Intracellular distribution of pancreatic tumor antigen purified from BHP-induced adenocarcinomas in Syrian hamsters

Pancreatic tumor antigen (PTA) was purified to apparent homogeneity from hamster pancreatic adenocarcinomas by a rapid and simple procedure using column chromatography on Mono P and Superose 6. Amino acid analysis indicated essential similarities between hamster PTA and human pancreatic cancer-associated antigen (PCAA, PCAAc), although differences in the contents of several amino acid residues between the two proteins did suggest species variation. Investigation of the binding pattern of antibody raised against PTA by peroxidase-labeled antibody immunocytochemistry revealed that, whereas PTA is absent or only faintly expressed in normal epithelium, it is very strongly positive in transplantable hamster pancreatic adenocarcinomas induced by nitrosamines. PTA was found to be distributed over the entire surface of neoplastic cells and it was concluded that the presence of PTA on the basolateral surface of malignant pancreatic epithelial cells, where it might have access to the blood circulation, could be one explanation for the observed elevated concentrations of PTA in the serum. PTA is thus a potential marker for hamster neoplastic pancreatobiliary duct-type cells.     

Clinical significance of serum p53 antigen in patients with pancreatic carcinomas.

BACKGROUND: Alterations in the p53 gene are often found in pancreatic cancer, and accumulation of the p53 protein has been noted in tumour cells. AIMS: To investigate whether serum p53 protein concentrations could be used as markers for p53 gene mutations in neoplasms of the pancreas. METHODS: Serum p53 protein concentrations were determined by an enzyme linked immunosorbent assay (ELISA) in 104 cases of pancreatic adenocarcinoma, and 61 matched formalin fixed tissue sections were also stained by an anti-p53 DO-7 monoclonal antibody. RESULTS: The mean serum concentration of p53 protein in the adenocarcinoma patients was 0.27 (SEM 0.02) ng/ml, and was significantly higher than in 35 healthy blood donors (0.15 (0.02) ng/ml, SD = 0.11) or in 15 cases of chronic pancreatitis (0.15 (0.02) ng/ml). Adopting an arbitrary cut off value for the serum p53 protein concentration of 0.37 ng/ml, which corresponded to a value 2 SD above the mean value from the healthy blood donors, positive serum p53 protein concentrations were found in 23 out of 104 (22.1%) patients with adenocarcinomas examined, 16 out of 47 (34.0%) patients with carcinomas with distant metastases, but only seven of 57 patients (12.3%) with carcinomas without metastases (p < 0.05). In 11 patients with pancreatic adenocarcinomas, the mean serum p53 protein concentration after tumour resection was 0.21 (0.05) ng/ml, and had decreased compared with the preoperative concentrations (0.25 (0.05) ng/ml) (P < 0.05). There were no significant associations between the serum concentrations of p53 protein and serum concentrations of markers such as CA19-9 or CEA; however, serum concentrations of p53 protein demonstrated a potential role as an additional tumour marker. Immunohistochemical studies disclosed that the p53 protein was expressed in 28 out of 61 pancreatic adenocarcinomas (45.9%). Serum p53 protein concentrations in the positively immunostained cases were significantly higher than in the negatively immunostained cases (0.35 (0.05) ng/ml v 0.15 (0.01) ng/ml; p < 0.005). Furthermore, positive immunostaining for p53 protein was found in eight out of 10 (80%) serum positive p53 protein cases with adenocarcinomas. CONCLUSION: An increase in serum p53 protein concentrations appears during the progression of pancreatic adenocarcinoma and correlates with the accumulation of p53 protein as a result of a mutation of the p53 gene. An analysis of p53 antigen concentrations can detect p53 gene alterations, which could be useful for the selection of treatment regimens.     

Elevated activity of pancreatic type amylase in the urine as an early indicator of pancreatic tumors in hamsters

Levels of amylase isozymes in the urine and serum of Syrian hamsters during pancreatic carcinogenesis, induced by N-nitrosobis(2-oxopropyl)amine (BOP), were investigated. BOP was injected subcutaneously (sc) into female Syrian golden hamsters at a dose of 10mg/kg once weekly for 6 wk and amylase activities in urine and serum samples were measured every other week from the first treatment of BOP. Although total amylase in the urine showed no remarkable changes, the pancreatic type isozyme demonstrated only very low levels for the first 6 wk and then from wk 8, became elevated showing continuously high levels in all animals thereafter. Animals were sacrificed at wk 10, 14, and 18. Dysplastic lesions of the pancreas developed in all the hamsters investigated. Furthermore, pancreatic adenocarcinomas were also observed in all animals sacrificed at wk 18. Thus, the results suggest that measurement of pancreatic isoamylase in the urine might allow early indication of pancreatic tumor development in hamsters.     

Hypercalcitoninemia in a patient with a recurrent goitre and insulinoma: a case report.

Serum calcitonin has become a very sensitive and specific marker for medullary thyroid carcinoma that should be determined in patients with nodular thyroid disease. However, a few earlier reports indicated that tumors other than medullary thyroid carcinoma including insulinomas arising from pancreatic islet cells may also produce calcitonin. Of the few cases of calcitonin-producing insulinomas previously reported, most had incomplete data or lack of documentation of the association between raised serum calcitonin concentration and immunohistochemical detection of calcitonin in pancreatic islet cell tumors. In this paper we are reporting a 54-year-old woman with a history of partial thyroidectomy for multinodular goitre at the age of 50 yrs, she was evaluated for a 2-months history of fasting hypoglycemia (plasma glucose 1.9 mmol/L during a supervised fast), raised serum insulin (at the time of hypoglycemia 88.8 microU/ml; normal, 5 - 35 microU/ml) and C-peptide levels (at the time of hypoglycemia 6.1 ng/ml; normal, 1.37 - 3.51 ng/ml), markedly increased serum calcitonin concentration (481 pg/ml; normal, < 9.9 pg/ml), and an enlarged residual thyroid gland. Aspiration biopsy of the thyroid was negative for parafollicular C-cell hyperplasia or medullary thyroid carcinoma. Abdominal ultrasound and CT scan revealed a tumor in the head of the pancreas, which was surgically removed. Histopathological evaluation of the pancreatic tumor showed typical features of a neuroendocrine neoplasm with strong immunostaining for both insulin and calcitonin. After removal of the pancreatic tumor, clinical symptoms resolved and biochemical markers normalized (serum insulin, 14.9 microU/ml; C-peptide, 3.0 ng/ml; calcitonin, 2.9 pg/ml) confirming the causal relationship between insulinoma and markedly increased serum calcitonin levels.     

Elevated activity of pancreatic type amylase in the urine as an early indicator of pancreatic tumors in hamsters

Levels of amylase isozymes in the urine and serum of Syrian hamsters during pancreatic carcinogenesis, induced by N-nitrosobis(2-oxopropyl)amine (BOP), were investigated. BOP was injected subcutaneously (sc) into female Syrian golden hamsters at a dose of 10mg/kg once weekly for 6 wk and amylase activities in urine and serum samples were measured every other week from the first treatment of BOP. Although total amylase in the urine showed no remarkable changes, the pancreatic type isozyme demonstrated only very low levels for the first 6 wk and then from wk 8, became elevated showing continuously high levels in all animals thereafter. Animals were sacrificed at wk 10, 14, and 18. Dysplastic lesions of the pancreas developed in all the hamsters investigated. Furthermore, pancreatic adenocarcinomas were also observed in all animals sacrificed at wk 18. Thus, the results suggest that measurement of pancreatic isoamylase in the urine might allow early indication of pancreatic tumor development in hamsters.     

Establishment and characterization of a cultured cell line derived from nitrosamine-induced pancreatic ductal adenocarcinoma in Syrian golden hamsters

Seven kinds of pancreatic ductal adenocarcinomas induced by N-nitrosobis(2-hydroxypropil)amine in Syrian golden hamsters were established as transplantable tumor lines on syngeneic animals. These tumor lines were all well or moderately differentiated adenocarcinomas, showing various velocities of growth, unrelated to the grade of histological differentiation. A cell line, designated HaP-T1, was established in continuous tissue culture from one of these homografts. The cells grew in a monolayered sheet with an approximately 17-hour population doubling time. Chromosomal analysis revealed that the modal chromosomal number of the cell line was 44. HaP-T1 cells showed apparent tumorigenicity both on syngeneic hamsters and athymic nude mice, but they grew much faster when injected into the former animals. Morphological characteristics of HaP-T1 cells and tumors induced by HaP-T1 inoculation in both animals revealed apparent epithelial characteristics resembling ductal adenocarcinoma of the pancreas. These transplantable tumor models will contribute to the further investigation in the field of pancreatic cancer.     

胰腺癌HMGB1表达及其与血行转移的关系研究

目的 探讨人胰腺癌高迁移率族蛋白B1(hiish mobility group protein B1,HMGB1)表达及其与血行转移的关系.方法 应用Western blot法检测68例胰腺癌患者、18例CP和21例健康者血清HMGB1水平,并对其中37例胰腺癌患者手术前后的血清HMGB1水平进行比较;应用免疫组织化学法检测67例胰腺癌组织HMGB1和CD31的表达.结果 胰腺癌、CP及健康者血清HMGB1水平分别为(119.7±54.5)ng/ml、(40.2±25.5)ng/ml和(13.1±4.3)ng/ml,相差非常显著(P<0.001).胰腺癌患者术后血清HMGB1水平为(69.3±5.1)ng/ml,显著低于术前的(120.2±8.2)ng/ml(P<0.001).胰腺癌组织HMGB1表达阳性率为43.6%,HMGB1表达与组织分化、TNM分期及转移有关,P均<0.01;HMGB1表达与血管密度呈显著正相关(r=0.76,P<0.0001),免疫组化显示,HMGB1表达阳性的肿瘤细胞多位于有腔血管周围,位于血管内的肿瘤细胞HMGB1阳性表达率为71%.结论 胰腺癌患者HMGB1呈高表达,表达HMGB1的肿瘤细胞易于进入血管内,与其血行转移有关.     

Multiparametric tumor marker (CA 19-9, CEA, AFP, POA) analyses of pancreatic juices and sera in pancreatic diseases

With respect to their diagnostic utility CA 19-9, CEA, AFP and POA were determined in pancreatic secretions and serum of patients suffering from pancreatic cancer (n = 76/55) or chronic pancreatitis (n = 79/45) and of controls (n = 81/42), respectively. While the determination of AFP and POA both in pancreatic secretions and serum does not permit a differential diagnosis, serum CEA (greater than 10 ng/ml) and CA 19-9 (greater than 50 U/ml) levels were indicative of pancreatic cancer in 30% and 83%, respectively, with a rate of false positive results of 5% and 8.5% confined to the chronic pancreatitis patients. A combination of tumor marker analyses, that is, serum CA 19-9 (greater than 50 U/ml) and pancreatic secretion CEA (greater than 70 ng/ml), proved to be positive in 92.9% of tumor patients with a maximum of 10.5% false positives. Likewise, values of serum CA 19-9 (greater than 50 U/ml) and serum CEA (greater than 10 ng/ml) were found in 85.8% of the pancreatic cancer patients with only 8.8% false positives, which were confined to the chronic pancreatitis patients. These results indicate the superiority of multiparametric tumor marker analyses for the diagnosis of pancreatic cancer, especially when including new monoclonal antibody defined tumor markers.     

胰腺内分泌肿瘤ghrelin和受体GHS-R1A的表达及患者血浆ghrelin、瘦素水平

目的 检测胰腺内分泌肿瘤患者血浆及肿瘤组织ghrelin水平、血浆瘦素水平,探讨它们之间的关系及临床意义.方法 采用ELISA法检测11例胰腺内分泌肿瘤患者的术前血浆ghrelin及瘦素水平,以28例正常志愿者作为对照.免疫组织化学染色法检测11个肿瘤和27个对照组织ghrelin及其受体GHS-R1A的表达.并与临床病理资料进行相关分析.结果 胰腺内分泌肿瘤患者血浆ghrelin水平为(16.0±5.0)pg/ml,显著低于对照组的(21.0±2.0)pg/ml(P=0.047);瘦素水平为(0.34±0.03)ng/ml,与对照组的(0.38±0.04)ng/ml无显著差异.肿瘤患者的血浆ghrelin与瘦素水平呈正相关(P=0.015),但与各项临床病理指标均不相关;对照组的血浆瘦素水平与体重指数呈正相关(P=0.002),而肿瘤患者两者不相关.肿瘤组织ghrelin的表达率明显低于对照组织(64%对100%,P=0.004),而GHS-R1A的表达率与对照组无显著差异.肿瘤组织ghrelin和GHS-R 1A的表达与各项临床病理指标均不相关.结论 胰腺内分泌肿瘤表达ghrelin及GHS-R1A,患者血浆ghrelin及瘦素水平发生变化.     

Acinar-islet cell carcinoma presenting as insulinoma

A case of acinar-islet cell carcinoma presenting as insulinoma is reported. The patient was a 28-year-old man who presented with two convulsive episodes. Fajans' index [immunoreactive insulin (IRI; μU/ml/ glucose mg/dl)] and Turner's [IRI (μU/ml) × 100/glucose (mg/dl)—30] index were high (2.8 and 308, respectively), as were serum proinsulin levels (550pg/ml). Abdominal computed tomography and angiography revealed a highly vascular tumor in the pancreatic tail and several similar tumors in the liver. Histologic features of a biopsy specimen from a hepatic tumor were those of a malignant pancreatic endocrine tumor. Insulin secretion by the liver metastases was confirmed by venous sampling after arterial stimulation with calcium. These findings led us to diagnose malignant insulinoma with liver metastases. Serum levels of α-fetoprotein and trypsin were markedly elevated, to 2234ng/ml (normal <10) and 22000ng/ml (normal<460) respectively, and these levels continued to rise with further growth of the liver metastases. Immunohistochemically, the metastatic liver tumor specimen was positive for α-fetoprotein, α1-antichymotrypsin, chromogranin A, and neuron-specific enolase. These findings of amphicrine features in the tumor were indicative of acinar-islet cell carcinoma that produced α-fetoprotein and trypsin in addition to insulin.     

The source of relaxin in pregnant Syrian hamsters

Serum immunoreactive relaxin (IR) was measured on days 8, 10, and 14 of gestation in intact and ovariectomized (day 8 of pregnancy) hamsters. In intact hamsters, IR increased from 3-4 ng/ml on day 8 to 20 ng/ml by day 14 of pregnancy. After ovariectomy on day 8, pregnancy failed, and IR decreased rapidly to 0.29 ng/ml on day 14. However, when pregnancy was maintained in ovariectomized hamsters by daily injections of 0.1 microgram 17 beta-estradiol and 4 mg progesterone, serum IR rose to levels similar to those in intact hamsters on days 10 and 14 of pregnancy (i.e. 15 and 20 ng/ml, respectively). Placentas were obtained from other groups of hamsters on days 11, 14, and 15 of pregnancy and homogenized for bioassay by the classical guinea pig pubic symphysis palpation bioassay. Homogenates of placentas obtained on days 14 and 15 contained, respectively, 4 and 10 micrograms eq porcine relaxin/serum relaxin/g fresh tissue. The placenta, rather than the ovary, appears to be the source of during pregnancy in the hamster.     

Blood-group antigen expression during pancreatic cancer induction in hamsters

The expression of blood group-related and tumor-associated antigens was examined in pancreatic adenocarcinomas and in the normal pancreas of hamsters to determine if this expression correlated with the host blood group and/or stage of carcinogenicity, respectively. Pancreatic tumors were induced by 4 weekly treatments of hamsters with N-nitrosobis(2-oxopropyl)amine (BOP) and analyzed immunohistochemically during different stages of tumor progression with polyclonal antibodies (PoAbs) and monoclonal antibodies (MoAbs) against A, B, O and Lewis (Le) isoantigens, including X, Y and CA 19-9 monosialoganglioside (gastrointestinal cancer antigen, GICA), as well as with PoAbs detecting human carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and the beta-subunit of human chronic gonadotropin (beta-HCG). The red blood cells of both control and tumor-bearing hamsters expressed AB and Le(a+b+)-like blood group types, as detected by polyvalent antisera. However, none of the MoAbs reacted with the hamster red blood cells. In the pancreas, all PoAbs against blood group antigens reacted with hyperplastic ducts and ductules at very early stages of carcinogenesis, as well as with neoplastic lesions, but not with normal pancreatic cells, except for the acinar cells, which were stained with PoAb-B, PoAb-Lea and PoAb-Leb. None of the MoAbs showed any affinity for the normal pancreatic cells; however, they reacted to various degrees with induced hyperplastic and neoplastic tissue. Reactivities of several MoAbs with malignant cells were greater than those with hyperplastic lesions: MoAb-B was highly reactive with all induced lesions, MoAb-A less reactive, and MoAb-H and MoAb-Ley (which has 6 sugar chains) detected only some cancer cells. Neither of the two MoAb-Lex (with 5 carbohydrate chains) reacted with carcinoma cells, although they did bind to a few hyperplastic cells. Neither MoAb-Lea and MoAb CA 19-9, nor PoAbs against CEA, AFP and beta-HCG, reacted with any normal, hyperplastic or malignant cells. These results demonstrate the differential reactivity of these PoAbs and MoAbs in normal and malignant pancreatic tissue and show that blood group antigens, especially the B isoantigens, are specific markers for induced pancreatic duct tumors in hamsters.     

Assay of serum elastase 1 in adenocarcinoma of the pancreas: diagnostic value, compared and combined study with serum CEA and CA 19-9

Serum elastase 1, CEA and, CA 19-9 titers were determined by radioimmunoassay in 113 patients with benign non pancreatic digestive disease, 88 patients with non pancreatic carcinoma, 25 patients with chronic pancreatitis and 40 patients with pancreatic carcinoma (of whom 34 were classified according to Fortner's staging classification), respectively: a) to evaluate the diagnostic value of elastase in pancreatic carcinoma, b) to compare and to study the value of its association with CEA and CA 19-9 for earlier detection of this type of cancer. The specificity of serum elastase (greater than 500 ng/dl) was greater than that of CA 19-9 (greater than 37 U/ml), (93.3 p. 100 vs 64.6 p. 100, p less than 0.01), but its sensitivity was significantly lower than that of CA 19-9 (27.5 p. 100 vs 82.5 p. 100; p less than 0.001). The sensitivity of CA 19-9 (greater than 37 U/ml) and/or elastase (greater than 500 ng/dl) was 85.2 p. 100 (greater, but not significantly, than CA 19-9 alone) and 91.6 p. 100 in Fortner stage I or II tumors (greater, but not significantly, than Fortner stage III tumors which were at 83.6 p. 100). The specificity of the combined test was 62 p. 100, lower (but not significantly) than CA 19-9 alone. As serum CEA (greater than 5 ng/ml) alone and in association with CA 19-9 was disappointing, it might be replaced by the elastase assay. The combined CA 19-9-elastase assay coupled with morphologic investigations could represent an attractive approach for earlier detection of this cancer.     

A non-acromegalic case of multiple endocrine neoplasia type 1 accompanied by a growth hormone-releasing hormone-producing pancreatic tumor

Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.     

Regulation of tonic gonadotropin release in prepubertal female hamsters

Basal serum gonadotropin levels were monitored weekly in female hamsters from birth to 10 weeks of age. Hamsters raised on three different photoperiods presented uniform pre- and postpubertal patterns of serum LH and FSH, suggesting that gonadotropin release in the young hamster occurs independently of ambient photoperiod. In all groups, serum LH levels increased gradually in animals up to 4 weeks of age, after which levels plateaued at 50--100 ng/ml. Serum FSH was markedly elevated in 2- and 3-week-old hamsters (800--1200 ng/ml), but remained at 200--400 ng/ml in all other groups. We next examined the change in the responsiveness of the pituitary to exogenous gonadotropin-releasing hormone (GnRH) challenge. Female hamsters 2 days of age failed to respond to any dose (0.025--1000 ng) of GnRH, while 10-day old females responded in typical dose-dependent fashion. GnRH-stimulated LH release first occurred in 6-day-old hamsters and was maximal by day 9, whereas FSH release first occurred on day 8 and was maximal by day 9. The prepubertal pattern of gonadotropin release can, in part, be explained on the basis of the development of pituitary GnRH sensitivity, which occurs independently of photoperiod.     

Location and type of gastric carcinoma in relation to pepsinogen I level in blood.

Serum pepsinogen I (PGI) levels were measured in 192 gastric carcinoma (GC) patients and 70 controls. Among GC patients serum PGI levels were not influenced by the following variables: age, sex, smoking, Borrmann's or Lauren's classification, tumor size, cellular differentiation, and layer of invasion. The mean serum PGI levels of tumors restricted to the body, antrum, or involving both areas were 64.8 +/- 37.6 ng/ml, 76.0 +/- 47.0 ng/ml, and 51.1 +/- 25.5 ng/ml, respectively (P < 0.005). Odds ratios of GC patients from the quartile of 262 serum PGI levels in the limits > or = 100 ng/ml, 70-99.9 ng/ml, 45-69.9 ng/ml, and < 45 ng/ml were 1.00, 0.76, 3.44, and 37.1, respectively (P < 0.001). The lower serum PGI levels of Chinese GC patients seem to be related to disease location rather than other characters of the tumor.     

Analysis of beta-catenin gene mutations in pancreatic tumors.

BACKGROUND/AIM: Mutations of the adenomatous polyposis coli (APC) tumor suppressor gene have been described in a subset of pancreatic carcinomas. The APC gene modulates the beta-catenin-Tcf pathway. The major player in this pathway is the beta-catenin protein encoded by the beta-catenin gene. A variety of different tumors, including colon, prostate, endometrial, and hepatocellular carcinomas, carry mutations in exon 3 of the beta-catenin gene. The aim of this study was to determine the role of the beta-catenin gene in the genesis of exocrine and endocrine tumors of the pancreas. METHODS: 78 ductal pancreatic adenocarcinomas, 14 ductal pancreatic cancer cell lines, and 33 endocrine pancreatic tumors were evaluated for mutations in exon 3 of the beta-catenin gene by single-strand conformation polymorphism analysis and direct DNA sequencing. In addition, 40 ductal pancreatic adenocarcinomas were analyzed for intracellular beta-catenin accumulation by immunohistochemistry, indicating alterations of the beta-catenin gene. RESULTS: Neither the 111 exocrine and endocrine pancreatic tumors nor the 14 pancreatic cancer cell lines carried mutations in exon 3 of the beta-catenin gene. Intracellular beta-catenin accumulation was not identified in any of the 40 pancreatic adenocarcinomas. CONCLUSION: These data suggest that the beta-catenin gene as the major player of the beta-catenin-Tcf pathway does not play an important role in the genesis of pancreatic tumors.     

Immunohistochemical characterization of endocrine cells in experimental exocrine pancreatic cancer in the Syrian golden hamster.

Fifty exocrine pancreatic adenocarcinomas and 57 benign tumors induced in Syrian hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) were examined for the presence of argyrophil cells antiinsulin, -glucagon, -somatostatin, -pancreatic polypeptide (PP), -gastrin/CCK, -vasoactive intestinal polypeptide (VIP), and - neuron-specific enolase (NSE) reactive cells. Argyrophil - and antihormone-reactive cells were found in the normal pancreatic ducts and in the acini, as well as in hyperplastic and atypical ducts/ductules, tubular complexes, benign lesions, and in 80% of ductal adenocarcinomas. Insulin and antiNSE-reactive cells were the most common, followed in decreasing frequency by glucagon, somatostatin, and PP cells. Antigastrin-/CCK-and -VIP-reactive cells were found in two cases. Argyrophil cells were present in about 60% of the tumors with Grimelius staining and in 55% of those with Churukian-Schenk staining. Insulin cells were seen in ductal cancer that had grown into a lymph node and in the lymph node metastases of another cancer. A novel finding was the presence of argyrophil and insulin cells within the lumen of some malignant glandular structures. Coexistence of several peptide cells was found in 52% of the cancers. The presence of argyrophil and hormone-producing cells in induced pancreatic ductal/ductular lesions further strengthens the existence of a close developmental relationship between exocrine and endocrine cells of the pancreas.     

Vasoactive intestinal peptide inhibits the growth of hamster pancreatic cancer but not human pancreatic cancer in vivo

We have previously shown that hamster H2T pancreatic ductal cancer has a receptor for vasoactive intestinal peptide (VIP) which is not present on a cell line of human pancreatic ductal cancer (MIA). The purpose of this study was to examine the effect of chronic administration of VIP on the growth of both H2T hamster pancreatic carcinoma and MIA human pancreatic carcinoma in vivo. The growth of H2T was studied in hamsters; a control group of six hamsters received 0.1% bovine serum albumin (BSA) in saline, and two treatment groups of six hamsters each received VIP (1 and 10 nmol/kg), all administered three times a day by i.p. injection for 35 days. Both doses of VIP inhibited the growth of H2T tumor (tumor area, weight, DNA, RNA, and protein content). The growth of MIA was studied in athymic Balb/c mice, one group of 10 received 0.1% BSA and the other 10 received VIP (1 nmol/kg), both three times a day by i.p. injection for 3 months. There was no difference in tumor growth rate between the two groups. Treatment with VIP did not have any effect on body weight or size of the normal pancreas in either the hamsters or the mice. We conclude that the differential response of hamster and human pancreatic cancer to VIP treatment may be due to the presence or absence of VIP receptors.     

Cerebrospinal fluid and serum carcinoembryonic antigen in brain tumors

Carcinoembryonic antigen (CEA) has been indicated to be a marker for brain tumors. In this study CEA was measured in serum and cerebrospinal fluid (CSF) of 14 patients with benign brain lesions, 16 with primary brain tumors and 8 with metastatic brain tumors by radioimmuno assay. Tumor cyst fluid CEA of 6 patients having intracranial tumors was also measured. The control group (n=20) had no neurological disease. The mean CEA levels in CSF for the control group, patients with benign tumors, primary tumors and metastatic tumors were 0.22 ng/ml, 0.31 ng/ml, 0.92 ng/ml, and 6.3 ng/ml respectively. Corresponding serum CEA levels were 2.5, 2.7, 3.0 and 5.2 ng/ml. Results showed that CEA level in CSF may play an important role in differential diagnosis of primary and metastatic brain tumors and consequently management of the treatment. To our knowledge this is the first such study on brain tumors from India.