Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zinostatin stimalamer (YM881) is an antitumor agent, chemically synthesized by coupling one molecule of neocarzinostatin (NCS), with 2 molecules of styrene maleic acid half-butylester copolymer. YM881 showed strong cytotoxicity to human (KB, ST4 and others) and mouse (P388, L1210) tumor cell lines and also drug-resistant tumor cell lines. The antitumor effects were observed in murine MM46, colon 26 and other tumor models. The antitumor activity was as effective as NCS or better than NCS at the effective dose ranges.
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PMID:[Antitumor effects of a new antitumor agent, zinostatin stimalamer (YM881)--effects on experimental tumors in vitro and in vivo]. 183 21

Intestinal absorption of neocarzinostatin (NCS) and smancs (copolystyrene maleic acid-conjugated NCS), in aqueous and oily formulations, was investigated after oral administration in mice. Blood concentrations of NCS and smancs were determined with a cytotoxicity assay employing the highly sensitive Epstein-Barr (EB) virus-transformed B-lymphoblastoid cell line, TK/B. Smancs was more efficiently absorbed from a medium-chain triglyceride solution (oily smancs) than from an aqueous solution in phosphate-buffered saline (PBS). The maximum blood concentration and the area under the concentration curve versus time course (AUC) of oily smancs were 9 and 11 times greater than those of the aqueous form of smancs, respectively. At 5 hr after administration of oily smancs, 0.044% of the total smancs dose was found in blood, whereas the parent compound NCS was not detectable at any time. When oily smancs was administered orally to sarcoma 180 tumor-bearing mice, a selective accumulation of smancs in tumor tissue was observed. These results indicated that a biologically active protein, which cannot be used orally, may be rendered orally active drug by conjugation with a hydrophobic polymer in combination with an oily formulation.
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PMID:Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation. 214 2

A new type of anticancer agent with an amphiphilic nature, poly(styrene-co-maleic acid)-conjugated neocarzinostatin (Smancs), was dissolved in lipid contrast medium Lipiodol (Smancs/Lpd, Gelbet Co., Paris, France). This medium was injected arterially and found to be an invaluable tool for highly sensitive computerized tomography (CT) image analysis of tumors. After the administration, CT images revealed high-density areas which corresponded to the location and size of liver cancer, the smallest being 4 mm in diameter. The deposition pattern of Smancs/Lpd in liver cancers by CT was classified into three types. In type A, Lipiodol was distributed relatively even in the tumor lesion, whereas in type B it was accumulated predominantly around the tumor's periphery although the central portion remaining low in density. A few cases exhibited type C pattern, which was a mixture of types A and B. Type A was found essentially in primary liver cancer, and types B and C in secondary liver cancer. Thus, the CT pattern was found to be useful for differential diagnosis. For a sufficient therapeutic effect, 0.08 ml of Smancs/Lpd per cm2 of the maximal CT cross-section of the tumor area was found to be necessary. As a routine protocol after Smancs/Lpd administration, CT scanning was recommended for primary liver cancer initially at 1 week and then once every month. Secondary liver cancer required more frequent CT follow-ups after the administration (on the third day, after 1 and 2 weeks, and every month) due to relatively rapid disappearance of the stain than in the primary liver cancer.
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PMID:Image enhancement in computerized tomography for sensitive diagnosis of liver cancer and semiquantitation of tumor selective drug targeting with oily contrast medium. 316 Apr 53

A new method for the treatment of solid tumor, in particular, primary and metastatic liver cancer using a hydrophobic-polymer conjugated macromolecular anticancer agent, smancs is described. Smancs was dissolving in a lipid contrast medium, Lipiodol, as an injection into the feeding artery. The marked antitumor effect was observed in both experimental animals and human trials. In the patients with hepatocellular carcinoma, both reductions in tumor size and alpha-feto-protein were observed in 91% of the patients. The survival period of the treated patient with highly advanced stage and inoperable cases was comparable to or better than that of resected cases. No major side effect such as bone marrow suppression or liver toxicity was observed due to selective drug delivery to the tumor. About half of the patients, however, showed a transitory fever (37-39 degrees C) for 1-3 days. The mechanism for such selective tumor targeting of anticancer agent appears to be due to the difference in the vascularity of tumor and normal tissue. Furthermore, we found that lack of lymphatic clearance system in the tumor made the prolonged and selective retention of such lipophilic drug in the tumor tissue possible. Another advantages of this method are found in radiological approaches. Differential diagnosis of primary or metastatic cancer became possible and dosing regimen can be determined since a presence of the contrast medium is restricted to the tumor area and it parallels to that of the drug being dissolved. Insufficiency in X-ray staining indicates a need for subsequent injection. The selective remaining of Lipiodol in the tumor for long period may help follow-up study as well.
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PMID:[Tumor selective drug delivery with lipid contrast medium (smancs/lipiodol): sustained antitumor effect, enhanced diagnostic value and quantification of dosage regimen]. 632 81

Zinostatin stimalamer (ZSS) is a new anticancer agent derived from neocarzinostatin (NCS), which is synthesized by conjugation of one molecule of NCS and two molecules of poly(styrene-co-maleic acid). ZSS exhibited potent in vitro and in vivo antitumor activity in preclinical experiments, and a clinical trial of the intra-arterial administration of ZSS with iodized oil on hepatocellular carcinoma showed potent antitumor activity. We investigated the effect of ZSS and NCS on antitumor resistance and found that pretreatment with either drug suppressed the growth of MethA tumors in Balb/c mice and induced tumor eradication when given separately by single administration at therapeutic doses between 1 day and 4 weeks before tumor transplantation. The findings that the cytocidal activity of these drugs was not detected in vivo at the time of tumor transplantation and that tumor regression was preceded by a period of transient growth suggested that tumor regression was due to host-mediated antitumor activity induced by these drugs. Pretreatment with ZSS or NCS also suppressed the growth of Colon 26 carcinoma and Sarcoma 180. The finding that NCS showed the same effect as ZSS suggests that poly(styrene-comaleic acid) is not essential for the induction of host-mediated antitumor activity. Furthermore, apo-ZSS, which lacks cytocidal activity, did not induce antitumor activity. From this, it is suggested that the cytocidal effect of ZSS involves the induction of host-mediated antitumor resistance. In athymic Balb/c nu/nu mice, pretreatment with ZSS or NCS did not induce tumor eradication, suggesting that mature T lymphocytes play an important role in tumor eradication. Challenging MethA was rejected without transient growth in mice that had been cured of MethA, but challenging Colon 26 was not, showing that anti-MethA resistance was augmented selectively in the MethA-eradicated mice. Splenocytes from MethA-bearing mice pretreated with the drug showed tumor-neutralizing activity beginning 14 days after tumor transplantation. Tumor-neutralizing activity was only induced after MethA transplantation. The effector cells of this tumor-neutralizing activity were Thy1.2+ T lymphocytes that had been passed through a nylon-wool column, but no significant augmentation of cell-mediated cytotoxic activity of splenocytes from MethA-eradicated mice was observed in vitro.
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PMID:Antitumor resistance induced by zinostatin stimalamer (ZSS), a polymer-conjugated neocarzinostatin (NCS) derivative. I. Meth A tumor eradication and tumor-neutralizing activity in mice pretreated with ZSS or NCS. 760 May 66

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3-4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19-45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC.
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PMID:Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma. 1206 70