ceruletide and Liver-Neoplasms

Topics: Alcohol Drinking; Animals; Carcinogens; Carcinoma, Pancreatic Ductal; Central Nervous System Depressants; Ceruletide; Cytokines; Diet, Western; Ethanol; Hepatocytes; Homeodomain Proteins; Liver Neoplasms; Mice; Mutation; Nicotine; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras); Trans-Activators

Pancreatic ductal adenocarcinoma (PDA), one of the deadliest human cancers, often involves somatic activation of K-Ras oncogenes. We report that selective expression of an endogenous K-Ras(G12V) oncogene in embryonic cells of acinar/centroacinar lineage results in pancreatic intraepithelial neoplasias (PanINs) and invasive PDA, suggesting that PDA originates by differentiation of acinar/centroacinar cells or their precursors into ductal-like cells. Surprisingly, adult mice become refractory to K-Ras(G12V)-induced PanINs and PDA. However, if these mice are challenged with a mild form of chronic pancreatitis, they develop the full spectrum of PanINs and invasive PDA. These observations suggest that, during adulthood, PDA stems from a combination of genetic (e.g., somatic K-Ras mutations) and nongenetic (e.g., tissue damage) events.

Topics: Animals; Carcinoma in Situ; Carcinoma, Pancreatic Ductal; Cell Lineage; Cell Transformation, Neoplastic; Ceruletide; Doxycycline; Genes, ras; Liver Neoplasms; Lung Neoplasms; Mice; Mice, Mutant Strains; Mutation; Neoplasm Invasiveness; Pancreas; Pancreatic Neoplasms; Pancreatitis, Chronic; Signal Transduction

The Human pancreatic carcinoma cell line KP-1N and its clone KP-1NL which has a high rate of liver metastasis were established. Ki-ras DNA point mutation on the codon 12 was found. The growth of KP-1N was stimulated by a physiological range of concentration (10(-11)-10(-10) M) of cholecystokinin and the increase was inhibited by the addition of a cholecystokinin receptor antagonist (CR 1505). Daily injections of CR 1505 (35 mg/kg) diminished the number of tumor colonies in the liver that were formed after an intrasplenic injection of the highly liver metastatic KP-1NL cells. These results suggest that cholecystokinin antagonists may be useful as growth inhibitors for some pancreatic cancer.

Topics: Adenocarcinoma; Animals; Ceruletide; Cholecystokinin; Humans; In Vitro Techniques; Liver Neoplasms; Mice; Mice, Nude; Pancreatic Neoplasms; Proglumide; Tumor Cells, Cultured

Transcatheter arterial embolization (TAE) with the concurrent use of caerulein was assessed for the purpose of preventing gallbladder complications often seen after TAE of hepatic carcinoma. Ninety-six cases with primary hepatic carcinoma, who had undergone TAE in the right hepatic arterial region over the past 4 years, were divided into three groups: 22 cases for which embolization was possible on a selective basis by passing the catheter to the peripheral side beyond the bifurcated region of the cystic artery; 40 cases who had undergone TAE in which caerulein was not administered, from the central side of the bifurcated region of the cystic artery; and 34 cases given 20 micrograms caerulein 15-30 min before TAE. A comparison was made using the abdominal pain, pyrexia, rate of leukocytosis and the US findings of the gallbladder as the indices of the gallbladder complications. As a result, it became evident that it was possible to prevent or alleviate gallbladder complications if caerulein were administered before TAE in cases where the embolizing substances were infused in the right hepatic artery from the central side of the bifurcated region of the cystic artery. It was conclusively shown that the gallbladder blood flow decreases if the organ is contracted by caerulein, which in turn causes a decrease in the inflow of the embolizing substances whereby complications are alleviated.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Ceruletide; Cholecystography; Embolization, Therapeutic; Female; Gallbladder; Hepatic Artery; Humans; Infarction; Liver Neoplasms; Male; Middle Aged

The severity of pain occurring in the right hypochondrium after transcatheter hepatic arterial embolization carried out in the treatment of malignant hepatic tumors was compared between a caerulein-treated group and a non-caerulein-treated group. The caerulein-treated group and the non-treated group each comprised nine patients Gelfoam powder was used as an occlusive agent. Even though there were no statistically significant differences between the two groups, the caerulein-treated group tended to demonstrate milder pain in the right hypochondricus, less incidence of tenderness and needed fewer administrations of analgesic than did the non-treated group. None of the three patients showing cystic artery contraction after the caerulein administration developed right hypochondricus pain or tenderness, or required the administration of analgesic. It was concluded that caerulein is useful in relieving right hypochondricus pain occurring after transcatheter hepatic arterial embolization.

Topics: Abdomen; Adolescent; Adult; Aged; Antineoplastic Agents; Catheterization, Peripheral; Ceruletide; Embolization, Therapeutic; Gallbladder; Hepatic Artery; Humans; Liver Neoplasms; Middle Aged; Pain

While transcatheter hepatic arterial embolization (TAE) has been extensively performed as a form of treatment for nonresectable malignant hepatic tumors, complications, such as abdominal pain, fever or leukocytosis due to gallbladder infarction by embolic materials frequently occur and have not yet been overcome. We devised a new procedure for reducing the incidence of gallbladder infarction by administering caerulein prior to TAE. Between 1984 and 1986, 63 patients with hepatocellular carcinoma were treated by TAE with the use of Gelfoam. These patients were divided into 3 groups. Fourteen patients underwent TAE in which the tip of the catheter was placed in the right hepatic artery distal to the origin of the cystic artery (group A). In the other patients the tip of the catheter was placed proximal to the origin of the cystic artery; 40 patients were not treated by caerulein (group B); 9 patients were administered caerulein 20 micrograms intramuscularly 15 to 30 minutes prior to TAE. The incidence of complications after TAE, such as abdominal pain, fever over 38 degrees C, leukocytosis and ultrasonographical abnormalities of the gallbladder was compared in these 3 groups. The results showed that in group C (TAE after administration of caerulein), the incidence of complications was significantly decreased compared with group B(TAE without caerulein). The authors suggest that post-TAE infarction of the gallbladder is effectively diminished by contracting it with caerulein.

Topics: Carcinoma, Hepatocellular; Ceruletide; Embolization, Therapeutic; Gallbladder; Humans; Infarction; Liver Neoplasms