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In this study, Rubus coreanus (R. coreanus) byproducts with high polyphenol content were fermented with R. coreanus-derived lactic acid bacteria (Lactobacillus plantarum GBL 16 and 17). Then the effect of R. coreanus-derived lactic acid bacteria fermented feed (RC-LAB fermented feed) with probiotics (Bacillus subtills, Aspergillus oryzae, Yeast) as a feed additive for pigs on the composition of intestinal microbes and the regulation of intestinal immune homeostasis was investigated. Seventy-two finishing Berkshire pigs were randomly allotted to four different treatment groups and 18 replicates. RC-LAB fermented feed with probiotics increased the genera Lactobacillus, Streptococcus, Mitsuokella, Prevotella, Bacteroides spp., Roseburia spp., and Faecalibacterium prausnitzii, which are beneficial bacteria of the digestive tract of pigs. Also, RC-LAB fermented feed with probiotics decreased the genera Clostridium, Terrisporobacter, Romboutsia, Kandleria, Megasphaera and Escherichia, which are harmful bacteria. In particular, the relative abundance of the genera Lactobacillus and Streptococcus increased by an average of 8.51% and 4.68% in the treatment groups and the classes Clostridia and genera Escherichia decreased by an average of 27.05% and 2.85% in the treatment groups. In mesenteric lymph nodes (MLN) and spleens, the mRNA expression of transcription factors and cytokines in Th1 and Treg cells increased and the mRNA expression of Th2 and Th17 transcription factors and cytokines decreased, indicating a regulatory effect on intestinal immune homeostasis. RC-LAB fermented feed regulates gut immune homeostasis by influencing the composition of beneficial and detrimental microorganisms in the gut and regulating the balance of Th1/Th2 and Th17/Treg cells.
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RATIONALE: In the thorax, Hodgkin lymphoma (HL) most frequently involves the anterior mediastinal and paratracheal regions and tends to spread to contiguous nodal groups. Enlarged lymph nodes typically have homogeneous soft tissue attenuation similar to that of muscle tissue on computed tomography (CT). PATIENT CONCERNS: A contrast-enhanced CT examination of a 19-year-old man with right-sided chest pain showed an intense, heterogeneously enhancing mass with organization of serpentine and dilated blood vessels in the right anterior mediastinum that had invaded the upper lobe of the right lung. DIAGNOSES: Following a wedge resection, histopathological examination showed Reed-Sternberg cells that were positive for CD-15 and CD-30, which is typical of HL. INTERVENTIONS: The patient was started treatment with 6 cycles of doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) regimen. OUTCOMES: After chemotherapy, the patient had shown a partial response to the treatment. LESSONS: This presentation of HL as an extremely hypervascular anterior mediastinal mass on CT imaging has not been previously reported in the literature. This case suggests that HL should be included in the differential diagnosis of a hypervascular anterior mediastinal mass, especially if the patient is a young adult.
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Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dissecação/métodos , Doença de Hodgkin , Neoplasias do Mediastino , Mediastino , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Diagnóstico Diferencial , Doxorrubicina/administração & dosagem , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Doença de Hodgkin/fisiopatologia , Doença de Hodgkin/terapia , Humanos , Pulmão/diagnóstico por imagem , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/fisiopatologia , Neoplasias do Mediastino/terapia , Mediastino/irrigação sanguínea , Mediastino/diagnóstico por imagem , Células de Reed-Sternberg/patologia , Fluxo Sanguíneo Regional , Tomografia Computadorizada por Raios X/métodos , Vimblastina/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Germ cell tumors (GCTs) in children are rare neoplasms with diverse pathological findings according to the site and age of presentation. The most common symptoms in children with mediastinal GCTs, which are nonspecific, are dyspnea, chest pain, cough, hemoptysis, vena cava occlusion syndrome, and fatigue/weakness. Because of these nonspecific symptoms, it is difficult to suspect a mediastinal mass. A posterior mediastinal tumor causing spinal cord compression is an important example of an oncologic emergency arising from a neurogenic tumor. CASE PRESENTATION: Children with posterior mediastinum GCTs can be easily mistaken as having a neurogenic tumor because of site of tumor origin. We treated our 7-year-old patient with emergency decompression surgery and high-dose steroid pulse therapy to prevent secondary injury to the spinal cord. Primary injury was a result of spinal cord compression due to the initial manifestation of GCT in the posterior mediastinum. Cisplatin-based chemotherapy was also administered. The patient was followed up regularly for 3 years and is undergoing rehabilitation without any signs of recurrence. CONCLUSIONS: We present an extremely rare case of a child with paraparesis caused by extradural spinal cord compression as the initial manifestation of GCT in the posterior mediastinum. The child was treated with emergency decompression surgery and high-dose pulse steroid therapy to prevent secondary injury to the spinal cord.
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Neoplasias do Mediastino/diagnóstico , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Compressão da Medula Espinal/etiologia , Criança , Humanos , Masculino , Neoplasias do Mediastino/complicações , Neoplasias Embrionárias de Células Germinativas/complicações , Vértebras TorácicasRESUMO
Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.
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Adenocarcinoma/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Incidência , Masculino , Microdissecção , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Reação em Cadeia da PolimeraseRESUMO
PURPOSE: This study was conducted to identify the effectiveness of a preoperative comprehensive geriatric assessment (CGA) for predicting postoperative morbidity in elderly patients who underwent surgery for colorectal cancer. METHODS: Elderly patients (≥70 years old) who underwent surgery for colorectal cancer at a tertiary hospital in Korea were identified, and their cases were analyzed using data from a prospectively collected database to establish an association between major postsurgical complications and 'high-risk' patient as defined by the CGA. RESULTS: A total of 240 patients, with a mean age of 76.7 ± 5.2 years, were enrolled. Ninety-five patients (39.6%) were classified as "high-risk" and 99 patients (41.3%) as having postoperative complications. The univariate analysis indicated that risk factors for postoperative complications were age, American Society of Anesthesiologists physical status classification, serum hemoglobin, carcinoembryonic antigen, cancer stage, and "high-risk" status. The multivariable analyses indicated that "high-risk" status (odds ratio, 2.107; 95% confidence interval, 1.168-3.804; P = 0.013) and elevated preoperative carcinoembryonic antigen (odds ratio, 2.561; 95% confidence interval, 1.346-4.871, P = 0.004) were independently associated with postoperative complications. A multivariable analysis of the individual CGA domains indicated that high comorbidities and low activities of daily living were significantly related with postoperative complications. CONCLUSION: A preoperative CGA indicating "high-risk" was associated with major postoperative complications in elderly patients who underwent surgery for colorectal cancer. Thus, using the CGA to identify elderly colorectal-cancer patients who should be given more care during postoperative management may be clinically beneficial.
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BACKGROUND AND AIM: Although many progresses have been achieved for inflammatory bowel disease (IBD), it is still remained as idiopathic disease to be completely controlled. MicroRNAs (miRNAs) have been identified as key players in many human diseases through degradation or translational inhibition of target genes. Because role of miRNAs in IBD is not completely understood yet, we need to identify miRNAs as novel targets for treatment of IBD. METHODS: Microarray analysis for miRNAs was performed using dextran sulfate sodium-induced colitis samples and selected differentially regulated miRNAs. Candidate genes were validated using in vitro system and IBD patient samples. Molecular mechanism for regulation of inflammatory signaling was identified using gene modulation system of miRNAs. RESULTS: We selected 14 upregulated and 15 downregulated miRNAs through microarray analysis. Among candidate miRNAs, significant upregulation of miR-132 and miR-223 was confirmed in inflamed mouse tissues as well as human IBD patient tissues. Through bioinformatics analysis, we identified FOXO3a as direct target of miRNAs and confirmed regulatory mechanism using luciferase assay. Expression of miRNAs clearly suppressed the level of IκBα through downregulation of FOXO3a, leading to enhanced NF-κB signaling to promote the production of pro-inflammatory cytokines. The downregulation of FOXO3a concurrent with upregulation of cytokines was significantly reversed by sequestration of miRNAs with miRNA sponges. CONCLUSIONS: Our findings provided the evidences that miR-132 and 223 are critical mediators in positive circuit for pathogenesis of IBD by negatively regulating FOXO3a to enhance the expression of inflammatory cytokines and can be a good therapeutic target for IBD treatment.
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Proteína Forkhead Box O3/genética , Doenças Inflamatórias Intestinais/genética , MicroRNAs/genética , Animais , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Biologia Computacional/métodos , Citocinas/metabolismo , Retroalimentação Fisiológica , Proteína Forkhead Box O3/biossíntese , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , CamundongosRESUMO
BACKGROUND: This study was designed to investigate the correlation between postoperative recurrence of hepatocellular carcinoma (HCC) and perioperative expression and dynamic changes in cancer stem cell (CSC) markers in tumors and peripheral blood. METHODS: In HCC patients who underwent curative resection (n = 64) or liver transplantation (LT) (n = 17), mRNA levels for K19, EpCAM, and CD44 in peripheral blood and HCC tissues before and after operation were examined using real-time RT-PCR. Postoperative recurrence was analyzed in patients who underwent resection. Study participants were divided into high and low ratio groups, according to the ratio of postoperative to preoperative mRNA levels for each marker. RESULTS: K19 and CD44 mRNA levels in HCC tissues were higher in patients with recurrence than those without recurrence (p < 0.05 for all). Preoperative peripheral levels of K19 and EpCAM mRNA were higher in LT patients than in resection patients, and they were also significantly higher in cirrhotic patients of Child-Pugh Class B or C than those of Child-Pugh Class A (p < 0.05 for all). A high ratio of K19 mRNA was associated with lower relapse-free rate. Additionally, a high ratio for both K19 and CD44 mRNA was an independent poor prognostic factor for relapse-free survival (hazard ratio = 3.382, p = 0.016). CONCLUSIONS: Preoperative peripheral levels of K19 and EpCAM mRNA were influenced by background liver status and HCC. Additionally, the ratio of postoperative to preoperative mRNA levels for CSC markers, especially K19 and CD44, was shown to be important to predict HCC recurrence.
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Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Recidiva Local de Neoplasia/sangue , Células Neoplásicas Circulantes/patologia , Células-Tronco Neoplásicas/patologia , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Hepatectomia , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Período Perioperatório , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
Ovarian carcinoma is a highly lethal malignancy due to frequent relapse and drug resistance. Cancer stem cells (CSCs) are thought to contribute significantly to disease relapse and drug resistance. In this study, a subpopulation of CSCs of ovarian carcinoma was isolated and the genes differentially expressed in these cells were identified to characterize CSCs and to find candidate biomarkers. Ovarian carcinoma cells from patients were primarily cultured, and spheroid-forming cells (SFCs) were isolated. The characteristic genes of SFCs were identified through cDNA microarray and validation by quantitative real-time polymerase chain reaction and immunohistochemistry, and the association of their expression with clinicopathologic parameters was analyzed. GSC (4.26-fold), VAV3 (7.05-fold), FOXA2 (12.06-fold), LEF1 (17.26-fold), COMP (21.33-fold), GRIN2A (9.36-fold), CD86 (23.14-fold), PYY (4.18-fold), NKX3-2 (10.35-fold), and PDK4 (74.26-fold) were significantly upregulated in SFCs compared with parental cancer cells. With validation for human ovarian carcinomas, LEF1, PYY, NKX3-2, and WNT3A were significantly upregulated in chemoresistant cancers compared with chemosensitive cancers. Overexpression of LEF1, VAV3, and NKX3-2 was significantly associated with distant metastasis by immunohistochemistry. VAV3 overexpression was an independent poor survival indicator (hazard ratio=15.27, P<0.05) by multivariate Cox analysis. The further functional assay revealed that VAV3 knockdown regulated CSC activation and ovarian cancer cell proliferation and sensitized paclitaxel (PTX)-resistant cancer cells to PTX treatment. Taken together, we identified by high-throughput analysis of CSCs that VAV3 overexpression is a novel biomarker for poor prognosis and survival in ovarian carcinoma.
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Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-vav/metabolismo , Idoso , Biomarcadores Tumorais/genética , Carcinoma/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Proteínas Proto-Oncogênicas c-vav/genética , Regulação para CimaRESUMO
Nodular regenerative hyperplasia (NRH) is an uncommon liver condition characterized by diffuse transformation of the hepatic parenchyma into regenerative nodules without fibrosis. Portal vasculopathy caused by abnormal hepatic venous flow may induce hepatocyte hyperplasia, which forms regenerative nodules. Underlying diseases or certain drugs may also be the cause of NRH. This condition is often underdiagnosed as the patients remain asymptomatic until development of portal hypertension, and histopathologic confirmation by liver biopsy is the only way of making a definite diagnosis. The management mainly involves prevention and treatment of the complications of portal hypertension. The frequency of diagnosis of NRH has increased rapidly in recent years, however, only a few cases have been reported in Korea. Here, we report on a case of NRH of the liver combined with toxic hepatitis.
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Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Hiperplasia Nodular Focal do Fígado/diagnóstico , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Bilirrubina/sangue , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/patologia , Úlcera Duodenal/patologia , Endoscopia do Sistema Digestório , Feminino , Hiperplasia Nodular Focal do Fígado/complicações , Hiperplasia Nodular Focal do Fígado/patologia , Humanos , Fígado/enzimologia , Fígado/patologia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Resistant hypertension (RH) may be one of the cause of the plateau in improving the control rate in hypertension (HT) management. The misdiagnosis of RH by clinic blood pressure (BP) is important clinical problem. Aim of the study were to investigate the prevalence of RH by ambulatory blood pressure monitoring (ABPM) and the factor associated with control status of ambulatory BPs. METHODS: For 1230 subjects taking one or more antihypertensive medication (AHM) enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) registry, the prevalence of RH was calculated which was defined as uncontrolled BP by three AHM classes including diuretic or BP in need of four or more AHM classes. The prevalence determined by clinic versus ambulatory BP was compared. RESULTS: The age was 59.3 ± 12.5 years, and 44.3 % were female (n = 1230). Among them 72 subjects were taking three AHM drugs including diuretics and 105 subjects were taking four or more AHM classes. With uncontrolled daytime ambulatory BP in 41 among 72 subjects, prevalence of RH was 11.9 % (146/1230). By using nighttime BP criteria, there was significant difference in the prevalence of RH for clinic versus nighttime BP (146/177 vs. 159/177, p = 0.0124). For control status of daytime BP, masked uncontrolled BP was 16.9 % and controlled BP with white-coat effect was 14.1 %. For nighttime BP control status, odd ratios for smoking (0.624), drinking (1.512), coronary artery disease (0.604), calcium antagonist (1.705), and loop diuretics (0.454) were all significant. CONCLUSION: The prevalence itself was 11.9 % by daytime BP and it was significantly higher when using nighttime BP criteria. Control status of daytime BP was misclassified in 31.0 %. Smoking, drinking, coronary artery disease, calcium antagonist, and loop diuretics were associated with nighttime BP control status.
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PURPOSE: This randomized, controlled animal study investigated the morphologic and histologic properties of rabbit orbital fat following injection of human orbital adipose-derived stem cells (hoADSCs). METHODS: The efficacy of hoADSCs was compared to that of hyaluronic acid gel (HAG) and human orbital stromal vascular fraction (hoSVF). A total of 30 orbits from 15 New Zealand white rabbits (25 weeks postnatal, 2500-3000 g) underwent injection with HAG (molecular weight [MW] 1,000,000, 0.5 mL, n = 10, HAG only), hoSVF (0.25 mL) mixed with HAG (0.25 mL, n = 10, HAG + hoSVF), or hoADSCs (0.25 mL) mixed with HAG (0.25 mL, n = 10, HAG + hoADSCs). The degree of proptosis, and the time course of changes were determined and compared among groups. RESULTS: The difference between the initial exophthalmometric value and that at 4 weeks after injection was 1.77 mm for HAG only and 2.01 mm for HAG + hoSVF. The difference between the initial value and that at 12 weeks decreased to 0.05 mm for HAG only and 0.24 mm for HAG + hoSVF. In contrast, injection of HAG + hoADSCs increased the exophthalmometric value by 2.43 mm at 4 weeks after injection, and this difference was maintained at 2.56 mm at 12 weeks. Histopathologic examination revealed specific inflammation around the injection materials at 4 weeks after injection, and inflammation subsided 8 weeks after injection in all three groups. CONCLUSIONS: Thus, transplantation of hoADSCs with HAG is a safe and effective technique for orbital fat volume expansion. This is a new and promising method for orbital reconstruction and aesthetic orbital volume augmentation.
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Adipócitos/citologia , Órbita/cirurgia , Transplante de Células-Tronco , Expansão de Tecido/métodos , Tecido Adiposo/citologia , Animais , Células Cultivadas , Exoftalmia/etiologia , Géis , Sobrevivência de Enxerto , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intraoculares , Órbita/anatomia & histologia , Coelhos , Medicina Regenerativa , Células-Tronco/citologia , Células Estromais/transplanteRESUMO
Although inactivation of the PTEN gene has been implicated in the development of resistance to the HER2 targeting antibody trastuzumab, the mechanisms mediating this resistance remain elusive. We generated trastuzumab resistant cells by knocking down PTEN expression in HER2 overexpressing breast cancer cell lines and demonstrate that development of trastuzumab resistance in these cells is mediated by activation of an IL6 inflammatory feedback loop leading to expansion of the cancer stem cell (CSC) population. Long term trastuzumab treatment generates highly enriched CSCs which display an EMT phenotype secreting over 100-fold more IL6 than parental cells. An IL6 receptor antibody interrupted this inflammatory feedback loop reducing the cancer stem cell population resulting in decreased tumor growth and metastasis in mouse xenographs. These studies demonstrate that trastuzumab resistance may be mediated by an IL6 inflammatory loop and suggest that blocking this loop may provide alternative strategy to overcome trastuzumab resistance.
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Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Células-Tronco Neoplásicas/metabolismo , Receptor ErbB-2/metabolismo , Animais , Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Inflamação/genética , Inflamação/patologia , Interleucina-6/genética , Interleucina-8/genética , Interleucina-8/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Receptor ErbB-2/genética , TrastuzumabRESUMO
BACKGROUND/AIMS: Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC. METHODOLOGY: A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC). RESULTS: The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status. CONCLUSIONS: The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).
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Proteínas Adaptadoras de Transdução de Sinal/análise , Biomarcadores Tumorais/análise , Carcinoma/química , Proteínas de Ligação a DNA/análise , Neoplasias Intestinais/química , Intestino Delgado/química , Proteína 2 Homóloga a MutS/análise , Proteínas Nucleares/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/genética , Carcinoma/mortalidade , Carcinoma/secundário , Distribuição de Qui-Quadrado , Reparo de Erro de Pareamento de DNA , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Intestinais/genética , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Estimativa de Kaplan-Meier , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Invasividade Neoplásica , Pâncreas/patologia , Prognóstico , República da Coreia , Neoplasias Retroperitoneais/secundário , Análise Serial de Tecidos , Adulto JovemRESUMO
UNLABELLED: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between HCC and CC has been shown to comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common genomic trait of stem-cell-like properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests that S-HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem-cell-like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of transforming growth factor beta (TGF-ß) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. CONCLUSION: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The expression of stem-cell-like traits and TGF-ß/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC. (HEPATOLOGY 2012;55:1776-1786).
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Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/genética , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Carcinoma Hepatocelular/mortalidade , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Feminino , Fibrose , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Transdução de Sinais , Fator de Crescimento Transformador beta/fisiologiaRESUMO
Primary effusion lymphoma (PEL) is a rare type of lymphoma that arises in the body cavity without detectable masses. It is associated with human herpes virus-8 (HHV-8), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV). Recently, PEL unrelated to viral infection has been reported and it has been termed HHV-8 unrelated primary effusion lymphoma-like lymphoma (HHV-8 unrelated PEL-like lymphoma). Here, we report a case of HHV-8 unrelated PEL-like lymphoma in an 80-year-old woman. Chest X-ray and computed tomography revealed left-sided pleural effusion. Pleural effusion analysis and mediastinoscopic biopsy showed atypical cells that had originated from the B cells. The cells were positive for CD20 and bcl-2, but negative for CD3, CD5, CD21, CD30, CD138, epithelial membrane antigen, and HHV-8. Serological tests for HIV and EBV were negative. Considering the patient's age, further treatments were not performed. She has shown good prognosis without chemotherapy for more than 18 months.
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Human herpesvirus 8-positive (HHV-8âº) and Epstein-Barr virus-positive (EBVâº) germinotropic lymphoproliferative disorder (GLD) is extremely rare and occurs most commonly in immunocompetent persons who are human immunodeficiency virus (HIV)-seronegative. It is also recognized as a favorable response to conventional chemotherapy. Here, we report a case of a 75-year-old man with an incidentally found mass in the neck, compatible with GLD, which was detected by positron emission tomography (PET). Computed tomography (CT) scan, PET, and bone marrow studies showed only the left neck mass and no evidence of metastasis. Excisional biopsy of the mass was performed. The patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. After these treatments, he remained disease-free for 19 months. To the best of our knowledge, only five cases of HHV-8âº, EBV⺠GLD have been documented. This is the first such case report in Asia.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Centro Germinativo/patologia , Infecções por Herpesviridae/complicações , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/isolamento & purificação , Linfoma/complicações , Linfoma/tratamento farmacológico , Idoso , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Centro Germinativo/virologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Infecções por Herpesviridae/virologia , Humanos , Linfoma/patologia , Linfoma/virologia , Masculino , Prednisona/uso terapêutico , Vincristina/uso terapêuticoRESUMO
UNLABELLED: There is a recently proposed subtype of hepatocellular carcinoma (HCC) that is histologically similar to usual HCC, but characterized by the expression of "stemness"-related markers. A large-scale study on two different cohorts of HCCs was performed to investigate the clinicopathologic features and epithelial-mesenchymal transition (EMT)-related protein expression status of this subtype of HCCs. The expression status of stemness-related (e.g., keratin 19 [K19], cluster of differentiation [CD]133, epithelial cell adhesion molecule [EpCAM], and c-kit) and EMT-related markers (e.g., snail, S100A4, urokinase plasminogen activator receptor [uPAR], ezrin, vimentin, E-cadherin, and matrix metalloproteinase [MMP]2) were examined using tissue microarrays from cohort 1 HCCs (n = 137). K19 protein expression in cohort 2 HCCs (n = 237) was correlated with the clinicopathologic parameters and messenger RNA (mRNA) levels of K19, uPAR, VIL2, Snail, Slug, and Twist. K19, EpCAM, c-kit, and CD133 positivity were observed in 18.2%, 35.0%, 34.3%, and 24.8%, respectively. K19 was most frequently expressed in combination with at least one other stemness-related marker (92.0%). K19-positive HCCs demonstrated more frequent major vessel invasion and increased tumor size, compared to K19-negative HCCs (P < 0.05). K19 was most significantly associated with EMT-related protein expression (e.g., vimentin, S100A4, uPAR, and ezrin) (P < 0.05) and a poor prognosis (overall survival: P = 0.018; disease-free survival: P = 0.007) in cohort 1. In cohort 2, HCCs with high K19 mRNA levels demonstrated higher mRNA levels of Snail, uPAR, and MMP2 (P < 0.05). K19-positive HCCs demonstrated more frequent microvascular invasion, fibrous stroma, and less tumor-capsule formation, compared to K19-negative HCCs (P < 0.05). K19 expression was a significant independent predictive factor of poor disease-free survival (P = 0.032). CONCLUSION: K19 was well correlated with clinicopathologic features of tumor aggressiveness, compared to other stemness-related proteins. K19-positive HCCs showed significantly increased EMT-related protein and mRNA expression, suggesting that they may acquire more invasive characteristics, compared to K19-negative HCCs through the up-regulation of EMT-associated genes.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Queratina-19/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Antígeno AC133 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos de Neoplasias/metabolismo , Biomarcadores/metabolismo , Biomarcadores Tumorais/genética , Moléculas de Adesão Celular/metabolismo , Estudos de Coortes , Molécula de Adesão da Célula Epitelial , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Glicoproteínas/metabolismo , Humanos , Queratina-19/genética , Masculino , Pessoa de Meia-Idade , Peptídeos/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-kit/metabolismo , Células-Tronco/metabolismo , Adulto JovemRESUMO
Small cell lung cancer (SCLC) is the leading cause of cancer death, with a high propensity for aggressiveness and metastasis even in an early stage. Thus, identification of biomarkers as early diagnostics and treatment is needed. In this study, we investigated differentially regulated proteins between human SCLC tissues and normal bronchial epithelium by proteomic analysis using two-dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Seven proteins and protein isoforms, including, γ-actin, tubulin α-1B, laminin B1, coactosin-like protein-1 (COTL-1), ubiquitin carboxyl-terminal esterase L1, ubiquitin-conjugating enzyme E2-25K, and carbonic anhydrase 1, were up-regulated more than 2 fold in SCLC tissues. In particular, up-regulated COTL-1 expression was validated by Western blot analysis, immunohistochemistry, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, most SCLC tissues (93%; 28/30) were COTL-1-positive in immunohistochemistry, whereas only 16% (10/64) of nonsmall cell lung cancer (NSLC) tissues were. Taken together, this SCLC proteomic data may help in establishing a human SCLC proteome database. COTL-1 may be a biomarker or a therapeutic target in SCLC patients.
Assuntos
Biomarcadores Tumorais/química , Neoplasias Pulmonares/metabolismo , Proteínas dos Microfilamentos/química , Proteômica/métodos , Carcinoma de Pequenas Células do Pulmão/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Brônquios/citologia , Eletroforese em Gel Bidimensional , Feminino , Humanos , Imuno-Histoquímica , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Reprodutibilidade dos Testes , Mucosa Respiratória/química , Mucosa Respiratória/citologia , Mucosa Respiratória/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Regulação para CimaRESUMO
Translational studies have explored the therapeutic effects of stem cells, raising hopes for the treatment of numerous diseases. Here, we evaluated the therapeutic effect of chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from human placenta and transplanted into rats with carbon tetrachloride (CCl(4))-injured livers. CP-MSCs were analyzed for hepatocyte-specific gene expression, indocyanine green (ICG) uptake, glycogen storage, and urea production following hepatogenic differentiation. PKH26-labeled CP-MSCs were directly transplanted into the livers of rats that had been exposed to CCl(4) (1.6 g/kg, twice per week for 9 weeks). Blood and liver tissue were analyzed at 1, 2, and 3 weeks post-transplantation. The expression of type I collagen (Col I) and matrix metalloproteinases (MMPs) was analyzed in rat T-HSC/Cl-6 hepatic stellate cells co-cultured with CP-MSCs following exposure to TGF-ß. The expression levels of α-smooth muscle actin (α-SMA) and Col I were lower in transplanted (TP) rats than in non-transplanted (Non-TP) animals (P < 0.05), whereas the expression levels of albumin and MMP-9 were increased. TP rats exhibited significantly higher uptake/excretion of ICG than non-TP rats (P < 0.005). In addition, collagen synthesis in T-HSC/Cl-6 cells exposed to TGF-ß was decreased by co-culture with CP-MSCs, which triggered the activation of MMP-2 and MMP-9. These results contribute to our understanding of the potential pathophysiological roles of CP-MSCs, including anti-fibrotic effects in liver disease, and provide a foundation for the development of new cell therapy-based strategies for the treatment of difficult-to-treat liver diseases.
Assuntos
Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/terapia , Hepatopatias/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Placenta/citologia , Animais , Western Blotting , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Hepatopatias/metabolismo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Gravidez , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/farmacologiaRESUMO
Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.