Peritoneal dissemination in gastric cancer is a common fatal clinical condition with few effective therapies available. We studied the therapeutic effect of a tumor-targeting drug delivery system that uses cisplatin-encapsulated and Tf-conjugated PEG liposomes (Tf-PEG liposomes) in nude mice with peritoneal dissemination of human gastric cancer cells. Small unilamellar Tf-PEG, PEG or DSPC/CH liposomes (bare liposomes) encapsulating cisplatin were prepared by reversephase evaporation followed by extrusion. Electron microscopic studies revealed that Tf-PEG liposomes were internal- Key words: liposome; targeting; transferrin; peritoneal dissemination; gastric cancerPeritoneal dissemination is the most frequent noncurative factor and the most common type of recurrence after curative surgery in patients with gastric cancer. 1 Control of this metastasis is one of the most important challenges in treating gastric cancer. There have been few reports of effective treatment for peritoneal dissemination in patients with gastric cancer. 2,3 As a clinical locoregional chemotherapy, various anticancer drugs in solution form have been administered i.p. to expose the drug directly to peritoneal tumor cells. 4 However, small water-soluble molecules, such as cisplatin or mitomycin C, are absorbed easily through the large peritoneal surface into the circulating blood. It is difficult to maintain a high drug concentration for a long time in the peritoneal cavity. 5,6 Therefore, i.p. administration of anticancer drugs in solution form does not always produce the desired effect.Liposomes, known to be drug carriers, have various advantages. 7,8 First, they encapsulate various drugs such as water-soluble, lipid-soluble or high m.w. substances and release them in a sustained manner. Second, the antigenicity and toxicity of liposomes are very low because they consist of lipid, which is a natural component of organisms. Third, the biodistribution of liposomes can be controlled by the size or lipid component. Fourth, various materials, such as antibodies or chemical compounds, can modify the surfaces of liposomes. However, the therapeutic application of liposomes has been limited by their rapid clearance from the bloodstream and by their uptake by the RES. Recent efforts have been made to reformulate the liposome composition, to reduce its affinity to the RES. Liposomes modified with amphipathic PEG are not readily taken up by macrophages in the RES and, hence, stay in the circulation for a relatively long time. 9 -14 To increase the therapeutic effect and decrease side effects, tumor-specific targeting therapy has been advocated. Intracellular targeting using iron-saturated Tf as a ligand for receptor-mediated endocytosis has attracted attention. Tf is a glycoprotein that transports ferric ions in the body and the Tf receptor is internalized into cells by endocytosis through the binding of Tf. This receptormediated endocytosis is a normal physiologic process by which iron is delivered to cells. [15][16][17] Also, the Tf receptor concen...
A transverse incision for distal gastrectomy may be more beneficial than an upper midline incision in attenuating postoperative wound pain, decreasing the incidence of postoperative pneumonia, and preventing postoperative intestinal obstruction.
The appearance of Hanganutziu and Deicher (HD) antibody in the sera of patients suffering from various diseases, including malignancies of some organs and liver disorders, was investigated by enzyme-linked immunosorbent assay using N-glycolylneuraminyl-lactosylceramide (HD3) and 4-O-acetyl-HD3 as the antigenic molecules. More than 25% of sera from patients suffering from malignancies, cholelithiasis and liver cirrhosis had HD antibody, whereas none of 41 sera from healthy persons had HD antibody. The percentage of HD antibody-positive patients was similar in stages I, II and III of gastric cancer and recurrence cases. Antibody titers of the positive patients in each stage were also not different from those in each other stage. These results indicated that HD antigenic expression on cancerous tissue is not dependent on the cancerous malignancy. The HD antibody level was elevated after surgical removal of cancerous tissues in 5 of 6 patients examined, indicating that tumor growth absorbed the serum antibody. Serum antibody against 4-O-acetyl-HD3 was detected independently of HD3 antibody in some cases; however, in most cases, correlation between the two antibody titers was observed.
The changes in the hepatic hemodynamics were promptly reflected in the biliary pressure in dogs. Both wedged hepatic venous pressure and portal venous pressure increased in response to the elevated biliary pressure, and conversely decreased following rapid biliary decompression, suggesting that the changes in the biliary pressure might affect the hepatic hemodynamics post-sinusoidally. It was supposed that too rapid biliary decompression might trigger the following consequences; 1) decrease in sinusoidal pressure, 2) increase in sinusoidal inflow, and 3) extravasation of intravascular fluid in the perivascular space. When these were not sufficiently compensated, they could trigger shock in the jaundiced patients.
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