Advanced searches left 3/3

KRAS - DOAJ

Summarized by Plex Scholar
Last Updated: 11 June 2022

* If you want to update the article please login/register

Differential Effects of Dietary Macronutrients on the Development of Oncogenic KRAS-Mediated Pancreatic Ductal Adenocarcinoma

"Obesity is a modifiable risk factor for pancreatic cancer," Pancreatic cancer's modifiable risk factor. " Mice carrying mutant KRAS are extremely vulnerable to obesogenic high-fat diet deficiencies leading to PDAC with high penetrance, according to Corcororating this epidemiological research. Using a mouse model that demonstrates an endogenous level of mutant KRAS G12D specifically in pancreatic acinar cells, we compared the differences between a high-carbohydrate diet, an HFD, and a high-protein diet in PDAC development in this research. Our analysis showed that although chronic HFD has lower tumorigenic capacity than chronic HFD, chronic HCD has promoted acinar-to-ductal hypoplasia and pancreatic intraepithelial neoplasia lesions with elevated inflammation, fibrosis, and cell proliferation in Kras G12D/+ mice with elevated inflammation, fibrosis, and cell proliferation in comparison to a normal diet. "Ablation of pancreatic acinar cell cyclooxygenase 2 in Kras G12D/+ mice ameliorated HCD's adverse effects, suggesting that diet-induced pancreatic inflammation is crucial for promoting oncogenic KRAS-mediated neoplasia. ".

Source link: https://doi.org/10.3390/cancers14112723


Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer

Pancreatic cell transplantation from the earliest stages of carcinogenesis is observed in > 95% of pancreatic ductal adenocarcinoma cases. " In PDAC patients compared to healthy individuals, the circulating rates of LAMC2, TNC, and PTX3 were significantly higher. According to TNC, the Receiver Operating Characteristics curve displayed good sensitivity and specificity for LAMC2 and PTX3, respectively, but not for TNC, and patients with high incidence of LAMC2 had significantly shorter overall survival. ".

Source link: https://doi.org/10.3390/cancers14112653


Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay

"KRAS is one of the most abundantly mutated oncogenes in cancer, and finding mutant KRAS with drugs has been difficult. " However, the recent FDA acceptance of the KRAS G12C specific inhibitor sotorasib has breathed new life into the quest to produce mutant KRAS inhibitors. Western blotting and ELISA assays are routinely used in order to investigate RAS inhibitors in cells and find new compounds that inhibit Ras signaling. The assay we developed was used to determine order potencies of allele specific inhibitors in cell lines harboring various activating KRAS mutations. While no inhibition of WT KRAS was found, MRTX-1133 had approximately 40 and 400 times less inhibitory potency against G12C and G12V mutant KRAS, respectively. A maximum decrease in RAS signaling was achieved when using the Lumit pERK immunoassay, and the potency of PROTAC compound LC-2 targeting selective degradation of KRAS G12C was also tested. ".

Source link: https://doi.org/10.1016/j.slasd.2022.03.001


KRAS Gene Copy Number as a Negative Predictive Biomarker for the Treatment of Metastatic Rectal Cancer With Cetuximab: A Case Report

"Patients with wild-type RAS and BRAF usually receive anti-EGFR monoclonal antibody therapy with cetuximab. " According to mCRC biomarker results, 30 percent of mCRC patients have RAS mutations, and RAS mutation status should be investigated when considering EGFR inhibitor therapy. Case PresentationA male patient with advanced rectal cancer and wild-type RAS and BRAF in a male patient with liver metastases was identified with rectal adenocarcinoma with wild-type RAS and BRAF. In addition, RAS and BRAF wild-type mCRC patients who are resistant to first-line FOLFIRI plus cetuximab therapy may respond well to the FOLFIRI plus cetuximab's "crechallenged" approach, according to this article.

Source link: https://doi.org/10.3389/fonc.2022.872630


Use of a highly sensitive lung cancer compact panel to detect KRAS G12D in the wash fluid from a lung tumor: A case report

"Abstract [Abstract] Using next-generation sequencing and the recently introduced Lung Cancer Compact Panel, we present a case of a pulmonary invasive mucinous adenocarcinoma harboring KRAS G12D, which was found in tumor samples containing a small number of tumor cells. " In the absence of EBUS transbronchial biopsy results using a map sheath, brush cytology was used to classify the tumor as class II. "The use of the Lung Cancer Compact Panel aided in the detection of KRAS G12D in the wash fluid of a brush cytology sample, resulting in a diagnosis of pulmonary invasive mucinous adenocarcinoma. ".

Source link: https://doi.org/10.1111/1759-7714.14439


Efficacy of first‐line immune checkpoint inhibitors in patients with advanced NSCLC with KRAS, MET, FGFR, RET, BRAF, and HER2 alterations

"Abstract Background" In patients with non-u2010small cell lung cancer harboring driver mutations, the effectiveness of immune checkpoint inhibitors is uncertain. In a realistic world setting, the aim of our investigation was to determine the first-u2010line ICI effectiveness in patients with NSCLC harboring KRAS, MET, FGFR, RET, BRAF, and HER2 mutations. Methods This single-u2010line ICI therapy was administered to patients with advanced NSCLC harboring KRAS, MET, FGFR, RET, BRAF, HER2 alterations, or driver 2010negative, according to a single u2010center retrospective cohort study. Thenocarcinoma was found among seventy-eight patients with NSCLC, 67% were women, 15% were neveru2010smokers, and 83% had adenocarcinoma. According to the median PFS, the median PFS for KRAS was 16. 2 for KRAS, 2. 8 for meteor, 11. 7 for other changes, and 10. 0 for driveru2010negative, respectively. Conclusions The benefit of the first-u2010line ICI was similar in modern NSCLC, except for MET modifications. ".

Source link: https://doi.org/10.1111/1759-7714.14448


New molecular mechanisms in cholangiocarcinoma: signals triggering interleukin-6 production in tumor cells and KRAS co-opted epigenetic mediators driving metabolic reprogramming

Cholangiocarcinoma is also a fatal tumor. " Rats' intrahepatic CCA levels mimic those of human iCCA, with histological and molecular features. CCA's pathogenetic shifts and therapeutic vulnerabilities in CCA may be captured by molecular investigation in bile, where we performed bile proteomic and metabolic studies that aid in the identification of yet unknown pathways that are relevant to human iCCA. We show that EGFR signaling and mutant KRASG12D can both stimulate IL6 production in CCA cells. Moreover, phosphoglycerate dehydrogenase, the rate-limiting enzyme in serine-glycine pathway, was upregulated in human iCCA correlating to G9a status. KRASG12D promoted PHGDH expression, glucose exchange toward serine synthesis, and improved CCA cell viability in a G9a activity-dependent manner. KRASG12D CAA cells were more sensitive to PHGDH and G9a inhibition than controls. In mouse iCCA, G9a pharmacological targeting reduced PHGDH expression, lowering PHGDH levels" has been reduced.

Source link: https://doi.org/10.1186/s13046-022-02386-2


FL118, acting as a ‘molecular glue degrader’, binds to dephosphorylates and degrades the oncoprotein DDX5 (p68) to control c‐Myc, survivin and mutant Kras against colorectal and pancreatic cancer with high efficacy

Pancreatic ductal adenocarcinoma, a difficult-to-u2010treat cancer, is expected to become the second most common cause of cancer-related deaths by 2030, according to u2010, while colorectal cancer is the third most common cancer and the third leading cause of cancer deaths. Conclusions Without decreasing DDX5 mRNA, we found that FL118 binds to dephosphorylates and degrades the DDX5 oncoprotein's dephosphorylates and degrades the DDX5 oncoprotein via the proteasome degradation pathway. Tumor formation is affected by genetic modification of DDX5 in PDAC cells. PDAC cells with DDX5 KO are unable to tolerate FL118 treatment, according to the PDAC cells with DDX5 KO. With low DDX5 expression, FL118 exhibits less effectiveness in PDAC and CRC tumours with high expression of DDX5, according to our human tumor model reports, although FL118 shows no results in PDAC and CRC tumours with a high level of DDX5. This will greatly affect patients with advanced PDAC or high CRC in the clinic, and FL118 precision medicine for patients with advanced PDAC or advanced CRC can be greatly reduced.

Source link: https://doi.org/10.1002/ctm2.881


Virtual Screening Based on Machine Learning Explores Mangrove Natural Products as KRAS G12C Inhibitors

"Mangrove secondary metabolites have numerous unique biological functions. " Lead compounds among them that might have harmed KRAS G12C have been found. We also performed molecular dynamics simulations to determine the lead compound's binding mode to KRAS G12C. When the lazypredict function package was first used, the random forest algorithm's Accuracy score and F1 score was higher, which can be used to distinguish the results. They maintained switch I and switch II, with MRTX849 conserving a novel binding system at the molecular level, as shown by a comparison with the positive control. Molecular dynamics research showed that they maintained a stable conformation with the target protein, so compound 44 and compound 14 might be potent inhibitors of the G12C mutants. These results show that the mangrove-derived secondary metabolite compound 44 and compound 14 may be potential therapeutic agents for KRAS G12C.

Source link: https://doi.org/10.3390/ph15050584


Arene Ru(II) Complexes Acted as Potential KRAS G-Quadruplex DNA Stabilizer Induced DNA Damage Mediated Apoptosis to Inhibit Breast Cancer Progress

"FLOW cytometric analysis, comet assay, and immunofluorescence demonstrate that 1 can cause apoptosis of MCF-7 cells and a phase arrest due to DNA damage. " In summary, the ready arene Ru complexes can be used as a promising candidate for inciting breast cancer cell apoptosis by binding and stabilizing KRAS G-quadruplex conformation on oncogene promoters.

Source link: https://doi.org/10.3390/molecules27103046

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions