Expression of interleukin 15 (IL-15) in human rhabdomyosarcoma,osteosarcoma and Ewing's sarcoma

Interleukin 15 (IL-15) is a recently discovered cytokine that stimulates lymphocyte proliferation and migration via a trimeric receptor sharing the β and γ signal transducing chains with the IL-2 receptor. IL-15 is typically produced by normal cells that do not release IL-2, but little information is currently available on human tumors. To assess whether human musculo-skeletal sarcomas produce IL-15, we analyzed surgical specimens and cell lines obtained from rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma. IL-15 mRNA was present in 9/9 surgical specimens (3 Ewing's sarcomas, 5 osteosarcomas and 1 rhabdomyosarcoma). The analysis of a panel of cell lines (7 derived from Ewing's sarcoma, 12 from osteosarcoma and 5 from rhabdomyosarcoma) showed that all rhabdomyosarcoma and osteosarcoma cell lines expressed IL-15 mRNA at levels ranging from low to high, while Ewing's sarcoma cells contained little or no IL-15 message. ELISA assays showed IL-15 release in a subset of rhabdomyosarcomas and osteosarcomas, but not in Ewing's sarcoma. The highest production of IL-15, in the picogram/ml range, was found in rhabdomyosarcoma cell lines RH30 and RD. Int. J.Cancer 71:732-736, 1997. © 1997 Wiley-Liss Inc.     

Surgical treatment of a congenital dacryocystocele by means of microdebrider marsupialization in a newborn

Congenital dacryocystocele is a rare clinical condition, more commonly unilateral, secondary to the defective canalization of the nasolacrimal duct. In case of failure of conservative treatment, surgical marsupialization is recommended. We describe the case of a 40‐day‐old male newborn treated by means of microdebrider marsupialization.     

Endocrine cell growths in atrophic body gastritis. Critical evaluation of a histological classification

The aim of the present study was to evaluate the correspondence of the classification of non-antral endocrine cell growths proposed by Solcia and co-workers with clinical features and non-endocrine mucosal changes. For this purpose, 94 cases of newly diagnosed atrophic body gastritis were investigated using endoscopic biopsies and compared with 18 control subjects. The patients were subdivided into the following four groups according to the most severe pattern of endocrine cell proliferation found in the body mucosa, as shown by chromogranin A immunostaining: group 1, normal pattern (7 cases, 7·5 per cent); group 2, simple hyperplasia (6 cases, 6·5 per cent); group 3, linear hyperplasia (24 cases, 25·8 per cent); group 4; micronodular hyperplasia (56 cases, 60·2 per cent). Adenomatoid hyperplasia was found in only one case, thus precluding further analysis. Patients in groups 1 and 2 had lower acid secretion, higher gastrin level, and higher mean scores in all histopathological variables of chronic gastritis considered by the Sydney system when compared with controls, but did not differ among them in any parameter investigated. When compared with groups 1 and 2, patients of groups 3 and 4 showed higher values of circulating gastrin, higher scores of glandular atrophy, and lower values of acid secretion and of mononuclear and neutrophil inflammatory cell infiltration. Moreover, group 4 patients differed significantly from those of group 3 in their higher gastrin levels and atrophy scores, and lower scores of neutrophil cell infiltration. On the basis of these results, it is proposed that for practical purposes the normal and the simple hyperplasia patterns may be incorporated into a single group. It is concluded that this classification in its simplified form, based on a qualitative histological approach, shows clinical relevance without the need to perform expensive, time-consuming morphometric evaluations. © 1997 John Wiley & Sons, Ltd.     

Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study

Chile's gallbladder cancer rates are among the highest in the world, being the leading cause of cancer deaths among Chilean women. To provide insights into the etiology of gallbladder cancer, we conducted an ecologic study examining the geographical variation of gallbladder cancer and several putative risk factors. The relative risk of dying from gallbladder cancer between 1985 and 2003 was estimated for each of the 333 Chilean counties, using a hierarchical Poisson regression model, adjusting for age, sex and geographical location. The risk of gallbladder cancer mortality was analyzed in relation to region, poverty, Amerindian (Mapuche) population, typhoid fever and access to cholecystectomy, using logistic regression analysis. There were 27,183 gallbladder cancer deaths, with age and sex-adjusted county mortality rates ranging from 8.2 to 12.4 per 100,000 inhabitants. Rates were highest in inland and southern regions. Compared to the northern-coast, the northern-inland region had a 10-fold risk (95% of confidence interval (95% CI): 2.4-42.2) and the southern-inland region had a 26-fold risk (95% CI: 6.0-114.2). Independent of region, other risk factors for gallbladder cancer included a high Mapuche population (Odds ratio (OR):3.9, 95% CI 1.8-8.7), high typhoid fever incidence (OR:2.9, 95% CI 1.2-6.9), high poverty (OR:5.1, 95% CI 1.6-15.9), low access to cholecystectomy (OR:3.9, 95% CI 1.5-10.1), low access to hospital care (OR:14.2, 95% CI 4.2-48.7) and high urbanization (OR:8.0, 95% CI 3.4-18.7). Our results suggest that gallbladder cancer in Chile may be related to both genetic factors and poor living conditions. Future analytic studies are needed to further clarify the role of these factors in gallbladder cancer etiology.     

Unusual complication after radiotherapy for breast cancer bronchiolitis obliterans organizing pneumonia case report and review of the literature

Breast-conserving surgery and postoperative radiotherapy play an important role in the treatment of early breast cancer. Bronchiolitis obliterans with organizing pneumonia (BOOP) is an uncommon syndrome reported to be one of the complications of adjuvant radiotherapy. We report the case of a 71-year-old woman who developed cough, dyspnea and fever three weeks after radiation therapy to the left breast for breast carcinoma. Chest X-ray and computed tomography scan demonstrated alveolar opacities within both lungs. Antibiotic therapy against any probable septic pathology did not improve the symptoms, while corticosteroid treatment resulted in rapid clinical improvement together with regression of the pulmonary opacities. Irradiation was thought to be the cause of the migratory pneumonitis, hence this case was clinically diagnosed as radiation-induced migratory pneumonitis similar to BOOP, without lung biopsy. The present case suggests that one should be mindful of this disease when treating patients with a history of irradiation to the breast. BOOP promptly responds to systemic corticosteroid therapy with rapid improvement of symptoms and regression of the pulmonary opacities.     

Induction of apoptosis in human neuroblastoma cells by abrogation of integrin-mediated cell adhesion

The survival, proliferation and differentiation of neuroblastoma (NB) cells are largely dependent on adhesion to extra-cellular matrix (ECM) proteins. Integrin occupancy seems to play a primary role. To elucidate the role of integrin heterodimers during neuronal cell death, we have analysed the changes in integrin expression in 2 human NB cell lines which represent different stages of neuronal maturation. Retinoic acid (RA) had different effects on the 2 NB cell lines: on LAN-5 cells it acted as a differentiation-promoting agent, while it had an anti-proliferative effect on GI-LI-N cells, driving them driving them to apoptosis. Indeed, this occurrence was evidenced by the visualization of a “DNA ladder” on gel electrophoresis, by propidium iodine staining, and by DNA flow cytofluorimetric analysis. RA treatment rapidly and drastically decreased integrin expression and cell adhesion on GI-LI-N cells. These findings were also obtained by treating both NB cell lines with the apoptotic agent fenretinide. Furthermore, treatment of NB cells with anti-sense oligonucleotides to β, integrin chain specifically induced chromatin condensation and nucleosomal DNA laddering. Moreover, blocking cell-matrix interations by means of perturbing antibody against β, subunit resulted in the induction of typical features of apoptotic cells. In conclusion, these findings incidate that abrogation of cell adhesion through down-modulation of integrin receptors plays a crucial role in the induction of neuroblastoma programmed cell death. Int. J. Cancer 70:688–698, 1997. © 1997 Wiley-Liss, Inc.     

Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Novel glucocorticoid receptor agonists in the treatment of asthma

Introduction: Inhaled corticosteroids are the only drugs that effectively suppress the airway inflammation, but they can induce considerable systemic and adverse effects when they are administered chronically at high doses. Consequently, the pharmaceutical industry is still searching for newer entities with an improved therapeutic index.

Areas covered: Herein, the authors review the research in the glucocorticoid field to identify ligands of the glucocorticoid receptor (GR). These ligands preferentially induce transrepression with little or no transactivating activity, in order to have a potent anti-inflammatory action and a low side-effects profile.

Expert opinion: Several agents have been synthesized, but few have been tested in experimental models of asthma. Furthermore, only three (BI-54903, GW870086X and AZD5423) have entered clinical development, although the development of at least one of them (BI-54903) was discontinued. The reason for the limited success so far obtained is that the model of transactivation versus transrepression is a too simplistic representation of GR activity. It is difficult to uncouple the therapeutic and harmful effects mediated by GR, but some useful information that might change the current perspective is appearing in the literature. The generation of gene expression ‘fingerprints’ produced by different GR agonists in target and off-target human tissues could be useful in identifying drug candidates with an improved therapeutic ratio.     

Relation between the socioeconomic status of the family and primary allergy prevention in infant feeding in Hajdu-Bihar County, Hungary

BACKGROUND: The relationship between socioeconomic status and preventive care is an important issue in public health practice in Hungary. Our aim was to investigate the association between the socioeconomic status and the present practice of primary allergy prevention in infant feeding in Hajdú-Bihar County, Hungary. METHODS: A questionnaire-based cross-sectional survey was performed among 3076 infants aged 0-6 months. We studied how socioeconomic status, type of settlement, allergic background of the family and skin symptoms indicative for allergy were related to primary allergy prevention in infant feeding. Prevalence odds ratios (ORs) were calculated by multiple logistic regression. RESULTS: Independent determinants of breast feeding were age [OR corresponding to one month change 0.74; 95% confidence interval (CI) 0.70-0.77], the female gender (OR 1.24; 95% CI 1.06-1.46), the socioeconomic status of the family (OR comparing the worst with the best category 0.63; 95% CI 0.43-0.93), and birth weight (OR comparing <1500 g to >2500 g category 0.17; 95% CI 0.07-0.41). Among supplementary nutrient users independent determinants of the use of hydrolysed infant formulae were the socioeconomic status (OR comparing the worst with the best category 0.06; 95% CI 0.01-0.27), the type of settlement (OR comparing village with town 0.48; 95% CI 0.28-0.80), history of allergy in the family (OR 2.30; 95% CI 1.28-4.11), and skin symptoms indicative of allergy (OR 3.46; 95% CI 1.96-6.14). CONCLUSION: Socioeconomic status is related to the implementation of primary allergy prevention in infant feeding.