Mismatch repair proteins and microsatellite instability in solid pseudopapillary neoplasm of the pancreas

Solid pseudopapillary neoplasms (SPNs) are rare solid pancreatic tumors mainly affecting young women. Despite the high percentage of favorable prognosis, they are considered as low grade malignant neoplasms, and metastases occur in 5%-15% of patients. Almost all SPNs (95%) have somatic activating mutations in the β-catenin gene [1].

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Phosphorylation and biosynthesis of high molecular weight proteins of tumor nuclear matrix

Our previous studies showed a predominance of high molecular weight protein group in tumor nuclear matrices. Contrary to normal cells, proteins of this group are preferentially phosphorylated. Phosphoproteins of hepatoma nuclear matrix are selectively subjected to rapid proteolysis. By alkali treatment and a monoclonal antibody against phosphotyrosyl residue the presence of two high molecular weight bands of phosphotyrosyl-containing proteins was detected in nuclear matrices of tumor but not of normal liver cells. High molecular weight protein group of tumor nuclear matrices revealed also a rapid turnover and preferential incorporation of labeled amino acids selectively inhibited by chloramphenicol.

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.

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.

Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

Effect of Boschniakia rossica on expression of GSTP,p53 and p21^(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats

AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21rasproteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21rasproteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H2O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21rasproteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH2Cl2 and H2O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H2O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH2CI2 and H2O extracts from BR exerted anti-inflammatory effect in rats and mice.

Presence of Fas and Bcl-2 proteins in BEL-7404 human hepatoma cells

AIM To study the expression of Fas and Bcl 2 proteins in BEL 7404 human hepatoma cells in order to analyze the possible relationship between cell growth regulation by alpha fetoprotein(AFP) and Fas/Bcl 2 proteins. METHODS BEL 7404 human hepatoma cells were maintained in RPMI 1640 medium supplemented with 10% new born calf serum. Cells adhered to coverslips were used to detect Fas and Bcl 2 protein expression by the avidin biotin complex (ABC) immunocytochemical assay. RESULTS Immunocytochemical study showed that essentially all the BEL 7404 human hepatoma cells could express Fas and Bcl 2 proteins, although in various amounts. No positive staining for Fas and Bcl 2 proteins was observed when cells were incubated with non relevant sera to establish the specificity. CONCLUSION Fas apoptosis signals and Bcl 2 rescue/survival signals from apoptosis are expressed in BEL 7404 human hepatoma cells. The finding strongly implys that AFP mediated cell apoptosis and growth enhancement are potentially associated with Fas and Bcl 2 proteins present in those cells.

Insulin-like growth factor binding protein-5 influences pancreatic cancer cell growth

AIM： To investigate the functional significance of insulin-like growth factor binding protein-5 （IGFBP-5） overexpression in pancreatic cancer （PaC）.METHODS： The effects of IGFBP-5 on cell growth were assessed by stable transfection of BxPC-3 and PANC-1 cell lines and measuring cell number and DNA synthesis. Alterations in the cell cycle were assessed by flow cytometry and immunoblot analyses. Changes in cell survival and signal transduction were evaluated after mitogen and phosphatidylinositol activated protein kinase 3-kinase （PI3K） inhibitor treatment.RESULTS： After serum deprivation, IGFBP-5 expression increased both cell number and DNA synthesis in BxPC-3 cells, but reduced cell number in PANC-1 cells. Consistent with this observation, cell cycle analysis of IGFBP-5-expressing cells revealed accelerated cell cycle progression in BxPC-3 and G2/M arrest of PANC-1 cells. Signal transduction analysis revealed that Akt activation was increased in BxPC-3, but reduced in PANC-1 cells that express IGFBP-5. Inhibition of PI3K with LY294002 suppressed extracellular signal-regulated kinase-1 and -2 （ERK1/2） activation in BxPC-3, but enhanced ERK1/2 activation in PANC-1 cells that express IGFBP-5. When MEK1/2 was blocked, Akt activation remained elevated in IGFBP-5 expressing PaC cells; however, inhibition of PI3K or MEK1/2 abrogated IGFBP-5-mediated cell survival.CONCLUSION： These results indicate that IGFBP-5 expression affects the cell cycle and survival signal pathways and thus it may be an important mediator of PaC cell growth.

Heat shock and other apoptosis-related proteins as therapeutic targets in prostate cancer

Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.

Altered expression of nuclear matrix proteins in etoposide induced apoptosis in HL-60 cells

The events of cell death and the expression of nuclear matrix protein (NMP) have been investigated in a promyelocytic leukemic cell line HL-60 induced with etoposide. By means of TUNEL assay, the nuclei displayed a characteristic morphology change, and the amount of apoptotic cells increased early and reached maximun about 39% after treatment with etoposide for 2 h. Nucleosomal DNA fragmentation was observed after treatment for 4 h. The morphological change of HL-60 cells, thus, occurred earlier than the appearance of DNA ladder. Total nuclear matrix proteins were analyzed by 2-dimensional gel electrophoresis. Differential expression of 59 nuclear matrix proteins was found in 4 h etoposide treated cells. Western blotting was then performed on three nuclear matrix acssociated proteins, PML, HSC70 and NuMA. The expression of the suppressor PML protein and heat shock protein HSC70 were significantly upregulated after etoposide treatment, while NuMA, a nuclear mitotic apparatus protein, was down regulated. These results demonstrate that significant biochemical alterations in nuclear matrix proteins take place during the apoptotic process.

Human Epididymis Protein-4 Gene Expression as a Biomarker in Patients with Ovarian Cancer in Iran

Introduction: Ovarian cancer is one of the most common malignancies in women and the fifth cause of cancer-related deaths in women worldwide. Contrary to the challenges in developing new clinical markers using the conventional methods, recent advances in genomics and proteomics have led to identification of candidate and promising biomarkers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4) is such a marker that has recently been reported to correlate with recurrence or progression of epithelial ovarian cancer. The purpose of this study was to measure the expression level of HE4 gene in women with ovarian cancer. Methodology: We evaluated and compared paraffin-embedded tissue samples of 20 ovarian cancer patients with 10 samples from healthy individuals. RNA was initially extracted from the samples and cDNA was synthetized. Gene expression level was then measured using real-time polymerase chain reaction (PCR). Results: Our results demonstrated that HE4 gene expression level was significantly higher in samples of patients with ovarian cancer compared with samples from healthy individuals. Moreover, higher levels of HE4 gene expression were associated with more advanced disease and larger tumor size. Conclusion: HE4 gene over-expression has the potential to be used as a biomarker for detecting early-stage ovarian cancer in women. Future more comprehensive studies are needed to confirm our findings.

Expressions and clinicopathologic significance of five heat shock proteins in esophageal squamous cell carcinoma

Objective： To investigate the expressions of heat shock protein （hsp） 10, hsp27, hsp60, hsp70 and hsp90a in esophageal squarnous cell carcinoma （ESCC） and normal tissues along the incisal margin （TIM）, and discuss the clinicopathologic features about their expressions. Methods： 120 specimens from ESCC and 36 specimens from TIM were made into tissue chips. The presence and the levels of expression of hspl0, hsp27, hsp60, hsp70 and hsp90a were observed on tissue chips by immunohistochemistry EnVision^TM. Their correlations to clinicopathologic features were analyzed. Results： The positive staining rates of hsp10, hsp27, hsp60, hsp70 and hsp90a in ESCC and TIM were 53.8% and 37.5%, 62.0% and 42.1%, 92.7% and 63.2%, 57.9% and 22.2%, 33.7% and 18.5% respectively. There were no statistical significances between the differential expressions of hsp10, hsp27 and hsp90a in ESCC and TIM （P 〉 0.05）, but there were great statistical significances about hsp60 and hsp70 （P 〈 0.01）. The level of hsp27 declined with the lower grade of differentiation of ESCC （P 〈 0.05）. Except for hsp27, the positive expressions of the other four HSPs had no correlation to the clinicopathologic features of ESCC. Conclusion： The expressions of hsp10, hsp27, hsp60, hsp70 and hsp90a in ESCC and TIM were a common event. The levels of hsp60 and hsp70 in ESCC were higher than those in TIM. The level of hsp27 declined with the lower grade of differentiation of ESCC showed that it may be play a role in the differentiation of ESCC.

超声诊断BI-RADS4级乳腺病灶

目的探讨恶性超声征象诊断BI-RADS 4级乳腺病变的价值。方法回顾性分析术前应用超声诊断为BI-RADS 4级的乳腺病变患者338例(405个病灶),将超声所见与手术病理结果进行对照。结果 "毛刺征"、"后方回声衰减"及"RI值≥0.7"为诊断特异度较高的超声征象,对乳腺癌的诊断特异度分别为98.36%(299/304)、90.12%(274/304)和86.24%(262/304)。结论 "毛刺征"、"后方回声衰减"及"RI值≥0.7"为特异度较高的超声征象,当出现这3个征象时,BI-RADS 4级评分倾向于4C级。

超声引导下导丝定位在触诊阴性的BI-RADSⅣ类及以上乳腺病变中的应用

目的探讨超声引导下导丝定位在触诊阴性的BI-RADSⅣ类及以上乳腺病变中的临床价值及应用技巧。方法回顾性分析我院2015年1月～2017年6月150例女性患者,临床触诊阴性且超声提示BI-RADSⅣ类及以上,术前通过超声引导下导丝定位,选择合理的穿刺点,定位针尽可能与皮肤垂直,术中沿导丝切除病灶。结果150例患者共检出BI-RADSⅣ类及以上乳腺病灶157枚,超声引导下导丝定位成功率100%,手术切除率100%。病理证实良性病例数100例,病灶107枚,恶性病例数50例,病灶50枚。良性病例行区段切除,恶性病例其中31例实施保乳手术,19例实施乳腺癌改良根治术。恶性病例穿刺点均一并手术切除,且未有因穿刺点选择不当而影响手术切口选择的病例。结论术前超声引导下导丝定位可以精准切除触诊阴性的BI-RADSⅣ类及以上乳腺病变。定位针尽可能与皮肤垂直,合理选择进针点,可以快速准确的切除病灶,又不会影响恶性病例后续手术切口的选择。

不同BIS值的全凭静脉麻醉对老年腹部手术患者术后认知功能的影响

目的探讨不同脑电双频谱指数(bispectral index,BIS)下全凭静脉麻醉对老年腹部手术患者术后认知功能的影响。方法选择在全凭静脉麻醉下行择期腹部手术的老年患者60例,年龄≥60岁,ASAⅠ~Ⅲ级,根据BIS值随机分为3组:V1(BIS=30~39)、V2(BIS=40~49)、V3(BIS=50~59)。所有患者于术前(T0)、术后1天(T1)、术后3天(T2)及术后5天(T3)以简易智力状态检查表(MMSE)与画钟试验(CDT)评估术后认知功能障碍(POCD)的发生。各组于围术期即麻醉前(TⅠ)、手术切皮即刻(TⅡ)、手术30min(TⅢ)、手术结束时(TⅣ)和出恢复室即刻(或ICU拔除气管导管即刻)(TⅤ)采静脉血测定血清S100β蛋白的浓度。结果3组患者术后MMSE评分、CDT评分及POCD发生情况,围术期血清S100β蛋白检测各时点组间比较差异均无统计学意义(P均>0.05)。完成本研究的53例患者中,T1时35例(66.0%)、T2时17例(32.1%)、T3时6例(11.3%)发生POCD。各组不同时间点组内POCD发生情况比较的趋势卡方检验差异有统计学意义(P<0.05)。结论麻醉深度对全凭静脉麻醉下老年腹部手术患者术后认知功能没有影响,POCD与麻醉手术后恢复时间有关。

钼靶钩丝定位在切除触诊阴性的BI-RADS Ⅳ级以上乳腺病变中的意义

目的:探讨乳腺钼靶X线摄影引导下钩丝定位活检技术对临床触诊阴性或触诊不良的BI-RADSⅣ级及以上乳腺病变的诊断意义。方法:选取2012年1月至2014年8月48例乳腺钼靶BI-RADSⅣ级及以上但临床触诊阴性或触诊不良的乳腺病变患者(其中双侧病变4例、单侧病变44例、共计52处病灶),进行钼靶X线摄影引导下钩丝定位活检术。结果:所有52处病灶中恶性病变13例(均单侧),其中0期占46.15%(6/13),Ⅰ期占38.46%(5/13),Ⅱ期占15.39%(2/13);良性病变39例,乳腺癌检出率为25.0%。钼靶BI-RADSⅣ级患者中良性病变39例,恶性病变10例;BI-RADSⅤ级患者中良性病变0例,恶性病变3例。Ⅳ、Ⅴ级中乳腺癌的阳性检出率分别为25.6%和100%。结论:钼靶辅助下钩丝定位活检可以精确切除临床触诊阴性或触诊不良的BI-RADSⅣ级及以上乳腺病灶,提高患者生活质量和改善预后,是一种安全、准确、费用低廉的诊断方法,值得国内临床广泛推广。

乳腺癌^(99m)Tc-MIBI影像与P-糖蛋白表达的相关性

为了探讨活体乳腺恶性肿瘤对99mTc-甲氧基异丁基异腈(99mTc-MIBI)的摄取和肿瘤细胞P-糖蛋白(P-glyco-protein,P-gp)表达间的关系。2003年10月~2005年12月对40例未经治疗的乳腺癌患者进行99mTc-MIBI早期(10min)与延迟(120min)平面显像,计算其外排率(WOR)。显像后1周内进行手术治疗或化疗,术后应用免疫组化方法检测肿瘤标本P-gp表达,结果进行统计学计算。结果:WOR在P-gp阳性者为(12.8±8.2)%,高于P-gp阴性者(1.2±6.2)%,差异有统计学意义,t=3.42,P=0.01;WOR与肿瘤大小成正相关。初步研究结果显示,乳腺恶性肿瘤对99mTc-MIBI的摄取与P-gp表达呈明显负相关,即肿瘤细胞高度表达P-gp时,99mTc-MIBI摄取较低,99mTc-MIBI显像和肿瘤细胞P-gp表达相关性好,可成为体内无创检测肿瘤组织P-gp表达及耐药性的重要手段。

乳癌组织中BI-1、Bcl-2和Bcl-xl蛋白的表达

目的:检测乳癌组织中Bax inhibitor-1(BI-1)、Bcl-2和Bcl-xl蛋白的表达,探讨可能的抗凋亡机制。方法:采用Western blot检测42例乳癌及配对正常乳腺组织中BI-1蛋白的表达;采用免疫组织化学方法检测42例乳癌组织中Bcl-2与Bcl-xl的表达。结果:乳癌组织中BI-1蛋白的相对表达量明显高于配对正常乳腺组织,P<0.05;乳癌组织中BI-1的表达与Bcl-2和Bcl-xl均呈正相关(r=0.356和0.375,P均<0.05)。结论:BI-1的过度表达可能促进了乳癌的发生。Bcl-2和Bcl-xl均参与了BI-1的抗凋亡过程。

BAMBI在非小细胞肺癌中的分布和mRNA表达

背景与目的BAMBI(BMP and activin membrane-bound inhibitor)与TGF-βⅠ型受体具有相似的结构,从而广泛参与TGF-β信号的调控。通过检测BAMBI在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达分布情况,探讨其与NSCLC临床病理因素之间的关系。方法63例NSCLC及癌旁正常组织标本用于免疫组织化学检测。其中31例新鲜肺癌组织及癌旁正常肺组织标本,术后立即投入液氮速冻之后,于-70℃保存,用于RT-PCR检测。结果BAMBI mRNA在癌旁组织中有较弱的表达,其在癌组织中的表达高于相应的癌旁组织(0.358±0.135 vs 0.249±0.129),差异具有统计学意义(P=0.003)。BAMBI蛋白主要表达在胞膜和靠近胞膜的胞浆,其在癌组织中的表达高于癌旁组织,两者差异具有统计学意义(P<0.01)。其蛋白和mRNA在NSCLC癌组织中的表达显著高于癌旁组织,其在肺鳞癌中的表达低于肺腺癌。结论BAMBI在非小细胞肺癌中表达明显增加,BAMBI的过表达与非小细胞肺癌的发生有关。