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ALT - Crossref

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Last Updated: 10 June 2022

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Abstract B14: ALT specific C-circle detection in a whole blood of cancer patients using qPCR assay

"Abstract" (Abstract) The aim of this study was to investigate a real-time qPCR assay that may be used in clinical research settings for the detection of Telomere DNA in tumors and peripheral blood of patients with cancers using Alternative Lengthening of Telomeres as their Telomere length Maintenance Mechanism. Telomeric C-circle DNA has been shown to be remarkably sensitive for ALT, enabling the first quantitative test for ALT use. ALT is also a potential escape route for tumor cells to survive under pressure from anti-telomerase therapy. C-circle DNA was found in osteosarcoma patients' blood and plasma using a radioactive probe, according to the new detection device. Here we report findings that the qPCR assay is at least 20 times more sensitive than its radioisotope predecessor and detects C-circle DNA in sarcoma patients' blood. Using the QIAmp Kit, 20 frozen whole blood and serum samples from patients with adenocarcinoma, sarcoma, desmoid fibrosarcoma, and melanoma were isolated from patients with adenocarcinoma, sarcoma, and melanoma. Positive results in both isotope and qPCR assay have been reported for three sarcoma samples. Two serum samples were positive in qPCR, but not in isotope assay. A clinically useful qPCR C-circle assay, which can also be used as a noninvasive blood-based test, and anti-telomerase antibody development can be used as a companion diagnostic device for anti-telomerase therapy and prognosis. Using qPCR assay, an ALT specific C-circle detection was found in a whole blood of cancer patients using qPCR assay. ".

Source link: https://doi.org/10.1158/1535-7163.targ-15-b14


NP-ALT, a Liposomal:Peptide Drug, Blocks p27Kip1 Phosphorylation to Induce Oxidative Stress, Necroptosis, and Regression in Therapy-Resistant Breast Cancer Cells

"Abstract Resistance to cyclin D-CDK4/6 inhibitors is unmet medical need that is often triggered by compensatory CDK2 activity. " Here we present a new way to minimize CDK4i resistance by using a therapeutic liposomal:peptide blend, NP-ALT, to reduce tyrosine phosphorylation of p27Kip1, which in turn limits both CDK4/6 and CDK2. NP-ALT inhibits proliferation in HR+ breast cancer cells, as well as CDK4i-resistant cell types, including triple negative breast cancer. Specifically, NP-ALT therapy, particularly in HR+ breast cancer cells, leads to ROS and RIPK1-dependent necroptosis. Here we show that NP-ALT causes necroptosis and tumor formation in treatment nau00efve, palbociclib-resistant, and endocrine-resistant BC cells and xenograft models, indicating that p27 is a potent therapeutic target to combat drug resistance. Implications: This research shows that blocking p27 tyrosine phosphorylation inhibits CDK4 and CDK2 production and results in ROS-dependent necroptosis, triggering ROS-dependent necroptosis, suggesting a new therapeutic strategy for endocrine and CDK4 inhibitor-resistant HR+ tumors. ".

Source link: https://doi.org/10.1158/1541-7786.mcr-21-0081


SLX4IP Promotes Telomere Maintenance in Androgen Receptor–Independent Castration-Resistant Prostate Cancer through ALT-like Telomeric PML Localization

"Abstract Description Abstract In advanced prostate cancer, resistance to androgen deprivation therapy is achieved by a variety of mechanisms, including loss of the androgen receptor that allows for AR-independent growth. " Our research focuses on finding telomere repair services that have been used by CRPC to ensure survival. Telomere elongation is responsible for telomere insistence immortality and avoidance of senescence, with the two TMM pathways containing telomerase and alternate lengthening of telomeres available. Here, we show that an AR-independence CRPC exhibits an atypical ALT-like phenotype with variable telomerase expression and activity, while AR-dependent models lack clear ALT hallmarks. In addition, AR-independence CRPC cells developed elevated SLX4IP, a protein that has been implicated in the propagation of ALT. An ALT-like phenotype and telomere maintenance were observed in AR-dependent C4-2B cells, which resulted in an ALT-dependent C4-2B cells with an ALT-like phenotype and telomere preservation. An atypical ALT-like phenotype in a SLX4IP-dependent manner was created by using an in vitro model of AR-independence progression and loss of AR in AR-dependent C4-2B cells.

Source link: https://doi.org/10.1158/1541-7786.mcr-20-0314


Functional Loss of ATRX and TERC Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells

"Here, we produce an ALT-positive adenocarcinoma cell line after functional inactivation of ATRX and telomerase in a telomerase-positive adenocarcinoma cell line. " Using CRISPR-cas9 nickase, two prostate cancer cell lines, LAPC-4 and CWR22Rv1 were developed in ATRX. Inactivating mutations in ATRX were introduced, resulting in inactivating mutations in ATRX. However, telomerase activity was still present in these ATRXKO cells, but it was still present in these ATRXKO cells. Telomerase activity was then crippled in these LAPC-4 ATRXKO cells by mutations in the TERC locus, the essential RNA component of telomerase. These LAPC-4 ATRXKO TERCmut cells continued to proliferate long-term and retained ALT-associated characteristics, demonstrating their reliance on the ALT mechanism for telomere repair. Implications: These prostate cancer cell line models are a unique way to investigate the distinctive molecular changes that occur after the introduction of ALT, and may be useful tools to determine ALT-specific therapies.

Source link: https://doi.org/10.1158/1541-7786.mcr-19-0654


Telomerase Suppresses Formation of ALT-Associated Single-Stranded Telomeric C-Circles

"Cells using ALT are characterized by the presence of ALT-associated promyelocytic leukemia bodies, long, heterogeneously sized telomeres, extrachromosomal circular DNA, and elevated telomeric recombination. " We found that liposarcomas containing APBs but lacking telomerase expression were always present in C-rich circles, and these C-circles were never present in the absence of APBs, indicating a close association between these two characteristics in ALT cells. Consistent with other studies, we discovered that liposarcomas containing APBs but lacking telomerase expression, were always present, and that in the absence of APBs. However, a rare subgroup of tumors with signs of telomere preservation by both telomerase and ALT did not contain C-circles, according to a rare subgroup of tumors without evidence of telomere repair. We used ALT cell lines engineered to express telomerase to test the theory that telomerase expression disrupts the tight link between APBs and C-circles. Introduction of telomerase enzyme activity in these ALT cells resulted in shorter telomeres with APB retention. ".

Source link: https://doi.org/10.1158/1541-7786.mcr-13-0013


Close Association between High Serum ALT and More Rapid Recurrence of Hepatocellular Carcinoma in Hepatectomized Patients with HCV-Associated Liver Cirrhosis and Hepatocellular Carcinoma

"We investigated whether or not a high serum alanine aminotransferase level is connected to a more rapid recurrence of hepatocellular carcinoma in hepatectomized patients with hepatitis C virus mediated liver cirrhosis and HCC. " Patients with HCV-LC and HCC of a single nodule with no histologic evidence of portal or hepatic vein invasion and who had been followed up for more than three years were included in the study. The mean interval in recurrent patients between hepatectomy and the first recurrence in the high ALT group was significantly shorter than that in the low ALT group. These results showed that HCC recurrence in the high ALT group was accelerated, meaning that the lowering of the ALT level after hepatectomy by anti-inflammatory drugs could prolong the comadic period by about two years in hepatectomized patients with HCC and HCV-LC. ".

Source link: https://doi.org/10.1159/000025019


Elevated AST/ALT ratio is associated with all-cause mortality in patients with stable coronary artery disease: a secondary analysis based on a retrospective cohort study

"Abstract" is a subpoena. The aim of this research is to investigate the correlation between the aspartate amino transferase /alanine aminotransferase ratio and all-cause mortality in stable coronary artery disease patients treated by percutaneous coronary intervention. ACM was present in 6 patients in the low group and 12 patients in the high group, with significant differences between the two groups. An elevated AST/ALT ratio was associated with increased ACM in stable ACD patients, according to the Kaplan U2013Meier study. Therefore, an elevated AST/ALT ratio in stable ACD patients is an independent prognostic factor for ACM.

Source link: https://doi.org/10.1038/s41598-022-13355-2


Elevation of AST/ALT Ratio in Association with Severity of Esophageal Varices in Patients with Hepatic Cirrhosis

"Objective: To determine the increase of AST/ALT ratio in patients with hepatic cirrhosis patients. In 20. 9% grade II, the Paquet grading system revealed that esophageal varices were present in a 20. 9% grade II. About 30 patients of liver cirrhosis were at a 27 percent risk of esophageal varices in a 35 percent prevalence. "The elevated ALT and AST are strongly linked to the occurrence of esophageal varices in cirrhosispatients" in hepatic cirrhosispatients.

Source link: https://doi.org/10.53350/pjmhs22165259


On Frogs, Monkeys, and Execution Memes: Exploring the Humor-Hate Nexus at the Intersection of Neo-Nazi and Alt-Right Movements in Sweden

"The paper, drawing on a digital content review of memes produced and distributed by the company reveals the place of humor, irony, and ambiguity among these cultural neo-Nazism's cultural neo-Nazi and Alt-right groups within Sweden today's neo-Nazi and various layers of meaning. ".

Source link: https://doi.org/10.1177/1527476420982234

* 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