Useful Therapeutic Target (useful + therapeutic_target)

Distribution by Scientific Domains

Selected Abstracts

Stat3 is required for anchorage-independent growth and metastasis but not for mammary tumor development downstream of the ErbB-2 oncogene,

Isaia Barbieri
Abstract The oncogenic transcription factor Stat3 is constitutively active in a high percentage of human tumors including mammary adenocarcinomas and is reported to participate in the ErbB-2 oncogene signaling. In order to assess the role of signal transducer and activator of transcription 3 (Stat3) in mammary tumorigenesis downstream of ErbB-2, we generated mice expressing the activated rat ErbB-2 (neu) but lacking Stat3 in the mammary epithelium. Stat3 is apparently not required for neu-driven mammary tumorigenesis as tumors developed similarly in both Stat3-sufficient and Stat3-deficient glands. However, short hairpin RNA (shRNA)-mediated Stat3 silencing in a neu-overexpressing tumor-derived cell line completely abolished both neu-driven anchorage-independent growth and lung metastasis. Our data suggest that Stat3 might be a useful therapeutic target in breast tumors showing amplification and/or overexpression of the ErbB-2 oncogene, which normally display aggressive, metastatic behavior. 2009 Wiley-Liss, Inc. [source]

Overexpression of yes-associated protein contributes to progression and poor prognosis of non-small-cell lung cancer

CANCER SCIENCE, Issue 5 2010
Yang Wang
Yes-associated protein (YAP), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene. This study aimed to assess the clinical significance and biological functions of YAP in non-small-cell lung cancer (NSCLC). We investigated the expression of YAP in 92 cases of NSCLC tissue by immunohistochemistry and found that YAP was expressed in 66.3% (61/92) cases and predominantly presented in the nucleus. The expression of YAP in NSCLC was significantly correlated with p-TNM stage (P = 0.0037) and lymph node metastasis (P = 0.0093). Importantly, YAP expression was associated with short overall survival. Further study in NSCLC cell lines in which YAP was either overexpressed or depleted confirmed that YAP markedly promoted cell proliferation and invasion. These results indicate that YAP plays an important role in NSCLC and might be a useful therapeutic target of NSCLC. (Cancer Sci 2010; 101: 1279,1285) [source]

Long-term effect of ghrelin on nutritional status and functional capacity in the elderly: a population-based cohort study

Mateu Serra-Prat
Summary Background, Ghrelin stimulates GH release and hunger at a central level. Ghrelin declines with age, which may be partially responsible for functional impairment and frailty. Objective, To describe the evolution of nutritional status and functional capacity of noninstitutionalized old people over a 2-year period, as well as to evaluate the relationship between ghrelin and long-term changes in nutritional and functional status in this population. Design, A population-based cohort study was designed in which 313 randomly selected persons, 70 years old or older, were followed for a 2-year period. Functional (Barthel and Guralnik scores and hand grip) and nutritional (MNA-SF, weight and BMI) assessments were performed during basal and 2-year follow-up visits. Ghrelin and hormonal components of the gonadotrophe and somatotrophe axis were determined. Results, During follow-up, 13% of men and 20% of women showed a >5% weight loss, and the nutritional status of 18% of men and 39% of women deteriorated. Men lost 121% and women lost 97% of their initial hand grip strength. In men, low basal ghrelin levels were associated with higher weight loss and poorer hand grip but not with the MNA-SF measure, whereas in women, low basal ghrelin levels were associated with a decline in nutritional status (MNA-SF) but not with weight loss and hand grip decline. Conclusion, Low ghrelin levels have been related to worsening nutritional status in a 2-year follow-up period in people 70 years old or older, which suggests this hormone could become a useful therapeutic target in the elderly. [source]

Glaucomatous optic nerve injury involves early astrocyte reactivity and late oligodendrocyte loss

GLIA, Issue 7 2010
Janice L. Son
Abstract Glaucoma, a neurodegenerative disease affecting retinal ganglion cells (RGC), is a leading cause of blindness. Since gliosis is common in neurodegenerative disorders, it is important to describe the changes occurring in various glial populations in glaucoma animal models in relation to axon loss, as only changes that occur early are likely to be useful therapeutic targets. Here, we describe changes occurring in glia within the myelinated portion of the optic nerve (ON) in both DBA/2J mice and in a rat ocular hypertension model. In both glaucoma animal models, we found only a modest loss of oligodendrocytes that occurred after axons had already degenerated. In DBA/2J mice there was proliferation of oligodendrocyte precursor cells (OPCs) and new oligodendrocyte generation. Activation of microglia was detected only in highly degenerated DBA/2J ONs. In contrast, a large increase in astrocyte reactivity occurred early in both animal models. These results are consistent with astrocytes playing a prominent role in regulating axon loss in glaucoma. 2010 Wiley-Liss, Inc. [source]

The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research,

CANCER, Issue 7 2002
Jose Luis Perez-Gracia M.D.
Abstract The investigation of genetic alterations that may be related to the prognosis of patients with malignant disease has become a frequently used strategy in recent years. Although some conclusions have been reached in certain studies, the complexity and the multifactorial nature of most neoplastic diseases makes it difficult to identify clinically relevant information, and the results of some studies have been of borderline significance or have been conflicting. In contrast, the identification and the study of patients or families with very characteristic phenotypes have yielded outstanding results in the identification of the genetic characteristics underlying such phenotypes. Although, in most cases, the individuals who are selected for these types of studies are characterized by a negative phenotype (i.e., individuals who are at increased risk for developing a specific disease), a few studies have been directed toward individuals with phenotypes that imply an unusually good prognosis (i.e., individuals who present with a decreased risk for developing specific diseases despite an important exposure to well-known risk factors). Therefore, it seems logical to develop this strategy further as a valid methodology for the study of other diseases, such as cancer. The study of individuals with phenotypes that imply an extremely good prognosis, such as long-term survivors of theoretically incurable malignancies or individuals who seem to be protected against a certain neoplastic disorder despite having a markedly increased risk for its development, may unveil genetic alterations that explain such characteristic phenotypes and may provide potentially useful therapeutic targets against these diseases. Cancer 2002;95:1605,10. 2002 American Cancer Society. DOI 10.1002/cncr.10877 [source]