Does a nanomolecule of carboplatin injected periocularly help in attaining higher intravitreal concentrations?

PURPOSE. To compare intravitreal concentration (VC) of commercially available carboplatin (CAC) and the novel nanomolecule carboplatin (NMC), after periocular injection. METHODS. The study was a comparative animal study involving 24 white Sprague-Dawley rats, aged between 6 weeks and 3 months. CAC was bound with a nanoparticulate carrier by co-acervation with a biocompatible and biodegradable protein BSA (bovine serum albumin). The particulate size, binding, and structure of the carrier was analyzed with dynamic light-scattering electron microscopy, FTIR (Fourier transform infrared) spectroscopy, and SDS-polyacrylamide gel electrophoresis. Twenty-four white rats were anesthetized. The right eye of each rat was injected with periocular CAC (1 mL) and the left eye with NMC (1 mL) by a trained ophthalmologist. Four mice each were euthanatized at days 1, 2, 3, 5, 7, 14, and 21 and both eyes were enucleated. The intravitreal concentrations of commercial carboplatin and nanomolecule carboplatin were determined with HPLC (high-performance liquid chromatography). Data were analyzed with the paired t-test. The main outcome measure was intravitreal concentrations CAC and NMC over time. RESULTS. The NMC vitreal concentration was higher than the CAC concentrations in all animals, until day 7 (P = 0.0001). On days 14 and 21, the CAC vitreal concentration was higher than the NMC concentrations in all animals (P = 0.0002). Overall, the mean vitreal concentration of NMC was greater than CAC. CONCLUSIONS. Nanoparticulate-bound carboplatin has greater transscleral transport than commercially available carboplatin, especially in the first week after injection and may help enhance the proven adjuvant efficacy of periocular carboplatin over and above systemic chemotherapy in treating human retinoblastoma, especially those with vitreal seeds. This trial is being published to establish a proof of principle for this method of therapy. (Invest Ophthalmol Vis Sci. 2009;50:5896-5900) DOI:10.1167/iovs.09-391

Castanea sativa Mill. bark extract exhibits chemopreventive properties triggering extrinsic apoptotic pathway in Jurkat cells

Abstract Background Chemoprevention represents the possibility to prevent, stop or reverse the cancerogenetic process. In this context the interest towards natural extracts and botanical drugs has constantly grown due to their phytochemical content. Castanea sativa Mill. (CSM) extracts showed to exert positive effect in the prevention/counteraction of chronic/degenerative diseases, therefore, we evaluated the potential chemopreventive effect of CSM bark extract. Methods Flow cytometry (FCM) analyses of Jurkat cells treated with CSM bark extract (0–500 μg·mL−1) for 24–72 h allowed evaluating its cytotoxicity and ability to induce apoptosis through the intrinsic or extrinsic pathways. Moreover, to evaluate CSM bark extract selectivity towards cancer cells, its cytotoxic and pro-apoptotic effect was also evaluated in human peripheral blood lymphocytes (PBL). Results CSM bark extract induced apoptosis in Jurkat cells in a dose- and time- dependent manner activating the extrinsic pathways as evidenced by the increase of activated caspase-8 positive cells. Moreover, IC50 calculated after 24 h treatment resulted 304 and 128 μg·mL−1 in PBL and Jurkat cells respectively. Conclusions Our data suggest that CSM bark extract might be considered an interesting potential anti-cancer agent, since it induces apoptosis in cancer cells without appreciable cytotoxic effects on non-transformed cells

Prevention of oral cancer

Oral cancer has become a major debilitating incidence in both genders alike. Oral cancer, a part of head and neck cancer, is a combination of two types of cancer: oral cavity cancer and oropharyngeal cancer. The most common type of oral cancer is the squamous cell carcinoma which represents more than 90% of oral cancer cases. There are in existence common types of oral cancer as well, in addition to precancerous or benign lesions and tumors. These lesions and tumors may lead to cancer if left untreated. There is an increased need to combat oral cancer and its benign or malignant precursors. There is no better way of starting this battle than prevention. Prevention against oral cancer is divided into three stages, namely, primary, secondary, and tertiary prevention. Primary prevention has its manifestations in the control and/or elimination of risk factors for cancer such as tobacco smoking, excessive alcohol consumption, chewing betel quid, prolonged sunlight exposure, and improper nutrition, among others. Secondary prevention encompasses screening tests and early diagnosis and treatment of diseases that may potentially cross over into malignancy. Tertiary prevention is indicated when a person has previously had cancer or oral cancer, also when a person is immunosuppressed or has GVHD due to stem cell transplant. This stage also includes gene mutation assessment, an estimate of personal cancer risk and seeking of personalized genetic recommendations. Current research also focuses on emerging gene therapy through employing adenoviruses. This chapter will address and focus on the aforementioned prevention strategies, elaborating and expanding on risk factors and how to decrease chances of developing oral cancer. Additionally we will look at barriers against prevention developing an intricate and complete picture of the links between methods of prevention and factors that hinder prevention. In exploring the details within the chapter, one can conclude that oral cancer is a disease that is preventable and controllable but habitually has been given little significance due to many factors. Oral cancer is typically discovered late in its development, most often when it has already metastasized to the lymph nodes, at which point prognosis becomes very poor. Therefore, we firmly believe that it is no longer viable that prevention be considered a person’s own responsibility but rather a matter of a group of health professionals. Oral cancer should be prevented through creating awareness, behavioral change, routine dental checkups, and policies that eradicate exposure to risk factors