Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines.

Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.

Radiographic assessment of the mandibular retromolar canal using cone-beam computed tomography.

OBJECTIVE: The 'retromolar' nerve is a collateral branch of the inferior alveolar nerve. Cone-beam computed tomography (CBCT) provides higher resolution images. This CBCT study reports the frequency of the retromolar nerve. MATERIALS AND METHODS: From 2007-2010 the CBCT study of 233 hemi-mandibles have been examined. The CBCT study was obtained from an investigation of the posterior mandibular region in 187 patients suffering from different pathologies and it was aimed at detecting in patients the presence of a retromolar canal and foramen. RESULTS: Thirty-four retromolar canals with a foramen were detected on 233 CBCT (14.6%) in 30 out of 187 patients (16%). In the 46 patients who underwent CBCT bilaterally, the retromolar canal was found in nine subjects (19.6%) and was present bilaterally in four subjects, for an incidence of 8.7%. CONCLUSIONS: The results suggest that the radiological frequency of the retromolar nerve is notable, with a possible relevance in the surgical approach of the mandibular retromolar area. The presence of a retromolar canal, well detected with CBCT, may warn clinicians about the possibility of inadequate pre-surgical anaesthesia, local intra-operative bleeding and post-operative alterations of the sensation in the third molar area.

Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: is it better than three dimensional conformal radiotherapy?

BACKGROUND: Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients. METHODS: Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints. RESULTS: Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs. CONCLUSIONS: In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be used with caution.

Role of radiation therapy in mycosis fungoides refractory to systemic therapy.

The long natural history of early stage mycosis fungoides (MF) makes its management a difficult problem. Skin lesions are sensitive to different therapies and a variety of treatment modalities have been used, such as topical nitrogen mustard, puvatherapy, UV-B, retinoids, radiation therapy, extracorporal photopheresis and systemic chemotherapy. For patients with refractory early stage MF, treatment selection is made by clinical parameters such as the age, sex and performance status of the patients, as well as the institutional expertise and the toxicity profiles of the different therapeutic approaches. We report radiation therapy in a relapsed/resistant stage IB patient with mycosis fungoides treated with local radiation therapy for symptomatic progression unresponsive to bexarotene therapy. Total skin electron beam therapy has been employed in early stage and for limited skin failure MF, while the role of local radiation therapy in MF is less defined. In our experience local radiotherapy has proved to be a very efficient, tolerable and cost effective approach in patients with MF unresponsive to systemic approaches.