Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q9UIJ5 (Rec)
 58,342 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tracheal mucosa of the Syrian golden hamster has been extensively employed as a model system for respiratory tract cell renewal, injury, and carcinogenesis. However, baseline cell kinetic data are not available for normal juvenile and adolescent animals in which the mucosa and cartilage are rapidly enlarging. The objective of this research was to elucidate alterations in cell kinetics, epithelial morphology, and gene expression in the trachea of hamsters at different ages. Cell kinetics were examined by 3H-thymidine labeling indices, morphology by light and electron microscopic examination, and gene expression by slot blot analysis. Results showed that mucosal epithelium of the young and adolescent hamster undergoes cyclic necrosis and cell shedding, exposing portions of the elastic basal lamina. Epithelial shedding was associated with hyperplasia and squamous metaplasia. Additionally, the labeling indices of mucosal epithelial cells and chondroblasts also exhibited variable patterns which were associated with a cyclic pattern of expression of c-fos and c-erbB2 proto-oncogenes and epidermal growth factor receptor.
Anat Rec 1992 Jun
PMID:Cell renewal and gene expression in the trachea of hamster at different ages. 160 90

The activation of cellular proto-oncogenes is related to the genesis and progression of neoplasias. Protein growth factors and their cellular receptors have been identified as products of some proto-oncogenes. The role of epidermal growth factor receptor (EGFr) in gliomas is presented. The expression of mRNA for platelet-derived growth factor (PDGF) and PDGF B-type receptor (PDGF-rec-B) in gliomas is analyzed. Gliomas express "in vivo" PDGF.B and PDGF-rec-B mRNAs. PDGF.B mRNA levels correlate with GFAP mRNA and does not correlate with the degree of malignancy. This is in agreement with the hypothesis of an autocrine growth stimulation in gliomas. However some findings seem to indicate that in these tumors the PDGF-rec-B is preferentially expressed by vascular elements. Thus, also a paracrine loop for endothelial cell growth stimulation may be suggested in malignant gliomas.
 ...
PMID:Oncogenes and growth factors in gliomas. 209 94

The liver undergoes a biochemical and morphological circadian transformation. In this paper, we document circadian variation in the binding parameters of the hepatic epidermal growth factor receptor (EGFR). Liver membranes were prepared from ad libitum fed or fasted male CD2F1 mice killed at different circadian phases at 4 h intervals. Bmax (maximum binding) and Kd (dissociation constant) varied in a rhythmic fashion. The range of change for Bmax along the 24 h time scale was 423%. For Kd, it was 162%. Both peaked late in the dark span, and decreased late in the light span. Fasting and EGF treatment reduced Bmax and the amplitude of circadian variation.
Anat Rec 1989 Aug
PMID:Circadian variation of epidermal growth factor receptor in mouse liver. 278 86

High expression of the epidermal growth factor receptor (EGFR) has been implicated in the development of pancreatic cancer. Gefitinib is an orally active and selective EGFR-TKI (EGFR-tyrosine kinase inhibitor) that blocks signal transduction pathways responsible for the proliferation and survival of cancer cells, and other host-dependent processes promoting cancer growth. This study investigated the anticancer effect of gefitinib on human pancreatic cancer cells and the molecular mechanism involved. We first evaluated the effect of gefitinib on cell proliferation with MTT assay and the results demonstrated that gefitinib significantly inhibited the proliferation of pancreatic cancer cells. Flow cytometric analysis showed that gefitinib induced a delay in cell cycle progression and a G0/G1 arrest together with a G2/M block; these were associated with increased expression of p27(Kip1) cyclin-dependent kinase inhibitor combined with decreased expression of aurora B. Besides, luciferase reporter assay revealed that transcriptional mechanism was responsible for the down-regulation of aurora B protein by gefitinib. Overall, the results suggest a mechanistic connection among these events to provide new insights into the mechanism underlying the antiproliferative effect of gefitinib on pancreatic cancer and supplement a theory basis of gefitinib in clinical treatment of pancreatic cancer.
Anat Rec (Hoboken) 2009 Aug
PMID:Gefitinib inhibits the proliferation of pancreatic cancer cells via cell cycle arrest. 1964 12

Mutations of the KRAS, BRAF, and PIK3CA genes have been reported in colorectal cancer (CRC), associated with resistance to epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy. These reports have mainly emanated from Western countries, however, and little is known about the mutation frequencies of these genes and their prognostic value in Asian patients with CRC. In this study, we analyzed the mutation frequencies of these three genes together with EGFR, and their association with overall survival in 61 Chinese patients with metastatic CRC (mCRC). Gene mutations were examined using pyrosequencing. Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis were used to assess the prognostic significance of mutations of these four genes for patients' survival. We found that the mutations of KRAS, BRAF, PIK3CA, and EGFR were present in 12 (19.7%), 3 (4.9%), 3 (4.9%), and 0 patients, respectively. Kaplan-Meier survival analysis showed that none of these gene mutations correlated significantly with patients' overall survival. Multivariate Cox proportional hazard analysis showed only treatment regimens and age to be independent prognostic factors. Our findings indicate that EGFR signaling network genes are frequently mutated in Chinese mCRC patients, and these gene mutations do not seem to be associated with patients' overall survival.
Anat Rec (Hoboken) 2010 Sep
PMID:Gene mutations in epidermal growth factor receptor signaling network and their association with survival in Chinese patients with metastatic colorectal cancers. 2065 41

Pancreatic cancer is a devastating malignancy, characterized by intrinsic or acquired resistance to conventional chemotherapies. Recent evidences suggest an involvement of tyrosine kinase pathway in the regulation of multidrug resistance (MDR) protein gene expression. The aim of this study was to test whether gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor could regulate the MDR protein gene expression and sensitize the resistant cancer cells to chemotherapy. The gene expression of MDR proteins (MRP1, MRP2, MRP3, and PGP) were evaluated by quantitative RT-PCR, and expression levels of various tyrosine kinases were investigated by quantitative RT-PCR and Western blot in pancreatic cancer cell line. MTT assay was used for evaluating the effect of chemotherapeutic agents. Chemotherapeutics induced drug resistance by regulating the gene expression of MDR proteins (MRP1, MRP2, and MRP3), and increased the gene expression of RAF1/ERK and the phosphorylation of ERK in pancreatic cancer Bxpc-3 cells. Gefitinib caused an inhibition of p-ERK tyrosine kinase activation in a dose-dependent manner, and reversed gemcitabine-induced RAF1/ERK gene expression and p-ERK activation. In addition, a reversal of MDR proteins gene expression was achieved by gefitinib, which sensitized resistant cells to gemcitabine. This study demonstrated that MDR of Bxpc-3 cell is involved in the RAF1/ERK tyrosine kinase pathway. Gefitinib reverses the MDR protein gene expression and restores sensitivity of resistant cells to gemcitabine via RAF1/ERK signaling pathway. Combination of gefitinib with conventional chemotherapeutic agents may offer a new approach for the treatment of patients with pancreatic cancer.
Anat Rec (Hoboken) 2012 Dec
PMID:Reversal of multidrug resistance by gefitinib via RAF1/ERK pathway in pancreatic cancer cell line. 2290 45

Although several studies detected the BRCA1 germ-line mutations in Chinese women with familial breast cancer, most of them did not employ conventional full gene sequencing, especially in eastern China. In addition, the clinicopathological features of BRCA1-associated breast cancer in Chinese women were not well investigated. In this study, we screened the complete coding regions and exon-intron boundaries of BRCA1 by polymerase chain reaction (PCR)-sequencing assay. Immunohistochemistry analyses were performed on tumor samples to detect the expression of estrogen receptor (ER), progesterone receptor (PR), P53, and human epidermal growth factor receptor-2 (HER-2). Breast cancer patients having one or more affected relatives referred from the Zhejiang Cancer Hospital, eastern China during 2008-2011 were selected for the study. A total of 62 familial breast cancer patients received the BRCA1 germ-line mutation screening. Five deleterious mutations were detected in this cohort. The mutation rate was 11.3% (7/62). We found two novel mutations (3414delC and 5,280 C > T) and two recurrent mutations (5,273 G > A and 5589del8). BRCA1 mutation tumors tended to be negative for ER, PR, and HER-2, and exhibited high histological grade compared with tumors without BRCA1 mutations. Our study suggests that recurrent mutations may exist in eastern Chinese women with familial breast cancer and PCR-sequencing assay is a useful tool to screen these mutations. It also suggests that BRCA1-associated breast cancers in Chinese women exhibit an aggressive phenotype.
Anat Rec (Hoboken) 2013 Feb
PMID:BRCA1 germ-line mutations and tumor characteristics in eastern Chinese women with familial breast cancer. 2317 48

The usefulness of various pathways inhibitors, Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), Infliximab, a monoclonal antibody which blocks the tumor necrosis factor-a (TNF-a), Erlotinib, a tyrosine protein kinase inhibitor of the epidermal growth factor receptor (EGFR), Metformin, an activator of AMP-activated protein kinase enzyme (AMPK) and vascular permeability reducers were explored in an ovarian hyperstimulation syndrome (OHSS) rat model. Sixty-three female Wistar rats were randomly divided in seven groups. The control group received saline, while the OHSS group received recombinant -- follicle-stimulating hormone (rec-FSH) for four consecutive days. The other five groups received rec-FSH for 4 d and Everolimus daily, Infliximab once, Erlotinib daily, Metformin daily and Vitamin C daily, respectively. All groups received human chorionic gonadotropin (hCG) at the fifth day. The efficacy of Everolimus administration for various intervals was also explored. Significantly reduced ovarian weight was observed in the Everolimus group (rec-FSH + hCG + mTOR inhibitor) compared to the OHSS group (p < 0.001). The Everolimus group also showed the lowest progesterone (PRG) concentration (p = 0.007). The Erlotinib group (rec-FSH + hCG + EGFR inhibitor) presented with the lowest graafian follicle number, while the Everolimus group was characterized by the lowest corpus luteum number. The vascular permeability and the estradiol levels did not differ between groups. Finally, the Everolimus intra-comparison showed no difference in all measured outcomes. Studying the different pathways linked to vascular endothelial growth factor (VEGF) pathway, we conclude that targeting mTOR pathways is beneficial for reducing ovarian weight and PRG levels in an OHSS animal model.
 ...
PMID:Everolimus, an mTOR pathway inhibitor, is highly successful on ovarian hyperstimulation syndrome by reducing ovarian weight and progesterone levels: a preclinical experimental randomized controlled study. 2617 31