Characterization of Oncolytic Vaccinia Virus Harboring the Human IFNB1 and CES2 Transgenes / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to assess characteristics of SJ-815, a novel oncolytic vaccinia virus lacking a functional thymidine kinase-encoding TK gene, and instead, having two human transgenes: the IFNB1 that encodes interferon β1, and the CES2 that encodes carboxylesterase 2, which metabolizes the prodrug, irinotecan, into cytotoxic SN-38. @*Materials and Methods@#Viral replication and dissemination of SJ-815 were measured by plaque assay and comet assay, respectively, and compared to the backbone of SJ-815, a modified Western Reserve virus named WI. Tumor cytotoxicity of SJ-815 (or mSJ-815, which has the murine IFNB1 transgene for mouse cancers) was evaluated using human and mouse cancer cells. Antitumor effects of SJ-815, with/without irinotecan, were evaluated using a human pancreatic cancer-bearing mouse model and a syngeneic melanoma-bearing mouse model. The SN-38/ irinotecan ratios in mouse melanoma tissue 4 days post irinotecan treatment were compared between groups with and without SJ-815 intravenous injection. @*Results@#SJ-815 demonstrated significantly lower viral replication and dissemination, but considerably stronger in vitro tumor cytotoxicity than WI. The combination use of SJ-815 plus irinotecan generated substantial tumor regression in the human pancreatic cancer model, and significantly prolonged survival in the melanoma model (hazard ratio, 0.11; 95% confidence interval, 0.02 to 0.50; p=0.013). The tumor SN-38/irinotecan ratios were over 3-fold higher in the group with SJ-815 than those without (p < 0.001). @*Conclusion@#SJ-815 demonstrates distinct characteristics gained from the inserted IFNB1 and CES2 transgenes. The potent antitumor effects of SJ-815, particularly when combined with irinotecan, against multiple solid tumors make SJ-815 an attractive candidate for further preclinical and clinical studies.

one-year evaluation of a free fissure sealant program

Statement of Problem: Pit and fissure sealant therapy has been approved as an effective measure in the prevention of occlusal dental caries. Resin based ma- terials are the most common materials used worldwide. A variety of resin based fissure sealants are produced and used. Most of them have been presented with ideal results in research environment. However, their effectiveness in the real life, especially in a mass application program such as Iran's oral health reform plan is not clear

Objectives: To evaluate the longevity of different fissure sealant applied in Iran's oral health reform plan in Fars Province [south of Iran] after one year

Materials and Methods: Seven counties were selected. One hundred 6- to 8-year-old school children who had undergone fissure sealant therapy in spring 2015 were randomly selected from each county. Their first molars were exam-ined to evaluate the status of the fissure sealants which were applied one year ago. Data on the type/brand of fissure sealant materials, type and experience of clinicians who applied them, existence of a chair-side assistant, and whether the children were caries-free at the time of fissure sealant application were collected from the existing reports

Results: Data of 1974 teeth from 598 children were used for the final analysis. The effects of type/brand of the material was significant on the final results and remained significant [p < 0.001] after adjustments for the level of fluoride, urban/rural area, upper/lower jaw, type of clinician who applied the sealant, existence of a chair-side assistant, and child's gender, age, and being caries-free

Conclusions: Many factors affect the success rate of a fissure sealant therapy program. The type/brand of the material remained significantly related to the success rate of the fissure sealant even after adjustments for other influencing factors. In this study, ClinproTM Sealant [3M/ESPE, USA] showed better longevity after one year of application

Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma

The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.

Transglutaminase 2 Expression Predicts Progression Free Survival in Non-Small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and in the constitutive activation of nuclear factor kappa B (NF-kappaB). We investigated the association of non-small cell lung cancer (NSCLC) treatment efficacy with TG2 and NF-kappaB expression in 120 patients: 102 with adenocarcinoma and 18 with other histologic types. All patients underwent surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based doublet chemotherapy as first-line treatment and 29 receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and NF-kappaB expression values were calculated semiquantitatively. The median TG2 value was 50 (range, 0-300) and the median NF-kappaB value was 20 (range, 0-240). Disease-free survival did not differ between the low- and high-TG2 groups. Among patients who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0 months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI, PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013). TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR-TKI.