Publications by authors named "O Sieber"
The onset and progression of cancer is associated with changes in the composition of the lipidome. Therefore, better understanding of the molecular mechanisms of these disease states requires detailed structural characterization of the individual lipids within the complex cellular milieu. Recently, changes in the unsaturation profile of membrane lipids have been observed in cancer cells and tissues, but assigning the position(s) of carbon-carbon double bonds in fatty acyl chains carried by membrane phospholipids, including the resolution of lipid regioisomers, has proven analytically challenging.
View Article and Find Full Text PDFDrug sensitivity testing of patient-derived tumor organoids (PDTOs) is a promising tool for personalizing cancer treatment. Here, we present a protocol for generation of and high-throughput drug testing with PDTOs. We describe detailed steps for PDTO establishment from colorectal cancer tissues, preparation of PDTOs for high-throughput drug testing, and quantification of drug testing results using image analysis.
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- * Research indicates that the effectiveness of this combination is hindered by its inability to induce cell death (apoptosis), despite changes in related proteins, suggesting that MCL-1 and BCL-X are overexpressed in BRAF CRCs.
- * Combining encorafenib with BCL-X inhibitors has shown promise in enhancing apoptosis in cancer cells, with one experimental approach (DT2216) resulting in increased cell death in lab tests and successful tumor growth reduction
Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments).
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- Mutations in the TP53 tumor suppressor gene are linked to cancer and poor responses to chemotherapy, often thought to be due to loss-of-function, dominant-negative effects, or gain-of-function activities.
- A study using CRISPR/Cas9 showed that eliminating various TP53 mutants did not change the growth or response to treatment of several cancer cell lines and organoids, suggesting that the gain-of-function effects may not be significant.
- The findings indicate that loss-of-function effects of TP53 are critical for tumor growth, while targeting mutant TP53 for its gain-of-function activities may not be an effective cancer treatment strategy.