Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thymic carcinoma, which is a rare epithelial neoplasm of the thymus gland, is different from thymoma in its clinical and pathological features. To clarify the mechanism underlying the aggressive behavior of thymic carcinoma, we examined the clinicopathologic features, aberrant methylation patterns of the tumor suppressor genes, and epidermal growth factor receptor (EGFRs) mutation in both thymic carcinomas and thymomas. Clinical data of 11 thymic cancers and 13 thymomas were reviewed. Resected samples of 5 thymic cancers and 6 thymomas selected from 24 cases were used for methylation and mutation studies. Positive tumor markers were more frequent in thymic cancers than in thymomas (p=0.0233), and the methylation index, which reflects the overall methylation pattern, was significantly higher in thymic carcinomas (p=0.0053). No tumors showed a mutation of EGFR, KRAS, and HER2. Thymic carcinoma is distinct from thymoma not only with respect to clinicopathological features, but also aberrant methylation patterns of the tumor suppressor genes.
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PMID:Aberrant methylation: common in thymic carcinomas, rare in thymomas. 1627 66

Over the last decade rates of violence among adolescent girls have increased. Within high-risk contexts, urgent calls for assessment options have resulted in the extension of adult and male-based instruments to adolescent females in spite of the absence of strong empirical support. The current study evaluates the downward extension of psychopathy within a population of female juvenile offenders (N=125). The convergent and predictive validity of the Psychopathy Checklist-Youth Version (PCL-YV) were evaluated within a structural equation modeling (SEM) framework. Results indicated that while a specific component of psychopathy, deficient affective experience, was related to aggression, the effect was negated once victimization experiences were entered into the models. In addition, PCL-YV scores were not predictive of future offending, while victimization experiences significantly increased the odds of re-offending. Implications for research, policy, and clinical practice are discussed.
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PMID:Nipping psychopathy in the bud: an examination of the convergent, predictive, and theoretical utility of the PCL-YV among adolescent girls. 1633 12

Recent gene profiling studies have identified a new breast cancer subtype, the basal-like group, which expresses genes characteristic of basal epithelial cells and is associated with poor clinical outcomes. However, the genes responsible for the aggressive behavior observed in this group are largely unknown. Here we report that the small heat shock protein alpha-basic-crystallin (alphaB-crystallin) was commonly expressed in basal-like tumors and predicted poor survival in breast cancer patients independently of other prognostic markers. We also demonstrate that overexpression of alphaB-crystallin transformed immortalized human mammary epithelial cells (MECs). In 3D basement membrane culture, alphaB-crystallin overexpression induced luminal filling and other neoplastic-like changes in mammary acini, while silencing alphaB-crystallin by RNA interference inhibited these abnormalities. alphaB-Crystallin overexpression also induced EGF- and anchorage-independent growth, increased cell migration and invasion, and constitutively activated the MAPK kinase/ERK (MEK/ERK) pathway. Moreover, the transformed phenotype conferred by alphaB-crystallin was suppressed by MEK inhibitors. In addition, immortalized human MECs overexpressing alphaB-crystallin formed invasive mammary carcinomas in nude mice that recapitulated aspects of human basal-like breast tumors. Collectively, our results indicate that alphaB-crystallin is a novel oncoprotein expressed in basal-like breast carcinomas that independently predicts shorter survival. Our data also implicate the MEK/ERK pathway as a potential therapeutic target for these tumors.
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PMID:AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. 1639 1

Sarcomatoid squamous cell carcinoma (SSCC) of the uterine cervix, characterized by biphasic components of sarcomatoid and squamous neoplastic cells, is a rare entity with uncertain pathogenesis. To date, less than 20 cases have been mentioned. Although the rarity of this diagnosis makes it difficult to draw firm conclusions from limited data, it does seem that SSCC is an aggressive tumor. In this study, we present a 31-year-old patient with abnormal vaginal bleeding. The diagnosis of SSCC was confirmed through pathologic examinations from hysterectomy specimen. Its epithelial origin was demonstrated by immunohistochemical studies. The expression of p53, HER2/neu, and c-kit was not enhanced in this tumor. Importantly, it was human papillomavirus type 16, positive by polymerase chain reaction and in situ hybridization studies. Enhanced immunostaining for phospho-retinoblastoma protein and decreased apoptosis compared with the squamous cell carcinoma counterpart were observed. This report characterizes the first description of molecular features in SSCC that may account for its aggressive behavior.
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PMID:Evidence of human papillomavirus infection, enhanced phosphorylation of retinoblastoma protein, and decreased apoptosis in sarcomatoid squamous cell carcinoma of uterine cervix. 1644 55

Recurrent corneal erosions in both traumatic and basal membrane dystrophy-associated conditions seem to show a similar pathogenesis for abnormal adhesion between corneal epithelium and stroma. The purpose of each conservative or surgical treatment is fast healing without any infections or recurrences. This paper compares the different excimer laser treatment options with emphasis on the so-called aggressive PTK. A total of 50 eyes of 50 patients with recurrent corneal erosions after mechanical trauma or with epithelial basement membrane dystrophy were treated with aggressive PTK after the second or third recurrence. Aggressive PTK was performed with an ablation of 10-15 microm. After the mean follow-up time of 41.8 months, a recurrence rate of 6% without a change of visual acuity and a hyperopic shift of +0.74 D were observed. The earliest recurrent erosion showed up after 33 and the latest after 65 months. In comparison to other forms of PTK such as transepithelial or conventional subepithelial PTK, aggressive PTK showed the lowest recurrence rate reported for a long-term follow-up.
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PMID:[Recurrent corneal erosion. Different treatment options with the excimer laser with emphasis on aggressive PTK]. 1670 49

Although there is a documented link between psychopathy and instrumental violence in adult offenders, the association between these constructs has not garnered significant attention in adolescent offenders. In this study, we evaluated the relationship between psychopathy and instrumental aggression in a sample of 122 male adolescents incarcerated in a state facility for serious and chronic offenders. We evaluated the primary (2-, 3-, and 4-factor) models of the Psychopathy Checklist: Youth Version (PCL:YV; Forth, Kosson, & Hare, 2003) and assessed their relationship to a separate 5-item measure of instrumental violence. CFA revealed good model fit for the 3- and 4-factor latent variable models of adolescent psychopathy and a single-factor model reflecting a 5-item measure of instrumental violence. Structural equation modeling results indicate that the 4-factor model accounted for 20% of the variance for instrumental violence. In contrast, the 3-factor model of the PCL:YV accounted for 8%, and the 2-factor model accounted for 5% of the variance associated with instrumental violence.
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PMID:Testing factor models of the Psychopathy Checklist: Youth Version and their association with instrumental aggression. 1685 88

Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.
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PMID:MET expression in sporadic renal cell carcinomas. 1689 11

Carcinoma of the thyroid gland is the most common malignancy of the endocrine system. Differentiated tumors are often curable with surgical resection and radioactive iodine. A small percentage of such patients, however, do not undergo remission and need new therapeutic approaches. Both anaplastic and medullary thyroid carcinomas exhibit aggressive behavior and are usually resistant to current therapeutic modalities. Thyroid carcinoma represents a fascinating model and a particularly promising paradigm for targeted therapy because some of the key oncogenic events are activating mutations of genes coding for tyrosine kinases, and these occur early in cancer development. A prototype is the RET proto-oncogene, a receptor tyrosine kinase, which is a key regulator of development and a 'hotspot' for oncogenic mutations. Mutations in the RET proto-oncogene have been identified as causative for papillary carcinoma and familial medullary thyroid carcinoma, making it an attractive target for selective inhibition in these subtypes. ZD 6474 has shown promising activity in preclinical models against RET kinase, and its contemporary inhibition of vascular endothelial growth factor and epidermal growth factor pathways renders it a very attractive drug for clinical trials in thyroid cancer. Activating point mutation of B-RAF can occur early in the development of papillary carcinoma. Moreover, papillary carcinomas with these mutations have more aggressive properties and are diagnosed more often at an advanced stage. Clinical evaluation of B-RAF-targeting drugs is undergoing and trials in thyroid cancer are planned. Agents that restore radioiodine uptake, such as histone deacetylase inhibitors and retinoids, represent another exciting field in new drug development in thyroid cancer.
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PMID:New molecular targeted therapies in thyroid cancer. 1694 Jul 97

The present study examined the concurrent relationship between psychopathy characteristics as measured by the PCL:YV and aggressive and antisocial behavior in a sample of 142 high-risk adolescent girls and boys. The unique relationship between each of three PCL:YV factors (Arrogant and Deceitful Interpersonal Style, Deficient Affective Experience, and Impulsive and Irresponsible Behavioral Style) and outcomes was evaluated to determine which aspects of psychopathy are most crucially linked to aggressive and antisocial behavior in adolescents. Dependent measures were expanded to include both relational and physical forms of aggression to better capture meaningful outcomes for girls and boys. Regression analyses showed that the relationships between psychopathic features and outcomes were equivalent for boys and girls, and that deficits in affect were most consistently associated with aggression. These findings are concordant with the well established finding in developmental research showing that deficits in empathy and affect regulation are associated with aggression.
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PMID:The relation of psychopathy to concurrent aggression and antisocial behavior in high-risk adolescent girls and boys. 1695 86

Overexpression of the erbB-1 (EGFR, epidermal growth factor receptor) and erbB-2 (HER2/neu) proteins contributes to the aggressive behavior of malignant tumors originating from the endometrium. We currently examined whether the trend of these proteins to overexpression is a direct effect of their gene transcriptional activities. Expression of the erbB-1/erbB-2 genes was measured applying the quantitative RT-PCR technique in 25 uterine carcinomas, 12 normal endometria, a carcinosarcoma and a case of botryoid sarcoma of the uterine cervix. We showed that erbB-1 mRNA was overexpressed in 48% (12/25) and erbB-2 mRNA was overexpressed in 8% (2/25) of the analysed tumors. The level of expression appeared to be significantly higher in the malignant tumors as compared to the benign ones for erbB-1 and for erbB-2 (p=0.0001 and p=0.008, respectively). A significant correlation between erbB-1 overexpression and tumor differentiation was found (Spearman rank correlation test, p<0.001). Concomitant erbB-1 and erbB-2 overexpression was detected only in 1 out of 25 (4%) uterine neoplasms. erbB-1 was overexpressed in a sarcoma botryoides of the uterine cervix. Our data suggest that erbB-1/erbB-2 overexpression is a direct effect of higher than normal transcriptional activity of the encoding genes in a subset of human endometrial carcinomas.
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PMID:Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium. 1754 77


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