zinostatin and Peritoneal-Neoplasms

A case of hepatocellular carcinoma, successfully treated with multimodal loco-regional treatments, is reported. An 80-year-old male presented with multiple pulmonary and peritoneal metastases 4 months after right heimihepatectomy for ruptured HCC. Bronchial artery infusion of mitomycin C induced pulmonary tumor regression and stabilization. Peritoneal tumor was treated by arterial infusion of SMANCS, followed by percutaneous injection of absolute ethanol, which ended in surgical removal in 28-postoperative month due to abscess formation. He had been well until right adrenal and left pulmonary metastases appeared. Resection of both metastases was carried out in 39-post hepatectomy month. Recurrent left pulmonary metastasis was treated with two sessions of bronchial artery infusion with no effect this time. Video-assisted partial resection of the left lung was performed in 54 post-hepatectomy month. But his AFP level kept rising. Eventually pulmonary metastasis recurred and tumor thrombus reached the left atrium 58 months after hepatectomy. He wanted no more treatment. He died of cerebral infarction caused by tumor thrombus. He enjoyed a good QOL for five years through multimodal loco-regional treatments.

Topics: Aged, 80 and over; Antineoplastic Agents; Bronchial Arteries; Carcinoma, Hepatocellular; Ethanol; Hepatectomy; Humans; Infusions, Intra-Arterial; Injections, Intralesional; Liver Neoplasms; Lung Neoplasms; Male; Maleic Anhydrides; Mitomycin; Peritoneal Neoplasms; Polystyrenes; Zinostatin

The monoclonal antibody A7 (Mab A7) against human colonic cancer also reacts with human gastric cancer at a high rate. We produced a conjugate of neocarzinostatin (NCS) with Mab A7 (A7-NCS). The in vitro anticancer effect of A7-NCS on the antigen-positive human gastric cancer cell line MKN45 was stronger than that of free NCS. Nude mice models of peritoneal dissemination were established by the intra-peritoneal inoculation of MKN45. These models were divided into three groups. The anticancer effect observed in the group that received the intra peritoneal injection of A7-NCS was superior to that observed in the group that received the intra-venous injection and the group that received no treatment. In conclusion, the intra-peritoneal injection of A7-NCS was a useful treatment method for the peritoneal dissemination of gastric cancer.

Topics: Adenocarcinoma; Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antigens, Neoplasm; Cell Line, Tumor; Humans; Infusions, Parenteral; Injections, Intravenous; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Seeding; Peritoneal Neoplasms; Stomach Neoplasms; Zinostatin

A7-NCS, which is a conjugate of the monoclonal antibody A7 against a human colonic cancer and the anticancer agent neocarzinostatin (NCS), reacts with human gastric cancers at a high rate. The anticancer effect of A7-NCS is stronger than that of free NCS. Nude mice models of peritoneal dissemination were established simply by intra-peritoneal inoculation of the antigen-positive human gastric cancer cell line MKN45. Using these models, the anticancer effect of A7-NCS against the peritoneal dissemination of gastric cancer was examined. The murine peritoneal dissemination models were divided into three groups. The anticancer effect of the group injected intra-peritoneally with A7-NCS 2 days after cancer inoculation was compared with that injected 18 days after inoculation. The anticancer effect in the 18-day group was inferior to that in the 2-day group, but was superior to that in the non-treated group. To get a better result in the 18-day group, which is in the advanced stage of peritoneal dissemination, repeated injection and the dose of A7-NCS should be examined.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Humans; Immunotoxins; Mice; Mice, Nude; Peritoneal Neoplasms; Stomach Neoplasms; Zinostatin

The murine monoclonal antibody A7 (MAb A7) is reactive against most human gastric cancer cell lines. Using a nude mouse peritoneal dissemination model of human gastric cancer, we investigated targeted chemotherapy using a conjugate of neocarzinostatin (NCS) with MAb A7 (A7-NCS). After demonstrating cytotoxicity of the complex against the human gastric cancer cell line MKN45 in vitro, we intraperitoneally injected A7-NCS, NCS or saline into nude mice bearing peritoneally disseminated human gastric cancer. A7-NCS inhibited peritoneal dissemination significantly more effectively than NCS. MAb A7 may prove to be an effective carrier for antineoplastic drugs in patients with peritoneal dissemination of gastric cancer.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Humans; Immunotoxins; Male; Mice; Mice, Nude; Neoplasm Transplantation; Peritoneal Neoplasms; Stomach Neoplasms; Tumor Cells, Cultured; Zinostatin

We assessed the efficacy of "two-route chemotherapy (TRC)" using neocarzinostatin (NCS) given ip and its antidote, N-(2-mercaptopropionyl)-glycine (tiopronin), given iv for peritoneally disseminated tumors in mice. Whether or not the single iv administration of tiopronin (800 mg/kg) at various times after NCS ip would decrease the lethal toxicity induced by NCS ip was given attention. When compared with the LD50 (4.4 mg/kg) of NCS ip alone, simultaneous or postadministration of tiopronin together with NCS ip increased the LD50 of NCS ip by 2.8 to 7.6 fold in a time-dependent manner. Chemotherapy experiments on ip disseminated tumors in mice were done to compare the antitumor effects of the following treatments, at two dose levels (75 and 100% of LD10) of NCS, with or without tiopronin: treatment with NCS ip alone and combined chemotherapy using NCS ip plus tiopronin iv, simultaneously or postadministered. Based on the survival time of the treated mice, the groups given NCS plus tiopronin (postadministration, 15 or 25 min later) showed a significantly superior survival time to that of the group given NCS ip alone. The side effects, evaluated in terms of the changes in body weight and number of WBC of the mice, were not significantly different among the groups treated with 100% of LD10 of NCS.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Injections, Intraperitoneal; Injections, Intravenous; Leukocyte Count; Male; Mice; Peritoneal Neoplasms; Tiopronin; Zinostatin