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ras gene mutations in Malaysian leukemia patients

Chin IY, Koh CL, Bosco JJ

Acta Haematol., 1992;87(1-2):107-8.
PMID: 1585764
Matched MeSH terms: Genes, ras/genetics*
Stability and expression of K-ras mimotopes in freeze-dried recombinant Lactococcus lactis NZ3900-fermented milk powder during storage in vacuum packaging

How YH, Teo MYM, In LLA, Yeo SK, Bhandari B, Yusof YA, et al.

J Appl Microbiol, 2024 Jul 02;135(7).
PMID: 38955370 DOI: 10.1093/jambio/lxae162

AIMS: This study aims to evaluate the storage stability of the freeze-dried recombinant Lactococcus lactis NZ3900-fermented milk powder expressing K-ras (Kristen rat sarcoma viral oncogene homolog) mimotopes targeting colorectal cancer in vacuum packaging.
METHODS AND RESULTS: The freeze-dried L. lactis-fermented milk powder stored in 4-ply retortable polypropylene (RCPP)-polyamide (PA)-aluminium (AL)-polyethylene terephthalate (PET) and aluminium polyethylene (ALPE) was evaluated throughout 49 days of accelerated storage (38°C and 90% relative humidity). The fermented milk powder stored in 4-ply packaging remained above 6 log10 CFU g-1 viability, displayed lower moisture content (6.1%), higher flowability (43° angle of repose), water solubility (62%), and survivability of L. lactis after simulated gastric and intestinal digestion (>82%) than ALPE packaging after 42 days of accelerated storage. K-ras mimotope expression was detected intracellularly and extracellularly in the freeze-dried L. lactis-fermented milk powder upon storage.
CONCLUSIONS: This suggests that fermented milk powder is a suitable food carrier for this live oral vaccine.

Matched MeSH terms: Genes, ras/genetics
Fulltext Identification of NRAS Diagnostic Biomarkers and Drug Targets for Endometrial Cancer-An Integrated in Silico Approach

Alessandro L, Low KE, Abushelaibi A, Lim SE, Cheng WH, Chang SK, et al.

Int J Mol Sci, 2022 Nov 18;23(22).
PMID: 36430761 DOI: 10.3390/ijms232214285

The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6−33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as “damaging”, and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein−protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan−Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers.

Matched MeSH terms: Genes, ras
Fulltext Predominance of G to A codon 12 mutation K-ras gene in Dukes' B colorectal cancer

Zulhabri O, Rahman J, Ismail S, Isa MR, Wan Zurinah WN

Singapore Med J, 2012 Jan;53(1):26-31.
PMID: 22252179

K-ras gene mutations in codons 12 and 13 are one of the earliest events in colon carcinogenesis.

Matched MeSH terms: Genes, ras*
Fulltext Analysis of ras gene mutations in acute myeloid leukemia by the polymerase chain reaction and oligonucleotide probes

Chin YM, Bosco JJ, Koh CL

Singapore Med J, 1992 Feb;33(1):48-50.
PMID: 1598607

In vitro deoxyribonucleic acid (DNA) amplification by the polymerase chain reaction (PCR) followed by hybridization with oligonucleotide probes were used to study ras gene mutations in acute myeloid leukemia (AML). The DNA of 30 AML patients at presentation of the disease at the University of Malaya Hospital, Kuala Lumpur were screened for ras gene mutations in codons 12, 13 and 61 of the N-ras, K-ras and H-ras genes. Four patients (13.3%) had ras gene mutations. They were all below their early thirties in age. Of the four patients with ras gene mutations, three were M3 and one was M4 according to the French American British (FAB) classification of AML.

Matched MeSH terms: Genes, ras/genetics*
Fulltext Mapping kras gene in colon cancer pathway using string and cytoscape software

Sandya Menon Prabhakaran Menon, Asita Elengoe

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):15-15.
MyJurnal

Introduction: Colorectal cancer is one of the top three most commonly occurring cancer worldwide with more than 1.8 million cases in 2018. In Malaysia, colorectal cancer is the most common cancer in males and the second most common cancer in females. Albeit being the second most common form of cancer in Malaysia, there is a lack of a formal or structured national colorectal cancer screening programme in Malaysia and it remains a low priority in healthcare planning and expenditure in Malaysia. The risk of developing colon cancer is greatly influenced by factors such as lifestyle habits, genetic inheritance, diet, weight, and exercise. Kras, the most frequently mutated oncogene in cancer, occurs in about 50 percent of colorectal cancers. Methods: This study maps the kras gene involved in colon cancer pathway, using bioinformatics applications such as STRING version 11.0 and Cytoscape version 3.7.0 to provide a clear visualisation of all the related and involved proteins and genes that interact with this kras gene in the pathway. Results: The 3391 protein interactions were assembled and visualized in y organic form. Six spe-cific non-overlapping clusters of various sizes, which emerged from the huge network of protein-interactors using MCODE version 1.32 clustering algorithm were found. Biological Networks Gene Ontology (BiNGO) was used to determine two ontologies (molecular function and biological process) involved in the protein network. Based on the resulting protein-protein network interaction map, each interaction plays an important role in the cell cycle, meta-bolic pathways and signal transduction. Conclusion: Understanding these interactions provide insight into cellular activities and thus assist in the understanding of the aetiology of disease.

Matched MeSH terms: Genes, ras
Absence of Ras, c-myc and Epidermal Growth Factor Receptor (EGFR) Mutations in Human Gliomas and its Clinical Factors Associated with Pathological Grading After Six Years of Diagnosis in North East Malaysian Patients

Ghazali MM, Mohd Zan MS, Yusof AA, Abdullah JM, Jaffar H, Ariff AR, et al.

Malays J Med Sci, 2005 Jul;12(2):27-33.
PMID: 22605955 MyJurnal

Neoplastic transformation appears to be a multi-step process in which the normal controls of cell proliferation and cell-cell interaction are lost, thus transforming normal cells into cancer. The tumorigenic process involves the interplay between oncogenes and tumour suppressor genes. In this study, we have selected the ras family, c-myc and epidermal growth factor receptor (EGFR) genes to detect whether their abnormalities are associated with the expression and progression of glioma cases in Malay patients. We have used the polymerase chain reaction-single stranded conformation polymorphism followed by direct sequencing for the study. For the ras gene family, we screened the point mutations in codons 12 and 61 of the H-, K-, and N-ras gene; for EGFR and c-myc, we analyzed only the exon 1 in glioma samples. In mutational screening analyses of the ras family, c-myc and EGFR gene, there was no mobility shift observed in any tumour analyzed. All patterns of single stranded conformation polymorphism (SSCP) band observed in tumour samples were normal compared to those in normal samples. The DNA sequencing results in all high-grade tumours showed that all base sequences were normal. All 48 patients survived after five years of treatment. In simple logistic regression analysis, variables which were found to be significant were hemiplegia (p=0.047) and response radiotherapy (p=0.003). Hemiplegics were 25 times more likely to have high pathological grade compared to those without. Patients with vascular involvement were 5.5 times more likely to have higher pathological grade. However, these findings were not significant in multivariate analysis. Patients who had radiotherapy were nearly 14 times more likely to have higher pathological grade. Multivariate analysis revealed that patients with hemiplegia were more likely to have higher pathological grade (p= 0.008). Those with higher pathological grading were 80 times more likely to have radiotherapy (p=0.004).

Matched MeSH terms: Genes, ras
Fulltext PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CA9 and VEGF, in human cancer cell lines

Shafee N, Kaluz S, Ru N, Stanbridge EJ

Cancer Lett, 2009 Sep 8;282(1):109-15.
PMID: 19342157 DOI: 10.1016/j.canlet.2009.03.004

The phosphatidylinositol 3-kinase/Akt (PI3K) pathway regulates hypoxia-inducible factor (HIF) activity. Higher expression of HIF-1alpha and carbonic anhydrase IX (CAIX), a hypoxia-inducible gene, in HT10806TG fibrosarcoma cells (mutant N-ras allele), compared to derivative MCH603 cells (deleted mutant N-ras allele), correlated with increased PI3K activity. Constitutive activation of the PI3K pathway in MCH603/PI3K(act) cells increased HIF-1alpha but, surprisingly, decreased CAIX levels. The cell-type specific inhibitory effect on CAIX was confirmed at the transcriptional level whereas epigenetic modifications of CA9 were ruled out. In summary, our data do not substantiate the generalization that PI3K upregulation leads to increased HIF activity.

Matched MeSH terms: Genes, ras