Radiofrequency treatment alters cancer cell phenotype.

The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease.

Gold nanoparticles stabilized with MPEG-grafted poly(l-lysine): in vitro and in vivo evaluation of a potential theranostic agent.

As the number of diagnostic and therapeutic applications utilizing gold nanoparticles (AuNPs) increases, so does the need for AuNPs that are stable in vivo, biocompatible, and suitable for bioconjugation. We investigated a strategy for AuNP stabilization that uses methoxypolyethylene glycol-graft-poly(l-lysine) copolymer (MPEG-gPLL) bearing free amino groups as a stabilizing molecule. MPEG-gPLL injected into water solutions of HAuCl4 with or without trisodium citrate resulted in spherical (Zav = 36 nm), monodisperse (PDI = 0.

The effects of non-invasive radiofrequency treatment and hyperthermia on malignant and nonmalignant cells.

Background: Exposure of biological subjects to electromagnetic fields with a high frequency is associated with temperature elevation. In our recent studies, we reported that non-invasive radiofrequency (RF) treatment at 13.56 MHz with the field ranging from 1 KeV to 20 KeV/m2 inhibits tumor progression in animals with abdominal tumor xenografts and enhances the anticancer effect of chemotherapy.

Noninvasive radiofrequency treatment effect on mitochondria in pancreatic cancer cells.

Background: The development of novel therapeutic approaches for cancer therapy is important, especially for tumors that have poor response or develop resistance to standard chemotherapy and radiation. We discovered that noninvasive radiofrequency (RF) fields can affect cancer cells but not normal cells, inhibit progression of tumors in mice, and enhance the anticancer effects of chemotherapy. However, it remains unclear what physiological and molecular mechanisms this treatment induces inside cells.

Autophagy and enhanced chemosensitivity in experimental pancreatic cancers induced by noninvasive radiofrequency field treatment.

Background: Patients with pancreatic ductal adenocarcinoma (PDAC) have limited therapeutic options and poor response to the standard gemcitabine (GCB)-based chemotherapy. In the current study, the authors investigated the feasibility of noninvasive short-wave radiofrequency (RF) electric fields to improve the cytotoxic effect of GCB on PDAC cells and determined its mechanism of action.

Methods: The cytotoxicity of RF alone and in combination with GCB was studied in vitro on normal pancreatic human pancreatic ductal epithelial cells and different PDAC cell lines by flow cytometry, and in vivo on ectopic and orthotopic human PDAC xenograft models in mice.

Tumor selective hyperthermia induced by short-wave capacitively-coupled RF electric-fields.

There is a renewed interest in developing high-intensity short wave capacitively-coupled radiofrequency (RF) electric-fields for nanoparticle-mediated tumor-targeted hyperthermia. However, the direct thermal effects of such high-intensity electric-fields (13.56 MHZ, 600 W) on normal and tumor tissues are not completely understood.

The histone deacetylase inhibitor, MS-275 (entinostat), downregulates c-FLIP, sensitizes osteosarcoma cells to FasL, and induces the regression of osteosarcoma lung metastases.

The purpose of this study was to determine the effects of the histone deacetylase inhibitor, MS-275, on the Fas signaling pathway and susceptibility of osteosarcoma (OS) to Fas ligand (FasL)-induced cell death. OS metastasizes almost exclusively to the lungs. We have shown that Fas expression in OS cells is inversely correlated with their metastatic potential.

Inhibition of Cdc42-interacting protein 4 (CIP4) impairs osteosarcoma tumor progression.

Background: In patients with Osteosarcoma (OS), larger primary tumor size correlates with higher metastasis incidence and lower overall survival. Identifying the mechanisms that control primary tumor growth can lead to the new therapeutic approaches and improve prognosis. Cytoskeleton regulatory molecules play an important role in tumor cells proliferation and motility.

Effect of the histone deacetylase inhibitor SNDX-275 on Fas signaling in osteosarcoma cells and the feasibility of its topical application for the treatment of osteosarcoma lung metastases.

Background: Patients with lung metastases from osteosarcoma (OS) have poor response to salvage therapy. Understanding the mechanisms involved in the metastatic process of OS may lead to new effective therapeutic approaches. The authors reported previously that up-regulation of the Fas receptor by transfecting OS cells with Fas plasmid inhibited the in vivo growth of metastases in the lungs.

Fas expression in metastatic osteosarcoma cells is not regulated by CpG island methylation.

Fas expression in osteosarcoma (OS) cells is inversely correlated with the metastatic potential of OS to the lung. The purpose of this study was to determine whether loss of Fas expression in metastatic OS cells is secondary to DNA methylation of CpG islands in the Fas gene. SAOS-2 cells have high levels of Fas expression and do not form lung metastases when injected intravenously, whereas LM7 cells have low levels of Fas expression and do produce lung metastases.

COX-2 expression correlates with survival in patients with osteosarcoma lung metastases.

The purpose of this study was to determine whether a correlation exists between tumor cyclooxygenase (COX)-2 expression and disease-specific survival in patients with osteosarcoma lung metastases. Thirty-six patients diagnosed with osteosarcoma lung metastases between the years 1990 and 2001 were included in this retrospective study. The majority of the patients (72%) presented newly -diagnosed osteosarcoma lung metastases whereas the remaining patients (28%) presented recurrent disease.

Exploratory analysis of Fas gene polymorphisms in pediatric osteosarcoma patients.

Defective apoptosis signaling by the Fas pathway has carcinogenic implications. We analyzed 123 pediatric patients with osteosarcoma for Fas single nucleotide polymorphisms: 2 of the promoter region (-1377 G>A and -670 A>G) and 2 of the coding region (exon 3 18272 A>G and exon 7 22628 C>T). As a comparison group, we used 510 adults without a history of cancer.

Intranasal granulocyte-macrophage colony-stimulating factor reduces the Aspergillus burden in an immunosuppressed murine model of pulmonary aspergillosis.

We demonstrated that intranasal granulocyte-macrophage colony-stimulating factor given to immunosuppressed mice infected with pulmonary aspergillosis resulted in a sixfold reduction in the lung fungal burden compared to the result for saline-treated mice (P = 0.045). These data suggest that lung-targeted immunotherapy may be complementary to antifungal agents and may improve patient responses.

Fas-negative osteosarcoma tumor cells are selected during metastasis to the lungs: the role of the Fas pathway in the metastatic process of osteosarcoma.

Low expression of Fas by different tumors including osteosarcoma, correlates with poor prognosis. We found that osteosarcoma lung metastases from patients expressed negligible amounts of Fas, but primary tumors often expressed high Fas levels. The reason for this discrepancy is unknown.

Expression of granulocyte-colony-stimulating factor and its receptor in human Ewing sarcoma cells and patient tumor specimens: potential consequences of granulocyte-colony-stimulating factor administration.

Background: Ewing sarcoma (ES) is a highly vascular malignancy. It has been demonstrated that both angiogenesis and vasculogenesis contribute to the growth of ES tumors. Granulocyte-colony-stimulating factor (G-CSF), a cytokine known to stimulate bone marrow (BM) stem cell production and angiogenesis, is routinely administered to ES patients after chemotherapy.

Corruption of the Fas pathway delays the pulmonary clearance of murine osteosarcoma cells, enhances their metastatic potential, and reduces the effect of aerosol gemcitabine.

Purpose: Pulmonary metastases continue to be a significant problem in osteosarcoma. Apoptosis dysfunction is known to influence tumor development. Fas (CD95, APO-1)/FasL is one of the most extensively studied apoptotic pathways.

Intranasal interleukin-12 gene therapy enhanced the activity of ifosfamide against osteosarcoma lung metastases.

Background: Cyclophosphamide (CTX) and ifosfamide (IFX) are alkylating agents used to treat osteosarcoma (OS). It was previously demonstrated that the sensitivity of OS cells to 4-hydroperoxycyclophosphamide (4-HC, the active metabolite of CTX) is augmented by interleukin (IL)-12 in vitro through a mechanism involving the Fas/FasL pathway. The purpose of these studies was to determine whether this synergistic effect is operational in vivo.

Interleukin-12 up-regulates Fas expression in human osteosarcoma and Ewing's sarcoma cells by enhancing its promoter activity.

Interleukin-12 (IL-12) has shown significant antitumor activity in several preclinical animal tumor models. Our previous studies showed that IL-12 inhibited tumor growth in human osteosarcoma and Ewing's sarcoma animal model. Decreased Fas expression in osteosarcoma increased the lung metastatic potential.

Fas expression in lung metastasis from osteosarcoma patients.

The authors' animal studies have shown that the metastatic potential of osteosarcoma (OS) cells correlates inversely with Fas expression-that is, Fas-negative cells metastasize but Fas-positive cells do not. One reason for this in the context of OS lung metastases may be that Fas-positive cells are eliminated by engagement with the Fas ligand (FasL) constitutively expressed on the surface of pneumocytes, whereas Fas-negative tumor cells are not. The purpose of this study was to determine the status of Fas expression in OS lung metastases from patients.

Aerosol gemcitabine inhibits the growth of primary osteosarcoma and osteosarcoma lung metastases.

Osteosacarcoma (OS) lung metastases are often resistant to chemotherapy. Most anticancer drugs are administered systemically. In many cases this is followed by dose-dependent toxicity, which may not allow the achievement of therapeutic levels in lungs to eradicate metastases.

Increased Fas expression reduces the metastatic potential of human osteosarcoma cells.

Purpose: The process of metastasis requires the single tumor cell that seeds the metastatic clone to complete a complex series of steps. Identifying factors responsible for these steps is essential in developing and improving targeted therapy for metastasis. Resistance to receptor-mediated cell death, such as the Fas/Fas ligand pathway, is one mechanism commonly exploited by metastatic cell populations.

Cyclosporin A aerosol improves the anticancer effect of paclitaxel aerosol in mice.

The objective of this study was to assess the effect of cyclosporin A liposome aerosol on the anticancer activity of paclitaxel (PTX) liposome aerosol against renal cell carcinoma (Renca) pulmonary metastases in mice. Cyclosporin A (CsA) was administered as a liposome aerosol for one-half hour before starting one-half hour treatment with PTX liposome aerosol (CsA/PTX), and in a second groups of animals cyclosporin A liposome aerosol was given before PTX for one-half hour and also later by mixing a second dose of cyclosporin A aerosol with PTX aerosol and extending the treatment period to one hour (CsA/PTX + CsA). In one experiment, PTX and CsA/PTX aerosols were significantly more effective compared to untreated controls against renal cell cancer as measured by lung weights and tumor surface areas.

Biodistribution and pharmacokinetics of aerosol and intravenously administered DNA-polyethyleneimine complexes: optimization of pulmonary delivery and retention.

This report describes the time-dependent biodistribution of human p53 plasmid delivered in aerosol with polyethyleneimine in mice compared to the distribution of this material following intravenous injection. Area-under-the-curve values for p53 plasmid after inhalation were 2.8-fold greater than values after intravenous administration, despite the fact that the delivered aerosol dose was one-fifth the intravenous dose.

Paclitaxel (taxol) and taxoid derivates for lung cancer treatment: potential for aerosol delivery.

Paclitaxel (PTX, Taxol) has revolutionized cancer treatment in the past decade and is recognized as one of the biggest advances in oncology medicine. In spite of the good clinical efficacy shown by PTX, there is still a growing need to achieve better safety and pharmacokinetic profile of PTX in patients. The standard delivery modalities of intravenous infusion result in multiple side effects, and targeting of the drug to specific areas within the body can result in better efficacy and lower toxicity.