Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Immunohistochemical characterization of endocrine cells in experimental exocrine pancreatic cancer in the Syrian golden hamster. 135 11

An interim analysis of the current EORTC studies in advanced testicular cancer indicates that (a) for low volume metastatic disease the addition of bleomycin (B) to etoposide (E) and cisplatinum (P) may not be necessary, and (b) for high volume metastatic disease the alternating schedule of PVB/BEP is not superior to treatment with BEP. Future studies will subdivide patients into 3 groups. Those with low volume metastatic disease will receive EP using 2 dose schedules for cisplatin. Those with high volume metastases will receive either BEP or etoposide, ifosfamide and cisplatinum (VIP). Those with ultra-high volume metastases will receive BOP/VIP, possibly randomised against another intensive chemotherapy schedule.
 ...
PMID:Potential advances in combination chemotherapy for advanced testicular cancer. 245 13

Proliferation of endocrine cells was found to occur during early, i.e., first 12 weeks, exocrine pancreatic carcinogenesis after 6 weekly treatments of Syrian hamsters with the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). Cells containing insulin (Ins), glucagon (Glu), and somatostatin (Som) were noted in all stages of tumor development and were present in adenocarcinomas and in metastases to the liver. Some of the cancer cells were of amphicrine (hybrid) type, i.e., produced both mucin and endocrine substances. Measurement of these hormones revealed a significant decrease in plasma Ins during early stages of carcinogenesis with concomitant increase of Ins level in pancreatic juice at 12 weeks after 6 weekly BOP treatments. Plasma Glu and Som were not changed. The changes noted, particularly in relation to Ins, suggest that proliferation of endocrine cells in pancreatic carcinogenesis may be associated with alterations in hormone secretion.
 ...
PMID:Alteration of pancreatic endocrine cell patterns and their secretion during pancreatic carcinogenesis in the hamster model. 257 21

Hormones, particularly gonadotropins, have been implicated in the development of ovarian cancer. Chronic administration of agonistic analogs of luteinizing-hormone releasing-hormone (LH-RH) induces an inhibition of the pituitary-gonadal axis. The blockade of the release of luteinizing-hormone and follicle-stimulating hormone (FSH) may exert a possible therapeutic effect on ovarian cancer. We examined the results of prolonged administration of D-Trp-6-LH-RH, an agonistic analog of LH-RH in experimental ovarian cancer. We used the recently developed ovarian cancer model in rats, which is produced by treatment of pregnant rats with N-nitrosobis(2-oxopropyl)amine (BOP), following which a high incidence of ovarian tumors are induced in the offspring. In morphologic aspects the induced tumor resembles human ovarian neoplasms. Once a month administration of a delayed release preparation of microcapsules of D-Trp-6-LH-RH prolonged the survival and decreased tumor growth and the incidence of metastases. Additional experimental and clinical studies are needed to determine the efficacy of the treatment with LH-RH analogs in ovarian cancer.
 ...
PMID:Treatment of experimental ovarian carcinoma with monthly injection of the agonist D-Trp-6-LH-RH: a preliminary report. 296 36

To examine the role of diabetes in pancreatic cancer, 4 groups of Chinese hamsters--2 from genetically diabetic and 2 from non-diabetic lines--were treated with N-nitrosobis(2-oxo-propyl)amine (BOP) at different dose levels and intervals. In one group (referred to as the VA group), BOP was given weekly at a 5 mg/kg body wt. level for 18 or 23 weeks, whereas the other group (the EP group) received a weekly dose of 2.5 mg/kg body wt. for life. Except for diet and experimental design, all other laboratory conditions were similar in the two institutions. No VA hamster developed tumors. Three of 22 non-diabetic EP hamsters (but none of the diabetic hamsters) developed pancreatic hyperplastic and neoplastic lesions, comprising ductular cell adenomas (3 hamsters), carcinoma in situ (1 hamster), a well-differentiated adenocarcinoma (1 hamster), and a poorly differentiated adenocarcinoma (1 hamster) with regional lymph node metastases. In addition, over 50% of the EP hamsters had neoplasms for which the incidences and morphology did not vary between diabetic and non-diabetic groups or between the sexes. These were primarily of the liver (cholangiomas), lungs (adenomas) and skin (trichoepitheliomas, squamous cell carcinomas). The differing carcinogenic response of the two hamster groups to BOP apparently is not related to the total BOP dose, but rather to other factors, including the length of observation time.
 ...
PMID:Pancreatic carcinogenicity of N-nitrosobis(2-oxopropyl)-amine in diabetic and non-diabetic Chinese hamsters. 381 30

Weekly intragastric application of N-nitrosobis(2-oxopropyl) amine (BOP) at a dose of 10 mg/kg body wt induced prostatic cancer in 5 out of 15 MRC rats. Hyperplasia and metaplasia of the prostatic gland were found in 13 rats with or without cancer. All tumors had developed in the dorsal lobe, had reached a size of up to 20 mm and were invasive. Distant metastases were not observed. Although hyperplastic lesion were of a glandular type, all carcinomas had squamous cell character. All cases of prostatic cancer were associated with papillomas or carcinomas of the urethral epithelium, which had initially developed in the colliculus seminalis. The induction of prostatic cancer for the first time by a systemic application by a nitrosamine provides a promising model for understanding basic principals of prostatic cancer.
 ...
PMID:A new prostatic cancer model: systemic induction of prostatic cancer in rats by a nitrosamine. 617 36

The synthetic dithiolethione Oltipraz has marked cancer chemopreventive and phase II enzyme inducing activity in various animal carcinogenesis models, but has not been examined in any animal models of ductal pancreatic cancer relevant to the human disease. The chemopreventive potential of Oltipraz on pancreatic tumor incidence and multiplicity was examined in the N-nitrosobis(2-oxopropyl)-amine (BOP)-induced ductal pancreatic adenocarcinoma model in Syrian hamsters. Animals were maintained on control semipurified diets or semipurified diets containing 300 and 600 mg/kg Oltipraz beginning 2 weeks prior to BOP initiation and throughout the 26 week study. Oltipraz at 300 mg/kg had no effect on the incidence or multiplicity of preneoplastic, neoplastic or metastatic lesions, while at 600 mg/kg dietary Oltipraz the incidence of pancreatic adenocarcinomas was reduced significantly (P < or = 0.05) compared to BOP-treated controls. Dietary Oltipraz at both doses had a significant influence on reducing mortality and morbidity in tumor-bearing animals with metastatic disease. At 26 weeks, total hepatic glutathione-S transferase (GST) activity and GST mu activity were elevated significantly in Oltipraz-treated animals, while total pancreatic GST activity was reduced, albeit not significantly. Serum lipase activity, a marker for pancreatic damage, exhibited a progressive decline in BOP-treated animals administered Oltipraz compared to BOP-treated controls at 12 weeks of the study; by week 26, lipase activity was comparable in all groups and reduced compared to activity at week 12. Positive nuclear immunostaining for the p53 tumor suppressor protein, a hallmark of human pancreatic cancer and a transient response to DNA damage, was observed in only a small percentage of BOP-induced pancreatic lesions and was not influenced Oltipraz administration. Further chemoprevention and pharmacologic studies of Oltipraz in relevant animal models of ductal pancreatic cancer could provide a foundation for future studies in human populations at potential risk for pancreatic cancer.
 ...
PMID:Chemopreventive activity of Oltipraz against N-nitrosobis(2-oxopropyl)amine (BOP)-induced ductal pancreatic carcinoma development and effects on survival of Syrian golden hamsters. 755 69

The liver is the most common site of metastasis in pancreatic cancer, and there are no promising strategies to treat it. Angiostatin, a kringle-containing fragment of plasminogen, is a potent inhibitor of angiogenesis. The effect of angiostatin on liver metastasis in pancreatic cancer was investigated by using our established hamster model of liver metastasis. Pancreatic cancer cells (PGHAM-1, 1 x 10(6)) derived from N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumor in Syrian golden hamsters were transplanted into the spleen of female hamsters, and the animals were subcutaneously injected with angiostatin and saline. Subsequently, the macroscopic appearance of liver surface metastases was evaluated. In addition, histological sections of the liver metastases were analyzed for neovascularization, proliferation, and apoptosis on the basis of von Willebrand factor, argyrophilic nucleolar organizer region (Ag-NOR), and TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, respectively. The results showed significant tumor growth retardation and inhibition of angiogenesis in metastatic liver tumors in response to treatment with angiostatin. Moreover, the metastases remained in a nearly dormant state due to a balance between apoptosis and proliferation of the tumor, with no detectable side effects. This is the first experimental trial of angiostatin on pancreatic cancer and liver metastasis. The results suggest that angiostatin therapy could be effective against liver metastases of pancreatic cancer.
 ...
PMID:Effect of angiostatin on liver metastasis of pancreatic cancer in hamsters. 1092 Feb 80

The influence of pancreatic biopsy during laparoscopy with carbon dioxide (CO2) and helium on the incidence of port site and liver metastasis in pancreatic carcinoma is still unknown. Ductal adenocarcinoma of the pancreas was induced in Syrian hamsters (n = 30) by injection of N-nitrosobis-2-oxopropylamin (BOP, 10 mg/kg body weight/week) for 12 weeks. In week 13, hamsters were randomized in 3 groups (n = 10): While in group 1 (gr. 1) a laparotomy and biopsy of pancreatic lymph nodes was performed, gr. 2 and gr. 3 underwent a laparoscopic biopsy either with CO2 or helium. Therefore, one trocar was located in the left (biopsy) and the right abdominal wall (camera). In the 18th week all animals were sacrificed and the incidence of abdominal wall, port site and liver metastases was histologically determined. While there were abdominal wall metastases after laparotomy in 10% (n = 1), we observed trocar metastases in the CO2 group in 20% (n = 2). However, there were no trocar metastases in the helium group. The incidence of liver metastasis did not differ between the laparotomy and the helium group (20% vs 30%), but was increased in the CO2 group (60%). Laparoscopic biopsy of pancreatic lymph nodes with CO2 increased the incidence of port site and liver metastases in pancreatic cancer. The helium group was equal to the laparotomy group in this respect. Thus, staging laparoscopy with helium might become an alternative to explorative laparotomy in pancreatic cancer.
Clin Exp Metastasis 2000
PMID:The impact of laparoscopic biopsy of pancreatic lymph nodes with helium and carbon dioxide on port site and liver metastasis in BOP-induced pancreatic cancer in hamster. 1120 32

Only about half of patients with a poor-prognosis non-seminomatous germ-cell tumours can achieve a cure. The aim of this phase II study was to assess the efficacy and toxicity of a dose-dense alternating chemotherapy regimen in this subset of patients. High volume non-seminomatous germ-cell tumours was defined as follows: at least two sites of non pulmonary metastases, an extragonadal primary tumour, a serum human chorionic gonadotropin level higher than 10 000 mIU x ml(-1), or a alpha-foetoprotein level higher than 2000 mIU ml(-1). Patients who fulfilled these criteria were treated with the so-called BOP-CISCA-POMB-ACE regimen (bleomycin, vincristine, and cisplatin; cisplatin, cyclophosphamide, and doxorubicin; cisplatin, vincristine, methotrexate, and bleomycin; etoposide, dactinomycin, and cyclophosphamide) plus granulocyte colony-stimulating factor. A total of 58 patients were enrolled. Patients were retrospectively classified according to the International Germ-Cell Cancer Consensus Group classification; 38 patients (66%) had poor-prognosis disease and 19 patients (33%) had intermediate-prognosis. Patients received a median of 2.5 courses (range 0.25 to five courses) of the BOP-CISCA-POMB-ACE regimen. Forty-two patients (72.4%) had a complete response to therapy. With a median follow-up time of 31 months, the 3-year progression-free survival rate was 71% (95% confidence interval, 60 to 84%) and the 3-year overall survival rate was 73% (95% confidence interval: 62 to 86%). The 3-year PFS rates were 83% (95% confidence interval: 68 to 100%) in the intermediate-prognosis group and 65% (95% confidence interval: 51 to 82%) in the poor-prognosis group. Early side effects included mainly grade 4 haematologic toxicity (neutropaenia in 79% of patients, thrombocytopaenia in 69%, anaemia in 22%), grade 4 stomatitis (19%), and four early deaths (7% of patients), at least partially related to toxicity. The dose-dense BOP-CISCA-POMB-ACE regimen is highly active in patients with non-seminomatous germ-cell tumours classified as intermediate-prognosis or poor-prognosis according to the International Germ-Cell Cancer Consensus Group. Because outcomes with this regimen compare favourably with outcome after standard therapy, dose-dense chemotherapy should be further investigated in this subset of patients.
 ...
PMID:Alternating dose-dense chemotherapy in patients with high volume disseminated non-seminomatous germ cell tumours. 1208 4


1