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Chemistry (Weinheim An Der Bergstrasse,... Oct 2018Despite evidence that histone H3 and H4 proteins may act as the precursor for orientating the DNA sequence to form nucleosome structures, there is no direct evidence of...
Despite evidence that histone H3 and H4 proteins may act as the precursor for orientating the DNA sequence to form nucleosome structures, there is no direct evidence of the formed compact structure. Here, it is demonstrated that a histone H3-H4 octasome could be constructed without the involvement of histone H2A-H2B under in vitro reconstitution conditions. Atomic force microscopy was used to obtain the first direct observation of the octasome structure, which exhibited a similar core-protein size as that of a nucleosome but with a shorter core histone-binding DNA region. The octasome also displayed a one-step histone-dissociation pattern under heat treatment, distinct micrococcal nuclease and peplomycin accessibility, which suggests a different wrapping pattern to that in nucleosomes.
PubMed: 30088306
DOI: 10.1002/chem.201804010 -
Nihon Rinsho. Japanese Journal of... Feb 2015
Topics: Antibiotics, Antineoplastic; Bleomycin; Dactinomycin; Humans; Mitomycin; Neoplasms; Peplomycin
PubMed: 25831749
DOI: No ID Found -
International Journal of Oral and... Aug 2020The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial...
Preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma.
The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Fluorouracil; Humans; Mouth Neoplasms; Neoplasm Recurrence, Local; Peplomycin; Taxoids
PubMed: 32070653
DOI: 10.1016/j.ijom.2020.01.024 -
Hematological Oncology Jun 2017Nasal natural killer (NK)/T-cell lymphoma (NNKTL) displays unusual clinicopathological features, and the prognosis is very poor, even in the early stages of the disease....
Nasal natural killer (NK)/T-cell lymphoma (NNKTL) displays unusual clinicopathological features, and the prognosis is very poor, even in the early stages of the disease. For early stage NNKTL, we have developed a novel chemoradiotherapy regimen incorporating arterial infusion chemotherapy, administered via the superficial temporal artery, in combination with radiotherapy. The novel arterial infusion regimen consists of ifosfamide, carboplatin, methotrexate, peplomycin, and etoposide (MPVIC-P). From 2003 to 2011, 12 patients with early stage NNKTL were treated with the MPVIC-P regimen via arterial infusion with concomitant radiotherapy (54 Gy). We have previously reported on the presence of Epstein-Barr virus (EBV) genetic DNA in NNKTL. Therefore, the effect of the treatment was evaluated by using both clinical findings and serum EBV DNA copy number. The observation period ranged from 39 months to 111 months post-treatment (median: 81 months). All 12 patients achieved and maintained complete remission and, to date, show no sign of relapse. Serum EBV DNA copy numbers decreased to below detectable levels in all 12 patients tested. Manageable mucositis was the most common grade 3-4 toxicity, and it was seen in 10 (83%) patients. However, grade 3-4 hematological toxicity was only seen in 4 (33%) patients. We conclude that our regimen of intra-maxillary arterial chemotherapy with concomitant radiotherapy is an effective treatment with minimal toxicity for early stage NNKTL. Copyright © 2015 John Wiley & Sons, Ltd.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Female; Humans; Infusions, Intra-Arterial; Killer Cells, Natural; Lymphoma, Extranodal NK-T-Cell; Lymphoma, T-Cell; Male; Middle Aged; Neoplasm Staging; Nose Neoplasms
PubMed: 26563973
DOI: 10.1002/hon.2273 -
European Journal of Surgical Oncology :... Mar 2015Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear.
Efficacy and safety of systemic chemotherapy and intra-arterial chemotherapy with/without radiotherapy for bladder preservation or as neo-adjuvant therapy in patients with muscle-invasive bladder cancer: a single-centre study of 163 patients.
INTRODUCTION
Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear.
MATERIALS AND METHODS
The anti-tumour effects and adverse events were evaluated in 163 MIBC patients who received systemic chemotherapy (SC, n = 34), intra-arterial chemotherapy (IAC, n = 50), or combined IAC and radiotherapy (IAC + R, n = 79).
RESULTS
Pathological complete responses were observed in 17.6%, 22.0%, and 43.0% of patients in the SC, IAC, and IAC + R groups, respectively, with respective 5-year overall survival rates of 42.0%, 46.7%, and 50.3%. Multivariate analysis showed that successful IAC + R protocol administration was a significant predictor for survival (hazard ratio = 0.16, p = 0.028). The incidence of severe adverse events was higher in the IAC + R group (36.7%) than in the SC (9.8%) and IAC groups (16.0%).
CONCLUSIONS
IAC + R was useful for patients with MIBC. Successful completion and optimal patient selection were important for this treatment strategy.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Transitional Cell; Chemoradiotherapy; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Cisplatin; Cystectomy; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Invasiveness; Organ Sparing Treatments; Peplomycin; Prognosis; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 25312685
DOI: 10.1016/j.ejso.2014.07.043 -
BMC Cancer Dec 2020The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important....
BACKGROUND
The prognosis of advanced oral cancer remains dismal. While multimodal therapy is beneficial, maintaining the quality of life of long-term survivors is important. Therefore, risk-adapted treatment regimens need to be designed. We herein investigated whether pathological responses in oral cancer patients treated with preoperative chemoradiotherapy predict locoregional recurrence.
METHODS
We retrospectively reviewed the data of 51 oral cancer patients who received preoperative radiotherapy and concurrent pepleomycin, followed by curative surgery at our institution between January 2009 and June 2018. Each patient received preoperative external beam irradiation to the primary tumor and lymphatics (2 Gy per day for approximately 3 weeks) concurrent with pepleomycin (2.5 mg/day). Surgery was performed approximately 3-4 weeks after the completion of preoperative chemoradiotherapy. Pathological responses were defined based on the grading system of Oboshi and Shimosato.
RESULTS
Eight, 22, 16, and 5 patients had Oboshi and Shimosato grades 2a, 2b, 3, and 4, respectively. Favorable pathological responses (grades 3 and 4) were observed in 41.2% of patients (21 out of 51 patients). The pathological response and number of pathological lymph node metastases were identified as significant prognostic factors for locoregional control in the univariate analysis. Three-year locoregional control rates were 100 and 56.6% in patients with favorable and unfavorable pathological responses, respectively.
CONCLUSIONS
The present study demonstrated that pathological tumor responses to preoperative chemoradiotherapy are a useful predictive factor for locoregional control.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Female; Follow-Up Studies; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Lymphatic Irradiation; Lymphatic Metastasis; Male; Middle Aged; Mouth Neoplasms; Neck Dissection; Neoadjuvant Therapy; Peplomycin; Pneumonia, Aspiration; Radiotherapy Dosage; Radiotherapy, Conformal; Retrospective Studies; Treatment Outcome; Xerostomia
PubMed: 33302897
DOI: 10.1186/s12885-020-07707-2 -
Chembiochem : a European Journal of... Apr 2018Capillary electrophoresis, coupled with DNA 5' Texas Red labeling, was used to investigate the ability of MNase, Fe peplomycin, and duocarmycin B to access the...
Capillary electrophoresis, coupled with DNA 5' Texas Red labeling, was used to investigate the ability of MNase, Fe peplomycin, and duocarmycin B to access the nucleosome. Distinct accessibility patterns of these species to the nucleosome were observed. MNase was completely prevented from approaching the nucleosome core and exhibited a higher site specificity for targeting DNA sites located close to the core region. Intercalation of peplomycin in the nucleosomal core region was highly suppressed, but reaction sites located at the ends of the nucleosomal core remained accessible, which implied flexibility of the core DNA end. Duocarmycin B was able to enter and react in the core region, although its alkylating efficiency decreased significantly.
Topics: DNA; DNA Cleavage; Duocarmycins; Electrophoresis, Capillary; Ferrous Compounds; Indoles; Micrococcal Nuclease; Nucleosomes; Peplomycin; Pyrrolidinones
PubMed: 29334166
DOI: 10.1002/cbic.201700643 -
Dermatology (Basel, Switzerland) 2015Continuous intra-arterial administration of peplomycin (PEP) through a tumor-feeding artery using an intravascular indwelling catheter is one of the best treatments for...
BACKGROUND
Continuous intra-arterial administration of peplomycin (PEP) through a tumor-feeding artery using an intravascular indwelling catheter is one of the best treatments for cutaneous squamous cell carcinoma (SCC) on cosmetic areas. Although this reagent is useful for the treatment of SCC, its immunomodulatory effect on the tumor microenvironment is still unknown.
OBJECTIVE/METHODS
In this study, we investigated the immunomodulatory effects of PEP on the tumor-infiltrating regulatory T cells and tumor-associated macrophages as well as CD8(+)TIA-1(+) cytotoxic T cells in the lesional skin of 5 patients with SCC on the lips.
RESULTS
Our data suggest that, in addition to the direct antitumor effects, PEP decreased immunosuppressive cells and increased cytotoxic T lymphocytes at the tumor sites, which might maintain antitumor immune response against SCC.
Topics: Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Humans; Immunomodulation; Infusions, Intra-Arterial; Lip; Macrophages; Neovascularization, Pathologic; Peplomycin; Skin Neoplasms; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory
PubMed: 25678188
DOI: 10.1159/000369166 -
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 -
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