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Czech Republic

Cancer Statistics
Population in 2012: 10.6m
People newly diagnosed with cancer (excluding NMSC) / yr: 57,600
Age-standardised rate, incidence per 100,000 people/yr: 293.8
Risk of getting cancer before age 75:29.3%
People dying from cancer /yr: 26,900
Data from IARC GlobalCan (2012)
Czech Cancer Organisations
Major Cancer Centres
Latest Research Publications from the Czech Republic

Czech Cancer Organisations (9 links)

Major Cancer Centres (4 links)

Latest Research Publications from the Czech Republic

Palumbo C, Pecoraro A, Knipper S, et al.
Survival and Complication Rates of Metastasectomy in Patients With Metastatic Renal Cell Carcinoma Treated Exclusively With Targeted Therapy: A Combined Population-based Analysis.
Anticancer Res. 2019; 39(8):4357-4361 [PubMed] Related Publications
AIM: This study analyzed the effect of metastasectomy on overall mortality (OM) and perioperative outcomes in patients with metastatic renal cell carcinoma (mRCC) treated exclusively with targeted therapy.
MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (2006-2015), Kaplan-Meier analyses and multivariable Cox regression models tested for OM. Using the National Inpatient Sample (NIS) database (2006-2015), complication rates and in-hospital mortality were evaluated.
RESULTS: Within the SEER database, 437 (12.2%) out of 3,654 patients underwent metastasectomy. Metastasectomy was associated with lower OM risk (median survival 11 vs. 9 months, hazard ratio=0.83; p=0.002). Within the NIS database, 351 such patients were identified. Complications and in-hospital mortality were 55.0% and 4.6%, respectively.
CONCLUSION: Metastasectomy in patients with mRCC treated exclusively with targeted therapy is associated with lower OM risk, however, based on short duration of expected survival. Complications and in-hospital mortality rates are not negligible.

Cepelova M, Kruseova J, Luks A, et al.
Accelerated atherosclerosis, hyperlipoproteinemia and insulin resistance in long-term survivors of Hodgkin lymphoma during childhood and adolescence.
Neoplasma. 2019; 2019 [PubMed] Related Publications
Long-term survivors of Hodgkin lymphoma during childhood or adolescence (HL survivors) are at high risk of developing treatment-related late cardiovascular sequelae. In our study we evaluated the presence of modifiable cardiovascular risk factors (hypertension, hyperlipoproteinemia, hyperinsulinemia, obesity), endothelial and inflammatory markers (E-selectin, PAI-1, hs-CRP) and atherosclerotic changes in the common carotid arteries. Assessment was performed in 80 young adult Hodgkin lymphoma long-term survivors at more than 10 years after the potentially cardiovascular toxic anticancer treatment (median age at evaluation 34.7 years; range 24.1-40.9 years). The HL survivors were compared with 83 age- and gender-matched healthy volunteers. The HL survivors showed unfavorable lipid profiles compared to those of healthy controls: triglycerides (p=0.01), total cholesterol (p=0.0004), low density lipoprotein cholesterol (p=0.005). In HL survivors, we found a higher prevalence of hypertension (p=0.004) and insulin resistance - HOMA-IR (p=0.0002). Ultrasonographic examination of both common carotid arteries revealed a higher prevalence of atherosclerotic plaques (p=0.0009) and higher carotid intima-media thickness (p<0.0001) in HL survivors. Markers of oxidative stress (advanced oxidation protein products, oxidized low-density lipoprotein), inflammation (hs-CRP) and endothelial dysfunction (E-selectin, PAI-1) were also higher in HL survivors (p<0.0001, p=0.0002, p=0.0031, p=0.0087, p=0.004, respectively). Adult survivors of Hodgkin lymphoma during childhood and adolescence need closer follow-up with screening of metabolic syndrome components, unfavorable lifestyle factors and early management of these risk factors.

Jirkovska M, Novak T, Malinova B, Lohynska R
Three-dimensional conformal radiotherapy versus intensity modulated radiotherapy with simultaneous integrated boost in the treatment of locally advanced head and neck carcinoma.
Neoplasma. 2019; 2019 [PubMed] Related Publications
The treatment of locally advanced head and neck cancer (LAHNC) requires a multimodality approach. Radiotherapy with combination of chemotherapy are demonstrated to be effective, however, the treatment intensification leads to increased toxicity at the same time. The implementation of three-dimensional conformal radiotherapy (3D-CRT) allowed to irradiate the treatment volume more precisely with better surrounding healthy tissue sparing. Intensity modulated radiotherapy (IMRT) facilitated higher conformity in dose shaping to target volume. IMRT with simultaneous integrated boost (IMRT-SIB) offered the possibility to deliver individualized dose levels within one fraction and enabled escalation of the dose per fraction and radiotherapy acceleration. The aim of our study was to compare the technique of 3D-CRT and IMRT-SIB in the treatment of LAHNC and evaluate the treatment outcome and the treatment-related toxicity. 262 patients in 3D-CRT group and 263 patients in IMRT-SIB group underwent the radical treatment for LAHNC between 1/1998 and 12/2016. No statistically significant differences in locoregional control (LCR) and overall survival (OS) were found between the two groups. Acute toxicity and xerostomia were significantly reduced in the patients treated by IMRT-SIB. IMRT-SIB is a safe radiotherapy method where less toxicity was proven without compromising local control and overall survival.

Sima P, Richter J, Vetvicka V
Glucans as New Anticancer Agents.
Anticancer Res. 2019; 39(7):3373-3378 [PubMed] Related Publications
For decades, glucans have been studied for their biological and immunological activities. The scientific community has mainly focused on immune reactions, but other areas, such as cholesterol levels and diabetic retinopathy, have shown the positive effects of glucan supplementation. However, the majority of studies focused on possible cancer suppression, where glucans showed clear and significant effects on numerous types of cancers, leading not only to clinical trials, but to approval as an official drug. The aim of this review is to describe the current knowledge of this field.

Fraňková S, Urbánek P, Husa P, et al.
Chronic hepatitis C in the Czech Republic: Forecasting the disease burden.
Cent Eur J Public Health. 2019; 27(2):93-98 [PubMed] Related Publications
OBJECTIVE: Chronic HCV infection is associated with cirrhosis of the liver, hepatocellular carcinoma (HCC), and liver transplantation. HCV disease burden and the impact of new potent direct acting antivirals (DAAs) in the Czech Republic are unknown.
METHODS: Using a modelling framework, HCV disease progression in the Czech Republic was predicted to 2030 under the current standard of care treatment structure. In addition, two strategies to reduce the future burden of HCV infection were modelled: an incremental increase in treatment annually and WHO targets.
RESULTS: The number of viremic infected individuals in the Czech Republic is estimated to peak in 2026 (n = 55,130) and to decline by 0.5% by 2030 (n = 54,840). The number of individuals with compensated cirrhosis (n = 1,400), decompensated cirrhosis (n = 80), HCC (n = 70), and liver-related deaths (n = 60) is estimated to more than double by 2030. Through aggressive increases in diagnosis and treatment, HCV related mortality may decrease by 70% by 2030.
CONCLUSIONS: Disease burden associated with chronic HCV infection is projected to peak in the Czech Republic in 30-40 years. Assuming that the current portion of DAAs used remains constant, a significant reduction in HCV disease burden is possible through increased diagnosis and treatment through 2030. This analysis provides evidence in order to facilitate the development of national strategies for HCV care and management in the Czech Republic.

Spicka I, Ocio EM, Oakervee HE, et al.
Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma.
Ann Hematol. 2019; 98(9):2139-2150 [PubMed] Free Access to Full Article Related Publications
The randomized phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma after at least three but not more than six prior regimens, including at least bortezomib and lenalidomide or thalidomide. Patients were randomly assigned (2:1) to receive plitidepsin 5 mg/m

Jorda R, Lopes SMM, Řezníčková E, et al.
Tetrahydropyrazolo[1,5-a]pyridine-fused steroids and their in vitro biological evaluation in prostate cancer.
Eur J Med Chem. 2019; 178:168-176 [PubMed] Related Publications
The androgen receptor (AR) is a steroid hormone receptor and its high expression and disruption of its regulation are strongly implicated in prostate cancer (PCa) development. One of the current therapies includes application of steroidal antiandrogens leading to blockade of the AR action by the abrogation of AR-mediated signaling. We introduced here novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused steroidal compounds, described their synthesis based on [8π+2π] cycloaddition reactions of diazafulvenium methides with different steroidal scaffolds and showed their biological evaluation in different prostate cancer cell lines in vitro. Our results showed the ability of novel compounds to suppress the expression of known androgen receptor targets, Nkx3.1 and PSA in two prostate cell lines, 22Rv1 and VCaP. Candidate compound diminished the transcription of AR-regulated genes in the reporter cell line in a concentration-dependent manner. Antiproliferative activity of the most promising steroid was studied by clonogenic assay and induction of apoptosis in treated cells was documented by immunoblot detection of cleaved PARP.

Cechova M, Chocholaty M, Zima T, et al.
The Significance of Pregnancy-associated Plasma Protein a Serum Concentration in Clear Cell Renal Cell Carcinoma.
Anticancer Res. 2019; 39(6):3249-3253 [PubMed] Related Publications
BACKGROUND/AIM: Proteinase pregnancy-associated plasma protein A (PAPP-A) modulates the cell growth and carcinogenesis process. Its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to evaluate the significance of PAPP-A serum concentration in diagnosis, follow-up and prognosis of ccRCC patients.
MATERIALS AND METHODS: In a prospective study including 121 patients who underwent radical or partial nephrectomy for ccRCC [localized ccRCC without relapse (n=80), localized ccRCC with later relapse (n=26), primary metastatic cancer (n=15)] PAPP-A serum concentration was assessed preoperatively and in certain subgroups also postoperatively.
RESULTS: PAPP-A serum concentration showed no statistically significant difference between ccRCC and controls and among ccRCC subgroups, respectively. Disease stage and Fuhrman's grade were not shown to affect PAPP-A concentration. The dynamics of postoperative PAPP-A concentrations did not reveal any significance and PAPP-A was not a prognostic factor for cancer related or overall survival.
CONCLUSION: PAPP-A serum concentration does not seem to be a useful biomarker in ccRCC.

Michalová Z, Čoma M, Kičová M, et al.
Overexpression of Galectin-3 in Chronic Lymphocytic Leukemia Is Associated With 17p Deletion: A Short Report.
Anticancer Res. 2019; 39(6):2805-2810 [PubMed] Related Publications
BACKGROUND/AIM: Galectins belong to the family of galactose-binding proteins known to play an important role in the processes of cell proliferation, differentiation, migration and neoplastic progression. Herein, we studied the expression of galectin-3 (Gal-3) in chronic lymphocytic leukemia (CLL).
MATERIALS AND METHODS: The expression of Gal-3 was analyzed by means of multiparametric flow cytometry in normal and pathological B-cells from peripheral blood and bone marrow samples of 67 patients with CLL.
RESULTS: Pathological B-cells expressed significantly higher levels of cytoplasmic Gal-3 than normal B-cells. Moreover, overexpression of cytoplasmic Gal-3 was observed in the prognostically poorest subgroup of CLL patients, namely those with 17p deletion.
CONCLUSION: Our results indicate a possible role of galectin-3 in CLL pathophysiology and its potential value as a prognostic marker and therapeutic target.

Dusek J, Skoda J, Holas O, et al.
Stilbene compound trans-3,4,5,4´-tetramethoxystilbene, a potential anticancer drug, regulates constitutive androstane receptor (Car) target genes, but does not possess proliferative activity in mouse liver.
Toxicol Lett. 2019; 313:1-10 [PubMed] Related Publications
The constitutive androstane receptor(CAR) activation is connected with mitogenic effects leading to liver hyperplasia and tumorigenesis in rodents. CAR activators, including phenobarbital, are considered rodent non-genotoxic carcinogens. Recently, trans-3,4,5,4´-tetramethoxystilbene(TMS), a potential anticancer drug (DMU-212), have been shown to alleviate N-nitrosodiethylamine/phenobarbital-induced liver carcinogenesis. We studied whether TMS inhibits mouse Car to protect from the PB-induced tumorigenesis. Unexpectedly, we identified TMS as a murine CAR agonist in reporter gene experiments, in mouse hepatocytes, and in C57BL/6 mice in vivo. TMS up-regulated Car target genes Cyp2b10, Cyp2c29 and Cyp2c55 mRNAs, but down-regulated expression of genes involved in gluconeogenesis and lipogenesis. TMS did not change or down-regulate genes involved in liver proliferation or apoptosis such as Mki67, Foxm1, Myc, Mcl1, Pcna, Bcl2, or Mdm2, which were up-regulated by another Car ligand TCPOBOP. TMS did not increase liver weight and had no significant effect on Ki67 and Pcna labeling indices in mouse liver in vivo. In murine hepatic AML12 cells, we confirmed a Car-independent proapoptotic effect of TMS. We conclude that TMS is a Car ligand with limited effects on hepatocyte proliferation, likely due to promoting apoptosis in mouse hepatic cells, while controlling Car target genes involved in xenobiotic and endobiotic metabolism.

Meißner R, Kočišek J, Feketeová L, et al.
Low-energy electrons transform the nimorazole molecule into a radiosensitiser.
Nat Commun. 2019; 10(1):2388 [PubMed] Free Access to Full Article Related Publications
While matter is irradiated with highly-energetic particles, it may become chemically modified. Thereby, the reactions of free low-energy electrons (LEEs) formed as secondary particles play an important role. It is unknown to what degree and by which mechanism LEEs contribute to the action of electron-affinic radiosensitisers applied in radiotherapy of hypoxic tumours. Here we show that LEEs effectively cause the reduction of the radiosensitiser nimorazole via associative electron attachment with the cross-section exceeding most of known molecules. This supports the hypothesis that nimorazole is selectively cytotoxic to tumour cells due to reduction of the molecule as prerequisite for accumulation in the cell. In contrast, dissociative electron attachment, commonly believed to be the source of chemical activity of LEEs, represents only a minor reaction channel which is further suppressed upon hydration. Our results show that LEEs may strongly contribute to the radiosensitising effect of nimorazole via associative electron attachment.

Hatina J, Boesch M, Sopper S, et al.
Ovarian Cancer Stem Cell Heterogeneity.
Adv Exp Med Biol. 2019; 1139:201-221 [PubMed] Related Publications
Ovarian carcinoma features pronounced clinical, histopathological, and molecular heterogeneity. There is good reason to believe that parts of this heterogeneity can be explained by differences in the respective cell of origin, with a self-renewing fallopian tube secretory cell being likely responsible for initiation of an overwhelming majority of high-grade serous ovarian carcinomas (i.e., type II tumors according to the recent dualistic classification), whereas there are several mutually non-exclusive possibilities for the initiation of type I tumors, including ovarian surface epithelium stem cells, endometrial cells, or even cells of extra-Müllerian origin. Interestingly, both fallopian tube self-renewing secretory cells and ovarian surface epithelium stem cells seem to be characterized by an overlapping array of stemness signaling pathways, especially Wnt/β-catenin. Apart from this variability in the respective cell of origin, the particular clinical behavior of ovarian carcinoma strongly suggests an underlying stem cell component with a crucial impact. This becomes especially evident in high-grade serous ovarian carcinomas treated with classical chemotherapy, which entails a gradual evolution of chemoresistant disease without any apparent selection of clones carrying obvious chemoresistance-associated mutations. Several cell surface markers (e.g., CD24, CD44, CD117, CD133, and ROR1) as well as functional approaches (ALDEFLUOR™ and side population assays) have been used to identify and characterize putative ovarian carcinoma stem cells. We have recently shown that side population cells exhibit marked heterogeneity on their own, which can hamper their straightforward therapeutic targeting. An alternative strategy for stemness-depleting interventions is to target the stem cell niche, i.e., the specific microanatomical structure that secures stem cell maintenance and survival through provision of a set of stem cell-promoting and differentiation-antagonizing factors. Besides identifying direct or indirect therapeutic targets, profiling of side population cells and other ovarian carcinoma stem cell subpopulations can reveal relevant prognostic markers, as exemplified by our recent discovery of the Vav3.1 transcript variant, which filters out a fraction of prognostically unfavorable ovarian carcinoma cases.

Kripnerova M, Parmar HS, Pesta M, et al.
Urothelial Cancer Stem Cell Heterogeneity.
Adv Exp Med Biol. 2019; 1139:127-151 [PubMed] Related Publications
Urothelial carcinoma is a tumor type featuring pronounced intertumoral heterogeneity and a high mutational and epigenetic load. The two major histopathological urothelial carcinoma types - the non-muscle-invasive and muscle-invasive urothelial carcinoma - markedly differ in terms of their respective typical mutational profiles and also by their probable cells of origin, that is, a urothelial basal cell for muscle-invasive carcinomas and a urothelial intermediate cell for at least a large part of non-muscle-invasive carcinomas. Both non-muscle-invasive and muscle-invasive urothelial carcinomas can be further classified into discrete intrinsic subtypes based on their typical transcriptomic profiles. Urothelial carcinogenesis shows a number of parallels to a urothelial regenerative response. Both of these processes seem to be dominated by specific stem cell populations. In the last years, the nature and location of urothelial stem cell(s) have been subject to many controversies, which now seem to be settled down, favoring the existence of a largely single urothelial stem cell type located among basal cells. Basal cell markers have also been amply used to identify urothelial carcinoma stem cells, especially in muscle-invasive disease, but they proved useful even in some non-muscle-invasive tumors. Analyses on molecular nature of urothelial carcinoma stem cells performed till now point to their great heterogeneity, both during the tumor development and upon intertumoral comparison, sexual dimorphism providing a special example of the latter. Moreover, urothelial cancer stem cells are endowed with intrinsic plasticity, whereby they can modulate their stemness in relation to other tumor-related traits, especially motility and invasiveness. Such transitional modulations suggest underlying epigenetic mechanisms and, even within this context, inter- and intratumoral heterogeneity becomes apparent. Multiple molecular aspects of urothelial cancer stem cell biology markedly influence therapeutic response, implying their knowledge as a prerequisite to improved therapies of this disease. At the same time, the notion of urothelial cancer stem cell heterogeneity implies that this therapeutic benefit would be most probably and most efficiently achieved within the context of individualized antitumor therapy.

Samec M, Liskova A, Kubatka P, et al.
The role of dietary phytochemicals in the carcinogenesis via the modulation of miRNA expression.
J Cancer Res Clin Oncol. 2019; 145(7):1665-1679 [PubMed] Related Publications
PURPOSE: Phytochemicals are naturally occurring plant-derived compounds and some of them have the potential to serve as anticancer drugs. Based on recent evidence, aberrantly regulated expression of microRNAs (miRNAs) is closely associated with malignancy. MicroRNAs are characterized as small non-coding RNAs functioning as posttranscriptional regulators of gene expression. Accordingly, miRNAs regulate various target genes, some of which are involved in the process of carcinogenesis.
RESULTS: This comprehensive review emphasizes the anticancer potential of phytochemicals, either isolated or in combination, mediated by miRNAs. The ability to modulate the expression of miRNAs demonstrates their importance as regulators of tumorigenesis. Phytochemicals as anticancer agents targeting miRNAs are widely studied in preclinical in vitro and in vivo research. Unfortunately, their anticancer efficacy in targeting miRNAs is less investigated in clinical research.
CONCLUSIONS: Significant anticancer properties of phytochemicals as regulators of miRNA expression have been proven, but more studies investigating their clinical relevance are needed.

Guselnikova O, Dvorankova B, Kakisheva K, et al.
Rapid SERS-based recognition of cell secretome on the folic acid-functionalized gold gratings.
Anal Bioanal Chem. 2019; 411(15):3309-3319 [PubMed] Related Publications
Nowadays, functionalization of the plasmon-supported nanostructured surface is considered as a powerful tool for tumour cell recognition. In this study, the SERS on a surface plasmon polariton-supported gold grating functionalized with folic acid was used to demonstrate an unpretentious recognition of melanoma-associated fibroblasts. Using cultivation media conditioned by different cells, we were able to detect reproducible differences in the secretome of melanoma-associated and normal control fibroblasts. The homogeneous distribution of plasmon energy along the grating surface was proved to provide excellent SERS signal reproducibility, while, to increase the affinity of (bio)molecules to SERS substrate, folic acid molecules were covalently grafted to the gold gratings. As proof of concept, fibroblasts were cultured in vitro, and culture media from the normal and tumour-associated lines were collected and analysed with our proposed SERS substrates. Identifying individual peaks of the Raman spectra as well as comparing their relative intensities, we showed that the proposed functional SERS platform can recognise the melanoma-associated cells without the need for further statistical spectral evaluation directly. We also demonstrated that the SERS chip created provided a stable SERS signal over a period of 90 days without loss of sensitivity. Graphical abstract.

Dušek L, Mužík J, Krejčí D
Epidemiology of gallbladder and bile duct malignancies in the Czech Republic.
Cas Lek Cesk. 2019; 158(2):52-56 [PubMed] Related Publications
Overview of epidemiology focused on tumors of the bile ducts and gallbladder is based on data of the National Cancer Registry and its newly validated and published data from 2016. In most recent period 2012-2016, 1013 patients were annually (in average) diagnosed with tumors of the bile ducts and gallbladder in the Czech Republic. In the same time, average annual mortality of this disease reached value 836. Prevalence of bile ducts and gallbladder cancer reached 1723 in 2016 and in comparison, with the value measured in 2006, it increased by 28 %. More than 50 % of bile ducts and gallbladder cancers are diagnosed in advanced clinical stages (stage III+) which makes prognosis of patients worse and limits reachable results of therapy.

Hideghéty K, Brunner S, Cheesman A, et al.
Anticancer Res. 2019; 39(5):2265-2276 [PubMed] Related Publications
The aim of this review was to define appropriate

Rini BI, Powles T, Atkins MB, et al.
Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial.
Lancet. 2019; 393(10189):2404-2415 [PubMed] Related Publications
BACKGROUND: A phase 2 trial showed improved progression-free survival for atezolizumab plus bevacizumab versus sunitinib in patients with metastatic renal cell carcinoma who express programmed death-ligand 1 (PD-L1). Here, we report results of IMmotion151, a phase 3 trial comparing atezolizumab plus bevacizumab versus sunitinib in first-line metastatic renal cell carcinoma.
METHODS: In this multicentre, open-label, phase 3, randomised controlled trial, patients with a component of clear cell or sarcomatoid histology and who were previously untreated, were recruited from 152 academic medical centres and community oncology practices in 21 countries, mainly in Europe, North America, and the Asia-Pacific region, and were randomly assigned 1:1 to either atezolizumab 1200 mg plus bevacizumab 15 mg/kg intravenously once every 3 weeks or sunitinib 50 mg orally once daily for 4 weeks on, 2 weeks off. A permuted-block randomisation (block size of 4) was applied to obtain a balanced assignment to each treatment group with respect to the stratification factors. Study investigators and participants were not masked to treatment allocation. Patients, investigators, independent radiology committee members, and the sponsor were masked to PD-L1 expression status. Co-primary endpoints were investigator-assessed progression-free survival in the PD-L1 positive population and overall survival in the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, number NCT02420821.
FINDINGS: Of 915 patients enrolled between May 20, 2015, and Oct 12, 2016, 454 were randomly assigned to the atezolizumab plus bevacizumab group and 461 to the sunitinib group. 362 (40%) of 915 patients had PD-L1 positive disease. Median follow-up was 15 months at the primary progression-free survival analysis and 24 months at the overall survival interim analysis. In the PD-L1 positive population, the median progression-free survival was 11·2 months in the atezolizumab plus bevacizumab group versus 7·7 months in the sunitinib group (hazard ratio [HR] 0·74 [95% CI 0·57-0·96]; p=0·0217). In the ITT population, median overall survival had an HR of 0·93 (0·76-1·14) and the results did not cross the significance boundary at the interim analysis. 182 (40%) of 451 patients in the atezolizumab plus bevacizumab group and 240 (54%) of 446 patients in the sunitinib group had treatment-related grade 3-4 adverse events: 24 (5%) in the atezolizumab plus bevacizumab group and 37 (8%) in the sunitinib group had treatment-related all-grade adverse events, which led to treatment-regimen discontinuation.
INTERPRETATION: Atezolizumab plus bevacizumab prolonged progression-free survival versus sunitinib in patients with metastatic renal cell carcinoma and showed a favourable safety profile. Longer-term follow-up is necessary to establish whether a survival benefit will emerge. These study results support atezolizumab plus bevacizumab as a first-line treatment option for selected patients with advanced renal cell carcinoma.
FUNDING: F Hoffmann-La Roche Ltd and Genentech Inc.

Janikova A, Chloupkova R, Campr V, et al.
First-line therapy for T cell lymphomas: a retrospective population-based analysis of 906 T cell lymphoma patients.
Ann Hematol. 2019; 98(8):1961-1972 [PubMed] Related Publications
Peripheral T cell lymphomas (PTLs) have a globally poor prognosis. The CHOP regimen shows insufficient efficacy; first-line consolidation with autologous stem cell transplantation (auto-SCT) is a promising strategy but has never been confirmed by randomized data. We analyzed retrospectively 906 patients diagnosed with PTL between 1999 and 2015. Chemotherapy was given to 862 patients, and 412 of them were < 60 years. In this subset, we compared induction with CHOP (n = 113) vs. CHOEP (n = 68) and tested auto-SCT (n = 79) vs. no SCT (n = 73) in the intent-to-treat analysis. The median age of the whole cohort at diagnosis was 60 years (range; 18-91); the median follow-up was 4.3 years (range; 0.1-17.8). A shorter overall survival (OS) was associated with the male gender, age ≥ 60 years, stage III/IV, performance status ≥ 2, bulky tumor ≥ 10 cm, and elevated LDH. CHOEP induction showed a better 5-year PFS (25.0% vs. 32.9%; p.001), and 5-year OS (65.6% vs. 47.6%; p.008) than CHOP. Auto-SCT compared to no SCT brought a 5-year OS of 49.2% vs. 59.5% (p.187). Auto-SCT did not influence the OS in low-risk or low-intermediate risk PTLs. The high-intermediate and high-risk IPIs displayed a worse 5-year OS in auto-SCT arm (17.7% vs.46.2%; p.049); however, 73.9% of the patients never received planned auto-SCT. Our population-based analysis showed the superiority of CHOEP over CHOP in first-line treatment. We confirm the 5-year OS of around 50% in PTLs undergoing auto-SCT. However, the intended auto-SCT could not be given in 73.9% of the high-risk PTLs.

Hatina J, Kripnerova M, Houfkova K, et al.
Sarcoma Stem Cell Heterogeneity.
Adv Exp Med Biol. 2019; 1123:95-118 [PubMed] Related Publications
Sarcomas represent an extensive group of divergent malignant diseases, with the only common characteristic of being derived from mesenchymal cells. As such, sarcomas are by definition very heterogeneous, and this heterogeneity does not manifest only upon intertumoral comparison on a bulk tumor level but can be extended to intratumoral level. Whereas part of this intratumoral heterogeneity could be understood in terms of clonal genetic evolution, an essential part includes a hierarchical relationship between sarcoma cells, governed by both genetic and epigenetic influences, signals that sarcoma cells are exposed to, and intrinsic developmental programs derived from sarcoma cells of origin. The notion of this functional hierarchy operating within each tumor implies the existence of sarcoma stem cells, which may originate from mesenchymal stem cells, and indeed, mesenchymal stem cells have been used to establish several crucial experimental sarcoma models and to trace down their respective stem cell populations. Mesenchymal stem cells themselves are heterogeneous, and, moreover, there are alternative possibilities for sarcoma cells of origin, like neural crest-derived stem cells, or mesenchymal committed precursor cells, or - in rhabdomyosarcoma - muscle satellite cells. These various origins result in substantial heterogeneity in possible sarcoma initiation. Genetic and epigenetic changes associated with sarcomagenesis profoundly impact the biology of sarcoma stem cells. For pediatric sarcomas featuring discrete reciprocal translocations and largely stable karyotypes, the translocation-activated oncogenes could be crucial factors that confer stemness, principally by modifying transcriptome and interfering with normal epigenetic regulation; the most extensively studied examples of this process are myxoid/round cell liposarcoma, Ewing sarcoma, and synovial sarcoma. For adult sarcomas, which have typically complex and unstable karyotypes, stemness might be defined more operationally, as a reflection of actual assembly of genetically and epigenetically conditioned stemness factors, with dedifferentiated liposarcoma providing a most thoroughly studied example. Alternatively, stemness can be imposed by tumor microenvironment, as extensively documented in osteosarcoma. In spite of this heterogeneity in both sarcoma initiation and underlying stemness biology, some of the molecular mechanisms of stemness might be remarkably similar in diverse sarcoma types, like abrogation of classical tumor suppressors pRb and p53, activation of Sox-2, or inhibition of canonical Wnt/β-catenin signaling. Moreover, even some stem cell markers initially characterized for their stem cell enrichment capacity in various carcinomas or leukemias seem to function quite similarly in various sarcomas. Understanding the biology of sarcoma stem cells could significantly improve sarcoma patient clinical care, leading to both better patient stratification and, hopefully, development of more effective therapeutic options.

Pačínková A, Popovici V
Cross-platform Data Analysis Reveals a Generic Gene Expression Signature for Microsatellite Instability in Colorectal Cancer.
Biomed Res Int. 2019; 2019:6763596 [PubMed] Free Access to Full Article Related Publications
The dysfunction of the DNA mismatch repair system results in microsatellite instability (MSI). MSI plays a central role in the development of multiple human cancers. In colon cancer, despite being associated with resistance to 5-fluorouracil treatment, MSI is a favourable prognostic marker. In gastric and endometrial cancers, its prognostic value is not so well established. Nevertheless, recognising the MSI tumours may be important for predicting the therapeutic effect of immune checkpoint inhibitors. Several gene expression signatures were trained on microarray data sets to understand the regulatory mechanisms underlying microsatellite instability in colorectal cancer. A wealth of expression data already exists in the form of microarray data sets. However, the RNA-seq has become a routine for transcriptome analysis. A new MSI gene expression signature presented here is the first to be valid across two different platforms, microarrays and RNA-seq. In the case of colon cancer, its estimated performance was (

Hurník P, Žiak D, Dluhošová J, et al.
Another case of coincidental Giardia infection and pancreatic cancer.
Parasitol Int. 2019; 71:160-162 [PubMed] Related Publications
Until now, few cases of coincidental giardiasis and pancreatic tumors have been described. Among these cases, three described giardiasis cases coincided with confirmed pancreatic cancer. We present another case of Giardia infection coexisting with pancreatic cancer in a 67-year-old man who suffered from stenosis of the distal ductus choledochus combined with a hypoechoic mass in the head of the pancreas. The diagnostic conclusion of suspicious adenocarcinoma was based on endoscopic ultrasound fine-needle aspiration (EUS-FNA) biopsy and confirmed by a partial duodenopancreatectomy. On bloody cytology smears prepared from the EUS-FNA specimen, trophozoites of Giardia intestinalis accompanying an inflammatory background and features that fulfilled the morphological criteria of malignancy were observed. In histological sections from the duodenopancreatectomy specimens, the parasites were observed attached to the epithelium, but individual Giardia parasites were also observed beneath the epithelial lining. According to conventional genotyping, the infecting Giardia belonged to sub-assemblage AII.

Simonidesova S, Hamsikova E, Ludvikova V, et al.
Prognostic value of posttreatment HPV-specific antibodies in patients with oropharyngeal tumors.
J Surg Oncol. 2019; 120(2):117-124 [PubMed] Related Publications
BACKGROUND: The presence of human papillomavirus (HPV)-specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7-specific antibodies appears to be associated with a better prognosis.
METHODS: This prospective study with follow-up focused on the persistence and prognostic value of antibodies specific for HR HPV-derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment.
RESULTS: The level of HPV-specific antibodies decreased on the 1-year follow-up and the decrease during the long follow-up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1-year follow up was associated with better overall as well as disease-specific survival of patients.
CONCLUSIONS: The data suggest that the pretreatment level of HPV-specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1-year follow-up is predictive of better survival of HN patients.

Kubatka P, Uramova S, Kello M, et al.
Anticancer Activities of
Int J Mol Sci. 2019; 20(7) [PubMed] Free Access to Full Article Related Publications
Naturally-occurring mixtures of phytochemicals present in plant foods are proposed to possess tumor-suppressive activities. In this work, we aimed to evaluate the antitumor effects of

Yeung AWK, Horbańczuk M, Tzvetkov NT, et al.
Curcumin: Total-Scale Analysis of the Scientific Literature.
Molecules. 2019; 24(7) [PubMed] Free Access to Full Article Related Publications
The current study aimed to provide a comprehensive bibliometric overview of the literature on curcumin, complementing the previous reviews and meta-analyses on its potential health benefits. Bibliometric data for the current analysis were extracted from the Web of Science Core Collection database, using the search string TOPIC=("curcumin*"), and analyzed by the VOSviewer software. The search yielded 18,036 manuscripts. The ratio of original articles to reviews was 10.4:1. More than half of the papers have been published since 2014. The major contributing countries were the United States, China, India, Japan, and South Korea. These publications were mainly published in journals representing the following scientific disciplines: biochemistry, chemistry, oncology, and pharmacology. There was a significant positive correlation between the total publication count and averaged citations per manuscript for affiliations, but not for countries/regions and journals. Chemicals that were frequently mentioned in the keywords of evaluated curcumin publications included curcuminoids, resveratrol, chitosan, flavonoids, quercetin, and polyphenols. The literature mainly focused on curcumin's effects against cancer, inflammation, and oxidative stress. Cancer types most frequently investigated were breast, colon, colorectal, pancreatic, and prostate cancers.

Fazio G, Massa V, Grioni A, et al.
First evidence of a paediatric patient with Cornelia de Lange syndrome with acute lymphoblastic leukaemia.
J Clin Pathol. 2019; 72(8):558-561 [PubMed] Related Publications
Cornelia de Lange syndrome (CdLS) is a rare autosomal-dominant genetic disorder characterised by prenatal and postnatal growth and mental retardation, facial dysmorphism and upper limb abnormalities. Germline mutations of cohesin complex genes

Sterbova M, Pazourkova E, Santorova-Pospisilova S, et al.
The use of Human Inflammatory Response and Autoimmunity RT2 lncRNA PCR Array for plasma examination in breast cancer patients prior to therapy.
Neoplasma. 2019; 2019:641-646 [PubMed] Related Publications
Long non-coding RNAs (lncRNAs) are defined as RNA molecules longer than 200 nucleotides with poor protein-coding capacity and key functions in regulation of gene expression. Dysregulations of lncRNAs (e.g. HOTAIR and MALAT I) were detected in plasma of breast cancer (BC) patients. Plasma samples are examined as liquid biopsies for purposes of non-invasive diagnostics therefore the research of plasma lncRNAs as potential plasma biomarkers became highly topical. 84 lncRNAs were profiled in 18 plasma samples - 9 BC patients and 9 age-matched healthy - using Human Inflammatory Response & Autoimmunity RT2 lncRNA PCR Array. Total RNA from plasma samples was isolated using miRNeasy Serum/Plasma Kit. Although a pre-amplification recommended for quantification from small starting RNA amounts was used, only 3 lncRNAs (A2ML1-AS1, GAS5 and SNHG5) were detected in all plasma samples. A total of 72 lncRNAs (e.g. HOTAIR or MALAT I) were detected only in some samples and 9 lncRNAs were not detected in any samples. No significant differences were observed in levels of plasma lncRNAs between the BC patients and healthy controls despite the fact that our panel contained also the lncRNAs whose levels were previously reported as significantly different in plasma or cancer tissues (e.g. GAS5, HOTAIR, MALAT I) in BC patients. Detection of lncRNAs in plasma is due to their low concentrations quite difficult as compared with tissues. Our findings suggest that analysis of plasma lncRNAs using this technology is not suitable for use as non-invasive diagnostic tool in BC patients.

Miesbauerová M, Tommola S, Šteiner P, et al.
Cytopathological features of secretory carcinoma of salivary glands and ancillary techniques in its diagnostics: impact of new Milan system for reporting salivary gland cytopathology.
APMIS. 2019; 127(7):491-502 [PubMed] Related Publications
Secretory carcinoma (SC) of salivary glands is a newly described low-grade malignancy characterized by the presence of ETV6 rearrangement. Only a few cases and very small series with cytomorphology were reported so far. Six cases of fine-needle aspirations (FNAs) from afterward histologically, immunohistochemically and genetically confirmed SCs were retrieved from the archives of the authors. Ancillary immunocytochemistry (ICC) and translocation detection were performed on cell blocks (CBs). All aspirates were sufficiently cellular and cells were arranged in more or less cohesive groups with only mild nuclear polymorphism. The cytoplasm was eosinophilic, granulated and vacuolated, especially in CBs. Secretory material within the microcystic spaces was periodic acid-Schiff (PAS) positive. Triple positivity of immunomarkers S-100 protein, mammaglobin and vimentin was present. The proliferation index was low. Ancillary techniques suggested the possibility of SC in a few cytology cases; nevertheless, the final diagnosis was based on histomorphology, immunohistochemistry and genetics. The SC of salivary glands is detectable pre-operatively using ICC and genetics. The presence of the diagnostic ETV6 rearrangement increases the accuracy of FNA to the maximum. According to the Milan system, cases genetically not confirmed should be categorized as Suspicious for Malignancy or Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP), both requiring surgery.

Melichar B, Dvorak J, Kamaradova K, et al.
Hepatic arterial infusion in liver tumors of unknown, uncertain or unusual primary: single-center experience.
J BUON. 2019 Jan-Feb; 24(1):143-149 [PubMed] Related Publications
PURPOSE: The aim of the present study was to analyze a single-center experience with hepatic arterial infusion (HAI) in patients with unknown or uncertain primary or tumors not usually treated with HAI.
METHODS: A retrospective analysis of 14 patients treated between 1996 and 2003 for liver tumors of unknown, uncertain or unusual primary was performed.
RESULTS: All patients were treated with HAI combination regimens based on 5-fluorouracil and folinic acid. The response was not evaluable in most patients, predominantly because of only a single course of therapy could be administered and no cases of partial or complete response were noted. The median survival of all patients was 6.6 months (5-year survival 14%).
CONCLUSION: The present data demonstrate limited efficacy of HAI in patients with liver tumors of unknown, uncertain or unusual primary. HAI should not be offered to these patients.

Möbius S, Schenk T, Himsel D, et al.
Results of the European survey on the assessment of deep molecular response in chronic phase CML patients during tyrosine kinase inhibitor therapy (EUREKA registry).
J Cancer Res Clin Oncol. 2019; 145(6):1645-1650 [PubMed] Related Publications
PURPOSE: The advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR-ABL1 transcripts by real-time quantitative PCR every 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR
METHODS: Data were collected on the standardized assessment of molecular response in the context of real-life practice. BCR-ABL1 transcript levels after > 2 years of TKI therapy were evaluated for DMR by local laboratories as well as standardized EUTOS laboratories. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out.
RESULTS: Between 2014 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR-ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n = 197 (6.51%); MMR, n = 496 (16.40%); MR
CONCLUSIONS: Multicenter DMR assessment is feasible in the context of real-life clinical practice in Europe. Information on the BCR-ABL1 transcript type at diagnosis is crucial to accurately monitor patients' molecular response during or after TKI therapy.

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