Randomised controlled trial on the effect of simethicone bowel preparation on rectal variability during image-guided radiation therapy for prostate cancer (SPoRT study).

INTRODUCTION: The purpose of this study was to assess whether simethicone reduces the rectal volume (RV) and gas volume (GV), to increase treatment accuracy and to decrease toxicity of prostate radiation therapy. METHODS: 30 patients were randomised to simethicone or no intervention. Cone-beam computed tomography (CBCT) scans were performed on Days 1-3 and weekly until completion of radiation. RV and GV were measured using volume delineation. Toxicity data were collected. RESULTS: 264 CBCTs were analysed. RV and GV were not significantly different in the simethicone group compared with the control group at each time point (P >0.05) after adjusting for Week 0 values as a covariate. The simethicone group showed an average reduction in RV and GV of 10% and 21%, respectively, compared with the control group (P >0.05). Standard deviations were calculated over 10 time points, which were grouped to represent the first 2-3 weeks of radiation therapy versus subsequent weeks. These were not significantly different between the simethicone and control group. However, there was a statistically significant decrease in the variability of RV at time points 6-10 compared with time points 1-5 within the simethicone group (P = 0.012), but no significant difference was found between these grouped time points in the control group (P = 0.581). The toxicity questionnaires showed no significant difference between the groups. CONCLUSIONS: Simethicone did not decrease the RV or GV overall. However, simethicone appeared to significantly decrease the RV variability from Week three onwards. This suggests that taking simethicone two to three weeks before starting radiation therapy may reduce RV variability, although a larger study is needed to confirm this.

Timing of fluorodeoxyglucose positron emission tomography maximum standardized uptake value for diagnosis of local recurrence of non-small cell lung cancer after stereotactic body radiation therapy.

INTRODUCTION: After treatment with stereotactic body radiation therapy (SBRT), local recurrence of non-small cell cancer (NSCLC) can be difficult to differentiate from radiation-induced changes. Maximum standardized uptake value (SUVmax), measured with 18-F-Fluorodeoxyglucose positron emission tomography (FDG-PET), can have false positives due to acute radiation inflammation. The primary study objective was to determine the utility of SUVmax > 5 to identify local recurrence later than 9 months after SBRT. METHOD: A retrospective review was performed of FDG-PET scans for suspicious CT findings after SBRT treatment of stage 1 NSCLC. SUVmax was measured including surrounding opacification. Outcome measures were local recurrence, progression free survival, and overall survival. Receiver operator curve analysis, sensitivity, specificity, and Kaplan-Meier analysis were performed. RESULTS: Of 118 patients treated, 42 patients had eligible FDG-PET scans. They received SBRT (48-60Gy in 3-8 fractions) for 49 NSCLC and had 101 follow-up PET scans. The median time to first PET scan was 9.3 months, and the median follow-up period was 22.4 months. Local recurrence was diagnosed in 12 patients, at a median of 16 months. Due to selection bias, the included patients had poorer outcomes than the entire cohort, with progression free survival (PFS) at 1, 2, and 3 years of 82.7%, 57.8%, and 45.8%; and overall survival of 97.9%, 79.9%, and 59.1%, respectively. Thirty FDG-PET scans were performed within 9 months, of which 17% were false positives. A total of 71 FDG-PET scans were performed beyond 9 months, and the median SUVmax was significantly higher for patients with local recurrence (7.48 vs. 2.14, P < .0001). SUVmax > 5 has a sensitivity of 91% (95% CI 62%-99.8%) and 100% (89.1%-100%). CONCLUSION: For local recurrence of NSCLC, SUVmax > 5 on FDG-PET scan has good sensitivity and specificity after 6 months, but is highest beyond 9 months after SBRT.

[Effect of Velcade combined with Dexamethasone on multiple myeloma].

OBJECTIVE: To compare the effect and safety between Velcade-Dexamethasone (VD)and revised Vinorebine+Pirarubicin+ Dexamethasone (VAD) regiment for multiple myeloma (MM). METHODS: Thirty-six patients with MM were reviewed, 16 of whom were treated with VD (VD Group) and the others with VAD. European Group for Blood and Marrow Transplant (EBMT) criteria and National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) were chosen to analyze the efficacy and side effects. RESULTS: In the VD group and the revised VAD group, the rates of complete response, partial response, minimal response, no change and progress disease were 50% vs. 5%, 25% vs. 25%, 18.8% vs. 15%, 6.2% vs. 35% and 0 vs. 20%, respectively. The total response rates were 93.8% vs 45%. There was significant difference in the overall response rate between the 2 groups (P<0.05). The side effects were less serious, and the endurance was better in the VD group than those in the revised VAD group. No serious effects of hematology and cardiology were seen, and good endurance was showed in the renal dysfunction in the VD group. CONCLUSION: Velcade combined with dexamethasone is a safe and effective regiment for multiple myeloma with good safety and endurance.

Molecular features and expression of DAZAP2 in human multiple myeloma.

BACKGROUND: In our previous study, we found that DAZAP2 was the most significantly down regulated gene when differential screening of complementary DNA (cDNA) chips were used to analyze mRNA isolated from bone marrow mononuclear cells from newly diagnosed multiple myeloma (MM) patients without anticancer treatment. In this study, we observed DAZAP2 mRNA and protein expression in the mononuclear cells from MM bone marrow and investigated its role in the pathogenesis of MM. METHODS: The full-length cDNA of DAZAP2 was cloned and sequenced from mononuclear cells from human bone marrow. The nucleotide and amino acid sequences of DAZAP2 were analyzed using the ClustalW program. A dendrogram was constructed by multiple sequence alignment using ClustalW and amino acid sequence identity/similarity was derived based on comparisons attained using the MegAlign software. The recombinant pEGFP expression vector was constructed and the confocal microscopy was used for the localization of the DAZAP2 protein in transfected COS7 cells. The expression of DAZAP2 mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and the expression level of DAZAP2 protein was detected by Western blotting analysis in MM samples. RESULTS: DAZAP2 proteins of vertebrates is highly conserved in evolution. It contains a proline-rich region, several potential SH2 and SH3 domain-binding motifs and a possible protein kinase C (PKC) phosphorylation site. We showed by confocal microscopy that the DAZAP2 protein predominantly resides in the cytoplasm with a discrete pattern of punctuated distribution. The expression of DAZAP2 was not detected in 24 of 36 MM samples by semi-quantitative RT-PCR. In contrast, DAZAP2 expression was detected in all 30 normal controls. The expression level of DAZAP2 protein was assayed by Western blotting analysis, showing a robust down-regulation in MM patients (P < 0.001) that matched with the results of the RT-PCR. CONCLUSIONS: DAZAP2 is downregulated in MM samples and it may be a signal molecule in MM cells. DAZAP2 is involved in the pathogenesis of MM and could be used as a genetic marker for MM.

[Detection of glutathione S-transferase and lung resistance-related proteins in acute leukemia and its clinical significance].

OBJECTIVE: To explore the relationship among intracellular glutathione S-transferase activity (GST), the expression of lung resistance-related proteins (LRP) in acute leukemia, and its clinical effects. METHODS: The GST activity of bone marrow mononuclear cells and LRP expression in 57 acute leukemia patients were detected by the spectrophotometry assay and immuno-cytochemistry (SABC), respectively. RESULTS: The GST activity of bone marrow mononuclear cells in the acute leukemia group was significantly higher than that of the control group (P < 0.01). The GST activity of mononuclear cells in acute leukemia was positively correlated with the percentage of blast in the bone marrow (r = 0.30, P < 0.05). The GST activity of mononuclear cells in the untreated acute leukemia group was obviously higher than that of the complete remission group (P <0.01). The GST activity in the refractory or relapsed acute leukemia group was significantly higher than that of the complete remission group and untreated leukemia group (P <0.05). In post-chemotherapy 13 of 17 the LRP-positive patients were the non-remission, 12 of the 20 LRP-negative patients were the complete remission. The curative rate of the LRP-positive group was the significantly lower than the LRP-negative group (P < 0.05). The GST activities of non-remission patients in the LRP-positive and LRP-negative group obviously increased. CONCLUSION: The increase of GST activity in the bone marrow mononuclear cells is related to the clinical curative effects and the proliferation of blast in acute leukemia. Detection of LRP and GST activities in acute leukemia may have a reference value in judging the leukemia with drug resistance and estimating the prognosis.

The structure, expression and function prediction of DAZAP2, a down-regulated gene in multiple myeloma.

In our previous studies, DAZAP2 gene expression was down-regulated in untreated patients of multiple myeloma (MM). For better studying the structure and function of DAZAP2, a full-length cDNA was isolated from mononuclear cells of a normal human bone marrow, sequenced and deposited to Genbank (AY430097). This sequence has an identical ORF (open reading frame) as the NM_014764 from human testis and the D31767 from human cell line KG-1. Phylogenetic analysis and structure prediction reveal that DAZAP2 homologues are highly conserved throughout evolution and share a polyproline region and several potential SH2/SH3 binding sites. DAZAP2 occurs as a single-copy gene with a four-exon organization. We further noticed that the functional DAZAP2 gene is located on Chromosome 12 and its pseudogene gene is on Chromosome 2 with electronic location of human chromosome in Genbank, though no genetic abnormalities of MM have been reported on Chromosome 12. The ORF of human DAZAP2 encodes a 17-kDa protein, which is highly similar to mouse Prtb. The DAZAP2 protein is mainly localized in cytoplasm with a discrete pattern of punctuated distribution. DAZAP2 may associate with carcinogenesis of MM and participate in yet-to-be identified signaling pathways to regulate proliferation and differentiation of plasma cells.