Aspisol inhibits tumor growth and induces apoptosis in breast cancer

Nonsteroidal anti-inflammatory drugs inhibit cell proliferation and induce apoptosis in various cancer cell lines, which is considered to be an important mechanism for their anti-tumor activity and cancer prevention. However, the molecular mechanisms through which these compounds induce apoptosis are not well understood. Aim: to determine the effects of nonselective cyclooxygenase-2 (COX-2) inhibitor, aspisol on breast cancer cells in vitro and in vivo. Methods: The cytotoxic activity of aspisol was evaluated by MTT assay. The apoptosis index of cells was measured by flow cytometry. Immunohistochemical staining was used to detect expressions of COX-2 and caspase-3 in MDA-MB-231 cells. The expression of bcl-2 and bax was analyzed by Western blot analysis. The content of prostaglandin E2 (PGE2) in MDA-MB-231 cells was estimated by ELISA. In vivo apoptosis of the tumor cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Results: Our results showed that aspisol reduced viability of MDA-MB-231 cells in time- and dose- dependent fashions and induced apoptosis by increase of caspase-3 and bax expressions while decrease of COX-2 and bcl-2 expression in vitro. In addition, exposure to aspisol decreased the basal release of PGE2. In vivo, aspisol also inhibited the proliferation of breast cancer cells and induced their apoptosis. Conclusions: Our in vitro and in vivo data indicated that the antitumor effects of aspisol on breast cancer cells was probably mediated by the induction of apoptosis, and it could be linked to the downregulation of the COX-2 or bcl-2 expression and up-regulation of caspase-3 or bax expression.Нестероидные противовоспалительные препараты ингибируют пролиферацию клеток и вызывают апоптоз во многих опухолевых клеточных линиях, что считается важным механизмом их противоопухолевой активности и профилактики развития рака. Тем не менее молекулярные механизмы апоптотического действия этих препаратов изучены недостаточно. Цель: изучить действие неспецифического ингибитора циклогексиназы-2 (COX-2) — аспизола — на злокачественные клетки рака молочной железы in vitro и in vivo. Методы: выживаемоть клеток MDA-MB-231 определяли с помощью MTT-теста. Апоптотический индекс измеряли с помощью проточной цитометрии и иммуногистохимическим окрашиванием с антителами против COX-2 и каспазы-3. Экспрессию bcl-2 и bax изучали с помощью Вестерн-блот-анализа. Содержание простагландина E2 (PGE2 ) в клетках MDA-MB-231 оценивали методом ELISA. In vivo апоптоз опухолевых клеток определяли путем выявления разрывов ДНК с помощью концевой дезоксинуклеот-идилтранферазы (метод TUNEL). Результаты: показано, что в зависимости от времени инкубации и дозы аспизол угнетал рост клеток MDA-MB-231 in vitro и вызывал их апоптоз на фоне повышения экспрессии каспазы-3 и bax, а также снижения экспрессии COX-2 и bcl-2. В условиях in vivo аспизол также ингибировал пролиферацию злокачественных клеток рака молочной железы и вызывал их апоптоз. Выводы: данные, полученные in vitro и in vivo, свидетельствуют о противоопухолевом эффекте аспизола на клетки рака молочной железы, что скорее всего опосредовано его проапоптотическим действием и может быть связано со снижением экспрессии COX-2 и bcl-2, а также повышением экспрессии каспазы-3 и bax

Superconductivity and single crystal growth of Ni0:05TaS2

Superconductivity was discovered in a Ni0:05TaS2 single crystal. A Ni0:05TaS2 single crystal was successfully grown via the NaCl/KCl flux method. The obtained lattice constant c of Ni0:05TaS2 is 1.1999 nm, which is significantly smaller than that of 2H-TaS2 (1.208 nm). Electrical resistivity and magnetization measurements reveal that the superconductivity transition temperature of Ni0:05TaS2 is enhanced from 0.8 K (2H-TaS2) to 3.9 K. The charge-density-wave transition of the matrix compound 2H-TaS2 is suppressed in Ni0:05TaS2. The success of Ni0:05TaS2 single crystal growth via a NaCl/KCl flux demonstrates that NaCl/KCl flux method will be a feasible method for single crystal growth of the layered transition metal dichalcogenides.Comment: 13pages, 6 figures, Published in SS

Single crystal growth and characterizations of Cu0.03TaS2 superconductors

Single crystal of Cu0.03TaS2 with low copper intercalated content was successfully grown via chemical iodine-vapor transport. The structural characterization results show that the copper intercalated 2H-Cu0.03TaS2 single crystal has the same structure of the CdI2-type structure as the parent 2H-TaS2 crystal. Electrical resistivity and magnetization measurements reveal that 2H-Cu0.03TaS2 becomes a superconductor below 4.2 K. Besides, electrical resistivity and Hall effects results show that a charge density wave transition occurs at TCDW = 50 K.Comment: 14 pages, 6 figures,revised versio

Effects of inhomogeneous broadening on reflection spectra of Bragg multiple quantum well structures with a defect

The reflection spectrum of a multiple quantum well structure with an inserted defect well is considered. The defect is characterized by the exciton frequency different from that of the host's wells. It is shown that for relatively short structures, the defect produces significant modifications of the reflection spectrum, which can be useful for optoelectronic applications. Inhomogeneous broadening is shown to affect the spectrum in a non-trivial way, which cannot be described by the standard linear dispersion theory. A method of measuring parameters of both homogeneous and inhomogeneous broadenings of the defect well from a single CW reflection spectrum is suggested.Comment: 27 pages, 6 eps figures; RevTe

Protons in near earth orbit

The proton spectrum in the kinetic energy range 0.1 to 200 GeV was measured by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at an altitude of 380 km. Above the geomagnetic cutoff the observed spectrum is parameterized by a power law. Below the geomagnetic cutoff a substantial second spectrum was observed concentrated at equatorial latitudes with a flux ~ 70 m^-2 sec^-1 sr^-1. Most of these second spectrum protons follow a complicated trajectory and originate from a restricted geographic region.Comment: 19 pages, Latex, 7 .eps figure

Search for antihelium in cosmic rays

The Alpha Magnetic Spectrometer (AMS) was flown on the space shuttle Discovery during flight STS-91 in a 51.7 degree orbit at altitudes between 320 and 390 km. A total of 2.86 * 10^6 helium nuclei were observed in the rigidity range 1 to 140 GV. No antihelium nuclei were detected at any rigidity. An upper limit on the flux ratio of antihelium to helium of < 1.1 * 10^-6 is obtained.Comment: 18 pages, Latex, 9 .eps figure

A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01

The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics experiment that will study cosmic rays in the $\sim 100 \mathrm{MeV}$ to $1 \mathrm{TeV}$ range and will be installed on the International Space Station (ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected $10^8$ cosmic ray triggers. Part of the \emph{Mir} space station was within the AMS-01 field of view during the four day \emph{Mir} docking phase of this flight. We have reconstructed an image of this part of the \emph{Mir} space station using secondary $\pi^-$ and $\mu^-$ emissions from primary cosmic rays interacting with \emph{Mir}. This is the first time this reconstruction was performed in AMS-01, and it is important for understanding potential backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor stylistic and grammer change

Viability analysis and apoptosis induction of breast cancer cells in a microfluidic device: effect of cytostatic drugs

Breast cancer is the leading cause of cancer deaths among non-smoking women worldwide. At the moment the treatment regime is such that patients receive different chemotherapeutic and/or hormonal treatments dependent on the hormone receptor status, the menopausal status and age. However, in vitro sensitivity testing of tumor biopsies could rationalize and improve the choice of chemo- and hormone therapy. Lab-on-a-Chip devices, using microfluidic techniques, make detailed cellular analysis possible using fewer cells, enabling working with a patients’ own cells and performing chemo- and hormone sensitivity testing in an ex vivo setting. This article describes the development of two microfluidic devices made in poly(dimethylsiloxane) (PDMS) to validate the cell culture properties and analyze the chemosensitivity of MCF-7 cells (estrogen receptor positive human breast cancer cells) in response to the drug staurosporine (SSP). In both cases, cell viability was assessed using the life-stain Calcein-AM (CAAM) and the death dye propidium iodide (PI). MCF-7 cells could be statically cultured for up to 7 days in the microfluidic chip. A 30 min flow with SSP and a subsequent 24 h static incubation in the incubator induced apoptosis in MCF-7 cells, as shown by a disappearance of the aggregate-like morphology, a decrease in CAAM staining and an increase in PI staining. This work provides valuable leads to develop a microfluidic chip to test the chemosensitivity of tumor cells in response to therapeutics and in this way improve cancer treatment towards personalized medicine

Teaching the Process of Molecular Phylogeny and Systematics: A Multi-Part Inquiry-Based Exercise

Three approaches to molecular phylogenetics are demonstrated to biology students as they explore molecular data from Homo sapiens and four related primates. By analyzing DNA sequences, protein sequences, and chromosomal maps, students are repeatedly challenged to develop hypotheses regarding the ancestry of the five species. Although these exercises were designed to supplement and enhance classroom instruction on phylogeny, cladistics, and systematics in the context of a postsecondary majors-level introductory biology course, the activities themselves require very little prior student exposure to these topics. Thus, they are well suited for students in a wide range of educational levels, including a biology class at the secondary level. In implementing this exercise, we have observed measurable gains, both in student comprehension of molecular phylogeny and in their acceptance of modern evolutionary theory. By engaging students in modern phylogenetic activities, these students better understood how biologists are currently using molecular data to develop a more complete picture of the shared ancestry of all living things