Dietary energy restriction does not inhibit pancreatic carcinogenesis by N-nitrosobis-2-(oxopropyl)amine in the Syrian hamster

Dietary energy restriction was previously shown to be effective in preventing a wide range of experimentally induced cancers. Studies were conducted to assess the influence on pancreatic carcinogenesis of dietary energy restrictions (reduced fat and carbohydrate) of 10%, 20% or 40% in comparison with control in Syrian hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Two carcinogenesis studies were conducted. One used a single treatment with 20 mg BOP/kg body weight and followed hamsters for 102 weeks following treatment, and the other used three weekly treatments of 20 mg BOP/kg body weight and followed hamsters for 45 weeks after treatment. Hamsters were fed control or energy restricted diet beginning the week following the last BOP treatment. Pancreatic carcinomas were induced in 9-18% of the hamsters in the first experiment and in 59-66% of the animals in the second. Dietary energy restriction did not influence carcinoma incidence in either study, and in the second experiment the multiplicity of tumors was higher in the 40% energy restriction (ER) group than in control hamsters. Plasma corticosterone was suppressed by BOP treatment, particularly in the 20% and 40% ER hamsters in the second experiment, and diet or BOP treatment did not significantly alter plasma cortisol. Pancreatic protein kinase Czeta measured by Western blot was highest in the cytosol and particulate fractions of the 40% ER hamsters in the first experiment. These results indicate that dietary energy restriction is not effective in the prevention of BOP induced pancreatic carcinogenesis in the Syrian hamster.     

Rapid relief of anxiety in cancer patients with both alprazolam and placebo

This study evaluated 36 cancer patients who were enrolled in a randomized, double-blind, placebo-controlled trial conducted over a 4-week period to evaluate the efficacy of alprazolam in the treatment of anxiety associated with cancer. Hamilton Anxiety Scale scores declined significantly between baseline and the end of the first week of the study in both treatment groups. There was no significant difference in response between the patients receiving alprazolam and placebo. Similar results were obtained from other instruments. These results suggest that nondrug factors or spontaneous improvement may play a more important role than pharmacotherapy in the treatment of anxiety associated with cancer.     

Characterization of the bioactive form and molecular determinants of recognition of cyclic enkephalin peptides at the delta-opioid receptor

An extensive and systematic search strategy to determine the conformational profile of 12 cyclic disulfide-bridged opioid peptides with varying affinities at the delta receptor has been carried out to identify the structure that is recognized by the delta receptor for each analogue. The methods and procedures used here for the conformational search have already been validated for [D-Pen2,D-Pen5] enkephalin (DPDPE), one member of this family. Use of these methods led to a low-energy solution conformation of DPDPE in excellent agreement with all the geometric properties deduced from its solution nmr spectra. Each of the analogue was subjected to the same procedure, involving a combination of molecular dynamics simulations at high and low temperature. The study was repeated in two environmental conditions, an apolar environment, simulated by using a distance-dependent dielectric constant, and a polar environment by embedding the peptides in a high constant dielectric (epsilon = 80). An automated comparison of the different conformers based on their backbone rms and average distance between the key aromatic moieties was followed by graphic analysis using maximum structural overlap. The cross-comparison of the conformations for each analogue revealed a unique conformer that may be recognized by the delta receptor for each high-affinity analogue that permitted maintaining the critical elements required for recognition in a simple spatial orientation, while maximizing similarity in other regions.     

Ewing sarcoma. Diagnostic imaging

Ewing's sarcoma is a highly malignant neoplasm of the bone whose origin is still uncertain. A strong relationship exists between Ewing's sarcoma and tumors of neural origin (Ewing family of tumors). Ewing's sarcoma must be distinguished from other round-cell tumors like lymphoma and neuroblastoma and also must be differentiated from osteogenic sarcomas. On plain radiographs, Ewing's sarcoma appears as a lytic or mixed lytic-sclerotic, rarely as predominantly sclerotic lesion with margins Lodwick grade III. It is located primarily in the diaphyseal and metadiaphyseal regions of the long bones of the lower extremities. A large soft tissue tumor is usually present. Magnetic resonance imaging is the imaging modality of choice to evaluate the extent of the primary lesion, to monitor the response to neoadjuvant chemotherapy and to follow up non-resected Ewing's sarcomas. Bone scintigraphy is necessary to detect skeletal metastasis, and 201thallium scanning has been shown to be sensitive in the monitoring of treatment response. Today, computed tomography is not longer used to image the tumor site; however, spiral CT of the lungs plays a central role as a staging and follow-up tool.     

Comparative severity of respiratory lesions of sialodacryoadenitis virus and Sendai virus infections in LEW and F344 rats

In several chronic diseases, lesions are more severe in LEW rats than in F344 rats. To determine whether or not acute viral diseases also are more severe in LEW rats than in F344 rats, we inoculated 6-7-week-old LEW and F344 rats with 10(7.2) cell culture infective units of sialodacryoadenitis virus or 10(4.7) infective units of Sendai virus. Twenty-four rats of each strain were given each virus. Lesions in nasal passages, tracheas, intrapulmonary airways, and pulmonary alveoli in 6 or 12 rats inoculated with each virus were assessed by scoring 5, 10, and 14 days after inoculation. Both viruses caused typical patchy necrotizing rhinitis, tracheitis, bronchitis, and bronchiolitis, with multifocal pneumonitis, in rats of both strains. Mean lesion indices for LEW rats given sialodacryoadenitis virus were significantly different from those for F344 rats for nasal passages on days 10 (0.999 vs. 0.680) and 14 (0.736 vs. 0.278), bronchi on day 5 (0.479 vs. 0.361), and alveoli on day 5 (0.677 vs. 0.275). Lesion indices for LEW rats given Sendai virus were significantly different from those for F344 rats for nasal passages on days 10 (1.000 vs. 0.611) and 14 (0.778 vs. 0.583); trachea on day 10 (0.625 vs. 0.028); bronchi on days 5 (0.476 vs. 0.331), 10 (0.123 vs. 0.013), and 14 (0.038 vs. 0); and alveoli on days 5 (0.413 vs. 0.114) and 10 (0.185 vs. 0.020). Thus, at the tested doses, both viruses caused more severe respiratory tract lesions in LEW rats than in F344 rats.     

Interleukin-1 beta-converting enzyme mediates cisplatin-induced apoptosis in malignant glioma cells

Increasing the susceptibility of tumor cells to apoptotic cell death following chemotherapy is of importance to the outcome of cancer treatment. Although the tumor suppressor gene p53 is required for efficient induction of apoptosis by chemotherapeutic agents, it is not the only apoptosis mediator gene. The molecular mechanisms mediating apoptosis following chemotherapy via p53-dependent or p53-independent pathways remain unclear. We show here that cis-diamminedichloroplatinum (cisplatin) induces the expression of interleukin-1 beta-converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, in murine and human malignant glioma cells during apoptosis regardless of their p53 status. Furthermore, overexpression of the murine ICE gene induces apoptosis in these tumor cells. The apoptosis induced by cisplatin treatment or murine ICE overexpression can be suppressed by the tetrapeptide ICE inhibitor Ac-YVAD-CMK or the apoptosis inhibitors bcl-2 or bcl-2-related bcl-XL gene. These findings suggest that ICE may mediate apoptosis induced by chemotherapy, and its induction could represent a novel approach for the effective treatment of malignant glioma.     

A Customized Radiation Sensor for Ionization Collection

The measurement of absorbed doses is fundamental to radiation biology and oncology. A customized parallel plate radiation sensor was designed and fabricated as a precursor to investigating novel materials, such as carbon nanotubes, as a substitute for conventional metallic conducting plates or active volume medium. This sensor contains two thick and large-area electrodes that provide the sensor with a good signal-to-noise ratio. The 6 MV and 15 MV photon beams produced by a Varian Clinac 21 EX medical linear accelerator were used in the experiments. The linear accelerator was calibrated such that 1 monitor unit (MU) produces 1 cGy of dose in water with depth of 5 cm for a calibration geometry of source-to-axis distance equal to 100 cm and 10times10 cm² field size at the point of measurement. Ionization measurements were performed by varying the bias voltages, electrode separations, exposures, and angles of the incident beam to characterize the sensor. Signal saturation characteristics of the sensor with different electrode separations and exposures were investigated. This sensor displayed excellent linear response to exposure up to 600 MU. An analytical modeling using the pencil beam model and simulations based on device configuration were given to explain the results. In oblique incident beam experiments, the prototype sensor showed an accurate response compared to simulation results for a small field size of 1times1 cm². The sensor was tested to be suitable in the study of ionization collection efficiencies for different materials