One of the hallmarks of hormone receptor (HR)-positive breast cancer is its dependence on the phosphatidylinositol-3-kinase (PI3K) pathway. Here, we review the epidemiologic, functional, and ...pharmacologic interactions between oncogenic PI3K and the estrogen receptor (ER). We discuss the epidemiology of PI3K pathway alterations, mechanisms of resistance to PI3K inhibitors, and the current mechanistic landscape of crosstalk between PI3K and ER, which provide the rationale for dual ER and PI3K inhibition and is now a standard of care in the treatment of ER+ PIK3CA-mutant metastatic breast cancer. We outline newer studies in this field that delineate the clinically relevant overlaps between PI3K and parallel signaling pathways, insulin signaling, and ER epigenetic modifiers. We also identify several caveats with the current data and propose new strategies to overcome these bottlenecks.
Electrochemical capacity retention of nearly X-ray amorphous nanostructured manganese oxide (nanoMnO2) synthesized by mixing directly KMnO4 with ethylene glycol under ambient conditions for ...supercapacitor studies is enhanced significantly. Although X-ray diffraction (XRD) pattern of nanoMnO2 shows poor crystallinity, it is found that by Mn K-edge X-ray absorption near edge structure (XANES) measurement that the nanoMnO2 obtained is locally arranged in a δ-MnO2-type layered structure composed of edge-shared network of MnO6 octahedra. Field emission scanning electron microscopy and XANES measurements show that nanoMnO2 contains nearly spherical shaped morphology with δ-MnO2 structure, and 1D nanorods of α-MnO2 type structure (powder XRD) in the annealed (600 °C) sample. Volumetric nitrogen adsorption−desorption isotherms, inductively coupled plasma analysis, and thermal analysis are carried out to obtain physicochemical properties such as surface area (230 m2 g−1), porosity of nanoMnO2 (secondary mesopores of diameter 14.5 nm), water content, composition, etc., which lead to the promising electrochemical properties as an electrode for supercapacitor. The nanoMnO2 shows a very high stability even after 1200 cycles with capacity retention of about 250 F g−1.
Partial anomalous pulmonary venous return (PAPVR) is a rare congenital cardiovascularcondition in which some of the pulmonary veins drain into the systemiccirculation. We report on the cadaveric ...dissection of a 71-year-old Caucasian maledonor who died of chronic obstructive pulmonary disease with hypertension. Wenoted a faint incisional scar on the thorax extending from the parasternal regionat the 4th intercostal level to the midaxillary line. Since the straight-line incisionfollowed the ribs and the scar was quite faint, surgery probably occurred whenthe donor was young. We also observed numerous surgical interventions of theheart, lungs, and vasculature to correct various defects.The morphology of the heart was normal, but was shifted more to the rightside. An atrial septal defect (ASD) was closed with sutures. The right superiorpulmonary vein that drained into the superior vena cava (SVC) was ligated closeto the SVC and the right inferior, left superior, and inferior pulmonary veins alldrained directly into the left atrium. We noticed a dilated coronary sinus enteringthe right atrium adjacent to the ASD; the ostium of the coronary sinus noticeablylacked the normal valve-like structure. We initially thought the right lung wasa “horseshoe” lung, but realised that it was a “hypogenetic” lung with PAPVR andan accessory diaphragm. Compared to the left, the right secondary bronchi weremuch narrower and branched uncharacteristically, as seen in hypogenetic lungsyndrome. The inferior lobe was highly disorganised, severely hypoplastic, andexhibited uncharacteristic morphology. The superior bronchopulmonary segmentwas markedly hypoplastic. The posterior and medial basal segments were notonly hypoplastic and slender, but also extended like a tail to the left pulmonarycavity behind the heart/pericardium and in front of the oesophagus and aorta.The right lung, though hypoplastic, demonstrated patent bronchi and the lobeswere inflatable. Based on the hypogenetic lung and PAPVR, we conclude that thedonor exhibited ‘scimitar’ lung.
The synthesis of pure nanostrip orthorhombic V2O5 was carried out by a simple two-step procedure, with the formation of a vanadyl ethylene glycolate precursor and postcalcination treatment. The ...precursor and the final product were characterized for its phase and composition by powder X-ray diffraction, infrared spectroscopy, thermal analysis, and X-ray photoelectron spectroscopy. The morphological changes were investigated using field emission scanning electron microscopy and transmission electron microscopy. It was found that the individual strips have around the following dimensions: length, 1.3 μm; width, 332 nm; thickness, 45 nm. The electrochemical lithium intercalation and deintercalation of nanostrip V2O5 was investigated by cyclic voltammetry, galvanostatic charge−discharge cycling, galvanostatic intermittent titration technique, and electrochemical impedance spectroscopy. From charge−discharge cycling, the initial discharge capacity of the nanostrip was found to be about 427 mAh g−1. However, it decreased due to inherent phase changes on repeated cycling.
A porous carbon foam (CF) electrode modified with a reduced graphene oxide-Ag (rGO-Ag) nanocomposite has been fabricated to purify water. It can perform as an antibacterial device by killing ...pathogenic microbes with the aid of a 1.5 V battery, with very little power consumption. The device is recycled ten times with good performance for long term usage. It is shown that the device may be implemented as a fast water purifier to deactivate the pathogens in drinking water.
The effects of astrocytic dynamics on the blood oxygen-level dependent (BOLD) response are modeled. The dynamics are represented via an astrocytic response function that approximates the effects of ...astrocytic activity, including delay between neural activity and hemodynamic response. The astrocytic response function is incorporated into a spatiotemporal hemodynamic model to predict the BOLD response measured using functional magnetic resonance imaging (fMRI). Adding astrocytic dynamics is shown to significantly improve the ability of the model to robustly reproduce the spatiotemporal properties of the experimental data such as characteristic frequency and time-to-peak. Moreover, the results are consistent across different astrocytic response functions, thus a simple impulsive form suffices to model the effective time delay of astrocytic responses. Finally, the results yield improved estimates of previously reported hemodynamic parameters, such as natural frequency and decay rate of the flow signal, which are consistent with experimentally verified physiological limits. The techniques developed in this study will contribute to improved analysis of BOLD-fMRI data.
•Astrocytic dynamics are incorporated into a spatiotemporal hemodynamic model.•The effects approximate time delay between neural activity and hemodynamic response.•Adding astrocytic dynamics improves prediction and interpretation of fMRI data.•Better estimates of previously reported hemodynamic parameters are obtained.•Results can improve future data analyses and spatiotemporal fMRI deconvolution.
A novel in situ core@shell structure consisting of nanoparticles of Ag (Ag Nps) and AgI in agarose matrix (Ag@AgI/agarose) has been synthesized as a hybrid, in order to have an efficient ...antibacterial agent for repetitive usage with no toxicity. The synthesized core@shell structure is very well characterized by XRD, UV–visible, photoluminescence, and TEM. A detailed antibacterial studies including repetitive cycles are carried out on Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria in saline water, both in dark and on exposure to visible light. The hybrid could be recycled for the antibacterial activity and is nontoxic toward human cervical cancer cells (HeLa cells). The water insoluble Ag@AgI in agarose matrix forms a good coating on quartz, having good mechanical strength. EPR and TEM studies are carried out on the Ag@AgI/agarose and the bacteria, respectively, to elucidate a possible mechanism for killing of the bacteria.
The electrochemical behavior of chemically precipitated cobalt hydroxide is studied by cyclic voltammetry and galvanostatic charge/discharge cycling. When cycled in the potential range between the ...oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER), the electrode undergoes two pairs of reactions. The pair of current peaks close to the OER is attributed to quasi-reversible oxidation of Co(OH)
2 to CoOOH, whereas the pair of current peaks close to the HER is due to quasi-reversible reduction of Co(OH)
2 to Co. The peak current values of both reactions do not show dependence on alkali concentration. Possible mechanisms are proposed for the reactions, in which the diffusion of dissolved Co(OH)
2 prior to the electron-transfer step is considered to be the rate-determining step. Considering the fact that the Co(OH)
2/CoOOH and Co(OH)
2/Co reactions are separated by a potential difference of about 1.2
V, a galvanic cell is constructed by using two Co(OH)
2 electrodes in 6
M KOH. On charging, the positive electrode attained a stable potential of about 0.4
V versus Hg/HgO, OH
− and the negative electrode attained a stable potential of about −0.8
V versus Hg/HgO, OH
−, thus resulting in an open circuit cell voltage of about 1.2
V. By discharging the cell, a capacity of 15
mA
h
g
−1 of Co(OH)
2 is obtained over about 15 charge/discharge cycles. The charged electrodes are analyzed by powder XRD and IR spectroscopy and the presence of Co and CoOOH in the negative and positive electrodes, respectively, is confirmed. Although the cell is not commercially viable, the concept of a “double hydroxide” is demonstrated akin to the “double sulfate” principle of lead-acid batteries. It is expected that Ni(OH)
2, which is isostructural to Co(OH)
2, may also show a similar behavior.
Abstract The PI3K pathway has long remained a fertile ground for drug discovery in cancer, including in estrogen receptor positive metastatic breast cancer. It has also remained a pathway difficult ...to drug effectively due to on target toxicities. New strategies to overcome these toxicities have manifested in novel drug types and management strategies for patients. Here I discuss the PI3K pathway in signaling and oncogenesis, current therapies inhibiting PI3K, mechanisms limiting efficacy, and increasing the PI3K therapeutic window with a focus on mutant selective PI3K inhibitors. Finally, I will expound on the translational future of the PI3K field, highlighting advances in biomarker discovery, tumor correlative analysis, and patient advocacy. Citation Format: N. Vasan. PI3K past, present, and future abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED10-01.
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