zinostatin and Rectal-Neoplasms

The significance and effectiveness of adjuvant intraoperative chemotherapy using subserosal or submucosal administration of Neocarzinostatin (NCS) and CH 40 for gastric cancer and colorectal cancer were studied. Tissue NCS concentration of proximal lymph nodes were higher than for distant lymph nodes, while the immunocompetency of distant lymph nodes (lower NCS concentration) showed slightly higher activity than that of proximal lymph nodes. From these results, it is suggested that loco-regional administration of NCS might be effective for chemical lymph node cleaning of the cancer.

Topics: Carbon; Chemotherapy, Adjuvant; Colonic Neoplasms; Gastric Mucosa; Humans; Injections, Intralesional; Lymph Nodes; Lymphocyte Activation; Rectal Neoplasms; Stomach Neoplasms; Zinostatin

Monoclonal antibody-drug conjugates were applied as a clinical trial for patients who, based on the experimental study, had colorectal cancer. Monoclonal antibody A7, from a mouse splenocyte immunized against human colon cancer, was used as a drug carrier for colon cancer. The anti-cancer drugs mitomycin C (MMC) and neocarzinostatin (NCS) were bound covalently to A7 to form the conjugates A7-MMC and A7-NCS. The in vitro cytotoxic effects of the conjugates on SW1116 cells were stronger than those on free MMC or NCS. The conjugate A7-NCS, when administered to nude mice, brought about the highest NCS tumor concentration, whereas normal immunoglobulin G (IgG)-NCS distributed evenly in all tissues. The conjugates showed a strong antitumor effect on colon cancer transplanted into nude mice. Forty-one patients with colorectal cancer, including ten patients with postoperative metastasis, were given A7-NCS. The immunoperoxidase and drug concentration studies of the resected specimens showed that NCS was localized specifically in cancer. Patients receiving the conjugate did not experience serious adverse effects. Of the eight patients with postoperative liver metastasis, three showed evidence of tumor reduction on computed tomography (CT) scan and three claimed pain relief. The conjugate did not benefit patients with multiple lung metastasis or peritoneal metastasis.

Topics: Adult; Aged; Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Colonic Neoplasms; Drug Evaluation; Female; Humans; Liver Neoplasms; Male; Mice; Mice, Nude; Middle Aged; Mitomycin; Mitomycins; Neoplasm Transplantation; Rectal Neoplasms; Tumor Cells, Cultured; Zinostatin

Monoclonal antibody, A7, produced from a mouse splenocyte immunized against human colon cancer was used as drug carrier for colon cancer. A7 had not ADCC and ADMC activity but had ACD activity. Anticancer drug, mitomycin C (MMC), and neocarzinostatin (NCS), were covalently bound to A7 to form the conjugates, A7-MMC, and, A7-NCS. In vitro cytotoxic effect of the conjugates on SW1116 was much stronger than that of free MMC or free NCS. The conjugates, A7-NCS, administered in nude mice brought about the highest NCS concentration in tumor, while normal IgG-NCS distributed evenly in all the tissues. The conjugates showed strong antitumor effect on colon cancer transplanted in nude mice. Forty one patients with colorectal cancer including 10 patients with postoperative metastasis were given A7-NCS. The immunoperoxidase and drug concentration studies of the resected specimens revealed that NCS was found to be localized specifically in cancer. There was no serious adverse effect in the patients receiving the conjugate. Of eight patients with postoperative liver metastasis, three showed evidence of tumor reduction on CT scan and three claimed pain relief. The conjugate was of no benefit to the patients with multiple lung metastasis and peritoneal metastasis.

Topics: Adult; Aged; Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Colonic Neoplasms; Humans; Immunotoxins; Mice; Mice, Nude; Middle Aged; Mitomycin; Mitomycins; Neoplasm Transplantation; Rectal Neoplasms; Zinostatin

For targeting chemotherapy of colorectal carcinoma, mitomycin C (MMC) and neocarzinostatin (NCS) were covalently bound to monoclonal antibody A7 which is highly specific to human colon cancer. The in vitro cytotoxic effects of the conjugates A7-MMC and A7-NCS on SW1116 were 77 times and 4 times stronger than those of the free MMC and free NCS, respectively. An in vivo study in nude mice bearing human colon carcinoma revealed that monoclonal antibody A7 alone had no effect, and that A7-MMC and A7-NCS had greater inhibitory effects than the free MMC and NCS, respectively. Thirty-five patients with carcinoma of the colon and rectum including 6 with postoperative liver metastasis, one with postoperative lung metastasis and one with postoperative peritoneal metastasis, were given the A7-NCS conjugate consisting of between 15 and 90 mg of antibody and between 1,000 and 6,000 units of NCS. Immunoperoxidase study of resected specimens revealed selective localization of NCS in the cancer cells. The conjugate had no serious adverse effects. Five of the six patients with postoperative liver metastasis responded favorably to the conjugate, showing a decrease in tumor size on CT scan or relief of pain. The conjugate was of no benefit to patients with multiple lung metastasis or peritoneal metastasis. The effect on other patients with surgically resected carcinoma remains to be determined by a follow-up study.

Topics: Adenocarcinoma; Aged; Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Colonic Neoplasms; Female; Humans; Immunotoxins; Male; Mice; Mice, Nude; Middle Aged; Mitomycin; Mitomycins; Rectal Neoplasms; Zinostatin

Topics: Animals; Antibiotics, Antineoplastic; Catheterization; Colonic Neoplasms; Dogs; Fluorouracil; Humans; Iontophoresis; Rats; Rectal Neoplasms; Zinostatin