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At least 19 recordsLinked to original sources
PubMed1988

A peplomycin-supersensitive cell line lacking activation of poly(adenosine diphosphate ribose) synthetase by peplomycin.

In peplomycin-supersensitive Chinese hamster lung cells, the increase in poly(ADP-ribose) synthesizing activity following peplomycin treatment was significantly reduced as compared with the parental lung cells, suggesting that peplomycin-supersensitive lung cells may have some deficiency in DNA repair. On the contrary, peplomycin-supersensitive ovary cells, which undergo increased DNA damage induced by peplomycin, showed normally increased poly(ADP-ribose) polymerizing activity compared with the parental ovary cells. Relationship between poly(ADP-ribose) polymerase and peplomycin sensitivity was discussed.

Animals↗
PubMed1991

[Clinical effect on tumor regression and tissue concentration of peplomycin treated with peplomycin emulsion in hydroxypropylcellulosum].

Peplomycin emulsified in hydroxypropyl cellulosum (HPC-PEP) was prepared for intravesical chemotherapy. Clinical efficacy of HPC-PEP and tissue concentration of peplomycin (PEP) were studied in 12 patients with bladder tumor. Histopathology showed transitional cell carcinoma; 2 in grade 1,8 in grade 2, and 2 in grade 3. The total volume of 30 ml HPC-PEP was prepared from a mixture of 2% HPC and 90 mg PEP in 15 ml saline, and was intravesically administered through a urethral catheter and retained for two hours. Clinical evaluation 7 days after the initial instillation demonstrated good tumor regression in 2, good response in 5, and no change in 5. The mean PEP level in tumor tissue was 0.36 microgram/gr after 7 days and 0.19 microgram/gr even after 14 days. These clinical observations and tissue levels of PEP suggest that HPC-PEP might be useful as an intravesical instillation agent for bladder tumor.

Administration, Intravesical↗
PubMed1983

Peplomycin sulfate and pulmonary fibrosis: hydroxyproline, uronic acid, proline hydroxylase and glucosamine 6-phosphate synthetase in lungs of hamsters treated with peplomycin.

Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate synthetase (EC 2.6.1.16) in lungs of hamsters treated with PLM were studied and compared with those of hamsters treated with bleomycin (BLM). PLM, when administered intraperitoneally, one injection daily for 10 consecutive days, at either a high- (5 mg/kg) or low- (2.8 mg/kg) dosage-level, caused no significant increase of lung hydroxyproline and uronic acid as compared with controls. BLM on the other hand effected a significant increase in lung hydroxyproline on the high-dosage level (5 mg/kg) but not on the low-dosage level (2.8 mg/kg). In contrast, when administering PLM intratracheally, the concentrations of hydroxyproline in lungs increased 20% over the control levels. A transient increase of proline hydroxylase and glucosamine 6-phosphate synthetase also occurred shortly after the instillation. These increases were also observed in the corresponding groups treated with BLM, which confirmed the previous observations by other investigators. However, the magnitude of the increase was relatively lower in those values of PLM as compared with those of BLM. These data suggested that (1) PLM, when administered with multiple dosages intraperitoneally, showed no significant effect on the elevation of lung hydroxyproline; (2) PLM, when administered with a dose intratracheally, induced pulmonary fibrosis similar to that caused by BLM. However, the hydroxyproline accumulation in lungs of PLM-treated hamsters was less than in those of the BLM-treated; (3) The fibrotic effect on the lungs caused by either PLM or BLM was probably attributed to acceleration of the syntheses of collagen and acidic glycosaminoglycans.

Animals↗
PubMed1990

[Instillation of a new anticancer preparation for the treatment of superficial bladder cancer: comparison of clinical efficacy between peplomycin emulsion in hydroxypropylcellulosum and peplomycin in saline solution on tumor reduction].

Clinical efficacy of a new preparation of peplomycin emulsion in hydroxypropylcellulosum (HPC-PEP) was studied in 26 patients to compared with that in 14 patients administered with 60 mg of PEP in 20 ml saline (S-PEP). The HPC-PEP was a mixture of 90 mg PEP suspended in 30 ml of 1% HPC. Both of preparations were retained in the bladder cavity over an hour after the instillation. Intravesical instillation was performed once for the patients with HPC-PEP, and 10 times repeatedly for the patients with S-PEP. A clinical evaluation was made on the basis of cytoscopic finding and cytology one week after the final instillation. According to the degree of tumor reduction, the results were classified into "disappearance", "greater than 50% reduction," and "no alteration or further growth" of primary tumor, which were referred respectively to "complete response (CR)", "partial response (PR)" and "not changed (NC)". The rates of CR and response were 27 and 73% respectively for the HPC-PEP administered patients, which were significantly higher than those of 8 and 43% respectively for the patients with S-PEP. In terms of configuration and number of tumor, intravesical HPC-PEP treatment was found to be superior to intravesical S-PEP treatment. In HPC-PEP treatment, a series of untoward symptoms such as bladder irritability and leukopenia was encountered at a frequency of 8%, which is much less than those seen in the S-PEP treatment. These clinical date suggest that HPC-PEP treatment against the superficial bladder tumors is superior to conventional S-PEP instillation in terms of administration frequency and potent doses available to tumor reduction.

Administration, Intravesical↗
PubMed1987

[Phase II study of peplomycin in breast cancer. A cooperative study. Clinical Study Group of Peplomycin for Breast Cancer in Japan].

A phase II study of peplomycin, an analogue of bleomycin, was carried out in 42 patients with advanced or recurrent breast cancer by a cooperative group consisting of 15 institutes throughout Japan, and the following results were obtained. Among the 42 patients, 38 were evaluable, in whom the overall response rate was 7.9% (3/38). For the various histologic types, the response rate was 33.3% (2/6) for papillotubular carcinoma and 9.1% (1/11) for medullary tubular carcinoma. The response rate was 33.3% (2/6) in patients without prior treatment and 3.1% (1/32) in those with prior treatment. Side effects of nausea, anorexia, malaise, alopecia and pyrexia occurred frequently, and a decrease in WBC and an increase in GOT were observed temporally. Pulmonary toxicity was observed in 7 patients.

Adult↗
PubMed1989

Occurrence of an anti-peplomycin IgE antibody cross-reacting with bleomycin in a patient with cervical uterine cancer.

An allergic reaction to peplomycin was observed in a patient with cervical uterine cancer who had previously been treated with peplomycin. A positive Prausnitz-Küstner test and its elimination after heat treatment of the serum showed the production of anti-peplomycin IgE antibody. Peplomycin was coupled to a paper disc and a sensitive radioallergosorbent test for peplomycin was developed to quantitate the antibody. Patient serum IgE and IgG were purified by DE52 column chromatography; the IgE fraction contained binding activity to peplomycin. A competition test revealed that the antibody bound to both peplomycin and bleomycin. DNA, RNA, and mononucleotides had no effect on antibody binding, but the antibody inhibited peplomycin's activity.

Aged↗
PubMed1988

Reduced pulmonary toxicity of peplomycin in a new drug-delivery system.

Pulmonary toxicity was examined by means of Matsuda and Takahashi's procedure in peplomycin solution, and two types of a new dosage form of peplomycin (PEP-CH), which has peplomycin adsorbed on to activated carbon particles. One was PEP-CH IP, and is designed for intraperitoneal administration. The other was PEP-CH IM, for intramuscular administration. Male mice of ICR strain received a bolus injection of 50 mg kg-1 peplomycin in the form of aqueous solutions PEP-CH IP and PEP-CH IM. The survival rate was 100% after 5 weeks in both groups that were administered PEP-CH. The rate was 50% for the group given peplomycin solution intraperitoneally, and 70% for the group given peplomycin solution intramuscularly. Five weeks after administration the mice were killed, and the grade and the incidence of pulmonary fibrosis were evaluated histologically. The grade and incidence of pulmonary fibrosis were zero in the two groups given PEP-CH. The grade was 0.33 and 1.76, and the incidence was 60% and 86%, respectively, in the group given peplomycin solution intraperitoneally and in the group given peplomycin solution intramuscularly.

Adsorption↗
PubMed1983

Phase I evaluation of peplomycin with special reference to pulmonary toxicity.

In the search for bleomycin analogues with less pulmonary toxicity than bleomycin itself, peplomycin was selected for a phase I clinical trial, based on experimental animal data. Eighteen patients received peplomycin at three exploratory levels. Six patients were treated at a level of 5 mg/m2, 8 patients at 10 mg/m2 and 4 patients at 15 mg/m2 of peplomycin, each dosage being given twice weekly intravenously. Pulmonary function tests were performed prior to treatment and serially thereafter. Pulmonary toxicity was encountered when the administered total dose of peplomycin was in the range 190-350 mg in patients who had received either 10 or 15 mg/m2 twice weekly. Pulmonary toxicity was not observed when the dosage of peplomycin was restricted to 5 mg/m2 twice weekly. During the trial no haematological, hepatic or renal changes induced by the drug were observed. Skin changes, stomatitis and fever were observed with increasing frequency the higher the cumulative dose of peplomycin, and these effects were similar to those seen with bleomycin. Two of fifteen patients with cervical cancer obtained a partial response, lasting 1 and 2 months respectively. Although peplomycin is free from pulmonary toxicity at a dose of 5 mg/m2 twice weekly, the maximum tolerated cumulative dose has still to be defined.

Adult↗
PubMed1994

Determination of peplomycin in mouse tissues and biofluids by radioimmunoassay.

Peplomycin, an antitumour antibiotic analogue of bleomycin, was measured in mouse tissues using a rapid radioimmunoassay. Antiserum, obtained by immunizing rabbits with peplomycin-bovine serum albumin conjugate, showed no significant cross-reactivity with the closely related peplomycin analogues bleomycin and liblomycin, nor with a number of other structurally unrelated antitumour drugs. The assay is sensitive and can detect peplomycin levels as low as 2 ng ml-1. The relative intra- and inter-assay standard deviation is < or = 5%, indicating good assay reproducibility. Peplomycin levels in mouse tissues were easily determined without extraction. Fifteen minutes after administration of a single intraperitoneal dose of peplomycin at 8.5 mg kg-1 (1/10 of LD50), high drug levels were found in plasma (46 micrograms ml-1), kidneys (38 micrograms g-1), urine and bladder (32 micrograms ml-1), followed by gastrointestinal tract (13 micrograms g-1), lung (8 micrograms g-1), spleen (3.7 micrograms g-1), heart (3.6 micrograms g-1), gall bladder (2.7 micrograms g-1), liver (2 micrograms g-1), and brain (0.6 microgram g-1). The total amount of drug in all these organs accounted for more than 80% of the dose administered. We conclude that the radioimmunoassay is sensitive and reproducible and is an ideal tool for measuring peplomycin in tissues and biofluids for pharmacological studies.

Animals↗
PubMed1989

[Continuous subcutaneous infusion of peplomycin in oral squamous carcinoma].

To determine the effect of continuous subcutaneous infusion of peplomycin on both antitumor activity and pulmonary toxicity, thirty-two patients with previously untreated oral squamous carcinoma were given peplomycin via osmotic microinfusion pump (SP-5, Nipro Co., Ltd.) at a daily dose of 5.0 mg subcutaneously. The mean dosage of peplomycin given was 79.8 mg. An overall response rate of 62.5% was achieved, with 21.9% complete response, and 40.6% partial response. The maximum reduction of tumor volume for responder could be generally observed when peplomycin was given at about 60 mg continuously. The most frequently encountered toxicity was a mucocutaneous reaction, manifested by stomatitis (34.4%) and skin eruption (18.8%), but they were mild and tolerable. A local skin reaction also occurred at the site of drug injection, and an ulcer formation developed in 12.5% of patients. Monitoring of pulmonary function by means of PaO2 revealed that 32.0% of patients had a decrease over 10% after peplomycin administration. However, interstitial pneumonitis eventually occurred in only one patient (3.1%). In conclusion, the regimen of continuous infusion of peplomycin is a useful method to administer peplomycin safely without reducing the antitumor effect compared to conventional intermittent injection.

Adult↗
PubMed1982

Selective enhancement of the cytotoxicity of the bleomycin derivative, peplomycin, by local anesthetics alone and combined with hyperthermia.

The effect of local anesthetics alone and combined with hyperthermia on the cytotoxic effect of the bleomycin derivative, peplomycin, was studied in FM3A and HeLa cells. Noncytotoxic doses of the local anesthetics procaine, lidocaine, butacaine, tetracaine, and dibucaine enhanced peplomycin cytotoxicity. This enhancement correlated with the reported anesthetic potency of these agents. Combination of lidocaine (3 to 6 mM) and moderate hyperthermia (40 and 41 degrees) greatly enhanced peplomycin cytotoxicity, although these doses of lidocaine alone were ineffective at 37 degrees, and the temperatures alone enhanced the cytotoxicity only slightly. Cell sensitization to peplomycin cytotoxicity induced by lidocaine combined with 41 degrees hyperthermia produced a decrease in cell survival that depended on the dose of lidocaine and the dose and duration of peplomycin treatment. Lidocaine at 37 or 41 degrees did not enhance the cytotoxicity of Adriamycin, mitomycin C, and cis-diamminedichloroplatinum(II), suggesting a unique interaction with peplomycin. The enhancing effect of lidocaine on peplomycin-induced cell killing was found to increase as pH increased within the range of 7.0 to 8.0.

Anesthetics, Local↗
PubMed1988

Peplomycin. DNA breakage and in vivo inhibition of DNA polymerases and ligase from human normal and leukemic cells.

Peplomycin, a bleomycin-related cytostatic agent, was tested on DNA polymerases and DNA ligase. These enzymes were purified from normal human immunocompetent cells (thymocytes and lymphocytes) and from peripheral blast cells from different kinds of acute lymphoblastic and acute non-lymphoblastic leukemia. At low concentration ranges (1-25 microM) this compound was found to strongly inhibit polymerase alpha and ligase from leukemic cells while being less effective on the enzyme activity from normal thymocytes and lymphocytes. At the DNA level, low concentrations of peplomycin resulted in the induction of dose-dependent single-stranded breaks. The incubation of peplomycin (5 microM) with plasmid DNA resulted in its degradation as observed by agarose gel electrophoresis. Lowering the peplomycin concentration showed that ligase inhibition takes place prior to this phenomenon. The decreased formation of the ligase--adenylate complex under the effect of peplomycin is consistent with a direct interaction between the drug and the enzyme. These results are discussed in terms of possible selective cytostatic effects of peplomycin on leukemic cells.

Bleomycin↗
PubMed1990

In vitro and in vivo induction of squamous cell carcinoma antigen (SCC) in a uterine cervical cancer cell line (SKG-IIIa) with peplomycin and sodium butyrate.

In order to investigate the effect of an antisquamous cell carcinoma drug, peplomycin, the new analogue of bleomycin, on the production of a squamous cell carcinoma-associated tumor marker termed "SCC" (or TA-4), we carried out in vitro and in vivo experiments using the uterine cervical epidermoid cancer cell line SKG-IIIa, together with the investigation of the effect of sodium butyrate which was reported to be one of the representative gene modulators. In vitro production of SCC was biochemically and immunocytochemically confirmed in SKG-IIIa cells. Immunocytochemistry using anti-SCC antibody revealed that the total number of SCC-positive cells increased after the treatment with peplomycin (1.6 fold) or sodium butyrate (1.5 fold). The total amount of SCC in cultured medium, intracellular SCC, and cell debris during 5 days of culturation also increased with peplomycin (1.8 fold) and sodium butyrate (1.4 fold). These data strongly suggest that SCC production of SKG-IIIa cells is stimulated by peplomycin and sodium butyrate in vitro. In vivo experiments were also performed by administering peplomycin to nude rats with heterotransplanted tumors of SKG-IIIa, and transient elevations of serum SCC level (113% to 238% of the initial values) were observed, suggesting that SCC production of cancer cells is also stimulated by peplomycin in vivo.

Animals↗
PubMedDate not supplied

Peplomycin and bleomycin effects on human colon cancer cells.

The lethal effects of peplomycin and bleomycin on cultured human colon cancer cells (LoVo) were compared by using the technique of inhibition of colony formation. The survival of LoVo cells after treatment for 1 h with either peplomycin or bleomycin was characterized by a biphasic exponential curve. When the exposure time was extended to 24 h, both drugs produced much greater cytotoxic effects, with survival decreased to less than 0.10% for bleomycin and less than 0.02% for peplomycin. Both peplomycin and bleomycin, in a dose-dependent manner, inhibited the incorporation of thymidine into cells. On an equal-weight basis, the cytotoxicity of peplomycin (24-h exposure) was similar to that of bleomycin. Both agent also inhibited the incorporation of leucine and uridine after 24 h of drug exposure, but to a lesser extent than inhibition of thymidine incorporation. However, after 1 h of exposure, such inhibitory effects were minimal. These results demonstrate that prolonged peplomycin or bleomycin exposure produces greater cell-kill than shorter drug exposure. Schedules with continuous drug administration should be explored clinically.

Bleomycin↗
PubMed1987

[Modification of the cytotoxic effect of peplomycin by cepharanthine].

The cytotoxicity of peplomycin modified by cepharanthine, was studied on in vitro cultured Chinese Hamster V-79 cells. Cepharanthine alone showed almost no cytotoxicity on this tumor system. It was revealed that cepharanthine enhanced the cell killing action of peplomycin and also promoted the recovering process from the effects of peplomycin. The enhancing effect increased with an increase of the concentration at the lower concentrations but there were limitations at the higher concentrations. The bi-phasic properties specific to peplomycin on the dose-survival curves were unchanged even in combination with cepharanthine was observed in the recovering process from the effects of peplomycin. From these results, cepharanthine seemed not to affect on the mechanism of action of peplomycin.

Alkaloids↗
PubMed1981

Chemotherapy of advanced prostatic cancer with peplomycin.

Peplomycin, a new anticancer agent, was produced as a side-chain derivative of bleomycin to reduce the incidence of pulmonary complications. Intramuscular injections of 5-10 mg of peplomycin were given 3 times a week to 35 patients with stages C and D disease. Patients were evaluated at the end of 12 weeks using the National Prostatic Cancer Project criteria. A response rate of 26% was achieved when peplomycin was used as the primary treatment. Prostatic cancer patients resistant to standard endocrine therapy had a 17% response rate to peplomycin therapy. Bone metastases were not influenced by this agent. The main side effects of peplomycin are fever and respiratory disturbances, but the incidence of these conditions is lower than that experience with bleomycin.

Acid Phosphatase↗