结直肠筛状粉刺型腺癌的临床病理特征与预后的关系

目的探讨结直肠筛状粉刺型腺癌的临床病理特征与预后的关系。方法分析比较24例结直肠筛状粉刺型腺癌与278例普通型结直肠腺癌的临床分期、脉管侵犯、淋巴结转移和遗传学特点等。结果结直肠筛状粉刺型腺癌临床分期较晚,Ⅲ+Ⅳ期所占比例(87.5%)及淋巴结转移率(87.5%)均明显高于普通型结直肠腺癌(42.4%,42.4%),差异具有统计学意义(P<0.05);结直肠筛状粉刺型腺癌脉管侵犯率(87.5%)明显高于普通型结直肠腺癌(22.7%),差异具有统计学意义(P<0.05)。患者年龄、性别和分子遗传学KRAS及BRAF突变在两组间差异均无统计学意义(P>0.05)。结论结直肠筛状粉刺型腺癌具有独特的形态学特征,易侵犯脉管和淋巴结转移,临床分期较晚,预后较差。

Research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer

Dual-layer spectral detector CT is a new spectrum CT imaging technology based on detector being able to obtain both images similar to true plain and spectral images in one time scanning.The reconstructed multi-parameter spectral images can not only improve image quality,enhance tissue contrast,increase the visualization and detection ability of occult lesions,but also provide qualitative and quantitative analysis of the lesions,so as to provide more imaging information and multi-dimensional diagnostic basis.The research progresses of dual-layer spectral detector CT for preoperative evaluation on colorectal cancer were reviewed in this article.

microRNA-139-5p及其靶基因Notch1在结直肠癌中的作用

目的：探讨microRNA-139-5p（miR-139-5p）在结直肠癌中的表达及其对结直肠癌细胞转移和侵袭的影响。方法：用荧光定量PCR方法检测miR-139-5p在结直肠癌组织与不同结直肠癌细胞株中的表达变化;用Boyden小室分析和伤口愈合实验检测miR-139-5p转染及miR-139-5p抑制对结直肠癌细胞转移和侵袭能力的影响;生物信息学方法预测miR-139-5p的靶基因,并采用荧光素酶报告基因实验验证,Western blot方法检测miR-139-5p转染对靶基因表达的影响。结果：与各自的正常对照组比较,结直肠癌组织与结直肠癌细胞系中miR-139-5p表达均明显降低（P〈0.05）。结直肠癌DLD1细胞和HCT116细胞转染miR-139-5p后,转移与侵袭能力均明显降低（均P〈0.05）,而miR-139-5p抑制剂处理后,两种细胞的的侵袭能力均明显增强（均P〈0.05）。生物信息学预测显示,Notch1是miR-139-5p的靶基因,且得到荧光素报告实验结果证实。Western blot结果显示,转染miR-139-5p后,结直肠癌DLD1细胞和HCT116细胞中Notch1蛋白表达均明显下调（均P〈0.05）。结论：miR-139-5p可能通过调节Notch1的表达而抑制肿瘤细胞的转移和侵袭,而下调的miR-139-5p可能在结直肠癌的发生发展中起了重要作用。

优质康复模式对结直肠癌患者术后焦虑抑郁情绪及生活质量的影响

目的 探讨优质康复模式对结直肠癌患者术后焦虑抑郁情绪及生活质量的影响.方法 60例结直肠癌患者按随机数字表法分为观察组与对照组,各30例.对照组采用常规专业康复措施.观察组在常规专业康复措施的基础上,实施优质康复模式.采用焦虑自评量表（SAS）和抑郁自评量表（SDS）观察患者的心理状态,采用生活质量量表（SF-36）观察患者的生活质量.结果 术后2周时,观察组SAS、SDS评分分别为（47.5±5.2）分、（49.7±5.7）分,低于对照组的（55.2±6.3）分、（53.4±5.8）分（t=5.163、2.492,均P＜0.01）;观察组总体健康、生理功能、生理职能、躯体疼痛、活力、社会功能、情感职能、精神健康等生活质量评分分别为（79.06±3.78）分、（79.57±3.96）分、（78.39±3.71）分、（76.98±3.52）分、（77.59±4.16）分、（75.52±4.85）分、（79.28 ±4.91）分、（78.31±4.27）分,均高于对照组的（74.19 ±4.07）分、（75.24±4.12）分、（71.92±4.38）分、（73.25±3.47）分、（74.06±4.13）分、（72.17±4.21）分、（74.65±4.35）分、（73.87±3.92）分（t=4.802、4.150、6.174、4.133、3.298、2.857、3.866,均P＜0.01）.结论 优质康复模式能明显改善结直肠癌患者术后的焦虑抑郁情绪,并明显改善患者的生活质量.

FOXP4的表达及其对β-catenin转录的调控在结直肠癌中的作用

背景与目的:FOXP转录因子家族已被证明在多种肿瘤中发挥重要作用,但其成员FOXP4在结直肠癌中的作用尚未见报道,故本研究探讨FOXP4在结直肠癌中的表达,及其与患者临床病理特征、预后的关系,并探讨其潜在的作用机制。方法:采用免疫组化和RT-PCR检测50例结直肠癌患者癌组织以及癌旁正常组织标本中FOXP4的表达,并分析其与患者临床病理特征的关系;利用GEIPA数据库分析结直肠癌组织构FOXP4的表达情况,及其与患者生存率的关系。构建稳定过表达或敲减FOXP4的结直肠癌细胞系,分别用CCK8与Transwell法检测各结直肠癌细胞系增殖能力与迁移能力的变化。根据AnimalTFDB 3.0数据库预测FOXP4可能的靶启动子,分别用CHIP实验、荧光素酶报告基因、RT-PCR和Western blot验证FOXP4与靶启动子结合能力及对相应靶基因转录的调控作用。最后,对靶基因的功能进行验证。结果:临床标本与GEIPA数据库分析均显示,结直肠癌组织中FOXP4的表达量明显升高,其表达量与患者肿瘤大小、分化程度及TNM分期明显有关,高表达FOXP4的患者总体生存率明显降低(均P<0.05)。CCK8与Transwell实验结果显示,FOXP4过表达的结直肠癌细胞的增殖、迁移能力明显增强,而FOXP4低表达的结直肠癌细胞的增殖、迁移明显减弱(均P<0.05)。AnimalTFDB 3.0数据库分析显示,β-catenin的启动子可能是FOXP4的靶启动子;ChIP实验证明FOXP4可以识别β-catenin启动子区域;荧光素酶实验显示FOXP4仅可识别野生型的β-catenin序列;RT-PCR和Western blot分析发现FOXP4过表达可增加β-catenin基因及蛋白的表达水平。β-catenin抑制剂处理后,FOXP4过表达对结直肠癌细胞增殖与迁移能力的增强作用被取消(均P<0.05)。结论:FOXP4的表达在结直肠癌中增高,且与患者的恶性临床病理特征及不良预后密切相关。FOXP4过表达可能是通过调控β-catenin转录促进结直肠癌细胞的增殖及迁移。综上提示,FOXP4结直肠癌的发生发展中起了重要作用,可作为结直肠癌的潜在治疗靶点。

Oncoprotein expression and inhibition of apoptosis during colorectal tumorigenesis

AIMS To study bcl-2 and P53 protein expression and inhibition of apoptosis during colorectal tumorigenesis. METHODS Expression of bcl -2 and p53 in 45 colorectal ade- nomas and 61 colorectal carcinomas was detected by immunohis- tochemical staining. RESULTS The bcl-2 and P53 protein expression was uniformly negative in normal mucosa,whereas bcl-2 and p53 positive rates were significantly higher in adenoma and carcinoma than in nor- reals(P<0.01 ).The area with strong bcl-2 expression was of- ten the area with severely dysplasia.In colorectal adenoma,ex- pression of p53 increased with the increasing size and dysplasia, in adenomas≥20 mm being higher than adenomas<10 mm(77, 8% vs 35.0%,P<0.05).p53 was relevant to differentiation and Duke's staging.A significant inverse correlation was found between bcl-2 and p53 in immunostaining in the adenomas,but not in the carcinomas.Furthermore,carcinomas with a high per- centage of bcl-2 positive cells were significantly more likely to have low rates of apoptosis. CONCLUSIONS These results suggest that bcl-2 gene appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis,p53 expression plays an important role in the develop- ment and malignant change of colorectal adenoma,bcl-2 and p53 may be used as a good marker relating to cell apoptosis.

Down-regulation of Wnt Antagonist,SFRP1 in Colorectal Tumorigenesis

OBJECTIVE To assess the functional change of SFRP1 （secreted frizzled-related protein1）, in colorectal tumorigenesis. METHODS Immunohistochemical investigation and the semiquantitative reverse transcription-polymerase chain reaction （RT-PCR） were used to assess the expression of SFRP1, β-catenin （β-cat） and E-caderin （E-cad） in matched samples of normal colorectal mucosa, adenomas and cancers. RESULTS SFRP1 mRNA expression was down-regulated in the neoplasms, and abnormal expressions of β-cat and E-cad were found in colorectal adenomas and colorectal cancers. CONCLUSION Down-regulation of SFRP1 observed is consistent with its acting as a tumor suppressor gene in colorectal tumorigenesis.

Changing patterns of colorectal cancer in China over a period of 20 years

AIM： To determine whether any changes have occurred on the patterns of colorectal cancer in China. METHODS： Data from 21 Chinese articles published from 1980 to 1999, were used to analyze the time trend of colorectal cancer according to the patients＇age at diagnosis, sex, the site of the tumor, stage, and the pathology. RESULTS： From 1980s to 1990s, the mean age of the colorectal cancer patients has increased. The percentage of the female patients rose. The distribution of colorectal carcinoma shows a predominance of rectal cancer. However, the proportion of proximal colon cancer （induding transverse and ascending colon） increased significantly accompanied by a decline in the percentage of rectal cancer. Similarity in the percentage of distal colon cancer between two decades was revealed. In the 1990s, statistically more Stage B patients were found than those in 1980s. In addition, databases show a significant decrease in the Stage D cases. The proportion of adenocarcinoma increased, but the mucinous adenocarcinoma decreased during two decades. CONCLUSION： These findings indicate that the pattern of colorectal cancer in China has been changing. Especially, a proximal shift due to the increasing proportion of ascending and transverse colon cancer has occurred in China.

Hereditary non-polyposis colorectal cancer: The rise and fall of a confusing term

The term Hereditary Non-Polyposis Colorectal Cancer （HNPCC） is a poor descriptor of the syndrome described by Lynch. Over the last decade, the term has been applied to heterogeneous groups of families meeting limited clinical criteria, for example the Amsterdam criteria. It is now apparent that not all Amsterdam criteria-positive families have the Lynch syndrome. The term HNPCC has also been applied to clinical scenarios in which CRCs with DNA microsateUite instability are diagnosed but in which there is no vertical transmission of an altered DNA mismatch repair （MMR） gene. A term that has multiple, mutually incompatible meanings is highly problematic, particularly when it may influence the management of an individual family. The Lynch syndrome is best understood as a hereditary predisposition to malignancy that is explained by a germline mutation in a DNA MMR gene. The diagnosis does not depend in an absolute sense on any particular family pedigree structure or age of onset of malignancy. Families with a strong family history of colorectal cancer that do not have Lynch syndrome have been grouped as ‘Familial Colorectal Cancer Type-X＇. The first step in characterizing these cancer families is to distinguish them from Lynch syndrome. The term HNPCC no longer serves any useful purpose and should be phased out.

Clinical significance of type V_I pit pattern subclassification in determining the depth of invasion of colorectal neoplasms

AIM: To clarify whether subclassification of the type VI pit pattern on the basis of magnifying colonoscopy findings is useful in determining the type and depth of invasion of colorectal neoplasms.METHODS: We retrospectively analyzed 272 colorectal neoplasms (117 dysplasias and 155 submucosal invasive carcinomas; 228 patients) with a type V pit pattern [type VI, n = 202; type VN, n = 70 (Kudo and Tsuruta classification system)]. We divided lesions with a type VI pit pattern into two subclasses, mildly irregular lesions and severely irregular lesions, according to the prominent and detailed magnifying colonoscopy findings. We examined the relation between these two subclasses and histology/invasion depth.RESULTS: One hundred and four lesions (51.5%) were judged to be mildly irregular, and 98 lesions (48.5%) were judged to be severely irregular. Ninety-seven (93.3%) mildly irregular lesions showed dysplasias or submucosal invasion of less than 1000 μm (SM < 1000 μm). Fifty-five (56.1%) severely irregular lesions showed submucosal invasion equal to or deeper than 1000 μm (SM ≥ 1000 μm). Mild irregularity was found significantly more often in dysplasias or lesions with SM < 1000 μm than in lesions with SM ≥ 1000 μm (P < 0.01).CONCLUSION: Subclassification of the type VI pit pattern is useful for identifying dysplasias or lesions with SM < 1000 μm.

Promoter hypomethylation and reactivation of MAGE-A1 and MAGE-A3 genes in colorectal cancer cell lines and cancer tissues

AIM： To verify the expression and methylation status of the MAGE-A1 and MAGE-A3 genes in colorectal cancer tissues and cancer cell lines. METHODS： We evaluated promoter demethylation status of the MAGE-A1 and MAGE-A3 genes by RT-PCR analysis and methylation-specific PCR （MS-PCR）, as well as sequencing analysis, after sodium bisulfite modification in 32 colorectal cancer cell lines and 87 cancer tissues. RESULTS： Of the 32 cell lines, MAGE-A1 and MAGE-A3 expressions were observed in 59% and 66%, respectively. Subsequent to sodium bisulfite modification and MSPCR analysis, the promoter hypomethylation of MAGE-A1 and MAGE-A3 was confirmed in both at 81% each. Promoter hypomethylation of MAGE-A1 and MAGE-A3 in colorectal cancer tissues was observed in 43% and 77%, respectively. Hypomethylation of MAGE-A1 and MAGE-A3 genes in corresponding normal tissues were observed in 2% and 6%, respectively. CONCLUSION： The promoter hypomethylation of MAGE genes up-regulates its expression in colorectal carcinomas as well as in gastric cancers and might play a significant role in the development and progression of human colorectal carcinomas.

Tiaml gene expression and its significance in colorectal carcinoma

AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiaml gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptase-polymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiaml expression with the invasive ability was also analyzed. RESULTS: Tiaml gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116, LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiaml gene was highly related to the metastatic potential of colorectal carcinoma cells. CONCLUSION: Tiaml gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

MUC1 and colorectal cancer pathophysiology considerations

Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and coinvestigators showed recently that MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through β-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-β-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound.

The expression of glucose regulated protein-94 in colorectal carcinoma cells treated by sodium butyrate

The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.

Relationship between serum calcium and CA 19-9 levels in colorectal cancer

AIM:To examine the calcium metabolism of colorectal cancer (CRC)in patients with colorectal cancer and control patients. METHODS:Seventy newly diagnosed CRC patients were included.The healthy control group was age and gender matched(n=32).Particular attention was devoted to the relationship between serum calcium of patients,and levels of AFP,CEA,carbohydrate antigen 19-9(CA 19-9)(that could be considered as prognostic factors).Furthermore,the Ca-sensing receptor(CaSR)gene A986S polymorphism was investigated in these patients,as well as the relationship between different CaSR genotypes and the data stated above. RESULTS:A lower level of ionized calcium(also corrected for albumin)was found in the serum of CRC patients with normal 25(OH)vitamin D levels.The ionized calcium concentration was inversely correlated with the serum level of CA.19-9.There was no difference in the distribution of CaSR genotypes,between CRC patients and general population.The genotypes did not correlate with other data examined. CONCLUSION:Based on these results,lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer.

Expression of a novel apoptosis inhibitor-survivin in colorectal carcinoma

AIM： To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS： Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNE） were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma. RESULTS： The survivin positive unit （PU） was higher in cancerous tissues （38.76±5.14） than in para-cancerous （25.17±7.26） or normal tissues （0.57±0.03） （P〈0.05）. The apoptosis index （AI） of para-cancerous tissues was （7.51±2.63%） higher than cancerous tissues （4.65±1.76%）. The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma. CONCLUSION： Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.

Detection of micrometastasis in peripheral blood by multi-sampling in patients with colorectal cancer

AIM: To evaluate the reverse transcriptase-PCR assay and multiple sampling for detection of cytokeratin-positive cells in peripheral blood of colorectal carcinoma patients and to investigate the clinical significance of micrometastasis in peripheral blood.METHODS: The expression of CK20 mRNA by RT-PCR was investigated in bone marrow, portal vein and peripheral blood in 58 colorectal cancer patients and 12 controls without known cancer. The peripheral blood was sampled twice at intervals of 3 d before operation. All the patients were followed up for one year.RESULTS: There was no positive expression of CK20mRNA in 12 volunteers. The positive expression of CK20mRNA was 77.6% (45/58) in bone marrow, and that in portal vein was 74.1% (43/58) of colorectal carcinoma patients.The positive expression of CK20mRNA cells in peripheral blood rose from 44.8% (26/58) to 69.0% (40/58) (P＜0.01).The total positivity of CK20mRNA expression in peripheral blood was similar to the positivity of CK20mRNA in bone marrow and portal vein. The positive rates became higher in later clinical stages than in early stages. The CK20mRNA positive patients had a higher relapse rate within one year than the CK20mRNA negative patients.CONCLUSION: Multiple blood sampling can increase the detection of tumor cells in peripheral blood by RT-PCR for CK20mRNA in colorectal carcinoma patients and it is as sensitive and specific as that of bone marrow and portal vein. This technique may be reliable and convenient to diagnose micrometastasis of colorectal carcinoma and has an important significance in determining the prognosis of cancer patients.

Expression of ST13 in colorectal cancer and adjacent normal tissues

AIM: To investigate the in situ expression of suppressionof tumorigenecity 13 (ST13) mRNA in both colorectal cancer and adjacent normal tissues.METHODS: Colorectal cancer cell lines SW1116, SW620and CoLo205 were enrolled to confirm the feasibility of the in situ hybridization procedure. Seven colorectal cancer and adjacent normal tissues were included for RNA-RNA in situ hybridization.RESULTS: The expression of ST13 in the seven normal colon tissues was positive and the positive signals appeared in mucosal cells. Only three of the seven colorectal cancer tissues had positive hybridization signals that appeared in adenocarcinoma cells.CONCLUSION: The expression of ST13 decreases in colorectal cancer tissue compared with that in adjacent normal tissue. ST13 is mostly expressed in colorectal epithelia and adenocarcinoma cells.

Application of rational emotive behavior therapy in patients with colorectal cancer undergoing adjuvant chemotherapy

Objective:This study aimed to explore the effects of our rational emotive behavior therapy(REBT)program on symptoms,anxiety,depression,and sleep state in patients with colorectal cancer(CRC)undergoing chemotherapy.Methods:From October 2020 to May 2021,fifty-six patients with CRC in a hospital in the Hunan Province were randomly divided into an intervention group(n=28)and a control group(n=28).The patients in the intervention group completed a 6-week REBT program based on routine nursing care,including four courses:1)establish a relationship and formulate health files;2)group communications and study symptom management;3)continuously provide health knowledge and strengthen healthy behavior;and 4)review the treatment and summary.The control group maintained routine nursing care.The simplified Chinese version of the Memorial Symptom Assessment Scale Short Form(MSASeSFeSC),the Hospital Anxiety and Depression Scale(HADS),and the Pittsburgh Sleep Quality Index(PSQI)scale were used to investigate and compare the intervention effects of the two groups at baseline(T1,before the intervention),four weeks(T2),and six weeks(T3)after the intervention.Results:The intervention group was significantly improved in symptoms,anxiety,depression,and sleep state,compared with the control group.At T2,MSASeSFeSC(24.43±4.26 vs.28.07±3.91),symptom distress(17.29±4.04 vs.19.39±3.59),symptom frequency(7.14±1.51 vs.8.68±1.42),HADS(13.68±3.38 vs.15.86±3.79),anxiety(3.89±1.85 vs.5.18±2.18),and depression(9.79±2.06 vs.10.68±2.23),showed that the difference between the two groups was statistically significant(P<0.05).At T3,MSASeSFeSC(23.89±3.54 vs.30.14±3.94),symptom distress(17.61±3.52 vs.21.32±3.57),symptom frequency(6.29±1.49 vs.8.82±1.47),HADS(11.82±2.57 vs.16.29±3.13),anxiety(3.21±1.64 vs.5.61±1.77),and depression(8.61±1.52 vs.10.68±1.81),showed that the difference between the two groups was statistically significant(P<0.05).The sleep state of the intervention group was better than the control group at T3,with decreased score of PSQI[4.00(3.00,8.00)vs.9.00(7.00,12.50),Z=-3.706,P<0.001].Conclusion:The 6-week REBT program can effectively improve the symptom,anxiety,depression,and sleep state of patients with CRC undergoing chemotherapy,which could as a care plan for patients with CRC who are repeatedly admitted to the hospital for chemotherapy.