Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Ovarian and omental ependymomas in peritoneal washings: cytologic and immunocytochemical features

The cytologic findings in peritoneal washings of two women, one of whom had an ovarian ependymoma and the other a primary omental ependymoma, are reported. The ependymomas were characterized by the presence of numerous, isolated, spindle and stellate cells as well as groups of cells forming true rosettes. The tumor cells displayed slightly pleomorphic, round-to-oval eccentric nuclei and abundant fibrillary cytoplasm with tapering cytoplasmic processes. In addition, one of the patients had numerous papillae and cell clusters with associated psammoma bodies indistinguishable from those found in low-grade serous carcinoma. The demonstration of glial fibrillary acidic protein (GFAP) in both cases by immunocytochemical procedures indicates the usefulness of this method in cytologic preparations to confirm the diagnosis of these uncommon neoplasms.     

Radium-228 determination of natural waters via concentration on manganese dioxide and separation using Diphonix ion exchange resin

The objective of this work was to establish a new procedure for ²²⁸Ra determination of natural waters via preconcentration of radium on MnO₂ and separation of its daughter, ²²⁸Ac, using Diphonix ion exchange resin. Following removal of potential interferences via passage through an initial Diphonix Resin column, the first daughter of ²²⁸Ra, ²²⁸Ac, is isolated by chromatographic separation via a second Diphonix column. A holding time of >30 h for ²²⁸Ac ingrowth in between the two column separations ensures secular equilibrium. Barium-133 is used as a yield tracer. Actinium-228 is eluted from the second Diphonix Resin with 5 ml 1 M 1-Hydroxyethane-1,1-diphosphonic acid (HEDPA) and quantified by addition of scintillation cocktail and LSC counting. Radium (and ¹³³Ba) from the load and rinse solutions from the 2nd Diphonix column may be prepared for alpha spectrometry (for determination of ²²³Ra, ²²⁴Ra, and ²²⁶Ra) by BaSO₄ microprecipitation and filtration. Decontamination tests indicate that U, Th, and Ra series nuclides do not interfere with these measurements, although high contents of ⁹⁰Sr (⁹⁰Y) require additional treatment for accurate measurement of ²²⁸Ra. Addition of stable Sr as a “hold back” carrier during the initial MnO₂ preconcentration step was shown to remove most ⁹⁰Sr interference.     

Long-term faecal continence in infants born with anorectal malformations.

In a retrospective study of 92 patients admitted between 1975 and 1986 with anorectal malformations, we reviewed the faecal continence according to the level of their anomaly using a scoring system taken from Pescatori et al. The results of the different operative procedures were compared. Forty-seven of the 50 patients in the low anomaly group had complete faecal continence. Two died from associated anomalies and one infant had incomplete continence. This child had an associated neural tube defect. Of eight patients in the intermediate group, three had good results while two were incontinent: three patients died from associated anomalies. There were 34 patients with high anomalies, 27 of whom showed a wide range of faecal control from complete continence to different degrees of incontinence. Seven infants died from septicaemia and/or associated anomalies. The anatomical level of the lesion and the presence or absence of any associated neurological defect were the main determinants of outcome. The sex of the child and the operative procedure employed to correct the anomaly appeared to be less important.     

Breast carcinoma with choriocarcinomatous features

Although breast carcinomas have been shown to produce various ectopic substances, including human chorionic gonadotropin, it is rare to identify morphologic differentiation compatible with the hormone produced by a tumor. Presently, only eight cases of breast carcinoma with focal choriocarcinomatous differentiation have been reported in the literature. This article describes the pathologic findings, immunohistochemical profile, and clinical course in two additional cases of this unusual variant of breast carcinoma. In the first case, the tumor had morphologic features suggestive of medullary carcinoma, and the patient is doing well 12 months after presentation. In the second case, the tumor was locally advanced at presentation with histologic features consistent with metaplastic carcinoma having squamous, sarcomatoid, and choriocarcinomatous elements. The patient presented with extensive multifocal metastases 6 months after the initial presentation and is not responding well to standard or experimental treatment regimen. Immunostaining for the beta subunit of human chorionic gonadotropin was localized mostly, but not entirely, to multinucleated syncytiotrophoblast-like giant cells within both tumors.     

The role of gene rearrangements for antigen receptors in the diagnosis of lymphoma obtained by fine-needle aspiration. A study of 63 cases with concomitant immunophenotyping

To assess the efficacy of performing genotyping in addition to immunophenotyping as an adjunct to cytologic diagnosis, 63 consecutive patients with fine-needle aspirates of lymphoproliferative lesions who had concurrent immunophenotyping and genotyping performed on fine-needle aspirate cell suspensions were studied. Thirty-nine of 63 specimens (62%) that appeared to contain non-Hodgkin's lymphoma and that proved to be of B-cell lineage by genotyping were accurately phenotyped and shown to be monotypic for immunoglobulin light chains by cell suspension immunocytochemistry. Genotyping facilitated lineage assignment and/or confirmed clonality in 17 of 63 specimens (27%) that were difficult to determine based on morphologic data. These include cases of atypical lymphoid proliferations with polyclonal or inconclusive markers (n = 6), peripheral T-cell lymphoma (n = 3), extracutaneous mycosis fungoides (n = 1), lymphoblastic lymphoma (n = 4), null cell lymphoma (n = 1), and specimens with equivocal or technically unsatisfactory markers (n = 2). Based on these results, it is proposed that genotyping for lineage assignment and/or clonality be performed to include cases of atypical lymphoid proliferations, T-cell malignant neoplasms, lymphoid malignant neoplasms with equivocal markers, and differentiation of lymphoid from nonlymphoid neoplasms. Genotyping by antigen-receptor gene rearrangement appears to be redundant in cases with mature B-cell phenotypes that demonstrate monoclonality by immunophenotyping.