Metronidazole as a radiosensitizer and high-dose radiation in advanced vulvovaginal malignancies,a pilot study

Advanced vulvovaginal cancers have a survival of less than 25% in 5 years when treated with radiotherapy alone. The radiosensitizer metronidazole was used with unconventional radiation fractions in 10 patients. Local control was achieved in 9 out of 10 patients treated. Five of 10 patients have remained free of disease 9–30 months postdiagnosis. Two patients died with metastatic disease, but with local control. In only 1 patient did this approach fail to control local disease. The outcome of these 10 patients represents a significant improvement over conventional radiation. A randomized prospective study has been started on the basis of this pilot study.     

Total IgE synthesis in diabetic children

Antibodies (ICA and other organ-specific and non-organ-specific antibodies), HLA histocompatibility antigens and serum IgE levels were analysed in 27 diabetic children aged 2 to 14 years. The results obtained are as follows : 59% of examined subjects had ICA; the HLA-B8 incidence in our diabetic patients was significantly higher (p less than 0.0005) than in normal population; serum IgE levels were higher than +1 SD in 67% of patients; this percentage reaches 76% in diabetics with ICA and 86% in diabetics with ICA and HLA-B8. Enhancement of IgE production could be the consequence of a reduction in the number and/or function of suppressor T lymphocytes.     

Use of a nonionic contrast medium (Omnipaque 350) in hysterosalpingography. A comparison with ionic contrast media

The comparative adequacy was investigated of a nonionic contrast medium (iohexol) versus the ionic contrast medium usually employed in hysterosalpingography. The contrast radiologic features and the radiodiagnostic possibilities of both cm are definitely good. The nonionic contrast medium diffuses quickly and causes the uterine cavity to expand less than ionic contrast media do, thus allowing a better depiction of mucosal and/or parietal pathology. Moreover, nonionic cm allows tubal patency and peritoneal diffusion to be clearly demonstrated, particularly in uncertain cases. As compared to ionic cm, Iohexol did not cause any side effects, except for a mild discomfort. Our results lead us to suggest the use of nonionic contrast medium as the routine contrast medium in hysterosalpingography.     

Measurements of radiation dose distributions for shielded cervical applicators

Cervical applicators with shielded ovoids are employed to reduce dose to the rectum and bladder. Because of asymmetries introduced by the shields, dose distribution calculations for individual patients will require extensive computer reference data for the ovoid sources. Requisite 3-D dose distributions were measured for an unshielded and a shielded ovoid containing a Cs-137 source, using a computerized system employing a diode in a water phantom. The probe stops at each measurement point and accumulates dose for several seconds. The system automates horizontal positioning of the detector and angular motion of the ovoid to obtain dose in one plane. The detector is moved manually to other planes for a complete three dimensional set of measurements. In order to suppress the energy and directional dependence of the diode, final dose distributions are calculated from ratios of shielded to unshielded data in conjunction with independently measured TLD data for unshielded sources.     

Ebastine inhibits T cell migration, production of Th2-type cytokines and proinflammatory cytokines

BACKGROUND: Cytokine imbalance and cellular migration to inflammatory sites are critical components of allergic diseases. Redirecting cytokine imbalance and inhibiting cell migration therefore represent important therapeutic strategies for the treatment of these disorders. OBJECTIVES: To study the in vitro effect of ebastine, a novel non-sedating H1 receptor antagonist, on cytokine secretion and migration of activated T cells, as well as production of pro-inflammatory cytokines by macrophages. METHODS: Peripheral T cells obtained from healthy volunteers were cultured in wells coated with the combination of anti-CD3 monoclonal antibody (mAb) and anti-CD26 mAb, anti-CD3 mAb and anti-CD28 mAb, or anti-CD3 mAb with PMA, in the presence or absence of ebastine. T cell proliferation and the production of cytokines were measured by [3H]thymidine incorporation assay and ELISA, respectively. In addition, transendothelial migration of T cells and production of pro-inflammatory cytokines by macrophages were examined. RESULTS: Ebastine inhibited T cell proliferation and the production of IL-4, IL-5, IL-6, and TNF-alpha by T cells under each co-stimulatory condition tested, whereas it exhibited no effect on the production of IL-2 or IFN-gamma. In addition, T cell migration and the production of such pro-inflammatory cytokines as TNF-alpha and IL-6 by macrophages were inhibited by ebastine. CONCLUSIONS: These results indicate that ebastine has a specific inhibitory effect on Th2-type cytokine production. Moreover, ebastine inhibited T cell migration and pro-inflammatory cytokine production by T cells and macrophages, suggesting that ebastine might be useful for the treatment of T cell-mediated allergic inflammatory disorders, including asthma, atopic dermatitis, and Th2-type autoimmune diseases.     

Microinvasive breast cancer: pathological parameters,cancer subtypes distribution,and correlation with axillary lymph nodes invasion. Results of a large single-institution series

Background

Microinvasive breast cancer is a rare entity in which an invasive component not exceeding 1 mm is found, mostly in a ductal carcinoma in situ setting. Its diagnosis can be difficult and must rely upon immunohistochemistry markers. Many studies have analyzed pathological characteristics of this cancer to delineate its biological profile and possibly identify risk factors of axillary lymph nodes infiltration, which might be present and therefore clinically relevant. Starting from a relative large number of cases we aimed to analyze pathological data, cancer subtypes distribution, and their correlation to nodal metastasis, comparing our results to the existing recent literature.

Methods

All cases of microinvasive breast cancer were retrieved from institutional database from 1992 to 2014. Pathological parameters were analyzed for entire cohort. Moreover, cases submitted to standardized sentinel node biopsy in a restricted period, 2000–2014, were selected to correlate pathology and cancer subtype to axillary lymph nodes status.

Results

174 cases (1.4 % of operated breast cancers) were evaluated in the larger period, 1992–2014. Neither specific pathological parameters were expressed nor a peculiar cancer subtype was represented. 126 cases were selected for axillary staging analysis. Eighteen cases (14.3 %) had lymph nodes metastasis, 10 ITCs (7.9 %), 3 micrometastases (2.4 %), and 5 macrometastases (4 %). An associated intraductal component of carcinoma over 20 mm in maximum dimension resulted significant at multivariate analysis, but only if including ITCs, while this risk factor was not reproduced for micro- and macrometastases only.

Conclusions

Microinvasive breast cancer does not seem to have specific pathological and biological traits. An associated intraductal component of carcinoma >20 mm in size is a specific risk factor for ITCs nodal metastasis. Its clinical significance is anyway limited and therefore sentinel node biopsy should be performed case by case and not routinely.

     

The Involvement of Microtubular Disruption in Methylmercury-Induced Apoptosis in Neuronal and Nonneuronal Cell Lines

Methylmercury (MeHg) is known to interfere with cell cycle progression by disruption of microtubules. The relationship between the changes in cell cycle and the induction of apoptosis caused by MeHg was investigated in cultured mammalian cells. MeHg caused nuclear fragmentation and DNA ladder formation in rat pheochromocytoma (PC12) and mouse neuroblastoma cells exposed to MeHg. Flow cytometric analysis revealed that the occurrence of apoptosis was preceded by the accumulation of cells in G2/M after MeHg treatment. Exposure to colchicine, a well-characterized mitotic inhibitor, also caused G2/M-phase arrest followed by the appearance of apoptotic cells. These results suggest that G2/M-phase arrest through the disruption of microtubules is an important event in the development of apoptosis by MeHg. MeHg treatment led to G2/M-phase arrest followed by apoptosis in nonneuronal HeLa cells also. Bcl-2 was phosphorylated by MeHg treatment in HeLa cells but not in PC12 cells; however, p53 expression was not changed in either cell line. Thus, MeHg induces apoptosis via a p53-independent pathway in both cell lines, however, different pathways may be activated after the disruption of microtubules in PC12 and HeLa cells.     

Immunohistochemical detection of three serum protease inhibitors in mouse skeletal muscle by confocal laser scanning microscopy

The tissue-associated counterpart of some plasmatic protease inhibitors has been studied in mouse skeletal muscle by combining immunoperoxidase confocal microscopy and Western blot analysis. To remove serum contamination all experiments were performed on C57 BL/10 adult mice perfused extensively with physiological solution under deep anesthesia. The following serum inhibitors were investigated in skeletal muscle by immunoperoxidase staining: alpha-2-macroglobulin (alpha2M), antithrombin III (ATIII) and inter-alpha-trypsin inhibitor (ITI). The resulting localization patterns were analysed by laser transmittance scanning at 488 nm using a confocal microscope. Images obtained from a series of optical sections were then digitally intensified by a computerized program, allowing detection of even negligible amounts of immunoreaction product. In all muscles examined (soleus and extensor digitorum longus mm.) an extracellular (endomysial) localization was apparent for all inhibitors. By contrast remarkable differences were observed for the intracellular component: in fact alpha2M was present in about a half of the muscle fibers; ATIII was present inside all fibers; intracellular ITI was completely absent. Western blotting analysis of muscle homogenate was performed to biochemically characterize the above immunoreactivities. In preliminary experiments alpha2M-related immunoreactivity could not be found in the soluble fraction of perfused muscle, confirming an absence of serum contamination after in vivo perfusion. By contrast experiments on detergent-solubilized extracts (0.3% Triton X-100) revealed that tissue-bound alpha2M consisted of two main bands (168-166 KDa) and a minor component (35 KDa); ATIII of a single band (50 KDA); ITI of four bands (180, 50, 45, 40 KDa). These results confirmed that the specific immunoreactivities visualized by morphological techniques corresponded to muscle-associated plasmatic inhibitors. The present data suggest that in mouse skeletal muscle i) numerous tissue-associated plasmatic inhibitors may protect the extracellular matrix from an excess of proteolysis; ii) a more restricted set of inhibitors may be also involved in the down-regulation of intracellular proteolytic processes.