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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 -
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 -
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 -
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 -
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 -
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 -
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 -
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 -
Yakugaku Zasshi : Journal of the... 2011No true immunocytochemistry (ICC) for drugs nor its application to pharmacokinetic studies is available. Recently, our studies have shown that ICC for drugs is extremely... (Review)
Review
No true immunocytochemistry (ICC) for drugs nor its application to pharmacokinetic studies is available. Recently, our studies have shown that ICC for drugs is extremely useful for such studies by utilizing easy and safe techniques, and gives direct evidence of drug localization. We have therefore developed antibodies and a series of pretreatment conditions for the immunodetection of drugs and have localized sites of drug uptake or accumulation in several tissues of rats following the administration of drugs. This review describes preparation of anti-drug antibody, specificity of antibody, fixation of drug in situ in rat tissues and cells, treatment of paraffin section specimens prior to immunoreaction, precision, and their application to a variety of types of antibiotics anti-cancer anthracyclines daunorubicin, doxorubicin, and epirubicin, bleomycin analog peplomycin, antimicrobial agents gentamicin, and amoxicillin. ICC for the anti-cancer anthracyclines demonstrated that the drug accumulates in a characteristic pattern in the heart, liver, kidney, gastrointestinal tract, and hair follicles, which represent the sites targeted by the drug toxicity. Some, but not all, of these drug accumulations are associated with the induction of apoptosis. It was also noted that there are striking differences in accumulation among the anthracyclines in rat tissues, maybe contributing the mechanisms of the differences in anti-tumor activities of the anthracyclines. Both ICCs for gentamicin and peplomycin identified characteristic necrotic-like cells in the specific sites of the kidney, suggesting the sites are readily affected by some chemotherapeutic agents. ICC for amoxicillin demonstrated that the sites of the drug accumulation in small intestine, liver and kidney are closely correlated with the specific sites in which certain transporter systems for penicillin occur. Thus, an ICC method is a potential new tool for pharmacokinetic studies of wide variety types of drugs containing a primary amino group(s) in their molecules.
Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Cells; Gentamicins; Hair Follicle; Immunohistochemistry; Kidney; Liver; Rats; Sensitivity and Specificity; Tissue Distribution
PubMed: 21628984
DOI: 10.1248/yakushi.131.949