Fine-needle sampling of a case of carcinoma of the breast with neuroendocrine differentiation

Fine-needle sampling was performed in a woman with a left breast lump. The cytologic diagnosis was consistent with a poorly-differentiated carcinoma. Cytologic features included medium-to-large, round, and spindle-shaped cells with scanty cytoplasm, nuclear molding, and rosette-like structures. Histology revealed an endocrine pattern. Immunohistochemical staining was positive for epithelial and neuroendocrine markers, and electron microscopy showed many small membrane-bound electron-dense granules, confirming the diagnosis of breast carcinoma with neuroendocrine differentiation. DNA flow cytometry and cytogenetic analyses revealed a near-tetraploid tumor. Diagn Cytopathol 1996;14:233–237. © 1996 Wiley-Liss, Inc.     

Novel engineered TRAIL-based chimeric protein strongly inhibits tumor growth and bypasses TRAIL resistance

Targeting of the TRAIL-DR4/5 pathway was proposed as a promising approach for specific induction of apoptosis in cancer cells. Clinical trials, however, showed inadequate efficiency of TRAIL as a monotherapy. It is a widely held view that the application of multifunctional molecules or combination therapy may lead to substantial improvement. Here, we demonstrate the effectiveness and safety of a novel chimeric protein, AD-O51.4, which is a TRAIL equipped with positively charged VEGFA-derived effector peptides. The study was performed in multiple cancer cell line- and patient-derived xenografts. A pharmacokinetic profile was established in monkeys. AD-O51.4 strongly inhibits tumor growth, even leading to complete long-term tumor remission. Neither mice nor monkeys treated with AD-O51.4 demonstrate symptoms of drug toxicity. AD-O51.4 exhibits a satisfactory half-life in plasma and accumulates preferentially in tumors. The cellular mechanism of AD-O51.4 activity involves both cytotoxic effects in tumor cells and antiangiogenic effects on the endothelium. The presence of DRs in cancer cells is crucial for AD-O51.4-driven apoptosis execution. The TRAIL component of the fusion molecule serves as an apoptosis inducer and a cellular anchor for the effector peptides in TRAIL-sensitive and TRAIL-resistant cancer cells, respectively. The FADD-dependent pathway, however, seems to be not indispensable in death signal transduction; thus, AD-O51.4 is capable of bypassing the refractoriness of TRAIL. AD-O51.4-driven cell death, which exceeds TRAIL activity, is achieved due to the N-terminally fused polypeptide, containing VEGFA-derived effector peptides. The high anticancer efficiency of AD-O51.4 combined with its safety has led to the entry of AD-O51.4 into toxicological studies.     

The Influence of Low-Molecular-Weight Monomers (TEGDMA,HDDMA, HEMA) on the Properties of Selected Matrices and Composites Based on Bis-GMA and UDMA

Bisphenol A-glycidyl methacrylate (bis-GMA) and urethane dimethacrylate (UDMA) are usually combined with low-viscosity monomers to obtain more desirable viscosity, handling characteristics and general properties. The present study determined the flexural strength (FS), flexural modulus (FM), diametral tensile strength (DTS), and hardness (HV) of five matrices and composites based on these resins. The polymerization shrinkage stress (PSS) was also studied for the composites. The polymer matrices were formed using bis-GMA and UDMA. TEGDMA, HEMA and HDDMA acted as co-monomers. The composites had 45 wt.% of filler content. The highest FS and FM were obtained from the UDMA/bis-GMA/TEGDMA/HEMA matrix and the composite (matrix + filler). The best DTS values were obtained from the UDMA/bis-GMA/HEMA matrix and the composite. One of the lowest values of FS, FM, and DTS was obtained from the UDMA/bis-GMA/HDDMA matrix and the composite. All the composites demonstrated similar hardness values. The lowest polymerization shrinkage stress was observed for the UDMA/bis-GMA/TEGDMA/HEMA composite, and the highest PSS was observed for the UDMA/bis-GMA/TEGDMA/HDDMA composite. The addition of HEMA had a positive effect on the properties of the tested materials, which may be related to the improved mobility of the bis-GMA and UDMA monomers.     

The influence of chronic stress on multiple opioid peptide systems in the rat: pronounced effects upon dynorphin in spinal cord

Recurrent exposure to intermittent electrical foot-shock (30 min, twice daily) for 7 days caused an increase in immunoreactive (ir) dynorphin and ir-alpha-neo-endorphin in lumbar and cervical (but not thoracic) spinal cord as measured 16 h following the final session. At this time the level of ir-Met-enkephalin-Arg6-Gly7-Leu8 (MEAGL) was also increased at the lumbar level. An acute foot-shock depleted spinal cord dynorphin in chronically stressed but not in naive rats. No alterations in levels of ir-dynorphin or ir-MEAGL were seen in discrete brain tissues. In contrast to the brain, where no effects were seen, the levels of beta-endorphin increased in both lobes of the pituitary. This change, however, was not accompanied by an alteration in levels of beta-endorphin in plasma. These data show that chronic foot-shock stress selectively influences particular pools of opioid peptides, predominantly those derived from proenkephalin B in the spinal cord and from proopiomelanocortin in the anterior pituitary. It is suggested that alterations observed in the spinal cord reflect enhanced activity of the proenkephalin B system in response to chronic nociceptive stimulation.