Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Zinostatin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1991

[Study on the intra-tumor tissue concentration of zinostatin stimalamer in the liver following intra-arterial injection of zinostatin stimalamer (YM881) suspension].

A suspension of zinostatin stimalamer (YM881), an antitumor protein antibiotic in iodized poppy oil-fatty acid ester, was injected into the hepatic artery of 2 patients who received surgical treatment of hepatic tumors. Single doses of 4 mg of zinostatin stimalamer were injected into the hepatic artery by Seldinger's method. Two and 4 weeks after the dose, tissue samples were collected from the tumor and non-tumor regions close to and distant (normal tissues) from the tumor, and zinostatin stimalamer concentrations in these tissues were assayed by RIA. In one of the two patients, plasma concentrations of the drug were also assayed. Concentrations of zinostatin stimalamer in the tumor tissues (381.8 ng/g) were about 55 times greater than those in the normal tissue (6.9 ng/g) in patient No. 1 (week 4), and about 17 times in patients No. 2 (13.9 ng/g in the normal tissue and 229.8 ng/g in the tumor tissues in week 2). Plasma concentrations were assayed in patient No. 2, and were 510.3 ng/ml after one hr., 385.3 ng/ml after 3 hrs., 184.4 ng/ml after 6 hrs., and 45.4 ng/ml after 24 hrs., with a half life of 7.1 hrs. These results indicate that zinostatin stimalamer suspended in iodized poppy oil fatty acid ester persisted in the hepatic tumor tissues at the high concentrations, when injected into the hepatic artery, but was eliminated fairly rapidly from the plasma.

Aged↗
PubMed2003

A phase I study of hepatic arterial infusion chemotherapy with zinostatin stimalamer alone for hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion of zinostatin stimalamer and lipiodol emulsion shows a moderate activity against hepatocellular carcinoma. However, the anti-tumor activity of zinostatin stimalamer alone is uncertain. METHODS: The primary endpoint was to evaluate the frequency of dose-limiting toxicity and determine the maximum-tolerated dose of zinostatin stimalamer when used by intra-arterial infusion. The candidates for this study were patients with hepatocellular carcinoma no longer amenable to established forms of treatment. Hepatic arterial infusion chemotherapy was performed by selectively introducing a catheter into the hepatic artery with zinostatin stimalamer alone. Treatment was repeated at 4-8-week intervals until disease progression or the appearance of unacceptable toxicity. The starting dose of zinostatin stimalamer was 3 mg/m(2), and doses were increased in 1 mg/m(2) increments in successive cohorts. At least three patients were treated at each dose level and three additional patients were treated in the presence of dose-limiting toxicity. RESULTS: Twelve patients were entered into this trial. Dose-limiting toxicity was observed in one of six patients at 3 mg/m(2), and in two of six patients at 4 mg/m(2). The maximum-tolerated dose was judged to be 3 mg/m(2) with liver dysfunction and serum creatinine increase as the dose-limiting toxicity. There was one early death suggested to be related to the protocol treatment. None of the 12 patients achieved an objective tumor response. CONCLUSION: Hepatic arterial infusion with a zinostatin stimalamer of 3 mg/m(2) may be tolerated, but not active, in patients with far advanced hepatocellular carcinoma.

Aged↗
PubMed1981

Zinostatin and doxorubicin. A combination phase I study.

Because of encouraging single-agent activity for both zinostatin and doxorubicin in hepatocellular cancer, a phase I tolerance study with these drugs in combination was undertaken. The dose of zinostatin given daily for 5 consecutive days and repeated every 6 weeks was fixed at 2250 units/M2. The starting dose of doxorubicin was 45 mg/m2 on days 1 and 22 of every 6-week cycle, but this was escalated or deescalated by increments of 33% as tolerated. The occurrence of unpredictable severe and prolonged cumulative myelosuppressive toxicity in most patients resulted in considerable management difficulties. In addition, three patients developed congestive heart failure at cumulative doxorubicin doses ranging from 195 to 270 mg/m2 and two patients developed possible drug-related nephrotoxicity. Until reasons for the pharmacogenetic variability observed with zinostatin are defined, combination studies employing this drug are not recommended.

Antibiotics, Antineoplastic↗
PubMed1984

Phase II study of PALA, amsacrine, teniposide, and zinostatin in small cell lung carcinoma (EST 2579).

Eighty-two patients with small cell lung carcinoma refractory to standard chemotherapy were entered in this phase II randomized study of PALA, amsacrine, teniposide, and zinostatin. Of the 66 evaluable patients, one partial response occurred among 17 patients treated with teniposide and no responses occurred with the other drugs. Two patients each treated with amsacrine and teniposide experienced life-threatening hematologic toxic effects and one patient treated with zinostatin died of thrombocytopenic pulmonary hemorrhage. The overall median patient survival was 9.6 weeks. Weight loss greater than or equal to 5% prior to therapy, extensive disease, and a nonambulatory status were associated with poor survival.

Aminoacridines↗
PubMed1995

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.

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.

Animals↗
PubMedDate not supplied

Transarterial chemotherapy with zinostatin stimalamer for hepatocellular carcinoma.

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). Thirty HCC patients underwent transcatheter arterial injection of 4 mg SMANCS-lipiodol emulsion. Their responses were evaluated by computed tomography 1 month after treatment. Complete response (CR) was defined as disappearance or 100% necrosis of all tumors. Partial response (PR) was defined as > or = 50% reduction and/or > or = 50% necrosis. We regarded the lipiodol accumulation in tumors as being necrotic. CR and PR were observed in 8 patients (27%) and 4 patients (13%), respectively, and the overall response rate (CR + PR/all patients) was 40% (12/30). Of 12 patients whose serum alpha-fetoprotein levels had been more than 200 ng/ml before treatment, 5 patients (42%) showed more than 50% reduction in this level within 1 month after treatment. Toxicity was quite acceptable, although grade 4 toxicity (WHO) was observed as liver dysfunction in 1 patient. Transarterial chemotherapy with SMANCS, which is well tolerated, appears to have moderate antitumor effect in patients with HCC.

Adolescent↗
PubMed2002

Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma.

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.

Adult↗
PubMed1991

[Phase I study of YM881 (zinostatin stimalamer) suspension by hepatic arterial infusion. Research Group for Intra-arterial Infusion Therapy with YM881].

A phase I study of YM-881 (zinostatin stimalamer), neocarzinostatin combined with butylesterified styrene maleate, suspended in iodized poppy oil ethyl ester, was conducted in patients with hepatocellular carcinoma by giving single intra-arterial infusions via catheters inserted by Seldinger's method. Four dose levels, 2, 4, 6, and 8 mg, were tested. Major adverse reactions were fever, anorexia, nausea, vomiting, and abnormal hepatic function. Both the incidence and severity of adverse reactions tended to increase with the 8 mg dose. Tumor regression of 50% or more occurred in one receiving 2 mg and one receiving 4 mg. The results of the study suggest that doses of 6 mg or less may be appropriate for the phase II studies.

Adult↗
PubMed1991

[Phase II study of YM881 (zinostatin stimalamer) suspension injected into the hepatic artery. Research Group for Intra-arterial Injection Therapy with YM881].

A phase II study of YM 881 (zinostatin stimalamer) to determine the response and safety was conducted in patients with hepatocellular carcinoma by injecting a suspension of the drug into the hepatic artery. Repeated doses of 4 to 6 mg of the drug were given every 4 weeks so that the tumor tissues were filled with the suspension. Of the 195 registered patients, 15 were ineligible for the study, 8 dropped out, and data were missing for 5. A total of 167 patients completed the study. Response was assessed in the 167 patients who completed the study. CR was found in one, PR in 59, MR in 25, NC in 67, and PD in 15, with a response rate of 35.9. The safety of the drug was assessed in 177, excluding ineligible patients and 3 who dropped out because of the concurrent use of other drugs. Adverse reactions were found in 93.2% of the patients, and abnormal values in clinical laboratory tests in 60.5%. Major unwanted symptoms included fever, nausea, vomiting, and anorexia. Major abnormal changes in laboratory tests were elevated total bilirubin and LDH and abnormal hepatic function. About half the patients had malaise and pain related to the intra-arterial infusion therapy. The one year survival rate was 56.9%, and the duration of survival of 50% of the patients was 407 days.

Adult↗
PubMed1991

[Phase I clinical study of zinostatin stimalamer (YM 881) by intravenous injection].

A phase I clinical study by intravenous injection of zinostatin stimalamer (YM 881), a protein anti-cancer drug, was conducted in 50 patients with malignant tumors. The initial dose was 0.5 mg/m2 (n) in the single dose test, and 0.2 mg/m2/day in the repeated dose test for 5 successive days. Doses were increased up to 12n according to the modified Fibonacci's method in both the single and repeated dose tests. The dose limiting factor was thrombopenia in both the single and repeated dose tests. The maximum tolerated dose was 6.0 mg/m2 (12n) in the single dose test, and the subtoxic dose was 2.4 mg/m2/day in the five day repeated dose study. These results indicate that dose of 1.0 to 1.4 mg/m2/day (5 n to 7 n) are appropriate for the phase II repeated dose study.

Adult↗
PubMed1991

[Early phase II study of YM 881 (zinostatin stimalamer) by intravenous injection. Research group for intravenous YM 881].

An early phase II multicentered study of YM 881 (zinostatin stimalamer) was conducted in 36 patients to investigate response and the safety of the drug in malignant tumors. The response could be evaluated in 18 patients, one with brain tumor, 2 with lung cancer, one with breast cancer, one with liver cancer, one with pancreatic cancer, 6 with gastric cancer, and 6 with colon cancer. PR was found in the patient with brain tumor. Major subjective unwanted effects were gastrointestinal symptoms. Objective evidence of hematological changes (thrombocytopenia, decreased hematocrit, and lymphocytopenia) was also obtained.

Adult↗
PubMed1991

[Antitumor effects of a new antitumor agent, zinostatin stimalamer (YM881)--effects on experimental tumors in vitro and in vivo].

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.

Animals↗
PubMed1991

[Action mechanisms of zinostatin stimalamer (YM881)].

The mechanism of action of zinostatin stimalamer (YM881) was studied. YM881 suppressed colony formation of HeLa cells dose-dependently, and showed cytocidal activity. The compound inhibited DNA synthesis, but neither RNA nor protein synthesis in L1210 cells, and caused cellular DNA strand breaks in HeLa cells and DNA cleavage of PM2 phage supercoiled DNA. YM881 was also shown to cause typical G2/M arrest on L1210 cell cycle, and inhibited DNA polymerase alpha of HeLa cells, but only at high concentrations. Present study showed that antitumor and cytotoxic mechanisms of YM881 were identical to neocarzinostatin (NCS) and due to the cellular DNA strand breaks caused by direct DNA-cleaving activity and the subsequent inhibition of DNA synthesis.

Animals↗
PubMed1987

Potentiation of cytotoxicity of zinostatin under acidic conditions in vitro and in vivo.

The cytotoxicity and antitumor effects of zinostatin (NCS) were examined under various conditions of pH using cultured HeLa cells and a transplantable tumor line of WKA rats. The cytotoxicity of NCS against HeLa cells was highly dependent on the pH at ranges of 6-8. When HeLa cells were treated with 0.075 microgram/ml of NCS, the survival rate was about 1% at pH 6.0, while it was near 90% at pH 7.4 and pH 8.0. Even at pH 6.5-6.75, the survival rate was about 50% lower than that seen with pH 7.4 and pH 8.0. The ratio of the dose of NCS for a 90% cell mortality at pH 6.0 to that at pH 7.4 was less than one-seventh. Antitumor effects were assessed by local intra-arterial infusion against tumors 4 or 9 days after inoculation of 10(6) RBT-1 tumor cells into the thigh of rats. When NCS (0.7 mg/kg) in phosphate-buffered saline (PBS) (pH 7.4) or 5 mM lactate (about pH 3.0) was administered, the ratio of average tumor weight about 2 weeks after treatment (tumor weight of the rats given NCS in PBS/tumor weight of the rats given NCS in lactate) was 3.2 or 1.7 for the rats treated 4 or 9 days after tumor inoculation, respectively. Lactate or PBS alone had no effect on the growth of tumor. After treatment there was no difference in body weight change between the group treated with NCS in lactate and the group treated with NCS in PBS. We conclude that the cytotoxicity of NCS was potentiated under acidic conditions, both in vitro and in vivo.

Animals↗
PubMed1994

[Anti-tumor activity of zinostatin stimalamer (YM 881) examined by human hepatoma cells in vitro and VX2 liver tumor in vivo].

Anti-tumor activities of zinostatin stimalamer (YM 881) were examined using human hepatoma cell lines (SK-Hep1 and HuH 2) and VX2 liver tumor-bearing rabbits. YM881 inhibited the growth of human hepatoma cells in a dose-dependent manner. The IC50 values of YM881 against SK-Hep 1 and HuH 2 cells were 6.7 and 27 mM, respectively. In VX2 tumor-bearing rabbits, administration of YM 881 suspended in iodinated fatty acid ethylesters of poppyseed oil (YM 881/Lipiodol suspension, 0.2 mg/0.2 ml/body) into the hepatic artery showed significant (p < 0.01, vs sham-operated and Lipiodol-treated groups) inhibitory effects on the growth and pathological changes 1 and 2 weeks after administration. On the other hand, Lipiodol (0.2 ml/body) showed a tendency to inhibit the growth of VX2 tumor (p < 0.1, vs sham-operated group) 1 week after administration, but it showed only moderate effects on the VX2 tumor growth 2 weeks after administration. Minimal necrosis was observed 1 and 2 weeks after administration of Lipiodol, and these pathological findings were similar to those in the sham-operated group. From the present study, it is suggested that YM 881/Lipiodol suspension showed the anti-tumor activity against VX2 tumor-bearing rabbits, presumably due to the inhibition of the growth of hepatoma cell by YM 881 per se. On the other hand, Lipiodol is considered to augment the anti-tumor activity by maintaining high YM881 concentrations in tumor tissue.

Animals↗
PubMed1996

Changes in cellular components of spleen and lymph node cells and the effector cells responsible for Meth A tumor eradication induced by zinostatin stimalamer.

We reported previously that pretreatment with zinostatin stimalamer (ZSS) eradicated Meth A tumors in BALB/c mice. We herein investigated cellular components of spleen and lymph node cells of Meth A-bearing ZSS-pretreated mice by flow cytometry; the antitumor effector cells by in vivo depletion of T cells, NK cells, or macrophages; and host-mediated antitumor activity associated with ZSS treatment after tumor transplantation. ZSS given on day-3 transiently decreased the number of spleen cells. The percentage of T cells increased, but B cells and macrophages decreased. B cells decreased in inguinal lymph nodes in Meth A-bearing ZSS-pretreated mice, but increased in Meth A-bearing control mice. In vivo depletion experiments using antibodies or carrageenan showed that antitumor effector cells for tumor eradication are Thy1.2+/Lyt2.2+ and that at least a part of them are asialo GM1+. Thy1.2+/Lyt2.2+/asialoGM1- cells are important in generation of the antitumor activity of ZSS; however, L3T4+ T cells are also involved in initiation of tumor eradication. The result of ZSS treatment after tumor transplantation suggests that ZSS might exhibit antitumor activity by augementating host-mediated antitumor resistance, as well as its intrinsic cytocidal activity.

Animals↗
PubMed1996

[A case of recurrent multiple HCC after surgical resection showing regression by two TAEs using 5-FU and zinostatin stimalamer].

A-68-year-old man had hepatocellular carcinoma (HCC) in the area of S6 segment which was resected surgically. Three months after surgery, multiple recurrent lesions were found in both lobes of the liver. A transcatheter arterial embolization (TAE) with 5-FU and zinostatin stimalamer (SMANCS) was done. After TAE, the tumor mass disappeared in the right lobe and reduced to 10% in the left lobe. Although mass lesions remained unchanged for 3 months, the increased of AFP (143.9 ng/ml) was noticed after 4 months. Ten months after the second TAE with 5-FU and SMANCS, the disappearance of tumor masses was confirmed by diagnostic images.

Aged↗
PubMed1996

Antitumor activity of zinostatin stimalamer (YM881) in human hepatoma cell lines and VX2 liver tumor-bearing rabbits.

Antitumor activities of zinostatin stimalamer (YM881) were examined in human hepatoma cell lines (SK-Hep1 and HuH2) and VX2 liver tumor-bearing rabbits. YM881 inhibited the growth of human hepatoma cells in a dose-dependent manner. The IC50 values of YM881 causing a 50% inhibition of growth of SK-Hep1 and HuH2 cells were 6.7 and 27 nM, respectively. In VX2 tumor-bearing rabbits, administration of YM881 suspended in Lipiodol, an iodinated fatty acid ethylester of poppyseed oil, (YM881/Lipiodol suspension, 0.2 mg/0.2 ml/body) into the hepatic artery showed significant (p < 0.01, vs. sham-operated and Lipiodol-treated groups) inhibitory effects on tumor growth and histopathological changes at 1 and 2 weeks after administration. In contrast, Lipiodol (0.2 ml/body) tended to inhibit the growth of VX2 tumor (p < 0.1, vs. sham-operated group) at 1 week after administration, but showed only moderate effects at 2 weeks after administration. Minimal necrosis was observed at 1 and 2 weeks after administration of Lipiodol, and histopathological findings were similar to those in the sham-operated group. From the present study, it is suggested that YM881/Lipiodol suspension showed antitumor activity in VX2 tumor-bearing rabbits presumably due to the inhibition of the growth of hepatoma cells by YM881 itself. Lipiodol, on the other hand, is considered to augment the antitumor activity of YM881 by maintaining high YM881 concentrations in tumor tissue.

Animals↗