Evaluation of the Key Advantages between Two Modalities of Boronophenylalanine Administration for Clinical Boron Neutron Capture Therapy Using an Animal Model.

In clinical boron neutron capture therapy (BNCT), boronophenylalanine (BPA) administrations through one-step infusion (OSI) and two-step infusion (TSI) are the most widely used. This study compared the advantages of OSI and TSI using a human oral squamous cell carcinoma-bearing animal model. OSI was administered at a high-dose rate of 20 mg/kg/min for 20 min (total dose: 400 mg/kg) as the first step infusion. TSI was a prolonged infusion at a low-dose rate of 1.67 mg/kg/min for 15, 30, 45, and 60 min (total dose: 25, 50, 75, and 100 mg/kg) following the first step infusion. The sigmoid Emax model was used to evaluate the boron accumulation effect in the tumor. The advantages of TSI were observed to be greater than those of OSI. The observed advantages of TSI were as follows: a stable level of boron concentration in blood; tumor to blood boron ratio (T/B); tumor to muscle boron ratio (T/M); and skin to blood boron ratio (S/B). The boron accumulation effect in tumors increased to 68.98%. Thus, effective boron concentration in these tumor cells was achieved to enhance the lethal damage in BNCT treatment. Boron concentration in the blood was equal to that in the skin. Therefore, the equivalent dose was accurately estimated for the skin.

Traditional Herbal Medicine Mediated Regulations during Head and Neck Carcinogenesis.

Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. It is well recognized that environmental challenges such as smoking, viral infection and alcohol consumption are key factors underlying HNSCC pathogenesis. Other than major clinical interventions (e.g., surgical resection, chemical and radiotherapy) that have been routinely practiced over years, adjuvant anticancer agents from Traditional Herbal Medicine (THM) are proposed, either alone or together with conventional therapies, to be experimentally effective for improving treatment efficacy in different cancers including HNSCCs. At a cellular and molecular basis, THM extracts could modulate different malignant indices via distinct signaling pathways and provide better control in HNSCC malignancy and its clinical complications such as radiotherapy-induced xerostomia/oral mucositis. In this article, we aim to systemically review the impacts of THM in regulating HNSCC tumorous identities and its potential perspective for clinical use.

Arsenic trioxide-mediated suppression of miR-182-5p is associated with potent anti-oxidant effects through up-regulation of SESN2.

Arsenic trioxide (ATO) is a traditional Chinese medicine that can induce oxidative stress for treatment of cancer cells. However, ATO may generate anti-oxidative responses to compromise the cytotoxic effect, but the underlying mechanisms remain unclear. Here we found that ATO could inhibit miR-182-5p expression in patient-derived primary S1 glioblastoma (GBM) cells accompanied by up-regulation of Sestrin-2 (SESN2) mRNA, a known anti-oxidant molecule. This phenomenon was also detected in a U87MG glioma cell line, human lung adenocarcinoma H1299 cell line and A549 cell line. Pretreatment with a free radical scavenger N-acetylcysteine (NAC) reduced the oxidative stress induced by ATO. Concomitantly, ATO mediated suppression of miR-182-5p and enhancement of SESN2 expression were also compromised. The MTT assay further showed that ATO induced cytotoxicity was enhanced by transfection of miR-182-5p mimics. Overexpression of miR-182-5p mimics significantly suppressed the expression of SENS2 and a firefly luciferase reporter gene fused to 3'- untranslated region (UTR) of SESN2 mRNA. Use of ribonucleoprotein immunoprecipitation (RNP-IP), ATO mediated suppression of miR-182-5p led to the stabilization of SESN2 mRNA as a result of Argonaute-2 (AGO2) dependent gene silencing. Furthermore, high expression of miR-182-5p and low expression of SESN2 mRNA tend to be associated with longer survival of glioma or lung cancer patients using public available gene expression datasets and online tools for prediction of clinical outcomes. Taken together, current data suggest that the miR-182-5p/SENS2 pathway is involved in ATO induced anti-oxidant responses, which may be important for the design of novel strategy for cancer treatment.

Therapeutic efficacy evaluation of curcumin on human oral squamous cell carcinoma xenograft using multimodalities of molecular imaging.

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity; however the treatment approaches are still unsatisfactory. We used a luciferase-transfected animal model to evaluate the therapeutic effects of curcumin. Human oral squamous cell carcinoma SAS cell line was stably transfected with luc gene, named SAS/luc cells. For the in vivo study, they were inoculated subcutaneously to 6-week-old male NOD/SCID mice which were separated into four groups for intraperitoneal injection (i.p.) of curcumin: control, daily with 35 mg/kg, 70 mg/kg every 2 days, and 100 mg/kg every 3 days. We applied SAS/luc bearing animal model and bioluminescent imaging (BLI) to study the inhibition effect of curcumin on tumor growth. The cytotoxic effect of curcumin on SAS/luc cells was mainly at G2/M phase and a significant dose dependent increase of the apoptotic SAS/luc cells as represented by sub-G1 phase was shown. Therapeutic efficacy evaluated by both caliper assay and BLI showed a significant difference between curcumin-treated mice and the controls (p < 0.01). The significant inhibition effects of curcumin on the proliferation and the growth of human OSCC are observed both in vitro and in vivo. No significant body weight change (i.e. within 20%) was observed in all SAS/luc-bearing mice with or without curcumin treatment. This SAS/luc human OSCC bearing animal model combined with multimodalities of molecular imaging permits a sensitive and non-invasive approach to evaluate the therapeutic efficacy in vivo.