A bioavailability study on microbeads and nanoliposomes fabricated by dense carbon dioxide technologies using human-primary monocytes and flow cytometry assay.

Supercritical Emulsion Extraction (SEE) and Supercritical assisted Liposome formation (SuperLip), use dense gases such as carbon dioxide (dCO2) to fabricate advanced micro/nanocarriers. SEE uses dCO2 to extract solvent from the oily phase of an emulsion and obtain biopolymer microbead; For this study, poly-Lactic Acid (PLA) microbeads of 1 ±â€¯0.2 µm in mean size loaded at 1 µg/mgPLA with Rhodamine B (ROD) were prepared by SEE; the beads showed a solvent residue lower than 10 ppm and encapsulated the fluorochrome with an efficiency of 90%. SuperLip uses dCO2 to enhance lipid/ethanol/water mixing and to promote the ethanol extraction from liposome suspension. In this case, phosphatidyl-choline (PC) vesicles with a mean size of 0.2 ±â€¯0.05 µm and loaded with Fluorescein Iso-ThioCyanate (FITC) at 8 µg/mgPC were prepared; small unilamellar structure was observed for all the vesicles with FITC encapsulation efficiency of 80%. Ethanol residue of 50 ppm was measured in all the liposome suspensions. The bioavailability of microbeads and nanoliposomes was assessed through incubation with human monocytes previously isolated from healthy donors' blood. A specifically optimized protocol that allowed their quenching on the cell surface was developed to monitor by flow cytometer assay only the cell population that effectively internalized the carriers. When microbeads were tested, the percentage of alive internalizing monocytes was of about 30%. An internalization of 96.1 ±â€¯21% was, instead, obtained at dosage of 0.1 mg/mL for nanoliposomes. In this last case, monocytes showed a vitality of almost 100% after vesicles internalization at all the concentrations studied; on the other hand, cell apoptosis progressively increased in a dose/response manner, after polymer microbeads phagocytosis. The proposed data suggested that dCO2 technologies can be reliably used to fabricate intracellular carriers.

p53 regulates the mevalonate pathway in human glioblastoma multiforme.

The mevalonate (MVA) pathway is an important metabolic pathway implicated in multiple aspects of tumorigenesis. In this study, we provided evidence that p53 induces the expression of a group of enzymes of the MVA pathway including 3'-hydroxy-3'-methylglutaryl-coenzyme A reductase, MVA kinase, farnesyl diphosphate synthase and farnesyl diphosphate farnesyl transferase 1, in the human glioblastoma multiforme cell line, U343 cells, and in normal human astrocytes, NHAs. Genetic and pharmacologic perturbation of p53 directly influences the expression of these genes. Furthermore, p53 is recruited to the gene promoters in designated p53-responsive elements, thereby increasing their transcription. Such effect was abolished by site-directed mutagenesis in the p53-responsive element of promoter of the genes. These findings highlight another aspect of p53 functions unrelated to tumor suppression and suggest p53 as a novel regulator of the MVA pathway providing insight into the role of this pathway in cancer progression.

Anandamide inhibits breast tumor-induced angiogenesis.

Breast cancer is one of the most frequently diagnosed malignancies and a leading cause of cancer death in women. Great advances in the treatment of primary tumors have led to a significant increment in the overall survival rates, however recurrence and metastatic disease, the underlying cause of death, are still a medical challenge. Breast cancer is highly dependent on neovascularization to progress. In the last years several anti-angiogenic drugs have been developed and administered to patients in combination with chemotherapeutic drugs. Collected preclinical evidence has proposed the endocannabinoid system as a potential target in cancer. The endocannabinoid anandamide has been reported to affect breast cancer growth at multiple levels, by inhibiting proliferation, migration and invasiveness in vitro and in vivo and by directly inhibiting angiogenesis. Aim of the present work is to investigate if anandamide is able to affect the proangiogenic phenotype of the highly invasive and metastatic breast cancer cells MDA-MB-231. We found that following anandamide treatment, MDAMB-231 cells lose their ability to stimulate endothelial cells proliferation in vitro, due to a significant inhibition of all the pro-angiogenic factors produced by these cells. This finding adds another piece of evidence to the anti-tumor efficacy of anandamide in breast cancer.

[Vitamin E in the treatment of pregnancy complicated by uterine myoma]. / La vitamina E nel trattamento delle gravidanze associate a miomi uterini.

The authors describe the encouraging results obtained in the treatment of uterine myomas during pregnancy, using vitamin E at a dose of 300 mg times a day, starting the administration from the time of the first examination of the patient, which took place between week 6 and 12 of gestation. A group of 25 women underwent treatment, aged between 25 and 41 years old, of whom 15 were primigravidas and 10 with one or more previous pregnancies, suffering from uterine myomas in pregnancy, and observed between 1986 and 1994. All the pregnancies continued to term and elective cesarean section was performed associated with single or multiple myomectomy. The neonatal outcome was satisfactory in all cases and no collateral effects were observed in either mothers or fetuses.

[A case of uterine leiomyosarcoma in a young patient]. / Su di un caso di leiomiosarcoma uterino in giovane età.

The authors, after a short review of the literature, report a clinical case observed by them. They describe a case of unsuspected uterine leiomyosarcoma diagnosed after a miomectomy and they discuss the question about therapeutic management.