Octa-ammonium POSS-conjugated single-walled carbon nanotubes as vehicles for targeted delivery of paclitaxel

Background: Carbon nanotubes (CNTs) have unique physical and chemical properties. Furthermore, novel properties can be developed by attachment or encapsulation of functional groups. These unique properties facilitate the use of CNTs in drug delivery. We developed a new nanomedicine consisting of a nanocarrier, cell-targeting molecule, and chemotherapeutic drug and assessed its efficacy in vitro. Methods: The efficacy of a single-walled carbon nanotubes (SWCNTs)-based nanoconjugate system is assessed in the targeted delivery of paclitaxel (PTX) to cancer cells. SWCNTs were oxidized and reacted with octa-ammonium polyhedral oligomeric silsesquioxanes (octa-ammonium POSS) to render them biocompatible and water dispersable. The functionalized SWCNTs were loaded with PTX, a chemotherapeutic agent toxic to cancer cells, and Tn218 antibodies for cancer cell targeting. The nanohybrid composites were characterized with transmission electron microscopy (TEM), Fourier transform infrared (FTIR), and ultraviolet-visible-near-infrared (UV-Vis-NIR). Additionally, their cytotoxic effects on Colon cancer cell (HT-29) and Breast cancer cell (MCF-7) lines were assessed in vitro. Results: TEM, FTIR, and UV-Vis-NIR studies confirmed side-wall functionalization of SWCNT with COOH-groups, PTX, POSS, and antibodies. Increased cell death was observed with PTX-POSS-SWCNT, PTX-POSS-Ab-SWCNT, and free PTX compared to functionalized-SWCNT (f-SWCNT), POSS-SWCNT, and cell-only controls at 48 and 72 h time intervals in both cell lines. At all time intervals, there was no significant cell death in the POSS-SWCNT samples compared to cell-only controls. Conclusion: The PTX-based nanocomposites were shown to be as cytotoxic as free PTX. This important finding indicates successful release of PTX from the nanocomposites and further reiterates the potential of SWCNTs to deliver drugs directly to targeted cells and tissues

Medicinal leeches and the microsurgeon: A four-year study, clinical series and risk benefit review

Background: There are case reports and small series in the literature relating to the use of medicinal leeches by plastic surgeons; however, larger series from individual units are rare. The aim of this article is to present a comprehensive 4-year case series of the use of medicinal leeches, discuss the current evidence regarding indications, risks, and benefits and highlight the recent updates regarding leech speciation. Methods: Patients prescribed leeches in a 4-year period (July 2004–2008) were collated from hospital pharmacy records (N = 35). The number of leeches used, demographic, clinical, and microbiological details were retrospectively analyzed. Results: Thirty-five patients were treated with leeches. The age range was 2 to 98 years (mean = 49.3). Leeches were most commonly used for venous congestion in pedicled flaps and replantations. Blood transfusions were necessary in 12 cases (34%) [mean = 2.8 units, range 2–5 units]. Our infection rate was 20% (7/35) including five infections with Aeromonas spp. (14.2%). The proportion of patients becoming infected after leech therapy was significantly greater in the group of patients that did not receive prophylactic antibiotic treatment (Fisher's Exact test P = 0.0005). In total, 14 cases (40%) were salvaged in entirety, in 7 cases 80% or more, in 2 cases 50 to 79%, and in 1 case less than 50% of the tissues were salvaged. In 11 cases (31%), the tissues were totally lost. Conclusion: Our study highlights both the benefits and the risks to patients in selected clinical situations and also the potential risks. The routine use of antibiotic prophylaxis is supported. In view of the emerging evidence that Hirudo verbana are now used as standard leech therapy, and the primary pathogen is Aeromonas veronii, until a large prospective multicenter study is published, large series of patients treated with leeches should be reported. © 2011 Wiley-Liss, Inc. Microsurgery, 2011

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Application of OctaAmmonium-POSS functionalized single walled carbon nanotubes for thermal treatment of cancer

Introduction: Single walled carbon nanotubes (SWCNTs) have distinctive physical and chemical properties. Additionally, innovative properties can be established to match the clinical need by attachment of functional groups to the SWCNT. In this experiment SWCNT was functionalized with OctaAmmonium-POSS. Evidence suggests that functionalization of SWCNT with OctaAmmonium-POSS would augment the dispersion of SWCNT. We further postulate that functionalization of SWCNT with OctaAmmonium-POSS would enhance the temperature increase of SWCNT upon exposure to NIR laser irradiation. Methods: Functionalization of SWCNT was conferred by refluxing with acid and OctaAmmonium-POSS. Fourier Transform Infrared (FTIR) test UV-visible spectroscopy and morphology analysis using Transmission Electron Microscopy (TEM) confirmed successful functionalization of SWCNT. NIR irradiation of samples was conducted using an 808 nm laser at 1 watt. Temperature changes were documented using a thermal camera. A HT-29 colorectal cancer cell line was used as a model for photothermal ablation. Cell viability test was performed using trypan blue and fluorescence activated cell sorting (FACS) technique. Graph plotting and statistical analysis was conducted using Graph Pad Prism. Results: Following the functionalization process, TEM images showed a layer on the surface of the SWCNT. In the FTIR experiment, results illustrated the presence of the -COOH group on the functionalized SWCNTs. Upon further functionalization of SWCNT with OctaAmmonium-POSS, various peaks determined the formation of amide bond between the POSS molecule and functionalized SWCNT. The UV-visible spectra also determine the successful functionalization of the SWCNT following its treatment with acid and OctaAmmonium-POSS. Upon exposure to NIR, OctaAmmonium-POSS-SWCNT was the only treatment group that illustrated significantly higher temperature increase than the other treatment groups. Additionally cell death of NIR irradiated OctaAmmonium-POSS-SWCNT was statistically significant compared to other treatment groups. Conclusion: OctaAmmonium-POSS was used to render SWCNT biocompatible and water dispersible. Observation from this study determines that functionalization with OctaAmmonium-POSS show greater temperature increase compared to pristine SWCNTs upon its exposure NIR. This significant temperature increase is due to increasing the solubility of SWCNT following its functionalization with OctaAmmonium-POSS

Carbon nanotubes in the diagnosis and treatment of malignant melanoma

The potential role of carbon nanotubes (CNTs) in the diagnosis and treatment of malignant melanoma (MM) is still an emerging area of research. To date, there is strong evidence for the efficiency of CNTs in this therapeutic area, despite their unique physical, mechanical and biological properties. In this review, the application of CNTs in cancer diagnostics and treatment is reviewed, and consideration is given to the toxicity issues associated with their use

A new era of cancer treatment: carbon nanotubes as drug delivery tools

Cancer is a generic term that encompasses a group of diseases characterized by an uncontrolled proliferation of cells. There are over 200 different types of cancer, each of which gains its nomenclature according to the type of tissue the cell originates in. Many patients who succumb to cancer do not die as a result of the primary tumor, but because of the systemic effects of metastases on other regions away from the original site. One of the aims of cancer therapy is to prevent the metastatic process as early as possible. There are currently many therapies in clinical use, and recent advances in biotechnology lend credence to the potential of nanotechnology in the fight against cancer. Nanomaterials such as carbon nanotubes (CNTs), quantum dots, and dendrimers have unique properties that can be exploited for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials with nanometer-sized diameters and axial symmetry, giving them unique properties that can be exploited in the diagnosis and treatment of cancer. In addition, CNTs have the potential to deliver drugs directly to targeted cells and tissues. Alongside the rapid advances in the development of nanotechnology-based materials, elucidating the toxicity of nanoparticles is also imperative. Hence, in this review, we seek to explore the biomedical applications of CNTs, with particular emphasis on their use as therapeutic platforms in oncology

Strategies to Improve Homing of Stem Cells to achieve better Efficacy in Stem Cell Therapy

Stem/progenitor cell based therapeutic approach in our daily routine clinical practice, has been elusive dream in medical sciences and improvement of stem cell homing as one of major challenges in cell therapy programs, has been considered a promising milestone. It has been proved that stem/progenitor cells exhibit a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). Treatment with chemical compounds, preconditioning of the cells with hypoxia, cytokine and growth factor priming of the cells, genetic modifications, coating of cell surface with antibodies, glycoengineering, coating of stem cells with homing ligands by streptavidin linkers are some of strategies to increase the ability of stem cells to respond to the migratory stimuli. On the other side to modulate target sites to be more attractive for stem cells, some strategies like direct injection of chemokines, direct transfection of the target tissue with chemokine encoding genes, injection of ectopic chemokine expressing cells, application of scaffolds, electrical fields and low level laser have been introduced. These extensive investigations have provided significant potentials to enhance targeted stem/progenitor cells homing. Meanwhile there are still some limitations to apply these findings in clinics. To overcome these limitations, further studies should be aimed, unveiling the molecular and cellular mechanisms underlying endogenous cell trafficking during physiological and pathological events like embryogenesis, inflammation, wound healing, or cancer metastasis. Keywords: Cell therapy, Homing, Stem cells

Ability of serum C-reactive protein and white blood cell cout in predicting acute schemic stroke. A short -term follow-up study

Background: Stroke is one of the leading causes of mortality and long-term morbidity. The aim of the present study was to determine the ability of baseline serum C-reactive protein (CRP) and white blood cell count (WBC) values in predicting the outcome of acute ischemic stroke (AIS). Methods: This study consisted of patients with first AIS referred to Poursina Hospital, Rasht, Iran. Severity of stroke was determined according to the National Institute of Health (NIH) Stroke Scale at the time of admission. Serum CRP levels and WBC count were measured at the time of admission. All patients were followed-up for 90 days after discharge and the severity of stroke was assessed using modified Rankin Scale. Receiver operating characteristic curve analysis was used for calculating the most appropriate cutoff point of CRP and WBC count for differentiating patients with and without poor outcome at the end of the study period. Results: A total of 53 out of 102 patients (52%) had poor outcome. The most appropriate cutoff value for CRP in differentiating patients with and without poor outcome was 8.5mg/l (sensitivity: 73.1%, specificity: 69.4%) and for WBC the difference did not reach to a significant level. The cutoff points of CRP > 10.5 mg/ml yielded a predictive ability at sensitivity: 75%, specificity: 63.8% whereas predictive ability of WBC for mortality was at a borderline level. Conclusion: These findings indicate that high levels of serum CRP in AIS at the time of admission is associated with poor prognosis. However, this study found no ability for WBC in predicting AIS outcom

<em>In vitro</em> cytotoxic and apoptotic activities of <em>Allium paradoxum</em> (M. Bieb.) G. Don extract on human breast cancer cell line

247-254Researchers from all pharmaceutical fields are trying to find new drugs from natural origin with less toxicity. In northern Hyrcanian forests Iran, Allium paradoxum (M. Bieb.) G. Don has traditionally used as food and vegetable. Previously studies reports, this plant has a medicinal potential for anti-oxidant and anti-hemolytic activities. In this regard, we evaluated the anti-tumor activity of hydroalcoholic extract of A. paradoxum (M. Bieb.) G. Don in different concentrations on human breast cancer cell line (MCF-7). MTT assay was performed with MCF-7 cancer cell line and also evaluation of apoptotic effect, Bax and Bcl-2 expression in MCF7 cells were analyzed by real time RT-PCR. The results showed that the A. paradoxum (M. Bieb.) G. Don extracts decrease the viability of MCF-7 cell line in a dose-dependent manner and the most effective concentration of this extracts after 24 h treatment was 100 μM. Apoptosis induction was confirmed by fluorescence microscopy and plant extracts display a pro-apoptotic effect by down-regulated and up-regulated the expression of Bcl-2 and BAX in tumor cells, respectively. In conclusion, the study was confirmed pro-apoptotic and cytotoxicity effect of A. paradoxum (M. Bieb.) G. Don extract against MCF-7 cell lines. Based on being natural, low cost, accessibility, and noteworthy advantages of this product, it seems that A. paradoxum (M. Bieb.) G. Don has a potential source for isolation of novel anticancer agents for a drug