Objective To discuss the expression and mutation of β-catenin gene in breast carcinoma.Methods 119 breast carcinomas, 72 adenosis of breast tissues and 40 normal breast tissues were studied.Using immunohistochemistry studies to detect the expressions of β-catenin, then analyzing their relationship with the clinicopathological features of breast carcinomas. Gene mutation of β-catenin (exon 3) in 44 cases of breast carcinoma were analyzed by polymerase chain reaction (PCR) and then by direct sequencing.ResultsIn 40 cases of normal breast tissues, epithelial cells showed equally strong membranous of β-catenin protein at the cell-cell boundaries. The abnormal rate of β-catenin in breast carcinomas (78.15 %) was much higher than that of adenosis of breast tissues (44.44 %), the significant correlation was found (P＜0.01). The abnormal expression of β-catenin was associated with lymph node metastasis (P=0.031). Mutation of β-catenin gene was not detected in 44 cases of breast carcinoma, while the abnormal rate of β-catenin in 44 cases of breast carcinoma was 77.30 %. Conclusionβ-catenin abnormal expression could be considered as an useful marker for determining metastasis and prognosis of human breast carcinoma and for guiding treatment. β-catenin abnormal expression is not caused by β-catenin gene mutation, maybe by other mechanisms. It needs further study.

Objective To compare the dose to the contralateral breast, ipsilateral lung, and the whole lung in the tangential field radiotherapy for primary breast cancer using the dynamic wedge or physical wedge. Methods With thirteen breast cancer patients chosen, the dose distribution was computed for the plan used in practical treatment with the dynamic wedge and physical wedge. Plans were compared using dose volume histograms for the contralateral breast, ipsilateral lung and the whole lung. As for the contralateral breast, the dose distributions were not computed for the whole breast but computed for the two regions similar to a rectangular area in the axial slice and parts of the whole breast. The mean dose was used to evaluate CB1, CB2 and ipsilateral lung, and V_ 20 was used to evaluate the whole lung. The treatment planning system used was Varian CadPlan. An ionization chamber in a water phantom was used to measure some point doses to simulate the dose to the contralateral breast. Results When using the 30? dynamic wedge, the mean dose to CB1 and CB2 was 1.5%-3.9% and 1.1%- 2.6% , and the mean dose to the ipsilateral lung was 4.1%-14.7%. When using the 30? physical wedge, the mean dose to CB1 and CB2 were 1.5%-4.4% and 1.2%-3.0%, respectively, and the mean dose to the ipsilateral lung was 4.4%-15.2%. The values of V_ 20 were equal. When using the 15? dynamic wedge, the mean dose to CB1 and CB2 decreased compared to 15? physical wedge, but the value reduced was smaller than when using 30? wedge. Also, the measured results verified that the dose to the normal tissue is reduced using the dynamic wedge. Conclusions The mean dose to the contralateral breast was reduced by using the dynamic wedge instead of the physical wedge, and the mean dose to the ipsilateral lung or V_ 20 is reduced or equal to each other. So the probability of normal tissue complication such as a second breast malignancy or pneumonitis associated with radiotherapy are likely to be reduced.

Objective To evaluate the clinical feasibility of quality assurance of intensity modulated radiation therapy(IMRT) through a series of clinical case studies. Methods Helios inverse planning system was used to provide optimized IMRT treatment plans for brain tumor, nasopharyngeal carcinoma, pancreatic cancer, spinal metastatic tumor and prostatic cancer. To verify the conformation between the fluence map of each beam predicted by the planning system and that actually delivered, a piece of film under a homogeneous polystyrene phantom was irradiated vertically with each of the beams to record the deposited dose. This measured fluence map was compared with that predicted by the planning. The dose distribution was recorded by irradiating the film in an anthropomorphic phantom using patients' treatment plan, then compared with that predicted by the planning. An ionization chamber in a water phantom was used to measure the central point dose and another eccentric point dose. Results The fluence map measured by the film was well consistent with that predicted by the planning. The error between the measured dose and predicted dose in the central point was less than 3%, whereas the error of the dose in another eccentric point varied greatly. The isodose distribution (on axial plane) measured by the film was consisent with the predicted one. Conclusions The procedures for quality assurance of IMRT are feasible in our experience.

OBJECTIVE: To explore the driving gene of hepatocellular carcinoma (HCC) occurrence and progression and its potential as new therapeutic target of HCC. METHODS: The transcriptome and genomic data of 858 HCC tissues and 493 adjacent tissues were obtained from TCGA, GEO, and ICGC databases. Gene Set Enrichment Analysis (GSEA) identified EHHADH (encoding enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase) as the hub gene in the significantly enriched differential pathways in HCC. The downregulation of EHHADH expression at the transcriptome level was found to correlate with TP53 mutation based on analysis of the TCGA- HCC dataset, and the mechanism by which TP53 mutation caused EHHADH downregulation was explored through correlation analysis. Analysis of the data from the Metascape database suggested that EHHADH was strongly correlated with the ferroptosis signaling pathway in HCC progression, and to verify this result, immunohistochemical staining was used to examine EHHADH expression in 30 HCC tissues and paired adjacent tissues. RESULTS: All the 3 HCC datasets showed signficnatly lowered EHHADH expression in HCC tissues as compared with the adjacent tissues (P < 0.05) with a close correlation with the degree of hepatocyte de-differentiation (P < 0.01). The somatic landscape of HCC cohort in TCGA dataset showed that HCC patients had the highest genomic TP53 mutation rate. The transcriptomic level of PPARGC1A, the upstream gene of EHHADH, was significantly downregulated in HCC patients with TP53 mutation as compared with those without the mutation (P < 0.05), and was significantly correlated with EHHADH expression level. GO and KEGG enrichment analyses showed that EHHADH expression was significantly correlated with abnormal fatty acid metabolism in HCC. The immunohistochemical results showd that the expression level of EHHADH in HCC tissues was down-regulated, and its expression level was related to the degree of hepatocytes de-differentiation and the process of ferroptosis. CONCLUSION TP53 mutations may induce abnormal expression of PPARGC1A to cause downregulation of EHHADH expression in HCC. The low expression of EHHADH is closely associated with aggravation of de-differentiation and ferroptosis escape in HCC tissues, suggesting the potential of EHHADH as a therapeutic target for HCC.
Humans ; Carcinoma, Hepatocellular/genetics* ; Transcriptome ; Liver Neoplasms/genetics* ; Gene Expression Profiling ; Fatty Acids ; Peroxisomal Bifunctional Enzyme