM) and transmission electron microscope (TEM), and its drug loading (DL), encapsulation ratio (ER), and drug-release curve in vitro were detected by UV-Vis-NIR Spectrophotometer. RESULTS: The Gemcitabine-loaded nanovesicles is a kind of hollow nanosphere with the mean size of 200.6 nm, DL of 4.14% and ER of 20.54%. The nanovesicles showed its excellent controlled-release characteristic in the experiment of drug release in vitro. CONCLUSION: The nanovesicles prepared from PEG-PDLLA can be served as one of carriers for Gemcitabine with good performance of drug controlled-release. It will provide a reliable experimental base for the further researches in vivo.
Assuntos
Preparações de Ação Retardada/farmacocinética , Desoxicitidina/análogos & derivados , Preparações de Ação Retardada/química , Desoxicitidina/química , Desoxicitidina/farmacocinética , Desenho de Fármacos , Imunossupressores/química , Imunossupressores/farmacocinética , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanopartículas/ultraestrutura , GencitabinaRESUMO
OBJECTIVE: To investigate the factors that affect the prognosis of primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL). METHODS: The clinical data of 116 patients with pathologically confirmed PGI-NHL we treated from January 1993 to December 2003 were analyzed retrospectively. Kaplan-Meier survival analysis was used for analyzing the survival of the patients, and Log-rank test was performed to compare the survival rates in relation to different prognostic factors. RESULTS: The 3-year and 5-year survival rates of the patients were 63.8% (74/116) and 48.2% (40/83), respectively. Univariate analysis revealed that the factors affecting the prognosis of the patients included the presence of B symptom, tumor size, clinical stage, pathological type, depth of invasion, and treatment methods. The patients with B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, and invasion beyond the serosa who received only surgical management had poorer prognosis than those free of B symptom with tumor size <10 cm, early clinical stage (stages I(E) and II(E)), B-cell type, and submucosal or serosal invasion managed with chemotherapy alone or in combination with surgery. Multivariate analysis showed that B symptom, tumor size no less than 10 cm, advanced clinical stage (stages III(E) and IV(E)), T-cell type, invasion beyond the serosa, and surgery alone were independently associated with poor prognosis. CONCLUSION: The tumor size, clinical stage, pathological type, treatment methods are the independent factors affecting the prognosis of patients with PGI-NHL.
Assuntos
Neoplasias Gastrointestinais/patologia , Linfoma não Hodgkin/patologia , Adolescente , Adulto , Idoso , Criança , Feminino , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/mortalidade , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: The Bmi-1 gene is a transcriptional repressor involved in oncogenesis in various human cancers. Here, we examine Bmi-1 expression in gastric carcinoma (GC) and investigates whether its expression correlates with patient prognosis. METHODS: Immunohistochemistry was performed using an anti-Bmi-1 antibody on primary tumor samples of 146 cases of GC. The association between Bmi-1 expression and the clinicopathological status and prognosis of GC patients was statistically analyzed. Furthermore, reverse transcription-PCR (RT-PCR) and Western blotting were performed to determine the expression levels of Bmi-1 in an additional 8 GC and the adjacent non-cancerous samples. RESULTS: Using immunohistochemistry, we found that 99 of 146 paraffin-embedded GC samples expressed Bmi-1 extensively. Statistical analysis showed that Bmi-1 overexpression was highly correlated with tumor size, clinical stage, lymph node metastasis and T classification (P < 0.05), Patients with Bmi-1 expression had shorter overall survival time than those without Bmi-1 expression (P < 0.01). Multivariate analysis indicated that Bmi-1 expression is an independent prognostic factor of GC. RT-PCR and Western blotting showed that Bmi-1 was up-regulated at both the transcriptional and translational levels in the GC tissues compared with the adjacent non-cancerous tissues. CONCLUSIONS: Bmi-1 may serve as a valuable marker for diagnosis and prognosis of GC.
Assuntos
Carcinoma/metabolismo , Carcinoma/mortalidade , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Idoso , Carcinoma/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Complexo Repressor Polycomb 1 , Valor Preditivo dos Testes , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
BACKGROUND & OBJECTIVE: For gastric stromal tumor (GST), the low incidence and high diversity in endoscopic and pathologic manifestations lead to misdiagnosis. This study was to explore the features of GST in endoscopy and clinicopathology. METHODS: Clinical data of 42 GST patients, treated at the Second Affiliated Hospital of Sun Yat-sen University from Jan. 1996 to Jan. 2006, were analyzed for their clinicopathologic and endoscopic features. The expression of CD117, CD34, smooth muscle actin (SMA), Desmin and S-100 were detected by immunohistochemistry. Their correlations to clinicopathologic features of GST were analyzed. RESULTS: Of the 42 cases of GST, 21 (50.0%) were at the fundus, 14 (33.3%) at the body, and 7 (16.7%) at the antrum; 17 (40.5%) were benign, 14 (33.3%) borderline, 11 (26.2%) malignant. Endoscopically, GST presented submucosal hemispheroid or polypoid protuberant lesions with clear border. While the positive rate of gastroendoscopic biopsy was low. Of the 42 cases, 29 were spindle cell type, 5 were epithelial cell type, and 8 were mixed type. The positive rates of CD34 and CD117 were 92.86% and 78.57%. CONCLUSIONS: GST has unique morphologic features. Combined detection of CD117 and CD34 benefits the diagnosis of GST.