Sodium-glucose cotransporter 2 inhibitors and diabetic ketoacidosis: A case series from three academic institutions

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have recently been associated with diabetic ketoacidosis (DKA). Initial case reports were largely among patients using SGLT2i off label in the setting of type 1 diabetes and were unusual because of limited associated hyperglycemia. More recently, the problem has been specifically noted in patients with type 2 diabetes. Meta-analysis of data from initial randomized controlled trials of SGLT2i suggests little risk of DKA (,0.1%) in patients with type 2 diabetes

The mTOR inhibitor, everolimus (RAD001), overcomes resistance to imatinib in quiescent Ph-positive acute lymphoblastic leukemia cells

In Ph-positive (Ph+) leukemia, the quiescent cell state is one of the reasons for resistance to the BCR-ABL-kinase inhibitor, imatinib. In order to examine the mechanisms of resistance due to quiescence and the effect of the mammalian target of rapamycin inhibitor, everolimus, for such a resistant population, we used Ph+ acute lymphoblastic leukemia patient cells serially xenotransplanted into NOD/SCID/IL2rγnull (NOG) mice. Spleen cells from leukemic mice showed a higher percentage of slow-cycling G0 cells in the CD34+CD38− population compared with the CD34+CD38+ and CD34− populations. After ex vivo imatinib treatment, more residual cells were observed in the CD34+CD38− population than in the other populations. Although slow-cycling G0 cells were insensitive to imatinib in spite of BCR-ABL and CrkL dephosphorylation, combination treatment with everolimus induced substantial cell death, including that of the CD34+CD38− population, with p70-S6 K dephosphorylation and decrease of MCL-1 expression. The leukemic non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse system with the in vivo combination treatment with imatinib and everolimus showed a decrease of tumor burden including CD34+ cells. These results imply that treatment with everolimus can overcome resistance to imatinib in Ph+ leukemia due to quiescence

Topological and Optical Properties of Passeriformes’ Feathers: Biological UV Reflector Antenna

This manuscript explores the topological and optical properties of a Passeriformes bird feather. Inside the feather, the layers of keratin and melanin are responsible for light reflection, transmission, and absorption; notably, the miniature composition of melanosome barbules plays a crucial role in its reflective properties. We adopted a multilayer interference model to investigate light propagation throughout the Passeriformes plume. As a result, we obtained all necessary simulated results, such as resonance band, efficiency, and electromagnetic radiation patterns of the Passeriformes plume, and they were verified with the experimental results reported in the literature study regarding light reflectivity through its internal geometry. Interestingly, we discovered that the interior structure of the Passeriformes plume functions similarly to a UV reflector antenna

Alteration of Akt activity increases chemotherapeutic drug and hormonal resistance in breast cancer yet confers an achilles heel by sensitization to targeted therapy

Breast cancer ranks as the second most common cause of cancer death among women in the United States. Only lung cancer, which results primarily from cigarette smoking, induces more cancer deaths in women in the USA. Approximately 1 in 7 women in the United States will be diagnozed with breast cancer during her lifetime (Jemal et al., 2004). Over 210,000 new cases of breast cancer are diagnozed in the United States each year (Centers for Disease Control and Prevention, 2006 Centers for Disease Control and Prevention, Cancer: symptoms of breast cancer, Centers for Disease Control and Prevention, Atlanta, GA (2006) http://www.cdc.gov/cancer/breast/basic_info/symptoms.htm.Centers for Disease Control and Prevention, 2006). Breast cancer is the cause of death of over 40,000 women in the United States each year. Many drugs have been demonstrated to extend survival of breast cancer patients. Anticancer agents frequently used to treat breast cancer include chemotherapeutic drugs such as methotrexate, 5-fluorouracil (5-FU), cyclophosphamide, anthracyclines, taxanes, monoclonal antibodies such as trastuzumab, hormonal based therapeutics such as tamoxifen and aromatase inhibitors. Mechanisms by which these agents inhibit breast cancer progression vary from drug to drug. While these drugs are the mainstay of chemo, immuno and hormonal therapy of breast cancer, a common problem with these treatments is the development of drug resistance. Breast cancer cells can become drug resistant by multiple mechanisms which include: increased expression of membrane transporters which transport the toxic drug out of the cell or modify/detoxify the drug, increased expression of signaling and anti-apoptotic pathways as well as other mechanisms which allow the cells to grow in the presence of the drug. This manuscript will discuss some of the mechanisms by which the altered expression of key signaling and apoptotic pathways may lead to breast cancer drug resistance and how targeting these pathways may result in the suppression of neoplastic growth