SummaryBackgroundThe broad spectrum of oxidative damage DNA biomarkers: urinary excretion of 8-oxodG (8-oxo-7,8-dihydro-2′-deoxyguanosine), 8-oxoGua (8-oxo-7,8-dihydroguanine) as well as the level of oxidative damage DNA in leukocytes, was analyzed in cancer patients and healthy subjects.Material/Methods222 cancer patients and 134 healthy volunteers were included in the analysis, using methodologies which involve HPLC (high-performance liquid chromatography) prepurification followed by gas chromatography with isotope dilution mass spectrometry detection and HPLC/EC.ResultsFor the whole patient population (n=222) the median values of 8-oxoGua and 8-oxodG in urine samples were 12.44 (interquartile range: 8.14–20.33) [nmol/24 hr] and 6.05 (3.12–15.38) [nmol/24 hr], respectively. The median values of 8-oxoGua and 8-oxodG in urine samples of the control group (n=85) were 7.7 (4.65–10.15) [nmol/24 hr] and 2.2 (1.7–2.8) [nmol/24 hr], respectively. The level of 8-oxodG in DNA isolated from leukocytes of the patient population (n=179) and of the control group (n=134) was 4.93 (3.46–9.27) per 10’6 dG and 4.46 (3.82–5.31) per 10’6 dG, respectively.ConclusionsThe results suggest that oxidative stress in cancer patients, demonstrated by augmented amounts of these modifications in urine, could be typical not only for affected tissue but also for other tissues and even the whole organism. An assay that enables the determination of levels of basic markers of oxidative stress might be applied in clinical practice as an additional, helpful marker to diagnose cancer.
Purpose HPV is involved in the development of some head and neck squamous-cell carcinomas (HNSCC). It was suggested that only transcriptionally active virus can induce carcinogenesis, therefore, the aim of our study was to analyze the frequency of active HPV infection, virus type, and its prognostic role in HNSCC patients. Methods Status of active HPV infection was assessed for 155 HNSCC patients based on p16 expression and HPV DNA presence. Univariate and multivariate analyses with Cox proportional regression model were performed to select independent prognostic factors. Results Active HPV infection was detected in 20.65% of patients. We identified 16.0, 40.9 and 1.7% of HPV positive oral cavity, oropharyngeal, and laryngeal cancer cases, respectively. HPV16 was dominant (81.25%) followed by HPV35 (9.38%) and double infections with HPV16 and 35 (6.25%) or HPV35 and 18 (3.12%). Patients with active HPV infection demonstrated significantly higher survival than HPV negative ones (OS 80.89% vs. 37.08%, p = 0.000; DFS 93.0% vs. 53.35%, p = 0.000, respectively). Longer OS and DFS were maintained for infected patients when oropharyngeal and non-oropharyngeal cases were analyzed separately. Interestingly, all patients infected with other than HPV16 types survived 5 years without cancer progression. In the analyzed group of 155 patients the strongest independent favourable prognostic factor for both OS and DFS was HPV presence. Conclusions High prevalence of HPV-driven HNSCC (mostly within oropharynx) was detected, with HPV16 type the most frequent, followed by HPV35 and HPV18. The presence of active HPV infection improved survival of both oropharyngeal and non-oropharyngeal cancer patients and should be taken into account in treatment planning.
Purpose Presentation of long-term results of radiation treatment in patients with T1 glottic cancer and evaluation of prognostic factors. Methods We performed a retrospective analysis in a group of 569 patients with T1 squamous cell glottic carcinoma treated with radiotherapy at the Center of Oncology in Cracow between 1977 and 2007. In all, 503 (88%) patients presented with T1a stage disease and 66 (12%) with T1b. Anterior commissure infiltration was present in 179 (31%) patients. Average hemoglobin level prior to therapy was 13.9 g/dl. Using the body mass index (BMI), 114 (20%) patients were underweight, and 91 (16%) were overweight. Median time between collecting tumor specimen and beginning of radiotherapy was 56 days (range 14–145 days). Treatment regimen was normofractionated with single fraction ≤2 Gy in 102 (18%) and hypofractionated in 467 (82%) patients. Results The 5‑ and 10-year overall survival (OS), disease-specific survival (DSS) and local control (LC) rates were 85 and 68%, 88 and 86%, 89 and 87%, respectively. Multivariate analysis showed that tobacco smoking, low hemoglobin level (<13 g/dl), anterior commissure infiltration, fraction dose ≤2 Gy and time from collecting specimen to beginning of therapy longer than 30 days had negative impact on LC and DSS. Patients’ age over 60 years, worse performance status and malnutrition (BMI <18.5) had negative impacts on OS. Conclusions Radiotherapy is a highly effective treatment method in patients with T1N0M0 glottic cancer. LC and DSS may be improved following hypofractionation, smoking cessation, and shortening of waiting-time until start of treatment. OS was mainly influenced by nutritional and performance status.
The purpose of the study was to analyse the influence of HPV infection on the outcome of a randomized clinical trial of conventional (CF) versus 7-days-a-week postoperative radiotherapy (p-CAIR) for squamous cell cancer of the head and neck (SCCHN). Between 2001 and 2004, 279 patients with high-risk SCC of the larynx or cancer of the oral cavity/oropharynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week or 7 days a week (Radiother Oncol 87:155–163, 2008). The presence of HPV DNA in 131 archival paraffin blocks was assessed with multiplex quantitative real-time PCR using five consensus primers for the conservative L1 region and molecular beacon probes targeting 14 high-risk HPV subtypes. Following the RT-PCR procedure, we could determine the presence and type of HPV16, HPV18 and the other 12 less frequent oncogenic subtypes. Out of 131 samples, 9 were positive for HPV infection (6.9%), all of them with HPV16 subtype. None of the 65 laryngeal tumours was HPV positive. The 5-year LRC in HPV-positive patients was 100%, compared to 58% in the HPV-negative group (p = 0.02, log-rank test). Amongst 122 patients with HPV-negative tumours, 5-year LRC was 50.3% in p-CF versus 65.2 in p-CAIR (p = 0.37). HPV infection was associated with low expression of EGFR and cyclin D. This study demonstrates a favourable outcome for HPV-positive patients with SCCHN treated with postoperative radiotherapy. While considering the small number of HPV+ tumours, the data set can be considered as hypothesis generating only, the outcome raises new questions on the necessity of aggressive postoperative treatment in HPV+ patients.
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