Interaction Between Breast Cancer Cells and Adipose Tissue Cells Derived from Fat Grafting.

BACKGROUND: Adipose tissue transplantation has the benefit of providing both regenerative and aesthetic outcomes in breast cancer treatment. However, the transplanted tissue can stimulate the growth of residual cancer cells. OBJECTIVES: The aim of this study is to identify the interactions between adipose tissue cell subpopulations and human cancer cell lines. METHODS: Intact adipose tissue from lipofilling procedures as well as fibroblasts derived from adipose tissue, were cocultured in the presence of MDA-MB-231, MCF-7 e ZR-75-1 breast cancer cell lines. The influence on cancer cell lines of fibroblasts, induced to differentiate into specific adipocytes, was also assayed. RESULTS: All cancer cell lines displayed a significant increase in proliferation rate when cocultured in the presence of either intact adipose tissue or induced adipocytes. To a lesser extent, uninduced fibroblasts stimulate breast cancer cell proliferation. CONCLUSIONS: Recent studies have shown that the microenvironment surrounding breast cancer cells may stimulate growth and promote progression of residual cancer cells when surgery is performed on the main tumor mass. Accordingly, the graft of adipose tissue could potentially promote or accelerate the development of a subclinical tumor or support its locoregional recurrence. Our data suggest that adipocytes have a remarkable influence on the proliferation of cancer cell lines. The oncological safety of the lipofilling procedure outcome is still debated; thus, further studies and consistent follow-up examination are needed.

A comparative evaluation between new ternary zirconium alloys as alternative metals for orthopedic and dental prosthetic devices.

PURPOSE: We assessed in vitro the corrosion behavior and biocompatibility of four Zr-based alloys (Zr97.5 Nb1.5VM1.0  ; VM, valve metal: Ti, Mo, W, Ta; at%) to be used as implant materials, comparing the results with grade-2 titanium, a biocompatible metal standard. METHODS: Corrosion resistance was investigated by open circuit potential and electrochemical impedance spectroscopy measurements as a function of exposure time to an artificial physiological environment (Ringer's solution). Human bone marrow stromal cells were used to evaluate biocompatibility of the alloys and their influence on growth kinetics and cell osteogenic differentiation through histochemical and gene expression analyses. RESULTS: Open circuit potential values indicated that Zr-based alloys and grade-2 Ti undergo spontaneous passivation in the simulated aggressive environment. High impedance values for all samples demonstrated improved corrosion resistance of the oxide film, with the best protection characteristics displayed by Zr97.5  Nb1.5Ta1.0. Cells seeded on all surfaces showed the same growth kinetics, although matrix mineralization and alkaline phosphatase activity were maximal on Zr97.5  Nb1.5Mo1.0 and Zr97.5   Nb1.5Ta1.0. Markers of ongoing proliferation, however, such as podocalyxin and CD49f, were still overexpressed on Zr97.5   Nb1.5   Mo1.0 even upon osteoinduction. No relevant effects were noted for the CD146-expressing population of bone progenitors. Nonetheless, the presence of a more differentiated cell population on Zr97.5Nb1.5Ta1.0 samples was inferable by comparing mineralization data and transcript levels of osteogenic markers (osteocalcin, osteopontin, bone sialoprotein, and RUNX2). CONCLUSIONS: The combination of passivation, corrosion resistance and satisfactory biotolerance to bone progenitors make the Zr-based alloys promising implant materials. Among those we tested, Zr97.5Nb1.5Ta1.0 seems to be the most appealing.

The impact of long-term exposure to space environment on adult mammalian organisms: a study on mouse thyroid and testis.

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis.In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10(-7)M and 10(-8)M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains.In testes, immunofluorescent reaction for 3ß- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1ß were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3ß and 17ß steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 ß expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. -90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules.Space-induced changes of structure and function of thyroid and testis/epididymis could be responsible for variations of hormone levels in human during space missions. More research, hopefully a reflight of MDS, would be needed to establish whether the space environment acts directly on the peripheral glands or induces changes in the hypotalamus-pituitary-glandular axis.

Efects of growth hormone and cadmium on the transcription regulation of two metallothionein isoforms.

The effect of growth hormone (GH) and cadmium (Cd) on metallothionein (MT) expression was investigated in hepatoma cells. In fish the constitutive isoform MT-B and the metal-responsive MT-A are expressed. Real-time RT-PCR revealed that: Cd up-regulates mostly MT-A, GH slightly induces MT-B and the GH/Cd combination induces synergistically both MTs. Perturbations in Ca2+ levels suppressed or reduced the Cd-induction of MTs and abolished the GH/Cd synergy. Similar results were obtained by inhibition of tyrosine kinases. Also the signaling molecules recruited by the GH receptor responded differently to GH and Cd, with ERKs showing a synergistic activation upon GH/Cd. The following conclusions can be drawn: (1) cytosolic Ca2+ is mainly involved in MT-A regulation; (2) both Ca2+ and tyrosine phosphorylation are essential for Cd-induction and GH/Cd synergy on MTs. The synergy could depend on interactions in different signaling pathways, leading to a differential recruitment of MTF-1 and AP-1 transcription factors.

Retinoids and human breast cancer: in vivo effects of an antagonist for RAR-alpha.

The aim of the present study was to evaluate the in vivo effects of the RAR-alpha selective antagonist Ro 41-5253 on a xenograft animal model for breast cancer. Our observations indicate a lack of toxic side effects of the drug, even when used at high dosages. It is interesting to note that using Ro 41-5253 at dosages of 10, 30 and 100 mg/kg/die resulted in a slight, but significant inhibition of cell growth. The data obtained in this study represents the basis for a further evaluation of Ro 41-5253 anti-neoplastic activity on transgenic breast cancer animal models.

Synergistic effect of the anti-HER-2/neu antibody and cisplatin in immortalized and primary mesothelioma cell lines.

Malignant mesothelioma (MM) still remains a therapeutic and diagnostic problem to which new therapeutic perspectives are being continuously tried and tested. Three different primary cultures (MMGe-1, MES MM 98, and MES 1) and one immortalized cell line (MSTO 211 H) of human MM were studied in order to evaluate the HER-2/neu expression. Three out of four cell lines showed a different level of c-erbB-2 expression, the highest being detected on the MSTO 211 H cell line (fibroblastic phenotype), whereas MMGe-1 resulted negative. The effect of the anti-HER-2/neu antibody (Trastuzumab) alone, and in combination with cisplatin (CDDP) at different doses (ranging from 0.1 to 100 microg/ml), was studied on all the c-erB-2 positive cell lines. Trastuzumab was able to inhibit cell proliferation in a time-dependent manner, with growth inhibition also obtained at low concentrations (0.1-1 microg/ml). Combined treatment with Trastuzumab (10 microg/ml) and CDDP (1 microg/ml) showed synergism. Our results were encouraging, and suggest a rationale for further investigations in a clinical setting.