摘要:

The interaction of estramustine and estromustine, cytotoxic metabolites of estramustine phosphate (Estracyt), with protein-binding sites in rat pancreatic tissue was examined. These compounds were bound with relatively high affinity (Kd10 nmol/L) to binding sites constituting 0.02–0.03% of total protein. Further characterization of these binding sites revealed a native molecular weight of 24–30,000 a sedimentation coefficient of 3.4 S, and a heterogenous surface-charge distribution by ion-exchange chromatography. Removal of endogenously bound ligand(s) by acetone precipitation or charcoal treatment increased binding significantly. Similar binding sites were present in two of two human pancreatic tumors, but was low or absent in the only histopathologically normal pancreas examined as well as in serum and pancreatic juice. These binding sites were distinct from the “estrogen-binding protein” reported in normal pancreas from various species, but were similar to the “estramustine-binding protein” (EMBP) in rat ventral prostate with respect to ligand specificity and the positive effect of endogenous ligand removal on binding. Furthermore, specimens demonstrating presence of these binding sites also indicated cross-reactivity with antibodies raised against the latter protein, suggesting an immunochemical relation between estra-/estromustine-binding sites in the pancreas and rat prostate EMBP. The presence of high-affinity sites for estramustine and estromustine in human pancreatic carcinomas make this type of tumor a possible target tissue for compounds that exert antiproliferative as well as antimitotic activity in vitro.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by flow cytometry in 46 patients whose disease had been detected and treated with surgery. Lymph node involvement was observed at the time of diagnosis in 36% of patients with diploid tumors and in 79% of patients with aneuploid tumors (p= 0.017), but no clear relation to metastasis could be observed (p= 0.201). The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors (p= 0.007). Ail patients who underwent radical surgery had diploid DNA content and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and none of the aneupioid cases survived 1 year. Over the 1-year period, in order of importance, the type of treatment (p< 0.001), DNA ploidy (p= 0.004), tumor size (p= 0.0046), and lymph node status (p= 0.027) predicted survival. Aneuploidy showed a significant association with decreased cumulative survivalp= 0.015), and a suggestive relationship with SPF was found. The results suggest that DNA ploidy of pancreatic cancer can be used in dividing the patients into different prognostic groups. The value of the detection of aneuploidy, however, is limited, because diploid pancreatic cancers are also generally rapidly fatal.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The nuclear T3receptors in rat pancreas exhibit a characteristic maturation pattern during development and are subjected to autologous regulation by thyroid hormones. To see if glucocorticoids also regulate T3receptors in the pancreas, rats at various age groups were subjected to experimental conditions that altered their glucocorticoid status and the corresponding changes in nuclear T3receptors, and exocrine enzymes in their pancreata were evaluated. Hydrocortisone administration to normal suckling and weaning rats did not change total T3binding capacity or the dissociation constant as measured at 30°C (Kd30). A significant increase in the degree of occupancy of the T° receptor was found at 5–10 days after treatment with hydrocortisone (42.2 + 4.1% vs. 19.2 + 2.0%). T3binding capacity and exocrine enzyme concentrations were significantly reduced in both adrenalectomized (Adx) pups and adults, indicating a continuous dependency on glucocorticoid from preweaning to adulthood. In adrenalectomized rat pups, either T4or glucocorticoid replacement alone restored T3binding capacity and exocrine enzyme concentrations. T3and glucocorticoid were given together to Adx rats, the level of stimulation of both pancreatic T3binding capacity and exocrine enzyme concentrations was found to be equal to the sum of the stimulation by each of these hormones when given alone. Furthermore, a good correlation was found between Bmax30(Bmaxmeasured at 30°C, representing total sites) for T3binding and exocrine enzyme activities in different groups following various experimental treatments. These findings provide further evidence that thyroxine can act directly on the rat pancreas presumably through the T3receptor in regulating the postnatal development of the exocrine enzymes.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

There is strong evidence indicating that the pancreas is under the influence of sex steroid hormones, and that it may even participate in their biosynthesis and metabolism. In the present study, [3H]testosterone was perfused into the isolated canine pancreas, and measured in the effluent with several of its metabolites (5a-dihydrotestosterone, androstenedione, and estradiol). Results show that testosterone is readily transformed by the canine pancreas. The main product found in the effluent is androstenedione. The testis and spleen were also perfused with [3H]testosterone and used as controls. In both cases, this hormone appeared mostly unchanged in the effluent as compared to the pancreatic perfusion (p<0.0001). From our data, we conclude that the canine pancreas has the capacity to transform sex steroid hormones, and could be considered an extragonadal site of sex steroid biosynthesis.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Pretreatment of rat pancreatic acini with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) for 5 or 10 min reduced cytosolic free calcium and amylase secretion stimulated by submaximal concentration (10−6M) of carbachol in a dose-dependent manner. 10−7MTPA inhibited initial amylase secretion and had no effect on sustained secretion stimulated by 10 10−7Mcarbachol. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), a protein kinase C inhibitor, partially blocked these inhibitory effects of TPA. Cytosolic calcium concentration and initial amylase secretion were recovered with 1o-100 μM H7 in TPA-treated acini. H7 was more effective thanN-(2-guanidinoethyl)-5-isoquinoline-sulfonamide hydrochloride in increasing cytosolic free calcium in TPA-treated acini. TPA completely blocked an increase in cytosolic free calcium by 10mMNaF. These findings indicated that TPA caused the inhibitory effects by means of activating protein kinase C, and suggested that protein kinase C might regulate enzyme secretion by inhibiting calcium mobilization, probably through a postreceptor-mediated mechanism.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A case of malignant T-cell lymphoma of the pancreas is presented. Previously reported histological data confirming this disease are reviewed to elucidate features that may suggest this disease and how to differentiate between T- and B-cell lymphoma of the pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0885-3177    

出版商:OVID    

年代:1991

数据来源: OVID