Tucatinib and stereotactic radiosurgery in the management of HER2 positive breast cancer brain metastases.

PURPOSE: HER2-positive breast cancer has a high risk of brain metastasis. Stereotactic radiosurgery (SRS) is standard of care for limited brain metastases. Tucatinib, a HER2-targeted tyrosine kinase inhibitor, has demonstrated intracranial efficacy in the HER2-CLIMB Trial. However, it is unknown whether tucatinib with SRS is safe or effective. METHODS: A retrospective analysis of HER2-positive breast cancer treated with SRS and tucatinib for brain metastases management was performed. All patients received tucatinib and SRS for the management of active brain metastases. The primary endpoint was local and distant brain tumor control. Secondary endpoints were intracranial progression free survival (CNS-PFS), systemic PFS, overall survival (OS), and neurotoxicity. RESULTS: A total of 135 lesions treated with SRS over 39 treatment sessions in 22 patients were identified. Median follow-up from tucatinib initiation was 20.8 months. Local brain control was 94% at 12-months and 81% at 24-months. Distant brain control was 39% at 12-months and 26% at 24-months. Median survival was 21.2 months, with 12- and 24-month OS rates of 84% and 50%, respectively. Median CNS-PFS was 11.3 months, with 12- and 24-month CNS-PFS rates of 44.9% at both time points. Median systemic PFS was not reached, with 12- and 24-month systemic PFS rates of 86% and 57%, respectively. Symptomatic radiation necrosis occurred in 6 (4%) lesions. No additional unexpected toxicities were noted. CONCLUSIONS: SRS in combination with tucatinib, capecitabine, and trastuzumab appears to be a safe and feasible treatment for HER2 + brain metastases. Further prospective evaluation of potential synergistic effects is warranted.

Effect of proton pump inhibitors on Magnesium levels in Type II diabetic patients: a single centre study from Saudi Arabia.

OBJECTIVE: In recent years, increasing evidence suggests an association between low Magnesium levels and type 2 diabetes mellitus. It has also been reported that the use of proton pump inhibitors may induce hypomagnesemia. Although some case reports have described patients with Proton Pump Inhibitor-induced hypomagnesemia, the impact of Proton Pump Inhibitor use on hypomagnesemia has not been fully clarified in comparative studies. The objective of the study was to determine the Magnesium levels in patients with diabetes who are taking proton pump inhibitors and also to correlate the Magnesium levels in diabetic patients who take proton pump inhibitors with those not taking proton pump inhibitors. PATIENTS AND METHODS: A cross-sectional study was carried out in the study population comprising adult patients attending internal medicine clinics in King Khalid Hospital, Majmaah, KSA. A total of 200 patients who gave informed consent were recruited into the study over one year. RESULTS: Overall prevalence of hypomagnesemia was observed among 128 patients out of 200 (64%) diabetic patients. Relatively more patients with hypomagnesemia were found in group 2 (without PPI use) (38.5%) compared to group 1 (with PPI use) (25.5%). A statistically significant difference was not observed in group 1 using proton pump inhibitors and group 2 not using proton pump inhibitors (p-value = 0.473). CONCLUSIONS: Hypomagnesemia is seen in diabetic patients and patients who take proton pump inhibitors. There was no statistically significant difference in Magnesium levels in diabetic patients, irrespective of proton pump inhibitor use.

Apoptosis induced by copper oxide quantum dots in cultured C2C12 cells via caspase 3 and caspase 7: a study on cytotoxicity assessment.

We report herein the synthesis and characterization of copper oxide quantum dots and their cytotoxic impact on mouse C2C12 cells. The utilized CuO quantum dots were prepared by the one-pot wet chemical method using copper acetate and hexamethylenetetramine as precursors. The physicochemical characterization of the synthesized CuO quantum dots was carried out using X-ray diffraction, energy-dispersive X-ray analysis, and transmission electron microscopy. To examine the in vitro cytotoxicity, C2C12 cell lines were treated with different concentrations of as-prepared quantum dots and the viability of cells was analyzed using Cell Counting Kit-8 assay at regular time intervals. The morphology of the treated C2C12 cells was observed under a phase-contrast microscope, whereas the quantification of cell viability was carried out via confocal laser scanning microscopy. To gain insight into the mechanism of cell death, we examined the effect of CuO quantum dots on the candidate genes such as caspases 3 and 7, which are key mediators of apoptotic events. In vitro investigations of the biological effect of CuO quantum dots have shown that it binds genomic DNA, decreases significantly the viability of cells in culture in a concentration (10-20 µg/mL) dependent manner, and inhibits mitochondrial caspases 3 and 7. To sum up, the elucidation of the pathways is to help in understanding CuO quantum dot-induced effects and evaluating CuO quantum dot-related hazards to human health.

Comparison between the electrical properties of ZnO nanowires based field effect transistors fabricated by back- and top-gate approaches.

Large-quality, well-crystallized growth of ZnO nanowires was done via non-catalytic thermal evaporation process on silicon substrate only by using metallic zinc powder and oxygen as source materials for zinc and oxygen, respectively. The electrical properties of the as-grown ZnO nanowires were examined by fabricating a single nanowire based FETs which were fabricated via two approaches, i.e., back- and top-gate approaches by using electron beam lithography (EBL) and photolithography processes. ZnO FETs electrical properties were characterized by I(DS)-V(DS) and I(DS)-V(GS) measurement. The fabricated single ZnO nanowire based FETs by back- and top-gate approaches exhibited field effect mobilities of approximately 4.25 and approximately 12.76 cm2/Vs, respectively. Moreover, the carrier concentrations for the fabricated back- and top-gate FETs were approximately 1.6 x 10(17) and approximately 1.37 x 10(18) cm(-3), respectively. From our studies it was observed that the fabricated top-gate FETs exhibited higher and good electrical properties as compared to ZnO nanowire FETs fabricated using back-gate approaches.

Low-temperature growth and properties of CuO structures prepared by aqueous solution process.

The effects of additives on the morphologies of CuO structures have been examined in this study. Two different morphologies of CuO structures, i.e., flower-shaped and ellipsoidal-shaped have been synthesized via a facile and low-cost simple solution method by using two different additive molecules, i.e., hexamethylenetetramine and triethylamine, respectively. From detailed morphological observations, it was concluded that the morphologies of CuO structures are strongly dependant on the use of specific additives molecules and by using a particular additive, a specific CuO structures can be obtained. The synthesized products were examined in detail in terms of their structural properties. The detailed structural characterizations exhibited the nanocrystalline nature with monoclinic structure for the as-synthesized flower-shaped and ellipsoidal-shaped CuO structures.