胃癌患者肿瘤标志物检测的临床价值分析

目的探讨血清肿瘤标志物在胃癌疗效观察、术后预后判断和复发监测中的临床价值。方法用化学发光法及放免法检测302例胃癌患者血清CEA、CA19-9、CA72-4水平,计算各检测指标阳性率。结果 CEA、CA19-9、CA72-4阳性率与胃癌病程呈正相关,尤其在III期、IV期较I期、II期明显增高(P<0.05)。肿瘤标志物联合检测较单项检测阳性率明显增高(P<0.05),但各组合间无明显差异(P>0.05)。结论 CEA、CA19-9、CA72-4联合检测利于提高胃癌患者诊断率。

肺癌的神经内分泌特征

肺癌细胞能产生许多神经内分泌物质，使患者表现出一定的症状和体征，对肺癌的诊断和治疗具有重要意义。本文对近几年来有关肺癌神经内分泌特征的研究作一综述。

The Expression and Clinical Significance of Fas and FasL in Lung Cancer

Objective: To investigate the expression and clinical significance of Fas andFasL in lung cancer. Methods: SP immunohistochemical technique was used to detect the expression ofFas and FasL in 46 cases of lung cancer and 30 cases of adjacent non-neoplastic tissue. Results:Down-regulation, of Fas and up-regulation of FasL were found in lung carcinoma. The levels of Fasexpression in squamous cell carcinoma, adenocarcinoma and SCLC were significantly lower than that ofadjacent normal tissues (P<0. 01) , while the expression levels of FasL were the opposite (P< 0.05). Fas expression was associated with high histological grade and no metastasis (P<0. 05). FasLexpression was related to histological grade, late clinical stage and metastasis (P<0. 05). BothFas and FasL expression was not related to the histological type of lung cancer (P>0. 05). Thelevel of Fas expression was negatively related to that of FasL (P<0. 05). Conclusion:Down-regulation of Fas and up-regulation of FasL may work in coordination with the occurrence,development and metastasis of lung cancer. Fas or FasL can be used as one of markers in earlydiagnosis of lung cancer. Therefore, the combined assay may be helpful in predicting the grade ofmalignancy and the prognosis of patients with lung cancer.

Colorectal cancer screening by non-invasive metabolic biomarker fecal tumor M2-PK

AIM: To evaluate the utility of the innovative fecal tumor M2-Pyruvate kinase (M2-PK) test in our daily clinical routine, as a marker for the pre-selection of patients who should subsequently undergo colonoscopy for the diagnosis or exclusion of colorectal cancer. METHODS: Fecal tumor M2-PK was measured in stool samples of 96 study participants (33 patients with colorectal cancer, 21 patients with rectal carcinoma and 42 controls) who all underwent total colonoscopy. RESULTS: In 39 of 42 individuals in the control group, fecal tumor M2-PK was below 4.0 kU/L (93% specificity). Colorectal tumors were accompanied by a highly significant increase (P < 0.001) in fecal tumor M2- PK levels (median: colon carcinoma, 23.1 kU/L; rectal carcinoma, 6.9 kU/L; colorectal carcinoma, 14.7 kU/L), which correlated with Duke’s staging and T-classification. The overall sensitivity was 78% for colorectal cancer, increasing from 60% for stage T1 to 100% for stage T4 and from 60% for Duke’s A to 90% for Duke’s D tumors. CONCLUSION: Fecal tumor M2-PK is an appropriately sensitive tool to pre-select those patients requiring colonoscopy for the further diagnostic confirmation or exclusion of colorectal cancer.

C-reactive protein,procalcitonin,interleukin-6,vascular endothelial growth factor and oxidative metabolites in diagnosis of infection and staging in patients with gastric cancer

AIM:The current study was to determine the serum/pLasma levels of VEGF,IL-6,malondialdehyde (MDA),nitric oxide (NO),PCT and CRP in gastric carcinoma and correlation with the stages of the disease and accompanying infection. METHODS:We examined the levels of serum VEGF,IL-6, PCT,CRP and plasma MDA,NO in 42 preoperative gastric cancer patients and 23 healthy subjects.There were infection anamneses that had no definite origin in 19 cancer patients. RESULTS:The VEGF levels (mean±SD; pg/mL) were 478.05±178.29 and 473.85±131.24 in gastric cancer patients with and without infection,respectively,and these values were not significantly different (P>0.05).The levels of VEGF, CRP,PCT,It-6,MDA and NO in cancer patients were significantly higher than those in healthy controls and the levels of CRP,PCT,It-6,MDA and NO were statistically increased in infection group when compared with non- infection group (P<0.001). CONCLUSION:Although serum VEGF concentrations were increased in gastric cancer,this increase might not be related to infection.CRP,PCT,IL-6,MDA and NO have obvious drawbacks in the diagnosis of infections in cancer patients. These markers may not help to identify infections in the primary evaluation of cancer patients and hence to avoid unnecessary antibiotic treatments as well as hospitalization. According to the results of this study,IL-6,MDA,NO and especially VEGF can be used as useful parameters to diagnose and grade gastric cancer.

Comparative proteomics analysis of human gastric cancer

AIM: To isolate and identify differentially expressed proteins between cancer and normal tissues of gastric cancer by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). METHODS: Soluble fraction proteins of gastric cancer tissues and paired normal tissues were separated by 2-DE. The differentially expressed proteins were selected and identified by MALDI-TOF-MS and database search. RESULTS: 2-DE profiles with high resolution and reproducibility were obtained. Twenty-three protein spots were excised from sliver staining gel and digested in gel by trypsin, in which fifteen protein spots were identified successfully. Among the identified proteins, there were ten over-expressed and five under-expressed proteins in stomach cancer tissues compared with normal tissues. CONCLUSION: In this study, the well-resolved, reproducible 2-DE patterns of human gastric cancer tissue and paired normal tissue were established and optimized and certain differentially-expressed proteins were identified. The combined use of 2-DE and MS provides an effective approach to screen for potential tumor markers.

Levels of v5 and v6 CD44 splice variants in serum of patients with colorectal cancer are not correlated with pT stage,histopathological grade of malignancy and clinical features

AIM:This study was designed to compare the levels of v5 and v6 splice variants of CD44 evaluated using EITSA test in the serum of patients with colorectal cancer in different stages of progression of the disease estimated in pT stage according to WHO score,histopathological grade of malignancy and some clinicopathological features. METHODS:The serum obtained from 114 persons with colorectal adenocarcinomas was examined using ELISA method,pT stage and grade of malignancy of the tumour were examined in formalin fixed and paraffin embedded materials obtained during operation. RESULTS:Only the level of CD44 v5 in the serum of patients before operation with G2 pT4 tumour was lower than that in other probes and the difference was statistically significant. We did not find any other correlations between the level of v5 and v6 CD44 variants and other evaluated parameters. CONCLUSION:The level of CD44 v5 and v6 estimated by ELISA test in the serum can not be used as a prognostic factor in colorectal cancer.

Strategy to differentiate autoimmune pancreatitis from pancreas cancer

Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include:fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed en- hancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.

Serum tumor markers for detection of hepatocellular carcinoma

Hepatocellular carcinoma （HCC） is one of the most frequent malignant tumors and is the second most common cause of cancer death in China. Therefore, it is very important to detect this disease and the recurrence at its earlier period. Serum tumor markers, as the effective method for detecting hepatocellular carcinoma for a long time, could be divided into 4 categories： oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines. Serum alpha fetoprotein （AFP） is the most widely used tumor marker in detecting patients with hepatocellular carcinoma, and has been proven to have capability of prefiguring the prognosis. However, it has been indicated that AFP-L3 and DCP excel AFP in differentiating hepatocellular carcinoma from nonmalignant hepatopathy and detecting small hepatocellular carcinoma. Some tumor markers, such as human cervical cancer oncogene and human telomerase reverse transcriptase mRNA, have also been indicated to have higher accuracies than AFP. Furthermore, some other tumor markers, such as glypican-3, gamma-glutamyl transferase Ⅱ, alpha-Ifucosidase, transforming growth factor-beta1, tumorspecific growth factor, have been indicated to be available supplementaries to AFP in the detection. AFP mRNA has been shown to correlate with the metastasis and recurrence of HCC, and it may be the most useful marker to prefigure the prognosis. Some other markers, such as gamma-glutamyl transferase mRNA, vascular endothelial growth factor, and interleukin-8, could also be used as available prognostic indicators, and the simultaneous determination of AFP and these markers may detect the recurrence of HCC at its earlier period.

Multiple biomarkers of colorectal tumor in a differential diagnosis model:A quantitative study

AIM:To evaluate the multiple biomarkers of colorectal tumor and their potential usage in early diagnosis of colorectal cancers. METHODS:Multiple biomarkers (DNA contents,AgNOR, PCNA,p53,c-erbB-2) in 10 normal colorectal mucosae,37 colorectal adenomas and 55 colorectal cancers were analyzed quantitatively in the computed processing imaging system. Discrimination patterns were employed to evaluate the significance of single and multiple indices in diagnosis of colorectal cancers. RESULTS:The mean values of the analyzed parameters increased in order of the normal mucosa,adenoma and adenocarcinoma,and this tendency reflected the progression of colorectal malignancy.The parameters including DNA index,positive rates,densities of AgNOR,c-erbB-2,and p53, shape and density of nucleus were relatively valuable for diagnoses.Then a diagnostic discrimination model was established.The samples were confirmed with the model, the sensitivity rates in cancer group and adenoma group were 96.36% and 89.19%,respectively.The value of proliferating cell nuclear antigen (PCNA) in early diagnosis of colorectal cancers was uncertain. CONCLUSION:The quantitative evaluation of some parameters for colorectal tumor can provide reproducible data for differential diagnosis.The established diagnostic discrimination model may be of clinicopathological value, and can make the early diagnosis of colorectal cancer possible.

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.

Transcription factor PDX-1 in human colorectal adenocarcinoma:A potential tumor marker?

AIM: To examine the expression of pancreatic duodenal homeobox-1 (PDX-1) transcription factor in human colorectal cancer. METHODS: RT-PCR, Western blotting, and immuno-histochemistry were performed to determine the expression pattern of transcription factor PDX-1 in primary colorectal tumor, hepatic metastasis, and benign colon tissue from a single patient. RESULTS: The highest PDX-1 transcription levels were detected in the metastasis material. Lower levels of PDX-1 were found to be present in the primary tumor, while normal colon tissue failed to express detectable levels of PDX-1. Western blot data revealed a PDX-1 expression pattern identical to that of mRNA expression. Immunohistochemistry confirmed high metastasis PDX-1 expression, lower levels in the primary tumor, and the presence of only traces of PDX-1 in normal colon tissue. CONCLUSION: These data argue for further evaluation of PDX-1 as a biomarker for colorectal cancer.

CT diagnosis of recurrence after pancreatic cancer:Is there a pattern?

AIM:To investigate predilection sites of recurrence of pancreatic cancer by computed tomography(CT)in follow-up after surgery. METHODS:Seventy seven patients with recurrence after pancreatic cancer surgery were retrospectively identified.The operative technique,R-status,T-stage and development of tumor markers were evaluated. Two radiologists analyzed CT scans with consensus readings.Location of local recurrence,lymph node recurrence and organ metastases were noted.Surgery and progression of findings on follow-up CT were con-sidered as reference standard. RESULTS:The mean follow-up interval was 3.9± 1.8 mo,with a mean relapse-free interval of 12.9± 10.4 mo.The predominant site of recurrence was local (65%),followed by lymph node(17%),liver metastasis (11%)and peritoneal carcinosis(7%).Local recurrence emerged at the superior mesenteric artery(n=28),the hepatic artery(n=8),in an area defined by the surrounding vessels:celiac trunk,portal vein,inferior vena cava(n=22),and in a space limited by the mesenteric artery,portal vein and inferior vena cava(n=17). Lymph node recurrence occurred in the mesenteric root and left lateral to the aorta.Recurrence was confirmed by surgery(n=22)and follow-up CT(n=55).Tumor markers[carbohydrate antigen 19-9(CA19-9),carcinoembryonic antigen(CEA)]increased in accordance with signs of recurrence in most cases(86%CA19-9;79.2% CEA). CONCLUSION:Specific changes of local and lymph node recurrence can be found in the course of the cardinal peripancreatic vessels.The superior mesenteric artery is the leading structure for recurrence.

Correlation between Expression of P38 MAPK-Signaling and uPA in Breast Cancer

OBJECTIVE To study the expression of phosphorylated p38 mitogen-activated protein kinase （p-p38） and uPA and the correlation of their expression with breast cancer clinicopathological characteristics, and to investigate the role of the p38MAPK-signaling pathway in regulating uPA expression in breast cancer cells.METHODS Immunohistochemistry （S-P） was used to test the expression of p-p38 and uPA in 60 specimens of breast cancer tissues. Western blots were adopted to detect expression of the p-p38 and uPA proteins in MDA-MB-231 and MCF-7 breast cancer cells, and uPA expression after treatment with SB203580, a specific inhibitor of p38 MAPK.RESULTS The positive rate of the p-p38 protein and uPA protein expression in the breast cancer tissues was 56.7% and 60.0%,respectively. The expression of p-p38 was positively related to the expression of uPA （r = 0.316, P 〈 0.05）. The expression of p-p38 and uPA was related to lymph node metastasis and the TNM stage （P 〈 0.05）, but it was not related to the patient＇s age or tumor size （P 〉 0.05）. The expression of p-p38 and uPA in MDA- MB-231 cells was higher than that in MCF-7 cells. SB203580 inhibited the p38 MAPK pathway and reduced uPA protein expression.CONCLUSION The p38 MAPK-signaling pathway promotes breast cancer malignant progression by up-regulating uPA expression ,and it may be an important process in breast cancer invasion and metastasis.

Change of SPARC expression after chemotherapy in gastric cancer

Objective： The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine （SPARC） expression changes after chemotherapy in gastric cancer （GC） is unclear, qqais study investigated the influence of chemotherapy on SPARC expression in GC. Methods： Immunohistochemistry was used to analyze SPARC expression in 132 GC cases （including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy）. SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression. Results： SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPAKC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy; gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. Conclusiou： SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy.

Monoclonal immunoscintigraphy for detection of metastasis and recurrence of colorectal cancer

AIM:To assess the clinical role of monoclonal immunoscintigraphy for the detection of metastasis and recurrence of colorectal cancer.METHODS:Monoclonal immunoscintigraphy was performed in patients operated on for colorectal adenocar-cinoma suspected of local recurrence and metastatic disease.The results were compared with conventional diagnostics.RESULTS:Immunoscintigraphic investigation was done in 53 patients.Tumor recurrence occurred in 38 patients,and was confirmed by other diagnostic modalities in 35.In 15 patients,immunoscintigraphic findings were negative,and confirmed in 14 with other diagnostic methods.Comparative analysis confirmed good correlation of immunoscintigraphic findings and the results of conventional diagnostics and the level of tumor marker carcinoembryonic antigen.Statistical analysis of parameters of radiopharmaceutical groups imacis,indimacis and oncoscint presented homogenous characteristics all of three radiopharmaceuticals.The analysis of immunoscintigraphic target focus was clearly improved using tomography.CONCLUSION:Immunoscintigraphy is highly specific and has a good predictive value in local recurrence of colorectal cancer.

MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

Epithelial ovarian cancer(EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers(mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as micro RNAs(miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish mi RNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers.

Associations Between Epidermal Growth Factor Receptor Gene Mutation and Serum Tumor Markers in Advanced Lung Adenocarcinomas: A Retrospective Study

Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.

Pancreatic Cancer with Normal CA 19-9 and Lewis Antigen Negative--Case Report

Pancreatic cancer is an aggressive and lethal disease that affects especially older population. Its more relevant tumor marker is CA 19-9 （carbohydrate antigen 19-9）, although it can be elevated in others clinical situations, like cholangitis and cholestasis. Otherwise, a small people subset, like our patient, do not produce this tumor marker, as on blood as in the tumor, because they are incapable to express the Lewis Antigen. Therefore, this case report is about a patient without Lewis Antigen express and CA 19-9 low levels. We will report a rapid disease progression, despite of low CA 19-9, comparing with available data that often show better prognosis in this setting. Conclusion： Low levels of CA 19-9 do not predict good response or better prognosis in patients that do not express Lewis Antigen.

Tumor Vascular Markers： Possibilities for Detection of Breast Carcinoma

Breast cancer is one of the world＇s most urgent health problems. The first symptoms of mammary malignancies are manifested only at an advanced stage with significant mortality. Detecting this disease at an early stage gives the majority of patients a better chance of survival. The aim was to search for changes in gene expression of specific tumor vascular markers like death receptor 6 （Dr6） and glycoprotein M6B （Gpm6B） in the blood of patients with breast cancer. All subjects were divided into two groups. First group with patients are with different grades of breats tumors （n = 30）. Second group consists from healthy women （n = 15）. After isolation of mRNA from blood, RT-PCR was followed by gel electrophoresis. For statistical analysis one-way ANOVA was used with Student＇s T test using GraphPad InStat software. Significant changes in mRNA levels of gene Dr6 in all grades of first stage breast cancer were detected. The mRNA levels of Dr6 showed a rising tendency from GI （116% higher value than control） to G3 （198% higher than control）. During monitoring of the mRNA level of Gpm6B, a weaker increase was observed than in Dr6. The difference in GI was only 8% higher compared with controls and 44% at G3. From our results it can be concluded that DR6 is a more suitable marker for the diagnosis of breast malignancies in the early stages than Gpm6B. In our work, a non-invasive method for more timely and precise determination of the earlier stages of breast cancer is described, which could also contribute to monitoring the effectiveness of treatment, or regression of this disease.