Tumor size and prognosis in aggressively treated osteosarcoma

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.     

Keratoacanthoma

The keratoacanthoma is a common cutaneous neoplasm that most often occurs on sun-exposed sites in light-skinned persons of middle age or older. It is considered the prototype of cutaneous pseudo-malignancies because it is a rapidly growing tumor with a histologic pattern resembling squamous cell carcinoma. It may be best viewed as an aborted malignancy that only rarely progresses into an invasive squamous cell carcinoma. It is most likely derived from hair follicle cells. The common type of keratoacanthoma and its many variants are discussed with emphasis on clinical and histologic features, biologic behavior, and response to therapy.     

Reduced skin tumor development in cyclin D1-deficient mice highlights the oncogenic ras pathway in vivo

Cyclin D1 is part of a cell cycle control node consistently deregulated in most human cancers. However, studies with cyclin D1-null mice indicate that it is dispensable for normal mouse development as well as cell growth in culture. Here, we provide evidence that ras-mediated tumorigenesis depends on signaling pathways that act preferentially through cyclin D1. Cyclin D1 expression and the activity of its associated kinase are up-regulated in keratinocytes in response to oncogenic ras. Furthermore, cyclin D1 deficiency results in up to an 80% decrease in the development of squamous tumors generated through either grafting of retroviral ras-transduced keratinocytes, phorbol ester treatment of ras transgenic mice, or two-stage carcinogenesis.     

Animal by-products contaminated with Salmonella in the diets of lactating dairy cows

As part of a total mixed ration, two rumen-fistulated dairy cows were fed meat and bone meal that had been artificially contaminated with Salmonella spp. Samples from the rumen, feces, and milk were taken 3 d/wk and cultured for salmonella. Rectal temperatures and rumen pH were also measured at the time of sample collection. Over the 2-mo study, salmonella were intermittently recovered from rumen contents, from feces, and from necropsy specimens of rumen contents, cecal contents, and mesenteric lymph nodes. No excretion of salmonella in milk was detected. An elevated rumen pH was associated with increased isolation of salmonella. No clinical illness was observed for either cow. Meat and bone meal that has been contaminated with low concentrations of salmonella is unlikely to result in clinical illness in healthy adult lactating cows. However, dairy producers should continue to be concerned about feed biosecurity and water contamination of animal by-products to prevent and control contamination by salmonella.     

Effect of bile/pancreatic secretions on absorption of radioactive or stable zinc. In vivo and in vitro studies

Biliary/pancreatic (B/P) secretions are a major component of endogenous secretions, and endogenously secreted Zn is a primary means of Zn homeostasis. This study examined whether B/P fluid alters the absorption/reabsorption of Zn and, in doing so, whether this contributes to homeostatic control of Zn. Animal experiments utilized rats fed 10 or 300 micrograms Zn/kg diet. An open-ended gut perfusion study in which 65Zn-labeled B/P fluid or 67Zn-labeled and digested diet found significantly decreased Zn absorption from B/P fluid. Although Zn absorption from both sources was less in animals fed diets higher in Zn, there was no interaction of treatment and diet. Further studies utilizing cultured human colon carcinoma cells (CACO-2) as in vitro models of gut enterocytes found that the presence of B/P fluid significantly decreased Zn retention and/or transport and resulted in a redistribution of cellular Zn after 1200 min of incubation. These studies show that a substance in B/P fluid can decrease the absorption of Zn and also suggest that dietary Zn and Zn associated with B/P secretions are absorbed from distinct pools. However, the lack of an interactive effect with diet, and the amount of time required to see differences in CACO-2 cells, suggest that differences in absorption are not a major contributor to Zn homeostasis.     

(S)-Reutericyclin: Susceptibility Testing and In Vivo Effect on Murine Fecal Microbiome and Volatile Organic Compounds

We aimed to assess the in vitro antimicrobial activity and the in vivo effect on the murine fecal microbiome and volatile organic compound (VOC) profile of (S)-reutericyclin. The antimicrobial activity of (S)-reutericyclin was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Staphylococcus (S.) epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa and Propionibacterium acnes. Reutericyclin or water were gavage fed to male BALBc mice for 7 weeks. Thereafter stool samples underwent 16S based microbiome analysis and VOC analysis by gas chromatography mass spectrometry (GC-MS). (S)-reutericyclin inhibited growth of S. epidermidis only. Oral (S)-reutericyclin treatment caused a trend towards reduced alpha diversity. Beta diversity was significantly influenced by reutericyclin. Linear discriminant analysis Effect Size (LEfSe) analysis showed an increase of Streptococcus and Muribaculum as well as a decrease of butyrate producing Ruminoclostridium, Roseburia and Eubacterium in the reutericyclin group. VOC analysis revealed significant increases of pentane and heptane and decreases of 2,3-butanedione and 2-heptanone in reutericyclin animals. The antimicrobial activity of (S)-reutericyclin differs from reports of (R)-reutericyclin with inhibitory effects on a multitude of Gram-positive bacteria reported in the literature. In vivo (S)-reutericyclin treatment led to a microbiome shift towards dysbiosis and distinct alterations of the fecal VOC profile.     

Patterns of Iridoid Glycoside Production and Induction in Plantago lanceolata and the Importance of Plant Age

Induction of allelochemicals is one way that plants efficiently deploy defenses against herbivory. In two separate experiments we investigated the time course of this inductive response and the importance of the timing of herbivory for Plantago lanceolata (Plantaginaceae). We found a localized induced response of catalpol and the ratio of catalpol to total iridoid glycosides in damaged leaves that was evident at d 6 after caterpillars of the specialist Junonia coenia were put onto the plants. On the whole plant level, we detected small, but significant changes in the iridoid glycoside metabolism of P. lanceolata on several different days following herbivory. We also found considerable change in the amounts of allelochemicals produced during P. lanceolata's ontogeny. This ontogenetic effect might help to explain some of the reasons why induction may be difficult to detect in P. lanceolata. We also investigated the importance of the timing of herbivory on P. lanceolata's inductive response, but neither herbivory after 5 wk of growth nor after 6 or 7 wk of growth induced an increase in aucubin or catalpol.     

Evaluation of Reorientation Techniques and Distractors for Walking in Large Virtual Environments

Vir tual Environments (VEs) that use a real-walking locomotion interface have typically been restricted in size to the area of the tracked lab space. Techniques proposed to lift this size constraint, enabling real walking in VEs that are larger than the tracked lab space, all require reorientation techniques (ROTs) in the worst-case situation—when a user is close to walking out of the tracked space. We propose a new ROT using visual and audial distractors—objects in the VE that the user focuses on while the VE rotates—and compare our method to current ROTs through three user studies. ROTs using distractors were preferred and ranked more natural by users. Our findings also suggest that improving visual realism and adding sound increased a user's feeling of presence. Users were also less aware of the rotating VE when ROTs with distractors were used.     

Absolute calibration of photostimulable image plate detectors used as (0.5-20 MeV) high-energy proton detectors

In this paper, the absolute calibration of photostimulable image plates (IPs) used as proton detectors is presented. The calibration is performed in a wide range of proton energies (0.5-20 MeV) by exposing simultaneously the IP and calibrated detectors (radiochromic films and solid state detector CR39) to a source of broadband laser-accelerated protons, which are spectrally resolved. The final result is a calibration curve that enables retrieving the proton number from the IP signal.     

Molecular structures and conformational studies of triarylcyclopropyl and related nonsteroidal antiestrogens

Molecular structures and conformational characteristics of a series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X-ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational-search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity.