Serological and immunohistochemical studies on sialylated carbohydrate antigens in colorectal carcinoma.

Sialylated carbohydrate antigens, such as CA19-9 (sialyl Lea), CA-50 (sialyl Le4), CSLEX1 (sialyl Lex) and SLX (sialyl Lex-i), were assayed in the same preoperative serum samples of 63 patients with colorectal cancer, and compared with CEA. In addition immunohistochemical expressions of sialyl Lea, sialyl lex and sialyl Lex-i antigens were studied in 62 colorectal carcinomas and 42 normal mucosal sites remote from the malignant lesion using monoclonal antibodies CSLEA1, CSLEX1 and FH-6, respectively, in order to elucidate their tumor-specificity and clinical usefulness as a tumor-associated antigen. Serologically, the percent positive rates of CA19-9, CA-50, CSLEX1, SLX and CEA were 30.2%, 17.7%, 23.8%, 16.1% and 44.4%, respectively. In dukes' A and B, these sialylated carbohydrate antigens, especially CSLEX1 and SLX, showed low positive rates, but the percent positive rates of CSLEX1 and SLX correlated with operative radicality. The positive spectrum of CSLEX1 differed from that of CA19-9 in sera, and CEA had no correlation with these two antigens. The immunohistochemical expression rates of sialyl Lea, sialyl Lex and sialyl Lex-i were 88.1%, 17.0% and 9.5% in normal mucosa, but were 77.8%, 90.5% and 71.4% in carcinoma, respectively. These data suggested that the type 2 chain antigens CSLEX1 and SLX, which have high tumor-specificity compared with CA19-9, may be useful in preoperative diagnosis for extension of carcinoma and operative radicality, although early diagnosis using these sialylated carbohydrate antigens may be difficult, while the combined use of CA19-9, CSLEX1 and CEA should make it possible to detect a wide range of colorectal cancer patients.     

SHH mRNA在人胰腺癌组织及细胞系中的表达及意义

目的检测Sonic Hedgehog(SHH)mRNA在人胰腺癌组织及细胞系中的表达,探讨SHH mRNA在胰腺癌发生和发展中的作用。方法收集本实验室保存的6株人胰腺癌细胞系及30例胰腺癌和相应癌旁正常胰腺组织,应用半定量RT-PCR方法检测SHH mRNA的表达。结果6株人胰腺癌细胞系中均有SHH mRNA高表达;胰腺癌组织SHH mRNA表达率为86.7%,表达强度为0.785±0.070,癌旁正常胰腺组织SHH mRNA表达率为40.0%,表达强度为0.463±0.055,两者具有显著性差异(P<0.01)。SHH mRNA的表达水平与胰腺癌的肿瘤大小、分化程度、淋巴结转移均无相关性。结论胰腺癌存在SHH mRNA的高表达,这可能是胰腺癌发生的早期事件。     

Expression of major histocompatibility antigens on pancreatic islet cells.

Insulin-dependent diabetes mellitus is often accompanied by manifestations of autoimmunity and is frequently associated with certain HLA haplotypes, predominantly DR3 and DR4. Because the major histocompatibility antigens are important determinants of the immune response in various tissues, we have investigated their expression on the pancreatic islet cells. Human, mouse, or rat islets of Langerhans, as well as lymphocytes or other differentiated cells, were biosynthetically labeled with radioactive amino acids, lysed in detergent, and immunoprecipitated with several antisera specific for major histocompatibility antigenic groups. The immunoprecipitates were analyzed by NaDodSo4/polyacrylamide gel electrophoresis under reducing conditions followed by autoradiography. The major histocompatibility antigens corresponding to the H-2 K,D molecules in mice, the H1-A in rats, and the HLA-A, -B, and -C in humans were precipitated from both islet and lymphocyte lysates and were accompanied by beta 2-microglobulin. Binding of H-2 antibodies to islet cells was also confirmed by a radioligand assay using 125I-labeled protein A and by indirect immunofluorescence. Analyses in the fluorescence-activated cell sorter revealed that greater than 95% of the cells in the beta-cell-rich fraction were fluorescent, providing further evidence that the pancreatic beta cells express the major histocompatibility antigens. Monoclonal antibodies or mouse alloantisera against HLA-DR or Ia antigens did not react with labeled pancreatic islet cell proteins.     

Copper and zinc concentrations, and superoxide dismutase activities in malignant and nonmalignant tissues of female reproductive organs

The copper and zinc concentrations in 44 malignant and 48 nonmalignant women tissue samples of reproductive organs in women were measured. In malignant samples, the mean copper concentrations were 110%, 76%, and 38% higher for cervix, endometrium and ovary than the nonmalignant ones. The zinc concentrations in the analysed malignant tissues were lower than that in the corresponding nonmalignant tissues. The results of superoxide dismutase activities determinations demonstrate a considerable lowering of the enzymatic capacities to remove free oxygen radical in malignant tissues. A hypothesis for possible mechanism involving elevated copper concentrations, and decreased zinc concentrations, which may be responsible for malignant processes, are presented.     

SHH mRNA在人胰腺癌组织及细胞系中的表达及意义

目的 检测Sonic Hedgehog(SHH)mRNA在人胰腺癌组织及细胞系中的表达,探讨SHH mRNA在胰腺癌发生和发展中的作用.方法 收集本实验室保存的6株人胰腺癌细胞系及30例胰腺癌和相应癌旁正常胰腺组织,应用半定量RT-PCR方法检测SHH mRNA的表达.结果 6株人胰腺癌细胞系中均有SHH mRNA高表达;胰腺癌组织SHH mRNA表达率为86.7%,表达强度为0.785±0.070,癌旁正常胰腺组织SHH mRNA表达率为40.0%,表达强度为0.463±0.055,两者具有显著性差异(P＜0.01).SHH mRNA的表达水平与胰腺癌的肿瘤大小、分化程度、淋巴结转移均无相关性.结论 胰腺癌存在SHH mRNA的高表达,这可能是胰腺癌发生的早期事件.     

Expression of Ia-like antigens on cultured human malignant melanoma cell lines.

Human malignant melanoma cell lines were found to bear Ia-like cell surface determinants demonstrable by hetero- or alloantisera and by direct identification of the characteristic bimolecular glycoprotein complex. Immunoprecipitation confirmed the presence of Ia determinants on the bimolecular complex. The quantity of Ia molecules determined by these methods and by absorption experiments was relatively constant for each cell line. Among different lines, however, the amount of Ia antigens ranged from a level equal to that expressed by B-cell lines to a small fraction of this amount. This variation in level of Ia contrasted with the more uniform amount of beta2-microglobulin detected on the cell surface. The Ia alloantigen specificity DRw2 was the most frequently encountered specificity. Ia determinants were also found on the surface of an epidermoid carcinoma line, but not on various other cell lines of normal or neoplastic origin.     

肿瘤-睾丸抗原SSX在胰腺癌中的表达及其生物意义

目的探讨肿瘤-睾丸抗原(CTA)SSX及其亚型在胰腺癌的表达情况,为胰腺癌的免疫治疗提供实验依据。方法应用免疫组织化学S-P法对52例胰腺癌组织及癌旁组织中SSX的表达情况进行检测,并应用逆转录聚合酶链反应(RT-PCR)方法检测SSX的亚型SSX-2、SSX-4的表达情况。结果 SSX在胰腺癌的阳性表达率为48.08%;SSX的阳性表达与患者的年龄、性别、病变部位、分化程度均无明显相关关系(P>0.05);SSX的表达与肿瘤的浸润转移呈负相关(r=-0.306,P=0.028)。在SSX的亚型中,SSX-2表达率较高。结论胰腺癌中SSX的高表达与肿瘤的转移呈明显的负相关关系;SSX的阳性表达在胰腺癌中呈现簇生现象,SSX-2的表达较高。     

Sialylated Lewis(x) and sialylated Lewis(a) as tumor-associated carbohydrate antigens in sera of patients with gastric cancer--usefulness of combination assay of these two antigens

Sialylated Lewis(x) and sialylated Lewis(a) antigens, which are structural isomer each other, were serologically tested to determine the clinicopathological differences and correlation between two antigens, and were also compared with those of serum CEA in 141 patients with gastric cancer. Percent positives in sialylated Lewis(a), CEA and sialylated Lewis(x) showed 26.9%, 21.8% and 17.0% respectively. Percent positive of sialylated Lewis(x) correlated with degree of liver metastasis and peritoneal dissemination. Therefore, it is emphasized that the role of sialylated Lewis(x) is characteristics of detecting a presence of liver metastasis and/or peritoneal dissemination. On the other hand, sialylated Lewis(a) showed high percent positive in cases which had lymph nodes metastasis and mucinous or papillary adenocarcinomas. These two carbohydrate antigens indicated no correlation (r = 0.062) in the spectrum of sera. It is suggested that combination assay of sialylated Lewis(x) and sialylated Lewis(a) is useful in detecting many gastric cancer patients including CEA-negative one.     

Evaluation of carbohydrate antigens 19-9 and 12-5 in patients with pancreatic cancer

The diagnostic value of the tumor-associated antigens Ca 19-9 and Ca 12-5 was tested in 130 subjects (38 healthy controls, 37 carcinomas of the pancreas, 23 chronic pancreatitis, 23 extrapancreatic gastrointestinal cancers, 9 endocrine pancreatic tumors). Ca 19-9 levels above 37 U/ml were obtained in 67.6% and Ca 12-5 levels above 39 U/ml in 45.9% of carcinomas of the pancreas, 4.3 and 8.7%, respectively, of chronic pancreatis, 21.7 and 17.4% of extrapancreatic gastrointestinal tumors, and 0 and 11.1% of endocrine pancreatic tumors and in none of the healthy controls. Results of preoperative determination of Ca 19-9 and Ca 12-5 gave a sensitivity of 67.6 and 45.9%, a specificity of 91.8 and 90.9%, a predictive value of a positive test of 80.6 and 70.8%. When elevation of both antigens was required, sensitivity decreased to 32.4% but specificity rose to 97.3%. All but one of the pancreatic cancer patients were at stage 3 and 4. The only patient with pancreatic cancer in stage 1 had normal levels of both markers. Ca 19-9 and Ca 12-5, whether alone or associated, represent a good diagnostic test for differentiating pancreatic cancer from chronic pancreatitis. Due to the low sensitivity of both markers, the tests are of limited value when any other diagnostic evidence of pancreatic cancer is absent.     

Expression of Ezrin, HGF, C-met in pancreatic cancer and non-cancerous pancreatic tissues of rats

BACKGROUND:Recent studies have confirmed that the expression of Ezrin,hepatocyte growth factor(HGF)and its receptor(C-met)is related to the genesis,progress,invasion and metastasis of some malignant tumors.Researches have also found that the biological function of Ezrin is closely related to HGF/C-met in malignant tumors.However,there is no report on the expression levels of Ezrin,HGF and C-met in rat pancreatic cancer induced by dimethylbenzanthracene (DMBA).This study aimed to detect the expression of Ezrin, HGF and C-met in rat pancreatic cancer and non-cancerous pancreatic tissues,and assess its effect in cancer induction by DMBA. METHODS:Ninety Sprague-Dawley rats were divided into 3 groups randomly:40 in a pancreatic cancer model group (group A),40 in a trichostatin A(TSA)intervention group (group B),and 10 in a control group(group C).DMBA was directly implanted into the parenchyma of rat pancreas in group A+group B.The rats of group B were treated with 1 ml of TSA saline solution(1μg/ml)via intraperitoneal injection weekly.The carcinogenesis of rats executed within 3-5 months in groups A and B was observed by macrograph and microscopy. Meanwhile,the rats in group C were executed within 5 months. The EnVision TM immunohistochemistry for detecting the expression levels of Ezrin,HGF and C-met was used in paraffinembedded sections of the pancreatic specimens. RESULTS:The incidence of pancreatic cancer in group A was 48.6%and in group B 33.3%.The maximal diameter of tumor mass was significantly larger in group A than that in group B(P0.05).No pathological changes were observed , in the pancreas of group C and other main organs of groups A and B.The positive rates of Ezrin,HGF and C-met were significantly higher in ductal adenocarcinoma than in non- cancerous pancreatic tissues of groups A and B(P0.01).The positive rates of Ezrin,HGF and C-met were significantly higher in ductal adenocarcinoma of group A than those in non- cancerous pancreatic tissues of group A(P0.05),but there was no significant difference in group B(P0.05).The positive rates of Ezrin,HGF and C-met in non-cancerous pancreatic tissues proved mild to severe atypical hyperplasia of the ductal epithelia.The pancreas of group C and 2 cases of fibrosarcoma showed the negative expression of Ezrin,HGF and C-met.There was a trend of consistency in the expression of Ezrin,HGF and C-met in ductal adenocarcinoma(P0.05 or P0.01). CONCLUSIONS:DMBA directly implanted into the parenchyma of the pancreas can produce a model of pancreatic cancer with a high incidence in a short time.TSA might inhibit the carcinogenesis and growth of pancreatic cancer,and its effects may be related to the inhibition of the expression of Ezrin,HGF and C-met during the process.Ezrin,HGF and C-met may have positive effects on the carcinogenesis of rat pancreas.     

Comparative evaluation of sialylated carbohydrate antigens, KL-6, CA19-9 and SLX as serum markers for interstitial pneumonia

Abstract We compared diagnostic values of three serum carbohydrate antigens, KL-6, CA19-9 and SLX to discriminate interstitial pneumonia (IP) from alveolar pneumonia and healthy volunteers. Subjects consisted of 13 patients with idiopathic pulmonary fibrosis and 10 associated with collagen vascular diseases, 12 patients with sarcoidosis and 70 controls (52 healthy volunteers and 18 patients with alveolar pneumonia). Cut-off values were determined at the level at which the diagnostic accuracy became the highest for each marker, 449 U/mL for KL-6, 26 U/mL for CA19-9 and 41 U/mL for SLX. The sensitivity, the specificity and the diagnostic accuracy were 74.3% (26/35), 98.6% (69/70) and 90.5% (95/105) in KL-6, 42.9% (15/35), 94.3% (66/70) and 77.1% (81/105) in CA19-9, and 20.0% (7/35) and 95.7% (67/70) and 70.5% (74/105) in SLX, respectively. Receiver operating characteristic curves revealed that KL-6 was far superior to both CA19-9 and SLX. These results suggest that KL-6 is the best marker for interstitial pneumonia among these carbohydrate antigens.     

Fibronectin concentration in ascites differentiates between malignant and nonmalignant ascites

Differentiation between malignant and nonmalignant ascites by means of laboratory parameters has so far not been completely achieved. One hundred and four patients with ascites (34 malignant, 51 cirrhotic, and 19 other) were studied for fibronectin concentration in ascites. The first 47 patients (13 malignant and 34 cirrhotic) were used to determine mean values and standard deviation (178 +/- 96 vs. 8.3 +/- 15.3 micrograms/ml) and to define a cutoff concentration between both groups (75 micrograms/ml). Several other parameters were analyzed simultaneously in these patients (total protein: 3.93 +/- 1.46 vs. 1.50 +/- 1.02 g/dl; white cell count: 2022 +/- 1153 vs. 569 +/- 405/mm3; lactic acid: 3.86 +/- 2.57 vs. 1.83 +/- 0.72 mmol/L; lactic acid dehydrogenase: 357 +/- 329 vs. 61 +/- 35 U/L; serum/ascites ratio of lactic acid dehydrogenase: 1.11 +/- 1.13 vs. 4.06 +/- 2.00; pH: 7.275 +/- 0.229 vs. 7.513 +/- 0.042). Their accuracy (mean of sensitivity and specificity) was always less than 87% due to a considerable overlap between both groups. Five patients with other causes of ascites could not be classified at all. Application of fibronectin determination on the subsequent 57 patients (21 malignant, 17 cirrhotic, and 19 other) revealed a sensitivity, specificity, and negative and positive accuracy for malignant ascites of 100%. Calculation of these parameters for all 104 patients gave identical values. The inclusion of 3 patients without final diagnosis in the group of nonmalignant ascites reduced specificity to 97.1 and positive accuracy to 94.4%. However, these values were superior to all other methods used so far. Fibronectin determination in ascites in combination with other parameters suitable for exclusion of infectious or pancreatic origin of ascites may prove useful in the differential diagnosis of ascites.     

Complex carbohydrate malabsorption in exocrine pancreatic insufficiency.

The magnitude of complex carbohydrate malabsorption in exocrine pancreatic insufficiency has not been well quantified in the past. The quantity of carbohydrate malabsorbed after a rice starch (100 g) meal in 20 patients with chronic pancreatitis (n = 10) or pancreatic cancer (n = 10) was therefore estimated. Patients had a three day stool fat collection (80 g/24 hour fat intake), a lactulose (20 g), and a rice flour (100 g) breath hydrogen test. Normal controls (n = 29) had a postprandial H2 increase < or = 14 ppm and malabsorbed (mean (SEM)) 1.12 (0.44) (range 0-11.10) g of the 100 g of carbohydrate ingested. Patients malabsorbed significantly more carbohydrate (11.36 (2.23) (range 8.90-32.60) g, F1.47 = 29.92, p < 0.001). The number of patients with fat (> 7 g, n = 8) or carbohydrate (increase in H2 > or = 20 ppm, n = 10) malabsorption was not different (chi 2 = 0.10, p = 0.75). There was a significant correlation between faecal fat and amount of malabsorbed carbohydrate (r = 0.60, F1.17 = 9.70, p = 0.006) and faecal fat and stool wet weight (r = 0.57, F1.18 = 8.67, p < 0.009), but not between stool wet weight and amount of malabsorbed carbohydrate (r = 0.28, F1.17 = 1.45, p = 0.25). Although patients with exocrine pancreatic insufficiency malabsorb 10%-30% of the ingested complex carbohydrate, the main determinant of stool wet weight could be faecal fat.     

chemerin及其受体在小鼠体内外表达的研究

目的观察chemerin及其受体chemerinR基因在小鼠各脏器中的表达谱以及两者在3T3-L1脂肪细胞诱导分化过程中表达水平的变化。方法提取正常小鼠肝脏、脂肪、胃、脾脏、肾脏、心脏、骨骼肌等脏器组织中总RNA,采用半定量逆转录PCR技术检测其中chemerin及chemerinR基因水平;体外培养3T3-L1脂肪细胞,应用1-甲基-3-异丁基黄嘌呤（MIX）、地塞米松、胰岛素诱导其分化,采用适时PCR技术检测诱导分化不同时间脂肪细胞中chemerin及chemerinR基因的表达水平。结果 chemerin及chemerinR基因在小鼠体内广泛表达,以脂肪组织和肝脏为甚;二者低表达于3T3-L1前脂肪细胞中,并随前脂肪细胞诱导分化成熟表达水平呈逐渐上调趋势。结论 chemerin及其受体基因可能有利于脂肪细胞的分化成熟。     

Managing nonmalignant chronic abdominal pain and malignant bowel obstruction

Evaluation of abdominal pain requires an understanding of the possible causes(benign or malignant) and recognition of typical patterns and clinical presentation. Abdominal pain has multiple causes; associated signs and symptoms may aid in the diagnosis. Remember that some patients will not have a textbook presentation, and unusual causes for pain must be considered. Those with chronic pancreatitis with structural complications should be operated on early, whereas those with other types of chronic pancreatitis should receive medical therapy focusing on alleviating symptoms. Control of the most troublesome symptoms will provide the best management for IBS. Pharmacologic success in bowel obstruction depends on the level and degree of obstruction. Decision making is based on reasonable expectations of survival, treatment-related success, performance status, and goals of care. Quality of life will be enhanced by appropriate symptom management.     

肾小球肾炎肾组织megsin的表达及其意义

目的 :观察megsin在肾小球肾炎患者肾小球内表达及其特点 ,对原发性肾小球肾炎 (IgA肾病 ,IgAN)和继发性肾小球肾炎 (狼疮性肾炎 ,LN)进行研究。　 方法 :应用针对人类megsin的多克隆抗体 ,采用免疫组化法检测肾活检组织中肾小球内megsin的表达 ,其中IgAN 10例、LN 2 0例 ,并采用半定量方法与正常肾组织和轻微病变性肾病进行比较。　 结果 :正常肾组织和轻微病变性肾病均可表达一定量的megsin ,而在IgAN和LN的肾小球内megsin均表达明显增加。megsin仅表达于肾小球系膜区域 ,小管间质未见表达。在IgAN系膜增生性病变中megsin表达量较硬化性病变明显增多 (P <0 0 5 )。而在LN肾小球megsin的表达量虽较正常肾组织和轻微病变型肾病显著增多 ,但与原发性肾小球肾炎IgAN相比较 ,其表达量少 ,即使在LNⅣ型时。　 结论 :megsin在原发性和继发性肾小球肾炎均有一定的表达 ,并在其疾病进程中以及肾小球系膜功能调节中起一定作用 ,但在原发性和继发性肾小球肾炎中megsin的表达调节可能存在不同的机制     

Differential expression of GRK isoforms in nonmalignant and malignant human granulosa cells

Granulosa cell tumors are serious ovarian neoplasms that can occur in women of all ages. While there have been numerous attempts to understand the cause of these malignancies, the pathogenesis of granulosa cell tumors (GCTs) still remains largely unknown. G-protein coupled receptor kinases (GRKs) are important regulators of signal transduction through the process of receptor desensitization and internalization. Receptors that are regulated by GRKs are members of the large family of seven-transmembrane receptors and include the follicle stimulating hormone receptor (FSHR). In granulosa cells, the FSH signaling system is responsible for cell proliferation, differentiation, and steroidogenesis. In the studies presented, we examined GRK mRNA and protein expression in nonmalignant human granulosa cells, in KGN cells, a human GCT cell line, and in a panel of human GCT samples. The KGN tumor cells express significantly less GRK4 α/β protein and higher levels of GRK2 and GRK4 γ/δ protein as compared to nonmalignant human granulosa cells. In human GCT samples, GRK4 α/β protein was detected in 3 of the 13 tumor samples, whereas γ/δ proteins expression was detected in all samples. These findings suggest that GRK protein expression is altered in GCTs and may be involved in the pathogenesis of these tumors.