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.     

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.     

Fine-needle aspiration cytology of recurrent and metastatic mixed mesodermal tumors

We report the cytological and clinical findings of 16 fine-needle aspirates (FNAs) performed on recurrent (n = 6) and metastatic (n = 10) mixed mesodermal tumors (MMMTs). The median interval between the primary diagnosis and FNA was 16 mo. Primary sites were the endometrium (n = 11), the ovary (n = 3), the cervix (n = 1), and pelvic soft tissue (n = 1). Primary tumors showed carcinoma with homologous mesenchymal components in 13 cases and focal heterologous elements in three (two chondrosarcomas and one rhabdomyosarcoma). The FNAs showed carcinoma in all 16 cases, with adenocarcinoma differentiation in three, Mesenchymal elements were identified in aspirates of three recurrent and two metastatic lesions. They were all homologous. No heterologous mesenchymal elements were identified in the aspirates. We conclude that mesenchymal components in FNAs of MMMTs are less likely to be seen in metastatic lesions, and that heterologous mesenchymal components are rarely seen in these aspirates even in recurrent disease. These findings confirm that the epithelial component is responsible for the malignant behavior of MMMTs, and suggest that these lesions may need to be classified as sarcomatoid carcinomas rather than true carcinosarcomas. Diagn Cytopathol 1994;11:328–332. © 1994 Wiley-Liss, Inc.     

Expression of BAG-1 and BcL-2 Proteins Before and After Neoadjuvant Chemotherapy of Locally Advanced Breast Cancer

It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p = 0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy.