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International Journal of Hyperthermia :... 1996Eight patients with primary cancer of the oral cavity were preoperatively treated by combined treatment with hyperthermia and chemotherapy. They received two courses of...
Eight patients with primary cancer of the oral cavity were preoperatively treated by combined treatment with hyperthermia and chemotherapy. They received two courses of chemotherapy, which included intra-arterial infusion of 100 mg of cisplatin (CDDP) and 25 mg of peplomycin (PEP) via the superficial temporal artery. The patients also received interstitial hyperthermia for 45 min once a week using the Implant Heating System (IHS) with chemotherapy. IHS consists of ferromagnetic implant, induction coil and generator to produce high frequency magnetic field. The ferromagnetic implant is made of Fe-Pt alloy (Fe: 73%, Pt: 27%), and has a Curie temperature of 68 degrees C. As a result, clinical complete response (CR) was observed in seven patients and partial response (PR) in one, and postoperative pathological examination showed no residual tumour cells in any specimen. Combined interstitial hyperthermia by IHS and chemotherapy is thus found to be an effective therapeutic method for treating oral cancers.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Female; Ferric Compounds; Humans; Hyperthermia, Induced; Infusions, Intra-Arterial; Male; Middle Aged; Mouth Neoplasms; Peplomycin; Prostheses and Implants; Tongue Neoplasms
PubMed: 8676007
DOI: 10.3109/02656739609023688 -
Japanese Journal of Pharmacology Sep 2001To explore the mechanism of pulmonary fibrosis by bleomycin and its derivative, peplomycin (PLM), we examined the influence of PLM on signal transduction in human...
To explore the mechanism of pulmonary fibrosis by bleomycin and its derivative, peplomycin (PLM), we examined the influence of PLM on signal transduction in human peripheral blood lymphocytes (HL), monocytes (HM) and fibroblasts (HF). Tyrosine phosphorylation of multiple proteins in HL and HM were induced by 0.001 to 0.05 microg/ml and by 0.01 to 0.5 microg/ml of PLM, respectively. In HF, 116-kDa protein was phosphorylated 0.2 to 5 microg/ml of PLM. When HL were treated with 0.01 microg/ml of PLM, phosphorylation of p56lck and activation of extracellular-signal related kinase-2 (ERK2) were induced. ERK2 was also activated in HM. Coordinately, the ratio of p21ras-binding GTP/GDP was increased by PLM. As well as interleukin-2, PLM induced tyrosine phosphorylation of JAK-3. In addition, PLM upregulated the nuclear translocation of nuclear factor-kappa B and the expression of c-myc-mRNA in HL, HM and HF. Furthermore, 0.01 to 0.001 microg/ml PLM enhanced the cytokine generation by HL and HM, and 1 to 5 microg/ml PLM increased cytokine generation and collagen synthesis by HF. These upregulatory effects of PLM were abrogated by pretreatment of the cells with a tyrosine kinase inhibitor. These results indicate that PLM upregulates signal transduction in a variety of cell types and the upregulation may induce pulmonary fibrosis.
Topics: Antibiotics, Antineoplastic; Cells, Cultured; Fibroblasts; Genes, myc; Humans; Lymphocytes; Mitogen-Activated Protein Kinase 1; Monocytes; NF-kappa B; Oncogene Protein p21(ras); Peplomycin; Phosphorylation; RNA, Messenger; Signal Transduction; Tyrosine; Up-Regulation
PubMed: 11676197
DOI: 10.1254/jjp.87.41 -
Hinyokika Kiyo. Acta Urologica Japonica Jan 1985To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were...
To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were intraperitoneally injected to 63-day-old Wistar rats. The anticancer agents were administered as follows: Cyclophosphamide (CPM) was used at the dose of 8 mg/kg for 7 days. Methotrexate (MTX), actinomycin-D (ACD) and cis-platinum (CDDP), 163 micrograms/kg, 8 micrograms/kg and 833 micrograms/kg for 5 days, respectively. Nitrogen mustard (NM), bleomycin (BLM), peplomycin (PLM), adriamycin (ADM), vincristine (VCR), and vinblastine (VBL), 500 micrograms/kg, 250 micrograms/kg, 170 micrograms/kg, 2.5 mg/kg, 33 micrograms/kg and 83 micrograms/kg, twice in a week, respectively. The rats were killed on the fifth day after completion of the schedule. Then, the weight of the body, the prostate, the epididymis and the adrenal gland were measured. In addition, 5 alpha-reductase activities and histological findings in the prostate were examined. For determination of 5 alpha-reductase activities, cell-free homogenate obtained from the rat ventral prostate was incubated with C14-testosterone at 37 degrees C for 30 minutes in an atmosphere of 95% of O2 and 5% of CO2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using the solvent system with benzene acetone, 4:1 (v/v). 5 alpha-Reductase activity was determined with the sum of dihydrotestosterone (DHT) and androstanediol converted from testosterone and indicated as pmol product/mg protein. The 5 alpha-reductase activity was employed as a biological marker for the degree of androgenic dependency in the prostate. The results were summarized as follows. CDDP significantly reduced the weight of the body (p less than 0.001, n = 7), but not the activity of 5 alpha-reductase. NM and VBL had a specific action to reduce the weight of the prostate (p less than 0.01, n = 8) without causing loss of body weight. NM and VBL showed no influence on 5 alpha-reductase activities. The activity of 5 alpha-reductase was markedly damaged by BLM (p less than 0.05, n = 6) and PLM (p less than 0.05, n = 5). However no significant reduction was recognized in the weight of the body and the prostate. CPM, MTX, ACD, ADM and VCR were ineffectual on the body and the prostate weight and 5 alpha-reductase activities. In the histological examination, atrophy and degeneration of the glandular epithelium were revealed in the prostate treated with NM, VBL and CDDP.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Animals; Antineoplastic Agents; Bleomycin; Body Weight; Cholestenone 5 alpha-Reductase; Cisplatin; Cyclophosphamide; Dactinomycin; Doxorubicin; Male; Mechlorethamine; Methotrexate; Organ Size; Oxidoreductases; Peplomycin; Prostate; Rats; Vinblastine; Vincristine
PubMed: 2581430
DOI: No ID Found -
Dermatology and Therapy Dec 2015Flagellate erythema presents as erythematous, individual and intermingled, linear streaks in a whiplash-like pattern. Several conditions, including antineoplastic...
INTRODUCTION
Flagellate erythema presents as erythematous, individual and intermingled, linear streaks in a whiplash-like pattern. Several conditions, including antineoplastic agents, have been associated with flagellate erythema. A woman with metastatic breast cancer who developed flagellate erythema after receiving trastuzumab is described and the features of flagellate erythema associated with other antineoplastic agents are reviewed.
METHODS
PubMed was used to search the following terms, separately and in combination: agent, antineoplastic, bendamustine, bleomycin, breast, cancer, chemotherapy, dermatitis, dermatosis, docetaxel, erythema, flagellate, Herceptin, pigmentation, peplomycin, therapy, and trastuzumab. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated.
RESULTS
The woman's pruritus and skin lesions promptly resolved after treatment with corticosteroids (oral and topical) and antihistamines (oral); premedication with dexamethasone prior to each subsequent trastuzumab treatment prevented recurrence of flagellate erythema. Chemotherapy-induced flagellate erythema was initially described in oncology patients who received bleomycin. In addition to trastuzumab, other antineoplastic agents that have been associated with the development of flagellate erythema include bendamustine, docetaxel, and peplomycin.
CONCLUSION
Cutaneous adverse events to trastuzumab are uncommon. However, flagellate erythema should be added to the potential side effects of trastuzumab. In addition, trastuzumab should be added to the list of antineoplastic agents that may be associated with flagellate erythema.
PubMed: 26506993
DOI: 10.1007/s13555-015-0085-2 -
Journal of Biological Inorganic... Jan 2017The antibiotics known as bleomycins constitute a family of natural products clinically employed for the treatment of a wide spectrum of cancers. The drug acts as an...
The antibiotics known as bleomycins constitute a family of natural products clinically employed for the treatment of a wide spectrum of cancers. The drug acts as an antitumor agent by virtue of the ability of a metal complex of the antibiotic to cleave DNA. Bleomycins are differentiated by their C-terminal regions. Previous structural studies involving metal-bleomycin-DNA triads have allowed the identification of the bithiazole-(C-terminus substituent) segment in this molecule as the one that most closely interacts with DNA. Three different modes of binding of metallo-bleomycins to DNA (partial or total intercalation of the bithiazole unit between DNA bases, or binding to the minor groove) have been proposed in the literature. The therapeutic use of bleomycin is frequently associated with the development of pulmonary fibrosis. The severity of this side effect has been attributed to the C-terminus of the antibiotic by some researchers. The degree of pulmonary toxicity of bleomycin-A and -A, were found to be higher than those of bleomycin-B and peplomycin. Since the introduction of Blenoxane to clinical medicine in 1972, attempts have been made at modifying the basic bleomycin structure at the C-terminus to improve its therapeutic index. However, the pharmacological and toxicological importance of particular C-termini on bleomycin remains unclear. The present study was designed to determine the effect of Zn(II)bleomycin-A, -A, -B, and Zn(II)peplomycin on the structure of a DNA hairpin containing the 5'-GC-3' binding site. We provide evidence that different Zn(II)bleomycins affect the structure of the tested DNA segment in different fashions.
Topics: Anti-Bacterial Agents; Binding Sites; Bleomycin; DNA; Inverted Repeat Sequences; Magnetic Resonance Spectroscopy
PubMed: 27858165
DOI: 10.1007/s00775-016-1413-4 -
Hinyokika Kiyo. Acta Urologica Japonica Jul 1985Two VPM-CisCF chemotherapy regimens (vincristine (VCR), peplomycin (PEP), methotrexate (MTX), cis-diamminedichloroplatinum (II) (CDDP), cytosine arabinoside (Ara-C) and...
[Sequential combination chemotherapy consisting of vincristine, peplomycin, methotrexate, cis-diamminedichloroplatinum (II), cytosine arabinoside and 5-fluorouracil, for advanced urothelial cancer].
Two VPM-CisCF chemotherapy regimens (vincristine (VCR), peplomycin (PEP), methotrexate (MTX), cis-diamminedichloroplatinum (II) (CDDP), cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), established using human bladder cancer xenografts in nude mice were applied for advanced urothelial cancer. VPM-CisCF (I) consisted of 0.4 mg/m2 VCR on days 1 and 4, 2 mg/m2 PEP on days 1-7, 2 mg/m2 MTX on days 2, 3, 5 and 6, 20 mg/m2 CDDP on days 8, 20 mg/m2 Ara-C on days 8 and 13, and 150 mg/m2 5-FU on days 10-12. VPM-CisCF (II) consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PEP on days 1-4, 3 mg/m2 MTX on days 2 and 3, 35 mg/m2 CDDP on day 4, 20 mg/m2 Ara-C on days 4 and 7, and 200 mg/m2 5-FU on days 5 and 6. These doses were adjusted for each case: the above mentioned dose x [(80/(40 + Age))2 + (Karnofsky's performance status/100)2]. VPM-CisCF (I) was administered to 6 patients (bladder cancer and transitional cell carcinoma), intra-arterially in two cases. One patient showed a complete response and survived for 7 months, three partial response (PR) surviving for 13, 8 and 37 (arterial-infused case) months, one showed minor response (MR) surviving for 4 months, and one had no change (NC) surviving for 5 months. VPM-CisCF (II) was administered to 11 patients (1 ureteral cancer, 1 renal pelvic cancer, 9 bladder cancer, and 10 transitional cell carcinoma except a case of mixed type of transitional cell carcinoma and squamous cell carcinoma). Four of the patients who had PR survived for 9, 8, 8 and 7 (alive) months, two who had MR survived for 8 and 4 months, three who had NC survived for 6, 4 and 4 months, and who two had progressive disease survived for 8 and 6 months. The major toxicities were myelosuppression and gastrointestinal symptoms, especially nausea and vomiting, but the treatment was well-tolerated.
Topics: Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cisplatin; Cytarabine; Female; Fluorouracil; Humans; Kidney Neoplasms; Male; Methotrexate; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; Peplomycin; Ureteral Neoplasms; Urinary Bladder Neoplasms; Vincristine
PubMed: 2414981
DOI: No ID Found -
Japanese Journal of Cancer Research :... Nov 1990Like bleomycin and peplomycin, libromycin, a newly developed bleomycin-group antibiotic, was potentiated 130-fold against Chinese hamster V79 cells (V79/S) and 47-fold... (Comparative Study)
Comparative Study
Like bleomycin and peplomycin, libromycin, a newly developed bleomycin-group antibiotic, was potentiated 130-fold against Chinese hamster V79 cells (V79/S) and 47-fold against its multidrug-resistant mutant (V79/ADM) by N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine (SDB-ethylenediamine) at 10 and 3 micrograms/ml, respectively. But neocarzinostatin, known to cause DNA strand scission as bleomycins do, was potentiated only twofold. This suggests that the high potentiation by SDB-ethylenediamine is unique to the bleomycin-group antibiotics. Isobologram analysis revealed that the combined effect of peplomycin and SDB-ethylenediamine was highly synergistic. SDB-ethylenediamine did not increase the intracellular accumulation of [3H]peplomycin in V79/S cells. Analyses by an alkaline elution method demonstrated that single strand scission in DNA of intact V79/S cells caused by 1-h incubation with peplomycin was greatly stimulated by pre- and co-existence of SDB-ethylenediamine, but DNA strand breaks in isolated nuclei were not affected. Apparently some cytoplasmic constituent(s) is involved in the potentiation mechanism. SDB-ethylenediamine did not block the DNA repair which occurred after the removal of peplomycin from the medium. Two fragments of SDB-ethylenediamine, solanesol (polyprenoid moiety) and a diamine component (verapamil-like moiety), were not synergistic with peplomycin, even when they were mixed together. This indicates that the steric conformation of the intact SDB-ethylenediamine molecule is important for the activity.
Topics: Animals; Antineoplastic Agents; Bleomycin; Cell Division; Cells, Cultured; Cricetinae; DNA Damage; Drug Synergism; Ethylenediamines; In Vitro Techniques; Peplomycin; Terpenes; Zinostatin
PubMed: 1702416
DOI: 10.1111/j.1349-7006.1990.tb02532.x -
Journal of Biological Inorganic... Oct 2017Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These...
Interaction of Zn(II)bleomycin-A and Zn(II)peplomycin with a DNA hairpin containing the 5'-GT-3' binding site in comparison with the 5'-GC-3' binding site studied by NMR spectroscopy.
Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These antibiotics have the ability to chelate a metal center, mainly Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by their C-terminal regions. Although this antibiotic family is a successful course of treatment for some types of cancers, it is known to cause pulmonary fibrosis. Previous studies have identified that bleomycin-related pulmonary toxicity is linked to the C-terminal region of these drugs. This region has been shown to closely interact with DNA. We examined the binding of Zn(II)peplomycin and Zn(II)bleomycin-A to a DNA hairpin of sequence 5'-CCAGTATTTTTACTGG-3', containing the binding site 5'-GT-3', and compared the results with those obtained from our studies of the same MBLMs bound to a DNA hairpin containing the binding site 5'-GC-3'. We provide evidence that the DNA base sequence has a strong impact in the final structure of the drug-target complex.
Topics: Antibiotics, Antineoplastic; Binding Sites; Bleomycin; DNA; Humans; Neoplasms; Nuclear Magnetic Resonance, Biomolecular; Peplomycin; Zinc
PubMed: 28748309
DOI: 10.1007/s00775-017-1482-z -
Hinyokika Kiyo. Acta Urologica Japonica Apr 1990In a 44-year-old man with persistent back-pain for 3 months duration, radiological and echological investigations revealed prostatic mass lesion with multiple... (Review)
Review
In a 44-year-old man with persistent back-pain for 3 months duration, radiological and echological investigations revealed prostatic mass lesion with multiple osteoblastic involvements. Transrectal biopsy to the prostate demonstrated pathohistologically poorly differentiated adenocarcinoma (Gleason's score 4-4:8). Serum ACP, ALP and IAP were elevated at the initial diagnosis pathologically. The clinical and pathological stage was D2, without metastasis to lung and liver. Combination chemo-endocrine therapy (methotrexate, adriamycin, pepleomycin, Estracyt and tegafur) with bilateral orchiectomies was performed exclusively as initial treatment. These consecutive treatments brought remarkable reduction of the prostatic mass lesion, decrease of tumor markers to normal range, rapid improvement of subjective symptoms and distinct decrease of abnormal activity in bone scintigram. More than 3 years survival was obtained, and normal performance-status was kept. Prostatic cancer in middle-aged adults is reviewed and discussed.
Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Doxorubicin; Estramustine; Humans; Male; Methotrexate; Nitrogen Mustard Compounds; Orchiectomy; Peplomycin; Prostatic Neoplasms; Remission Induction; Tegafur
PubMed: 1696064
DOI: No ID Found -
Hinyokika Kiyo. Acta Urologica Japonica Jan 1991Peplomycin emulsified in hydroxypropyl cellulosum (HPC-PEP) was prepared for intravesical chemotherapy. Clinical efficacy of HPC-PEP and tissue concentration of...
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.
Topics: Administration, Intravesical; Adult; Aged; Bleomycin; Carcinoma, Transitional Cell; Cellulose; Delayed-Action Preparations; Emulsions; Female; Humans; Male; Middle Aged; Peplomycin; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 1707215
DOI: No ID Found