Prognostic value of T-cells between primary colorectal cancer (pCRC) and its paired synchronous and metachronous liver metastasis (LM) is underinvestigated and is the subject of the present study. We enrolled into this retrospective cohort study patients, who underwent resection of both pCRC and synchronous LM (N = 55) or metachronous LM (N = 44). After immunohistochemical staining for CD3+, CD8+, and CD45R0+ whole slides were scanned and T-cell densities were quantified using QuPath software in tumor center (TC), inner margin (IM), outer margin (OM), and peritumor zone (PT) of pCRC and LM. High densities of CD8+ T-cells in TC, OM and PT of synchronous LM were associated with longer disease-free survival (DFS). Greater densities of CD3+ T-cells in IM and PT and CD8+ T-cells in IM, OM and PT in synchronous LM over pCRC were associated with longer DFS. Greater densities of CD8+ T-cells in the TC and IM and CD3+ T-cells in the IM of pCRC were found in the metachronous over synchronous group. The first novel finding demonstrated that high density of CD8+ T cells in synchronous LM were associated with favorable outcome. The second finding of high CD8+ cell density in pCRC in metachronous over synchronous CRC may provide a mechanistic basis for the delay of metastatic spread. Both findings could be applied clinically with own reference values.

• MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• dospělí MeSH
• kolorektální nádory * patologie   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetné primární nádory patologie   imunologie   MeSH
• nádory jater * sekundární   imunologie   patologie   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• sekundární malignity patologie   MeSH
• senioři MeSH
• T-lymfocyty imunologie   patologie   MeSH
• tumor infiltrující lymfocyty imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this subtype is still a matter of debate. In this study, we investigated whether stool miRNA profiles of CRC patients differ in patients with mucinous histopathological subtypes compared to non-mucinous cancers. In this respect, we also explored how the stool miRNA signature reported in our previous multicentric study behaves in this histotype. Small-RNA sequencing was performed in fecal and tissue samples of an Italian cohort (n = 172), including 27 CRC with mucinous morphology (mucinous cancers with ≥ 50% mucinous morphology and those with mucinous component ≥ 5% but < 50%), 58 non-mucinous CRC, and 87 colonoscopy-negative controls. Results were compared with fecal miRNA profiles of a cohort from the Czech Republic (n = 98). Most of the differentially expressed (DE) stool miRNAs (n = 324) were in common between CRC with mucinous morphology and non-mucinous histopathological subtypes in comparison with healthy controls. Interestingly, the altered levels of 25 fecal miRNAs previously identified distinguishing CRC cases from controls in both cohorts were also confirmed after stratification for mucinous morphology. Forty-nine miRNAs were DE exclusively in CRC with mucinous morphology and 61 in non-mucinous CRC. Mucinous cancers and those with mucinous component showed fairly similar profiles that were comparable in the Czech cohort. Among the stool DE miRNAs observed in CRC with mucinous morphology, 20 were also altered in the comparison between tumor and adjacent mucosa tissue. This study highlights miRNAs specifically altered in CRC with mucinous morphology. Nevertheless, the performance of our stool miRNA signature in accurately distinguishing CRC cases from controls was not significantly affected by this histological subtype. This aspect further supports the use of stool miRNAs for noninvasive diagnosis and screening strategies.

• MeSH
• feces * chemie   MeSH
• kohortové studie MeSH
• kolorektální nádory * genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• mucinózní adenokarcinom * genetika   patologie   MeSH
• nádorové biomarkery genetika   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• zprávy MeSH

• MeSH
• gastrointestinální nádory terapie   MeSH
• neoadjuvantní terapie MeSH
• Publikační typ
• úvodní články MeSH

• Publikační typ
• úvodníky MeSH

Hepatocellular carcinoma (HCC) is primary liver cancer, frequently diagnosed at advanced stages with limited therapeutic options. MicroRNAs (miRNAs) regulate target gene expression and through inhibitory competitive binding of miRNA influence cellular processes including carcinogenesis. Extensive evidence proved that certain miRNA's are specifically expressed in neoplastic tissues of HCC patients and are confirmed as important factors that can participate in the regulation of key signalling pathways in cancer cells. As such, miRNAs have a great potential in the clinical diagnosis and treatment of HCC and can improve the limitations of standard diagnosis and treatment. Long non-coding RNAs (lncRNAs) have a critical role in the development and progression of HCC. HCC-related lncRNAs have been demonstrated to exhibit abnormal expression and contribute to transformation process (such as proliferation, apoptosis, accelerated vascular formation, and gain of invasive potential) through their interaction with DNA, RNA, or proteins. LncRNAs can bind mRNAs to release their target mRNA and enable its translation. These lncRNA-miRNA networks regulate cancer cell expression and so its proliferation, apoptosis, invasion, metastasis, angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and autophagy. In this narrative review, we focus on miRNA and lncRNA in HCC tumor tissue and their interaction as current tools, and biomarkers and therapeutic targets unravelled in recent years.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Esophageal cancer (EC) and gastric cancer (GC) are fatal cancers with a relatively late age of onset. Age is a negative risk factor for survival in many cancers and our aim was to analyze age-specific survival in EC and GC using the recently updated NORDCAN database. NORDCAN data originate from the Danish, Finnish, Norwegian, and Swedish nationwide cancer registries covering years 1972 through 2021 inviting for comparison of 50-year survival trends between the countries. Relative 1- and 5-year survival and 5/1-year conditional survival (i.e., survival in those who were alive in Year 1 to survive additional 4 years) were analyzed. Survival in EC showed large gains for patients below age 80 years, 5-year survival in Norwegian men reaching 30% and in women over 30% but for 80-89 year old survival remained at 10%. In contrast, hardly any gain was seen among the 80-89 year patients for 1-year survival and small gains in 5 year and 5/1-year survival. Survival gaps between age-groups increased over time. For GC there was also a clear age-related negative survival gradient but the survival gaps between the age groups did not widen over time; Norwegian male and female 5-year survival for 80-89 year old was about 20%. The age-specific survival difference in GC arose in Year 1 and did not essentially increase in 5-year survival. While there were differences in survival improvements between the countries, poor survival of the 80-89 year old patients was shared by all of them. To conclude, survival has improved steadily in younger GC and EC patients in most Nordic countries. While the 80-89 year old population accounts for nearly a quarter of all patients and their poor survival depressed overall survival, which can therefore be increased further by improving diagnostics, treatment and care of elderly EC and GC patients.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory jícnu * mortalita   epidemiologie   MeSH
• nádory žaludku * mortalita   epidemiologie   MeSH
• registrace * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Skandinávie a severské státy MeSH

INTRODUCTION: Thyroid cancer (TC) is diagnosed in several histological types which differ in their clinical characteristics and survival. We aim to describe how they influence TC survival in Sweden. METHODS: Cancer data were obtained from the Swedish cancer registry between years 1999 and 2018, and these were used to analyze relative survival. RESULTS: Relative survival for all TC improved when analyzed in 10-year periods, and female survival improved more than male survival. Female survival advantage appeared to be present also for specific histological types, although case numbers were low for rare types. Female 5-year relative survival for TC was 100% for follicular, 95.1% for oncocytic, 93.4% for papillary, 89.7% for medullary, and 6.1% for anaplastic cancer. Among the clinical TNM classes, only T4 and M1 stages were associated with decreased survival compared to T1-3 and M0. Anaplastic cancer presented most often at high T and M1 stages, in contrast to other TC. Curiously, the diagnostic age for anaplastic M1 patients was lower than that for M0 patients. Both anaplastic and medullary cancers did not show age-dependent increases in the probability of metastases, in contrast to the main histological types. This could indicate the presence of several types of anaplastic and medullary cancers. CONCLUSION: The poor survival for anaplastic TC is an extreme contrast to the excellent survival of differentiated TC. As less than 20% of anaplastic cancer patients survived one year, urgent diagnosis and initiation of treatment are important. Facilitated treatment pathways have been instituted in Denmark resulting in improved survival. Anaplastic cancer should be a target of a major research focus.

• Publikační typ
• časopisecké články MeSH

Analýza molekulárních biomarkerů umožňujících predikci reakce nádorů na léčbu a zavedení optimální metody pro jejich sledování představují zásadní výzvy současného translačního výzkumu. Tento projekt má za cíl prozkoumat využitelnost metody sekvenování příští generace pro hledání genetických biomarkerů, specifických pro českou populaci, které by umožnily rozdělení pacientů se solidními nádory do prognosticky významných skupin. V rámci projektu bude studován genetický profil pacientů se solidními nádory léčenými adjuvantní terapií režimy založenými na nukleosidových analozích, taxanech a platinových derivátech. Metoda celoexomového sekvenování bude poprvé použita ke studiu tohoto fenoménu u českých pacientů s malignitami. Výsledky studie budou porovnány s daty ve veřejně dostupných databázích, např. TCGA, ICGC a s výstupy projektu NCLG, který mapuje genetickou variabilitu obecné české populace. Hlavním výstupem projektu bude validovaný panel zárodečných variant a somaticky významných genů pro další studie a analýza účinnosti panelového sekvenování, ve srovnání s celoexomovým přístupem.; Search for molecular biomarkers enabling prediction of cancer treatment efficacy and establishment of optimal method for their assessment represent major opportunities, but also challenges in translational research. This project aims to explore feasibility of the next generation sequencing method for discovery of Czech population-specific genetic biomarkers for stratification of cancer patients into prognostically meaningful groups. Genetic background of patients treated with adjuvant chemotherapy regimens based on nucleoside analogs, taxanes and platinum derivatives will be explored by whole exome profiling method in cancer patients of Czech origin for the first time. Results will be compared with data in publicly available databases as TCGA and ICGC and with data from Czech NCGM genetic variability project. Panel of germline variants and somatically relevant genes for prognostication of patients will subsequently be validated and its cost efficacy and benefit will be evaluated in comparison with the whole exome approach.

• Klíčová slova
• prognosis, sekvenování nové generace, Next generation sequencing, therapy, nádor, cancer, terapie, proveditelnost, feasibility, prognoza,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Anastomotický leak a poruchy pasáže zažívacím traktem způsobené tvorbou peritoneálních adhezí patří mezi zásadní pooperační komplikace v kolorektální chirurgii. Na trhu nejsou k dispozici materiály, které by tyto komplikace spolehlivě eliminovaly. Cílem projektu je vyvinout unikátní dvouvrstvý nanovlákenný materiál s odlišnými vlastnostmi jednotlivých stran pro krytí chirurgických anastomóz. Materiál se bude skládat ze syntetických biokompatibilních a biodegradabilních polymerů a bude připraven kombinací electrospinningu a electrosprayingu na NanospiderTM. Vnitřní polymerní vlákna přilnou k anastomóze a podpoří hojení. Morfologie vnější antiadhezivní strany bude inspirována nativním superhydrofobním lotosovým povrchem a bude sloužit jako prevence adhezí. Materiály budou analyzovány in vitro testy za použití NIH/3T3 fibroblastů. Přilnavost k tkáni bude testována mechanicky. Funkce materiálu bude popsána na prasečím modelu komplikovaného hojení anastomózy na tračníku s třítýdenní observací zvířat zakončenou systematickým hodnocením peritoneálních adhezí a kvality anastomózy.; Anastomotic leakage and gastrointestinal obstruction due to formation of peritoneal adhesions are major postoperative complications in colorectal surgery. There are no available materials on the market capable of preventing such complications. The aim of the project is to develop a unique double-layered nanofibrous material to cover the intestinal anastomoses. The material will be composed of synthetic biocompatible and biodegradable polymers and prepared by combining the electrospinning and the electrospraying via NanospiderTM. The inner polymeric fibers will adhere to anastomosis and support healing. The outer anti-adhesive side will be inspired by the natural superhydrophobic lotus leaf structure and thus prevent the adhesions. The materials will be assessed in vitro using NIH/3T3 fibroblasts. The adhesion to tissue will be tested mechanically. The functionality of the material will be described in experimental model of complicated healing of colonic anastomosis on pig with three weeks observation period concluded with evaluation of peritoneal adhesions and anastomotic healing.

• Klíčová slova
• biokompatibilita, biocompatibility, nanovlákna, nanofibers, biodegradabilita, biodegradability, gastrointestinální anastomóza, anastomotický leak, pooperační adheze, abdominální chirurgie, superhydrofobicita, gastrointestinal anastomosis, anastomotic leakage, postoperative adhesion, abdominal surgery, superhydrophobic surface,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR