OBJECTIVETo investigate the correlation between the expression of key proto-oncogenes playing major roles in tumorigenic process and abnormal sarring.

METHODSImmunohistochemical technique was performed to detect the expressions of c-myc, c-fos and ras p21 proteins on hypertrophic scars, keloids and normal skin. Image analysis was used to compare their quantitative difference of expression.

RESULTSC-myc and c-fos expressions on the nucleus of fibroblasts of hypertrophic and keloid scars were significantly higher than normal skin controls, and there was no difference between the two lesions. Ras p21 expression was not detected on the fibroblasts of hypertrophic and keloid scars.

CONCLUSION1. c-myc and c-fos oncogenes are activated on hypertrophic and keloid scars, which may contribute to proliferation and differentiation of fibroblasts, synthesis and degradation of collagen and regulation of cytokines and induce abnormal scarring, the mechanisms of their effects remain to be further studied. 2. Ras gene may not mutate or its mutations may not play a major role in the process of abnormal scarring. 3. Only part of proto-oncogenes moderately expressed on abnormal scars. The expression of multiple oncogenes does not coexist in abnormal scars may be the cause of their less chances to induce malignant transformation.

Cicatrix, Hypertrophic ; metabolism ; Humans ; Immunohistochemistry ; Proto-Oncogene Proteins c-fos ; analysis ; Proto-Oncogene Proteins c-myc ; analysis ; Proto-Oncogene Proteins p21(ras) ; analysis ; Proto-Oncogenes

Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; classification ; drug therapy ; genetics ; pathology ; Humans ; Microsatellite Instability ; Mutation ; Polymorphism, Single Nucleotide ; Precision Medicine ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins B-raf ; genetics ; Proto-Oncogene Proteins p21(ras) ; ras Proteins ; genetics

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80%-85% of all patients with lung cancer, the majority of patients with lung cancer at the time of diagnosis is in the advanced stage. The development of target therapy based on has changed the mode of treatment in patients with advanced NSCLC. In NSCLC, epidermal growth factor receptor mutation (EGFR) fusion with echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) has been shown to be a powerful biomarker. It is well known that KRAS is also NSCLC one of the most common mutations in oncogenes, although more than 20 years ago KRAS mutation was found in NSCLC. At present, although there are many drugs used to treat NSCLC patients with KRAS mutation, there is no selective or specific inhibitor for the direct elimination of KRAS activity. NSCLC patients with KRAS mutation have poor responsiveness to most systemic therapy. However, individualized therapy for activated signaling pathways with targeted drugs has a good effect on the prognosis of NSCLC patients with KRAS mutation. In addition, the prognostic and predictive role of KRAS mutation in NSCLC remains unclear. In this review, we focus on the research progress of NSCLC with KRAS mutation, including molecular biology, clinicopathological features, prognosis and prediction of KRAS mutation, which will help to improve the understanding of NSCLC in KRAS mutation.
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Animals ; Carcinoma, Non-Small-Cell Lung ; enzymology ; genetics ; Humans ; Lung Neoplasms ; enzymology ; genetics ; Mutation ; Proto-Oncogene Proteins p21(ras) ; genetics

OBJECTIVE: To investigate the function of RAS protein on the progression of the T-ALL cell lines in vitro. METHODS: The DNA of the T-ALL cells was purified then amplified the coding regions of three RAS genes (KRAS, NRAS, HRAS) by PCR reaction. After T-A cloning, the coding regions of KRAS, NRAS and HRAS were sequenced by Sanger Sequencing. The siRNA oligonucleotides were cloned into the pSEH-361 vector, which were then packaged into retroviral together with pAMPHO and pVSVG in the HEK-293T cells. The T-ALL cells were infected with the retrovirus. The gene expressions were detected by qRT-PCR and Western blot. The T-ALL cells were stained with Annexin V-PE/7-AAD and the apoptotic cells were detected by flow cytometry. The T-ALL cells were stained with Hoechst 33258, and the cell cycle distribution was determined by flow cytometry. The expression of cleaved-Caspase 3 was stained with antibody and observed with fluorescence microscope. RESULTS: For RAS genes, beside the Loucy and the P12-ICH cells harbored KRAS c.6187G>A (p.KRAS^G12D) homozygous mutant, no missense mutation of RAS was found in other T-ALL cells genome. The pan RAS inhibitor compound 3144 showed toxicity to all tested T-ALL cells, except PEER (IC₅₀=47.916 μmol/L). Similarly, Tipifarnib induced apoptosis of multiple T-ALL cell lines except for the PEER cells (IC₅₀=94.2265 μmol/L). After KRAS knock-down, the T-ALL cells showed significant apoptosis and an arrested cell cycle. CONCLUSION The KRAS protein is vital for the progression of the T-ALL cells in vitro, it is a potential therapeutic target for T-ALL patients.
Apoptosis ; Cell Line ; Cell Proliferation ; Humans ; Mutation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Proto-Oncogene Proteins p21(ras)/genetics*

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
Humans ; Glycosylation ; Pancreatic Neoplasms/pathology* ; Adenocarcinoma ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Glycoproteins ; Mass Spectrometry ; Biomarkers/metabolism* ; Polysaccharides

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

Adenocarcinoma ; classification ; genetics ; pathology ; Adenocarcinoma, Bronchiolo-Alveolar ; genetics ; pathology ; Exons ; Humans ; Lung Neoplasms ; classification ; genetics ; pathology ; Mutation ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor ; genetics ; ras Proteins ; genetics

Female ; Genes, p53 ; immunology ; Humans ; Ovarian Neoplasms ; genetics ; pathology ; Ovary ; pathology ; Proto-Oncogene Proteins ; immunology ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Proto-Oncogenes ; immunology ; Sertoli-Leydig Cell Tumor ; genetics ; pathology ; ras Proteins ; immunology ; metabolism

PURPOSE: The products of the ras oncogene are proteins of 188 or 189 amino acids and 21,000 molecular weights, termed simply p21 proteins. But the exact roles of c-ras proteins in cell proliferation and differentiation as well as in neoplastic transformation are little understood. The purpose of this study is to investigate the function of the p21 protein to the human colon cancer cell lines according to the exposure time and dosage of p21. METHODS: The authors divided tumor cell lines into 3 groups as follows; group 1 (control, colon cancer cell lines without administration of p21 or polyclonal antibody), group 2 (administration of p21 with labelling of 3H-thymidine and leucine), group 3 (simultaneous administration of p21 protein and polyclonal antibody with labelling of 3H-thymidine and 3H-leucine). After deciding the most effective dose of p21 protein and culture time with target cells in preliminary studies, the morphologic changes of target cells with administration of p21 protein and the p21 expression and interaction with anti-p21 polyclonal antibody were examined by phase contrast microscopy each other. RESULTS: The results were obtained as follows: 1. The most effective dose of the p21 with the colon cancer cell in increase uptake of 3H-thymidine and 3H-leucine were 50 ng but there were some differences in culture time of the 3H-leucine; 96 hours in SBA-1, 72 hours in HT-29 and 120 hours in SW-1116. 2. The increase uptakes of the 3H-thymidine by the different dosage of p21, 50 ng vs 200 ng were 131% (50 ng), 160% (200 ng) in SBA-1, 203% (50 ng), 123% (200 ng) in HT-29, and 127% (50 ng), 189% (200 ng) in SW-1116; and increase uptakes of 3H-leucine were 130% (50 ng), 159% (200 ng) in SBA-1, 113% (50 ng), 165% (200 ng), and 164% (50 ng), 169% (200 ng) in SW-1116. 3. There were some cellular proliferation and morphological changes of the colon cancer cells such as ruffling of the cell membrane, vesicle formation or rounding of the cell after administration of the mutant p21, but such changes were not observed after simultaneous administration of the mutant p21 and anti-p21 polyclonal antibody. CONCLUSIONS: The role of p21 protein has not been to make manifest wholly. In our study, the p21 protein induce the cell proliferation and morphological changes.
Amino Acids ; Cell Line* ; Cell Line, Tumor ; Cell Membrane ; Cell Proliferation ; Colon* ; Colonic Neoplasms* ; DNA* ; Genes, ras ; Humans ; Microscopy, Phase-Contrast ; Molecular Weight ; Proto-Oncogene Proteins p21(ras)

OBJECTIVE: To investigate the clinical characteristics of RAS gene mutations in patients with acute myeloid leukemia (AML). METHODS: 43 myeloid gene mutations were detected using next-generation sequencing (NGS) in 180 patients with AML who were first diagnosed between May 2011 and February 2021. The molecular and clinical features of RAS gene mutations and their effects on efficacy and survival of patients were retrospectively analyzed. RESULTS: Among 180 AML patients, the proportion of mutations in RAS pathway-related genes were NRAS (14.4%), KRAS (2.2%), FLT3-ITD (13.8%), PTPN11 (7.7%), KIT (5.0%), FLT3-TKD (3.8%) and CBL (2.7%). Seventy-three (40.6%) AML patients had gene mutations associated with the RAS pathway.The number of peripheral blood white blood cells and the proportion of bone marrow primitive juvenile cells in patients with NRAS/KRAS gene mutation were higher than those of patient with RAS wild-type, the difference was statistically significant (P<0.05). NRAS/KRAS gene mutations were significantly associated with the CBL gene mutation(r=0.287). In young AML patients (age <60 years), there were no significant differences in complete response rate (CR), progression-free survival (PFS), and overall survival (OS) between patients with RAS gene mutation and those with wild-type(P>0.05). In elderly AML patients (age≥60 years), PFS and OS in RAS mutants were significantly lower than those in wild-type patients(P<0.05). CONCLUSION In AML patients, RAS gene mutation is relatively common, and RAS gene mutation is associated with clinical characteristics and efficacy of patients, and may be a molecular marker of poor prognosis for elderly AML.
Aged ; Genes, ras ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; Retrospective Studies ; fms-Like Tyrosine Kinase 3/genetics*