Study on expression and clinical significance of ARD1 in nasopharyngeal carcinoma / 重庆医学

Objective To detect and explore the expression of ARD1 and its clinical significance in the nasopharyngeal in-flammatory tissue ,nasopharyngeal carcinoma group and its subgroups .Methods Expression of ARD1 in nasopharyngeal carcinoma (56 cases) and nasopharyngeal inflammatory tissue (20 cases) were detected by immunohistochemical staining SP ,the correlation between the expression of ARD1 and age ,gender ,histological grade ,TNM clinical stage and tumor metastasis were analysed . Results The positive expression rate of ARD1 were 10 .00% (2/20) ,55 .35% (31/56) in the nasopharyngeal inflammatory tissue and nasopharyngeal carcinoma ,respectively .The expression level of ARD1 in nasopharyngeal carcinoma was significantly higher than in the nasopharyngeal inflammatory tissue ,the difference was significant (P 0 .05) .Conclusion The expression of ARD1 is high in nasopharyngeal carcinoma ,and has a closely correlation with diffferentiation level of tumor ,which suggested that ARD1 may be involved in the the occurrence and development of nasopharyngeal carcinoma .However ,further research needs to be done for its mechanism in the nasopharyngeal car-cinoma .

HIF-1α pathway: role, regulation and intervention for cancer therapy

Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O2 levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.

Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions

Hypoxia-inducible factor (HIF-1) is an oxygen-dependent transcriptional activator, which plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and one of three subunits (HIF-1alpha, HIF-2alpha or HIF-3alpha). The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, and phosphorylation. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, and p300/CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)- mediated ubiquitin-proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, in the hypoxia condition, HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation/survival, and glucose/iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1a itself or HIF-1alpha interacting proteins inhibit tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. This review summarizes the molecular mechanism of HIF-1a stability, the biological functions of HIF-1 and its potential applications of cancer therapies.

HIF-1alpha: a Valid Therapeutic Target for Tumor Therapy / Journal of the Korean Cancer Association, 대한암학회지

Hypoxia plays a major role in the induction of angiogenesis during tumor development. One mechanism by which tumor cells respond to a reduced oxygen level is via the activation of hypoxia-inducible factor-1 (HIF-1). HIF-1 is an oxygen-dependent transcriptional activator that plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and the highly regulated HIF-1 alpha subunits. The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, phosphorylation and sumoyaltion. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, SUMO and p300/ CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)-mediated ubiquitin/proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, under the hypoxia condition, the HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Under hypoxic conditions, HIF-1 eventually acts as a master regulator of numerous hypoxia-inducible genes. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation and survival, and to glucose and iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1alpha itself or the blocking of HIF-1alpha interacting proteins inhibits tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. Therefore, this review summarizes the molecular mechanism of HIF-1alpha stability, the biological functions of HIF-1 and its potential applications for cancer therapies.