Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, liver metastases from a patient with a pancreatic glucagonoma producing the syndrome have been investigated histologically, ultrastructurally, and immunocytochemically. A comparison has also been made between the metastases and the primary pancreatic tumor investigated in a parallel study. In the metastatic tissue, glucagon-, pancreatic polypeptide (PP)-, and somatostatin-containing cells were found together with a majority of cells without any immunoreactivity. Glucagon-positive cells were much more numerous than PP- and somatostatin-immunoreactive cells. As in the primary tumor, double immunogold staining of ultrathin sections demonstrated the co-existence of glucagon and PP immunoreactivities in most of the granulated cells, but PP immunolabeling was often faint, so that it probably could not be revealed by the PAP method in light microscopical sections. Such a finding, together with the histological and ultrastructural features, is consistent with an ontogenic and phylogenetic primitiveness of the metastatic cell population.
Pancreas 1989
PMID:A malignant tumor of the pancreas producing glucagonoma syndrome: immunocytochemistry and ultrastructure of liver metastases and comparison with the primary tumor. 254 78

The clinical evolution of type I multiple endocrine neoplasia (MEN I) was studied in 45 patients among a consecutive series of 172 with Zollinger-Ellison syndrome (ZES). These 172 patients were seen in our hospital between 1959 and 1989. Diarrhea was half as frequent in ZES-MEN I as in sporadic ZES cases. At diagnosis, mean basal acid output and serum gastrin levels in MEN I patients (28.8 +/- 6.6 mmol/h and 587 +/- 487 pg/ml, respectively) were not different from those observed in the others with sporadic ZES. Laparotomy was performed in all 36 patients with no diffuse liver involvement to attempt the removal of gastrinomas. Twenty-nine patients had adenomas, located in the pancreas in 21, in the duodenal wall in 3, and in both in 5. Adenomas were multiple in 23 cases (78%). No tumor was found in seven patients. Twenty-nine of the 36 operated patients were tumor-free after surgery; 7 died in the postoperative period between 1959 and 1970. Median follow-up of the 38 other patients was 95 months (range 17-278 months). Among the 24 patients without residual tumor at discharge (group I), biological and/or morphological evidence of a persistent or recurrent source of gastrin was obtained in 22. Among the 14 patients with residual tumor (group II), an increase in tumor size was seen in 5 after a median of 27 months (range 9-36 months), while no change occurred in 9 after 54 months (3-100 months). Actuarial survival curves were not different, either in group I versus group II patients (67 and 72% at 5-year follow-up, respectively) or in MEN I versus sporadic ZES patients. Apparently, complete resection of primary tumor did not reduce the incidence of subsequent liver metastases. In all, 21 of the 45 patients had malignant gastrinomas (47%), consisting of liver metastases in 14 (31%), metastatic lymph nodes in 11 (24%), and lung metastases in 2 (4%). Monitoring of fundic argyrophil cells disclosed hyperplasia in 13 of the 14 MEN I patients (92%), and 5 had invasive carcinoid tumors. Taken together, these results prompt us to recommend that in ZES-MEN I patients, surgery should be avoided and oxyntic mucosa regularly monitored.
Pancreas 1993 May
PMID:Clinical, anatomical, and evolutive features of patients with the Zollinger-Ellison syndrome combined with type I multiple endocrine neoplasia. 809 74

Calcitonin release has rarely been reported in patients (pts) with neuroendocrine pancreatic tumors (NPT). The aim of this study was to describe the characteristics of calcitonin-secreting tumors (CST) of the pancreas. Serum calcitonin determination was part of the prospective evaluation of 66 pts with NPT referred to our institution over a 3-year period. Six pts (9%) had elevated calcitonin levels [at least twice the limit of the normal value (N)]. Abdominal ultrasonography, computed tomography scan, and endoscopic ultrasound were performed to identify the primary tumor(s) and metastases. Immunostaining using anticalcitonin and other antibodies was performed on the surgical resection specimen (four pts) or biopsy of liver metastases (two pts). Three of the six pts (four males, two females; median age, 51.5 years) had diarrhea. Serum calcitonin levels (median, range) were 17.5 N (6N-40N). Slight elevations in serum somatostatin (1.2N-2.3N) were associated in three pts. Pancreatic tumors were single in five of six pts and evenly distributed in the head and in the tail. Five pts had metastases, mainly in the liver. Multiple endocrine neoplasia type I was present in one pt. Immunostaining using calcitonin and somatostatin antibodies was positive in four pts each, respectively, and areas that were positive for one peptide were negative for the other. Diarrhea disappeared in the two pts who responded to treatment of the tumor(s). Three of the four pts with liver metastases died from tumor progression after 2, 10, and 24 months, respectively. CST of the pancreas are often malignant and can be considered as functional in half of the cases, irrespective of the serum calcitonin levels. Somatostatin secretion is often associated. Although rare, calcitonin secretion should be investigated in NPT pts presenting with diarrhea that cannot be explained by an increase in other hormone levels or in patients with nonfunctioning NPT.
Pancreas 1998 May
PMID:Calcitonin-secreting tumors of the pancreas: about six cases. 959 18

In this study, we evaluated the prognostic significance of both p53 overexpression and proliferating activity in 133 primary ductal pancreatic carcinomas and in their regional synchronous lymph node metastases by immunohistochemistry, by using DO7 and MIB1 monoclonal antibodies, respectively. Tumor samples and lymph nodes were obtained from formalin-fixed, paraffin-embedded archival material of patients operated on between 1976 and 1996. Patients had a well-documented clinical history and were given accurate follow-up. p53 accumulation was observed in 77 (54%) of 133 primary tumors and in 22 (44%) of 50 patients with nodal metastases. The p53 overexpression was directly related to proliferating activity (p = 0.01) in the primary tumors. A significant direct correlation was present between the p53 expression in the primary tumor and in nodal metastases (p = 0.01); the same occurred for proliferating activity by MIB1 (p = 0.002). The patients' overall survival was affected by the presence of nodal (p = 0.02) and distant (p = 0.0001) metastases. The p53 immunoreactivity in nodal metastases was associated with a statistically significant decrease in the postoperative survival period (p = 0.005). Multivariate analysis confirmed these results, and the only two parameters that maintained statistical significance were M1 status (p = 0.0006) and p53 overexpression in nodal metastases (p = 0.01).
Pancreas 1999 Jul
PMID:p53 overexpression in lymph node metastases predicts clinical outcome in ductal pancreatic cancer. 1041 88

Adenocarcinoma of the pancreas generally remains an incurable disease by available treatment modalities, demanding the development of a suitable cell-culture/animal model and the discovery and evaluation of novel therapeutic agents. We report the clonal preservation of a human pancreatic cell line (KCI-MOH1) established from a 74-year-old African-American man diagnosed with pancreatic cancer. Initially the human primary tumor was grown as a xenograft in SCID mice and, subsequently, a cell line was established from tumors grown as a xenograft as reported in our earlier publication. The molecular characterization of the primary tumor, the tumors grown as xenograft, and the cell line all revealed similar genotypic properties. By using an automated DNA sequencer, a K-ras mutation (codon 12, GGT to CGT, Gly to Arg) was detected in the pancreatic tumor tissue taken from the patient, whereas no p53 mutation was detected. The same K-ras mutation and unaltered p53 was also found in the xenograft tumor and in the KCI-MOH1 cell line. Chromosome analysis of the cultured cells revealed: 42,XY,add(3)(p11.2),der(7)t(7;12) (p22;q12),-10,-12,add (14)(p11),-18,add (20)(q13),-22/84, idemx2, which is the same chromosome complement found in xenograft tumors. The KCI-MOH1 cell line grows well in tissue culture and forms tumors in the SCID mice when implanted subcutaneously, as well as in orthotopic sites. The KCI-MOH1 cell line-derived SCID mouse xenograft model was used for efficacy evaluation of bryostatin 1, auristatin-PE, spongistatin 1, and gemcitabine alone and in combination. Tumor growth inhibition (T/C expressed as percentage), tumor growth delay (T - C), and log 10 kill for these agents were 38%, 22 days, and 0.53; 15%, 30 days, and 0.80; 24%, 25 days, and 0.66; and 10%, 33 days, and 0.90, respectively. When given in combination, two of seven gemcitabine + auristatin-PE-treated animals were free of tumors for 150 days and were considered cured. Animals treated with a combination of bryostatin 1 and gemcitabine and a combination of spongistatin and gemcitabine produced remissions in only one of seven mice. From these results, we conclude that (a) this is the first study illustrating that clonal characteristics of primary pancreatic tumors remained unchanged when implanted in mice and as a permanent cell line grown in vitro; and (b) there is a synergistic effect between gemcitabine and selected marine products tested in this study, which is more apparent in the gemcitabine and auristatin-PE combination. The results of this preliminary study suggest that these agents should be explored clinically in the treatment of pancreatic cancer.
Pancreas 1999 Nov
PMID:Clonal preservation of human pancreatic cell line derived from primary pancreatic adenocarcinoma. 1054 95

The study of pancreatic cancer (PaCa) requires orthotopic, clinically relevant animal models. The aims of this study were to establish an orthotopic model of ductal pancreatic adenocarcinoma in immunocompetent Lewis rats and to develop a scoring system to quantify local tumor infiltration and distant metastasis. Cells (10(7)) of the rat ductal PaCa cell line DSL-6A/C1 were injected s.c. into donor rats. After 8 weeks, either three (IPL-3) or five (IPL-5) fragments (1 mm3) of the resulting s.c. tumors were microsurgically implanted into the pancreas of recipient rats. In another series of animals, 10(7) DSL-6A/C1 cells were directly injected (INJ) into the pancreas. All animals were monitored daily until death or for 16 weeks. At autopsy, volume of primary tumors and ascites, local and systemic tumor spread, and histologic phenotype were assessed. IPL-5 resulted in significantly larger tumors (12,224 +/- 1,933 mm3), more local infiltration and systemic spread (score: 18.3 +/- 2.0 points), severe clinical tumor disease, and lethality (50%) in comparison to the other induction techniques (IPL-3: 283 +/- 115 mm3/3.5 +/- 0.8 points/0; INJ: 752 +/- 207 mm3/4.3 +/- 0.8 points/8%). Histologic examination revealed moderately to well-differentiated ductal tumors, surrounded by dense stroma. Intraperitoneal tumor dissemination in the INJ group occurred simultaneous with primary tumor growth, indicating PaCa cell spread during injection. Orthotopic implantation of five DSL-6A/C1 tumor fragments into the rat pancreas provides a valid clinical model of ductal pancreatic adenocarcinoma in immunocompetent rodents for preclinical treatment studies. The dissemination score we used permitted quantification of local and systemic tumor spread.
Pancreas 2001 Mar
PMID:An improved clinical model of orthotopic pancreatic cancer in immunocompetent Lewis rats. 1124 64

Lymphoepithelial carcinoma is a relatively common malignancy in the nasopharyngeal region, but it rarely occurs at other sites. We report a lymphoepithelial carcinoma in the pancreas of a 65-year-old male patient operated on for a gastric stump carcinoma 7 years previously. The solitary tumor in the pancreas presented as a circumscribed lesion and measured 5.5 cm in diameter. The tumor was densely infiltrated by lymphocytes, and the neoplastic cells fulfilled all criteria for a lymphoepithelial carcinoma. Several peripancreatic lymph node metastases were observed. Marked reactivity for Epstein-Barr virus (EBV) early RNA (EBER) was detected in the majority of tumor cells using in situ hybridization. Nuclear EBER signals were also detected in the previously operated gastric stump adenocarcinoma, which also exhibited focal lymphocytic infiltration but otherwise displayed a histology different from lymphoepithelial carcinoma and did not show local recurrence. Even though an unusually late metastasis of the gastric carcinoma cannot be ruled out, we favor the hypothesis that this patient developed an EBV-related pancreatic lymphoepithelial carcinoma as a second primary tumor, based on the considerable delay of this tumor manifestation, the unusual site, the pathologic presentation, the exclusively peripancreatic nodal spread, and the different histology of the lesion.
Pancreas 2004 Jan
PMID:Epstein-Barr virus-associated lymphoepithelial carcinoma in the pancreas. 1470 38

The Japan Pancreas Society (JPS) published the fifth Japanese edition of the General Rules for the Study of Pancreatic Cancer in 2002, the same year that the Union Internationale Contre le Cancer (UICC) published its sixth edition. The JPS fifth edition had been revised, based on data from 18,629 cases of carcinoma of the pancreas registered by the JPS (1981-1996) with the goal of making the General Rules simple, easy to understand, and reliable for predicting outcome. The 2 classifications are compared by analyzing the data on 3979 resected patients with tubular adenocarcinoma of the pancreatic head registered by the JPS, focusing on the reliability of predicting outcome. In the extent of the primary tumor (T category), survival rates differed significantly among the 4 groups (T1, T2, T3, T4) in the JPS and UICC classifications. In the extent of lymph node metastasis (N category), survival rates differed significantly among the 4 groups (N0, N1, N2, N3) in the JPS classification and also did significantly between the 2 groups (N0, N1) in the UICC classification. In the stage grouping, however, 2 classifications differed considerably. More than half of the cases of UICC stage II are equivalent to JPS stage IV. Comparison of survival curves according to stage reveals that stratification is much better in the JPS classification than in the UICC classification. These results indicate that the JPS classification is more reliable for predicting outcome as compared with the UICC classification.
Pancreas 2004 Apr
PMID:Classification of pancreatic cancer: comparison of Japanese and UICC classifications. 1508 62

Whereas mucinous cystadenomas of the pancreas are considered premalignant, serous cystadenomas are believed to remain benign. We present a case of an 80-year-old woman with a primary tumor of the pancreas that was histologically classified as serous cystadenocarcinoma. Because preoperatively available criteria that determine malignancy in serous lesions are lacking, observation is the preferred option in serous cystadenomas. Operating every serous lesion is not justified. Reviewing all reports of serous cystadenocarcinomas that have been published to date, we are providing recommendations for the management of this rare entity.
Pancreas 2005 Aug
PMID:Serous cystadenocarcinoma of the pancreas: management of a rare entity. 1602 6

Pancreatic adenocarcinoma is a genetic disease showing somatic mutations of multiple genes, including SMAD4. SMAD4 is a tumor suppressor gene that is inactivated in a sub-set of pancreatic adenocarcinoma, either by the intragenic mutation of one allele in combination with the loss of the other allele or by homozygous deletion of both alleles. This study examines SMAD4 expression in fine-needle aspiration cell blocks from patients with pancreatic adenocarcinoma, as well as a variety of human cancers, in order to assess its viability as a tumor marker. A total of 100 patients with pancreatic adenocarcinoma, with diagnostic material from fine-needle aspiration cell blocks were selected for this study. In addition cancers from different sites were examined in multitumor tissue microarrays, which included two tissue cores from neoplastic surgical resection specimens. Cancers studied included endometrium (n = 100), colon (n = 100), ovary (n = 100), lung (n = 100), breast (n = 100), and malignant melanoma (n = 100). The sections were immunostained with SMAD4 using pressure cooker antigen retrieval labeled polymer horseradish peroxidase (DAKO), and the DAKO autostainer. Immunohistochemical expression was scored as negative, 1+, 2+, 3+. Only 2+ and 3+ staining was considered as positive staining. SMAD4 staining was nuclear and the results for tumor cell positivity for primary sites studied are as follows: Pancreas (80/100; 80%), endometrium (0/100; 0%), colon (0/100; 0%), ovary (3/100; 3%), lung (0/100; 0%), breast (2/100; 2%), and malignant melanoma (4/100; 4%). This study suggests that SMAD4 is an important marker for confirming a diagnosis of pancreatic adenocarcinoma as a primary tumor, as well as when it presents as a metastatic tumor on small fine-needle aspirate samples.
 ...
PMID:The utility of SMAD4 as a diagnostic immunohistochemical marker for pancreatic adenocarcinoma, and its expression in other solid tumors. 1785 80


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