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Magnetochemistry (Basel, Switzerland) 2018Bleomycins are antitumor antibiotics that can chelate a metal center and cause site-specific DNA cleavage at 5'-Gpyrimidine-3' regions of DNA. These antibiotics are...
Bleomycins are antitumor antibiotics that can chelate a metal center and cause site-specific DNA cleavage at 5'-Gpyrimidine-3' regions of DNA. These antibiotics are successful in the treatment of various cancers, but are known to cause pulmonary fibrosis to patients under bleomycin regimes. Substantial research has resulted in the development of over 300 bleomycin analogs, aiming to improve the therapeutic index of the drug. Previous studies have proposed that the lung toxicity caused by bleomycin is related to the C-terminal regions of these drugs, which have been shown to closely interact with DNA in metal-bleomycin-DNA complexes. Some of the research studying metallo-bleomycin-DNA interactions have suggested three different binding modes of the metal form of the drug to DNA, including total and/or partial intercalation, and minor groove binding. However, there is still lack of consensus regarding this matter, and solid conclusions on the subject have not yet been established. Previously we investigated the diverse levels of disruption caused to DNA hairpins containing 5'-GC-3' and 5'-GT-3' binding sites, which are consequence of the binding of bleomycins with different C-termini. The results of these investigation indicate that both the DNA-binding site and the bleomycin C-termini have an impact on the final conformations of drug and target. The present study focuses on the structural alterations exhibited by Zn(II)bleomycin-A, -B, -A and Zn(II)peplomycin upon binding to DNA hairpins containing 5'-GC-3' and 5'-GT-3' binding sites. Evidence that each Zn(II)bleomycin is structurally affected depending on both its C-terminus and the DNA-binding site present in the hairpin is provided.
PubMed: 30464999
DOI: 10.3390/magnetochemistry4010004 -
Anticancer Research Apr 2017Continuous intra-arterial (IA) administration of peplomycin (PEP) through a tumor-feeding artery is one of the most effective treatments for cutaneous squamous cell...
BACKGROUND
Continuous intra-arterial (IA) administration of peplomycin (PEP) through a tumor-feeding artery is one of the most effective treatments for cutaneous squamous cell carcinoma (cSCC) in cosmetic areas.
PATIENTS AND METHODS
In order to determine the effective and safe dose of PEP and the curative rate of IA-PEP, we retrospectively investigated a case series of 24 patients with cSCC on the lips who were treated with IA-PEP.
RESULTS
IA-PEP reduced the tumor mass in all 24 cases (100%). A complete response occurred in 17 patients (70.8%), and a partial response occurred in seven (29.2%). Moreover, 17 patients (70.8%) were cured, three patients developed cervical lymph node metastasis (12.5%), and four developed local recurrence (16.7%). Three out of the 24 patients developed interstitial pneumonia (12.5%).
CONCLUSION
Low-dose IA-PEP administered through a superficial temporal artery was a highly effective treatment that achieved a curative response for 70.8% of patients with cSCC on the lips.
Topics: Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Female; Humans; Infusions, Intra-Arterial; Lip Neoplasms; Male; Middle Aged; Neoplasm Staging; Peplomycin; Prognosis; Retrospective Studies; Skin Neoplasms; Temporal Arteries
PubMed: 28373456
DOI: 10.21873/anticanres.11526 -
European Journal of Dermatology : EJD Apr 2022
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Humans; Infusions, Intra-Arterial; Lip; Peplomycin
PubMed: 35866907
DOI: 10.1684/ejd.2022.4235 -
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 -
Plastic and Reconstructive Surgery.... Feb 2019In the field of plastic surgery, subcutaneous masses in the buttocks are frequently observed. However, squamous cell carcinoma (SCC) after epidermoid cyst, which appears...
In the field of plastic surgery, subcutaneous masses in the buttocks are frequently observed. However, squamous cell carcinoma (SCC) after epidermoid cyst, which appears in the presacral space, is extremely rare. This report described a case of a 71-year-old woman, who previously received a skin incision by a doctor for treating a cystic lesion in the buttock; she was diagnosed with SCC by preoperative biopsy at the authors' department. In addition, computed tomography suspected that the tumor originated in the presacral space. Under general anesthesia, an extended resection of the malignant tumor with gastrointestinal surgery was performed. After resection, the defect of buttocks region was reconstructed with a V-Y advancement gluteus maximus myocutaneous flap. After pathological examination the tumor was diagnosed as SCC after epidermoid cyst; peplomycin sulfate at 50 mg/d was administered intramuscularly for 2 weeks as chemotherapy. No wound complications were observed after surgery, and no recurrence was noted for 5 years. For managing tumor in the gluteal region, a possibility of malignancy must be considered, and thorough radiographic studies must be pursued before surgery.
PubMed: 30881827
DOI: 10.1097/GOX.0000000000002069 -
Case Reports in Dermatology Sep 2014Cutaneous squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer and tends to develop in sun-exposed cosmetic areas, including the ear. In this...
Cutaneous squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer and tends to develop in sun-exposed cosmetic areas, including the ear. In this report, we describe two cases of SCC on the ear successfully treated with intra-arterial administration of peplomycin through a superficial temporal artery. In addition to this selective chemotherapy, we administered oral tegafur, which achieved complete remission of the tumor. These findings suggest that intra-arterial administration of peplomycin with tegafur is one of the optimal therapies for the treatment of SCC developing on the ear.
PubMed: 25408647
DOI: 10.1159/000367804