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1.
Medicine (Baltimore) ; 98(26): e16207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261569

RESUMO

The cell-surface glycoprotein, mesothelin, is normally present on mesothelial cells. Overexpression of mesothelin has been reported in many tumors and is correlated with poor outcome. We investigated the clinicopathologic significance of mesothelin expression in colorectal adenocarcinoma with microsatellites instability (MSI) status.Mesothelin expression was evaluated immunohistochemically in tissue microarray blocks from 390 colorectal adenocarcinoma samples. Mesothelin expression was interpreted according to the intensity and extent. A score of 2 was considered high expression. We analyzed the correlation between mesothelin expression and clinicopathologic characteristics.High mesothelin expression was observed in 177 (45.4%) out of 390 colorectal adenocarcinoma samples and was significantly associated with high histologic grade (P = .037), lymphatic invasion (P = .028), lymph node metastasis (P = .028), and high AJCC stage (P = .026). Kaplan-Meier survival curves revealed no significant difference between patients with high mesothelin expression and patients with low mesothelin expression in both recurrence-free survival (RFS) and cancer-specific survival (P = .609 and P = .167, respectively). In subgroup survival analyses, high mesothelin expression was associated with poor RFS in the MSI-High group of colorectal adenocarcinoma (P = .004).High mesothelin expression was significantly associated with aggressive phenotypes and poor patient outcome in MSI-High colorectal adenocarcinoma.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteínas Ligadas por GPI/metabolismo , Instabilidade de Microssatélites , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Análise Serial de Tecidos
2.
Biochem Biophys Res Commun ; 513(1): 213-218, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-30954220

RESUMO

Rare cold-inducible 2 (RCI2) proteins are small hydrophobic proteins that are known to be localized in cellular membranes. The function of RCI2 proteins has been reported to be associated with low-temperature, salt, and drought stress tolerances as a membrane potential regulator; however, the specific functions are still unknown. The PIP2 (plasma membrane intrinsic protein 2) aquaporins are proteins that transport water and small solutes into the cell. The expression and activity of PIP2 proteins, like RCI2, are also related to salt- and drought-stress tolerance. In this study, we identified novel protein interactions between RCI2 and PIP2; 1, including protein accumulation changes in the bioenergy crop Camelina sativa L. under various NaCl stress conditions. Accumulation of both CsRCI2E and CsRCI2F proteins increased with NaCl stress; however, to differing levels depending on the NaCl stress intensity. A co-immunoprecipitation test revealed interaction between CsRCI2E-CsPIP2 and CsRCI2F-CsPIP2. Moreover, co-expression of the four CsRCI2 proteins with CsPIP2; 1 in Xenopus laevis oocytes reduced water transport activity. Furthermore, the abundance of CsPIP2; 1 protein was decreased under CsRCI2E and CsRCI2F co-expression. These results suggest that NaCl-induced expression of CsRCI2E and CsRCI2F contributes to the regulation of CsPIP2; 1.

3.
Cancer Lett ; 454: 44-52, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-30980864

RESUMO

Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer death worldwide. To study how mycoplasma infection affects HCC progression, we investigated the characteristics of mycoplasma-infected tumor tissues and circulating tumor cells (CTCs) in HCC patients. The mycoplasmal membrane protein p37 showed significant correlations with higher histologic stages and vascular invasion and predicted poor disease-free survival of HCC patients. p37-positive CTCs were detected in 42 out of 47 HCC patients (89%). p37-positive circulating cells were also detected in 4 out of 10 healthy donors (40%), and all were epithelial cell adhesion molecule (EpCAM)-positive. In HCC patients, most of p37-negative CTCs (95%) showed intermediate phenotype with neither EpCAM nor vimentin expression, but p37-positive CTCs were EpCAM-positive (44%), vimentin-positive (32%), and both negative (24%), suggesting that EpCAM-positive CTCs are enriched with mycoplasma infection. Mycoplasma infection promoted migratory capacity of HCC cells with increased expression of EpCAM. Immunoprecipitation analysis revealed that p37 associates with EpCAM. The results suggest that mycoplasma infection promotes tumor progression in HCC patients via interaction of the mycoplasmal p37 and EpCAM.

4.
Acta Chir Belg ; : 1-6, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30614387

RESUMO

BACKGROUND: Extranodal tumor extension (ENTE) is considered a poor prognostic factor in colorectal cancer (CRC). This study aimed to investigate the risk factors for recurrence according to ENTE status in stage III CRC. METHODS: We retrospectively evaluated 169 consecutive stage III CRC patients. All patients underwent a curative resection between 2005 and 2010. The presence or absence of ENTE was assessed in the resected lymph nodes. RESULTS: ENTE was observed in 65 (38.5%). Recurrence occurred in 38 patients (22.5%) and was more frequent (p = .041) in the ENTE (+) group. Disease-free survival (p = .016) was significantly shorter in the ENTE (+) group than in the ENTE (-) group. In a univariable analysis, recurrence was associated with vascular invasion (p = .006), perforation (p = .024) in the ENTE (-) group and perforation (p = .048) in the ENTE (+) group. In a Cox's regression test, vascular invasion (p = .014) and the higher ratio of metastatic lymph nodes/total removed lymph nodes (MLN/TLN) (0.009) in the ENTE (-) group and perforation (p = .025) in the ENTE (+) group were independent risk factors of recurrence. CONCLUSIONS: Vascular invasion and the higher ratio of MLN/TLN in ENTE (-) patients and perforation in ENTE (+) patients were independent risk factors of recurrence.

5.
BMC Cancer ; 18(1): 1244, 2018 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541499

RESUMO

BACKGROUND: SSBP2, single-stranded DNA binding protein 2, is a subunit of the ssDNA-binding complex that is involved in the maintenance of genome stability. The majority of previous studies have suggested a tumor-suppressive role of SSBP2, which is silenced by promoter hypermethylation in several human malignancies, such as hematologic malignancies, prostate cancer, esophageal squamous cell carcinoma, ovarian cancer, and gallbladder cancer. However, an oncogenic role of SSBP2 has been suggested in glioblastoma patients. We investigated the clinicopathologic significance of SSBP2 expression in hepatocellular carcinoma. METHODS: We constructed tissue microarrays consisting of 21 normal liver parenchyma and 213 hepatocellular carcinoma tissues with corresponding adjacent non-neoplastic tissues. SSBP2 expression was investigated by immunohistochemistry, and positive expression was defined as more than 10% of the tumor cells to show nuclear staining. We then analyzed the correlations between SSBP2 expression and various clinicopathologic characteristics, and further studied the role of SSBP2 in cell growth and migration. RESULTS: Hepatocytes were negative for SSBP2 immunohistochemistry in all normal liver samples, whereas the nuclei of normal bile duct epithelium and sinusoidal endothelium were immunoreactive. Positive immunoreactivity was found in one (0.6%) out of 180 non-neoplastic liver tissue samples adjacent to the tumor and in 16 (8.5%) out of 189 hepatocellular carcinomas. Positive SSBP2 expression was significantly correlated with tumor multifocality (P = 0.027, chi-square test), high histologic grade (P = 0.003, chi-square test), and frequent vascular invasion (P = 0.001, chi-square test). Kaplan-Meier survival curves revealed that patients with SSBP2 expression had poor prognosis in both disease-free and overall survival (P = 0.004 and P = 0.026, respectively, log-rank test). SSBP2-positive tumors also had a higher Ki-67 proliferation index (P <  0.001, t-test). Furthermore, downregulation of SSBP2 in the Huh7 cell line inhibited cell migration (P = 0.022, t-test) with altered expression of epithelial-mesenchymal transition markers. CONCLUSIONS: The minority of hepatocellular carcinomas expressed SSBP2 by immunohistochemistry, whereas normal hepatocytes were negative. SSBP2-positive hepatocellular carcinomas were significantly associated with aggressive phenotypes and poor clinical outcome.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Proteínas de Ligação a DNA/biossíntese , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Idoso , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Feminino , Seguimentos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Taxa de Sobrevida/tendências
6.
Medicine (Baltimore) ; 97(25): e10996, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29923982

RESUMO

Lung cancer is the most common cause of cancer-associated death worldwide. Postoperative relapse and subsequent metastasis result in a high mortality rate, even in early stage lung cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and are frequently dysregulated in various cancers. The aim of this study was to identify recurrence-associated miRNAs in early stage lung cancer. To screen for differentially expressed miRNAs related to postoperative recurrence, miRNA microarray data derived from stage I lung adenocarcinoma formalin-fixed paraffin-embedded (FFPE) tissue samples (n = 6) and publically available the Cancer Genome Atlas (TCGA) data were analyzed. An independent sample (n = 29) was used to validate candidate miRNAs by quantitative real-time polymerase chain reaction (qRT-PCR). In miRNA expression profiling, we identified 60 significantly dysregulated miRNAs in the relapsed group. Additionally, 20 dysregulated miRNAs were found using TCGA data set. Three miRNAs (let-7g-5p, miR-143-3p, and miR-374a-5p) were associated with postoperative recurrence in both microarray and TCGA data sets. All 3 candidate miRNAs were validated in the independent cohort of stage I adenocarcinoma by qRT-PCR. We discovered 3 recurrence-associated miRNAs of stage I lung adenocarcinoma samples using FFPE tissue, which showed possible clinical utility as biomarkers predicting recurrence after curative surgery. Further investigation of the functional properties of these miRNAs is needed.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Pneumonectomia/efeitos adversos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pneumonectomia/métodos , República da Coreia
7.
Arch Pathol Lab Med ; 142(3): 420-423, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29494224

RESUMO

Intraductal tubulopapillary neoplasm is a rare tumor that the World Health Organization recognized in 2010 as a subtype of premalignant pancreatic neoplasms. It is important to distinguish it from other intraductal neoplasms, including intraductal papillary mucinous neoplasm, pancreatic ductal adenocarcinoma, and intraductal variant of acinar cell carcinoma, because intraductal tubulopapillary neoplasm has a favorable prognosis. Histopathologically, intraductal tubulopapillary neoplasms are characterized by tubulopapillary growth, uniform high-grade cytologic atypia, frequent necrotic foci, evident ductal differentiation, and absence of mucin. Intraductal tubulopapillary neoplasms show distinct immunohistochemical and molecular findings, with positive cytokeratin 7, cytokeratin 19, MUC1, and MUC6, and somatic PIK3CA mutations (2 of 11; 18%), and low rates of KRAS (2 of 20; 10%), TP53 (5 of 22; 23%), and BRAF (2 of 13; 15%) mutations. These differences also highlight the fact that intraductal tubulopapillary pancreatic neoplasm is distinct from other similar neoplasms.

8.
J Clin Pathol ; 71(9): 806-813, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29588373

RESUMO

AIMS: Forkhead box O (FOXO) transcription factors, consisting of FOXO1, FOXO3a, FOXO4 and FOXO6, are involved in carcinogenesis and tumour progression. Recent studies have suggested that FOXOs act as tumour suppressors in a variety of human cancers. This study investigated the clinicopathological significance of FOXOs in triple-negative breast cancer (TNBC). METHODS: FOXO protein expressions were assessed by immunohistochemistry in 125 TNBC tissues. Correlations between FOXO protein expression and various clinicopathological parameters, including patients' survival, were investigated. MDA-MB-468 cell line was used for in vitro cell proliferation and migration assay. RESULTS: FOXO1 protein expression was not observed in all 125 TNBC tissues. FOXO4 and FOXO6 protein expressions were detected in 11 (8.8%) and 14 (11.2%) TNBC tissues, respectively. Loss of FOXO4 expression was significantly associated with high histological grade (P=0.014, χ2 test), and TNBCs with positive FOXO6 expression correlated with high grade (P=0.020, χ2 test). FOXO3a expression was detected in 40 (32%) TNBC cases and correlated with adverse clinicopathological features, such as lymph node metastasis (P=0.021, χ2 test), perineural invasion (P=0.013, χ2 test) and higher Ki-67 proliferation index (P=0.048, t-test). Additionally, FOXO3a expression was significantly associated with poor disease-free survival (P=0.015, log-rank test). In the in vitro study, siRNA-mediated FOXO3a knockdown in the MDA-MB-468 cell line inhibited cell proliferation and migration. CONCLUSION: Among FOXO members, FOXO3a may have a potential role in promoting tumour cell migration and proliferation and may serve as a prognostic biomarker and a potential therapeutic target for TNBC.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteína Forkhead Box O3/metabolismo , Metástase Linfática , Neoplasias de Mama Triplo Negativas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
9.
Am J Clin Pathol ; 149(2): 117-127, 2018 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-29365018

RESUMO

Objectives: Recent research has demonstrated that forkhead box O3a (FoxO3a) may function as an oncogenic transcription factor. We sought to validate the clinicopathologic significance of FoxO3a expression in hepatocellular carcinoma (HCC). Methods: Western blotting and immunohistochemistry were used to determine FoxO3a expression. In vitro cell proliferation and migration assays were performed in a HepG2 cell line. Results: FoxO3a was overexpressed in 121 (64.71%) cases of HCC. FoxO3a overexpression was associated with aggressive phenotypes of HCC, such as histologic grade (P < .001), stage (P = .031), and small vessel invasion (P < .001). FoxO3a overexpression was also correlated with poor disease-free survival in both univariate and multivariate survival analyses (P = .001 and P = .018, respectively). Downregulation of FoxO3a in a HepG2 cell line inhibited cell proliferation and migration. Conclusions: These results suggest a role for FoxO3a in HCC progression and support the potential use as a prognostic biomarker.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteína Forkhead Box O3/metabolismo , Neoplasias Hepáticas/metabolismo , Fenótipo , Western Blotting , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação para Baixo , Células Hep G2 , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Análise de Sobrevida , Análise Serial de Tecidos , Regulação para Cima
10.
Clin Cancer Res ; 23(18): 5648-5656, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28536309

RESUMO

Purpose: Tumor-derived cell-free DNA (cfDNA) in plasma can be used for molecular testing and provide an attractive alternative to tumor tissue. Commonly used PCR-based technologies can test for limited number of alterations at the time. Therefore, novel ultrasensitive technologies capable of testing for a broad spectrum of molecular alterations are needed to further personalized cancer therapy.Experimental Design: We developed a highly sensitive ultradeep next-generation sequencing (NGS) assay using reagents from TruSeqNano library preparation and NexteraRapid Capture target enrichment kits to generate plasma cfDNA sequencing libraries for mutational analysis in 61 cancer-related genes using common bioinformatics tools. The results were retrospectively compared with molecular testing of archival primary or metastatic tumor tissue obtained at different points of clinical care.Results: In a study of 55 patients with advanced cancer, the ultradeep NGS assay detected 82% (complete detection) to 87% (complete and partial detection) of the aberrations identified in discordantly collected corresponding archival tumor tissue. Patients with a low variant allele frequency (VAF) of mutant cfDNA survived longer than those with a high VAF did (P = 0.018). In patients undergoing systemic therapy, radiological response was positively associated with changes in cfDNA VAF (P = 0.02), and compared with unchanged/increased mutant cfDNA VAF, decreased cfDNA VAF was associated with longer time to treatment failure (TTF; P = 0.03).Conclusions: Ultradeep NGS assay has good sensitivity compared with conventional clinical mutation testing of archival specimens. A high VAF in mutant cfDNA corresponded with shorter survival. Changes in VAF of mutated cfDNA were associated with TTF. Clin Cancer Res; 23(18); 5648-56. ©2017 AACR.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias/diagnóstico , Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Sequenciamento de Nucleotídeos em Larga Escala/normas , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/mortalidade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Head Neck Pathol ; 11(2): 162-167, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27550513

RESUMO

Anaplastic transformation of papillary thyroid carcinoma (PTC) at distant metastatic sites is extremely rare, and there have been fewer than 20 reported cases in the literature. A 61-year-old woman presented with 1-week history of dyspnea. Her past medical history was remarkable because, 19 years ago, she underwent nearly total thyroidectomy and radical neck dissection due to PTC. Computed tomography of the chest revealed a 1.7 cm nodule in the lung and diffuse pleural thickening. Gun biopsy of the lung nodule revealed metastatic PTC with typical histology. However, the pleural biopsy predominantly showed anaplastic pleomorphic and spindle sarcomatoid carcinoma with microscopic focus of PTC. Immunohistochemical results showed both anaplastic sarcomatoid and PTC components positive for TTF-1, galectin-3 and PAX-8, thus supporting anaplastic transformation of PTC at the metastatic site. Subsequently the patient received 1 cycle of cisplatin-based chemotherapy but died from the disease 4 months after diagnosis. Although it is rare, anaplastic transformation of PTC should be considered during differential diagnosis of patients who present with exclusive sarcomatoid morphology at metastatic sites and have a history of PTC. We report another case of anaplastic transformation of PTC, found at pleural metastasis, together with the immunohistochemical profile and a literature review.


Assuntos
Carcinoma Papilar/secundário , Transformação Celular Neoplásica/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pleurais/secundário , Neoplasias da Glândula Tireoide/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide
12.
J Pathol Transl Med ; 50(5): 327-36, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27580127

RESUMO

BACKGROUND: Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown. METHODS: Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated. RESULTS: E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p < .001) but was not correlated with patient's survival. Thirty-two cases (13.3%) showed at least focal nuclear Prrx-1 immunoreactivity while all non-neoplastic livers (n = 22) were negative. Prrx-1 expression was not associated with E-cadherin loss, survival or recurrence rates, pathologic factors, or the Ki-67 labeling index. Twenty tumors that were positive for E-cadherin and Prrx-1 had significantly higher nuclear grades than the rest of the cohort (p = .037). In Cox proportional hazard models, E-cadherin loss and large vessel invasion were independent prognostic factors for shorter disease-free survival. Cirrhosis and high Ki-67 index (> 40%) were independent prognostic factors for shorter overall survival. CONCLUSIONS: Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

13.
Gastroenterol Res Pract ; 2016: 5620765, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27195006

RESUMO

Background. This study investigated the clinicopathologic significance of extranodal tumor extension in colorectal adenocarcinoma with lymph node metastasis. Method. Included were 419 patients who underwent curative resection for primary colorectal adenocarcinoma. Results. Extranodal tumor extension was observed more frequently in tumors with ulceroinfiltrative gross type (p = 0.026), higher histologic grade (p = 0.012), high grade tumor budding (p = 0.003), vascular invasion (p < 0.001), perineural invasion (p = 0.015), tumor deposit (p < 0.001), high ratio of metastatic/total lymph nodes (p < 0.001), and high pN stage (p < 0.001). Overall survival was significantly different between an extranodal tumor extension (-) group and an extranodal tumor extension (+) group for both N1 (p = 0.022) and N2 homogeneous staging (p = 0.007). Both overall (p = 0.002) and disease-free survival (p = 0.001) were significantly different between the two groups in an N1a homogeneous group and overall survival was significantly different (p = 0.016) in an N2b homogeneous group. Conclusion. Our study demonstrated that extranodal tumor extension was a useful prognostic factor for colorectal adenocarcinoma with lymph node metastasis, especially in homogeneous pN staging groups.

14.
Ann Coloproctol ; 32(1): 20-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26962532

RESUMO

PURPOSE: The purposes of this study were to investigate the distribution of the visceral fat area (VFA) and general obesity and to compare visceral and general obesity as predictors of surgical outcomes of a colorectal cancer resection. METHODS: The prospectively collected data of 102 patients with preoperatively-diagnosed sigmoid colon or rectal cancer who had undergone a curative resection at Pusan National University Yangsan Hospital between April 2011 and September 2012 were reviewed retrospectively. Men with a VFA of >130 cm(2) and women with a VFA of >90 cm(2) were classified as obese (VFA-O, n = 22), and the remaining patients were classified as nonobese (VFA-NO, n = 80). RESULTS: No differences in morbidity, mortality, postoperative bowel recovery, and readmission rate after surgery were observed between the 2 groups. However, a significantly higher number of harvested lymph nodes was observed in the VFA-NO group compared with the VFA-O group (19.0 ± 1.0 vs. 13.5 ± 1.2, respectively, P = 0.001). CONCLUSION: Visceral obesity has no influence on intraoperative difficulties, postoperative complications, and postoperative recovery in patients with sigmoid colon or rectal cancer.

15.
World J Surg ; 40(6): 1412-21, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26796885

RESUMO

BACKGROUND: Cholecystectomy might contribute to the development of hepatic steatosis through metabolic changes. The biologic alteration of the enterohepatic circulation of bile acids and the alteration of the metabolic activity of bile acid that follows cholecystectomy may contribute to hepatic steatosis. This prospective study was conducted to clarify the possibility of steatosis development after cholecystectomy. METHODS: From October 2013 to July 2014, 82 consecutive patients with a presumptive diagnosis of gallbladder disease were cholecystectomized. Liver parenchymal steatosis was measured using ultrasound and the hepatic steatosis index. RESULTS: In all 82 patients, the hepatic steatosis index was found to be significantly correlated with the US fatty liver grade (Spearman's correlation r (2) = 0.331, P < 0.001). A total of 62 patients were followed up for 3 months. Comparison with the initial grade showed that 12 (18.5 %) patients had worsened from normal to mild (n = 10), from mild to moderate (n = 1), and from mild to severe (n = 1). The other patients stayed at their initial grade except one patient who improved (from moderated to mild). Analysis of laboratory findings showed that white blood cell count, aspartate transaminase, alanine transaminase level, and total bilirubin level were decreased. However, serum albumin and high-density lipoprotein cholesterol levels significantly increased. CONCLUSIONS: Hepatic steatosis significantly developed 3 months after cholecystectomy. Therefore, cholecystectomy might be considered a risk factor for hepatic steatosis, but the relationship should be confirmed with long-term follow-up from a large group of patients.


Assuntos
Colecistectomia/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Adulto , Idoso , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Progressão da Doença , Feminino , Seguimentos , Humanos , Lipoproteínas HDL/sangue , Fígado/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Estudos Prospectivos , Albumina Sérica/metabolismo , Índice de Gravidade de Doença , Ultrassonografia/métodos
16.
Proc Natl Acad Sci U S A ; 112(33): 10467-72, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26240372

RESUMO

We use a microfabricated ecology with a doxorubicin gradient and population fragmentation to produce a strong Darwinian selective pressure that drives forward the rapid emergence of doxorubicin resistance in multiple myeloma (MM) cancer cells. RNA sequencing of the resistant cells was used to examine (i) emergence of genes with high de novo substitution densities (i.e., hot genes) and (ii) genes never substituted (i.e., cold genes). The set of cold genes, which were 21% of the genes sequenced, were further winnowed down by examining excess expression levels. Both the most highly substituted genes and the most highly expressed never-substituted genes were biased in age toward the most ancient of genes. This would support the model that cancer represents a revision back to ancient forms of life adapted to high fitness under extreme stress, and suggests that these ancient genes may be targets for cancer therapy.


Assuntos
Antineoplásicos/química , Resistencia a Medicamentos Antineoplásicos/genética , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Análise Mutacional de DNA , Doxorrubicina/química , Duplicação Gênica , Genoma Humano , Humanos , Concentração Inibidora 50 , Proteínas Luminescentes/metabolismo , Microfluídica , Modelos Estatísticos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Análise de Sequência de RNA , Transcriptoma
17.
J Breast Cancer ; 18(1): 1-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25834604

RESUMO

PURPOSE: Dual-specificity protein phosphatase 4 (DUSP4), also known as mitogen-activated protein kinase phosphatase (MKP) 2 is a member of the inducible nuclear MKP group. The role of DUSP4 in cancer development and progression appears to vary with the type of malignancy. The purpose of this study was to investigate DUSP4 expression in a case series of invasive ductal carcinoma of the breast. METHODS: We constructed tissue microarrays consisting of 16, 14, 47, and 266 cases of normal breast tissue, usual ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma, respectively. DUSP4 expression was investigated by immunohistochemistry. RESULTS: Cytoplasmic DUSP4 expression was observed. DUSP4 was more frequently expressed in malignant than in benign cases (p=0.024). The mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (p=0.019). DUSP4 expression was significantly correlated with a larger tumor size (>2 cm, p=0.015). There was no significant correlation between overall survival or disease-free survival and DUSP4 expression in all 266 patients. We evaluated the impact of DUSP4 expression on the survival of 120 patients with T1-stage tumors. Interestingly, Kaplan-Meier survival curves revealed that DUSP4 expression had a significant effect on both overall patient survival (p=0.034, log-rank test) and disease-free survival (p=0.045, log-rank test). In early T-stage breast cancer, DUSP4 expression was associated with a worse prognosis. CONCLUSION: DUSP4 is frequently upregulated in breast malignancy, and may play an important role in cancer development and progression. In addition, it may be a marker of adverse prognosis, especially in patients with early T1-stage cancer.

18.
Chem Commun (Camb) ; 51(29): 6407-10, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25766869

RESUMO

To improve the optoelectronic properties of hematite film as a photoanode, hematite film was orientated on the (012) plane by the secondary growth of organized microcrystals. The resultant film showed promising photoelectrochemical effects compared with a randomly oriented one, with a maximum photocurrent of 0.8 mA cm(-2) at 1.23 V vs. RHE under the illumination of 1 sun.

19.
Gastroenterol Res Pract ; 2015: 283764, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25688264

RESUMO

The role of dual-specificity protein phosphatase 4 (DUSP4) appears to vary with the type of malignant tumors and is still controversial. The purpose of our study was to clarify the exact role of DUSP4 expression in colorectal adenocarcinoma. We constructed tissue microarrays and investigated DUSP4 expression by immunohistochemistry. DUSP4 was more frequently expressed in adenocarcinomas and lymph node/distant metastases compared to that in normal colorectal tissues and tubular adenomas (P < 0.001). Mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (P < 0.001). DUSP4 expression was significantly correlated with older age (P = 0.017), male gender (P = 0.036), larger tumor size (P = 0.014), nonmucinous tumor type (P = 0.023), and higher T stage (P = 0.040). Kaplan-Meier survival curves revealed a significant effect of DUSP4 expression on both overall survival and disease-free survival in AJCC stage I (P = 0.008 and P = 0.003, resp., log-rank test) and male gender (P = 0.017 and P = 0.049, resp., log-rank test). DUSP4 protein is frequently upregulated in colorectal adenocarcinoma and may play an important role in carcinogenesis and cancer progression and may be a marker of adverse prognosis.

20.
J Breast Cancer ; 18(4): 323-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26770238

RESUMO

PURPOSE: Deregulation of microRNA-370 (miR-370) has been reported in various cancers, in which it can act as either an oncogene or a tumor suppressor gene. However, the clinicopathologic significance of miR-370 expression in breast cancer has not been studied. METHODS: The expression of miR-370 was determined with quantitative real-time polymerase chain reaction in 60 formalin-fixed, paraffin-embedded primary breast cancer tissues. Additionally, the protein expression levels of previously known targets of miR-370, such as FOXM1, FOXO1, and FOXO3a, were detected using immunohistochemistry. Finally, we analyzed its correlation with target protein expression, clinicopathologic features, and clinical outcome. RESULTS: High levels of miR-370 expression correlated with lymph node metastasis (p=0.009), advanced stage (p=0.002), and frequent perineural invasion (p=0.042). Moreover, patients with high miR-370 expression had poor disease-free survival compared with the low-expression group. However, no correlation was observed between miR-370 and its target protein expression. CONCLUSION: Our results indicate that upregulation of miR-370 in breast cancer is correlated with breast cancer progression and that it might be a potential biomarker for predicting clinical outcomes.

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