PubMed | University of Sfax, National Cancer Institute, St Elisabeth Cancer Institute, Slovak Academy of Sciences and 2 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016
Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs.Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome.None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including 3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression.In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.
Raneta O.,Comenius University |
Ondrus D.,Comenius University |
Bella V.,St Elisabeth Cancer Institute
Klinicka Onkologie | Year: 2012
Backgrounds: Breast cancer presents a serious medical and social problem worldwide. Early detection is key to effective breast cancer treatment. Therefore, scientists are consistently looking for new diagnostic techniques that would be more efficient, easy to use and safe for the patient. The main task of this study was to evaluate the feasibility of a novel low-cost non-invasive technique called electrical impedance tomography (EIT) and to determine whether EIT can qualitatively supplement the existing traditional imaging techniques in the process of breast cancer diagnostics. Patients and Methods: Randomly selected patients with mammographic and/or sonographic abnormalities were involved into the study. In total, 808 patients aged 18-94 (mean 54) years participated in the survey. Exclusion criteria involved previous breast surgery, breast core biopsy or fine needle aspiration within the last 1 and 3 months, respectively. Furthermore, patients with implanted electrically powered devices (cardioverter, pacemaker) and patients previously treated by chemo-radiotherapy were also excluded. The EIT examination was performed using the electrical impedance computer mammograph MEIK developed by the Institute of Radio Engineering and Electronics, Russian Academy of Sciences. Results: The following results were obtained: sensitivity of EIT was 87%, X-ray mammography (MMG) 89% and ultrasonography (USG) 91%; specificity of EIT was 85%, MMG 91% and USG 84%. Negative predictive value (NPV) of all three modalities showed nearly equal values, with slight advantage of the USG. MMG had the highest positive predictive (PPV) value (83%), EIT had the lowest (63%). Sensitivity increased to 96% and 98%, respectively, when combinations EIT + MMG and EIT + USG were used. The specificity increased to 79% for EIT + MMG and 71% for EIT + USG. EIT + MMG and EIT + USG NPV remained the same. PPV was 65% and 58%, respectively for the EIT + MMG and EIT + USG combination. Conclusion: Our study findings are comparable to those of other similar studies. Although the EIT is a promising method and deserves close attention of specialists, it cannot replace MMG and/or USG examination as it does not provide information on structural changes to the breast. It can, however, provide very useful additional information about metabolic processes in the body. But in order to show its full potential some improvements should be held.
Furdova A.,Comenius University |
Slezak P.,Slovak Academy of Sciences |
Chorvath M.,St Elisabeth Cancer Institute |
Waczulikova I.,Comenius University |
And 2 more authors.
Neoplasma | Year: 2010
To report the treatment outcome and possible survival difference between radical surgical treatment (enucleation) or stereotactic radiosurgery (SRS). LINAC stereotactic radiosurgery is an alternative treatment for posterior uveal melanoma used in Slovakia since 1999. The study analyzed patients treated for posterior uveal melanoma in the period 2001-2008. The aim of the study was to compare the relapse-free survival in the cohort of patients primarily treated with surgery (enucleation) or SRS. A total number of 84 patients were included, treatment was determined on a case-by-case basis. We reviewed the records of patients with ciliary body or choroidal melanoma treated by enucleation - 44 patients (52%) and SRS - 40 patients (48%). The therapeutic attitude was established on the basis of ophthalmoscopy, ultrasound (A, B mode), other ophthalmological findings, visual acuity, and general status of each patient. Volume of the tumor was calculated using the formula: "π/6 x length x width x height" for each patient. All of the patients before decision to "conservative" attitude therapy underwent MRI examination. The therapeutic dose in SRS patients group was 35.0-38.0Gy. The data were analyzed using Kaplan - Meier survival method for the differences in survival rates between the treatment groups, and afterwards by Cox ́s proportional hazard method with predictors involved. Among the baseline covariates evaluated, only age affected the prognosis for survival to a statistically important, however not significant degree. The risk of death among patients treated with enucleation relative to those treated with stereotaxy after adjustment for baseline characteristics of patients, age, and tumor volumes was not significant [1.82] (95% CI, 0.46 to 7.30; P = 0.396). The overall five-year survival rate for patients with posterior uveal melanoma was 72%. Treatment by either primary enucleation or SRS according to our results does not appear to influence the development of metastases in patients with uveal melanoma; the survival prognosis is essentially determined by the stage and character of the tumor. No survival difference attributable to stereotactic irradiation of uveal melanoma has been demonstrated in this retrospective study. A small difference is possible, but a clinically meaningful difference in mortality rates, whether from all causes or from metastatic melanoma, is unlikely. Treatment by either radical surgical attitude (enucleation) or "conservative" LINAC- SRS does not appear to influence the survival rate in patients with uveal melanoma.
Spanik S.,Comenius University |
Spanikova B.,St Elisabeth Cancer Institute
Bratislava Medical Journal | Year: 2010
Purpose: Recent data indicate that women with breast cancer receiving aromatase inhibitors (AIs) are at increase risk of osteoporosis. Patients and methods: We evaluated 263 patients in our study, 42 receiving AI (22 - Arimidex, 20 - Femara), 69 selective estrogen receptor modulater (SERM - Tamoxifen), in 72 the therapy with SERM was changed for AI and 80 were in follow-up without hormonal therapy. We measured BMD by whole-body densitometer Hologic explorer. BMD of proximal femur and L spine was measured and evaluated and in case of degenerative changes also the region of distal forearm. We evaluated T-score. 43. Results: 35 % of the patients had decline of BMD to T-score of osteoporosis and only 13.31 % of patients had normal bone density. 53.13 % of the treated patients had BMD level of osteoporosis versus 40.2 % of untreated patients or patients treated for less than one year. 3.13 % of treated patients had normal BMD versus 16.58 % of untreated patients (p=0.015). Conclusions: We confirm the influence of adjuvant AI therapy on decline of BMD in early breast cancer patients in our study. The bone loss was statistically significant in patients whose therapy lasted at least one year (Fig. 6, Ref. 20). Full Text (Free, PDF) www.bmj.sk.
Ondrusova M.,Slovak Academy of Sciences |
Ondrusova M.,St Elisabeth University Of Health And Social Work |
Mrinakova B.,St Elisabeth Cancer Institute |
Ondrus D.,Comenius University |
And 2 more authors.
Neoplasma | Year: 2013
An increase in melanoma incidence in the Slovak Republic (SR) is evident during approximately the same time and maybe caused by changes in socio-economic status. The paper analyses national trends in incidence, mortality, survival and clinical stages of invasive cutaneous melanoma in the SR from 1968-2007. The trends in incidence and mortality have been extracted between 1968-2007 period by the joinpoint regression analysis, clinical stages were analysed in 1978-2003. Survival data were extracted from the national database resources. Socio-economic changes, which reflected in increase in the number of holidaymakers to seaside and mountainous destinations happened in the country in the y.1989. Subsequently, according to joinpoint in 1997, acceleration of increment of the incidence values of melanoma was recorded in both sexes. Mortality was increasing in males continuously, in females the stabilization was registered after the year 1999. Lower rates of relative survival might be influenced by delayed accessibility to adjuvant treatment. The number of cases diagnosed in clinical stage I increased significantly. The changes in the intensity and excessive sunbathing during vacations might be one of many factors that participate in subsequent acceleration of the increment of incidence not only in the SR.
Raneta O.,Comenius University |
Bella V.,St Elisabeth Cancer Institute |
Bellova L.,St Elisabeth Cancer Institute |
Zamecnikova E.,St Elisabeth Cancer Institute
Neoplasma | Year: 2013
Our study involved 870 eligible women with suspected pathological breast lesion discovered by mammography (MMG) or ultrasound examination (USG) which were recommended to pass histological examination to verify the diagnosis. All patients included in our study were divided into two age groups: the 1st group - patients older than 40 years (total of 724 patients), the 2nd group - patients younger than 40 years (total of 146 patients). The purpose of our study was to analyze the possibilities of electrical impedance tomography (EIT) implementation to the differential diagnosis of pathologic lesions of the breast either solely, or in a combination with MMG/USG. The following results were obtained: in the 1st group the average specificity of MMG was 79.5%; when added EIT the average specificity decreased to 72.8%. The sensitivity of MMG, by contrast, increased from 87.8% when using it as an independent method to 94.5% when added EIT. In the 2nd group the average specificity of USG was 90.2%; when added EIT the average specificity decreased to 86.4%. Similarly, as in the 1st group the sensitivity of USG increased from 86.7% when using it as an independent method to 93.3% when added EIT. Analysis of false-negative results of electrical impedance tomography depending on the stage of the process has shown that as the earlier stage of the disease and as the smaller is the dimensions of the tumor, the higher is the number of falsenegative results. In addition, we observed the dependence of the false-negative results of the tumor grade. The results of our study show that the use of EIT in addition to MMG/USG can improve the sensitivity of these methods and to increase the rate of early detection of breast cancer with minimal economic costs and highly qualified staff time expenditures.
Stanko P.,Comenius University |
Stanko P.,St Elisabeth Cancer Institute |
Kaiserova K.,St Elisabeth Cancer Institute |
Altanerova V.,St Elisabeth Cancer Institute |
And 2 more authors.
Biomedical Papers | Year: 2014
Conclusions. Dental pulp mesenchymal stem cells cultivated in vitro under the same conditions as MSCs from bone marrow, adipose tissue and umbilical cord tissue can be distinguished by pluripotent stem cell gene expression profile.Methods. Four strains of dental pulp stem cells (DP-MSCs) were isolated from dental pulp tissue fragments adhered to plastic tissue culture dishes. Mesenchymal stem cells derived from umbilical cord tissue (UBC-MSCs) were isolated with the same technique. Bone marrow derived mesenchymal stem cells (BM-MSCs) were isolated from nucleated cells of bone marrow obtained by density gradient centrifugation. Human mesenchymal stem cells from adipose tissue (AT-MSCs) were isolated by collagenase digestion. All kinds of MSCs used in this study were cultivated in low glucose DMEM containing 5% or human platelet extract. All stem cell manipulation was performed in GMP conditions. Expression of 15 pluripotent stem cells genes on the level of proteins was measured by Proteome Profiler Human Pluripotent Stem Cell Array. Induction of MSCs to in vitro differentiation to adipocytes, osteoblasts, chondroblasts was achieved by cultivation of cells in appropriate differentiation medium.Aims. Our aims were to characterize human mesenchymal stem cells isolated from various tissues by pluripotent stem cells gene expression profile.Results. All MSCs tested were phenotypically similar and of fibroblastoid morphology. DP-MSCs and UBC-MSCs were more proliferative than bone marrow BM-MSCs and AT-MSCs. Protein expression of 15 genes typical for pluripotent stem cells distinguished them into two groups. While the gene expression profiles of BM-MSC, AT-MSCs and UBC-MSCs were similar, DP-MSCS differed in relative gene expression on the level of their products in several genes. © 2014, PALACKY UNIV. All rights reserved.
Altaner C.,Slovak Academy of Sciences |
Altaner C.,St Elisabeth Cancer Institute |
Altanerova V.,St Elisabeth Cancer Institute |
Cihova M.,Slovak Academy of Sciences |
And 5 more authors.
International Journal of Cancer | Year: 2014
Suicide gene therapy mediated by mesenchymal stem cells with their ability to engraft into tumors makes these therapeutic stem cells an attractive tool to activate prodrugs directly within the tumor mass. In this study, we evaluated the therapeutic efficacy of human mesenchymal stem cells derived from bone marrow and from adipose tissue, engineered to express the suicide gene cytosine deaminase::uracil phosphoribosyltransferase to treat intracerebral rat C6 glioblastoma in a simulated clinical therapeutic scenario. Intracerebrally grown glioblastoma was treated by resection and subsequently with single or repeated intracerebral inoculations of therapeutic stem cells followed by a continuous intracerebroventricular delivery of 5-fluorocytosine using an osmotic pump. Kaplan-Meier survival curves revealed that surgical resection of the tumor increased the survival time of the resected animals depending on the extent of surgical intervention. However, direct injections of therapeutic stem cells into the brain tissue surrounding the postoperative resection cavity led to a curative outcome in a significant number of treated animals. Moreover, the continuous supply of therapeutic stem cells into the brain with growing glioblastoma by osmotic pumps together with continuous prodrug delivery also proved to be therapeutically efficient. We assume that observed curative therapy of glioblastoma by stem cell-mediated prodrug gene therapy might be caused by the destruction of both tumor cells and the niche where glioblastoma initiating cells reside. What's new? One reason that glioblastomas are so difficult to treat is the persistence of chemo-and radio-resistant cancer stem cells. If suicide genes could be delivered directly to these cells, combination therapy might be more effective. In this study, the authors used non-maligant stem cells, called mesenchymal stem cells (MSCs), to treat glioblastomas in rats. The MSCs were engineered to express the suicide gene cytosine deaminase::uracil phosphoribosyltransferase (CDy::UPRT), then injected into the brain with 5-fluorocytosine. This resulted in strong inhibition of tumor growth, and a significant number of animals appeared to be completely cured. © 2013 UICC.
PubMed | Social Republic and St Elisabeth Cancer Institute
Type: | Journal: American journal of men's health | Year: 2016
The aim of the study was to investigate the influence of therapeutic modalities and sexual hormone levels on changes in bone mineral density (BMD) in testicular cancer (TC) survivors. In a cross-sectional descriptive, long-term follow-up study, a total of 1,249 long-term TC survivors were evaluated according to treatment modality: orchiectomy (OE) only, OE + chemotherapy (CT), or OE + radiotherapy (RT). Luteinizing hormone (LH), total testosterone (TST), marker of bone resorption (-carboxyl-terminal cross-linking telopeptide of type I collagen-CTx), and BMD were evaluated. Standard statistical techniques were used to test the differences between groups of patients. TST decrease was observed in 46/313 TC survivors after OE alone, in 103/665 after OE + CT, and in 66/271 after OE + RT. LH increase was observed in 23/313 TC survivors after OE alone, in 154/665 after OE + CT, and in 43/271 after OE + RT. CTx increase was observed in 116/313 TC survivors after OE alone, in 324/665 after OE + CT, and in 82/271 after OE + RT. Osteopenia/osteoporosis occurred in 136/313 TC survivors after OE alone, in 298/665 after OE + CT, and in 139/271 after OE + RT. TC survivors after RT have statistically significant decreased TST levels, increased LH and nonsignificant worse BMD (osteopenia/osteoporosis) in comparison with TC survivors after OE alone or CT. TST decrease and LH increase were statistically significant, more frequently observed in patients with osteopenia/osteoporosis. Examination of TST is an important part of follow-up in TC survivors with bilateral as well as unilateral disease. The important part of standard examination algorithm should be also the osteological examination of TC survivors mainly in patients with androgen deficiency.
PubMed | St Elisabeth Cancer Institute
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
e19739 Background: The standard therapy of thyroid carcinomas (TC) consists of total or nearly total thyroidectomy. Then the whole-life substitution therapy by oral thyroxine (TBone mineral density (BMD) was measured by dual energy photon x-ray absorptiometry in the lumbar spine and hips. BMD was classified using T score in postmenopausal women and more than 50 years old men. We classified Z score in premenopausal women and younger than 50 years men. C-terminal cross-linked telopeptides of type I collagen (CTX) were measured using ELISA. Additionally serum TSH and fTWe included 165 TC patients in the study. There were 13 men and 152 women, the mean duration of thyroid suppressive therapy was 7. 2 years (0 - 24 years). The patients exhibit osteporosis in 31%, whereas 30% had normal BMD. The incidence of osteoporosis appeared to increase with age but did not correlate with duration of thyroid suppressive therapy. TSH levels slightly correlated with decrease in BMD.The long term survivors from TC after total thyroidectomy on thyroid suppressive therapy have higher risk of osteoporosis and therefore we recommend BMD testing and appropriate measures according to results.