Highlights • A higher level of cfDNA was found in patients with OPSCC than non-OPSCC patients. • A level of cfDNA in N2–N3 positive disease is significantly higher than in N0–N1. • A level of cfDNA ...in stage IV is significantly higher than in I–III stages. • 14% of HNSCC patients were HPV16/18-positive in plasma (96.4% cases possess HPV16).
Human papilloma virus (HPV) is highly frequent among patients with anal squamous cell carcinoma, but the viral load (VL) differs between patients. This study aimed to compare the rate of HPV ...positivity, HPV16VL, p16
INK4A
and p53 expression between treatment naive and recurrent anal cancer patients. HPV was genotyped via AmpliSens® HPV HCR-genotype-titre-FRT kit. HPV16 VL was determined via quantitative polymerase chain reaction-based in-house test. p16
INK4A
and p53 expression was tested via immunohistochemistry. The cohort comprised 13 treatment-naive and 17 recurrent anal SCC patients. High-risk HPV was detected in 87% of cases, and HPV16 (73%) was the predominant genotype. The rate of HPV positivity was higher among women and nonsmokers, and majority of HPV-positive cases were also p16
INK4A
-positive. All p53-negative tumors were HPV16-positive. The most predominant p53 staining pattern in the HPV-positive group was scattered type, whereas it was diffuse type in the HPV-negative group. The HPV16 VL was higher in the treatment-naive group. Further, in the treatment-naive group, cases with scattered staining pattern of p53 had higher HPV16 VL than cases with diffuse staining pattern. The opposite result was noted in the recurrent cancer group. Moreover, p16-positive cases with scattered p53 staining pattern in the treatment naive group had higher HPV16 VL than their counterparts in the recurrent cancer group. In conclusion, the HPV VL, as is the association between VL and p16
INK4A
/p53, is in an inversed trend in treatment naive and recurrent cancer patients, highlighting the importance of HPV VL measurement in anal SCC.
Implementation of anal squamous cell carcinoma (ASCC) treatment modifications requires reliable patient risk stratification. The circulating tumor-related human papillomavirus type 16 (ctHPV16) may ...play a role in predicting survival or assessing treatment response.
The study included 62 ASCC patients treated with chemoradiotherapy. A threshold of 2.5 was used to determine the maximum standardized uptake value (SUVmax). The ctHPV16 viral load (VL) was quantified by qPCR.
In the multivariate Cox analysis, lower SUVmax (
= 0.047) and ctHPV16-positive (
= 0.054) proved to be independent prognostic factors for favorable overall survival (OS). In the subgroup with the higher SUVmax, ctHPV16 and nodal (N) status were independent prognostic factors with
= 0.022 for ctHPV16 and
= 0.053 for N. The best survival rate (95%) presented ctHPV16-positive/N-negative patients. High ctHPV16 VL tended to be slightly specific for patients younger than 63 years (
= 0.152). The decrease in ctHPV16 VL to undetectable level after the end of treatment correlated with the overall clinical response.
A prognostic stratification by SUVmax, ctHPV16 and N-positive status allows consideration of more aggressive treatment in high-risk patients (those with high SUVmax, ctHPV16-negative, and N-positive) or de-intensification of therapy in low-risk patients (those with low SUVmax, ctHPV16-positive and N-negative). However, prospective clinical trials on a large group are needed.
Introduction The availability and non-invasiveness of circulating cell-free DNA (cfDNA) opens up new possibilities for real-time serial testing. The relationship between cfDNA concentration, clinical ...factors and suitability for monitoring was analyzed in patients with newly diagnosed anal squamous cell carcinoma (ASCC). Material and methods Blood samples were collected at several points during and after treatment. Patients were homogeneously treated with chemoradiotherapy. Results The concentration of cfDNA strongly correlated with the tumor volume (r = 0.9, p = 0.00006) and number of neutrophils (r = 0.706, p = 0.0069). Monitoring of cfDNA levels during treatment showed an increase after initiation of therapy, a peak at the end of treatment with significantly higher values for advanced than in T1/T2 tumors, and a decrease (T3/T4) during follow-up. However, neither the concentration of cfDNA before treatment nor its changes correlated with the response to chemoradiotherapy. There was no association between baseline cfDNA levels and T, N, age and gender. Conclusions Substantial changes in plasma cfDNA content can be observed after chemoradiotherapy for ASCC. However, the small number of cases studied makes it difficult to assess the usefulness of the cfDNA test.
Analysis of circulating cell-free DNA in blood is considered as a liquid biopsy, which enables non-invasive and repetitive investigation of the tumor DNA. The potential clinical usefulness of ...circulating DNA is frequently examined in lung cancer. Thus, our aim was assessment if chemotherapy influences the circulating DNA concentration.
Fifty-seven lung cancer patients in advanced stages of the disease were examined. Quantification of circulating DNA was determined by TERT amplification.
Distant metastases and chemotherapy were significantly connected with circulating DNA level. Patients treated with conventional chemotherapy had statistically lower circulating DNA levels when compared to patients not treated with chemotherapy. Histological types of tumor and smoking status were not associated with circulating DNA concentration. In this study, we have also genotyped the EGFR mutations in exon 19 of circulating DNA using the TaqMan PCR assays. One patient carried a deletion (2235-49del in EGFR), which has been confirmed by sequencing.
Circulating DNA is easy to obtain, convenient biological material, although quantitative analysis cannot be used as diagnostic tool, but it can be applied to determination of EGFR mutations, basis of the tyrosine kinase inhibitors application.
Intoxication of rats with thioacetamide (TAA) is a model system to investigate mechanisms involved in liver cell death and tissue reconstitution. Our study was undertaken to determine by ...immunohistochemistry the expression pattern of the cytoprotective chaperone proteins HSC70 and HSP25 and proliferation markers cyclin D1 and PCNA in livers of Wistar rats intraperitoneally injected with TAA at a single dose of 50 mg/kg. For each protein studied we observed distinct dynamic changes in appearance and localization in liver lobules. During 24-36 h after TAA injection the HSC70 cytoplasmic immunoreaction gradually disappeared from hepatocytes localized around central veins and a shift of immunostaining to cell nuclei took place. Then, 36-48 h after TAA injection the HSC70 cytoplasmic immunoreaction reappeared with the highest intensity in hepatocytes surrounding the areas of inflammatory cells. HSP25, undetectable in control hepatocytes began to appear at approximately 36 h after TAA injection and HSP25-immunopositive cells formed a characteristic ring around areas of inflammation. Of the proteins studied, the most rapid reaction to TAA was observed for cyclin D1. As early as 15 min after TAA administration cyclin D1-positive hepatocytes appeared in intermediate and periportal areas of liver lobules and a subsequent shift of staining to centrilobular hepatocytes took place at 36 and 48 h. There was no correlation of cyclin D1 localization either with PCNA-positive cells or mitotic cells. Our observations suggest that in TAA-treated livers HSP25 and HSC70 proteins can play an anti-inflammatory role, and the early and distinct cyclin D1 expression is not related to proliferation of hepatocytes.
The expression pattern of stress (heat shock) proteins (HSPs) in cancer cells is frequently different from that observed in normal cells; most often some stress-inducible HSPs are constitutively and ...highly expressed. The objective of this study was to determine the prognostic significance of stress proteins HSP70i and HSP27 in non-small cell lung carcinoma (NSCLC).
An immunohistochemical procedure that enables unambiguous detection of HSP70i protein was used.
Strong HSP70i staining showed a survival advantage, although multivariate analysis did not confirm this result. There was an evident correlation between HSP27 overexpression and survival of patients and the results were confirmed by multivariate analysis: 70% of patients with HSP27-negative tumors died within one year after the surgery.
Our data suggest that HSP27 and HSP70i positivity may represent a favorable prognostic factor in NSCLC.
The present report is a follow-up to our previous molecular epidemiology studies on DNA damage in residents of the industrial region of Upper Silesia. The study was designed to focus on environmental ...exposure to airborne pollutants; other exposures or confounding factors (e.g. smoking status and age) were eliminated. A Silesian population consisting of 67 donors was compared to 72 inhabitants of a less polluted but similarly urbanized area, surrounded by a rural part of Poland. In both regions the donors were non-smoking females with similar age range, and occupation. Eight biomarkers including urinary mutagenicity and 1-hydroxypyrene, polycylic aromatic hydrocarbon PAH-DNA adducts in oral mucosa, sister chromatid exchanges (SCE), high frequency cells (HFC), chromosomal aberrations (CA), and sensitivity to bleomycin in lymphocytes as well as glutathione
s-transferase (GSTM1)/cytochrome P4501A1 (CYP1A1) genotypes were evaluated in samples collected in summer and winter seasons. All the biomarkers of internal and biological doses of mutagens and their early biologic effects indicated statistically significant increases in the Silesian group when compared to the controls. Immunohistochemical quantitation of PAH-DNA adducts additionally revealed significant seasonal changes in the levels of adducts. No influence of susceptibility genotypes (GSTM1 and CYP1A1) on biomarker levels was observed.
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