Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

The gene is frequently mutated and abnormally activated in many cancers，and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors，which can be one of the key targets for anti-tumor therapy. gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways，such as lipid synthesis pathways and degradation pathways. Similarly，lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and ，to provide insight in therapeutic strategies of lipid metabolism for -driven tumors.
Genes, ras ; Humans ; Lipid Metabolism/genetics* ; Neoplasms/genetics* ; Signal Transduction ; ras Proteins/metabolism*

In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib.
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Adenocarcinoma ; drug therapy ; enzymology ; genetics ; pathology ; Adenocarcinoma of Lung ; Aged ; Antineoplastic Agents ; therapeutic use ; Humans ; Indoles ; therapeutic use ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Male ; Mutation ; Proto-Oncogene Proteins p21(ras) ; genetics ; metabolism ; Quinolines ; therapeutic use

BACKGROUND: The incidence of lung cancer is gradually increased, and the cystic fibrosis transmembrane conductance regulator (CFTR) has recently demonstrated to have an implication in the deoncogenesis and malignant transformation of many types of cancers. The aim of this study is to investigate impacts of CFTR on the malignant features of lung adenocarcinoma A549 cells. METHODS: The capacity of cell proliferation, migration, invasion and clonogenicity of non-small cell lung cancer A549 cells were detected by CCK8 cell proliferation assay, cell scratch assay, Transwell cell invasion assay and clone formation assay, respectively. Meanwhile, the effect of CFTR gene on the expression of cancer stem cell related transcriptional factors was also detected by immunoblotting (Western blot) assay. RESULTS: An overexpression of CFTR gene in A549 cells significantly inhibited the malignant capacity of A549 cells, including potencies of cell proliferation, migration, invasion and colony formation; while knockdown of CFTR gene expression by RNA interference in A549 cells resulted in an opposite effect seen in above cells overexpressing CFTR gene. Mechanistically, immunoblotting assay further revealed that the ectopic expression of CFTR gene led an inhibitory expression of stem cell-related transcriptional factors SOX2 and OCT3/4, and cancer stem cell surface marker CD133 in A549 cells, while a knockdown of CFTR expression yielded a moderately increased expression of these gene. However, an alteration of CFTR gene expression had neither effect on the expression of putative lung cancer stem cell marker aldehyde dehydrogenase1 (ALDH1), nor the frequency of ALDH1A-positive cells in A549 cells, as ascertained by the immunoblotting assay and cytometry analysis, respectively. CONCLUSIONS The CFTR exhibited an inhibitory role in the malignancy of lung adenocarcinoma A549 cells, suggesting that it may be a novel potential target for lung cancer treatment. However, its functions in other lung adenocarcinoma cell lines and its underlying molecular mechanisms require further investigation.
A549 Cells ; Adenocarcinoma ; pathology ; Adenocarcinoma of Lung ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; metabolism ; Humans ; Lung Neoplasms ; pathology ; Mutation ; Neoplasm Invasiveness ; Neoplastic Stem Cells ; pathology ; Proto-Oncogene Proteins p21(ras) ; genetics

OBJECTIVETo investigate the role of Rheb (mTOR activator) in AML development by measuring Rheb expression in bone marrow of adult AML patients and in AML cell line HL-60.

METHODSReal-time PCR assay was used to measure the Rheb mRNA expression in 27 AML patients and 29 ITP patients as control. The relationship between Rheb mRNA expression and age, AML subtype, fusion gene, splenomegaly, hepatomegaly and survival of AML patients was analyzed and compared. In addition, HL-60 cell line over-expressing Rheb was established, and the HL-60 cells and HL-60 cells with overexpression of Rheb were treated with Ara-C of different concentrations, the proliferation level was detected by CCK-8 method, and the IC50 was calculated.

RESULTSThe mRNA level of Rheb in AML patients was similar to that in ITP patients (control). Interestingly, higher expression of Rheb was associated with better survival and was sensitive to Ara-C treatment. However, the expression level of Rheb was not associated with age, AML subtype, fusion gene, and hepatomegaly of patients. Lower expression level of Rheb was associated with splenomegaly. In vitro analysis of HL-60 line indicated that overexpression of Rheb could increased the cell sensitivity to Ara-C treatment (IC50=0.54 µmol/L) and caused HL-60 cell apoptosis.

CONCLUSIONThe lower Rheb expression is a poor prognostic indicator for AML patients, which is associated with AML splenomegaly, the patients and HL-60 cells with low expression of Rheb are insensitive to Ara-C treatment.

Adult ; Apoptosis ; Bone Marrow ; metabolism ; Cytarabine ; pharmacology ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; pathology ; Monomeric GTP-Binding Proteins ; genetics ; metabolism ; Neuropeptides ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Ras Homolog Enriched in Brain Protein ; Real-Time Polymerase Chain Reaction ; Spleen ; pathology

BACKGROUNDCervical cancer is the second most common cancer of woman in the world, and human papillomavirus (HPV) infection plays an important role in the development of most of the cases. IκB kinase β (IKKβ) is a kinase-mediating nuclear factor kappa B (NF-κB) activation by phosphorylating the inhibitor of NF-κB (IκB) and is related by some diseases caused by virus infection. However, there is little known about the correlation between IKKβ and HPV infection in cervical cancer. This study aimed to investigate the expression of IKKβ protein in cervical cancer tissues and effects of inflammation on HPV positive or negative cervical cancer cells through detecting the expression of IKKβ, IκBα, p53, and p21 proteins after treated with lipopolysaccharide (LPS) to mimic bacterial infection. We also examined the effects of LPS on cervical cancer cells after blocking IKKβ with pharmacological inhibitor.

METHODSThirty-six matched specimens of cervical cancer and adjacent normal tissues were collected and analyzed in the study. The expression of IKKβ in the tissue specimens was determined by immunohistochemical staining. In addition, Western blot was used to detect the expression level changes of IKKβ, IκBα, p53, and p21 after LPS stimulated in the HPV16+ (SiHa) and HPV16- (C33A) cervical cancer cell lines. Furthermore, the effects of IKKβ inhibitor SC-514 on LPS-induced expression change of these proteins were investigated.

RESULTSThe expression of IKKβ was higher in cervical cancer than adjacent normal tissues, and there was no significant difference between tumor differentiation, size, and invasive depth with IKKβ expression. The LPS, which increased the expression level of IKKβ protein but decreased in the IκBα, p53 and p21 proteins, was illustrated in HPV16+ (SiHa) but not in HPV16- (C33A) cells. Moreover, IKKβ inhibitor SC-514 totally reversed the upregulation of IKKβ and downregulation of p53 and p21 by LPS in SiHa cells.

CONCLUSIONSIKKβ may mediate the downregulation of p53 and p21 by LPS in HPV16+ cervical cancer cells.

Cell Line, Tumor ; Down-Regulation ; drug effects ; Female ; Human papillomavirus 16 ; pathogenicity ; Humans ; I-kappa B Kinase ; antagonists & inhibitors ; metabolism ; Lipopolysaccharides ; pharmacology ; Proto-Oncogene Proteins p21(ras) ; metabolism ; Thiophenes ; pharmacology ; Tumor Suppressor Protein p53 ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; virology

EGFR and KRAS mutations are two of the most common mutations that are present in lung cancer. Screening and detecting these mutations are of issue these days, and many different methods and tissue samples are currently used to effectively detect these two mutations. In this study, we aimed to evaluate the testing for EGFR and KRAS mutations by pyrosequencing method, and compared the yield of cytology versus histology specimens in a consecutive series of patients with lung cancer. We retrospectively reviewed EGFR and KRAS mutation results of 399 (patients with EGFR mutation test) and 323 patients (patients with KRAS mutation test) diagnosed with lung cancer in Konkuk University Medical Center from 2008 to 2014. Among them, 60 patients had received both EGFR and KRAS mutation studies. We compared the detection rate of EGFR and KRAS tests in cytology, biopsy, and resection specimens. EGFR and KRAS mutations were detected in 29.8% and 8.7% of total patients, and the positive mutation results of EGFR and KRAS were mutually exclusive. The detection rate of EGFR mutation in cytology was higher than non-cytology (biopsy or resection) materials (cytology: 48.5%, non-cytology: 26.1%), and the detection rate of KRAS mutation in cytology specimens was comparable to non-cytology specimens (cytology: 8.3%, non-cytology: 8.7%). We suggest that cytology specimens are good alternatives that can readily substitute tissue samples for testing both EGFR and KRAS mutations. Moreover, pyrosequencing method is highly sensitive in detecting EGFR and KRAS mutations in lung cancer patients.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/genetics/metabolism/*pathology ; DNA Mutational Analysis ; DNA, Neoplasm/chemistry/metabolism ; Female ; Humans ; Lung Neoplasms/genetics/metabolism/*pathology ; Male ; Middle Aged ; Mutation ; Receptor, Epidermal Growth Factor/*genetics/metabolism ; Retrospective Studies ; ras Proteins/*genetics/metabolism

OBJECTIVETo explore the role of RAS/PI3K pathway in the impairment of long-term potentiation (LTP) induced by acute aluminum (Al) treatment in rats in vivo.

METHODSFirst, different dosages of aluminum-maltolate complex [Al(mal)3] were given to rats via acute intracerebroventricular (i.c.v.) injection. Following Al exposure, the RAS activity of rat hippocampus were detected by ELISA assay after the hippocampal LTP recording by field potentiation technique in vivo. Second, the antagonism on the aluminum-induced suppression of hippocampal LTP was observed after the treatment of the RAS activator epidermal growth factor (EGF). Finally, the antagonism on the downstream molecules (PKB activity and the phosphorylation of GluR1 S831 and S845) were tested by ELISA and West-blot assays at the same time.

RESULTSWith the increasing aluminum dosage, a gradually decreasing in RAS activity of the rat hippocampus was produced after a gradually suppressing on LTP. The aluminum-induced early suppression of hippocampal LTP was antagonized by the RAS activator epidermal growth factor (EGF). And the EGF treatment produced changes similar to those observed for LTP between the groups on PKB activity as well as the phosphorylation of GluR1 S831 and S845.

CONCLUSIONThe RAS→PI3K/PKB→GluR1 S831 and S845 signal transduction pathway may be involved in the inhibition of hippocampal LTP by aluminum exposure in rats. However, the mechanisms underlying this observation need further investigation.

Aluminum ; toxicity ; Animals ; Epidermal Growth Factor ; metabolism ; Hippocampus ; drug effects ; metabolism ; Injections, Intraventricular ; Long-Term Potentiation ; drug effects ; Male ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Rats ; Receptors, AMPA ; metabolism ; Signal Transduction ; drug effects ; ras Proteins ; metabolism

Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein malfunction and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracellular signaling pathways that can protect against or delay this pathogenic process. Here, we show that the DYNC1I1 deficiency, a neuron-specific dynein intermediate chain, causes neuronal atrophy in primary hippocampal neurons. With this cellular model, we are able to find that activation of RAS-RAF-MEK signaling protects against neuronal atrophy induced by DYNC1I1 deficiency, which relies on MEK-dependent autophagy in neuron. Moreover, we further reveal that BRAF also protects against neuronal atrophy induced by mitochondrial impairment. These findings demonstrate protective roles of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic target for clinical intervention.
Animals ; Cell Line ; Cytoplasmic Dyneins ; genetics ; metabolism ; Hippocampus ; metabolism ; pathology ; MAP Kinase Kinase Kinases ; genetics ; metabolism ; MAP Kinase Signaling System ; Mice ; Mice, Knockout ; Neurodegenerative Diseases ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; ras Proteins ; genetics ; metabolism

No abstract available.
Base Sequence ; Child, Preschool ; DNA/chemistry/metabolism ; Female ; Humans ; Mutation ; Nevus, Pigmented/diagnosis/*genetics ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins p21(ras)/*genetics ; Republic of Korea ; Skin/pathology ; Skin Neoplasms/diagnosis/*genetics ; Syndrome