Predicting Hepatotoxicity in Patients Receiving T-DM1 Treatment using ALT Blood Concentrations

During cancer treatments, it is imperative to keep a close eye on the side effects of whatever drug you are using to target the infected cells. For example, many drugs will target cancerous cells by attaching themselves onto different receptors on the membranes of the cells. However, these treatments are not always exact in affecting only the cancerous cells. One of the major side effects of these drugs is that different types of non-cancerous cells are accidentally killed during the process of cancer treatments when the drug latches onto the similar receptors of those cells. For example, when the antibody-drug conjugate trastuzumab emtansine (T-DM1) is administered into the bloodstream it will accidentally target and kill liver cells in the patient’s body due to the liver cells’ CKAP5 receptors attaching to T-DM1 molecules. When these healthy liver cells die, they release alanine aminotransferase (ALT) as well as aspartate aminotransferase (AST). There is a silver lining to this, however, as these enzymes can be used to track liver cell death. So that raises the question: can we quantify the amount of liver cell damage from T-DM1 treatment by studying the relationship between the dosage of T-DM1 and the concentration of ALT in the bloodstream? We chose to focus on ALT rather than AST due to ALT primarily being released by liver cells, whereas AST can be released by the liver, brain, lungs, and other organs in the body [1]. Thus by modeling the concentration of ALT released by specific dosages of T-DM1, the patients’ recorded ALT levels can be referenced to find an optimal dosage to lower ALT levels while still being considered an efficient treatment

An 1800-year alkenone-based reconstruction of sea surface temperature from the San Lazaro (Soledad) Basin Baja California, Mexico

PCM00-78 box (C) and Kasten (KII-IV) cores were taken in the San Lazaro Basin (SLB) (sometimes referred to as the Soledad Basin) at (25° 10'N, 112° 45'W). The SLB is a suboxic fault-bounded basin 50 km offshore of the Baja California peninsula, with a surface area of ~3000 km2 and a water depth of 540 m. Weak-to-absent bioturbation promotes the preservation of laminated sediments, facilitating high-resolution SST reconstruction. Box core PCM00-78C was stratigraphically tied to Kasten core PCM00-KI via natural Pb decay and reconstructed SST measurements are reported here on a composite depth scale covering all sediment cores. Additional age control is provided by 137Cs and radiocarbon measurements (see manuscript for further details)