THE EXPRESSIONS OF HBV X GENE AND ets-2, IGF-Ⅰ, c-myc AND N-ras ONCOGENES IN HUMAN HEPATOCELLULAR CARCINOMA AND TUMOR-ADJACENT TISSUES

The expressions of HBV X gene and ets-2, IGF-I, c-myc and N-ras were studied in 7 pairs of human primary hepatocellular carcinoma (PHC) and tumor-adjacent tissues, using RNA hybridization and im-munoblot methods. The results showed that specific 17 and 28 kD HBV X gene products (HBxAg) were existed in a portion of PHC and tumor-adjacent tissues. The 17 kD HBxAg was detected in the sera of 3 patients who also had 17 kD HBxAg in their liver tissues. Multiple expressions of oncogenes such as ets-2, c-myc and N-ras were observed in PHC and tumor-adjacent tissues that had HBxAg expressed, indicating HBxAg might function as a transactivator in the course of intracellular proto-oncogene activation. It is also observed that in some tumor-adjacnet tissues the expressions of ets-2, c-myc and N-ras were higher than those in corresponding PHC. The relationship of HBxAg to the expression of est-2, IGF-Ⅱ, c-myc and their possible roles in the carcinogenesis of PHC are discussed.

Novel methylation gene panel in adjacent normal tissues predicts poor prognosis of colorectal cancer in Taiwan

BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.

Paraben Content in Adjacent Normal-malignant Breast Tissues from Women with Breast Cancer

Objective Accumulation of estrogenic compounds and other carcinogens in normal breast tissues contributes to unpredictable breast cancer incidence during adolescence and throughout life.To assess the role of parabens in this phenomenon,the paraben content of adjacent normal-malignant breast tissues is measured in women with breast cancer living in Isfahan Province,Iran.Methods Adjacent normal-malignant breast tissue samples were obtained from 53 subjects.The parabens including methyl-paraben(Me PB),ethyl-paraben(Et PB),propyl-paraben(Pr PB),and butylparaben(Bu PB)were extracted from the sample supernatant and then subjected to gas chromatography analysis.Results Some risk factors for breast cancer were stimulated by parabens in adjacent malignant-normal breast tissues among young and middle-aged women with breast cancer.We observed a significant association for dose-response pattern of Me PB[OR=98.34(11.43–185.2),P=0.027]for both ER+and PR+women and Me PB[OR=164.3(CI:112.3–216.3),P<0.001]for HER2+women than women with negative receptors.The risk of 95-fold increase in Me PB dose and 164-fold increase in∑PBs dose were significant for women with hereditary breast cancer in first-degree relatives.Conclusions These results may promote future epidemiology studies and strategies to improve women's lifestyle and consume paraben-free products.

Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods.METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integratingsphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable.RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength,and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength.There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa,and there were also large differences in these value ranges between both colon muscle layer/chorion. There are the same orders of magnitude in the absorption coefficients for four kinds of colon tissues. The scattering coefficients of these tissues exceed the absorption coefficients by at least two orders of magnitude.CONCLUSION: There were large differences in the three optical parameters between normal and adenomatous human colon mucosa/submucosa at the same laser wavelength, and there were also large differences in these parameters between both colon muscle layer/chorion at the same laser wavelength. Large differences in optical parameters indicate that there were large differences in compositions and structures between both colon mucosa/submucosa, and between both colon muscle layer/chorion.Optical parameters for four kinds of colon tissues are wavelength dependent, and these differences would be useful and helpful in clinical applications of laser and tumors photodynamic therapy (PDT).

Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response

Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research, The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PublVled literature search was conducted using the following keywords and combination of terms： radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways： （1） to generate gene signatures to identify sensitive and resistant populations （prognosis）; （2） to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack （diagnosis）; （3） to identify genes and pathways involved in tissue response to injury （mechanistic）. In this article we will review all （relevant） papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

Selection and Validation of Reference Genes for Normalization of RT-qPCR Analysis in Developing or Abiotic-Stressed Tissues of Loquat (Eriobotrya japonica)

Loquat(Eriobotrya japonica Lindl.)is a subtropical evergreen fruit tree that produces fruits with abundant nutrients and medicinal components.Confirming suitable reference genes for a set of loquat samples before qRT-PCR experiments is essential for the accurate quantification of gene expression.In this study,eight candidate reference genes were selected from our previously published RNA-seq data,and primers for each candidate reference gene were designed and evaluated.The Cq values of the candidate reference genes were calculated by RT-qPCR in 31 different loquat samples,including 12 subgroups of developing or abiotic-stressed tissues.Different combinations of stable reference genes were screened according to a comprehensive rank,which was synthesized from the results of four algorithms,including the geNorm,NormFinder,BestKeeper andΔCt methods.The screened reference genes were verified by normalizing EjLGA1 in each subgroup.The obtained suitable combinations of reference genes for accurate normalization were GAPDH,EF1αand ACT for floral development;GAPDH,UBCE and ACT for fruit setting;EF1α,GAPDH and eIF2B for fruit ripening;ACT,EF1αand UBCE for leaves under heat stress;eIF2B,UBCE and EF1αfor leaves under freezing stress;EF1α,TUA and UBCE for leaves under salt stress;ACT,EF1αand eIF2B for immature pulp under freezing stress;ACT,UBCE and eIF2B for immature seeds under freezing stress;EF1α,eIF2B and UBCE for both immature pulp and seeds under freezing stress;UBCE,TUB and TUA for red-fleshed fruits under cold-storage stress;eIF2B,RPS3 and TUB for white-fleshed fruits under coldstorage stress;and eIF2B,UBCE and RPS3 for both red-and white-fleshed fruits under cold-storage stress.This study obtained different combinations of stable reference genes for accurate normalization in twelve subgroups of developing or abiotic-stressed tissues in loquat.To our knowledge,this is the first report to obtain stable reference genes for normalizing gene expression of abiotic-stressed tissues in E.japonica.The use of the three most stable reference genes could increase the reliability of future quantification experiments.

A NEW METHOD TO CONSTRUCT A FULL-LENGTH cDNA LIBRARY OF HUMAN NORMAL BLADDER TISSUE

Objective Using template switch mechanism at the 5’ end of mRNA technique (SMART) to construct a full length cDNA library of human normal bladder tissue. Methods The novel procedures used the template switching activity of powerscript reverse transcriptase to synthesize and anchor first strand cDNA in one step. Following reverse transcription, 5 cycles of PCR were performed using a modified oligo(dT) primer and an anchor primer to enrich the full length cDNA population with 1.0 g human normal bladder poly(A) + RNA, then double strand cDNA was synthesized. After digestion with sfiI and size fractionation by CHROMA SPIN 400 columns, double strand cDNA was ligated into λ TripIEx 2 vector and was packaged. We determined the titer of the primary library and the percentage of recombinant clones and finally amplified the library. Results The titer of the cDNA library constructed was 2.1×10 6 pfu·mL -1 , and the amplified cDNA library was 6×10 11 pfu·mL -1 , the percentage of recombination clones was 99%. Conclusion Using SMART technique helps us to construct full length cDNA library with high efficiency and high capacity which lays solid foundation for screening target genes of bladder diseases with probes and antibodies.

Differential Expression of Genes Involved in Cell Polarity, EMT and Cell-Fate in Breast Cancer and Corresponding Normal Tissue

Objectives: Cell polarity and epithelial morphology are peculiar features of cells forming the terminal ductal lobular unit, and they are early lost during neoplastic transformation because of an epithelial-mesenchymal transition (EMT). To understand these early events we analyzed a set of 125 genes related to cell polarity, EMT and cell-fate decision in 26 breast cancer specimens and corresponding patient-matched normal tissue. Methods: The difference of gene expression was explored by t-paired test. In addition, to evidence latent variables accounting for genes correlations, a Factor Analysis was applied as exploratory technique. Results: Among the 90 differentially expressed genes, those coding for cell polarity complexes, apical-junctional components and luminal cytokeratins were overexpressed in tumor samples (suggesting a terminally differentiated phenotype) whereas those coding for stemness-associated features or related with EMT were expressed in normal tissues but not in tumor samples, suggesting the persistence of stem/progenitor cells. Factor analysis confirmed these findings and indicated that the difference between tumors and normal tissues can be synthesized in three main features representative of specific molecular/morphological alterations. Conclusions: The a priori definition of a selected panel of genes and the application of an exploratory statistical approach, greatly contribute to reduce the intrinsic biological complexity of tumor specimens and to describe the difference between tumor specimens and corresponding histologically normal tissues.

Doppler Tissue Imaging Assessment of Left Ventricular Systolic Dyssynchrony in Severe Heart Failure Patients With a Normal QRS Duration

Objectives To assess the prevalence of systolic dyssynchrony of the left ventricular （LV） walls in patients of heart failure（HF） with a normal QRS duration by Doppler tissue imaging （DTI）. Methods 20 patients of HF with a normal QRS duration and 20 healthy individuals were investigated with DTI to quantitatively analyze their pulsed-wave Doppler spectrum of basal and middle segments in six walls of left ventricle. The time between the onset of the QRS complex of the surface ECG and the onset of the systolic wave of pulsed-wave Doppler spectrum was measured （TS）. LV systolic synchronization was assessed by the maximal difference （MD） in time of TS, the standard deviation （SD） and the coefficient of variation （CV） of TS in the all 12 LV segments. Results When a TS-MD of TS〉 53.08 ms, a TS-SD of TS 〉18.08 ms and a TS-CV of TS 〉 0.91 （＋1.65 SD of normal controls） was used to define significant systolic dyssynchrony, the prevalence of systolic dyssynchrony was 55.0 %, 55.0 % and 55.0 %, respectively, in the HF patients group, significantly higher than those in the normal control and the locations of delayed contraction of these patients were different. Conclusions LV systolic dyssynchrony could be commonly demonstrated by DTI in HF patients with a normal QRS duration. This finding will support the view about the possibility that more HF patients could benefit from cardiac resynchronization therapy.

Study on normal ophthalmic tissues among ocular volume and extraocular muscles structure measurement by HR-MRI

Objective: To measure the ocular volume and extraocular muscles of healthy people using the high-resolution magnetic reso-nance imaging (HR-MRI) technology, to provide parameters support for eye research, teaching and diagnosis. Methods: The study collected 100 cases of normal subjects (200 eyes) from November 2012 to December 2013, including 50 males and 50 females, accepted line HR-orbital MRI, and image processing software was applied to morphology and statistical analysis. The extraocular muscles, muscle belly level horizontal diameter and maximum diameter vertical diameter were mea-sured. Results: The volume of the vitreous cavity (4.51 ± 0.26) cm3 had no significant difference with the anatomic normal value (p= .148);The volumes of the ocular globe, the anterior chamber and the lens cavity were (5.05 ± 0.21) cm3, (0.24 ± 0.26) cm3, (0.23 ± 0.14) cm3, with no statistic differences compared with those of the anatomic normal values. The extraocular muscles of normal Chinese were symmetrical on the two sides. The relationships of the short diameters of extraocular muscles in the maximum planes were: inferior rectus muscle (IR) > medial rectus muscle (MR) > superior rectus (SR) > lateral rectus muscle (LR). Those of the long diameters of extraocular muscles were: LR > MR > SR > IR. Conclusions: MRI can be used for measuring ocular volume and sizes of extraocular muscles. Compared with the anatomic normal value, the sizes of extraocular muscles can also be assessed by the symmetry on the two sides and by observing the usual rule of extraocular muscles.

Comparative Proteome Analysis of Human Lung Squamous Carcinoma Tissue

Objective： To establish the two-dimensional electrophoresis profiles with high resolution and reproducibility from human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue, and to identify differential expression tumor-associated proteins by using proteome analysis. Methods： Comparative proteome analysis with 20 human lung squamous carcinoma tissues and the paired normal bronchial epithelial tissues adjacent to tumors was carried out. The total proteins of human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis （2-DE） and silver staining. The differential expression proteins were analyzed and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. Results： （1） Well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained. For tumor tissue, average spots of 3 gels were 1567±46, and 1436±54 spots were matched with an average matching rate of 91.6%. For control, average spots of 3 gels were 1349±58, and 1228±35 spots were matched with an average matching rate of 91.03%. The average position deviation of matched spots was 0.924±0.128 mm in IEF direction, and 1.022±0.205 mm in SDS-PAGE direction; （2） A total of 1178±56 spots were matched between the eleetrophoretie maps of 20 human lung squamous carcinoma tissues and paired normal tumor-adjacent bronchial epithelial tissues. Seventy-six differentially expressed proteins were screened; （3） Sixty-eight differential proteins were identified by PMF, some proteins were the products of oneogenes, and others involved in the regulation of cell cycle and signal transduetion; （4） In order to validate the reliability of the identified results, the expression of 3 proteins mdm2, c-jun and EGFR, which was correlated with lung squamous carcinoma, was detected by immunohistoehemieal staining and Western blot analysis. The results revealed that mdm2, c-jun and EGFR were up-regulated in lung squamous carcinomas, whereas they were down-regulated in adjacent normal bronchial epithelial tissues, normal lung tissues and inflammatory pseudotumor, which was consistent with our proteome analysis results. Conclusion： The well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were established and 68 differential proteins were characterized by applying comparative proteome analysis successfully. These results will provide scientific foundation for screening the molecular biomarker used to diagnose and treat lung squamous carcinoma, as well as to improve the patient＇s prognosis and provide new clue for the research of lung squamous carcinogenic mechanism.

Sparing lung tissue with virtual block method in VMAT planning for locally advanced non-small cell lung cancer

This study aimed to exploit a new virtual block method to spare normal lung tissue in VMAT planning for patients with locally advanced non-small cell lung cancer(LA-NSCLC).The previous method was used to manually restrict the angle of the beam passing through,which ignored the location and shape of large targets that varied between different slices and did not block the beamlets precisely.Unlike the previous method,this new virtual block method was used to block the beamlets when necessary by closing the multi-leaf collimator(MLC)at prerequisite angles.The algorithm for closing the MLC depended on the thickness of the beamlets passing through the lungs and avoided only the entrance radiation beamlet.Moreover,this block can be automatically contoured.A retrospective study was performed to compare the VMAT plans with and without the virtual block method for 17 LANSCLC patients,named the block plan(B-plan)/non-block plan(N-plan).All cases were selected in this study because of the large tumor size and unmet dose constraints of the lungs.In addition to the maximum dose constraint for the virtual block,B-plans adopted identical optimization parameters to N-plans for each patient.These two types of plans were compared in terms of dosimetric indices and plan scores.The results were statistically analyzed using the Wilcoxon nonparametric signed-rank test.B-plans have advantages in the following dosimetric metrics that have statistical significance(p<0.05):(1)lower V_(5)/V_(10)/D_(mean)/normal tissue complication probability(NTCP)of total lungs;(2)reductions in V_(5)/V_(10)for the contralateral lung;(3)decrease in Dmean/V_(40)of the heart;(4)decrease in esophagus V_(40);(5)reductions in Dmean,V_(5)/V_(10) of normal tissue.B-plans(82.51±7.07)achieved higher-quality scores than N-plans(80.74±7.22).The new virtual block spared the lungs as well as other normal structures in VMAT planning for LA-NSCLC.Thus,the block method may decrease the risk of radiation-related toxicity in patients.

Expression of splice variants of CD44 in tumor－adjacent tissue of human primary liver cancer

The expression of metastasis-associated splice variants of CD44 in tumor-adjacent tissue was studied in 31 patients with primary liver cancer. In the patients with more metastatic evidence of liver cancer, the expression of splice variants of CD44 was found higher in tumor-adjacent tissue than in tumor tissue itself, suggesting that the expression of splice variants of CD44 in tumor-adjacent tissue may be a more useful indicator than that in turnor tissue itself for evaluating metastatic potential of primary liver cancer.

Glycosylated and non-glycosylated quantum dot-displayed peptides trafficked indiscriminately inside lung cancer cells but discriminately sorted in normal lung cells: An indispensable part in nanoparticle-based intracellular drug delivery

Difference in sub-cellular trafficking of glycosylated and naked peptides, between normal and lung cancer cells, was established. Normal lung tissue discriminately sorted glycosylated from non-glycosylated peptides by allowing golgi localization of the glycosylated peptides while restricting golgi entry of the naked peptides. This mechanism was surprisingly not observed in its cancer cell counterpart. Lung cancer cells tend to allow unrestricted localization of both glycosylated and naked peptides in the golgi apparatus. This newly discovered difference in sub-cellular trafficking between normal and lung cancer cells could potentially be used as an effective strategy in targeted intracellular delivery, especially targeting golgi-resident enzymes for possible treatment of diseases associated with glycans and glycoproteins, such as, congenital disease of glycosylation(CDG). This very important detail in intracellular trafficking inside normal and cancer cells is an indispensable part in nanoparticle-based intracellular drug delivery.

基于放射生物学模型的非小细胞肺癌不同放射治疗方案对比研究

目的:基于非小细胞肺癌(NSCLC)放疗评估的生物模型,对比不同放射治疗方案在肿瘤控制概率(TCP)和正常组织并发症概率(NTCP)的差异。方法:采集2021年4月至2022年7月就诊于天津医科大学总医院的15例NSCLC患者放疗资料,所有患者分别采用低分辨率泊松(TCP-Poisson-LQ)模型、Zaider-Minerbo(TCP-ZM)模型和TCP-Logit模型拟合TCP曲线,采用Lyman-Kutcher-Burman(LKB)模型和线性二次(LQ)模型拟合NTCP曲线,比较不同模型在肿瘤控制率、放射性肺炎和放射性心包炎上的适用性,并比较常规放疗方案(方案1)、最大治疗增益比方案(方案2)和平均肺剂量(MLD)<20 Gy时最大分割次数方案(方案3)在TCP和NTCP中的差异。结果:TCP-Poisson-LQ模型在60~70 Gy处的平均TCP为(87.2±11.92)%,符合临床所需剂量。全肺平均受量<26 Gy时,NTCP-LQ模型计算的放射性肺炎发生率高于NTCP-LKB模型。在不同方案的比较中,方案3的TCP均值为(81.56±11.20)%,高于其他两种方案(60.28±8.04)%和(69.46±18.09)%,差异均有统计学意义(t=-6.196、-1.969,P<0.05)。方案3的平均放射性肺炎的发生率为(19.24±0.43)%,高于方案1和方案2的(15.07±3.24)%和(15.89±4.55)%,差异有统计学意义(t=-5.878、-2.386,P<0.05)。结论:采用Poisson-LQ模型和NTCP-LQ模型分别计算NSCLC患者的TCP和放射性肺炎发生率较为合理,MLD<20 Gy时最大分割次数方案(方案3)可以在保证治疗安全的前提下有效提高TCP。

非小细胞肺癌质子-光子混合放疗计划的可行性研究

目的比较非小细胞肺癌(NSCLC)质子调强放射治疗(IMPT)和光子调强放射治疗(IMRT)的剂量学参数和正常组织并发症概率(NTCP),并探讨质子-光子混合放疗在NSCLC中的可行性和最佳模式。方法回顾性选取2020年11月至2022年4月于中国科学技术大学附属第一医院离子医学中心放疗科行根治性放疗NSCLC病人共8例,对8例病人分别制作IMPT和IMRT计划,IMPT计划采用的相对生物学效应(RBE)值为1.1,处方剂量为60 GyE/30次,对优化后计划的剂量学参数,放射性肺炎、食管毒性、2年死亡率指标的NTCP结果进行比较并分析,根据NTCP阈值或ΔNTCP的阈值方式选择合适的质子-光子混合放疗模式。结果所有NSCLC病人的IMPT及IMRT计划均符合要求,剂量体积直方图剂量学参数显示IMPT和IMRT计划的适形性指数[1.28(1.13,1.43)比1.12(1.05,1.18),P=0.068]和均匀性指数[0.09(0.08,0.15)比0.11(0.08,0.16),P=0.327]均差异无统计学意义,IMPT对比IMRT计划患肺平均剂量[9.38(4.28,13.78)Gy比12.27(7.95,15.41)Gy,P=0.012]、心脏平均剂量[5.59(1.01,8.50)Gy比8.23(6.61,15.82)Gy,P=0.012]、食管平均剂量[10.53(0.04,21.62)Gy比13.05(3.84,23.69)Gy,P=0.036]有降低(P<0.05)。此外IMPT计划的双肺V_(5 Gy)、双肺V_(20 Gy)、双肺V_(30 Gy)、患肺V_(5 Gy)、患肺V_(20 Gy)、心脏V_(30 Gy)、心脏V_(40 Gy)和脊髓D2%均明显降低(P<0.05)。IMPT可以将病人放射性肺炎[8.35(3.36,15.80)%比12.80(6.51,19.53)%,P=0.012]、食管毒性[20.43(0.21,42.58)%比26.03(5.43,46.30)%,P=0.036]及2年死亡率[43.28(34.58,48.27)%比48.78(42.74,56.20)%,P=0.012]的概率显著降低,ΔNTCP值分别为3.33(3.08,4.42)%,5.22(1.51,9.17)%和5.96(3.02,11.13)%。最后选择观察指标的NTCP阈值或ΔNTCP的阈值确定质子-光子混合放疗模式,结果显示使用ΔNTCP阈值方式进行混合更具优势。结论质子-光子混合放疗计划是可行的,可增加NSCLC病人的治疗获益和质子治疗可及性,选择ΔNTCP阈值方式进行混合放疗更具方便性及实用性。

胃癌患者组织中XPNPEP2、EZRIN的表达及意义

目的通过对胃癌及癌旁正常组织氨肽酶P2(XPNPEP2)、埃兹蛋白(EZRIN)的表达情况,探讨二者在胃癌发生、发展时的表达情况及临床意义。方法选取2020年2月至2022年12月于枣庄市立医院胃肠外科就诊的患者,就诊前无任何治疗措施,经组织病理诊断胃癌组96例及正常对照组64例。应用免疫组织化学方法检测胃癌及癌旁正常组织中的XPNPEP2和EZRIN的表达水平。结合临床资料分析其表达情况与患者年龄、性别、肿瘤大小、TNM分期、浸润转移情况的关系。结果病例组XPNPEP2、EZRIN阳性表达率分别为67.71%、63.54%,均高于对照组的26.56%、29.69%,差异有统计学意义(P<0.05);在不同TNM分期、是否发生浸润转移的患者中XPNPEP2阳性表达率组间比较,差异有统计学意义(P<0.05);XPNPEP2、EZRIN阳性表达率与患者年龄、性别、肿瘤大小无关,差异无统计学意义(P>0.05)。结论胃癌组织中XPNPEP2、EZRIN蛋表达水平升高,二者高表达与胃癌TNM分期、肿瘤浸润转移显著相关,在胃癌发生、侵袭、转移过程中发挥了重要作用,可能提示预后不良。

Close relationship between mediators of inflammation and pancreatic cancer:Our experience

In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer.Cancer of the pancreas remains one of the deadliest cancer types.The highest incidence and mortality rates of pancreatic cancer are found in developed countries.Trends of pancreatic cancer incidence and mortality vary considerably worldwide.A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease.Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche.In this editorial,we highlight the foundational studies that have driven our understanding of these processes.In our experimental center,we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer.We focused on the role of mast cells(MCs).MCs contain pro-angiogenic factors,including tryptase,that are associated with increased angiogenesis in various tumors.In this editorial,we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue.The assessment includes the density of c-Kit receptor-positive MCs,the density of tryptase-positive MCs,the area of tryptasepositive MCs,and angiogenesis in terms of microvascularization density.

Proteomic Comparison of Two-Dimensional Gel Electrophoresis Profiles from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorp-tion/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load. The average deviation of spot position was 0.733±0.101 mm in IEF direction, and 0.925±0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190±72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls. Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduc-tion. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis. These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

Con A affinity glycoproteomics of normal human liver tissue

In order to establish the novel high throughput, high efficiency and low cost technological platform for the research of N-glycoproteomics, to resolve the significance of characteristic expression profile of glycoprotein and to find the proteins with biological functional importance, the glycoproteins with high-mannose core and the two antennary types were purified and enriched by the Con A affinity chromatography. Con A affinity protein expression profiles of normal human liver tissue were gener- ated by using SDS-PAGE, two-dimensional electrophoresis (2-DE) followed by fast fluorescence stain- ing based on multiplexed proteomics (MP) technology. 301 visible protein spots on the gel were de- tected and 85 of glycoproteins were further successfully identified via peptide mass fingerprinting (PMF) by a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF- MS/MS) and annotated to IPI databases. Identified glycoproteins definitely take part in the regulation of cell cycle and metabolic processes. The glycosylation sites were predicted with NetNGlyc 1.0 and NetOGlyc 3.1 software, meanwhile they were classified according to the geneontology methods. The construction of Con A affinity glycoprotein database of normal human liver tissue would contribute to the subsequent research.