Tung-Tien Sun

Pyruvate kinase M2 (PKM2) has been shown to promote tumorigenesis by facilitating the Warburg effect and enhancing the activities of oncoproteins. However, this paradigm has recently been challenged by studies in which the absence of PKM2 failed to inhibit and instead accelerated tumorigenesis in mouse models. These results seem inconsistent with the fact that most human tumors overexpress PKM2. To further elucidate the role of PKM2 in tumorigenesis, we investigated the effect of PKM2 knockout in oncogenic HRAS-driven urothelial carcinoma. While PKM2 ablation in mouse urothelial cells did not affect tumor initiation, it impaired the growth and maintenance of HRAS-driven tumors. Chemical inhibition of PKM2 recapitulated these effects. Both conditions substantially reduced complex formation of PKM2 with STAT3, their nuclear translocation, and HIF1α- and VEGF-related angiogenesis …

OBJECTIVE: Atorvastatin has been suggested to reduce hematoma volume and improve neurological outcomes in patients with chronic subdural hematoma (CSDH). However, the benefits and harms of atorvastatin use after surgery in elderly patients are not well studied. PATIENTS AND METHODS: We conducted a retrospective trial to analyze older people (> 60 years) with CSDH, those who were treated with surgical intervention. Patients were assigned to study group if they received oral atorvastatin after surgery at least 1 week, and patients without atorvastatin medication postoperatively were assigned to control group. The primary outcome was the overall rate of recurrence at 1 month after surgery. The main secondary endpoints were the scores on the modified Rankin Scale (mRS), hematoma volume, mortality, and complications after surgery. RESULTS: A total of 49 eligible patients were included—21 in the study group and 28 in the control group. The baseline characteristics were similar between the 2 groups. At 1 month, recurrence of subdual hematoma requiring repeat surgery was reported in 4 of 21 patients (19.0%) in the study group and in 5 of 28 patients (17.9%) in the control group (p= 0.915). The hematoma volume was similar between the 2 groups (p= 0.979). A favorable outcome (a score of 2 or less on the mRS) occurred in 90.5% of patients in the study group and in 96.4% of those in the control group (p= 0.390). CONCLUSIONS: In older people with CSDH, postoperative atorvastatin use barely reduces the incidence of recurrence and hematoma volume.

Human chromosome 9p21.3 is susceptible to inactivation in cell immortalization and diseases, such as cancer, coronary artery disease and type-2 diabetes. Although this locus encodes three cyclin-dependent kinase (CDK) inhibitors (p15INK4B, p14ARF and p16INK4A), our understanding of their functions and modes of action is limited to the latter two. Here, we show that in vitro p15INK4B is markedly stronger than p16INK4A in inhibiting pRb1 phosphorylation, E2F activity and cell-cycle progression. In mice, urothelial cells expressing oncogenic HRas and lacking p15INK4B, but not those expressing HRas and lacking p16INK4A, develop early-onset bladder tumors. The potency of CDKN2B/p15INK4B in tumor suppression relies on its strong binding via key N-terminal residues to and inhibition of CDK4/CDK6. p15INK4B also binds and inhibits enolase-1, a glycolytic enzyme upregulated in most cancer types. Our …

Although the ability to read scientific papers efficiently and critically is an essential skill for graduate students, it is rarely taught systematically. Thus, some students read papers from-the-beginning-to-the-end and word-by-word, which is laborious and unproductive. In this paper, I discuss active reading, ie, reading with questions in mind. Thus, the students read the abstract and introduction looking for answers to several specific questions and do a brief literature search. Armed with this knowledge, they “predict”/design the first figure, and compare it with what is in the paper; and repeat this interrogation for other figures. This method allows a high degree of student-author interaction, enabling the students to gain a deeper understanding of how the experiments are designed and learn critical paper evaluation. I also present a course to teach this method. Although this method is initially time-consuming, with practice and …

INTRODUCTION AND OBJECTIVEUrothelium that covers much of the urinary tract has a very long (6 – 12 month) lifespan to serve as a constant permeability barrier, and as such, it must possess efficient mechanisms to handle cellular dysfunctional proteins and urinary toxins in order to stay healthy. Such “detoxification” mechanisms are particularly needed during urinary obstruction or infection when increased amounts of cell surface membranes are endocytosed for degradation or when urothelial cells are exposed to carcinogens. Despite their critical importance, these mechanisms have not been delineated. When analyzing a diverse array of mouse models lacking individual uroplakins or sorting nexin 31 or exposed to arsenite, we discovered a urothelial mitochondria-based detoxification mechanism that is functionally convergent from divergent causes and whose deficiency may play a major role in urothelial …