Eva Hamsíková - Academia.edu (original) (raw)

Papers by Eva Hamsíková

Archives of Virology, 1990

Several vaccinia virus recombinants inducing the synthesis of the middle surface (M) protein of h... more Several vaccinia virus recombinants inducing the synthesis of the middle surface (M) protein of hepatitis B virus (HBV) were constructed. One of them, denoted v137, was examined in some detail. The virus replicated nearly to the same extent in various cell lines, viz. human embryo diploid fibroblast LEP and MRC-5 cells, rabbit embryo fibroblast REF cells, TK-rat RAT-2 cells, and green monkey CV-1 cells. However, the production of M protein was found considerably lower in the human LEP and MRC-5 than in the other cells examined. In addition, the kinetics of M formation were different in these two cell systems, LEP cells lagging significantly behind CV-1 cells. The lowlevel production of M protein in LEP cells was not increased by repeated v137 passages in LEP ceils, nor by a passage in a laboratory worker accidentally infected with the v137 virus, nor by shortening the leader sequence preceding the translation initiation codon. The greater part of the M antigen was found to be cell associated, more so in the cells of human than monkey origin. From the major HBV S antigen (HBsAg) isolated from the plasma of chronically infected subjects, the antigen released by cell destruction differed by binding to polymerized human albumin. This property was utilized in ELISA to detect anti-preS2 antibody. Rabbits inoculated intradermally with the v137 virus developed antibodies reactive in this assay as well as with a synthetic peptide corresponding in the amino acids 14-34 of the NH2terminus of the HBsAg preS2 region. 182 L. Kutinovfi et al.

European Archives of Oto-Rhino-Laryngology, 2008

Prognostic factors are important for treatment decisions as they help adapt the therapy on a case... more Prognostic factors are important for treatment decisions as they help adapt the therapy on a case-to-case basis. Nodal status, number of positive nodes, and presence of extracapsular spread are considered to be the important prognostic factors in head and neck cancer. Some studies suggest that human papillomavirus (HPV) status also inXuences the outcome of the treatment. This inXuence can be explained by the variation in tendency to develop regional metastases and by variation in the type of neck node involvement. The study objectives were to compare patients with HPV positive and HPV-negative tumors for survival and prevalence and type of regional metastasis, to identify prognostic factors and to test whether HPV presence is an independent factor of survival. The study included 81 patients treated by surgery including neck dissection for oral or oropharyngeal squamous cell cancer. A computerized medical report was completed for each patient. Analysis of the tumor specimen for the HPV DNA presence was done on paraYn-Wxed tissue. HPV DNA detection and typing were performed by PCR with GP5 + / GP6 + BIO primers and reverse line blot hybridization. Overall, 64% (52/81) of tumors were HPV positive with 80% in the tonsillar site. HPV-positive patients had signiWcantly better both overall (73 vs. 35%) (P = 0.0112) and disease-speciWc (79 vs. 45%) (P = 0.0015) survival rates than HPV-negative patients. No signiWcant diVerences were found in the pN classiWcation, in the number of positive nodes and the presence of extracapsular spread in the involved nodes between HPV positive and HPV-negative tumors. Multivariate analysis showed that signiWcant prognostic factors of survival were the presence of HPV in the tumor, extracapsular spread and tumor size. HPV was the most signiWcant prognostic factor in the studied group of patients with oropharyngeal tumors (HR = 0.27, 95%CI 0.12-0.61) and possibly should be considered in treatment decisions.

OncoImmunology, 2015

Kynurenine and uric acid levels in chronic myeloid leukemia patients, OncoImmunology, 4:3, ... more 2015) Kynurenine and uric acid levels in chronic myeloid leukemia patients, OncoImmunology, 4:3, e992646, Indoleamine 2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan 2,3-dioxygenase (TDO) represent some of the key immune regulators. Their increased activity has been demonstrated in a number of human malignancies but not yet in chronic myeloid leukemia (CML). In the present study, the activity of these enzymes was tested in 29 CML patients and 28 healthy subjects by monitoring the kynurenine (KYN)/tryptophan ratio. Serum samples taken prior to the therapy displayed a highly significant difference in KYN levels between the patient and control groups. However, increased KYN levels were detected in only 13 (44.8%) of these CML patients. The KYN levels in pretreatment sera of the patients correlated with the tumor burden. There was also a strong correlation between KYN levels and uric acid levels (UA). This suggests but does not prove the possible involvement of UA in activating IDO family of enzymes. Whenever tested, the increased KYN levels normalized in the course of the therapy. Patients with normal KYN levels in their pretreatment sera and subsequently treated with interferon-a, showed a transitory increase in their KYN levels. The present data indicate that CML should be added to the malignancies with an increased activity of the IDO family of enzymes and suggest that IDO inhibitors may be used in the treatment of CML patients.

PLOS One, 2011

BackgroundThe HPV prevalence and genotype distribution are important for the estimation of the im... more BackgroundThe HPV prevalence and genotype distribution are important for the estimation of the impact of HPV-based cervical cancer screening and HPV vaccination on the incidence of diseases etiologically linked to HPVs. The HPV genotype distribution varies across different geographical regions. Therefore, we investigated the type-specific HPV prevalence in Czech women and men with anogenital diseases.MethodsWe analyzed 157 squamous cell carcinoma

European Urology Supplements, 2010

introduction & objectives: Many human malignancies are associated with infection. The aim of the ... more introduction & objectives: Many human malignancies are associated with infection. The aim of the study was to compare plasma antibody levels against common genitourinary pathogens in prostate cancer (PC) patients and benign prostate hyperplasia (BPH) patients.

European Urology Supplements, 2011

introduction & objectives: Infection plays a role in the pathogenesis of many human malignancies.... more introduction & objectives: Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) belongs to these has been investigated in several studies so far with inconsistent methodology and disappointing results. The aim of the study was to compare seroprevalence and serum antibody levels in PCa and benign prostate hyperplasia (BPH) patients and to correlate histopathological findings in tissue specimens with tumor grade and stage.

European Urology Supplements, 2009

Oral Oncology Supplement, 2005

vIoleeular biology 5 133 metastases have occured. Oral mucosal malignant melanoma is rare, compri... more vIoleeular biology 5 133 metastases have occured. Oral mucosal malignant melanoma is rare, comprises much less than 1% of all melanomas, and is much more aggressive than its cutaneous counterpart. Cathepsins are useful markers for identifying patients who are suffering from breast cancer or colorectal cancer. Cathepsm

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 1997

To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antib... more To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI],...

Apmis, 2007

Tachezy R, Jirasek T, Salakova M, Ludvikova V, Kubecova M, Horak L, Mandys V, Hamsikova E. Human ... more Tachezy R, Jirasek T, Salakova M, Ludvikova V, Kubecova M, Horak L, Mandys V, Hamsikova E. Human papillomavirus infection and tumours of the anal canal: correlation of histology, PCR detection in paraffin sections and serology. APMIS 2007;115:195-203. Human papillomavirus infection is an important etiological factor in squamous cell carcinoma of the anus (SCCA). Different histological variants of anal carcinomas displaying squamous differentiation, previously classified as separate tumours, were recently reclassified as SCCA by the WHO. In our recent study the presence of HPV was detected by PCR in biopsy specimens of 42 different anal tumours, including SCCA and its histological variants (nΩ22), adenocarcinomas (nΩ5), tubulovillous adenomas (nΩ5) and anal condylomas (nΩ10). HR HPV16 (high risk -HR) was detected in 18 of SCCA specimens (81.8%). All histological variants, i.e. tumours with basaloid, squamous and mixed histological patterns, were represented among the HPV-positive cancers. Four tumours (18.2%) were HPV negative. Low-risk (LR) HPV types were not detected within the SCCA group. HPV16 was identified in one adenocarcinoma, while four cases were HPV negative. Two adenomas showed presence of HPV16; one showed simultaneous positivity for HPV33. The remaining three tumours were HPV negative. Seven anal condylomas (70%) were LR HPV 6 and/or 11 positive, while three were HPV negative. The presence of HR HPV types was not observed in anal condylomas. Our results provide further evidence in support of the etiological role of HR HPV infection in the development of SCCA regardless of its histological appearance.

In view of the increasing interest in the immunotherapy of CML it seems highly desirable to broad... more In view of the increasing interest in the immunotherapy of CML it seems highly desirable to broaden the present knowledge on the immune reac- tivity of CML patients. A group of 24 patients and 24 healthy controls were studied for the total of 15 immunological parameters, including the prevalence of antibodies against human herpesviruses and papil- lomaviruses. To clearly discriminate

Oral Oncology, 2006

We investigated whether herpes simplex viruses, HSV-1 and HSV-2, are cofactors of head and neck c... more We investigated whether herpes simplex viruses, HSV-1 and HSV-2, are cofactors of head and neck cancer (HNC) in association with tobacco, alcohol, or HPV-16 infection. The study included 164 HNC cases and 295 controls. Serologic tests were used to distinguish HSV-1 and HSV-2. Antibodies to anti-VLP HPV-16 and HPV-16 E6 and E7 were evaluated by ELISA. After adjusting for age, tobacco, alcohol use, and number of sexual partners, risk of cancer was not significantly increased in those with HSV-1 [adjusted odds ratio (OR)=0.7] or HSV-2 (OR=0.8) compared to HSV-negative patients. Although heavy use of tobacco, alcohol and HPV-16 infection was associated with an increased risk of HNC, the adjusted risk among those infected with HSV-1 or HSV-2 lowered the odds compared to those who were not infected. Heavy smokers (OR=1.7) and heavy drinkers infected with HSV-1 (OR=4.2) or HSV-2 (smokers: OR=1.6; drinkers: OR=3.2) had lower odds compared to seronegative HSV-1 heavy users (smokers: OR=2.5; drinkers: OR=5.5) or HSV-2 (smokers: OR=1.9; drinkers: OR=6.2). Those seropositive to HPV-16 E6 and/or E7 but not HSV-1 (OR=27.4) or HSV-2 (OR=18.0) had higher risk of HNC compared to those infected with HSV-1 (OR=16.7) or HSV-2 (not estimable). These findings suggest that seropositivity to HSV-1 and HSV-2, although not independent risk factors for HNC, may modify the risk of HNC associated with exposure to tobacco, alcohol, or HPV-HR.

Oral Diseases, 2005

OBJECTIVE: An association between high-risk human papillomavirus (HR HPV) infection and a risk of... more OBJECTIVE: An association between high-risk human papillomavirus (HR HPV) infection and a risk of development of a subgroup of head and neck cancers has been proposed recently. The main risk factors of oral and oropharyngal cancer observed in our population are smoking and alcohol consumption. The incidence of oral/ oropharyngeal tumours in the Czech Republic is relatively high and there are no data available about the prevalence of HPV DNA presence in these tumours. MATERIALS AND METHODS: Eighty patients with a primary oropharyngeal cancer were enrolled. The presence of HPV DNA has been evaluated by polymerase chain reaction in 68 cases from which the tumour tissue and demographical and clinical data were available. The typing of HPV was performed by nucleotide DNA sequencing. RESULTS: The HPV DNA was detected in 51.5% of samples tested. Among the HPV DNA positive tumours, 80% contained HPV16. In the analysed group there were 54 men and 14 women. The prevalence of HPV DNA was lower in oral (25%) than in oropharyngeal (57%) tumours, and higher in never smokers (100%) and never drinkers (68.8%). HPV DNA presence was not related to gender, age, number of lifetime sexual partners or practice of oral-genital sex, size of tumour or presence of regional metastases. CONCLUSIONS: The difference in the prevalence of HPV DNA positive tumours between cases of oral cavity and oropharyngeal carcinoma exposed and not exposed to tobacco or alcohol support the theory that HPV DNA positive tumours form an aetiologically distinct subgroup of head and neck tumours. , 181-185

Journal of Medical Virology, 2009

The association between human papillomavirus (HPV) infection and the development of head and neck... more The association between human papillomavirus (HPV) infection and the development of head and neck cancer has been documented recently. In this study on 86 head and neck cancer patients and 124 controls, data regarding demographics, behavioral risk factors, and risks related to HPV exposure were collected. HPV detection was carried out using polymerase chain reaction in the tumors and in oral exfoliated cells, and HPV typing by a reverse line blot assay specific for 37 HPV types. Sera were tested by an enzymelinked immunosorbent assay specific for HPV proteins. Head and neck cancer cases report significantly more oral-anal contact (P ¼ 0.02) and tobacco and alcohol use than controls (P ¼ 0.001; P ¼ 0.02, respectively). High-risk HPV DNA was detected in 43% of oral washings of cases and 4% of controls (P < 0.0001). The association between the presence of high-risk HPV DNA in oral exfoliated cells and in tumor tissues was statistically significant (adjusted P < 0.0001). The prevalence of HPV-specific antibodies was significantly higher in cases than in controls (adjusted P < 0.0001). These results provide epidemiological and immunological evidence for HR HPV as a strong risk factor (OR ¼ 44.3, P < 0.0001) for head and neck cancer, even after controlling for age, tobacco and alcohol use. The detection of high-risk HPV DNA in oral exfoliated cells and HPV-specific antibodies in serum can be considered as clinically relevant surrogate markers for the presence of a HPV-associated head and neck cancer, with a high sensitivity (83%) and specificity (88%).

Journal of Medical Virology, 1994

Journal of General Virology, 1991

The entire amino acid sequence of human cytomegalovirus (HCMV) 150K matrix phosphoprotein (pp150)... more The entire amino acid sequence of human cytomegalovirus (HCMV) 150K matrix phosphoprotein (pp150), consisting of 1048 amino acid residues, was divided into 95 overlapping 20 amino acid peptides which were synthesized on polyethylene rods. The rods were subjected to ELISA with pooled anti-HCMV-positive and anti-HCMV-negative sera. Four peptides recognized by the anti-HCMV-positi~,e pool only were synthesized by the solid-phase method and their reactivity in a conventional ELISA, using a panel of 14 individual anti-HCMV-negative and 20 anti-HCMVpositive antisera, was evaluated; three peptides were found to be specifically reactive. Results obtained with one of these peptides (residues 595 to 614) in ELISA showed a good correlation with those obtained using a routinely performed complement fixation test.

International Journal of Cancer, 2008

The cellular tumor suppressor p16 is strongly overexpressed in cervical cancers and precancers. W... more The cellular tumor suppressor p16 is strongly overexpressed in cervical cancers and precancers. We have previously demonstrated that infiltrating T lymphocytes reactive against p16 can be found in cervical cancer patients. Here, we analyzed whether p16 induces humoral immune responses. Sera of patients with cervical cancer, oropharyngeal cancer, colorectal cancer and autoimmune disease were included. A total of 919 sera were analyzed, including 486 matched sera from a cervical cancer case control study. p16 antibodies were analyzed in Western blot and a newly developed peptide ELISA covering the complete p16 protein. In addition, a Luminex-based multiplex assay was used for simultaneous detection of antibodies directed against p16, p53, HPV16 E6 and HPV16 E7. In all entities, only low p16 antibody reactivity was observed. Epitope mapping revealed 2 predominant epitope regions of the p16 protein. No significant difference in p16 antibody frequency (OR 5 0.9; 95% CI 5 0.6-1.3) and p53 antibody frequency (OR 5 0.6; 95% CI 5 0.3-1.2) was found between patients and healthy controls in the cervical cancer case control study. Antibodies against the HPV16 oncoproteins E6 and E7 were detected more frequently in cervical cancer patients when compared with healthy controls (E6 OR 5 27.8; 95% CI 5 11.1-69.7, E7 OR 5 5.7; 95% CI 5 2.9-11.1). In conclusion, despite the strong expression of p16 and the observed induction of cellular immune responses, antibody reactivity against p16 was observed only at very low levels independent of the disease background.

International Journal of Cancer, 2007

We examined antibody response to VLP HPV-16, HPV-16 E6 and E7 antibodies as potential seromarkers... more We examined antibody response to VLP HPV-16, HPV-16 E6 and E7 antibodies as potential seromarkers of HPV-related head and neck cancer (HNC). The study included 204 HNC cases and 326 controls evaluated for HPV presence in sera using ELISAs for anti-HPV VLP antibodies and HPV-16 E6 and/or E7 antibodies, and in tumor tissue using PCR and DNA sequencing. Anti-HPV-16 VLP was detected in 33.8% of cases and 22.4% of controls, anti-E6 in 20.6% of cases and 0.9% of controls and anti-E7 in 18.6% of cases and 0.6% of controls. HPV-16 DNA was detected in 26.1% of tumors. The adjusted risk of HNC was elevated among those seropositive for HPV-16 VLP (odds ratio (OR) 5 1.7, 1.1-2.5), E6 (OR 5 32.8,). Compared to HPV DNA-negative/seronegative cases, tumor HPV-16 cases had increased risk of detection with anti-VLP antibodies (OR 5 6.8, 3.1-14.9). The odds were more pronounced among cases seropositive for E6 (OR 5 69.0, 19.3-247) or E7 (OR 5 50.1, 14.7-171). Antibodies against E6 or E7 were associated with risk of cancer in the oral cavity (OR 5 5.1, 1.2-22.4) and oropharynx (OR 5 72.8,, and with disease characteristics: stage, grade and nodal status. Anti-E6 and/or E7 antibodies were found in 74% of tumor HPV-16 positive cases but in only 5% of tumor HPV-negative cases (K 50.7, 0.6-0.8) suggesting good correlation between the serologic marker and HPV tumor status. Antibodies to HPV-16 E6 and/or E7 represent a more specific biomarker than anti-HPV-16 VLP of an HPV-related HNC. Because of the survival advantage of HPV-related HNC, HPV-16 E6/E7 detection may be useful in therapy targeted for HPV-related tumors. '

International Journal of Cancer, 1996

This study evaluates the association of antibodies against HPV-16-derived peptides with cervical ... more This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/ 1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a L1-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%,7.2%,11.7%,12.6% respectively) than in Spain (17.1 %, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR = 2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden.

International Journal of Cancer, 2010

High-risk human papillomavirus types (HPV-HR) are associated with head and neck cancer (HNC) risk... more High-risk human papillomavirus types (HPV-HR) are associated with head and neck cancer (HNC) risk and better survival. Most patients with HPV-HR DNA-positive tumors develop anti-HPV E6/E7 antibodies; however, it is unclear whether those who mount an immune response have similar risk factors or clinical outcomes as those who do not. HPV-16 DNA tumor-positive HNC cases were evaluated for HPV-16 E6 and E7 antibodies using a GST capture ELISA system. Among 57 HPV-16 DNA tumorpositive HNC cases, 67% were detected with HPV-16 E6 and/or E7 antibodies. Male gender (76% vs. 42%, p 5 0.02), younger age (63% vs. 16%, p 5 0.001) but not tobacco or alcohol were associated with E6 and/or E7 seropositivity. Seropositivity was associated more often with late stage (76%), poor grade (65%), positive nodes (82%). and in the oropharynx (82%), Median disease-specific and recurrence-free survival were longer in E6 and/or E7 seropositive compared to E6/E7-negative cases (2.2 years vs. 1.4 years, both outcomes), although results were not statistically significant. When examined jointly with p16 expression, E6 and/or E7-positive/p16-positive cases had better disease-specific (2.1 years vs. 1.1 years, p 5 0.06) and recurrence-free (2.3 years vs. 1.1 years, p 5 0.03) survival compared to E6-/E7-/p16-cases. These findings suggest there are 2 distinct HNC patient groups with HPV DNA-positive tumors, distinguishable by E6 and/or E7 antibody status. Differences in antibody status are associated with distinct risk factors and clinical outcomes. This information can be available as a simple blood test at initial presentation, before the removal of tissue through biopsy or surgery.