Repeated Radionuclide therapy in metastatic paraganglioma leading to the highest reported cumulative activity of 131I-MIBG

Objective

To examine the efficacy of different radiation doses after achievement of a complete response to chemotherapy in diffuse large B-cell lymphoma (DLBCL).

Methods

Patients with stage I-IV DLBCL treated from 1995?C2009 at Duke Cancer Institute who achieved a complete response to chemotherapy were reviewed. In-field control, event-free survival, and overall survival were calculated using the Kaplan-Meier method. Dose response was evaluated by grouping treated sites by delivered radiation dose.

Results

105 patients were treated with RT to 214 disease sites. Chemotherapy (median 6 cycles) was R-CHOP (65%), CHOP (26%), R-CNOP (2%), or other (7%). Post-chemotherapy imaging was PET/CT (88%), gallium with CT (1%), or CT only (11%). The median RT dose was 30?Gy (range, 12?C40?Gy). The median radiation dose was higher for patients with stage I-II disease compared with patients with stage III-IV disease (30 versus 24.5?Gy, p?<?0.001). Five-year in-field control, event-free survival, and overall survival for all patients was 94% (95% CI: 89-99%), 84% (95% CI: 77-92%), and 91% (95% CI: 85-97%), respectively. Six patients developed an in-field recurrence at 10 sites, without a clear dose response. In-field failure was higher at sites????10?cm (14% versus 4%, p?=?0.06).

Conclusion

In-field control was excellent with a combined modality approach when a complete response was achieved after chemotherapy without a clear radiation dose response.     

Preparation of [61Cu]-2-acetylpyridine thiosemicarbazone complex as a possible PET tracer for malignancies.

Due to the interesting anti-proliferative properties of copper-thiosemicarbazone complexes, the production of a (61)Cu-labeled thiosemicarbazone, i.e. 2-acetylpyridine thiosemicarbazone (APTS) was investigated. Copper-61 (T(1/2)=3.33 h) was produced via the (64)Zn(p,alpha)(61)Cu nuclear reaction using a natural zinc target irradiated with 22 MeV protons for 500 microAh. The (61)Cu was separated from the irradiated target material by a two-step method and converted to acetate; this yielded a final activity of 222 GBq (6.0 Ci), with a radiochemical yield of >95%. The (61)Cu-acetate was mixed with 2-acetylpyridine thiosemicarbazone for 30 min at room temperature to yield [(61)Cu]APTS with a radiochemical yield of more than 80%. Colorimetric methods showed that residual chemical impurities in the product were below the accepted limits. Radio thin layer chromatography (RTLC) showed a radiochemical purity of more than 99% after C(18) column chromatography. A specific activity of about 370-740 MBq/mmol (10-20 Ci/mmol) was obtained. The stability of the final product was checked in the absence and presence of human serum at 37 degrees C for up to 3 h. The partition coefficient of the final complex was also determined.     

Improvement of Varian a-Si EPID dosimetry measurements using a lead-shielded support-arm

Dosimetry measurements with Varian amorphous silicon electronic portal imaging devices (a-Si EPIDs) are affected by the backscattered radiation from the EPID support arm. In this study, the nonuniform backscatter from an E-type support arm was reduced by fixing a thick (12.2 × 10.5 × 0.5 cm³) piece of lead on top of the arm, and the remaining backscatter was modeled and included in an existing dose prediction algorithm. The applied backscatter kernel was the average of kernels on different regions of the EPID over the arm. The lead-shielded arm reduced the nonuniform backscatter component by about 50% for field sizes ranging from 3 × 3 to 30 × 30 cm² and the field symmetry improved for medium to large fields up to 3%. Gamma evaluation of the measured and modeled doses (2%, 2-mm criteria) showed that using the lead-shielded arm in the model increased the number of points with Gamma index <1 by 5.7% and decreased the mean Gamma by 0.201. Even using the lead alone (no modeling) could increase the number of points with Gamma index <1 by 4.7% and decrease the mean Gamma by 0.153. This is a simple and easy method to decrease the nonuniform arm backscatter and improve the accuracy of dosimetry measurements with the existing EPIDs used for clinical applications.     

Synthesis, calcium-channel blocking activity, and conformational analysis of some novel 1,4-dihydropyridines: application of PM3 and DFT computational methods

Novel 1,4-dihydropyridines were synthesized and subjected to calcium-channel blocking evaluation and conformational analysis using semi-empirical (PM3) and density functional theory (DFT) as computational methods. All molecules had a boat-like 1,4-dihydropyridine ring in both the methods. In PM3 method almost 54% of the molecules were deviated from planarity, but in DFT method all the molecules had perfect flattened-boat conformation. Using both the methods, the C-4 substituent was pseudoaxial with its phenylamino substitution in sp orientation in 82.14% of the molecules. Trans–trans and cis–cis conformation had the greatest and lowest proportion in the molecules, respectively. Trans–trans conformers which possessed sp conformation for the substituted group on the imidazole ring were active calcium-channel blocking agents.     

Long-term association of nut consumption and cardiometabolic risk factors

Background and aimsLong-term associations between nut consumption and cardiometabolic risk factors are not well known. We investigated the relationship between nut consumption and cardiometabolic risk factors including dyslipidemia, hypertension, diabetes mellitus (DM), and obesity in a cohort of Iranian adults.Methods and resultsThe study was conducted within the framework of the Isfahan Cohort Study on 1387 healthy participants. The participants were followed up for 12 years. A validated food frequency questionnaire was completed, and anthropometric measurements, blood pressure, and fasting serum lipids and blood sugar were evaluated in three phases. Mixed-effects binary logistic regression was applied to examine the associations between nut consumption and cardiometabolic risk factors. The participants were classified according to the tertiles of nut consumption as cut-points, and associations were evaluated between the thirds of nut intake.Subjects in the last third were less likely to have hypercholesterolemia [OR (95% CI): 0.76 (0.60–0.97)], hypertriglyceridemia [OR (95% CI): 0.74 (0.58–0.93)], and obesity [OR (95% CI): 0.79 (0.50–0.98)] but more likely to have DM [OR (95% CI): 1.85 (1.27–2.68)] than those in the first third. However, after adjustment for various potential confounders, the associations remained significant only for obesity [OR (95% CI): 0.67 (0.48–0.94)] and DM [OR (95% CI): 2.23 (1.37–3.64)].ConclusionAfter adjustment for potential confounders, we observed an inverse association for nut consumption and obesity but positive association for DM and nut intake. On the basis of our findings, it is suggested that incorporation of nuts into people's usual diet may have beneficial effects for individuals with lower risk such as subjects without DM.     

Immunogenicity of Multi-Epitope DNA and Peptide Vaccine Candidates Based on Core,E2, NS3 and NS5B HCV Epitopes in BALB/c Mice

Background:

Hypervariability of HCV proteins is an important obstacle to design an efficient vaccine for HCV infection. Multi-epitope vaccines containing conserved epitopes of the virus could be a promising approach for protection against HCV.

Objectives:

Cellular and humoral immune responses against multi-epitope DNA and peptide vaccines were evaluated in BALB/c mice.

Materials and Methods:

In this experimental study, multi-epitope DNA- and peptide-based vaccines for HCV infection harboring immunodominant CD8+ T cell epitopes (HLA-A2 and H2-Dd) from Core (132-142), NS3 (1073-1081) and NS5B (2727-2735), a Th CD4+ epitope from NS3 (1248-1262) and a B-cell epitope from E2 (412-426) were designed. Multi-epitope DNA and peptide vaccines were tested in two regimens as heterologous DNA/peptide (group 1) and homologous peptide/peptide (group 2) prime/boost vaccine in BALB/c mice model. Electroporation was used for delivery of the DNA vaccine. Peptide vaccine was formulated with Montanide ISA 720 (M720) as adjuvant. Cytokine assay and antibody detection were performed to analyze the immune responses.

Results:

Mice immunized with multi-epitope peptide formulated with M720 developed higher HCV-specific levels of total IgG, IgG1 and IgG2a than those immunized with multi-epitope DNA vaccine. IFN-γ levels in group 2 were significantly higher than group 1 (i.e. 3 weeks after the last immunization; 37.61 ± 2.39 vs. 14.43 ± 0.43, P < 0.05). Moreover, group 2 had a higher IFN-γ/IL-4 ratio compared to group 1, suggesting a shift toward Th1 response. In addition, in the present study, induced immune responses were long lasting and stable after 9 weeks of the last immunization.

Conclusions:

Evaluation of multi-epitope DNA and peptide-vaccines confirmed their specific immunogenicity in BALB/c mice. However, lower Th1 immune responses in mice immunized with DNA vaccine suggests further investigations to improve the immunogenicity of the multi-epitope DNA vaccine through immune enhancers.     

Teucrium polium in prevention of steatohepatitis in rats

Background: In this study, we tried to evaluate whether the ethyl acetate (EtOAc) extract of Teucrium polium, with a high antioxidant activity, is able to prevent the incidence of nonalcoholic steatohepatitis. Methods: Nonalcoholic steatohepatitis was induced in male N‐Mary rats using a methionine/choline‐deficient (MCD) diet. Rats were given normal diet (A), normal diet+EtOAc extract (B), MCD diet (C) and MCD diet+EtOAc (D). Results: The MCD diet led to grade 1 liver steatosis, inflammation and ballooning degeneration. In group D, these factors abated to grade 0 in 80% of the rats. In groups receiving the EtOAc extract, lipoprotein profiles had significantly improved relative to those not receiving the extract. Also, a dramatic reduction was observed in the sera alkaline phosphatase, aspartate aminotransferase and alanine aminoteransferase activities. The activities of the liver superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes were also enhanced. Conclusion: The EtOAc extract could reverse the adverse effects of the MCD diet.     

Chorionic Bump in First-trimester Sonography

Objectives

The present research was motivated by providing new insight into early pregnancies with a chorionic bump diagnosis in first-trimester sonography and its impact on live birth rate.