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The COVID-19 pandemic caused drastic social changes for many people, including separation from friends and coworkers, enforced close contact with family, and reductions in mobility. Here we assess the extent to which people's evolutionarily-relevant basic motivations and goals-fundamental social motives such as Affiliation and Kin Care-might have been affected. To address this question, we gathered data on fundamental social motives in 42 countries (N = 15,915) across two waves, including 19 countries (N = 10,907) for which data were gathered both before and during the pandemic (pre-pandemic wave: 32 countries, N = 8998; 3302 male, 5585 female; M age = 24.43, SD = 7.91; mid-pandemic wave: 29 countries, N = 6917; 2249 male, 4218 female; M age = 28.59, SD = 11.31). Samples include data collected online (e.g., Prolific, MTurk), at universities, and via community sampling. We found that Disease Avoidance motivation was substantially higher during the pandemic, and that most of the other fundamental social motives showed small, yet significant, differences across waves. Most sensibly, concern with caring for one's children was higher during the pandemic, and concerns with Mate Seeking and Status were lower. Earlier findings showing the prioritization of family motives over mating motives (and even over Disease Avoidance motives) were replicated during the pandemic. Finally, well-being remained positively associated with family-related motives and negatively associated with mating motives during the pandemic, as in the pre-pandemic samples. Our results provide further evidence for the robust primacy of family-related motivations even during this unique disruption of social life.
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PURPOSE: To evaluate the clinicopathological features of and prognosis associated with sporadic colorectal cancer (CRC) in Japanese patients younger than 40 years old. METHODS: The subjects of this study were patients with sporadic stage 0-III CRC, who underwent curative resection between 2004 and 2012 at the Cancer Institute Hospital. Clinicopathological characteristics and survival were compared between the young (<40 years; n = 81) and older groups (≥40 years; n = 2257). RESULTS: The median age was 36 years in the young group and 64 years in the older group. Young patients had a lower incidence of right-sided colon cancer (14 vs 28 %) and a higher incidence of rectal cancer (47 vs 32 %; P < 0.0001). The number of retrieved lymph nodes was significantly higher in the young group than in the older group (P = 0.0049). The young patients had similar overall survival and relapse-free survival to their older counterparts, except for overall survival in stage II patients (P = 0.0229). However, multivariate analysis indicated that age was not an independent prognostic factor for overall survival in patients with stage II CRC. CONCLUSIONS: Young Japanese patients with sporadic CRC have unique characteristics such as a high incidence of rectal cancer and similar pathological features; however, they appear to have comparable survival to older patients.
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Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics, and was recently recognized as a variant of squamous cell carcinoma (SCC). We previously revealed genetic and epigenetic alterations associated with esophageal SCCs in relation to clinical outcome, including mutations in KRAS, BRAF, and PIK3CA, p53 expression, and long interspersed nucleotide element-1 (LINE-1) methylation, a surrogate marker for global DNA methylation level. In this study, we explored these features in BSCC. METHODS: A database of 502 esophageal cancers was used to evaluate the clinical and molecular characteristics of BSCC. KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation were analyzed by pyrosequencing. RESULTS: Of 502 tumors, 22 (4.4 %) were pathologically diagnosed as BSCC, and 440 (87 %) as SCC. No prognostic differences between BSCC and SCC cases were identified (p = 0.41). KRAS or BRAF mutations were not observed in BSCCs. While 23 % of SCC tumors harbored a PIK3CA mutation, all BSCC cases were wild-type for PIK3CA (p = 0.002), and there were no differences in p53 expression between BSCCs and SCCs (p = 0.57), as assessed by immunohistochemistry. Furthermore, BSCC tissues exhibited significantly lower levels of LINE-1 methylation than SCC tissues (p < 0.0001). CONCLUSIONS: These findings imply that esophageal BSCC and SCC retain different cellular phenotypes with distinct genetic and epigenetic alterations; thus, tailored therapeutic strategies should be developed against each cancer type.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patologia , Classe I de Fosfatidilinositol 3-Quinases , Metilação de DNA , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Taxa de Sobrevida , Proteína Supressora de Tumor p53/análiseRESUMO
BACKGROUND: Insulin like growth factor 2 gene (IGF2) is normally imprinted. Loss of imprinting (LOI) of IGF2 in humans is associated with an increased risk of cancer and is controlled by CpG-rich regions known as differentially methylated regions (DMRs). Specifically, the methylation level at IGF2 DMR0 is correlated with IGF2 LOI and is a suggested surrogate marker for IGF2 LOI. A relationship between IGF2 DMR0 hypomethylation and poor prognosis has been shown in colorectal cancer. However, to our knowledge, no study has examined the relationships among the IGF2 DMR0 methylation level, LOI, and clinical outcome in esophageal squamous cell carcinoma (ESCC). METHODS: The IGF2 imprinting status was screened using ApaI polymorphism, and IGF2 protein expression was evaluated by immunohistochemistry with 30 ESCC tissue specimens. For survival analysis, IGF2 DMR0 methylation was measured using a bisulfite pyrosequencing assay with 216 ESCC tissue specimens. RESULTS: Twelve (40 %) of 30 cases were informative (i.e., heterozygous for ApaI), and 5 (42 %) of 12 informative cases displayed IGF2 LOI. IGF2 LOI cases exhibited lower DMR0 methylation levels (mean 23 %) than IGF2 non-LOI cases (37 %). The IGF2 DMR0 methylation level was significantly associated with IGF2 protein expression. Among 202 patients eligible for survival analysis, IGF2 DMR0 hypomethylation was significantly associated with higher cancer-specific mortality. CONCLUSIONS: The IGF2 DMR0 methylation level in ESCC was associated with IGF2 LOI and IGF2 protein expression. In addition, IGF2 DMR0 hypomethylation was associated with a shorter survival time, suggesting its potential role as a prognostic biomarker.
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Carcinoma de Células Escamosas/genética , Metilação de DNA , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , Impressão Genômica , Fator de Crescimento Insulin-Like II/genética , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , DNA de Neoplasias/genética , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Fator de Crescimento Insulin-Like II/metabolismo , Metástase Linfática , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Taxa de SobrevidaRESUMO
Epigenetic alterations, such as DNA methylation, histone modification and the loss of genome imprinting, are important indicators of human carcinogenesis. DNA methylation is a fundamental epigenetic process that modulates the gene expression levels. In cancer cells, DNA methylation may be altered in two principle ways: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Long interspersed element-1 (LINE-1 or L1) is a repetitive DNA retrotransposon that duplicates via a copy-and-paste genetic mechanism. Since LINE-1 constitutes a substantial portion (approximately 17 %) of the human genome, the extent of LINE-1 methylation is regarded to be a surrogate marker of global DNA methylation. Measuring the level of LINE-1 methylation using pyrosequencing technology has emerged as a cost-effective and high-throughput method for assessing the global DNA methylation status. In some types of gastrointestinal (GI) cancers, LINE-1 hypomethylation is strongly associated with a poor prognosis, supporting its potential role as a prognostic marker. In addition, the LINE-1 methylation level may prove to be a useful clinical biomarker for assessing the risk of cancer or predicting the chemotherapeutic efficacy of treatment in patients with GI cancers. In this article, we summarize current knowledge regarding LINE-1 methylation and its clinical implications in GI cancers, including colorectal cancer, gastric cancer and esophageal cancer.
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Metilação de DNA , Epigênese Genética/genética , Neoplasias Gastrointestinais/genética , Elementos Nucleotídeos Longos e Dispersos/genética , Biomarcadores Tumorais , Ilhas de CpG/genética , DNA/genética , Genoma Humano/genética , Humanos , Prognóstico , Sequências Repetitivas de Ácido Nucleico , Retroelementos , RiscoRESUMO
PURPOSE: We evaluated the need for primary tumor resection in patients with colorectal cancer (CRC) and synchronous unresectable metastases who underwent chemotherapy, and identified the associations between the primary tumor characteristics and risk of intestinal obstruction or perforation. METHODS: We retrospectively analyzed the survival and complication rates of patients with synchronous metastatic CRC treated between April 2005 and December 2011. RESULTS: Of 131 patients, 68 underwent primary tumor resection before chemotherapy, and 63 were treated without resection before chemotherapy. The overall survival (OS) did not significantly differ between the two groups (log-rank P = 0.53). In the resection group, 12 patients (17.6%) developed postoperative complications. In the non-resection group, 16 patients (25.4%) required surgical intervention owing to obstruction or perforation during their treatment. Surgical intervention did not affect the OS. A circumferential tumor was a risk factor for obstruction or perforation of the colorectum in non-resected patients (odds ratio = 11.163; P = 0.006). CONCLUSION: Resection of primary tumors before chemotherapy is unnecessary in selected patients with synchronous metastatic colorectal cancer. A circumferential tumor is a risk factor for obstruction or perforation during chemotherapy in cases without primary tumor resection.
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Neoplasias Colorretais/secundário , Neoplasias Colorretais/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Fluoruracila/administração & dosagem , Humanos , Obstrução Intestinal/etiologia , Perfuração Intestinal/etiologia , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Epidermal growth factor receptor (EGFR) signaling is one of the most promising targets for molecular-targeted therapies in esophageal squamous cell carcinoma (ESCC). Thus, the molecular diagnosis of KRAS and BRAF mutations is clinically important in therapeutic decision making. However, the frequency of KRAS and BRAF mutations in ESCCs remains inconclusive because of the limited sample sizes of previous studies (all N ≤ 80). Pyrosequencing is a nonelectrophoretic nucleotide extension sequencing technology that can be used for mutation testing. METHODS: The frequency of KRAS and BRAF mutations was examined using a nonbiased database of 203 resected ESCCs and a high-throughput pyrosequencing assay. RESULTS: The validity of the KRAS pyrosequencing method was initially demonstrated by detection of all 4 types of KRAS mutations [c.35G>T (codon 12 GGT>GTT), c.35G>A (codon 12 GGT>GAT), c.34G>T (codon 12 GGT>TGT), c.38G>A mutation (codon 13 GGC>GAC)], which had been previously diagnosed using Scorpion-ARMS technology, in 9 colon cancer tissues (9 of 9; 100 %). Similar results were demonstrated for BRAF mutational status in 3 colon cancer cell lines (HCT116, Colo201, and HT29), which were validated by Sanger dideoxy sequencing. Subsequently, the KRAS mutation was found to be extremely rare (1 of 203; 0.5 %), and the BRAF mutation was absent (0 of 203; 0 %), in the dataset of 203 ESCCs. CONCLUSIONS: These results suggest that KRAS and BRAF mutations play a limited role in the development of ESCC and that mutation analysis is not useful as a screening test for sensitivity to anti-EGFR therapy in ESCC.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Análise Mutacional de DNA , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Terapia de Alvo Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Literatura de Revisão como Assunto , Células Tumorais CultivadasRESUMO
BACKGROUND: Genome-wide DNA hypomethylation plays an important role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, LINE-1 methylation level is attracting interest as a predictive marker for patient prognosis. However, the prognostic significance of LINE-1 hypomethylation in gastric cancer remains unclear. METHODS: Using 203 resected gastric cancer specimens, we quantified LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for the clinical and pathological variables. RESULTS: Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p < 0.0001; n = 74). Tumoral LINE-1 methylation range was 11.6-97.5 on a 0-100 scale (n = 203; mean 71.4, median 74.4, standard deviation 12.9). LINE-1 hypomethylation was significantly associated with shorter overall survival [log-rank p = 0.029; univariate HR 2.01, 95 % confidence interval (CI) 1.09-3.99, p = 0.023; stage-matched HR 1.88, 95 % CI 1.02-3.74, p = 0.041; multivariate HR 1.98, 95 % CI 1.04-4.04, p = 0.036]. No significant effect modification was observed by any of the covariates in survival analysis (all p interaction >0.25). CONCLUSIONS: LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker.
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Biomarcadores Tumorais/genética , Metilação de DNA , Elementos Nucleotídeos Longos e Dispersos/genética , Neoplasias Gástricas/genética , Sulfitos/química , Idoso , Feminino , Seguimentos , Instabilidade Genômica , Humanos , Masculino , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Análise de Sequência de DNA , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVES: Delay-discounting, wherein the subjective value for delayed gain or loss decreases, has been attracting much attention from the social sciences as well as neuroscience and has been suggested asbeing related to reward processing in the brain. As reported, the feedback-related negativity (FRN), an electrophysiological measure of reward processing, increased by delayed-monetary gain and ΔFRN, which is the difference in FRNs for loss and gain at a certain time point, had no significant correlation with delay-discounting for gain. Thus, although a delay for gain could affect FRN, it is unclear whether FRN capturing such a delay effect has a direct relationship with delay-discounting in both gain and loss domains. METHODS: In this study, we introduced a delay-specific indicator, ΔFRNdelay, that is, the difference between FRN with and without delays, and investigated its direct relationship during the doors task with the discounting rate measured by the delay-discounting task in both the gain and loss domains. RESULTS: We found that, for loss, the delay enhanced FRN, whereas no such effect was observed for gains, and that this indicator was significantly correlated with delay-discounting in both domains. CONCLUSIONS: To our knowledge, this study is the first to suggest that FRN is sensitive to the effects of delay in losses on reward processing and that the new indicator directly corresponds to changes in subjective value as measured by delay-discounting.
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Hérnia Diafragmática , Deformidades Congênitas dos Membros , Humanos , Encéfalo , Recompensa , FáciesRESUMO
A 49-year-old woman was admitted to our hospital under suspicion of an enlarging hepatic tumor, which had been previously diagnosed to be a cavernous hemangioma. Computed tomography revealed three enhanced tumors, one measuring 15 cm in diameter within the right lobe of the liver and two intrahepatic metastases in Couinaud's hepatic segments 3 and 5. We diagnosed the patient to have primary liver cancer, and suspected a combined liver tumor preoperatively. We performed a right trisectionectomy with radiofrequency ablation of the intrahepatic metastasis in S3. According to the immunohistochemical findings of the resected specimen and the findings of postoperative imaging studies, the tumor was diagnosed to be a primary neuroendocrine tumor in the liver. The patient is presently alive without recurrence at 33 months after the operation.
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Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Hepatectomia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
What motives do people prioritize in their social lives? Historically, social psychologists, especially those adopting an evolutionary perspective, have devoted a great deal of research attention to sexual attraction and romantic-partner choice (mate seeking). Research on long-term familial bonds (mate retention and kin care) has been less thoroughly connected to relevant comparative and evolutionary work on other species, and in the case of kin care, these bonds have been less well researched. Examining varied sources of data from 27 societies around the world, we found that people generally view familial motives as primary in importance and mate-seeking motives as relatively low in importance. Compared with other groups, college students, single people, and men place relatively higher emphasis on mate seeking, but even those samples rated kin-care motives as more important. Furthermore, motives linked to long-term familial bonds are positively associated with psychological well-being, but mate-seeking motives are associated with anxiety and depression. We address theoretical and empirical reasons why there has been extensive research on mate seeking and why people prioritize goals related to long-term familial bonds over mating goals. Reallocating relatively greater research effort toward long-term familial relationships would likely yield many interesting new findings relevant to everyday people's highest social priorities.
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Relações Familiares , Objetivos , Relações Interpessoais , Recompensa , Comportamento Sexual , Comportamento Social , Adulto , Comparação Transcultural , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Error-related negativity is an event-related potential component that is observed when participants make errors and reflects action monitoring that involves error detection. In this study, an over-response error (responding with both hands when participants were asked to respond with only one hand) and an under-response error (responding with one hand when asked to respond with both hands) were assessed by the characteristics of the error-related negativity during a modified Eriksen flankers task. The results indicated that a bimanual response error also elicited the error-related negativity, and that the onset latency of the error-related negativity was shorter for an over-response error than for an under-response error. Thus, these results suggest that the error-detection process is more sensitive to an unnecessary response than to an insufficient response.
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Discriminação Psicológica/fisiologia , Potenciais Evocados/fisiologia , Lateralidade Funcional/fisiologia , Tempo de Reação/fisiologia , Adulto , Análise de Variância , Eletroencefalografia/métodos , Eletromiografia/métodos , Eletroculografia/métodos , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologiaRESUMO
BACKGROUND: The aim of this study was to investigate the usefulness of a triaxial accelerometer for the clinical assessment of standing and gait impairment in ataxic patients quantitatively. Fifty-one patients with spinocerebellar ataxia (SCA) or multiple system atrophy with predominant cerebellar ataxia (MSA-C) and 56 healthy control subjects were enrolled. The subjects, with a triaxial accelerometer on their back, were indicated to stand for 30 s in four different conditions (eyes opened or closed, and feet apart or together) and then to walk 10 m for a total of 12 times on a flat floor at their usual walking speed. In standing analysis, the degree of body sway was assessed. In gait analysis, gait velocity, cadence, step length, step regularity (auto-correlation coefficient: AC), step repeatability (cross-correlation coefficient) and the degree of body sway (The ratio of root mean square in each direction to the root mean square vector magnitude: RMSR) were evaluated. RESULTS: The degree of body sway in each standing condition and all parameters in gait showed a significant difference between the patients and control subjects. The AC and RMSR values, as well as the Scale for the Assessment and Rating of Ataxia score, showed a strong correlation with disease duration. CONCLUSIONS: Various parameters obtained by a triaxial accelerometer can be sensitive and objective markers for the assessment and follow-up of standing and gait impairment in ataxic patients.
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Mammalian DNA is epigenetically marked by 5'-cytosine methylation (5-methylcytosine [5-mC]). The Ten-eleven translocation (TET) enzymes (TET1, TET2, and TET3) are implicated in DNA demethylation, through dioxygenase activity that converts 5-mC to 5-hydroxymethylcytosine (5-hmC). Although decreased TET is reportedly associated with decreased 5-hmC levels in various cancers, functions of 5-hmC and TET expression in esophageal squamous cell carcinoma (ESCC) are unclear. We used ELISA and immunohistochemistry tests to analyze 5-hmC status in ESCC tissues, RT-qPCR to analyze TET family mRNA expression in normal and tumor tissues, and pyrosequencing to quantify LINE-1 (i.e., global DNA methylation) levels. ELISA and immunohistochemical testing showed 5-hmC levels were significantly lower in ESCC than in paired normal tissues (P < 0.0001). TET2 expression was significantly lower in ESCCs than paired normal tissues (P < 0.0001), and significantly associated with 5-hmC levels in ESCCs (P = 0.003, r = 0.33). 5-hmC levels were also significantly associated with LINE-1 methylation level (P = 0.0002, r = 0.39). Patients with low 5-hmC levels had shorter overall survival than those with higher levels, although not significantly so (P = 0.084). In conclusion, 5-hmC expression was decreased in ESCC tissues, and was associated with TET2 expression level. TET2 reduction and subsequent 5-hmC loss might affect ESCC development.
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Carcinoma de Células Escamosas/genética , Citosina/análogos & derivados , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias Esofágicas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , 5-Metilcitosina/química , Idoso , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Sobrevivência Celular , Citosina/química , Metilação de DNA , Dioxigenases , Ensaio de Imunoadsorção Enzimática , Epigênese Genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Mucosa Intestinal/patologia , Estimativa de Kaplan-Meier , Elementos Nucleotídeos Longos e Dispersos/genética , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sequência de DNARESUMO
The DNA methylation alterations occurring in human cancers have two types: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Recently, to assess global DNA methylation, long interspersed nucleotide element 1 (LINE-1) retrotransposons, constituting a substantial portion of the human genome, attracts much attention. The aim of the current study was to clarify the significance of LINE-1 methylation level for epigenetic field defects and the relationships among LINE-1 methylation level in gastric mucosae, clinical and pathological features, including infection by Helicobacter pylori (H. pylori), a bacterium implicated in gastric cancer. By bisulfite-PCR pyrosequencing, we quantified the LINE-1 methylation levels in noncancerous gastric mucosae and cancer tissues from 87 gastric cancer patients, in gastric mucosae from 17 autopsied individuals without gastric cancers and in 20 gastric fresh frozen samples from non-gastric cancer patients. LINE-1 methylation in the noncancerous gastric mucosae of gastric cancer patients was significantly higher than in cancer tissues (P = 0.0006), but significantly lower than in the gastric mucosae of the autopsied individuals (P = 0.026), suggesting the formation of epigenetic field defect in noncancerous gastric mucosae. Moreover, LINE-1 hypomethylation of noncancerous gastric mucosae in gastric cancer patients significantly correlated with H. pylori infection (P = 0.037). We prospectively confirmed the similar result in 20 non-gastric cancer patients (P = 0.010). LINE-1 hypomethylation of gastric mucosae significantly correlated with H. pylori infection, supporting the potential of LINE-1 methylation level as a surrogate marker of epigenetic field defects for gastric cancer cancerization, particularly induced by H. pylori.
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Metilação de DNA , Epigenômica , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Elementos Nucleotídeos Longos e Dispersos/genética , Neoplasias Gástricas/microbiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ilhas de CpG , Feminino , Seguimentos , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Regiões Promotoras Genéticas , Estudos Prospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: Global DNA hypomethylation plays a crucial role in genomic instability and carcinogenesis. DNA methylation of the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level, and is attracting interest as a useful marker for predicting cancer prognosis. Our previous study using more than 200 esophageal squamous cell carcinoma (ESCC) specimens demonstrated the significant relationship between LINE-1 hypomethylation and poor prognosis. However, the mechanism by which LINE-1 hypomethylation affects aggressive tumor behavior has yet to be revealed. EXPERIMENTAL DESIGN: To examine the relationship between LINE-1 hypomethylation and DNA copy number variations, we investigated LINE-1-hypomethylated and LINE-1-hypermethylated ESCC tumors by comparative genomic hybridization array. RESULTS: LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6. LINE-1 methylation levels were significantly associated with CDK6 mRNA and CDK6 protein expression levels in ESCC specimens. In our cohort of 129 patients with ESCC, cases with CDK6-positive expression experienced worse clinical outcome compared with those with CDK6-negative expression, supporting the oncogenic role of CDK6 in ESCC. In addition, we found that the prognostic impact of LINE-1 hypomethylation might be attenuated by CDK6 expression. CONCLUSION: LINE-1 hypomethylation (i.e., global DNA hypomethylation) in ESCC might contribute to the acquisition of aggressive tumor behavior through genomic gains of oncogenes such as CDK6.
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Carcinoma de Células Escamosas/genética , Quinase 6 Dependente de Ciclina/genética , Variações do Número de Cópias de DNA , Metilação de DNA , Neoplasias Esofágicas/genética , Amplificação de Genes , Elementos Nucleotídeos Longos e Dispersos/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Aberrações Cromossômicas , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 6 Dependente de Ciclina/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Feminino , Expressão Gênica , Humanos , Masculino , PrognósticoRESUMO
Previous work has shown that emotional control is highly valued in Asian culture. However, little is known about how this cultural value might influence emotional processing. Here, we hypothesized that Asians are 'culturally trained' to down-regulate emotional processing when required to suppress emotional expressions. Such down-regulation, however, is unlikely for European Americans because their culture values emotional expression (vs control) more. To test these predictions, we adopted the parietal late positive potential (LPP) of the event-related potential as an objective indicator of emotional processing. Both Asian and European Americans were exposed to either unpleasant or neutral pictures while instructed to either attend or suppress expression of emotions. Both groups showed an equally pronounced parietal positivity â¼600 ms post-stimulus. As predicted, however, Asians subsequently showed a significant decrease of the parietal LPP in the suppression (vs attend) condition. The initial positivity completely disappeared 2000 ms post-stimulus. In contrast, for European Americans the parietal LPP suppression effect was completely absent although there was an early occurring, sustained increase in frontal positivity in the suppression (vs attend) condition. Implications for culture and emotion research are discussed.
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Córtex Cerebral/fisiologia , Cultura , Emoções/fisiologia , Potenciais Evocados Visuais/fisiologia , Inibição Psicológica , Adolescente , Asiático , Mapeamento Encefálico , Variação Contingente Negativa/fisiologia , Eletroencefalografia , Eletroculografia , Feminino , Humanos , Masculino , Estimulação Luminosa , População Branca , Adulto JovemRESUMO
PURPOSE: PIK3CA encodes the catalytic subunit of PI3K, p110α. Mutant PIK3CA stimulates the AKT pathway and promotes cancer cell proliferation. PIK3CA mutations have been associated with poor prognosis in patients with colorectal or lung cancer. In contrast, the relationship between PIK3CA mutations and favorable prognoses has been shown in breast cancer. However, the influence of PIK3CA mutations on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. EXPERIMENTAL DESIGN: Using a nonbiased database of 219 curatively resected ESCCs and eight esophageal cancer cell lines, we evaluated PIK3CA mutational status by pyrosequencing. The expression of p53 and phosphorylated AKT (i.e., AKT activation) was evaluated by immunohistochemistry. RESULTS: PIK3CA mutations in exon 9 and/or 20 were detected in 46 cases (21%). No ESCC cell line harbored PIK3CA mutations. PIK3CA mutations were significantly associated with phosphorylated AKT expression, but not with p53 expression, sex, age at surgery, tobacco use, alcohol use, or histologic grade. Compared with wild-type PIK3CA cases, patients with PIK3CA mutations in exons 9 and/or 20 experienced significantly better disease-free survival [log-rank P = 0.0089; univariate HR: 0.37, 95% confidence interval (CI): 0.15-0.75, P = 0.0042; multivariate HR: 0.34, 95% CI: 0.10-0.86, P = 0.021] and overall survival (log-rank P = 0.012; univariate HR: 0.38, 95% CI: 0.16-0.78, P = 0.0060; multivariate HR: 0.35, 95% CI: 0.10-0.90, P = 0.028). CONCLUSION: PIK3CA mutations in ESCC are associated with longer survival, suggesting its role as a prognostic biomarker. Future studies are needed to confirm this association and to elucidate the exact mechanisms by which PIK3CA mutations affect tumor behavior.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Fosfatidilinositol 3-Quinases/genética , Idoso , Sequência de Bases , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Éxons , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Prognóstico , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismoRESUMO
It is generally accepted that overexpression of p53 protein is associated with poor prognosis in gastric, lung, and other types of cancer. However, the prognostic significance of p53 aberrations in esophageal cancer remains unclear. This is the largest study (n = 266) examining clinical and prognostic features of p53 immunohistochemical expression in esophageal squamous cell carcinoma. In 139 (52%) esophageal tumors, nuclear immunoreactivity for p53 protein was detected. p53 aberrant expression was not associated with sex, age, preoperative treatment, TNM stage, or histological grade. Furthermore, p53 expression did not correlate with disease-free survival (P = 0.73) or overall survival (P = 0.62). In addition, no significant modification effect by any of the covariates in the survival analysis was observed (all P > 0.15). In conclusion, our large-scale study demonstrates that p53 expression has no impact on the prognosis of esophageal squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Proteína Supressora de Tumor p53/genética , Idoso , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago , Humanos , Imuno-Histoquímica/métodos , Prognóstico , Análise de SobrevidaRESUMO
An emerging literature indicates that dispositional bias in causal attribution of social behavior is weaker for people with working-class (vs. middle-class) backgrounds. However, it is unknown whether this difference is also present in spontaneous forms of trait inference. In the current work, American undergraduates were asked to merely memorize many pairings of a target face and a trait-implying behavior. In a subsequent lexical judgment task, after each face was presented as a fixation, either an implied trait or its antonym was given as a target. As expected, participants with college-educated parents (middle class) showed a strong N400 event-related potential component to the antonym (vs. the implied trait), suggesting spontaneous trait inference during the memorization phase. In contrast, those with high-school-educated parents (working class) showed no such effect. It is important to note that the N400 spontaneous trait inference effect was associated with perceived significance of dispositions in accounting for social behaviors.