Methanolic extract of Kigelia africana and wound healing: an in vitro study.

OBJECTIVE: Kigelia africana (Lam.) Benth. (Bignoniaceae) syn. Kigelia pinnata (Jacq. DC) is a tropical plant that is native to tropical Africa. The aim of this study was to determine if a methanolic extract prepared from Kigelia africana (KAE) can promote wound healing in treated human normal epidermal keratinocyte (HaCaT) cells and human normal foreskin fibroblast cell line (BJ) cells compared with untreated cells. METHOD: Experimental steps included: the methanolic extraction of the leaf and fruit of the Kigelia africana plant; the preparation of HaCaT and BJ cell lines; cell culture with a stable tetrazolium salt-based proliferation assay; and the evaluation of the wound healing effect of KAE (2µg/ml) in BJ and HaCaT cells. The phytochemical contents of KAE were determined using liquid chromatography quadrupole time-of-flight mass spectrometry. RESULTS: The following molecules were identified as being present in the KAE, among others: cholesterol sulfate; lignoceric acid; embelin; isostearic acid; linoleic acid; dioctyl phthalate; arg-pro-thr; 15-methyl-15(S)-PGE1; sucrose; benzododecinium (Ajatin); and 9-Octadecenamide (oleamide). KAE effected faster wound healing in treated cells compared with untreated cells for both cell lines. HaCaT cells that had been mechanically injured and treated with KAE healed completely in 48 hours compared with 72 hours for untreated HaCaT cells. Treated BJ cells healed completely in 72 hours compared with 96 hours for untreated BJ cells. Concentrations of KAE up to 300µg/ml had a very low cytotoxic effect on treated BJ and HaCaT cells. CONCLUSION: The experimental data in this study support the potential of KAE-based wound healing treatment to accelerate wound healing.

Combining histone deacetylase inhibitors (HDACis) with other therapies for cancer therapy.

Histone deacetylases (HDACs) play an important role in regulating the expression of genes involved in tumorigenesis and tumor maintenance, and hence they have been considered as key targets in cancer therapy. As a novel category of antitumor agents, histone deacetylase inhibitors (HDACis) can induce cell cycle arrest, apoptosis, and differentiation in cancer cells, ultimately combating cancer. Although in the United States, the use of HDACis for the treatment of certain cancers has been approved, the therapeutic efficacy of HDACis as a single therapeutic agent in solid tumorshas been unsatisfactory and drug resistance may yet occur. To enhance therapeutic efficacy and limit drug resistance, numerous combination therapies involving HDACis in synergy with other antitumor therapies have been studied. In this review, we describe the classification of HDACs. Moreover, we summarize the antitumor mechanism of the HDACis for targeting key cellular processes of cancers (cell cycle, apoptosis, angiogenesis, DNA repair, and immune response). In addition, we outline the major developments of other antitumor therapies in combination with HDACis, including chemotherapy, radiotherapy, phototherapy, targeted therapy, and immunotherapy. Finally, we discuss the current state and challenges of HDACis-drugs combinations in future clinical studies, with the aim of optimizing the antitumor effect of such combinations.

An in-vivo pilot study into the effects of FDG-mNP in cancer in mice.

PURPOSE: Previously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice. MATERIALS AND METHODS: FDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points. RESULTS: In prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months. CONCLUSION: Intravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.

A Pilot Study Into the Use of FDG-mNP as an Alternative Approach in Neuroblastoma Cell Hyperthermia.

Herein, we present a pilot study concerning the use of fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNP) as a potential agent in magnetic nanoparticle mediated neuroblastoma cancer cell hyperthermia. This approach makes use of the 'Warburg effect', utilizing the fact that cancer cells have a higher metabolic rate than normal cells. FDG-mNP were synthesized, then applied to the SH-SY5Y neuroblastoma cancer cell line and exposed to an ac magnetic field. 3D Calorimetry was performed on the FDG-mNP compound. Simulations were performed using SEMCAD X software using Thelonious, (an anatomically correct male child model) in order to understand more about the end requirements with respect to cancer cell destruction. We investigated FDG-mNP mediated neuroblastoma cytotoxicity in conjunction with ac magnetic field exposure. Results are presented for 3D FDG-mNP SAR mnp (10.86 ± 0.99 W/g of particles) using a therapeutic dose of 0.83 mg/ mL. Human model simulations suggest that 43 W/kg SAR Theo would be required to obtain 42 °C within the centre of a liver tumor (Tumor size, bounding box x = 64, y = 61, z = 65 [mm]), and that the temperature distribution is inhomogeneous within the tumor. Our study suggests that this approach could potentially be used to increase the temperature within cells that would result in cancer cell death due to hyperthermia. Further development of this research will also involve using whole tumors removed from living organisms in conjunction with magnetic resonance imaging and positron emission tomography.

Prostate MRSI predicts outcome in radical prostatectomy patients.

BACKGROUND: New non-invasive methods are needed for sub-stratifying high-risk prostate cancer patients. Magnetic resonance spectroscopic imaging (MRSI) maps metabolites in prostate cancer, providing information on tumor aggressiveness and volume. PURPOSE: To investigate the correlation between MRSI and treatment failure (TF) after radical prostatectomy (RP). METHODS: Two-hundred sixty-two patients who underwent endorectal MRI/MRSI followed by RP at our institution from 2003 to 2007 were studied. MRI stage, number of voxels in the MRSI index lesion (NILV), number of high-grade voxels (NHGV), and number of voxels containing undetectable polyamines (NUPV) were derived. Clinical outcome was followed until August, 2014. Treatment failure was defined as 1) biochemical recurrence (BCR), 2) persistently detectable PSA after RP, or 3) adjuvant therapy initiated in the absence of BCR. MRI/MRSI features and clinical parameters were compared to TF by univariate Cox Proportional Hazards Regression. After backward selection, each MRSI parameter was included in a separate regression model adjusted for NCCN-based clinical risk score (CRS), number of biopsy cores positive (NPC), and MRI stage. RESULTS: In univariate analysis, all clinical variables were associated with TF in addition to MRI stage, NILV, NHGV, and NUPV. In multivariate analysis, NILV, NHGV, and NUPV were also significant risk factors for TF (p=0.016, p=0.002, p=0.006, respectively). The association between the number of tumor voxels with undetectable polyamines and the probability of treatment failure has not been previously reported. The number of MRSI cancer voxels correlated with extracapsular extension (ECE) (p<0.0001). CONCLUSIONS: MRSI was associated with post-radical prostatectomy treatment failure in models adjusted for the number of positive biopsy cores and clinical risk score. This is the first report that in radical prostatectomy patients MRSI has an association with treatment failure independent of the number of positive biopsy cores. MRSI may help the clinician determine whether patients with high risk disease who undergo RP are candidates for specialized additional treatment.