Cancer Signaling, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Published: September 2010
AI Article Synopsis
Article Abstract
The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is frequently disrupted in cancer and implicated in multiple aspects of tumor growth and survival. In addition, increased activity of this pathway in cancer is associated with resistance to chemotherapeutic agents. Therefore, it has been hypothesized that PI3K inhibitors could help to overcome resistance to chemotherapies. We used preclinical cancer models to determine the effects of combining the DNA-damaging drug doxorubicin with GDC-0941, a class I PI3K inhibitor that is currently being tested in early-stage clinical trials. We found that PI3K inhibition significantly increased apoptosis and enhanced the antitumor effects of doxorubicin in a defined set of breast and ovarian cancer models. Doxorubicin treatment caused an increase in the amount of nuclear phospho-Akt(Ser473) in cancer cells that rely on the PI3K pathway for survival. This increased phospho-Akt(Ser473) response to doxorubicin correlates with the strength of GDC-0941's effect to augment doxorubicin action. These studies predict that clinical use of combination therapies with GDC-0941 in addition to DNA-damaging agents will be effective in tumors that rely on the PI3K pathway for survival.
Ethnopharmacological Relevance: Acne vulgaris is a common skin disease affecting the pilosebaceous unit, in which abnormal sebum secretion and inflammation play crucial roles. The traditional Chinese medicine Tanreqing has been utilized in dermatology to effectively treat various diseases. However, its effects and underlying mechanisms in acne vulgaris remain unclear.
In clinical settings, glioma patients often develop secondary resistance to first-line chemotherapy drugs. Vincristine has been reported for its application in cancer chemotherapy, but its molecular mechanism of action remains unclear. This study aimed to identify potential targets of vincristine in glioma using network pharmacology and to experimentally validate the possible molecular mechanisms against glioma.
Decidualization of endometrial stromal cells is a prerequisite for successful embryo implantation and early pregnancy. Decidualization dysregulation results in implantation failure. In our previous study, we reported that PAI-1 is abnormally downregulated in the endometrial tissue samples of patients with recurrent implantation failure.
Department of Photochemistry (Synthetic Unit), Chemical Industries Research Institute, National Research Centre, Cairo 12622, Egypt. Electronic address:
An efficient synthesis of a series of uracil analogous was performed to obtain new potential anticancer agents. The cytotoxic effect of the synthesized derivatives was assessed in vitro against three cancer cell lines, namely hepatic cancer (HepG-2), colon cancer (HCT-116), and breast cancer (MCF-7). Among the tested compounds, 5, 11 and 15 stood as potent uracil derivatives with pan cytotoxicity against the 3 cell lines out-performing the reference compound 5-FU.
Epithelial-mesenchymal transition (EMT) is a critical stage in the metastasis of gastric cancer (GC). Further clarification of the EMT process in GC is still needed. This study examined the effects of the NEDD4L/BICC1 axis on GC proliferation and the EMT process.
