The glycolytic enzyme activity of the human cervix uteri.

The activity of the following enzymes was studied in normal, precancerous, and malignant biopsies from the human cervix uteri: hexokinase (HK), phosphofructokinase (PFK), pyruvate-kinase (PK), lactate dehydrogenase (LDH), and glucose-6-phosphate dehydrogenase (G-6-PDH). In precancerous conditions, i.e., dysplasia and carcinoma in situ without any signs of invasive carcinoma, only PK showed moderate but significant activity increases. A rise in enzyme activity in biopsies histologically classified as carcinoma in situ was found to signal the presence of invasive carcinoma in other parts of the cervix. In invasive carcinomas of the cervix, all the enzymes studied showed a two- to four-fold increase (p less than 0.01) as compared to the normal cervix. The present study failed to reveal significant differences between enzyme activities in biopsies from patients in Stage I, II, and III; no correlation could be established between enzyme activity and prognosis.     

Prediction of portal vein invasion by hepatocellular carcinoma: a correlations between portal vein tumor thrombus and biochemical tests.

Hepatocellular carcinoma patients were categorized into three grades according to the extent of portal vein invasion by the tumor. Correlations between the extent of portal vein invasion and values of alpha-fetoprotein (AFP), and various biochemical tests were examined. The extent of portal vein invasion by the tumor significantly correlated with the values of glutamic oxaloacetic transaminase (GOT), glutamic oxaloacetic transaminase: glutamic pyrubic transaminase (GOT:GPT), lactic dehydrogenase (LDH), alkaline phosphatase, leucinaminopeptidase (LAP), gamma-glutamic transpeptidase (gamma-GTP) and log10AFP. Results of the multivariate logistic regression analysis showed the values of LAP, LDH, log10AFP and GOT:GPT to be statistically significant independent indicators of portal vein invasion by hepatocellular carcinoma. The calculated probability for portal vein tumor thrombus, which was derived from the results of a step wise multivariate logistic regression procedure, revealed high accuracy and specificity for predictability. To design effective therapy and to predict the prognosis, it would be beneficial to obtain additional information from this calculated probability in patients with hepatocellular carcinoma.     

膜联蛋白Ⅰ在多种癌组织中的表达

目的检测分析多种癌组织中膜联蛋白(annexin)Ⅰ的表达情况,探讨其表达变化规律与不同器官的相同和不同组织学类型癌的发生发展的相关性。方法构建的628例癌组织芯片中,食管鳞癌208例,其他14种器官的相同或不同组织学类型癌组织420例。以相应正常组织作对照。用免疫组化方法检测annexinⅠ的表达情况。结果annexinⅠ在多器官(食管、肺、喉、宫颈)的鳞癌表达下降,分化差者表达更低;在多种腺癌(胃和结直肠腺癌、胰腺导管腺癌、甲状腺乳头状癌和肾透明细胞癌)中表达上调,分化差者表达更高。结论annexinⅠ在多种癌组织中的表达有明显差异,并与组织学类型和分化程度明显相关。annexinⅠ在多种癌的发生中可能有重要作用。     

Creatine kinase B subunit as a biomarker for small cell carcinoma of the lung: comparison with gamma-enolase

Concentrations of creatine kinase (CK) B subunit (CK-B) in tumor tissues and in sera of patients with various lung carcinomas were determined, together with the concentrations of neuron-specific gamma-enolase (gamma subunit of a gamma and gamma gamma enolases), by the use of a sensitive enzyme immunoassay method. The CK-B and gamma-enolase levels were enhanced in tissues of small cell carcinoma of the lung. The average tissue contents of CK-B in small cell carcinoma (SCCL), adenocarcinoma (ADCL) and squamous cell carcinoma (ECCL) of the lung, and normal lung were 2320, 308, 163, and 372 ng/mg protein, respectively. The contents of gamma-enolase in those tissues were 1460, 276, 225, and 42.7 ng/mg protein, respectively. Serum CK-B concentrations in healthy adults (n = 100) were 0.53 +/- 0.22 ng/ml and ranged from 0.25 to 1.44 ng/ml, but they were significantly increased (greater than 1.5 ng/ml) in some patients with SCCL (26/42 cases, 62%), ADCL (7/36, 19%), ECCL (7/37, 19%), and large cell carcinoma of the lung (LCCL, 4/13, 31%). Serum CK-B was also enhanced in some patients with breast carcinoma and in a few cases in carcinomas of the stomach, colon and pancreas. Serum concentrations of CK-B were well correlated with those of gamma-enolase in patients with SCCL (r = 0.667, n = 83, P less than 0.01) and LCCL (r = 0.689, n = 20, P less than 0.01), but poorly in patients with ADCL and ECCL. Since serum CK-B concentrations in patients with SCCL changed in parallel with the clinical course during treatment, serum CK-B may also be a useful biomarker, as well as neuron-specific gamma-enolase, for monitoring the clinical course of patients with SCCL.     

Carcinoma-related alterations of glycosyltransferases in human tissues

The glycosyltransferases responsible for catalyzing additions of A, B, and H sugars to cellular acceptors were studied in 23 cases of primary carcinoma. The carcinomas were derived from mouth, tongue, larynx, lung, cervix, esophagus, stomach, and colon. Comparisons of A, B, and H enzymes were made between mucosal extracts from tumor and from normal adjacent tissue and, in the case of gastrointestinal tract, extracts derived from mucosae of individuals free of disease. The most prevalent finding was that of alpha-2-fucosyltransferase (H enzyme) deficiency in tumor extracts from Group A, B, and O patients in relation to the normal tissue counterpart (20 cases). Exceptions were observed in one case of carcinoma of the stomach and in two of seven cases of carcinoma of rectum or sigmoid. In four of nine Group A patients (carcinoma of the mouth, tongue, ascending and transverse colon), N-acetylgalactosaminyltransferases (A enzymes) were demonstrated but were deficient in relation to the normal adjacent counterpart. A enzymes were not demonstrable in normal and tumor extracts from distal colon in five cases. Differences between tumor extracts and normal adjacent tissue were noted in D-galactosyltransferase (B enzyme) derived from carcinomas of larynx and esophagus, but B enzyme was not demonstrated in tumor or normal tissue derived from the sigmoid colon. Study of the normal distribution of H enzyme in gastrointestinal mucosa indicated the presence of relatively high enzyme levels in stomach and upper intestine but low levels in distal colon.     

Localization of Immunoreactive Somatostatin in Tumor Tissues Derived from Various Organs

A sensitive and specific radioimmunoassay system has been developedfor measuring somatostatin in tissues. Immunization of rabbitwith somatostatin yielded the specific anti-somatostatin antibodythat did not cross-react with various hormones tested. The radioimmunoassaysystem could detect as little as 6 pg of somatostatin. The recoveryof somatostatin added to tissues was 67.8 ± 3.7%. Inhibitioncurves of the extracts obtained from a normal pancreas and twogastric carcinomas were parallel to those obtained with syntheticsomatostatin. Immunoreactive(IR) somatostatin was not detectablein normal and tumor tissues of the lung and kidney, except intwo out of seven lung carcinomas. However, variable amountsof IR-somatostatin (0.3–13.6 ng/g wet wt.) were detectedin carcinomas of the pancreas and stomach, although the valueswere lower than those in respective control tissues. A caseof medullary carcinoma of the thyroid showed relatively highlevels of serum calcitonin and tissue IR-somatostatin in bothprimary and metastatic carcinoma. These data suggest that somemalignant tumors could produce somatostatin-like substance,but its significance remains to be elucidated.     

Chemopreventive activity of a macrofungus Phellinus rimosus against N-nitrosodiethylamine induced hepatocellular carcinoma in rat

Chemoprevention is an important alternative approach to control cancer. Chemical substances with multiple inhibitory properties would be a welcome addition to the class of chemopreventive drugs. In this study, we investigated the antioxidant, anti-inflammatory, antimutagenic and cancer preventive activities of aqueous extract of a macrofungus Phellinus rimosus (Berk) Pilat. The extract exhibited superoxide anion (O2-), hydroxyl radical (*OH), nitric oxide (NO*) scavenging and lipid peroxidation inhibiting activities. The inhibitory concentrations required by the extract to scavenge 50% (IC50) of the superoxide anion, hydroxyl radical and nitric oxide generated were 126 +/- 5.1, 71 +/- 4.7 and 31 +/- 4.5 microg/ml respectively. The concentration required to inhibit 50% of Fe2+ induced lipid peroxidation in rat liver homogenate was 318 +/- 2.4 microg/ml. The extract showed significant (P<0.05) anti-inflammatory activity in a dose dependent manner. Extract (100 mg/kg body wt, p.o) inhibited 44.5, 45.4 and 47% carrageenen, dextran and formalin induced inflammations respectively. The antimutagenic activity was determined by the Ames' Salmonella mutagenecity assay using histidine mutant Salmonella typhimurium strains. The extract at concentration of 5 mg/plate showed antimutagenecity against benzo[a]pyrene (B[a]P) and 4-nitro-o-pheneylenediamine (NPDA) induced mutations of TA98 and TA100 respectively. Anticarcinogenic activity was evaluated using N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma (HCC) in rats. Serum gamma glutamyl transpeptidase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) activities and lipid peroxidation level (MDA) were elevated significantly (P<0.05) in the NDEA alone treated group of animals. Treatment of the extract (25 and 50 mg/kg body wt, p.o.) prior to the NDEA administration decreased the serum GGT, GOT, GPT and ALP activities and MDA level in a dose dependent manner. The NDEA alone treated animals showed altered serum albumin/globulin ratio (A:G ratio), hyperfibrinogenaemia, increased hepatic glutathione S-transferase (GST) activity, glutathione-peroxidsae (GPx) activity and reduced glutathione (GSH) level compared to the extract plus NDEA treated group. The extract also inhibited in vitro aniline hydroxylase (AH) activity of rat liver induced by phenobarbitone in a dose dependent manner. The results, thus suggest the significant chemopreventive properties of the aqueous extract of the Phellinus rimosus against NDEA induced hepatocellular carcinoma by its antioxidant, anti-inflammatory and antimutagenic activities.     

羟基喜树碱抗癌谱的实验研究

目的 :预测羟基喜树碱 (OPT)的抗癌谱 ,指导临床用药。方法 :收集我院 2 0 0 0年 6月～ 2 0 0 0年 11月 96例手术切除的肿瘤标本 ,行肿瘤细胞原代培养 ,用MTT法对OPT进行体外药敏试验。抑制率≥ 5 0 %为敏感 ,推荐临床使用 ;<30 %为耐药。结果 :OPT平均敏感率为 2 5 .5 % ,耐药率为 4 2 .6%。各类肿瘤敏感率为乳腺癌 (5 0 .0 % ) >贲门腺癌 (4 1.7% ) >胃癌、宫颈癌 (33.3% ) >食管癌 (30 .4 % ) >结肠癌、膀胱癌 (2 5 .0 % ) >卵巢癌、肺癌 (16.7% ) >肾癌、甲状腺癌 (0 ) ;耐药率依次为甲状腺癌(10 0 0 % ) >膀胱癌 (75 .0 % ) >食管癌 (5 2 .0 % ) >肺癌、宫颈癌、肾癌 (5 0 .0 % ) >胃癌、卵巢癌 (33.3% )>乳腺癌、贲门腺癌、结肠癌 (2 5 .0 % )。结论 :OPT的抗癌谱为乳腺癌、贲门腺癌、结肠癌、胃癌、卵巢癌、肺癌、宫颈癌。肾癌、甲状腺癌不推荐使用     

Intrinsic angiotensin II-generating system in human pancreatic cancer tissues

To clarify whether an intrinsic angiotensin II-generating system exists in human advanced pancreatic cancer tissues, we measured angiotensin II concentration and angiotensin converting enzyme (ACE) activity in tissues of normal pancreas, pancreatic cancers, colon cancers and hepatocellular carcinomas. After the surgically resected specimens were homogenized, angiotensin II concentration and ACE activity in tissues were measured using the florisil method and Kasahara's method, respectively. Tissue angiotensin II levels in pancreatic cancers (n = 13) were significantly higher than those of normal pancreas (n = 7), colon cancers (n = 7), or hepatocellular carcinomas (n = 7). However, there was no significant difference in tissue ACE activity between them. This study provides in vivo evidence of ACE-independent angiotensin II-generating system in human pancreatic cancer tissues and suggests that this locally-formed angiotensin II influences the microenvironment of pancreatic cancer tissues in a paracrine fashion.     

Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines

Recently, shortened telomere length and increased telomerase activity have been demonstrated in various human cancers. In the study reported here, we ascertained whether gene changes are characteristic of pancreatic cancers. Hamster duct carcinomas and cell lines were investigated by Southern blot analysis for telomere restriction fragment (TRF) length and by the telomeric repeat amplification protocol (TRAP) assay for telomerase activity. Comparison with normal pancreas and spleen revealed shortened TRF length and markedly increased telomerase activity in primary pancreatic duct carcinomas induced by the rapid-production model as well as in a transplantable carcinoma and the cell lines. The enzyme level was 86.0–215.7 times the low levels found in control pancreas and spleen tissues. Late-passage Syrian hamster embryo cells, known to be immortalized and tumorigenic, had shorter TRFs than the original cells in primary culture did. These results indicate that hamster pancreatic duct carcinoma cells are immortalized, with the potential for proliferation ad infinitum, and provide a model for basic therapeutic research into the substances targeting telomerase. Mol. Carcinog. 18:153–159, 1997. © 1997 Wiley-Liss, Inc.     

免疫聚合酶链反应技术检测胃癌血清MG_7-抗原

采用免疫聚合酶链反应技术检测胃癌患者血清中的MG－Ag，评价该方法在临床血清诊断中的价值。分别检测胃癌100例、食管癌17例、结肠癌9例、肝癌14例，子宫颈癌6例，其血清诊断阳性率分别为84．0％、17.6／、44．4％。肝癌及子宫颈癌未检出。胃溃疡及慢性胃炎血清诊断率为77％及5．9％，检测结果以胃癌阳性率最高。此方法可用于胃癌患者的血清学诊断，亦可用于高危人群的胃癌普查，有利于早期诊断，早期治疗。     

Elf regimen in advanced gastrointestinal malignancies - an analysis of its clinical effectiveness and toxicity

A multi-institutional phase 11 study of the combination of levofolinic acid 100 mg/m2, VP16 120 mg/m2 and 5-fluorouracil 500 mg/m2 for 3 consecutive days was carried out on a series of 73 evaluable patients with low performance status affected by locally advanced and/or metastatic gastrointestinal carcinomas. Site of primary tumor were: stomach 26, large bowel 20, pancreas 16, gall-bladder 5, and liver 6. Among patients with gastric carcinoma, 2 patients (8%) had a complete response with a mean duration of 6.8+ months, and 9 (35%) had a partial response with a mean duration of 5.8+ months, for an overall response rate of 43%. Overall response rate was largely unsatisfactory in colorectal carcinoma (20%), pancreatic (12%), gall-bladder and liver carcinomas. The treatment was very well tolerated with no grade 4 toxicity over a total of 267 cycles administered. Grade 3 leukopenia was seen in 25% of cases, and grade 2 thrombocytopenia in 18%. Vomiting never exceeded grade 2. Thus, the ELF regimen is quite active in advanced gastric carcinoma, and may be recommended as palliative treatment of patients who cannot receive intensive chemotherapy. On the other hand, it cannot be considered active in colorectal, pancreatic, gall-bladder and liver carcinomas, and its use should be discouraged in these neoplasms.     

Collagenolytic activity of cervix carcinoma]

We estimated collagenolytic activity of 10 invasive carcinomas of the cervix by means of a biological assay. Collagenolysis was found in 7 specimens. In order to detect the origin of the collagenolytic enzyme additional inhibition studies with ethylendiaminetetraacetate and normal human serum were performed. Normal human serum inhibited the enzymatic process by a mean percentage of 14.9%, EDTA up to 9.1%. D-penicillamine and 1.10-o-phenanthroline which inhibit collagenase specifically stopped the enzymatic activity of the tumor completely. According to our results it can be suggested that the collagenolytic activity of carcinoma of the cervix uteri is not derived from serum or from polymorphonuclear cells but is created by the tumor itself.     

CA 19-9 and pancreatic adenocarcinoma

The diagnostic place value of CA 19-9, a tumor-associated antigen, was tested in 611 patients. This group of patients included 273 patients who suffered from a malignant disease (48 patients with pancreatic carcinomas and 225 patients with extrapancreatic malignant growths) and 338 patients with benign diseases (66 patients with chronic pancreatitis, 36 patients with acute pancreatitis, and 236 patients with general surgical diseases). In 93% of the patients with pancreatic carcinoma (media value, 528 U/ml), in 37% and 19% of the patients with carcinoma of the stomach and colorectal carcinomas (median value 8 U/ml), respectively, the CA 19-9 value was estimated as being above the normal limits of 6 to 37 U/ml. A sensitivity of 93% and a specificity of 85%, as well as a total accuracy of 82%, were established in pancreatic carcinoma during preoperative observation. The preoperatively raised CA 19-9 concentration in patients with pancreatic carcinomas dropped after curative resection of the carcinoma to within normal limits. However, a serum concentration of less than 37 U/ml was not recorded in any CA 19-9 estimation after a palliative surgical intervention, or in any case of inoperable carcinomas.     

Poly (C) avid ribonuclease estimation in patients with solid tumors. A critical evaluation

Activity of Poly (C) avid ribonuclease was estimated in sera of 129 patients with different malignancies. All patients had histologically verified carcinomas, normal renal function, and no signs of acute catabolic condition. Activity values were compared with those of normal subjects (U-test, Mann and Whitney) separately for each age decade and type of carcinoma. Patients with ovarian and bronchus carcinoma had statistically elevated activity values throughout all age groups. Colon carcinoma patients showed elevated values in most instances. In patients with pancreatic carcinoma a difference could be detected in only one age group (51-60 years of age). No significant elevation of enzyme activity was detected in carcinoma of the stomach and of the prostate. It is concluded that there are carcinomas leading to elevated ribonuclease activity, although the biological basis of this phenomenon is not understood. No special sensitivity nor specificity of ribonuclease elevation could be demonstrated in pancreatic carcinoma patients. Up to now the usefulness of ribonuclease estimation in prospective carcinoma detection remains questionable.     

The clinical relevance of the tumor marker CA 19-9 in the diagnosing and monitoring of pancreatic carcinoma

The tumor marker test CA19-9 is based on monoclonal antibody to colonic carcinoma cell lines. In this study, the utility of the tumor marker in the diagnosis of pancreatic carcinoma was evaluated. CA19-9 is strongly expressed in most tissue specimens from pancreatic carcinomas. However, this antigen is also found in normal pancreas and specimens from chronic pancreatitis. CA19-9 is released into the circulation, and was found in increased concentrations (greater than 37 U/ml) in 87% of the patients with pancreatic carcinoma (N = 145), as compared with only 13% in the group of patients with benign diseases (N = 1081) and 29% of those with extrapancreatic malignancies (N = 691). The preoperatively raised CA19-9 concentration in patients with stage I of pancreatic carcinoma decreased after curative resection of the carcinoma to values within normal range. However, in no CA19-9 estimation following a palliative surgical intervention of stage III and IV patients or in cases of inoperable carcinomas was a serum concentration of less than 37 U/ml recorded. The mean survival rate of stage I patients was 29 months, whereas it was only 6 months for stage III, IV and patients with inoperable carcinomas.     

Effect of cadmium pretreatment on nickel toxicity

Pretreatment with nickel has earlier been shown to protect against cadmium intoxication. The effect of cadmium pretreatment on the nephro- and hepatotoxicity of nickel has been investigated. The administration of cadmium (6 mg/kg, i.m., once) to rats significantly enhanced urinary excretion of ALP, LDH, GOT, amino acids and proteins and increased the activity of serum ALP, GOT, and GPT, while the administration of nickel (6 mg/kg, i.p., 3 days) altered these parameters less significantly. These changes in urine and serum were used as a measure of renal and hepatic damage. The administration of nickel for three days, one week after cadmium treatment, caused significantly more marked enzymuria, aminoaciduria, proteinuria and an increase in the activity of serum enzymes than induced by either of them individually. However, cadmium pretreatment had no influence on urinary excretion or hepatic uptake of nickel, but increased renal uptake of nickel on the fourth day. The results suggest that cadmium enhances the nephro- and hepatotoxicity of nickel.     

A clinical evaluation of carbohydrate antigen 19-9 and carcinoembryonic antigen in patients with pancreatic carcinoma

We have studied serum carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) in 221 persons to assess their usefulness in the diagnosis of pancreatic carcinoma. Although serum CA 19-9 and CEA in all healthy controls were within normal limits, the positive ratings of serum CA 19-9 and CEA in all benign disease were 9.8% and 18.1%, respectively. Sensitivity of serum CA 19-9 for pancreatic carcinoma was 70.5%, which was higher than that found in healthy controls, benign disease, and other malignant disease except biliary carcinoma; but sensitivity of serum CEA levels (67.7%) was not different from that seen in malignant disease. Three of 34 patients (8.8%) with pancreatic carcinoma who had a above-normal levels of serum CA 19-9 but not serum CEA were resectable. Although there was no correlation between serum CA 19-9 and CEA, advanced stages of pancreatic, gastric, and colorectal carcinoma tend to show high serum CA 19-9 and CEA, but no statistical differences were observed in relation to the stages of these carcinomas. Comparative studies of serum CA 19-9 and CEA for sensitivity and the predictive value of true positive and negative results for detecting pancreatic, gastric, and colorectal carcinoma showed that serum CA 19-9 has significantly higher sensitivity and predictive value of true positive results for pancreatic carcinoma than for gastric and colorectal carcinoma (P less than 0.05). However, serum CEA measurements did not show any difference between these carcinomas, and the highest predictive value of a true negative result for excluding pancreatic carcinoma was also observed in serum CA 19-9. These results indicate that although the CA 19-9 assay is not specific for pancreatic carcinoma, it is more useful adjunct method for diagnosing pancreatic carcinoma, possibly in resectable stages.