Casein kinase 2α regulates glioblastoma brain tumor-initiating cell growth through the ß-catenin pathway.

Glioblastoma (GBM) is the most common and fatal primary brain tumor in humans, and it is essential that new and better therapies are developed to treat this disease. Previous research suggests that casein kinase 2 (CK2) may be a promising therapeutic target for GBMs. CK2 has enhanced expression or activity in numerous cancers, including GBM, and it has been demonstrated that inhibitors of CK2 regressed tumor growth in GBM xenograft mouse models. Our studies demonstrate that the CK2 subunit, CK2α, is overexpressed in and has an important role in regulating brain tumor-initiating cells (BTIC) in GBM. Initial studies showed that two GBM cell lines (U87-MG and U138) transduced with CK2α had enhanced proliferation and anchorage-independent growth. Inhibition of CKα using siRNA or small-molecule inhibitors (TBBz, CX-4945) reduced cell growth, decreased tumor size, and increased survival rates in GBM xenograft mouse models. We also verified that inhibition of CK2α decreased the activity of a well-known GBM-initiating cell regulator, ß-catenin. Loss of CK2α decreased two ß-catenin-regulated genes that are involved in GBM-initiating cell growth, OCT4 and NANOG. To determine the importance of CK2α in GBM stem cell maintenance, we reduced CK2α activity in primary GBM samples and tumor spheres derived from GBM patients. We discovered that loss of CK2α activity reduced the sphere-forming capacity of BTIC and decreased numerous GBM stem cell markers, including CD133, CD90, CD49f and A2B5. Our study suggests that CK2α is involved in GBM tumorigenesis by maintaining BTIC through the regulation of ß-catenin.

The role of the c-Jun N-terminal kinase 2-α-isoform in non-small cell lung carcinoma tumorigenesis.

The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase family and have been implicated in tumorigenesis. One isoform in particular, JNK2α, has been shown to be frequently activated in primary brain tumors, to enhance several tumorigenic phenotypes and to increase tumor formation in mice. As JNK is frequently activated in non-small cell lung carcinoma (NSCLC), we investigated the role of the JNK2α isoform in NSCLC formation by examining its expression in primary tumors and by modulating its expression in cultured cell lines. We discovered that 60% of the tested primary NSCLC tumors had three-fold higher JNK2 protein and two- to three-fold higher JNK2α mRNA expression than normal lung control tissue. To determine the importance of JNK2α in NSCLC progression, we reduced JNK2α expression in multiple NSCLC cell lines using short hairpin RNA. Cell lines deficient in JNK2α had decreased cellular growth and anchorage-independent growth, and the tumors were four-fold smaller in mass. To elucidate the mechanism by which JNK2α induces NSCLC growth, we analyzed the JNK substrate, signal transducer and activator of transcription 3 (STAT3). Our data demonstrates for the first time that JNK2α can regulate the transcriptional activity of STAT3 by phosphorylating the Ser727 residue, thereby regulating the expression of oncogenic genes, such as c-Myc. Furthermore, reintroduction of JNK2α2 or STAT3 restored the tumorigenicity of the NSCLC cells, demonstrating that JNK2α is important for NSCLC progression. Our studies reveal a novel mechanism in which phosphorylation of STAT3 is mediated by a constitutively active JNK2 isoform, JNK2α.

Highly variable acquisition rates of Ixodes scapularis (Acari: Ixodidae) by birds on an Atlantic barrier island.

Acquisition of ticks by bird hosts is a central process in the transmission cycles of many tick-borne zoonoses, but tick recruitment by birds has received little direct study. We documented acquisition of Ixodes scapularis Say on birds at Fire Island, NY, by removing ticks from mist-netted birds, and recording the number of ticks on birds recaptured within 4 d of release. Eight bird species acquired at least 0.8 ticks bird(-1) day(-1) during the seasonal peak for at least one age class of I. scapularis. Gray Catbirds, Eastern Towhees, Common Yellowthroats, and Northern Waterthrushes collectively accounted for 83% of all tick acquisitions; and six individuals apportioned among Black-billed Cuckoo, Gray Catbird, Eastern Towhee, and Common Yellowthroat were simultaneously infested with both larvae and nymphs. Bird species with the highest acquisition rates were generally ground foragers, whereas birds that did not acquire ticks in our samples generally foraged above the ground. Tick acquisition by birds did not differ between deciduous and coniferous forests. Among the 15 bird species with the highest recruitment rates, acquisition of nymphs was not correlated with acquisition of larvae. Tick acquisition rates by individual bird species were not correlated with the reservoir competence of those species for Lyme borreliae. However, birds with high tick acquisition rates can contribute large numbers of infected ticks, and thus help maintain the enzootic cycle, even if their levels of reservoir competence are relatively low.

Preparation, physicochemical characterization and drug release studies of albendazole solid dispersions.

Albendazole (ALB) solid dispersions were prepared by codissolvation and solvent evaporation technique using water soluble carrier such as polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) to improve the aqueous solubility of the drug and thus enhancing its bioavailability. The physicochemical characteristics of these solid dispersions were performed by scanning electron microscopy (SEM), X-ray diffraction (XRD), fourier-transform infrared (FT-IR) spectroscopy and dissolution rate analyses. SEM was used to clarify the surface and shape characteristics of the different samples. All characteristic bands of albendazole are seen in the FT-IR spectra of solid dispersions. Basically no significant changes in the frequency and shape of albendazole were noticed which leads to the conclusion that no strong interaction between the drug and the polymer exists in the solid dispersion (SD) particles. The degree of crystallinity of ALB decreased and also differed with the SD of different polymers. Dissolution rate and percent dissolution efficiency were significantly increased in the solid dispersions in comparison with drug alone. The drug release kinetics was ascertained by using F-test statistics using kinetic models of zero order, first order, Higuchi and Hixson-Crowell. Albendazole formed solid dispersions with water soluble polymers like PVP and PEG and the dissolution rate of the drug in the SD system was faster when the ratio of polymer to drug was greater. First order model may be used for explaining the kinetics of drug release from all the SD formulations as suggested by F-test.

Combination carboplatin and radiotherapy in the management of stage II testicular seminoma: comparison with radiotherapy treatment alone.

PURPOSE: To assess the results of treatment in 33 patients with stage IIA/B seminoma who were treated with carboplatin and radiotherapy (RT) between January 1989 and December 1996. PATIENTS AND METHODS: Thirty patients received single course single agent carboplatin (400 mg/m2 or area under curve (AUC 7), two patients received two courses carboplatin, and one patient received single course carboplatin and etoposide, all 4-6 weeks prior to infra-diaphragmatic RT. Results were retrospectively compared with those obtained for 80 patients treated from 1970 to 1998 with radiotherapy alone. RESULTS: There was minimal toxicity associated with the use of carboplatin prior to RT. With a median follow-up of 4 years (range 2-70 months) 2/33 patients treated with chemotherapy and RT have relapsed, 5-year relapse free survival (RFS) = 96.9% (95% confidence interval (CI) 72.9-99.4%), and one patient has died of progressive disease, 5-year overall survival (OS) = 96.7%. With a median follow-up of 11.2 years (range 6 months to 25.8 years) 15/80 patients treated with RT alone have relapsed, 5-year RFS = 80.7% (95% CI 70.1-87.9%), including 13/61 patients treated with infra-diaphragmatic RT, 5-year RFS = 77.9%, and 2/19 treated with additional supra-diaphragmatic RT, 5-year RFS = 89.5% (P = 0.277). Eleven out of 80 patients have died, 5-year OS = 94.7%. For stage IIA, 1/14 patients treated with chemotherapy and RT have relapsed, 5-year RFS = 92.3%, compared with 5/34 treated with infra-diaphragmatic RT alone 5-year, RFS = 84.9% (P = 0.527). For stage IIB, 1/19 patients relapsed (at 69 months) following chemotherapy and RT (5-year RFS = 100%), whereas 8/27 relapsed following infra-diaphragmatic RT alone, 5-year RFS = 69.4% (P = 0.0595). CONCLUSION: Infradiaphragmatic RT alone cures the majority of patients with stage II seminoma, but the relapse rate remains high particularly for patients with stage IIB disease. As compared with historical controls, carboplatin with RT appears to reduce the relapse rate in stage II seminoma with minimal additional toxicity and the results approach statistical significance for stage IIB patients. Confirmation would require a phase III randomized comparison.

Finite difference solution for graded-index cylindrical dielectric waveguides: a scalar wave approximation.

A simple numerical method based on finite differences to solve the scalar wave equation encountered in optical fibers is presented. The method uses the Ricatti transformation to the scalar wave equation and is capable of analyzing fibers of arbitrary refractive index profiles. Achieving errors as low as 0.005% for propagation constants is possible for lower-order modes. However, the error seems to increase for frequencies closer to cutoff.

Plant regeneration via somatic embryogenesis in the seeded diploid banana Musa ornata Roxb.

Somatic embryos of a seeded diploid ornamental banana (Musa ornata Roxb.) were obtained from zygotic embryos cultured on semi-solid Murashige and Skoog (MS) (1962) medium with the auxin 2,4-D (0.5, 1, 2 mg/l) and 5% CW. Removal of 2,4-D and transferral to Schenk and Hildebrandt (SH) (1972) salts with CW followed by basal MS led to embryo germination and growth. Plantlet production was obtained using filter paper bridges in liquid half-strength SH medium with 1% sucrose. The remarkable phenotypic fidelity of somatic embryos to that of zygotic embryos and the presence of a haustorium-like outgrowth on the somatic embryos is described.

Plant regeneration via somatic embryogenesis in the seeded diploid banana Musa ornata Roxb.

Somatic embryos of a seeded diploid ornamental banana (Musa ornata Roxb.) were obtained from zygotic embryos cultured on semi-solid Murashige and Skoog (MS) (1962) medium with the auxin 2,4-D (0.5, 1, 2 mg/l) and 5% CW. Removal of 2,4-D and transferral to Schenk and Hildebrandt (SH) (1972) salts with CW followed by basal MS led to embryo germination and growth. Plantlet production was obtained using filter paper bridges in liquid half-strength SH medium with 1% sucrose. The remarkable phenotypic fidelity of somatic embryos to that of zygotic embryos and the presence of a haustorium-like outgrowth on the somatic embryos is described.

Optical absorption characteristics of neutron irradiated heavy metal fluoride glasses.

Samples of ZBLA and HBLA glasses were subjected to various fluences of neutron irradiation, and the spectral dependence of optical absorption was measured before and after irradiation. The IR edge was found to be unaffected by neutron irradiation for the fluences used. However, a red shift occurred at the UV edge which slightly recovered after three weeks.

Adventitious shoot production from calloid cultures of banana.

Isolated tips (approx. 2 mm long) from aseptic, multiplying shoot cultures of the triploid dessert banana clone 'Highgate' were tested for their morphogenetic responsiveness to hormone treatments on semisolid media. Medium containing Murashige and Skoog (1962) salts, p-chlorophenoxyacetic acid, and kinetin produced a compact calloid mass. Protuberances disclosed by SEM as rounded, button-shaped, and pointed outgrowths resembling fasciated shoots were formed in profusion. Sections showed many meristematic regions, some associated with distinct leaf primordia. Formation and growth of successive leaves yielded small, elongated, adventitious shoots with constricted bases. Transferral to a basal MS medium with 1 mg/l 1-naphthaleneacetic acid (NAA) led to the formation of rooted plantlets.

Three-photon absorption in direct-gap crystals.

Third-order time-dependent perturbation theory, utilizing parabolic and nonparabolic energy bands and calculated (from band structure) higher bands as intermediate levels, and a Keldysh first-order model are used to calculate three-photon-absorption coefficients of several direct-gap crystals. Third-order perturbation results for CdS at 1.06 microm agree well with the experimental data.

ABO blood group distributions in diarrhoea cases including cholera in Calcutta.

A double blind study on determination of ABO blood groups of 210 cholera patients, 44 diarrhoea cases due to Vibrio parahaemolyticus, and 148 diarrhoea cases from whom no vibrios could be isolated (control group), was conducted in Calcutta. A statistically significant difference was found in blood group 'O' when comparison was made between control and cholera groups. No significant association was, however, notices between V. parahaemolyticus-induced diarrhoea and ABO blood groups.

Numerical solution of the scalar-wave equation for inhomogeneous cylindrical dielectric waveguides.

An initial-value algorithm derived from the Ricatti transformation of the scalar-wave equation is used to find the eigenvalues of inhomogeneous cylindrical dielectric waveguides. The numerical accuracy of the technique is investigated for cladded parabolic and step-index cylindrical refractive-index profiles.

Optical phenomena in infrared materials: introduction.

The topical meeting on Optical Phenomena in Infrared Materials, sponsored jointly by the Optical Society of America and the U.S. Air Force Office of Scientific Research, was held in December 1976. The meeting stressed research on optical effects in materials for modern IR applications such as laser windows, solar energy conversion, infrared detection and integrated optics. The November 1977 issue of Applied Optics publishes a representative selection of the papers given.