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DNA Repair Jul 2014TDP1 and TDP2 were discovered and named based on the fact they process 3'- and 5'-DNA ends by excising irreversible protein tyrosyl-DNA complexes involving... (Review)
Review
TDP1 and TDP2 were discovered and named based on the fact they process 3'- and 5'-DNA ends by excising irreversible protein tyrosyl-DNA complexes involving topoisomerases I and II, respectively. Yet, both enzymes have an extended spectrum of activities. TDP1 not only excises trapped topoisomerases I (Top1 in the nucleus and Top1mt in mitochondria), but also repairs oxidative damage-induced 3'-phosphoglycolates and alkylation damage-induced DNA breaks, and excises chain terminating anticancer and antiviral nucleosides in the nucleus and mitochondria. The repair function of TDP2 is devoted to the excision of topoisomerase II- and potentially topoisomerases III-DNA adducts. TDP2 is also essential for the life cycle of picornaviruses (important human and bovine pathogens) as it unlinks VPg proteins from the 5'-end of the viral RNA genome. Moreover, TDP2 has been involved in signal transduction (under the former names of TTRAP or EAPII). The DNA repair partners of TDP1 include PARP1, XRCC1, ligase III and PNKP from the base excision repair (BER) pathway. By contrast, TDP2 repair functions are coordinated with Ku and ligase IV in the non-homologous end joining pathway (NHEJ). This article summarizes and compares the biochemistry, functions, and post-translational regulation of TDP1 and TDP2, as well as the relevance of TDP1 and TDP2 as determinants of response to anticancer agents. We discuss the rationale for developing TDP inhibitors for combinations with topoisomerase inhibitors (topotecan, irinotecan, doxorubicin, etoposide, mitoxantrone) and DNA damaging agents (temozolomide, bleomycin, cytarabine, and ionizing radiation), and as novel antiviral agents.
Topics: Animals; Antineoplastic Agents; Antiviral Agents; Cattle; DNA End-Joining Repair; DNA Topoisomerases, Type I; DNA-Binding Proteins; Humans; Neoplasms; Nuclear Proteins; Phosphoric Diester Hydrolases; Picornaviridae; RNA, Viral; Signal Transduction; Transcription Factors
PubMed: 24856239
DOI: 10.1016/j.dnarep.2014.03.020 -
Journal of Cutaneous and Aesthetic... 2019The incidence of melanoma and nonmelanoma skin cancers is increasing in the United Kingdom. Surgical excision carries the highest cure rates for all skin cancers and is... (Review)
Review
BACKGROUND
The incidence of melanoma and nonmelanoma skin cancers is increasing in the United Kingdom. Surgical excision carries the highest cure rates for all skin cancers and is the first-line treatment for melanomas and high-risk nonmelanoma cancers. This is most commonly performed by general practitioners (GPs), dermatologists, and plastic surgeons.
OBJECTIVE
The aim of this study was to identify which health-care professionals achieve the best outcomes following surgical excision of skin cancer lesions.
MATERIALS AND METHODS
A comprehensive search of the Cochrane Library and PubMed databases was conducted. PRISMA guidelines were adhered to throughout.
RESULTS
Six studies were identified and reviewed. Dermatologists were most likely to excise lesions adequately, and GPs were the least likely. Dermatologists displayed the greatest diagnostic accuracy, and excisions led by them had the highest overall and disease-free survival rates. Plastic surgeons were most likely to excise complex lesions on difficult-to-treat areas.
CONCLUSION
Dermatologists can excise many skin lesions adequately, but plastic surgeons should continue to take an active role in complex or anatomically challenging lesions. There is a need for more validated training for GPs in the management of skin cancers. Further studies incorporating a randomized control protocol are needed to definitely assess who is best placed to surgically excise these lesions.
PubMed: 31619886
DOI: 10.4103/JCAS.JCAS_174_18 -
World Journal of Clinical Oncology Feb 2016The primary goal of breast-conserving surgery (BCS) is to obtain tumour-free resection margins. Margins positive or focally positive for tumour cells are associated with... (Review)
Review
The primary goal of breast-conserving surgery (BCS) is to obtain tumour-free resection margins. Margins positive or focally positive for tumour cells are associated with a high risk of local recurrence, and in the case of tumour-positive margins, re-excision or even mastectomy are sometimes needed to achieve definite clear margins. Unfortunately, tumour-involved margins and re-excisions after lumpectomy are still reported in up to 40% of patients and additionally, unnecessary large excision volumes are described. A secondary goal of BCS is the cosmetic outcome and one of the main determinants of worse cosmetic outcome is a large excision volume. Up to 30% of unsatisfied cosmetic outcome is reported. Therefore, the search for better surgical techniques to improve margin status, excision volume and consequently, cosmetic outcome has continued. Nowadays, the most commonly used localization methods for BCS of non-palpable breast cancers are wire-guided localization (WGL) and radio-guided localization (RGL). WGL and RGL are invasive procedures that need to be performed pre-operatively with technical and scheduling difficulties. For palpable breast cancer, tumour excision is usually guided by tactile skills of the surgeon performing "blind" surgery. One of the surgical techniques pursuing the aims of radicality and small excision volumes includes intra-operative ultrasound (IOUS). The best evidence available demonstrates benefits of IOUS with a significantly high proportion of negative margins compared with other localization techniques in palpable and non-palpable breast cancer. Additionally, IOUS is non-invasive, easy to learn and can centralize the tumour in the excised specimen with low amount of healthy breast tissue being excised. This could lead to better cosmetic results of BCS. Despite the advantages of IOUS, only a small amount of surgeons are performing this technique. This review aims to highlight the position of ultrasound-guided surgery for malignant breast tumours in the search for better oncological and cosmetic outcomes.
PubMed: 26862490
DOI: 10.5306/wjco.v7.i1.44 -
World Journal of Gastroenterology Oct 2014Complete mesocolic excision is a relatively new concept in western literature. It follows the same concept of total mesorectal excision and units' routinely performing... (Review)
Review
Complete mesocolic excision is a relatively new concept in western literature. It follows the same concept of total mesorectal excision and units' routinely performing complete mesocolic excisions have good pathological results as well as good improvements in overall survival, disease free survival and local recurrence. And yet unlike total mesorectal excision, uptake in the West has been relatively slow with many units sceptical of the true benefits gained by taking up a more technically challenging and potentially more morbid procedure when there is a paucity of literature to support these claims. This article reviews complete mesocolic excision for colon cancer, attempting to identify the risks and benefits of the technique and particularly looking at the reasons why its uptake has not been universal. It also discusses the similarities of a complete mesocolic excision to a colon resection with a D3 lymphadenectomy as well as the role of a laparoscopic approach to this technique. Considering a D3 lymphadenectomy has been the standard of care for stage II and III colon cancers in many of our Asian neighbours for over 20 years, combining this data with data on complete mesocolic excision may provide enough evidence to support or refute the need for complete mesocolic excisions. Maybe there might be lessons to be learnt from our colleagues in the east.
Topics: Asia; Attitude of Health Personnel; Colectomy; Colorectal Neoplasms; Diffusion of Innovation; Healthcare Disparities; Humans; Laparoscopy; Lymph Node Excision; Neoplasm Staging; Patient Selection; Practice Patterns, Physicians'; Risk Factors; Treatment Outcome; Western World
PubMed: 25339817
DOI: 10.3748/wjg.v20.i39.14301 -
DNA Repair May 2020Topoisomerases are essential enzymes solving DNA topological problems such as supercoils, knots and catenanes that arise from replication, transcription, chromatin... (Review)
Review
Topoisomerases are essential enzymes solving DNA topological problems such as supercoils, knots and catenanes that arise from replication, transcription, chromatin remodeling and other nucleic acid metabolic processes. They are also the targets of widely used anticancer drugs (e.g. topotecan, irinotecan, enhertu, etoposide, doxorubicin, mitoxantrone) and fluoroquinolone antibiotics (e.g. ciprofloxacin and levofloxacin). Topoisomerases manipulate DNA topology by cleaving one DNA strand (TOP1 and TOP3 enzymes) or both in concert (TOP2 enzymes) through the formation of transient enzyme-DNA cleavage complexes (TOPcc) with phosphotyrosyl linkages between DNA ends and the catalytic tyrosyl residue of the enzymes. Failure in the self-resealing of TOPcc results in persistent TOPcc (which we refer it to as topoisomerase DNA-protein crosslinks (TOP-DPC)) that threaten genome integrity and lead to cancers and neurodegenerative diseases. The cell prevents the accumulation of topoisomerase-mediated DNA damage by excising TOP-DPC and ligating the associated breaks using multiple pathways conserved in eukaryotes. Tyrosyl-DNA phosphodiesterases (TDP1 and TDP2) cleave the tyrosyl-DNA bonds whereas structure-specific endonucleases such as Mre11 and XPF (Rad1) incise the DNA phosphodiester backbone to remove the TOP-DPC along with the adjacent DNA segment. The proteasome and metalloproteases of the WSS1/Spartan family typify proteolytic repair pathways that debulk TOP-DPC to make the peptide-DNA bonds accessible to the TDPs and endonucleases. The purpose of this review is to summarize our current understanding of how the cell excises TOP-DPC and why, when and where the cell recruits one specific mechanism for repairing topoisomerase-mediated DNA damage, acquiring resistance to therapeutic topoisomerase inhibitors and avoiding genomic instability, cancers and neurodegenerative diseases.
Topics: DNA; DNA Adducts; DNA Repair; DNA Topoisomerases, Type I; Humans; Phosphoric Diester Hydrolases; Topoisomerase Inhibitors
PubMed: 32200233
DOI: 10.1016/j.dnarep.2020.102837 -
Clinical and Experimental Dental... Dec 2022The primary aim of this ex vivo study was to evaluate thermal damage and cutting efficiency of micro and super pulsed diode lasers. The secondary aim was to suggest a...
OBJECTIVES
The primary aim of this ex vivo study was to evaluate thermal damage and cutting efficiency of micro and super pulsed diode lasers. The secondary aim was to suggest a guideline to perform simple surgical excisions adequate for histopathological evaluation.
MATERIAL AND METHODS
Ten groups of 10 specimens of pig tongues were excised using a blade (G1), a micro pulsed (G2-G9), and a super pulsed diode (G10) lasers. Different output power, pulse duration, pulse interval, and duty cycle were tested. Quantitative measures of thermal damage and excision times were recorded. Statistical analysis was performed at a significance level of 5%.
RESULTS
The control group (G1) presented no thermal damage. Within the laser groups (G2-G10), no statistically significant differences in depth of thermal damage (µm) were noted. G3 showed significantly less area of thermal damage (mm ) when compared with G7 and G9 (p < .05). The median excision time of the control group and super pulsed diode laser group were significantly lower (p < .001) than the micro pulsed diode laser groups.
CONCLUSIONS
The cutting efficiency of the super pulsed diode laser is comparable to traditional blade, and with appropriate parameters, these lasers can produce predictable surgical outcomes with less collateral damage.
Topics: Swine; Animals; Lasers, Semiconductor; Laser Therapy; Tongue
PubMed: 36218194
DOI: 10.1002/cre2.670 -
The British Journal of Dermatology Jun 2021Keratinocyte or nonmelanoma skin cancer (NMSC) is the commonest malignancy worldwide. The usual treatment is surgical excision. Current guidelines underestimate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Keratinocyte or nonmelanoma skin cancer (NMSC) is the commonest malignancy worldwide. The usual treatment is surgical excision. Current guidelines underestimate incomplete excision rates.
OBJECTIVES
We aimed to determine the risk of incomplete excision of NMSCs through a systematic review and meta-analysis of primary clinical studies.
METHODS
A PRISMA-compliant systematic review and meta-analysis was performed using methodology proposed by Cochrane (PROSPERO CRD42019157936). A comprehensive search strategy was applied to MEDLINE, Embase, Scopus, CINAHL, EMCare, Cochrane Library and the grey literature (January 2000-27 November 2019). All studies were included except those on Mohs micrographic surgery, frozen section or biopsies. Abstract screening and data extraction were performed in duplicate. Risk of bias was assessed using a tool for prevalence/incidence studies. The primary outcome was the proportion of incomplete surgical excisions. A random-effects model for pooling of binomial data was used. Differences between proportions were assessed by subgroup meta-analysis and meta-regression, which were presented as risk ratios (RRs).
RESULTS
Searching identified 3477 records, with 110 studies included, comprising 53 796 patients with 106 832 basal cell carcinomas (BCCs) and 21 569 squamous cell carcinomas (SCCs). The proportion of incomplete excisions for BCC was 11·0% [95% confidence interval (CI) 9·7-12·4] and for SCC 9·4% (95% CI 7·6-11·4). Proportions of incomplete excisions by specialty were: dermatology, BCCs 6·2% and SCCs 4·7%; plastic surgery, BCCs 9·4% and SCCs 8·2%; general practitioners, BCCs 20·4% and SCCs 18·9%. The risk of incomplete excision for general practitioners was four times that of dermatologists for both BCCs (RR 3·9, 95% CI 2·0-7·3) and SCCs (RR 4·8, 95% CI 1·0-22·8). Studies were heterogeneous (I = 98%) and at high risk of bias.
CONCLUSIONS
The proportion of incomplete excisions is higher than previously reported. Excisions performed by specialists may lower the risk of incomplete excision.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Keratinocytes; Mohs Surgery; Skin Neoplasms
PubMed: 33131067
DOI: 10.1111/bjd.19660 -
Asian Journal of Urology Jul 2016Treatment of clinically-organ confined high grade urothelial carcinoma of the upper tract has historically comprised open nephroureterectomy, with the distal ureter and... (Review)
Review
Treatment of clinically-organ confined high grade urothelial carcinoma of the upper tract has historically comprised open nephroureterectomy, with the distal ureter and bladder cuff mobilized through a separate open pelvic incision. To decrease morbidity, urologists have increasingly adopted laparoscopy and robotics in performing nephroureterectomy. In many published series of laparoscopic nephroureterectomy, the distal ureter and bladder cuff are detached from the bladder endoscopically by a variation of the "pluck" technique, with the resulting bladder defect left to heal by prolonged indwelling urethral catheter drainage. While the distal ureter and bladder cuff can be excised laparoscopically, it does require advanced laparoscopic skills. With the wrist articulation and stereoscopic vision in robotic surgery, robotic nephroureterectomy (RNU) and bladder cuff excision can be performed in antegrade fashion to mimic the open technique together with the ability to intracorporeally close the bladder defect in a watertight, mucosa to mucosa fashion after excising the bladder cuff. In this review, we discuss the published minimally invasive techniques in resecting the distal ureter and bladder cuff during laparoscopic and RNU.
PubMed: 29264178
DOI: 10.1016/j.ajur.2016.04.001