Long Term Assessment for Delayed Toxicities of Radiotherapy for Cervical Cancer Patient with Systemic Lupus Erythematosus

Using Radiation in patients with systemic lupus erythematosus (SLE), especially if discoid lesions are present within the radiation field, is associated with modest increase in the risk of acute and delayed toxicity. Thus, its use is relatively contraindicated. Here-in we describe a patient with active SLE and grade 4 renal dysfunction who presented with locally advanced cervical cancer Radiologically stage IIB (by CT and MRI), was treated with radiotherapy alone using intensity modulated radiotherapy (IMRT) in 2008. Patient did not experience any grade 3 or 4 acute toxicities which were reported before. Over the last ten years of follow up she did not experience any delayed toxicity, which supports the patient adapted radiotherapy with novel radiation therapy techniques. Keywords: Pelvic radiotherapy, SLE, Acute and late toxicity

Pre-clinical study of IRDye800CW-nimotuzumab formulation, stability, pharmacokinetics, and safety

Background Epidermal growth factor receptor (EGFR) is a target for cancer therapy as it is overexpressed in a wide variety of cancers. Therapeutic antibodies that bind EGFR are being evaluated in clinical trials as imaging agents for positron emission tomography and image-guided surgery. However, some of these antibodies have safety concerns such as infusion reactions, limiting their use in imaging applications. Nimotuzumab is a therapeutic monoclonal antibody that is specific for EGFR and has been used as a therapy in a number of countries. Methods Formulation of IRDye800CW-nimotuzumab for a clinical trial application was prepared. The physical, chemical, and pharmaceutical properties were tested to develop the specifications to determine stability of the product. The acute and delayed toxicities were tested and IRDye800CW-nimotuzumab was determined to be non-toxic. Non-compartmental pharmacokinetics analysis was used to determine the half-life of IRDye800CW-nimotuzumab. Results IRDye800CW-nimotuzumab was determined to be non-toxic from the acute and delayed toxicity study. The half-life of IRDye800CW-nimotuzumab was determined to be 38 ± 1.5 h. A bi-exponential analysis was also used which gave a t1/2 alpha of 1.5 h and t1/2 beta of 40.8 h. Conclusions Here, we show preclinical studies demonstrating that nimotuzumab conjugated to IRDye800CW is safe and does not exhibit toxicities commonly associated with EGFR targeting antibodies.

Allanblackia floribunda Seed Extract Attenuates the Ethanol-Induced Gastric Ulcer in Rats via the Inhibition of TNF-α and INF-γ Levels and Modulation in the Expression of Ki67 Protein

Allanblackia floribunda has been used to treat an upset stomach in African traditional medicine, but its efficacy and safety have not been scientifically studied. The present research is aimed at assessing the antiulcer property of the seed extract of the plant to validate its traditional claim. Rats were pretreated with three doses of aqueous extract of A. floribunda (AFE) at 30, 100, and 300 mg/kg or omeprazole 10 mg/kg for 1 hr before the acute gastric ulcer was induced by oral administration of 5 mL/kg of 98% ethanol. The animals were sacrificed under anesthesia, and the stomach and blood were collected. The gross histology of the stomach, percentage protection conferred by the treatment, gastric pH, and serum TNF-α and INF-γ were assessed as well as the expression of Ki67 antigens. The antioxidant properties as well as the acute toxicity profile of the plant extract were also assessed. The results show that A. floribunda conferred significant protection on the rats against gastric ulceration with % protection of 46.15, 57.69, and 65.38 for AFE 30, 100, and 300 mg/kg, respectively, as well as 69.23% for omeprazole 10 mg/kg. The plant extract caused marked reductions in gastric pH, TNF-α, and INF-γ with statistical significance ( p < 0.001 ) for AFE 300 mg/kg and omeprazole 10 mg/kg. Also, the plant showed good antioxidant activity comparable to gallic acid. Furthermore, the plant extract modulated the expression of Ki67 antigens. All animals survived the 14-day delayed toxicity test with no significant differences in physical, hematological, and biochemical parameters between rats orally administered with supratherapeutic doses of AFE (5000 mg/kg) or normal saline. The study established that the gastroprotective effect of the seed extract of A. floribunda is attributable to its antisecretory, antioxidant, and anti-inflammatory properties. Additionally, the plant was found to promote ulcer healing via the modulation of the expression Ki67 and was safe at supratherapeutic doses.

Preparation and Biological Evaluation of 67Gallium- Labeled Iranian Hemiscorpius Lepturus Scorpion Venom

Background: The Hemiscorpius lepturus (H. lepturus) is a deadly scorpion species living in the southern Iran. Objective: H. lepturus induces delayed toxicity symptoms and understanding the long term biodistribution/ biokinetic of the venom is of great interest in toxicology. Methods: A Ga-67 labeled venom was prepared using a DOTA -conjugated venom followed by radiolabeling using 67GaCl3 at 40°C for 90 min. The purification of the radiolabeled venom was performed using size exclusion-chromatography (radiochemical purity 71%). The radiolabeled venom was stable in the final solution in the presence of human serum at 37°C for 72 hours. The tissue distribution was studied in blood, heart, liver, spleen, muscle, brain, kidney, intestine and skin tissues at the intervals of 1, 4, 24, 48 and 72 hours using tissue counting and SPECT imaging. Results: The radiolabeled venom mixture obtained with an estimated molar activity of 0.52 MBq/μg. The main accumulation tissues during the first 72 hours were kidneys, blood, liver, intestines, stomach and skin, respectively. Therefore, it is likely that H. lepturus’ clinical effects and renal toxicity are primary and caused by direct effects of the H. lepturus venom. Conclusion: The results have largely shown the direct clinical effects on the studied tissues during the 72-hour period and antivenom administration can strongly alleviate the toxicity effects as early as 72 hours in the management of the patients.

Field Distance Effects of Fipronil and Chlorfenapyr as Soil Termiticides Against the Desert Subterranean Termite, Heterotermes aureus (Blattodea: Rhinotermitidae)

A desirable trait of termiticides is that they suppress termite activity at a distance from the site of application. Fipronil and chlorfenapyr are two non-repellent termiticides that display delayed toxicity and are therefore good candidates for yielding distance effects. We assessed their effects as soil-applied termiticides for the management of the desert subterranean termite, Heterotermes aureus (Snyder), under field conditions in southern Arizona. Our approach involved recording termite activity within field experimental grids consisting of termite monitoring stations at selected distances from a termiticide application perimeter. Fipronil-treated plots experienced large and significant reductions in termite presence and abundance relative to controls in stations immediately adjacent to treated soil. However, there was no evidence of reductions in termite activity in stations further away from the soil treatment. In contrast, termite abundance and presence in stations decreased relatively to controls after chlorfenapyr application in whole experimental grids and in several grid sections spatially separated from treated soil. These reductions were especially evident in the five central stations surrounded by the treatment perimeter and in the furthest set of stations. The spatial pattern of changes in chlorfenapyr plots was consistent with termiticide transfer as a mechanism behind distance effects. The impact of fipronil and chlorfenapyr on termite populations in our study suggests that they can both be useful for the management of H. aureus, although each might be suited for differentmanagement goals. Our results also suggest that perimeter treatments alone are not sufficient to accomplish full control of large H. aureus infestations.