1,720,987 research outputs found
Role of Nerve Growth Factor (NGF) and its receptors in cancer growth: an in vitro and in vivo study.
No full textEFFECTS OF GW441756 ON SARCOMA CELL LINES EXPRESSING NGF RECEPTOR TYROSINE KINASE A (TrKA)
No full textA NOVEL LOCALIZATION OF LOW-AFFINITY NERVE GROWTH FACTOR RECEPTOR (P75) IN NORMAL AND NEOPLASTIC HUMAN PROSTATE. AN IMMUNOHISTOCHEMICAL AND IMMUNOCYTOCHEMICAL STUDY
No full textBackground and Aim: The biological role of never growth
factor and its p75 receptor in prostate cancer is still
controversial. The aim of this work was to evaluate the
localization of p75 in normal and neoplastic human prostate
as prognostic marker.
Patients and Methods: Human samples of normal and
prostate cancer were analyzed at light and ultrastructural
levels (transmission electron microscopy, TEM). At the light
microscopical level, p75 immunoreactivity (IR) in normal
human prostate was restricted to the basal cells of the acini, at
epithelial-stromal junction. This result was confirmed by
TEM. Normal prostatic stromal cells were p75 negative,
except for nerves and blood vessels. Prostatic intraepithelial
neoplasia showed a relevant proliferation of the epithelial
compartment, inclusive of the basal cells that remained p75
IR. However, samples of adenocarcinoma, medium to high
grade neoplasia, showed different patterns of p75 localization.
In fact, while basal cells of the epithelial compartment
became progressively p75 negative, a novel strong p75 IR
was detected in the stromal compartment, adjacent to the
neoplastic acini. Ultrastructural analysis showed that the
stromal p75 IR was localized on plasma membrane of smooth
muscle cells. Other stromal cells were p75 negative. The
amount of p75 IR in the stroma seems to be positively
correlated to Gleason score.
Results: Our study shows a novel morphological
localization of p75 in the stroma of prostate tumour. The
positive correlation of this stromal localization with the
tumour malignancy suggests a progressive dedifferentiation
of the smooth muscle cells that are normally p75 negative.
This dedifferentiation of neoplastic smooth muscle cells
around the neoplastic acini could be relevant for metastatic
invasion of the stroma.
Conclusion: Our findings of p75 in the stromal
compartment of prostate cancer shows that it could be a novel
marker for a better definition of the prostatic cancer
malignancy and prognosis
The tricyclic antidepressant amitriptyline is cytotoxic to HTB114 human leiomyosarcoma and induces p75NTR-dependent apoptosis.
No full textNerve growth factor (NGF) receptors, TrKA and p75, are being investigated in cancer therapy. Our previous data show that, in HTB114 uterine leiomyosarcoma cells, p75-dependent apoptosis is inducible by cytotoxic drugs and can suppress nerve growth factor-dependent growth. Although amitriptyline can kill cancer cells and bind TrKA/B, its effects on p75-dependent apoptosis are unknown. The aim of this paper was to evaluate the antineoplastic potential of amitriptyline, and the role of p75-dependent apoptosis in the chemoresistant uterine HTB114 leiomyosarcoma. Using proliferation assays and fluorescence-activated cell sorting analysis, we found that amitriptyline caused a marked reduction in HTB114 cell viability, associated with the parallel upregulation of p75 expression. This converted the TrKA-proliferating cells into TrKA/p75, leading to downregulation of TrKA-prosurvival signaling (AKT) and activation of p75-dependent apoptosis (through caspase-3). Overall, we provide novel evidence that HTB114 uterine leiomyosarcoma cells are highly sensitive to amitriptyline, supporting the role of p75-dependent apoptosis as a novel cytotoxic mechanism of this drug and of p75 as an inducible stress receptor and a novel target in clinical oncology
A role for NGF and its receptors TrKA and p75NTR in the progression of COPD
No full textNerve growth factor and its receptors, TrkA and p75NTR, are involved in inflammation and airways diseases, but their role in chronic obstructive pulmonary disease is still unclear and not well investigated. our data indicate the stage dependent variation of nerve growth factor and its receptors in chronic obstructive pulmonary disease progression. In fact, for the first time, this study evaluates the presence of nerve growth factor and its receptors in serum and in peripheral blood mononuclear cells of patients with different stages of chronic obstructive pulmonary disease compared to healthy subjects, non-smoker and current smoker. Serum monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-10 and forced expiratory volume in 1 s were also analyzed. Compared to healthy subjects, chronic obstructive pulmonary disease patients presented a staging-dependent increase in serum nerve growth factor, negatively correlated to forced expiratory volume in 1 s and positively to monocyte chemoattractant Protein-1. The percentage of p75NTR+ peripheral blood mononuclear cells increased in early stages of chronic obstructive pulmonary disease (I-II), while TrKA+ peripheral blood mononuclear cells increased in late stages (III-IV). Our data demonstrate the involvement and modulation of nerve growth factor and its receptors in chronic obstructive pulmonary disease and in its staging
LY294002 induces in vitro apoptosis and overexpression of p75NTR in human uterine leiomyosarcoma HTB 114 cells
No full textUterine leiomyosarcoma is a severe neoplasia resistant to conventional therapies. In previous studies, we have shown that human SK-UT-1 (ATCC HTB114) uterine leiomyosarcoma cell line secretes nerve growth factor (NGF) and expresses its receptors tyrosine kinase A receptor (TrKA) and low affinity nerve growth factor receptor (p75NTR). Furthermore, we have demonstrated that direct chemical inhibition or IgG neutralization of TrKA receptor induce apoptosis through p75NTR. In the present study, HTB114 cells were exposed to the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 with and without β-NGF: apoptosis, cell cycle, activation of caspase-3 and protein kinase B (AKT) and TrKA/p75NTR phenotypic expression were evaluated. According to the type of exposure, LY294002 not only induced a relevant increase in apoptosis, but also produced a novel and unexpected phenotypic modulation of the NGF receptors with a downregulation of TrKA and an upregulation of p75NTR. This latter increase enhanced HTB114 apoptosis. Our study confirms that the interference on NGF transduction is a promising therapeutical approach in uterine leiomyosarcoma
Modulation of Nerve Growth Factor receptors in human monocytes and their influence in pulmonary inflammatory diseases
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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